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CLINICAL STATEMENTS AND GUIDELINES

January 2, 2024 Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 e64

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

significant difference in resting heart rate between the 2 groups at 12 months. Adverse effects were less common in the digoxin group. A large metaanalysis of 75 studies and approximately 620 000 patients found a significantly increased risk of death in digoxin users overall but, when limited to 7 RCTs (∼8400 patients), no difference in mortality rate was observed between digoxin or placebo— of note, these 7 RCTs in the subanalysis were in patients with concomitant HF.9 A post hoc sensitivity analysis assessing the impact of digoxin on mortality in patients with HF and concomitant AF found no impact on overall mortality in patients taking digoxin, most with HFrEF. 4.	 MDPIT (Multicenter Diltiazem Postinfarction Trial)

demonstrated an association of worsening HF in patients with a recent MI, with LV dysfunction randomized to diltiazem. Among those with a baseline EF of <40%, late HF appeared in significantly more patients receiving diltiazem compared with placebo (21% versus 12%; P=0.004). Life table analysis in patients with an EF of <40% confirmed significantly more frequent late HF in those taking diltiazem. In addition, the diltiazem-associated rise in the frequency of late congestive heart failure (CHF) was progressively greater with increasingly severe decrements in baseline EF.10

5 The safety and efficacy of dronedarone, origi-

nally designed as an antiarrhythmic to maintain sinus rhythm in patients with AF, was addressed in several seminal trials.18–20 PALLAS (Palbociclib Collaborative Adjuvant Study) was designed to investigate whether dronedarone would reduce major vascular events or hospitalizations in patients with permanent AF. The benefits of dronedarone in patients with permanent AF were initially suggested from the ERATO (Efficacy and Safety of Dronedarone for the Control of ventricular rate during atrial fibrillation) trial, which showed a significant reduction in the ventricular response for patients with paroxysmal and permanent AF in the 24-hour setting, which were carried forward in a 6-month follow-up.12 PALLAS randomized approximately 3200 patients with permanent AF at high risk for adverse events. The trial was terminated early, because of the strong signal for harm in 43 patients receiving dronedarone versus 19 receiving placebo, namely death (13/21 due to arrhythmia), stroke, and hospitalization for HF.12

7.3 Atrioventricular Nodal Ablation (AVNA)

Recommendations for AVNA Referenced studies that support the recommendations are summarized in the Online Data Supplement. COR LOE Recommendations

1 C-LD 1 In patients with AF and a persistently rapid

ventricular response who undergo AVNA, initial pacemaker lower rate programming should be 80 to 90 bpm to reduce the risk of sudden death.1,2

2a B-R 2 In patients with AF and uncontrolled rapid ventricular

response refractory to rate-control medications (who are not candidates for or in whom rhythm control has been unsuccessful), AVNA can be useful to improve symptoms and QOL.3–6

1 B-NR 3 In patients with AF who are planned to undergo

AVNA, implantation of a pacemaker before the ablation (ie, before or same day of ablation) is recommended to ensure adequacy of the pacing leads before performing ablation.7–9

2b C-LD 4.	 In patients with AF with normal EF undergoing AVNA,

conduction system pacing of the His bundle10–13 or left bundle area12,13 may be reasonable.

Synopsis AVNA provides ventricular rate control effectively and without medications yet creates dependence on pacing.3 Consideration of the consequences of lifelong pacemaker implantation, particularly with respect to age and comorbidities, is central to decision-making regarding benefit.

Figure 18. AF Long-Term Rate Control. Colors correspond to Table 2. AF indicates atrial fibrillation; LVEF, left ventricular ejection fraction; and NDCC, nondihydropyridine calcium channel blocker.

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