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Sudden cardiac death.

Abstract: Sudden cardiac death (SCD) due to ventricular tachyarrhythmias is a leading cause of death in the United States. Various etiologies, including ischemic and nonischemic cardiomyopathies, hypertrophic cardiomyopathy, valvular or congenital heart diseases and other less common disorders, may result in SCD. Beta blockers are the only class of medications that have been shown to be beneficial in the primary prevention of SCD. However, recently, aldosterone antagonism early after myocardial infarction has also been shown to significantly reduce the risk of SCD. Multiple trials have elaborated on the potential benefits of implantable cardioverter defibrillators (ICD) in appropriately selected patients. However, there is still some controversy regarding the optimum period for ICD implantation, and its cost-effectiveness. An evidence-based approach to primary and secondary prevention of SCD is presented. Management of out-of-hospital cardiac arrest is briefly discussed.

Key Words: sudden cardiac death, ischemic and nonischemic cardiomyopathies, antiarrhythmic drugs, implantable cardioverter defibrillator, cost effectiveness

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Sudden cardiac death (SCD) is defined as unexpected natural death from a cardiac cause heralded by abrupt loss of consciousness within a short time period, generally less than 1 hour from the onset of symptoms. Pre-existing heart disease may or may not have been known to be present, but the time and mode of death are unexpected. (1) The majority of such sudden deaths are caused by acute ventricular tachyarrhythmias, often triggered by acute coronary events, which may occur in persons without known cardiac disease or in association with structural heart disease.

Epidemiology

In the United States, it is estimated that SCD accounts for approximately 250,000 to 400,000 deaths annually, (2) and approximately 50% of left ventricular systolic dysfunction mortality. (3) The incidence of SCD increases with age and is 2 to 3 times higher among men than women. (4) There is an association between the arrhythmic mechanism for SCD and the outcome of resuscitation. When the initial rhythm is asystole or pulseless electrical activity, the survival rate is low and when it is performed out of hospital, very few (<10%) survive to hospitalization and virtually none survive to be discharged from the hospital. The outcome is significantly better when the initial rhythm is a sustained ventricular tachyarrhythmia. Approximately 25% of patients with ventricular fibrillation (VF) survive to be discharged. (5) In those with hemodynamically unstable ventricular tachycardia (VT), the survival rate is 65 to 70%. (6)

Etiology

Atherosclerotic coronary artery disease (CAD) remains the predominant substrate for SCD accounting for 80% of cases of fatal arrhythmias (Table 1). An analysis made in the Framingham population of 5,209 men and women free of identified heart disease at baseline showed that 46% of men and 34% of women with SCD had CAD as the most likely etiology of their cardiac arrest. (2) The extent of the vessel disease involvement seems to have a greater predictive value than the location of specific lesions in the coronary arteries. In survivors of cardiac arrest, CAD with vessels exhibiting more than 75% cross-sectional stenosis are found in 40 to 86% of patients, depending on age and sex of the population studied. (2)

The most common arrhythmia found during resuscitation in patients with CAD is VF, but VT that degenerates into VF frequently precedes it. The most common underlying mechanism seen in monomorphic VT in adult patients with CAD appears to be re-entry based on several electrophysiologic studies (EPS). Polymorphic VT without QT prolongation can be seen in most patients with CAD and occurs especially in patients with acute myocardial ischemia. (7)

About 10 to 15% of instances of sudden cardiac death occur in patients with left ventricular dysfunction but no evidence of prior myocardial infarction (MI). These patients have nonischemic or dilated cardiomyopathy (NICM) and account for the second largest number of sudden deaths from cardiac causes. (7) Hypertrophic cardiomyopathy (HCM) results from a genetic disorder in the genes that encode the cardiac muscle sarcomere. The prevalence of HCM in the general population is 1 in 500. (8) The annual rate of SCD in HCM is 2 to 4% in adults and 4 to 6% in children and adolescents. High-risk markers for SCD in these patients are, a prior episode of SCD or sustained VT, family history of SCD, a diverse genotype, recurrent syncope, multiple episodes of nonsustained VT and severe (>3 cm) left ventricular hypertrophy (LVH).

