Siontis, Konstantinos C.

Abstract Atrial fibrillation (AF) is increasingly diagnosed early, close to its first occurrence due to: (i) increased public awareness with self-screening; (ii) health care initiatives including population screening and opportunistic case finding; and (iii) increased use and surveillance of implantable cardiac devices. At its onset, AF is often low burden, and cardiovascular co-morbidities may be absent or at an early stage. Thus, the management of recent-onset AF has become an issue of growing importance. Professional guidelines have traditionally focused on anticoagulant thromboprophylaxis, generally recommending a cautious approach to rhythm control, and priority has been given to rate control to alleviate symptoms. In recent guidelines, the importance of managing lifestyle and co-morbidities has increased. The AF-SCREEN collaboration proposes that a vigorous approach to active management of recent-onset AF may be warranted. This includes addressing co-morbidities and promoting healthy lifestyles to prevent the emergence or progression of AF and associated cardiovascular disease, as well as the initiation of active rhythm control ± anticoagulation to prevent AF-related morbidity and mortality, including stroke and heart failure (HF). Intuitively, intervention early after AF onset would be beneficial since lifestyle and co-morbidity management, plus rhythm control and anticoagulation, are important contributors to improved outcomes in patients with established AF, but robust evidence is lacking for recent-onset AF. There is a delicate balance between achieving favourable outcomes such as preventing strokes, HF and AF progression vs the complications and potential adverse effects of interventions. Given the serious long-term consequences, innovative approaches are necessary to determine the value and risks of initiating active therapy very early in the course of AF. More data are needed to guide the best management of recent-onset AF, bearing AF burden in mind. Long-term studies using large national databases linked to electronic medical records and rhythm monitoring devices offer excellent opportunities. Shorter-term studies focusing on reducing AF burden to slow AF progression and studies focusing on outcomes such as HF could be used in both randomized clinical trials and observational cohort studies.

Abstract Background Although a rhythm control strategy is associated with an overall better prognosis in atrial fibrillation (AF), current guidelines suggest that only highly selected asymptomatic patients may be considered candidates for AF catheter ablation. Therefore, this study aimed to evaluate the association between symptom status and clinical outcomes in patients with AF. Methods A comprehensive search of Medline, the Cochrane Library, and Scopus was conducted up until September 30, 2024. Study selection, data extraction, and quality assessment were performed independently by three reviewers. Random-effects meta-analyses were used to pool the evidence. Results A total of 36 studies, comprising 217,850 participants, were included. Frequentist analysis revealed no significant difference between symptomatic and asymptomatic AF patients in terms of all-cause mortality [hazard ratio (HR) = 0.97, 95% confidence interval (CI)= (0.80, 1.17)], cardiovascular mortality (HR= 1.04, 95% CI= [0.72, 1.49]), thromboembolism (HR= 1.06, 95% CI= [0.87, 1.28]), stroke (HR= 1.06, 95% CI= [0.84, 1.34]), hospitalization (HR= 1.34, 95% CI= [0.89, 2.02]), and myocardial infarction (HR= 0.98, 95% CI= [0.70, 1.36]). However, symptomatic patients exhibited a 33% increased risk of new-onset heart failure (HR= 1.33, 95% CI= [1.19, 1.49]) and a 30% reduced risk of progression to permanent AF (HR= 0.70, 95% CI= [0.54, 0.89]). Bayesian analysis produced similar results, although the association between symptom status and new-onset heart failure was not statistically significant [HR = 1.27, 95% credible interval (CrI)= (0.76, 1.93); Bayes factor (BF10)= 1.2]. Symptomatic patients had higher odds of receiving antiarrhythmic drugs (odds ratio [OR]= 1.64, 95% CI= [1.33, 2.03]) and ablation therapy (OR= 1.47, 95% CI= [1.06, 2.05]) compared to their asymptomatic counterparts. Conclusions The risk of major clinical outcomes does not significantly differ between AF patients with and without symptoms. However, asymptomatic patients have a higher risk of progressing to permanent AF.

ABSTRACT Background Obesity is an important risk factor associated with atrial fibrillation (AF). The impact of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on recurrent AF among patients undergoing catheter ablation is not well described. Objective This study aimed to evaluate the effect of GLP‐1 RA on the recurrence of AF among obese patients after catheter ablation. Methods Utilizing the TriNetX research network, we identified patients aged over 18 with obesity (BMI ≥ 30) who underwent AF ablation from January 1, 2015, to December 1, 2022, using Current Procedural Terminology codes. Patients were categorized based on their baseline GLP‐1 RA use. Through propensity‐score matching, each cohort comprised 1558 patients. The primary outcome encompassed a composite of cardioversion, initiation of new antiarrhythmic drug (AAD) therapy, or redo AF ablation. Additional outcomes during the 12‐month follow‐up included AF readmission, heart failure readmissions, readmissions due to ischemic stroke, and mortality, with a separate analysis done for patients with BMI > 40. Results GLP‐1 RA use in patients with obesity undergoing AF ablation was linked to a significantly reduced risk of cardioversion, new AAD therapy, and the need for redo AF ablation (hazard ratio [HR] 0.72 [0.65–0.80]; p < 0.001). At 12 months, individuals on GLP‐1 agonists exhibited a lower likelihood of mortality (HR 0.61 [0.40–0.93]; p < 0.001). Although all other secondary outcomes were lower in the GLP‐1 RA group, there was no significant difference in ischemic stroke between the groups. These results were consistent among patients with BMI > 40, although apart from ischemic stroke, there was no difference in mortality between the two groups. Conclusion The utilization of GLP‐1 RA in individuals with obesity is linked to a decreased likelihood of arrhythmia recurrence following AF ablation, leading to a reduced requirement for cardioversion, AAD therapy, or redo AF ablation.

