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

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Abstract
BACKGROUND: The time constant of isovolumic relaxation (tau) 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 tau. 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 tau was calculated from these hemodynamic data (tau 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; tau 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 tau: 1) adding actual LA V wave pressure (to yield tau LA); 2) adding 10 mm Hg (tau 10); and 3) no adjustment at all (actual VA gradient used to calculate tau 0). The agreement between tau H and the three Doppler estimates of tau was assessed by linear regression and by the mean and standard deviation of the error between the measurements (delta tau). the measurements (delta tau). tau H ranged from 29 to 135 msec. Without correction for LA pressure, the Doppler estimate of tau seriously underestimated tau H: tau 0 = 0.30 tau H + 9.4, r = 0.79, delta tau = -35 +/- 18 msec. This error was almost completely eliminated by adding actual LA pressure to the VA pressure gradient: tau LA = 0.92 tau H + 7.6, r = 0.95, delta tau = 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: tau 10 = 0.89 tau H + 4.9, r = 0.88, delta tau = -2 +/- 12 msec. In general, tau 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 tau 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 tau. Because mitral regurgitation is very common in cardiac patients, this method may allow more routine assessment of tau 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.