P4684Differential right ventricular adaptation patterns to chronic pressure overload

Abstract Background Right ventricular (RV) dysfunction is the most important prognostic factor in chronic pulmonary hypertension (PH), but its underlying mechanisms are unknown. Clinical observation and prior experimental work suggest that RV pressure overload is not the only cause since the degree of RV adaptation varies with similar RV end-systolic pressures. Purpose Our aim was to characterize serial RV adaptation by cardiac magnetic resonance (CMR) in 3 different experimental large-animal models of increased afterload: a model of chronic postcapillary PH, a model of PH secondary to systemic-to-pulmonary shunt and a model of mechanical RV pressure overload (generated by pulmonary artery [PA] banding). Methods Four-week old piglets underwent pulmonary vein banding surgery to generate the chronic postcapillary PH model (n=20), aorto-pulmonary shunt (n=6), PA banding (n=7) or sham operation (n=7). They were followed up monthly with CMR and right heart catheterization (RHC). All procedures followed the “Principles of laboratory animal care”. Comparison of continuous variables among groups was performed with Mann-Whitney U test. Results Animals with either postcapillary PH or PH secondary to aorto-pulmonary shunt presented significant RV dilatation, hypertrophy and dysfunction that was maintained during follow-up (median RV end-systolic volume [RVESV]=32.6 ml/m2 for postcapillary PH and 32.6 ml/m2 for shunt vs. 16.1 ml/m2 in sham controls; median RV ejection fraction [RVEF]=61.5% for postcapillary PH and 60.5% for shunt vs. 69.6% in sham controls at the end of follow-up). Animals with PA banding also presented with significant RV dilatation and hypertrophy at the first month follow-up, but unlike all other groups, they developed reverse RV remodeling from the second month onwards and maintained normal RV volumes and RVEF values until the end of follow-up despite having severe RV hypertrophy (RV mass 22.6 g/m2 in PA banding vs. 16.1 g/m2 in controls at the 4th month follow-up; Figure). CMR parameters (median values). Conclusion In PH there is a maladaptive RV hypertrophy that is not present in a model of progressive RV pressure overload without alterations of the pulmonary circulation. Increased RV pressure overload alone does not fully explain PH-associated RV dysfunction. Further research is needed to clarify the underlying mechanisms of adaptive and maladaptive hypertrophy in PH. Acknowledgement/Funding The CNIC is supported by the Ministerio de Ciencia, Innovaciόn y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence