Ventricular Systolic Dysfunction

Systolic dysfunction refers to impaired ventricular contraction (loss of inotropy). In chronic heart failure, this is most likely results from changes in the signal transduction mechanisms regulating cardiac excitation-contraction coupling. Losing cardiac inotropy (i.e., decreased contractility) causes a downward shift in the Frank-Starling curve (red curve in figure). This results in a decrease in stroke volume and a compensatory increase in preload (often measured as ventricular end-diastolic pressure or pulmonary capillary wedge pressure) because of incomplete ventricular emptying, which leads to an increase in ventricular end-diastolic volume and pressure. Therefore, there is a downward/rightward shift in the operating point on the Frank-Starling curve (point A to B). The increase in preload is a compensatory response that activates the Frank-Starling mechanism to help maintain stroke volume despite the loss of inotropy. If preload did not increase, the decline in stroke volume would be even greater for a given loss of inotropy. With systolic dysfunction, there is also an increase in blood volume that contributes to increased ventricular filling and end-diastolic volume and pressure. Ventricular remodeling occurs in chronic failure, leading to anatomic dilation of the ventricle.

The effects of an acute loss of intrinsic inotropy on stroke volume and end-diastolic and end-systolic volumes are best depicted using ventricular pressure-volume loops (see figure). Loss of intrinsic inotropy decreases the slope of the end-systolic pressure-volume relationship (ESPVR). This leads to an increase in end-systolic volume (red loop). There is also an increase in end-diastolic volume (compensatory increase in preload), but this increase is not as great as the increase in end-systolic volume. Therefore, the net effect is a decrease in stroke volume (shown as decreased width of the pressure-volume loop). Because stroke volume decreases and end-diastolic volume increases, there is a substantial reduction in ejection fraction (EF). In the figure, EF decreases from 58 to 31%. Stroke work (area within the loop) is also decreased. Heart failure caused by systolic dysfunction is commonly referred to as heart failure with reduced ejection fraction (HFrEF). Note that with acute systolic dysfunction, there is no change in the end-diastolic pressure-volume relationship (EDPVR). In contrast, with chronic systolic dysfunction, the EDPVR relationship would shift downward and to the right as the ventricle responds by remodeling (anatomic dilation), which increases the venticular compliance.

The force-velocity relationship provides insight into why a loss of contractility reduces stroke volume (see figure). Briefly, at a given preload and afterload, a loss of inotropy results in a decrease in the shortening velocity of cardiac fibers. Because there is only a finite period of time available for ejection, reduced ejection velocity results in less blood ejected per stroke. The residual volume of blood within the ventricle (end-systolic volume) is increased, as shown previously, because less blood is ejected.

The reason preload increases as inotropy declines acutely is that the increased end-systolic volume is added to the venous return filling the ventricle. For example, if end-systolic volume is normally 50 ml of blood and it is increased to 80 ml in failure, this extra residual volume added to the incoming venous return leads to an increase in end-diastolic volume and pressure.

An important and deleterious consequence of systolic dysfunction is the increase in end-diastolic pressure. If the left ventricle is involved, then left atrial and pulmonary venous pressures also rise. This can lead to pulmonary congestion and edema. If the right ventricle is in systolic failure, the increase in end-diastolic pressure will be reflected backwards into the right atrium and systemic venous vasculature. This can lead to peripheral edema and ascites.

Treatment for systolic dysfunction involves the use of inotropic drugs, afterload reducing drugs, venous dilators, and diuretics. Inotropic drugs include digoxin and drugs that stimulate the heart via beta-adrenoceptor activation or inhibition of cAMP-dependent phosphodiesterase. Afterload reducing drugs (e.g., arterial vasodilators) augment ventricular ejection by increasing the velocity of fiber shortening (see force-velocity relationship). Venous dilators and diuretics are used to reduce ventricular preload and venous pressures (pulmonary and systemic) rather than augmenting systolic function directly.

Revised 01/29/2023