Heart failure with preserved ejection fraction: who are our patients?
A David Do Carmo, A Silvestre, B Passos, C Gomes, I Ambrioso, M Urpina Matias, M Custodio Roldao, M Anastacio, R Lourenco Martins, J Barrocas, C Rodrigues, S Furtado, J Fernandes, C FonsecaAbstract
Abstract
Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for approximately half of all HF cases and represents a clinically heterogeneous syndrome, associated with multiple pathophysiological mechanisms and a high burden of comorbidities. Recent phenotype profiling frameworks suggest that stratifying HFpEF patients according to comorbidity-driven clinical phenotypes may enhance disease characterization and enable more personalized management beyond conventional HF therapy.
Purpose
To characterize HFpEF patients according to clinical phenotypes and evaluate patterns of phenotype-directed therapies and clinical outcomes.
Methods
Retrospective observational study of HFpEF patients followed in the outpatient HF Clinic of a tertiary reference center in Lisbon, during 2024. Clinical phenotypes were defined in accordance with HFpEF profiles: cardiometabolic (hypertension, diabetes mellitus, obesity, dyslipidaemia, chronic kidney disease (CKD)); atrial fibrillation (AF)-predominant and Ischaemic. Overlapping phenotypes were permitted. Demographic data, NYHA class, comorbidities and directed therapy (e.g. anti-obesity therapy) were recorded. Disease-modifying therapies DMT, sodium–glucose cotransporter-2 inhibitors (iSGLT2) and finerenone, and mortality were also evaluated.
Results
A total of 285 patients were included, 61.4% women, with a mean age of 80.3 years. Most patients were mildly symptomatic (81.4% in NYHA class I–II). The burden of comorbidities was high, with a dominant cardiometabolic profile including hypertension (90.2%), diabetes mellitus (43.2%), obesity (33.0%), CKD (32.3%) and dyslipidemia (59.6%), frequently overlapping with an AF-predominant phenotype (60% of patients). Among patients with AF, 94.8% were treated with oral anticoagulation and 76.0% were receiving beta-blockers. Despite a 33% prevalence of obesity, only 19,1% of obese patients were receiving anti-obesity therapy. Ischemic phenotype defined by coronary artery disease was present in 14.7%, of whom 26.2% had undergone coronary revascularization. Additional comorbidities included chronic obstructive pulmonary disease (19.3%), current or previous smoking (22.5%), alcohol use disorder (13.7%) and depression (21.4%). Regarding HFpEF therapy, 18.9% of patients were receiving both pillars, while 54.7% were treated with iSGLT2 alone and 1.8% with finerenone alone; 10.2% of patients were not receiving any DMT. All-cause mortality was 10.2%, mainly due to non-HF related causes (86%).
Conclusion
This real-world stable HFpEF population exhibits a high burden of comorbidities with predominant cardiometabolic phenotype, frequently associated with atrial fibrillation. This highlights the systemic nature of HFpEF reinforcing the need for a multidimensional therapeutic strategy focused on cardiovascular risk factor control and AF management. Phenotypic profiling emerges as an essential tool to support a more personalized and prognosis-oriented approach in HFpEF.