Sudden cardiac death in heart failure

SCD-HeFT = Sudden Cardiac Death in Heart Failure Trial. 

The results of MADIT II were met with some skepticism, but later confirmed by the recent Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) [24]. This study evaluated the benefit of ICD therapy versus amiodarone or placebo as primary prevention in over 2,500 patients with stable NYHA class II or III heart failure and EF < 35%, without the requirement for NSVT or EPS. Patients with both ischemic and nonischemic etiologies for cardiomyopathy were included. Over a follow-up of 4 years, there was no benefit of amiodarone over placebo for overall mortality, but ICD therapy resulted in a significant 23% reduction in overall mortality [p = 0.007] (Fig. 3.5). The benefit of ICD therapy was comparable for ischemic and nonischemic cardiomyopathy. 

The indications for implantation of an ICD have expanded considerably (Table 17-7). Initially, its efficacy was evaluated in patients who had already suffered a documented episode of ventricular tachycardia or ventricular fibrillation (secondary prevention), but now primary prevention trials have been published or are being planned. These results will help clinicians in choosing the proper therapy for patients with life-threatening arrhythmias. For instance, the Sudden Cardiac Death in Heart Failure Trial (SCD-Heft) is a primary prevention trial that evaluated survival in patients withLV dysfunction... 

Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an Implantable Cardioverter-Defibrillator for Congestive Heart Failure. Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. N Engl J Med 2005 352(3) 225—37. 

Gold MR, Ip JH, Costantini O, Poole JE, et al. Role of microvolt T-wave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction Primary results from the T-wave alternans Sudden Cardiac Death in Heart Failure Trial substudy. Circulation 2008 118 2022-8. 

Uretsky, B.F. and R.G. Sheahan, Primary prevention of sudden cardiac death in heart failure will the solution be shocking J Am Coll Cardiol, 1997. 30(7) p. 1589-97. 

Bayes-Genis A, Vazquez R, Bayes de Luna A et al. For the MUSIC Study Group. Left atrial enlargement and NT-proBNP as predictors of sudden cardiac death in patients with heart failure. Eur J Heart Fail. 2007 Jun 12 [Epub ahead of print]... 

La Rovere MT, Pinna GD, Maestri R. Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patients. Circulation 2003 107(4) 565—70. 

La Rovere MT, Pinna GD, Maestri R et al (2003) Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patients. Circulation 107 565—570 Li N, Venkatesan Ml, Miguel A et al (2000) Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element. J Immunol 165 3393-3401... 

VF is electrical anarchy of the ventricle resulting in no cardiac output and cardiovascular collapse. Sudden cardiac death occurs most commonly in patients with ischemic heart disease and primary myocardial disease associated with LV dysfunction. VF associated with acute MI may be classified as either (1) primary (an uncomplicated MI not associated with heart failure [HF]) or (2) secondary or complicated (an MI complicated by HF). 

Marks, A. R. (2001). Ryanodine Receptors/Calcium Release Channels in Heart Failure and Sudden Cardiac Death. . / Mol Cell Cardiol 33(4) 615-24. 

Phrommintikul, A., and Chattipakorn, N. (2006). Roles of Cardiac Ryanodine Receptor in Heart Failure and Sudden Cardiac Death. Int J Cardiol 112(2) 142-52. 

Marks, A. R. 2001. Ryanodine receptors/calcium release channels in heart failure and sudden cardiac death. J. Mol. Cell. Cardiol. 33 615-624. 

A. L. Goldberger, L. Findley, M. J. Blackburn, and A. J. Mandell, Nonliear dynamics of heart failure implications of long-wavelength cardiopulmonary osciallations. Am. Heart J. 107, 612-615 (1984) G. A. Myers, G. J. Martin, and N. M. Magrid et al. Power spectral analysis of heart rate variability in sudden cardiac death Comparison to other methods. IEEE Trans. Biomed. Eng. 33, 1149-1156 (1986). 

Adverse Effects. Digoxin can produce a variety of cardiac and noncardiac adverse effects, but it is usually well tolerated by most patients (Table 14-11). Noncardiac adverse effects frequently involve the central nervous system or gastrointestinal system but also may be nonspeciflc (e.g., fatigue or weakness). Cardiac manifestations include numerous different arrhythmias that are believed to be caused by multiple electrophysio logic effects (see Table 14-11). Cardiac arrhythmias may be the flrst evidence of toxicity in a patient (before any noncardiac symptoms occur). Rhythm disturbances are of particular concern because patients with chronic heart failure are aheady at increased risk for sudden cardiac death presumably owing... 

The adverse effects associated with the use of verapamil include constipation, sinus node blockade, prolongation of the PR interval, AV dissociation, hypotension, and pulmonary congestion." The risks may outweigh the benefits in patients with (1) a markedly elevated pulmonary capillary wedge pressure or pulmonary artery occlusion pressure, (2) a history of paroxysmal nocturnal dyspnea or orthopnea, (3) sick sinus syndrome or significant AV nodal disease in the absence of a permanent pacemaker, (4) low systolic blood pressure, and (5) a substantial outflow gradient.Verapamil should be avoided inpatients with heart failure owing to systolic dysfunction. There is no evidence that either /3-blockade or verapamil protects the patient from sudden cardiac death. 

The clinical consequences of significant mitral regurgitation are numerous and include impaired quality of life (particularly with dyspnea and fatigue on exertion), left ventricular enlargement and dysfunction, arrhythmias such as atrial fibrillation, secondary pulmonary hypertension and sudden cardiac death. Concomitant mitral regurgitation can be particularly deleterious in patients with either congestive heart failure or ischemic heart disease (15,16). 

In an SCD-HeFT (Sudden Cardiac Death Heart Failure Trial) substudy of MTWA, 490 patients were enrolled at 37 sites and followed for a mean of 35 months prospectively with a composite of primary endpoint of SCD, sustained ventricular arrhythmias, or an appropriate ICD discharge. This was a sick population of heart failure patients. MTWA was positive in 37%, negative in 22%, and indeterminate in 41%. There is no significant difference in survival between the MTWA positive and negative patients in the ICD and placebo arms. Mortality did not differ significantly between groups. These data indicate that MTWA results are frequently indeterminate and their ability to predict outcomes is limited. 

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