Retrospective studies have shown that patients with severe chronic heart failure who receive long-term treatment with positive inotropic agents have a high mortality rate, but in the absence of controlled trials it remains unclear whether the high incidence of fatal cardiovascular events in these patients is related to treatment or to the severity of the underlying disease. Most of the evidence that suggests a detrimental effect of positive inotropic therapy on survival remains circumstantial. The pooling of data from long-term studies of patients after an acute myocardial infarction suggests that use of digitalis may be associated with an unfavorable effect on survival. The prolonged administration of intravenous or oral catecholamines is associated with a high mortality rate, which may not be seen in similar patients treated conventionally. The presence of intrinsic sympathomimetic activity appears to neutralize the benefits of beta-blockade during the first year after an acute myocardial infarction; treatment with such agents after the first year may increase mortality. Long-term treatment with phosphodiesterase inhibitors is associated with a high mortality rate, which exceeds that reported in earlier years with vasodilator therapy. Nevertheless, most of these studies of positive intropic agents were not performed to evaluate the issue of survival and did not randomly assign patients to treatment groups. Hence, we do not know that the patients entered into these studies were truly comparable to their proposed control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients with congestive heart failure have a high incidence of sudden cardiac death that is attributed to ventricular arrhythmias. The mortality rate in a group of patients with class III and IV heart failure is about 40% per year, and half of the deaths are sudden. Half of the patients with New York Heart Association class III or IV heart failure have unsustained ventricular tachycardia detected on a 24 hr continuous electrocardiographic recording. The presence of ventricular tachycardia in patients with congestive heart failure increases the probability of dying; in class III or IV heart failure, the presence of unsustained ventricular tachycardia on a 24 hr continuous ECG recording increases the odds of dying about threefold over a 1 to 2 year follow-up period. Many electrical, mechanical, humoral, and electrolyte abnormalities may promote ventricular arrhythmias in patients with heart failure. Correction of these predisposing factors could reduce the risk of lethal ventricular arrhythmias and therefore every effort should be made to do so. Because there has been no definitive study of the impact of antiarrhythmic drug treatment on the survival of patients with heart failure and ventricular arrhythmias, the role of therapy with antiarrhythmic drugs remains uncertain at the present time.

The high mortality of heart failure is associated with hemodynamic abnormalities, depressed cardiac function, and reduced exercise capacity. That these factors can be modified by drug treatment is of potential prognostic significance. Hemodynamic variables are related to survival, and long-term prognosis is better in patients with only midly abnormal cardiac output or ventricular filling pressures. Indexes of left ventricular function such as ejection or shortening fraction tend to be higher in patients who survive for longer periods. The relation between exercise capacity and survival, however, is unclear. Those patients with severe exercise intolerance (maximal oxygen uptake below 10 ml/min/kg) or with severe symptoms are at great risk of dying. However, exercise capacity and functional class are not related to prognosis when all classes of patients are considered together, especially if class IV patients are excluded. Most of the available data derive from retrospective analyses of trials involving heterogeneous patient populations and aimed at improving left ventricular performance or functional capacity. Large prospective trials aimed primarily at affecting mortality in a broad spectrum of patients are needed to learn more about determinants of survival in heart failure.

Over the past several decades, pharmacologic advances have made it possible to markedly alleviate symptoms in most patients with congestive heart failure. However, the prognosis for these patients remains poor. Five years after the onset of congestive heart failure, only approximately 50% of patients are alive; when cardiac failure develops after myocardial infarction mortality is even higher. Survival rates are only 40% to 60% after 1 year in patients with advanced symptoms who are followed in referral centers. Thirty to fifty percent of deaths are sudden and unexpected. Mortality is highest in patients with severe or progressive symptoms, but it appears to be unrelated to the cause of heart failure or its duration. In general, rate of survival is lowest in patients with the most severe depression of left ventricular function, but no hemodynamic index is capable of providing prognostic information in individual patients. Survival is also reduced in patients with frequent ventricular arrhythmias, marked electrolyte disturbances, and elevated plasma catecholamines, but again, none of these measurements are powerful discriminators between survivors and nonsurvivors. A number of pharmacologic and other interventions have the potential to alter the prognosis of congestive heart failure, either by improving or perhaps even by worsening survival. The pooled data from several short-term controlled trials have raised the possibility that the angiotensin converting-enzyme inhibitors may have a beneficial effect on survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased ventricular volume is one of the most powerful predictors of reduced survival in patients with heart disease. Despite its well-documented prognostic significance, the magnitude of the progression of ventricular dilatation from the acute to the chronic phase of myocardial infarction has only recently been appreciated. In an experimental preparation of myocardial infarction in rats, left ventricular cavitary volume increased progressively even after histologic resolution of the infarct region. We hypothesized that this remodeling of the infarcted left ventricle was a response to an increase in both systolic and diastolic wall stresses and that captopril, by reducing wall stress, would attenuate the process. For comparably sized infarcts, the captopril-treated rats had smaller ventricular volumes at common distending pressures, yet they had maintained or improved cardiac output. Most importantly, long-term captopril therapy also prolonged the survival of these rats with experimental myocardial infarction. The implication of these animal studies is that the potential exists for the attenuation of progressive ventricular enlargement and improvement of survival of patients recovering from a myocardial infarction. At the present time, no information is available in patients as to the therapeutic potential of interrupting this insidious process of ventricular dilatation in order to improve survival. Clinical trials are required to determine whether salutary benefits similar to those observed in animals can be provided to patients recovering from a myocardial infarction.

