Evaluation of organized atrial arrhythmias after cryptogenic stroke.

Background: Long-term rhythm monitoring to detect atrial fibrillation (AF) following a cryptogenic stroke (CS) is well established. However, the burden of organized atrial arrhythmias in this population is not well defined. Objective: The purpose of this study was to assess the incidence and risk factors for organized atrial arrhythmias in patients with CS. Methods: We evaluated all patients with CS who received an insertable cardiac monitor (ICM) between October 2014 and April 2020. All ICM transmissions categorized as AF, tachycardia, or bradycardia were reviewed. We evaluated the time to detection of organized AF and the combination of either organized atrial arrhythmia or AF. Results: A total of 195 CS patients with ICMs were included (51% men; mean age 66 ± 12 years; mean CHA2DS2-VASC score 4.6). Over mean follow-up of 18.9 ± 11.2 months, organized atrial arrhythmias lasting ≥30 seconds were detected in 45 patients (23%), of whom 62% did not have AF. Seventeen patients had both organized atrial arrhythmia and AF, and another 21 patients had AF only. Compared to those with normal left atrial size, patients with left atrial enlargement had a higher adjusted risk for development of atrial arrhythmias (mild left atrial enlargement: hazard ratio 1.99; 95% confidence interval 1.06-3.75; moderate/severe left atrial enlargement: hazard ratio 3.06; 95% confidence interval 1.58-5.92). Conclusion: Organized atrial arrhythmias lasting ≥30 seconds are detected in nearly one-fourth of CS patients. Two-thirds of these patients did not have AF. Further studies are required to evaluate the impact of organized atrial arrhythmias on recurrent stroke risk.

Predictors of nonpulmonary vein triggers for atrial fibrillation: A clinical risk score.

BACKGROUND: Targeting non-pulmonary vein triggers (NPVTs) after pulmonary vein isolation may reduce atrial fibrillation (AF) recurrence. Isoproterenol infusion and cardioversion of spontaneous or induced AF can provoke NPVTs but typically require vasopressor support and increased procedural time. OBJECTIVE: The purpose of this study was to identify risk factors for the presence of NPVTs and create a risk score to identify higher-risk subgroups. METHODS: Using the AF ablation registry at the Hospital of the University of Pennsylvania, we included consecutive patients who underwent AF ablation between January 2021 and December 2022. We excluded patients who did not receive NPVT provocation testing after failing to demonstrate spontaneous NPVTs. NPVTs were defined as non-pulmonary vein ectopic beats triggering AF or focal atrial tachycardia. We used risk factors associated with NPVTs with P <.1 in multivariable logistic regression model to create a risk score in a randomly split derivation set (80%) and tested its predictive accuracy in the validation set (20%). RESULTS: In 1530 AF ablations included, NPVTs were observed in 235 (15.4%). In the derivation set, female sex (odds ratio [OR] 1.40; 95% confidence interval [CI] 0.96-2.03; P = .080), sinus node dysfunction (OR 1.67; 95% CI 0.98-2.87; P = .060), previous AF ablation (OR 2.50; 95% CI 1.70-3.65; P <.001), and left atrial scar (OR 2.90; 95% CI 1.94-4.36; P <.001) were risk factors associated with NPVTs. The risk score created from these risk factors (PRE2SSS2 score; [PRE]vious ablation: 2 points, female [S]ex: 1 point, [S]inus node dysfunction: 1 point, left atrial [S]car: 2 points) had good predictive accuracy in the validation cohort (area under the receiver operating characteristic curve 0.728; 95% CI 0.648-0.807). CONCLUSION: A risk score incorporating predictors for NPVTs may allow provocation of triggers to be performed in patients with greatest expected yield.

Accuracy of symptoms and pulse checking for detecting atrial fibrillation following catheter ablation.

BACKGROUND: There is growing interest in the possibility of discontinuing oral anticoagulation following successful catheter ablation of atrial fibrillation (AF). However, it remains unknown whether patients can accurately detect arrhythmia recurrences following ablation. We therefore sought to characterize the accuracy of pulse checking and arrhythmia symptoms for the identification of AF following ablation. METHODS: This prospective cohort study included patients at the Hospital of the University of Pennsylvania with an insertable cardiac monitor (ICM) treated with catheter ablation for AF who recorded the results from minimum twice daily pulse checks and additionally with arrhythmia symptoms into a diary for 2 months following their procedure. Accuracy of this self-assessment protocol was determined by comparison to ICM-detected AF. RESULTS: A total of 55 patients (age 69 ± 8 years, 30 (55%) male, CHA2DS2VASc score 3.2 ± 1. 5) were included. Patients recorded a total of 5911 pulse checks, and there were 280 episodes of ICM-documented AF among 26 patients with an average duration of 2.5 ± 3.3 h. Among 362 episodes of patient-suspected AF, 134 correlated with ICM-identified AF (37% true positive rate). Of the 5549 pulse checks that did not identify AF, 196 correlated with ICM-identified AF (4% false negative rate). Twice daily pulse checking had a sensitivity of 47% and a specificity of 96% for identifying each episode of AF. CONCLUSIONS: Our data indicate that a strategy of pulse checks and symptom assessment is insufficient to identify all episodes of AF in many patients following catheter ablation.

