CHF: What works and what doesn't? (Proceedings)
Congestive heart failure (CHF) is not a primary disease; rather it is the clinical manifestation of the failing heart and describes a syndrome characterized by complex interactions of the heart with neurohumoral compensatory responses. 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 cardiac 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. During this initial phase, falling CO results in a decrease in blood pressure, which rapidly stimulates the adrenergic system. Sympathetic stimulation can rapidly normalize a mild drop in CO via increased inotropy and heart rate; however, in order to preserve blood flow to the heart and brain, arterial vasoconstriction also occurs. 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 initially 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 produce a proportionate increase CO.
It is at this point that the exuberance of the compensatory mechanisms of the heart is 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 aid particular structural deficits. Therapy of CHF is generally palliative, as the underlying cause of most cardiac disease cannot be addressed. 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 pharmacological manipulation.