Improving outcomes in HFpEF with advanced CKD: temporal trends from the SHEBAHEART Registry
D Hochstein, D Sternik, V Copeland, R Loutati, S Elimeleh, N Halabi, O Ofek, D Roth, R Kunin, P Beckerman, E MaorAbstract
Background
Patients with advanced chronic kidney disease (CKD) and heart failure (HF) are systematically underrepresented in clinical trials despite comprising a substantial proportion of real-world HF populations [1]. Whether contemporary care has translated into improved outcomes in this high-risk group particularly among heart failure with preserved ejection fraction (HFpEF) patients, in whom cardiorenal pathophysiology is central remains incompletely defined [2–5].
Purpose
To evaluate temporal changes in the mortality risk associated with advanced CKD in a real-world HF population, and to determine whether these trends differ according to HF phenotype, with particular focus on HFpEF.
Methods
We performed a retrospective cohort study of 15,381 HF patients in the SHEBAHEART registry (January 2009–October 2025) at a tertiary care center. Patients were stratified by kidney function: advanced CKD (eGFR 15–45 mL/min/1.73m²) versus non-advanced CKD (eGFR ≥45 mL/min/1.73m²). Temporal trends were evaluated by comparing an early (2009–2016) and late (2016–2025) period. The primary outcome was all-cause mortality, assessed using Kaplan–Meier methods and Cox proportional hazards models with period-by-CKD interaction terms; analyses were further stratified by HF phenotype (HFpEF vs HFrEF).
Results
Among 15,381 patients (age 72±14 years, 60% male), 3,595 (23%) had advanced CKD. Over a median 3.6-year follow-up, 5,018 (33%) patients died. Advanced CKD was consistently associated with higher mortality. Overall, the excess mortality risk associated with advanced CKD attenuated over time (HR 1.80 [95% CI 1.69–1.91] in 2009–2016 vs 1.66 [1.53–1.81] in 2016–2025; p for interaction=0.06). This temporal improvement was driven by HFpEF, where the advanced CKD-associated excess risk declined substantially (HR 1.73 to 1.48; p for interaction=0.003). In contrast, HFrEF patients demonstrated only minimal change over time (HR 1.84 to 1.81). Uptake of contemporary HF therapies increased in the later era, including broader use of guideline-directed agents among patients with advanced CKD [2–4].
Conclusions
In this large single-center real-world HF cohort, advanced CKD remained associated with markedly higher mortality; however, the relative excess risk narrowed over the past decade, with the clearest improvement observed in HFpEF. These findings are consistent with increasing implementation of contemporary HF strategies in routine practice and support proactive use of evidence-based therapies in HFpEF patients with advanced CKD [2–4].Spline HFrEF vs HFpEF