Pacemaker-induced cardiomyopathy in the sheep: RVA but not RVOT pacing results in a heart failure cellular phenotype

Chronic RV apical pacing can have adverse effects on LV function and up to 10% ofpatients develop Pacemaker-induced Cardiomyopathy. The pathophysiology of thisis incompletely understood, although previous work has shown that alteredventricular activation patterns can cause abnormal calcium handling and apoptosis.The aim of this work was to determine whether physiological-rate RV apical pacingcould cause a cellular heart failure phenotype and if this could be prevented bypacing from the RV outflow tract (RVOT).Adult sheep were paced at physiological heart rates for 3 months from the RV apexor RVOT. Another group underwent rapid ventricular pacing to cause tachycardiainducedheart failure. Cardiomyocytes from the LV free wall were studied usingpatch clamp techniques and confocal microscopy.RV apical pacing caused a cellular phenotype similar to heart failure, withattenuation of the calcium transient, reduction of ICa-L and disruption of T-tubules.These features did not occur with RVOT pacing.Changes appeared prior to clinical or echocardiographic evidence of heart failureand may therefore represent the initial stages of Pacemaker-inducedCardiomyopathy.