Kinematic Modeling-based Left Ventricular Diastatic (Passive) Chamber Stiffness Determination with In-Vivo Validation

Abstract

The slope of the diastatic pressure–volume relationship (D-PVR) defines passive left ventricular (LV) stiffness $\mathcal{K}.$ Although $\mathcal{K}$ 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, $\mathcal{K}_{{\text{E-}}{\text{wave}}}$, 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 $\mathcal{K}_{{\text{E-}}{\text{wave}}}$. 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 $\mathcal{K}_{{\text{E-}}{\text{wave}}}$ was compared to experimentally measured $\mathcal{K}_{\text{CATH}}$ via linear regression yielding as follows: $\mathcal{K}_{{\text{E-}}{\text{wave}}} = \alpha {\mathcal{K}}_{\text{CATH}} + b\;(R^{2} = 0.92),$ where, α = 0.995 and b = 0.02. We conclude that echocardiographically determined diastatic passive chamber stiffness, $\mathcal{K}_{{\text{E-}}{\text{wave}}}$, provides an excellent estimate of simultaneous, gold standard (P–V)-defined diastatic stiffness, $\mathcal{K}_{\text{CATH}}$. Hence, in chambers at diastasis, passive LV stiffness can be accurately determined by means of suitable analysis of Doppler E-waves (transmitral flow).

Appendix 1

Simultaneous Acquisition of Echocardiographic and High Fidelity Hemodynamic Data

Before arterial access, in the catheterization laboratory, a full 2-D echo-Doppler study is performed by an ASE-certified sonographer in accordance with ASE criteria.29 After appropriate sterile skin prep and drape, local anesthesia (1% xylocaine) is given and percutaneous right or left femoral arterial access is obtained in preparation for catheterization and angiography, using a valved sheath (6-F, Arrow Inc, Reading, PA). After arterial access and placement of a 64-cm sheath (Arrow Inc, Reading, PA), a 6F micromanometer-tipped pigtail (triple pressure transducer) pressure–volume, conductance catheter (Model 560-1, 560-5, Millar Instruments, Houston, TX) is directed into the mid-LV in a retrograde fashion across the aortic valve under fluoroscopic guidance. Before insertion, the manometer-tipped catheter is calibrated against “zero” by submersion just below the surface of NS bath at 37 °C, and again after insertion relative to hydrostatic “zero” using the lumen with respect to the mid-thoracic fluid-filled transducer (HP). It is balanced using a transducer control unit (Model TC-510, Millar Instruments, Houston, TX), and pressures are fed to the catheterization laboratory amplifier (Quinton Diagnostics, Bothell, WA or GE Healthcare, Milwaukee, WI) and simultaneously into the input ports of the physiological amplifier of the Doppler imaging system for synchronization (Philips iE33). With the patient supine, apical 4-chamber views using a 2.5-MHz transducer are obtained by the sonographer, with the sample volume gated at 1.5–5 mm directed between the tips of the mitral valve leaflets and orthogonal to the MV plane. Continuous wave Doppler is used to record aortic outflow and mitral inflow from the apical view for determination of the lateral IVRT using a sweep speed of 10 cm/s. Doppler tissue imaging (DTI) of the medial and the lateral mitral annulus, and M-mode images are also recorded. To synchronize the hemodynamic data with the Doppler data a fiducial marker in the form of a square wave is fed from the catheter–transducer control unit. The LV and AO pressures, and LV volumes from the conductance catheter and one ECG channel are also simultaneously recorded on disk. Simultaneous Doppler data, LVP and conductance volume are obtained for a minimum of 30 consecutive beats during quiet respiration. After data acquisition, the diagnostic catheterization procedure is performed in the usual manner.