Other cardiac disorders, such as valvular or congenital heart diseases, acquired infiltrative disorders, primary electrophysiological disorders, and the known genetically determined ion-channel abnormalities, account for only a small proportion of the sudden deaths that occur in the general population. (7)

Mechanisms of SCD from Arrhythmias

In the majority of patients with episodes of SCD, a structural cardiac abnormality is often the causative basis for SCD (Fig. 1). (9) VT degenerating first to VF and later to asystole appears to be the most common pathophysiological cascade involved in fatal arrhythmias. In patients without underlying ischemic heart disease or cardiomyopathy, polymorphic VT and torsade de pointes caused by various genetic or acquired cardiac abnormalities, such as ion-channel abnormalities, acquired long-QT syndrome, or LVH commonly contribute to the initiation of life-threatening arrhythmias. Bradyarrhythmia or electromechanical dissociation are also frequently recorded as the primary electrical event at the time of sudden death, particularly in patients with advanced heart disease. (7)

[FIGURE 1 OMITTED]

In patients with ischemic heart disease, fatal arrhythmias are usually triggered by two common patterns; ventricular tachyarrhythmia triggered by acute myocardial ischemia in patients with or without pre-existing myocardial scarring, and ventricular tachyarrhythmia related to an anatomic substrate (usually scarring from a previous infarction) without active or clinically obvious myocardial ischemia. Myocardial ischemia, especially in the acute setting, is generally considered to be the most common factor triggering fatal arrhythmias. (10)

While SCD in patients with prior MI is thought mainly to be the result of re-entrant ventricular arrhythmias originating from the subendocardial surface of infarcted myocardium, the mechanism of SCD in patients with NICM is less well understood. Identification of patients with NICM at high risk for sudden death is complicated by the inadequate predictive accuracy of both electrophysiologic studies (EPS) and noninvasive tests in this patient population. (11)

Clinical Evaluation of SCD Survivors

A thorough history from the patient and/or witness can provide valuable insight into the specific circumstances surrounding the SCD and the future risk of SCD. Conventional risk factors like smoking, diabetes, hypertension and hyperlipidemia have low power to discriminate the individual person at risk for sudden death from arrhythmias.

Heart failure (HF) as defined by impairment of functional capacity, and degree of left ventricular dysfunction as measured on echocardiogram, are powerful predictors of the risk of death from cardiac causes but have relatively low specificity as predictors of death from arrhythmias. Electrocardiographic (EKG) variables like LVH, width of QRS, and QT dispersion likewise have low power to predict death from arrhythmias. Specific abnormalities, eg, prolonged QT interval, Brugada syndrome characterized by right bundle branch block with ST elevation in V1, right ventricular dysplasia manifested as ST segment and T wave abnormalities in leads V1 and V2 and delta waves in Wolff-Parkinson-White syndrome are highly specific for underlying electrophysiological abnormalities, but not the risk of SCD. In high resolution EKG, late potentials on signal-averaged electrocardiography have a high negative predictive value but low positive predictive value. The value of heart rate variability and baroreceptor sensitivity, markers of autonomic nervous function, in predicting SCD is similarly unknown. (7)

EPS in contrast provide a high degree of accuracy in predicting SCD in specific high-risk subgroups, eg, those with clinical presentation of sustained VT or cardiac arrest without an identifiable transient trigger or in patients with unexplained syncope without a documented arrhythmic event. They are less often used than in the preimplantable cardioverter-defibrillator (ICD) era, but are still performed to provide insight into the type of arrhythmias involved in SCD survivors and to some extent, the best course of treatment. Information obtained during EPS on mechanism, rate, morphology, origin and hemodynamic stability is helpful in determining whether the patient is a candidate for an ICD, catheter ablation therapy, surgical therapy or rarely, serial drug testing. Induction of sustained monomorphic VT is the generally accepted endpoint for programmed stimulation, while induction of nonsustained ventricular arrhythmias, polymorphic VT or VF, may be nonspecific findings. In cardiac arrest survivors, sustained monomorphic VT can be induced by ventricular stimulation in 50 to 60%, polymorphic VT or VF in another 10 to 20%, and nonsustained VT or no arrhythmias in the remaining patients. (9) The sensitivity and validity of the results of electrophysiological testing seem to be better for patients with a previous MI than for those with NICM. (12)

Recent trials of survivors of cardiac arrest have shown improved survival when ICD therapy is given without prior EPS. Accordingly, EPS are not often used in survivors of SCD. The routine use of EPS following MI and in patients with NICM is controversial and the appropriate endpoints are unclear.

