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INTRODUCTION
Since the 1960s, important advances have been made in resuscitation of patients from
sudden cardiac death (SCD). Despite these advances, rates of survival to hospital discharge range from only 2 to 30% (generally 510%); rates of survival with intact neurological status are even lower (1). Approximately 400,000 out-of-hospital sudden deaths
occur in the United States each year (2). These grim statistics point to the importance of
prevention in approaching the problem of SCD from a public health standpoint.
It has been estimated that one-half to two-thirds of out-of-hospital sudden death is
caused by ventricular arrhythmias (VA) (ventricular tachycardia [VT] and ventricular
fibrillation [VF]) (3). Bradyarrhythmias, such as complete atrioventricular block and
asystole, are a less frequent cause of arrhythmic sudden death. A substantial minority of
cases of apparent SCD may be because of nonarrhythmic causes, such as massive pulmonary embolus, ruptured aortic aneurysm or dissection, or stroke (4). Because most research
into prevention of SCD has focused on VA, this subject will form the basis for this chapter.
Preventive strategies will be considered according to the etiology of cardiac disease.
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Cardiopulmonary Resuscitation
Coronary atherosclerotic plaques of any size may rupture, triggering platelet adhesion,
thrombus formation, and acute myocardial infarction (AMI). Serious VAs, especially
VFs, are common in this setting, and they account for a substantial proportion of deaths
from AMI, particularly in the prehospital setting. Later in the course of infarction, the
infarct zone undergoes cellular and tissue remodeling with the laying of collagen scar and
ventricular dilatation. This process creates the anatomic substrate for future VAs, particular sustained monomorphic VT.
23
Year of publication
1981
1986
2001
1989, 1991
1992
1996
2000
1997
1997
Result
Improved survival with propranolol
Improved survival with atenolol
Improved survival with carvedilol
Increased mortality with flecainide or encainide
Increased mortality with moricizine
Increased mortality with D-sotalol
No effect of dofetilide on mortality
No effect of amiodarone on mortality
No effect of amiodarone on mortality
moricizine, led to a re-examination of the use of these agents in patients with CAD and
other forms of structural heart disease (13,14). There is now general agreement that type
I antiarrhythmic drugs, particularly type Ic agents, should be avoided in patients with
CAD because of the pro-arrhythmic effects demonstrated in CAST.
A similar increased risk of death was seen in a trial of the class III antiarrhythmic D-sotalol
in postinfarction patients (15). The Survival With Oral D-Sotalol trial recruited 3121 patients
with LV ejection fraction (EF) of 0.40 or less and prior MI. Patients were randomly
assigned to long-term treatment with D -sotalol (a pure type III anti-arrhythmic agent with
no `-blocking activity) or matching placebo. After a mean follow-up period of 150 days
and halfway into recruitment, the trial was stopped early because of a 65% increased
relative risk of mortality in the D -sotalol treatment arm (5 vs 3.1% in placebo group, p = 0.006).
The excess mortality was felt to be because of an increase in arrhythmic deaths.
In contrast, a large trial of dofetilide, another pure class III antiarrhythmic drug, found
no increase in mortality on survivors of MI (16). The Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) Study Group randomized 1510 patients
with recent MI and LVEF of 0.35 or less to treatment with dofetilide (dose based on
creatinine clearance) or matching placebo. After a median follow-up of 456 days, mortality was nearly identical in the two groups (31 vs 32%, respectively, p = 0.61).
Amiodarone, a unique antiarrhythmic drug that exhibits actions of all four VaughnWilliams drug classes, was originally developed as an anti-anginal medication. On the
basis of its efficacy in the treatment of recurrent VA and its safety compared with other
antiarrhythmic drugs in survivors of cardiac arrest (CA), two large trials were organized
to test its efficacy in high-risk survivors of AMI (17,18). The European Myocardial
Infarction Amiodarone Trial (EMIAT) enrolled 1486 patients 5 or more days after MI
only on the basis of depressed LVEF of 0.40 or less (19). Patients were treated with
amiodarone (200 mg per day after loading) or placebo. After a median follow-up period
of 21 months, overall mortality was identical in the two groups (14% in each, p = 0.96).
The Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT) studied 1202 patients enrolled 642 days after AMI, who had frequent ventricular premature
contractions or nonsustained VT; LV systolic dysfunction was not required for entry into
the trial (20). Patients were treated with amiodarone (200 mg per day after loading) or
placebo and followed for a mean of 1.8 years. No significant difference in overall mortality was found (9.4% in the amiodarone group vs 11.4% in the placebo group, p = 0.129).
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Cardiopulmonary Resuscitation
Both EMIAT and CAMIAT did find a reduction in death ascribed to arrhythmia, but the
significance of this finding in the absence of overall mortality benefit has been questioned. A posthoc analysis of both trials suggested a possible synergistic benefit of
amiodarone and `-blockers, but this remains to be demonstrated prospectively.
In summary, proven medical therapy for primary prevention of sudden death in
patients with CAD is limited to `-blocker use. Type I antiarrhythmic drugs and D-sotalol
have been shown to be harmful in this population. Amiodarone and dofetilide had a
neutral effect on all-cause mortality and are relatively safe to use for treatment of symptomatic arrhythmias in patients with CAD.
25
Fig. 1. Tiered therapy of VAs by the ICD. The figure shows stored single-channel telemetry strip
during an episode of ventricular tachyarrhythmia in a patient with an implantable cardioverter
defibrillator who was hospitalized. A ventricular premature beat initiates sustained monomorphic ventricular tachycardia (VT 1). Four cycles of antitachycardia pacing (ATP 1-4) fail to
terminate the arrhythmia. A low-energy cardioversion (CV 1) results in a different morphology
of monomorphic VT (VT 2). A second low-energy cardioversion (CV 2) results in polymorphic
VT (PVT). After the first high-energy defibrillation (DF 1), the rhythm degenerates into ventricular fibrillation (VF). A second high-energy defibrillation (DF 2), results in restoration of
sinus rhythm.
next decade, and the limitations of anti-arrhythmic drugs were exposed through randomized clinical trials, the ICD gained increasing favor for treatment of CA survivors. In this
setting, several clinical trials were organized to test the efficacy of the ICD in secondary
prevention (for patients who had survived a sustained life-threatening VA) and primary
prevention (for high-risk patients without history of sustained arrhythmia) of SCD
(Tables 2 and 3).
ICD FOR SECONDARY PREVENTION IN CAD
The first published trial comparing the ICD and conventional medical therapy for
secondary prevention of SCD was the Anti-arrhythmics Versus Implantable Defibrillator
(AVID) trial (23). This National Institutes of Health (NIH)-sponsored multicenter study
enrolled 1016 patients in 56 North American centers who were resuscitated from VF or
sustained VT between 1993 and 1997. The mean age of enrolled patients was 65 years
and the mean LVEF was 0.32. Eighty-one percent of patients had CAD and 67% had a
history of MI. Patients were randomly assigned to receive an ICD or to treatment with
anti-arrhythmic drug therapy, predominantly amiodarone (96% of assigned patients).
Over a mean follow-up period of 18 months, 122 of 509 patients (24%) in the antiarrhythmic drug therapy group died vs only 80 of 507 patients (16%) assigned to receive
an ICD. This difference corresponds to a 33% relative risk reduction and an 8% absolute
risk reduction in total mortality in favor of the ICD (p < 0.02). Of note, this treatment
effect was demonstrated despite a significant crossover to ICD therapy in the drug therapy
arm, reaching 25% at 3 years.
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Cardiopulmonary Resuscitation
Fig. 2. Treatment of different ventricular arrhythmias in the same patients with an implantable
cardioverter defibrillator (ICD). The figure shows stored internal electrograms and marker channels of two episodes of sustained monomorphic ventricular arrhythmia in a 38-year-old man with
cardiac sarcoidosis. The first event shown in A is an episode of ventricular fibrillation that was
successfully treated with a single 20-J internal defibrillation by the ICD, restoring the patient to
sinus rhythm. The second event shown in B is an episode of sustained monomorphic ventricular
tachycardia with a rate of 200 bpm successfully treated with a single sequence of 8 beats of antitachycardia pacing.
Strengths of the AVID trial include its relatively large size, NIH sponsorship, and its
use of total mortality as an unambiguous and unquestionably important primary endpoint. Because the trial included only a small proportion of patients without CAD, it is
difficult to draw conclusions about benefit of ICD in other subgroups. No placebo group
was used, raising the question of whether the some of the apparent benefit of the ICD was
because of a detrimental effect of amiodarone; other trials, however, have demonstrated
the safety of amiodarone in patients with structural heart disease. Finally, `-blocker use
was much greater in the ICD arm (about 40%) compared to the drug therapy arm (10
15%), probably because of the bradycardic effects of amiodarone; this discrepancy might
account for some of the apparent benefit of the ICD. Despite these criticisms, the AVID
trial has led to the ICD becoming the treatment of choice for survivors of CA without
contraindications to its use.
