H y p e r t e n s i o n an d

Arrhythmias
Muhammad R. Afzal, MD, Salvatore Savona, MD, Omar Mohamed, MD,
Aayah Mohamed-Osman, MD, Steven J. Kalbfleisch, MD, FHRS*

KEYWORDS
 Hypertension  Atrial fibrillation  Ventricular tachycardia  Sudden cardiac death

KEY POINTS
 Hypertension is the most common risk factor for cardiovascular diseases and is associated with
development and progression of various atrial and ventricular arrhythmias.
 Left ventricular hypertrophy resulting from chronic hypertension leads to progressive ventricular
dysfunction and left atrial enlargement, which predispose for development of atrial and ventricular
arrhythmias.
 Prompt intervention, including preemptive screening for hypertension in high-risk patients, aggres-
sive lifestyle modifications, and pharmacotherapy, can halt the progression of hypertensive heart
disease and thus development of atrial and ventricular arrhythmias.

INTRODUCTION of pharmacotherapy for hypertension and AF can in-

crease the risk of orthostatic hypotension, especially
Hypertension remains a significant risk for the in the elderly.11 The development of hypertension in-
development of adverse cardiovascular events creases the risk of sudden cardiac death and ven-
and continues to increase in prevalence.1 The in- tricular arrhythmias, as well as adversely affecting
crease in the prevalence of hypertension is attrib- the conduction system.7,12–14
uted to multiple risk factors including dietary The complex interplay between hypertension and
indiscretions, obesity, obstructive sleep apnea cardiac arrhythmias in the face of increasing preva-
and aging populations.2 Hypertension manifests lence of both disorders warrants a detailed under-
in the form of various cardiovascular diseases standing of the pathogenesis to appropriately
including heart failure (HF), coronary artery dis- curtail the implications of hypertensive heart disease
ease, and various arrhythmias including atrial fibril- and cardiac arrhythmias. This review summarizes
lation (AF), ventricular arrhythmias, and sudden the existing literature on the association of hyperten-
cardiac death.1,3 sion and cardiac arrhythmias with an emphasis on
Hypertension is the most common risk factor for the pathophysiology and management.
the development of AF.4–9 Development of AF in pa-
tients with hypertension has several implications,
EPIDEMIOLOGY
the most important of which is the increased risk of
thromboembolism and stroke. Depending on the Hypertension is the most common risk factor for
degree of left ventricular hypertrophy (LVH), AF cardiovascular diseases with an estimated preva-
can be a precipitant of HF, particularly HF with pre- lence of 29% in 2011 to 2014.2 The prevalence
served ejection fraction (HFpEF).10 The combination of hypertension increased with age, from 7.3%
heartfailure.theclinics.com

Conflict of Interest: None.

Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center, 473 West 12th Avenue,
Suite 200, Columbus, OH 43210, USA
* Corresponding author.
E-mail address: [email protected]

Heart Failure Clin 15 (2019) 543–550

https://doi.org/10.1016/j.hfc.2019.06.011
1551-7136/19/Ó 2019 Elsevier Inc. All rights reserved.
544 Afzal et al

