What global diastolic function is, what it is not, and how to measure it

Abstract

Leonardo da Vinci's observation (circa 1511) that "the atria or filling chambers contract together while the pumping chambers or ventricles are relaxing and vice versa," the dynamics of four-chamber heart function, and of diastolic function (DF) in particular, are not generally appreciated. We view DF from a global perspective, while characterizing it in terms of causality and clinical relevance. Our models derive from the insight that global DF is ultimately a result of forces generated by elastic recoil, modulated by cross-bridge relaxation, and load. The interaction between recoil and relaxation results in physical wall motion that generates pressure gradients that drive fluid flow, while epicardial wall motion is constrained by the pericardial sac. Traditional DF indexes (, E/E=, etc.) are not derived from causal mechanisms and are interpreted as approximating either stiffness or relaxation, but not both, thereby limiting the accuracy of DF quantification. Our derived kinematic models of isovolumic relaxation and suction-initiated filling are extensively validated, quantify the balance between stiffness and relaxation, and provide novel mechanistic physiological insight. For example, causality-based modeling provides load-independent indexes of DF and reveals that both stiffness and relaxation modify traditional DF indexes. The method has revealed that the in vivo left ventricular equilibrium volume occurs at diastasis, predicted novel relationships between filling and wall motion, and quantified causal relationships between ventricular and atrial function. In summary, by using governing physiological principles as a guide, we define what global DF is, what it is not, and how to measure it. diastolic function; echocardiography; hemodynamics; mathematical modeling; suction pump LEFT VENTRICULAR (LV) DIASTOLIC dysfunction is typically reported and indexed as either an increase in myocardial stiffness or a slowing of relaxation (i.e., cross-bridge dissociation). In actuality, diastolic function (DF) is the result of the continuous interaction between the restoring force of elastic recoil and the opposing force generated by cross bridges that have yet to uncouple from the previous systole. The restoring forces seek to lengthen the muscle, while the cross-bridge forces previously acted to shorten the muscle. The simultaneous action of these two opposing forces during both isovolumic relaxation (IVR) and filling result in wall motion, constrained by pericardial sac volume, and simultaneous generation of pressure gradients. This review discusses the governing physical laws and the constraints of DF, as well as which indexes of DF are consistent with diastolic physiology. Deriving and evaluating indexes of DF using this conceptual framework both clarifies and advances our understanding of DF and diastolic dysfunction in health and disease. Physiology of DiastoleCardiovascular physiology is taught using the Wiggers diagram, which segments the cardiac cycle into systole and diastole ( Fig. 1) (49, 124). Systole begins...

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