Two smaller trials of ICD therapy in secondary prevention of SCD have been reported
since the AVID trial was published. The first, the Canadian Implantable Defibrillator
Study (CIDS), enrolled 659 patients with an episode of unstable sustained VA in 24
centers in Canada, Australia, and the United States between 1990 and 1997 (24). Baseline
patient characteristics were similar to those of the AVID population, with a mean age of
63.5 years, mean LVEF of 0.34, and an 82% prevalence of CAD. After a mean follow-
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Table 2
ICD Trials for Primary and Secondary Prevention of SCD
Trial
Primary or
Year
secondary
of
prevention publication
AVID (23)
CIDS (24)
CASH (25)
MADIT (26)
MUSST (27)
CABG-Patch (28)
MADIT-II (29)
Secondary
Secondary
Secondary
Primary
Primary
Primary
Primary
1997
2000
2000
1996
1999
1997
2002
Number
of
patients
Mean
follow-up
(months)
Relative
risk
reduction
Absolute
risk
reduction
1016
659
288
196
704
900
1232
18
36
57
27
39
32
20
33%
28%
18%
59%
60%
8%
28%
8%
4.3%
8%
23%
31%
1.7%
5.6%
p-value
p < 0.02
p = 0.14
p = 0.08
p = 0.009
p < 0.001
p = NS
p = 0.016
Table 3
Nonischemic Cardiomyopathies Associated With Sudden CA
Dilated cardiomyopathies
Idiopathic
Postviral
Alcohol-related
Valvular heart disease
Postpartum
Familial
Chagas disease
Hypertrophic cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
Cardiac sarcoidosis
Cardiac amyloidosis
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29
receiving an ICD and 55% in those who did not (adjusted relative risk of overall mortality
0.40, p < 0.001). In fact, patients treated with anti-arrhythmic drugs without an ICD had
a trend toward higher mortality than the control arm of the study, possibly because of a
high use of type I anti-arrhythmic agents in the drug-therapy group (26% at initial hospital
discharge). Thus, although MUSTT had a complex design, which was not primarily
intended to test the efficacy of the ICD, its results supported the apparent benefit of the
ICD for primary prophylaxis demonstrated in MADIT and led to widespread use of the
ICD in high-risk coronary patients for this indication.
In contrast to MADIT and MUSST, the Coronary Artery Bypass Graft (CABG) Patch
trial used a different test (signal-averaged ECG) to identify high-risk CAD patients and
found no benefit to prophylactic epicardial ICD implantation in the population studied
(28). This NIH-sponsored study screened patients less than 80 years old with LVEF of
0.35 or less who were scheduled for CABG surgery at 37 centers in the United States and
Germany between 1990 and 1996. Patients were screened with signal-averaged electrocardiography (SAECG), a variation of the standard surface ECG used to analyze QRS
complexes for prolongation or the presence of late potentials, which reflect myocardial
scarring and substrate for VAs. A pilot study had shown that patients with abnormal
SAECG had a mortality rate in the 2 years after CABG surgery twice as high as patients
with normal SAECG, which is in line with previous studies of this technique. Neither
nonsustained VT nor invasive EP study was required for study entry.
After screening, 900 patients were assigned randomly to receive an epicardial ICD
system at the time of CABG surgery (446 patients) or to CABG surgery alone (454
patients). Baseline characteristics were similar to MADIT patients, with a mean age of
64 years, mean LVEF of 0.27, and 73% with NYHA class II or III heart failure symptoms.
Ninety-one percent of patients had two- (36%) or three- (55%) vessel CAD. After an
average follow-up of 32 months, the trial was terminated because of a lack of efficacy,
at which point 101 of 446 (22.6%) patients in the ICD arm had died vs 95 of 454 (20.9%)
patients in the control arm. No subgroups were identified that appeared to benefit from
the ICD.
There are several possible explanations for the difference in outcome between the
CABG-Patch Trial and other trials, which demonstrate efficacy of the ICD for primary
prophylaxis. These include relatively low mortality rate in the control arm, an independent anti-arrhythmic effect of complete revascularization, use of epicardial devices, and
potential harmful effect of prolonging operative time with ICD implant and testing.
The Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) was
recently published and may significantly expand the population eligible for primary
prophylaxis of SCD with the ICD (29). This industry-sponsored trial randomized 1232
patients in 76 US and European centers with prior MI (1 month or more before entry) and
LVEF of 0.30 or less to receive a transvenous ICD or usual medical therapy. Patients were
not required to have any spontaneous or induced arrhythmias for entry. Enrolled patients
had a mean age of 64 years and a mean LVEF of 0.23. In contrast to MADIT, `-blocker
use was high (70% in each arm). After a mean follow-up of 20 months, 19.8% of patients
in the usual therapy group had died, and 14.2% of patients in the ICD arm (p = 0.016),
indicating a hazard ratio of 0.69 in favor of the ICD arm, and an absolute risk reduction
of 5.6%. There were no statistically significant interactions with baseline characteristics,
but patients with lower LVEFs and those with wider QRS duration showed trend toward
greater benefit from the ICD. An unexplained trend toward higher rates of hospitalization
for heart failure was also present in the ICD arm.
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DILATED CARDIOMYOPATHY
Although not as common as CAD, several other forms of cardiomyopathy (listed in
Table 2) are associated with an elevated risk of SCD. The most prevalent of these is
dilated cardiomyopathy (DCM). Numerous studies have shown that patients with DCM
have significantly elevated risk of all-cause mortality and SCD, and that degree of risk
correlates with heart failure class (33). Interestingly, although patients with the most
severe heart failure symptoms have the highest mortality rates, the proportion of deaths
classified as because of SCD is lower than in those with lower heart failure class; the
31
proportion of deaths because of pump failure rises accordingly. Other important risk
factors for arrhythmic mortality in DCM include degree of LV dilatation, impairment of
LV systolic function, and increased QRS duration, especially with left bundle branch
block. Frequency of nonsustained VT has also been shown to increase risk of mortality
in one study (34), but another failed to show this association (35). Syncope, regardless
of etiology, was shown in one study to increase risk of mortality nearly fourfold (36).
Although recognized as an insensitive marker, inducibility of sustained VAs at invasive
EP study also seems to confer elevated risk of death (37).
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those at very high risk. Alternatively, CHF-STAT included a much longer follow-up
period, and hence GESICA might have shown less benefit for amiodarone if patients had
been followed longer. No clear consensus exists for utility of amiodarone for primary
prevention of SCD in the heart failure population because of the conflicting results of
these two trials. Preliminary results of the Sudden Cardiac Death in Heart Rate Failure
Trial (SCD-HeFT; see below) also suggest that amiodarone does not prolong survival in
heart failure patients.
ICD FOR DCM
Patients with DCM who are resuscitated from sustained VT or VF warrant strong
consideration for ICD therapy based on AVID and the other secondary prevention
studies discussed above. ICDs are also appropriate for patients with symptoms consistent with VA (such as syncope) who have inducible VAs at EP study. Based on natural
history studies, unexplained syncope is considered by some to constitute an indication
for an ICD in patients with DCM. Other indications for ICD implantation in this group
need to be defined.
To date, there have been no completed large-scale randomized trials of the ICD for
primary prevention of SCD in patients with DCM. One small pilot trial conducted in
Germany randomized 104 patients with DCM and LV ejection of 0.30 or less to ICD or
usual therapy (42). After 5 years of follow-up, there was no significant difference in
mortality between the two groups. Lack of efficacy of the ICD was ascribed to lowerthan-expected mortality in this group. The Amiovert trial, recently reported in abstract
form, compared ICD therapy with amiodarone in 178 patients with nonischemic cardiomyopathy and nonsustained VT (43). This trial also appeared to be underpowered to
detect a treatment effect of the ICD, and was terminated prematurely having shown no
significant difference in outcome between the two groups.
The SCD-HeFT is a multicenter study that has enrolled approx 2500 patients with
DCM because of any cause with LVEF of 0.35 or less and class II or III heart failure
symptoms (44). Patients were randomly assigned to ICD implantation, amiodarone
therapy, or placebo in a 1:1:1 fashion. Follow-up was completed in 2003 and preliminary results were presented at the annual Scientific Sessions of the American College
of Cardiology in March 2004 (available at www.sicr.org). After a mean follow-up
period of 45 months, there was a statistically significant 23% relative reduction in allcause mortality in the patients assigned to ICD therapy. Patients with ischemic and nonischemic etiologies of heart failure appeared to benefit equally. There was no significant
mortality difference in patients assigned to amiodarone treatment. Assuming these
results are confirmed in the final published report, SCD-HeFT may result in significant
expansion in patients eligible for ICD therapy for primary prevention of SCD.
