2021 ESC Guidelines On Cardiac Pacing and Cardiac Resynchronization Therapy

ESC GUIDELINES
European Heart Journal (2021) 00, 1 94 doi:10.1093/eurheartj/ehab364

—
2021 ESC Guidelines on cardiac pacing

and cardiac resynchronization therapy
Developed by the Task Force on cardiac pacing and cardiac
resynchronization therapy of the European Society of Cardiology
(ESC)
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With the special contribution of the European Heart Rhythm
Association (EHRA)
Authors/Task Force Members: of patiensMichael Glikson * (Chairperson) (Israel),

Jens Cosedis Nielsen* (Chairperson) (Denmark), Mads Brix Kronborg (Task Force
Coordinator) (Denmark), Yoav Michowitz (Task Force Coordinator) (Israel),
Angelo Auricchio (Switzerland), Israel Moshe Barbash (Israel), Jose´ A. Barrabe´s
(Spain), Giuseppe Boriani (Italy), Frieder Braunschweig (Sweden), Michele Brignole
(Italy), Haran Burri (Switzerland), Andrew J. S. Coats (United Kingdom),
Jean-Claude Deharo (France), Victoria Delgado (Netherlands), Gerhard-Paul Diller
(Germany), Carsten W. Israel (Germany), Andre Keren (Israel), Reinoud E. Knops
(Netherlands), Dipak Kotecha (United Kingdom), Christophe Leclercq (France),
* Corresponding authors: Michael Glikson, Jesselson Integrated Heart Center, Shaare Zedek Medical Center and Hebrew University Faculty of Medicine, Jerusalem, Israel, Tel: þ972 2
6555975, Email: [email protected].
Jens Cosedis Nielsen, Department of Clinical Medicine, Aarhus University and Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark, Tel: þ45
78 45 20 39, Email: [email protected].
Author/Task Force Member affiliations: listed in Author information.
ESC Clinical Practice Guidelines Committee (CPG): listed in the Appendix.
ESC subspecialty communities having participated in the development of this document:
Associations: Association for Acute CardioVascular Care (ACVC), Association of Cardiovascular Nursing & Allied Professions (ACNAP), European Association of Cardiovascular
Imaging (EACVI), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA).
Councils: Council for Cardiology Practice, Council on Basic Cardiovascular Science, Council on Cardiovascular Genomics, Council on Hypertension, Council on Stroke.
Working Groups: Adult Congenital Heart Disease, Cardiac Cellular Electrophysiology, Cardiovascular Regenerative and Reparative Medicine, Cardiovascular Surgery, e- Cardiology,
Myocardial and Pericardial Diseases.
Patient Forum
The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC Guidelines
may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher
of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC ([email protected]).
Disclaimer: The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their
publication. The ESC is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by
the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC Guidelines fully into account when
exercising their clinical judgement, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the ESC Guidelines do not override, in
any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that
patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official
updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective
ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of
prescription.
This article has been co-published with permission in the European Heart Journal and EP Europace. VC the European Society of Cardiology 2021. All rights reserved.
The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article. For permissions, please email
[email protected].
2 ESC Guidelines
Be´ la Merkely (Hungary), Christoph Starck (Germany), Ingela Thyle´ n (Sweden),

Jose´ Maria Tolosana (Spain), ESC Scientific Document Group
Document Reviewers: Francisco Leyva (CPG Review Coordinator) (United Kingdom), Cecilia Linde (CPG
Review Coordinator) (Sweden), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Elena Arbelo (Spain),
Riccardo Asteggiano (Italy), Gonzalo Baroń-Esquivias (Spain), Johann Bauersachs (Germany),
Mauro Biffi (Italy), Ulrika Birgersdotter-Green (United States of America ), Maria Grazia Bongiorni (Italy),
Michael A. Borger (Germany), Jelena Cˇ elutkiene_ (Lithuania), Maja Cikes (Croatia), Jean-Claude Daubert
(France), Inga Drossart (Belgium), Kenneth Ellenbogen (United States of America), Perry M. Elliott
(United Kingdom), Larissa Fabritz (United Kingdom), Volkmar Falk (Germany), Laurent Fauchier (France),
Francisco Ferna´ ndez-Avile´ s (Spain), Dan Foldager (Denmark), Fredrik Gadler (Sweden), Pastora Gallego Garcia De

Vinuesa (Spain), Bulent Gorenek (Turkey), Jose M. Guerra (Spain), Kristina Hermann Haugaa (Norway), Jeroen
Hendriks (Netherlands), Thomas Kahan (Sweden), Hugo A. Katus (Germany), Aleksandra Konradi (Russia),
Konstantinos C. Koskinas (Switzerland), Hannah Law (United Kingdom), Basil S. Lewis (Israel), Nicholas John
Linker (United Kingdom), Maja-Lisa Løchen (Norway), Joost Lumens (Netherlands), Julia Mascherbauer (Austria),
Wilfried Mullens (Belgium), Klaudia Vivien Nagy (Hungary), Eva Prescott (Denmark), Pekka Raatikainen (Finland),
Amina Rakisheva (Kazakhstan), Tobias Reichlin (Switzerland), Renato Pietro Ricci (Italy), Evgeny Shlyakhto (Russia),
Marta Sitges (Spain), Miguel Sousa-Uva (Portugal), Richard Sutton (Monaco), Piotr Suwalski (Poland), Jesper Hastrup
Svendsen (Denmark),
Rhian M. Touyz (United Kingdom), Isabelle C. Van Gelder (Netherlands), Kevin Vernooy (Netherlands), Johannes
Waltenberger (Germany), Zachary Whinnett (United Kingdom), Klaus K. Witte (United Kingdom)
All experts involved in the development of these guidelines have submitted declarations of interest. These have
been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report
is also available on the ESC website www.escardio.org/guidelines
For the Supplementary Data which include background information and detailed discussion of the data that
have provided the basis for the guidelines see European Heart Journal online
...................................................................................................................................................................................................
KeywordsGuidelines • cardiac pacing • cardiac resynchronization therapy • pacemaker • heart failure • syncope • atrial fibrillation • conduction system pacing • p
Table of contents .
3.4.3 Cardiac resynchronization therapy (endo-and/or
.. epicardial).....................................................................................14
1 Preamble..............................................................................................6 .
3.4.4 Alternative methods (conduction system pacing,
2 Introduction.........................................................................................8 .. leadless pacing)..............................................................................................14
2.1 Evidence review.............................................................................................8 .
3.4.4.1 Conduction system pacing.......................................................14
2.2 Relationships with industry......................................................................8
.. 3.4.4.2 Leadless pacing.......................................................................14
2.3 What is new in these guidelines...............................................................8 .
3.4.5 Pacing modes........................................................................................14
2.3.1 New concepts and new sections.......................................................8 .. 3.4.6 Rate-responsive pacing.........................................................................14
2.3.2 New recommendations in 2021........................................................9 .
3.5 Sex differences.............................................................................................14
2.3.3 Changes in cardiac pacing and cardiac resynchronization therapy .. 4 Evaluation of the patient with suspected or documented
guideline recommendations since 2013....................................................11 .
bradycardia or conduction system disease........................................................14
3 Background.......................................................................................11 .. 4.1 History and physical examination..........................................................14
3.1 Epidemiology.............................................................................11 .
4.2 Electrocardiogram..................................................................................16
3.2 Natural history.......................................................................................12 .. 4.3 Non-invasive evaluation..............................................................................16
3.3 Pathophysiology and classification of bradyarrhythmias .
considered for permanent cardiac pacing therapy........................................12 . 4.3.1 Ambulatory electrocardiographic monitoring................................16
. 4.3.2 Exercise testing.....................................................................................16
3.4 Types and modes of pacing: general description.........................................13
3.4.1 Endocardial pacing...............................................................................13 .. 4.3.3 Imaging........................................................................................................16
. 4.3.4 Laboratory tests..............................................................................17
3.4.2 Epicardial pacing..................................................................................13 .
. 4.3.5 Genetic testing......................................................................................17
ESC Guidelines 3
4.3.6 Sleep evaluation...................................................................................19 system pacing...............................................................................34

4.3.7 Tilt testing......................................................................................19 6.4 Patients with conventional pacemaker or implantable
4.4 Implantable monitors.............................................................................19 cardioverter defibrillator who need upgrade to cardiac
4.5 Electrophysiology study.........................................................................20 resynchronization therapy............................................................................35
5 Cardiac pacing for bradycardia and conduction system disease..........................21
5.1 Pacing for sinus node dysfunction...............................................................21
5.1.1 Indications for pacing......................................................................21
5.1.1.1..................................................Sinus node dysfunction
21
5.1.1.2 Bradycardia—tachycardia form of sinus node
dysfunction........................................................................ 22
5.1.2 Pacing mode and algorithm selection...................................................22
5.2 Pacing for atrioventricular block............................................................24
5.2.1.1.....................................First-degree atrioventricular block
24
5.2.1.2 Second-degree type I atrioventricular block
(Mobitz type I or Wenckebach).......................................................24
5.2.1.3 Second-degree Mobitz type II, 2:1, and advanced
atrioventricular block (also named high-grade atrioventricular
block, where the P:QRS ratio is 3:1 or higher), third-degree
atrioventricular block........................................................................24
5.2.1.4.....................................Paroxysmal atrioventricular block
24
5.2.2.1..................................Dual-chamber vs. ventricular pacing
25
5.2.2.2 Atrioventricular block in the case of permanent atrial
fibrillation.......................................................................25
5.3 Pacing for conduction disorders without atrioventricular block..............26
5.3.1.1....................Bundle branch block and unexplained syncope
26
5.3.1.2 Bundle branch block, unexplained syncope, and
abnormal electrophysiological study....................................................26
5.3.1.3.......................................Alternating bundle branch block
27
5.3.1................................Bundle branch block without symptoms
27
5.3.1.4................................Patients with neuromuscular diseases
27
5.4 Pacing for reflex syncope.............................................................................28
5.5 Pacing for suspected (undocumented) bradycardia......................................30
5.5.1 Recurrent undiagnosed syncope...........................................................30
5.5.2 Recurrent falls.................................................................................30
6 Cardiac resynchronization therapy................................................................30
6.1 Epidemiology, prognosis, and pathophysiology of heart
failure suitable for cardiac resynchronization therapy by
biventricular pacing......................................................................................30
6.2 Indication for cardiac resynchronization therapy: patients
in sinus rhythm.................................................................................31
6.3 Patients in atrial fibrillation....................................................................33
6.3.1 Patients with atrial fibrillation and heart failure who
are candidates for cardiac resynchronization therapy...............................33
6.3.2 Patients with uncontrolled heart rate who are candidates
for atrioventricular junction ablation (irrespective
of QRS duration).....................................................................................33
6.3.3 Emerging novel modalities for CRT: role of conduction
4 ESC Guidelines
.
6.5 Pacing in patients with reduced left ventricular ejection
. fraction and a conventional indication for antibradycardia
.
.
pacing...............................................................................................36
. .
6.6 Benefit of adding implantable cardioverter defibrillator in
.
patients with indications for cardiac resynchronization therapy..................36
. .
6.7 Factors influencing the efficacy of cardiac resynchronization
.
therapy: role of imaging techniques...................................................................37
. .
7 Alternative pacing strategies and sites.................................................................38
.
. 7.1 Septal pacing................................................................................................38
. 7.2 His bundle pacing.........................................................................................38
. 7.2.1 Implantation and follow-up............................................................38
.
. 7.2.2 Indications............................................................................................40
. 7.2.2 Pacing for bradycardia.....................................................................40
.
.

7.2.2 Pace and ablate.................................................................................40
. 7.2.2 Role in cardiac resynchronization therapy..................................40
.
. 7.3 Left bundle branch area pacing....................................................................41
. 7.4 Leadless pacing.............................................................................................41
.
.
8 Indications for pacing in specific conditions..................................................42
. 8.1 Pacing in acute myocardial infarction..........................................................42
.
.
8.2 Pacing after cardiac surgery and heart transplantation................................42
. 8.2.1 Pacing after coronary artery bypass graft and valve
.
.
surgery..........................................................................................42
. 8.2.2 Pacing after heart transplantation.........................................................43
.
.
8.2.3 Pacing after tricuspid valve surgery.....................................................43
. 8.3 Pacing after transcatheter aortic valve implantation...............................44
.
.
8.4 Cardiac pacing and cardiac resynchronization therapy in
. .
congenital heart disease.....................................................................................46
.
8.4.1 Sinus node dysfunction and bradycardia—tachycardia
. .
syndrome......................................................................................46
.
.. 8.4.1.1 Indications for pacemaker implantation...................................46
8.4.2 Congenital atrioventricular block...................................................46
.
. 8.4.2.1 Indications for pacemaker implantation...................................46
. 8.4.3 Post-operative atrioventricular block.............................................47
. 8.4.3.1 Indications for pacemaker implantation...................................47
.
. 8.4.4 Cardiac resynchronization...............................................................47
. 8.5 Pacing in hypertrophic cardiomyopathy.................................................47
.
. 8.5.1 Bradyarrhythmia..............................................................................47
. 8.5.2 Pacing for the management of left ventricular outflow
.
. tract obstruction.................................................................................47
. 8.5.3 Pacemaker implantation following septal myectomy
.
.
and alcohol septal ablation............................................................................48
. 8.5.4 Cardiac resynchronization therapy in end-stage
.
.
hypertrophic cardiomyopathy.................................................................48
. 8.6 Pacing in rare diseases..................................................................................48
.
.
8.6.1 LongQT syndrome..........................................................................48
. 8.6.2 Neuromuscular diseases.......................................................................48
.
.
8.6.3 Dilated cardiomyopathy with lamin A/C mutation.......................49
. 8.6.4 Mitochondrial cytopathies..............................................................49
.
.
8.6.5 Infiltrative and metabolic diseases.......................................................49
. .
8.6.6 Inflammatory diseases..........................................................................49
.
8.6.6.1 Sarcoidosis...............................................................................50
. .
8.7 Cardiac pacing in pregnancy........................................................................50
.
. 9 Special considerations on device implantations and perioperative
. management...............................................................................................50
. 9.1 General considerations...........................................................................50
.
. 9.2 Antibiotic prophylaxis...........................................................................50
.
. 9.3 Operative environment and skin antisepsis.............................................50
ESC Guidelines 5
9.4 Management of anticoagulation..............................................................51

.
9.5 Venous access..................................................................................51 Recommendations for cardiac pacing in patients
9.6 Lead considerations......................................................................................52 .. with suspected (undocumented) syncope and unexplained falls.......................30
.
9.7 Lead position..............................................................................52 Recommendations for cardiac resynchronization therapy in
9.8 Device pocket.............................................................................52 .. patients in sinus rhythm....................................................................................32
.
10. .Complications of cardiac pacing and cardiac resynchronization therapy Recommendations for cardiac resynchronization therapy in
.......................................................................................................53 .. patients with persistent or permanent atrial fibrillation...................................35
.
10.1 General complications..........................................................................53 Recommendation for upgrade from right ventricular pacing to
10.2 Specific complications...............................................................................54 .. cardiac resynchronization therapy....................................................................35
.
10.2.1 Lead complications.......................................................................54 Recommendation for patients with heart failure and
10.2.2Haematoma........................................................................54
.. atrioventricular block.......................................................................................36
.
10.2.3Infection.............................................................................54 . Recommendations for adding a defibrillator with cardiac
10.2.4 Tricuspid valve interference.........................................................54 . resynchronization therapy................................................................................37
10.2.5Other..................................................................................55 .. Recommendations for using His bundle pacing................................................41
.

11 Management considerations..............................................................................55 Recommendations for using leadless pacing (leadless pacemaker).......................42
11.1 Magnetic resonance imaging in patients with implanted .. Recommendations for cardiac pacing after acute myocardial
cardiac devices.................................................................................55 . infarction..............................................................................................42
11.2 Radiation therapy in pacemaker patients...................................................57 .. Recommendations for cardiac pacing after cardiac surgery and
11.3 Temporary pacing................................................................................58 . heart transplantation.........................................................................................44
11.4 Peri-operative management in patients with cardiovascular implantable .. Recommendations for cardiac pacing after transcatheter aortic
electronic devices.........................................................................................59 .
valve implantation............................................................................................46
11.5 Cardiovascular implantable electronic devices and sports .. Recommendations for cardiac pacing in patients with congenital
activity..............................................................................................59 .
heart disease............................................................................................................47
11.6 When pacing is no longer indicated.....................................................60 .. Recommendations for pacing in hypertrophic obstructive
11.7 Device follow-up.................................................................................60
.
cardiomyopathy....................................................................................48
12 Patient-centred care and shared decision-making in cardiac .. Recommendations for cardiac pacing in rare diseases...........................................48
pacing and cardiac resynchronization therapy........................................................61
.
Recommendation for patients with LMNA gene mutations...........................49
13 Quality indicators............................................................................61 .. Recommendations for pacing in Kearns—Sayre syndrome..............................49
.
14 Key messages........................................................................................63 Recommendations for pacing in cardiac sarcoidosis..............................................50
15 Gaps in evidence.............................................................................64 .. Recommendations regarding device implantations and
.
16 ‘What to do’ and ‘what not to do’ messages from the peri-operative management...............................................................................53
guidelines.............................................................................................65 .. Recommendations for performing magnetic resonance imaging
17 Supplementary data............................................................................................67
.
. in pacemaker patients.............................................................................................57
. Recommendations regarding temporary cardiac pacing........................................59
.
18 Author Information . . . . .. . . . . . . .. . . . .. . . . . . . .. . . . .. . . . . . . .. . . . . 68 . Recommendation when pacing is no longer indicated.....................................60
19 Appendix . . . . . . . . . .. . . . . . . . . . . . .. . . . .. . . . . . . .. . . . .. . . . . . . .. . . . . 70
. Recommendations for pacemaker and cardiac resynchronization
.
20 References .. . . . . . . .. . . . . . . . . . . . .. . . . .. . . . . . . .. . . . .. . . . . . . .. . . . . 70 . therapy-pacemaker follow-up..........................................................................61
. Recommendation regarding patient-centred care in cardiac pacing
.. and cardiac resynchronization therapy..............................................................61
.
Tables of Recommendations ..
List of tables
Recommendations for non-invasive evaluation . . . .. . . . .. . . . . . . .. . . . . 16 ...
Recommendation for ambulatory electrocardiographic . Table 1 Classes of recommendations........................................................................7
monitoring . . . .. . . . . . . .. . . . . . . . . . . . .. . . . .. . . . . . . .. . . . .. . . . . . . .. . . . . 17 Table 2 Levels of evidence........................................................................................7
. Table 3 New concepts and sections in current guidelines...................................8
Recommendations for exercise testing . . . . . . . . . . .. . . . .. . . . . . . .. . . . . 17 .
Table 4 New recommendations in 2021............................................................9
Recommendations regarding imaging before implantation . . . . . . . . . . . 18
.. Table 5 Changes in cardiac pacing and cardiac resynchronization
Recommendations for laboratory tests . . . . . .. .. . .. . . . .. . . . .. . .. . . . . 18 .
Recommendations for genetic testing . . . .. . . . . . . .. . . . .. . . . . . . .. . . . . 19 . therapy guideline recommendations since 2013................................................11
Recommendation for sleep evaluation . . . .. . . . . . . .. . . . .. . . . . . . .. . . . . 19
. Table 6 Drugs that may cause bradycardia or conduction
Recommendation for tilt testing . . . . .. . . . .. . . . . . . .. . . . .. . . . . . . .. . . . . 19 .. disorders...............................................................................................15
Recommendations
Recommendation forforimplantable electrophysiology loop recorders study..............................................21
. . . . . .. . . . . . . .. . . . . 19
. Table 7 Intrinsic and extrinsic causes of bradycardia.............................................16
Recommendations for pacing in sinus node dysfunction........................................24 .. Table 8 Choice of ambulatory electrocardiographic monitoring
Recommendations for pacing for atrioventricular block..................................25 . depending on symptom frequency....................................................................17
Recommendations for pacing in patients with .. Table 9 Advantages and disadvantages of a ‘backup’ ventricular
bundle branch block.............................................................................27 . lead with His bundle pacing..............................................................................40
Recommendations for pacing for reflex syncope..............................................30 .. Table 10 Predictors for permanent pacing after transcatheter
.
aortic valve implantation..................................................................................45
6 ESC Guidelines
Table 11 Management of anticoagulation in pacemaker . AVB Atrioventricular block

..
procedures............................................................................................51
AVJ Atrioventricular junction
Table 12 Complications of pacemaker and cardiac .
AVN Atrioventricular node
..
resynchronization therapy implantation...........................................................54
BBB Bundle branch block
Table 13 Frequency of follow-up for routine pacemaker and .
BLOCK-HF Biventricular versus RV pacing in patients
cardiac resynchronization therapy, either in person alone or
.. with AV block (trial)
combined with remote device management.....................................................60 .
b.p.m. Beats per minute
Table 14 Topics and content that may be included in patient
.. BRUISE CONTROL Bridge or Continue Coumadin for
education..............................................................................................62 .
Device Surgery Randomized Controlled
Table 15 A selection of the developed quality indicators for patients
.. Trial
undergoing cardiovascular implantable electronic device .
BRUISE CONTROL-2 Randomized Controlled Trial of
implantation.........................................................................................63
.. Continued Versus Interrupted Direct
.
List of figures ..
Oral Anti-Coagulant at the Time of

. Device Surgery
Figure 1 Central Illustration.............................................................................12 CABG Coronary artery bypass graft
Figure 2 Classification of documented and suspected .. CARE-HF CArdiac REsynchronization in Heart
bradyarrhythmias.................................................................................13 .. Failure (trial)
Figure 3 Initial evaluation of patients with symptoms suggestive of bradycardia . CHD Congenital heart disease
..............................................................................................................15 .. CI Confidence interval
Figure 4 Evaluation of bradycardia and conduction disease . CIED Cardiovascular implantable electronic
algorithm..............................................................................................20 .. device
Figure 5 Optimal pacing mode and algorithm selection in sinus . CMR Cardiovascular magnetic resonance
node dysfunction and atrioventricular block....................................................23 .. COMPANION COmparison of Medical therapy, PAcing
Figure 6 Decision algorithm for patients with unexplained syncope .
aNd defibrillatION (trial)
and bundle branch block...................................................................................26 .. CPAP Continuous positive airway pressure
Figure 7 Decision pathway for cardiac pacing in patients with .
CRT Cardiac resynchronization therapy
reflex syncope......................................................................................28 .. CRT-D Defibrillator with cardiac
Figure 8 Summary of indications for pacing in patients >40 years .
resynchronization therapy
of age with reflex syncope................................................................................29 .. CRT-P Cardiac resynchronization therapy-
Figure 9 Indication for atrioventricular junction ablation in patients with
.
pacemaker
symptomatic permanent atrial fibrillation or persistent atrial .. CSM Carotid sinus massage
fibrillation unsuitable for atrial fibrillation ablation.........................................34
.
CSS Carotid sinus syndrome
Figure 10 Patient’s clinical characteristics and preference to be .. CT Computed tomography
considered for the decision-making between cardiac
.
DANPACE DANish Multicenter Randomized
resynchronization therapy pacemaker or defibrillator.....................................38 .. Trial on Single Lead Atrial PACing vs.
Figure 11 Three patients with different types of transitions in
.
Dual Chamber Pacing in Sick Sinus
QRS morphology with His bundle pacing and decrementing .. Syndrome
.
pacing output........................................................................................39 DDD Dual-chamber, atrioventricular pacing
Figure 12 Management of conduction abnormalities after .. ECG Electrocardiogram/electrocardiographic
transcatheter aortic valve implantation.............................................................45
.. Echo-CRT Echocardiography Guided Cardiac
Figure 13 Integrated management of patients with pacemaker and . Resynchronization Therapy (trial)
cardiac resynchronization therapy.....................................................................56 .. EF Ejection fraction
Figure 14 Flowchart for evaluating magnetic resonance imaging in pacemaker . EHRA European Heart Rhythm Association
patients.................................................................................................57 .. EMI Electromagnetic interference
Figure 15 Pacemaker management during radiation therapy..................................58 . EORP EurObservational Research Programme
Figure 16 Example of shared decision-making in patients .. EPS Electrophysiology study
considered for pacemaker/CRT implantation...................................................62 .
ESC European Society of Cardiology
.. EuroHeart European Unified Registries On Heart
.
Care Evaluation and Randomized Trials
Abbreviations and acronyms .. HBP His bundle pacing
.
AF Atrial fibrillation HCM Hypertrophic cardiomyopathy
.. HF Heart failure
APAF Ablate and Pace in Atrial Fibrillation .
(trial) HFmrEF Heart failure with mildly reduced ejection
.. fraction
ATP Antitachycardia pacing .
HFpEF Heart failure with preserved ejection
AV Atrioventricular .
. fraction
ESC Guidelines 7
.
HFrEF Heart failure with reduced ejection SAR Specific absorption rate
fraction .. SAS Sleep apnoea syndrome
.
HOT-CRT His-optimized cardiac resynchronization SCD Sudden cardiac death
therapy .. SND Sinus node dysfunction
.
HR Hazard ratio SR Sinus rhythm
.. TAVI Transcatheter aortic valve implantation
HV His—ventricular interval (time from the .
beginning of the H deflection to the VKA Vitamin K antagonist
earliest onset of ventricular depolarization
.. WRAP-IT World-wide Randomized Antibiotic
.
recorded in any lead, electrophysiology Envelope Infection Prevention Trial
study of the heart) ..
.
ICD Implantable cardioverter-defibrillator .
ILR Implantable loop recorder . 1 Preamble
LBBB Left bundle branch block ..

LGE Late gadolinium contrast enhanced . Guidelines summarize and evaluate available evidence with the aim of
.
LQTS Long QT syndrome assisting health professionals in proposing the best management
LV Left ventricular
.. strategies for an individual patient with a given condition. Guidelines
.
LVEF Left ventricular ejection fraction and their recommendations should facilitate decision-making of
.. health professionals in their daily practice. However, the final deci-
MADIT-CRT Multicenter Automatic Defibrillator .
Implantation with Cardiac sions concerning an individual patient must be made by the responsi-
.. ble health professional(s) in consultation with the patient and
Resynchronization Therapy (trial) .
MI Myocardial infarction caregiver, as appropriate.
.. A great number of guidelines have been issued in recent years by
MIRACLE Multicenter Insync RAndomized Clinical .
the European Society of Cardiology (ESC), as well as by other soci-
Evaluation (trial) .. eties and organizations. Because of their impact on clinical practice,
MOST MOde Selection Trial in Sinus-Node .
quality criteria for the development of guidelines have been estab-
..
Dysfunction
MRI Magnetic resonance imaging lished in order to make all decisions transparent to the user. The rec-
MUSTIC MUltisite STimulation In .. ommendations for formulating and issuing ESC Guidelines can be
Cardiomyopathies (trial)
. found on the ESC website (https://www.escardio.org/Guidelines).
NOAC Non-vitamin K antagonist oral .. The ESC Guidelines represent the official position of the ESC on a
anticoagulant
. given topic and are regularly updated.
NYHA New York Heart Association .. In addition to the publication of Clinical Practice Guidelines, the ESC
. carries out the EurObservational Research Programme of international
OAC Oral anticoagulant
OMT Optimal medical therapy .. registries of cardiovascular diseases and interventions which are essen-
.
OR Odds ratio tial to assess diagnostic/therapeutic processes, use of resources, and
PATH-CHF PAcing THerapies in Congestive Heart .. adherence to guidelines. These registries aim at providing a better
.
Failure (trial) understanding of medical practice in Europe and around the world,
PCCD Progressive cardiac conduction disease .. based on high-quality data collected during routine clinical practice.
.
PCI Percutaneous coronary intervention Furthermore, the ESC has developed and embedded in this docu-
PET Positron emission tomography .. ment a set of quality indicators (QIs), which are tools to evaluate the
.
PM Pacemaker level of implementation of the guidelines and may be used by the
RA Right atrium/atrial
.. ESC, hospitals, healthcare providers, and professionals to measure
.
RAFT Resynchronization—Defibrillation for clinical practice as well as in educational programmes, alongside the
Ambulatory Heart Failure Trial
.. key messages from the guidelines, to improve quality of care and clini-
.
RBBB Right bundle branch block cal outcomes.
.. The Members of this Task Force were selected by the ESC, includ-
RCT Randomized controlled trial .
RESET-CRT Re-evaluation of Optimal Re- ing representation from its relevant ESC subspecialty groups, in order
.. to represent professionals involved with the medical care of patients
synchronisation Therapy in Patients with .
Chronic Heart Failure (trial) with this pathology. Selected experts in the field undertook a com-
REVERSE REsynchronization reVErses Remodelling in .. prehensive review of the published evidence for management of a
Systolic left vEntricular dysfunction (trial) .. given condition according to ESC Clinical Practice Guidelines
RV Right ventricular/right ventricle . Committee (CPG) policy. A critical evaluation of diagnostic and ther-
RVA Right ventricular apical .. apeutic procedures was performed, including assessment of the
RVOT Right ventricular outflow tract . risk—benefit ratio. The level of evidence and the strength of the rec-
RVS Right ventricular septum .. ommendation of particular management options were weighed and
S. aureus Staphylococcus aureus
. graded according to pre-defined scales, as outlined below.
.. The experts of the writing and reviewing panels provided declara-
.
tion of interest forms for all relationships that might be perceived as
8 ESC Guidelines
Table 1 Classes of recommendations
Classes of recommendations Wording to use
Class I Evidence and/or general agreement that a Is recommended or is indicated

given treatment or procedure is
Class II

Class IIa Weight of evidence/opinion is in Should be considered
Class IIb May be considered

established by evidence/opinion.
Class III Evidence or general agreement that the given Is not recommended
treatment or procedure is not useful/effective,
©ESC 2021
and in some cases
may be harmful.
Table 2 Levels of evidence
Level of Data derived from multiple randomized clinical trials or

evidence A meta-analyses.
Level of Data derived from a single randomized clinical trial or

evidence B large non-randomized studies.
Level of Consensus of opinion of the experts and/or small studies,

©ESC 2021
evidence C retrospective studies, registries.
.
real or potential sources of conflicts of interest. Their declarations of endorsement process of these Guidelines. The ESC Guidelines
.. undergo extensive review by the CPG and external experts. After
interest were reviewed according to the ESC declaration of interest rules .
and can be found on the ESC website (http://www.escardio.org/ appropriate revisions, the guidelines are signed-off by all the
.. experts involved in the Task Force. The finalized document is
guidelines) and have been compiled in a report and published in a .
supplementary document simultaneously with the guidelines. signed-off by the CPG for publication in the European Heart
.. Journal. The guidelines were developed after careful consideration
This process ensures transparency and prevents potential biases in the .
development and review processes. Any changes in declarations of interest . of the scientific and medical knowledge and the evidence available
that arose during the writing period were notified to the ESC and . at the time of their dating.
updated. The Task Force received its entire financial support from the ESC .. The task of developing ESC Guidelines also includes the creation
without any involvement from the healthcare industry. . of educational tools and implementation programmes for the recom-
The ESC CPG supervises and coordinates the preparation of new .. mendations including condensed pocket guideline versions, summary
guidelines. The Committee is also responsible for the . slides, summary cards for non-specialists, and an electronic version
ESC Guidelines 9
.
for digital applications (smartphones, etc.). These versions are abridged Pericardial Diseases, as well as the Association of Cardiovascular
.. Nursing & Allied Professions.
and thus, for more detailed information, the user should always access .
to the full text version of the guidelines, which is freely available via the ESC .
website and hosted on the EHJ website. The National Cardiac Societies . 2.1 Evidence review
of the ESC are encouraged to endorse, adopt, translate, and implement all .. This document is divided into sections, each with a section coordina-
ESC Guidelines. Implementation programmes are needed because it has
.
tor and several authors. They were asked to thoroughly review the
been shown that the outcome of disease may be favourably influenced by .. recent literature on their topics, and to come up with recommenda-
the thorough application of clinical recommendations.
.
tions and grade them by classification as well as by level of evidence.
Health professionals are encouraged to take the ESC Guidelines fully .. Where data seemed controversial, a methodologist (Dipak Kotecha)
.
into account when exercising their clinical judgement, as well as in the was asked to evaluate the strength of the evidence and to assist in
determination and the implementation of preventive, diagnostic, or .. determining the class of recommendation and level of evidence. All
.
therapeutic medical strategies. However, the ESC Guidelines do not recommendations were voted on by all authors of the document and
override in any way whatsoever the individual responsibility of health .. were accepted only if supported by at least 75% of the co-authors.
.

professionals to make appropriate and accurate decisions in consideration The leaders (Jens Cosedis Nielsen and Michael Glikson) and the
of each patient’s health condition and in consultation with that patient or .. coordinators of this document (Yoav Michowitz and Mads Brix
.
the patient’s caregiver where appropriate and/or necessary. It is also the Kronborg) were responsible for alignment of the recommendations
health professional’s responsibility to verify the rules and regulations .. between sections, and several members of the writing committee
.
applicable in each country to drugs and devices at the time of were responsible for overlap with other ESC Guidelines, such as the
prescription. .. HF guidelines and the valvular heart disease guidelines.
..
.
2.2 Relationships with industry
2 Introduction .. All work in this document was voluntary and all co-authors were
.
required to declare and prove that they do not have conflicts of inter-
Pacing is an important part of electrophysiology and of cardiology in .. ests, as defined recently by the Scientific Guideline Committee of the
general. Whereas some of the situations requiring pacing are clear and have
.
ESC and the ESC board.
not changed over the years, many others have evolved and have been the ...
subject of extensive recent research, such as pacing after syncope (section 2.3 What is new in these guidelines
5), pacing following transcatheter aortic valve implantation (TAVI; .. 2.3.1 New concepts and new sections
section 8), cardiac resynchronization therapy (CRT) for heart failure
..
(HF) and for prevention of pacing-induced cardiomyopathy (section 6), .
Table 3 New concepts and sections in current
and pacing in various infiltrative and inflammatory diseases of the heart, as
.. guidelines
well as in different cardiomyopathies (section 8). Other novel topics .
include new diagnostic tools for decision-making on pacing (section 4), as . Concept/section Section
.
well as a whole new area of pacing the His bundle and the left bundle . New section on types and modes of pacing, including conduction system pacing and le
3.4
branch (section 7). In addition, attention has increased in other areas, . New section on sex differences in pacing
. New section on evaluation of patients for pacing Expanded and updated section on CRT
such as how to systematically minimize procedural risk and avoid . New section on alternative pacing strategies and sites Expanded and 3.5updated section on
complications of cardiac pacing (section 9), how to manage patients with . A new section on implantation and perioperative management, including 4 perioperative
. An expanded revised section on CIED complications A new section 6 on various manage
pacemakers in special situations, such as when magnetic resonance imaging . 7
(MRI) or irradiation are needed (section 11), how to follow patients with . including MRI, radiotherapy, temporary pacing, periopera-
. tive management, sport activity, and follow up 8
a pacemaker with emphasis on the use of remote monitoring, and how to . A new section on patient-centred care
include shared decision-making in caring for this patient population .
.
(section 12). .
The last pacing guidelines of the European Society of Cardiology .
.
(ESC) were published in 2013; therefore, a new set of guidelines was felt to . 9
be timely and necessary. .
.
To address these topics, a Task Force was established to create the new . 10
guidelines. As well as receiving the input of leading experts in the field of . 11
.
pacing, the Task Force was enhanced by representatives from the .
Association for Acute CardioVascular Care, the Heart Failure .
.
ESC 2021
Association, the European Association of Cardiothoracic Surgery, the . 12

European Association of Percutaneous Cardiovascular Interventions, .
.
the ESC Working Group on Myocardial and . CIED = cardiovascular implantable electronic device; CRT = cardiac resynchroni-
. zation therapy; MRI = magnetic resonance imaging; TAVI = transcatheter aortic
. valve implantation.
10 ESC Guidelines
2.3.2 New recommendations in 2021 . Laboratory tests

. In addition to preimplant laboratory tests,d specific
Table 4 New recommendations in 2021
.
. laboratory tests are recommended in patients with
. clinical suspicion for potential causes of bradycardia
. I C
Recommendations Classa Levelb . (e.g. thyroid function tests, Lyme titre, digitalis level,
. potassium, calcium, and
Evaluation of the patient with suspected or documented
.
. pH) to diagnose and treat these conditions.
brady- .
cardia or conduction system disease . Sleep evaluation
. Screening for SAS is recommended in patients
Monitoring .
In patients with infrequent (less than once a month) . with symptoms of SAS and in the presence of
I C
. severe bradycardia or advanced AVB during
unexplained syncope or other symptoms suspected .
to be caused by bradycardia, in whom a . sleep.
I A . Electrophysiological study

comprehensive evaluation did not demonstrate a .
cause, long-term ambulatory monitor- . In patients with syncope and bifascicular block,
. EPS should be considered when syncope remains
ing with an ILR is recommended. .
Ambulatory electrocardiographic monitoring is . unexplained after non-invasive evaluation or when
. an immediate decision about pacing is needed due IIa B
recommended in the evaluation of patients with .
suspected bradycardia to correlate rhythm dis-
I C . to severity, unless empirical pacemaker
. implantation is preferred (especially
turbances with symptoms. .
Carotid massage . in elderly and frail patients).
. In patients with syncope and sinus bradycardia, EPS
Once carotid stenosis is ruled outc, carotid sinus .
massage is recommended in patients with syncope . may be considered when non-invasive tests have failed
IIb B
. to show a correlation between syn-
of unknown origin compatible with a reflex I B .
mechanism or with symptoms related to pres- . cope and bradycardia.
. Genetics
sure/manipulation of the carotid sinus area. .
Tilt test
. Genetic testing should be considered in patients
. with early onset (age <50 years) of progressive IIa C
Tilt testing should be considered in patients with .
IIa B . cardiac conduction disease.
suspected recurrent reflex syncope. . Genetic testing should be considered in family members
Exercise test .
. following the identification of a patho- genic genetic
Exercise testing is recommended in patients who . variant that explains the clinical phenotype of cardiac IIa C
experience symptoms suspicious of brady- I C .
. conduction disease in an
cardia during or immediately after exertion. . index case.
In patients with suspected chronotropic incom- .
. Cardiac pacing for bradycardia and conduction system
petence, exercise testing should be considered IIa B . disease
to confirm the diagnosis. .
. Pacing is indicated in symptomatic patients with the
In patients with intra-ventricular conduction dis- . bradycardia-tachycardia form of SND to correct
ease or AVB of unknown level, exercise testing IIb C .
. bradyarrhythmias and enable pharmacological I B
may be considered to expose infranodal block. . treatment, unless ablation of the
Imaging .
. tachyarrhythmia is preferred.
Cardiac imaging is recommended in patients with . Pacing is indicated in patients with atrial arrhyth-
suspected or documented symptomatic bradycardia .
. mia (mainly AF) and permanent or paroxysmal
I C
to evaluate the presence of structural heart disease,
I C
. third- or high-degree AVB irrespective of
to determine left ventricular systolic function, and .
. symptoms.
to diagnose potential . In patients with SND and DDD PM, minimiza-
causes of conduction disturbances. .
. tion of unnecessary ventricular pacing through I A
Multimodality imaging (CMR, CT, PET) should be . programming is recommended.
considered for myocardial tissue characterization .
. Dual chamber cardiac pacing is indicated to reduce
in the diagnosis of specific pathologies associated . recurrent syncope in patients aged >40 years with
with conduction abnormalities needing pacemaker
IIa C .
. severe, unpredictable, recurrent syncope who
implantation, particularly in . have:
patients younger than 60 years. .
. • spontaneous documented symptomatic asys- I A
.
Continued . tolic pause/s >3 s or asymptomatic pause/s
. >6 s due to sinus arrest or AVB; or
.
. • cardioinhibitory carotid sinus syndrome; or
. • asystolic syncope during tilt testing.
.
.
Continued
ESC Guidelines 11
.
In patients with recurrent unexplained falls, the . HBP with a ventricular backup lead may be con-
.
same assessment as for unexplained syncope IIa C . sidered in patients in whom a “pace-and-ablate”
should be considered. . strategy for rapidly conducted supraventricular IIb C
.
AF ablation should be considered as a strategy to . arrhythmia is indicated, particularly when intrin-
avoid pacemaker implantation in patients with AF- . sic QRS is narrow.
.
related bradycardia or symptomatic pre- automaticity IIa C . HBP may be considered as an alternative to right
pauses, after AF conversion, taking . ventricular pacing in patients with AVB and LVEF
. IIb C
into account the clinical situation. . >40%, who are anticipated to have >20% ven-
In patients with the bradycardia-tachycardia var- . tricular pacing.
.
iant of SND, programming of atrial ATP may be IIb B . Leadless pacing
considered. . Leadless pacemakers should be considered as an
.
.

