Active Monitoring for AtriaL FIbrillation (AMALFI): Rationale, protocol, and pilot for a pragmatic, randomized, controlled trial of remote screening for asymptomatic atrial fibrillation.

Abstract

Objectives: Screening for asymptomatic atrial fibrillation (AF) might reduce cardioembolic strokes and screening for asymptomatic AF is recommended by some international guidelines. However, any impact of AF screening on clinical outcomes depends on a sustained increase in AF detection and anticoagulation use over time than would have occurred with routine care alone, highlighting the importance of long-term studies to generate the evidence needed to justify establishing formal screening programs. AMALFI aims to establish the long-term efficacy and cost-effectiveness of remote screening for asymptomatic AF in older individuals at increased risk of stroke using a noninvasive 14-day continuous ECG monitoring patch in UK primary care. This paper describes the study protocol and baseline characteristics of included participants.

Methods: AMALFI (ISCRTN 15544176) recruited individuals aged ≥65 years with CHA₂DS₂-VASc score ≥3 (men) or ≥4 (women) with no previous diagnosis of AF/atrial flutter from 27 UK primary care practices. Participants were randomized to ECG monitoring (Zio XT, iRhythm Technologies; intervention) or usual care (control). Those allocated to ECG monitoring were sent and returned the patch by mail. After wear, participants returned the patch to the device manufacturer where ECG data were analyzed via a deep-learned AI algorithm and confirmed by qualified cardiographic technicians. A final report was sent to study investigators, and those indicating AF or other arrhythmias considered by the study team to be clinically actionable were communicated to general practitioners (GPs) immediately by secure email. Additionally, GPs were notified by mail of the presence or absence of AF episodes ≥30 seconds, and of the burden of AF for each of their participants who wore a patch. The letter included signposting to relevant guidelines and findings were managed at the GP's discretion. Participants allocated to the control group were not required to undertake any action. The primary study outcome is the rate of new AF detection at 2.5 years, with secondary outcomes including time spent with a known AF diagnosis at 5 years of follow-up, and analyses of these outcomes by predefined age and sex subgroups. Exploratory outcomes will assess randomized assessments of time to AF detection within 2.5 and 5 years after randomization, time spent with a known AF diagnosis up to 2.5 years from randomization, and anticoagulation exposure within 2.5 and 5 years after randomization. Other exploratory long-term assessments include randomized comparisons of numbers and proportions of hospitalizations (total and cardiovascular), ischemic stroke, major bleed, and death (all-cause and cardiovascular) in both groups.

Results: Between 2019 and 2022, AMALFI randomized 5,040 people in England to screening versus usual care using mail-based invitations. Participant mean age was 77 ± 6 years, with 2360 (46.8%) female; median CHA₂DS₂-VASc score was 4 (IQR 3-5). Follow-up data on AF diagnosis, other clinical diagnoses, prescription of oral anticoagulation and other medications, primary care encounters, referrals for secondary care, and clinical events are currently being collected from primary care practices, complemented via linkage to national-level databases including dispensing data, hospital admissions, and death records. AF detection rates will be assessed at 2.5 and 5 years after randomization, and long-term cost-effectiveness will be analyzed.

Conclusion: AMALFI will provide randomized evidence on the actionable time window of opportunity for intervention generated by remote screening for asymptomatic AF in the UK using a noninvasive long-term continuous monitoring ECG patch, and the cost-effectiveness of this approach. Such data may further elucidate existing patterns of routine AF diagnosis and management, and provide important insights to guide future discussions into nationwide AF screening in the UK. AMALFI results will be reported in 2025 and 2027.