The Pharmacologic Treatment of Heart Failure cont.
- Page 1: Causes of Heart Failure
- THIS PAGE: Pathophysiology of Heart Failure
- Page 3: Rationale for Drug Therapy
- Page 4: Classes of Drugs Used to Treat Heart Failure
Pathophysiology of Heart Failure
Cardiac and Vascular Changes
Acccompanying Heart Failure
- Decreased stroke volume and cardiac output
- Increased end-diastolic pressure
- Increased systemic vascular resistance
- Decreased arterial pressure
- Decreased venous compliance
- Increased venous pressure
- Increased blood volume
The following is a brief summary of changes in cardiac and systemic vascular function that occur during heart failure. More details can be found by CLICKING HERE.
Overall, heart failure causes 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. Global 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. This occurs anatomically when there is ventricular hypertrophy, and it can be caused by impaired relaxation of the ventricle. To summarize, systolic dysfunction is related to impaired contractile properties whereas diastolic dysfunction is related to the inability of the ventricle to fill because of decreased compliance.
Both systolic and diastolic dysfunction result in a higher ventricular end-diastolic pressure (increased filling pressure). This serves as a compensatory mechanism by augmenting the force of contraction and therefore stroke volume by the Frank-Starling mechanism. This mechanism helps to maintain stroke volume; however, if the systolic or diastolic dysfunction becomes too severe, then the capacity of this mechanism to maintain stroke becomes exhausted and stroke volume can decline significantly. In some types of heart failure (e.g., dilated cardiomyopathy), the ventricle can dilate to very large volumes through remodeling as it attempts to maintain stroke volume and to limit the increase in end-diastolic pressure.
The reduction in cardiac output associated with heart failure precipitates changes in systemic and pulmonary vascular function, and renal function. These changes occur as the result of venous pooling of blood, reduced organ perfusion, and activation of neurohumoral compensatory mechanisms. Reduced ventricular stroke volume leads to venous pooling of blood, which elevates venous blood volume and pressure. For example, in left ventricular failure, left atrial and pulmonary venous pressures and volumes increase. This pulmonary congestion can lead to pulmonary edema and shortness of breath (dyspnea). Right ventricular failure, whether alone or as a consequence of left ventricular failure, causes blood volume to increase in the systemic venous circulation leading to elevated venous pressures and systemic edema. Reduced perfusion of the kidneys decreases sodium and water excretion, which in turn causes blood volume to increase. This further increases venous pressures (and edema); however, the increased blood volume serves as an important compensatory mechanism to increase cardiac preload which helps to maintain stroke volume through the Frank-Starling mechanism.
Neurohumoral activation is very important compensatory mechanism because it helps to maintain arterial pressure. Neurohumoral responses include activation of sympathetic adrenergic nerves and the renin-angiotensin-aldosterone 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 (increased venous pressure), cardiac stimulation, and increased blood volume. Although these neurohumoral responses serve as important compensatory mechanisms, 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. Some of these mechanisms, such as sympathetic activation and increased angiotensin II, stimulate cardiac remodeling that may be beneficial in the short-term, but harmful in the long-term.