Dual-chamber cardiac pacing may be considered to alternative to transvenous pacemakers when no upper
reduce syncope recurrences in patients with the
. extremity venous access exists or when risk of
IIb B . IIa B
clinical features of adenosine-sensitive . device pocket infection is particularly high, such as
. previous infection and patients on
syncope. .
Cardiac resynchronization therapy . haemodialysis.
.
In patients who are candidates for an ICD and who . Leadless pacemakers may be considered as an
have CRT indication, implantation of a I A . alternative to standard single lead ventricular
. IIb C
CRT-D is recommended. . pacing, taking into consideration life expectancy
In patients who are candidates for CRT, implan- . and using shared decision-making.
.
tation of a CRT-D should be considered after
IIa B . Indications for pacing in specific conditions
individual risk assessment and using shared deci- . Pacing in acute myocardial infarction
.
sion-making. . Implantation of a permanent pacemaker is indicated
In patients with symptomatic AF and an uncon- . with the same recommendations as in a general
.
trolled heart rate who are candidates for AVJ . population (section 5.2) when AVB does not resolve I C
ablation (irrespective of QRS duration), CRT rather IIa C . within a waiting period of at least 5
.
than standard RV pacing should be con- . days after MI.
sidered in patients with HFmrEF. . In selected patients with AVB in context of anterior
.
In patients with symptomatic AF and an uncontrolled . wall MI and acute HF, early device implanta- IIb C
heart rate who are candidates for AVJ ablation . tion (CRT-D/CRT-P) may be considered.
IIa B .
(irrespective of QRS duration), RV pac- . Pacing in cardiac surgery
ing should be considered in patients with HFpEF. . 1) High-degree or complete AVB after cardiac
.
In patients with symptomatic AF and an uncon- . surgery. A period of clinical observation for at least
trolled heart rate who are candidates for AVJ . 5 days is indicated in order to assess whether the
IIb B .
ablation (irrespective of QRS duration), CRT . rhythm disturbance is transient and resolves.
may be considered in patients with HFpEF. . However, in the case of complete AVB with low or
I C
.
Alternate site pacing . no escape rhythm when resolution is unlikely, this
His bundle pacing . observation period can be
.
In patients treated with HBP, device program- . shortened.
ming tailored to specific requirements of His I C . SND after cardiac surgery and heart transplantation.
.
bundle pacing is recommended. . Before permanent pacemaker implantation, a period
In CRT candidates in whom coronary sinus lead
. IIa C
. of observation for up to 6 weeks should
implantation is unsuccessful, HBP should be con- . be considered.
IIa B .
sidered as a treatment option along with other . Chronotropic incompetence after heart trans-
techniques such as surgical epicardial lead. . plantation. Cardiac pacing should be considered for
.
In patients treated with HBP, implantation of a right . chronotropic incompetence persisting more than 6 IIa C
ventricular lead used as “backup” for pacing should . weeks after heart transplantation to
.
be considered in specific situations (e.g. pacemaker- . improve quality of life.
dependency, high-grade AVB, infranodal block, high . Continued
IIa C .
pacing threshold, planned AVJ ablation), or for .
sensing in case of issues with detection (e.g. risk of .
.
ventricular undersensing .
or oversensing of atrial/His potentials). .
.
.
Continued
.
.
.
12 ESC Guidelines
.
Surgery for valvular endocarditis and intraoperative . Ambulatory ECG monitoringg or electrophysiol-
.
complete AVB. Immediate epicardial pacemaker . ogy studyh may be considered for TAVI patients with
implantation should be considered in patients with . pre-existing conduction abnormality who develop IIb C
.
surgery for valvular endocarditis and complete AVB . further prolongation of QRS or PR
if one of the following predictors of persistence is IIa C . >20 ms.
.
present: preoperative conduction abnormality, . Prophylactic permanent pacemaker implantation is
Staphylococcus aureus infection, intracardiac . not indicated before TAVI in patients with III C
.
abscess, tricuspid valve . RBBB and no indication for permanent pacing.
involvement, or previous valvular surgery. . Various syndromes
.
Patients requiring pacing at the time of tricuspid . In patients with neuromuscular diseases such as
valve surgery. Transvalvular leads should be avoided . myotonic dystrophy type 1 and any second- or
. I C

and epicardial ventricular leads used. During . third-degree AVB or HV >_70 ms, with or with-
tricuspid valve surgery, removal of pre- existing . out symptoms, permanent pacing is indicated.i
.
transvalvular leads should be considered and . In patients with LMNA gene mutations, including
preferred over sewing-in the lead between the IIa C . Emery-Dreifuss and limb girdle muscular dystro-
.
annulus and a bio-prosthesis or annuloplasty ring. In . phies who fulfil conventional criteria for pacemaker
the case of an isolated tricuspid annuloplasty based
. implantation or who have prolonged PR with LBBB, IIa C
.
on an individual risk-benefit analysis, a pre-existing . ICD implantation with pacing capabilities should be
right ventricular lead may be left in
.
. considered if at least 1-year sur-
place without jailing it between ring and annulus. . vival is expected.
.
Patients requiring pacing after biological tricuspid . In patients with Kearns-Sayre syndrome who have
valve replacement/tricuspid valve ring repair. . PR prolongation, any degree of AVB, bundle
. IIa C
When ventricular pacing is indicated, transvenous . branch block, or fascicular block, permanent
implantation of a coronary sinus lead or minimally . pacing should be considered.
IIa C .
invasive placement of an epicardial ventricular lead . In patients with neuromuscular disease such as
should be considered and preferred over a . myotonic dystrophy type 1 with PR >_240 ms or
. IIb C
transvenous transvalvular . QRS duration >_120 ms, permanent pacemaker
approach. . implantation may be considered.i
.
Patients requiring pacing after mechanical tricuspid . In patients with Kearns-Sayre Syndrome without
valve replacement. Implantation of a trans- III C . cardiac conduction disorder, permanent pacing may IIb C
.
valvular right ventricular lead should be avoided. . be considered prophylactically.
Pacing in transcatheter aortic valve implantation . Sarcoidosis
.
Permanent pacing is recommended in patients with . In patients with cardiac sarcoidosis who have
complete or high-degree AVB that persists I B . permanent or transient AVB, implantation of a
. IIa C
for 24 - 48 h after TAVI. . device capable of cardiac pacing should be
Permanent pacing is recommended in patients . considered.i
I C .
with new onset alternating BBB after TAVI. . In patients with sarcoidosis and indication for
Earlye permanent pacing should be considered in . permanent pacing who have LVEF <50%, implantation IIa C
.
patients with pre-existing RBBB who develop any . of a CRT-D should be considered.
further conduction disturbance during or
IIa B . Special considerations on device implantations and periopera-
.
after TAVI.f . tive management
Ambulatory ECG monitoringg or an electro- . Administration of preoperative antibiotic prophylaxis
.
physiology studyh should be considered for patients . within 1 h of skin incision is recom- I A
with new LBBB with QRS >150 ms or PR >240 ms IIa C . mended to reduce risk of CIED infection.
.
with no further prolongation during . Chlorhexidine alcohol instead of povidone- iodine
>48 h after TAVI.
. alcohol should be considered for skin IIa B
.
. antisepsis.
Continued . Continued
.
.
.
ESC Guidelines 13
.
For venous access, the cephalic or axillary vein . In-office routine follow-up of single- and dual- chamber
IIa B .
should be considered as first choice. . pacemakers may be spaced by up to 24 months in
For implantation of coronary sinus leads, quadri-
. patients on remote device
IIa A
IIa C .
polar leads should be considered as first choice. . management.
.
To confirm target ventricular lead position, use of . Temporary pacing
multiple fluoroscopic views should be IIa C . Temporary transvenous pacing is recommended in
.
considered. . cases of haemodynamic-compromising bra-
I C
Rinsing the device pocket with normal saline solution . dyarrhythmia refractory to intravenous chrono-
.
before wound closure should be IIa C . tropic drugs.
considered. . Transcutaneous pacing should be considered in cases
.
In patients undergoing a reintervention CIED procedure, . of haemodynamic compromising bradyarrhythmia
IIa C
the use of an antibiotic-eluting enve- IIb B . when temporary transvenous pacing is
.

lope may be considered. . not possible or available.
Pacing of the mid-ventricular septum may be considered . Temporary transvenous pacing should be con-
.
in patients with a high risk of perfora- IIb C . sidered when immediate pacing is indicated and
tion (elderly, previous perforation). . pacing indications are expected to be reversible, such
. IIa C
In pacemaker implantations in patients with pos- . as in the context of myocardial ischaemia,
sible pocket issues such as increased risk of ero- sion . myocarditis, electrolyte disturbances, toxic
.
due to low body mass index, Twiddler’s syndrome or IIb C . exposure, or after cardiac surgery.
aesthetic reasons, a submuscular . Temporary transvenous pacing should be considered as
.
device pocket may be considered. . a bridge to permanent pacemaker implantation, when this
Heparin-bridging of anticoagulated patients is . procedure is not immediately available or possible due IIa C
III A .
not recommended. . to concomitant
Permanent pacemaker implantation is not rec- . infection.
.
ommended in patients with fever. Pacemaker . For long-term temporary transvenous pacing, an
implantation should be delayed until the patient
III B . active fixation lead inserted through the skin and
. IIa C
has been afebrile for at least 24 h. . connected to an external pacemaker should be
Management considerations
. considered.
.
Remote monitoring . Miscellaneous
Remote device management is recommended to
. When pacing is no longer indicated, a decision on the
.
reduce number of in-office follow-up in patients . management strategy should be based on an
. individual risk-benefit analysis in a shared decision- I C
with pacemakers who have difficulties to attend in-
I A .
office visits (e.g. due to reduced mobility or other . making process together with the
.
commitments or according to patient . patient.
preference). . MRI may be considered in pacemaker patients with
.
Remote monitoring is recommended in case of a . abandoned transvenous leads if no alterna- IIb C
device component that has been recalled or is on . tive imaging modality is available.
.
advisory, to enable early detection of actionable
I C . Continued
events in patients, particularly those who are at .
.
increased risk (e.g. in case of pacemaker- .
dependency). .
.
.
Continued .
.
14 ESC Guidelines
. .
Patient-centred care .
.
In patients considered for pacemaker or CRT, the .
decision should be based on the best available .
.
evidence with consideration of individual risk- .
benefits of each option, the patient´s preferences, .
.
and goals of care, and it is recommended to follow I C .
an integrated care approach and use the principles .
.
of patient- centred care and shared decision making .
ESC 2021
in .
.
the consultation. .
.
AF = atrial fibrillation; ATP = antitachycardia pacing; AV = atrioventricular; AVB .
= atrioventricular block; AVJ = atrioventricular junction; BBB = bundle branch block; .
BMI = body mass index; CIED = cardiovascular implantable electronic device; CMR = .
cardiovascular magnetic resonance; CRT = cardiac resynchroniza- .
tion therapy; CRT-D =
.
defibrillator with cardiac resynchronization therapy; CRT-P = cardiac resynchronization
.
therapy-pacemaker; CSM = carotid sinus massage; CT = computed tomography; DDD =
.
dual-chamber, atrioventricular .
pacing; ECG = electrocardiogram; EPS = electrophysiology study; HBP = His bundle
.
pacing; HF = heart failure; HFmrEF = heart failure with mildly reduced ejection fraction;
.
HFpEF = heart failure with preserved ejection fraction; HV = .
His ventricular interval;
.
ICD—= implantable cardioverter-defibrillator; ILR = implantable loop recorder; LBBB =
left bundle branch block; LV = left ventricular; .
LVEF = left ventricular ejection fraction;
MI = myocardial infarction; MRI = mag-
.
netic resonance imaging; OMT = optimal
.
medical therapy; PET = positron emis- .
sion tomography; PR = PR interval; QRS = Q, R, and S waves; RBBB = right .
bundle branch block; RV = right ventricular; SAS = sleep apnoea syndrome; SND .
= sinus node dysfunction; SR = sinus rhythm; TAVI = transcatheter aortic valve .
implantation. .
a .
b
Class of recommendation.
Level of evidence.
.
c
CSM should not be undertaken in patients with previous transient ischaemic
.
.
attack, stroke, or known carotid stenosis. Carotid auscultation should be performed .
.
before carotid sinus massage. If a carotid bruit is present, carotid ultrasound should be
performed to exclude carotid disease
. d
Complete blood counts, prothrombin time, partial thromboplastin time, serum .
creatinine, and electrolytes.
. .
.
e
Immediately after procedure or within 24 h.
f
Transient high-degree AVB, PR prolongation, or QRS axis change.
g
.
Ambulatory continuous ECG monitoring (implantable or external) for 7 30—
days.
..
h
Electrophysiology study with HV >_70 ms may be considered positive for perma-
.
nent pacing. .
i .
Whenever pacing is indicated in neuromuscular disease, an ICD should be con-
sidered according to relevant guidelines.
.
.
.
.
.
.
2.3.3 Changes in cardiac pacing and cardiac
. .
resynchronization therapy guideline recommendations
.
since 2013
..
.
.
Table 5 Changes in cardiac pacing and cardiac
https://academic.oup.com/eurheartj/article/42/35/342
. resynchronization therapy guideline recommendations .

since 2013
. .
.
. 2013 2021 .
.
Class
............................
a
.
Cardiac pacing for bradycardia and conduction system .
disease .
.
In patients with syncope, cardiac pacing may be .
considered to reduce recurrent syncope when .
IIa IIb .
asymptomatic pause(s) >6 s due to sinus arrest .
.
are documented. Continued .
358547 by guest on 10 May 2022
ESC 2021
ESC Guidelines 15
AF = atrial fibrillation; AVB = atrioventricular block; AVJ = atrioventricular junction;
CRT = cardiac resynchronization therapy; HFrEF = heart failure with reduced ejection
Cardiac resynchronization therapy
fraction; ICD = implantable cardioverter-defibrillator; LBBB = left bundle branch block;
Patients who have received a conventional pace- LVEF = left ventricular ejection fraction; MRI = magnetic resonance imaging; NYHA = New
maker or an ICD and who subsequently develop York Heart Association; OMT = optimal medical therapy; RV = right ventricular; SR =
sinus rhythm.
symptomatic HF with LVEF <_35% despite OMT a
I IIa
and who have a significantb proportion of RV pacing b
A limit of 20% RV pacing for considering interventions for pacing-induced HF is
should be considered for upgrade to supported by observational data. However, there are no data to support that any
percentage of RV pacing can be considered as defining a true limit below which RV
CRT. pacing is safe and beyond which RV pacing is harmful.
CRT rather than RV pacing is recommended for c
Combination of MRI conditional generator and lead(s) from the same
patients with HFrEF (<40%) regardless of NYHA manufacturer.
class who have an indication for ventricular pacing IIa I

and high-degree AVB in order to reduce
morbidity. This includes patients with AF. 3 Background
CRT should be considered for symptomatic patients
with HF in SR with LVEF <_35%, a QRS duration 3.1 Epidemiology
of 130—149 ms, and LBBB QRS mor- I IIa The prevalence and incidence of pacemaker implantation are unknown
phology despite OMT, to improve symptoms in many countries, yet several estimations have been published based on
and reduce morbidity and mortality. the analysis of large observational studies and data- bases. There is
In patients with symptomatic AF and uncontrolled considerable variability in reported pacemaker implant rates between
heart rate who are candidates for AVJ ablation European countries, ranging from <25
IIa I
(irrespective of QRS duration), CRT is
recommended in patients with HFrEF.
Specific indications for pacing
In patients with congenital heart disease, pacing may be
considered for persistent postoperative bifascicular
IIa IIb
block associated with transient com-
plete AVB.
Management considerations
In patients with MRI-conditional pacemaker sys-
temsc, MRI can be performed safely following IIa I
manufacturer instructions.
In patients with non-MRI-conditional pacemaker
systems, MRI should be considered if no alternative
imaging mode is available and if no epicardial leads, IIb IIa
abandoned or damaged leads, or lead
adaptors/extenders are present.
16 ESC Guidelines
New in these guidelines
Pacing in TAVI patients

CRT indications

HBP in bradycardia or CRT
Leadless pacing
Minimizing complication risk Pacing in patients

Pacing
within
rare
patients
diseases
after cardiac surgery
Preimplant evaluation Pacing for bradycardia High risk reflex syncope
Figure 1 The 2021 ESC Guidelines on cardiac pacing and CRT present new and updated recommendations for these treatments in relevant patient populations.
.
pacemaker-treated patients.9—12 In contrast, SND follows an unpre-
pacemaker implantations per million people in Azerbaijan, Bosnia and
.. dictable course, and there is no evidence to show that pacemaker
Herzegovina, and Kyrgyzstan, to >1000 implantations per million .
therapy results in improved prognosis.13—15
..
people in France, Italy, and Sweden.1 These differences may result from
under- or overtreatment with pacemaker therapy in some countries, or Improving life expectancy is not, however, the only objective of
from variations in sociodemographic characteristics and pathological ... pacemaker therapy. Quality of life is an essential metric for measuring
conditions. There is a continuous growth in the use of pacemakers due to . a patient’s clinical status and outcome, and provides a holistic picture
the increasing life expectancy and age- of clinical treatment effectiveness.16 Studies have been unanimous in
. finding improved quality of life in patients receiving pacing
ing of populations.2—8 The estimated number of patients globally .
17—22
undergoing pacemaker implantation has increased steadily up to an . therapy.
annual implant rate of ~1 million devices.2 Degeneration of the cardiac .
..
conduction system and changes in intercellular conduc- . 3.3 Pathophysiology and classification of
tion can be manifestations of cardiac pathology or non-cardiac bradyarrhythmias considered for
disease, and are most prevalent in older patients. Therefore, most ..
permanent cardiac pacing therapy
bradycardias requiring cardiac pacing are observed in the elderly, with .. Definitions of various conduction disturbances are presented in
.. Supplementary Table 1.
>80% of pacemakers being implanted in patients above the age of 65
years. . Sinus bradycardia can be considered physiological in response to
.. specific situations, such as in well-conditioned athletes, young individ-
3.2 Natural history . uals, and during sleep. Pathological bradyarrhythmias are dependent
High-degree atrioventricular block (AVB) and sinus node dysfunction .. on their underlying cause and can be broadly categorized into intrin-
(SND) are the most common indications for permanent pacemaker
. sic and extrinsic aetiologies. Advanced age and age-related degenera-
therapy. Conservatively treated (i.e. non-paced) patients with high- .. tive changes are important intrinsic causes of modifications in
degree AVB have notably poorer survival compared with
.
electrical impulse initiation and propagation of the conduction
ESC Guidelines 17
Patient with bradycardia-related symptoms
Y Persistent bradycardia
Sinus node disease

N
AV block
Sinus rhythm Atrial fibrillation

Documented arrhythmia (ECG/Holter/monitor)
Y N
(suspected)
Intrinsic
Paroxysmal AV block BBB
Sino-atrial block and sinus arresta
Atrial fibrillation with slow ventricular condition Reflex syncope
Carotid sinus Tilt-induced
Extrinsic (functional) Vagally induced sinus arrest or AV block Adenosine hypersensitivityb
Idiopathic AV block
Unexplained syncope
Figure 2 Classification of documented and suspected bradyarrhythmias. AV = atrioventricular; BBB = bundle branch block; ECG = electrocardiogram.
a
Including the bradycardia—tachycardia form of sick sinus syndrome. bDeharo et al.32 Figure adapted from Brignole et al.33
system. In addition, genetic mutations have been linked to conduction .

3.4 Types and modes of pacing: general
.. description
disorders (see section 4.3.5), and atrial cardiomyopathy23 may be a
specific disease that can result in supraventricular tachyarrhythmia, SND,
and atrioventricular node (AVN) disease.24 .. 3.4.1 Endocardial pacing
.
It is essential to differentiate reversible from non-reversible causes Endocardial lead-based pacemakers consist of a pulse generator com-
of bradycardia. Potential reversible causes of bradycardia include .. monly placed in the pectoral region and transvenous lead(s)
.
adverse drug effects, myocardial infarction (MI), toxic exposure, implanted into the myocardium with the ability to sense cardiac activ-
infections, surgery, and electrolyte disorders. In a study including 277 .. ity and provide therapeutic cardiac stimulation. Since the introduc-
.
patients referred to the emergency department with bradycardia, tion of transvenous endocardial pacemakers in the 1960s, major
electrolyte disorders were the underlying cause in 4%, intoxication in 6%, .. technological advances have improved their efficacy and safety. In
.
acute MI in 14%, and adverse drug effects in 21%.25 general, pacemaker implantation is considered a low-risk procedure,
In the case of non-reversible pathological causes of slow heart rate, the .. yet it is not exempt from device- and procedure-related complica-
.
presence and severity of symptoms play an essential role in the tions and malfunction. Pacemaker implantation is covered in detail in
consideration for permanent antibradycardia pacemaker therapy. This .. a recent European Heart Rhythm Association (EHRA) consensus
.
may be challenging in patients with competing mechanisms for their
.. document.
34
symptoms. In general, candidates for pacing therapy can be broadly

classified into two groups: patients with persistent bradycardia and
.
.
patients with intermittent [with or without electrocardiographic . 3.4.2 Epicardial pacing
(ECG) documentation] bradycardia. Persistent bradycardia usually
. Some clinical scenarios dictate implantation of an epicardial pace-
indicates an intrinsic disease in the sinus node tissue or the .. maker system. These include patients with congenital anomalies and
. no venous access to the heart or with an open shunt between the
atrioventricular (AV) conduction system, whereas intermittent
bradycardia can be a result of a wide variety of intrinsic and extrinsic .. right and left sides of the circulation, recurrent device infections,
. occluded veins, and—most commonly today—in conjunction with
pathological processes, as illus-
trated in Figure 2.26—31 .. open cardiac surgery. Epicardial leads are currently implanted using
.
. various (minimally invasive) thoracotomy or thoracoscopy and
. robotic techniques.35
18 ESC Guidelines
.
3.4.3 Cardiac resynchronization therapy (endo- and/or heart rate during emotional or physical activity by sensing body
.. motion/acceleration, minute ventilation, intracardiac impedance, or
epicardial) .
Cardiac dyssynchrony is a difference in the timing of electrical and other surrogates of physical and mental stress, and are indicated in
mechanical activation of the ventricles, which can result in impaired
.. cases of chronotropic incompetence.51—57 Dual-sensing rate-respon-
.
cardiac efficiency. CRT delivers biventricular pacing to correct elec- 36 . sive pacing (e.g. accelerometer and minute ventilation) may be used
tromechanical dyssynchrony in order to increase cardiac output. In in selected patients. 58A brief overview of the most commonly used
multiple trials, CRT has shown a significant morbidity and mortality .
rate-responsive pacing sensors is given in Supplementary Table 3.
benefit in specific patient groups with reduced left ventricular ejection ..
fraction (LVEF).37—40 .
.
. 3.5 Sex differences
3.4.4 Alternative methods (conduction system pacing, .. Pacing indications and complication rates differ between male and
leadless pacing) . female patients. In male patients, primary pacemaker implantation is
3.4.4.1 Conduction system pacing .. more often indicated for AVB and less so for SND and atrial fibrilla-
. tion (AF) with bradycardia.59,60 In female patients, the rate of

Compared with right ventricular (RV) pacing, His bundle pacing
(HBP) provides a more physiological simultaneous electrical activation .. procedure-related adverse events is significantly higher, corrected
of the ventricles via the His—Purkinje system. HBP can restore .
for age and type of device. This higher rate is driven mostly by pneu-
conduction in a subset of patients with high-degree AVB, and shorten .. mothorax, pericardial effusion, and pocket haematomas.59—61
QRS duration in some patients with left bundle branch block (LBBB) or .
Possible explanations for this are a smaller body size in women and
right bundle branch block (RBBB).41—44 More studies are ongoing and .. anatomical differences, such as smaller vein diameters and RV
required to evaluate whether HBP has clinical benefits over CRT
.
diameters.
or RV pacing. In addition, left bundle branch area pacing is being ..
studied as a pacing modality for patients in whom the conduction disease .
.
is too distal for HBP (see section 7.3). .
. 4 Evaluation of the patient with
3.4.4.2 Leadless pacing ..
suspected or documented
Miniaturized, intracardiac leadless pacemakers have been introduced. These ..
devices are inserted percutaneously through the femoral vein and . bradycardia or conduction system
implanted directly in the RV wall using customized catheter- based disease
delivery systems. The first-generation leadless pacemakers ...
have been proven to provide effective single-chamber pacing therapy.45 4.1 History and physical examination
—50
Albeit a promising technology, potential difficulty with leadless .. A careful history and physical examination are essential for the evalu-
pacemaker retrieval at the end of service is a limitation. Thus .. ation of patients with suspected or documented bradycardia
far, there are no randomized controlled data available to compare . (Figure 3). Current guidelines emphasize the importance of the his-
clinical outcomes between leadless pacing and single-chamber transvenous .. tory and physical examination in the initial evaluation, particularly for
pacing. .
identifying patients with structural heart disease.62,63
.. A complete history should include family history, comprehensive
.
3.4.5 Pacing modes cardiovascular risk assessment, and recent/historical diagnoses that
Technological advances in pacemaker therapy have resulted in a wide variety .. may cause bradycardia. The history should be focused on frequency,
.
of pacing modalities. Pacemakers can sense the heart’s intrinsic electrical severity, and duration of symptoms that might suggest bradycardia or
activity and restore the rate and AV sequence of cardiac activation. .. conduction system disease. The relationship of symptoms to physical
.
Abnormal cardiac automaticity and conduction may be treated by single- activity, emotional distress, positional changes, medical treatment
lead atrial sensing/pacing, single-lead ventricular sensing/pacing, single .. (Table 6), and typical triggers (e.g. urination, defecation, cough, pro-
.
leads that pace the right ventricle (RV) and sense both the atrium and longed standing, and shaving) should be explored too, as well as pulse
ventricle, and dual-lead systems that sense and pace the right atrium (RA) .. rate if measured during an episode.
.
and RV. For common pacing modes, refer to Supplementary Table 2. Family history may be especially important in young patients with
The choice of the optimal pacing mode in the presence of conduction
.. progressive cardiac conduction disease either isolated or in associa-
.
disturbances is driven by the underlying morbidity, the impact of pacing .. tion with cardiomyopathies and/or myopathies.
64,65
therapy on morbidity, and the potential harmful effect of the chosen Physical examination should focus on manifestations of bradycar-
pacing modality. The choice of pacing modes in specific situations is .. dia and signs of underlying structural heart disease or systemic disor-
discussed in section 5. . ders (Table 7). Symptomatic slow peripheral pulses should be
.. confirmed with cardiac auscultation or ECG to ensure that other
. rhythms are not misrepresented as bradycardia (e.g. premature ven-
3.4.6 Rate-responsive pacing
The sinus node modulates the heart rate during different types and loads .. tricular contractions).
. Autonomic regulation disorders are important in the differential
of exercise (i.e. physical exercise, emotions, postural change, and fever)
proportional to the metabolic demand. Rate-responsive pacemaker .. diagnosis of syncope or near syncope, and, therefore, orthostatic
.
systems strive to produce an appropriate compensatory . changes in heart rate and blood pressure may help in the evaluation
. of the patients.
ESC Guidelines 19
Electrocardiograma
Evaluación inicial de pacientes con síntomas sugestivos de bradicardia (SND o bloqueo AV)
Historia Examen físico Imagen cardiaca
Riesgo cardiovascular
Historial completo
centrado en los
síntomas.
Historia familiar
Tratamiento médico

Figure 3 Initial evaluation of patients with symptoms suggestive of bradycardia. AVB = atrioventricular block; ECG = electrocardiogram; SND = sinus node
dysfunction.
.
Table 6 Drugs that may cause bradycardia or conduction
. Table 6 Continued
disorders
Continued
20 ESC Guidelines
. . .
. . .
. . . Sinus node AVB
. .
Sinus node AVB . bradycardia
. .
bradycardia . Others
. Beta-blockers 1 . 1 .
. . . Muscle relaxants 1 –
. Antihypertensives . . Cannabis 1 –
. Non-dihydropyridine calcium channel 1 .
. 1
.
. . Propofol 1 –
. blockers . .
. . . Ticagrelor 1 1
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Methyldopa 1 . – .
. High-dose corticosteroids 1 –
. Clonidine 1 . – .
. . . Chloroquine – 1
. Antiarrhythmics . . AVB = atrioventricular block.
. Amiodarone 1 . 1 H2 antagonists 1 1
Dronedarone 1 1 Proton pump inhibitors 1 –
Sotalol 1 1 Chemotherapy
Flecainide 1 1 Arsenic trioxide 1 1
Propafenone 1 1 Bortezomib 1 1
Procainamide – 1 Capecitabine 1 –
Disopyramide 1 1 Cisplatin 1 –
Adenosine 1 1 Cyclophosphamide 1 1
Digoxin 1 1 Doxorubicin 1 –
Ivabradine 1 – Epirubicin 1 –
Psychoactive and neuroactive drugs 5-fluorouracil 1 1

Donepezil 1 1 Ifosfamide 1 –
Lithium 1 1 Interleukin-2 1 –
Opioid analgesics 1 – Methotrexate 1 –
Phenothiazine 1 1 Mitroxantrone 1 1
Phenytoin 1 1 Paclitaxel 1 –
Selective serotonin reuptake inhibitors – 1 Rituximab 1 1
Tricyclic antidepressants – 1 Thalidomide 1 1
Carbamazepine 1 1 Anthracycline – 1
Taxane – 1
ESC Guidelines 21
.
Table 7 Intrinsic and extrinsic causes of . Table 7 Continued
bradycardia .
Sinus AVJ .
. Sinus AVJ
bradycardia disturbances . bradycardia disturbances
or SND . or SND
Intrinsic .
. Hypothermia 1 1
Idiopathic (ageing, degenerative) 1 1 . Neurological disorders
Infarction/ischaemia 1 1
.
. Increased intracranial pressure 1 1
Cardiomyopathies 1 1 . Central nervous system tumours 1 1
.
Genetic disorders 1 1 .
ESC 2021
Temporal epilepsy 1 1
Infiltrative diseases . Obstructive sleep apnoea 1 1
.
Sarcoidosis 1 1 .
Amyloidosis 1 1 . AV = atrioventricular; AVB = atrioventricular block; AVJ = atrioventricular junc-
. tion; SND = sinus node dysfunction.

Haemochromatosis 1 1 . Adapted from Mangrum et al. and Da Costa et al.
71 72a
Collagen vascular diseases .

.
Rheumatoid arthritis 1 1 .
Scleroderma 1 1 .
.
Systemic lupus erythematosus 1 1 .
Carotid sinus massage (CSM) can be helpful in any patient >_40
Storage diseases 1 1 .. years old with symptoms suggestive of carotid sinus syndrome (CSS):
Neuromuscular diseases 1 1 .
syncope or near syncope elicited by tight collars, shaving, or turning
Infectious diseases .. the head. 66,67 Methodology and response to CSM are described in
.
Endocarditis (perivalvular abscess) – 1 section 4.1 in the Supplementary data. Diagnosis of CSS requires both
Chagas disease 1 1 .. the reproduction of spontaneous symptoms during CSM and clinical
.
Myocarditis – 1 features of spontaneous syncope compatible with a reflex
.. mechanism.68—70
Lyme disease – 1
.
Diphtheria – 1 ..
Toxoplasmosis – 1 4.2 Electrocardiogram
..
Congenital heart diseases 1 1 Together with the history and physical examination, the resting ECG
Cardiac surgery .. is an essential component of the initial evaluation of patients with
.
Coronary artery bypass grafting 1 1 documented or suspected bradycardia. A 12-lead ECG or a rhythm
.. strip during the symptomatic episode provides the definitive
Valve surgery (including 1 1 .
transcatheter aortic valve diagnosis.
.. For those in whom physical examination suggests a bradycardia, a
replacement) .
12-lead ECG is useful to confirm the rhythm, rate, nature, and extent
Maze operation 1 –
.. of conduction disturbance (Supplementary Table 1). Furthermore, an
Heart transplant 1 1 .
ECG may provide information about structural heart or systemic ill-
Radiation therapy 1 1 .. ness (e.g. LV hypertrophy, Q waves, prolonged QT interval, and low
Intended or iatrogenic AVB – 1 .
voltage) that predict adverse outcomes in symptomatic patients.62
Sinus tachycardia ablation 1 – ...
Extrinsic 4.3 Non-invasive evaluation
Physical training (sports) 1 1 ..
Vagal reflex 1 1
.
. Recommendations for non-invasive evaluation
Drug effects 1 1 .
.
Idiopathic paroxysmal AVB – 1 . Recomendaciones Clasea Nivelb
Electrolyte imbalance .
. Una vez descartada la estenosis carotídeac, se
Hypokalaemia 1 1 . recomienda la CSM en pacientes con síncope de origen
Hyperkalaemia 1 1 . desconocido compatible con un mecanismo reflejo o con
. síntomas relacionados con la presión/manipulación de la
I B
ESC 2021
Hypercalcaemia 1 1 .
Hypermagnesaemia 1 1 . zona del seno carotídeo.
.
Metabolic disorders .
. CSM = masaje del seno carotideo.
Hypothyroidism 1 1 . a
Anorexia 1 1 . b
Clase de recomendación
Nivel de evidencia
Hypoxia 1 1
. c
CSM no debe realizarse en pacientes con un ataque isquémico transitorio previo, accidente
.
Acidosis 1 1 cerebrovascular o estenosis carotídea conocida. La auscultación carotídea debe realizarse antes de la CSM. Si
hay un soplo carotídeo, se debe realizar una ecografía carotídea para excluir la presencia de enfermedad
carotídea..
Continued
22 ESC Guidelines
.
4.3.1 Ambulatory electrocardiographic . Exercise testing can be used to diagnose symptomatic chrono-
. tropic incompetence, defined as an inability to increase the heart rate
monitoring
The intermittent nature of most symptomatic bradycardia secondary to .. commensurate with the increased metabolic demands of physical
. activity.74,75 The most commonly used definition of chronotropic
conduction system disease often requires prolonged ambulatory ECG
monitoring to correlate rhythm disturbances with symptoms. This .. incompetence has been failure to reach 80% of the expected heart
. rate reserve. Expected heart rate reserve is defined as the difference
monitoring allows detection of interruption of AV conduction by
either primary disease of the conductive system, a vagal or neuro- .. between the age-predicted maximal heart rate (220 age) and the
. —
cardiogenic mechanism, or reflex AV block.72,72a resting heart rate. However, some medical treatments and comor-
Ambulatory ECG identifies defects of sinus automaticity, which .. bidities cause exercise intolerance and make the diagnosis of chrono-
.
includes sinus pauses, sinus bradycardia, bradycardia—tachycardia tropic incompetence by exercise testing more difficult.
syndrome, asystole post-conversion of atrial flutter or AF, and chro- .. In patients with exercise-related symptoms, the development or
.
notropic incompetence. progression of AVB may occasionally be the underlying cause.
Different versions of ambulatory ECG monitoring have been
.. Tachycardia-related exercise-induced second-degree and complete
.

reviewed recently in a comprehensive expert consensus AVB have been shown to be located distal to the AVN and predict
(Supplementary Table 4).73 Ambulatory ECG selection depends on the
.. progression to permanent AVB.76—78 Usually, these patients show
.
frequency and nature of the symptoms (Table 8). intraventricular conduction abnormalities on the resting ECG, but a
.. normal resting ECG has also been described in such cases.77,79
.
Exercise testing may expose advanced infranodal AVB in the pres-
.. ence of conduction system disease of uncertain location.
.
Table 8 Choice of ambulatory electrocardiographic In rare cases, conduction disturbances induced by exercise are
monitoring depending on symptom frequency .
. caused by myocardial ischaemia or coronary vasospasm, and exercise
testing may reproduce the symptoms.80,81
..
Frequency of
symptom There are no data supporting an indication for exercise testing in
Daily 24-h Holter ECG or in-hospital telemetric .. patients without exercise-related symptoms. Exercise testing may be
monitoring . useful in selected patients to distinguish AVN from conduction dis-
Every 48—72 h 24—48—72 h Holter ECG .. turbances in the His — Purkinje system below the AVN in the setting
Every week 7-day Holter ECG/external loop recorder/
. of conduction disturbance at an unclear level.
external patch recorder .
Every month External loop recorder/external patch .
. Recommendations for exercise testing
ESC 2021
recorder/handheld ECG recorder .

