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Computer models of cardiac electro-mechanics (EM) show promise as an effective means for the quantitative analysis of clinical data and, potentially, for predicting therapeutic responses. To realize such advanced applications methodological key challenges must be addressed. Enhanced computational efficiency and robustness is crucial to facilitate, within tractable time frames, model personalization, the simulation of prolonged observation periods under a broad range of conditions, and physiological completeness encompassing therapy-relevant mechanisms is needed to endow models with predictive capabilities beyond the mere replication of observations. Here, we introduce a universal feature-complete cardiac EM modeling framework that builds on a flexible method for coupling a 3D model of bi-ventricular EM to the physiologically comprehensive 0D CircAdapt model representing atrial mechanics and closed-loop circulation. A detailed mathematical description is given and efficiency, robustness, and accuracy of numerical scheme and solver implementation are evaluated. After parameterization and stabilization of the coupled 3D–0D model to a limit cycle under baseline conditions, the model's ability to replicate physiological behaviors is demonstrated, by simulating the transient response to alterations in loading conditions and contractility, as induced by experimental protocols used for assessing systolic and diastolic ventricular properties. Mechanistic completeness and computational efficiency of this novel model render advanced applications geared towards predicting acute outcomes of EM therapies feasible. [Display omitted] • Physiologically comprehensive 3D–0D closed loop model of heart and circulation. • Major advance in computational efficiency, facilitating model personalization. • Flexible coupling scheme for mixing 3D and 0D representations of cardiac chambers. • Proven physiological predictive power under a broad range of experimental protocols. • Key technology for enabling electro-mechanical modeling to predict therapy responses. • First simulations of transient electro-mechanical responses between limit cycles. [ABSTRACT FROM AUTHOR]

To examine how end systole differs from end ejection and also whether the slope of the end systolic pressure-volume relation can be approximated to that of the end ejection pressure-volume relation, nine isolated, perfused, paced canine hearts ejecting into a hydraulic loading system that simulated the aortic input impedance of a dog's arterial tree were studied. To measure left ventricular volume changes the heart was placed in a plethysmograph. Peripheral resistance (Rp) and arterial compliance (C) were independently varied from 1.9 (Rp=1.9) to 3.3, 6.4, and 9.6 × 108 Pa·m−3·s (Rp run) with a constant value of compliance 1.3 × 10−9 Pa−1·m3 (C=1.3), and from C=0.4 to C=0.8, C=1.3 and C=2.3 (C run) with a constant value of resistance (Rp=6.4). Five pressure-volume loops were obtained by changing the end diastolic volume at each value of compliance and peripheral resistance. It was clearly shown that ventricular ejection continued after end systole and the time duration between end systole and end ejection became longer with increasing arterial compliance (24(4) at C=0.4 vs 49(4) ms at C=2.3, p<0.001), while the time duration between end diastole and end systole was constant regardless of afterload impedance change. Regarding the left ventricular pressure-volume relation the end systolic relation was almost linear (r≥0.98) and the slope was not significantly affected by change in any afterload impedance tested. End ejection pressure-volume relation was also linear (r≥0.97) and the slopes in the peripheral resistance and compliance runs were lower than those of the end systolic pressure-volume relation in each corresponding run. The former slopes decreased at smaller values of Rp or larger values of C — namely, 4.4(0.6) at Rp=9.6 vs 3.6(0.6) at Rp=1.9, p<0.05; 4.8(0.6) at C=0.4 vs 3.1(0.5) mm·Hg·ml−1 at C=2.3, p<0.001. Thus it is concluded that end ejection is usually different from end systole and the time difference between them is affected by changes in arterial compliance. In addition, the slope of end ejection pressure-volume relation was dependent on the changes in afterload impedance and cannot be approximated to that of the end systolic pressure-volume relation. [ABSTRACT FROM PUBLISHER]