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

Abstract

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.

Keywords: outcome; pressure‐volume relationship; pulmonary hypertension; right ventricular dysfunction.

Figure 1. Forest plot comparing RVEF and coupling metrics.

Forest Plot of Hazard Ratios and 95% CIs for RV ejection fraction (RVEF), Multi‐beat (MB) Effective arterial elastance (Ea), MB end‐systolic elastance (Ees), MB Ees/Ea ratio, single‐beat (SB) Ees, SB Ees/Ea ratio, and Stroke volume/end‐systolic volume (SV/ESV).

Figure 2. Multi‐beat Ees/Ea best predicts clinical worsening (CW) by receiver operator curve (ROC) analysis.

Multi‐beat Ees/Ea significantly predicted CW with an Area Under the Curve (AUC) of 0.780. By ROC analysis, right ventricle (RV) ejection fraction, single‐beat Ees/Ea, and stroke volume/end‐systolic volume (SV/ESV) were not able to predict CW.

Figure 3. Multi‐beat Ees/Ea Predicts Time to Clinical Worsening (CW).

Multi‐beat Ees/Ea, using a cut off of <0.65, was also able to significantly predict time to CW in Kaplan–Meier Survival Analysis.

Figure 4. Other metrics vary in predicting time to clinical worsening (CW).

RV ejection fraction (RVEF) and Stroke Volume/End‐diastolic Volume (SV/ESV) were also able to predict time to CW in Kaplan–Meier Survival Analysis. Single‐beat Ees/Ea did not significantly predict time to CW. Since Area Under the Curve (AUC) analysis was non‐significant for all 3, median values for all 3 variables were used as the cutoff.