Worsening kidney function is a known prognostic factor in heart failure with reduced ejection fraction (HFrEF), but a new analysis suggests this decline accelerates up to a year before a major heart failure (HF) event. The study examined data from two clinical trials, EPHESUS and EMPHASIS-HF, and the real-world BARCELONA cohort.¹

This post-hoc analysis assessed longitudinal changes in estimated glomerular filtration rate (eGFR) using individual patient data. The study included 8,587 patients with HFrEF from the EPHESUS and EMPHASIS-HF trials and 2,048 patients from the BARCELONA cohort. Researchers examined eGFR trajectories before and after a primary composite endpoint, defined as HF hospitalisation or death from HF progression.

In the pooled data from EPHESUS and EMPHASIS-HF, 14.1% of patients experienced an HF-related event over a median follow-up of 17.1 months. Those who had an event showed a significantly steeper decline in eGFR in the year preceding it, with an average decline of -4.83 mL/min/1.73 m²/year compared to -1.18 mL/min/1.73 m²/year in patients who remained event-free. In the year following an event, eGFR continued to decline, though at a slower rate of -3.45 mL/min/1.73 m²/year.

These findings were consistent in the BARCELONA cohort, where 33.8% of patients had an HF event over a median follow-up of 47.0 months. The average eGFR decline was -5.77 mL/min/1.73 m²/year in the year before an event versus -1.35 mL/min/1.73 m²/year in those without an event. The decline persisted in the year after an event at a rate of -3.04 mL/min/1.73 m²/year. The analysis also found that a worsening New York Heart Association (NYHA) class paralleled the steeper eGFR decline before HF events.

These findings suggest that a notable acceleration in kidney function decline occurs long before a clinical HF event, rather than being solely a consequence of it. This challenges the reliance on static eGFR thresholds and points towards the potential utility of monitoring eGFR slopes over time to identify at-risk individuals earlier. The authors noted, “In HFrEF, kidney function decline may precede a HF hospitalization or death by up to 1 year, linking to symptomatic congestion.” They added that, “Monitoring eGFR slopes rather than relying solely on specific cut-off values may allow early detection of at-risk patients.”¹ This approach could enable more timely and proactive interventions.

The authors acknowledged that the trials analysed predate the widespread use of newer therapies like SGLT2 inhibitors and sacubitril/valsartan. Future analyses in contemporary trial populations are needed to determine how these agents may influence the observed eGFR trajectories around HF events.

This study was supported by the French National Research Agency, the French PIA, the Région Lorraine, and the European Union.

References

1. Kobayashi M, Bayes-Genis A, Duarte K, et al. Kidney function trajectories before and after hospitalization for heart failure with reduced ejection fraction. Eur Heart J. 2025;46(43):4583–4593. https://doi.org/10.1093/eurheartj/ehaf457

2. Chatur S, Vaduganathan M, Peikert A, et al. Longitudinal trajectories in renal function before and after heart failure hospitalization among patients with heart failure with preserved ejection fraction in the PARAGON-HF trial. Eur J Heart Fail. 2022;24:1906–14. https://doi.org/10.1002/ejhf.2638

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