HFpEF as the predominant and underrecognized heart failure phenotype in type 2 diabetes: evidence from the DIABET-IC study

Abstract

[Abstract] Background: Heart failure (HF) is a major complication of type 2 diabetes (T2D), with HF with preserved ejection fraction (HFpEF) now representing the most frequent phenotype. However, its clinical profile, prognosis, and treatment patterns compared with HF with reduced ejection fraction (HFrEF) remain insufficiently characterized.

Objectives: To compare characteristics, outcomes, and longitudinal management of HFpEF versus HFrEF in T2D patients.

Methods: This prespecified subanalysis of the nationwide, prospective DIABET-IC cohort included 1517 patients with T2D recruited across 58 Spanish centers and followed for three years. HF phenotypes were defined according to the 2016 ESC guidelines criteria. Baseline characteristics, outcomes (mortality, hospitalizations, and progression), and therapeutic patterns were assessed.

Results: At baseline, 490 patients had HF (50.2% HFrEF, 30.6% HFpEF, 19.2% HFmrEF). HFpEF patients were older, more often female, and had higher prevalence of obesity, hypertension, and metabolic syndrome, whereas HFrEF was more strongly associated with ischemic heart disease, prior ST-elevation myocardial infarction (STEMI), and conduction disturbances. During follow-up, HFpEF was the predominant incident phenotype (46.6% of new cases), and 4.7% progressed to HFrEF. Mortality was similarly elevated in both phenotypes; HF hospitalizations tended to be higher in HFrEF, while acute coronary syndromes were more frequent in HFpEF. HFrEF patients more often received guideline-directed therapies, whereas the pre-guideline era for HFpEF, with greater uptake of SGLT2 inhibitors over time, limited used of GLP-1 receptor agonists. Notably, > 20% of HFpEF patients had natriuretic peptide levels below diagnostic thresholds, highlighting underdiagnosis.

Conclusions: HFpEF is the most frequent HF phenotype in the T2D population, with outcomes comparable to HFrEF yet frequently underdiagnosed and undertreated. Improved screening strategies and broader adoption of evidence-based therapies-particularly SGLT2 inhibitors-are urgently needed for this high-risk population.