Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

O fficial reprint from UpToDate ®

www.uptodate.com ©2020 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Secondary prevention of sudden cardiac death in heart

failure and cardiomyopathy
Authors: Joseph E Marine, MD, FACC, FHRS, Andrea M Russo, MD, FACC, FHRS
Section Editors: Bradley P Knight, MD, FACC, Samuel Lévy, MD
Deputy Editor: Brian C Downey, MD, FACC

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature rev iew current through: Mar 2020. | This topic last updated: Jan 04, 2019.

INTRODUCTION

Life-threatening ventricular arrhythmias, including sustained ventricular tachycardia (VT) and

ventricular fibrillation (VF), are common in patients with heart failure (HF) and cardiomyopathy
and may lead to sudden cardiac death (SCD). Secondary prevention of SCD refers to medical or
interventional therapy undertaken to prevent SCD in patients who have experienced symptomatic
life-threatening sustained VT/VF or have been successfully resuscitated from sudden cardiac
arrest. The secondary prevention of SCD in patients with HF and cardiomyopathy will be
reviewed here, with emphasis on the role of implantable cardioverter-defibrillators (ICDs). The
different types of ventricular arrhythmias, the effects of HF therapy on ventricular arrhythmias, and
the role of electrophysiologic testing are discussed separately. (See "Ventricular arrhythmias:
Overview in patients with heart failure and cardiomyopathy".)

The approaches to the treatment of ventricular arrhythmias related to specific heart muscle
diseases, such as hypertrophic cardiomyopathy, arrhythmogenic right ventricular
cardiomyopathy and isolated left ventricular noncompaction, are discussed elsewhere. (See
"Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis" and "Isolated left
ventricular noncompaction in adults: Clinical manifestations and diagnosis" and "Hypertrophic
cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk".)

1 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

EPIDEMIOLOGY

While the exact percentages and mode of death in patients with HF vary with HF class and type
of cardiomyopathy, progressive pump failure, unexpected SCD, and SCD during episodes of
clinical worsening of HF each account for approximately one-third of deaths in HF patients [1].
Ventricular tachycardia (VT) and ventricular fibrillation (VF) are the most common arrhythmic
causes of SCD, although bradyarrhythmias and pulseless electrical activity (PEA) are
responsible in 5 to 33 percent of cases [2,3].

More severe HF is associated with a higher overall mortality rate and a higher absolute rate of
SCD, but a decreasing proportion of SCD to total deaths. This trend was illustrated in the MERIT-
HF (Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure) trial in which
patients with increasing HF class (NYHA class II, III and IV) had increasing rates of SCD at one
year (6.3, 10.5, and 18.6 percent, respectively), but a decreasing percentage of deaths that were
classified as SCD (64, 59, and 33 percent, respectively) [4].

Patients who have received an implantable cardioverter-defibrillator (ICD) for secondary

prevention have significantly higher rates of recurrent ventricular arrhythmias triggering
appropriate ICD intervention than recipients of primary prevention ICDs, approximately threefold
higher in one national registry from Israel [5]. Although ICD therapy improves survival of patients
who suffered prior sudden cardiac arrest, mortality remains high. The mechanisms of death in
such patients were illustrated in analyses from several secondary prevention ICD studies [6-8]:

● Nonarrhythmic cardiac death, usually progressive HF – 45 to 50 percent

● Arrhythmic death – 20 to 35 percent
● Noncardiac death, primarily renal and pulmonary disease – 20 to 30 percent

Arrhythmic death can occur despite recognition and termination of tachyarrhythmias by the ICD
[9]. These deaths often result from PEA, also called electromechanical dissociation (EMD), or
acute cardiac mechanical dysfunction [7-9]. PEA or bradyarrhythmias may be the mechanism of
SCD in up to 40 percent of patients [7,8]. However, post-mortem interrogation of ICDs
demonstrated that 25 percent of sudden deaths in ICD patients (representing 5 percent of all
deaths) were caused by inability to defibrillate VF [8]. This situation may occur with VT/VF storm
or refractory myocardial ischemia/infarction.

SECONDARY PREVENTION OF SCD

2 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

Patients with HF or cardiomyopathy who survive an episode of sudden cardiac arrest (SCA) or
experience sustained ventricular tachycardia (VT) are at high risk of future sustained arrhythmic
events and SCD.

Our approach — We proceed with implantable cardioverter-defibrillator (ICD) implantation in

most survivors of SCA due to sustained VT or ventricular fibrillation (VF), after completely
reversible causes are excluded. (See 'Reversible causes of SCA or sustained VT' below.)

Antiarrhythmic medications and/or catheter ablation should be used as adjunctive therapy to ICD
implantation. In rare instances, antiarrhythmic drugs and/or catheter ablation may be selected
as primary therapy for patients who refuse or who are not considered candidates for ICD therapy.
These recommendations are in broad agreement with 2017 guidelines published by the
American Heart Association/American College of Cardiology/Heart Rhythm Society
(AHA/ACC/HRS) [10].

Reversible causes of SCA or sustained VT — In some survivors of SCA or sustained VT, a

transient or reversible cause (eg, acute myocardial ischemia [MI], electrolyte disturbances,
medication-related proarrhythmia, etc) can be identified which is felt to have caused the acute
problem. Initial treatment should be directed at the underlying disorder. However, prior to
concluding that SCA was due to a reversible cause, a thorough evaluation should be performed,
usually involving a heart rhythm specialist. For example, in a patient who presents with VF and is
found to have mild hypokalemia, it is generally not appropriate to assign the cause of the SCA
just to the low potassium level.

Correction of a reversible cause of SCA or sustained VT is most likely to be adequate in one of

several settings:

● Polymorphic VT or VF that is preceded by clear evidence of MI or acute MI – In such cases,

revascularization is often adequate for the purpose of reducing the risk of SCD. However,
some of these patients will later qualify for a primary prevention ICD due to severe left
ventricular (LV) systolic dysfunction (MADIT II criteria) or systolic dysfunction and HF (SCD-
HeFT criteria). Guideline-directed medical therapy should be applied, and follow-up
evaluation with a cardiologist soon after discharge should be arranged for additional risk
stratification. A repeat evaluation of LV function is recommended >40 days post-MI and >90
days after revascularization to determine if the patient qualifies for ICD implantation based
on primary prevention indications [10]. (See "Incidence of and risk stratification for sudden
cardiac death after myocardial infarction".)

● Polymorphic VT in the setting of acquired QT prolongation – In such cases, withdrawal of the

3 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

offending drug and avoidance of other QT prolonging medications may be adequate to

reduce the risk of SCD. (See "Acquired long QT syndrome: Clinical manifestations,
diagnosis, and management".)

