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............................................................................................................................................................................. for the prevention of thromboembolic events in patients with AF and without severe mitral stenosis and/or mechanical valve prosthesis, as they have similar efficacy to vitamin K antagonists (VKAs) but a lower risk of intracranial haemorrhage.528

LA appendage closure can be considered in patients with HF and AF who have a contraindication to oral anticoagulation though data from randomized trials have not included patients with contraindications to oral anticoagulants.529,530

Rate control Data regarding rate control are not conclusive for the patients with AF and HF. A strategy of lenient rate control, defined by a resting heart rate <110 b.p.m., was compared to a strategy of strict rate control, defined by a heart rate <80 b.p.m. at rest and <110 b.p.m. during moderate exercise, in RACE II and in a pooled analysis of RACE and AFFIRM.152,531 The studies showed no differences in outcome between the two strategies. However, only 10% of the patients in RACE II and 17% of those in the pooled analysis had a history of HF hospitalization or NYHA class IIIII, respectively.152,531 Higher heart rates are associated with worse outcomes in observational studies.532,533 Thus, a lenient rate control is an acceptable initial approach with, however, treatment targeting a lower heart rate in case of persistent symptoms or cardiac dysfunction likely related to tachycardia (e.g. tachycardia-induced cardiomyopathy).7,534 Beta-blockers can be used for rate control in patients with HFrEF or HFmrEF because of their established safety in these patients (see section 5.3.2).7,534,535 Digoxin or digitoxin can be considered when the ventricular rate remains high, despite beta-blockers, or when beta-blockers are contraindicated or not tolerated.151,493,536 It may therefore be considered also an alternative to beta-blockers. For patients with NYHA class IV and/or haemodynamic instability, i.v. amiodarone can be considered to reduce ventricular rate.537 For HFpEF, there is a paucity of evidence to demonstrate efficacy of any agent. The RATE-AF trial compared digoxin with bisoprolol in patients with persistent AF and NYHA class IIIV symptoms. Compared with bisoprolol, digoxin had the same effect on QOL at 6 months (primary endpoint) and a better effect on EHRA and NYHA functional class.536 Only 19% of the patients had LVEF <50% so that most of the patients can be considered as having HFmrEF or HFpEF.536 AV node ablation can be considered in patients with poor ventricular rate control despite medical treatment not eligible for rhythm control by catheter ablation or in patients with biventricular pacing.7,538540

Rhythm control Urgent electrical cardioversion is recommended in the setting of acute worsening HF in patients presenting with rapid ventricular rates and haemodynamic instability, after consideration of the thromboembolic risk. Cardioversion should be considered also to improve symptoms in patients who have persistent and symptomatic AF, despite optimal pharmacological management. In patients who do not receive chronic therapy with oral anticoagulant and with AF onset >48 h, at least 3 weeks of therapeutic anticoagulation or a transoesophageal echocardiography is needed before cardioversion.7 When pharmacological cardioversion is preferred, amiodarone is the drug of choice as other antiarrhythmic drugs (i.e. propafenone, flecainide, dronedarone) are associated with worse outcomes in HFrEF.186,534,541544 Amiodarone can help maintain HF patients in SR after cardioversion.545,546

Trials including patients with HF and comparing rate control and rhythm control strategies with the latter based on antiarrhythmic drugs failed to show any benefit of one strategy over the other.547550 More recently, EAST-AFNET 4, enrolling patients with early AF, 28.6% with HF, was stopped early after a median follow-up of 5.1 years for a lower occurrence of the primary outcome of death, stroke, or hospitalization for worsening HF or ACS in the patients assigned to early rhythm control vs. those assigned to usual care.551 However, the patients assigned to the rhythm control strategy had a closer follow-up, which may have influenced their better outcome. Catheter ablation was performed in a minority of the patients in the rhythm control arm (19.4%).551 LA catheter ablation was compared with MT, rate or rhythm control strategy, in 363 patients with persistent or paroxysmal AF, LVEF <35% and an implanted device (ICD or CRT-D) enrolled in the CASTLE-AF trial.552 The primary endpoint of all-cause death or HF hospitalizations occurred in fewer patients in the ablation group vs. the MT group, 51 patients (28.5%) vs. 82 (44.6%) [hazard ratio (HR); 95% confidence interval (CI), 0.62; 0.430.87; P =0.007]. Also, other endpoints, all-cause or CV death or worsening HF, were reduced by catheter ablation.552 This trial suggests that catheter ablation can improve the prognosis of patients with HFrEF. However, it enrolled a highly selected population, 363 of 3013 patients, was not blinded, had crossovers between the two treatment strategies and the number of events observed was low: 24 (13.4%) vs. 46 (25.0%) all-cause deaths and 37 (20.7%) vs. 66 (35.9%) HF hospitalizations in the ablation and MT groups, respectively.552 The CABANA trial was an investigator-initiated, open-label, multicentre, randomized trial enrolling 2204 patients with symptomatic AF. The trial failed to show a benefit of AF ablation strategy over medical care on the primary composite endpoint of death, disabling stroke, serious bleeding, or cardiac arrest in the overall population.553 In an analysis of the 778 patients (35%) with NYHA class symptoms >II, the primary outcome occurred in 34 patients (9.0%) in the catheter ablation group vs. 49 (12.3%) in the drug therapy group (HR; 95% CI, 0.64; 0.410.99).554 However, also in this trial, the number of events was small and HF was defined based only on symptoms with LVEF available in 73% of the patients and >50% and 4049% in 79% and 11.7% of the cases, respectively.554 Both CASTLE-AF and CABANA showed a highly significant effect of catheter ablation on patients’ symptoms.552554 Two other prospective trials enrolled patients with HFrEF and persistent AF, who were randomized to catheter ablation or MT in one trial (AMICA trial, n = 140), and to catheter ablation or amiodarone in the other one (AATAC trial, n = 203).555,556 The first trial failed to show any difference in the LVEF increase between the two groups.555 The second trial showed superiority of catheter ablation with respect of AF recurrence, the primary endpoint, with also a reduction in unplanned hospitalizations and mortality.556 In contrast with the AMICA trial,555 but in accordance with CASTLE-AF,552 AATAC also showed a benefit of catheter ablation on LVEF.556 In conclusion, there is insufficient evidence in favour of a strategy of rhythm control with antiarrhythmic drugs vs. rate control in patients with HF and AF.547551 The results of randomized trials with Downloaded from academic.oup.com/eurheartj/article/42/36/3599/6358045 by guest on 07 October 2026