Cardiac catheterization should be performed in all survivors of SCD to establish the presence, extent and severity of CAD. Data obtained from coronary angiography can help determine the feasibility of treatment strategies, such as myocardial revascularization and is also helpful to define coronary anomalies and other forms of congenital heart disease. Moreover, the data supporting the benefit of ICD in patients with ischemic cardiomyopathy (ICM) is much stronger than in patients with NICM and evidence of ischemia on cardiac catheterization will favor the use of ICD in selected high-risk populations.

Prevention of SCD

Therapeutic strategies for the prevention of sudden death from cardiac causes may be divided into two general categories--primary prevention and secondary prevention. Primary prevention refers to the prevention of the first life-threatening arrhythmic event, such as sustained VT, VF, or cardiac arrest. Secondary prevention refers to the prevention of a recurrence of a potentially fatal arrhythmia or cardiac arrest among patients who have had clinical events of that type. Within each category, the two most commonly applied specific strategies are the use of antiarrhythmic drugs (AADs) and the use of ICD. The evidence regarding these approaches is stronger for ICM than for NICM.

Primary Prevention

Antiarrhythmic Drugs

Until now, the only class of medication that had been shown to reduce the incidence of sudden death was beta blockers, especially among patients with lower ejection fractions. (13) Most of these trials included patients after acute MI and were not assigned specifically to evaluate the risk of SCD. Recently, in a subanalysis of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), eplerenone given at a dose of 25 mg/d between 3 and 14 days (mean of 7.3 d) after MI led to a 37% reduction in the risk of sudden cardiac death. (14)

Results from trials involving other classes of AADs have been disappointing. The most dramatic of these trials was the Cardiac Arrhythmia Suppression Trial (CAST), (15) which evaluated whether suppression of asymptomatic premature ventricular contractions (PVC) after an acute MI would reduce arrhythmic death. The drugs used were encainide, flecainide and moricizine. Although these drugs did suppress PVCs, the study was stopped prematurely because of increased total mortality in the antiarrhythmic group. The Survival with Oral D-Sotalol Trial (16) tested the effect of D-sotalol, a sotalol isomer without a [beta]-blocking effect, and also demonstrated increased proarrhythmia by the active drug. (9) In the early 1990s, two major trials of amiodarone in patients who had an MI, the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT) (17) and the European Myocardial Infarct Amiodarone Trial (EMIAT) (18) demonstrated no overall survival benefit, even though there was significant reduction in the arrhythmic death rate. This was recently confirmed in the Sudden Cardiac Death Heart Failure Trial (SCD-HeFT) (19) which showed no significant difference in mortality among the amiodarone group versus the control group.

Among patients with NICM there is now evidence that standard treatment of nonischemic cardiomyopathy reduces morbidity and mortality. Several studies have shown improved survival with the use of ACE inhibitor as well as [beta]-blockers. Early trials with the use of [beta]-blockers showed an impact in morbidity and mortality, reducing the rate of sudden death in this population. Amiodarone also has shown a trend toward reduced mortality among those with NICM. (9)

Implantable Cardioverter Defibrillator

The disappointing results from pharmacological studies encouraged many clinicians to look for nonpharmacological approaches for the primary prevention of SCD. The cornerstone of this approach is ICD. To date, ten primary prevention trials have been reported including patients with both ischemic and nonischemic cardiomyopathies. (9,19) The results of these trials are summarized in Tables 2a (20-25) and 2b. (26-29)

A recently published meta-analysis (19) of all ten trials showed a 25% relative reduction in all-cause mortality with the ICD (P = 0.003, 95% confidence interval 9-37%). All-cause mortality in the control group for the 10 studies was 26.4%, compared with 18.5% in the ICD group (absolute mortality reduction of 7.9%, number needed to treat = 13). Similarly, another meta-analysis of ICDs for the prevention of mortality in patients with NICM suggested that ICD therapy might reduce all-cause mortality by 31% over medical therapy in patients with NICM. (30)

