Pathophysiology of heart failure

Pathophysiology of Heart failure

Overall, the changes in cardiac function associated with heart failure result in a decrease in cardiac output. This results from a decline in stroke volume that is due to systolic dysfunction, diastolic dysfunction, or a combination of the two. Briefly, systolic dysfunction results from a loss of intrinsic inotropy (contractility), most likely due to alterations in signal transduction mechanisms responsible for regulating inotropy. Systolic dysfunction can also result from the loss of viable, contracting muscle as occurs following acute myocardial infarction. Diastolic dysfunction refers to the diastolic properties of the ventricle and occurs when the ventricle becomes less compliant (i.e., "stiffer"), which impairs ventricular filling. Both systolic and diastolic dysfunction result in a higher ventricular end-diastolic pressure, which serves as a compensatory mechanism by utilizing the Frank-Starling mechanism to augment stroke volume. In some types of heart failure (e.g., dilated cardiomyopathy), the ventricle dilates as preload pressures increase in order to to recruit the Frank-Starling mechanism in an attempt to maintain normal stroke volumes.

Neurohumoral responses include activation of sympathetic nerves and the renin-angiotensin system, and increased release of antidiuretic hormone (vasopressin) and atrial natriuretic peptide. The net effect of these neurohumoral responses is to produce arterial vasoconstriction (to help maintain arterial pressure), venous constriction (to increase venous pressure), and increased blood volume. In general, these neurohumoral responses can be viewed as compensatory mechanisms, but they can also aggravate heart failure by increasing ventricular afterload (which depresses stroke volume) and increasing preload to the point where pulmonary or systemic congestion and edema occur. Therefore, it is important to understand the pathophysiology of heart failure because it serves as the rationale for drug therapy.


In order to compensate for reduced cardiac output during heart failure, feedback mechanisms within the body try to maintain normal arterial pressure by constricting arterial resistance vessels through activation of the sympathetic adrenergic nervous system, thereby increasing systemic vascular resistance. Veins are also constricted to elevate venous pressure. Arterial baroreceptors are important components of this feedback system. Humoral activation, particularly the renin-angiotensin system and antidiuretic hormone (vasopressin) also contribute to systemic vasoconstriction.


In heart failure, there is a compensatory increase in blood volume that serves to increase ventricular preload and thereby enhance stroke volume by the Frank-Starling mechanism. Blood volume is augmented by a number of factors. Reduced renal perfusion results in decreased urine output and retention of fluid. Furthermore, a combination of reduced renal perfusion and sympathetic activation of the kidneys stimulates the release of renin, thereby activating the renin-angiotensin system. This, in turn, enhances aldosterone secretion. There is also an increase in circulating arginine vasopressin (antidiuretic hormone) that contributes to renal retention of water. The final outcome of humoral activation is an increase in renal reabsorption of sodium and water. The resultant increase in blood volume helps to maintain cardiac output; however, the increased volume can be deleterious because it raises venous pressures, which can lead to pulmonary and systemic edema. When edema occurs in the lungs, this can result in exertional dyspnea (shortness of breath during exertion). Therefore, most patients in heart failure are treated with diuretic drugs to reduce blood volume and venous pressures in order to reduce edema.