● VF occurring in the setting of Wolff-Parkinson-White syndrome in patients with a structurally

normal heart – These patients are adequately treated with catheter ablation of the accessory
pathway. (See "Treatment of symptomatic arrhythmias associated with the Wolff-Parkinson-
White syndrome".)

● Idiopathic monomorphic VT occurring in the setting of a structurally normal heart – Such

patients are usually adequately treated with medical therapy or catheter ablation. (See
"Ventricular tachycardia in the absence of apparent structural heart disease".)

● VT/VF occurring in the setting of intentional or accidental drug overdose – Examples include
cocaine, amphetamines, digoxin, tricyclic antidepressants, and antiarrhythmic drugs.

In most other cases, life-threatening ventricular arrhythmias should not be attributed solely to a
reversible disorder, and patients should be evaluated according to standard approaches to
secondary prevention.

Evidence for use of ICD therapy — Most patients with HF or cardiomyopathy who have
sustained VT or VF are candidates for ICD therapy. The indications for ICD implantation for
secondary prevention of SCD are presented here (table 1), while those for primary prevention
are discussed separately. (See 'Our approach' above and "Primary prevention of sudden cardiac
death in heart failure and cardiomyopathy".)

AVID trial — In the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, 1016 patients
who presented with (a) resuscitated VF, (b) sustained VT with syncope, or (c) sustained VT with
BP <80 mmHg or significant symptoms (near-syncope, CHF, or angina) suggesting
hemodynamic compromise and LV ejection fraction (LVEF) ≤40 percent were randomized to
treatment with either an ICD or antiarrhythmic drugs (primarily amiodarone [96 percent]) [11]. The
following findings were noted:

● The trial was stopped when a significant survival benefit was observed in patients receiving
the ICD compared with those treated with antiarrhythmic agents (sotalol or amiodarone).
The unadjusted survival for the ICD versus drug groups was 89 versus 82 percent at one
year, 82 versus 75 percent at two years, and 75 versus 65 percent at three years.

● The major effect of the ICD was to prevent arrhythmic death (4.7 versus 10.8 percent with
antiarrhythmic drugs); nonarrhythmic cardiac death was equivalent, while patients treated

4 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

with antiarrhythmic drugs had an insignificantly greater incidence of noncardiac death,

primarily from renal and pulmonary causes [6].

● In patients with an LVEF ≥35 percent, there was no significant difference in survival between
ICD and antiarrhythmic drugs (83.4 versus 82.7 percent at two years), while in those with an
LVEF between 20 and 34 percent, survival was significantly better with the ICD (83 versus 72
percent) [12]. Among the relatively small number of patients with an LVEF <20 percent,
survival tended to be better with the ICD (72 versus 64 percent), but the difference did not
reach statistical significance.

CASH trial — In the Cardiac Arrest Survival in Hamburg (CASH) trial, 349 survivors of cardiac
arrest due to documented VT or VF were randomly assigned to treatment with an ICD,
metoprolol, propafenone, or amiodarone [13]. Assignment to propafenone was discontinued
prematurely when interim analysis revealed a 61 percent higher mortality than that seen in
patients randomized to ICD therapy.

After a mean follow-up of 57 months, there was a non-significant reduction in total mortality in
patients receiving an ICD compared with those treated with amiodarone or metoprolol (36.4
versus 44.9 percent). The secondary end point of SCD was significantly reduced by the ICD
compared with drug therapy (13 versus 33 percent).

CIDS trial — In the Canadian Implantable Defibrillator Study (CIDS) 659 patients with
resuscitated VT/VF or syncope deemed to be secondary to VT/VF were randomly assigned to
amiodarone or ICD therapy and followed for five years [14]. In those treated with an ICD, there
were non-significant reductions in total mortality (8.3 versus 10.2 percent per year) and SCD (3
versus 4.5 percent per year).

Meta-analysis — A significant mortality benefit with ICD therapy was noted in the AVID trial,
while nonsignificant trends toward reduced mortality with ICD therapy were noted in the CASH
and CIDS trials. The lack of statistical significance in the last two trials could have represented a
beta error as the trials were underpowered to detect a significant difference of the magnitude
observed. In addition, it is possible that patients considered by their clinicians to be good
candidates for ICD therapy would be less likely to be enrolled and subjected to randomization,
thus favoring the control group.

In a meta-analysis of the AVID, CASH, and CIDS trials along with a fourth smaller trial, the
following findings were noted [15]:

● Patients with an ICD had a significant reduction in total mortality compared with those
receiving antiarrhythmic therapy (hazard ratio [HR] 0.75, 95% CI 0.64-0.87).

5 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

● Patients with an ICD had a 50 percent reduction in SCD (HR 0.50, 95% CI 0.34-0.62).

● The absolute reduction in all-cause mortality was 7 percent, meaning that 15 patients
needed to be treated to prevent one death.

A second meta-analysis of AVID, CIDS, and CASH came to similar conclusions, finding a 28
percent relative risk reduction in all-cause mortality and a 50 percent reduction in arrhythmic
death [16]. Patients with LVEF >35 percent had less benefit from ICD therapy than those with EF
≤35 percent.

A subsequent meta-analysis of AVID, CIDS, and CASH further quantitated the benefit of the ICD
in secondary prevention patients, finding a two-year absolute risk reduction in total mortality of 8
percent, with a number needed to treat to achieve mortality benefit of 13 [17].

Contemporary observational cohort studies — The evidence supporting ICD therapy for
secondary prevention rests upon randomized clinical trials that were conducted in the 1980s
and 1990s. However, more contemporary observational studies or registries support these
findings. In a cohort of 6996 patients with new onset ventricular arrhythmia in the setting of
preexisting coronary heart disease and HF (from the National Veterans Administration
database), 1442 patients had an ICD implanted [18]. At three-year follow-up, the patients who
received an ICD had significant reductions in all-cause and cardiovascular mortality compared
with those without an ICD (37 versus 55 percent and 23 versus 36 percent, respectively;
adjusted odds ratio 0.52 for all-cause mortality and 0.56 for cardiovascular mortality), with no
difference in noncardiac death. The benefit occurred despite a significantly lower frequency of
use of angiotensin converting enzyme (ACE) inhibitors, beta blockers, and statins. This
reduction in risk of death (28 percent) was similar to that seen in AVID (31 percent). In a smaller
study of 357 patients who received an ICD for secondary prevention with much longer follow-up
(mean 82 months), 208 persons (59 percent) received an ICD therapy for ventricular
tachyarrhythmia, while 44 percent of participants died without receiving any ICD therapy [19]. An
analysis of the NCDR ICD Registry evaluated mortality in 46,685 patients with ICDs implanted
for secondary prevention indications in contemporary practice [20]. The mortality rate in this
registry at one year was 10 percent compared with 8 to 11 percent among ICD patients enrolled
in the secondary prevention randomized clinical trials (AVID, CIDS, CASH). Overall, the
magnitude of the benefit of ICD therapy for secondary prevention in this real-world cohort was
similar to or greater than that in the randomized trials, although mortality also remains high due
to significant comorbidities.

