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.

The Dahl strain of genetically salt-resistant (DR) and salt-sensitive (DS) rats affords an opportunity to explore mechanisms responsible for salt resistance and sensitivity. Dahl sensitive rats exhibit abnormalities in sympathetic neural control of the circulation and in renal sodium handling. Since cardiac baroreflexes participate in regulation of sympathetic nerve activity and sodium excretion, we have evaluated cardiac baroreflex function in DR and DS rats. This article briefly reviews evidence that cardiac sensory endings with vagal afferents are reset to a higher threshold in DS rats before elevation of arterial or cardiac filling pressures, as a result of this resetting, cardiac baroreflex inhibition of sympathetic nerve activity during volume expansion is impaired in prehypertensive DS rats, a high-sodium diet enhances the gain of cardiac baroreflex inhibition of sympathetic nerve activity in DR but not DS rats, and atrial natriuretic factor stimulates cardiac sensory receptors with vagal afferents. Taken together, these studies prompt speculation that humoral factors released during intake of a high-sodium diet may sensitize cardiac baroreflexes and thereby protect against sodium retention and hypertension. An absence of this compensatory adjustment or plasticity in cardiac baroreflex function in DS rats may predispose to salt-induced hypertension.

The endogenous opioid system includes three major families of peptides: dynorphins (derived from pre-proenkephalin B), endorphins (derived from pre-proopiomelanocortin), and enkephalins (derived from pre-proenkephalin A). Multiple species of opioid peptides are derived from these major precursors and many of them possess potent cardiovascular properties. Opioid peptides and opioid receptors, of which multiple forms have been defined, are present in the central nervous system and peripheral neural elements. In the central nervous system, opioid peptides and receptors are found in forebrain and hindbrain nuclei involved in baroregulation, sympathoadrenal activation, and several other vital autonomic functions. In the periphery, opioid peptides are found in autonomic ganglia, adrenal gland, heart, and other organs; multiple opioid receptors are also found in vascular tissue, heart, and kidneys. Although little is known to date on the regulatory mechanisms of the opioid system in normal cardiovascular states, it became clear that cardiovascular stress situations substantially modify the activity of the endogenous opioid system. The purpose of this review is to clarify the sites of interaction of the opioid system with all major components of the cardiovascular system and indicate the potential role of this system in the ontogenesis of cardiac malfunction, vascular diseases, and hypertension.

The extracellular structural protein, collagen, is responsible for the functional integrity of the myocardium permitting reversible interdigitation and transmission of force between contracting myocytes. In the pressure-overloaded, hypertrophied myocardium, clinical and experimental evidence indicates that the proportion of collagen relative to muscle is increased. Factors that appear to influence collagen growth during the hypertrophic process include age, species, the rapidity with which the overload occurs, the nature of the lesion leading to the pressure-overload, and the severity and duration of the overload. Morphologically, the heart's collagen matrix consists of a complex weave with tendinous insertions that surrounds myocytes grouping them into myofibers, strands of collagen that connect adjoining myofibers, and collagenous struts that join myocytes to other myocytes and capillaries. In a primate preparation of perinephritis with systemic hypertension, it was observed that the tendinous elements of the weave and the strands of collagen lying between myofibers were increased in number and physical dimension. The functional consequences of a remodeling of the collagen matrix that accompanied myocardial hypertrophy remain to be elucidated. A better understanding of the dynamic behavior of the collagen matrix may offer new insights into the pathogenesis of ventricular dysfunction that accompanies the chronic pressure-overloaded state.