ICD use is associated with side effects both at the time of implantation and during follow-up. Even though the advent of smaller devices has largely decreased the surgical complications of ICD implantation, the estimated risk of surgery including infection and sedation complications is still around 1%. (31) Other potential complications that may occur, but are fortunately rare, include bleeding/hematoma, pneumothorax, thrombosis and cardiac perforation. Lead fractures or failure in the insulation can cause false signals, which, when detected, prompt delivery of inappropriate shocks. (32)

Frequent shocks, whether appropriately delivered during a ventricular arrhythmia or inappropriately delivered in the absence of an arrhythmia, are the most common complication encountered after implantation of ICD. In the Automatic Defibrillator Implantation Trial (MADIT II), the rate of inappropriate shocks was around 10%. (26) Recently, Sweeny et al (33) demonstrated that the use of ICDs for both primary and secondary prevention is associated with a 15% rate of inappropriate shocks. In contrast, after four years of follow-up in the SCD-HeFT trial, slightly more than 20% of implanted ICDs had fired appropriately, a firing rate similar to that found in MADIT II. (34)

When the shocks are appropriate, antitachycardia pacing can be reprogrammed to improve its effectiveness, antiarrhythmic-drug therapy can be instituted or changed, or catheter ablation can be performed. (35) Interim hospitalization for HF and for coronary events, no beta blockers, digitalis use, blood urea nitrogen > 25, body mass index [greater than or equal to] 30 kg/[m.sup.2] and New York Heart Association functional class > II are shown to be associated with increased risk for appropriate ICD therapy. (36) When shocks are inappropriately delivered because of supraventricular arrhythmias in the detection zone, reprogramming of the defibrillator to include an arrhythmia-discrimination algorithm, drug therapy, or an ablation procedure may be helpful. Finally, a correlation between poor quality of life scores and ICD shocks has also been shown in multiple trials. (37-39) Conversely, quality of life may actually improve modestly after ICD implantation. (33)

Secondary Prevention

Antiarrhythmic Drugs

Treatment of patients who have already survived one episode of aborted SCD has tilted decisively toward ICD therapy, as the risk of arrhythmic recurrence is very high despite use of all available AADs. In clinical practice, drug therapy is often used in combination with ICD. AADs may be needed early after resuscitation to stabilize the patient, or they may be needed to decrease the frequency of shocks, to terminate the arrhythmia along with antitachycardia pacing, or to treat atrial arrhythmias. (40) The class III antiarrhythmics, sotalol and amiodarone, are the two most widely used medications under these circumstances.

Implantable Cardioverter Defibrillator

There is now convincing evidence that ICD therapy is superior to class III AADs or [beta]-blocker monotherapy in reducing mortality rates in patients with a history of SCD. The three trials that compared ICD therapy with AADs therapy are summarized in Table 3. (41-43)

A meta-analysis of the secondary prevention trials in SCD showed an overall reduction in total mortality of 28% (95% confidence interval, 13-40%; P = 0.006). (18) Over an estimated follow-up period of 6 years, the mean increase in survival with defibrillator therapy, as compared with drug therapy, was 4.4 months.

A key question is the cost-effectiveness of ICD therapy. Renal dialysis is considered a standard in the United States for cost-effective medical therapy at roughly $50,000 per life-year saved. With ICD, the answer depends on the population studied. Analysis of the first MADIT, which included patients at extremely high risk for SCD, showed that ICD therapy costs about $27,000 per life-year saved, while a cost analysis of the MADIT-II trial with a lower risk population showed a cost for one patient of $43,200. (44,45) In the Antiarrhythmics versus Implantable Defibrillators (AVID) trial, a secondary prevention trial, cost analysis similarly showed a one patient cost of $43,200. (45) Recently, Sanders et al demonstrated that the lifetime cost per quality-adjusted year of life gained by the implantation of an ICD ranged from $34,000 to $70,200 among patients whose expected relative benefit was 23% or greater, thereby approximating the usually acceptable threshold of about $35,000 to $50,000, on the basis of the presumed cost of Medicare's end-stage renal disease program. (46) However, it should be noted that no therapy should be assumed to have a single, simple value for cost-effectiveness, since its cost-effectiveness can vary substantially depending on the type of patient being considered. (46,47)

