The isovolumic relaxation to early rapid filling relation: Kinematic model based prediction with in vivo validation

Abstract

Although catheterization is the gold standard, Doppler echocardiography is the preferred diastolic function (DF) characterization method. The physiology of diastole requires continuity of left ventricular pressure (LVP)-generating forces before and after mitral valve opening (MVO). Correlations between isovolumic relaxation (IVR) indexes such as tau (time-constant of IVR) and noninvasive, Doppler E-wave-derived metrics, such as peak A-V gradient or deceleration time (DT), have been established. However, what has been missing is the model-predicted causal link that connects isovolumic relaxation (IVR) to suction-initiated filling (E-wave). The physiology requires that model-predicted terminal force of IVR (Ft IVR) and model-predicted initial force of early rapid filling (Fi E-wave) after MVO be correlated. For validation, simultaneous (conductance catheter) P-V and E-wave data from 20 subjects (mean age 57 years, 13 men) having normal LV ejection fraction (LVEF>50%) and a physiologic range of LV end-diastolic pressure (LVEDP) were analyzed. For each cardiac cycle, the previously validated kinematic (Chung) model for isovolumic pressure decay and the Parametrized Diastolic Filling (PDF) kinematic model for the subsequent E-wave provided Ft IVR and Fi E-wave respectively. For all 20 subjects (15 beats/subject, 308 beats), linear regression yielded Ft IVR = α Fi E-wave + b (R = 0.80), where α = 1.62 and b = 1.32. We conclude that model-based analysis of IVR and of the E-wave elucidates DF mechanisms common to both. The observed in vivo relationship provides novel insight into diastole itself and the model-based causal mechanistic relationship that couples IVR to early rapid filling.