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.