<1 per month ILR .
. Recommendations Classa Levelb
ECG = electrocardiogram; ILR = implantable loop recorder. Adapted .
from Brignole et al.33 . Exercise testing is recommended in patients who
.
. experience symptoms suspicious of bradycardia
I C
. during or immediately after
.
. exertion.62,74—80
. In patients with suspected chronotropic incompetence,
Recommendation for ambulatory electrocardiographic .
monitoring . exercise testing should be considered IIa B
. to confirm the diagnosis.74,75
.
Recommendation Classa Levelb . In patients with intraventricular conduction dis-
. ease or AVB of unknown level, exercise testing
Ambulatory ECG monitoring is recommended in the . IIb C
. ESC 2021
may be considered to expose infranodal
evaluation of patients with suspected bradycardia to
I C . block.76,77,79
correlate rhythm disturbances with .
ESC 2021
.
symptoms.73 . AVB = atrioventricular block.
. a
ECG = electrocardiogram. . b
Level of evidence.
a
Class of recommendation. .
b
Level of evidence. .
.
.
..
. 4.3.3 Imaging
In patients with suspected or documented symptomatic bradycardia,
4.3.2 Exercise testing .. the use of cardiac imaging is recommended to evaluate the presence
Exercise testing may be useful in selected patients with suspected .
of structural heart disease, to determine LV systolic function, and to
bradycardia during or shortly after exertion. Symptoms occurring .. diagnose potential reversible causes of conduction disturbances
during exercise are likely to be due to cardiac causes, whereas symptoms
occurring after exercise are usually caused by a reflex mechanism. .. (Table 7).
. Echocardiography is the most commonly available imaging techni-
.
. que for evaluation of the above factors. It can also be used in the
ESC Guidelines 23
context of haemodynamic instability. When coronary artery disease

Recommendations for laboratory tests
.
is suspected, coronary computed tomography (CT), angiography, or
.
.
82
stress imaging is recommended. Cardiovascular magnetic reso- . Recommendations Classa Levelb
nance (CMR) and nuclear imaging techniques provide information on .
tissue characterization (inflammation, fibrosis/scar) and should be
. In addition to pre-implantation laboratory tests,c
. specific laboratory tests are recommended in patients
considered before pacemaker implantation when specific aetiologies .
associated with conduction abnormalities are suspected (specially in
. with clinical suspicion for potential underlying causes
. of reversible bradycardia (e.g. thyroid function tests, I C
young patients). Late gadolinium contrast enhanced (LGE) and T2 CMR .
techniques allow the diagnosis of specific causes of conduction
. Lyme titre, digitalis level, potassium, calcium, and
.
ESC 2021
pH) to diagnose and
disturbances (i.e. sarcoidosis and myocarditis). Late gadolinium contrast .
enhancement CMR helps in the decision-making of individuals with
. treat these conditions.90—94
.
arrhythmic events; the presence of large areas of LGE (scar/fibrosis) has .
. a
been linked to an increased risk of ventricular arrhythmias regardless of . b
Level of evidence.
. c

LVEF and may indicate the need for an implantable . Complete blood counts, prothrombin time, partial thromboplastin time, serum
creatinine, and electrolytes.
cardioverter-defibrillator (ICD).83—85 T2 CMR sequences are suited .
for the detection of myocardial inflammation (i.e. oedema and hyper- .
.
aemia) as a potential cause of transitory conduction abnormalities that .
may not need permanent pacemaker implantation. 86 Similarly, positron .
.. 4.3.5 Genetic testing
emission tomography (PET) combined with CMR or CT helps in the Most cardiac conduction disorders are due to either ageing or struc-
diagnosis of inflammatory activity status of infiltrative cardiomyopathies
.
tural abnormalities of the cardiac conduction system caused by
(i.e. sarcoidosis).87,88 .. underlying structural heart disease. Genes responsible for inherited
.. cardiac diseases associated with cardiac conduction disorders have
Recommendations regarding imaging before . been identified.65,95,96
implantation .. Genetic mutations have been linked to a range of abnormalities
. that may present in isolated forms of cardiac conduction disorder or
Recomendación Clasea Nivelb .
.. in association with cardiomyopathy, congenital cardiac anomalies, or
Se recomiendan las imágenes cardíacas en pacientes con extra-cardiac disorders. Most genetically mediated cardiac conduc-
bradicardia sintomática sospechada o documentada para . tion disorders have an autosomal dominant mode of inheritance65,95
evaluar la presencia de cardiopatía estructural,
determinar la función sistólica del VI y diagnosticar .. (Supplementary Table 5).
causas potenciales de trastornos de la conducción.
I C .
Progressive cardiac conduction disease (PCCD) may be
.. diagnosed in the presence of unexplained progressive conduction
.
abnormalities in young (<50 years) individuals with structurally nor-
Se debe considerar la imagenología multimodal (RMC, .. mal hearts in the absence of skeletal myopathies, especially if there is
TC o PET) para la caracterización del tejido miocárdico .
a family history of PCCD.97 Common PCCD-associated genes are
en el diagnóstico de patologías específicas asociadas con .. SCN5A and TRPM4 for isolated forms and LMNA for PCCD associ-
anomalías de la conducción que requieran la IIa C .
implantación de un marcapasos, particularmente en ated with HF.
pacientes menores de 60 años. .. The diagnosis of PCCD in an index patient is based on clinical data
.
ESC 2021
including history, family history, and 12-lead ECG. The potential pres-
.. ence of congenital heart disease (CHD) and/or cardiomyopathy must
RMC = resonancia magnética cardiovascular; TC = tomografía computarizada; VI = .
be investigated with cardiac imaging.
..
ventrículo izquierdo; PET = tomografía por emisión de positrones
. Early-onset PCCD, either isolated or with concomitant structural

a
Recomendación de clase
heart disease, should prompt consideration of PCCD genetic testing,
b
Nivel de evidencia. .. particularly in patients with a positive family history of conduction
. abnormalities, pacemaker implants, or sudden death.97
.. A consensus panel has endorsed mutation-specific genetic testing
.. for family members and appropriate relatives after the identification
4.3.4 Laboratory tests . of a PCCD causative mutation in an index case. Such testing can be
Laboratory tests, including full blood counts, prothrombin time, partial .. deferred in asymptomatic children because of the age-dependent
thromboplastin time, renal function, and electrolyte measurements, . nature of cardiac conduction diseases and incomplete penetrance.65
are warranted as part of pre-procedural planning for pacemaker .. However, every case should be individually evaluated depending of
implantation. .
the risk of the detected mutation.
Bradycardia or AVB may be secondary to other conditions (Table .. Asymptomatic family members who are positive for the family’s
7). When suspected, laboratory data are useful for identifying and .
PCCD-associated mutation should be regularly followed for devel-
treating these conditions (e.g. thyroid function, Lyme titre to diagnose .. opment of cardiac conduction disease-related symptoms, deteriora-
myocarditis in a young person with AVB, endocarditis, .
. tion of cardiac conduction, and beginning of HF.
hyperkalaemia, digitalis levels, and hypercalcaemia).89—94
24 ESC Guidelines
.
Recommendations for genetic testing .. 4.3.7 Tilt testing
. Tilt testing should be considered to confirm a diagnosis of reflex syn-
Recommendations Classa Levelb cope in patients in whom this diagnosis was suspected but not con-
Se deben considerar pruebas genéticas en pacientes con
.. firmed by initial evaluation.62,107 The endpoint of tilt testing is the
inicio temprano (edad <50 años) de enfermedad de IIa C .. reproduction of symptoms along with the characteristic circulatory
conducción cardíaca progresiva.c . pattern of the reflex syncope. The methodology and classification of
Las pruebas genéticas deben considerarse en los .. responses are described in section 4.2 in the Supplementary data and
miembros de la familia después de la identificación de . in Supplementary Figure 1.
una variante genética patógena que explica el fenotipo
IIa C .. A positive cardioinhibitory response to tilt testing predicts, with
clínico de la enfermedad de conducción cardíaca en un .
ESC 2021
caso índice. high probability, asystolic spontaneous syncope; this finding is rele-
.. vant for therapy when cardiac pacing is considered (see section 5.4).
.
Conversely, the presence of a positive vasodepressor, a mixed
..
a
response, or even a negative response does not exclude asystole dur-

Level of evidence.
b
Progressive cardiac conduction disease: prolonged P wave duration, PR interval, and

c . ing spontaneous syncope.62
QRS widening with axis deviation.96 .
.
. Recommendation for tilt testing
.
4.3.6 Sleep evaluation
.
. Recommendation Class Level
a b
Nocturnal bradyarrhythmias are common in the general population. In .
ESC 2021
most circumstances, these are physiological, vagally mediated . Tilt testing should be considered in patients with
. suspected recurrent reflex syncope. 62
IIa B
asymptomatic events, which do not require intervention.98—100 .
.
Patients with sleep apnoea syndrome (SAS) have a higher preva- a
.
lence of sleep-related bradycardia (both sinus and conduction system b
Level of evidence.
related) during apnoeic episodes.101,102 SAS-induced hypoxaemia is a key ..
mechanism leading to an increased vagal tone and bradycardic rhythm .
.
disorders.101,102 Another rare mechanism of sleep-related bradycardia .
(usually in the form of prolonged sinus arrest) is rapid eye movement .
. 4.4 Implantable monitors
sleep-related bradycardia, unrelated to apnoea. This mechanism can also
be diagnosed by polysomnography.103 Although most cases quoted in the .. Patients with infrequent symptoms of bradycardia (less than once per
. month) need a longer duration of ECG monitoring. For these
.. patients, the implantable loop recorder (ILR) is an ideal diagnostic
literature have been treated with pacemakers, the evidence for this is
scant, and there is no consensus on how to treat these patients.103 . tool given its capacity for prolonged monitoring (up to 3 years) and
.. without the need for active patient participation (Table 8).
Treatment with continuous positive airway pressure (CPAP) alle-
viates obstructive sleep apnoea-related symptoms and improves car- . In patients with unexplained syncope after the initial evaluation
.. and infrequent symptoms (less than once a month), several studies
diovascular outcomes. Appropriate treatment reduces episodes of
bradycardia by 72 89%,—
104
and patients are unlikely104—106
to develop .
have demonstrated a higher efficacy of initial ILR implantation com-
.. pared with a conventional strategy.
108—112
Many conditions diagnosed by
symptomatic bradycardia at long-term follow-up. Therefore, ILR are bradycardia mediated. For further discussion on the
patients with asymptomatic nocturnal bradyarrhythmias or cardiac .
. diagnostic roles of ILR and ambulatory ECG, and indications for their
conduction diseases should be evaluated for SAS. If the diagnosis is .
use, refer to the ESC Guidelines for the diagnosis and management of
confirmed, treatment of sleep apnoea with CPAP and weight loss can be
.. syncope.62
effective in improving bradyarrhythmias occurring during sleep, and .
permanent pacing should be avoided. In patients with known or suspected .
SAS and symptomatic bradyarrhythmias not associated with sleep, a
.
.
more complex assessment of the risks associated with bradyarrhythmias . Recommendation for implantable loop recorders
vs. the benefit of cardiac pacing is needed.
.
.
. Recommendation Classa Levelb
.
Recommendation for sleep evaluation . In patients with infrequent (less than once a month)
. unexplained syncope or other symptoms suspected
.
Recommendation Classa Levelb . to be caused by bradycardia, in whom a
. comprehensive evaluation did not demonstrate a I A
Screening for SAS is recommended in patients with .
symptoms of SAS and in the presence of severe . cause, long-term ambulat
.
ESC 2021
I C
bradycardia or advanced AVB during . ory monitoring with an ILR is
ESC 2021
101—106 . recommended.108—112
sleep. ..
ILR = implantable loop recorder.
AVB = atrioventricular block; SAS = sleep apnoea syndrome. . a
a
Class of recommendation. . b
Level of evidence.
Level of evidence.
.
b
ESC Guidelines 25
4.5 Electrophysiology study .

In patients with syncope and sinus bradycardia, the pre-test
The development of non-invasive ambulatory ECG technologies has .. probability of bradycardia-related syncope increases when there is a
reduced the need for the electrophysiology study (EPS) as a diagnostic test. .
sinus bradycardia (<50 b.p.m.) or sinoatrial block. Observational
EPS is generally an adjunctive tool in the evaluation of patients with .. studies have shown a relationship between prolonged sinus node
syncope in whom bradycardia is suspected but has not been .
recovery time with syncope and the effect of pacing on
documented after non-invasive evaluation (Figure 4). The goal of an EPS .. symptoms.113,114
in the context of bradycardia evaluation is to identify abnormal .
In patients with syncope and bifascicular block, a prolonged
sinus node function or the anatomical location of the cardiac conduction .
. His—ventricular interval (HV) >_70 ms, or HV >_100 ms after pharma-
disorders (in the AVN or in the His—Purkinje system distal to the
AVN). .. cological stress (ajmaline, procainamide, flecainide, or disopyramide),
. or induction of second- or third-degree AVB by atrial pacing or by

26 ESC Guidelines
ESC Guidelines 27
.
be considered as an appropriate indication for permanent pacing
pharmacological stress, identifies a group at higher risk of developing
.. only when bradycardia due to SND is symptomatic.126 Patients with
AVB.115—122 .
SND may manifest symptoms attributable to bradyarrhythmia and/or
..
The efficacy of EPS for the diagnosis of syncope is highest in
patients with sinus bradycardia, bifascicular block, and suspected symptoms of accompanying atrial tachyarrhythmias in the bradycar-
tachycardia,62 and lowest in patients with syncope, a normal ECG, no .. dia—tachycardia form of the disease. Symptoms may be present
. either at rest or at the end of the tachyarrhythmic episode (conver-
structural heart disease, and no palpitations. Therefore, EPS is preferred
over ILR in patients with syncope who have a high pre-test probability .. sion pause also named pre-automaticity pause), or develop during
. exercise, and may range from mild fatigue to light-headedness, dizzy
for significant conduction disease (e.g. abnormal ECG, BBB, ischaemic
heart disease, or scar-related cardiomyopathy). For patients with a low .. spells, near-syncope, to syncope. Dyspnoea on exertion may be
. related to chronotropic incompetence. Syncope is a common mani-
pre-test probability (no structural heart disease, normal ECG), ILR is
preferred over EPS. EPS is also preferred when there is a high likelihood .. festation of SND and has been reported in 50% of patients who
. receive a pacemaker for SND.127
that another syncopal episode will be dan- gerous or life-threatening and an
immediate diagnosis is likely if EPS is performed. .. Establishing a correlation between symptoms and bradyarrhyth-
.

A negative EPS does not exclude an arrhythmic syncope, and further mia is a crucial step in decision-making. However, age, concomitant
evaluation is warranted. Approximately one-third of patients with a .. heart disease, and other comorbidities may pose difficulties in
.
negative EPS in whom an ILR is implanted develop AVB at follow-up.123 establishing a clear cause effect
— relationship between SND and
.. symptoms.
.
Recommendations for electrophysiology study The effect of cardiac pacing on the natural history of bradyarrhyth-
.. mias was evaluated in non-randomized studies undertaken at the
Recomendaciones a b
.
beginning of the pacemaker era, which suggested a symptomatic
Clase Nivel
.. improvement with cardiac pacing.128—131 This was confirmed by one
En pacientes con síncope y bloqueo bifascicular, se debe .
considerar la EEF cuando el síncope permanece sin randomized controlled trial (RCT)14 in which 107 patients (aged 73
explicación después de una evaluación no invasiva o .. ± 11 years) with symptomatic SND were randomized to no treat-
cuando se necesita una decisión inmediata sobre el .
ment, oral theophylline, or dual-chamber (DDD) rate-responsive
marcapasos debido a la gravedad, a menos que se IIa B .. pacemaker therapy. In this study, the occurrence of syncope and HF
prefiera la implantación de un marcapasos empírico .
(especialmente en pacientes ancianos y frágiles). was lower in the pacemaker group during a follow-up of 19 ± 14
.. months.
En pacientes con síncope y bradicardia sinusal, se puede .. In patients presenting with exercise intolerance in whom chrono-
considerar la EPS cuando las pruebas no invasivas no han . tropic incompetence has been identified, the usefulness of cardiac
podido mostrar una correlación entre el síncope y la IIb B .. pacing is uncertain, and the decision to implant a pacemaker in such
bradicardia. . patients should be made on a case by case basis.
..
ESC 2021
In some cases, symptomatic bradyarrhythmias may be related to

EPS = estudio de electrofisiología . transient, potentially reversible, or treatable conditions (section 4,
. aClass of recommendation. .. Table 7). In such cases, correction of these factors is required,
.
whereas permanent pacing is not indicated. In clinical practice, it is
Level of evidence.
..
b
crucial to distinguish physiological bradycardia (due to autonomic

.
influences or training effects) from inappropriate bradycardia that
.. requires permanent cardiac pacing. For example, sinus bradycardia,
.
even when it is 40 50 — b.p.m. while at rest or as slow as 30 b.p.m.
.. while sleeping, particularly in trained athletes, could be accepted as a
.
physiological finding that does not require cardiac pacing.
5 Cardiac pacing for .. Asymptomatic bradycardia (due to either sinus pauses or AVB epi-
.
bradycardia and conduction sodes) is not uncommon and warrants interpretation in the clinical
.. context of the patient: in healthy subjects, pauses >2.5 s are uncom-
system disease .
mon, but this per se does not necessarily constitute a clinical disorder;
5.1 Pacing for sinus node dysfunction .. asymptomatic bradyarrhythmias are common in athletes.
132
In the
SND, also known as sick sinus syndrome, comprises a wide spectrum of .
. absence of published trials, no recommendations for bradycardia
sinoatrial dysfunctions, ranging from sinus bradycardia, sinoatrial block, . detected in asymptomatic patients can be made. On the other hand,
and sinus arrest to bradycardia—tachycardia syndrome.124,125
.
in patients investigated for syncope in whom asymptomatic pause(s)
An additional manifestation of SND is an inadequate chronotropic .. >6 s due to sinus arrest are eventually documented, pacing may be
response to exercise, reported as chronotropic incompetence.
... indicated. Indeed, such patients constituted a small minority of those
. included in an observational study and a randomized trial on pacing in
133,134
5.1.1 Indications for pacing . reflex syncope. In patients presenting with sleep-related
5.1.1.1 Sinus node dysfunction . asymptomatic intermittent bradycardia (sinus bradycardia or AVB),
In general, pacing for asymptomatic SND has never been shown to affect .. sleep apnoea and rapid eye movement sleep-related bradycardia
prognosis, as opposed to pacing for AVB. Therefore, SND can . should be considered as possible causes.
28 ESC Guidelines
5.1.1.2 Bradycardia—tachycardia form of sinus node dysfunction .

Syndrome (DANPACE), which enrolled 1415 patients followed for a
The bradycardia—tachycardia variant of SND is the most common form, .. mean of 5.4 years, found no difference between DDD(R) and AAIR
and is characterized by progressive, age-related, degenerative .
fibrosis of the sinus node tissue and atrial myocardium. pacing in all-cause mortality.127 The DANPACE trial also found a
Bradyarrhythmias can be associated with various forms of atrial .. higher incidence of paroxysmal AF [hazard ratio (HR) 1.27] and a
tachyarrhythmias, including AF.125 In this form of SND, the bradyar- .. two-fold increased risk of pacemaker reoperation with AAIR, with
rhythmias may correspond to atrial pauses due to sinoatrial blocks or may . AVB developing in 0.6—1.9% of patients every year.127 These findings
be due to overdrive suppression after an atrial tachyarrhythmia.135 .. support the routine use of DDD(R) rather than AAIR pacing in
Atrial tachyarrhythmias may be present at the time of diagnosis,
. patients with SND.
typically with sinus arrest and asystolic pauses at the termination of atrial .. In view of these data, DDD(R) is the pacing mode of first choice in
tachyarrhythmias or after device implant. Control of atrial
. SND (Figure 5). Unnecessary RV pacing should be systematically
.. avoided in patients with SND, because it may cause AF and deteriora-
.
tion 144,148
of HF, particularly if systolic function is impaired or border-
tachyarrhythmias in patients presenting with high ventricular rates . line. This can be achieved by programming of the AV interval

may be difficult before implant, as drugs prescribed for rate control may .
or using specific algorithms for minimizing RV pacing. Programming
worsen bradyarrhythmias. Ablation of the atrial tachyarrhythmia, mainly .. an excessively long AV interval to avoid RV pacing in patients with
AF, has been proposed in lieu of pacing and continuing medi- cations for .
prolonged AV conduction may be disadvantageous from a haemody-
selected patients,136—138 but no data are available from .. namic point of view by causing diastolic mitral regurgitation, which
RCTs to show whether catheter ablation of AF is non-inferior to car- .
may lead to symptoms and/or AF.144,149,150
diac pacing with respect to bradycardia-related symptoms in patients with .. Pacing algorithms for minimizing ventricular pacing are often used
bradycardia—tachycardia syndrome.139 If drug treatment is chosen, .
in SND.144,151 A meta-analysis of algorithms for minimizing RV pacing
bradyarrhythmias during drug treatment for rate or rhythm .. failed to show a significant effect compared with conventional DDD
control may be managed by dose reduction or discontinuation as an .
pacing in patients with normal ventricular function with regard to
alternative to cardiac pacing, but in many cases bradyarrhythmias .. endpoints such as incidence of persistent/permanent AF, all-cause
persist.
.
hospitalization, and all-cause mortality.152 However, the rationale for
. reducing unnecessary RV pacing remains strong and is coupled with
.
the benefits of extending device longevity.151,152 Some manufacturer-
5.1.2 Pacing mode and algorithm selection .. specific algorithms are more effective in minimizing ventricular pacing,
In patients with SND, controlled studies found that DDD was superior .. but may confer disadvantages in allowing decoupling between atria
to single-chamber ventricular pacing in reducing the incidence of AF. . and ventricles.153,154 Rarely, algorithms designed to minimize ventric-
These studies also showed some effect of DDD pacing on the occurrence .. ular pacing can cause life-threatening ventricular arrhythmias that are
of stroke.140,141 Dual-chamber pacing reduces the risk of pacemaker . pause dependent or pause triggered.155—158 No direct comparison
syndrome, which may occur in more than a quarter of patients with .. of these algorithms has been performed so far, but pooled data from
SND.21,142 Pacemaker syndrome is associated with a reduction in quality . randomized trials do not show clear-cut superiority of any specific
of life and usually justifies the preference for DDD vs. ventricular .. algorithm in improving clinical outcome.152,159
rate-modulated pacing in SND, when reasonable.143 Potential .
In patients with severely reduced LVEF and a SND indication for
exceptions are very elderly and/or frail patients with infrequent pauses .. pacing, in whom a high percentage of ventricular pacing is expected,
who have limited functional capacity and/or a short expected survival. In .
an indication for CRT or HBP should be evaluated (see section 6 on
these patients, the benefit of DDD(R) vs. VVIR pacing is expected to .. CRT and section 7 on HBP).
have limited or no clinical impact, and the incremental risk of .
The role of pacing algorithms for preventing AF has been the sub-
complications related to the second atrial lead required in DDD(R) .. ject of controversy. A series of algorithms for preventing/suppressing
implants should also be considered when choosing the pacing mode. In .
AF has been tested, such as dynamic atrial overdrive pacing, atrial
patients with SND treated with a DDD pacemaker, programming of the .. pacing in response to atrial premature beats, pacing in response to
AV interval and specific algorithms for minimizing RV pacing may .
exercise, and post-mode-switch pacing. The clinical evaluation of
further reduce the risk of AF and par- .
these algorithms, also applied at different atrial pacing sites, is not
ticularly of persistent AF.144 Dual-chamber pacing is safer and more
127
.
convincing and no clinical benefit with regard to major clinical end-
sustainable than atrial-only pacing modes used in the past, even . points has been demonstrated. 160,161
though single-lead atrial pacing was found to be superior to single- lead
.
Atrial antitachycardia pacing [ATP; i.e. delivery of atrial stimuli at
ventricular pacing.145,146 The results of studies that evaluated different .. high frequencies to convert an atrial tachyarrhythmia to sinus rhythm
..
pacing modes in bradyarrhythmias, including in some cases both SND and
(SR)] has also been tested for reducing the atrial tachyarrhythmia
AVB, are shown in Supplementary Table 6. . burden and counteracting the tendency over time towards progres-
..
With regard to the choice between DDD(R) and atrial pacing atrial
sion to permanent AF. 162 Conventional delivery of atrial ATP in a
sensing inhibited-response rate-adaptive (AAIR) pacing, an RCT with only . way that mirrors the delivery of ventricular ATP (bursts/ramp at
177 patients suggested a reduced risk of AF with AAIR.147 However, the
.. arrhythmia onset) has a relatively low success rate, and indeed the tri-
most recent DANish Multicenter Randomized Trial on Single Lead Atrial . als based on conventional atrial ATP showed no benefit on AF bur-
PACing vs. Dual Chamber Pacing in Sick Sinus .
. den or clinical events.163 A new form of ATP delivery has been
ESC Guidelines 29
Optimal pacing mode in sinus node dysfunction and atrio-ventricular block
SND AV block
Persistent or paroxysmal Persistent or paroxysmal

Persistent Paroxysmal Persistent Paroxysmal
Chronotropic incompetence?
SND no SND AF
Y N
Sinus rhythm: DDD + AVM AF: VVI +

Default option DDDR DDD DDD(R)a rate hysteresis
DDD(R)a DDD VVIR
+ AVM + AVM + AVM
Single chamber AAI(R)a VVI(R)a

Any reasonSingle Single chamber AAI
to avoid 2chamber VVI(R)a VDD VDD
leadsbAAIR
Significant comorbidity VVI + rate hysteresis VVI +

VVIR VVI VVI
rate hysteresis
Figure 5 Optimal pacing mode and algorithm selection in sinus node dysfunction and atrioventricular block. AF = atrial fibrillation; AV = atrioventricular; AVM =
atrioventricular management [i.e. AV delay programming (avoiding values >230 ms) or specific algorithms to avoid/reduce unnecessary ventricular pacing]; CRT =
cardiac resynchronization therapy; SND = sinus node dysfunction. a(R) indicates that the programming of such a pacing mode is preferred only in the case of
chronotropic incompetence. bReasons to avoid two leads include young age and limited venous access. Note: in patients who are candidates for a VVI/VDD
pacemaker, a leadless pacemaker may be considered (see section 7). For combined CRT indications, see section 6. Adapted from Brignole et al.62
.
proposed, specifically aimed at reducing atrial tachyarrhythmias, and its conventional DDD(R)]. The positive effect on the primary endpoint
efficacy in reducing the progression to permanent AF was validated
.. was due to a lower rate of progression to permanent AF. A post-hoc
.
in an RCT.162,164 . analysis indicated that this form of atrial ATP was an independent
162,164,165
In this trial,164 the primary composite outcome at 2 years (death, predictor of permanent or persistent AF reduction. In
cardiovascular hospitalizations, or permanent AF) was significantly .
CHD, where re-entrant atrial arrhythmias are very common, use of
reduced in patients with a device combining ATP and algorithms for .. DDD(R) pacemakers with atrial ATP may be considered (see section
minimizing RV pacing [36% relative risk reduction compared with .
. 8 on pacing in CHD).
30 ESC Guidelines
.
AVB, manifestations of fatigue, exertional intolerance, and HF are
Recommendations for pacing in sinus node .. sometimes underestimated. Deterioration of cognitive functions is
dysfunction .
often only speculative so that the possibilities of improvement after
Recommendations Classa Levelb .
implantation of a pacemaker are unpredictable and unlikely. Death in
In patients with SND and a DDD pacemaker, .. patients with untreated AVB is due not only to HF secondary to low
.
minimization of unnecessary ventricular pacing cardiac output, but also to SCD caused by prolonged asystole or
through programming is
I A .
. bradycardia-triggered ventricular tachyarrhythmia. Although RCTs of
recommended.144,151,159,164,166—169 pacing in AVB have not been performed, it is clear from several
Pacing is indicated in SND when symptoms can clearly
.
observational studies that pacing prevents recurrence of syncope and
be attributed to I B
.
improves survival.10—12
bradyarrhythmias.14,128—131 ..
Pacing is indicated in symptomatic patients with the .
. 5.2.1.1 First-degree atrioventricular block
bradycardia—tachycardia form of SND in order to . Usually the prognosis is good in the absence of structural heart175
..

correct bradyarrhythmias and enable disease, and progression to high-degree block is uncommon. The
I B
pharmacological treatment, unless ablation of . indication for pacing relies on an established correlation between
the tachyarrhythmia is .. symptoms and AVB. There is weak evidence to show that marked PR
preferred.17,20,21,136—138,170,171 .
prolongation (i.e. >_300 ms), particularly when it persists or is pro-
In patients who present chronotropic incompetence .. longed during exercise, can lead to symptoms similar to pacemaker
and have clear symptoms during exercise, DDD with .
IIa B syndrome and/or that these can improve with pacing.176 Symptom
rate-responsive pacing should be .. correlation is crucial, although it may be difficult if these are non-
considered.172,173 .
specific and subtle. In the absence of a clear correlation, a pacemaker
AF ablation should be considered as a strategy to .. is generally not indicated.
avoid pacemaker implantation in patients with AF- .
IIa C
..
related bradycardia or symptomatic pre- automaticity 5.2.1.2 Second-degree type I atrioventricular block (Mobitz type I or
pauses, after AF conversion, taking
.
Wenckebach)
into account the clinical situation.136—139,174 .. In addition to the presence or absence of symptoms, the risk of pro-
.
In patients with the bradycardia—tachycardia gression to higher degrees of AVB should be considered. Supranodal
variant of SND, programming of atrial ATP may IIb B
..
. block has a benign course, and the risk of progression to type II or a
be considered.164,165 higher degree of AV block is low. Small, retrospective studies have
In patients with syncope, cardiac pacing may be
..
suggested that, over the long term, this type of AVB carries a higher
considered to reduce recurrent syncope when .
asymptomatic pause(s) >6 s due to sinus arrest
IIb C .. risk of death in patients aged >_45 years in the absence of pacemaker
implantation.177,178 Infranodal block (rare in this form of block) car-
is documented.133,134 .
.. ries a high risk of progression to complete heart block, syncope, and
Pacing may be considered in SND when symp- sudden death, and warrants pacing even in the absence of
.
toms are likely to be due to bradyarrhythmias, when IIb C symptoms.179,180
the evidence is not conclusive. ..
.
Pacing is not recommended in patients with bra- . 5.2.1.3 Second-degree Mobitz type II, 2:1, and advanced atrioventricular
dyarrhythmias related to SND that are asympto- .
III C block (also named high-grade atrioventricular block, where the P:QRS
matic or due to transient causes that can be .. ratio is 3:1 or higher), third-degree atrioventricular block
ESC 2021
corrected and prevented.33 .

In the absence of a reversible cause, due to the risk of occurrence of
.. severe symptoms and/or possible progression towards a more
.
ATP = antitachycardia pacing; DDD = dual-chamber, atrioventricular pacing; SND severe or complete AVB, patients should receive a pacemaker even
= sinus node dysfunction. .. in the absence of symptoms. In asymptomatic patients in whom a 2:1
a
AVB is found incidentally, the decision for implantation should be
Level of evidence.
..
b
made on a case by case basis including distinction between nodal and

.
infranodal AVB. This distinction may be based on observations such
.. as PR or PP interval prolongation before AVB, the effect of exercise
.
on AV conduction, and an EPS.
5.2 Pacing for atrioventricular block ...
5.2.1.4 Paroxysmal atrioventricular block
5.2.1 Indications for pacing .. Because of the risk of syncope and SCD and of the potential progres-
Treatment of AVB aims at ameliorating symptoms and preventing .
sion to permanent AVB, the indications for pacing are the same for
..
syncope and sudden cardiac death (SCD). First-degree AVB is usually
asymptomatic. Syncope and dizziness are mainly observed in high- paroxysmal as for permanent AVB. It is crucial to rule out a reversible
degree and complete AVB, especially in the paroxysmal forms. HF .. cause and to recognize the reflex forms of AVB, which may not need
symptoms are more common in chronic AVB with permanent brady-
. pacing. Documentation of infranodal block by EPS or the documenta-
cardia, but can also be observed in first-degree AVB with a very pro- .. tion of initiation of the block by atrial or ventricular premature beats,
longed PR interval. Given the commonly advanced age at onset of
. or increased heart rate (tachy-dependent AVB) or decreased heart
ESC Guidelines 31
.
symptoms due to bradycardia and of high-degree or infranodal block,
rate (brady-dependent AVB), support a diagnosis of intrinsic infranodal .. pacing is unlikely to be beneficial and is not indicated.
AVB.27 .
In patients with AF who undergo atrioventricular junction (AVJ)
.. ablation to control rapid ventricular rates, there is evidence to show
5.2.2 Pacing mode and algorithm selection
.. that AVJ ablation plus RV pacing improves symptoms and quality of
5.2.2.1 Dual-chamber vs. ventricular pacing . life.192 In contrast, neutral results were found regarding the progres-
Large, randomized, parallel trials that included patients with only . sion of HF, hospitalization, and mortality,193 except in one study.194
AVB181 or with AVB and/or SND140 failed to show superiority of .. Compared with pharmacological rate control, AVJ ablation and CRT
DDD over ventricular pacing with regard to mortality, and have not ... reduced the risks of death due to HF, hospitalization due to HF, or
consistently shown superiority in terms of quality of life or morbidity worsening HF by 62%, and improved specific symptoms of AF by
(including stroke or transient ischaemic attack and AF). 20,140,181 Dual- . 195
chamber pacing is beneficial over ventricular pacing due to the avoidance . 36% in elderly patients with permanent AF and narrow QRS. In
.
of pacemaker syndrome, which occurred in up to a quarter of other studies, this beneficial effect 166,196
was limited to patients with HF or
patients with AVB in these trials. In a meta-analysis of 20 crossover .. reduced ejection fraction (EF). For further discussion of the
.

role of CRT following AVJ ablation, refer to section 6. There is weak
trials, DDD was associated with an improved exercise capacity compared .. evidence to support a benefit from para-Hisian and Hisian pacing
with ventricular pacing. However, the effect was driven by non-rate- .
after AVJ ablation for refractory AF.197— 200 For further discussion,
modulated ventricular pacemakers, and no benefit was observed from .. refer to section 7.
the comparison of DDD with VVIR pacing. 182 Pacemaker syndrome is
.
associated with reduction in quality of life and may require a . Recommendations for pacing for atrioventricular block
reintervention for upgrading, justifying the preference for DDD when .
reasonable (i.e. in patients who do not present with significant frailty, .
very advanced age, significant comorbidities limiting their life .
expectancy, or a very limited mobility). Another consideration is the . Pacing is indicated in patients in SR with perma-
.
diagnosis of AF, which is more reliable from device data in patients with . nent or paroxysmal third- or second-degree type 2,
DDD pacemakers. On a case by case basis, in frail elderly patients, . infranodal 2:1, or high-degree AVB, irre-
I C
.
and/or when AVB is paroxysmal and pacing anticipated to be . spective of symptoms.c 9—12
infrequent, VVIR pacing may be considered as it carries a lower . Pacing is indicated in patients with atrial arrhyth-
.
complication rate.140 . mia (mainly AF) and permanent or paroxysmal
There is strong evidence to show that chronic conventional RV . third- or high-degree AVB irrespective of
I C
.
pacing may be deleterious in some patients and may lead to LV dys- . symptoms.
function and HF,148 even when AV synchrony is maintained.183 This effect . In patients with permanent AF in need of a pace-
.
is only partly explained by the abnormal activation sequence and may . maker, ventricular pacing with rate response I C
involve myocardial perfusion, and humoral, cellular, and . function is recommended.201—204
molecular changes. 184,185 Compared with a matched control cohort,
..
Pacing should be considered in patients with sec-
.
patients with a pacemaker and an RV lead have an increased risk of HF, ond-degree type 1 AVB that causes symptoms or is
.
which is also associated with older age, previous MI, kidney dis- . ease, and found to be located at intra- or infra-His
IIa C
. levels at EPS.177—180
male sex.186 Pacing-induced cardiomyopathy occurs 186—188
in ..
10—20% of patients after 2—4 years of RV pacing. It is associ- In patients with AVB, DDD should be preferred over
. .
ated with a >20% RV pacing burden. 187—190 However, there are no data to single-chamber ventricular pacing to avoid
. IIa A
support that any percentage of RV pacing can be considered . as defining a cardiac pacing.
pacemaker syndrome Any high-degree
and to improve quality of or infranodal block is also an indica-
. tion for pacing, even in the absence of symptoms. In the absence of
life.20,140,181,182
true limit below which RV pacing is safe and beyond which RV pacing is.
harmful. For discussion of potential indications for . CRT and/or HBP to Permanent pacemaker implantation should be
. considered for patients with persistent symptoms
prevent pacing-induced cardiomyopathy, please refer to sections 6 and 7..
similar to those of pacemaker syndrome and clearly IIa C
.
. attributable to first-degree AVB (PR
.
5.2.2.2 Atrioventricular block in the case of permanent atrial fibrillation . >0.3 s).205—207
. Pacing is not recommended in patients with AVB due
In the presence of AF, AVB should be suspected if the ventricular rate. to transient causes that can be corrected III C
is slow and the ventricular rhythm regular. During prolonged . and prevented.
.
monitoring, long ventricular pauses may be detected.191 In patients with.
AF and no permanent AVB or symptoms, there is no identifiable,
. .
minimum pause duration as an indication for pacing. In the absence of
.
a potentially reversible cause, bradycardia or inappropriate chrono-
.
.
tropic response (due to either intermittent or complete AVB) associ-
.
ated or reasonably correlated with symptoms is an indication for
.
32 ESC Guidelines
ESC 2021
AF = atrial fibrillation; AVB = atrioventricular block; DDD = dual-chamber, atrio-
ventricular pacing; EPS = electrophysiology study; SR = sinus rhythm.
a
b
Level of evidence.
c
In asymptomatic narrow QRS complex and 2:1 AVB, pacing may be avoided if supra-
Hisian block is clinically suspected (concomitant Wenckebach is observed and block
disappears with exercise) or demonstrated at EPS.
ESC Guidelines 33
.
Isolated fascicular block and BBB are rarely associated with symp-
In patients with AF, compared with fixed rate pacing, rate-
.. toms; however, their presence may be a marker for underlying struc-
responsive pacing is associated with better exercise performance, .
tural heart disease. The presence or absence of symptoms referable
..
improved daily activities, a decrease in symptoms of shortness of breath,
chest pain, and palpitations, and improved quality of to intermittent bradycardia will guide the evaluation of these patients.
life.201—203 It has also been shown to improve heart rate and blood ..
pressure response to mental stress compared with fixed rate pacing.204
. 5.3.1 Indications for pacing
Therefore, rate-adaptive pacing is the pacing mode of first choice. .. 5.3.1.1 Bundle branch block and unexplained syncope
Fixed-rate VVI pacing should be reserved for older sedentary patients
. Although syncope is not associated with an increased incidence of
who have very limited activity. Commonly, the minimum rate is .. sudden death in patients with preserved cardiac function, a high inci-
programmed higher (e.g. 70 b.p.m.) than for patients in SR in
.
dence of total deaths (about one-third sudden) was observed in
an attempt to compensate for loss of active atrial filling. .. patients with BBB and HF, previous MI, or low EF.
208—210
Indeed, in
.
those with low EF, syncope is a risk factor for death.211
.. Unfortunately, ventricular-programmed stimulation does not seem
5.3 Pacing for conduction disorders .

to identify these patients correctly; therefore, an ICD or a defibrilla-
without atrioventricular block .. tor with CRT (CRT-D) is indicated in patients with BBB and LVEF
.
This section focuses on patients with 1:1 AV conduction and QRS <35% for the prevention of SCD (Figure 6).63
abnormalities caused by delayed or blocked conduction of the His— ..
. 5.3.1.2 Bundle branch block, unexplained syncope, and abnormal elec-
Purkinje system: BBB, fascicular block in isolation or in combina-
tion with BBB, and non-specific intraventricular delay. Bifascicular .. trophysiological study
.
block is defined as LBBB or the combination of RBBB and with left Electrophysiological assessment includes measurement of the
.
anterior or posterior fascicular block. . HV at baseline, with stress by incremental atrial pacing or by
Decision algorithm for patients with unexplained syncope and BBB
Bifascicular block
Y LVEF ≤ 35%
Elderly and frail patients at risk of traumatic recurrrences

Y
EPS/CSM
No diagnosisDiagnosis ILR
No diagnosis Diagnosis
ICD/CRT-D Clinical follow-up Adapted therapy Pacemaker implant
Figure 6 Decision algorithm for patients with unexplained syncope and bundle branch block. BBB = bundle branch block; CRT-D = defibrillator with cardiac
resynchronization therapy; CSM = carotid sinus massage; EPS = electrophysiology study; ICD = implantable cardioverter-defibrillator; ILR = implantable loop
recorder; LVEF = left ventricular ejection fraction.
34 ESC Guidelines
pharmacological provocation (ajmaline, procainamide, or flecainide).

