0181: Mechanisms of ventricular dysfunction and dyssynchrony in repaired tetralogy of Fallot: an animal study

BackgroundTetralogy of Fallot (TOF) is associated with increasingly recognized late morbidity due to arrhythmias and right heart failure. Better understanding of the underlying mechanisms of these issues is needed to facilitate new therapeutic approaches. We aim to identify mechanisms generating arrhythmias in a swine model of repaired TOF with progressive right ventricular (RV) dysfunction.MethodsSurgery to mimic repaired TOF was done in 24 piglets (using a previously validated model); 24 animals served as control. Two, 4 and 6 months after surgery respectively, animals were sacrified for subsequent analysis. Haemodynamic parameters and ventricular remodeling were analyzed by cardiac magnetic resonance (CMR) and echocardiography before sacrifice. In isolated perfused hearts, electrical activity was measured by optical mapping. Sarcoplasmic reticular calcium handling and proteins involved in calcium management were studied in single myocytes.ResultsCompared with control animals, a right bundle branch block was present and the action potential (AP) duration was increased in the RV with a mechanical delay observed at 2 and 4 months post-operative in operated groups (p