Ventricular Diastolic Dysfunction
Ventricular function is highly dependent upon preload as demonstrated by the Frank-Starling relationship. Therefore, if ventricular filling (preload) is impaired, this will lead to a decrease in stroke volume. The term "diastolic dysfunction" refers to changes in ventricular diastolic properties that have an adverse effect on ventricular filling and stroke volume. About 50% of heart failure patients have diastolic dysfunction, with or without normal systolic function as determined by normal ejection fractions.
Ventricular filling (i.e., end-diastolic volume and hence sarcomere length) depends on the venous return and compliance of the ventricle during diastole. A reduction in ventricular compliance, as occurs in ventricular hypertrophy, increases the slope of the ventricular end-diastolic pressure-volume relationship (EDPVR) and results in less ventricular filling (decreased end-diastolic volume) and a greater end-diastolic pressure (elevated pulmonary capillary wedge pressures) as shown in the figure (red loop). Stroke volume, indicated by the width of the pressure-volume loop, decreases. Depending on the relative change in stroke volume and end-diastolic volume, there may or may not be a small decrease in ejection fraction. The EF of the control loop in the figure is 58% compared to 54% in red loop representing diastolic dysfunction. Heart failure caused by diastolic dysfunction is commonly refered to as heart failure with preserved ejection fraction (HFpEF). Because stroke volume is decreased, there will also be a decrease in ventricular stroke work.
A second mechanism that is non-anatomical, can also contribute to diastolic dysfunction: impaired ventricular relaxation (reduced lusitropy). Near the end of the cycle of excitation-contraction coupling in the myocyte, the sarcoplasmic reticulum actively sequesters Ca++ so that the concentration of Ca++ in the vicinity of troponin-C is reduced allowing the Ca++ to leave its binding sites on the troponin-C and thereby permit disengagement of actin from myosin. This is a necessary step to achieve rapid and complete relaxation of the myocyte. If this mechanism is impaired (e.g., by reduced rate of Ca++ uptake by the sarcoplasmic reticulum), or by other mechanisms that contribute to myocyte relaxation, then the rate and perhaps the extent of relaxation are decreased. This will reduce the rate of ventricular filling, particularly during the phase of rapid filling.
An important and deleterious consequence of diastolic dysfunction is the rise in end-diastolic pressure. If the left ventricle is involved, then left atrial and pulmonary venous pressures will also rise. This can lead to pulmonary congestion and edema. If the right ventricle is in diastolic failure, the increase in end-diastolic pressure will be reflected back into the right atrium and systemic venous vessels. This can lead to peripheral edema and ascites. The rise in venous pressures also occur because of an increase in blood volume due to activation of the renin-angiotensin-aldosterone system, which causes renal retention of sodium and water.