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Abstract

Congestive heart failure may result from cardiovascular overload, from systolic or from diastolic dysfunction. Diastolic left ventricular dysfunction may result from structural resistance to filling such as induced by pericardial constraint, right ventricular compression, increased chamber stiffness (hypertrophy) and increased myocardial stiffness (fibrosis). A distinct and functional etiology of diastolic dysfunction is slow and incomplete myocardial relaxation. Relaxation may be slowed by pathological processes such as hypertrophy, ischemia and by asynchronous left ventricular function. The present contribution analyses the occurrence of slow and incomplete myocardial relaxation in response to changes in systolic pressure and in response to changes in venous return. The regulation of myocardial relaxation by load is critically dependent on the transition from myocardial contraction to relaxation, which occurs in dogs when 82% of peak isovolumetric pressure has developed or at a relative load of 0.82. This corresponds to early ejection in normal hearts, but is situated even before aortic valve opening in severely diseased hearts. When load is developed beyond this transition, relaxation becomes slow and even incomplete. This is load dependent diastolic dysfunction. Load dependent diastolic dysfunction occurs in normal hearts facing heavy afterload and in severely diseased hearts even with normal hemodynamic parameters. This dysfunction should contribute to elevating filling pressures in most patients with severe congestive heart failure. This dysfunction can be reverted by decreasing systolic pressures or by decreasing venous return. Load dependent diastolic dysfunction gives us an additional reason to aggressively treat CHF patients with diuretics and vasodilators.

Late Systolic Myocardial Loading Is Associated With Left Atrial Dysfunction in Hypertension

“…This may be because of intrinsic differences in cellular processes between early and late ejection. Loading during active cross-bridge formation (early systolic load) increases the number of interacting cross-bridges (cooperative activity), 27 a physiologic mechanism that allows adequate matching of the number of cross-bridges with systolic load. However, when increased load occurs after the onset of myocardial relaxation, the number of interacting cross-bridges can no longer adapt, which results in a mismatch between the number of cross-bridges and load, and an increased stress imposed on individual cross-bridges.…”

“…However, when increased load occurs after the onset of myocardial relaxation, the number of interacting cross-bridges can no longer adapt, which results in a mismatch between the number of cross-bridges and load, and an increased stress imposed on individual cross-bridges. 27 Of note, the timing of transition from myocardial fiber contraction to relaxation differs from the timing of transition from ventricular systole to diastole, normally occurs early during the ejection phase, 27–29 and is related to the descending limb of the myocyte cytoplasmic calcium transient. 27,28 In addition to the acute effect of late systolic load on diastolic function demonstrated in various studies, late systolic load has been shown to induce more LV remodeling and fibrosis than early systolic load.…”

“…27 Of note, the timing of transition from myocardial fiber contraction to relaxation differs from the timing of transition from ventricular systole to diastole, normally occurs early during the ejection phase, 27–29 and is related to the descending limb of the myocyte cytoplasmic calcium transient. 27,28 In addition to the acute effect of late systolic load on diastolic function demonstrated in various studies, late systolic load has been shown to induce more LV remodeling and fibrosis than early systolic load. 30 LV fibrosis may increase diastolic passive stiffness of the LV, imposing excessive load on the atrial myocardium, ultimately contributing to LA dysfunction.…”

Heart failure with preserved ejection fraction

“…Increases in load thus produce greater increases in blood pressure, which can accentuate impairment in relaxation and diastolic stiffness and predispose to flash pulmonary edema [43, 115]. Decreases in load due to overdiuresis or vasodilators result in exaggerated decreases in blood pressure and limit the improvement in stroke volume with afterload reduction, which figures so prominently into therapeutic strategies in HFrEF (Fig.…”

Pulsatile Load Components, Resistive Load and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis (MESA)

“…In contrast, loads imposed late in systole do not lead to increased cross-bridges, instead increasing the load on each individual cross-bridge. This could lead to an earlier onset, but slowed rate, of relaxation(41,42) and potentially, the activation of unfavorable signaling pathways that promote maladaptive hypertrophy. Further work is needed to understand the molecular mechanisms by which late systolic load may impact myocardial remodeling and failure.…”