Sudden Cardiac Death

Definitie – Moartea Subita Cardiaca

 Natural death of cardiac cause in a person with or

without known cardiac pathology in whom:
⚫ The moment and modality of death is unexpected
⚫ Shortly after a possible prodrome (< 1h)
⚫ If not witnessed: in a person in stable condition 24 hrs. before
the event

 The term “ ” is preferred for the

resuscitated subjects
Underlying Arrhythmias of
Sudden Cardiac Arrest

Bayés de Luna A. Am Heart J. 1989;117:151-159.

 Magnitude of SCA in the U.S.

Stroke3 167,366

SCA claims more

450,000 SCA4
lives each year
Lung Cancer2 than these other
157,400 diseases combined

Breast Cancer2 40,600

AIDS1 42,156

1 U.S. Census Bureau, Statistical Abstract of the United States: 2001.

2 American Cancer Society, Inc., Surveillance Research, Cancer Facts and Figures 2001.
3 2002 Heart and Stroke Statistical Update, American Heart Association.
4 Zheng Z. Circulation. 2001;104:2158-2163.
 From Substrate to VT and SCD
General CV Immaging
(eco, MRI…) Repolarization reserve
risk factors
…….. μVTWA
HR turbulence
External ………….
factors
Structural
myocardial
substrate
Stress test,
Holter(ischemia)
Modulatory
………….
factors VT/VF
Functional
myocardial
EPS
substrate ………
* Ventricular Extrasystoles…
 SCD incidence and total events
Relative Absolute

Overall incidence in
adult population

High coronary
risk subgroup

Any prior coronary

event

Special risk population 0 1 2 5 10 20 30 0 100,000 200,000 300,000

SCD incidence Events/year
(% per year)

Myerburg RJ. - Sudden Cardiac Death: Exploring the Limits of Our Knowledge. J Cardiovasc Electrophysiol 2001.
 SCA Risk Factors Well Documented

Low Left Ventricular Ejection About 45% of all SCA victims

Fraction (LVEF) have LVEF < 30%1
Heart Failure (HF) 25% overall death in 2.5 years;
and 50% die of SCA2
Prior Myocardial Infarction (MI) SCD occurs at four times the
and HF rate of the general population3
Prior Ventricular Tachycardia Risk of arrhythmic death is
(VT), Ventricular Fibrillation (VF) 18% after three years of a prior
or SCA event4

Note: Any combination of these factors increases the risk of SCA.

Risk of Sudden Death: GISSI-2 Trial
1.00 1.00

0.98 p log-rank 0.002 0.98

0.96 0.96
Survival

Survival
0.94 0.94

0.92 0.92
p log-rank 0.0001
0.90 0.90

0.88 0.88
A B
0.86 0.86
0 30 60 90 120 150 180 0 30 60 90 120 150 180
Days Days

Patients without Patients with

No PVBs
LV Dysfunction LV Dysfunction
1-10 PVBs/h
> 10 PVBs/h

Maggioni AP. Circulation. 1993;87:312-322.

Proportion of Sudden Death Survivors
with Acute MI
100
Acute Transmural MI (n = 39)

80
Total group (N = 245)
Percent survival

60

40 All other ECGs (n = 200)

20

0
0 2 4 6 12 18 24 30 36 42 48
Time (months)

< 20% of sudden death survivors have an acute MI

Sudden death associated with acute MI has a better prognosis

Cobb LA. Circulation. 1975;51(III):223.

SAECG

Filtered QRS duration >114

msec
●Terminal (last 40 msec)
QRS root mean square
voltage <20 mcV
●Low amplitude (<40mcV)
late potential duration >38
msec
Identificarea substratului: fQRS
(fenomenul Das)
Identificarea substratului: fQRS
(fenomenul Das)
ICD
 NNT to save a life
50
45 Dugs
40 37
35
30 28
26
25 ICD
CRT-D CRT 20
20
14

Amiodarone
14

Simvastatin
15

Metoprolol
11

Captopril
9 10
10
5
0
AVID MADIT II SCD-HeFT COMPANION CARE-HF SAVE Merit-HF 4S Amiodarone
(3 Yr) (3 Yr) (4 Yr) (1 Yr) (1 Yr) (2.5 Yr) (3.5 Yr) (1 Yr) (6 Yr) metaanaliza
(2 Yr)

NNTx years = 100 / (% Mortality in Control Group – % Mortality in Treatment Group)

It all started when arrhythmias were
noticed to run in families
 1957: the first formal description

 “A combination of deaf-mutism and a peculiar heart

disease has been observed in 4 children in a family of
6. the parents were not related and were…quite
healthy”

 “The deaf-mutism children…..suffered from fainting

attacks….Three of the deaf-mutism children died
suddenly at ages of 4,5 and 9.”

Jervell A, Lange-Nielsen F – Am Heart J 1957

 1978: catecholaminergic tachycardia

 “We identified in 1978…disease

occuring in children over 3 years
with apparently normal
hearts……Syncope mainly occur
during exertion or emotional
experiences. The
electrocardiogram is normal
(particularly QT interval).”

