The Right Ventricular-Pulmonary Arterial Coupling and Diastolic Function Response to Therapy in Pulmonary Arterial Hypertension

Abstract Background Multiparametric risk assessment is used in pulmonary arterial hypertension (PAH) to target therapy. However, this strategy is imperfect as most patients remain in intermediate or high risk after initial treatment with low risk being the goal. Metrics of right ventricular (RV) adaptation are promising tools that may help refine our therapeutic strategy. Research Question Does RV adaptation predict therapeutic response over time? Study Design and Methods We evaluated 52 incident treatment naive patients with advanced PAH by catheterization and cardiac imaging longitudinally at baseline, follow-up 1 (∼3 mo.) and follow-up 2 (∼18 mo.). All patients were placed on goal-directed therapy with parenteral treprostinil and/or combination therapy with treatment escalation if functional class I-II was not achieved. Therapeutic response was evaluated at follow-up 1 as non-responders (died) or responders and again at follow-up 2 as super-responders (low risk) or partial-responders (high/intermediate risk). Multiparametric risk was based on a simplified ERS/ESC guideline score. RV adaptation was evaluated with the single-beat coupling ratio (Ees/Ea) and diastolic function with diastolic elastance (Eed). Data are expressed as mean±SD or odds ratio [95%CI]. Results Nine patients (17%) were non-responders. PAH-directed therapy improved ERS low risk from 1 (2%) at baseline to 23 (55%) at follow-up 2. Ees/Ea at presentation was non-significantly higher in responders (0.9±0.4) versus non-responders (0.6±0.4, p=0.09) but was unable to predict super-responder status at follow-up 2 (odds ratio 1.40 [0.28-7.0], p=0.84). Baseline RVEF and change in Eed successfully predicted super-responder status at follow-up 2 (odds ratio 1.15 [1.0-1.27], p=0.009 and 0.29 [0.86-0.96], p=0.04, respectively). Interpretation In patients with advanced PAH, RV-PA coupling could not discriminate irreversible RV failure (non-responders) at presentation but showed a late trend to improvement by follow-up 2. Early change in Eed and baseline RVEF were the best predictors of therapeutic response.