LV twisting and untwisting in HCM: Ejection begets filling

Abstract

Conventional and emerging concepts on mechanisms by which hypertrophic cardiomyopathy (HCM) engenders diastolic dysfunction are surveyed. A shift from familiar left ventricular (LV) diastolic function approaches to large-scale (twist-untwist) and small-scale (titin unfoldingrefolding, etc.) wall rebound models, incorporating interaction and dynamic distortions and rearrangements of myofiber sheets and ultrastructural constituents, is suggested. Such an emerging new paradigm of diastolic dynamics, emphasizing the relationship of myofiber sheet and ultraconstituent distortion to LV mechanics and end-systolic shape, might clarify intricate patterns of early diastolic rebound and suction, needed for LV filling in many of the polymorphic phenotypes of HCM.Janus was a Roman deity with 2 faces (Janus bifrons), looking backward and forward simultaneously just as gates look in both directions (Figure 1). He too watched entrances and exits, and his shrines were located at crossing places or intersections. The left ventricle as Janus bifronsThe pumping left ventricle forms the intersection or central link (Figure 1) between the lowpressure and the high-pressure systems of the circulatory ensemble. 1 It is a suctioncompression positive-displacement pump, exhibiting both self-regulating properties as an independent organ and dependent properties as part of the overall circulation. In diastole, it adapts to the low-pressure system from which it draws blood, whereas, in systole, it adjusts to the high-pressure system into which it must force blood. For that reason, it needs to alternate between the widely disparate functional-structural requirements of systole and diastole. 1 Since like Janus it can look directly backward and forward, into the low-and high-pressure systems, it displays remarkable Janus-like characteristics. Hence, it subserves at times incongruous functions, such as when excessive wall hypertrophy in response to a systolic pressure overload is associated with diminished diastolic distending wall stress levels and, not uncommonly, with increased muscle stiffness, both of which may then be responsible for impaired left ventricular (LV) diastolic filling. [2][3][4] Almost all forms of heart disease and most strikingly hypertrophic cardiomyopathy (HCM) alter ventricular structure. The changes in

Left ventricular torsion, energetics, and diastolic function in normal human aging

“…TSR has been shown to increase with aging, and this relative subendocardial dysfunction has been postulated to be due to subendocardial fibrosis (19). Subendocardial dysfunction should logically lead to a proportionate reduction in longitudinal shortening, due to the subendocardial fiber direction, as shown in hypertrophic cardiomyopathy (26): our data show a consistent trend for reduced longitudinal shortening with increasing age to accompany the rise in TSR (Table 2), although this does not reach statistical significance with this number of subjects.…”

Calcific Aortic Valve Disease: Part 1—Molecular Pathogenetic Aspects, Hemodynamics, and Adaptive Feedbacks

“…In the diagnostic evaluation of the patient with CAVD/AVS, examination of all four cardiac valves and checking for other lesions that might be mistaken for aortic valvular disease are important; e.g., other diagnostic possibilities might include a subaortic membrane, mitral regurgitation, ventricular septal defect, and hypertrophic cardiomyopathy [13, 41, 54, 62, 74, 79, 83, 87]. A thorough examination encompasses exclusion/confirmation of each differential diagnosis, as well as the appraisal of the aortic valve itself.…”

“…Moreover, endurance exercise training may delay age related deterioration of LV longitudinal function [52]. These echocardiographic findings distinguish pathological from physiological hypertrophy (see Section on Contrasting Physiological and Pathological Cardiac Hypertrophy in the companion Part 2 of this Article); however, studies on the effects of endurance training on rotational mechanics (LV torsion, or twisting and untwisting [53, 54]) have shown conflicting results. 2-Dimensional (2D) and 3D Doppler velocimetry are suitable means both for gauging the severity of AVS by measuring orifice jet velocity and pressure gradients—a mean gradient ≥ 30 mm Hg usually represents clinically significant aortic stenosis—and for estimating the aortic valve area by applying the continuity equation [13, 45, 55–61].…”

Mechanotransduction Mechanisms for Intraventricular Diastolic Vortex Forces and Myocardial Deformations: Part 2

“…Elastin is a highly cross-linked polymer that organizes as fibers or sheets in the ECM. It provides the ventricles with remarkable mechanical properties; most notably, with elastic recoil allowing their myocardial wall laminae to twist under systolic contractile stresses – like torsion-springs under a torque, or twisting force – and then to rebound to their previous state in early diastole, reinforcing rapid filling, especially during hyperdynamic circumstances [47,48]. The elasticity of elastic fibers arises from their hydrophobic regions [49], which are stretched out by tensile forces – such as are exerted by the diastolic vortex – and spontaneously reaggregate when the force is released.…”

“…Advances in nanotechnology for cytomechanical investigations nowadays allow direct measurement of forces at cellular, subcellular, and macromolecular scales [48]. The mechanical microenvironment of the myocardial cells that are being subjected to the cyclic (quasi-periodic) diastolic vortical forces is specified by way of forces transmitted across cell-to-cell junctions and through myocardial cell attachments to the ECM.…”