Machine learning for prediction of ventricular arrhythmia episodes from intracardiac electrograms of automatic implantable cardioverter-defibrillators.

BACKGROUND: Despite effectiveness of the implantable cardioverter-defibrillator (ICD) in saving patients with life-threatening ventricular arrhythmias (VAs), the temporal occurrence of VA after ICD implantation is unpredictable. OBJECTIVE: The study aimed to apply machine learning (ML) to intracardiac electrograms (IEGMs) recorded by ICDs as a unique biomarker for predicting impending VAs. METHODS: The study included 13,516 patients who received Biotronik ICDs and enrolled in the CERTITUDE registry between January 1, 2010, and December 31, 2020. Database extraction included IEGMs from standard quarterly transmissions and VA event episodes. The processed IEGM data were pulled from device transmissions stored in a centralized Home Monitoring Service Center and reformatted into an analyzable format. Long-range (baseline or first scheduled remote recording), mid-range (scheduled remote recording every 90 days), or short-range predictions (IEGM within 5 seconds before the VA onset) were used to determine whether ML-processed IEGMs predicted impending VA events. Convolutional neural network classifiers using ResNet architecture were employed. RESULTS: Of 13,516 patients (male, 72%; age, 67.5 ± 11.9 years), 301,647 IEGM recordings were collected; 27,845 episodes of sustained ventricular tachycardia or ventricular fibrillation were observed in 4467 patients (33.0%). Neural networks based on convolutional neural networks using ResNet-like architectures on far-field IEGMs yielded an area under the curve of 0.83 with a 95% confidence interval of 0.79-0.87 in the short term, whereas the long-range and mid-range analyses had minimal predictive value for VA events. CONCLUSION: In this study, applying ML to ICD-acquired IEGMs predicted impending ventricular tachycardia or ventricular fibrillation events seconds before they occurred, whereas midterm to long-term predictions were not successful. This could have important implications for future device therapies.

Incidence and Outcomes of New-Onset Right Bundle Branch Block Following Transcatheter Aortic Valve Replacement.

BACKGROUND: The incidence and prognosis of right bundle branch block (RBBB) following transcatheter aortic valve replacement (TAVR) are unknown. Hence, we sought to characterize the incidence of post-TAVR RBBB and determine associated risks of permanent pacemaker (PPM) implantation and mortality. METHODS: All patients 18 years and above without preexisting RBBB or PPM who underwent TAVR at US Mayo Clinic sites and Mayo Clinic Health Systems from June 2010 to May 2021 were evaluated. Post-TAVR RBBB was defined as new-onset RBBB in the postimplantation period. The risks of PPM implantation (within 90 days) and mortality following TAVR were compared for patients with and without post-TAVR RBBB using Kaplan-Meier analysis and Cox proportional hazards modeling. The risks of PPM implantation (within 90 days) and mortality following TAVR were compared for patients with and without post-TAVR RBBB using Kaplan-Meier analysis and Cox proportional hazards modeling. RESULTS: Of 1992 patients, 15 (0.75%) experienced new RBBB post-TAVR. There was a higher degree of valve oversizing among patients with new RBBB post-TAVR versus those without (17.9% versus 10.0%; P=0.034). Ten patients (66.7%) with post-TAVR RBBB experienced high-grade atrioventricular block and underwent PPM implantation (median 1 day; Q1, 0.2 and Q3, 4), compared with 268/1977 (13.6%) without RBBB. Following propensity score adjustment for covariates (age, sex, balloon-expandable valve, annulus diameter, and valve oversizing), post-TAVR RBBB was significantly associated with PPM implantation (hazard ratio, 8.36 [95% CI, 4.19-16.7]; P<0.001). No statistically significant increase in mortality was seen with post-TAVR RBBB (hazard ratio, 0.83 [95% CI, 0.33-2.11]; P=0.69), adjusting for age and sex. CONCLUSIONS: Although infrequent, post-TAVR RBBB was associated with elevated PPM implantation risk. The mechanisms for its development and its clinical prognosis require further study.

Anatomy of the Ventricular Outflow Tracts: An Electrophysiology Perspective.

Outflow tract ventricular arrhythmias are the most common type of idiopathic ventricular arrhythmia. A systematic understanding of the outflow tract anatomy improves procedural efficacy and enables electrophysiologists to anticipate and prevent complications. This review emphasizes the three-dimensional spatial relationships between the ventricular outflow tracts using seven anatomical principles. In turn, each principle is elaborated on from a clinical perspective relevant for the practicing electrophysiologist. The developmental anatomy of the outflow tracts is also discussed and reinforced with a clinical case.

