Kinematic modeling-based left ventricular diastatic (passive) chamber stiffness determination with in-vivo validation

The slope of the diastatic pressure-volume relationship (D-PVR) defines passive left ventricular (LV) stiffness κ. Although κ is a relative measure, cardiac catheterization, which is an absolute measurement method, is used to obtain the former. Echocardiography, including transmitral flow velocity (Doppler E-wave) analysis, is the preferred quantitative diastolic function (DF) assessment method. However, E-wave analysis can provide only relative, rather than absolute pressure information. We hypothesized that physiologic mechanism-based modeling of E-waves allows derivation of the D-PVR(E-wave) whose slope, κ(E-wave), provides E-wave-derived diastatic, passive chamber stiffness. Our kinematic model of filling and Bernoulli's equation were used to derive expressions for diastatic pressure and volume on a beat-by-beat basis, thereby generating D-PVR(E-wave), and κ(E-wave). For validation, simultaneous (conductance catheter) P-V and echocardiographic E-wave data from 30 subjects (444 total cardiac cycles) having normal LV ejection fraction (LVEF) were analyzed. For each subject (15 beats average) model-predicted κ(E-wave) was compared to experimentally measured κ(CATH) via linear regression yielding as follows: κ(E-wave) = ακ(CATH) + b (R(2) = 0.92), where, α = 0.995 and b = 0.02. We conclude that echocardiographically determined diastatic passive chamber stiffness, κ(E-wave), provides an excellent estimate of simultaneous, gold standard (P-V)-defined diastatic stiffness, κ(CATH). Hence, in chambers at diastasis, passive LV stiffness can be accurately determined by means of suitable analysis of Doppler E-waves (transmitral flow).