Modification of the association between age and mortality in heart failure by frailty status

AIMS: Heart failure (HF) disproportionately affects older patients, yet evidence guiding management in the oldest and frailest patients remains limited. We evaluated the influence of age and frailty on mortality and use of guideline-directed medical therapy (GDMT). METHODS AND RESULTS: Using nationwide Danish registry data, we identified all patients with new-onset HF (2013-2022), stratified by age (<65, 65-79, ≥80 years) and frailty status according to the Hospital Frailty Risk Score (low, intermediate, high). We assessed all-cause and cardiovascular mortality two years after HF diagnosis and evaluated GDMT use across age and frailty groups using logistic regression. Among 79,193 patients with HF, 24% were aged <65 years, 41% 65-79, and 35% ≥80. Frailty significantly modified the association between age and mortality (interaction p<0.001). Patients with high frailty reached comparable two-year mortality risks at younger ages than patients with lower frailty. The following had similar two-year mortality: low-frailty patients aged 80 years (22.1%, 95% CI, 21.4-22.8), intermediate-frailty patients aged 70 years (22.8%, 21.9-23.8), and high-frailty patients aged 47 (22.8%, 18.0-28.4). Similar results were seen for cardiovascular mortality. GDMT use was lower in high frailty than low frailty patients across all age groups. Moreover, within each frailty group, patients aged ≥80 years had lower odds of receiving GDMT compared to those aged <65 (reference). CONCLUSION: Frailty alters mortality risk in HF beyond chronological age, resulting in prognostic heterogeneity regardless of age. Our findings support the need for both frailty-informed and age-based management strategies in HF across all ages.