Heart failure with supranormal ejection fraction as a new HF phenotype. Clinical profile and prognosis of patients with based on the Heart Failure Observational Study of the Polish Cardiac Society

Abstract Over recent years, heart failure (HF) with supranormal ejection fraction (snEF) has been postulated as a distinct phenotype of heart failure. It has been proven that patients with snEF (defined as EF ≥60% or ≥65%, depending on the analysis) have a suboptimal response to pharmacological treatment (with flozins being the only drugs proven effective in patients with snEF), lower rates of atrial fibrillation or coronary disease, and a worse prognosis. Based on the HEROES (Heart Failure Observational Study of the Polish Cardiac Society) [1], we aimed to identify HFsnEF patients, assess their clinical profile, and evaluate all-cause mortality (median follow-up: 485 days, interquartile range (IQR): 397–599 days). We analyzed all patients with HF with preserved ejection fraction (≥50%) and divided them into two groups: (1) EF 50–59% and (2) EF ≥60%. We compared the groups using chi-square statistics and the Mann-Whitney test, where appropriate. Survival analysis was performed using the Kaplan-Meier method. Among the 1,422 patients with HF included in the HEROES study, 321 were classified as HFpEF, including 209 with EF 50–59% and 112 with EF ≥60%. The overall median age was 73 years, with a nearly equal gender distribution (men: 50.8%, women: 49.2%) in the HFpEF group. Comparing patients with EF ≥60% to those with EF 50–59%, we found no significant differences in sex distribution, age, NYHA class, pharmacological treatment, or history of diabetes, chronic kidney disease, or chronic obstructive pulmonary disease. There were also no significant differences in NT-proBNP levels, body mass index, or quality of life as measured by KCCQ-12. However, compared to patients with EF 50–59%, those with HFsnEF (≥60%) had lower rates of atrial fibrillation (44.6% vs. 58.9%; p=0.01), were less likely to have a history of previous myocardial infarction (9.8% vs. 25.4%; p<0.001, including previous percutaneous coronary interventions: 10.7% vs. 19.6%; p=0.04), and had a lower prevalence of stroke history (3.6% vs. 10.0%; p=0.04). There was no significant difference in overall mortality (all-cause death) between the two groups (10.7% for the snEF group vs. 14.4% for the EF 50–59% group; p=0.39). However, the time to death was over three times shorter in the snEF group—median: 70.5 days (IQR: 27.5–152.5 days) vs. 220 days (IQR: 100–386 days); p=0.007. Additionally, survival analysis showed significantly worse prognosis for the snEF group (Fig. 1; p=0.004). Our results align with the limited existing reports on HFsnEF, suggesting that heart failure with supranormal ejection fraction may represent a distinct and novel HF phenotype.