Recommendations for pacing in patients with bundle
branch block
.
Scheinman et al. studied the prognostic value of the HV: the progres-
.
.
sion rate to AVB at 4 years was 4% in patients with HV <70 ms, 12%
.
Recommendations Classa Levelb
in patients with HV between 70 and 100 ms, and 24% in patients with .
In patients with unexplained syncope and bifas-
. cicular block, a pacemaker is indicated in the
HV >100 ms.
121
Development of intra- or infra-His block at incre- . presence of either a baseline HV of >_70 ms, sec-
I B
. ond- or third-degree intra- or infra-Hisian block
mental atrial pacing or by pharmacological stress test increases the .
sensitivity and positive predictive value of the EPS to identify patients . who during incremental atrial pacing, or an abnormal
. response to pharmacological challenge.119,120
will develop AVB.116—118,120,122,212 A positive EPS yielded a positive.
Pacing is indicated in patients with alternating
predictive value as high as 80% to identify patients who develop . I C
. BBB with or without symptoms.
AVB. This finding has been indirectly confirmed by a study that . Pacing may be considered in selected patients with
showed a significant reduction in syncopal recurrences in patients .
. unexplained syncope and bifascicular block without
IIb B
with positive EPS treated with a pacemaker, compared with a control
group of untreated patients with a negative EPS. 119
In patients with . EPS (elderly, frail patients, high-risk and/
or recurrent syncope).213

unexplained syncope and bifascicular block, EPS is highly sensitive in
. Pacing is not recommended for asymptomatic
III B
BBB or bifascicular block.115,121,215
.
identifying patients with intermittent or impending high-degree AVB.
.
BBB = bundle branch block; EPS = electrophysiology study; HV =
.
However, a negative EPS cannot rule out intermittent/paroxysmal
.
AVB as the cause of syncope. Indeed, in patients with a negative EPS, .
intermittent or stable AVB was documented by ILR in 50%
.
~ of cases.
.
Therefore, elderly patients with bifascicular block and unexplained
ESC 2021
.
.
syncope might benefit from an empirical pacemaker, especially in
His —ventricular interval.
. a
unpredictable and recurrent syncope that exposes the patient to a

.
high risk of traumatic recurrences. The decision to implant a pacemaker minority of these patients will develop AVB (1 2% per
115,121,215
in these patients should be based on individual risk benefit evaluation.213
—
5.3.1.3 Alternating bundle branch block
This rare condition refers to situations in which there is clear ECG
evidence for block in all three fascicles on successive ECGs; examples are
LBBB and RBBB morphologies on successive ECGs, or RBBB with
associated left anterior fascicular block on one ECG and left posterior
fascicular block on another ECG. 214 There is general consensus that this
phenomenon is associated with significant infranodal disease and that
patients will progress rapidly toward AVB. Therefore, a pacemaker
should be implanted as soon as the alternating BBB is detected, even in the
absence of symptoms.
5.3.1.4 Bundle branch block without symptoms

Permanent pacemaker implantation is not indicated for BBB without
symptoms, with the exception of alternating BBB, because only a
—
ESC Guidelines 35
. Class of recommendation. .
. b
interval, programming AV hysteresis, or other specific algorithms
. preventing unnecessary RV pacing, play a particularly important role
.
. .. in this patient group.144,148
. .
. In patients in SR, the optimal pacing mode is DDD. The strong evi-
.
5.3.2 Pacing mode and algorithm selection .. dence of superiority of DDD vs. VVI pacing is limited to improvement
In intermittent bradycardia, pacing may be required only for short .
. . in symptoms and quality of life. Conversely, there is strong evidence
.
periods. In this situation, the benefits of bradycardia and pause pre- .. of non-superiority with regard to survival and morbidity.20
vention must be weighed against the detrimental effects of perma- .
. . Therefore, in elderly or frail patients with intermittent bradycardia,
.
nent pacing, particularly pacing-induced HF. Low base-rate
.. the decision regarding the pacing mode should be made on an individ-
programming to achieve backup pacing, and manual adaptation of AV .
year). The risks of pacemaker implantation and long-term .. ual basis, taking into consideration the increased complication risk
and costs of DDD (Figure 5).
transvenous lead complications are higher than the benefits of pacemaker .
. VDD may be a pacing mode alternative for patients with advanced
implantation.216,217 . AV conduction abnormalities and spared sinus node function. In
.. comparison with DDD, VDD system implantation is associated with
5.3.1.5 Patients with neuromuscular diseases
In patients with neuromuscular diseases, cardiac pacing should be . fewer complications, shorter procedure and fluoroscopy times, and a
..
218
high incidence of atrial undersensing. Potential atrial undersensing
considered, as any degree of fascicular block can progress unpredict- ably, . is contributing to the low use of this system as most operators are
even in the absence of symptoms (see section 8.5). .
. aiming for AV synchrony.
36 ESC Guidelines
.
rate of syncope with pacing of 15% at 2 years, significantly lower
5.4 Pacing for reflex syncope .. than the 37% rate observed in unpaced controls.219 The 3-year
Permanent pacemaker therapy may be effective if asystole is a dominant .
recurrence rate was similar in patients with cardioinhibitory carotid
feature of reflex syncope. Establishing a relationship between symptoms .. sinus syndrome (16%), asystolic tilt response (23%), and spontane-
and bradycardia should be the goal of the clinical evaluation of patients .
ous asystole documented by ILR (24%), suggesting similar indica-
with syncope and a normal baseline ECG. The efficacy of pacing depends .. tions and similar results for the three forms of reflex syncope.220
on the clinical setting. The fact that pacing is effective does not mean it is .
Whilst some scepticism prevails over the diagnostic accuracy of tilt
always necessary. In patients with reflex syncope, cardiac pacing should .. testing for the diagnosis of syncope, emerging evidence supports
be the last resort and should only be .
considered in highly selected patients [i.e. those >40 years of age the use of tilt testing in the assessment of reflex hypotensive sus-
(mostly >60 years), affected by severe forms of reflex syncope with .. ceptibility.
107,221
Thus, tilt testing may be considered to identify
.
patients with an associated usually antecedent hypotensive
frequent recurrences associated with a high risk of injury, often without a .. response that would be less likely to respond to permanent cardiac
prodrome]. The 2018 ESC Guidelines on syncope62 give a detailed .
pacing. Patients with hypotensive susceptibility need measures
description of the diagnostic pathway and indications for pacing, and ..

. directed to counteract hypotensive susceptibility in addition to car-
provide the evidence from trials that support such recommendations.
diac pacing (e.g. physical counterpressure manoeuvres, discontinu-
Figure 7 summarizes the suggested decision pathway. .. ation/reduction of hypotensive drugs, and administration of
The algorithm shown in Figure 7 has been prospectively validated in a
multicentre pragmatic study, which showed a low recurrence .. fludrocortisone or midodrine).
.
Management of cardiac pacing in patients with reflex syncope
Y Severe, recurrent, unpredictable syncopes, age > 40 years N
Perform carotid sinus massage and tilt table test
Cardioinhibitory carotid sinus syndrome

Y Positive tilt-test N
N Y
Asystolic tilt-test Y
Implant a DDD PM and counteract
hypotensive susceptibility (Class I) Implant a DDD PM (Class I)
N
Implantable loop recorder
Asystole Y Positive tilt-test N
N
Pacing not indicated (Class III)
Figure 7 Decision pathway for cardiac pacing in patients with reflex syncope. DDD = dual-chamber, atrioventricular pacing. Note: cardioinhibitory carotid sinus
syndrome is defined when the spontaneous syncope is reproduced by the carotid sinus massage in the presence of an asystolic pause >3 s; asystolic tilt positive test is
defined when the spontaneous syncope is reproduced in the presence of an asystolic pause >3 s. A symptomatic asystolic pause(s) >3 s or asymptomatic pause(s) >6
s due to sinus arrest, atrioventricular block, or the combination of the two similarly define asystole detected by implantable loop recorder. Figure adapted from
Brignole et al.62
ESC Guidelines 37
.
5.4.1 Indications for pacing vs. in 21 (46%) patients who had received a sham pacemaker pro-
This Task Force found sufficient evidence in the literature to recom- .. grammed off (P = 0.0001). In a propensity score-matched compari-
.
mend pacing in highly selected patients with reflex syncope (i.e. those son study,229 the 5-year actuarial syncope-free rate was 81% in the
>40 years of age with severe recurrent unpredictable syncopal episodes .. pacing group and 53% in propensity-matched patients (P = 0.005; HR
.
when asystole has been documented, induced by either CSM or tilt = 0.25). Finally, the BioSync CLS trial was a multicentre RCT that
testing, or recorded through a monitoring system)133,222—228
.. investigated the usefulness of the tilt-table test to select candidates
.
(see Supplementary Table 7). There is sufficient evidence that DDD for cardiac pacing.228 Patients aged >_40 years who had at least two
pacing should be considered in order to reduce recurrence of syncope in
.. episodes of unpredictable severe reflex syncope during the past year
.
patients with dominant cardioinhibitory CSS (asystolic pause and a tilt-induced syncope with an asystolic pause >3 s were random-
.. ized to receive either an active (63 patients) or an inactive (64
>3 s and spontaneous syncope during CSM) and in those in whom there .
is a correlation between spontaneous symptoms and ECG who are >40 patients) dual-chamber pacemaker with close loop stimulation. The
.. study showed that, after a median follow-up of 11.2 months, syncope
years of age and have severe recurrent unpredictable syncope.62 Permanent .
pacemaker therapy may be effective if asystole is a dominant feature of occurred in significantly fewer patients in the pacing group than in the
..

control group [10 (16%) vs. 34 (53%), respectively; HR 0.23; P =
reflex syncope. Establishing a correlation between symptoms and .
bradycardia should be the goal of the clinical evaluation of patients with 0.00005). This study supports inclusion of tilt testing as a useful
syncope and a normal baseline ECG. The efficacy of pacing depends on .. method to select patients with reflex syncope for cardiac pacing.
the clinical setting. A comparison of results in different settings is .. Based on the results of the above studies, sufficient evidence exists
presented in Supplementary Table 8. Since the publication of the 2018 . to upgrade from IIb to I the indication for pacing in patients aged >40
ESC Guidelines on syncope,62 some trials have added relevant .. years with asystolic tilt response >3 s. Figure 8 summarizes the rec-
information regarding the subset of patients with tilt-induced asystolic . ommended indication for pacing. Although there is also a rationale
vasovagal syncope. The SPAIN trial was a multicentre, randomized, .. for pacing in patients aged <_40 years who have the same severity cri-
controlled, crossover study, performed in 46 patients aged >40 years
. teria as those >40 years, this Task Force cannot make any recom-
affected by severely recurrent (>5 episodes during life) syncope and .. mendation due to the lack of evidence from trials addressing this
cardioinhibitory tilt test response (defined as bradycardia <40 b.p.m.
.
specific population.
lasting >10 s or asystole .. There is weak evidence that DDD may be useful in reducing recur-
>3 s).226 During the 24-month follow-up, syncope recurred in 4 (9%)
.
rences of syncope in62patients with the clinical features of adenosine-
patients treated with a DDD pacemaker with closed loop stimulation .. sensitive syncope. In a small multicentre trial performed in 80 highly
.
Indications for pacing in patients above age 40 with reflex syncope
Y Spontaneous asystolic pause(s)
N
Test-induced asystolic pause(s)
Y
CI-CSS
Pacing indicated (Class I)

Asystolic tilt
Extrinsic (functional) vagally-mediated or adenosine-sensitive
Undocumented syncope
Pacing indicated (Class I) Pacing not indicated (Class III)

Pacing indicated Adenosine
(Class I) induced AV block > 10 sec Pacing indicated (Class IIb)
Figure 8 Summary of indications for pacing in patients >40 years of age with reflex syncope. CI-CSS = cardioinhibitory carotid sinus syndrome. Note:
spontaneous asystolic pause = 3 s symptomatic or 6 s asymptomatic. Adapted from Brignole et al.62
38 ESC Guidelines
.
selected elderly patients with unexplained unpredictable syncope who . 5.5.1 Recurrent undiagnosed syncope
. In patients with unexplained syncope at the end of a complete work-
had induction of third-degree AVB of >_10 s to intravenous injec- tion
of a bolus of 20 mg of adenosine triphosphate, DDD significantly reduced .. up and absence of any conduction disturbance, the lack of a rationale
. and the negative results of small studies234,235 give sufficient evidence
the 2-year syncope recurrence rate from 69% in the control group to 23%
in the active group.230 Finally, cardiac pacing is not indicated in the .. of inefficacy of cardiac pacing. Thus, cardiac pacing is not recom-
.
absence of a documented cardioinhibitory reflex.231,232 mended until a diagnosis is made (Figure 8).
..
.
5.4.2 Pacing mode and algorithm selection . 5.5.2 Recurrent falls
Even if the quality of evidence is weak, DDD pacing is widely pre- .. Between 15% and 20% of unexplained falls may be syncopal in nature,
ferred in clinical practice to single-chamber RV pacing in counteracting . possibly bradyarrhythmic. Retrograde amnesia, which is frequent in
blood pressure fall and preventing symptom recurrences. In patients . the falling elderly, is responsible for misinterpretation of the event.62
with tilt-induced vasovagal syncope, DDD was used mostly with a rate- .. The management of unexplained falls should be the same as that for
drop response feature that provides rapid DDD if the device detects a .. unexplained syncope (see section 5.4.1). In a randomized double-

rapid decrease in heart rate. A comparison between DDD closed-loop . blind trial,236 cardiac pacing was ineffective in preventing recurrences
stimulation and conventional DDD has been performed by means of a .. in patients with an unexplained fall in whom carotid sinus hypersensi-
crossover design in two small studies. Both studies showed fewer .
tivity was unable to induce syncope.
.
syncope recurrences with closed-loop stimula-
233 .and dur-
.
tion, both in the acute setting during repeated tilt testing Recommendations for cardiac pacing in patients with
ing 18-month clinical follow-up. However, until a formal parallel

227 . suspected (undocumented) syncope and unexplained
trial is performed, no recommendation can be given regarding the .
. falls
selection of the pacing mode (i.e. DDD with rate-drop response or DDD .
with closed-loop stimulation) and its programming.
.
.
. In patients with recurrent unexplained falls, the
. same assessment as for unexplained syncope should IIa C
Recommendations for pacing for reflex syncope .
. be considered.62
. Pacing is not recommended in patients with
. unexplained falls in the absence of any other III B
Dual-chamber cardiac pacing is indicated to reduce . documented indication.236
.
recurrent syncope in patients aged >40 years, with . Pacing is not recommended in patients with unexplained
.
ESC 2021
severe, unpredictable, recurrent syncope who syncope without evidence of SND III C
.
have: . or conduction disturbance.234,235
• spontaneous documented symptomatic asys- ..
I A SND = sinus node dysfunction.
tolic pause(s) >3 s or asymptomatic pause(s) . a
>6 s due to sinus arrest or AVB; or .
. b
Level of evidence.
• cardioinhibitory carotid sinus syndrome; or .
asystolic syncope during tilt .
•
.
testing.62,219,220,226,228,229 ..
Dual-chamber cardiac pacing may be considered to
.
6 Cardiac resynchronization
reduce syncope recurrences in patients with the
therapy
...
IIb B
clinical features of adenosine-sensitive
syncope.230 6.1 Epidemiology, prognosis, and
..
ESC 2021
Cardiac pacing is not indicated in the absence of

III B pathophysiology of heart failure suitable
a documented cardioinhibitory reflex.231,232
.. for cardiac resynchronization therapy by
AVB = atrioventricular block. .. biventricular pacing
Class of recommendation. bLevel
.
a
of evidence.
.. The prevalence of HF in the developed world approximates 1 2% —
of the adult population, rising to >_10% among people aged >70
.
years.237 The prevalence of HF is increasing (by 23% over the past
.. decade according to one estimate) mainly due to the ageing of the
5.5 Pacing for suspected .
(undocumented) bradycardia . population, with the age-specific incidence actually declining.238—241
. There are three distinct phenotypes of HF based on the measure-
In patients with recurrent unexplained syncope or falls at the end of the
conventional work-up, ILR monitoring should be considered in an ... ment of LVEF [<40%, HF with reduced EF (HFrEF); 40 49%, — HF
. with mildly reduced EF (HFmrEF); and >_50%, HF with preserved EF
attempt to document a spontaneous relapse instead of embarking on
. (HFpEF)].242 CRT is clinically useful mainly for patients with HFrEF
empiric cardiac pacing.62
. and LVEF <_35%. Patients with HFrEF constitute ~50% of the entire
ESC Guidelines 39
.
population with HF, and HFrEF is less prevalent among individuals aged had an ischaemic cardiomyopathy. At 7-year follow-up, the subgroup
.. of patients with LBBB, NYHA functional class I, and ischaemic cardio-
70 years or older. The prognosis of HF varies according to the defined .
population. In contemporary clinical trials of HFrEF, 1-year mortality myopathy showed a non-significant trend towards lower risk of death
.. from any cause [relative risk 0.66, 95% confidence interval (CI)
rates of ~6% are seen, whereas in large registry-based sur- .
veys, 1-year mortality rates exceed 20% in patients recently hospital- . 0.30 —1.42; P = 0.29]. Therefore, present CRT recommendations are
ized for HF, but are closer to 6% in those recruited with stable . applicable to all patients in NYHA functional class II—IV of any
outpatient HF.243 The concept of CRT is based on the fact that in .. aetiology.
patients with HF and LV systolic dysfunction, high-grade intraventricular
. The MUltisite STimulation In Cardiomyopathies (MUSTIC),256,257
conduction delays are frequently observed, with a prevalence of ... Multicenter Insync RAndomized Clinical Evaluation (MIRACLE),
. PAcing THerapies in Congestive Heart Failure (PATH-CHF) I and
QRS duration >120 ms in 25—50% of patients and of LBBB in 15—
27% of cases. Moreover, in such patients, AV dyssynchrony is also often . II,58,254,255,259 COmparison of Medical therapy, PAcing aNd
present with prolonged
244—246 PR on the surface ECG in up to . defibrillatION (COMPANION),260 and CArdiac REsynchronization in
39,261
52% of cases. These electrical abnormalities may result in AV, . Heart Failure (CARE-HF) trials compared the effect of CRT vs.

interventricular, and intra-LV mechanical dyssynchrony.247,248 . guideline-directed medical therapy in NYHA functional class III or IV; in
Recommendations for CRT are based on the results of the major .. contrast, most recent trials have compared CRT-D with ICD on top
RCTs of CRT, most of which have been restricted to the ~60% of .
of best medical therapy in NYHA functional class II.37,40,262—266 Few
HFrEF patients who are in SR. CRT is recommended (in addition to .. studies have compared CRT-pacemaker (CRT-P) with conventional
guideline-directed medical therapy) in only defined subsets of the HF .
pacing.190,267,268 Most studies of CRT have specified that LVEF should
patient population, the majority being symptomatic HF patients in SR with .. be <_35%, but MADIT-CRT40 and the Resynchronization
a reduced LVEF and a QRS duration >_130 ms. Other smaller groups . —
Defibrillation for Ambulatory Heart Failure Trial (RAFT)37 considered
that may be considered for CRT include New York Heart Association .. an LVEF <_30%, and the REsynchronization reVErses Remodelling in
(NYHA) class III or IV HF patients in AF with a reduced LVEF and a .
Systolic left vEntricular dysfunction (REVERSE) trial262 specified <_40%.
QRS duration >_130 ms, provided a strategy to ensure biventricular .
. Relatively few patients with an LVEF of 35—40% have been random-
capture is in place or the patient is expected to return to SR, and .
occasionally as an upgrade from a conventional pacemaker or an ICD in
.. ized, but an individual participant data meta-analysis suggests no dimin-
ution of the effect of CRT in this group.33
HFrEF patients who develop worsening HF with a high rate of ventricular
.
Not all patients respond favourably to CRT. Several characteristics
pacing. A recent survey in the USA, which derived .. predict reduction in ventricular volume (reverse remodelling) and
a nationally representative estimate of the entire US population of
.
improvement in morbidity and mortality. QRS width predicts CRT
hospitalized patients, found that over a 10-year period (2003—2012), there .. response and was the inclusion criterion in all randomized trials (for
were an estimated 378 247 CRT-D implantations, representing
.
ECG criteria for LBBB and RBBB, see Supplementary Table 1). QRS
249
~40 000 per year, or roughly 135 per million per year. In Europe, .. morphology has been related to a beneficial response to CRT.
previous estimates have reported that ~400 patients per million ... Several studies have shown that patients with LBBB morphology are
population per year might be suitable for CRT. This was based on an . more likely to respond favourably, whereas there is less certainty
269,270
estimated prevalence of 35% for LVEF <_35% in a representative HF . about patients with non-LBBB morphology. Sipahi et al. per-
population, of which 41% of patients were estimated to have a QRS . formed a meta-analysis in which they examined 33 clinical trials inves-
duration >_120 ms. The change to a higher threshold of QRS duration of .. tigating the effect of QRS morphology on CRT, but only four
130 ms will reduce these estimates modestly.250,251 In Sweden, a recent . (COMPANION, CARE-HF, MADIT-CRT, and RAFT) included out-
survey of 12 807 HFrEF patients showed that 7% had received CRT and .. comes according to QRS morphology. When they evaluated the
69% had no indication for CRT, but 24% had an indication and had not .
effect of CRT on composite adverse clinical events in 3349 patients
received CRT. These data highlight the underuse of CRT.252,253 Finally, .. with LBBB at baseline, they observed a 36% reduction in risk with the
the Task Force stresses the point that the decision to implant CRT requires .
use of CRT (relative risk 0.64, 95% CI 0.52 0.77; — P < 0.00001).
a shared decision-making with the patient. .. However, such benefit was not observed in patients with non-LBBB
.
conduction abnormalities (relative risk 0.97, 95% CI 0.82 1.15; —P<
.. 0.75). When the analysis was limited to trials without ICD (CARE-HF
6.2 Indication for cardiac .
and COMPANION), the benefit of CRT was still observed only in
resynchronization therapy: patients in .. patients with LBBB (P < 0.000001). In a meta-analysis excluding
sinus rhythm .
COMPANION and MADIT-CRT, LBBB was not found to be a pre-
CRT improves cardiac function, symptoms, and well-being, and reduces .. dictor of mortality, in contrast to QRS duration.266 In a recent large
.
morbidity and mortality in an appropriately selected group of HF patients. meta-analysis of five RCTs (COMPANION, CARE-HF, MADIT-CRT,
CRT also improves quality-adjusted life-years among patients with .. RAFT, and REVERSE) including 6523 participants (1766 with non-
.
moderate to severe HF. The beneficial effects of CRT have been LBBB QRS morphology), CRT was not associated with a reduction in
extensively proven in patients with NYHA class II, III, and .. death and/or HF hospitalization in patients with non-LBBB QRS mor-
— .
IV.3 ,39,40,254 266 In contrast, there is rather limited evidence of CRT
7
. phology (HR 0.99, 95% CI 0.82 - 1.2).271 As patients have been aggre-
benefit in patients
40,265 with NYHA functional class I and ischaemic cardio- . gated in the non-LBBB category in nearly all studies and post-hoc
myopathy. In the Multicenter Automatic Defibrillator .. analyses on the beneficial effect of QRS morphology in CRT, it is not
Implantation with Cardiac Resynchronization Therapy (MADIT- . possible to provide a separate recommendation for CRT in patients
CRT) study,265 a total of 265 (7.8%) of 1820 patients were class I and .
. presenting with diffuse intraventricular conduction disturbance and
40 ESC Guidelines
.
RBBB.272—277 Patients with RBBB do not benefit from CRT278 unless they .. ECG criteria of intraventricular conduction disturbance, LBBB, and
show a so-called masked LBBB on ECG,277 characterized by a . non-LBBB have not been consistently defined and reported in any of
287,288
broad, slurred, sometimes notched R wave on leads I and aVL, . the past CRT studies. Similarly, the modality of QRS measure-
together with a leftward axis deviation. Individualized positioning of the . ment (automatic or manual, and ECG recording machine) was not
LV lead is crucial in these patients. .. reported in CRT studies. However, the selection of ECG criteria
An important recent notion is the possible role played by a pro- . appears to influence hard endpoints.287—290 Similarly, ECG recording
longed PR in HF patients with non-LBBB. A few single-centre studies and .. modality and ECG manufacturer have been shown to possibly affect
two post-hoc analyses of large RCTs (COMPANION and MADIT- .
the automatically measured QRS duration.
CRT) indicated a potential benefit of implanting CRT in this patient .. Finally, CRT is considered in patients on optimal medical treatment
subgroup.244,279,280 In MADIT-CRT, the subgroup of non- LBBB .
(OMT), including beta-blockers, angiotensin-converting enzyme
patients who had a prolonged PR did benefit from CRT-D, with a 73% .. inhibitors, or angiotensin receptor blockers, and mineralocorticoid
reduction in the risk of HF or death and an 81% reduction in .
receptor antagonists. However, a study raises the question of the
the risk of all-cause mortality compared with ICD-only therapy. 279
.In . timing of CRT, because the efficacy of the medical treatment can be
.

non LBBB patients with normal PR, CRT-D was associated with a trend limited in patients with LBBB, suggesting considering CRT sooner.291
towards an increased risk of HF or death and a >2-fold higher mortality .. Moreover, whereas everyday clinical practice supports the use of
compared with ICD therapy, suggesting a bidirectional significant .
interaction. However, the data are too limited to give a .. sacubitril/valsartan, ivabradine, and sodium glucose
— co-transporter-
2 inhibitors, it must be emphasized that in the landmark trials
recommendation.279 .
documenting the efficacy of these drugs, very few patients had an
The results of the MADIT-CRT, REVERSE, and RAFT trials suggest that .. indication for CRT. Thus, there are no strong data to support the
in patients with LBBB, there is likely to be potential benefit in all patients .
mandatory use of these drugs before considering CRT.292—295
with LBBB regardless of QRS duration, and that no cut-off point can be .
identified clearly to exclude patients who will not .
Recommendations for cardiac resynchronization ther-
272,273,275
.
respond according to the QRS duration. In contrast, any .. apy in patients in sinus rhythm
benefit of CRT in patients with non-LBBB is evident mostly in those ..
with a QRS duration >_150 ms. Importantly, as shown in the MADIT- Recommendations Classa Levelb
.
CRT long-term study and RAFT, the benefit in patients with QRS
. LBBB QRS morphology
<150 ms appeared later during follow-up.265,273 . CRT is recommended for symptomatic patients
.
The Echocardiography Guided Cardiac Resynchronization . with HF in SR with LVEF <_35%, QRS duration
Therapy (Echo-CRT) trial suggested possible harm from CRT when . >_150 ms, and LBBB QRS morphology despite I A
.
baseline echocardiographic mechanical dyssynchrony in patients with . OMT, in order to improve symptoms and reduce
QRS duration <130 ms is used.264,281 Therefore, selection of CRT .. morbidity and mortality.37,39,40,254—266,283,284
patients based solely on the use of cardiac imaging data is strongly dis- . CRT should be considered for symptomatic patients
couraged in patients with so-called ‘narrow’ QRS (i.e. <130 ms).
. with HF in SR with LVEF <_35%, QRS duration 130
Individual patient data pooled from three CRT-D vs. ICD trials
..
—149 ms, and LBBB QRS morphol-
enrolling predominantly patients with NYHA class II HF showed that
. IIa B
282 .. ogy despite OMT, in order to improve symp-
women are more likely to respond than men. In the US Food and toms and reduce morbidity and mortality.37,39,40,254—
Drug Administration meta-analysis of patient-level data, Zusterzeel et
.
283
al. found that the main difference occurred in patients with LBBB .. 266,283,284
. Non-LBBB QRS morphology

.
and a QRS of 130 — 149 ms. In this group, women had a 76% reduc-
tion in HF or death [absolute CRT-D to ICD difference, 23% (HR . . CRT should be considered for symptomatic patients
. with HF in SR with LVEF <_35%, QRS duration
0.24, 95% CI 0.11 —0.53; P < 0.001)] and a 76% reduction in death
. >_150 ms, and non-LBBB QRS morphology IIa B
alone [absolute difference 9% (HR 0.24, 95% CI 0.06 0.89;— P = . 0.03)], despite OMT, in order to improve symp-
.
whereas there was no significant benefit in men for HF or death. toms and reduce morbidity.37,39,40,254—266,283,284
[absolute difference 4% (HR 0.85, 95% CI 0.60 1.21; P =— . . CRT may be considered for symptomatic patients
0.38)] or death alone [absolute difference 2% (HR 0.86, 95% CI . with HF in SR with LVEF <_35%, QRS duration 130
0.49—1.52; P = 0.60)]. A possible explanation for the greater benefit . —149 ms, and non-LBBB QRS mor- IIb B
. phology despite OMT, in order to improve
of CRT in women has been attributed to sex difference in LV size, as . sex-
.
specific differences in response disappear when QRS duration is normalized symptoms and reduce morbidity.273—278,281
.
to LV end-diastolic volume.284 Recently, computer mod- elling confirmed. QRS duration
that sex differences in the LV size account for a sig- . nificant proportion of CRT is not indicated in patients with HF and
ESC 2021
.
the sex difference in QRS duration, and provided a possible mechanistic.
QRS duration <130 ms without an indication for RV III A
explanation for the sex difference in . CRT response.285,286 Simulations

pacing.264,282
. .
accounting for the smaller LV size in female CRT patients predict 9 - 13 ms
lower QRS duration thresh- . .
olds for females. As with other ECG parameters (e.g. duration of QT .
and corrected QT), it is conceivable that QRS duration also has to
.
.
reflect sex difference.
ESC Guidelines 41
CRT = cardiac resynchronization therapy; HF = heart failure; LBBB = left bundle branch
block; LVEF = left ventricular ejection fraction; OMT = optimal medical therapy; SR
= sinus rhythm.
a
b
Level of evidence.
42 ESC Guidelines
.
In conclusion, despite the weak evidence due to lack of large,
6.3 Patients in atrial fibrillation .. randomized trials, the prevailing opinion of experts is in favour of the
This section considers indications for CRT in patients with permanent .
usefulness of CRT in patients with permanent AF and NYHA class III
AF or persistent AF unsuitable for AF ablation or after unsuccessful AF .. and IV with the same indications as for patients in SR, provided that
ablation. AF ablation has been reported to improve LVEF and reduce the .
AVJ ablation is added in those patients with incomplete (<90 - 95%)
HF hospitalization rate in selected patients. In particular, AF ablation is .. biventricular capture due to AF (Figure 9). However, there are other
recommended for reversing LV dysfunction in AF patients when .
causes for incomplete biventricular pacing such as frequent prema-
tachycardia-induced cardiomyopathy is highly prob- able, regardless of .. ture ventricular beats, which may need to be treated (with drugs or
symptoms.296 Therefore, CRT should be considered in those patients
.. ablation) before considering AVJ ablation. Importantly, evaluation of
with persistent AF and HFrEF when AF ablation cannot be performed . the biventricular pacing percentage is mainly given by the percentage
or is declined by the patient. With regard to indications for rate
... of biventricular pacing using device memory, which does not reflect
control therapy and in particular to AVJ . exactly the rate of effective biventricular capture. Holter monitoring
ablation, refer to the ESC Guidelines for the management of AF.296 309,310
. may help to assess the real biventricular capture percentage. A
.

. new algorithm has been developed that can continuously assess the
effective biventricular pacing.311
6.3.1 Patients with atrial fibrillation and heart ..
failure who are candidates for cardiac For patients with permanent AF, there are no data supporting the
resynchronization therapy A major determinant of the success .. difference in the magnitude of response to CRT according to the
.
of CRT is the effective delivery of biventricular pacing. A particular QRS morphology or a QRS duration cut-off of 150 ms.
aspect of AF patients is that AF rhythm with fast ventricular rate and .. It is important to remember that limited data are available for
.
irregularity may interfere with adequate biventricular pacing patients in NYHA class II.
delivery. AF may reduce the rate of effective biventricular capture ..
.
by creating spontaneous, fusion, or pseudo-fusion beats. A high rate ..
of biventricular pacing is not reached in two-thirds of patients with 6.3.2 Patients with uncontrolled heart rate who are
.
persistent or permanent AF.297 .. candidates for atrioventricular junction ablation
Data from large registries show that AF patients undergoing CRT have . (irrespective of QRS duration)
an increased risk of mortality even after adjusting for several clinical AVJ ablation should be considered to control heart rate in patients
variables.297—299 In most AF patients with intact AV conduc- .. unresponsive or intolerant to intensive rate and rhythm control ther-
tion, an adequate biventricular pacing delivery can be achieved only .. apy, or who are ineligible for AF ablation, accepting that these
by means of AVJ ablation.300—302 A substudy of the RAFT trial300 was
. patients will become pacemaker dependent.296 In particular, AVJ
unable to show benefit of CRT without AVJ ablation with regard to ... ablation combined with CRT may be preferred to AF ablation in
the combined endpoint of death or hospitalization for HF; notably, only . severely symptomatic patients with permanent AF and at least one
47% of the patients had a biventricular capture >90%. The decision to hospitalization for HF.296
perform AVJ ablation is still a matter of debate, but most studies have
.. AVJ ablation and permanent pacing from the RV apex provides
shown improvements in LV function, functional capacity, exercise .. highly efficient rate control and regularization of the ventricular
capacity, and survival (with the same magnitude as in patients with
.
response in AF, and improves symptoms in selected patients.192 A
SR).301 Gasparini et al.302 compared total mortality of 443 AF patients .. large study with a propensity score-matched control group194
.
who received AVJ ablation (n = 443) and of 895 AF patients who showed a 53% reduction in total mortality in patients who underwent
received rate-slowing drugs with the mortality of 6046 patients who were .. AVJ ablation compared with those treated with pharmacological rate
.
in SR. The long-term survival after CRT among patients with AF and control therapy. A class IIa indication is provided in the 2020 ESC
AVJ ablation was similar to that observed among patients in SR (HR .. Guidelines on AF.296
.
0.93); the mortality was higher for AF patients treated with rate- The downside of RV pacing, however, is that it induces LV dyssyn-
.
slowing drugs (HR 1.52). The most common rate- controlling drugs used . chrony in ~50% of patients,312 and that this may lead to worsening of
in AF are beta-blockers; although safe even in the context of AF and . HF symptoms in a minority. In the majority of patients, AVJ ablation
HFrEF, they do not necessarily have the same benefit as in patients with .. improves LVEF even with RV apical (RVA) pacing due to amelioration
.
SR303 and the benefit risk ratio is influenced by — other cardiovascular of tachycardia-induced LV dysfunction, which commonly exists in
comorbidities.304,305 In a systematic review and meta-analysis,306 AVJ .. these patients. CRT may prevent RV pacing-induced LV dyssyn-
.
ablation, compared with no AVJ ablation, reduced mortality by 37% chrony. The multicentre, randomized, prospective Ablate and Pace in
and reduced the rate of non- response by 59% in patients with .. Atrial Fibrillation (APAF) trial313 included 186 patients in whom a
biventricular pacing <90%, but showed no benefit in those with >_90% .. CRT or RV pacing device was implanted, followed by AVJ ablation.
biventricular pacing. Similarly, Tolosana et al. observed the same rate of . During a median follow-up of 20 months, CRT significantly reduced
responders (defined as .. by 63% the primary composite endpoint of death due to HF, hospital-
>_10% decrease in end-systolic volume) in AF patients who received . ization due to HF, or worsening of HF. The beneficial effects of CRT
AVJ ablation or rate-slowing drugs and patients in SR who had .. were similar in patients with an EF <_35%, NYHA class >_III, and QRS
adequate biventricular pacing (97, 94, and 97%, respectively). 307 . width >_120 ms, and in other patients with EF>35% or NYHA class
Importantly, AVJ ablation did not improve survival for patients in AF .. < III or narrow QRS. Compared with the RV pacing group, respond-
treated with CRT compared with those treated with rate-slowing .
ers increased from 63% to 83% (P ¼ 0.003).314 A meta-analysis of
drugs when an adequate biventricular pacing was achieved either with .
. 696 patients from five trials showed a 62% reduction in
ablation (97%) or with drugs (94%).308
ESC Guidelines 43
Management of atrio-ventricular junction ablation in patients with:

ORPersistent AF unsuitable for atrial fibrillation ablation Permanent AF
Controlled heart rate
Y N
Candidate for CRT Candidate for AVJ ablation
CRT LVEF < 50%

if QRS ≥ 130 ms (Class IIa)
Y N

LVEF 40% ≤ LVEF LVEF < 50% (HFmrEF)
< 40% (HFrEF)
BiV BiV CRT CRT RV pacing (Class IIa)

> 90 – 95%a < 90 – 95%a (Class I) (Class IIa)
CRT
(Class IIb)
OR
HBP HBP
(Class IIb) (Class IIb)
No AVJ AVJ ablation (Class IIa)

AVJ ablation
ablation
Figure 9 Indication for atrioventricular junction ablation in patients with symptomatic permanent atrial fibrillation or persistent atrial fibrillation unsuitable for
atrial fibrillation ablation. AF = atrial fibrillation; AVJ = atrioventricular junction; BiV = biventricular; CRT = cardiac resynchronization therapy; ESC
= European Society of Cardiology; HBP = His bundle pacing; HFmrEF = heart failure with mildly reduced ejection fraction; HFrEF = heart failure with reduced
ejection fraction; LVEF = left ventricular ejection fraction; QRS = Q, R, and S waves; RV = right ventricular/right ventricle. aDue to a rapid ventricular response.
Note: the figure is based on the recommendations in the ESC Guidelines on AF.296
.
hospitalization for HF and a modest improvement in LVEF compared with physical limitations of AF at 1-year follow-up (P = 0.004). In contrast to
RV pacing, but not in 6-min walked distance and quality of life assessed
.. the main composite endpoint, the greatest symptomatic improve-
.
by means of the Minnesota Living with Heart Failure ques- ments were observed in patients with LVEF >35% (P = 0.0003).
.
. the APAF-CRT RCT, 102 elderly patients (mean age
tionnaire.315 In In conclusion, there is evidence from randomized trials of an addi-
72 years) with permanent AF, a narrow QRS (<_110 ms), and at least .
tional benefit of performing CRT pacing in patients with reduced EF,
one hospitalization for HF in the previous year were randomized to AVJ .. who are candidates for AVJ ablation for rate control to reduce hospi-
ablation and CRT or to pharmacological rate control therapy.195 After a .
talization and improve quality of life. There is evidence that CRT is
median follow-up of 16 months, the primary composite outcome of HF .. superior to RV pacing in relieving symptoms, but not mortality and
death, hospitalization due to HF, or worsening HF had occurred in 10 .
hospitalization in patients with mid-range reduced systolic function
patients (20%) in the ablation (AVJ) plus CRT arm and in 20 patients .. (Figure 9).
(38%) in the drug control arm (HR 0.38; P = 0.013). The results were .
.
mostly driven by a reduction in hospitalization for HF. The HR was . 6.3.3 Emerging novel modalities for CRT: role of
0.18 (P = 0.01) in patients with LVEF <_35% and 0.62 (P = 0.36) in
.. conduction system pacing
those with LVEF >35%. Furthermore, patients undergoing AVJ ablation .
HBP, alone or in conjunction with coronary sinus pacing, is a
and CRT had a 36% reduction in the specific symptoms and .
. promising novel technique for delivering CRT, useful in AF patients
44 ESC Guidelines
undergoing AVJ ablation.198,199,316—318 Non-conventional CRT using .

hospitalizations, which may be reduced by programming to maximize
HBP coronary sinus pacing (so-called ‘His-optimized CRT’) or left .. intrinsic conduction or prevented by CRT.
148,183,190,324
Previously,
bundle branch area pacing, in comparison with conventional CRT, .
the benefit of CRT upgrade had been investigated only by observatio-
can achieve a narrower QRS with a ‘quasi-normal’ axis morphology, .. nal controlled trials and registries,
325—339
mainly comparing upgrade
echocardiographic improvement of mechanical resynchronization .
with de novo CRT; in early, small, observational pre- vs. post-CRT
indexes, and a better short-term clinical outcome.319—321 In general, the .. studies;340—346 and in crossover trials,347—350 providing only limited
potential benefit of HBP depends on the ability to achieve a .
clinical outcome data.
narrow QRS complex that is similar to the native QRS complex, .. Based on a recent meta-analysis of observational studies, mostly
rather than on the LVEF. Widespread adoption of this technique relies .
single-centre,351 echocardiographic and functional response as well
upon further validation of its efficacy in large RCTs and .
as the risk of mortality or HF events was similar in patients after de
improvements in lead design, delivery tools, and devices (see .
novo vs. upgrade CRT; however, in previous subgroup analyses from
.. large, randomized, prospective trials such as RAFT,
37
section 7). . morbidity or
mortality benefit was not confirmed.
..
Recommendations for cardiac resynchronization