Despite the evolving favorable cost-effectiveness of ICD, the costs associated with their use remain substantial. It is anticipated that the number of Medicare beneficiaries who are eligible for an ICD is about 500,000. (48) If all of these patients receive ICDs, the cost will be approximately $15 billion, further straining an already overburdened health care system. (49) Thus, further cost-effectiveness studies, subgroup analysis or pooling of data, longer trials, lower ICD prices and better ways of identifying the patients who will benefit the most is needed for better resource utilization and avoidance of inappropriately costly care. Centers for Medicare and Medicaid Services (CMS) has indeed proposed the development of additional evidence through one or more large-scale prospective, observational studies or registries which would allow for longer follow-up and better real-world estimates of costs and benefits. (50)

Approach to the SCD Patient

Primary Prevention

It is now generally accepted that patients with ICM, documented prior MI and measured left ventricular ejection fraction (LVEF) [less than or equal to] 35% are candidates for ICD placement (Fig. 2). However, the exact time at which ICD should be placed in still not clear. Recent evidence suggests that ICD placement up until 40 days status post MI is not associated with any survival benefit and thus patients should not receive ICD during this time period. During this early post MI period, eplerenone at a dose of 25 mg/d should be given to all patients unless contraindicated. In patients with CAD who present for evaluation of syncope and near syncope of unknown cause, the first step involves the estimation of LV function. If LV function is impaired, an EPS is performed. If inducible VT or VF is documented, an ICD is implanted. In contrast, if LV function or the EPS is normal, other causes, eg, neurologic, vasovagal, bradycardia, etc., should be considered.

Despite lack of definitive data, ICD implantation has been recommended recently by Medicare in patients with NICM > 9 months and a measured LVEF [less than or equal to] 30%.

[FIGURE 2 OMITTED]

Secondary Prevention

For secondary prevention following an episode of aborted SCD, patients who do not have significant comorbidities are almost always treated with an ICD. Families of patients who have significant comorbidities sometimes elect no treatment, reasoning that SCD is most often a painless way to die. Other patients in this group are treated with amiodarone at higher doses (usually 400 mg p.o. q.d.) after the initial loading dose of 10 g, on the basis that it is the most effective drug for this purpose and that it usually does not cause serious side effects during the first few years of administration even at higher doses.

Management of Out-of-Hospital Cardiac Arrest (OHCA)

The survival rate of OHCA patients to hospital discharge is disappointing. Overall survival is less than 5% in the United States and Canada. VF is the predominant rhythm in the first 3 to 5 minutes after OHCA in a public setting.

Recently, a three-phase model of cardiopulmonary resuscitation (CPR) to reflect the time-sensitive progression of pathophysiologic response to cardiac arrest and its treatment has been described. (51) The first phase includes approximately the first 4 minutes after the patient collapses and is called the electrical phase. During this first phase, immediate defibrillation with biphasic waveforms should be the standard of care.

The second phase involves approximately minute 4 up to minute 10 after the onset of VF, and is called the circulatory phase. Restoration of organized electrical activity during this phase does not necessarily result in an adequate contractile response. During this phase, promoting cardiac and cerebral oxygen delivery by effective chest compression/ventilation (that allows adequate venous return to the heart) and delaying defibrillation seem to yield better survival outcomes. Initiating CPR before restoration of organized electrical activity may promote the washout of deleterious metabolic factors and may allow oxygen delivery to already ischemic tissues. Pharmacological treatment during the circulatory phase includes the early use of amiodarone for shock-resistant VF and/or refibrillation. Vasopressin should be considered when high doses of vasopressors are suspected to be needed, especially if asystole is documented. High doses of epinephrine should be avoided because the deleterious effects of this intervention probably outweigh its benefits.

The third phase begins approximately 10 minutes after the onset of VF and is called the metabolic phase. During this phase, the consequences of prolonged periods of tissue ischemia may resemble a state of sepsis, resulting in release into circulation of tumor necrosis factor, endotoxins and cytokines, all of which suppress myocardial contractility. In the metabolic phase, hypothermia (32 to 34[degrees]C) may be helpful for survivors of OHCA. (52)

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A well-spent day brings happy sleep.
--Leonardo da Vinci


Sheharyar Ali, MD, and Eduardo S. Antezano, MD

From the Division of General Internal Medicine & Cardiology, VA Medical Center, Des Moines, IA.

Reprint requests to Sheharyar Ali, MD, 9425 Ironwood Lane, Johnston, IA 50131. Email: dr_sheharyar@yahoo.com

Accepted January 31, 2006.

