Highlight
– In the ARREST‑AF randomized clinical trial (n=122), a structured physician‑led lifestyle and cardiometabolic risk factor management program (LRFM) delivered around the time of first‑time catheter ablation increased the proportion of patients free from atrial arrhythmia over 12 months (61.3% vs 40.0%, P = .03). Hazard ratio for recurrence was 0.53 (95% CI, 0.32–0.89).
– LRFM produced clinically meaningful improvements in weight (mean −9.0 kg) and systolic blood pressure (mean −10.8 mm Hg) at 12 months and improved AF symptom scores compared with usual care.
Background
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a major cause of stroke, heart failure, reduced quality of life, and healthcare utilization. Catheter ablation—most commonly pulmonary vein isolation (PVI)—is an established rhythm control strategy for symptomatic paroxysmal and persistent AF, but long‑term success is imperfect: arrhythmia recurrence accumulates over time and multiple procedures are frequently required.
Observational cohorts and secondary analyses have suggested that targeted modification of modifiable risk factors (notably weight reduction, blood pressure control, treatment of sleep apnea, glycemic control, and exercise/fitness improvements) improves AF burden and may enhance outcomes after ablation. Prior studies were predominantly nonrandomized. High‑quality randomized evidence addressing whether structured risk factor management improves ablation outcomes has been limited until now.
Study design (ARREST‑AF)
ARREST‑AF was an open‑label, multicenter randomized clinical trial conducted at three centers in Adelaide, South Australia, with enrollment between July 2014 and September 2018 and 12‑month follow‑up. The trial tested whether a tailored, physician‑led lifestyle and risk factor management program (LRFM) delivered around the time of first‑time catheter ablation would improve rhythm outcomes compared with usual care (UC).
Key eligibility: patients with symptomatic, nonpermanent AF undergoing first‑time catheter ablation, body mass index (BMI) ≥27 kg/m2, and at least one additional cardiometabolic risk factor. Participants were randomized 1:1 to LRFM or UC at the time of ablation. All patients underwent PVI; additional lesion sets were at the operator’s discretion. Ablation teams and the AF management team providing guideline‑directed AF care were blinded to randomization with respect to procedural decisions.
Interventions: the LRFM arm enrolled patients into a structured, physician‑led clinic focused on individualized reduction of modifiable risk factors (weight loss, blood pressure control, diabetes and lipid management, sleep apnea screening/therapy, exercise prescription, and other lifestyle measures). The UC arm received standard information about risk factor management from their treating physician but were not enrolled into the structured clinic.
Primary outcome: proportion of patients free from AF in the 12‑month period after ablation. Secondary outcomes included AF symptom severity, changes in weight, waist circumference, and blood pressure, and safety outcomes.
Key findings
Population: 122 participants were randomized (mean age 60 ± 10 years; 67% male; mean BMI 33 ± 5 kg/m2). Sixty‑two patients were assigned to LRFM and 60 to UC.
Primary outcome
At 12 months after ablation, freedom from AF was achieved in 38 of 62 patients (61.3%) in the LRFM group versus 24 of 60 patients (40.0%) in the UC group (absolute difference 21.3 percentage points; P = .03). Time‑to‑event analysis yielded a hazard ratio for recurrent arrhythmia of 0.53 (95% CI, 0.32–0.89) favoring LRFM.
Secondary clinical outcomes
AF symptom severity improved more in the LRFM group (mean difference −2.0; 95% CI, −3.7 to −0.3), indicating better symptom control and quality of life measures related to rhythm. There were no signalable safety concerns attributed to the LRFM intervention in the published report.
Risk factor changes
LRFM delivered substantial cardiometabolic benefits at 12 months compared with UC: mean body weight reduction −9.0 kg (95% CI, −11.1 to −6.8 kg), mean waist circumference reduction −7.0 cm (95% CI, −9.4 to −4.5 cm), and mean systolic blood pressure reduction −10.8 mm Hg (95% CI, −16.1 to −5.5 mm Hg). There was no statistically significant difference in diastolic blood pressure (mean −3.5 mm Hg; 95% CI, −7.2 to 0.2 mm Hg).
Interpretation of effect size
The observed absolute improvement in arrhythmia‑free status of ~21 percentage points at 12 months is clinically meaningful. The hazard ratio (0.53) indicates roughly a 47% relative reduction in the risk of recurrent symptomatic arrhythmia over one year. The magnitude of weight loss and blood pressure reduction achieved in LRFM are consistent with clinically relevant reductions in cardiovascular risk and plausibly mediate part of the improved rhythm outcome.
Expert commentary and critical appraisal
Strengths
- Randomized design testing a pragmatic, clinic‑based intervention addresses a key evidence gap left by prior observational cohorts.
- Clear, clinically relevant primary endpoint (freedom from AF over 12 months) and concordant improvements in patient‑reported symptoms and objective risk factor measures strengthen causal inference.
