Noninvasive measurement of the time constant of left ventricular relaxation using the continuous-wave doppler velocity profile of mitral regurgitation

Background. The time constant of isovolumic relaxation (τ) is an important parameter of ventricular diastolic function, but the need for invasive measurement with high-fidelity catheters has limited its use in general clinical cardiology. The Doppler mitral regurgitant velocity spectrum can be used to estimate left ventricular (LV) pressure throughout systole and may provide a new noninvasive method for estimating τ. Methods and Results. Mitral regurgitation was produced in nine dogs, and ventricular relaxation was adjusted pharmacologically and with hypothermia. High-fidelity ventricular pressures were recorded, and τ was calculated from these hemodynamic data (τ_H) assuming a zero-pressure asymptote. Continuous-wave mitral regurgitant velocity profiles were obtained, and the ventriculo-atrial (VA) pressure gradient was calculated by the simplified Bernoulli equation; τ was calculated from the Doppler data from the time of maximal negative dP/dt until LV-LA pressure crossover. Three methods were used to correct the Doppler VA gradient to better approximate the LV pressure before calculating τ: 1) adding actual LA V wave pressure (to yield τ_LA); 2) adding 10 mm Hg (τ₁₀); and 3) no adjustment at all (actual VA gradient used to calculate τ₀). The agreement between τ_H and the three Doppler estimates of τ was assessed by linear regression and by the mean and standard deviation of the error between the measurements (Δτ). τ_H ranged from 29 to 135 msec. Without correction for LA pressure, the Doppler estimate of τ seriously underestimated τ_H: τ₀=0.30τ_H+9.4, r=0.79, Δτ=-35±18 msec. This error was almost completely eliminated by adding actual LA pressure to the VA pressure gradient: τ_LA=0.927τ_H+7.6, r=0.95, Δτ=2±7 msec. Addition of a fixed LA pressure estimate of 10 mm Hg to the VA gradient yielded an estimate that was almost as good: τ₁₀=0.89τ_H+4.9, τ=0.88, Δτ=-2±12 msec. In general, τ was overestimated when actual LA pressure was below this assumed value, and vice versa. Numerical analysis demonstrated that assuming LA pressure to be 10 mm Hg should yield estimates of τ accurate to ±15% between true LA pressures of 5 and 20 mm Hg. Conclusions. This study demonstrates that the Doppler mitral regurgitant velocity profile can be used to provide a direct and noninvasive measurement of τ. Because mitral regurgitation is very common in cardiac patients, this method may allow more routine assessment of τ in clinical and research settings, leading to a better understanding of the role of impaired ventricular relaxation in diastolic dysfunction and the effect of therapeutic interventions.