The Left and Right Ventricles Respond Differently to Variation of Pacing Delays in Cardiac Resynchronization Therapy: A Combined Experimental- Computational Approach

Abstract

Introduction: Timing of atrial, right (RV), and left ventricular (LV) stimulation in cardiac resynchronization therapy (CRT) is known to affect electrical activation and pump function of the LV. In this study, we used computer simulations, with input from animal experiments, to investigate the effect of varying pacing delays on both LV and RV electrical dyssynchrony and contractile function.Methods: A pacing protocol was performed in dogs with atrioventricular block (N = 6), using 100 different combinations of atrial (A)-LV and A-RV pacing delays. Regional LV and RV electrical activation times were measured using 112 electrodes and LV and RV pressures were measured with catheter-tip micromanometers. Contractile response to a pacing delay was defined as relative change of the maximum rate of LV and RV pressure rise (dP/dtmax) compared to RV pacing with an A-RV delay of 125 ms. The pacing protocol was simulated in the CircAdapt model of cardiovascular system dynamics, using the experimentally acquired electrical mapping data as input.Results: Ventricular electrical activation changed with changes in the amount of LV or RV pre-excitation. The resulting changes in dP/dtmax differed markedly between the LV and RV. Pacing the LV 10–50 ms before the RV led to the largest increases in LV dP/dtmax. In contrast, RV dP/dtmax was highest with RV pre-excitation and decreased up to 33% with LV pre-excitation. These opposite patterns of changes in RV and LV dP/dtmax were reproduced by the simulations. The simulations extended these observations by showing that changes in steady-state biventricular cardiac output differed from changes in both LV and RV dP/dtmax. The model allowed to explain the discrepant changes in dP/dtmax and cardiac output by coupling between atria and ventricles as well as between the ventricles.Conclusion: The LV and the RV respond in a opposite manner to variation in the amount of LV or RV pre-excitation. Computer simulations capture LV and RV behavior during pacing delay variation and may be used in the design of new CRT optimization studies.

Aortic acceleration as a noninvasive index of left ventricular contractility in the mouse

“…The end systolic pressure–volume relationship is considered as the “gold standard” index of left ventricular contractility but the maximal rate of change of left ventricular pressure (+ dP/dt max or P′) is considered as a reasonable alternative index of contractility 27 . This index has been used in humans 2 , 28 – 30 large animals 7 , 8 , 31 , 32 and more recently in small animals such as mice 16 , 18 , 19 , 21 , 22 , 24 , 33 . While humans and large animals survive the invasive measurement of left ventricular pressure, in mice this measurement is made acutely and the study is terminal, making longitudinal/serial studies of cardiac contractility/performance impossible.…”

“…It is derived from the high-fidelity pressure signal measured invasively, using an intravascular pressure catheter. The invasive technique is frequently used in patients 1 , 2 and in large animal research 3 , 4 . While complications are infrequent, repeated invasive pressure measurements are avoided in patients 5 .…”

Prevention of non-response to cardiac resynchronization therapy: points to remember

“…Regardless of the place where the left ventricular electrodes are implanted, the ultimate goal is to maximize left ventricular output volume. A new study shows computer simulations capture LV and RV behavior during pacing delay variation and may be used in the design of new CRT optimization studies [30].…”

Right ventricular phenotype, function, and failure: a journey from evolution to clinics

“…The mechanisms of RV failure, its detection and follow-up, and more specifically the different responses of the RV to pressure versus volume overload are still incompletely understood. Despite many apparent similarities between the LV and RV, there are significant differences on a morphological, physiological, and molecular level, evidenced by different responses of the ventricles to current HF therapies [6,[16][17][18][19][20][21][22]. Notably, RV failure is not an entity on itself but rather a continuum of clinical symptoms related to increased severities of disease states [3,6,17] and associated with significant morbidity and mortality both in patients with HF with reduced [23,24] and preserved [25,26] ejection fraction (HFpEF).…”