Clinical outcomes are also influenced by the clinical characteristics
therapy in patients with persistent or permanent
atrial fibrillation
... of patients referred to CRT upgrade. Based on data from the
. European CRT Survey II,352 a high-volume registry, and clinical char-
351
. Recommendations Class a
Level b acteristics from previous studies, patients referred for a CRT
. upgrade differ from patients referred for de novo CRT implantation:
1) In patients with HF with permanent AF who are candidates .. they are older (even compared with those in RCTs), mainly male
for CRT: . patients, and have more comorbidities such as AF, ischaemic heart
1A) CRT should be considered for patients with HF .. disease, anaemia, and renal failure.
and LVEF <_35% in NYHA class III or IV despite .
On average, the number of upgrade procedures reaches 23% of
OMT if they are in AF and have intrinsic QRS >_130 .. total CRT implantations, 60% from a conventional device and 40%
ms, provided a strategy to ensure biventricular IIa C .
from an ICD352 in ESC countries, showing significant regional differ-
capture is in place, in order to .. ences regarding the type of implanted device, such as CRT-P or
improve symptoms and reduce morbidity and .
CRT-D.352,353
mortality.302,306,307,322 .. Regarding procedure-related complications, several studies
1B) AVJ ablation should be added in the case of .
described a higher burden during upgrade procedures, ranging from
incomplete biventricular pacing (<90—95%) due IIa B .. 6.8% to 20.9% compared with de novo implantations.339,354 This was
to conducted AF.297—302 .
. not confirmed in a recent analysis of registry data, where upgrades
2) In patients with symptomatic AF and an uncontrolled heart had similar complication rates to de novo implantations. 352 Notably,
.
rate who are candidates for AVJ ablation (irrespective of QRS 82% of these procedures were performed in high-volume centres.
duration): .. However, data on the long-term infection rates or lead revisions after
.
2A) CRT is recommended in patients with CRT upgrade are scarce.354,355
HFrEF.196,197,306,308
I B .. The first prospective, randomized trial, the BUDAPEST CRT
.
2B) CRT rather than standard RV pacing should Upgrade study, is still ongoing, but may clarify these questions.356
..
IIa C
be considered in patients with HFmrEF.
2C) RV pacing should be considered in patients .
IIa B .
with HFpEF.188,196,323 .
.
2021
2D) CRT may be considered in patients with .. Recommendation for upgrade from right ventricular
ESC
IIb C
HFpEF. pacing to cardiac resynchronization therapy
.
.
AF = atrial fibrillation; AVJ = atrioventricular junction; CRT = cardiac resynchroniza-
.
tion therapy; EF = ejection fraction; HF = heart failure; HFrEF = heart failure with . Patients who have received a conventional pace-
reduced ejection fraction (<40%); HFmrEF = heart failure with mildly reduced ejection .
fraction (40 - 49%); HFpEF = heart failure with preserved ejection fraction (>_50%) . maker or an ICD and who subsequently develop
according to the 2021 ESC HF Guidelines; 242 LVEF = left ventricular ejection fraction; NYHA . symptomatic HF with LVEF <_35% despite OMT,
= New York Heart Association; RV = right ventricular. . IIa B
. and who have a significantc proportion of RV pacing,
ESC 2021
a
b
Level of evidence. . should be considered for upgrade to
.
. CRT.37,148,185,190,324—352
.
. CRT = cardiac resynchronization therapy; HF = heart failure; ICD = implantable
.
6.4 Patients with conventional .
.
cardioverter-defibrillator; LVEF = left ventricular ejection fraction; OMT = opti-
mal medical therapy; RV = right ventricular.
pacemaker or implantable cardioverter .
a
b
defibrillator who need upgrade to .. c

Level of evidence.
A limit of 20% RV pacing for considering interventions for pacing-induced HF is
cardiac resynchronization therapy .
.
supported by observational data. However, there are no data to support that any
percentage of RV pacing can be considered as defining a true limit below which
Several studies have demonstrated the deleterious effect of chronic RV . RV pacing is safe and beyond which RV pacing is harmful.
pacing with respect to an increased risk of HF symptoms or .
ESC Guidelines 45
.
over CRT-P by reducing arrhythmic death, it does also add ICD-
6.5 Pacing in patients with reduced left .. specific risks such as lead failure and inappropriate shocks, as well as
ventricular ejection fraction and a .
costs.
conventional indication for .. COMPANION is the only trial to randomize patients to CRT-P or
.
antibradycardia pacing CRT-D, but was designed to assess the effects of CRT compared
Three randomized trials proved the superiority of biventricular pacing .. with OMT.260 Crucially, it was not designed to compare CRT-D and
.
over RV pacing in patients with moderate to severe systolic dysfunction CRT-P. CRT-P was associated with a marginally non-significant
who required antibradycardia pacing to improve quality of life, NYHA .. reduction in the risk of all-cause mortality (HR 0.76, 95% CI
class, and echocardiographic response.190,357,358 In the Biventricular .. 0.58 - 1.01; P = 0.06), whereas CRT-D was associated with a signifi-
versus RV pacing in patients with AV block (BLOCK HF) trial, 691 . cant, 36% risk reduction (HR 0.64, 95% CI 0.48—0.86; P = 0.004).
patients with AVN disease and an indication for pacemaker with a .. Analysis of cause-specific mortality showed that SCD was significantly
mildly reduced EF (<50% by inclusion criteria, average 42.9% in the . reduced by CRT-D (HR 0.44, 95% CI 0.23 - 0.86; P = 0.02) but not
pacemaker group) were randomized to biventricular or RV pacing with or .. CRT-P (HR 1.21, 95% CI 0.7 2.07; — P = 0.50).
363

without 190
an ICD, and followed for an average of 37 Nevertheless, the CARE-HF extension study proved that CRT-P
months. The primary endpoint (a composite of >_15% increase in ..
alone reduced the risk of dying suddenly by 5.6%. 261 In line with these
the LV end-systolic volume, HF events, or mortality) was significantly .

findings, subgroup analyses from RCTs in mild HF consistently found
improved in those assigned to CRT. CRT response is high among
.. 364—368
a reduction in ventricular arrhythmias with CRT. These effects
patients with systolic dysfunction and expected frequent RV pacing. .
were especially observed among CRT responders, suggesting that
Based on the MOde Selection Trial in Sinus-Node Dysfunction .. the reduction in SCD risk is related to the extent of reverse LV
(MOST),183 at least 40% RV pacing is associated with an increased risk of .
remodelling with CRT.
HF hospitalization or AF. .. Meta-analyses have drawn different conclusions on the matter. In
For patients with normal or preserved EF, data on benefit of CRT are .
the study by Al-Majed et al.,369 the survival benefit of CRT was largely
conflicting with respect to hospitalization, and no mortality benefit was .. driven by a reduction in HF-related mortality, but SCD was not
shown.166,268,323,359 However, adverse remodelling caused by RV pacing
.
reduced. Lam et al.370 showed that CRT-D significantly reduced mor-
was prevented by biventricular pacing, especially during long-term .. tality compared with medical therapy alone [odds ratio (OR) 0.57,
follow up.323,359,360 A single-centre study showed that .
>20% RV pacing was associated with deleterious LV remodelling in
. 95% CI 0.40 —0.80], but not when compared with ICD without CRT
. (OR 0.82, 95% CI 0.57—1.18) or CRT-P (OR 0.85, 95% CI
patients with AVB and preserved LVEF. 188 Frailty should also be taken
... 0.60 —1.22). However, more recently, a network meta-analysis of 13
into account in deciding on CRT implantation, because of the higher costs randomized trials including >12 000 patients found that CRT-D
.
and high complication rates of this procedure. reduced total mortality by 19% (95% CI 1 33%, unadjusted) com-
.. pared with CRT-P.275
—
Recommendation for patients with heart failure and ... Some recent large observational studies highlighted the impor-
atrioventricular block . tance of HF aetiology in the assessment of potential benefits of CRT-
371—373
. D over CRT-P. CRT-D was associated with a significant risk
Recommendation Classa Levelb
. reduction in all-cause mortality compared with CRT-P in patients
.. with ischaemic cardiomyopathy. However, this difference was not
CRT rather than RV pacing is recommended for . found in patients with non-ischaemic cardiomyopathy.
patients with HFrEF (<40%) regardless of NYHA
.. These findings are consistent with the results from the DANISH
class who have an indication for ventricular pacing
I A
.
study, which assigned 1116 patients with HF and non-ischaemic cardi-
and high-degree AVB in order to reduce morbidity.
..
ESC 2021
omyopathy to receive either a primary prophylactic ICD or usual

This includes patients with .
clinical care alone.374 In both groups, 58% of patients also had CRT.
AF.183,190,196,268,313,323,357—359,361,362 .. Subgroup analysis showed that CRT-D was not superior to CRT-P in
.
AF = atrial fibrillation; AVB = atrioventricular block; CRT = cardiac resynchroni- reducing the primary outcome of all-cause mortality (HR 0.91, 95%
zation therapy; HF = heart failure; HFrEF = heart failure with reduced ejection .. CI 0.64 1.29; P = 0.59) after a median follow-up of 67.6 months.
fraction (<40%) according to the 2021 ESC HF Guidelines; 242 NYHA = New York . —
However, in a large multicentre registry of >50 000 patients, CRT-D
Heart Association; RV = right ventricular.
.. was associated with a significantly lower observed mortality.375
.
a
b
Level of evidence. Similar results were found in a recent propensity-matched cohort,
.. where CRT-D was associated with a significantly lower all-cause
.
mortality than CRT-P in patients with ischaemic aetiology and in
.. patients with non-ischaemic HF under 75 years old.
376
Furthermore,
6.6 Benefit of adding implantable .
the CeRtiTuDe Cohort study showed better survival in CRT-D
377
cardioverter defibrillator in patients with .. vs. CRT-P mainly due to a reduction of non-SCD. In an Italian multi-
indications for cardiac resynchronization .. centre CRT registry, the only independent predictor of mortality was
therapy . the lack of an ICD.378 Whereas these studies are limited by their
The mortality benefit of CRT-D over CRT-P is still unclear, mostly .. observational design, important novel information on the issue of
because no head to head RCTs have been designed to compare these two . CRT-D vs. CRT-P is expected to come from an ongoing randomized
.
treatments. While CRT-D may further improve survival . trial, Re-evaluation of Optimal Re-synchronisation Therapy in
46 ESC Guidelines
. of the LV in relation to the LV lead position389,390 have been associ-

Patients with Chronic Heart Failure (RESET-CRT; ClinicalTrials.gov
Identifier NCT03494933). .. ated with response to CRT. LVEF is the only parameter included in
.
In conclusion, prospective randomized trials are lacking, and available the guidelines for the selection of patients for CRT and is key to
data are insufficient to firmly prove a superiority of CRT-D over CRT-P. .. define the type of HF (<40%, HFrEF; 40 49%, HFmrEF; and >_50%,
. —
However, it is important to consider that CRT trials in mild HFpEF).242 Echocardiography is the imaging technique of first choice
HF almost exclusively included patients with an ICD, 37,40,262
and that .. for the assessment of LVEF. However, when intravenous contrast is
survival benefit of CRT without an ICD is uncertain in this particular .
not available and the acoustic window does not allow accurate
group. Furthermore, observational data point towards significant survival .. assessment of LVEF, CMR or nuclear imaging should be consid-
benefits by CRT-D over CRT-P in patients with ischaemic cardi- .
ered.242 Strain imaging (based on echocardiography or CMR) to
omyopathy, while no clear benefit has been shown in those with non- .. quantify LV systolic function has shown incremental prognostic value
ischaemic cardiomyopathy. .
in HF, and allows assessment of LV mechanical dys-
Further predictive power concerning the risk of ventricular .. synchrony.384,391—393 CMR with LGE techniques (which show the
arrhythmia 379,380
may be derived by contrast-enhanced CMR-guided scar .
. presence of myocardial scar tissue) provide the best resolution to dif-
characterization. When discussing the choice between CRT-D ferentiate ischaemic cardiomyopathy and non-ischaemic cardiomy-

and CRT-P, it is particularly important to consider general predictors of .
opathy.394 The location (posterolateral) and extent (transmural vs.
ICD effectiveness such as age and comorbidities associated with a mortality .. non-transmural and percentage of LV mass) of LGE on CMR or with
...
risk that competes with sudden arrhythmic death. Thus, the addition of
nuclear techniques has been associated with the benefit from
ICD to CRT should be considered, especially in younger patients with a CRT.380,387,395,396 Severe mitral regurgitation,397 lack of significant
good survival prognosis, ischaemic aetiology, and a favourable
.
electromechanical LV dyssynchrony,384,385,392 and RV systolic dys-
comorbidity profile or presence of myocardial fibrosis (Figure 10). .. function398 have been associated with less improvement in clinical
Moreover, the benefit of the ICD is governed by the balance between
.. symptoms and reduced survival after CRT. Several imaging techni-
the risk of SCD and the risk of death from other causes, as well as . ques have been tested to assess LV mechanical dyssynchrony, but
comorbidities. Generally, the rate of sudden arrhythmic death in primary
.. most measures of LV dyssynchrony have not been tested in random-
prevention appears to be declining (1%/ year). .
ized trials including patients with HFrEF and wide QRS.399 The pres-
Owing to the complexity of the matter and the lack of clear evi-
.. ence of septal flash and apical rocking,400 time differences based on
.
radial strain and patterns of regional longitudinal strain,384,392,401—403
dence, it is particularly important that the choice between CRT-P .. non-invasive and invasive ECG mapping, 385,404 and vector-cardiogra-
and CRT-D is guided by a process of shared decision-making between .
phy405 have been proposed as novel techniques to predict response
patients and clinicians, taking into account both medical facts and patient .. to CRT. Furthermore, LV myocardial work assessed with speckle-
values. .
tracking echocardiography has been associated with survival in CRT
.. 406
recipients. Coronary sinus venography is commonly performed to
.
detect a suitable coronary vein in which to deploy an LV lead.
Recommendations for adding a defibrillator with car- .. Randomized trials have not systematically demonstrated that the
diac resynchronization therapy .
guidance of LV lead implantation based on imaging (assessing myocar-
.. dial scar or site of latest activation) is superior to standard prac-
tice.389,390,407,408 Initial experience on using artificial intelligence to
In patients who are candidates for an ICD and .. combine clinical, electrical, and imaging parameters to define pheno-
who have CRT indication, implantation of a I A
.
types of patients that will benefit from CRT is promising, but more
CRT-D is recommended.260,369,370,381 .. data are needed.409
In patients who are candidates for CRT, implan-
.. Significant (moderate to severe and severe) secondary mitral
tation of a CRT-D should be considered after . regurgitation is frequent among candidates for CRT and has been
ESC 2021
IIa B
individual risk assessment and using shared deci-
.. shown to affect long-term survival as well as response to ther-
sion-making.382,383 . apy.406,410 406
CRT can improve mitral regurgitation in as many as 40% of
.
CRT = cardiac resynchronization therapy; CRT-D = defibrillator with cardiac . patients. However, in 60% of patients, significant mitral regurgita-
resynchronization therapy; ICD = implantable cardioverter-defibrillator. . tion is not corrected and, at long-term follow-up, progression of the
..
a
Level of evidence. underlying disease may lead to further deterioration of mitral valve
.
b
function and poor prognosis. Transcatheter edge-to-edge mitral

.. valve repair has been demonstrated to improve the response to CRT
.
in registries.411—414 However, results from recent RCTs including
.. patients with symptomatic severe secondary mitral regurgitation
6.7 Factors influencing the efficacy of .
despite guideline-directed medical therapy (including CRT when indi-
cardiac resynchronization therapy: role .. cated) have not consistently shown a benefit from transcatheter
of imaging techniques .
edge-to-edge mitral valve repair.415,416
The role of cardiac imaging in selecting HF patients for CRT has been .. Therefore, selection of patients for CRT based on imaging is lim-
evaluated mostly in observational analyses. Cardiac dyssynchrony,384—
.
ited to the measurement of LVEF, whereas the assessment of other
.
386
myocardial scar,387,388 and site of latest activation . factors such as extent of myocardial scar, presence of mitral
ESC Guidelines 47
+ CRT-P
Shared decision making Other factors in favor of choosing

CRT-P rather than CRT-D:
Patient with indication for CRT Non-ischaemic cardiomyopathy Short life expectancy M
Age

Shared decision making
CRT-D
-
- Myocardial Fibrosis on CMR+
Figure 10 Patient’s clinical characteristics and preference to be considered for the decision-making between cardiac resynchronization therapy pacemaker or
defibrillator. CRT-P = cardiac resynchronization therapy-pacemaker; CRT-D = defibrillator with cardiac resynchronization therapy; CMR = cardiovascular
magnetic resonance.
.
regurgitation, or RV systolic function is important in identifying 7.2 His bundle pacing
potential non-responders that may need additional treatment (mitral valve ..
HBP was first reported in humans in 2000,199 and is steadily gaining
intervention, for example). .. interest for providing a more physiological alternative to RV pacing. It
Alternatives to conventional coronary sinus pacing for CRT (epi- .
may also correct intraventricular conduction delay in a subset of
cardial, endocardial) are described in section 6.1 in the Supplementary .. patients, thereby providing an alternative to biventricular pacing for
data.
.
treating HF. The advent of new tools has greatly facilitated implanta-
.. tion, which has become routine in a growing number of centres. HBP
.
is used in lieu of RV pacing, in lieu of biventricular pacing, and as His-
7 Alternative pacing strategies .. optimized CRT (HOT-CRT),319 which exploits a synergistic effect
.
between HBP and RV pacing, LV pacing, or biventricular pacing to
and sites .. improve synchrony. There is growing evidence, mainly from observa-
.
Alternative RV pacing sites (as opposed to RVA pacing) include pacing tional studies, that HBP may be safe and effective in these settings
.. (Supplementary Table 10), although large RCTs and long-term follow-
from the RV outflow tract (RVOT), the mid and high RV septum (RVS), .
.. up are still lacking. With more data on safety and effectiveness,
422
HBP, para-Hisian pacing, and left bundle branch area pacing, which
includes LV septal pacing and left bundle branch pacing. HBP is likely to play a growing role in pacing therapy in the future.
..
.
7.1 Septal pacing .. 7.2.1 Implantation and follow-up
Since the 2013 ESC Guidelines,33 two randomized trials found no dif- . The use of guiding catheters to deliver leads has facilitated implanta-
tion, with success rates exceeding 80%. 422
In an international registry,
.. implant success was 87% after a learning curve of 40 cases.423
ference in clinical outcomes between RVS and RVA pacing in the setting of
AVB417 or CRT,418 respectively. A meta-analysis reported an
echocardiographic benefit of RVS pacing in patients with pre-existing .. Selective HBP is easily recognized by an isoelectric interval (corre-
reduced LVEF.419 In an observational study, RVS pacing was associated
. sponding to the HV) between the pacing spike and QRS onset,
with a lower risk of perforation.420 However, true RVS pacing is not .. whereas with non-selective HBP, a ‘pseudo-delta’ wave is observed
easily obtained and ascertained,421 and neither beneficial nor harmful
. due to capture of local myocardium.424 In addition, correction of BBB
effects of RVS pacing compared with RVA pacing have been shown on .. may be observed (Figure 11). It is important to distinguish non-
relevant clinical endpoints (Supplementary Table 9). Current evidence
. selective HBP from para-Hisian pacing (where there is no capture of
does not support systematically recommending either RVS or RVA .. conduction tissue) by evaluating transitions in QRS morphology by
pacing for all patients.
.
reducing pacing output or with pacing manoeuvres. 425
48 ESC Guidelines
A V
B V
C V
NS-HBP S-HBP NS-HBP Myo S-HBP corr+ S-HBP corr-

A B C
Output (V/0.5ms) 8
7
6
5 NS-HBPNS-HBP S-HBP corr+ Thresholds
4 His Myocardium Bundle branch
3
2
1 S-HBP corr-
0 S-HBP Myo
LOC
LOC LOC
Figure 11 Three patients with different types of transitions in QRS morphology with His bundle pacing and decrementing pacing output. BBB = bundle branch
block; Corr± = with/without correction of bundle branch block; LBBB = left bundle branch block; LOC = loss of capture; Myo = myocardium; NSHBP = non-
selective His bundle pacing; S-HBP = selective His bundle pacing. (A) Non-selective to selective His capture. Note the presence of a ‘pseudo-delta’ wave with non-
selective capture and an isoelectric interval after the pacing spike with selective capture. (B) Non-selective His capture to myocardial capture only. (C) Selective His
capture with correction of BBB to selective His capture with LBBB. Note: the graph on the right of the panel shows a schematic representation of the different
thresholds in the three instances.
ESC Guidelines 49
.
fare better in terms of HF hospitalizations than patients with RV pac-
Table 9 Advantages and disadvantages of a ‘backup’ .. ing if the percentage of ventricular pacing is >20% (HR 0.54; P =
ventricular lead with His bundle pacing .
0.01).42 Of note, the average baseline LVEF in patients with HBP in
Advantages .. that study was 55% and the average QRS duration was 105 ms. HBP
.
Increased safety (in case of loss of capture of the HBP lead) may therefore avoid clinical deterioration in these patients, particu-
•
.. larly if the intrinsic QRS is narrow or if BBB is corrected by HBP.
• Can be used for sensing (lower risk of ventricular undersensing, no risk .
of His or atrial oversensing) In a series of 100 patients with AVB undergoing HBP by experi-
• Programming of pacing output with lower safety margins .. enced operators, implantation was successful in 41/54 (76%) patients
• May serve to narrow the QRS with fusion pacing in the case of selective- .. with infranodal AVB and higher in the case of nodal block (93%; P <
HBP with uncorrected RBBB . 0.05).433 Over a mean follow-up of 19 ± 12 months, lead revision
Disadvantages .. was necessary in 2/41 (5%) patients with infranodal block and in 3/43
• Higher cost
. (7%) with nodal block. Notably, the average LVEF in this series was
• More transvenous hardware .. 54%, and there are no data reported specifically on HBP in patients
.

Risk associated with the additional lead (e.g. ventricular perforation) with AVB and reduced LVEF. HBP is an option in patients with a nar-
..
•
More complex programming row QRS or if HBP corrects BBB, but otherwise biventricular pacing
•
“Off-label” use (current regulatory approval and MRI-conditionality for
.
is indicated.
ESC 2021
..
•
HBP is only granted for His leads connected to the RV port) There is a need for RCTs to compare the safety and efficacy of
.
HBP with RV pacing. It is important to balance the potential benefits
HBP = His bundle pacing; MRI = magnetic resonance imaging; RBBB = right bundle .. of HBP with the aforementioned issues of higher capture thresholds
branch block. .
and shorter battery longevity, a higher rate of lead revision, and more
.. frequent sensing issues, compared with RV pacing. It is also important
Compared with RV pacing, HBP capture thresholds are on average
.
to consider the operator’s experience and expertise with HBP, and
higher and sensing amplitudes lower. A recent observational study raised .. whether a backup ventricular pacing lead is indicated. The patient’s
concern with regard to increasing HBP pacing thresholds with
.
. safety should be first and foremost in decision-making.
intermediate follow-up. 426 The higher capture thresholds lead to
shorter battery longevity (at 5 years there were 9% generator changes .
7.2.2.2 Pace and ablate
with HBP compared with 1% with RVP).427 Capture thresholds of HBP .. Seven observational series, totalling >240 patients treated with a
at implantation should aim to be <2.0 V/1 ms (or <2.5 V/ .
‘pace-and-ablate’ strategy for rapidly conducted AF, found an
0.4 ms) and bipolar R-wave sensing amplitude >2.0 mV. With experi- .. improvement in LVEF and NYHA class compared with baseline with
ence, thresholds decrease as implanters gain confidence to reposition leads. .
HBP.197—199,434 Long-term results with a median of 3 years of follow-
Sensing issues include not only ventricular undersensing, but also .. up have been reported, with favourable outcomes.434 A single-
..
oversensing of atrial or His potentials (which may be potentially lethal in
blinded, randomized, crossover study in 16 patients compared HBP
a pacemaker-dependent patient). . with RVA pacing over 6 months and found better NYHA and 6-min
..
An RV backup lead should be considered if the implanter is inex-
walk distance with HBP, without differences in echocardiographic
perienced, or if there are high capture thresholds or sensing issues in . parameters.200 However, only four patients in this study had con-
pacemaker-dependent patients, in those scheduled for AVN ablation
.. firmed HBP (with para-Hisian pacing in the remaining patients).
(where there is a risk of compromising HBP), or in patients with high- . These 197,198
studies included patients with reduced as well as preserved
degree or infranodal block. Pros and cons are listed in Table 9. .. LVEF, and QRS width was on average <120 ms. HBP is of par-
Several series have shown that the rate of mid-term lead revision .
318,423,427,428 ticular interest in patients with a normal baseline QRS morphology as
is relatively high at ~7%, (and reported to be as high as . it preserves intrinsic ventricular synchrony, However, a caveat is that
11%426), and is higher than RV pacing, which is 2—3%.427,429 .
AVJ ablation may result in an increase in HBP capture thresholds or
Therefore, it is advisable to follow-up these patients at least once .. in lead dislodgments in a minority of patients.
197,199,318,426
Owing to
every 6 months or place them on remote monitoring (ensuring that .
these issues and risk of HBP lead failure, a backup RV lead should be
automatic threshold measurements correspond to those measured .. considered.
manually, as this may not be the case and depends on device configu- .
ration).430 Device programming should take into account specific
..
7.2.2.3 Role in cardiac resynchronization therapy
requirements for HBP, which are covered in detail elsewhere.431,432 .
In 1977, Narula showed that pacing of the His bundle can correct
.. LBBB in a subset of patients, implying a proximal site of conduction
7.2.2 Indications
.
disturbance with longitudinal dissociation within the His bundle.435 A
7.2.2.1 Pacing for bradycardia .. recent mapping study reported intra-Hisian block in 46% of patients
.
One study reported that in patients with AVB and normal baseline with LBBB, in whom 94% were corrected by temporary HBP.436 HBP
LVEF, the incidence of RV pacing-induced cardiomyopathy was 12.3% .. may therefore be used in lieu of biventricular pacing for HBP-based
and the risk was increased if the percentage of ventricular pacing was .. CRT, as some data have shown that results are comparable (see
>_20% (HR 6.76; P = 0.002).188 However, there are no data to support . Supplementary Table 10).437—439 Nevertheless, especially in CRT can-
that any percentage of RV pacing can be considered as defining a true limit .. didates with LBBB, biventricular pacing has more solid evidence of
below which RV pacing is safe and beyond which RV pacing is harmful. . efficacy and safety, and therefore remains first-line therapy. However,
Observational data indicate that patients with HBP .
. HBP should be considered as a bailout solution in the case of failed
50 ESC Guidelines
LV lead implantation along with other options such as surgical epicardial . HBP may be considered as an alternative to RV
leads424,440 (see section 6.7). An interesting population is patients with .
RBBB, who are known to respond less well to biventricular pacing, in . pacing in patients with AVB and LVEF >40%, who
ESC 2021
. are anticipated to have >20% ventricular
IIb C
whom HBP has shown promising preliminary results in a series of 37 .
patients.441 HBP may sometimes incompletely correct BBB, and can be . pacing.42,433
.
used in conjunction with RV, LV, or biventricular pacing, as in the HOT- . AVB = atrioventricular block; AVJ = atrioventricular junction; CRT = cardiac
. resynchronization therapy; HBP = His bundle pacing; LVEF = left ventricular ejec-
CRT study.319 This is of particular interest in patients with permanent AF, . tion fraction; RV = right ventricular.
in whom a His lead may be connected to the vacant atrial port, thus . a
offering additional therapeutic options.
. b
Level of evidence.
..
.
7.3 Left bundle branch area pacing .
.
With left bundle branch area pacing, the lead is implanted slightly distal . 7.4 Leadless pacing
to the His bundle and is screwed deep in the LV septum, ideally to ... Leadless pacemakers have been developed to address limitations typ-

capture the left bundle branch.442 Advantages of this technique are
ically related to pulse generator pocket and transvenous leads of con-
.
that electrical parameters are usually excellent, it may be successful in. ventional pacemaker systems. Currently, two leadless pacemaker systems
blocks that are too distal to be treated with HBP, and it also facili- . tates AVJ have been studied in clinical trials, of which one is currently available for
.
ablation, which may be challenging with HBP. However, . clinical use. Both are inserted into the RV cavity by a femoral venous
although the technique is very promising, data on this modality are
. approach using a specially designed catheter-based delivery system.
still scarce (Supplementary Table 11), and there is concern regarding .
.
A number of prospective registries have reported that implantation
long-term lead performance and feasibility of lead extraction.
.
success rates are high, with adequate electrical results both at implant and
Recommendations for using left bundle branch area pacing cannot .
.
at follow-up (Supplementary Table 13). ‘Real-world’ results of one
therefore be formulated at this stage. However, conduction system
.
leadless pacemaker system, including 1817 patients, reported serious
pacing (which includes HBP and left bundle branch area pacing) is .
.
adverse events in 2.7% of patients.50 The prevalence of leadless device
.
very likely to play a growing role in the future, and the current rec- infections is low as the principal sources of infection (i.e. the subdermal
.
ommendations will probably need to be revised once more solid evi- . dence surgical pocket and pacemaker leads) are absent. However, during the initial
. operator experience, there was a higher incidence of peri-operative major
of safety and efficacy (from randomized trials) is published. A comparison.
of RV pacing, HBP, and left bundle branch area pacing is . .
complications (6.5%), including perforation and tamponade, vascular
provided in Supplementary Table 12. complications, ventricular arrhythmias, and death.445 These data highlight
.. the importance of adequate training and supervision in this domain when
. starting with leadless pacemaker implantation. In addition, implanting
.
Recommendations for using His bundle pacing physicians should have the same competency and accreditation as those
. required for standard transvenous pacing to be able to offer the most
. suitable system for a given patient. Implantation of leadless pacemakers
. should be performed in an adequate setting (i.e. with high- resolution
. multiplane fluoroscopy) and with cardiac surgery available on site due to
In patients treated with HBP, device program- . the risk of tamponade, which may be more difficult to manage than with
.
ming tailored to specific requirements of HBP is I C . standard pacing.446,447
recommended.430,431 . Leadless pacemakers that only function in the VVI(R) mode restrict
.
In CRT candidates in whom coronary sinus lead . indications to patients with AF or very infrequent pacing (e.g. paroxysmal
implantation is unsuccessful, HBP should be con- . AVB). Recently, VDD pacing (by detection of atrial contraction by the
.
sidered as a treatment option along with other IIa B . accelerometer) has been introduced, which extends
techniques such as surgical epicardial lead.318,424,440,443 . indications to patients with AVB with preserved sinus node function. AV
.
. synchrony is maintained 70—90% of the time, depending on the patient’s
In patients treated with HBP, implantation of an RV . position and activity, based on data from two studies includ-
.
lead used as ‘backup’ for pacing should be considered . ing 73 patients in SR and high-degree AV block.448 There may in future
in specific situations (e.g. pacemaker dependency, . be an alternative to standard DDD pacemakers in selected patients if
.
high-grade AVB, infranodal block, high pacing . the potential benefits of leadless pacing outweigh the potential benefits
threshold, planned AVJ ablation) or for sensing in the
IIa C . of 100% AV synchrony, atrial pacing, and atrial arrhythmia monitoring.
.
case of issues with detection (e.g. risk of ventricular . Indications for leadless pacemakers include obstruction of the venous
undersensing or over-
. route used for standard pacemaker implantation (e.g. bilateral venous
.
sensing of atrial/His potentials).423,426,444 . thoracic outlet syndrome or chronic obstruction of the superior vena
. cava), pocket issues (e.g. in the case of cachexia or demen- tia), or
HBP with a ventricular backup lead may be considered .
in patients in whom a ‘pace-and-ablate’ strategy for . particularly increased infection risk [e.g. in the case of dialysis
.
rapidly conducted supraventricular arrhythmia is IIb C .
indicated, particularly when the .
.
intrinsic QRS is narrow.197,199,200,318 ..
Continued
.
.
ESC Guidelines 51
.
recommended in patients with AVB who have not yet received
.. reperfusion therapy.469 AVB may require temporary pacing in the
or previous cardiovascular implantable electronic device (CIED)
infection]. Observational data showed that a leadless pacemaker was a safe
pacing alternative in patients with previous device infection and explant, and .. presence of refractory symptoms or haemodynamic compromise,
in patients on chronic haemodialysis. Whereas observational data indicate
. but most often resolves spontaneously within a few days and only a
high efficacy and low complication rates with leadless pacemakers,50 .. minority of patients require permanent pacing. 451,454,456,458,462 In
there are currently no data from RCTs documenting the long-term safety
. patients with persistent intraventricular conduction abnormalities
and efficacy of leadless vs. standard transvenous pacemakers, and therefore .. and transient AVB in whom permanent pacing was recommended in
the indication for a leadless
. the past, there is no evidence that permanent cardiac pacing
pacemaker should be carefully considered on a case by case basis. .. improves outcome. 454,470 These patients frequently have HF and
The absence of long-term data on leadless pacemaker performance and .
poor LV function, and should be evaluated for ICD, CRT-P, or CRT-
limited data on retrievability and end-of-life strategy449 require careful .. D rather than conventional pacing if an early device implantation is
consideration before selecting leadless pacemaker therapy, especially for .
considered.471
younger patients (e.g. with a life expectancy >20 years). .. If AVB does not resolve within 10 days, a permanent pacemaker
.

should be implanted. In the absence of robust scientific data, the wait-
.. ing period before pacemaker implantation has to be decided individu-
Recommendations for using leadless pacing (leadless .
pacemaker) ally. It may last up to 10 days but can be shortened to 5 days
.. depending on the occluded vessel, time delay, and success of revascu-
.
Recommendations Classa Levelb larization. Conditions favouring consideration of earlier pacemaker
.. implantation include unsuccessful or late revascularization, anterior
Leadless pacemakers should be considered as an .
MI, bifascicular block or AV block before MI, and progression of AV
alternative to transvenous pacemakers when no upper .. block within the first days after MI. Sick sinus syndrome after occlu-
extremity venous access exists or when risk of .
IIa B sion of the right coronary artery resolves in most cases. If revasculari-
device pocket infection is particularly high, such as
.. zation is incomplete, pacemaker implantation can usually still be
previous infection and patients on
haemodialysis.45,47—50,450 .. postponed and implantation only be performed if symptoms due to
. sinus bradycardia persist.
..
Leadless pacemakers may be considered as an
alternative to standard single-lead ventricular
IIb C .
. Recommendations for cardiac pacing after acute myo-
ESC 2021
pacing, taking into consideration life expectancy

and using shared decision-making.45,47—50 . cardial infarction
.
.
a
Recommendations Class
a
Level
b
b
. Implantation of a permanent pacemaker is indi-
. cated with the same recommendations as in a general
.
. population (section 5.2) when AVB does not
8 Indications for pacing in . resolve within a waiting period of at least 5
I C
.
specific conditions . days after MI.
.
. In selected patients with AVB in the context of anterior
8.1 Pacing in acute myocardial infarction . wall MI and acute HF, early device implantation (CRT-
In patients with acute MI, significant bradyarrhythmia may occur due . IIb C
. D/CRT-P) may be
to autonomic influences or damage of the conduction system by . considered. 471
.
ESC 2021
ischaemia and/or reperfusion. The right coronary artery supplies the . Pacing is not recommended if AVB resolves after
sinus node in 60% and the AVN and His bundle in 90% of . revascularization or spontaneously. 454—456,458
III B
patients.451,452 AVB is located above the His bundle in most patients .
.
with inferior infarction, but is usually infra-Hisian and pre- . AVB = atrioventricular block; CRT-D = defibrillator with cardiac resynchroniza-
ceded by intraventricular conduction disturbances in anterior . tion therapy; CRT-P = cardiac resynchronization therapy-pacemaker; MI = myo-
. cardial infarction.
infarction.451,453—457 . a
. Class of recommendation.
b
Level of evidence.
The incidence of high-degree AVB in patients with ST-segment ele- .
vation MI has declined to 3 4% — in the primary percutaneous coro- .
.
nary intervention era.458—460 High-degree AVB is most frequent in . 8.2 Pacing after cardiac surgery and
inferior or inferolateral infarctions.455,458—461 .. heart transplantation
Patients with high-degree AVB have higher clinical risk and .
8.2.1 Pacing after coronary artery bypass graft and
larger infarctions especially when AVB complicates an anterior .. valve surgery
infarction.458—460,462,463 New-onset intraventricular conduction dis- .
turbance is also associated with larger infarctions.464—467 . AVB may occur in 1—4% of cases after cardiac surgery and in
Sinus bradycardia and AVB at presentation can be vagally me-
. ~8% after repeat valve surgery.472—476 SND may occur after right
455,468 .
. lateral473,474
atriotomy or transseptal superior approaches to the mitral
diated and may respond to atropine. Revascularization is . valve.
52 ESC Guidelines
.
Pacemaker implantation is more frequent after valvular than after . or third-degree AVB. There have been doubts about the long-term
coronary artery bypass graft (CABG) surgery. 477 In clinical practice, an
. performance of epicardial leads, but recent data indicate, at least for
observation period of 3 7 days — is usually applied before implanting a .. epicardial LV leads, performance comparable with transvenous
permanent pacemaker473 to allow regression of transient bradycardias.
. leads.486
The ideal timing of pacemaker implantation after cardiac .. Ventricular pacing after mechanical tricuspid valve replacement
. using a coronary sinus lead appears safe and feasible, but only results
surgery remains a topic of controversy, due to the fact that 60—70%
of patients implanted for SND and up to 25% of those implanted for AVB .. from small patient cohorts have been published. Procedural success
. of implantation was 100% in 23 patients; after 5.3 ± 2.8 years, 96% of
are not pacemaker dependent at follow-up.473,478 In the case of complete
AVB occurring within the first 24 h after valvular surgery and .. leads were functional with stable pacing and sensing parameters.487
.
persisting for 48 h, resolution within the next 1—2 weeks is HBP is emerging as a more physiological method of ventricular
unlikely and earlier implantation of a pacemaker may be consid- .. pacing and may evolve into a possible solution in patients with AV
.
ered.479,480 The same approach appears reasonable for complete AVB with conduction disease after tricuspid valve surgery. One study investi-
a low rate of escape rhythm. 473 The situation in CHD surgery and in .. gating 30 patients with HBP after cardiac valve operations reported
.