among adults aged 18% to 39% to 32.2% among related to the status of hypertensive heart dis-
those aged 40% to 59%, and 64.9% among those ease.21 With the progression of hypertensive heart
aged 60 and over. A similar pattern was found disease as manifested by cardiac remodeling, the
among both men (8.4% for those aged 18%– incidence of AF, ventricular arrhythmias, and sud-
39%, 34.6% for 40%–59%, and 63.1% for 60) den death increases. The following factors are
and women (6.1% for those aged 18%–39%, attributed to the development of cardiac arrhyth-
29.9% for 40%–59%, and 66.5% for 60). The mias in patients with hypertension: LVH, increased
increased prevalence in hypertension is depicted left atrial size, activation of the sympathetic ner-
in Fig. 1. The prevalence is projected to increase vous system (SNS) and renin–angiotensin–aldo-
to 41.4% in 2030. sterone system (RAAS), electrical abnormalities,
Hypertension is associated with cardiac arrhyth- and microvascular ischemia. Fig. 2 depicts the
mias and particularly AF, which is considered the various aspects of arrhythmogenesis in patients
most common sustained arrhythmia in adults. with hypertension, and Box 1 outlines risk
The estimated prevalence of AF in the United factors modification in patients diagnosed with
States is approximately 5.2 million, and is expected hypertension.
to increase to 12.1 million by 2030.15 Hypertension
is associated with a 1.8-fold increased risk of Left Ventricular Hypertrophy
developing new-onset AF and a 1.5-fold increased
Chronic hypertension is strongly related to the
risk of progression to permanent AF.4 The lifetime
development of LVH that promotes the develop-
risk for the development of AF in this population
ment of cardiac arrhythmias. Chronic increases
is as high as 25% at 40 years of age.5 Almost
in afterload and intracardiac pressure promote hy-
60% of patients with AF have hypertension.7
pertrophy of cardiac myocytes and stimulates
Owing to the aging population, a 2 to 3 times in-
cardiac fibroblasts. Hypertrophy of the cardiac
crease in the total number of patients with AF is ex-
myocytes and collagen deposition from cardiac
pected over the next 20 to 30 years.16–18
fibroblasts result in increased mass of the myocar-
Hypertension is also associated with ventricular
dium.22 Diastolic dysfunction is the initial func-
arrhythmias and sudden cardiac death. The inci-
tional maladaptation from LVH, with progressive
dence of sudden cardiac death is 350,000 events
remodeling resulting in decreased systolic
per year in United States.13 The presence of LVH
function.10
and AF increase the risk of sudden cardiac death
by 3- to 4-fold as shown in a secondary analysis
Increased Left Atrial Size
of the LIFE study.19 Similarly, a history of hyperten-
sion was an independent predictor of in-hospital Left atrial size is a valuable parameter to assess
ventricular fibrillation.20 the chronicity of AF.23 Chronic elevation in the
left ventricular end-diastolic pressure leads to
PATHOGENESIS OF ARRHYTHMIAS IN increased left atrial pressure. Chronic elevation
HYPERTENSION of the left atrial pressure results in chamber
enlargement.24 Atrial stretch leads to electrical
The association between hypertension and ar- dissociation among muscle bundles and facilitates
rhythmias is complex. In hypertensive patients the initiation and maintenance of AF as it allows
with no other cardiac risk factors, the incidence multiple small reentrant wavelet to sustain AF.
and prevalence of cardiac arrhythmias is directly Thus, AF is maintained and induced by tissue

Fig. 1. The increase in prevalence of

hypertension as a function of age is
depicted from 2011 to 2014. The in-
crease is consistent regardless of
gender.
 Hypertension and Arrhythmias 545

Hypertension

Renin-Angiotenisn Sympathec ANS

Acvaon acvaon

Electrical changes Structural changes

EADs Myocyte hypertrophy

Cellular/Microscopic DADs ECM expansion Cellular/Microscopic
Changes Slowing of CV CX43 dysfuncon Changes
Shortening of the AERP Myofibroblasormaon

QRS widening Increased LAVI

Gross/Macroscopic QT dispersion Increased LVMI Gross/Macroscopic
changes P wave broadening Reduced LA and LV changes
PR interval prolongaon strain

Clinical manifestaons

Frequent PACs and AF

PVCs
Ventricular tachycardia
TdP

Intervenon

Eliminaon of triggers
Risk factor modificaon Blockage of RAAS and
Substrate modificaon
Adequate blood Sympathec ANS
with scar modificaon
pressure control Sympathec system
Neurohumeroal
Table 1 Table 2 blunng

Fig. 2. Mechanisms and manifestations of arrhythmogenesis in patients with hypertension. Hypertension influences
arrhythmia genesis through macro and microscopic modifications to the cardiac environment, resulting in electrical
and structural changes. The clinical manifestations of these changes are arrhythmias and electrophysiologic alter-
ations such as PACs, PVCs, AF, bundle branch block, QT prolongation, etc. Blood pressure control targeting the
renin-angiotensin system and SNS may abate these processes. AERP, atrial effective refractory period; ANS, auto-
nomic nervous system; CV, conduction velocity; CX43, Connexin 43; DAD, delayed afterpolarization; EAD, early
afterpolarization; ECM, extracellular matrix; LAVI, left atrial volume index; LVMI, left ventricular mass index;
PACs, premature atrial contractions; PVCs, premature ventricular contractions; TdP, torsades de pointes.