RELATED ARTICLE: Key Points

* Sudden cardiac death (SCD) is the leading cause of death in the United States.

* Atherosclerotic coronary artery disease (CAD) remains the predominant substrate for SCD.

* The most common arrhythmia found during resuscitation in patients with CAD is ventricular fibrillation (VF) but ventricular tachycardia (VT) that degenerates into VF frequently precedes it. The most common underlying mechanism seen in monomorphic VT in adult patients with CAD appears to be re-entry.

* Until now the only medication in primary prevention that has been shown to reduce the incidence of SCD is beta blockers. Antiarrhythmic drugs (AADs) have not been shown to reduce the incidence of SCD in primary prevention and may have a proarrhythmic effect. Recently, eplerenone has also been shown to be effective in the primary prevention of SCD following myocardial infarction.

* Implantable cardioverter defibrillator (ICD) has been shown to decrease the incidence of SCD in primary prevention in patients with LV systolic dysfunction, as well as in secondary prevention when compared to antiarrhythmic therapy.
Table 1. Causes of sudden cardiac death in the adult population

Causes Men Women

CAD 80% 42%
DCM 10% 18%
VHD 5% 18%
Normal 3% 9%
Other 2% 13%

CAD, coronary artery disease; DCM, dilated cardiomyopathy; VHD, valvular
heart disease.

Table 2a. Sudden cardiac death primary prevention trials

Trial
(year reported) Population Additional risk markers

MADIT (1996) (20) 196 patients with MI longer Asymptomatic NSVT with
 than 3 weeks before entry inducible VT not
 and LVEF suppressed by IV
 [less than or equal to] procainamide
 0.35
CABG-Patch 1055 patients undergoing Abnormal SAECG
 (1997) (21) CABG with LVEF
 [less than or equal to]
 0.35
MUSTT (1999) (22) 704 patients with ischemic Inducible, sustained
 cardiomyopathy and LVEF ventricular
 [less than or equal to] tachyarrhythmias
 0.40
CAT (2002) (23) 104 patients with recent None
 onset nonischemic
 cardiomyopathy and LVEF
 [less than or equal to]
 0.30
MADIT II 1232 patients with prior MI None
 (2002) (24) and LVEF
 [less than or equal to]
 0.30
AMIOVIRT 101 patients with NSVT
 (2003) (25) nonischemic
 cardiomyopathy and LVEF
 [less than or equal to]
 0.35

Trial Mortality treatment vs
(year reported) Intervention and follow up placebo

MADIT (1996) (20) 95 pts randomized to ICD, 16% vs 39% (P = 0.009)
 101 to AAD (mostly
 amiodarone) Follow up
 27 months
CABG-Patch 466 pts randomized to ICD 23% vs 21% (P = 0.64)
 (1997) (21) 454 to usual care--no
 protocol-driven AAD
 therapy instituted
 Follow up 32 months
MUSTT (1999) (22) 351 pts assigned to EPS 42% vs 48% (P = 0.06)
 guided therapy (161
 ICDs without
 randomization); 353 to
 receive no AAD therapy
 Follow up 39 months
CAT (2002) (23) 50 randomized to ICD, 54 26% vs 50% (P = 0.55)
 to conventional therapy
 Follow up 23 months
MADIT II 742 pts randomized to 14.2% vs 19.8%
 (2002) (24) ICD, 490 to optimal (P = 0.016)
 medical therapy
 Follow up 20 months
AMIOVIRT (2003) 51 pts randomized to ICD, 12% vs 13% (P = 0.80)
 (25) 52 to amiodarone
 Follow up 24 months

AAD, antiarrhythmic drugs; AMIOVIRT, Amiodarone versus Implantable
Cardioverter-Defibrillator Randomized Trial in patients with nonischemic
cardiomyopathy; CABG-Patch, Coronary Artery Bypass Graft Patch trial;
CAT, Cardiomyopathy Trial; EP, electrophysiology: ICD, implantable
cardioverter defibrillator; LVEF, left ventricular ejection fraction;
MADIT, Multicenter Automatic Defibrillator Implantation Trial; MI,
myocardial infarction; MUSTT, Multicenter Unsustained Tachycardia Trial;
NSVT, nonsustained ventricular tachycardia; SAECG, signal-averaged
electrocardiogram; VT, ventricular tachycardia; pts, patients.

