Right ventricular function and its coupling to pulmonary circulation predicts exercise tolerance in systolic heart failure

Aims Right ventricular (RV) dysfunction, pulmonary hypertension, and exercise intolerance have prognostic values, but their interrelation is not fully understood. We investigated how RV function alone and its coupling with pulmonary circulation (RVPA) predict cardio-respiratory fitness in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results The Evaluation of Resynchronization Therapy for Heart Failure (EARTH) study included 205 HFrEF patients with narrow (n = 85) and prolonged (n = 120) QRS duration undergoing implantable cardioverter defibrillator implantation. All patients underwent a comprehensive evaluation with exercise tolerance tests and echocardiography. We investigated the correlations at baseline between RV parameters (size, function [tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV-FAC), and RV myocardial performance index (RV-MPI)], pulmonary artery systolic pressure (PASP), and tricuspid regurgitation}; left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVi), and left atrial volume index (LAVi); and cardiopulmonary exercise test (CPET) [peak VO2, minute ventilation/carbon dioxide production (VE/VCO2), 6 min walk distance (6MWD), and submaximal exercise duration (SED)]. We also studied the relationship between RV-PA coupling (TAPSE/PASP ratio) and echocardiographic parameters in patients with both data available. Univariate and multivariate linear regression models were used. Patients enrolled in EARTH (overall population) were mostly male (73.2%), mean age 61.0 +/- 9.8 years, New York Heart Association class II-III (87.8%), mean LVEF of 26.6 +/- 7.7%, and reduced peak VO2 (15.1 +/- 4.6 ml/kg/min). Of these, 100 had both TAPSE and PASP available (TAPSE/PASP population): they exhibited higher BNP, wider QRS duration, larger LVEDVi, with more having tricuspid regurgitation compared with the 105 patients for whom these values were not available (all P < 0.05). RV-FAC (beta = 7.5), LAVi (beta = -0.1), and sex (female, beta = -1.9) predicted peak VO2 in the overall population (all P = 0.01). When available, TAPSE/PASP ratio was the only echocardiographic parameter associated with peak VO2 (beta = 6.8; P < 0.01), a threshold 50.45 predicting a peak VO2 <= 14 ml/kg/min (0.39 for VO2 <= 12). RV-MPI was the only echocardiographic parameter associated with ventilatory inefficiency (VE/VCO2) and 6MWD = 21.9 and beta = -69.3, respectively, both P < 0.01) in the overall population. In presence of TAPSE/PASP, it became an important predictor for those two CPET (beta = -18.0 and beta = 72.4, respectively, both P < 0.01), together with RV-MPI (beta = 18.5, P < 0.01) for VE/VCO2. Tricuspid regurgitation predicted SED (beta = -3.2, P = 0.03). Conclusions Right ventricular function assessed by echocardiography (RV-MPI and RV-FAC) is closely associated with exercise tolerance in patients with HFrEF. When the TAPSE/PASP ratio is available, this marker of RV-PA coupling becomes the stronger echocardiographic predictor of exercise capacity in this population, highlighting its potential role as a screening tool to identify patients with reduced exercise capacity and potentially triage them to formal peak VO2 and/or evaluation for advanced HF therapies.