Pathophysiology of heart failure

Cardiac dysfunction precipitates changes in vascular function, blood volume, and neurohormonal status. These changes serve as compensatory mechanisms to help maintain cardiac output and arterial blood pressure. However, these compensatory changes over months and years can worsen cardiac function. Overall, the changes in cardiac function associated with heart failure (HF) 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. 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 (MI). 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 dysfunctions 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 this chapter, we discuss the various types of cardiac insults and morbidities/conditions that can cause myocardial damage (directly or indirectly) in humans, thereby precipitating chronic systolic HF. Particular focus is given to the pathophysiological mechanisms by which they initiate or aggravate the development of clinical HF.