Table 2b. Sudden cardiac death primary prevention trials (latest trials)

 Additional risk
Trial (year reported) Population markers

COMPANION (2004) (26) 1520 patients with ischemic QRS duration > 120
 and nonischemic ms
 cardiomyopathy with LVEF
 [less than or equal to]
 35
DEFINITE (2004) (27) 458 patients with Nonsustained
 nonischemic ventricular
 cardiomyopathy with LVEF tachycardia or
 [less than or equal to] frequent premature
 36 ventricular
 complexes
DINAMIT (2004) (28) 674 patients within 6-40 Depressed heart rate
 days of MI with LVEF variability
 [less than or equal to]
 35
SCD-HeFT (2004) (29) 2521 patients with ischemic None
 and nonischemic
 cardiomyopathy with LVEF
 [less than or equal to]
 0.35

 Intervention and Mortality treatment
Trial (year reported) follow up vs placebo

COMPANION (2004) (26) 309 randomized to 19% in optimum medical
 optimum medical therapy, 15% in CRT and
 therapy, 595 to 12% in CRT-D group
 CRT-D, 617 to CRT (P = 0.06 with CRT and
 Follow up 16 months p = 0.004 with CRT-D)
DEFINITE (2004) (27) 229 randomized to ICD, 8.1% vs 13.8% (P = 0.06)
 229 to standard
 medical therapy
 Follow up 29 months
DINAMIT (2004) (28) 332 randomized to ICD, 7.5% vs 6.9% (P = 0.66)
 342 to optimized
 medical therapy
 Follow up 30 months
SCD-HeFT (2004) (29) 847 randomized to 22% in ICD group, 28% in
 optimized medical amiodarone group and
 therapy, 845 to 29% in control group
 optimized medical (P = 0.007)
 therapy and
 amiodarone and 829
 to an ICD Follow up
 48 months

COMPANION, Comparison of Medical therapy, Packing, and Defibrillation in
Patients with Left Ventricular Systolic Dysfunction trial: CRT, cardiac
resynchronization therapy; CRT-D, cardiac resynchronization therapy with
defibrillation capability; DEFINITE, Defibrillators in Non-Ischemic
cardiomyopathy Treatment Evaluation trial; DINAMIT, Defibrillator in
Acute Myocardial Infarction Trial; ICD, implantable cardioverter
defibrillator; LVEF, left ventricular ejection fraction: MI. myocardial
infarction; SCD-HeFT, Sudden Cardiac Death in Patients with Heart
Failure Trial.

Table 3. Sudden cardiac death secondary prevention trials

 Mortality
Trial Intervention and treatment vs
(year reported) Population follow up placebo

AVID (1997) (41) 1016 patients who 507 pts randomized 24.6% vs 35.9%
 survived cardiac to ICD, 590 to (P < 0.02)
 arrest, had amiodarone or
 sustained VT sotalol
 with syncope or Follow up 36
 sustained VT and months
 LVEF < 40% with
 either
 hypotension,
 chest pain or
 presyncope
 during VT
CIDS (2000) (42) 659 patients with 328 pts randomized 8.3% vs 10.2%
 resuscitated VF to ICD, 331 to (P = 0.14)
 or VT or with amiodarone
 unmonitored Follow up 36
 syncope months
CASH (2000) (43) 346 survivors of 99 pts randomized 36.4% vs 44.4%
 cardiac arrest to ICD, 92 to (P = 0.08)
 secondary to amiodarone, 97
 documented to metoprolol
 ventricular (propafenone arm
 arrhythmias stopped early
 due to excessive
 mortality)
 Follow up 24
 months

AVID, Antiarrhythmics Versus Implantable Defibrillators trial; CASH,
Cardiac Arrest Study Hamburg trial; CIDS, Canadian Implantable
Defibrillator Study trial; ICD, implantable cardioverter defibrillator;
LVEF, left ventricular ejection fraction; VF, ventricular fibrillation;
VT, ventricular tachycardia: pts, patients.
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Title Annotation:Review Article
Author:Antezano, Eduardo S.
Publication:Southern Medical Journal
Geographic Code:1USA
Date:May 1, 2006
Words:6218
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