Interplay of Electrical Wavefronts as Determinant of the Response to Cardiac Resynchronization Therapy in Dyssynchronous Canine Hearts

BACKGROUND—The relative contribution of electromechanical synchronization and ventricular filling to the optimal hemodynamic effect in cardiac resynchronization therapy (CRT) during adjustment of stimulation-timings is incompletely understood. We investigated whether optimal hemodynamic effect in CRT requires collision of pacing-induced and intrinsic activation waves and optimal filling of the left ventricle (LV). METHODS AND RESULTS—CRT was performed in dogs with chronic left bundle–branch block (n=8) or atrioventricular (AV) block (n=6) through atrial (A), right ventricular (RV) apex, and LV-basolateral pacing. A 100 randomized combinations of A-LV/A-RV intervals were tested. Total activation time (TAT) was calculated from >100 contact mapping electrodes. Mechanical interventricular dyssynchrony was determined as the time delay between upslopes of LV and RV pressure curves. Settings providing an increase in LVdP/dtmax (maximal rate of rise of left ventricular pressure) of ≥90% of the maximum LVdP/dtmax value were defined as optimal (CRTopt). Filling was assessed by changes in LV end-diastolic volume (EDV; conductance catheter technique). In all hearts, CRTopt was observed during multiple settings, providing an average LVdP/dtmax increase of ≈15%. In AV-block hearts, CRTopt exclusively depended on interventricular-interval and not on AV-interval. In left bundle–branch block hearts, CRTopt occurred at A-LV intervals that allowed fusion of LV-pacing–derived activation with right bundle–derived activation. In all animals, CRTopt occurred at settings resulting in the largest decrease in TAT and mechanical interventricular dyssynchrony, whereas LV EDV hardly changed. CONCLUSIONS—In left bundle–branch block and AV-block hearts, optimal hemodynamic effect of CRT depends on optimal interplay between pacing-induced and intrinsic activation waves and the corresponding mechanical resynchronization rather than filling.