Faculty Bibliography

BACKGROUND:Prior studies have shown that addition of posterior wall isolation (PWI) may reduce atrial fibrillation recurrence in patients with persistent atrial fibrillation. No data on PWI in paroxysmal AF (pAF) patients with normal left atrial voltage is available, to date. OBJECTIVE:This study sought to evaluate the efficacy of PWI in addition to pulmonary vein isolation (PVI) in patients presenting with pAF and normal left atrial voltage. METHODS:Consecutive patient registry analysis was performed on all patients with pAF and normal left atrial voltage undergoing initial radiofrequency ablation from November 1, 2018 to November 15, 2019. Primary endpoint was recurrence of atrial arrhythmia including AF, atrial tachycardia (AT) or atrial flutter (AFL). RESULTS:A total of 321 patients were studied, 214 in the PVI group and 107 in the PWI+PVI group. Recurrence of any atrial arrhythmia occurred in 18.2% of patients in the PVI group and 16.8% in the PVI+PWI cohort (p=0.58). At one year, recurrence was 14.0% in the PVI group and 15.0% in the PWI+PVI group (p=0.96). There was a lower AT/AFL recurrence in the PVI+PWI group, not reaching significance (3.7% in the PWI+PVI group vs. 7.9% in PVI group, p=0.31). Need for carina lesions predicted recurrence in the PVI-only group. CONCLUSIONS:Addition of PWI to PVI in pAF patients undergoing their first ablation did not reduce the frequency of atrial arrhythmia recurrence. This warrants further study in a prospective trial. This article is protected by copyright. All rights reserved.

PURPOSE/OBJECTIVE:Catheter ablation procedures for atrial fibrillation (AF) were significantly curtailed during the peak of coronavirus disease 2019 (COVID-19) pandemic to conserve healthcare resources and limit exposure. There is little data regarding peri-procedural outcomes of medical procedures during the COVID-19 pandemic. We enacted protocols to safely reboot AF ablation while limiting healthcare resource utilization. We aimed to evaluate acute and subacute outcomes of protocols instituted for reboot of AF ablation during the COVID-19 pandemic. METHODS:Perioperative healthcare utilization and acute procedural outcomes were analyzed for consecutive patients undergoing AF ablation under COVID-19 protocols (2020 cohort; n=111) and compared to those of patients who underwent AF ablation during the same time period in 2019 (2019 cohort; n=200). Newly implemented practices included preoperative COVID-19 testing, selective transesophageal echocardiography (TEE), utilization of venous closure, and same-day discharge when clinically appropriate. RESULTS:Pre-ablation COVID-19 testing was positive in 1 of 111 patients. There were 0 cases ablation-related COVID-19 transmission and 0 major complications in either cohort. Pre-procedure TEE was performed in significantly fewer 2020 cohort patients compared to the 2019 cohort patients (68.4% vs. 97.5%, p <0.001, respectively) despite greater prevalence of persistent arrhythmia in the 2020 cohort. Same-day discharge was achieved in 68% of patients in the 2020 cohort, compared to 0% of patients in the 2019 cohort. CONCLUSIONS:Our findings demonstrate the feasibility of safe resumption of complex electrophysiology procedures during the COVID-19 pandemic, reducing healthcare utilization and maintaining quality of care. Protocols instituted may be generalizable to other types of procedures and settings.

BACKGROUND:More than 3 million cardiovascular implantable electronic devices (CIEDs) are implanted annually. There are minimal data regarding the timing of diagnosis of acute complications after implantation. It remains unclear whether patients can be safely discharged less than 24 hours postimplantation. OBJECTIVE:The purpose of this study was to determine the precise timing of acute complication diagnosis after CIED implantation and optimal timing for same-day discharge. METHODS:A retrospective cohort analysis of adults 18 years or older who underwent CIED implantation at a large urban quaternary care medical center between June 1, 2015, and March 30, 2020, was performed. Standard of care included overnight observation and chest radiography 6 and 24 hours postprocedure. Medical records were reviewed for the timing of diagnosis of acute complications. Acute complications included pneumothorax, hemothorax, pericardial effusion, lead dislodgment, and implant site hematoma requiring surgical intervention. RESULTS:A total of 2421 patients underwent implantation. Pericardial effusion or cardiac tamponade was diagnosed in 13 patients (0.53%), pneumothorax or hemothorax in 19 patients (0.78%), lead dislodgment in 11 patients (0.45%), and hematomas requiring surgical intervention in 5 patients (0.2%). Of the 48 acute complications, 43 (90%) occurred either within 6 hours or more than 24 hours after the procedure. Only 3 acute complications identified between 6 and 24 hours required intervention during the index hospitalization (0.12% of all cases). CONCLUSION/CONCLUSIONS:Most acute complications are diagnosed either within the first 6 hours or more than 24 hours after implantation. With rare exception, patients can be considered for discharge after 6 hours of appropriate monitoring.