Effect in elderly patients — Randomized clinical trials evaluating the role of the ICD for
secondary prevention included only a minority of patients who were ≥75 years old. A meta-

6 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

analysis of pooled individual patient data from three major randomized trials (CASH, CIDS, and
AVID) comparing ICD with antiarrhythmic therapy for secondary prevention included 252 patients
(out of 1866 total, or 13.5 percent) who were ≥75 years old [21]. This meta-analysis suggested
that the survival benefit from ICD therapy may be reduced in elderly patients compared with
younger patients [21-23]. In contrast, other studies have shown older patients to benefit equally
from primary or secondary prevention ICD therapy as younger patients [24,25].

While clinical trials enrolled relatively few older adult patients, the National Cardiovascular Data
Registry ICD Registry provides the ability to examine outcomes in much larger numbers of
patients in real-life clinical practice. In an analysis of 12,420 Medicare patients who were ages
65 years or older (mean age 75 years) who underwent initial ICD implantation between 2006
and 2009 for secondary prevention of SCD, the overall risk of death at two years was 21.8
percent [26]. However, there was a twofold difference in total mortality between patients ≥80
years of age and those who were ages 65 to 69 years (28.9 versus 14.7 percent; adjusted risk
ratio 2.01, 95% CI 1.85-2.33). The study did not include a control group of similarly matched
patients without an ICD; therefore no conclusions can be drawn about any potential total
mortality benefit from placing the ICD for secondary prevention. However, nearly four in five
patients over age 65 years who received an ICD for secondary prevention were alive two years
later, indicating that age alone should not be the deciding criterion for ICD placement. Rather,
multiple clinical factors should be considered including comorbidities, functional status, and
competing risks of mortality, with the patient and family engaged in a shared decision-making
process.

These results suggest that ICD use in elderly patients should be individualized. Patients with
few comorbidities may benefit, while those with significant other illnesses may be more likely to
die of non-arrhythmic causes. Clinicians should consider issues of competing mortality risk, co-
morbidities, risk of complications, and patient preferences for end-of-life care. In addition,
treatment options should be carefully discussed with patients and families to allow shared
decision making.

Effect in heart failure — Patients who are being evaluated for an ICD for secondary
prevention and who have at least class II HF symptoms, significant LV systolic dysfunction, left
bundle branch block, and a QRS duration ≥150 milliseconds should be strongly considered for
an ICD that also provides cardiac resynchronization therapy (CRT). Some patients with a QRS
duration of 120 to <150 milliseconds, those with non-LBBB conduction delays, and class I
ischemic patients may also be candidates for CRT [27]. This is discussed in greater detail
elsewhere. (See "Cardiac resynchronization therapy in heart failure: Indications" and "Primary
prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Use of an

7 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

ICD'.)

Patients with syncope — Some of the randomized trials of ICDs for the secondary prevention
of SCD included patients with syncope and either spontaneous or induced sustained VT. For
patients with HF or cardiomyopathy who have had syncope and either induced or spontaneous
VT, we recommend treatment with an ICD for secondary prevention of SCD [10].

Based upon observational data from patients with nonischemic cardiomyopathy, severe LV
dysfunction, and unexplained syncope, ICD implantation is also often appropriate. Most patients
with ischemic cardiomyopathy and an LVEF ≤35 percent qualify for ICD therapy even without
syncope based upon the results of the MADIT-II and SCD-HeFT trials.

The best approach for managing patients with an LVEF >35 percent and unexplained syncope is
not clear and likely varies according to the etiology of the cardiomyopathy. For such patients with
an ischemic cardiomyopathy, we generally perform an invasive electrophysiology (EP) study and,
if the patient has inducible VT, implant an ICD. For patients with a nonischemic cardiomyopathy,
an EP study is less informative, although it may reveal conduction abnormalities or bundle
branch reentrant VT. In such patients, decisions regarding ICD implantation should be
individualized based upon clinical circumstances, type of heart muscle disease, and patient
preference.

The 2017 AHA/ACC/HRS guidelines recommend the use of an ICD in patients with significant LV
dysfunction due to ischemic cardiomyopathy who have unexplained syncope [10]. However,
regardless of the history of syncope, many such patients will already qualify for an ICD for
primary prevention of SCD based upon SCD-HeFT criteria, and patients with ischemic
cardiomyopathy and severe LV dysfunction (ie, LVEF ≤30 to 35 percent) generally qualify for an
ICD based upon MADIT-II or SCD-HeFT criteria.

Patients with transient or reversible disorders — Patients with a life-threatening ventricular

tachyarrhythmia due to a transient or reversible cause (often an ischemic event) have been
thought to have a low risk for recurrent SCA after correction of the underlying precipitant.
However, many such patients remain at high risk for SCA, and the full clinical context should be
considered before concluding that VT/VF is entirely due to a transient or reversible cause [28,29].
As examples:

● While acute ischemic events occur in patients who may have had an antecedent MI or
multivessel disease, the presence of scar from a prior MI and progression of CHD both
increase the risk of future events. In the Antiarrhythmics Versus Implantable Defibrillators
(AVID) trial, patients identified with a potentially transient or correctable cause for VT/VF

8 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

(such as an ischemic event, electrolyte abnormalities, or drug reactions) remained at high

risk for death [28]. (See "Prognosis and outcomes following sudden cardiac arrest in
adults".)

● In a retrospective single-center cohort study of 1433 patients with SCA between 2000 and
2012 who survived to hospital discharge, 792 patients (55 percent) were felt to have a
reversible and correctable cause, which included evidence of acute MI or ischemia,
significant electrolyte or metabolic abnormality, or recent antiarrhythmic medication or illicit
drug use, with 207 patients (26 percent) with a reversible cause receiving an ICD [30]. Over
a mean follow-up of 3.8 years, 319 patients (40 percent) died, with ICD recipients having a
significantly lower mortality risk (HR 0.61 compared with patients without an ICD, 95% CI
0.47-0.80). The benefit was consistent across all subgroups with the exception of patients
whose reversible cause was MI/ischemia, in whom no mortality benefit was seen. While
patients with SCA in the setting of MI did not receive a mortality benefit from ICD therapy, it
should be noted that all of these patients underwent coronary revascularization before being
classified as having a reversible cause of SCA. Additionally, 32 of the ICD recipients (15
percent) received an appropriate ICD therapy during follow-up, including 21 percent of the
group without MI/ischemia, suggesting that SCA in the setting of a perceived reversible
cause may not always be related to the putative reversible cause. While this study is limited
by its retrospective, nonrandomized nature, it suggests caution on the part of clinicians
evaluating patients after cardiac arrest not to overestimate the potential for reversibility of
arrhythmic risk, particularly outside of the setting of acute MI.