Catheter Ablation of Atrial Fibrillation in Adult Congenital Heart Disease: Procedural Characteristics and Outcomes.

BACKGROUND: The outcomes of catheter ablation for atrial fibrillation in adults with congenital heart disease are not well described. METHODS: In a retrospective study of adult patients with congenital heart disease who underwent catheter ablation for atrial fibrillation between 2000 and 2020 at Mayo Clinic, procedural characteristics and outcomes were collected. The primary outcomes were atrial arrhythmia (AA) recurrence following a 3-month blanking period and repeat ablation. An arrhythmia clinical severity score was assessed pre- and post-ablation based on the duration of arrhythmia episodes, symptoms, cardioversion frequency, and antiarrhythmic drug use. RESULTS: One hundred forty-five patients (age, 57±12 years; 28% female; 63% paroxysmal atrial fibrillation) underwent 198 ablations with a median follow-up of 26 months (interquartile range, 14-69). One hundred ten, 26, and 9 patients had simple, moderate, and complex congenital heart disease, respectively. All patients underwent pulmonary vein isolation, and non-pulmonary vein targets were ablated in 79 (54%). AA recurrence at 12 months was 37% (95% CI, 29%-45%). On univariate analysis, increasing left atrial volume index was associated with higher odds of AA recurrence (odds ratio, 1.03 [1.00-1.06] per 1 mL/m2 increment; P=0.05). Noninducibility of atrial flutter was predictive of decreased odds of AA recurrence (odds ratio, 0.43 [0.21-0.90]; P=0.03). A second ablation was performed in 43 patients after a median of 20 (interquartile range, 8-37) months. Arrhythmia clinical severity scores improved following ablation, reflecting a decrease in symptoms, cardioversions, and antiarrhythmic drugs. CONCLUSIONS: Catheter ablation of atrial fibrillation is feasible and effective in patients with adult congenital heart disease and reduces symptoms. Recurrence of AA frequently requires repeat ablation.

Case report: A case of perinodal atrial tachycardia and review of the relevant clinical anatomy surrounding the retroaortic node.

A 70-year-old female presented with incessant supraventricular tachycardia that was refractory to metoprolol and sotalol. ECG revealed a narrow complex tachycardia with a rate of 163 beats per minute with a short RP relationship. She had salvos of atrial tachycardia which led to a severe reduction in ejection fraction as noted on echocardiography and hemodynamic instability. An electrophysiological study was performed, and findings suggested this to be an atrial tachycardia with earliest activation in the perinodal area. Radiofrequency ablation was carried out along the septum and associated structures to surround this region including the right atrium, non-coronary sinus of Valsalva, and the left atrium (anterior wall outside of the right superior pulmonary vein) to isolate this area and surround the focus with ablation lesions. The patient has done well post-procedure and continues to do well without any recurrence on low-dose flecainide at 8 months.

Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Cancer.

Background: The prevention of stroke in patients with atrial fibrillation (AF) and cancer is challenging because patients are at increased bleeding and thrombotic risk. Objectives: The authors sought to assess left atrial appendage occlusion (LAAO) as a safe and effective strategy for reducing stroke at no increased bleeding risk in cancer patients with AF. Methods: We reviewed patients with nonvalvular AF who underwent LAAO at Mayo Clinic sites from 2017 to 2020 and identified those who had undergone prior or current treatment for cancer. We compared the incidence of stroke, bleeding, device complications, and death with a control group who underwent LAAO without malignancy. Results: Fifty-five patients were included; 44 (80.0%) were male, and the mean age was 79.0 ± 6.1 years. The median CHA2Ds2-VASc score was 5 (Q1-Q3: 4-6), with 47 (85.5%) having a prior bleeding event. Over the first year, ischemic stroke occurred in 1 (1.4%) patient, bleeding complications in 5 (10.7%) patients, and death in 3 (6.5%) patients. Compared with controls who underwent LAAO without cancer, there was no significant difference in ischemic stroke (HR: 0.44; 95% CI: 0.10-1.97; P = 0.28), bleeding complication (HR: 0.71; 95% CI: 0.28-1.86; P = 0.19), or death (HR: 1.39; 95% CI: 0.73-2.64; P = 0.32). Conclusions: Within our cohort, LAAO in cancer patients was achieved with good procedural success and offered a reduction in stroke at no increased bleeding risk similar to noncancer patients.

