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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 January 2, 2024 e65

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

Small RCTs of AVNA and right ventricular pacing (RVP) have shown improvements in symptoms and QOL compared with medical rate control alone but found no significant differences in EF or other measures of cardiac performance.3,14 Progression to persistent AF is described in many patients with previously paroxysmal AF after AVNA.15,16 Antiarrhythmic drugs reduce the transition to permanent AF but do not improve QOL or echocardiographic parameters, and patients treated with antiarrhythmic drugs have more episodes of HF and hospitalizations.17 Early concerns regarding AVNA included risks for device-related complications, sudden cardiac death, and worsened HF. Deaths due to malignant arrhythmias have been nearly eradicated by programming higher lowerrate pacing in the early postprocedure period.1,2,18 The risks of HF may be ameliorated by non-RVP strategies, but data are limited in patients who do not have HF before AVNA.19 Overall, long-term data on outcomes after AVNA are limited, and no evidence supports AVNA as first-line therapy.9

Recommendation-Specific Supportive Text 1.	 Early observational studies showed a concerning incidence of sudden death after AVNA in 3% to 7% of patients.20,21 This immediate postprocedural risk results from ventricular fibrillation (VF) predominantly due to bradycardia, QT prolongation, and heterogeneity of repolarization. Initiation of VF is often pause dependent or occurs during a relatively slow pacing rate.18 Deaths due to malignant arrhythmias have been minimized by current protocols specifying higher lower-rate pacing in patients after AVNA in the early postprocedure period.1,2,18 Subsequent lower rate adjustment is performed over the course of several weeks. 2.	 AVNA and pacemaker implantation provide safe

and effective rate control in the fraction of patients with AF who cannot be effectively rate controlled with medical therapy3,4,22 and in whom sinus rhythm has failed or is not deemed to be effective. A meta-analysis of 6 small RCTs of studies comparing AVNA and pacemaker versus medical therapy or medical therapy with pacemaker including 323 subjects with paroxysmal or persistent AF showed improvement in symptoms and QOL in the AVNA group.6 No differences in survival, stroke, hospitalization, EF, or exercise capacity were found. There was no effect of AVNA on all-cause mortality in a pooled analysis.6 Nonrandomized studies have shown improvement in a range of clinical outcomes5 in addition to data showing improved EF in patients with suspected tachycardia-related cardiomyopathy after AVNA.23 These favorable findings in nonrandomized studies are likely subject to the placebo effect of device implantation. Early and late complication rates are not inconsequential, specifically in young patients in view of the risk of pacemaker-mediated cardiomyopathy, and longterm follow-up data are scant.9

3 Although few studies concerning AVNA and pac-

ing report complication rates for the pacemaker implant, the overall risk of lead dislodgement or failure is approximately 2%, and many operators perform both AVNA and pacemaker implant during the same procedure.9,13,24 Practice patterns vary, however, and a European survey indicated up to 80% of operators will choose to perform AVNA 1 to 3 months after pacemaker implantation to reduce risk of adverse outcome due to early lead dislodgement.25 In the prospective FOLLOWPACE registry from 23 centers in the Netherlands, lead dislodgment was the most frequent lead-related complication, occurring in 3.3% of patients within the first 2 months of implant.7 Relevant to the older age population usually undergoing AVNA, a pooled patient-level analysis of 4814 subjects from CTOPP (Canadian Trial of Physiologic Pacing), UKPACE (United Kingdom pacing and cardiovascular events), and Danish pacing trials—designed to compare pacemaker implantation complication rates in age <75 years versus age ≥75 years— found a higher risk of early complications in those age ≥75 years (5% versus 3%), driven by a higher rate of lead dislodgement (2%) and pneumothorax (1.6%).8 If AVNA and pacing are performed concomitantly, ideally, leads should be placed first to ensure adequate lead function. 4.	 HF after AVNA is attributed to the deleterious

effects of RVP,26 and risk is correlated with baseline cardiac function.9 The PAVE (Post AV Nodal Ablation Evaluation) trial compared outcomes in patient with persistent AF and uncontrolled rates undergoing AVNA and RVP with AVNA and biventricular pacing (BiVP) and found an improvement in 6-minute walk test and EF, but benefit was predominantly seen in subjects with EF <45% or New York Heart Association (NYHA) class II to III HF at baseline.27 Not all patients appear to be at high risk of HF after AVNA and RVP.28 Because the benefit is less and the risk of complications is higher in BiVP compared with conventional pacing, RVP is advised in patients with preserved EF undergoing AVNA.19 Conduction system pacing of the His bundle

or left bundle area offers promise to reduce the risk of RVP-induced cardiomyopathy and improve outcomes. Early studies have justifiably focused on patients with HF undergoing AVNA, and limited data are available in patients with preserved EF and no HF diagnosis.27 His bundle pacing with

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