Support for the concept that neurohormonal mechanisms play an important role in determining the survival of patients with severe chronic heart failure is derived from two lines of evidence: circulating levels of neurohormones are markedly elevated in patients who have a poor long-term prognosis and the survival of high-risk patients may be favorably modified by treatment with specific neurohormonal antagonists. Plasma norepinephrine is a major prognostic factor in patients with severe chronic heart failure, the most markedly elevated levels being observed in patients with the most unfavorable long-term prognosis. Data from uncontrolled studies suggest that low-dose beta-blockade may improve the survival of patients with dilated cardiomyopathy. Similar trends were noted in the Beta-Blocker Heart Attack Trial, in which patients with congestive heart failure before or accompanying their acute myocardial infarction experienced a significant reduction in sudden death when treated with beta-blockers. In contrast, there appeared to be little selective benefit in patients without heart failure, who presumably had low circulating levels of catecholamines. Similarly, serum sodium concentration is a major prognostic factor in patients with severe chronic heart failure, the shortest survival being observed in patients with the most severe hyponatremia. The poor long-term outcome of hyponatremic patients appears to be related to the marked elevation of plasma renin activity in these individuals, since (in retrospective studies) hyponatremic patients appeared to fare significantly better when treated with converting-enzyme inhibitors than when treated with vasodilator drugs that did not interfere with angiotensin II formation. In contrast, there appeared to be no selective benefit of converting-enzyme inhibition on the survival of patients with a normal serum sodium concentration, in whom plasma renin activity was low. These data suggest that neurohormonal systems may exert a deleterious effect on the survival of some patients with severe chronic heart failure, which may be favorably modified by long-term treatment with specific neurohormonal antagonists.

A series of neurohumoral systems are activated in congestive heart failure that contribute to the increased vascular resistance and sodium retention that characterize this disorder. Abnormalities in baroreceptor function are intrinsic to the pathophysiology of heart failure and may subserve the vasoconstrictive and volume overloaded state that defines patient morbidity. Blunted baroreceptor responses to high cardiac filling pressures or depressed cardiac function reduce afferent signals that normally inhibit sympathetic efferent activity, vasopressin release, and indirectly, renin secretion. The resulting increase in neurohumoral activity mediates the redistribution of blood flow that occurs in this disorder. Limb blood flow is usually reduced and may be responsible for exercise intolerance. Decreased renal blood flow and altered intrarenal hemodynamics contribute to sodium retention. In addition, renal vasoconstriction and elevated circulating levels of angiotensin II and vasopressin may contribute to hyponatremia by influencing free water intake and excretion. Hence, baroreceptor dysfunction may be a principal mechanism that contributes to neurohumoral activation and subsequent alteration in vascular resistance and sodium and water balance in congestive heart failure. It may not be coincidental that two principal markers of an unfavorable prognosis in patients with heart failure, high plasma norepinephrine levels and hyponatremia, share baroreceptor dysfunction as a common theme.

CBV for adults with aortic and mitral stenosis is investigational at the present time and should usually be performed within the guidelines of clinical investigation. The technology is an evolving one with regard to types of catheters and balloons, methods of catheter insertion and placement, and patients and valves that are suitable for and will respond well to CBV. The initial results range from disappointing to excellent and must be kept in perspective. The procedure is clearly a palliative one; ideal results are not being achieved at present. Some of the complications are very serious. Nevertheless, CBV is a most promising catheter interventional technique for patients with valvular heart disease. Proper selection of patients and complete reporting of results is important.