# Estimated atrial fibrillation burden on early rhythm-control and cardiovascular events in the EAST-AFNET 4 trial

## TL;DR

This study explores how the amount of time spent in atrial fibrillation affects cardiovascular outcomes in patients receiving rhythm-control therapy.

## Contribution

The study introduces a novel approach to estimate AF burden using AI-based ECG analysis and examines its impact on cardiovascular events.

## Key findings

- Lower AF burden was associated with fewer cardiovascular events in patients on rhythm-control therapy.
- Higher AF burden showed comparable event rates to usual care, suggesting a potential refinement in AF diagnosis.

## Abstract

Atrial fibrillation (AF) is currently diagnosed by ECG, creating a binary, lifelong diagnosis. AF burden, estimated as the proportion of time spent in AF, quantifies AF severity dynamically. AF burden can modulate the risk of AF-related outcomes. Whether AF burden modulates cardiovascular outcomes with rhythm-control therapy is unknown.

AF burden on early rhythm-control was estimated using supervised artificial-intelligence-based rhythm classification of patient-operated telemetric short-term ECGs in patients randomised to early rhythm-control in the EAST-AFNET 4 trial (NCT01288352, ISRCTN04708680, conducted between 2011 and 2020). ECGs were transmitted 1–2 times per week and during symptoms. A landmark was set at 12 months and efficacy and safety outcomes occurring during the subsequent 4.1 years of follow-up were compared by estimated AF burden quartiles (Q1–Q4).

In 1178 patients (70 years, 47% women, CHA2DS2-VA 2.8 ± 1.2) transmitting 303,308 ECGs over 5.1 years, (median 1/week, IQR 1; 2) estimated AF burden was 6% [0%; 22%] in the first year of follow-up. Estimated AF burden below the median was associated with low rates of cardiovascular death, stroke, or unplanned hospitalisation for heart failure or acute coronary syndrome (Q1: 2.0 events/100 patient-years; Q2: 2.6 events/100 patient-years). A higher estimated AF burden was associated with higher event rates (Q3: 4.8 events/100 patient-years; Q4: 4.2 events/100 patient-years), comparable to events with usual care (4.5 events/100 patient-years). Sensitivity analyses confirmed these findings.

These hypothesis-generating findings suggest that AF burden estimated by weekly short-term patient-operated ECGs modulates AF-related events on rhythm-control therapy. Pending validation and evaluation of residual confounding, estimation of AF burden can refine AF diagnosis.

EAST-AFNET4 was supported by a grant from the German Ministry of Education and Research (01 GI0204) via the German Center for Cardiovascular Research (DZHK), the 10.13039/100020028Atrial Fibrillation NETwork (AFNET), the European Heart Rhythm Association, 10.13039/100006279St. Jude Medical/Abbott, Sanofi, and the German Heart Foundation. These analyses received additional support from the 10.13039/501100000780European Union (grant agreement 965286 [MAESTRIA]), British Heart Foundation (AA/18/2/34218), German Center for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK, grant numbers DZHK FKZ 81X2800182, 81Z0710116, and 81Z0710110), 10.13039/501100001659German Research Foundation (Ki 509167694) and the 10.13039/501100003042Else Kröner-Fresenius Foundation, Dutch Heart Foundation (Grant number 01-002-2022-0118, EmbRACE), and the Leducq Foundation (2024, Immune Targets for Atrial Fibrillation).