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

Abstract

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 (RV-PA) 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 (β = 7.5), LAVi (β = -0.1), and sex (female, β = -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 (β = 6.8; P < 0.01), a threshold ≤0.45 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 (β = 21.9 and β = -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 (β = -18.0 and β = 72.4, respectively, both P < 0.01), together with RV-MPI (β = 18.5, P < 0.01) for VE/VCO₂ . Tricuspid regurgitation predicted SED (β = -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.

Trial registration: ClinicalTrials.gov NCT00901212.

Keywords: Echocardiography; Exercise tolerance; Heart failure with reduced ejection fraction; RV to pulmonary arterial coupling; Right ventricular function.

Figure 1

Right ventricular to pulmonary artery coupling as a measure of pulmonary artery compliance. Graphical representation of TAPSE (left) and PASP (right) measurements (top panel). PASP, pulmonary artery systolic pressure; TAPSE, tricuspid annular plane systolic excursion.

Figure 2

Relationship between TAPSE/PASP ratio and peak VO₂ in HFrEF population (n = 100). R ² = 0.10. PASP, pulmonary artery systolic pressure; TAPSE, tricuspid annular plane systolic excursion.

Figure 3

ROC curve depicting the sensitivity and specificity of TAPSE/PASP to predict a peak VO₂ result of ≤14 mL/kg/min. The AUC is 0.66 (P < 0.01), and the sensitivity and specificity are 0.63 and 0.62, respectively. The optimal threshold for a peak VO₂ result of ≤14 mL/kg/min is TAPSE/PASP of 0.45. AUC, area under the curve; PASP, pulmonary artery systolic pressure; ROC, receiver operating characteristic; TAPSE, tricuspid annular plane systolic excursion.

Figure 4

ROC curve depicting the sensitivity and specificity of TAPSE/PASP to predict a peak VO₂ ≤ 12 mL/kg/min. The AUC is 0.74 (P < 0.01), and the sensitivity and specificity are 0.91 and 0.50, respectively. The optimal threshold for a peak VO₂ ≤ 12 mL/kg/min is TAPSE/PASP of 0.39. AUC, area under the curve; PASP, pulmonary artery systolic pressure; ROC, receiver operating characteristic; TAPSE, tricuspid annular plane systolic excursion.