Substrate and arrhythmia characterization using the multi-electrode Optrell mapping catheter for ventricular arrhythmia ablation-a single-center experience.

BACKGROUND: The use of a multi-electrode Optrell mapping catheter during ventricular tachycardia (VT) or premature ventricular complex (PVC) ablation procedures has not been widely reported. OBJECTIVES: We aim to describe the feasibility and safety of using the Optrell multipolar mapping catheter (MPMC) to guide catheter ablation of VT and PVCs. METHODS: We conducted a single-center, retrospective evaluation of patients who underwent VT or PVC ablation between June and November 2022 utilizing the MPMC. RESULTS: A total of 20 patients met the inclusion criteria (13 VT and 7 PVC ablations, 80% male, 61 ± 15 years). High-density mapping was performed in the VT procedures with median 2753 points [IQR 1471-17,024] collected in the endocardium and 12,830 points [IQR 2319-30,010] in the epicardium. Operators noted challenges in manipulation of the MPMC in trabeculated endocardial regions or near valve apparatus. Late potentials (LPs) were detected in 11 cases, 7 of which had evidence of isochronal crowding demonstrated during late annotation mapping. Two patients who also underwent entrainment mapping had critical circuitry confirmed in regions of isochronal crowding. In the PVC group, high-density voltage and activation mapping was performed with a median 1058 points [IQR 534-3582] collected in the endocardium. CONCLUSIONS: This novel MPMC can be used safely and effectively to create high-density maps in LV endocardium or epicardium. Limitations of the catheter include a longer wait time for matrix formation prior to starting point collection and challenges in manipulation in certain regions.

Intraoperative ultrasound-guided pectoral nerve blocks for cardiac implantable device procedures.

BACKGROUND: Pectoral nerve (PECs) blocks are established regional anesthesia techniques that can provide analgesia to the anterior chest wall. Although commonly performed preoperatively by anesthesiologists, the feasibility of electrophysiologist-performed PECs blocks from within cardiac implantable electronic device (CIED) pockets at the time of implantation has not been established. The objective of this study is to assess the feasibility of routine PECs blocks performed by the electrophysiologist from within the exposed device pocket at the time of CIED procedures. METHODS: Patients undergoing CIED procedures underwent a PECs I block (15 cc of 1% lidocaine/0.25% bupivacaine) injected between the pectoralis major and minor muscles guided by ultrasound placed in the device pocket, or PECs II block, which included a second injection (15 cc) between pectoralis minor and serratus anterior muscles. Postoperatively, pain was assessed on a numeric scale (0-10) at 1, 2, 4, and 24 h, and 2 weeks after the procedure. RESULTS: Among 20 patients (age 65 ± 16 years, 70% male, 55% with history of chronic pain), PECs I (75%) and PECs II (25%) blocks were performed. The procedures were de novo implantation (n = 17) or device revision (n = 3). The average pain score in the first 4 h was 0.4 ± 0.8 and 0.3 ± 0.6 at 24 h after the procedure. During the 24-h postoperative period, 4 patients received opioids. Two patients were discharged with opioids for pain unrelated to the procedure. CONCLUSIONS: Intraoperative PECs blocks can be feasibly performed from within an exposed pocket at the time of CIED procedures with minimal postoperative pain.

Cardioneuroablation for the treatment of ictal-associated cardiac asystole: case report and literature review.

Background: Ictal-associated bradyarrhythmia or asystole can be a manifestation of malignant seizure syndromes. In patients with ictal-associated hypervagotonia and asystole, cardioneuroablation may provide a promising alternative to permanent pacemaker implantation. Case summary: We present a case of a 47-year-old female with a 1.5-year history of ongoing uncontrolled seizures with multiple semiologies despite multiple antiepileptic drugs who had episodes of symptomatic severe sinus bradycardia (15-30 b.p.m.) and sinus pauses (15-16 s). She underwent a successful cardioneuroablation for ictal-induced asystole with complete resolution of bradyarrhythmias. Discussion: This case highlights the utility of cardioneuroablation in patient with ictal-induced cardiac bradyarrhythmia and asystole. Cardioneuroablation may be an approach to avoid permanent pacemakers in this population.

