Beyond Cardiorenal Risk Factors: The Prognostic Role of Frailty in Acute Heart Failure
Background: Frailty is highly prevalent in acute heart failure (AHF), yet whether it is more strongly associated with all-cause mortality or with non-fatal heart-failure events, and whether it adds information beyond cardiac severity, is seldom examined. Methods: In a prospective single-center registry of 530 consecutive patients hospitalized for AHF (February 2023–June 2025), frailty was graded at admission by the Clinical Frailty Scale (CFS; strata 1–3, 4–5, 6–9, and CFS ≥ 5) from patient and collateral history. The primary outcome was 12-month all-cause mortality; first AHF rehospitalization was analyzed with death and renal replacement therapy (RRT) as competing events, using Aalen–Johansen cumulative incidence and cause-specific and Fine–Gray models. Incremental value was tested against a cardiorenal model (age, log NT-proBNP, admission estimated glomerular filtration rate and left ventricular ejection fraction [LVEF]). Results: Frailty was highly prevalent (CFS ≥ 5, 66.4%) and was associated with older age, female sex, renal impairment, right heart failure, multivalvular disease and higher, rather than lower, LVEF. Mortality rose steeply across strata (4.5%, 19.3%, 49.7%; hazard ratio 3.29 per stratum, 95% CI 2.43–4.45), whereas the cumulative incidence of first AHF rehospitalization rose less steeply (4.5%, 29.2%, 33.0%; cause-specific hazard ratio 1.86, 95% CI 1.42–2.45; subdistribution hazard ratio 1.51, 95% CI 1.19–1.92). Frail patients with below-median NT-proBNP had mortality comparable to that of patients with CFS < 5 and above-median NT-proBNP (24.3% vs. 22.0%). Adding CFS to the cardiorenal model improved discrimination (C-index 0.701 → 0.734; optimism-corrected 0.694 → 0.726; apparent ΔC-index 0.033, 95% CI 0.007–0.063) and fit (likelihood-ratio χ2 = 27.7, p < 0.001). Discharge prescription of disease-modifying therapy declined with increasing frailty. Conclusions: In elderly patients with AHF, frailty was more strongly associated with all-cause mortality than with documented non-fatal AHF rehospitalization, carried prognostic information complementary to natriuretic peptides, and added discrimination beyond cardiorenal variables, supporting structured frailty assessment alongside heart-failure-directed therapy.
Authors
- Yannis Pantazis (ORCID: https://orcid.org/0000-0002-2009-7562)
- Maria Tsigaridaki
- Maria Bachlitzanaki (ORCID: https://orcid.org/0009-0004-2432-7988)
- Georgios Aletras (ORCID: https://orcid.org/0009-0004-7238-7117)
- Maria E. Marketou (ORCID: https://orcid.org/0000-0003-1888-3430)
- M Stratinaki (ORCID: https://orcid.org/0000-0001-8720-1830)
- Emmanouil G Foukarakis (ORCID: https://orcid.org/0000-0002-1340-2282)
- Kostas Stylianou (ORCID: https://orcid.org/0000-0003-3678-9421)
- Michalis Hamilos
Institutions
- University of Crete (GR)
- The General Hospital of Heraklion "Venizeleio-Pananio" (GR)
- University Hospital of Heraklion (GR)
- Foundation for Research and Technology Hellas (GR)
Publication Details
- Journal
- Medicina
- Published
- 2026-10-08
- DOI
- https://doi.org/10.3390/medicina62101942
- Primary Topic
- Heart Failure Treatment and Management
- Type
- article
- Field-Weighted Citation Impact
- 0.00