Multi-beat right ventricular pulmonary arterial coupling predicts clinical worsening in PAH

Rationale:

Right ventricular (RV) dysfunction drives morbidity and mortality in pulmonary arterial hypertension (PAH). RV dysfunction in PAH is ideally measured by the ratio of RV to pulmonary arterial (RV-PA) coupling,
though its ability to predict clinically significant outcomes is unknown.

Objective:

To assess the predictive power of multi-beat (MB) RV-PA coupling, as determined by the ratio of MB-derived end-systolic elastance (Ees) to effective arterial elastance (Ea). Single-beat (SB)-derived Ees/Ea and other metrics were also assessed.

Methods:

Twenty-six subjects with PAH underwent same-day cardiac magnetic resonance imaging, right heart catheterization, and RV pressure-volume assessment (Millar, Houston, TX) with both MB and SB determination of Ees/Ea. Patients were treated with standard of care therapies and followed prospectively until they met criteria of clinical worsening (CW), as defined by >10% decline in 6-minute walk distance (6MWD), worsening New York Heart Association (NYHA) class, escalation of PAH therapy, RV failure hospitalization, or transplant/death.

Measurements and Main Results:

Subjects were 57±14 years of age; predominantly women (84%) with connective tissue disease (CTD) (69%); and largely NYHA class III (50%) at enrollment. Median follow-up was 38 months (range 9.6-60). Sixteen (62%) patients met the definition of CW, with some meeting multiple criteria: declining 6MWD (n=6), NYHA class (n=4), therapy escalation (n=8), RV failure hospitalization (n=6). MB Ees/Ea was significantly lower in CW patients (0.7±0.5 vs. 1.3±0.8, p=0.02). In Cox proportional hazard modeling, decreasing MB Ees/Ea was associated with increased risked of CW (HR 3.8, p=0.04). The optimal Ees/Ea cut-point predictive of CW was 0.65, defined by ROC (AUC 0.78, p=0.01). MB Ees/Ea below this cutpoint was significantly associated with adverse events (HR 5.1, p=0.001) (Figure 1). RV ejection fraction and stroke volume/end-systolic volume also predicted CW, whereas SB Ees/Ea did not (Figure 2).