Effects of Rhythm Control versus Rate Control on Atrial Fibrillation and Frailty Development in Older Patients: Protocol for the Cardioversion of Atrial Fibrillation and Frailty in the Elderly (CAFFE) Study, an Observational, Prospective Cohort Study

Background. Atrial fibrillation (AF), highly prevalent in older individuals. is associated with frailty and disability. AF therapy is based on rhythm-control (RhythmC), to restore sinus rhythm, or rate-control (RateC), to lower heart rate. Guidelines have not a preferred option for older people. Objectives. This study aims at evaluating if RhythmC is more effective than RateC to hinder frailty and disability progression. Methods. The CAFFE is a prospective, multicenter, observational, cohort study including 3 groups of patients, 1) >75 years, RhythmC; 2) 65-74 years, RhythmC; 3) >65 years, RateC, and a >65 years subjects group without overt chronic conditions (each group, N=40). At baseline, all subjects will undergo Comprehensive Geriatric Assessment – CGA, and an analysis of inflammation and metabolomics. At home, a device will evaluate rhythm, the activity profile and sleep. After one month, the CGA will be repeated. Results. The CAFFE study was funded as a Research Project of National Interest by the Italian Ministry of University and Research (October 2023). Ethical Committee final approval was given on June 2024. In October 2025, the coordinating center had enrolled 31/40 AF patients (age: 78±9 years; women: 25.8%; CHA2DS2-VA: 4.2±1.2; robust subjects: 43.3%). All centers are now completing the enrollment (N=103/160 subjects), and the analysis of inflammatory mediators is started. Main results should be published in summer 2027. Conclusions. The CAFFE study will evaluate the AF management strategy effectiveness in older patients. If RhythmC will slow frailty and disability, specific clinical trials should more definitely address this knowledge gap.