Diastolic chamber properties of the left ventricle assessed by global fitting of pressure-volume data: improving the gold standard of diastolic function

Abstract

.-In cardiovascular research, relaxation and stiffness are calculated from pressurevolume (PV) curves by separately fitting the data during the isovolumic and end-diastolic phases (end-diastolic PV relationship), respectively. This method is limited because it assumes uncoupled active and passive properties during these phases, it penalizes statistical power, and it cannot account for elastic restoring forces. We aimed to improve this analysis by implementing a method based on global optimization of all PV diastolic data. In 1,000 Monte Carlo experiments, the optimization algorithm recovered entered parameters of diastolic properties below and above the equilibrium volume (intraclass correlation coefficients ϭ 0.99). Inotropic modulation experiments in 26 pigs modified passive pressure generated by restoring forces due to changes in the operative and/or equilibrium volumes. Volume overload and coronary microembolization caused incomplete relaxation at end diastole (active pressure Ͼ 0.5 mmHg), rendering the end-diastolic PV relationship method ill-posed. In 28 patients undergoing PV cardiac catheterization, the new algorithm reduced the confidence intervals of stiffness parameters by one-fifth. The Jacobian matrix allowed visualizing the contribution of each property to instantaneous diastolic pressure on a per-patient basis. The algorithm allowed estimating stiffness from single-beat PV data (derivative of left ventricular pressure with respect to volume at end-diastolic volume intraclass correlation coefficient ϭ 0.65, error ϭ 0.07 Ϯ 0.24 mmHg/ml). Thus, in clinical and preclinical research, global optimization algorithms provide the most complete, accurate, and reproducible assessment of global left ventricular diastolic chamber properties from PV data. Using global optimization, we were able to fully uncouple relaxation and passive PV curves for the first time in the intact heart. diastolic function; hemodynamics; relaxation; diastolic stiffness; mechanical properties; left ventricle; pressure; diastole DIASTOLIC DYSFUNCTION is present to some degree in virtually all structural myocardial diseases, and, independent of its primary cause, this condition per se has become a major source of cardiovascular morbidity and mortality (23). Although the physiology of diastole has been a key field of preclinical research for decades, all treatments aimed to improve clinical outcome on the basis of modifying diastolic properties have been unsuccessful (8). Diastolic dysfunction is a generic term designating diverse abnormalities of left ventricular (LV) mechanical chamber properties, which all share a final stage of elevated left atrial pressure, pulmonary congestion, and heart failure. To improve therapeutic strategies, it is recognized that developing independent, unbiased, and robust indexes of each intrinsic diastolic property is mandatory (16).At the full-organ integration level, the analysis of LV pressure-volume (PV) data obtained during acute load manipulation is the current gold standard method for assessing di...

An integrative translational approach to study heart failure with preserved ejection fraction: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology

“…Nonetheless, serial evaluations and telemetry are feasible. Time‐honoured approaches have relied on a separate assessment of active relaxation and passive end‐diastolic stiffness but newer methods, based on global optimization fitting, may be of added value . Methodological aspects of open‐chest and closed‐chest approaches have been extensively reviewed .…”

Two-Layer Elastographic 3-D Traction Force Microscopy

“…To solve the overdetermined problem, we followed a least-squares approach using an iterative Levenberg-Marquardt algorithm that minimized a global cost function to calculate σ . This iterative algorithm is similar to those employed in our previous studies303132 and is summarized in Fig. 1b.…”

Influence of Activation Time on Hemodynamic Parameters: a Simulation Study

“…5(c) that have similar properties to the reported human PV loop [30][31][32]. To evaluate E max from PV loops, it was necessary to obtain values of p lv (t ES ) and V lv (t ES ) from at least 2 PV loops.…”