The 2017 AHA/ACC/HRS guidelines for the management of ventricular arrhythmias and the
prevention of sudden cardiac death recommend ICD therapy for patients who either survive SCA
or experience hemodynamically unstable VT or stable VT not due to "reversible causes" if
meaningful survival greater than one year is expected [10]. As defined in AVID, "potentially
reversible causes" may include acute MI, transient ischemia, electrolyte imbalance,
antiarrhythmic drug proarrhythmia, hypoxia, electrocution, drowning, or sepsis. Clinical judgment
is needed to discern which causes are entirely transient or reversible.

General opinion would support the following:

● Patients who experience cardiac arrest due to polymorphic VT or VF in the setting of acute
ischemia or an MI should be treated with revascularization for the purpose of reducing the
risk of SCD. Patients may be eligible for ICD therapy if they are considered ineligible for
complete revascularization.

● In general, patients with polymorphic VT or VF who also have electrolyte disorders should

9 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

be evaluated and treated in the same manner as other patients, including evaluation for ICD
therapy unless the electrolyte abnormalities are proved to be the cause of the arrhythmia.

● Patients who experience sustained monomorphic VT in the setting of antiarrhythmic drug

use or electrolyte abnormalities should be evaluated and treated in the same manner as
other patients. Antiarrhythmic drugs or electrolyte abnormalities should not be assumed to
be the sole cause of sustained monomorphic VT.

● Patients who experience polymorphic VT in the setting of acquired QT prolongation due to

drug therapy should be advised to avoid exposure to all agents associated with QT
prolongation. (See "Acquired long QT syndrome: Clinical manifestations, diagnosis, and
management".)

SCD despite ICD implantation — In the trials of ICD therapy for the secondary prevention of
SCD, approximately 20 to 35 percent of the deaths in patients with an ICD were due to SCD.
These deaths may result from pulseless electrical activity (PEA), pulmonary embolus, ruptured
aortic aneurysm, VT below rate detection cutoff, and, rarely, from ICD failure. Post-mortem
interrogation of ICDs revealed that the most common mechanism of SCD in patients was VT/VF
treated with an appropriate shock followed by PEA [8]. Increasingly frequent and refractory
episodes of VT/VF may reflect the terminal stage of severe HF, and such patients may succumb
from VT/VF storm despite appropriate function of the ICD. (See 'Epidemiology' above.)

Other treatment options — In addition to the ICD, several other pharmacologic and
nonpharmacologic therapies have been evaluated in survivors of SCD. None is considered an
adequate alternative to ICD therapy in most clinical circumstances, but each has a role in
selected patients.

Antiarrhythmic drugs — Antiarrhythmic drugs may be used to improve quality of life in

patients with frequent ventricular tachyarrhythmias leading to ICD shocks, or in those patients
who are not candidates for or who decline ICD implantation. In the presence of HF and/or
structural heart disease, antiarrhythmic drug therapy is limited to a small number of choices (ie,
amiodarone, sotalol, mexiletine) [10]. In patients who require an antiarrhythmic drug, we typically
prefer amiodarone in patients with HF and LV dysfunction due to its superior efficacy and
demonstration of safety in patients with HF and structural heart disease. Sotalol or mexiletine
may be alternative drugs for selected patients with structural heart disease who have an ICD.
Often, a beta blocker is coadministered with antiarrhythmic drugs, which do not have intrinsic
beta-blocker activity. Beta blockers are often separately indicated in patients with ventricular
arrhythmias due to coexistent HF, LV dysfunction, and/or coronary artery disease. In addition,
beta blockers have important antiarrhythmic action which may reduce recurrence of ventricular

10 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

arrhythmias. (See 'Beta blockers' below.)

In survivors of SCA, the need for adjunctive antiarrhythmic drug therapy is not uncommon, with
an antiarrhythmic drug being added to ICD therapy in 22 percent at two years in the AVID trial and
in 28 percent at five years in the CIDS trial [11,14].

In patients who have an ICD in place, there are two main indications for concomitant
antiarrhythmic drug therapy (most commonly amiodarone, sotalol, or mexiletine).

● To reduce the frequency of ventricular arrhythmias – In the AVID trial, frequent ICD shocks
were the primary reason for adding an antiarrhythmic drug (64 percent) [31]. Frequent
shocks impact quality of life. (See "Cardiac implantable electronic devices: Long-term
complications", section on 'Quality of life'.)

● To suppress supraventricular arrhythmias – Arrhythmias other than VT or VF may cause

symptoms or result in "inappropriate" discharges. Atrial fibrillation is by far the most
common of these arrhythmias. Dofetilide may also be a useful agent for treatment of atrial
fibrillation in patients with underlying structural heart disease.

Amiodarone is generally the preferred antiarrhythmic choice and was shown in the OPTIC trial to
be more effective than sotalol. However, this drug has more long-term side effects and drug
interactions than other antiarrhythmic agents. In some circumstances, therefore, it may be more
appropriate to use sotalol or mexiletine, despite the superior efficacy of amiodarone. In addition,
amiodarone may result in an increase in the defibrillation threshold, which could adversely affect
ICD shock efficacy. (See "Amiodarone: Adverse effects, potential toxicities, and approach to
monitoring" and "Amiodarone: Clinical uses", section on 'Drug interactions' and "Pharmacologic
therapy in survivors of sudden cardiac arrest", section on 'Choice of pharmacologic therapy'.)

While antiarrhythmic drugs are sometimes required to reduce the frequency of shocks and
improve a person's quality of life, a systematic review of 17 studies involving nearly 6000 ICD
recipients showed that shock prevention using antiarrhythmic therapy resulted in no
improvement in mortality [32]. (See "Pharmacologic therapy in survivors of sudden cardiac
arrest", section on 'Antiarrhythmic drugs'.)