children may be different (see section 8.4). successful permanent HBP in 93% of these patients.488 This study
In valvular endocarditis, predictors of AVB after surgery are pre-
.. included 10 patients with tricuspid valve annuloplasty.
.
operative conduction abnormalities, Staphylococcus aureus infection, After replacement by a mechanical valve, transvalvular lead
intracardiac abscess, tricuspid valve involvement, and previous valvular
.. placement is contraindicated, and implanting either a coronary
.
surgery.481 In patients with endocarditis and peri-operative AVB, early sinus lead for ventricular pacing or epicardial leads, which may be
.. placed minimally invasively, is recommended. To avoid damaging a
pacemaker implantation is reasonable, especially when one or more .
predicting factors are present. In light of the infected state of the repaired tricuspid valve or a tricuspid bioprosthesis, the optimal
.. solution in patients needing ventricular pacing after such surgery
patient, intra-operative implantation of an epicardial pacemaker system .
during valvular surgery may be reasonable despite the absence of solid should not include transvalvular lead implantation. Implanting a cor-
data on infection rates of epicardial vs. transvenous pacemaker systems. .. onary sinus lead for ventricular pacing or minimally invasively
.. placed epicardial leads is judged to be the preferred choice.
. However, as indicated in observational reports, transvalvular lead
8.2.2 Pacing after heart transplantation
.. implantation was used with acceptable results, 489 and still may be
SND is common and leads to permanent pacemaker implantation after . considered in selected patients after tricuspid valve annuloplasty,
heart transplantation in 8% of patients. 473 Possible causes of SND include
.. other types of repair, and replacement of a tricuspid valve by a
surgical trauma, sinus node artery damage, or ischaemia and prolonged . bioprosthesis.
cardiac ischaemic times.482,483 AVB is less common, and is probably
.. Performing tricuspid valve replacement in a patient with an exist-
related to inadequate preservation of the donor heart.473,483,484 .
ing RV lead, removal of the old RV lead and implantation of an epi-
Chronotropic incompetence is always present following standard .. cardial RV lead should be preferred over sewing in the existing lead
orthotopic heart transplantation, as a result of loss of autonomic control. .
between a bioprosthesis and annulus. The reasons are that sewing
As sinus node and AVN function improve during the first few weeks .. in the lead may be associated with higher risk of lead failure and, in
after transplantation, an observation period before pacemaker .
the case of future need for lead extraction, such a procedure is
implantation may allow spontaneous improvement of bradycardia.485 .. likely to require open heart surgery, which will be a reintervention
There is general consensus that patients in whom symptomatic .
with higher operative risk. In cases of tricuspid valve repair with a
bradycardia persists after the third postoperative week may require .. current annuloplasty ring with an open segment and without con-
permanent pacemaker implantation. DDD(R) mode with minimized .
comitant leaflet procedures, an existing RV lead may be left in place
ventricular pacing in the case of intact AVN conduction is .. without sewing it in between the ring and the annulus. However, even
recommended.483 .
in isolated annuloplasty procedures, an existing RV lead should
.. ideally be removed to avoid future lead-related complications to
.
8.2.3 Pacing after tricuspid valve surgery the repaired tricuspid valve and an epicardial RV lead should be
.
An underestimated aspect of the surgical management of tricuspid valve . implanted. Particularly in patients not in need of a dual-chamber
disease is to address trans-tricuspid pacemaker or ICD leads. Such leads .. device, the use of a leadless pacemaker for ventricular pacing may
can interfere with the function of a repaired tricuspid valve or tricuspid . serve as a feasible future alternative after tricuspid valve repair or
valve prosthesis. .. replacement by a bioprosthesis. However, experience is very lim-
Placing an epicardial RV lead at the time of tricuspid valve surgery is . ited, and no long-term data are available in this cohort. Crossing a
the most straightforward alternative in cases with type II second- .. mechanical tricuspid valve with the delivery sheath and a leadless
. pacemaker is contraindicated.
ESC Guidelines 53
.
Recommendations for cardiac pacing after cardiac . 7) Patients requiring pacing after mechan-
surgery and heart transplantation . ical tricuspid valve replacement
.
ESC 2021
III C
. Implantation of a transvalvular RV lead should
Recommendations Class a
Level b
. be avoided.
..
1) High-degree or complete AVB after . AVB = atrioventricular block; RV = right ventricular; SND = sinus node
cardiac surgery . dysfunction.
a
..
A period of clinical observation of at least 5 days b
Level of evidence.
is indicated to assess whether the rhythm .
disturbance is transient and resolves. I C .
.
However, in the case of complete AVB with low .
or no escape rhythm when resolution is unlikely, .
..
. 8.3 Pacing after transcatheter aortic
this observation period can be
shortened.473,478

valve implantation
2) Surgery for valvular endocarditis and ..
For extended literature on patients with pre-procedural RBBB and
intraoperative complete AVB .. post-procedural LBBB see sections 8.3.1 and 8.3.2 in the
Immediate epicardial pacemaker implantation should .
Supplementary data.
be considered in patients with surgery for valvular .. Rates of permanent pacemaker implantation after TAVI range
endocarditis and complete AVB if one of the .
IIa C between 3.4% and 25.9% in randomized trials and large regis-
following predictors of persistence is present: pre- .. tries.490—502 Whereas the association between pacing after TAVI and
operative conduction abnormality, Staphylococcus .
aureus infection, intracardiac abscess, tricuspid valve . in outcome is controversial,503—509 RV pacing may lead to deterioration
LV function.183,510,511 Thus, efforts to minimize unnecessary per-
involvement, or previous .
valvular surgery.481 . manent pacing are warranted.
. Predictors for permanent pacing (Table 10 and supplementary table
3) SND after cardiac surgery and heart .
transplantation . 14), especially RBBB, which has been identified as the most consistent and
. powerful predictor for permanent pacemaker implantation, should be
Before permanent pacemaker implantation, a period IIa C .
of observation of up to 6 weeks should . incorporated into procedural planning including transcatheter heart valve
. selection, implantation height, and balloon inflations.
be considered.473 .
4) Chronotropic incompetence after
. Patients with pre-existing advanced conduction system disease who
. may have an indication for permanent pacing irrespective of the TAVI
heart transplantation .
Cardiac pacing should be considered for chronotropic
. procedure need consultation with an electrophysiologist before the
IIa C . procedure. There is currently no evidence to support permanent
incompetence persisting for >6 weeks after heart .
. pacemaker implantation as a ‘prophylactic’ measure before TAVI in
transplantation to improve quality of . asymptomatic patients or in patients who do not meet the standard
life.485 .
. indications for pacemaker implantation.
5) Patients requiring pacing at the time of . A recommended approach for the management of conduction
tricuspid valve surgery .
. abnormalities after TAVI is detailed in Figure 12. Patients without new
Transvalvular leads should be avoided and epicardial . conduction disturbances post-TAVI are at very low risk of developing
ventricular leads used. During tricuspid valve .
. high-degree AVB.533—535 Conversely, management of patients with
surgery, removal of pre-existing transvalvular .
leads should be considered and preferred over . persistent complete or high-degree AVB should follow standard
IIa C . guidelines. Permanent pacemaker implantation appears warranted in
sewing in the lead between the annulus and a .
bioprosthesis or annuloplasty ring. In the case of an . patients with intraprocedural AVB that persists for 24 - 48 h after TAVI
. or appears later. Data to guide the management of patients with other
isolated tricuspid annuloplasty based .
on an individual risk—benefit analysis, a pre- . conduction abnormalities at baseline or post-procedure are more
. limited.
existing RV lead may be left in place without jail- .
ing it between ring and annulus. . Given the close anatomical proximity of the aortic valve and the left
. bundle branch, the most frequent conduction abnormality after
6) Patients requiring pacing after biologi- .
cal tricuspid valve replacement/tricuspid . TAVI is new-onset LBBB.504,536—538 Only a small minority of these
. patients require pacemaker implantation.536,537 Thus, EPS539—541 or long-
valve ring repair .
When ventricular pacing is indicated, transvenous . term monitoring536 in lieu of pacemaker implantation may be
. considered542,543 (see section 8 in the Supplementary data). Several
implantation of a coronary sinus lead or minimally IIa C .
invasive placement of an epicardial ventricular lead . high-risk subgroups of patients with new LBBB have been identified (see
. Figure 12, and section 8 in the Supplementary data). In such patients
should be considered and preferred over a .
transvenous transvalvular . with dynamic progression of conduction abnormalities after TAVI (new
. BBB with dynamic prolongation of QRS and/or PR), an extended
approach.487 .
. monitoring period in hospital of up to 5 days should be considered.
Continued
. Conversely, patients with new-onset LBBB but QRS
54 ESC Guidelines
Table 10 Predictors for permanent pacing after transcatheter aortic valve implantation
Characteristics References
ECG
Right BBB 512—528
517,521,525,527
PR-interval prolongation
517,525
Left anterior hemiblock
Patient
529
Older age (per 1-year increase)
518,519,525,529
Male sex
529
Larger body mass index (per 1-unit increase)
Anatomical
512,515
Severe mitral annular calcification
522
LV outflow tract calcifications

528,530
Membranous septum length
531
Porcelain aorta
519
Higher mean aortic valve gradient
Procedural
512,513,525,529,531
Self-expandable valve
517,518,520,522,528,532
Deeper valve implantation
524,529,532
Larger ratio between prosthesis diameter versus annulus or LV outflow tract diameter
ESC 2021
519,521,529
Balloon post-dilatation
531
TAVI in native valve vs. valve-in-valve procedure
AVB = atrioventricular block; BBB = bundle branch block; ECG = electrocardiogram; LV = left ventricular; TAVI = transcatheter aortic valve implantation. For more
detailed data, see Supplementary Tables 14 and 15.
Management of conduction abnormalities in patients after TAVI
Persistent new LBBB with QRS > 150 ms

Pre-existing conduction abnormality with prolongation of QRS (> 20 ms) or PR (> 20 ms)f
or PR > 240 ms with no further prolongation during > 48h after procedurec
Pre-existing RBBB with new
post-procedure conduction disturbanceb
Persistenta high degree AVB
New onset alternating BBB
Ambulatory ECG monitoring

Ambulatory
d (ClassECG
IIa) monitoringd (Class IIb)
OR OR
Permanent PM Permanent PM EPSe EPSe
(Class I) (Class IIa) (Class IIa) (Class IIb)
Figure 12 Management of conduction abnormalities after transcatheter aortic valve implantation. AF = atrial fibrillation; AV = atrioventricular; AVB =
atrioventricular block; BBB = bundle branch block; ECG = electrocardiogram; EPS = electrophysiology study; HV = His—ventricular interval; LBBB = left bundle
branch block; LVEF = left ventricular ejection fraction; PM = pacemaker; QRS = Q, R, and S waves; RBBB = right bundle branch block; TAVI = transcatheter
aortic valve implantation. a24-48 h post-procedure. bTransient high-degree AVB, PR prolongation, or axis change. cHigh-risk parameters for high-degree AV block in
patients with new-onset LBBB include: AF, prolonged PR interval, and LVEF <40%. dAmbulatory continuous ECG monitoring for 7 - 30 days. eEPS with HV >_70
ms may be considered positive for permanent pacing. fWith no further prolongation of QRS or PR during 48-h observation.
ESC Guidelines 55
.
<150 ms may not require further evaluation during hospitalization. When for pacemaker therapy in patients with CHD is based on expert con-
.. sensus and individual evaluation due to lack of evidence from RCTs.
EPS is contemplated, it should be performed >_3 days post- procedure .
and after the conduction abnormalities have stabilized. In the presence of an intracardiac shunt between the systemic and
.. pulmonary circulation, endovascular lead placement is relatively con-
The type of permanent pacemaker implanted should follow standard .
traindicated due to the risk of arterial embolism.551
guidance (see sections 5, 6, and 7). Given the low rates of long- term
.. The clinical presentation may vary considerably; even severe bra-
dependency on pacing,544,545 algorithms promoting spontaneous AV .
dycardia in congenital AVB may remain oligosymptomatic or asymp-
..
conduction should be used.
tomatic. Periodic Holter recordings may be useful for patients at
Recommendations for cardiac pacing after transcath-
.. specific risk of bradyarrhythmia.
.
eter aortic valve implantation .
.
. 8.4.1 Sinus node dysfunction and
. bradycardia—tachycardia syndrome
...

Permanent pacing is recommended in patients There is no evidence that SND directly leads to increased mortality
with complete or high-degree AVB that persists for I B . in CHD. However, it may be associated with a higher rate of post-
operative atrial flutter, with 1:1 AV conduction in CHD, and thus lead
..
24 - 48 h after TAVI.546
Permanent pacing is recommended in patients to morbidity and potentially mortality.552,553
with new-onset alternating BBB after TAVI.533,547 I C ..
. 8.4.1.1 Indications for pacemaker implantation
Earlyc permanent pacing should be considered in ... In patients with symptomatic chronotropic incompetence, pace-
patients with pre-existing RBBB who develop any . maker implantation is justified when other causes (see section 4) have
554,555
IIa B
further conduction disturbance during or . been ruled out. Increasing the heart rate through permanent
after TAVI.d
. pacing to prevent atrial arrhythmias may be considered.556 The
.. underlying evidence is weak, as the benefit of atrial-based pacing
Ambulatory ECG monitoringe or EPSf should be
considered for patients with new LBBB with QRS
. observed in patients without structural heart disease could not be
.. validated in CHD.
21,557,558
The general consensus is that if permanent
>150 ms or PR >240 ms with no further IIa C
.
prolongation during the >48 h after pacing is necessary, single-lead atrial-based pacing should be pre-
TAVI.536,537,548 .. ferred to limit the number of leads, especially in young patients with
.
Ambulatory ECG monitoringe or EPSf may be adequate AV conduction.559 In patients with congenitally corrected
considered for patients with a pre-existing conduction .. transposition of the great arteries requiring ventricular pacing
IIb C .
abnormality who develop prolongation because of high-degree AVB, CRT should be considered. Current
of QRS or PR >20 ms. g .. evidence to use devices with atrial antitachycardia pacing to treat
.
Prophylactic permanent pacemaker implantation is intra-atrial re-entrant tachycardias in patients with CHD560,561 is too
.. limited to make general recommendations.
ESC 2021
not indicated before TAVI in patients with III C

.
RBBB and no indication for permanent pacing. .
.
. 8.4.2 Congenital atrioventricular block
AF = atrial fibrillation; AVB = atrioventricular block; BBB = bundle branch block; .
A number of maternal or fetal factors can cause congenital heart
CRT = cardiac resynchronization therapy; ECG = electrocardiogram; EPS = elec-
.. block, particularly autoimmune diseases such as systemic lupus eryth-
trophysiology study; HV = His—ventricular interval; LBBB = left bundle branch
.
block; RBBB = right bundle branch block; SR = sinus rhythm; TAVI = transcatheter ematosus and Sjo¨gren syndrome (Supplementary Table 16).
aortic valve implantation. For the definition of alternating BBB, see section 5.3.1. .. Patients presenting with congenital AVB may be asymptomatic or
a
may present with reduced exercise capacity, syncopal attacks, con-
.. gestive HF, ventricular dysfunction, and dilatation. Rarely, in SCD,
b
Level of evidence.
c
Immediately after procedure or within 24 h.
d
Transient high-degree AVB, PR prolongation, or QRS axis change. .
congenital AVB is diagnosed as the cause.562,563 SCD may occur
Ambulatory continuous ECG monitoring (implantable or external) for 7 30 — .. through increased propensity to develop bradycardia-related ventric-
e
days.536,549 .
ular arrhythmias such as torsades-de-pointes.
...
f
EPS should be performed >_3 days after TAVI. Conduction delay with HV >_70 ms
may be considered positive for permanent pacing.540,541,550
g
With no further prolongation of QRS or PR during 48-h observation.
8.4.2.1 Indications for pacemaker implantation
.. There is general consensus that prophylactic pacing is indicated in
Note: CRT in patients requiring pacing after TAVI has the same indication as for
general patients (see section 6).
.. asymptomatic patients with any of the following risk factors: mean
. daytime heart rate <50 b.p.m., pauses greater than three times
8.4. Cardiac pacing and cardiac ... the cycle length of the ventricular escape rhythm, a broad QRS
resynchronization therapy in congenital . escape rhythm, prolonged QT interval, or complex ventricular
. ectopy.564—566 Clinical symptoms, such as syncope, pre-syncope, HF,
heart disease . or chronotropic incompetence, are indications for pacemaker
.. implantation.
Permanent pacing in patients with moderate or complex CHD 564,567,568
If ventricular dysfunction is attributed to hae-
should be performed in centres with a multidisciplinary team and .
expertise in CHD-related device therapy. Generally, decision-making . modynamic compromise 518,567
caused by bradycardia, permanent pacing
. may be indicated. Despite a modest quality of evidence, there
56 ESC Guidelines
is strong consensus that patients with third- or second-degree AVB .

(Mobitz type II) must receive permanent cardiac pacing therapy if .
In patients with persistent post-operative bifascicular
. block associated with transient complete IIb C
symptomatic or with risk factors. In asymptomatic patients without . risk
.
factors, opinion on the benefit of cardiac pacing diverges, and permanent AVB, permanent pacing may be considered.572
pacing may be considered.567,569 In patients with complex CHD and asymptomatic
. .
bradycardia (awake resting heart rate <40
. IIb C
. b.p.m. or pauses >3 s), permanent pacing may be
ESC 2021
8.4.3 Post-operative atrioventricular block considered on an individual basis.
.
. AVB = atrioventricular block; BBB = bundle branch block; b.p.m. = beats per
Post-operative high-degree AVB is estimated to occur in 1 3% —of
518,569,570
In children, transient ..
patients undergoing surgery for CHD. 571 . minute; CHD = congenital heart disease; ECG = electrocardiogram.
early post-operative AVB usually resolves within 7—10 days. In a
.
adults with CHD, there are no data to support a different waiting . b
Level of evidence.
period before deciding for permanent pacing post-operatively than after
.
.
other cardiac surgery. After recovery from complete AVB, bifascicular .
..

block occasionally persists, which is associated with an increased risk 8.4.4 Cardiac resynchronization
of late recurrent AVB and sudden death.572 The prognosis is poor for
.
Standard indications for CRT may be considered in CHD, taking into
patients with untreated post-operative complete AVB.573 .. account that the anatomy, morphology of the systemic ventricle, and
.
cause of dyssynchrony, as well as QRS morphology, may be atypi-
. cal.574 Multidisciplinary teams in experienced centres should be
8.4.3.1 Indications for pacemaker implantation .
There is a strong recommendation for permanent pacing in patients with
. involved in the decision-making process.
..
persistent second- or third-degree AVB. In patients with persistent
8.5 Pacing in hypertrophic
bifascicular block associated with transient AVB or permanent prolonged ..
cardiomyopathy
PR interval, consensus for pacemaker implantation is modest. Post- .. 8.5.1 Bradyarrhythmia
operative HV interval determination may help to estimate the risk in .
AVB in hypertrophic cardiomyopathy (HCM) should generally be
patients with prolonged PR or bifascicular block. 573 In patients with .. treated according to the recommendations in this guideline (see sec-
bifascicular block and long PR after surgery for CHD, the risk of .
tion 5.2). Certain genetically inherited subtypes of HCM are more
extensive damage to the conduction system is high,572 therefore .. prone to develop AVB, as is the case with transthyretin amyloidosis,
pacemaker implantation
HV measurement. may be
Implantation of indicated
epicardialeven
leadswithout
should be consid- .
. Anderson —Fabry and Danon diseases, PRKAG2 syndrome, and mito-
chondrial cytopathies. 575,576 An ICD/CRT-D rather than a pacemaker
ered during surgery in patients with complex CHD and a high lifetime .
risk of pacemaker implantation, in order to reduce the rate of
.. should be considered in patients with symptomatic bradycardia who
reoperation. . have LVEF <_35% or otherwise fulfil 576
the criteria for primary preven-
. tion of SCD by current guidelines. (For extended literature on con-
. duction disorders in HCM see the Supplementary data, section 8.5.)
..
.
Recommendations for cardiac pacing in patients with 8.5.2 Pacing for the management of left ventricular
congenital heart disease .. outflow tract obstruction
.
In patients with symptoms caused by LV outflow tract obstruction,
Recommendations Classa Levelb .. treatment options include drugs, surgery, septal alcohol ablation, and
.
In patients with congenital complete or high- AV sequential pacing with a short AV delay. Three small, randomized,
.. placebo-controlled studies and several long-term observational stud-
degree AVB, pacing is recommended if one of the .
following risk factors is present: ies reported reductions in LV outflow tract gradients, and variable
a. Symptoms
.. improvement in symptoms and quality of life with AV sequential
.
b. Pauses >3× the cycle length of the ventricular pacing.577—582 Myectomy achieved superior haemodynamic results
escape rhythm
I C .. compared with DDD pacing,583 but is a more invasive and higher risk
c. Broad QRS escape rhythm ... intervention. In one trial, a subgroup analysis suggested that older
d. Prolonged QT interval . patients (>65 years) 579
are more likely to benefit from DDD AV
e. Complex ventricular ectopy . sequential pacing. A recent meta-analysis—comprising 34 studies
f. Mean daytime heart rate <50 b.p.m. .
. and 1135 patients—found that pacing reduced the LV outflow gradient
In patients with congenital complete or high- . by 35%, with a non-significant trend towards reduction in NYHA
degree AVB, permanent pacing may be consid- IIb C .
. class.584
ered even if no risk factors are present.566 . Shared decision-making should be employed when considering the treatment of
.
Continued choice for patients with obstructive HCM.
ESC Guidelines 57
. As current ICDs provide all pacemaker functions, a standalone

Recommendations for pacing in hypertrophic obstruc-
tive cardiomyopathy .. pacemaker is rarely indicated in LQTS today. However, in individ-
. ual patients with LQTS and catecholamine-induced torsades-de-
.
Recommendations Classa Levelb pointes, shock therapy may be disadvantageous or even fatal; in
.. these cases, pacing and beta-blocker therapy alone without an
AV sequential pacing with short AV delay may be .
ICD may be used. Pacemaker instead of ICD implantation repre-
considered in patients in SR who have other pacing .. sents a treatment option in neonates and small infants with
or ICD indications if drug-refractory symptoms or .
IIb B LQTS,594 and an alternative in LQTS patients with symptomatic
baseline or provocable LV outflow tract gradients .. bradycardia (spontaneous or due to beta-blockers) if ventricular
>_50 mmHg are .
tachyarrhythmias are unlikely or if ICD implantation is not desired
present.576—581,584 .. (e.g. patient preference).
An indication for a pacemaker in LQTS exists in neonates and
considered in selected adults with drug-refractory .. infants with a 2:1 AVB due to excessive corrected QT prolongation
symptoms, >_50 mmHg baseline or provocable LV .

IIb B with long myocardial refractory periods.595
outflow tract gradient, in SR, who are unsuitable for or .. Temporary pacing at an increased rate (usually 90 - 120 b.p.m.) is an
unwilling to consider other invasive septal .
important treatment in LQTS patients with electrical storm, because
reduction therapies.576—581,584 .. an increase in the basic heart rate shortens the window of vulnerability
for reinduction of torsade de pointes ventricular tachycardia.
considered in selected patients with drug- ..
refractory symptoms, >_50 mmHg baseline or .
IIb C . 8.6.2 Neuromuscular diseases
provocable LV outflow tract gradients, in SR, at .
Neuromuscular diseases are a group of heterogeneous inherited dis-
ESC 2021
high risk of developing AVB during septal

.. orders affecting the skeletal muscle and frequently also involve the
ablation.585,586 .
heart (for extended literature on conduction disorders in neuromus-
AV = atrioventricular; AVB = atrioventricular block; ICD = implantable cardi- .. cular disease, see the supplementary literature on pacing in rare dis-
overter-defibrillator; LV = left ventricular; SR = sinus rhythm. .
ease and Supplementary Table 17). The cardiac phenotype variably
..
a
includes all types of cardiomyopathies, conduction defects with or

Level of evidence.
.
b
Pacing parameters should be optimized to achieve maximum pre-excitation of the RV without cardiomyopathies, and supraventricular and ventricular
apex with minimal compromise of LV filling (typically achieved with a resting sensed .. tachyarrhythmias.596—598 Duchenne, Becker, and limb-girdle types
AV interval of 100 ± 30 ms).587 .
2C, 2F, and 2I are muscular dystrophies in which the development of
.. dilated cardiomyopathy is common and usually the predominant fea-
8.5.3 Pacemaker implantation following septal .. ture. Arrhythmias and conduction disease can be associated with the
myectomy and alcohol septal ablation . development of cardiomyopathy.596—598 Such patients are consid-
In a study involving 2482 patients with obstructive HCM, 2.3% devel- .. ered for pacemakers or ICDs on the basis of guidelines used for
oped AVB after septal myectomy588 (only 0.6% in those with normal . other non-ischaemic cardiomyopathies.242 Myotonic dystrophy types
baseline conduction vs. 34.8% in patients with pre-existing RBBB).
576
.. 1 and 2, Emery —Dreifuss, and limb-girdle type 1B often present with
conduction disease and associated arrhythmias, and variably with car-
Alcohol septal ablation causes AVB in 7—20% of patients; those . 596,597
with pre-existing conduction defects, mainly LBBB, are at highest . diomyopathy. The recommendations present guidance in the
risk. 585 . instances where the recommendations for cardiac pacing differ from
those used for other patients with bradycardia.

8.5.4 Cardiac resynchronization therapy in end- .
.
stage hypertrophic cardiomyopathy 589
. Recommendations for cardiac pacing in rare diseases
Based on the findings of a small cohort study, CRT was given both .
. Recommendations Class
with sinus bradycardia; very long ventricular
a
Level
myocardial
b
refractory
a class IIa and a class IIb recommendation in previous guidelines for .
patients with HCM, HF, LBBB, and LVEF <50%.576,590 More recent . In patients with neuromuscular diseases such as
. .
studies did not demonstrate sustained efficacy of this therapy. 591—593
Until. myotonic dystrophy type 1 and any second- or third-
I C
further evidence becomes available, standard criteria for CRT
. degree AVB periods
or HV can cause
>_70 ms,2:1 AVB;
with sudden rate changes can trigger torsades-
or without
are recommended in patients with HCM (section 6). . —
symptoms, permanent pacing is indicated.c 599 602
. .
In patients with neuromuscular disease such as
. de-pointes tachycardia; and treatment with beta-blockers to suppress
. myotonic dystrophy type 1 with PR >_240 ms or
IIb C
8.6 Pacing in rare diseases .
QRS duration >_120 ms, permanent pacemaker
.
. implantation may be considered.c 600,603,604
8.6.1 Long QT syndrome sympathetic triggers of torsades-de-pointes may cause bradycardia.
.
There are multiple inter-relationships between the different forms of
. .
.
long QT syndrome (LQTS) and bradycardia: LQTS can be associated
.
58 ESC Guidelines
ESC 2021
AVB = atrioventricular block; CRT = cardiac resynchronization therapy; HV = His
ventricular
— interval; ICD = implantable cardioverter-defibrillator.
a
b
Level of evidence.
c
Whenever pacing is indicated in neuromuscular disease, CRT or an ICD should be
considered according to relevant guidelines.
ESC Guidelines 59
.
presentations.621,622 In Kearns Sayre
8.6.3 Dilated cardiomyopathy with lamin A/C mutation — syndrome, the most common
Mutations in the LMNA gene, which encodes lamin A and C intermediate
.. cardiac manifestation is conduction disease, which may progress to
.
filaments of the nuclear envelope, cause a variety of 605—607
inherited complete AVB and cause SCD.623—625
.
diseases defined as ‘laminopathies’. According to the type of .
mutation, they can lead to isolated cardiac disorders or additional Recommendations for pacing in Kearns—Sayre
.
syndrome
.
systemic or musculoskeletal disorders such as the Emery — Dreifuss ..
autosomal dominant variant or limb-girdle dystrophy. Around
5 10% of dilated cardiomyopathies are induced by LMNA gene
.. Recommendations Classa Levelb
— .
mutations, manifested as cardiac conduction disease, tachyarrhyth-
..
596,606—620 In patients with Kearns—Sayre syndrome who
mias, or impaired myocardial contractility. SND and con- have PR prolongation, any degree of AVB, BBB, or
. IIa C
duction disease are frequently the first manifestation, in many cases fascicular block, permanent pacing should be
with preserved LV size and function.
613,614
LMNA-related cardiomy- .. considered.c 621—625
.
opathy is more malignant than most other cardiomyopathies, carry- ing a In patients with Kearns—Sayre syndrome without

.
higher risk of SCD in asymptomatic mutation carriers with . preserved or cardiac conduction disorder, permanent
. IIb C
ESC 2021
only mildly decreased LV contractility.610—615 Pacemaker implantation. pacing may be considered
does not reduce the risk of SCD in these . prophylactically.c 621—625
. . AVB = atrioventricular block; BBB = bundle branch block; CRT = cardiac

patients. A meta-analysis of mode of death in LMNA mutations dem- resynchronization therapy; ICD = implantable cardioverter-defibrillator; PR = PR
onstrated that 46% of patients who died suddenly had an implanted . interval.
. a
pacemaker. Sudden death rates were similar in those with isolated . b
Level of evidence.
cardiomyopathy and those with an additional neuromuscular pheno- . type.611 c
Whenever pacing is indicated, CRT or an ICD should be considered according to the
.
with.
relevant guidelines.
Complex ventricular arrhythmias are common in patients
conduction disturbances.612,613,615 In two studies, patients with . .
LMNA mutations and an indication for permanent pacing underwent ..
ICD implantation, and appropriate ICD therapies occurred in 42%
612,613
.
and 52% of patients within 3 and 5 years, respectively. These .
findings led to the clinical practice to consider ICD rather than pace- .
614,620
.. 8.6.5 Infiltrative and metabolic diseases
maker implantation in LMNA-related conduction disease. For Infiltrative cardiomyopathy is secondary to abnormal deposition and
additional clinical risk factors for ventricular tachyarrhythmias and disorders, in which cardiomyopathies, conduction defects, and ventricular
sudden death found in patients with dilated cardiomyopathy due to arrhythmias are the most common cardiac
LMNA gene mutations, see Supplementary Table 18. CRT(D) should be
considered if the patient has AVB and LVEF <50%, and a high frequency of
ventricular pacing is expected (section 6 and Supplementary Table 18).
The risk score of life-threatening ventricular arrhythmia in laminopathies
can be predicted by a recently developed and validated module
(https://lmna-risk-vta.fr/).616
Recommendation for patients with LMNA gene muta-

tions (for references, see Supplementary Table 18)
Recommendation Classa Levelb
In patients with LMNA gene mutations, including Emery

—Dreifuss and limb-girdle muscular dystrophies who
fulfil conventional criteria for pace-
maker implantation or who have prolonged PR interval IIa C
with LBBB, ICD implantation with pacing capabilities
should be considered if at least 1-
year survival is expected.616
ICD = implantable cardioverter-defibrillator; LBBB, left bundle branch block.

a
b
Level of evidence.
8.6.4 Mitochondrial cytopathies

Mitochondrial cytopathies are a heterogeneous group of hereditary
60 ESC Guidelines
. .
. bodies), and physical reactions (radiation therapy) can cause inflam-
. accumulation of pathological products in the myocardial interstitium, .. matory heart disease. Involvement of the AVN and the conduction
while storage diseases lead to their intracellular accumulation. The .
. . system is more frequent than that of the sinus node. AVB may indi-
. main cause of infiltrative cardiomyopathy is amyloidosis, while stor- .. cate involvement of the septum in the inflammatory process and is a
ESC 2021
age diseases include haemochromatosis, Fabry’s disease, and glycogen .
. . predictor of adverse outcome. Ventricular arrhythmias may also
. storage diseases. In patients with cardiac amyloid, conduction defects,
.. occur because of myocardial pathology.
tachyarrhythmias, and SCD are common. Based upon current knowl- .
. edge, conventional indications should be used for pacing in this group . When inflammatory heart disease is complicated by bradycardia,
. . especially AVB, specific therapy should be applied if available, eventu-
of patients. .
. ally backed-up by temporary pacing or intravenous administration of
.
. .. isoprenaline. Otherwise, immunosuppressive therapy or awaiting
.
8.6.6 Inflammatory diseases . spontaneous resolution may be sufficient. If bradycardia does not
.
Infections (viral, bacterial including Borreliosis, protozoa, fungal, para- .. resolve within a clinically reasonable period or cannot be expected
.
sites), autoimmune (e.g. giant cell myocarditis, sarcoidosis, rheumatic . to resolve (e.g. after radiation therapy), permanent pacing is indi-
.
heart disease, connective tissue disease, eosinophilic myocarditis), .. cated. Before choosing a device type, the indication for an ICD and/
toxic (alcohol, cocaine, cancer therapies, especially monoclonal anti- .
or CRT rather than a single-chamber or DDD pacemaker should be
ESC Guidelines 61
.
considered because most causes of inflammatory disease causing bra- . pauses >3 ×the cycle length of the ventricular escape rhythm, wide
. QRS escape rhythm, prolonged QT interval, complex ventricular
dycardia may also result in reduced myocardial contractility and ven-
tricular fibrosis. .. ectopy, mean daytime heart rate <50 b.p.m.) is present. However,
. women with complete heart block who exhibit a slow, wide QRS
8.6.6.1 Sarcoidosis .. complex escape rhythm should undergo pacemaker implantation
. during pregnancy. The risks of pacemaker implantation are generally
Persistent or intermittent AVB can occur in sarcoidosis, which shows a
propensity to involve the basal intraventricular septum. In a Finnish .. low and can be performed safely, especially if the foetus is beyond 8
.
registry, 143 of 325 patients (44%) diagnosed with cardiac sarcoidosis had weeks gestation. A pacemaker for the alleviation of symptomatic bra-
Mobitz II second- or third-degree AVB in the absence of other .. dycardia can be implanted at any stage of pregnancy using echo guid-
.
explanatory cardiac disease.626 A history of syncope, pre-syncope, or ance or electroanatomic navigation minimizing fluoroscopy.636,637
palpitations points towards bradycardia, but also to potential ventricular ..
.
tachyarrhythmia. AVB is the most common clinical presentation
in patients with clinically evident cardiac sarcoidosis. 627,628 Diagnostic .. 9 Special considerations on device

steps include ECG monitoring, echocardiography, cardiac MRI, and .
myocardial or other involved tissue biopsy. Fluorodeoxyglucose-
. implantations and peri-operative
..
positron emission tomography may be useful. 629 The chances and time management
course of resolution of AVB with immunosuppressive therapy are not ..
clear,630 but may be low.88 Long-term data are available mainly from a . 9.1 General considerations
Canadian prospective study (32 patients),627 a Japanese retrospective .. Patients with clinical signs of active infection and/or fever should not
study (22 patients),628 and a Finnish registry (325 patients).626 .
undergo a permanent pacemaker (including leadless pacemaker)
Reversibility of conduction disorder is unpredictable and, even in .. implantation until they have been afebrile for at least 24 h. Febrile
patients with transient AVB, permanent pacing should be considered.631 .
patients who have been started on antibiotics should ideally receive a
Immunosuppressive treatment may increase risk of device infection. .. complete course of antibiotic treatment and should be afebrile for
However, there are no firm data to support device implantation before .
24 h after termination of antibiotic treatment before definite pace-
initiation of immunosuppressive medication. Patients with cardiac .. maker implantation is performed if acute pacing is not required. If
sarcoidosis and AVB are at high risk of SCD during long-term follow-up, .
possible, the use of temporary transvenous pacing should be avoided.
even if LVEF is >35%.626 Patients with even a .. In patients in need of acute pacing, temporary transvenous pacing
mild or moderate decrease in LVEF (35—49%) are at increased risk .
. should be established, preferably with jugular or axillar/lateral subcla-
. vian vein access.
638
In a multicentre, prospective study with 6319
of SCD.632,633 Therefore, in patients with cardiac sarcoidosis who have .
patients, fever within 24 h of implantation (OR 5.83, 95% CI
an indication for cardiac pacing and LVEF <50%, a CRT-D should be .
considered rather than a pacemaker634 (section 6). . 2.00—16.98) and temporary pacing before implantation (OR 2.46,
.
Recommendations
sarcoidosis for pacing in cardiac .. 95% CI 1.09 —5.13) were positively correlated with the occurrence
of device infection. 639 In the case of patients with chronic recurrent
.
infection, minimally invasive implantation of an epicardial pacemaker
Recommendations Classa Levelb .. may be considered.
..
In patients with cardiac sarcoidosis who have permanent .
9.2 Antibiotic prophylaxis
or transient AVB, implantation of a
IIa C .. The use of pre-operative systemic antibiotic prophylaxis is re-
device capable of cardiac pacing should be considered.c .
commended as the standard of care in pacemaker implantation
..
88,629,630
procedures. The risk of infection is significantly reduced with a single

In patients with sarcoidosis and an indication for .
ESC 2021
permanent pacing who have LVEF <50%, implan- IIa C .. dose of prophylactic antibiotic (cefazolin 1 2—g i.v. or flucloxacillin
1 2 g i.v.) given within 30 60 min [90 120 min for vancomycin
tation of a CRT-D should be considered.631,634 . — — —
(15 mg/kg)] before the procedure. 640 643
The antibiotic prophylaxis
AVB = atrioventricular block; CRT-D = defibrillator with cardiac resynchronization .. —
should cover S. aureus species, but routine coverage of methicillin-
therapy; ICD = implantable cardioverter-defibrillator; LVEF = left ventricular ejection .
resistant S. aureus is not recommended. The use of vancomycin
..
fraction.
a
Class of recommendation. should be guided by patient risk for methicillin-resistant S. aureus col-
Level of evidence.
..
b
onization and the prevalence of the bacterium in the corresponding
c
Whenever pacing is indicated in sarcoidosis, an ICD should be considered
according to the relevant guidelines.
. institution.638
.. In contrast, post-operative antibiotic prophylaxis does not reduce
. the incidence of infection.644,645
8.7 Cardiac pacing in pregnancy ..
.
Vaginal delivery carries no extra risks in a mother with congenital 9.3 Operative environment and skin
complete heart block, unless contraindicated for obstetric reasons.635 .. antisepsis
For women who have a stable, narrow complex junctional escape rhythm, .. The pacemaker implantation procedure should be performed in an
pacemaker implantation may not be necessary or can be deferred until after . operating environment that meets the standards of sterility as
delivery if none of the risk factors (syncope, .
. required for other surgical implant procedures.638,646
62 ESC Guidelines
.
Based on data from surgical and intravascular catheter procedures, skin .. depending on the clinical scenario and concomitant antiplatelet ther-
antisepsis should be performed using chlorhexidine alcohol — . apy, either stopping or continuing non-vitamin K antagonist oral anti- 652
647,648
instead of povidone-iodine—alcohol. In a large RCT comprising . coagulants might be reasonable at the time of device implantation.
2546 patients, chlorhexidine—alcohol was associated with a lower . Patients on dual antiplatelet therapy have a significantly increased
incidence of short-term intravascular catheter-related infections (HR 0.15, .. risk of post-operative pocket haematoma compared with patients
95% CI 0.05 - 0.41; P = 0.0002).647 . treated with aspirin alone or without antiplatelet therapy. In such
.
. cases, P2Y12 receptor inhibitors should be discontinued for 3—7 days
. (according to the specific drug) before the procedure where
9.4 Management of anticoagulation .. possible and based on an individualized risk assessment. 638,653,654
For
It is well known that the development of a pocket haematoma after the .
more details on the management of anticoagulation in the pacemaker
implantation of a pacemaker system significantly increases the risk for .. procedure, refer to Table 11.
subsequent pocket infection.641,643,649 The Bridge or Continue .
Coumadin for Device Surgery Randomized Controlled Trial (BRUISE
.
.
.

CONTROL) proved that a clinically significant pocket haematoma is an
.
independent risk factor for subsequent device infec- . 9.5 Venous access
tion (HR 7.7, 95% CI 2.9—20.5; P < 0.0001).649 Therefore, it is of
.
Transvenous lead implantation for pacemaker implantation is com-
utmost importance to take all steps to avoid post-operative pocket .. monly performed by venous access via the cephalic, subclavian, or
haematoma. .
axillary vein. In the case of clinical signs of venous occlusion of the
Heparin bridging for pacemaker implantation in patients anticoagu- .. subclavian vein or the innominate vein, pre-operative imaging (venog-
lated with a vitamin K antagonist leads to a significant 4.6-fold increase in
.
raphy or chest CT scan) may be useful in planning venous access or
post-operative pocket haematoma compared with a continued warfarin .. an alternative access ahead of the procedure. In the case of impossi-
strategy.650 International normalized ratio tapering and temporary shifting
.. ble superior venous access, appropriate, alternative approaches may
of dual antiplatelet to single antiplatelet administration may significantly . be transfemoral lead implantation, or implantation of a leadless
reduce the haematoma and infection rate by 75% and 74%, respectively,
.. device or epicardial leads.
compared with heparin bridging.651 . When using the Seldinger technique, there is a risk of a pneumo-
Regarding non-vitamin K antagonist oral anticoagulants, the .. thorax, haemothorax, inadvertent arterial puncture, and injury to the
Randomized Controlled Trial of Continued Versus Interrupted Direct . brachial plexus during venous puncture of the subclavian vein and
Oral Anti-Coagulant at the Time of Device Surgery (BRUISE .. (less so) the axillary vein. These risks are avoidable by using the ceph-
CONTROL-2) was stopped prematurely due to futility because the event .
rate was far lower than anticipated; however, it suggested that, . alic vein approach, which allows venous insertion of leads under
. direct vision. Subclavian vein access is associated with a 7.8-fold
Table 11 Management of anticoagulation in pacemaker procedures
Dual antiplatelet therapy655,656 NOAC652 VKA650 OAC 1 antiplatelet657

Thrombotic risk after PCI
Intermediate or low High
>1 month PCI <1 month PCI
>6 months acute coronary <6 months acute coronary
syndrome at index PCI syndrome at index PCI
Low procedural Continue aspirin AND Elective surgery: Consider Continue or interrupt as Continuea Continue OAC (VKAa or
bleeding risk First Discontinue P2Y12 inhibi- postponement Otherwise: per operator preference. If NOAC). Discontinue anti-
implant tors: Ticagrelor at least • Continue aspirin interruption, then based on platelet per patient-specific
3 days before surgery • Continue P2Y12 CrCl and specific NOAC risk/benefit analysis
Clopidogrel at least 5 days inhibitor
High procedural before surgery Prasugrel at Continue aspirin AND
bleeding risk Device least 7 days before surgery Discontinue P2Y12 inhibi-
exchange, upgrade/ tors: Ticagrelor at least 3
revision procedure days before surgery,
Clopidogrel at least 5 days
before surgery, Prasugrel at
ESC 2021
least 7 days before surgery.