- Intervention was pragmatic and scalable: a physician‑led clinic using established risk‑factor targets and therapies.
Limitations
- Open‑label design: participants and clinic staff were aware of allocation, raising potential performance and detection biases despite blinded procedural teams. Objective arrhythmia detection methods and blinded adjudication mitigate but do not eliminate bias risk.
- Sample size and geography: 122 patients across three centers in Adelaide limits generalizability, particularly to populations with different baseline risk profiles, health systems, or sociodemographics.
- Short follow‑up: 12 months is relevant but does not capture longer‑term durability of both rhythm benefits and sustained risk‑factor control; AF recurrence after ablation often continues beyond one year.
- Multicomponent intervention: LRFM combined weight loss, blood pressure control, sleep apnea management, and other measures, so the trial cannot determine the independent contribution of any single component to the improved ablation outcome.
- Selection criteria: inclusion required BMI ≥27 and ≥1 additional cardiometabolic risk factor; results may not apply to patients with normal weight or low cardiometabolic risk.
Biological plausibility
Several mechanistic pathways link cardiometabolic risk factors to atrial remodeling and AF: obesity and adiposity promote atrial enlargement, inflammation, and fatty infiltration; hypertension drives atrial pressure/volume overload and fibrosis; sleep apnea causes intermittent hypoxia and autonomic instability; diabetes and dyslipidemia contribute to myocardial fibrosis and autonomic dysfunction. Reversal or mitigation of these processes through weight loss and risk factor control plausibly reduces substrate progression and lowers recurrence after ablative excision of focal triggers.
Context with guideline recommendations
Contemporary AF guidelines (European Society of Cardiology 2020; AHA/ACC/HRS focused updates) emphasize integrated care and risk factor modification as central components of AF management and encourage addressing modifiable contributors when pursuing rhythm control, including ablation. ARREST‑AF provides randomized evidence supporting these guideline recommendations in the ablation setting.
Clinical implications and implementation considerations
For clinicians and electrophysiology programs, ARREST‑AF suggests that structured, physician‑led risk factor programs implemented around the time of first ablation can materially improve outcomes. Practical implications include:
- Screening: systematically assess BMI, blood pressure, glycemic status, lipids, and sleep apnea antecedents in all patients referred for ablation.
- Pre‑ and peri‑procedural optimization: where feasible, enroll patients in structured risk‑factor programs prior to ablation to achieve meaningful weight loss and BP control.
- Multidisciplinary care: integrated clinics (cardiology, electrophysiology, obesity medicine, sleep medicine, and allied health such as dietitians and physiotherapists) may be required for effective implementation.
- Equity and access: systems should consider strategies to deliver such programs at scale, including telehealth, group programs, and primary care integration to overcome resource limitations.
Research gaps and future directions
Key questions that follow from ARREST‑AF include:
- Durability: do the benefits persist beyond 12 months? Longer‑term follow‑up and repeat procedure rates should be assessed.
- Component efficacy: randomized factorial trials could determine which elements (weight loss vs BP control vs sleep apnea therapy) drive the greatest benefit.
- Cost‑effectiveness: formal economic analyses are needed to quantify the value of structured LRFM programs relative to additional ablation procedures and reduced downstream morbidity.
- Generalisability: replication in larger, more diverse populations and different healthcare settings is required.
Conclusion
The ARREST‑AF randomized clinical trial provides high‑quality evidence that aggressive, structured risk factor and weight management around the time of first‑time catheter ablation substantially improves 12‑month freedom from atrial arrhythmia compared with usual care in patients with elevated BMI and additional cardiometabolic risk factors. The intervention led to meaningful weight loss, improved blood pressure control, and symptom reduction—changes that are both clinically valuable and biologically plausible mechanisms for reduced AF recurrence. These findings reinforce guideline recommendations to integrate risk factor modification into comprehensive AF care and support the adoption of structured, multidisciplinary programs in clinical practice, while underscoring the need for longer‑term and implementation research.
Funding and trial registration
Trial registration: ANZCTR Registry Identifier: ACTRN12613000444785. The published report lists trial funding and disclosures (see citation below).
References
1. Pathak RK, Elliott AD, Lau DH, et al. Aggressive Risk Factor Reduction Study for Atrial Fibrillation Implications for Ablation Outcomes: The ARREST‑AF Randomized Clinical Trial. JAMA Cardiol. 2025 Oct 29:e254007. doi:10.1001/jamacardio.2025.4007. PMID: 41160038; PMCID: PMC12573115.
2. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio‑Thoracic Surgery (EACTS). Eur Heart J. 2021;42(5):373–498. doi:10.1093/eurheartj/ehaa612.
3. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update on atrial fibrillation: strategies for management of patients. Circulation. 2019;140:e125–e151. (Focused guideline update)
Note: Additional observational literature and consensus statements have previously suggested benefit from risk factor modification in AF; ARREST‑AF provides randomized evidence supporting those prior findings.
