Unrecognized heart failure with preserved ejection fraction in COPD: phenotyp-ing a prospective cohort using the HFA-PEFF score

Abstract

Diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) remains a challenge due to heterogeneous pathophysiology and substantial symptom overlap with non-cardiac causes of dyspnea, particularly in patients with other diseases such as chronic obstructive pulmonary disease (COPD). Assessing the probability of HFpEF using the HFA-PEFF score, we aimed to investigate the prevalence, clinical characteristics, and prognostic implications of potential HFpEF among patients with COPD. We prospectively included 701 participants in a cohort of patients with COPD without known HF. All participants underwent a comprehensive health examination including echocardiography. Participants were stratified and characterized according to HFpEF probability by the HFA-PEFF score, a guideline-recommended diagnostic algorithm integrating functional, morphological, and biomarker domains. Outcomes included HF hospitalization and hospitalization for cardiac arrhythmias ascertained through the national health registries. The associations between HFpEF probability and the outcomes were assessed using Cox proportional hazards regression models. Of 701 participants, 162 (23.1%) had a high probability (≥5 points), 488 (69.6%) an intermediate probability (3-4 points), and 51 (7.3%) a low probability (≤1 point) of HFpEF according to the HFA-PEFF score. Participants with a high probability were older and had a higher body mass index. Although higher HFpEF probability was associated with more severe dyspnea, lung function did not differ significantly across HFpEF probability groups. However, higher HFpEF probability was associated with impaired cardiac function, including lower global longitudinal strain, lower left ventricular ejection fraction and e′ velocity, and higher tricuspid regurgitation peak velocity (Figure 1).Hypertension was associated with a 1.6-fold increased odds of high HFpEF probability, while each 5-year age increase in age increased the odds by 1.36-fold (Figure 2). During a median follow-up of 3.0 years (IQR: 2.2 to 4.5), participants with a high probability of HFpEF had more than double the risk of hospitalization for HF and a 1.5-fold increased risk of hospitalization for cardiac arrhythmias compared with those with low-to-intermediate HFpEF probability, even after adjustment for age, sex, and FEV1% predicted (HF hospitalization: HR 2.1 [95% CI 1.03–4.4], p=0.042; arrhythmia hospitalization: HR 1.5 [1.04–2.3], p=0.033). In a COPD population without known heart failure, higher HFpEF probability was common and associated with cardiopulmonary risk factors, impaired cardiac function, and worse clinical outcomes. Incorporating structured HFpEF evaluation may improve risk stratification and early identification of heart failure in patients with COPD.