Chronic thromboEmbolic pulmonary hypertension risk ScOre evaLUation and validaTION: the CTEPH SOLUTION trial

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but serious complication of acute pulmonary embolism (PE) with severe prognosis if left untreated. Yet, high follow-up costs often lead to a significant delay in diagnosis, which adversely affects patient outcomes. This study aims to evaluate a simple risk scoring system to select patients for follow-up, improve follow-up scheduling, and reduce diagnostic delay for CTEPH. Methods: The CTEPH SOLUTION study, a multicenter observational study, included a derivation cohort of 546 patients with prior PE and a validation cohort of 209 patients with acute PE (PH validation cohort). Clinical data, laboratory tests, and echocardiographic assessments were collected at PE diagnosis, before discharge, and at 1-month follow-up. A risk score for the echocardiographic PH probability at 1 month was derived using logistic regression. The score was then validated for the outcome CTEPH using 539 PE patients from the FOCUS multicenter observational study (FOCUS validation cohort). Results: In the derivation cohort, 62 patients exhibited high echocardiographic probability of PH, with 14 confirmed CTEPH cases (2.6%). The risk score, incorporating idiopathic PE, submassive thrombosis, and echo-derived PASP, showed good discrimination (c-statistic 0.84). In the PH validation cohort, the score correctly classified patients with a sensitivity of 0.87 and a negative predictive value of 0.97 for a cutoff of 2.5. Further validation in the FOCUS cohort (15/539 patients with CTEPH, 2.8%) confirmed high discrimination (c-statistic 0.88) and negative predictive value of 1.00 for the cutoff of 2.5. Conclusion: The developed risk score effectively identifies patients at risk of CTEPH, facilitating timely follow-up and optimal resource allocation. It may contribute to reducing diagnostic delays and improving patient outcomes.