Other medical therapies

Beta blockers — The majority of patients who receive an ICD will be treated with a beta
blocker as part of the therapy for their underlying heart disease. Beta blockers confer an
additional survival benefit in patients with an MI, HF, congenital long QT syndrome, or
catecholaminergic polymorphic VT. Additional benefits of beta-blockers in ICD patients may

11 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

include reduction in inappropriate ICD shocks from sinus tachycardia and atrial fibrillation with a
rapid ventricular response. Careful attention to ICD programming, including programming a long
detection delay, may also reduce unnecessary ICD therapy [33,34]. (See "Beta blockers in the
management of chronic coronary syndrome" and "Initial pharmacologic therapy of heart failure
with reduced ejection fraction in adults", section on 'Beta blocker'.)

Among survivors of SCA who were eligible but not randomized in the AVID trial, beta-blocker use
was associated with improved survival in patients who were not treated with specific
antiarrhythmic therapy (adjusted RR 0.47, 95% CI 0.25-0.88) [35].

Lipid-lowering therapy — Most patients with CHD who have an ICD are treated with lipid-
lowering therapy. However, data on the effect of lipid-lowering therapy on ventricular arrhythmia
are mixed. [36,37]. Among 362 patients with CHD who received an ICD in the AVID trial, there
was a significant reduction in the risk of recurrence of VT or VF in the 83 patients receiving lipid-
lowering therapy (adjusted HR 0.40, 95% CI 0.15 to 0.58). Reduction in VT/VF was also seen
among statin-treated patients in one primary prevention ICD trial [38]. However, there are still no
randomized controlled trials to suggest that lipid-lowering therapy confers an independent
antiarrhythmic effect in patients with VT/VF. (See "Management of low density lipoprotein
cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)

There are mixed data on whether the administration of fish oil reduces the risk of recurrent
ventricular tachyarrhythmias. A meta-analysis of three fish oil trials showed no overall effect of
fish oil treatment on the risk of ICD discharge [39]. (See "Fish oil: Physiologic effects and
administration", section on 'Potential effects on cardiovascular and metabolic systems'.)

Ranolazine — Initially developed as an antianginal therapy, some studies have suggested

that ranolazine has antiarrhythmic properties, including one trial in which ranolazine reduced the
frequency of both supraventricular and ventricular arrhythmias within seven days of an acute
coronary syndrome. This prompted investigators to study the effectiveness of ranolazine in
reducing ventricular arrhythmias in patients with an ICD in the RAID trial, which randomized 1012
high-risk patients with ischemic or nonischemic cardiomyopathy and an ICD to receive either
ranolazine (1000 mg twice daily) or placebo in addition to usual care [40,41]. During a mean
follow-up of 28 months, there was a non-significant reduction in the primary end point of death or
appropriate ICD shock among patients in the ranolazine group compared with placebo (HR
0.84; 95% CI 0.67-1.05), with a pre-specified secondary analysis identifying a significant
reduction in recurrent ICD therapies (ATP and shocks) in the ranolazine group (HR 0.70; 95% CI
0.51-0.96). Compliance in the study was poor, however, with 50 percent of patients receiving
ranolazine and 40 percent of patients receiving placebo discontinuing the medication. Until

12 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

further data become available, suggesting a benefit, ranolazine should not be used routinely to
prevent VT/VF in patients with an ICD, but there may be select patients (eg, those with frequent
ICD therapies in spite of maximal medical therapy) in whom its use is reasonable.

Radiofrequency ablation — Similar to antiarrhythmic drugs, catheter ablation may be used

as adjunctive therapy to improve quality of life in patients with frequent ventricular
tachyarrhythmias leading to ICD shocks, or in those patients who are not candidates for or
refuse ICD placement. Catheter ablation alone without an ICD is rarely appropriate for patients
who survive cardiac arrest due to VT/VF or who have VT associated with structural heart disease.

Radiofrequency ablation (RFA) is often an effective treatment for VT, particularly monomorphic VT
due to reentry. In patients with a prior MI, the border zone of the infarct is frequently the site of the
reentrant circuit, and these sites are often amenable to endocardial catheter ablation [42]. In
contrast, patients with nonischemic cardiomyopathy may have multiple endocardial reentrant
circuits, epicardial or mid-myocardial circuits, or other mechanisms of VT (eg, triggered
arrhythmias or polymorphic VT) [43]. Due to the presence of more complex arrhythmic substrate,
endocardial RFA is less effective in patients with nonischemic cardiomyopathy, and an epicardial
approach may be required [44]. Catheter ablation may also be effective in selected patients with
polymorphic VT or VF associated with triggering PVCs arising in the right ventricular outflow tract
or His-Purkinje system [45]. (See "Overview of catheter ablation of cardiac arrhythmias".)

Catheter ablation of VT is considered in three settings:

● As an adjunct to an ICD in patients who have frequent ventricular arrhythmias and ICD
therapies. (See "Electrical storm and incessant ventricular tachycardia", section on 'Catheter
ablation'.)

● As an alternative to an ICD in patients who do not want or are not candidates for an ICD.

● As prophylactic adjunctive therapy in patients who initially presented with sustained VT and
received ICD therapy. A meta-analysis of five trials showed that this approach reduces the
risk of VT recurrence by 35 percent with no effect on mortality [46].

Arrhythmia surgery

Ischemic cardiomyopathy — Reentrant VT circuits associated with a chronic myocardial

infarct scar can be surgically resected. Arrhythmia surgery was used more commonly prior to the
advent of RFA, particularly in patients with an LV aneurysm and sustained monomorphic VT. The
successes of ICD implantation and RFA have made surgery for ventricular arrhythmias
appropriate only in rare circumstances. (See "Sustained monomorphic ventricular tachycardia in

13 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

patients with structural heart disease: Treatment and prognosis", section on 'Surgical therapy'.)

Nonischemic cardiomyopathy — Surgical treatment of VT/VF in patients with nonischemic

cardiomyopathy has not been well studied, but likely has a lower success rate than in ischemic
cardiomyopathy, given that the underlying myocardial disease tends to be diffuse without a
discrete scar or aneurysm present. In selected patients, however, there remains a role for
surgical treatment. In a study of eight patients in whom percutaneous ablation was not an
option, successful reduction in VT was reported in six of eight nonischemic cardiomyopathy
patients (75 percent) treated with surgical cryoablation [47].

Cardiac transplantation — Cardiac transplantation is occasionally required for patients with

incessant life-threatening ventricular arrhythmias, which cannot be controlled by medication or
catheter ablation. ICD therapy is generally contraindicated in patients with uncontrollable
incessant VT/VF, and such patients should proceed to mechanical support and transplantation if
they are candidates. (See "Heart transplantation in adults: Indications and contraindications",
section on 'Indications for transplantation'.)

Another scenario involves patients who are listed for cardiac transplantation who experience
cardiac arrest or symptomatic VT while on the waiting list. In such patients, there is an important
role for the ICD as a bridge to transplantation [48-52].