Identifying Origin of Nonpulmonary Vein Triggers Using 2 Stationary Linear Decapolar Catheters: A Novel Algorithm.

BACKGROUND: Targeting nonpulmonary vein triggers (NPVTs) of atrial fibrillation (AF) after pulmonary vein isolation can be challenging. NPVTs are often single ectopic beats with a surface P-wave obscured by a QRS or T-wave. OBJECTIVES: The goal of this study was to construct an algorithm to regionalize the site of origin of NPVTs using only intracardiac bipolar electrograms from 2 linear decapolar catheters positioned in the posterolateral right atrium (along the crista terminalis with the distal bipole pair in the superior vena cava) and in the proximal coronary sinus (CS). METHODS: After pulmonary vein isolation in 42 patients with AF, pacing from 15 typical anatomic NPVT sites was conducted. For each pacing site, the electrogram activation sequence was analyzed from the CS catheter (simultaneous/chevron/inverse chevron/distal-proximal/proximal-distal) and activation time (ie, CSCTAT) between the earliest electrograms from the 2 decapolar catheters was measured referencing the earliest CS electrogram; a negative CSCTAT value indicates the crista terminalis catheter electrogram was earlier, and a positive CSCTAT value indicates the CS catheter electrogram was earlier. A regionalization algorithm with high predictive value was defined and tested in a validation cohort with AF NPVTs localized with electroanatomic mapping. RESULTS: In the study patient cohort (71% male; 43% with persistent AF, 52% with left atrial dilation), the algorithm grouped with high precision (positive predictive value 81%-99%, specificity 94%-100%, and sensitivity 30%-94%) the 15 distinct pacing sites into 9 clinically useful regions. Algorithm testing in a 98 patient validation cohort showed predictive accuracy of 91%. CONCLUSIONS: An algorithm defined by the activation sequence and timing of electrograms from 2 linear multipolar catheters provided accurate regionalization of AF NPVTs to guide focused detailed mapping.

Utility of Very High-Output Pacing to Identify VT Circuits in Patients Manifesting Traditionally Inexcitable Scar.

BACKGROUND: Entrainment and pace mapping are used to identify critical components (CCs) of ventricular tachycardia (VT) circuits. In patients with dense myocardial scarring, VT circuits may elude capture at standard high pacing outputs (up to 10 mA at a 2-millisecond pulse width). OBJECTIVES: The purpose of this study was to assess the utility of very high-output pacing (V-HOP, 50 mA at 2 milliseconds) for identifying CCs of VT circuits after standard high pacing output failed to elicit capture in densely scarred myocardial tissue. METHODS: Our standard VT ablation approach included electroanatomic mapping for substrate characterization and entrainment and/or pace mapping to identify CCs of VT circuits. Patients that required V-HOP to capture sites of interest comprised the study cohort. Ablation endpoints were VT termination and noninducibility. RESULTS: Twenty-five patients (71 ± 10 years of age, all males) undergoing 26 VT ablations met the inclusion criteria. The mean left ventricular ejection fraction was 30% ± 14%, and 85% had ischemic cardiomyopathy. V-HOP was used to successfully entrain VT in 17 patients, yielding central isthmus sites in 10 and entrance/exit sites in 4. VT terminated with radiofrequency ablation at these sites in 15 patients. In 9 patients, V-HOP identified scar locations with a delayed exit. Acute procedural success was achieved in 24 patients without any adverse events. Over a follow-up period of 16 ± 21 months, 2 patients experienced VT recurrence requiring repeat ablation during which the same location was targeted successfully in 1 patient. CONCLUSIONS: In VT patients with a dense scar that is traditionally inexcitable, V-HOP can identify CCs of the re-entrant circuit and guide successful ablation.

Impact of Left Ventricular Papillary Muscle Ventricular Arrhythmia Ablation on Mitral Valve Function.

