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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 January 2, 2024 e93

Joglar et al 2023 Guideline for the Diagnosis and Management of Atrial Fibrillation

postcatheter ablation was associated with significant improvement in the mortality rate and HF hospitalization in patients with AF and HFrEF.2

2 Multiple RCTs in HFrEF have shown that in patients

with symptoms due to AF, ablation improves symptoms and QOL compared with a rate control or an antiarrhythmic drug strategy.3–13 In each of 3 metaanalyses, QOL was improved.3,10,13 Although in the past a trial of antiarrhythmic drugs was advised before pursuing catheter ablation, current data support ablation for AF as first-line therapy even before antiarrhythmic drugs; often patients require both. Data on LVEF, hospitalizations, and mortality rates are less robust, but nearly every larger RCT does show some benefit in these outcomes (Table 27). Characteristics that may identify patients with a higher likelihood of success or failure with AF catheter ablation are listed in Figure 24.43

3 Data for AF catheter ablation are far less robust

for HFpEF. The largest analysis for this group of patients was a subanalysis of the CABANA trial of patients with HF; in this subgroup analysis, 778 patients (35% of the study population) enrolled in the study who had NYHA class II HF experienced improvement in survival, freedom from AF recurrence, and improved QOL compared with the medical therapy group.14 Most of these had HFpEF. In this subanalysis, catheter ablation was associated with a reduction in the mortality rate and HF. A meta-analysis on catheter ablation in patients with HFpEF that included 7 studies and 764 patients showed the ablation to be safe and effective and associated with lower hospitalizations and the mortality rate.15

4 A small RCT in patients with persistent AF and HF

(most HFrEF) compared the effects of digoxin, carvedilol, and the combination.16 Combination therapy was associated with better rate control and symptom relief than monotherapy. The RATE-AF trial randomized 160 patients (≥60 years of age) with persistent AF and HF (81% with LVEF ≥50%) to digoxin or bisoprolol.17 No significant difference was noted in the primary endpoint of QOL at 6 months. Secondary outcomes, including natriuretic peptide levels, were significantly lower in the digoxin group, without a significant difference in resting heart rate at 12 months. Adverse effects were less common in the digoxin group. Observational and post hoc analyses have suggested an excess mortality with digoxin in patients with AF; however, residual confounding due to the use of digoxin in sicker patients may have a role.44 In patients with HF on digoxin chronically, post hoc analyses have suggested increased mortality rates and hospitalization with serum digoxin levels ≥1 ng/mL; levels <0.8 ng/mL in HF were associated with the lowest mortality rate, although the study was for therapy of HF and not AF.45 In the DAAF (Digitalis in Acute Atrial Fibrillation) trial of 239 patients (12% with HF), intravenous digoxin led to a significant decrease in heart rate at 2 hours compared with placebo. 5.	 In trials of critically ill patients, some of which

included a smaller proportion of patients with HF, intravenous amiodarone has been shown to be effective in controlling ventricular rates.18,19,46 In a randomized trial of 60 such patients (13 with HF), significant rate control was achieved with both intravenous diltiazem and intravenous amiodarone. However, intravenous diltiazem was associated with a significantly higher frequency of hypotension requiring discontinuation.19 In another retrospective study of 38 patients admitted to the intensive care unit (9 with HF), intravenous amiodarone was associated with a statistically significant decrease in ventricular rate without decrease in BP (and in some cases improved hemodynamics) compared with intravenous diltiazem and digoxin.18 Intravenous beta blockers may also cause hypotension and may not be tolerated in patients with HF and hemodynamic instability. Although less frequent, intravenous amiodarone can also be associated with hypotension, specifically with the intravenous bolus. The possibility of conversion to sinus rhythm with intravenous amiodarone and associated potential for thromboembolism, especially in patients with longer-standing AF not on anticoagulation, should factor into the risk-benefit decision when intravenous amiodarone is chosen for rate control. 6.	 Small RCTs of patients with medically refractory

AF and HF show that patients who undergo AVNA and conventional pacemaker implantation are less symptomatic and have improvements in QOL and exercise tolerance compared with subjects who are managed with medical rate control.20–22,47 A metaanalysis comparing outcomes with AVNA or medications showed, in 2 studies analyzing patients with reduced EF, a modest, yet significant +4% increase in EF in patients undergoing AVNA and RV pacing, while patients with normal EF at baseline did not show a significant change.48 A metaanalysis of 93 studies including 11 343 patients who underwent AVNA with either RV pacing or biventricular pacing showed periprocedural complications of arrhythmia, HF, and lead dislodgement in 2% to 2.5%,49 few long-term data, and worse outcomes in younger patients with reduced EF and RV pacing.49 Overall, these data showed improved mortality in patients with HF who are treated with cardiac resynchronization therapy (CRT), at the risk of increased device-related complications.49 The

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