Faculty Bibliography

BACKGROUND:Identifying nearfield and farfield signals is critical to mapping and ablating cardiac arrhythmias. This assessment is qualitative, depending on the "sharpness" of pulmonary vein (PV) electrograms. Electrogram peak frequency (PF) analysis is hypothesized to be a quantitative measure of signal proximity. OBJECTIVE:To confirm if PF defines nearfield versus farfield electrical signals and if it can be used during ablation to establish pulmonary vein isolation (PVI). METHODS:We created a cohort of 30 patients with AF undergoing PVI. Left atrial and PV maps of PF were generated before and after PVI. In the first 10 patients with paroxysmal AF (cohort 1), a cutoff value was selected to predict nearfield versus farfield signals. This cutoff was validated in a cohort of 10 patients with paroxysmal AF (cohort 2) and a cohort of 10 patients with persistent AF (cohort 3). RESULTS:PF was lower in farfield electrograms than nearfield electrograms. A PF cutoff of 300 Hz had a sensitivity of 93.2% (95% CI 81.3% - 98.6%) in cohort 1, 90.0% (95% CI 76.3 - 97.2) in cohort 2, and 98.6% (95% CI 90.1 - 99.7%) in cohort 3 for differentiating farfield from nearfield electrograms. The specificity was 100.0% (95% CI 98.2% - 100.0%) and the AUC was 0.99 (95% CI 0.97 - 1.00) in all patients. CONCLUSIONS:We confirmed the hypothesis that PF distinguishes nearfield from farfield electrograms. PF analysis improves the recognition of PV isolation. Mapping and ablation strategies utilizing PF should be pursued to improve ablation outcomes.

OBJECTIVES/OBJECTIVE:Assess the characteristics and management of patients with LAA thrombus despite compliance with oral anticoagulation (OAC). BACKGROUND:Atrial fibrillation guidelines consider 4 weeks of uninterrupted OAC sufficient to avoid transesophageal echocardiography to rule out left atrial appendage thrombus. However, some patients may exhibit persistent thrombus despite compliance with OAC. METHODS:Clinical history, management, and outcomes were reviewed for patients with LAA thrombus on preprocedural TEE presenting for an AF related procedure between 2021 and 2024. RESULTS:Sixty-five (1.8%) of 3653 preprocedural TEEs exhibited LAA thrombus. OAC compliance of at least 4 week was documented in 39 (60%) of these patients, including Apixaban 64%, Rivaroxaban 23%, Warfarin 8%, Dabigatran 5%. Two of these patients (3%) experienced an embolic event and 8 (12%) died during the follow up period. Resolution of LAA thrombus was documented in 12/32 patients, 6 who switched to Dabigatran, 2 to Eliquis, 1 to Warfarin, and 3 remained on Eliquis. LAA-occlusion was successfully performed in seven patients with persistent LAA thrombus. CHADS-VASc 3 or greater, HFrEF, or valvular AF were present in 37/39 of these patients. CONCLUSION/CONCLUSIONS:For 3653 patients who underwent Preprocedural TEE, 39 exhibited LAA thrombus despite compliance with OAC. Switching OAC or maintaining the same agent for longer period of time resolved the thrombus in 31% of cases. LAA-O was effective in cases where the thrombus did not resolve. Patients with non-valvular AF, compliance with OAC > 4 weeks, CHADS-VASc ≤ 2, and normal EF exhibited the lowest probability for not having a thrombus on TEE.

BACKGROUND:Left atrial appendage occlusion (LAA-O) with Amulet and Watchman FLX are approved for reducing stroke risk in patients with atrial fibrillation when oral anticoagulation is not tolerated. Real world clinical outcomes reported along with imaging data are needed to help clinicians choose between these two technologies and manage device-related complications. METHODS:The study retrospectively analyzed clinical, transesophageal (TEE), and available computed tomography (CT) data from 364 FLX and 292 Amulet procedures performed at an academic medical center over a 4-year period. RESULTS:were included. TTE LAA-orifice area correlated with CT-derived measurements. There were more late pericardial effusions for Amulet (3.1%) compared to FLX (0.3%), though the majority were conservatively managed. Mean procedure times were similar (FLX 64 ± 24, Amulet 65 ± 21 min) as were the rates of device related thrombus (FLX 1% and Amulet 1.4%). Clinically relevant peridevice leak (PDL) on follow-up TEE imaging was greater for FLX (16%) compared to Amulet (10%). Combined AF ablation-LAA-occlusion procedures exhibited lower rates of PDL and late pericardial effusions compared to solo procedures. CONCLUSIONS:Based on retrospective analysis, an initial strategy with Watchman FLX in patients with favorable LAA anatomy would reduce the risk of late pericardial effusions at the expense of a higher rate of clinically relevant PDL compared to Amulet. Combined AF ablation and LAA-O procedures exhibit less PDL.

Ventricular arrhythmias (VA) are a major cause of morbidity and mortality in patients with coronary artery disease (CAD). Current guidelines recommend revascularization of significant CAD to improve survival in patients with ventricular fibrillation (VF), polymorphic ventricular tachycardia (VT), or those who are post-cardiac arrest. However, revascularization is not recommended for CAD patients with suspected scar-mediated monomorphic VT. There is a paucity of data detailing the utility of revascularization in reducing VA in CAD patients who do not present with acute coronary syndrome (ACS) and are not immediately post-cardiac arrest, which is the focus of this review. Medline, Scopus, and the Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies addressing this question. Studies that included patients presenting with ACS or those who were immediately post-cardiac arrest at the time of revascularization were excluded. In total, five studies comprising 2663 patients were reviewed.

Underlying normal cardiac rhythm is a network of transcriptional programs that ensures normal impulse initiation and impulse propagation. We highlight work that shows how alterations in individual transcriptional networks can lead to increased arrhythmia susceptibility, cardiomyopathy, and congenital heart defects. Lastly, we focus on a study that leverages transcription factor biology to therapeutically modulate heart rhythm.

BACKGROUND:Recent evidence suggests atrial fibrillation (AF) causes cardiomyopathy due to remodeling driven by both irregular rate and rhythm. Atrial fibrillation (AF) ablation in patients with reduced ejection fraction (EF) ≤ 35% has been shown to improve EF and mortality. It is unknown whether the benefits of AF ablation among patients with reduced EF are affected by the degree of pre-ablation rate control. OBJECTIVES/OBJECTIVE:To evaluate AF ablation echocardiographic outcomes for patients who have EF ≤ 35% with varying degrees of pre-ablation rate control. METHODS:Single-center, retrospective study of patients with EF ≤ 35% undergoing first-time ablation of persistent AF. Primary analyses evaluated the degree to which pre-ablation rate control impacted echocardiographic outcomes. Rates of EF recovery to > 35% were compared at three different cutoffs: 110 bpm, 90 bpm, and 70 bpm. A linear regression analysis was then performed to evaluate whether baseline heart rate (HR) predicted change in EF. RESULTS: = 0.05, p = 0.07). CONCLUSIONS:Catheter ablation of persistent AF in patients with reduced EF frequently resulted in recovery in EF > 35%, irrespective of pre-ablation achieved rate control. While patients with HR > 70 bpm experienced a greater improvement in EF compared to those ≤ 70 bpm, patients with baseline HR below this target still experienced significant EF improvements. Further investigation into irregularity-mediated cardiomyopathy is warranted.