Background/UNASSIGNED:There is limited information on the long-term outcomes of ICDs in patients with inherited arrhythmia syndromes. Methods/UNASSIGNED:Prospective registry study of inherited arrhythmia patients with an ICD. Incidence of therapies and complications were measured as 5-year cumulative incidence proportions and analyzed with the Kaplan-Meier method. Incidence was compared by device indication, diagnosis type and device type. Cox-regression analysis was used to identify predictors of appropriate shock and device complication. Results/UNASSIGNED:123 patients with a mean follow up of 6.4 ± 4.8 years were included. The incidence of first appropriate shock was 56.52% vs 24.44%, p < 0.05 for cardiomyopathy and channelopathy patients, despite similar ejection fraction (61% vs 60%, p = 0.6). The incidence of first inappropriate shock was 13.46% vs 56.25%, p < 0.01 for single vs. multi-lead devices. The incidence of first lead complication was higher for multi-lead vs. single lead devices, 43.75% vs. 17.31%, p = 0.04. Patients with an ICD for secondary prevention were more likely to receive an appropriate shock than those with primary prevention indication (HR 2.21, CI 1.07-4.56, p = 0.03). Multi-lead devices were associated with higher risk of inappropriate shock (HR 3.99, CI 1.27-12.52, p = 0.02), with similar appropriate shock risk compared to single lead devices. In 26.5% of patients with dual chamber devices, atrial sensing or pacing was not utilized. Conclusion/UNASSIGNED:The rate of appropriate therapies and ICD complications in patients with inherited arrhythmia is high, particularly in cardiomyopathies with multi-lead devices. Risk-benefit ratio should be carefully considered when assessing the indication and type of device in this population.

Rhythm control strategies in patients with esophageal varices and atrial arrhythmias pose a unique challenge. The left atrium should be imaged for a thrombus prior to attempting cardioversion or ablation, but the presence of varices is a relative contraindication for transesophageal echocardiography. We present a safe, novel technique of evaluating for left atrial thrombus with simultaneous transesophageal echocardiography and esophagogastroduodenoscopy using slim probes in a patient with large, high-risk esophageal varices, and symptomatic atrial flutter with rapid ventricular rates despite medical therapy.

OBJECTIVE:Fibroblast growth factor homologous factors (FHFs) are brain and cardiac sodium channel-binding proteins that modulate channel density and inactivation gating. A recurrent de novo gain-of-function missense mutation in the FHF1(FGF12) gene (p.Arg52His) is associated with early infantile epileptic encephalopathy 47 (EIEE47; Online Mendelian Inheritance in Man database 617166). To determine whether the FHF1 missense mutation is sufficient to cause EIEE and to establish an animal model for EIEE47, we sought to engineer this mutation into mice. METHODS:protein. RESULTS:mice prior to seizure. SIGNIFICANCE/CONCLUSIONS:1.6 functional axis underlying altered brain sodium channel gating in epileptic encephalopathy.

OBJECTIVES/OBJECTIVE:This study sought to analyze high-frequency catheter excursion in relation to lesion quality markers in 20 consecutive patients undergoing first-time radiofrequency (RF) ablation for paroxysmal atrial fibrillation (AF). BACKGROUND:Ablation therapy for AF requires the delivery of durable lesions. The extent to which lesion sequence, catheter spatial stability, and anatomic location influence lesion formation during RF ablation of AF is not well understood. METHODS:Three-dimensional spatial excursion of the ablation catheter sampled at 60 Hz during pre-specified pairs of RF lesions was extracted from the CARTO3 System (Biosense Webster Inc., Irvine, California) and analyzed by using custom-developed MATLAB software (MathWorks, Natick, Massachusetts) to define precise catheter spatial stability during RF ablation. Ablation parameters including bipolar electrogram amplitude reduction, impedance decline and transmurality-associated unipolar electrogram (TUE) as evidence of lesion transmurality during lesion placement were recorded and analyzed. RESULTS:We collected 437,760 position data points during lesion placement. Ablation catheter spatial stability and lesion formation parameters varied considerably by anatomic location. Lesions placed immediately had similar bipolar electrogram amplitude reduction, smaller impedance decline, but higher likelihood of achieving TUE compared to delayed lesions. Greater catheter spatial stability correlated with lesser impedance decline. CONCLUSIONS:Lesion sequence, ablation catheter spatial stability, and anatomic location are important modifiers of RF lesion formation. Lesions placed immediately are more likely to exhibit TUE. Greater ablation catheter stability is associated with lesser impedance decline but greater likelihood of TUE.

