A single echocardiographic or hemodynamic parameter improves risk stratification in prevalent patients with pulmonary arterial hypertension

Abstract Introduction According to the ESC/ERS guidelines, prevalent patients with pulmonary arterial hypertension (PAH) are stratified in 4 classes with increasing risk of mortality based on clinical variables. Purpose We sought to determine whether the integration of transthoracic echocardiography (TTE) and/or right heart catheterization (RHC) data improves prognostication at follow-up in PAH. Methods We performed a retrospective analysis of FOCUS-PAH, an international, ongoing observational study of patients diagnosed with PAH in tertiary centers. Cox proportional hazards models were built to identify TTE and RHC variables associated with all-cause mortality, when added to the 4-strata risk classification. Model discrimination, survival differences, and echocardiographic/hemodynamic cutoffs were assessed by ROC curves, Kaplan-Meier analysis, and Youden index, respectively. Results We evaluated 197 patients, who underwent both TTE and RHC within the first year after PAH diagnosis between 2001 and 2023. Key characteristics across the ESC/ERS risk classes are shown in Figure 1. At multivariate analysis, only right atrial area (RAA) (HR 1.09 1.03-1.15 per 1 cm² increase) and the percent change from baseline of pulmonary vascular resistance (ΔPVR, HR 1.01 1.005-1.02 per 1% change) were independent predictors of mortality on top of the 4-strata. Mortality risk discrimination was significantly better when RAA (AUC 0.73 0.64-0.82 vs 0.66 0.57-0.76, P=0.02) or ΔPVR (AUC 0.74 0.65-0.83, P=0.002) were added to the 4-strata model. While no significant differences were found between the inclusion of either parameter, addition of both yielded the highest predictive accuracy (AUC 0.77 0.68-0.86; P=0.0005 vs 4-strata, P=0.002 vs 4-strata+RAA, and P=0.02 vs 4-strata+ΔPVR) and reclassified 16% of patients with events into more appropriate risk groups. The optimal thresholds to refine risk prediction were 26 cm² for RAA and 20% for ΔPVR. By applying these cutoffs, 2 subgroups with different mortality risk were identified within each ESC/ERS risk category (Figure 2). These results were confirmed in another 394 patients in FOCUS-PAH, who underwent only TTE or RHC at follow-up (121 31% at low, 144 36.6% at intermediate-low, 112 28.4% at intermediate-high, and 17 4.3% at high risk as per ERS/ERS clinical stratification). The AUC improved from 0.69 (0.63-0.76) to 0.73 (0.63-0.76) when RAA was added to the 4-strata model (P=0.007), and from 0.64 (0.56-0.72) to 0.68 (0.60-0.76) when ΔPVR was added (P=0.004). Conclusions Integration of a RAA or ΔPVR enhanced risk stratification at follow-up in this large, real-world cohort of patients with PAH, suggesting that TTE and RHC are equivalent to ameliorate prognostication and, possibly, management of PAH.