Mechano-electrical feedback during Cardiac Resynchronization Therapy?

Cardiac Resynchronization Therapy (CRT) has emerged as an important therapy to improve pump function in heart failure patients with left bundle branch block (LBBB). Using a multi-scale modeling approach, we investigated the effect of mechano-electrical feedback (MEF) during LBBB and CRT on cardiac function and dispersion of repolarization. Our model describes cellular electrophysiology and calcium handling as well as cardiac mechanics and hemodynamics. Ventricular electromechanics is represented by a single cardiac fiber, while physiological pressure-volume loops are obtained by simulating the systemic circulation. LBBB was simulated by activating the fiber at one end and CRT by simultaneous activation at both ends. Systolic function improved with onset of CRT, but diastolic function only improved after MEF. We conclude that MEF during LBBB may lead to an increase in dispersion of repolarization during onset of CRT, which may lead to impaired diastolic function and to ventricular arrhythmia.