Bridging with GP IIb/IIIa
inhibitors
CrCl = creatinine clearance; GP = glycoprotein; NOAC = non-vitamin K antagonist oral anticoagulant; OAC = oral anticoagulant; PCI = percutaneous coronary intervention; VKA = vitamin K antagonist.
a
Target international normalized ratio within therapeutic range.
ESC Guidelines 63
.
increased risk of pneumothorax.658 Prospective data on axillary vein developed to allow for full extractability in the long term. However,
.. the ease of extractability at long term has not yet been
puncture suggest a lower risk of access-related complications compared
with subclavian puncture.659 Ultrasound guidance for axillary vein
.
proven.667—669
puncture has been described as a helpful technique for achieving a safe and ...
9.7 Lead position
.. Ventricular pacing has traditionally been performed from the RV
uncomplicated puncture.660
With regards to lead failure after implantation, there is evidence that
the axillary vein route is associated with a lower rate of lead fail- ures in .. apex. Since the introduction of active fixation leads, alternative pacing
long-term follow-up. In a retrospective study comprising 409 patients . sites such as the RVOT septum or the mid-septum have been eval-
and mean follow-up of 73.6 ± 33.1 months, lead failure occurred in ... uated in order to provide more physiological pacing. However,
1.2% of patients with contrast-guided axillary vein puncture, 2.3% of . despite two decades of research, the clinical benefit of RV non-apical
pacing remains uncertain.670 This may be partly explained by variabil-
.. ity in the position of the lead, which is often unintentionally placed on
patients with cephalic vein cutdown, and 5.6% of patients with
subclavian vein puncture. In multivariable regression
analysis, the only predictor of lead failure was subclavian vein puncture .. the anterior free wall, where it may be associated with adverse out-
.

instead of axillary vein access (HR 0.26, 95% CI 0.071—0.954; P come.671—673 The main advantage of septal pacing probably lies in
= 0.042). When analysing the success rates of the different venous .. the avoidance of perforation of the free wall. In a study of 2200
.
access approaches, the cephalic vein approach showed the lowest success patients implanted with a pacemaker or ICD lead, an apical position
rate (78.2% vs. axillary vein 97.6% and subclavian vein 96.8%; P < .. was independently associated with cardiac perforation (OR 3.37; P =
.
0.001).661 0.024).420 A septal position may therefore be preferable in patients at
.. increased risk of perforation, such as elderly patients especially with a
.
9.6 Lead considerations body mass index <20 kg/m2, as well as women.670,674
In choosing between active or passive fixation pacemaker leads in the RA or .. Placing the lead on the mid-septum may be challenging (even more
.
RV, one should consider the potential for perforation and peri- carditis, as so in the RVOT septum, which is a smaller target area). The use of
well as extractability. Active fixation leads have a higher tendency to
.. multiple fluoroscopic views and specially shaped stylets is useful for
.
create pericardial effusions as well as overt perforations. Passive fixation this purpose and is outlined in a recent EHRA consensus paper.34 In
leads, due to the non-isodiametric design of the lead tip, may be a factor in
.. this context, it is important to mention that the accuracy and repro-
.
lower procedural success rates and higher risk for complications with lead ducibility of fluoroscopic assessment of RV lead positions is often
.. inaccurate.421
extraction, although this point is far from being clear and is still under .
evaluation.662 An RCT is required to clarify this issue. Multiple fluoroscopic views are also recommended for placing
Regarding perforations, an uncontrolled, non-randomized study .. RVA leads, to ensure there is no inadvertent placement of the lead in
comprising 3815 patients with implant of an RV lead showed no sig- .. a coronary sinus tributary or in the LV via an intracardiac shunt or
nificant difference with regards to myocardial perforations between active . arterial access.
and passive fixation leads (0.5% vs. 0.3%; P = 0.3).663 Active fixation leads .. The coronary sinus may be used for LV pacing without the need to
also allow selective site pacing in regions of the RV that are smooth . cross the tricuspid valve. It may also be used in the case of other diffi-
walled (e.g. the mid-septum). The RA is, however, thin walled, and .. culties in deploying an RV lead (e.g. in the case of a tricuspid valve
perforation of the RA free wall by active fixation leads has been . prosthesis). In selected patients, the outcome is similar to RV
demonstrated. Some implanting physicians prefer to implant passive .. pacing.675,676
leads in patients at elevated risk of perforation (e.g. elderly patients). .
The RA appendage is usually the preferred site for atrial pacing.
However, based on expert opinion and on the results of a single-centre, .. The lateral atrium may carry a risk of phrenic nerve capture.677,678
retrospective study on ICD leads (637 patients), in young patients, the
.
Alternative pacing sites to avoid AF such as Bachman’s bundle and
use of active fixation leads in the RA and RV is recommended in terms of .. the region of the coronary sinus ostium have not shown benefit and
future extractability.664
.
are not to be recommended in routine practice.679,680
Lead stability and phrenic nerve stimulation are important aspects of ..
.
coronary sinus lead implantation. With regards to both, quadripolar 9.8 Device pocket
leads seem to have relevant advantages. The rate of phrenic nerve stimulation .. In recent years, there has been increasing awareness of the device
.
requiring lead revision is significantly lower compared with that in pocket as a source of complications. Avoidance of pocket infections
bipolar coronary sinus leads.665,666 Furthermore, lead stability is .. has become a special focus in device therapy. The role of pocket hae-
.
increased because quadripolar leads can usually be implanted in the matomas in the development of infections has been discussed earlier.
wedged position. If implanted in an apical position due to wedging, the .. It is evident that besides adequate management of anticoagulation, a
use of the proximal poles avoids apical stimulation. Therefore, .. proper surgical technique with meticulous haemostasis is of utmost
quadripolar leads are recommended for coronary sinus lead . importance.
implantation. Active fixation LV leads via a side helix have been .. Most pacemakers are implanted with the creation of a subcutane-
developed, and results have proved reliable stability, easy access to the target . ous pocket.681 In patients with a low body mass index and therefore
pacing site, and stable LV pacing threshold in the long term. In .. little subcutaneous tissue, in the case of Twiddler’s syndrome, or for
comparison with passive fixation quadripolar leads, active fixation . aesthetic reasons, creation of a submuscular pocket may be prefera-
bipolar and quadripolar leads achieved similar results. The lead design .. ble. However, this may require deeper sedation for implantation and
with an active fixation mechanism via a side helix was .
. generator replacements due to pain. To date, there are no data from
. RCTs comparing the two approaches for creating device pockets.
64 ESC Guidelines
Historical data from 1000 patients with ICD implants showed signifi- . cantly In pacemaker implantations in patients with pos-
.
shorter procedural times for patients with subcutaneous device pockets.. sible pocket issues such as increased risk of ero- sion
No significant differences with regard to pocket hae- . . due to low body mass index, Twiddler’s syndrome, IIb C
matomas were found. There were no significant differences in the
cumulative percentages of patients free from complication during fol-
.. or for aesthetic reasons, a submuscu-
. lar device pocket may be considered.
low-up.682
Pocket irrigation at the end of the procedure with normal saline
.. Heparin bridging of anticoagulated patients is
III A
. not recommended.650,689
leads to dilution of possible contaminants and eliminates debris from . Permanent pacemaker implantation is not recommended
the wound before closure. 683,684 Addition of antibiotics to the rinsing
in patients with fever. Pacemaker implantation should be
. III B
ESC 2021
solution does not reduce the risk of device infections.683 delayed until the patient
The World-wide Randomized Antibiotic Envelope Infection
.
. has been afebrile for at least 24 h.638,639
Prevention Trial (WRAP-IT study) investigated the effect of an .
absorbable antibiotic-eluting envelope on the development of post-
..
operative CIED infections. A total of 6983 patients undergoing a CIED
. CIED = cardiovascular implantable electronic device.

a
.
pocket revision, generator replacement, or system upgrade, or initial b
Level of evidence.
implantation of a CRT-D were randomly assigned, in a 1:1 ratio, to ..
receive the antibiotic envelope or not. The rate of CIED infection in
.
.
patients who had the antibacterial envelope was 0.7% vs. 1.2% in the .
..
control group (HR 0.6, 95% CI 0.36 0.98; — P = 0.04). No effect on
685
infection rate was observed in the subgroup with pacemakers.685 ..

10 Complications of cardiac
Considering cost-effectiveness aspects, the use of an antibiotic envelope . pacing and cardiac
may be considered in pacemaker patients at high risk for CIED infections. resynchronization therapy
Risk factors to be considered in this context are end-stage renal disease, ...
chronic obstructive pulmonary disease, diabetes melli- tus, and device 10.1 General complications
replacement, revision, or upgrade procedures.638 .. Cardiac pacing and CRT are associated with a substantial risk of com-
.. plications (Table 12), most of which occur in the perioperative
. phase,429,690 but a sizable risk remains during long-term follow-up.691
Recommendations regarding device implantations
and peri-operative management ... Complication rates after dual-chamber pacemaker implantation in
. . the MOST trial were 4.8% at 30 days, 5.5% at 90 days, and 7.5% at 3
years.692 However, ‘real-life’ data indicate a higher risk.690,693 In a
.
recent study of >81 000 patients receiving de novo CIED implanta-
.. tions, major complications occurred in 8.2% within 90 days of hospi-
Administration of pre-operative antibiotic pro- .
tal discharge.694 Mortality in hospital (0.5%) and within 30 days (0.8%)
phylaxis within 1 h of skin incision is recom-
I A .. was low.
mended to reduce risk of CIED infection.641,643.686 .
Complication risks generally increase with the complexity of the
.. device and are more common in the context of a device upgrade or
Chlorhexidine—alcohol instead of povidone- iodine— .
lead revisions compared with de novo implantation. In a Danish
.. population-based cohort study, complications were observed in
alcohol should be considered for skin IIa B
antisepsis.647,648
.
For venous access, the cephalic or axillary vein
IIa B . 9.9% of patients at first device implantation and in 14.8% upon
upgrade or lead revision. 354 Procedures limited to replacement of
should be considered as first choice.658,659 .
the generator had a lower complication risk (5.9%). In the prospec-
.. tive REPLACE registry, a similar proportion (4%) of complication
To confirm target ventricular lead position, use of
multiple fluoroscopic views should be IIa C
considered. ... risks in the setting of generator replacement was reported, but much
For implantation of coronary sinus leads, quadri- . higher risks were found in695those with one or more additional lead
polar leads should be considered as first IIa C .. insertions (up to 15.3%). Accordingly, major complications were
choice.665,666,687 . particularly more common with CRT upgrade procedures, 339 a finding
Rinsing the device pocket with normal saline solution
. that was corroborated in a large US inpatient cohort and a pro-
.
before wound closure should be IIa C . spective Italian observational study. The rate of procedural com-
696
considered.683,684 . plications also increases with comorbidity burden.697

.
In patients undergoing a reintervention CIED . Thus, careful shared decision-making is warranted when considering
procedure, the use of an antibiotic-eluting envelope IIb B . upgrades to more complex systems. This also applies to prophylactic
.
may be considered.685,688 . replacement of recalled CIED generators and leads, a scenario in which
Pacing of the mid-ventricular septum may be . procedural risks should be carefully weighed against the risks associated with
.
considered in patients at high risk of perforation (e.g. . device or lead failure.698
elderly, previous perforation, low body
IIb C . Overall, complication rates are closely linked to individual and
.
mass index, women).420,674 . centre implantation volumes.429,658,693 Complications were increased by
. 60% in inexperienced operators who had performed fewer than
Continued
ESC Guidelines 65
.
25 implantations.429 Data from a large national quality assurance pro- passive fixation RA lead (OR 2.2) were the most important risk
.. predictors.
gramme for pacemakers and CRT-P showed that the annual hospital .
implantation volume was inversely related to complication rates, with A meta-analysis of 25 CRT trials noted mechanical complications
.. in 3.2% (including coronary sinus dissection or perforation, pericar-
the greatest difference observed between the lowest (1 - 50 .
dial effusion or tamponade, pneumothorax, and haemothorax), other
implantations/year) and the second lowest quintile (51—90 implanta-
.. lead problems in 6.2%, and infections in 1.4%. Peri-implantation
tions/year).699 Furthermore, emergency and out-of-hours procedures .
.. deaths occurred in 0.3%.
369
are associated with increased complication rates. 354 These data clearly
suggest that CIED procedures should be performed by operators and .
centres with a sufficient procedural volume. . 10.2.2 Haematoma
.. Pocket haematoma is a frequent complication (2.1 9.5%), which can
. usually be managed conservatively. Evacuation, required—in 0.3—2%
10.2 Specific complications .. of cases, is associated with an 15 times increased risk of infection.639
. Moreover, patients developing ~ pocket haematoma stay in hospital

10.2.1 Lead complications
.. longer and have a higher in-hospital mortality rate (2.0% vs. 0.7%).724
Pacemaker leads are a frequent source of complications due to dis- .
lodgement, insulation defects, lead fractures, and sensing or threshold . Hence, appropriate precautions are critical, and reoperation should
. be limited to patients with severe pain, persistent bleeding, distension
problems. In a Danish cohort, lead-related interventions (2.4%) were
the most common major complication. 354
LV leads have a particular . of the suture line, and imminent skin necrosis. Many haematomas can
propensity for complications700 such as dislodgement and coronary vein . be avoided by careful haemostasis and optimal management of anti-
dissection or perforation. In a nationwide registry, LV leads (4.3%) . platelet and anticoagulant drugs.
.
were more commonly associated with complications compared with
RA leads (2.3%) and RV leads (2.2%).
429
A CRT device (OR 3.3) and
.. 10.2.3 Infection
.
.. Infection is one of the most worrying CIED complications, causing
significant morbidity, mortality, and healthcare costs. 725,726
Infection
Table 12 Complications of pacemaker and .
rates are higher with device replacement or upgrade procedures,695
cardiac resynchronization therapy implantation .. as well as CRT or ICD implants compared with simple pacemaker
.
implantation.727 Olsen et al.702 reported the lifetime risk of system
Incidence of complications after CIED therapy %
.. infection in patients with: a pacemaker (1.19%), ICD (1.91%), CRT-P
Lead-related reintervention, ,,,, (including dislodgement, malposition, subclavian crush syndrome, etc.)
.. (2.18%), and CRT-D (3.35%). Specifically, patients undergoing reop-
,
1.0—5.9
CIED-related infections, <12 months,,,,,,
Superficial infection Pocket infections Systemic infections . erations, those with a previous device-related infection, men, and
CIED-related infections, >12 months— .. younger patients had a significantly higher risk of infection.
Pocket infections Systemic infections, 0.7—1.7 .
Similar findings have been reported in a large cohort of patients
Pneumothorax,,,,,,
. . receiving an ICD, with infection rates of 1.4% for single, 1.5% for dual,
Haemothorax Brachial plexus injury
Cardiac perforation,,,,
1.2 . and 2.0% for biventricular ICDs.728 In addition, early reintervention
.. (OR 2.70), previous valvular surgery (OR 1.53), reimplantation (OR
0.4
Coronary sinus dissection/perforation, Revision due to pain/discomfort,
0.5
Diaphragmatic stimulation requiring reintervention,,, Haematoma354,,,,,,,, .
1.1—4.6
Tricuspid regurgitation— Pacemaker syndrome,,
1.3 . . 1.35),
1.22),
renal failure on dialysis (OR 1.34), chronic lung disease (OR
cerebrovascular disease (OR 1.17), and warfarin use (OR 1.16)
0.5—1.2 . were associated with an increased risk of infection.702 Infections also
Generator/lead problem,,
Deep venous thrombosis (acute or chronic),,
Any complication,,,,,,, 0.5—2.2 .. occur more frequently with use of temporary pacing or other proce-
Mortality (<30 days), 0.1 .
dures before implantation (OR 2.5 and 5.8, respectively), early rein-
<0.1 .. terventions (OR 15), and lack of antibiotic prophylaxis (OR
0.3—0.7
.
0.7—2.1 . 2.5).639,729
. Further comprehensive information on how to prevent, diagnose,
0.1—0.4 .
and treat CIED infections has been provided in a recent EHRA con-
0.5—5 .. sensus document.642
2.1—5.3 .
5—15 .
.
1—20 . 10.2.4 Tricuspid valve interference
0.1—1.5
. CIED leads may interfere with tricuspid valve function intra-
.
0.1—2.6 . operatively by causing damage to the tricuspid valve leaflets or the
5—15
. subvalvular apparatus, or chronically after operation or lead extrac-
.
0.8—1.4 .. tion. This damage has been linked to haemodynamic deterioration
. and an adverse clinical outcome. In fact, moderate to severe tricus-
730
pid regurgitation is generally associated with excess mortality731,732

.. and occurs at a significantly higher rate in CIED patients.733 The prev-
.. alence of significant tricuspid regurgitation (defined as grade 2 or
ESC 2021
.
CIED = cardiovascular implantable electronic device. . above) following CIED implantation varies between 10% and 39%.
. Most studies attribute a greater harm with ICD leads and in the
66 ESC Guidelines
.
decision-making. The integrated-care approach has its origins in the
presence of multiple RV leads. 45,46,49,445,642,685,697,709,728,730—732 The issue .. chronic care model developed by Wagner et al.,740 and has the
of lead interference with bioprosthetic tricuspid valves or after .
potential to improve clinical and patient outcomes in arrhythmia
annuloplasty or repair is debated. Furthermore, there is no firm evidence .. management741—743 (see section 12). Relevant specialists to be
supporting that pacing-induced RV dyssynchrony significantly contributes .
included in the interdisciplinary team are included according to the
to tricuspid regurgitation. A recent study randomizing 63 patients to .. patient’s needs and local service availability (Figure 13).
pacing lead positions in the RV apex, RVS, or LV pacing via the coronary .
sinus did not affect the development of tricuspid regurgitation.734 The .
.
diagnostic work-up of CIED lead-related tricuspid regurgitation based on .
clinical, haemodynamic, and in particular echocardiographic (2D, 3D, and .
. 11.1 Magnetic resonance imaging in
Doppler) evaluation is often challenging.735 While clear guidance for .
patients with implanted cardiac devices
the management of tricuspid regurgitation in the presence of CIED leads is ..
still lacking, a high level of clinical suspicion is required, not discounting MRI is a frequent requirement in patients with implanted pacemakers.
the possibility that worsening HF may be a consequence of the mechanical .. It may cause adverse effects such as inappropriate device function
.

effect on tricuspid leaflet mobility or coaptation.730 General treatment due to device reset or sensing problems, interaction with the mag-
options include medical therapy aiming to relieve congestion and lead .. netic reed switch, induction of currents resulting in myocardial cap-
.
extraction with careful replacement, or use of alternative pacing ture, heating at the lead tip with changes in sensing or capture
strategies, such as LV pacing via the coronary sinus or epicardial
.. thresholds, or lead perforation. Risk factors for adverse events with
.
leads. However, transvenous lead extraction itself carries a risk of MRIs are listed in Supplementary Table 19.
damage to the tricuspid valve and, hence, worsening tricuspid
.. Currently, most manufacturers propose devices that are MRI con-
.
regurgitation. While leadless pacing eliminates the need for transvalvular ditional. It is the entire CIED system (i.e. combination of generator
leads, it may still negatively affect tricuspid valve function, potentially
.. and leads, which need to be from the same manufacturer) that deter-
.
due to mechanical interference and abnormal electrical and mechanical ven- mines MRI conditionality, and not the individual elements. MRI scans
.. may be limited to 1.5 T and a whole-body specific absorption rate
tricular activation.736 Indications for surgical valve repair or replacement .
in the context of CIED-induced tricuspid regurgitation follow current (SAR) <2 W/kg (head SAR <3.2 W/kg), but some models allow 3 T
.. and up to 4 W/kg whole-body SAR. The manufacturer may specify an
recommendations based on the presence of symptoms, severity of .
tricuspid regurgitation, and RV function. When considering tricuspid exemption period (usually 6 weeks) after implantation, but it may be
valve surgery, management of the RV lead should follow the .. reasonable to perform an MRI scan earlier if clinically warranted.
recommendations outlined in section 8.2.3.737 Methods for percutaneous .. There is ample evidence that MRIs can be performed safely in non-
tricuspid repair have recently gained major attention, but evidence in . conditional pacemakers, as long as a number of precautions are tak-
favour of such interventions in the context of lead-related tricuspid
. en.744—746 In 2017, the Heart Rhythm Society published an expert
regurgitation is still limited.738 .. consensus statement on MRIs in patients with CIEDs, which was
. . developed with and endorsed by a number of associations including
. the EHRA and several radiological associations.745 For detailed rec-
10.2.5 Other .
Increased complication risks have been observed in women (mainly
. ommendations on appropriate workflow and programming, see
.
pneumothorax and cardiac perforation) and in those with a low body
354,739 . Supplementary
.
Tables 20, 21, and 22 and Supplementary Figure 2.
. When leads are connected to a generator, the latter component
absorbs part of the energy and dissipates heat via the large surface
mass index. Patients older than 80 years were also found to .
have a lower risk of lead-related reinterventions compared with . area. Abandoned transvenous leads are prone to heating of the lead
.
patients aged 60—79 years (1.0% vs. 3.1%).354 tip by ~10◦C as shown by an in vitro study.747 It is, however, difficult
Finally, suboptimal atrioventricular synchrony may lead to the .. to extrapolate results from experimental models to the in vivo setting.
.
pacemaker syndrome, giving rise to cannon waves caused by simultaneous No adverse events were reported from four series totalling 125
atrial and ventricular contractions and symptoms of fatigue, dizziness, and .. patients with abandoned transvenous leads.748—751 The largest study
.
hypotension (see section 5). Long-term RV pacing induces a reported 80 patients749 who underwent 97 scans (including the
dyssynchronous ventricular activation pattern that may promote .. thoracic region), limited to an SAR <1.5 W/kg. Half of the cohort had
.
progressive LV dysfunction and clinical HF. Strategies to avoid and measurement of troponin levels before and after the scan, without
resolve the adverse effect of RV pacing have been discussed above
.. any significant changes. Therefore, 1.5 T MRI scans (limited to SAR
.
(section 6). . <1.5 W/kg) may be considered in selected patients, taking into
. account the risk—benefit ratio, particularly if the scans are extra-
.. thoracic and patients are not pacemaker dependent.
11 Management considerations . Epicardial leads connected to a generator result in a 10◦C increase
.. in temperature during in vitro testing, and by as much as 77◦C with
. abandoned epicardial
Integrated management of pacemaker and CRT patients, delivered by . leads.747 Data from 23 patients with epicardial
749—752
an interdisciplinary team in partnership with the patient and family, . leads have been reported, including 14 patients with aban-
should be adopted in order to deliver comprehensive treatment across . doned epicardial leads,749—751 without any adverse effect of MRI
the continuum of healthcare (see section 12). The integrated- care .. scans. Given the paucity of data related to safety in patients with epi-
approach is indicated in pacemaker and CRT patients to ensure a patient- .
centred approach and patient involvement in shared . cardial leads, lead adaptors/extenders, or damaged leads, recommen-
. dations cannot be made at this stage regarding MRIs in these patients.
ESC Guidelines 67
Integrated management of patients with pacemaker and CRT

Emphasising patient-centred care and shared decision making
Ensure optimal device

Pre-implant assessment and adherence to
selection and implantation
low-risk implantation surgery
Provide physiological pacing Structured follow-up with tailored device programming

and symptom control (remote monitoring and in-office)
Management of underlying Including stroke prevention in atrial fibrillation and

cardiac disease heart failure optimization
Patient education/
Including personal goals and/or action plan
self-management
Healthcare professional Including certifications for optimal quality

education in relevant specialities
Smoking cessation, alcohol, dietary

Lifestyle modification and exercise interventions
Psychosocial management
Psychological assessment and/or treatment
and support
Strategies to promote Educate patients about what to expect from the device and
medical adherence medical treatment using available technologies
Including different disciplines when relevant;

Multidisciplinary
electrophysiologists, cardiologists, nurses, allied professionals,
team approach
psychologist, dietician and pharmacist
Clear communication
between primary and
Including timely end-of-life discussions
secondary care
Figure 13 Integrated management of patients with pacemaker and cardiac resynchronization therapy. CRT = cardiac resynchronization therapy.
.
A flowchart summarizing the management of patients with a pace-
Evaluation must be made on a case by case basis by balancing the
.. maker undergoing MRI is shown in Figure 14.
advantages of MRI with the potential risks and availability of alternative .
There is evidence indicating that 1.5 T MRIs may be performed in
..
imaging methods and using shared decision-making.
In general, MRIs should always be performed in the context of a patients with temporary epicardial wires756 as well as with transve-
rigorously applied standardized institutional workflow, following the .. nous pacemaker active fixation leads implanted to externalized pace-
appropriate conditions of use (including programming).744,746,753—755 . makers used for temporary pacing.751
.
68 ESC Guidelines
Evaluating magnetic resonance imaging in pacemaker patients
Y MRI-conditional system
Past exemption period after implementation Alternative imaging mode available

Strongly reconsider MRIa Presence of epicardial leads,
Yor connected fractured leads, or lead adaptors/extenders
Y N Y N
Presence of abandoned leads
N
Y
MRI following conditions of use and standardized workflow MRI following appropriate standardized
MRI onlyworkflow
if benefits(Class
outweigh
IIa) risk (max. 1.5T,
(Class I) MRI Alternative imaging technique SAR < 1.5 W/Kg)
(Class IIb)
(Class IIa)
Figure 14 Flowchart for evaluating magnetic resonance imaging in pacemaker patients. MRI = magnetic resonance imaging; SAR = specific absorption rate. aConsider
only if there is no imaging alternative and the result of the test is crucial for applying life-saving therapies for the patient.
.
Recommendations for performing magnetic resonance .
11.2 Radiation therapy in pacemaker
imaging in pacemaker patients ..
patients
Recommendations Classa Levelb .. An increasing number of patients with CIEDs are referred for radio-
.
therapy,757 with a reported annual rate of 4.33 treatments per 100
In patients with MRI-conditional pacemaker sys- .. 000 person-years. Radiotherapy uses high-energy ionizing radiation
tems,c MRIs can be performed safely following I A .
including X-rays, gamma rays, and charged particles, which might
the manufacturer’s instructions.745,753—755 .. cause software and hardware errors in CIEDs, especially when pho-
In patients with non-MRI-conditional pacemaker .
systems, MRI should be considered if no alternative . ton radiation beam energy exceeds 6 758,759
10—MV, and the radiation dose
imaging mode is available and if no epicardial leads, IIa B . to the device is high (>2—10 Gy). Hard errors are rare, and are
most often due to direct irradiation to the device. This can cause irre-
abandoned or damaged leads, or lead .. versible hardware damage, requiring device replacement. Soft errors
.. are more common, and are associated with secondary neutron pro-
adaptors/extenders are present.744,746
MRI may be considered in pacemaker patients with . duction by irradiation.760 Such errors typically include resets of the
ESC 2021
.. device without causing structural damage, and can be solved without

abandoned transvenous leads if no alterna- IIb C
tive imaging modality is available.748—751 . replacement.757,759
MRI = magnetic resonance imaging. .. Electromagnetic interference during radiotherapy can cause
a
. oversensing, although this very rarely occurs in clinical practice.760
b
Level of evidence. .. Device relocation before radiotherapy is very rarely recom-
c
Combination of MRI-conditional generator and lead(s) from the same .
manufacturer. mended, and only if the current location of the device interferes
ESC Guidelines 69
.
with adequate tumour treatment or in very selected high-risk prophylactically764,765
when the need for pacing is anticipated (e.g. after car-
cases.
757,761
. diac surgery). Modalities for emergency temporary pacing
According to published recommendations for CIED .
patients,
745,759,762
the risk of malfunction (or adverse events) is higher .. include transvenous, epicardial, and transcutaneous approaches. The
transvenous approach often requires fluoroscopic guidance, although
in the following situations for pacemaker patients: .
echo-guided placement is also feasible.766 Balloon-tipped floating
.
With photon radiation applying energy >6—10 MV: the risk of mal- . catheters are easier to insert, more stable, and safer than semi-rigid
•
functions (usually soft errors) is due to secondary neutron pro- catheters.767,768 Patients who undergo transvenous temporary car-
duction, is not associated with the target zone, and cannot be .. diac pacing have a high risk for procedure-related complications (e.g.
shielded. .. cardiac perforation, bleeding, malfunction, arrhythmias, and acciden-
With a cumulative dose reaching the device >2 Gy (moderate risk) or . tal electrode displacement) and complications related to immobiliza-
..
•
>10 Gy (high-risk): the dose reaching the pacemaker can be esti- tion (e.g. infection, delirium, and thrombotic events). 764,765,769—775 In
mated before and measured during treatment, is correlated with . addition, previous temporary pacing is associated with an increased
. 639,641
the target zone, and can be shielded.
. risk of permanent pacemaker infection. A percutaneous trans-

• If the patient is pacemaker dependent. . venous active fixation lead connected to an external device is safer
.. and more comfortable for patients requiring prolonged temporary
Appropriate decision-making is suggested in Figure 15. .
pacing.776—779 There are no good data that support either a jugular
Experience with proton radiation therapy in CIED patients is limited. .. or axillar/subclavian access; however, intrathoracic subclavian punc-
However, compared with photon irradiation, this radiation modality .
ture should be avoided to reduce the risk of pneumothorax. A jugular
produces more secondary neutrons, which may affect the .. access should be preferred if implantation of a permanent ipsilateral
risk of device errors or failure.
763
Currently, no specific guidance can . device is planned. In selected cases where fast and efficient pacing is
be given regarding proton radiation therapy in CIED patients. . needed, a femoral access may be used. Owing to instability of passive
.
The specific recommendations of CIED manufacturers are leads placed through the femoral vein and immobilization of the
reported in Supplementary Table 23. .. patient, the duration of this approach should be as short as possible
.
until bradycardia has resolved or a more permanent solution has
.. been established. The epicardial approach is mostly used following
11.3 Temporary pacing .
cardiac surgery. Removal of these leads is associated with complica-
Temporary pacing can provide electronic cardiac stimulation in .. tions such as bleeding and tamponade.780—782 Transcutaneous tem-
patients with acute life-threatening bradycardia or can be placed .
. porary pacing is a fast and effective non-invasive method, but is not as
Pacemaker management in patients undergoing radiation therapy
Device-specific treatment planning considerations:a

Avoid direct radiation Limit cumulative dose
Reduce beam energy to minimize direct neutron radiation
Comprehensive PM evaluation before radiation therapy
Neutron-producing treatment ( > 10 MV)
Y N
Weekly comprehensive PM evaluation Comprehensive PM evaluation after end of radiation therapy
Figure 15 Pacemaker management during radiation therapy ECG = electrocardiographic; PM = pacemaker. aRelocation of the device, continuous ECG monitoring,
reprogramming, or magnet application are very rarely indicated.
70 ESC Guidelines
.
stable as the transvenous approach, and is limited by the need for 11.4 Peri-operative management in
..
continuous sedation.783 This modality should only be used in emergency
. patients with cardiovascular implantable
settings or when no other option is available, and under close
.
electronic devices
haemodynamic monitoring. 784 Before starting temporary pacing,
chronotropic medication should be considered, taking into account side . Advisory documents to help manage patients with CIEDs in the peri-
.
effects, contraindications, and interactions with other operative period have been issued by several professional societ-
medication. .. ies.
786—789
Supplementary Table 24 summarizes general
.
recommendations on the management of these patients.
This Task Force concludes that temporary transvenous pacing should .
be avoided if possible; when it is required, the lead should remain in • Electromagnetic interference (EMI) may induce oversensing
situ for as short a time as possible. The use of temporary pacing should
.. (more likely with unipolar leads), activation of rate-responsive
be limited to the emergency treatment of patients with severe .. sensors, device resetting, or other damage. The most common
bradyarrhythmia causing syncope and/or haemodynamic compromise, and
. source of EMI is electrocautery, although it is rare during bipolar
to cases in whom those bradyarrhythmias are anticipated. Temporary .. electrocautery >5 cm from the CIED and monopolar electro-
.

transvenous pacing is recommended when pacing indications are cautery below the umbilicus.790 To reduce the risk of EMI,
reversible, such as in the context of antiarrhythmic drug use, myocardial .. monopolar electrocautery should be applied in short (<5 s)
.
ischaemia, myocarditis, electrolyte disturbances, toxic exposure, after pulses, with the skin patches away from the area of the device.
cardiac surgery, or as a bridge to permanent pacemaker implantation .. Other sources of EMI include radiofrequency procedures, nerve
.
when this procedure is not immediately available or possible due to stimulators, and other electronic devices.
concomitant infection. Lastly, if a patient meets the permanent .. • The peri-operative strategy should be tailored based on the indi-
pacemaker implantation criteria, this proce-
.
vidual 786—789
needs and values of patients, procedure, and
dure should be performed promptly. .. device. Most procedures will not require any interven-
.
tion.791 In pacemaker-dependent patients, a magnet should be
.. applied during delivery of diathermy pulses, or, if EMI is likely to
Recommendations regarding temporary cardiac pacing .
occur or magnet stability cannot be guaranteed, the device
.. should be reprogrammed to an asynchronous mode (VOO/
DOO). The response to magnet application may differ between
Temporary transvenous pacing is recommended in .. device manufactures. CIEDs with a rate-responsive function
.
cases of haemodynamic-compromising bra- using an active sensor may also require magnet application or
dyarrhythmia refractory to intravenous chrono-
I C .. disabling of this function to prevent inappropriate rapid pacing.
.
tropic drugs.764,765 Post-operative CIED interrogation is recommended if malfunc-
Transcutaneous pacing should be considered in cases .. tion is suspected or if the device has been exposed to strong
of haemodynamic-compromising bradyarrhythmia
IIa C .. EMI.
when temporary transvenous pacing is .
not possible or available.783—785
.
. 11.5 Cardiovascular implantable
Temporary transvenous pacing should be con-
.. electronic devices and sports activity
sidered when immediate pacing is indicated and .
Regular exercise is strongly recommended for prevention of cardio-
pacing indications are expected to be reversible, such
IIa C .. vascular disease.792—795 Restrictions to patients with a pacemaker,
as in the context of myocardial ischaemia, .
where appropriate, are motivated by underlying cardiovascular dis-
myocarditis, electrolyte disturbances, toxic .. ease. Therefore, it is important to address issues of exercise and
exposure, or after cardiac surgery.771—773 .
sports participation with all pacemaker patients as part of a shared
Temporary transvenous pacing should be considered as .. decision-making process. Comprehensive recommendations for
a bridge to permanent pacemaker implantation when this .
physical activity in patients with cardiovascular disease have been
procedure is not immediately available or possible due IIa C
.. published.792,796
..
to concomitant
infection.771—773
There is consensus that contact sports (e.g. rugby or martial arts)
. should be avoided so as not to risk damage of device components or
..
For long-term temporary transvenous pacing, an active
haematoma at the implantation site. For participation in sports such
fixation lead inserted through the skin and
IIa C . as football, basketball, or baseball, special protective shields are rec-
ESC 2021
..
connected to an external pacemaker should be
ommended to reduce the risk of trauma to the device. Sport inter-
considered.641,776,777,779 . ests and right or left arm dominance should be considered when
.. selecting the implantation site, and submuscular placement can be
a
b
Level of evidence. considered to reduce the risk of impact. A lateral vascular access is
ESC Guidelines 71
.
preferable to prevent the risk of subclavian crush of the lead associated the device should be treated as a single entity, with programming tail-
with arm exercises above shoulder level. It is recommended to abstain
.. ored to meet the patient’s needs. The goals are to (i) ensure patient
.
from vigorous exercise and ipsilateral arm exercise for 4—6 safety; (ii) provide physiological pacing; (iii) improve patient quality of
.. life; (iv) improve patient clinical management; and (v) maximize device
weeks post-device implantation. .
Of note, recommendations regarding sports activity in patients with longevity. Requirement for follow-up of the underlying cardiac disease
.. should not be overlooked. In addition to the technical check and opti-
an ICD differ from those in pacemaker patients.797,798 .
mization of programming, proper counselling of the patient and his/her
.. family are necessary to meet these goals. The frequency of follow-up
.
11.6 When pacing is no longer indicated depends on the type of device (CRT and HBP are associated with
Different management options are available in patients with implanted .. more clinical or technical issues and need closer surveillance) and
pacemaker systems in whom pacing is no longer indicated: .. whether they are on remote device management (Table 13).
.
. • Remote device management includes remote follow-up with full
Leave pacemaker generator and pacemaker leads in situ. .
remote device interrogation at scheduled intervals (to replace

..
Explant pacemaker generator and abandon leads.
in-office visits), remote monitoring with unscheduled transmission
Explant pacemaker generator and leads. .
The feasibility of option 1 depends on the end-of-life behaviour of the of pre-defined alert events, and patient-initiated follow-up with
.. unscheduled interrogations as a result of a patient experiencing a
implanted generator, which is manufacturer dependent, and may be erratic .
and lead to complications in rare cases.799 Option 1 is the preferred real or perceived clinical event. Most studies have focused on
.. patients with ICDs and CRT-Ds, and have shown a significant
approach to selected frail and elderly patients. .
Option 2 comes with a low procedural risk but may be associated with reduction in delay between event detection/clinical decision, and
.. fewer inappropriate shocks.804 Two randomized non-inferiority
the disadvantages of lead abandonment, including future MRI. Especially .
trials with single-chamber805 or DDD805,806 pacemakers (no
..
in young patients, the potential necessary future requirement for lead
extraction of abandoned leads due to infection and the associated elevated CRT-P) showed that in-office visits can be safely spaced to
procedural risk due to longer duration of implantation procedure need to .. 18 —24 month intervals if patients are on remote monitoring
be taken into account. Several studies have shown increased complexity,
. with devices having automatic threshold algorithms. Spacing of
lower procedural success, and higher .. scheduled in-office visits is particularly convenient for elderly
complication rates of lead extraction procedures of abandoned
. patients with limited mobility, but also for young or midlle-aged
leads.800—803 .. patients with full-time jobs, family commitments, etc., and in spe-
.
Option 3 comes with the highest initial procedural risk, but elimi- cific situations (e.g. to avoid exposure during a pandemic).
nates all possibilities of future device-related complications. When .. • It is important to conduct remote device management with an
. appropriate set-up that delivers a structured approach to
performed in specialized high-volume centres with current extraction
tools, lead extraction procedures can be carried out with high complete .. remote follow-up and a timely response to alerts. Third-party
.
procedural success rates and low complication rates.802 providers can be useful to triage alerts and assist with this
This approach may be appropriate for the combination of a young . task. 807 Importantly, compliance with the General Data
.
patient, low risk for extraction, and an experienced extractor. .
Protection Regulation should be respected, as outlined in a
As part of a patient-centred approach, the decision in such situations .. recent ESC regulatory affairs/EHRA document.808
has to be based on an individual risk—benefit analysis in a shared decision- .
making process together with the patient and his/her carers.
.
.
This includes providing sufficient information to achieve an informed .
.
decision-making. Important factors to take into consideration are patient Table 13 Frequency of follow-up for routine pacemaker
age, patient condition, comorbidities, pacemaker system, lead implant .. and cardiac resynchronization therapy, either in person
. alone or combined with remote device management
duration, and the patient’s life expectancy. .
. In-office only In-office 1 remote
Recommendation when pacing is no longer indicated .
. All devices Within 72 h and 2—12 In-office within 72 h and 2—
. weeks after 12 weeks after
Recommendation Classa Levelb .
implantation implantation
.
When pacing is no longer indicated, the decision on . CRT-P or Every 6 months Remote every 6 months and
management strategy should be based on an individual . HBP in-office every 12 monthsa
I C .
ESC 2021
risk—benefit analysis in a shared deci- . Single/dual- Every 12 months then every Remote every 6 months and in-
.
ESC 2021
sion-making process together with the patient. chamber 3 - 6 months at signs of battery office every 18 - 24
.
. depletion monthsa
a
b
Level of evidence. . CRT-P = cardiac resynchronization therapy-pacemaker; HBP = His bundle
. pacing.
. a
Remote follow-up can only replace in-office visits if automatic capture threshold
. algorithms perform accurately (and are previously verified in-office).
11.7 Device follow-up . Note: additional in-office follow-up may be required (e.g. to verify the clinical
General principles of follow-up are covered here, as in-depth recom- .
. effect of modification of programming, or for follow-up a technical issue).
mendations are beyond the scope of this document. The patient and . Remote monitoring (i.e. of pre-defined alerts) should be implemented in all
. instances along with remote follow-ups.
72 ESC Guidelines
.
patient to make a balanced decision.824—826 Choosing the appropri-
Recommendations for pacemaker and cardiac
resynchronization therapy-pacemaker follow-up
.. ate educational material is an important component of promoting
.
the learning process of patients.827—830 Based on the patient’s needs
Recommendations Class a
Level b .. and preferences, the education should be performed before implan-
.
tation, at discharge, and during follow-up using a person-centred
Remote device management is recommended to .. approach (Table 14). All patients should receive a brochure provided
reduce the number of in-office follow-ups in .
by the manufacturer as well as a device identification card before
patients with pacemakers who have difficulties to
I A
.. discharge.
attend in-office visits (e.g. due to reduced mobility .
This Task Force emphasizes the importance of patient-centred
or other commitments, or according to .. care and shared decision-making between patients and clinicians. The
patient preference).805,806,809 .
decision to implant a pacemaker/CRT should be based on the best
Remote monitoring is recommended in the case of a .
. available evidence with consideration of the individual risk—benefits
..
device component that has been recalled or is on
of each option, the patient’s preferences, and goals of care. The con-
advisory, to enable early detection of actionable .

