Impact of Multidomain Frailty on the Mode of Death in Older Patients With Heart Failure: A Cohort Study.

Background: Although frailty is strongly associated with mortality in patients with heart failure (HF), the risk of which specific cause of death is associated with being complicated with frailty is unclear. We aimed to clarify the association between multidomain frailty and the causes of death in elderly patients hospitalized with HF.
Methods: We analyzed data from the FRAGILE-HF cohort, where patients aged 65 years and older, hospitalized with HF, were prospectively registered between 2016 and 2018 in 15 Japanese hospitals before discharge and followed up for 2 years. All patients were assessed for physical, social, and cognitive dysfunction, and categorized into 3 groups based on their number of frailty domains (FDs, 0-1, 2, and 3). Kaplan-Meier survival analysis was used to evaluate the association between the number of FDs and all-cause mortality, whereas Fine-Gray competing risk regression analysis was used for assessing the impact on cause-specific mortality.
Results: We analyzed 1181 patients with HF (81 years old in median, 57.4% were male), 530 (44.9%), 437 (37.0%), and 214 (18.1%) of whom were categorized into the FD 0 to 1, FD 2, and FD 3 groups, respectively. During the 2-year follow-up, 240 deaths were observed (99 HF deaths, 34 cardiovascular deaths, and 107 noncardiovascular deaths), and an increase in the number of FD was significantly associated with mortality (Log-rank: P <0.001). The Fine-Gray competing risk analysis adjusted for age and sex showed that FDs 2 (subdistribution hazard ratio, 1.77 [95% CI, 1.11-2.81]) and 3 (2.78, [95% CI, 1.69-4.59]) groups were associated with higher incidence of noncardiovascular death but not with HF and other cardiovascular deaths.
Conclusions: Although multidomain frailty is strongly associated with mortality in older patients with HF, it is mostly attributable to noncardiovascular death and not cardiovascular death, including HF death.
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023929.
Competing Interests: Disclosures Dr Matsue received an honorarium from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca and research grants from Pfizer Japan, Inc, Otsuka Pharmaceutical Co, EN Otsuka Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. Nobuyuki Kagiyama received grants from Philips, Asahi KASEI Corporation, Toho Holdings Co. Ltd, Inter Reha Co. Ltd, EchoNous, Inc., and AMI, Inc. Outside of the submitted work. Dr Kamiya received grants and honorarium from Eiken Chemical Co., Ltd. and a research grant from SoftBnk Corp. Dr Kasai is affiliated with a department sponsored by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi. The other authors declare no conflicts.