ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02753.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Heart failure, a major contributor to cardiovascular disease morbidity and mortality, is newly diagnosed in approximately 400,000 patients each year, and is particularly prevalent in individuals over age 65 years. Average mortality rates 5 years after diagnosis are 45–60%, and may be as high as 50% after 1 year for those with New York Heart Association class IV heart disease. Heart failure occurs when myocardial muscle dysfunction prevents the heart from pumping enough blood at normal cardiac pressures to meet the metabolic needs of the body, especially during exercise, and compensatory hemodynamic and neurohormonal mechanisms are overwhelmed or maladaptive. Pathologic classifications are broadly based on the presence of systolic (dilated cardiomyopathy) or diastolic (hypertrophic or restrictive cardiomyopathies) dysfunction. The etiologies of heart failure may include inadequate coronary blood flow, pressure or volume overload, cardiomyopathy, or pericardial disease. Coronary artery disease, idiopathic dilated cardiomyopathy, and hypertension are the most frequent causes, and certain drugs may also worsen myocardial function. When contractility is reduced, stroke volume and cardiac output are decreased, and alterations in the kidneys may induce fluid retention to compensate for the perceived low output and reduced circulating blood volume. Fluid retention in turn causes preload or filling pressure to increase and symptoms of pulmonary congestion to emerge. Depressed contractility also results in a reduction in blood pressure, leading to compensatory neurohormonal activation and vasoconstriction, which significantly elevate afterload and further reduce stroke volume. The overall approach to heart failure includes defining the etiology, identifying precipitant factors, and assessing the severity of myocardial dysfunction and clinical symptoms. By carefully characterizing the patient with congestive heart failure, the most effective plan of nonpharmacologic and pharmacologic interventions can be initiate

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02754.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Congestive heart failure (CHF) causes disabling symptoms and increases the likelihood of decreased survival. Diuretics, direct vasodilators, and angiotensin‐converting enzyme (ACE) inhibitors can be used to reduce symptoms, prolong life, or both, in these individuals. Diuretics induce sodium and water excretion, leading to decreased cardiac preload and wall tension, and an effective decrease of symptomatic pulmonary and systemic congestion. They have not yet been shown to prolong life in patients with CHF, however. Direct vasodilators, which induce venodilation, arterial dilation, or both (balanced vasodilators), may improve symptoms, and some but not all prolong life. Venodilators, such as nitrates, exert a venous pooling effect, decreasing cardiac preload and symptoms of congestion. Arterial dilators, such as hydralazine, decrease afterload and improve cardiac output. The combination of hydralazine and isosorbide dinitrate provides balanced vasodilation. It also improves survival, but is associated with a relatively high frequency of side effects necessitating discontinuation of one or both agents. The drugs are not approved by the Food and Drug Administration for the treatment of heart failure. Flosequinan, a new orally administered, long‐acting, balanced arteriovenous dilator, improves exercise tolerance and symptoms. However, preliminary analysis of data from a large, multicenter trial revealed increased mortality and hospitalization for worsening CHF. The drug has recently been withdrawn from the market. The ACE inhibitors can cause hemodynamic and neurohormonal changes that lead to a reduction of preload and afterload, decreasing symptoms of heart failure. They significantly decrease CHF mortality, and might also deter the development of overt heart failure in some asymptomatic patients with left ventricular dysfunct

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02755.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Despite recent evidence that angiotensin‐converting enzyme (ACE) inhibitors reduce mortality in patients with congestive heart failure (CHF), it is important to note that roughly 40% of patients with New York Heart Association class I—III disease treated with these agents died during 4‐year follow‐up in the treatment arm of two large trials. Given this high mortality rate, there is an obvious need for therapy beyond digoxin, diuretics, and ACE inhibitors. Digoxin is associated with favorable effects on exercise capacity, ejection fraction, and clinical symptomatology in the majority of patients with CHF. Its effects on mortality are unknown, but are the subject of a continuing trial sponsored by the National Institutes of Health. The β‐agonists are also associated with hemodynamic and clinical improvements in patients with CHF, but probably increase the risk of mortality, especially when taken on a long‐term basis. Therefore, their use should be limited to the short‐term management of acute exacerbations of CHF. Phosphodiesterase inhibitors, particularly milrinone, are associated with increased mortality in patients with CHF, apparently related to their arrhythmogenic effect. Little evidence exists that calcium channel blockers exert beneficial effects in patients with CHF (unlike their role in hypertrophic cardiomyopathy); indeed, first‐generation calcium channel blockers may be detrimental in patients with left ventricular dysfunction and they should generally be avoided in this setting. Treatment of ischemia in patients with CHF should be initiated with nitrates; low dosages of vasoselective dihydropyridine calcium channel blockers may be attempted

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02756.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Clinical research in the therapeutics of chronic congestive heart failure (CHF) has evolved from simple case reports and general‐response studies in the 1960s to large, randomized, controlled trials conducted in the late 1980s and 1990s. Cumulatively, the investigations show that angiotensin‐converting enzyme (ACE) inhibitors improve clinical status, exercise capacity, and survival; digoxin augments exercise capacity and, probably, clinical status, with unknown effects on survival; the vasodilator combination hydralazine‐nitrate improves survival, and perhaps clinical status and exercise capacity; and the new vasodilator flosequinan has a favorable effect on clinical status and exercise capacity, but is associated with an increased risk of mortality at 100 mg/day (this agent has subsequently been withdrawn voluntarily by the manufacturer from clinical use). Advances in study design and methodology, combined with the outcomes of major clinical trials, have resulted in new challenges in the investigation of CHF in humans. To date, only the ACE inhibitors have been shown to affect all of the major CHF therapeutic end points in a positive manner. Is it reasonable to expect similar results from all future drug interventions? If not, which end points should be targeted? Must the survival end point be investigated for all CHF drugs under development? Can studies be performed ethically without background ACE inhibitor therapy? Have the optimum duration and methods for therapeutic trials in humans been determined? Should controlled trials of nonhemodynamic and nonneurohormonal interventions (e.g., anticoagulation, magnesium, exercise regimens) be performed? How can the results of clinical trials best be applied in treating the broad range of patients encountered in practice? Despite our increasing sophistication in trial design and methodology, the challenges presented are not fully met by the currently available appro

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02757.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY