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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 January 2, 2024 e97

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

EF in conduction system pacing compared with the mixed RV/BivP group (46.5%±14.2% to 51.9%±11.2%; P=0.02) in conduction system pacing and 36.4%±16.1% to 39.5%±16% (P=0.04) in RV/BiVP.34 A combined endpoint of time to death or HF hospitalization was reduced in the conduction system pacing group in >2 years of follow-up, but extrapolation is limited due to the observational and selected nature of the population and because the RV/BiVP group had lower EF and wider QRS at baseline.34

11 The nondihydropyridine calcium channel block-

ers—diltiazem and verapamil—are negative inotropic agents and may not be tolerated in patients with HFrEF. In the acute setting, limited data from 2 retrospective analyses suggest the potential for increased morbidity with the use of diltiazem in patients with HFrEF, including worsening HF, need for inotropic support, or acute kidney injury.57,58 In the chronic setting, diltiazem had no impact on mortality in a trial of patients with nonischemic cardiomyopathy.59 However, in the multicenter randomized MDPIT of patients postacute MI, HF and cardiac events (cardiac death or nonfatal reinfarction) were more frequent in the patients with LVEF <40% or pulmonary congestion who were randomized to diltiazem. Among those with a baseline EF of <40%, late HF appeared in 12% receiving placebo and 21% receiving diltiazem (P=0.004). Life table analysis in patients with an EF of <40% confirmed more frequent late HF in those taking diltiazem (P=0.0017). In addition, the diltiazemassociated increase in the frequency of late HF was progressively greater with decreasing baseline EF.36 This increase in late HF was not seen in patients with pulmonary congestion at baseline but an EF of ≥40%, suggesting the association of diltiazem-related late HF was present only in those with systolic LV dysfunction. 12.	 The ANDROMEDA37 study was a randomized,

double-blind placebo-controlled study that tested the hypothesis that dronedarone would reduce the rate of hospitalization due to HF and possibly reduce mortality by reducing the incidence of arrhythmic death. The study enrolled patients who were hospitalized with new or worsening HF and who had at least 1 episode of NYHA class III or IV HF (shortness of breath on minimal exertion or at rest). More than 40% of the patients had NYHA class II HF at baseline. The investigators reported that, contrary to the study’s hypothesis, mortality was higher in the dronedarone group compared to that in the placebo group (8.1% versus 3.8%; HR, 2.13 [95% CI, 1.07-4.25]; P=0.03). The excess mortality was principally associated with worsening HF. 10 AF AND SPECIFIC PATIENT GROUPS

10.1 Management of Early Onset AF, Including

Genetic Testing Recommendations for Management of Early Onset AF, Including Genetic Testing Referenced studies that support the recommendations are summarized in the Online Data Supplement. COR LOE Recommendations

2b B-NR 1 In patients with an onset of unexplained AF before

30 years of age, electrophysiological study to evaluate and treat reentrant supraventricular tachyarrhythmias with a targeted ablation may be reasonable because of the high prevalence of reentrant arrhythmias in this group.1–3

2b B-NR 2 In patents with an onset of AF before 45 years of

age without obvious risk factors for AF, referral for genetic counseling, genetic testing for rare pathogenic variants, and surveillance for cardiomyopathy or arrhythmia syndromes may be reasonable.4,5

Synopsis Young patients are less likely to develop AF or associated strokes compared with older populations. Consumer-driven use of wearable devices is increasing and can lead to the diagnosis of AF at a young age.6 In those <30 years of age, reentrant SVTs (atrioventricular nodal reentrant tachycardia and atrioventricular reentrant tachycardia) are found in about 25% of patients.1–3 Targeted ablation of the reentrant tachycardia is followed by resolution of AF episodes in most of these young patients. However, additional factors need to be taken into consideration in young patients who present with AF. Growing evidence suggests that, in addition to risk factors for AF present in older populations, young patients who develop AF may also harbor susceptibility for inherited ion channel and cardiomyopathic disorders,4 even in those with normal echocardiograms.5 In addition to the standard workup for newly diagnosed AF, genetic testing for rare pathogenic variation, advanced imaging modalities, and surveillance screening could detect otherwise occult cardiomyopathy. Recommendation-Specific Supportive Text 1.	 Two retrospective observational cohort studies

included patients with onset of AF before the age of 21 years2 and 30 years1 who underwent electrophysiological study to assess for reentrant SVTs. The former study found atrioventricular node reentry tachycardia or atrioventricular reentry tachycardia in 39% of patients and the latter in 24%. In both studies, after targeted ablation of the reentry tachycardia, patients were observed for recurrence of AF for a median of about 1.5 years. The former study reported no recurrences of AF, and the latter study reported that 86% remained free of atrial arrhythmias. In an additional prospective cohort study of patients referred for AF ablation who had inducible atrioventricular node reentry tachycardia,

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