Pathophysiology of Heart Failure
The pathophysiology of heart failure involves changes in :
Cardiac dysfunction precipitates changes in vascular function, blood volume, and neurohumoral status. These changes serve as compensatory mechanisms to help maintain cardiac output (primarily by the Frank-Starling mechanism) and arterial blood pressure (by systemic vasoconstriction). However, these compensatory changes over months and years can worsen cardiac function. Therefore, some of the most effective treatments for chronic heart failure involve modulating non-cardiac factors such as arterial and venous pressures by administering vasodilator and diuretic drugs.
Cardiac and Vascular Changes
Accompanying Heart Failure
- Decreased stroke volume & cardiac output
- Increased end-diastolic pressure
- Ventricular dilation or hypertrophy
- Impaired filling (diastolic dysfunction)
- Reduced ejection fraction (systolic dysfunction)
- Increased systemic vascular resistance
- Decresed aterial pressure
- Impaired arterial pressure
- Impaired organ perfusion
- Decreased venous compliance
- Increased venous pressure
- Increased blood volume
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), which can be caused by 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. Reduced filling of the ventricle results in less ejection of blood. 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 anatomically, which helps to normalize the preload pressures by accomodating the increase in filled volume.
Therapeutic interventions to improve cardiac function in heart failure include the use of cardiostimulatory drugs (e.g., beta-agonists and digitalis) that stimulate heart rate and contractility, and vasodilator drugs that reduce ventricular afterload and thereby enhance stroke volume.
Compensatory Mechanisms During
- Frank-Starling mechanism
- Chronic ventricular dilation or hypertrophy
- Increased sympathetic adrenergic activity
- Reduced vagal activity to heart
- Renin-angiotensin-aldosterone system
- Vasopressin (antidiuretic hormone)
- Circulating catecholamines
- Natriuretic peptides
Neurohumoral responses occur during heart failure. These 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 to increase ventricular filling. 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 therapeutic intervention.
Some drug treatments for heart failure involve attenuating the neurohumoral changes. For example, certain beta-blockers have been shown to provide significant long-term benefit, quite likely because they block the effects of excessive sympathetic activation on the heart. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists are commonly used to treat heart failure by inhibiting the actions of the renin-angiotensin-aldosterone system.
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, especially in acute heart failure. Humoral activation, particularly the renin-angiotensin system and antidiuretic hormone (vasopressin) also contribute to systemic vasoconstriction.
Heightened sympathetic activity, and increased circulating angiotensin II and increased vasopressin contribute to an increase in systemic vascular resistance. Drugs that block some of these mechanisms, such angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, improve ventricular stroke volume by reducing afterload on the ventricle. Vasodilator drugs such as hydralazine and sodium nitroprusside are also used to reduce afterload on the ventricle and thereby enhance cardiac output.
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.