● In one study, 16 patients with a mean LVEF of 15 percent who were listed for heart
transplantation underwent ICD implantation for ventricular arrhythmias refractory to medical
therapy [48]. The ICD delivered appropriate shocks for tachyarrhythmias associated with
near syncope in all but one of the patients. Twelve patients underwent transplantation after a
mean of 156 days.

● In another study of 60 patients listed for heart transplantation who survived resuscitation
from sustained VT/VF, ICD implantation was associated with significantly improved survival.
Only 1 of 30 ICD patients (19 transplanted) versus 7 of 30 non-ICD patients (14
transplanted) died on the waiting list [53].

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Heart failure in adults"
and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac
implantable electronic devices".)

14 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5 th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10 th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)

● Beyond the Basics topic (see "Patient education: Heart failure (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● Patients with heart failure (HF) or cardiomyopathy who survive an episode of sudden cardiac
arrest (SCA) or experience sustained ventricular tachycardia (VT) are at high risk of future
arrhythmic events and sudden cardiac death (SCD). (See 'Secondary prevention of SCD'
above.)

● In some survivors of SCA or sustained VT, a transient or reversible cause (eg, acute
myocardial ischemia [MI], electrolyte disturbances, medication-related proarrhythmia, etc)
can be identified as being responsible for the SCA. Initial treatment should be directed at
the underlying disorder. However, prior to concluding that SCA was due to a reversible
cause, a thorough evaluation should be performed, usually involving a heart rhythm
specialist. (See 'Reversible causes of SCA or sustained VT' above.)

● Patients with HF and cardiomyopathy who survive an episode of SCA or have

hemodynamically unstable VT or stable VT are typically treated with implantable
cardioverter-defibrillator (ICD) therapy for secondary prevention if meaningful survival greater
than one year is expected.

• For survivors of SCA or sustained VT without a clearly reversible cause, we recommend

ICD implantation rather than antiarrhythmic drug therapy (Grade 1A). (See 'Evidence for
use of ICD therapy' above.)

15 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

• For survivors of SCA or sustained VT who are identified as having a definite transient or
reversible cause (eg, acute MI, acute infarction, severe electrolyte disturbances,
medication-related proarrhythmia, etc), in particular those whose cardiac rhythm is
polymorphic VT or ventricular fibrillation (VF), we do not recommend ICD implantation if
the etiology is clearly understood, the underlying cause is fully treated, and the condition
is unlikely to recur (Grade 1B). (See 'Reversible causes of SCA or sustained VT' above
and 'Patients with transient or reversible disorders' above.)

• For patients with HF or cardiomyopathy who have had syncope and either induced or
spontaneous VT, we recommend treatment with an ICD for secondary prevention of
SCD (Grade 1A). (See 'Patients with syncope' above.)

• For patients with nonischemic cardiomyopathy, significant LV dysfunction, and

unexplained syncope, we suggest ICD implantation (Grade 2B). Most patients with an
ischemic cardiomyopathy and left ventricular ejection fraction ≤35 percent already
qualify for an ICD based upon the results of the MADIT-II and SCD-HeFT trials. (See
'Patients with syncope' above.)

● Antiarrhythmic drugs may be used to improve quality of life in patients with frequent
ventricular tachyarrhythmias leading to ICD shocks, or in those patients who are not
candidates for or who decline ICD implantation. In patients who require an antiarrhythmic
drug, we typically prefer amiodarone in patients with HF and LV dysfunction due to its
superior efficacy and demonstration of safety in such patients. Sotalol and mexiletine may
be useful alternative drugs for selected patients. (See 'Antiarrhythmic drugs' above.)

● Similar to antiarrhythmic drugs, catheter ablation may be used as adjunctive therapy to

improve quality of life in patients with frequent ventricular tachyarrhythmias leading to ICD
shocks, or in those patients who are not candidates for or refuse ICD placement. Catheter
ablation alone without an ICD is rarely appropriate for patients who survive cardiac arrest
due to VT/VF or who have VT associated with structural heart disease. (See 'Radiofrequency
ablation' above.)

● The majority of patients who receive an ICD will be treated with a beta blocker as part of the
therapy for their underlying heart disease. (See 'Beta blockers' above.)

ACKNOWLEDGMENT

The authors and UpToDate would like to thank Dr. Phillip Podrid, Dr. Jie Cheng, Dr. Scott

16 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

Manaker, and Dr. Leonard Ganz, who contributed to earlier versions of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Narang R, Cleland JG, Erhardt L, et al. Mode of death in chronic heart failure. A request and
proposition for more accurate classification. Eur Heart J 1996; 17:1390.

2. Cleland JG, Erhardt L, Murray G, et al. Effect of ramipril on morbidity and mode of death
among survivors of acute myocardial infarction with clinical evidence of heart failure. A
report from the AIRE Study Investigators. Eur Heart J 1997; 18:41.

3. Greenberg H, Case RB, Moss AJ, et al. Analysis of mortality events in the Multicenter
Automatic Defibrillator Implantation Trial (MADIT-II). J Am Coll Cardiol 2004; 43:1459.

4. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised

Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999; 353:2001.

5. Sabbag A, Suleiman M, Laish-Farkash A, et al. Contemporary rates of appropriate shock

therapy in patients who receive implantable device therapy in a real-world setting: From the
Israeli ICD Registry. Heart Rhythm 2015; 12:2426.

6. Causes of death in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. J Am

Coll Cardiol 1999; 34:1552.

7. Grubman EM, Pavri BB, Shipman T, et al. Cardiac death and stored electrograms in
patients with third-generation implantable cardioverter-defibrillators. J Am Coll Cardiol
1998; 32:1056.

8. Mitchell LB, Pineda EA, Titus JL, et al. Sudden death in patients with implantable
cardioverter defibrillators: the importance of post-shock electromechanical dissociation. J
Am Coll Cardiol 2002; 39:1323.

9. Pires LA, Lehmann MH, Steinman RT, et al. Sudden death in implantable cardioverter-
defibrillator recipients: clinical context, arrhythmic events and device responses. J Am Coll
Cardiol 1999; 33:24.

10. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for

17 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden

Cardiac Death: A Report of the American College of Cardiology/American Heart
Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am
Coll Cardiol 2018; 72:e91.

11. Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of

antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from
near-fatal ventricular arrhythmias. N Engl J Med 1997; 337:1576.

12. Domanski MJ, Sakseena S, Epstein AE, et al. Relative effectiveness of the implantable
cardioverter-defibrillator and antiarrhythmic drugs in patients with varying degrees of left
ventricular dysfunction who have survived malignant ventricular arrhythmias. AVID
Investigators. Antiarrhythmics Versus Implantable Defibrillators. J Am Coll Cardiol 1999;
34:1090.

