Therapy of CHF: choices and controversies (Proceedings)


Therapy of CHF: choices and controversies (Proceedings)

Nov 01, 2010

Congestive heart failure (CHF) is not a primary disease; rather it is the manifestation of the failing heart that arises from neurohumoral compensation. The primary problems that underlie CHF can be diverse, but commonly involve myxomatous mitral valve disease (MMVD) or dilated cardiomyopathy (DCM) in dogs and hypertrophic cardiomyopathy in cats. Despite the diversity of the underlying problems, the body's repertoire of compensatory responses is largely lacking in plasticity. Therefore, the spectrum of signs that are seen in CHF are generally similar, irrespective of the origin of cardiac disease, with circulatory congestion and the resulting edema being the cardinal sign of CHF. The first step in the formation of edema in CHF is a decrease in cardiac output (CO) as a result of the primary cardiac condition. This drop in CO may initially be quite mild and can be quickly normalized by the compensatory mechanisms. Initially, as CO falls, the resulting drop in blood pressure rapidly stimulates the adrenergic system, causing increased inotropy and arterial vasoconstriction. Stimulation of the adrenergic system can rapidly normalize a mild drop in CO. Meanwhile, renal arterial vasoconstriction decreases glomerular filtration rate (GFR) and stimulates renin release, with resulting activation of the renin-angiotensin-aldosterone system (RAAS). Angiotensin II further contributes to vasoconstriction, whereas aldosterone and the fall in GFR increase the tubular reabsorption of sodium and water, increasing preload. The increased preload will further augment CO and a new equilibrium will be reached and temporarily maintained. This increase in preload will increase cardiac output by improving ventricular force in accordance with Starling's law of the heart. However, the increase in afterload will actually decrease cardiac output: . As the underlying cardiac abnormality worsens, falling CO and compensation also continue, until the resulting increase in preload overwhelms the ability of increased filling pressures in the ventricle to generate commensurately greater force according to Starling's law. The equation for CO given above will no longer strictly apply, as this equation operates within physiological constraints. In particular, increases in heart rate and preload will not indefinitely increase CO.

It is at this point that the exuberance of the compensatory mechanisms of the heart are operating to the detriment of the patient. The high preload contributes to both low plasma oncotic pressures and to high plasma hydrostatic pressures, such that the oncotic forces in the blood are insufficient to offset the hydrostatic pressures, resulting in leakage of fluid from the capillaries. As the neurohumoral pathways that promote and support CHF are generally similar between different etiologies of heart failure, symptomatic drug therapy for CHF also tends to be similar. Nevertheless, specific diseases do require that additional therapy be tailored to particular structural deficits. Therapy of CHF is generally palliative, as the underlying cause of most cardiac disease is beyond reach. As in other chronic, untreatable diseases, quality of life and financial issues will generally dictate the selection and duration of therapy. Symptomatic therapy to reduce edema is indicated. However, more direct pharmacological support for the failing heart, such as the use of positive inotropes, may also allow some amelioration of the primary problem, in the form of augmentation of cardiac function. Most cardiac drugs work on some factor or factors in the simplistic equation given above, with contractility, preload, and afterload being most amenable to treatment.

Preload can be rapidly reduced by the use of diuretics and nitrodilators. Nitroglycerin and nitroprusside are nitrodilators that act by stimulating the release of nitric oxide, which in turn relaxes vascular smooth muscle via the secondary messenger cGMP. Venodilation is predominant at low doses, but arterial vasodilation will also occur as the dose increases. Nitroglycerin appears to more specifically produce venodilation, and thus preload reduction, than does nitroprusside. As nitroprusside is administered intravenously, has a short duration of action, and can cause marked hypotension, it is used in the acute care setting. Nitroglycerin is usually administered as a topical gel in veterinary medicine, and tolerance rapidly develops, unlike in the case of nitroprusside. The most efficacious diuretics are the loop diuretics, furosemide and torsemide. Torsemide may be safer than furosemide, which is more likely to cause hypokalemia.1 The addition of a second mechanistic class of diuretic agent, such as a thiazide diuretic like chlorothiazide, will increase the diuretic effect. As these diuretic agents can result in hypokalemia, a potassium-sparing diuretic agent, such as spironolactone, may also be administered in combination with the more powerful diuretics. In addition to its potassium-sparing effects, spironolactone may have additional beneficial effects that result in reduced cardiac mortality in dogs with CHF.2