BACKGROUND:The prolongation in QT interval typically observed following cardiac arrest is considered to be multifactorial and induced by external triggers such as hypothermia therapy and exposure to antiarrhythmic medications. OBJECTIVE:To evaluate the corrected QT interval (QTc) dynamics in the first 10 days following cardiac arrest with respect to the etiology of arrest, hypothermia and QT prolonging medications. METHODS:We enrolled 104 adult survivors of cardiac arrest, where daily ECG was available for at least 3 days. We followed their QT and QRS intervals for the first 10 days of hospitalization. We used both Bazett and Fridericia formulas to correct for heart rate. For patients with QRS < 120 we analyzed the QTc interval (n = 90) and for patients with QRS > 120 ms we analyzed the JTc (n = 104) vs. including only the narrow QRS samples (n = 89). We stratified patients by 3 groups: (1) presence of ischemic heart disease (IHD) (2) treatment with hypothermia protocol, and (3) treatment with QTc prolonging medications. Additionally, genetic information obtained during hospitalization was analyzed. RESULTS:QTc and JTc intervals were significantly prolonged in the first 6 days. Maximal QTc/JTc prolongation was observed in day 2 (QTcB = 497 ± 55). There were no differences in daily QTc/JTc and QRS intervals in the first 2 days post arrest between patients with or without hypothermia induction but such difference. All subgroups demonstrated significantly prolonged QTc/JTc interval regardless of the presence of IHD, hypothermia protocol or QTc prolonging medication exposure. Our results were consistent for both Bazetts' and Frediricia correction and for any QRS duration. Prolongation of the JTcB beyond 382 ms after day 3 predicted sustained QTc/JTc prolongation beyond day 6 with an ROC of 0.78. CONCLUSIONS:QTc/JTc interval is significantly and independently prolonged post SCA, regardless of known QT prolonging triggers. Normalization of the QTc post cardiac arrest should be expected only after day 6 of hospitalization. Assessment of the QTc for adjudication of the etiology of arrest or for monitoring the effect of QT prolonging medications may be unreliable.

Background: Elevated intracardiac pressure due to heart failure induces electrical and structural remodeling in the left atrium (LA) that begets atrial myopathy and arrhythmias. The underlying molecular pathways that drive atrial remodeling during cardiac pressure overload are poorly defined. The purpose of this study is to characterize the response of the ETV1 signaling axis in the LA during cardiac pressure overload in humans and mouse models and explore the role of ETV1 in atrial electrical and structural remodeling. Methods: We performed gene expression profiling in 265 left atrial samples from patients who underwent cardiac surgery. Comparative gene expression profiling was performed between two murine models of cardiac pressure overload, transverse aortic constriction (TAC) banding and Angiotensin II (AngII) infusion, and a genetic model of Etv1 cardiomyocyte-selective knockout (Etv1^f/fMlc2a^Cre/+). Results: Using the Cleveland Clinic biobank of human LA specimens, we found that ETV1 expression is decreased in patients with reduced ejection fraction. Consistent with its role as an important mediator of the Neuregulin-1 (NRG1) signaling pathway and activator of rapid conduction gene programming, we identified a direct correlation between ETV1 expression level and NRG1, ERBB4, SCN5A, and GJA5 levels in human LA samples. In a similar fashion to heart failure patients, we showed that left atrial ETV1 expression is downregulated at the RNA and protein levels in murine pressure overload models. Comparative analysis of LA RNA-seq datasets from TAC and AngII treated mice showed a high Pearson correlation, reflecting a highly ordered process by which the LA undergoes electrical and structural remodeling. Cardiac pressure overload produced a consistent downregulation of ErbB4, Etv1, Scn5a, and Gja5 and upregulation of profibrotic gene programming, which includes Tgfbr1/2, Igf1, and numerous collagen genes. Etv1^f/fMlc2a^Cre/+ mice displayed atrial conduction disease and arrhythmias. Correspondingly, the LA from Etv1^f/fMlc2a^Cre/+ mice showed downregulation of rapid conduction genes and upregulation of profibrotic gene programming, whereas analysis of a gain-of-function ETV1 RNA-seq dataset from neonatal rat ventricular myocytes transduced with Etv1 showed reciprocal changes. Conclusions: ETV1 is downregulated in the LA during cardiac pressure overload, contributing to both electrical and structural remodeling.