Frequency-based analysis of the early rapid filling pressure-flow relation elucidates diastolic efficiency mechanisms

Stiffness- and relaxation-based diastolic function (DF) assessment can characterize the presence, severity, and mechanism of dysfunction. Although frequency-based characterization of arterial function is routine (input impedance, characteristic impedance, arterial wave reflection), DF assessment via frequency-based methods incorporating optimization/ efficiency criteria is lacking. By definition, optimal filling maximizes (E wave) volume and minimizes "loss" at constant stored elastic strain energy (which initiates mechanical, recoil-driven filling). In thermodynamic terms, optimal filling delivers all oscillatory power (rate of work) at the lowest harmonic. To assess early rapid filling optimization, simultaneous micromanometric left ventricular pressure and echocardiographic transmitral flow (Doppler E wave) were Fourier analyzed in 31 subjects. A validated kinematic filling model provided closed-form expressions for E wave contours and model parameters. Relaxation-based DF impairment is indicated by prolonged E wave deceleration time (DT). Optimization was assessed via regression between the dimensionless ratio of 2nd (Q2) and 3rd flow harmonics (Q3) to the lowest harmonic (Q1), i.e., (Q2/Q1) or (Q3/Q1) vs. DT or c, the filling model's viscosity/damping (energy loss) parameter. Results show that DT prolongation or increased c generated increased oscillatory power at higher harmonics (Q2/Q1 = 0.00091DT + 0.09837, r = 0.70; Q3/Q1 = 0.00053DT = 0.02747, r = 0.60; Q2/Q1 = 0.00614c + 0.15527, r = 0.91; Q3/Q1 = 0.00396c + 0.05373, r = 0.87). Because ideal filling is achieved when all oscillatory power is delivered at the lowest harmonic, the observed increase in power at higher harmonics is a measure of filling inefficiency. We conclude that frequency-based analysis facilitates assessment of filling efficiency and elucidates the mechanism by which diastolic dysfunction associated with prolonged DT impairs optimal filling.