Hypertrophic Cardiomyopathy
HCM is a group of diseases caused by inherited mutations in genes encoding protein
components of the cardiac sarcomere (45). To date, 11 different HCM-associated genes
33
have been identified; others likely remain to be discovered. The disease results in myocyte disorganization, progressive myocardial wall thickening, and diastolic dysfunction.
Increased LV wall thickening develops during childhood and adolescence and is usually
present by young adulthood in affected individuals. Some forms may develop systolic
dysfunction late in the course of disease. The disease was first characterized in patients
that had disproportionate thickening of the interventricular septum with dynamic LV
outflow tract gradient (idiopathic hypertrophic subaortic stenosis [IHSS]). Further studies have demonstrated that neither septal hypertrophy nor outflow tract gradient is a
requirement for the disease, and numerous different patterns of LV wall thickening have
been identified.
SCD as a result of VAs is believed to be the most common cause of death in HCM, with
annual incidence ranging from 1% per year in all patients and up to 5% per year in highrisk subgroups. The highest risk is present in patients who have survived a CA or episode
of sustained VT. These patients generally warrant ICD therapy for secondary prophylaxis. Other proposed markers of risk include extreme LVH with wall thickness greater
than 30 mm, frequent runs of nonsustained VT on Holter monitoring, history of unexplained syncope, hypotensive response to exercise, and malignant family history. Preliminary data suggest that some genotypes, particular certain mutations in `-myosin
heavy chain and cardiac troponin T, confer increased risk of SCD. Genotyping, however,
is not widely available and not currently practical for risk stratification. Younger patients
appear to be at higher risk, although a cut-off age indicating low risk has not been defined.
Resulting from the relative rarity of the disease and the overall low mortality rate,
it has been difficult to define effective therapies for prevention of SCD in HCM.
Vigorous physical exertion and participation in competitive sports should be proscribed. `-Blockers have been used based on their efficacy in other cardiac substrates;
a retrospective study also suggests effectiveness (46). Amiodarone has been used to
treat nonsustained and sustained VAs, but the potential for extracardiac adverse effects
with lifelong treatment in relatively young patients is substantial (47). There are no
controlled trials of ICD use in patients with HCM. Criteria for secondary prevention
are applied generally as with other AVID-eligible patients. There are no prospectively
defined criteria for ICD implantation for primary prophylaxis in this disease.
A retrospective cohort study of 128 patients with HCM who had ICDs implanted for
perceived high risk of SCD was recently reported (48). This study found that, over a mean
follow-up period of 3 years, 19 of 43 patients (44%) implanted for secondary prophylaxis
had appropriate ICD discharges for VT or VF, and 10 of 85 patients (12%) implanted for
primary prophylaxis did as well. This percentage is lower than that seen in primary
prophylaxis trials in patients with CAD or DCM. Because the ICD cannot distinguish
between truly life-threatening arrhythmias and VT which would terminate spontaneously without treatment, it is difficult to draw conclusions regarding mortality reduction
in this study. Moreover, 18 of 128 patients (14%) had device-related complications in the
3-year follow-up period, including 12 ICD lead failures. Thirty-two patients (25%) had
inappropriate ICD discharges for sinus tachycardia, atrial fibrillation, or ICD lead failure;
25 of these patients did not receive an appropriate discharge from the device. These data
underscore the potential complications of ICD therapy, particularly applied to young
people with long life expectancy. Thus, while this study suggests that some HCM patients
may benefit from ICD therapy, definitive data to guide patient selection for primary
prophylaxis are not currently available.
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Cardiopulmonary Resuscitation
Long QT Syndrome
The long QT syndrome (LQTS) is the most common of the cardiac ion channel diseases that cause SCD. The acquired form is most commonly caused by medications,
which prolong cardiac repolarization. For a complete updated list of medications associated with LQTS, the reader is referred to www.torsades.org. Other causes of acquired
LQTS include hypokalemia and hypomagnesemia; severe bradycardia, such as during
complete AV block; and neurological insults, such as subarachnoid hemorrhage and
stroke. The congenital form of the disease is associated with mutations in one of at least
six identified gene loci (LQT 16) (55). LQT1, LQT2, LQT5, and LQT6 are all caused
by mutations in different genes encoding for components of cardiac potassium channels,
but LQT3 is caused by mutations in the cardiac sodium channel. All result in prolonged
repolarization of the cardiac action potential with resulting prolongation of the QT interval and predisposition to torsades de pointes, which may in turn degenerate into VF.
