Early detection of left ventricular failure in right ventricular congenital heart diseases

Abstract

BackgroundEarly detection of left ventricular (LV) failure is crucial to improve prognosis of patients with right ventricular (RV) overload. ObjectivesWe aim to assess whether LV function is precociously affected in 2 surgical porcine models of moderate (Fallot repaired) and severe RV dysfunction (progressive pulmonary hypertension HP) at in vivo and in vitro levels. MethodsThree animals of each surgical group were compared with 6 controls/Sham. 4 months after surgeries, LV function was evaluated using echocardiography/strain compared with conductance catheter. At cellular level using isolated cardiomyocytes, calcium transients amplitude with relaxation time associated and sarcomere shortening were recorded using Ionoptix system. T-tubules network integrity (DI-4-ANEPPS) and colocalization (Immunofluorescence) between main Excitation/Contraction (EC) actors (Ca2+v1.2-Ryr) were analyzed. Contractile reserve was evaluated by adrenergic stimulation in-vivo and in-vitro (Dobutamine-isoproterenol). ResultsDespite RV dysfunctions in both groups, LV present hemodynamic impairment only in HP group (Longitudinal strain 9 versus 18%. Conductance catether with dobutamin: Elastance arterial 7.7 versus 1.32, SV 14 versus 75ml and tau (relaxation) 49 versus 27, P<0.05). In cardiomyocytes, we observe decrease of Ca2+ transient amplitude and cardiomyocytes contraction, acceleration of Ca2+ relaxation time, T-tubule network desorganisation and Cav1.2/Ryr decoupling (Fig. 1).In vivo and in vitro, adrenergic stimulations increase dysfunction. ConclusionIn vitro experiments pointed early abnormalities in LV EC particularly after adrenergic stimulation. A better understanding of cellular alterations could lead to survival improvement.