Therapy of new onset and refractory heart failure (Proceedings)
Diuretics (reduction in preload), vasodilators (reduction in preload or afterload), angiotensin converting-enzyme inhibitors (reduce afterload and preload, reduce fibrosis), and positive inotropic drugs (increase contractility, may reduce regurgitant volume) all have demonstrated the capacity to lessen the severity of mitral regurgitation and dilated cardiomyopathy under certain conditions. The relative merits of specific agents vary with the clinical circumstances of each patient. All therapeutic recommendations should be based on a complete cardiovascular evaluation to identify the specific requirements of each dog. The current standard of therapy for dogs with chronic congestive heart failure is combination therapy using diuretics, angiotensin converting enzyme inhibitors and positive inotropic agents. Dogs requiring medical therapy to control the signs of heart failure should avoid strenuous exercise although the potential benefits of sub-maximal exercise for cardiac rehabilitation are unknown. Increasingly severe exercise restriction should be enforced as the disease progresses. Some cardiologists promote low sodium diets although their benefits have not been proven by large, placebo-controlled studies to date. The prognosis varies with the stage of the disease and it is currently impossible to predict the rate of progression for an individual patient. Some factors that adversely affect the prognosis are:
Loop diuretics-furosemideLoop diuretics inhibit the Na/K/2Cl co-transporter in the ascending loop of Henle, causing obligatory loss of sodium and water into the urine. The oral absorption of furosemide is only 60 to 70% in healthy dogs and probably less in animals with heart failure. Furosemide is used to help control excessive plasma volume that ultimately contributes to the development of congestive heart failure while failing to augment cardiac contractility (plateau of the Frank-Starling curve). Diuretics are the most effective drugs available for the symptomatic short-term treatment of congestive heart failure in animals. They are administered to reduce blood volume and, thereby, to lower filling pressures and alleviate congestion and associated clinical signs. With judicious use of diuretics, indirect improvement in cardiac output may result from improved oxygenation as pulmonary function returns towards normal. Diuretics tend to decrease preload and can aggravate low cardiac output signs if used overzealously. Always use the lowest dose necessary to control signs.
Furosemide is approved for use in dogs, cats, and horses, and it has a very wide margin of safety. Rarely, it causes serious electrolyte imbalances. An occasional patient may develop hypokalemia, hyponatremia and hypochloremia (hypochloremic alkalosis), requiring temporary withdrawal of the drug or reduction in dosage. Excessive use can lead to dehydration, renal failure, low cardiac output, and circulatory collapse. These problems are most likely when high doses of furosemide are used with an angiotensin converting enzyme inhibitor, like enalapril. It appears that diuretics (all classes) activate systemic compensatory mechanisms, including the renin-angiotensin-aldosterone system and sympathetic nervous system. Thus, while these agents are the most effective drugs used in the short-term management of congestive heart failure, they have inherent limitations.
Angiotensin converting enzyme inhibitors: Enalapril, Benazepril
The angiotensin-converting enzyme inhibitors are the most important class of neurohormonal antagonists currently available for treating congestive heart failure. Inhibition of this strategic enzyme results in decreased formation of the circulating angiotensin II and a concomitant decline in blood aldosterone concentrations. By these mechanisms ACE inhibiting drugs are believed to palliate the deleterious consequences of vasoconstriction and sodium retention in patients with heart failure. Some of the anticipated hemodynamic changes resulting from ACE inhibition include decreased atrial and ventricular filling pressures, decreased peripheral vascular resistance, and increased cardiac output. Because ACE also inactivates bradykinin, tissue accumulation of this substance may contribute to the observed hemodynamic and cardiovascular effects of ACE inhibiting drugs. Bradykinin induces vasodilation directly and indirectly by increasing production of the prostaglandins, PGI2 and PGE2. Local or tissue renin-angiotensin systems have been demonstrated in a number of different organs, such as the kidney, brain, heart, blood vessels, and adrenal glands. These local renin-angiotensin systems are believed to regulate cellular growth. They may also play an important role in the development of the vascular changes and ventricular remodeling processes observed in patients with heart disease. Inhibition of ventricular remodeling might protect against the adverse consequences of myocardial fibrosis and the deterioration of left ventricular function, thereby offering an alternate explanation for increased survival in patients treated with ACE inhibitors.