BACKGROUND:Combined catheter ablation (CA) with percutaneous left atrial appendage closure (LAAC) may produce comprehensive treatment for atrial fibrillation (AF) whereby rhythm control is achieved and stroke risk is reduced without the need for chronic oral anticoagulation. However, the efficacy and safety of this strategy is still controversial. METHODS:This meta-analysis was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Medline, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. The risk of bias was assessed using the Modified Newcastle-Ottawa scale and Cochrane risk of bias tool. Eligible studies reported outcomes in patients with AF who underwent combined CA and LAAC vs CA alone. Studies performing CA without pulmonary vein isolation were excluded. RESULTS:Eight studies comprising 1878 patients were included (2 RCT, 6 observational). When comparing combined CA and LAAC vs CA alone, pooled results showed no difference in arrhythmia recurrence (risk ratio (RR) 1.04; 95% confidence interval (CI) 0.82-1.33), stroke or systemic embolism (RR 0.78; 95% CI 0.27-2.22), or major periprocedural complications (RR 1.28; 95% CI 0.28-5.89). Total procedure time was shorter with CA alone (mean difference 48.45 min; 95% CI 23.06-74.62). CONCLUSION/CONCLUSIONS:Combined CA with LAAC for AF is associated with similar rates of arrhythmia-free survival, stroke, and major periprocedural complications when compared to CA alone. A combined strategy may be as safe and efficacious for patients at moderate to high risk for bleeding events to negate the need for chronic oral anticoagulation.

BACKGROUND:Genetic testing is a cornerstone in the assessment of many cardiac diseases. However, variants are frequently classified as variants of unknown significance, limiting the utility of testing. Recently, the DeepMind group (Google) developed AlphaMissense, a unique artificial intelligence-based model, based on language model principles, for the prediction of missense variant pathogenicity. We aimed to report on the performance of AlphaMissense, accessed by VarCardio, an open web-based variant annotation engine, in a real-world cardiovascular genetics center. METHODS AND RESULTS/RESULTS:<0.001). Genotype-phenotype concordance was highly aligned using VarCard.io predictions, at 95.9% (95% CI, 92.8-97.9) concordance rate. For 109 variants classified as pathogenic, likely pathogenic, benign, or likely benign by ClinVar, concordance with VarCard.io was high (90.5%). CONCLUSIONS:AlphaMissense, accessed via VarCard.io, may be a highly efficient tool for cardiac genetic variant interpretation. The engine's notable performance in assessing variants that are classified as variants of unknown significance in ClinVar demonstrates its potential to enhance cardiac genetic testing.

BACKGROUND:Many patients with mildly to moderately reduced left ventricular ejection fraction (LVEF) who require permanent pacemaker (PPM) implantation do not have a concurrent indication for implantable cardioverter-defibrillator (ICD) therapy. However, the risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in this population is unknown. OBJECTIVE:The aim of this study was to describe the risk of VT/VF after PPM implantation in patients with mildly to moderately reduced LVEF. METHODS:Retrospective analysis was performed of 243 patients with LVEF between 35% and 49% who underwent PPM placement and did not meet indications for an ICD. The primary end point was occurrence of sustained VT/VF. Competing risks regression was performed to calculate subhazard ratios for the primary end point. RESULTS:Median follow-up was 27 months; 73% of patients were male, average age was 79 ± 10 years, average LVEF was 42% ± 4%, and 70% were New York Heart Association class II or above. Most PPMs were implanted for sick sinus syndrome (34%) or atrioventricular block (50%). Of 243 total patients, 11 (4.5%) met the primary end point of VT/VF. Multivessel coronary artery disease (CAD) was associated with significantly higher rates of VT/VF, with a subhazard ratio of 5.4 (95% CI, 1.5-20.1; P = .01). Of patients with multivessel CAD, 8 of 82 (9.8%) patients met the primary end point for an annualized risk of 4.3% per year. CONCLUSION:Patients with mildly to moderately reduced LVEF and multivessel CAD undergoing PPM implantation are at increased risk for the development of malignant ventricular arrhythmias. Patients in this population may benefit from additional risk stratification for VT/VF and consideration for upfront ICD implantation.