13. Kuck KH, Cappato R, Siebels J, Rüppel R. Randomized comparison of antiarrhythmic drug
therapy with implantable defibrillators in patients resuscitated from cardiac arrest : the
Cardiac Arrest Study Hamburg (CASH). Circulation 2000; 102:748.

14. Connolly SJ, Gent M, Roberts RS, et al. Canadian implantable defibrillator study (CIDS) : a
randomized trial of the implantable cardioverter defibrillator against amiodarone.
Circulation 2000; 101:1297.

15. Lee DS, Green LD, Liu PP, et al. Effectiveness of implantable defibrillators for preventing
arrhythmic events and death: a meta-analysis. J Am Coll Cardiol 2003; 41:1573.

16. Connolly SJ, Hallstrom AP, Cappato R, et al. Meta-analysis of the implantable cardioverter
defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs
Implantable Defibrillator study. Cardiac Arrest Study Hamburg . Canadian Implantable
Defibrillator Study. Eur Heart J 2000; 21:2071.

17. Betts TR, Sadarmin PP, Tomlinson DR, et al. Absolute risk reduction in total mortality with
implantable cardioverter defibrillators: analysis of primary and secondary prevention trial
data to aid risk/benefit analysis. Europace 2013; 15:813.

18. Chan PS, Hayward RA. Mortality reduction by implantable cardioverter-defibrillators in high-
risk patients with heart failure, ischemic heart disease, and new-onset ventricular
arrhythmia: an effectiveness study. J Am Coll Cardiol 2005; 45:1474.

19. Schaer B, Kühne M, Reichlin T, et al. Incidence of and predictors for appropriate

18 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

implantable cardioverter-defibrillator therapy in patients with a secondary preventive

implantable cardioverter-defibrillator indication. Europace 2016; 18:227.

20. Katz DF, Peterson P, Borne RT, et al. Survival After Secondary Prevention Implantable
Cardioverter-Defibrillator Placement: An Analysis From the NCDR ICD Registry. JACC Clin
Electrophysiol 2017; 3:20.

21. Healey JS, Hallstrom AP, Kuck KH, et al. Role of the implantable defibrillator among elderly
patients with a history of life-threatening ventricular arrhythmias. Eur Heart J 2007; 28:1746.

22. Panotopoulos PT, Axtell K, Anderson AJ, et al. Efficacy of the implantable cardioverter-
defibrillator in the elderly. J Am Coll Cardiol 1997; 29:556.

23. Narasimhan C, Dhala A, Axtell K, et al. Comparison of outcome of implantable cardioverter

defibrillator implantation in patients with severe versus moderately severe left ventricular
dysfunction secondary to atherosclerotic coronary artery disease. Am J Cardiol 1997;
80:1305.

24. Huang DT, Sesselberg HW, McNitt S, et al. Improved survival associated with prophylactic
implantable defibrillators in elderly patients with prior myocardial infarction and depressed
ventricular function: a MADIT-II substudy. J Cardiovasc Electrophysiol 2007; 18:833.

25. Duray G, Richter S, Manegold J, et al. Efficacy and safety of ICD therapy in a population of
elderly patients treated with optimal background medication. J Interv Card Electrophysiol
2005; 14:169.

26. Betz JK, Katz DF, Peterson PN, et al. Outcomes Among Older Patients Receiving
Implantable Cardioverter-Defibrillators for Secondary Prevention: From the NCDR ICD
Registry. J Am Coll Cardiol 2017; 69:265.

27. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on
the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction
Delay: A Report of the American College of Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol
2019; 74:e51.

28. Wyse DG, Friedman PL, Brodsky MA, et al. Life-threatening ventricular arrhythmias due to
transient or correctable causes: high risk for death in follow-up. J Am Coll Cardiol 2001;
38:1718.

19 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

29. Viskin S, Halkin A, Olgin JE. Treatable causes of sudden death: not really "treatable" or not
really the cause? J Am Coll Cardiol 2001; 38:1725.

30. Ladejobi A, Pasupula DK, Adhikari S, et al. Implantable Defibrillator Therapy in Cardiac
Arrest Survivors With a Reversible Cause. Circ Arrhythm Electrophysiol 2018; 11:e005940.

31. Steinberg JS, Martins J, Sadanandan S, et al. Antiarrhythmic drug use in the implantable
defibrillator arm of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study. Am
Heart J 2001; 142:520.

32. Ha AH, Ham I, Nair GM, et al. Implantable cardioverter-defibrillator shock prevention does
not reduce mortality: a systemic review. Heart Rhythm 2012; 9:2068.

33. Gasparini M, Proclemer A, Klersy C, et al. Effect of long-detection interval vs standard-

detection interval for implantable cardioverter-defibrillators on antitachycardia pacing and
shock delivery: the ADVANCE III randomized clinical trial. JAMA 2013; 309:1903.

34. Wilkoff BL, Fauchier L, Stiles MK, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert
consensus statement on optimal implantable cardioverter-defibrillator programming and
testing. Heart Rhythm 2016; 13:e50.

35. Exner DV, Reiffel JA, Epstein AE, et al. Beta-blocker use and survival in patients with
ventricular fibrillation or symptomatic ventricular tachycardia: the Antiarrhythmics Versus
Implantable Defibrillators (AVID) trial. J Am Coll Cardiol 1999; 34:325.

36. Mitchell LB, Powell JL, Gillis AM, et al. Are lipid-lowering drugs also antiarrhythmic drugs?
An analysis of the Antiarrhythmics versus Implantable Defibrillators (AVID) trial. J Am Coll
Cardiol 2003; 42:81.

37. De Sutter J, Tavernier R, De Buyzere M, et al. Lipid lowering drugs and recurrences of life-
threatening ventricular arrhythmias in high-risk patients. J Am Coll Cardiol 2000; 36:766.

38. Vyas AK, Guo H, Moss AJ, et al. Reduction in ventricular tachyarrhythmias with statins in the
Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. J Am Coll Cardiol 2006;
47:769.

39. Jenkins DJ, Josse AR, Beyene J, et al. Fish-oil supplementation in patients with
implantable cardioverter defibrillators: a meta-analysis. CMAJ 2008; 178:157.

40. Scirica BM, Morrow DA, Hod H, et al. Effect of ranolazine, an antianginal agent with novel

20 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

electrophysiological properties, on the incidence of arrhythmias in patients with non ST-

segment elevation acute coronary syndrome: results from the Metabolic Efficiency With
Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome
Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial.
Circulation 2007; 116:1647.

