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Quantification of Global Diastolic Function by Kinematic Modeling-based Analysis of Transmitral Flow via the Parametrized Diastolic Filling Formalism

Quantitative cardiac function assessment remains a challenge for physiologists and clinicians.&#160;Although historically invasive methods have comprised ...

Washington University in St. Louis

Pressure-volume (P-V) loop-based analysis facilitates thermodynamic assessment of left ventricular function in terms of work and energy. Typically these quantities are calculated for a cardiac cycle using the entire P-V loop, although thermodynamic analysis may be applied to a selected phase of the cardiac cycle, specifically, diastole. Diastolic function is routinely quantified by analysis of transmitral Doppler E-wave contours. The first law of thermodynamics requires that energy (ε) computed from the Doppler E-wave (εE-wave) and the same portion of the P-V loop (εP-V E-wave) be equivalent. These energies have not been previously derived nor have their predicted equivalence been experimentally validated. To test the hypothesis that εP-V E-wave and εE-wave are equivalent, we used a validated kinematic model of filling to derive εE-wave in terms of chamber stiffness, relaxation/viscoelasticity, and load. For validation, simultaneous (conductance catheter) P-V and echocadiographic data from 12 subjects (205 total cardiac cycles) having a range of diastolic function were analyzed. For each E-wave, εE-wave was compared with εP-V E-wave calculated from simultaneous P-V data. Linear regression yielded the following: εP-V E-wave=αεE-wave+b (R2=0.67), where α=0.95 and b=6e(-5). We conclude that E-wave-derived energy for suction-initiated early rapid filling εE-wave, quantitated via kinematic modeling, is equivalent to invasive P-V-defined filling energy. Hence, the thermodynamics of diastole via εE-wave generate a novel mechanism-based index of diastolic function suitable for in vivo phenotypic characterization.

The thermodynamics of diastole: kinematic modeling-based derivation of the P-V loop to transmitral flow energy relation 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).

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

Abstract Although catheterization is the gold standard, Doppler echocardiography is the preferred diastolic function (DF) characterization method. The physiology of diastole requires continuity of left ventricular pressure (LVP)-generating forces before and after mitral valve opening (MVO). Correlations between isovolumic relaxation (IVR) indexes such as tau (time-constant of IVR) and noninvasive, Doppler E-wave-derived metrics, such as peak A-V gradient or deceleration time (DT), have been established. However, what has been missing is the model-predicted causal link that connects isovolumic relaxation (IVR) to suction-initiated filling (E-wave). The physiology requires that model-predicted terminal force of IVR (Ft IVR) and model-predicted initial force of early rapid filling (Fi E-wave) after MVO be correlated. For validation, simultaneous (conductance catheter) P-V and E-wave data from 20 subjects (mean age 57 years, 13 men) having normal LV ejection fraction (LVEF>50%) and a physiologic range of LV end-diastolic pressure (LVEDP) were analyzed. For each cardiac cycle, the previously validated kinematic (Chung) model for isovolumic pressure decay and the Parametrized Diastolic Filling (PDF) kinematic model for the subsequent E-wave provided Ft IVR and Fi E-wave respectively. For all 20 subjects (15 beats/subject, 308 beats), linear regression yielded Ft IVR = α Fi E-wave + b (R = 0.80), where α = 1.62 and b = 1.32. We conclude that model-based analysis of IVR and of the E-wave elucidates DF mechanisms common to both. The observed in vivo relationship provides novel insight into diastole itself and the model-based causal mechanistic relationship that couples IVR to early rapid filling.

The isovolumic relaxation to early rapid filling relation: kinematic model based prediction with in vivo validation.

Pseudonormal Doppler E-wave filling patterns indicate diastolic dysfunction but are indistinguishable from the normal filling pattern. For accurate classification, maneuvers to alter load or to additionally measure peak E' are required. E-wave deceleration time (DT) has been fractionated into its stiffness (DTs) and relaxation (DTr) components (DT=DTs+DTr) by analyzing E-waves via the parametrized diastolic filling formalism. The method has been validated with DTs and DTr correlating with simultaneous catheterization-derived stiffness (dP/dV) and relaxation (τ) with r=0.82 and r=0.94, respectively. We hypothesize that DT fractionation can (1) distinguish between unblinded (E' known) normal versus pseudonormal age-matched groups with normal left ventricular ejection fraction, and (2) distinguish between blinded (E' unknown) normal versus pseudonormal groups, based solely on E-wave analysis.

Sina Mossahebi

Department of Physics,
Cardiovascular Biophysics Lab

Washington University in St. Louis

Quantification of Global Diastolic Function by Kinematic Modeling-based Analysis of Transmitral Flow via the Parametrized Diastolic Filling Formalism

Sina Mossahebi

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Physics,Cardiovascular Biophysics Lab

Washington University in St. Louis

Quantification of Global Diastolic Function by Kinematic Modeling-based Analysis of Transmitral Flow via the Parametrized Diastolic Filling Formalism

Department of Physics,
Cardiovascular Biophysics Lab