The subtle tine: Asymptomatic Micra perforation incidentally discovered during cardiac surgery.

A 70-year-old woman with longstanding persistent atrial fibrillation underwent Micra leadless pacemaker implantation and atrioventricular nodal ablation. No postprocedural complications were noted. She subsequently underwent surgical mitral valve replacement 4 years later. During the surgery, Micra tine perforation of the right ventricular free wall was seen. No device revision was performed due to her asymptomatic status and stable pacemaker position/function. Pericardial effusion is a known complication of Micra implantation. The incidence of tine perforation is unknown as many patients may be asymptomatic. The clinical consequences regarding adverse events, device functionality, and explantation/extraction risk profile remain to be determined.

Association of Spontaneous Coronary Artery Dissection With Atrial Arrhythmias.

The co-morbidities and long-term complications of spontaneous coronary artery dissection (SCAD) are incompletely understood. This study investigated the association of atrial arrhythmias (AA), defined as atrial fibrillation and atrial flutter, with SCAD in a patient registry and population-based cohort. This observational study was performed in 2 parts. The first was a retrospective study reviewing patients diagnosed with AA in the Mayo Clinic SCAD Registry. The second was a population-based, case-control study to assess AA in patients with SCAD compared with age- and gender-matched controls. Of 1,214 patients in the Mayo Clinic SCAD Registry, 45 patients (3.7%) with SCAD were identified with an AA. A total of 8 of those patients (17.8%) had a pre-SCAD AA; 20 (44.4%) had a peri-SCAD AA; and 17 (37.8%) had a post-SCAD AA. The univariate analysis did not reveal significant associations with traditional cardiovascular risk factors. In the population-based cohort, 5 patients with SCAD (4%) and 4 controls (1%) developed an AA before the date of SCAD for each patient (odds ratio 4.5, 95% confidence interval [CI] 1.05 to 19.0, p = 0.04). A total of 5 patients with SCAD (4%) and 3 controls (1%) developed an AA in the 10 years after SCAD (hazard ratio 6.3, 95% CI 1.2 to 32.8, p = 0.03). A subgroup of patients with SCAD experienced AA before and after SCAD. Patients with a history of SCAD were more likely to develop AA in the next 10 years than were age- and gender-matched healthy controls.

Sinus arrest in a p.Arg160X-DSP-positive patient without evidence of desmoplakin-mediated cardiomyopathy: a case report.

Background: Pathogenic/Likely pathogenic variants in DSP-encoded desmoplakin are strongly associated with arrhythmogenic cardiomyopathy (ACM). However, their contribution towards sinus node dysfunction has not been well-delineated. Case summary: A 74-year-old man with a pathogenic variant of DSP-encoded desmoplakin (c.478C >T; p.Arg160X) but no evidence of ACM presented with one episode of syncope in the setting of a gastrointestinal illness. Workup including echocardiography, cardiac magnetic resonance imaging, and Holter monitor did not show evidence of ACM or significant arrhythmias. One month later, he experienced several closely-spaced episodes of syncope associated with long sinus pauses and sinus arrest documented on telemetry. He underwent urgent dual chamber pacemaker implantation, during which a ventricular programmed stimulation study was performed and was negative for sustained ventricular arrhythmias. His syncopal episodes resolved and he had no recurrent events on three-month follow-up. Discussion: As highlighted here, DSP-encoded desmoplakin pathogenic/Likely pathogenic variants may contribute to isolated sinus node dysfunction. This clinical link should be further explored in larger studies involving patients with DSP variants.

Bipolar Electroporation Across the Interventricular Septum: Electrophysiological, Imaging, and Histopathological Characteristics.

