Rick Schreurs

40 Chapter 3 drop across the cardiac valves is related to flow velocity through the valve and valve area (Bernoulli’s principle). In addition, inertial effects due to blood mass on acceleration and deceleration are implemented in the valve module. Previously, simulations of mechanical and hemodynamic interventricular and atrio-ventricular interactions have been validated and applied under physiological and pathophysiological conditions [17–19]. Reference simulations of prolonged PR with normal contractility Similar to the animal experiments, a reference CircAdapt simulation was created in which AV-delay was prolonged. Starting from a simulation representing the normal adult human heart, all ventricular segments were delayed by 300ms relative to right atrial activation. In agreement with a prolonged pacing-induced atrial activation observed in the pigs (P width: 123±5ms), mean left atrial activation was delayed by 30ms relative to mean right atrial activation. Global contractility was decreased by 20% to incorporate the reduced contractile reserve due to anaesthetics. Atrial pacing rate was set to 100bpm, equal to the mean value in pigs (100±2bpm). Circulating blood volume and peripheral vascular resistance of the systemic circulation were adjusted to maintain a cardiac output of 5.1L/min and mean arterial pressure of 92mmHg in the reference simulations. The resulting values of circulating blood volume and peripheral vascular resistance were maintained during the AV-delay optimization protocol. Hemodynamic measurements of all other simulations were compared to the reference simulation. Reference simulations of prolonged PR with heart failure Starting from the reference simulation of prolonged PR with normal contractility, ventricular myocardial contractility was reduced to 50% of its normal value. Next, heart rate was decreased to 80bpm to match the heart rate in patients. Circulating blood volume and peripheral vascular resistance of the systemic circulation were adjusted to maintain a cardiac output of 4.2 L/min and mean arterial pressure of 92mmHg. As a result of these changes, LVEF was reduced to 34% in the heart failure reference simulation of prolonged PR. Sensitivity of hemodynamic effect by restoring AV-coupling in CircAdapt Similar to the animal experiment, AV-delay was decreased from 300ms to 50ms in CircAdapt simulations. Step size was set to 25ms, resulting in 10 shortened AV-delays. First, ventricular activation and atrial pacing rate were kept constant to isolate the hemodynamic effect of improving AV-coupling. Simulated hemodynamic changes induced by AV-delay shortening were compared to the measured values in animal experiments. To isolate the effect of pacing-induced ventricular dyssynchrony on hemodynamic function, simulations with dyssynchronous ventricular activation were performed. Starting from the reference heart failure simulation with prolonged PR-interval (300ms) and synchronous ventricular activation, ventricular dyssynchrony was induced concurrently with AV-delay shortening. In total, two subsets of simulations were performed with increased ventricular