quantification-global-diastolic-function-kinematic-modeling-based

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

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