Etiology and Risk Factors

The pathogenic electrical events leading to SCD are most commonly ventricular tachycardia (VT), ventricular fibrillation (VF), and eventually asystole (Fig. 30-2). Approximately 80% of SCDs involve VT, VF, or torsades de pointes; the remaining 20% are due to bradyarrhythmias. SCD is most commonly associated with underlying structural heart disease. Less than 20% of out-of-hospital victims of SCD recover to hospital discharge. The likelihood of resuscitation diminishes 10% for every minute of delay. It has been estimated that 50% of those who survive a cardiac arrest will die within 3 years. This underscores the importance of primary and secondary prevention.

Figure 30-2 Mechanisms of sudden cardiac death (SCD): Ischemic heart disease.

CAD, coronary artery disease; LV, left ventricular; LVEF, left ventricular ejection fraction; MI, myocardial infarction, VF, ventricular fibrillation; VT, ventricular tachycardia.

CAD accounts for 70% to 80% of SCD cases, especially in Western societies in patients over the age of 35. As such, two of the leading risk factors are previous heart attack and documented CAD. In those with chronic ischemic disease, the most powerful predictor is an ejection fraction (EF) less than 40%. Following CAD, patients with nonischemic cardiomyopathies (hypertrophic and dilated) and EF less than 40% are at the highest risk. Additional major risk factors for SCD include congestive heart failure of any etiology and prior history of cardiac arrest. Channelopathies, which result in an increased risk for cardiac arrhythmias, and congenital heart disease are less common causes of SCD.

Differential Diagnosis

The most common etiologies are discussed in the sections that follow (see also Box 30-1).

Ischemic Heart Disease

Overwhelmingly, the most common cause of SCD is ischemic heart disease resulting from coronary atherosclerosis. Arteritis, dissection, spasm, and congenital coronary anomalies are very rare causes associated with myocardial ischemia. CAD has been attributed to 70% to 80% of all SCDs. In a study of 84 survivors of out-of-hospital cardiac arrest, immediate coronary angiography revealed significant disease of probable etiologic significance in 71% of patients; approximately one half of these patients had complete occlusions. Acute occlusion of the left anterior descending or left circumflex coronary artery portends a higher risk of SCD. Patients with angina and prior MI are at much higher risk than those without any clinical manifestation of CAD. Unfortunately, SCD can be the first manifestation of CAD in one third of CAD patients.

Causes of SCD in the CAD population include myocardial ischemia or infarction, heart failure, electrolyte imbalance, drug toxicity, or primary (no precipitating cause identified). The probable mechanisms for VT or VF in patients with CAD are acute ischemia and reentry via myocardial scar, especially in those with a prior infarct. A meta-analysis of four non–ST-elevation MI (NSTEMI) trials found the risk of sustained or unstable ventricular arrhythmias (VT or VF) to be 2.1% (vs. 10% in ST-segment elevation MI, STEMI) during the initial hospital admission. Patients with VT and VF had the highest mortality rate in the first 30 days (>60%) post-MI, followed by patients with VF only (>45%), followed by patients with VT only (>30%). This trend was consistent at 6 months, correlating to a 5- to 15-fold increase in mortality within 6 months in patients with these arrhythmias. Patients in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO I) Trial, which studied fibrinolytic therapies for STEMI, demonstrated higher overall incidences of sustained arrhythmias than in NSTEMI patients: specifically, 3.5% for VT only, 4.0% for VF only, and 2.6% for both VT and VF. Of these arrhythmias, 80% to 85% occurred within the first 48 hours (“early”). In-hospital mortality and 1-year mortality (for those who survived longer than 30 days) after discharge of these patients were much higher among those with VT, VF, or VT and VF (18.6%, 24%, or 44% in-hospital, and 7.2%, 2.9%, or 7.1% 1 year, respectively) than patients without these arrhythmias (4.2% in-hospital, 2.7% 1-year). Patients with “late” (after the first 48 hours) ventricular arrhythmias had increased mortality at 1 year (24.7% for VT, 6.1% for VF, 4.7% for VT and VF) and were more likely to have had a previous MI, previous bypass surgery, and a longer time from the onset of MI and receiving treatment.

Nonischemic Cardiomyopathy

Idiopathic Dilated Cardiomyopathy

Ten to fifteen percent of SCD cases are attributable to cardiomyopathies not associated with CAD. In patients with dilated cardiomyopathies, the presence of nonsustained VT, syncope, and/or advanced heart failure are high-risk predictors. SCD is the major cause (up to 72% in some studies) of death in patients with nonischemic cardiomyopathy. Most fatal arrhythmias are thought to be tachyarrhythmias, mainly polymorphic, and less commonly monomorphic, VT. The primary mechanism of polymorphic VT and VF is unknown, but subendocardial scarring and interstitial and perivascular fibrosis are probably involved. A particular type of monomorphic VT (see Chapter 29) caused by bundle branch reentry is characteristic of nonischemic cardiomyopathy. In bundle branch reentry, a “macro” reentrant circuit involving both bundles, the Purkinje system, and the myocardium can be documented.

Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is an autosomal-dominant inherited disorder estimated to affect 1 in 500 adults (see Chapter 19 and Figure 30-3). The overall risk of SCD in patients with HCM is estimated at 1% to 4% per year, but within subgroups of patients with this disease the risk of SCD varies substantially. All first-degree relatives of a patient with HCM who had SCD must be screened. Generally, patients with HCM who are at highest risk for SCD are those with recurrent syncope, nonsustained VT on Holter monitoring, extreme left ventricular hypertrophy on echocardiogram (>30 mm), abnormal blood pressure response to exercise, and a positive family history of SCD from HCM. Careful evaluation for HCM is of utmost importance in young individuals because HCM is the most common cause of SCD in young athletes in the United States (Fig. 30-3, top). Genetic testing of first-degree relatives of an individual whose gene mutation has been identified may help establish risk but remains a controversial screening modality. Screening should include a detailed history and physical examination, ECG, and echocardiography.