remodeling owing to the changes in essential char- progression of both hypertension and various car-
acteristics of the atria.25,26 diac arrhythmias.27 Fig. 3 depicts the renin–
angiotensin system with associated therapeutic
Activation of Sympathetic Nervous System targets.
and Renin–Angiotensin–Aldosterone System Activation of the SNS results in peripheral vaso-
constriction, which leads to increased systemic
Activation of the SNS and the RAAS plays a key blood pressure. A heightened SNS reduces the re-
role in the development, maintenance, and fractory period of myocytes and promotes both
atrial and ventricular arrhythmias. Angiotensin II,
Box 1 a mediator of RAAS, is implicated for progression
Risk factor modification in hypertension of atrial and ventricular fibrosis. Pharmacologic in-
terventions targeting the SNS and the RAAS have
Blood pressure control per current guidelines
been shown to be beneficial for both hypertension
Cessation from tobacco containing products and cardiac arrhythmias.28,29
Minimizing alcohol intake (men 2 and
women 1 drink per day) Electrical Abnormalities Promoting
Regular physical activity Arrhythmogenesis in Patients with
Assessment and treatment of sleep apnea Hypertension
Screening for diabetes and hyperlipidemia Electrical changes occur early in hypertensive heart
Weight reduction and dietary modification disease. Two distinct abnormalities include the pro-
longation of atrial conduction velocity and a decrease
546 Afzal et al

Fig. 3. Renin–angiotensin system and therapeutic targets. Hormones, peptides, and receptors are depicted in the
blue boxes. Enzymes are depicted in the green boxes. Therapeutic agents are depicted in the red circles. ACE-I,
angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; MRA, mineralocorticoid
antagonist.

in atrial refractoriness. Additionally, triggered activity increased left ventricular mass. As coronary flow
through both early and delayed after depolarizations reserve decreases, there is an increased risk of
are thought to play a role in the initiation of AF related further ischemia and thus ventricular arrhythmias.34
to hypertensive heart disease.27,30 LVH also results in
QRS and QT prolongation as a result of prolonged MANAGEMENT OF ARRHYTHMIAS IN
action potential duration and QT dispersion, which PATIENTS WITH HYPERTENSION
can increase the propensity for early after depolariza- Atrial Fibrillation
tion, the mechanism for polymorphic ventricular
tachycardia/torsades de pointes.19,20,31 Appropriate control of blood pressure is associ-
ated with a decreased incidence of AF in several
studies. This decrease has been partly attributed
Microvascular Ischemia Leading to Ventricular
to the antiarrhythmic properties of antihyperten-
Arrhythmia
sive medications. The RAAS is the therapeutic
LVH is also associated with subendocardial ischemia target for the prevention of AF. Higher levels of
as a result of changes to the microvasculature.32 angiotensin II and angiotensin-converting en-
Local areas of ischemia produce myocardial scar, zymes are observed in patients with AF. In addition
as well as fibrosis, which are well-documented sub- to improved blood pressure control, angiotensin-
strates for ventricular arrhythmias and sudden car- converting enzyme inhibitors and angiotensin re-
diac death.33 Additionally, hypertension is a strong ceptor blockers theoretically provide antifibrotic
risk factor for the development of macrovascular and antiapoptotic actions.35,36 The antiarrhythmic
ischemia through obstructive coronary disease. effects of angiotensin receptor blockers was
Infarction scar provides a substrate for macro reen- observed in LIFE study, in which new-onset AF
trant arrhythmias such as ventricular tachycardia. occurred in only 150 losartan-treated patients
LVH also decreases coronary flow reserve owing to compared with 221 atenolol-treated patients.
 Hypertension and Arrhythmias 547

