Frailty Attenuates the Prognostic Value of Multimorbidity in Heart Failure - Insights From the Largest Tertiary Center in the Middle East
In brief
Frailty doubles death risk and nullifies most multimorbidity mortality signal in HF
In a cohort of 18,058 heart-failure patients, frailty was linked to a 91% higher risk of death, while having more than eight comorbidities raised mortality by only 20% overall. Among non-frail patients, high multimorbidity increased death risk by 42%, but in frail patients the excess risk fell to just 13%, suggesting frailty overrides comorbidity burden in prognosis.
- Journal
- Mayo Clinic proceedings (Q1)
- Published
- 31 August 2026
- Study design
- Retrospective cohort
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Viana Copeland, Boris Fishman, Shir Elimeleh, Ranel Loutati, Noam Makmal, Assi Milwidsky, et al.
- PMID
- 42674184
- DOI
- 10.1016/j.mayocp.2026.07.030
Why clinicians should know about it
- Picked for Internal Medicine (paper of the day, 2 September 2026): Frailty modifies multimorbidity prognostic value in HF
Abstract
OBJECTIVE: To evaluate whether frailty modifies the association of multimorbidity in HF. METHODS: A retrospective cohort study of HF patients. Multimorbidity was quantified using 26 conditions and categorized as low (≤4), intermediate (5-7), or high (>8). Frailty was defined using a multimodal construct integrating functional, nutritional, and biochemical domains. All-cause mortality was assessed using cox models with frailty-multimorbidity interaction testing. Charlson Comorbidity Index (CCI) was used for validation. RESULTS: Among 18,058 patients (median age 74 years; 62% male; 64% frail), 57% died over a median follow-up of 4.0 years (IQR 1.3-7.7). Multimorbidity burden comprised 30.5% low, 48% intermediate, and 21.5% high. Frailty was associated with a 91% higher mortality risk (adjusted HR 1.91; 95% CI 1.85-2.00). Compared with low multimorbidity, intermediate and high burden were associated with an independent 8% and 20% higher mortality risks, respectively (95% CI 1.02-1.14 and 1.13-1.27; both p<.001). However, the association of multimorbidity differed by frailty such that among non-frail patients, intermediate and high multimorbidity increased mortality by 18% and 42% whereas in frail patients, the association was attenuated, with no excess risk for intermediate burden and only 13% increase for high burden (p-for-interaction <.001). CCI analyses was consistent, though differed among females and HFpEF. CONCLUSION: Frailty fundamentally attenuates risk in HF, while multimorbidity stratifies prognosis only when physiological reserve is preserved.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.