Impact of frailty on mortality, functional outcome, and health status after out-of-hospital cardiac arrest: insights from the TTM2-trial

PURPOSE: To explore the association of frailty with mortality, functional outcome, and health status after out-of-hospital cardiac arrest. METHODS: This is a cohort-based secondary analysis of the Targeted Hypothermia versus Targeted Normothermia after out-of-hospital cardiac arrest (TTM2) trial, an international, prospective, multicentre study. Frailty was assessed using the Clinical Frailty Scale (1-9): fit (1-3), prefrail (4), frail (5), and severely frail (6-9). Main outcomes were mortality and poor functional outcome (modified Rankin Scale 4-6) at 6 and 24 months. Additional outcomes included neuroprognostication, withdrawal-of-life-sustaining-therapies (WLST), functional decline (retrospectively reported pre-arrest versus 6 month Glasgow Outcome Scale Extended score), health status (EQ-5D-5L, EQ-VAS), and life satisfaction at 6 and 24 months. RESULTS: Of 1861 participants, 240 (13%) were prefrail, and 188 (10%) were frail or severely frail. Mortality and poor functional outcome increased significantly with greater frailty. Compared to fit participants, adjusted ORs (95% CI) for 6 month mortality were: prefrail 2.7 (1.8-3.8), frail 3.7 (1.9-7.1), and severely frail 8.9 (4.2-18.7); and poor functional outcome: prefrail 2.9 (1.9-4.2), frail 3.9 (1.9-8.1), and severely frail 35.4 (8.4-148.8). Severely frail participants underwent neuroprognostication less often (p < 0.001), while WLST was more common in the prefrail, frail and severely frail (p < 0.001). Prefrail and frail survivors tended to report more frequent functional decline and lower health status, though with individual variation. CONCLUSION: Frailty was associated with a significantly increased risk of mortality and poor functional outcome after out-of-hospital cardiac arrest. Findings suggest more frequent functional decline and lower overall health status in frail survivors. TRIAL REGISTRATION: NCT02908308.