Coumel P & al - Br Heart J 1978

 Incidenta bolilor cardiace la tineri
atleti cu MSC
40
Incidenta (%)

35
30
25
20
15
10
5
0

SUA
Italia

DAVD = ARVD = displazie aritmogena de ventricul drept

Sportul este un risc pentru MS

➢ La
4.0 atletii adolescenti si tineri (fete si baieti)
RR = 2,5
MS la 100 000 persoane-an

activitatea
3.0
sportiva este asociata cu– 3,4
CI = 1,8 risc crescut
p < 0,001
de MS
2.0
➢ Sportul nu este cauza mortalitatii crescute, ci
1.0
triggerul MS la cei cu boala cardiaca structurala
0.0
predispozanta la aritmii ventriculare
atleti maligne
non-atleti

Corrado et al., JACC 2003; 42:1959

HCMP
SCD in CMP hipertrofica

SCD CMPH 50%

% SCD in CMPH Cauze de SCD la tineri atleti

N=5413
Urmarire 6 ani
SCD = 1,4% per an

HRS, 2006
Substratul aritmogen CMPH

Dezaliniere
ECG

www.cardiologyforum.org
CMH- ECG

Hein J.J. Wellens, Mary Conover. “The ECG in Emergency Decision Making”, Second Edition, Ed. ELSERVIER, p. 207
CMH - factori de risc

Maron BJ et al. American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic
Cardiomyopathy. European Heart Journal (2003) 24, 1965–1991
Molecular composition of the
desmosome

Desmoglein
Desmocollin
Desmoplakin

Plakophilin
Plakoglobin
Desmin

McKenna, ESC 2011

 Desmosomal mutation in
arrhythmogenic cardiomyopathy

Naxos
(plakoglobin) Intermediate
filament

ARVC8
(desmoplakin)

Plakophylin-2
Carvajal
(desmoplakin)

Desmoplakin Desmoglein Desmocollin Plakophilin Plakoglobin

McKenna, ESC 2011
AD 1

VS
VD

3
2
ARVD
 Cardiomiopatia (displazia) aritmogena a
ventriculului drept

Peters S. and Tru¨mmel M. Arrhythmogenic RV

Dysplasia-Cardiomyopathy. A.N.E.
2003;8(3):238–245

Shulin Wu et al. Epsilon Wave in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. PACE 2009; 32:59–63
Un element caracteristic al ARVD

Unda e
Cardiomiopatia (displazia) aritmogena a
ventriculului drept

Nasir K et al. Electrocardiographic Features of Arrhythmogenic Right Ventricular

Dysplasia/Cardiomyopathy According to Disease Severity: A Need to Broaden Diagnostic Criteria.
Circulation 2004;110;1527-1534
Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Proposed Modification of the Task Force Criteria Frank I.
Marcus et al. Circulation.2010; 121: 1533-1541
Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Proposed Modification of the Task Force Criteria Frank I.
Marcus et al. Circulation.2010; 121: 1533-1541
 Ion channels:
⚫ loss of function
⚫ gain of function
 APD
prolongation/shortening
 Trigerred activity
⚫ EAD / DAD
 Dispersion of
refractoriness
 Phase 2 re-entry
Canalele ionice: gain vs loss of function
~ LQT3 & LQT2 ~

K+

Na+
- Iks +INa
 Gene-centered classification of inherited
arrhythmogenic diseases
Plasmalemmal proteins SR proteins

IKs disease RyR receptor Calsequestrine

disease disease

LQT1 JNL2 LQT5 SQT1 JNL1 AF1 LQT11 CPVT1 CPVT2

IKr disease

LQT2 SQT2 AF3 LQT6 INa disease ICa disease

IK1 disease
LQT3 cBrS CCD1 SSS LQT9 LQT10 LQT12 BrS/SQT LQT8

SQT3 AF4 LQT7

Loss of function Gain of function

Ruan, Y. et al. Nat. Rev. Cardiol. 2009
 Supravietuirea in functie de QTc la pacientii cu LQT
genotipat

100
Supravietuire cumulata (%)

80 QTc < 446 msec

QTc 446-498 msec

60 QTc 468-499 msec

40

QTc > 500 msec

20
P<0,0001

10 20 30 40
Varsta (ani)
Priori S & al – Circulation 2003
 Frecventa triggerilor in LQT

Efort
70
Emotie
60 Somn
50 Altele

40

30

20

10

0
LQT1 LQT2 LQT3
(n=57) (n=49) (n=25)

Schwartz & al – Circulation 2001

Electrocardiograma

Long QT Syndrome Goldenberg I, Moss AJ. J Am Coll Cardiol 2008;51:2291–300

Tahiaritmii ventriculare in LQTS

Dept. of Pharmacology Charles University in Prague Faculty of Medicine (www.lfhk.cuni.cz)

Long QT Syndrome Goldenberg I, Moss AJ. J Am Coll Cardiol 2008;51:2291–300
Tratamentul LQTS

 Tratamentul torsadei varfurilor:

⚫ MgSO4 1-2g i.v. bolus in 5 min
⚫ MgSO4 1-2 g/h 4-6 ore
⚫ Daca este ineficient isoproterenol sau pacing pentru cresterea
frecventei cardiace