Abstract Aims Catheter ablation is commonly performed in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) for management of ventricular arrhythmias (VAs). The impact of catheter ablation on cardiac function is unknown. The aim is to assess the impact of catheter ablation for VAs on cardiac function in patients with ARVC. Methods and results This retrospective study included consecutive patients with ARVC who underwent catheter ablation for VAs. Cardiac and valvular functions were assessed on pre- and post-procedure cardiac imaging. The severities of tricuspid regurgitation, pulmonic regurgitation, right ventricular (RV) enlargement, and RV systolic dysfunction was graded as absent (=0), mild (=1), mild-moderate (=2), moderate (=3), moderate-severe (=4), or severe (=5). Thirty-four patients were included. Median age at the time of ablation was 49 [inter-quartile range (IQR), 23] years, and 10 (29%) patients were female. After a median follow-up of 1 (IQR, 0) day, 11 (34%) patients had worsening RV function, and 4 (12%) patients had worsening left ventricular ejection fraction (LVEF) &gt;5%. Five (15%) patients required inotropic support. After a median follow-up of 6.5 (IQR, 6.4) months, 20 (59%) patients had repeat transthoracic echocardiograms. Among patients with worsening RV function post-ablation, one-sixth (17%) had improvement in the RV function at follow-up. In contrast, among patients who had an acute drop in LVEF post-ablation, two-thirds (67%) had improvement at follow-up. Conclusion Right ventricular dysfunction following catheter ablation in patients with ARVC is common, affecting one-third of patients. Patients undergoing catheter ablation of VAs should be counselled on the potential negative impact of ablation on cardiac function.

ABSTRACT Background Incident atrial functional mitral regurgitation (AFMR) is associated with mortality. Transcatheter edge‐to‐edge repair (TEER) has shown effectiveness in improving MR and symptoms in AFMR, but previous studies lacked comparison to conservative management. We aimed to study the association of AFMR severity and mitral TEER with symptoms, heart failure hospitalizations (HFH) and all‐cause mortality in moderate/severe AFMR. Methods Consecutive adults with moderate/severe AFMR managed conservatively or with TEER 2010−2023 were identified retrospectively. To ensure similar technique in evaluation in the two groups, variables were obtained from the closest transthoracic echocardiogram before TEER in the TEER group. In addition to multivariable analysis, the association of TEER (vs. conservative management) with HFH and mortality was assessed using propensity‐score matched analyses; the propensity score was based on age, sex, EuroSCORE II, effective regurgitant orifice area, integrative MR severity, and NYHA class III/IV (vs. I/II). Results Among 230 patients with moderate/severe AFMR [mean age 77; 56% females], 46 were managed with TEER. Severe (vs. moderate) AFMR was independently associated with baseline NYHA class III/IV (multivariable OR 2.18 [95% CI 1.13−4.26]) and HFH [multivariable HR 2.75 (95% CI 1.25−6.03)] but not mortality ( p = 0.26). TEER improved MR to ≤ moderate in 93% but was not associated with lower HFH or death rates versus conservative management on multivariable or matched analysis. However, 1‐year NYHA improved more with TEER versus conservative management in patients with baseline NYHA class III/IV (62% vs. 27%, p = 0.03). Rhythm control was associated with improved survival (HR 0.38 [0.15−0.98]). Conclusions AFMR severity was associated with symptoms and HFH but not mortality. MR severity and NYHA class improved with TEER, but the association of TEER with HF hospitalizations or death remains unproven. Randomized studies are needed to evaluate the potential role of TEER and rhythm control on outcomes in AFMR.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy marked by increased left ventricular wall thickness, leading in some cases to left ventricular outflow tract (LVOT) obstruction, heart failure, and arrhythmias. Mavacamten, a selective allosteric inhibitor of cardiac myosin, has demonstrated benefits in improving hemodynamics and reducing LVOT obstruction. However, its impact on arrhythmic burden remains unclear, with reports of early atrial fibrillation (AF) risk contrasting with long-term reductions in arrhythmias. This study assesses the temporal patterns of Holter-detected arrhythmias in HCM patients treated with mavacamten. Methods: This retrospective study included HCM patients from three Mayo Clinic sites. Baseline demographic, clinical, and echocardiographic data were collected. Holter monitoring was performed at baseline, short-term (<6 months), and long-term (>6 months) follow-up. Arrhythmic events, including premature atrial contractions (PACs), premature ventricular contractions (PVCs), and supraventricular tachycardia (SVT), were analyzed using standardized rates per 24 h. Statistical comparisons utilized the Wilcoxon signed-rank test. Results: Twenty-seven patients (56% female, median age 66 years) were included. PACs, PVCs, and SVT duration transiently but not significantly increased at short-term follow-up but returned to baseline at long-term follow-up. No sustained or high-risk ventricular arrhythmias were observed. Conclusions: Mavacamten is associated with transient arrhythmic fluctuations early in treatment, followed by stabilization. These findings support its long-term electrophysiological safety and underscore the need for early rhythm monitoring. Further research should explore its role in arrhythmic risk stratification in HCM patients.

Abstract Advancements in machine learning and computing methods have given new life and great excitement to one of the most essential diagnostic tools to date—the electrocardiogram (ECG). The application of artificial intelligence‐enabled ECG (AI‐ECG) has resulted in the ability to identify electrocardiographic signatures of conventional and unique variables and pathologies, giving way to tremendous clinical potential. However, what these AI‐ECG models are detecting that the human eye is missing remains unclear. In this article, we highlight some of the recent developments in the field and their potential clinical implications, while also attempting to shed light on the physiologic and pathophysiologic features that enable these models to have such high diagnostic yield. © 2022 American Physiological Society. Compr Physiol 12:3417‐3424, 2022.