Multi‐Beat Right Ventricular‐Arterial Coupling Predicts Clinical Worsening in Pulmonary Arterial Hypertension

BACKGROUND: Although right ventricular (RV) to pulmonary arterial (RV‐PA) coupling is considered the gold standard in assessing RV dysfunction, its ability to predict clinically significant outcomes is poorly understood. We assessed the ability of RV‐PA coupling, determined by the ratio of multi‐beat (MB) end‐systolic elastance (Ees) to effective arterial elastance (Ea), to predict clinical outcomes. METHODS AND RESULTS: Twenty‐six subjects with pulmonary arterial hypertension (PAH) underwent same‐day cardiac magnetic resonance imaging, right heart catheterization, and RV pressure‐volume assessment with MB determination of Ees/Ea. RV ejection fraction (RVEF), stroke volume/end‐systolic volume, and single beat‐estimated Ees/Ea were also determined. Patients were treated with standard therapies and followed prospectively until they met criteria of clinical worsening (CW), as defined by ≥10% decline in 6‐minute walk distance, worsening World Health Organization (WHO) functional class, PAH therapy escalation, RV failure hospitalization, or transplant/death. Subjects were 57±14 years, largely WHO class III (50%) at enrollment, with preserved average RV ejection fraction (RVEF) (47±11%). Mean follow‐up was 3.2±1.3 years. Sixteen (62%) subjects met CW criteria. MB Ees/Ea was significantly lower in CW subjects (0.7±0.5 versus 1.3±0.8, P=0.02). The optimal MB Ees/Ea cut‐point predictive of CW was 0.65, defined by ROC (AUC 0.78, P=0.01). MB Ees/Ea below this cut‐point was significantly associated with time to CW (hazard ratio 5.1, P=0.001). MB Ees/Ea remained predictive of outcomes following multivariate adjustment for timing of PAH diagnosis and PAH diagnosis subtype. CONCLUSIONS: RV‐PA coupling as measured by MB Ees/Ea has prognostic significance in human PAH, even in a cohort with preserved RVEF.