Early markers of right ventricular involvement in experimental chronic postcapillary pulmonary hypertension

Abstract Background In chronic pulmonary hypertension (PH), the main cause of death is right ventricular (RV) failure. However, the onset of RV dysfunction varies significantly among patients. Early recognition of RV maladaptation would be highly relevant. Purpose To identify cardiac magnetic resonance (CMR)-derived parameters affected in early stages of PH before the development of RV dysfunction. Methods Experimental chronic PH was generated by pulmonary vein banding in 76 pigs whereas 14 animals underwent sham operation. Animals were followed-up monthly with right heart catheterization (RHC) and immediate CMR for a maximum of 9 months. CMR exams included a T1-mapping sequence to quantify equilibrium-extracellular volume (ECV) at the RV insertion points. Pairs of RHC and CMR examinations were compared among controls and PH with normal RV ejection fraction (RVEF≥55%) or reduced (REVF<55%) using ANCOVA test with Bonferroni correction. All procedures followed the “Principles of laboratory animal care”. Results In the presence of PH confirmed by RHC and normal RVEF, the RV displays significant hypertrophy and increased myocardial native T1 and ECV, despite preserved ventricular dimensions and PA flow (Fig 1B). In advanced stages of the disease, RV-AP uncoupling and reduced PA pulsatility develop together with RV dilatation and failure (Fig 1C). CMR parameters in sham and PH animals Sham controls (n=25 evaluations) PH with normal RVEF (n=155 evaluations) PH with low RVEF (n=70) RVEF (%) 62±5 61±4 47±8# RVEDV (mL/m2) 73±18 83±17 111±29# RVESV (mL/m2) 28±8 32±8 61±25# RV mass (g/m2) 17±4 23±5* 30±11# PA area (cm2/m2) 5.5±1.2 6.3±1.6 8.7±2.2# Native T1 anterior RVIP (ms) 983±75 1043±78* 1055±90# ECV anterior RVIP (%) 27±5 31±6* 36±7# Native T1 inferior RVIP (ms) 959±68 1022±71* 1032±99# ECV inferior RVIP (%) 25±5 31±6* 36±7# PA pulsatility (%) 29±6 27±7 21±3# Ea/Emax 40±16 47±11 97±65# RVEDV: RV end-diastolic volume; RVESV: RV end-systolic volume; RVIP: RV insertion point. *p<0.05 1 vs. 2; #1 vs. 3. NativeT1: control, PH-normal RV, RV dysf Conclusion RV hypertrophy and ECV expansion are early mechanisms in RV adaptation to postcapillary PH, whereas ventricular and PA dilatation, RV-PA uncoupling and reduced pulsatility appear in more advanced stages concurring with systolic dysfunction. 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