Hein J.J. Wellens, Mary Conover. “The ECG in Emergency Decision Making”, Second Edition, Ed. ELSERVIER, p. 177
 Tratamentul cronic al LQTS
 Beta-blocante:
⚫ Reprezinta prima linie de tratament pentru toti pacientii simptomatici
⚫ La pacientii cu risc inalt sau foarte inalt, unii autori recomanda inclusiv
la pacientii cu risc redus daca nu au CI
⚫ Foarte eficient in LQT1 (aritmii declansate de efort)
⚫ Mediu eficient in LQT2
⚫ Eficienta limitata in LQT3
 Denervarea simpatica: pacientii cu sincopa recurenta sub beta-
blocant si pacientii cu ICD si furtuna electrica
 Tratamentul LQTS

 Defibrilator cardiac implantabil (ICD)

⚫ Clar indicat la pacientii cu oprire cardiaca resuscitata
⚫ La pacientii cu sincope recurente sub terapie
⚫ La cererea pacientului
 Sindromul Brugada

 Descris in 1992
 Aspect ecg tipic
 Moarte subita
 Prevalenta 5/10000, mari variatii geografice
 4-12% din mortile subite, pana la 20% din mortile subita
la pacientii cu cord normal (prevalenta crescuta in Asia)
 Manifestari clinice - sindromul Brugada

 MS, sincope in a 4a decada de viata, cel mai frecvent

 Aritmiile apar in special in repaus, in timpul
somnului
 De 8-10 ori mai prevalent la barbati decat la
femei
 Aritmii supraventriculare: pana la 20% dintre pacienti
⚫ Eckardt L, Kirchhof P, Loh P, et al: Brugada syndrome and supraventricular tachyarrhythmias: a novel association? J Cardiovasc Electrophysiol
12:680-685, 2001
Schematic representation of the cardiac sodium
channel macromolecular complex
NH2

 subunit


Caveolin
subunit
(SCN5A)

Ankyrin

Calmodulin

COOH NH2 NEDD4-like

Syntrophyn

Cytoskeleton
Ruan, Y. et al. Nat. Rev. Cardiol. 2009
COOH
Fenotipul ECG in sd. Brugada

TIPUL 1 TIPUL 2 TIPUL 3

Sindromul Brugada - mecanisme

Begoña Benito, Ramon Brugada, Josep Brugada and Pedro Brugada. Brugada Syndrome.
Progress in Cardiovascular Diseases, Vol. 51, No. 1 (July/August), 2008: pp 1-22
Flecainide test
 ECG - sindromul Brugada
 In spatiile intercostale 2 si 3
 Semnificatie prognostica similara cu spatiul 4 intercostal
Miyamoto K, Yokokawa M, Tanaka K, et al: Diagnostic and prognostic value of a type 1 Brugada electrocardiogram at higher (third or second) V1 to V2 recording in men with Brugada
syndrome. Am J Cardiol 99:53-57, 2007
Tratament - sindromul Brugada

Begoña Benito, Ramon Brugada, Josep Brugada and Pedro Brugada. Brugada Syndrome.
Progress in Cardiovascular Diseases, Vol. 51, No. 1 (July/August), 2008: pp 1-22
 Sindromul de QT scurt

 1993 Alegra et al 6693 inregistrari Holter ecg:

susceptibilitatea la aritmii ventriculare se asociaza cu QT
scurt
 Descris prima data in 2000 la un pacient cu moarte
subita cardiaca provenind dintr-o familie cu FiA
 In 2003 au fost descrise doua familii cu QT scurt, aritmii
cardiace si o rata crescuta de MS
 Diagnostic si caracteristici clinice
 Interval QT scurt
 Segment ST scurt sau chiar absent, unda T inalta

•Scurtatrea perioadei
refractare ventriculare
•Scurtarea perioadei
refractare atriale
•Inducerea de FIV/TV la
60% la SEF
•Absenta scurtarii la efort a
intervalului QT

Lia Crotti, Erika Taravelli Giulia Girardengo

Peter J. Schwartz, “Congenital Short QT
Syndrome”, Indian Pacing and
Electrophysiology Journal 10 (2): 86-95
(2010)
Clinical CPVT
Stress test in CPVT

Rest

Exercise 0.5 min

(Bruce 1st)

Exercise 1 min
(Bruce 1st)

Exercise 1.5 mins

(Bruce 1st)

Recovery 4 mins

Full dosage of betablocker

 Genetica CPVT

 Aparitie familiala in aprox 30% din cazuri

 2001 Priori si colaboratorii: la nivelul cromozomului 1q42-q43:
codarea receptorului de ryanodina(RyR2); forma autosomal
dominanta
 Lahat si colab. 2003: 1p31-21: mutatie a genei calsequestrinei
(CASQ2): forma autosomal recesiva
 La un subiect: mutatie a genei Ankirinei B: manifestari asemanatoare
CPVT
Arrhythmogenic Mechanism in CPVT

Priori S, S. R .W. Chen, Circulation Research, 2011

An Unifying Concept of CPVT

Priori S, S. R .W. Chen, Circulation Research, 2011