BACKGROUND: Although efficacious, catheter ablation (CA) of ventricular arrhythmias (VAs) originating from left ventricular (LV) papillary muscles (PAPs) has the potential to affect mitral valve (MV) function. OBJECTIVES: The aim of this study was to determine whether lesions delivered during CA of VAs from LV PAPs affected MV function. METHODS: Consecutive patients undergoing CA of LV PAP VAs from January 2015 to December 2020 in whom both preprocedural and postprocedural transthoracic echocardiography was performed were included. Radiofrequency ablation was performed with an irrigated-tip catheter with or without contact force sensing and intracardiac echocardiographic guidance. The PAPs were delineated into segments: tip, body, and base. Pre- and post-CA transthoracic echocardiograms were reviewed to assess MV regurgitation, which was graded 0 (none), 1 (mild), 2 (moderate), or 3 (severe). A change of ≥2 grades from baseline was considered significant. RESULTS: A total of 103 patients (mean age 63 ± 15 years, 78% men) were included. VAs were ablated from the anterolateral PAP in 35% (n = 36), posteromedial PAP in 55% (n = 57), and both PAPs in 10% (n = 10). Lesion distribution was as follows: PAP tip in 52 (50%), PAP base in 34 (33%), PAP body in 13 (13%), and entire PAP in 4 (4%). The mean number of lesions delivered was 16 ± 13 (median 14). Of 103 patients, 102 (99%) showed no change in MV function. CONCLUSIONS: Using intracardiac echocardiographic guidance, lesions can be safely delivered on various aspects of this structure without adverse impact on MV function.

Safety of Pill-in-the-Pocket Class 1C Antiarrhythmic Drugs for Atrial Fibrillation.

BACKGROUND: Guidelines recommend that initial trial of a "pill-in-the-pocket" (PIP) Class 1C antiarrhythmic drug (AAD) for cardioversion of atrial fibrillation (AF) be performed in a monitored setting because of the potential for adverse reactions. OBJECTIVES: This study sought to characterize real-world, contemporary use of the PIP approach, including the setting of initiation and incidence of adverse events. METHODS: This retrospective cohort study included all patients at the Hospital of the University of Pennsylvania treated with a PIP approach for AF between 2007 and 2020. RESULTS: A total of 273 patients (age 56 ± 13 years; 182 [67%] male; CHA2DS2VASc score 1.1 ± 1.2) took a first dose of PIP AAD. Flecainide was used in 151 (55%) and propafenone in 122 (45%). The first dose of PIP AAD was taken in a monitored setting in 167 (62%). Significant adverse events occurred in 7 patients (3%), 2 of whom had taken the dose in a monitored setting. Significant adverse events included unexplained syncope (1 of 7), symptomatic bradycardia/hypotension (4 of 7), and 1:1 atrial flutter (2 of 7). All occurred in patients taking 300 mg of flecainide (n = 4) or 600 mg of propafenone (n = 3). Electrical cardioversion was performed in 29 (11%) patients because of failure of the AAD to terminate AF. One patient required intravenous fluids and vasopressors for 2 hours because of persistent hypotension and bradycardia. Two patients required permanent pacemakers for bradycardia. The remaining patients required no intervention. CONCLUSIONS: Our data support the current recommendation to initiate PIP AAD in a monitored setting because of rare significant adverse reactions that can require urgent intervention.

Extra-cardiac BCAA catabolism lowers blood pressure and protects from heart failure.

Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protective in models of heart failure (HF). How protection occurs remains unclear, although a causative block in cardiac BCAA oxidation is widely assumed. Here, we use in vivo isotope infusions to show that cardiac BCAA oxidation in fact increases, rather than decreases, in HF. Moreover, cardiac-specific activation of BCAA oxidation does not protect from HF even though systemic activation does. Lowering plasma and cardiac BCAAs also fails to confer significant protection, suggesting alternative mechanisms of protection. Surprisingly, activation of BCAA catabolism lowers blood pressure (BP), a known cardioprotective mechanism. BP lowering occurred independently of nitric oxide and reflected vascular resistance to adrenergic constriction. Mendelian randomization studies revealed that elevated plasma BCAAs portend higher BP in humans. Together, these data indicate that BCAA oxidation lowers vascular resistance, perhaps in part explaining cardioprotection in HF that is not mediated directly in cardiomyocytes.

Rare genetic variants explain missing heritability in smoking.

Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.

Longitudinal electrocardiographic assessment in Brugada syndrome.