Recognition of the ECG pattern in patients presenting with symptoms is an important component of sudden death prevention in this disorder (56). The ECG in LQTS is
highly variable in degree of QT prolongation and morphology of the T wave, which
may make recognition difficult. Detection of LQTS is an important reason for careful
review of the ECG in any patient presenting with palpitations or syncope. Occasion-
35
ally, the syndrome presents as a seizure disorder in young children. Once an affected
individual has been identified, family members should be screened for the disease.
The most important medical component of treatment for congenital LQTS is `-blocker
therapy. This medication has been shown to reduce incidence of syncope and sudden
death in congenital LQTS patients (57). Other treatments that have been shown to reduce
symptoms include left cardiac sympathectomy and permanent atrial pacing. Preliminary
data suggest that sodium channel blockade may be beneficial in the LQT3 subtype.
Criteria for ICD implantation are controversial, and the decision is difficult in young
patients with long life expectancy. Patients resuscitated from CA and those with recurrent
syncope because of torsade de pointes despite `-blockade are the most obvious candidates. Patients with syncope of undetermined etiology and patients with malignant family
history are often considered as well.
Brugada Syndrome
The Brugada syndrome is a recently described inherited disease consisting of an
abnormal ECG pattern (incomplete right bundle branch block with coved ST segment
elevation in leads V1V3) and idiopathic VF (58). In some cases, the ECG pattern is
elicited only after sodium-channel blockade. Patients usually present after resuscitation
from CA or, less commonly, with recurrent syncope. ICD implantation is currently the
only effective therapy for symptomatic individuals. Evaluation and treatment of asymptomatic patients and affected family members is controversial. One report suggests that
VT or VF inducibility at EP study has prognostic value (59). Although another report
reached the opposite conclusion (60).
Commotio Cordis
Commotio cordis has received attention as a cause of SCD in children and young
adults during sporting activities, particularly baseball and hockey (61). The mechanism is believed to be VF induced by a blow to the precordium during the vulnerable
period of the cardiac cycle (just prior to the peak of the T-wave). Most affected individuals have structurally normal hearts. Although very rare, events have a high mortality rate and wider impact on affected families and communities. Preventive efforts
have focused on use of softer baseballs and improved chest protection equipment.
FUTURE DIRECTIONS
Recent efforts to reduce the public health burden of SCD have focused on expansion
of indications for ICD therapy. These trials have clearly shown efficacy of the ICD in the
high-risk groups in which it has been studied. It has been noted that the majority of victims
of SCD do not have risk factors that would currently make them eligible for an ICD (62).
Although further reduction in implant-related complications may make the ICD effective
in lower risk patients, the cost-effectiveness ratios associated with this approach would
be prohibitively high without a reduction in ICD costs. Additionally, the long-term
economic, psychological, and health effects of chronic ICD therapy in low-risk populations are not yet well-understood, and it is unclear to what degree low-risk populations
would accept ICD therapy.
The disappointing history of anti-arrhythmic drug trials for prevention of SCD make
these agents unattractive for primary prophylaxis of SCD in lower risk groups. To be
useful for this purpose, an agent should have low cost and side-effect profile and negli-
36
Cardiopulmonary Resuscitation
gible proarrhythmic risk. Preliminary studies of t-3 polyunsaturated fatty acids (fish
oils) have shown marked protective effect against VF in animal models of ischemia and
infarction, possibly because of stabilizing effects on the membrane of the cardiomyocyte
(63). Further trials in humans will be required to demonstrate clinical efficacy.
In order to better target preventive therapies, others have worked on identifying novel
markers of high risk of SCD. A recent report has observed that patients with congestive
heart failure and depressed LVEF who had elevated brain natriuretic peptide levels (>130
pg/mL) had more than 10-fold higher risk of sudden death than those with lower values
(64). Other noninvasive electrocardiographic markers of risk include microvolt T-wave
alternans, heart rate variability, and heart rate turbulence. Whether any of these markers
can predict benefit of ICD or other preventive strategies remains to be proven (65).
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