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difference between beta-blockers and placebo for all-cause mortality in HFrEF with AF.133 However, these drugs have clear proof of safety and there may be other indications for these therapies beyond prognosis, including comorbidity management and symptom improvement. These and other therapies may also have dual functions, for example, beta-blockers or digoxin for rate control of AF, in addition to improving heart failure metrics and reducing hospitalization.48,185,186 More recent additions to HFrEF management, such as eplerenone, sacubitrilvalsartan, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, had substantial numbers of patients with AF enrolled in RCTs, with no evidence that AF status affected their ability to reduce cardiovascular mortality/heart failure hospitalization.134–136 Cardiac resynchronization therapy (CRT) in the context of HFrEF and AF is discussed in detail in the 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy, with an important focus on ensuring effective biventricular pacing (with a low threshold for considering atrioventricular node ablation).187 Patients who have heart failure with mildly reduced ejection fraction (HFmrEF) (LVEF 41%–49%) and AF should generally be treated according to guidance for HFrEF,137 albeit with limited evidence to date in AF.188–190 For treatment of HFpEF and AF,191 pre-specified subgroup data on AF from multiple large trials show that the SGLT2 inhibitors dapagliflozin, empaglifozin, and sotagliflozin are effective in improving prognosis.138–140 Appropriate management of heart failure has the potential to reduce recurrence of AF, e.g. by reducing adverse atrial and ventricular myocardial remodelling, but there are limited data for specific therapies. In the Routine versus Aggressive upstream rhythm Control for prevention of Early AF in heart failure (RACE 3) trial, combined management of mild-to-moderate heart failure with ACE inhibitors/ARBs, mineralocorticoid receptor antagonists, statins, and cardiac rehabilitation increased the maintenance of sinus rhythm on ambulatory monitoring at 12 months.39 This benefit was not preserved at the 5 year follow-up, although this may have been confounded by the lack of ongoing intervention beyond the initial 12 months.192

5.3 Type 2 diabetes mellitus

Diabetes mellitus is present in around 25% of patients with AF.193–195 Patients with both diabetes and AF have a worse prognosis,196 with increased healthcare utilization and excess mortality and cardiovascular events. The prevalence and incidence of AF and type 2 diabetes are widely increasing, thus making the association of these two conditions a public health challenge.195,197 Moreover, diabetes is a major factor influencing thromboembolic risk.198,199 Following catheter ablation of AF, diabetes and higher HbA1c are associated with increased length of stay and a greater recurrence of AF.200–203 In cohort studies, the management of diabetes mellitus as part of comprehensive risk factor management has been associated with reduced AF symptoms, burden, reversal of the type of AF (from persistent to paroxysmal or no AF), and improved maintenance of sinus rhythm.126–128 However, robust evidence is limited, and individual glucose-lowering medications have had variable effects on AF.204–206 There are emerging data of the use of SGLT2 and glucagon-like peptide-1 antagonists in patients with diabetes and AF that may impact on treatment choice in the near future. Importantly, diabetes frequently coexists with multiple risk factors in patients with AF, and a comprehensive approach to management is required. Further details are provided in the 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes.207

5.4 Obesity

Obesity frequently coexists with other risk factors that have been independently associated with the development of AF.208,209 Obesity (body mass index [BMI] ≥30 kg/m2) and being overweight (BMI >25 kg/m2) are associated with a greater risk of recurrent atrial arrhythmias after AF ablation (13% increase for every 5 kg/m2 higher BMI).210–212 In the setting of comprehensive risk factor management, weight loss of ≥10% in overweight and obese individuals with AF has been associated with reduced AF symptoms and AF burden in an RCT (aiming for BMI <27 kg/m2).125 Cohort studies have also shown a graded response to maintenance of sinus rhythm,126 improved ablation outcomes,128 and reversal of the type of AF127 commensurate with the degree of weight loss and risk factor management. However, in the Supervised Obesity Reduction Trial for AF Ablation Patients (SORT-AF) randomized trial in AF ablation patients, a sole weight loss intervention that achieved 4% loss in weight over 12 months did not impact ablation outcomes.213 This is consistent with the findings in LEGACY (Long-Term Effect of Goal directed weight management on Atrial Fibrillation Cohort: a 5 Year follow-up study) that showed that weight loss of ≤3% had no impact on AF recurrence.126 Observational studies have raised the possibility of a point of no return in terms of the benefit of weight loss,214 but also the possibility that bariatric surgery can improve symptoms and reduce AF recurrence.215–217

5.5 Obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is a highly prevalent condition, particularly in patients with AF.157,218 Optimal screening tools in the AF population are still under evaluation, although it may be reasonable to screen for OSA in patients where a rhythm control strategy is being pursued. Polysomnography or home sleep apnoea testing are suggested in preference to screening questionnaires.155–157,219 Questionnaires assessing daytime sleepiness are poor predictors of moderate-to-severe OSA.155 Which parameter should be used to focus on risk of AF in patients with OSA, and to guide OSA treatment in patients with AF, is still unclear.220,221 Observational studies have suggested that individuals with OSA not treated with continuous positive airway pressure (CPAP) respond poorly to treatments for AF, with an increased risk of recurrence after cardioversion or ablation.222 Conversely, OSA patients treated with CPAP seem to mitigate their propensity toward developing AF.148–153,222–224 A small randomized trial of CPAP vs. no therapy demonstrated reversal of atrial remodelling in individuals with moderate OSA.154 However, other small RCTs have failed to show a benefit of CPAP therapy on ablation outcomes225 or post-cardioversion.226 Data on the cardiovascular mortality benefit of CPAP therapy in OSA are inconclusive.227–230

5.6 Physical inactivity

Reduced cardiorespiratory fitness frequently coexists with other modifiable risk factors and has been associated with a greater recurrence of AF after catheter ablation.141 Better cardiorespiratory fitness has a demonstrated inverse relationship to AF burden in both middle-aged and elderly people.141 Small RCTs, meta-analyses, and observational Downloaded from academic.oup.com/eurheartj/article/45/36/3314/7738779 by guest on 07 October 2026