Patient-reported physical activity improves risk stratification beyond COMPERA 2.0 in PAH and CTEPH

Background Accurate risk stratification is essential in PAH and CTEPH. The COMPERA 2.0 model is based on World Health Organization functional class (WHO-FC), 6-minute walking distance (6MWD), and NT-proBNP, but does not include patient-reported outcomes. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is a validated, disease-specific patient-reported outcome questionnaire that evaluates symptoms, physical activity (PA), and quality of life. Purpose To determine whether adding CAMPHOR-PA to COMPERA 2.0 improves prediction of transplant-free survival, by enhancing risk discrimination/reclassification. Methods Data were obtained from the Swedish PAH & CTEPH registry (SPAHR). Patients diagnosed between 2008 and 2021 with complete baseline WHO-FC, 6MWD, NT-proBNP, and CAMPHOR data were included. Risk stratification was first performed according to the standard COMPERA 2.0 model, which assigns scores (1-4) to WHO-FC, 6MWD, and NT-proBNP and defines four risk strata based on the rounded mean of these components. To evaluate the incremental prognostic value of patient-reported physical activity, a modified COMPERA model was constructed by incorporating CAMPHOR-PA as an additional variable. CAMPHOR-PA was categorized into three levels (≤5, 6–10, ≥11 points) and scored analogously to COMPERA variables (1, 2, and 4, respectively). The modified risk score was calculated as the rounded mean of all four components (WHO-FC, 6MWD, NT-proBNP, and CAMPHOR-PA), maintaining the original COMPERA 2.0 scoring framework. Five-year transplant-free survival was analyzed using Kaplan–Meier estimates and log-rank tests. Model discrimination was assessed using Harrell’s C-index and time-dependent area under the curve (AUC) at 1, 3, and 5 years with bootstrap correction (B = 1000). One-year reclassification was evaluated using net reclassification improvement (NRI). Results The cohort included 326 patients (PAH n=245; CTEPH n=81), median age 69 [58; 75] years, 67% women. Median NT-proBNP was 1002 [312; 2760] and 6MWD 342 [234; 436]; most were WHO-FC III (Table 1). Adding CAMPHOR-PA improved discrimination (C-index 0.645 to 0.656; Δ+0.011). The largest gain occurred at 1 year (AUC 0.800 vs. 0.728; Δ+0.072), confirmed after bootstrap correction (Δ+0.071). The modified score reclassified 70 patients (21.5%), with NRI for events +0.385. Hazard ratios vs. low risk increased for intermediate-low (3.02 vs. 2.36) and high risk (8.62 vs. 5.93). Although separation of intermediate strata attenuated by year 3, the high-risk stratum maintained strong prognostic discrimination (HR 4.46 vs. 2.80) at 3 years (Figure 1). Conclusion Incorporating CAMPHOR-PA into COMPERA 2.0 improved short-term risk prediction and reclassification, supporting the incremental value of patient-reported physical activity in multidimensional risk assessment, particularly for early risk discrimination.