Background: The type 1 electrocardiographic (ECG) pattern diagnostic of Brugada syndrome (BrS) can be dynamic. Limited studies have rigorously evaluated the temporal stability of the Brugada ECG pattern. Objective: We sought to evaluate fluctuations of the Brugada pattern in serial resting ECGs from BrS patients managed within a large health care system. Methods: In our cohort of BrS patients with at least 2 standard, resting ECGs recorded on separate clinical encounters, we evaluated serial changes in the Brugada pattern and categorized patients into 1 of 3 groups: dynamic was defined as the presence of both type 1 and non-type 1 patterns in available ECGs; the provoked-only group was defined as having a non-type 1 Brugada pattern across resting ECGs; and the persistent group was defined as having a type 1 pattern on all ECGs. We also evaluated the clinical risk in this cohort according to the Shanghai risk score. Results: In 72 patients with BrS (mean age 46 ± 15 years, 69% male), 828 standard, resting ECGs were recorded over a median duration of 30.2 (interquartile range 6.3-68.1) months. The dynamic group comprised 50 (69% of the cohort) patients, the provoked-only group consisted of 17 patients (24% of the cohort), and the persistent group included 5 patients. No significant differences were detected in the total number of ECGs evaluated during the follow-up period between any of the groups. Only sinus node dysfunction and a prior cardiac arrest were associated with the persistent type 1 group. The majority of patients had a low annualized risk of lethal arrhythmic events. Conclusion: Most BrS patients have a dynamic Brugada pattern noted on longitudinal, resting ECGs. Expert consensus statements should provide clarity on the frequency of obtaining resting ECGs in patients suspected of having BrS during follow-up.

Utility of Prolonged Duration Endocardial Ablation for Ventricular Arrhythmias Originating From the Left Ventricular Summit.

OBJECTIVES: This study sought to explore whether prolonged duration (PD) radiofrequency ablation (RFA) from adjacent endocardial locations can improve catheter ablation (CA) outcomes of left ventricular summit (LVS) ventricular arrhythmias (Vas). BACKGROUND: CA of VAs originating from the LVS region can be challenging. METHODS: Patients undergoing CA of LVS VAs from January 1, 2015, to December 31, 2019, were included. Standard RFA approach involved incremental power titration (20-45 W) over 60-120 seconds with irrigated tip catheter to achieve 10%-12% impedance drop. Prolonged duration RFA involved similar power titration; however, lesion application was extended beyond 120 seconds (maximum 5 minutes). Lesions were confined to lowest aspect of aortic cusps and/or subvalvular LV outflow tract region (≤0.5 cm from the valve). Procedural success was defined as suppression of VA ≥30 minutes postablation and clinical success as no arrhythmia symptoms on follow-up and >80% reduction of VA burden on postprocedure monitor. RESULTS: This study included 102 patients (60±14 years old, 62% male): standard RFA in 80 and PD RFA in 38. Procedural success was achieved in 54 patients with standard and 32 patients with PD RFA (68% vs 84%; P = 0.05). Short-term clinical success was achieved in 48 patients (60%) with standard and 30 patients (79%) with PD RFA (P = 0.04). Two pericardial effusions occurred (1 in each group) and no steam pops were noted. Patients in whom standard RFA was successful were more likely to have R/S ratio >1 or absence of qS in lead I (odds ratio: 3.35; 95% CI: 1.20-9.35; P = 0.03). CONCLUSIONS: Prolonged duration RFA from adjacent endocardial locations is a safe and effective technique for successfully targeting challenging LVS VAs that fail standard RFA.

Characterization of the right ventricular substrate participating in postinfarction ventricular tachycardia.

BACKGROUND: The right ventricle (RV) is uncommonly implicated in postinfarction ventricular tachycardia (VT). The prevalence and features of the RV substrate participating in postinfarction VT are undefined. OBJECTIVES: The purpose of this study was to characterize critical right ventricular substrate (CRVS) involvement in patients with postinfarction VT. METHODS: We retrospectively reviewed 1279 patients with postinfarction VT undergoing catheter ablation at our center from January 2000 through May 2020. Cases with CRVS defined by conclusive demonstration of participation in VT with activation, entrainment, and/or pacemapping during sinus rhythm were identified. RESULTS: CRVS was identified in 27 of 1279 patients (2.1%): age 65 ± 13 years, 96% male, median left ventricular (LV) ejection fraction 25%, and 93% with left bundle branch block (LBBB) morphology VT. CRVS was identified by RV activation and/or entrainment mapping (n = 19) or by the presence of low-voltage abnormal electrograms with excellent pacemap for the targeted VT and noninducibility after ablation (n = 8). VT termination during RV ablation occurred in 15 patients. After median follow-up of 20 months (interquartile range 9-53 months) and median of 2 procedures (interquartile range 1-3), 22 of 27 patients (80%) had no VT recurrence and 11 (41%) died. CONCLUSION: The RV contains critical substrate elements of postinfarction VT in at least 2.1% of cases. RV mapping should be considered in cases in which LV mapping fails to demonstrate adequate targets, particularly in patients with LBBB morphology VT.