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1 Cardiovascular Biophysics Laboratory, Washington University in St. Louis, St. Louis, Missouri, United States
* To whom correspondence should be addressed. E-mail: sjk{at}wuphys.wustl.edu.
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 using frequency-based methods incorporating optimization/efficiency criteria are lacking. By definition, optimal filling maximizes (E-wave) volume, 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 (LVP) 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 (Q3) flow harmonics 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.
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