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Frailty and aging are two common conditions both associated with increased vulnerability to stressful events with high risk of adverse outcomes. Purpose To evaluate the association between frailty and aging and their impacts on clinical outcome in patients with heart failure with preserved ejection fraction (HFpEF). Methods Analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 757 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction ≥50% and brain natriuretic peptide ≥100pg/ml. We included 483 patients (age, 80±9 years; men, 45%; atrial fibrillation, 35%) whose follow-up data after survival discharge were available. Patients' frailty and aging were evaluated using the clinical frailty scale (CFS) and age quartiles (Q1: &amp;lt;76 years (n=122), Q2: 76–82 years (n=111), Q3: 82–87 years (n=127), Q4: &amp;gt;87 years (n=123)), respectively. The primary clinical endpoint was defined as the composite of death, re-hospitalization for heart failure, and cerebrovascular accident. Results The median (interquartile range) CFS rating was 3 (2–5), and there was a little correlation between CFS rating and age (r2=0.16, p&amp;lt;0.001). The prevalence of frailty, defined as a CFS rating &amp;gt;4 (n=132), was positively correlated with age quartiles (Q1: 9.0%, Q2: 21.4%, Q3: 29.9%, Q4: 48.0%, p&amp;lt;0.001). During the median follow-up period 396 days (interquartile range, 344–698) after discharge, the clinical endpoint was observed in 172 patients. The incidence was higher in patients with frailty than those without it (49.6% vs. 30.4%, log-rank p&amp;lt;0.001). It was also correlated with age quartiles (Q1: 23.0%, Q2: 34.2%, Q3: 36.2%, Q4: 48.8%, log-rank p=0.001). Multivariate Cox regression analysis revealed that frailty (hazard ratio, 1.52; 95% confidence interval, 1.09–2.10; p=0.013) and age (hazard ratio per quartile increase, 1.24; 95% confidence interval, 1.07–1.43; p=0.004) were both associated with the clinical endpoint. Subgroup analysis in 352 patients without frailty also revealed the significant impact of age on the endpoint (1.26; 1.06–1.51; p=0.008). However, in 131 patients with frailty, there was no significant impact of age on the endpoint (1.16; 0.90–1.51; p=0.25). Conclusions Frailty was common and was associated with aging in HFpEF patients. Although they were both associated with unfavorable events, aging was no longer a significant predictor of adverse outcomes under the frailty conditions. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.

The impact of frailty and aging on prognosis in patients with heart failure with preserved ejection fraction – insights from PURSUIT-HFpEF registry