41. Zareba W, Daubert JP, Beck CA, et al. Ranolazine in High-Risk Patients With Implanted
Cardioverter-Defibrillators: The RAID Trial. J Am Coll Cardiol 2018; 72:636.

42. Wissner E, Stevenson WG, Kuck KH. Catheter ablation of ventricular tachycardia in
ischaemic and non-ischaemic cardiomyopathy: where are we today? A clinical review. Eur
Heart J 2012; 33:1440.

43. Soejima K, Stevenson WG, Sapp JL, et al. Endocardial and epicardial radiofrequency
ablation of ventricular tachycardia associated with dilated cardiomyopathy: the importance
of low-voltage scars. J Am Coll Cardiol 2004; 43:1834.

44. Yamada T, Kay GN. Optimal ablation strategies for different types of ventricular
tachycardias. Nat Rev Cardiol 2012; 9:512.

45. Knecht S, Sacher F, Wright M, et al. Long-term follow-up of idiopathic ventricular fibrillation
ablation: a multicenter study. J Am Coll Cardiol 2009; 54:522.

46. Mallidi J, Nadkarni GN, Berger RD, et al. Meta-analysis of catheter ablation as an adjunct to
medical therapy for treatment of ventricular tachycardia in patients with structural heart
disease. Heart Rhythm 2011; 8:503.

47. Anter E, Hutchinson MD, Deo R, et al. Surgical ablation of refractory ventricular tachycardia
in patients with nonischemic cardiomyopathy. Circ Arrhythm Electrophysiol 2011; 4:494.

48. Jeevanandam V, Bielefeld MR, Auteri JS, et al. The implantable defibrillator: an electronic
bridge to cardiac transplantation. Circulation 1992; 86:II276.

49. Grimm M, Wieselthaler G, Avanessian R, et al. The impact of implantable cardioverter-

defibrillators on mortality among patients on the waiting list for heart transplantation. J
Thorac Cardiovasc Surg 1995; 110:532.

50. Bolling SF, Deeb GM, Morady F, et al. Automatic internal cardioverter defibrillator: a bridge to
heart transplantation. J Heart Lung Transplant 1991; 10:562.

51. Lorga-Filho A, Geelen P, Vanderheyden M, et al. Early benefit of implantable cardioverter

21 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

defibrillator therapy in patients waiting for cardiac transplantation. Pacing Clin

Electrophysiol 1998; 21:1747.

52. Saba S, Atiga WL, Barrington W, et al. Selected patients listed for cardiac transplantation
may benefit from defibrillator implantation regardless of an established indication. J Heart
Lung Transplant 2003; 22:411.

53. Grimm M, Grimm G, Zuckermann A, et al. ICD therapy in survivors of sudden cardiac death
awaiting heart transplantation. Ann Thorac Surg 1995; 59:916.

Topic 946 Version 29.0

22 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

GRAPHICS

Summary of secondary prevention ICD trials [1]

NCDR
Study A VID [2] CA SH [3] CIDS [4]
Cohort [5]

Years 1993 to 1997 1987 to 1998 1990 to 1997 2006 to 2009

Patients 1016 191 659 46,685

Mean age (years) 65±11 58±11 63±9 66±14

Male (%) 78 79 85 73

Follow-up (months) 18±12 57±34 36 None

CAD (%) 81 73 83 64

Nonischemic (%) 15 12 10 23

LVEF 32±13 46±19 34±14 36±15

Presenting arrhythmia (%)

VF 45 100 45 51

VT with LOC 21 0 16 NR

VT without LOC 34 0 24 27

Syncope 0 0 15 22

BB (%) 42 0 33 84

ACE-I/ARB (%) 69 45 NR 72

One-year mortality 17.7/10.7 15.2/8.1 11.2/9.5 NA/10.4

(%): Control/ICD

Two-year mortality 25.3/18.4 27.2/17.2 21.0/14.8 NA/16.4

(%): Control/ICD

ICD: implantable cardioverter-defibrillator; CAD: coronary artery disease; LVEF: left ventricular ejection fraction; VF:
ventricular fibrillation; VT: ventricular tachycardia; LOC: loss of consciousness; BB: beta blocker; ACE-I: angiotensin
converting enzyme inhibitor; ARB: angiotensin receptor blocker; NR: not recorded; NA: not applicable.

References:
1. Borne R, Katz D, Betz J, et al. Implantable Cardioverter-Defibrillators for Secondary Prevention of Sudden Cardiac
Death: A Review. J Am Heart Assoc 2017; 6:e005515.
2. Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy
with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997;
337:1576.
3. Kuck KH, Cappato R, Siebels J, Rüppel R. Randomized comparison of antiarrhythmic drug therapy with implantable
defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH). Circulation
2000; 102:748.
4. Connolly SJ, Gent M, Roberts RS, et al. Canadian implantable defibrillator study (CIDS): a randomized trial of the
implantable cardioverter defibrillator against amiodarone. Circulation 2000; 101:1297.
5. Katz DF, Peterson P, Borne RT, et al. Survival after secondary prevention ICD placement: an analysis from the
NCDR ICD Registry. JACC Clin Electrophysiol 2017; 3:20.

Graphic 116653 Version 1.0

23 of 24 4/24/2020, 11:03 PM
Secondary prevention of sudden cardiac death in heart failure and cardi... https://www.uptodate.com/contents/secondary-prevention-of-sudden-car...

Contributor Disclosures
Joseph E Marine, MD, FACC, FHRS Nothing to disclose Andrea M Russo, MD, FACC,
FHRS Grant/Research/Clinical Trial Support: Medtronic and Boston Scientific [Device/Arrhythmia (Implantable
cardioverter defibrillator)]; Boehringer Ingelheim [Drug/Anticoagulant (funding to hospital). Other Financial
Interest: Boston Scientific (steering committee for research trial) no honoraria, [Arrhythmias (ICDs)], Apple
(steering committee for research trial) no honoraria, [Arrhythmias (atrial fibrillation)]. Bradley P Knight, MD,
FACC Grant/Research/Clinical Trial Support: BSCI; MDT; Abbott; Biotronik; Biosense Webster [EP (implantable
devices and ablation tools)]. Speaker's Bureau: BSCI; MDT; Abbott; Biotronik; Biosense Webster [EP
(implantable devices and ablation tools)]; Baylis Medical. Consultant/Advisory Boards: BSCI; MDT; Abbott;
Biotronik; Biosense Webster; Apama Medical [EP (implantable devices and ablation tools)]. Sam uel Lévy,
MD Nothing to disclose Brian C Dow ney, MD, FACC Nothing to disclose

Contributor disclosures are review ed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

24 of 24 4/24/2020, 11:03 PM