Alfred E. Buxton, MD, Alpert Medical School of Brown University, reviewed studies on risk factors for sudden cardiac death (SCD). Although LVEF is a good predictor of total mortality after MI, population-based studies show that patients with low LVEF account for only half of those with SCD. Among patients who survive acute MI there has been a decline in the percentage with low LVEF, because of reperfusion therapy (Figure 1). In the GUSTO trial, 12% of acute MI survivors had LVEF ≤40%. A meta-analysis showed that LVEF does not predict the cause of death after MI.

Figure 1. Proportion of Patients Surviving Acute MI with Low EF is Decreasing. 【Click to enlarge】

Figure 2. Potential Risk Factors for Prediction of SCD. 【Click to enlarge】

Figure 3. Risk Stratification for Sudden Death: Major Issues 【Click to enlarge】

Figure 4. Conclusions 1 – Risk Stratification CAD. 【Click to enlarge】

Figure 5. Conclusions 2 – Risk Stratification. 【Click to enlarge】

In the MADIT II study post-MI patients with BUN ≥50 mg/dL and/or creatinine ≥2.5 mg/dL had no improvement in all-cause mortality with defibrillator therapy versus pharmacologic therapy. After eliminating patients with severe renal dysfunction, multivariate analysis identified NYHA Class >2 (HR=1.87, p=0.004), atrial fibrillation (HR=1.87, p=0.034), QRS >120 ms (HR=1.65, p=0.020), age >70 years (HR=1.57, p=0.042), and BUN 27-49 (HR=1.56, p=0.048) as risk factors for mortality. Patients with 1 or 2 of these factors had a significant survival benefit with ICD therapy. Patients with none and those with ≥3 risk factors had no survival benefit. Altogether, 46% of patients derived no survival benefit from an ICD. Thus, using current risk factors to guide ICD use, most post-MI patients who die suddenly are being missed.

Figures 2 and 3 list potential risk factors for SCD and major issues associated with them. In the ATRAMI study, patients with LVEF <35 and baroreflex sensitivity (BRS) <3 had markedly lower event-free survival (EFS) than those with LVEF <35 and BRS ≥3, LVEF ≥35 and BRS <3, or LVEF ≥35 and BRS ≥3 (p <0.001). Other studies have shown: Higher arrhythmic event rates in patients with T-wave alternans (TWA) and late potentials (LP) versus those with one or neither factor (p<0.0001); in patients with LVEF >40% post-MI, those with TWA had lower EFS versus patients without TWA (p <0.001); in post-MI patients with LVEF >35%, those with BRS <3 ms/mmHg had increased cardiovascular deaths versus patients with BRS ≥3 ms/mmHg (p <0.0001).

Multiple studies have demonstrated that sensitivity of single risk stratification tests is below 80%. MUSTT, the only prospective trial to study test sensitivity, using electrophysiologic testing (EPS) found that 18% of patients with inducible ventricular tachycardia (VT) had cardiac arrest versus 12% of those without inducible VT (p <0.001). Patients with inducible VT treated with ICD had lower risk for cardiac death (p <0.001).

Dr. Buxton’s conclusions are listed in Figures 4 and 5. “None of the studies address the population in which cardiac arrest is the initial manifestation of heart disease—a far greater challenge,” he concluded.

Reduced left ventricular ejection fraction (LVEF) is the best available predictor of sudden cardiac death (SCD) in patients with heart failure or prior myocardial infarction (MI). In the MADIT-II trial, implantable cardiac defibrillator (ICD) use reduced mortality by 31% over 2 years in post-MI patients with LVEF ≤30%. Dr. Tsuyoshi Shiga, Tokyo Women’s Medical University, discussed two trials of SCD in post-MI and heart failure patients conducted by his group.

The first study was conducted with the Heart Institute of Japan Acute Myocardial Infarction (HIJAMI)-II registry to determine the incidence of SCD according to LVEF in 4,122 consecutive acute MI survivors. Early reperfusion therapy was administered to 80% of the patients. The Kaplan-Meier 5-year mortality was 33.2% in patients with LVEF ≤30% (HR vs >40%=3.85, 95% CI 2.96-5.00, p <0.001), 20.3% in patients with LVEF >30%-≤40% (HR vs >40%=2.06, 95% CI 1.66-2.57, p<0.001), and 10.8% in those with LVEF >40%. The major causes of death in all three LVEF groups were heart failure and non-cardiac death. The Kaplan-Meier curve for 5-year SCD showed that SCD occurred in 4.0% of patients with LVEF ≤30% (HR vs >40%=5.99; 95% CI 2.73-13.14; p <0.001), 2.6% of patients with LVEF >30%-≤40% (HR vs >40%=3.37, 95% CI 1.74-6.50, p <0.001), and 0.8% in patients with LVEF >40%. These results demonstrate that reduced LVEF is a predictor of increased risk for SCD. MI survivors with reduced LVEF have a low incidence of SCD. ICD therapy makes a minor contribution to decreasing mortality in these patients.

Figure 1. Renal Dysfunction is an Independent Risk for Cardiovascular Events 【Click to enlarge】

Renal dysfunction is an independent risk factor for ischemic heart disease and heart failure (Figure 1). The second study evaluated the impact of renal dysfunction on the occurrence of life-threatening ventricular arrhythmia in high-risk heart failure patients with non-ischemic dilated cardiomyopathy (DCM) and an ICD (N=274). There was a higher incidence of ventricular arrhythmia requiring ICD therapy in patients with eGFR ≥60 mL/min/1.73m2 versus EGFR <60 mL/min/1.73m2 (p=0.0001). Multivariate analysis found four risk factors for occurrence of ventricular arrhythmia requiring ICD therapy: Secondary ICD indication (HR=1.96, 95% CI 1.27-3.04, p=0.003); eGFR <60 mL/min/1.73 m2 (HR=1.85, 95% CI 1.24-2.77, p=0.003), no beta-blocker (HR=1.64, 95% CI 1.06-2.53, p=0.025), and LVEF <35% (HR=1.63, 95% CI 1.04-2.56, p=0.035).