HFA-PEFF unmasks a hidden high-risk phenotype in CTEPH
C Silva, D Ferreira, D Cazeiro, M Vilela, J Cravo, S Esteves, J Pedro, I Araujo, B Andrade, J Sabido, F Salvaterra, T Guimaraes, N Lousada, F Pinto, R PlacidoAbstract
Introduction
Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe form of pulmonary hypertension with persistently high morbidity and mortality. Risk stratification usually relies on right-sided hemodynamics and functional status. Many patients have comorbidities that affect prognosis. The HFA-PEFF score, created to diagnose and stratify heart failure with preserved ejection fraction (HFpEF), integrates structural, functional and biomarker domains. Whether this multidimensional tool adds prognostic value in CTEPH is unknown. We aimed to evaluate the prognostic relevance of the HFA-PEFF score in a well-phenotyped cohort of confirmed CTEPH patients.
Methods
This study included patients with CTEPH diagnosed and followed at a tertiary PH centre between December 2013 and May 2024. Patients were stratified into low, intermediate, or high-risk of HFpEF according to the HFA-PEFF score. The primary endpoint was the composite of all-cause mortality and hospitalizations for any cause. Clinical, biochemical, imaging and hemodynamic variables were extracted from baseline assessment.
Results
A total of 54 patients (64.8% female) with a mean age of 66.2 years were included. The most frequent comorbidities included obstructive sleep apnea (20.4%) and pulmonary disease (25.9%). At baseline, the median NT-proBNP was 963.5 pg/mL [IQR 3738]; Echocardiography, pulmonary function tests and hemodynamic parameters are at Table 1. Most patients received targeted therapy (74.1%) and 35% underwent pulmonary endarterectomy. Regarding the functional status at baseline, the mean 6-minute walking distance was 264.6 ± 117.5 meters and 84% of the patients were in OMS class II–III. Based on the HFA-PEFF score, 7.4% of patients were had low risk of HFpEF, 61.1% had intermediate risk and 31.5% had high risk. After a median follow up of 12 months, the primary endpoint occurred in 33 patients (61.1%)- 27 hospitalizations and 6 deaths. Stratification according to HFpEF score showed that high-risk group experienced a higher incidence of events over time, while those in the low-risk group had a lower incidence. The difference between the groups was statistically significant (log-rank p = 0.041), indicating that the HFA-PEFF score effectively stratifies patients’ risk of events- Graph1 .
Conclusions
In this real-world CTEPH cohort, higher HFA-PEFF scores were strongly linked to greater hospitalization and mortality risk. These results indicate that the score reflects not only coexisting HFpEF but also serves as a prognostic marker in CTEPH. The algorithm appears to identify a vulnerable CTEPH–HFpEF phenotype with a clearly worse trajectory. Incorporating HFA-PEFF into baseline assessment may enhance risk stratification and support more individualized therapy.For image description, please refer to the figure legend and surrounding text.