These findings suggest a RAAS-specific effect. pressure is not arrhythmogenic per se; however,
Stronger evidence for prevention of AF by RAAS acute or chronic ventricular overload can lead to
blockage with angiotensin-converting enzyme in- electrophysiologic properties that may be even
hibitors or angiotensin receptor blockers was more important under pathologic conditions, such
shown in hypertensive patients with LVH and sys- as ischemic scars.40
tolic HF.37 Table 1 outlines therapies that have The management of PVCs in patients with and
been shown to decrease the incidence of new- without hypertension is similar. A 12-lead electro-
onset AF. cardiogram and a 24-hour Holter recording may
Optimal blood pressure control to prevent LVH help to potentially localize the site of origin and to
and left atrial enlargement with antihypertensive quantify premature ventricular beats.41 Transtho-
drugs seems to be important to prevent progres- racic echocardiography may be useful to assess
sion of AF. Although beta-blockers are frequently for other signs of hypertensive or structural heart
used for acute and chronic rate control in AF, disease, as well as to assess left ventricular systolic
they are not considered first-line therapies for hy- function. With regard to treatments for sustained
pertension. In a study of patients with hyperten- ventricular arrhythmias and prevention of sudden
sion, 85 patients with or without LVH had more cardiac death, hypertension does not modify the in-
atrial premature beats than an age-matched con- dications for implantable cardioverter-defibrillators
trol group.18 Beta-blockers and calcium antago- or ablation, as recommended by current
nists resulted in a decreased frequency of guidelines.42,43
premature atrial contractions. In a review of
12,000 patients with HF, the incidence of new- Ventricular Tachycardia, Ventricular
onset AF was significantly lower in patients who Fibrillation, and Sudden Cardiac Death
received beta-blockers, with a risk reduction of
27%. However, the findings of the LIFE study sug- Hypertension is a risk factor for sudden cardiac
gest RAAS blockade is superior to beta-blockade death, particularly in the context of increased LV
in treating patients with hypertension.9 Therapies mass.37 LVH is associated with long-term risk of
with associated trial results for the prevention of sudden cardiac death independent of blood pres-
new onset AF can be found in Table 1. sure, and the risk of sudden cardiac death in-
creases progressively with LV mass. The
proposed mechanisms to explain the relationship
Premature Ventricular Beats
between the presence of LVH and sudden cardiac
Ventricular arrhythmias are common among hyper- death include prolongation of repolarization,
tensive patients, and this association may have mismatch between oxygen supply and demand,
important clinical implications. Data from the reduced coronary flow reserve and subsequent
Atherosclerosis Risk in Communities (ARIC) study myocardial ischemia.44
of more than 15, 000 African American and white There is evidence that optimal control of blood
men and women showed that frequent or complex pressure and regression of LVH can result in a
ventricular ectopic beats are associated with high decreased incidence of sudden cardiac death.1,45
blood pressure.38 Epidemiologic data have shown It is also important to consider the potential influ-
that hypertension induced LVH is associated with ence of antihypertensive drugs on the risk of sud-
sustained ventricular arrhythmias.39 High blood den cardiac death. The use of thiazide diuretics

Table 1
Anti-hypertensive medications and prevention of new-onset AF

Treatment Trial/Study Results

Losartan Losartan Intervention For EndPoint A 33% decrease in new-onset
reduction in hypertension (LIFE) AF compared with treatment
with atenolol (3.5% vs 5.3%)
Valsartan Valsartan Antihypertensive Long-term A 16% decrease in new-onset
Use Evaluation Trial (VALUE) AF compared with amlodipine
Beta-blockers (bisoprolol, Prevention of atrial fibrillation A 27% decrease in new-onset
metoprolol, bucindolol, onset by beta-blocker treatment AF in beta-blocker treated
Carvedilol, nebivolol) in heart failure: a meta-analysis patients with congestive
heart failure compared with
placebo
548 Afzal et al