I C sultation should include whether the patient is a good candidate for
..
events in patients, particularly those who are at
pacemaker/CRT treatment, and possible alternative treatment
increased risk (e.g. in the case of . options should be discussed in a way that can be understood by
..
pacemaker dependency).
everyone involved in the discussion. Using the principles of shared
In-office routine follow-up of single- and dual- chamber . decision-making and informed consent/refusal, patients with
pacemakers may be spaced by up to 24 months in
IIa A .. decision-making capacity have the right to refuse pacemaker therapy,
patients on remote device . even if they are pacemaker dependent.
management.805,806 .
Remote device management of pacemakers should be
.
.
considered in order to provide earlier detection of
. Recommendation regarding patient-centred care and
clinical problems (e.g. arrhythmias) or technical IIa B . shared decision-making in cardiac pacing and cardiac
.
ESC 2021
issues (e.g. lead failure or battery resynchronization therapy

.
depletion).806,810 .
a
b
Level of evidence. . In patients considered for pacemaker or CRT, the
.
. decision should be based on the best available
. evidence with consideration of individual risk—
.
12 Patient-centred care and . benefits of each option, the patient’s pref-
. erences, and goals of care, and it is recom- I C
.
shared decision-making in cardiac . mended to follow an integrated care approach and
.
pacing and cardiac use the principles of patient-centred care and shared
ESC 2021
.
. decision-making in the
resynchronization therapy . consultation.831—836
..
Providing patient-centred care is a holistic process that emphasizes . CRT = cardiac resynchronization therapy.
a
partnerships in health between patient and clinician, acknowledging the . b

Level of evidence.
patient’s needs, beliefs, expectations, healthcare preferences, goals, and ..
values.811—813 In patient-centred care, the focus is on .
shared decision-making, accepting that patients generally prefer to
.
.
take an active role in decisions about their health. 814,815 This approach .
has been shown to improve health outcomes and healthcare
..
experiences.814,816 Clinicians have a duty to define and explain the . 13 Quality indicators
.
healthcare problem and make recommendations about the best available .
Quality indicators are tools that may be used to evaluate care quality,
evidence across all available options at the time, including no treatment, .. including that of processes of care and clinical outcomes.837 They
while ensuring that the patient’s values and preferences .
may also serve as a mechanism for enhancing adherence to guideline
are considered (Figure 16).817—820 .. recommendations through quality assurance endeavours and bench-
Decision aids, such as written information and/or the use of inter- .
marking of care providers.838 As such, the role of quality indicators in
active websites or web-based applications, can complement the clinicians’ .. driving quality improvement is increasingly recognized and attracts
counselling and thus facilitate shared decision-making. 822 When decision aids .
interest from healthcare authorities, professional organizations,
are used, patients feel more knowledgeable, have more accurate risk .. payers, and the public.839
perceptions, and take a more active part in the decision.823 In patients .
The ESC recognizes the need for measuring and reporting quality
with poor language or literacy skills, as well as in those with cognitive
.. and outcomes of cardiovascular care. One aspect of this is the devel-
impairment, communication strategies, including the help of a qualified
interpreter, is recommended, as this helps the .. opment and implementation of quality indicators for cardiovascular
. disease. The methodology by which the ESC quality indicators are
.
ESC Guidelines 73
Seek the patient’s participation
Define and explain the healthcare problem and communicate that a choice exists. Discuss possible alternative treatment options, including that patients with decision-makin
The consultation should be discussed in a way that can be understood by everyone involved in the discussion.
Encourage the patient to become involved in the consultation and invite family to participate.
Help the patient explore and compare treatment options
Provide an overview of the implantation process, and address all aspects of how the device works and the conditions it treats.
Discuss the benefits and risks with each option, including potential complications and treatment refusal.

Access the patient’s values and preferences
Supplement the counselling with different decision aids to facilitate SDM. In patients with poor language skills, cognitive impairment, or low health literacy, a variety of co
Take into account the patient´s preferences and goals of care, and what matters most to the patient.
Reach a decision with the patient
Make evidence based recommendations with consideration of individual risk-benefits of each option, while ensuring that the patient's beliefs, expectations, values, goals, and
Evaluate the patient’s decision
Evaluate if the decision is reasonable and understood.

Based on the patient´s needs and preferences, the education should be repeated prior discharge, and at the follow-up appointments using a person centred approach.
Figure 16 Example of shared decision-making in patients considered for pacemaker/CRT implantation. Modified from the principles of the SHARE
Approach.821CRT = Cardiac resynchronization therapy; PM = pacemaker; SDM = Shared Decision Making.
Table 14 Topics and content that may be included in patient education

Topics Content that may be included in patient education
Biophysiological Disease/condition, pacemaker indication, implantation process, possible periprocedural or late complications and malfunction,
pacemaker/CRT function and technical aspects, patient notifier (if applicable), battery replacement
Demonstration of pacemaker dummies
Functional Daily activities: mobility, physical activities and sports, possible physical restrictions (arm movements), sexual activities, driving
restrictions, travelling, wound care, medication use
Normal postoperative signs and symptoms and self-care; pain, stiffness in the shoulder, swelling or tenderness around the
pacemaker pocket
Financial Costs of treatment and rights in the social security system, insurance issues, sick leave
Emotional Possible emotions and reactions to pacemaker treatment: anxiety, worries, body image
Social Available support: telephone-based support, face-to-face group sessions, patient forums, and peer-support groups
Possible employment restrictions and electromagnetic interference
Ethical Rights and duties of patients and healthcare providers: consent/refusal of pacemaker or CRT therapy, or withdrawal of therapy
Information about registration in the national pacemaker registry
Practical Pacemaker identification card contact information to the pacemaker clinic

Follow-up routines: remotely or/and hospital based
ESC 2021
Where to get more information: reliable web-based information/sources, which organizations provide reliable health
information
CRT = cardiac resynchronization therapy.

74 ESC Guidelines
Table 15 A selection of the developed quality indicators for patients undergoing cardiovascular implantable electronic
device implantation
Quality indicator Domain
Centres providing CIED services should participate in at least one CIED registry Structural quality indicatora
Numerator: Number of centres participating in at least one registry for CIED
Centres providing CIED services should monitor and report the volume of procedures performed by individ- Structural quality indicator
ual operators on an annual basis
Numerator: Number of centres monitoring and reporting the volume of procedures performed by individual operators
Centres providing CIED services should have available resources (ambulatory ECG monitoring, echocardio- Structural quality indicator
gram) to stratify patients according to their risk for ventricular arrhythmias
Numerator: Number of centres with an available ambulatory ECG and echocardiogram service
Centres providing CIED services should have a preprocedural checklist to ensure discussion with the patient Structural quality indicator

regarding risks, benefits, and alternative treatment options
Numerator: Number of centres that have a checklist to ensure discussion with patient regarding risks, benefits, and alternative treatment options before
CIED implantation
Centres providing CIED services should have established protocols to follow-up patients within 2 - 12 weeks Structural quality indicator
following implantation
Numerator: Number of centres that have an established protocol to follow up patients within 2 - 12 weeks following CIED implantation
Proportion of patients considered for CIED implantation who receive prophylactic antibiotics 1 h before their Patient assessment
procedure
Numerator: Number of patients who receive antibiotics 1 h before their CIED implantation procedure
Denominator: Number of patients undergoing CIED implantation procedure
Annual rate of procedural complicationsb 30 days following CIED implantation Outcomes
Numerator: Number of patients who develop one or more procedural complicationsb within 30 days of CIED implantation
ESC 2021
Denominator: Number of patients undergoing CIED implantation procedure
CIED = cardiovascular implantable electronic device; ECG = electrocardiogram.

a
Structural quality indicators are binary measurements (yes/no), and thus only the numerator is defined.
b
CIED-related bleeding, pneumothorax, cardiac perforation, tamponade, pocket haematoma, lead displacement (all requiring intervention), or infection.
.
developed has been published.839 To date, a suite of quality indicators for . 14 Key messages
an initial tranche of cardiovascular conditions has been pro- .
.
duced.839,840 To facilitate quality improvement initiatives, the disease- . • In the evaluation of candidates for permanent pacemaker implan-
specific ESC quality indicators are included in corresponding ESC .. tation, a thorough and detailed pre-operative evaluation is rec-
Clinical Practice Guidelines.296,841 This is further enhanced by way of their . ommended. This should always include careful history taking and
integration in the ESC registries, such as the EurObservational Research .. physical examination, laboratory testing, documentation of the
Programme (EORP) and the European Unified Registries On Heart Care .
type of bradyarrhythmia requiring treatment, and cardiac imag-
Evaluation and Randomized Trials (EuroHeart) project.842 .. ing. In selected cases, additional tests, EPS, and/or genetic testing
A number of registries exist for patients undergoing CIED implan- .
843 are indicated.
.. • Ambulatory ECG monitoring is useful in the evaluation of
tation, providing ‘real-world’ data about the quality and outcomes .
of CIED care.702 However, there is a lack of a widely agreed set of
. patients with suspected bradycardia or cardiac conduction disorder,
quality indicators that encompasses the multifaceted nature of CIED . . to correlate rhythm disturbances with symptoms. Choice of type of
. monitoring should be based on frequency and nature of symptoms
care, and that serves as a bridge between clinical registries and
. and patient preferences.
guideline recommendations. Thus, and in parallel with the writing of . these
. • In patients with SND including those with bradycardia—
guidelines, a suite of quality indicators for patients undergoing CIED. tachycardia type of SND, when symptoms can clearly be attributed to
implantation was developed. The full list of these quality indica- . bradyarrhythmia, cardiac pacing is indicated.
. • In patients with SR and permanent or paroxysmal third- or
tors, as well as their specifications844
and development methodology,
has been published elsewhere, with a selection presented in ..
. second-degree type 2 or high-degree AVB, cardiac pacing is indicated
Table 15. . irrespective of symptoms.
ESC Guidelines 75
.
In patients with permanent AF and permanent or paroxysmal chlorhexidine — alcohol should be preferred for skin antisepsis,
•
AVB, single-lead ventricular pacing is indicated.
.. and cephalic or axillary vein access should be attempted as first
.
In patients with syncope and unexplained falls, the diagnosis should choice.
..
•
be ascertained using the available diagnostic methods before • Heparin bridging should be avoided in CIED procedures to mini-
.
pacemaker treatment is considered. mize the risk of haematoma and pocket infection.
In patients with symptomatic HF and LVEF <_35% despite OMT
.. • In patients undergoing a CIED reintervention procedure, using
• .
who are in SR and have LBBB QRS morphology, CRT is recom- an antibiotic-eluting envelope may be considered to reduce the
mended when QRS duration is >_150 ms, and should be consid- .. risk of infection.
.
ered when QRS duration is 130—149 ms. For patients with non- • In the majority of patients with a pacemaker or CRT, a well-
LBBB QRS morphology, evidence for benefit of CRT is less con- .. indicated MRI can be performed if no epicardial leads, aban-
.
vincing, especially with normal PR and QRS duration <150 ms. doned or damaged leads, or lead adaptors/extenders are
CRT should not be used in patients with HF and QRS duration .. present, and certain precautions are taken.
.
<130 ms, unless there is need for ventricular pacing. • Radiation therapy can be offered to patients with a pacemaker
..

Selection of patients for CRT based on imaging is limited to the or CRT if an individualized treatment planning and risk stratifica-
• .
measurement of LVEF, whereas the assessment of other factors, such as tion is done beforehand and the device is interrogated as recom-
extent of myocardial scar, presence of mitral regurgita- .. mended around the period of radiation therapy.
.
tion, or RV systolic function, is important to anticipate potential non- • Remote device management is valuable for earlier detection of
responders who may need additional treatments (e.g. mitral valve .. clinical problems and technical issues, and may allow longer spac-
.
intervention). ing between in-office follow-ups.
In patients with permanent AF, symptomatic HF, LVEF <_35%, .. • The principles of patient-centred care and shared decision-
•
. making should be used in the consultation both pre-operatively
and QRS >_130 ms who remain in NYHA class III or ambulatory
IV despite OMT, CRT should be considered. .. and during follow-up for patients considered for or living with a
.
For patients with AF and CRT, AVJ ablation should be consid- pacemaker or CRT.
..
•
ered when at least 90—95% effective biventricular pacing cannot be
achieved.
.
.
• For patients with high-degree AVB and an indication for cardiac .
pacing who have HFrEF (LVEF <40%), CRT rather than RV pacing is . 15 Gaps in evidence
recommended. ..
HBP may result in normal or near-normal ventricular activation, and
. Clinicians responsible for managing pacemaker and CRT candidates,
• . and patients, must frequently make treatment decisions without
..
is an attractive alternative to RV pacing. To date, no data from
adequate evidence or consensus of expert opinion. The following is a
randomized trials support that HBP is non-inferior to RV pacing .
with respect to safety and efficacy. Therefore, HBP may short list of selected, common issues that deserve to be addressed in
be considered for selected patients with AVB and LVEF >40%, who .. future clinical research.
.
are anticipated to have >20% ventricular pacing. . • Best pre-implant evaluation programme, including when to apply
• In patients offered HBP, implantation of an RV lead used as ... advanced imaging methods to ensure optimal choice of CIED for
‘backup’ for pacing should be considered individually. each patient.
HBP may correct ventricular conduction in a subset of patients with
.
• • Benefit of implementing genetic testing of CIED patients and
LBBB and may therefore be used in lieu of biventricular pacing for .. their relatives when conduction tissue disease is diagnosed.
HBP-based CRT in selected patients. .
• Whether use of rate-adaptive pacing in general is beneficial in
• In patients treated with HBP, device programming tailored to .. patients with SND.
specific requirements of HBP must be ensured. .
• Whether catheter ablation of AF without pacemaker implanta-
• Implanting a leadless pacemaker should be considered when no upper .. tion is non-inferior to pacemaker implantation with respect to
extremity venous access exists, when risk of device pocket .
freedom from bradycardia-related symptoms in patients with
infection is particularly increased, and in patients on .. symptomatic conversion pauses after AF.
haemodialysis. .
• In patients with reflex syncope, studies of which pacing mode is
• Patients undergoing TAVI are at increased risk of developing AVB. .. superior are needed.
Decisions regarding cardiac pacing after TAVI should be taken based .
• In patients with an indication for VVI pacing, the long-term effi-
upon pre-existing and new conduction disturbances. Ambulatory ECG .. cacy and safety of choosing leadless pacing need to be docu-
monitoring for 7—30 days or EPS may be con- .
mented in RCTs.
sidered in patients post-TAVI with new LBBB or progression of .. • In patients with HF, it remains to be shown that CRT improves
pre-existing conduction anomaly, but not yet any indication for a .
outcome in patients without LBBB.
pacemaker. .. • In patients with permanent/persistent AF, HF, and BBB, any ben-
In patients undergoing surgery for endocarditis or tricuspid valve .
• eficial effects of CRT remain to be proven in RCTs.
surgery who have or develop AVB under surgery, placement of .. • There is a lack of RCTs documenting the effect of CRT in
epicardial pacing leads during surgery should be considered. . patients with HF treated with novel HF drugs including sacubitril/
• To reduce the risk of complications, pre-operative anti- .. valsartan, ivabradine, and sodium glucose co-transporter-2
biotics must be administered before CIED procedures, . —
inhibitors.
76 ESC Guidelines
.
• The beneficial effects of upgrading to CRT from a standard pacemaker or
ICD in patients with HF and a high frequency of RV . pacing need to. • In symptomatic patients with end-stage HCM and LBBB, there is a
be documented.
. need to better define the criteria for CRT implantation and
When implanting the LV electrode, it is unknown whether tar- . . document the clinical features associated with sustained benefit from
• . the procedure.
geting the latest local activation mechanically or electrically
. • Optimal treatment including cardiac pacing for patients with
causes an improved effect of CRT and a better patient outcome.
congenital AVB should be investigated.
. • In pacemaker candidates with cardiomyopathies with >1 year
It is unknown whether employing any type of pre-implant imag- expected survival who do not fulfil standard criteria for ICD
•
. . implantation, criteria for ICD instead of pacemaker implantation
ing to decide about LV and RV lead placement in CRT may cause should be better defined.
• The optimal pre-operative handling in CIED implantations and
. potential use of pre-operative skin disinfection and/or pre-
.
better a patient outcome. hospitalization decolonization in S. aureus carriers remains to be
..

In patients with an indication for permanent pacing and need for determined.
•
.
a high frequency of RV pacing because of AVB, it is not known
. • The optimal approach for the different operational procedure
which patient and treatment characteristics predict development elements in CIED implantations, especially for choice of venous
. access, active or passive fixation leads in right-sided chambers,
specific pacing sites, use of haemostatic agents in the pocket,
of pacing-induced cardiomyopathy or HF.
. choice of suture types, and application of pressure dressing at the
end of the procedure remains to be determined.
.
• Patients with a need for immediate cardiac pacing occasionally
• In patients with AVB and an indication for cardiac pacing, the . long- present with fever and infection; typically, treatment includes
. temporary transvenous pacing and antibiotics, followed by
term efficacy and safety of HBP as an alternative to RV pacing need to.
be proven in RCTs. In addition, the selection of .
implantation of a permanent pacemaker after the infection has
patients most likely to benefit from HBP is not yet defined.. resolved. It is unknown whether immediate implantation of a
. permanent pacemaker after initiation of antibiotics would be
. inferior.
In patients with HF and an indication for CRT, the long-term effi-
•
. • The role of patient education, patient-centred care, and shared
cacy and safety of implementing HBP as an alternative to or ele-
. decision-making should be studied in CIED populations.
ment of CRT with biventricular pacing need to be proven in .
.
RCTs. In addition, the selection of CRT candidates who are most.
likely to benefit from HBP is not yet defined.
. .
• .
Further studies are needed to determine whether HBP could be
used to improve response in CRT non-responders.

.
The efficacy and safety of left bundle branch area pacing remain
•
. .
to be documented.
.
Superiority of a specific location for the RV lead (i.e. septal, out-
•
. .
flow tract, or apical) has not been documented for standard pac-
.
.
ing indicated for bradycardia or for CRT.
.
• Better prediction of who will develop AVB after TAVI is needed. .
16 ‘What to do’ and ‘what not to do’ messages from the Guidelines
............ ............
Evaluation of the patient with suspected or documented bradycardia or conduction system disease
Monitoring
Ambulatory ECG monitoring is recommended in the evaluation of patients with suspected bradycardia to correlate rhythm
I C
disturbances with symptoms.
ESC Guidelines 77
Carotid massage
Once carotid stenosis is ruled out,c CSM is recommended in patients with syncope of unknown origin compatible with a
I B
reflex mechanism or with symptoms related to pressure/manipulation of the carotid sinus area.
Exercise test
Exercise testing is recommended in patients who experience symptoms suspicious of bradycardia during or immediately after
I C
exertion.
Imaging
Cardiac imaging is recommended in patients with suspected or documented symptomatic bradycardia to evaluate the pres-
ence of structural heart disease, to determine LV systolic function, and to diagnose potential causes of conduction I C
disturbances.
Laboratory tests
In addition to pre-implant laboratory tests,d specific laboratory tests are recommended in patients with clinical suspicion for potential
causes of bradycardia (e.g. thyroid function tests, Lyme titre, digitalis level, potassium, calcium, and pH) to diagnose I C
and treat these conditions.
Continued
78 ESC Guidelines
Sleep evaluation
Screening for SAS is recommended in patients with symptoms of SAS and in the presence of severe bradycardia or advanced
I C
AVB during sleep.
Recommendation for implantable loop recorder
In patients with infrequent (less than once a month) unexplained syncope or other symptoms suspected to be caused by bradycardia in
whom a comprehensive evaluation did not demonstrate a cause, long-term ambulatory monitoring with an ILR is I A
recommended.
Cardiac pacing for bradycardia and conduction system disease
In patients with SND and a DDD pacemaker, minimization of unnecessary ventricular pacing through programming is
I A
recommended.
Pacing is indicated in SND when symptoms can clearly be attributed to bradyarrhythmias. I B
Pacing is indicated in symptomatic patients with the bradycardia—tachycardia form of SND to correct bradyarrhythmias and enable
I B
pharmacological treatment, unless ablation of the tachyarrhythmia is preferred.

Pacing is not recommended in patients with bradyarrhythmias related to SND which are asymptomatic or due to transient
III C
causes that can be corrected and prevented.
Pacing is indicated in patients in SR with permanent or paroxysmal third- or second-degree type 2, infranodal 2:1, or high-
I C
degree AVB, irrespective of symptoms.e
Pacing is indicated in patients with atrial arrhythmia (mainly AF) and permanent or paroxysmal third- or high-degree AVB,
I C
irrespective of symptoms.
In patients with permanent AF in need of a pacemaker, ventricular pacing with rate response function is recommended. I C
Pacing is not recommended in patients with AVB due to transient causes that can be corrected and prevented. III C
In patients with unexplained syncope and bifascicular block, a pacemaker is indicated in the presence of either a baseline HV interval of
>_70 ms, second- or third-degree intra- or infra-Hisian block during incremental atrial pacing, or abnormal response I B
to pharmacological challenge.
Pacing is indicated in patients with alternating BBB with or without symptoms. I C
Pacing is not recommended for asymptomatic BBB or bifascicular block. III B
Recommendations for pacing for reflex syncope
Dual-chamber cardiac pacing is indicated to reduce recurrent syncope in patients aged >40 years, with severe, unpredictable, recurrent
syncope who have:
• spontaneous documented symptomatic asystolic pause(s) >3 s or asymptomatic pause(s) >6 s due to sinus arrest or AVB; I A
or
• cardioinhibitory carotid sinus syndrome; or
• asystolic syncope during tilt testing.
Cardiac pacing is not indicated in the absence of a documented cardioinhibitory reflex. III B
Pacing is not recommended in patients with unexplained falls in the absence of any other documented indication. III B
Pacing is not recommended in patients with unexplained syncope without evidence of SND or conduction disturbance. III C
CRT
CRT is recommended for symptomatic patients with HF in SR with LVEF <_35%, QRS duration >_150 ms, and LBBB QRS mor-
I A
phology despite OMT, to improve symptoms and reduce morbidity and mortality.
CRT is not indicated in patients with HF and a QRS duration <130 ms without indication for RV pacing. III A
In patients with symptomatic AF and an uncontrolled heart rate who are candidates for AVJ ablation (irrespective of QRS
I B
duration), CRT is recommended in patients with HFrEF.
CRT rather than RV pacing is recommended for patients with HFrEF (<40%) regardless of NYHA class who have an indica-
I A
tion for ventricular pacing and high-degree AVB in order to reduce morbidity. This includes patients with AF.
In patients who are candidates for an ICD, and who have CRT indication, implantation of a CRT-D is recommended. I A
Recommendations for using His bundle pacing
In patients treated with His bundle pacing, device programming tailored to specific requirements of His bundle pacing is
I C
recommended.
Pacing in acute myocardial infarction
Implantation of a permanent pacemaker is indicated with the same recommendations as in a general population (section 5.2)
I C
when AVB does not resolve within a waiting period of at least 5 days after MI.
Pacing is not recommended if AVB resolves after revascularization or spontaneously. III B
Continued
ESC Guidelines 79
Recommendations for cardiac pacing after cardiac surgery and heart transplantation
High-degree or complete AVB after cardiac surgery: a period of clinical observation of at least 5 days is indicated to assess whether the
rhythm disturbance is transient and resolves. However, this observation period can be shortened in the case of I C
complete AVB with low or no escape rhythm when resolution is unlikely.
Patients requiring pacing after mechanical tricuspid valve replacement: implantation of a transvalvular RV lead should be avoided. III C
Recommendations for cardiac pacing after TAVI
Permanent pacing is recommended in patients with complete or high-degree AVB that persists for 24 - 48 h after TAVI. I B
Permanent pacing is recommended in patients with new-onset alternating BBB after TAVI. I C
Prophylactic permanent pacemaker implantation is not indicated before TAVI in patients with RBBB and no indication for per-
III C
manent pacing.
Recommendations for cardiac pacing in patients with congenital heart disease
In patients with congenital complete or high-degree AVB, pacing is recommended if one of the following risk factors is present:

i. Symptoms
ii. Pauses >3× the cycle length of the ventricular escape rhythm
iii. Broad QRS escape rhythm I C
iv.Prolonged QT interval
v. Complex ventricular ectopy
vi.Mean daytime heart rate <50 b.p.m.
Recommendations for cardiac pacing in rare diseases
In patients with neuromuscular diseases such as myotonic dystrophy type 1 and any second- or third-degree AVB or HV >_70
I C
ms, with or without symptoms, permanent pacing is indicated.f
Recommendations regarding device implantations and peri-operative management
Administration of pre-operative antibiotic prophylaxis within1h of skin incision is recommended to reduce the risk of CIED infection. I A
Heparin bridging of anticoagulated patients is not recommended. III A
Permanent pacemaker implantation is not recommended in patients with fever. Pacemaker implantation should be delayed
III B
until the patient has been afebrile for at least 24 h.
Recommendations for performing magnetic resonance imaging in pacemaker patients
In patients with MRI-conditional pacemaker systems,g MRI can be performed safely following the manufacturer’s instructions. I A
Recommendations regarding temporary cardiac pacing
Temporary transvenous pacing is recommended in cases of haemodynamic-compromising bradyarrhythmia refractory to
I C
intravenous chronotropic drugs.
Recommendation when pacing is no longer indicated
When pacing is no longer indicated, the decision on management strategy should be based on an individual risk—benefit analysis in a
I C
shared decision-making process together with the patient.
Recommendations for pacemaker and cardiac resynchronization therapy-pacemaker follow-up
Remote device management is recommended to reduce the number of in-office follow-up visits in patients with pacemakers who
I A
have difficulties in attending in-office visits (e.g. due to reduced mobility or other commitments, or according to patient preference).
Remote monitoring is recommended in the case of a device component that has been recalled or is on advisory, to enable early
I C
detection of actionable events in patients, particularly those who are at increased risk (e.g. in case of pacemaker dependency).
Recommendation regarding patient-centred care in cardiac pacing and cardiac resynchronization therapy
In patients considered for a pacemaker or CRT, the decision should be based on the best available evidence with consideration of
individual risk—benefits of each option, the patient’s preferences, and goals of care, and it is recommended to follow I C
an integrated care approach and use the principles of patient-centred care and shared decision-making in the consultation.
ESC 2021
AF = atrial fibrillation; AVB = atrioventricular block; AVJ = atrioventricular junction; BBB = bundle branch block; b.p.m. = beats per minute; CIED = cardiovascular implantable electronic device; CRT = cardiac
resynchronization therapy; CRT-D = defibrillator with cardiac resynchronization therapy; CSM = carotid sinus massage; DDD = dual-chamber, atrioventricular pacing; ECG = electrocardiogram; EPS =
electrophysiology study; HF = heart failure; HFrEF = heart failure with reduced ejection fraction; HV = His ventricular interval; ICD = implantable cardioverter-defibrillator; ILR = implantable loop
recorder; LBBB = left bundle— branch block; LV = left ventricular; LVEF = left ventricular ejection fraction; MI = myocardial infarction; MRI = magnetic resonance imaging; NYHA = New York Heart
Association; OMT = optimal medical therapy; RBBB = right bundle branch block; RV = right ventricular; SAS = sleep apnoea syndrome; SND = sinus node dysfunction; SR = sinus rhythm; TAVI = transcatheter
aortic valve implantation. aClass of recommendation.
b
Level of evidence.
c
CSM should not be undertaken in patients with previous transient ischaemic attack, stroke, or known carotid stenosis. Carotid auscultation should be performed before CSM. If a carotid
bruit is present, carotid ultrasound should be performed to exclude carotid disease.
d
Complete blood counts, prothrombin time, partial thromboplastin time, serum creatinine, and electrolytes.
e
In asymptomatic narrow QRS complex and 2:1 AVB, pacing may be avoided if supra-Hisian block is clinically suspected (concomitant Wenckebach is observed and block disappears with
exercise) or demonstrated at EPS.
f
Whenever pacing is indicated in neuromuscular disease, CRT or an implantable cardioverter-defibrillator should be considered according to relevant guidelines.
g
Combination of MRI conditional generator and lead(s) from the same manufacturer.
80 ESC Guidelines
17 Supplementary data .
Coordinator) (Sweden), Magdy Abdelhamid (Egypt), Victor Aboyans
Supplementary data with additional Supplementary Figures, Tables, and text
.. (France), Elena Arbelo (Spain), Riccardo Asteggiano (Italy), Gonzalo
.
complementing the full text are available on the European Heart Journal Baroń-Esquivias (Spain), Johann Bauersachs (Germany), Mauro Biffi
website and via the ESC website at https://www.escardio.org/ guidelines. .. (Italy), Ulrika Birgersdotter-Green (United States of America ), Maria
.
Grazia Bongiorni (Italy), Michael A. Borger (Germany), Jelena
.. Cˇ elutkiene_ (Lithuania), Maja Cikes (Croatia), Jean-Claude Daubert
.
18 Author Information (France), Inga Drossart (Belgium), Kenneth Ellenbogen (United
.. States of America), Perry M. Elliott (United Kingdom), Larissa Fabritz
Author/Task Force Member Affiliations: Mads Brix .. (United Kingdom), Volkmar Falk (Germany), Laurent Fauchier
Kronborg, Department of Cardiology, Aarhus University Hospital, . (France), Francisco Fernández-Avile´s (Spain), Dan Foldager
Aarhus N, Denmark; Yoav Michowitz, Jesselson Integrated Heart .. (Denmark), Fredrik Gadler (Sweden), Pastora Gallego Garcia De
Center, Faculty of Medicine, Hebrew University, Shaare Zedek . Vinuesa (Spain), Bulent Gorenek (Turkey), Jose M. Guerra (Spain),
Medical Center, Jerusalem, Israel; Angelo Auricchio, Department of .. Kristina Hermann Haugaa (Norway), Jeroen Hendriks (Netherlands),
.

Cardiology, Istituto Cardiocentro Ticino, Lugano, Switzerland; Israel
Thomas Kahan (Sweden), Hugo A. Katus (Germany), Aleksandra
Moshe Barbash, Leviev Heart Center, Sheba Medical Center, .. Konradi (Russia), Konstantinos C. Koskinas (Switzerland), Hannah
Sackler Faculty of Medicine, Tel Aviv University, Ramat Gan, Israel; Jose .
Law (United Kingdom), Basil S. Lewis (Israel), Nicholas John Linker
´ A. Barrabe´s, Department of Cardiology, Vall d’Hebron Hospital .. (United Kingdom), Maja-Lisa Løchen (Norway), Joost Lumens
Universitari, Universitat Autonoma de Barcelona, CIBERCV, Barcelona, .
(Netherlands), Julia Mascherbauer (Austria), Wilfried Mullens
Spain; Giuseppe Boriani, Cardiology Division, Department of .. (Belgium), KlaudiaVivien Nagy (Hungary), Eva Prescott (Denmark),
Biomedical, Metabolic and Neural Sciences, University of Modena .
Pekka Raatikainen (Finland), Amina Rakisheva (Kazakhstan), Tobias
and Reggio Emilia, Modena, Italy; Frieder Braunschweig, .. Reichlin (Switzerland), Renato Pietro Ricci (Italy), Evgeny Shlyakhto
Department of Cardiology, Karolinska University Hospital, .
(Russia), Marta Sitges (Spain), Miguel Sousa-Uva (Portugal), Richard
Stockholm, Sweden; Michele Brignole, Cardiology, IRCCS Istituto .. Sutton (Monaco), Piotr Suwalski (Poland), Jesper Hastrup Svendsen
Auxologico Italiano, Milan, Italy; Haran Burri, Cardiology, .
(Denmark), Rhian M. Touyz (United Kingdom), Isabelle C. Van
University Hospital of Geneva, Geneva, Switzerland; Andrew J. S. .. Gelder (Netherlands), Kevin Vernooy (Netherlands), Johannes
Coats, Faculty of Medicine, University of Warwick, Coventry, .
Waltenberger (Germany), Zachary Whinnett (United Kingdom),
United Kingdom; Jean-Claude Deharo, Cardiology La Timone, .. Klaus K. Witte (United Kingdom).
Aix Marseille Universite´, Marseille, France; Victoria .
Delgado, Cardiology, Leiden University Medical Center, Leiden,
..
. ESC National Cardiac Societies actively involved in the review
Netherlands; Gerhard-Paul Diller, Department of Cardiology III,
process of the 2021 ESC Guidelines on cardiac pacing and cardiac
Adult Congenital and Valvular Heart Disease, University Hospital .. resynchronization therapy: Algeria: Algerian Society of Cardiology,
..
Muenster, Muenster, Germany; Carsten W. Israel, Department of
Brahim Kichou; Armenia: Armenian Cardiologists Association,
Medicine-Cardiology, Diabetology and Nephrology, Bethel-Clinic, . Armen Khachatryan; Austria: Austrian Society of Cardiology,
..
Bielefeld, Germany; Andre Keren, Cardiology, Hadassah-Hebrew
Daniel Scherr; Belarus: Belorussian Scientific Society of
University Hospital, Jerusalem, Israel; Reinoud E. Knops, . Cardiologists, Alexandr Chasnoits; Belgium: Belgian Society of
Cardiology and Electrophysiology, Amsterdam University Medical
.. Cardiology, Georges H. Mairesse; Bosnia and Herzegovina:
Center, Amsterdam, Netherlands; Dipak Kotecha, Institute of . Association of Cardiologists of Bosnia and Herzegovina, Mugdim
Cardiovascular Sciences, University of Birmingham, Birmingham, .. Bajric; Bulgaria: Bulgarian Society of Cardiology, Vasil Velchev;
United Kingdom; Christophe Leclercq, Department of Cadiology, .
Croatia: Croatian Cardiac Society, Vedran Velagic; Cyprus:
Rennes University Hospital, Rennes, France; Be´la Merkely, Heart .. Cyprus Society of Cardiology, Elias Papasavvas; Czech Republic:
and Vascular Center, Semmelweis University, Budapest, Hungary; .
Czech Society of Cardiology, Milos Taborsky; Denmark: Danish
Christoph Starck, Department of Cardiothoracic & Vascular .. Society of Cardiology, Michael Vinther; Egypt: Egyptian Society of
Surgery, German Heart Center Berlin, Berlin, Germany; Ingela .
Cardiology, John Kamel Zarif Tawadros; Estonia: Estonian Society
Thyle´ n, Department of Health, Medicine and Caring Sciences, .. of Cardiology, Ju¨ri Voitk; Finland: Finnish Cardiac Society, Jarkko
Linko¨ ping University, Linko¨ ping, Sweden; Jose´ Maria .
Karvonen; France: French Society of Cardiology, Paul Milliez;
Tolosana, Arrhythmia Section, Cardiovascular Institute, Hospital .. Georgia: Georgian Society of Cardiology, Kakhaber Etsadashvili;
Clinic, University of Barcelona, Barcelona, Catalonia, Spain. .
Germany: German Cardiac Society, Christian Veltmann; Greece:
.. Hellenic Society of Cardiology, Nikolaos Fragakis; Hungary:
.
Hungarian Society of Cardiology, Laszlo Alajos Gelle´r; Ireland: Irish
19 Appendix .. Cardiac Society, Richard Sheahan; Israel: Israel Heart Society,
.
Avishag Laish-Farkash; Italy: Italian Federation of Cardiology,
..
ESC Scientific Document Group
Includes Document Reviewers and ESC National Cardiac Societies. Massimo Zecchin; Kazakhstan: Association of Cardiologists of
.. Kazakhstan, Ayan Abdrakhmanov; Kosovo (Republic of): Kosovo
Document Reviewers: Francisco Leyva (CPG Review . Society of Cardiology, Ibadete Bytyçi; Kyrgyzstan: Kyrgyz Society
Coordinator) (United Kingdom), Cecilia Linde (CPG Review .. of Cardiology, Kurbanbek Kalysov; Latvia: Latvian Society of
. Cardiology, Oskars Kalejs; Lebanon: Lebanese Society
.
. of Cardiology, Bernard Abi-Saleh; Lithuania: Lithuanian Society of
ESC Guidelines 81
. 6. Ector H, Rickards AF, Kappenberger L, Linde C, Vardas P, Oto A, Santini M,

Cardiology, Germanas Marinskis; Luxembourg: Luxembourg .
Society of Cardiology, Laurent Groben; Malta: Maltese Cardiac . Sutton R, Working Group on Cardiac Pacing. The World Survey of Cardiac
. Pacing and Implantable Cardioverter Defibrillators: calendar year 1997—Europe.
Society, Mark Adrian Sammut; Moldova (Republic of): Moldavian . Pacing Clin Electrophysiol 2001;24:863 — 868.
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2021 ESC Guidelines On Cardiac Pacing and Cardiac Resynchronization Therapy

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2021 ESC Guidelines On Cardiac Pacing and Cardiac Resynchronization Therapy

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ESC GUIDELINES

European Heart Journal (2021) 00, 1 94 doi:10.1093/eurheartj/ehab364

2021 ESC Guidelines on cardiac pacing

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Authors/Task Force Members: of patiensMichael Glikson * (Chairperson) (Israel),

Be´ la Merkely (Hungary), Christoph Starck (Germany), Ingela Thyle´ n (Sweden),

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4.3.6 Sleep evaluation...................................................................................19 system pacing...............................................................................34

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9.4 Management of anticoagulation..............................................................51

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Table 11 Management of anticoagulation in pacemaker . AVB Atrioventricular block

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Table 1 Classes of recommendations

Classes of recommendations Wording to use

Class I Evidence and/or general agreement that a Is recommended or is indicated

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Class IIb May be considered

Table 2 Levels of evidence

Level of Data derived from multiple randomized clinical trials or

Level of Data derived from a single randomized clinical trial or

Level of Consensus of opinion of the experts and/or small studies,

evidence C retrospective studies, registries.

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Association, the European Association of Cardiothoracic Surgery, the . 12

2.3.2 New recommendations in 2021 . Laboratory tests

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. resynchronization therapy guideline recommendations .

class who have an indication for ventricular pac- ing IIa I

New in these guidelines

Pacing in TAVI patients

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Minimizing complication risk Pacing in patients

Patient with bradycardia-related symptoms

Sinus node disease

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system. In addition, genetic mutations have been linked to conduction .

symptoms. In general, candidates for pacing ther- apy can be broadly

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Historia Examen físico Imagen cardiaca

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Psychoactive and neuroactive drugs 5-fluorouracil 1 1

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Collagen vascular diseases .

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recorder/handheld ECG recorder .

context of haemodynamic instability. When coronary artery disease

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. Early-onset PCCD, either isolated or with concomitant structural

response, or even a negative response does not exclude asystole dur-

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Progressive cardiac conduction disease: prolonged P wave duration, PR interval, and

Nocturnal bradyarrhythmias are common in the general population. In .

4.5 Electrophysiology study .

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