Congestive heart failure--pathophysiology and medical treatment.
Although the etiology of congestive heart failure is complex, a disturbance of myocardial function due to ischemic heart disease or various forms of cardiomyopathy is by far the leading causative factor. In the early stages of failure various cardiac compensating mechanisms, such as hypertrophy, an increase in contractility and the Frank-Starling mechanism, prevent a major reduction in function. With ongoing failure, myocardial muscle function further deteriorates because of a disturbance in myocardial energy utilization, abnormalities in sympathetic neurotransmitter metabolism, a reduction in beta-receptor density, and, more importantly, a derangement of intracellular calcium transport. The subsequent reduction in cardiac output leads to activation of peripheral neurohumoral mechanisms, including sympathetic stimulation, an increase in circulating norepinephrine, stimulation of the renin-angiotensin-aldosterone system (RAAS), and increased arginine vasopressin production, which result in arterial and venous vasoconstriction, redistribution of tissue blood flow, and an increase in circulating blood volume. The adjustments, however, lead to a vicious circle, where heart function is further depressed by the increase in afterload, whereas the changes in the venous bed and the increase in circulating volume ultimately result in congestion. At this point, digitalis and diuretics alone are no longer sufficiently effective and vasodilators are indicated, possibly combined, in the later stages of failure, with positive inotropic drugs. The angiotensin converting-enzyme inhibiting agents seem particularly useful in this context, presumably because of their complex mode of action, interfering with the neurohumoral systems and peripheral vasculature at multiple sites. Particularly with these agents, a remarkable improvement in clinical condition and exercise capacity has been observed. Even so, the long-term prognosis in patients with severe congestive heart failure is still extremely poor with one-year mortality rates in New York Heart Association class III and IV patients ranging from 34% to 48%. In this article, the pathophysiology of congestive heart failure and the potential of drug therapy are further discussed.
W J
WJ
Remme
D001341:Autonomic Nervous System / Q000503:physiopathology; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000627:therapeutic use; D004070:Digitalis; D004232:Diuretics / Q000627:therapeutic use; D004734:Energy Metabolism; D006321:Heart / Q000294:innervation / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D009566:Nitrates / Q000494:pharmacology / Q000627:therapeutic use; D010946:Plants, Medicinal; D010947:Plants, Toxic; D012964:Sodium / Q000378:metabolism; D013566:Sympathomimetics / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000627:therapeutic use
D002316:Cardiotonic Agents; D004232:Diuretics; D009566:Nitrates; D013566:Sympathomimetics; D014665:Vasodilator Agents; D012964:Sodium; D002118:Calcium