has been associated with a dose-dependent in- and data from contemporary real-world AF regis-
crease in sudden cardiac death, probably by tries shows that physicians often underestimate
increasing the risk of hypokalemia, QT prolonga- the significance of hypertension as a stroke risk
tion, QT dispersion, and the propensity for arrhyth- factor, despite clearly positive net clinical benefit
mogenic early and delayed after-depolarizations.44 (the balance of stroke reduction against serious
Antihypertensive therapy with angiotensin receptor bleeding) of oral anticoagulation in patients with 1
blockers and angiotensin-converting enzyme inhib- or more stroke risk factors in contemporary large
itors was associated with a decreased risk of sud- AF cohorts.51
den cardiac death.29,46 This finding provides
some supportive evidence for blocking the RAAS ECONOMIC IMPACT OF HYPERTENSION AND
in hypertensive patients at high risk of sudden car- ARRHYTHMIAS
diac death.
The high prevalence of both hypertension and AF
IMPLICATIONS OF SUBOPTIMAL TREATMENT and the increasing costs for their treatment consti-
OF ARRHYTHMIAS AND HYPERTENSION tute an important financial burden; therefore, many
Heart Failure economic analyses have been done with the aim
to assess the cost effectiveness of treating these
Almost 50% of patients with HF have HFpEF.10 diseases. In these analyses the focus is mainly
Most common precipitants for HFpEF include un- on the risk of stroke and the savings that can be
controlled hypertension and AF, the 2 conditions obtained by preventing stroke occurrence and
that require aggressive management during an the consequent health care resources for hospital-
episode of decompensated HF. The incidence of ization, rehabilitation, and assistance resulting
HFpEF increases with advancing age, hyperten- from disability, which are associated with high
sion, diabetes, obesity, and chronic renal dysfunc- direct and indirect costs.43,52
tion. All these risk factors are also implicated for The stroke associated with AF lead to significant
the onset and progression of AF. Rhythm control debility and the cost of taking care of such patients
or aggressive rate control for AF is needed for is greater than the costs for stroke unrelated to AF.
the appropriate management of HFpEF. Similarly, Several studies performed after novel oral antico-
aggressive blood pressure control is crucial during agulants became available have shown that these
an acute exacerbation of HFpEF.43,47 medications are cost effective despite a higher
initial cost owing to the significant decrease in
Orthostatic Hypotension intracranial bleeding and stroke prevention.53
Treatment of hypertension in elderly patients with Finally, from an economic perspective, it is
AF has implications. The incidence of orthostatic noteworthy to stress that, because AF is frequently
hypotension in elderly patients receiving antihy- asymptomatic, opportunistic screening for
pertensive medications is high and an anticipated asymptomatic AF is indicated to institute antith-
increased risk of falling may inappropriately pre- romboembolic prophylaxis in patients at risk, and
vent the use of anticoagulation for stroke preven- proved to be cost effective.54,55
tion.48 Similarly, the concomitant use of certain
antidepressants, antipsychotics, or drugs for Par- SUMMARY
kinson disease with antihypertensive medications
(eg, diuretics, alpha-blockers, beta-blockers, cal- Experimental and epidemiologic studies have
cium channel blockers, RAAS blockers, and ni- established a close link between hypertension,
trates) may increase the risk of orthostatic LVH, and various cardiac arrhythmias. Chronic hy-
hypotension. When possible, patients should be pertension results in the alteration of cardiac he-
monitored for ambulatory standing blood pressure modynamic, structural, and electrophysiological
to appropriately screen for fall risk.49 properties and leads to the development of AF,
ventricular arrhythmias, and sudden cardiac
death. Optimal management of hypertension with
Thromboembolism and Increased Bleeding
different agents to lower blood pressure and,
Risk
more important, to regress LVH can prevent AF
Optimal blood pressure control is crucial for both and sudden cardiac death. Treatment with
stroke and bleeding risk reduction in patients angiotensin-converting enzyme inhibitors and
with AF taking oral anticoagulation.50 Given its angiotensin receptor blockers has been shown to
high prevalence among patients with AF, hyper- decrease ventricular ectopy and sudden cardiac
tension may often be the single risk factor death. Beta-blocker therapy also should be
requiring a decision on oral anticoagulation use, considered in patients who require additional
 Hypertension and Arrhythmias 549

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the 21st century. Int J Cardiol 2013;167:1807–24.
16. Seccia TM, Caroccia B, Muiesan ML, et al. Atrial
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