BACKGROUND: Pulsed electric field (PEF) ablation is an emerging modality for the treatment of cardiac arrhythmias. Data regarding effects on the interventricular septum are limited, and the optimal delivery protocol and electrode configuration remain undefined. OBJECTIVES: This study sought to evaluate the electrophysiological, imaging, and histological characteristics of bipolar direct-current PEF delivered across the interventricular septum. METHODS: PEF was applied between identical solid-tip ablation catheters positioned on either side of the septum in a chronic canine model. Intracardiac and surface electrophysiological data were recorded following delivery. In 4 animals, cardiac magnetic resonance (CMR) was performed early (6 ± 2 days) and late (30 ± 2 days) postablation. After 4 weeks of survival, cardiac specimens were sectioned for histopathological analysis. RESULTS: In 8 canines, PEF was delivered in 27 separate septal sites (45 ± 17 J/site) with either microsecond or nanosecond PEF. Acute complications included transient complete atrioventricular block in 5 animals (63%) after delivery at the anterobasal septum, with right bundle branch block persisting in 3 (38%). Ventricular fibrillation occurred in 1 animal during microsecond but not nanosecond PEF. Postprocedural CMR showed prominent edema and significant left ventricular systolic dysfunction, which recovered with late imaging. At 4 weeks, 36 individual well-demarcated lesions were demonstrated by CMR and histopathology. Lesion depth measured by histology was 2.6 ± 2.1 mm (maximum 10.9 mm and near transmural). CONCLUSIONS: Bipolar PEF ablation of the interventricular septum is feasible and can produce near transmural lesions. Myocardial stunning, edema, and conduction system injury may occur transiently. Further studies are required to optimize safe delivery and efficacious lesions.

Novel insights into the substrate involved in maintenance of ventricular fibrillation: results from continuous multipolar mapping in a canine model.

BACKGROUND: While the triggers for ventricular fibrillation (VF) are well-known, the substrate required for its maintenance remains elusive. We have previously demonstrated dynamic spatiotemporal changes across VF from electrical induction of VF to asystole. Those data suggested that VF drivers seemed to reside in the distal RV and LV. However, signals from these areas were not recorded continuously. The aim of this study was to map these regions of significance with stationary basket electrodes from induction to asystole to provide further insights into the critical substrate for VF rhythm sustenance in canines. METHODS: In six healthy canines, three multipolar basket catheters were positioned in the distal right ventricle (RV), RV outflow tract, and distal left ventricle (LV), and remained in place throughout the study. VF was induced via direct current application from an electrophysiologic catheter. Surface and intracardiac electrograms were recorded simultaneously and continuously from baseline, throughout VF, and until asystole, in order to get a complete electrophysiologic analysis of VF. Focused data analysis was also performed via two defined stages of VF: early VF (immediately after induction of VF to 10 min) and late VF (after 10 min up to VF termination and asystole). RESULTS: VF was continuously mapped for a mean duration of 54 ± 9 min (range 42-70 min). Immediately after initiation of VF in the early phase, the distal LV region appeared to drive the maintenance of VF. Towards the terminal stage of VF, the distal RV region appeared to be responsible for VF persistence. In all canines, we noted local termination of VF in the LV, while VF on surface ECG continued; conversely, subsequent spontaneous termination of VF in the RV was associated with termination of VF on surface ECG into a ventricular escape rhythm. Continuous mapping of VF showed trends towards an increase in peak-to-peak ventricular electrogram cycle length (p = 0.06) and a decrease in the ventricular electrogram amplitude (p = 0.06) after 40 min. Once we could no longer discern surface QRS activity, we demonstrated local ventricular myocardial capture in both the RV and LV but could not reinitiate sustained VF despite aggressive ventricular burst pacing. CONCLUSIONS: This study describes the evolution of VF from electrical initiation to spontaneous VF termination without hemodynamic support in healthy canines. These data are hypothesis-generating and suggest that critical substrate for VF maintenance may reside in both the distal RV and LV depending on stage of VF. Further studies are needed to replicate these findings with hemodynamic support and to translate such findings into clinical practice. Ventricular fibrillation maintenance may be dependent on critical structures in the distal RV. ECG: electrocardiogram; LV: left ventricle; RV: right ventricle; RVOT: right ventricular outflow tract; VF: ventricular fibrillation.

Direct Oral Anticoagulant Versus Warfarin After Left Atrial Appendage Closure With WATCHMAN: Updated Systematic Review and Meta-analysis.

In the pivotal WATCHMAN trials, warfarin was used for post-procedural anticoagulation in the first 45 days after left atrial appendage closure. We aimed to investigate the efficacy and safety of direct oral anticoagulant (DOAC) versus warfarin after WATCHMAN. We performed a literature search of 5 electronic databases to identify studies comparing DOAC with warfarin after WATCHMAN. We pooled outcomes for the efficacy (thromboembolism, device-related thrombus [DRT], peridevice leak [PDL] >5 mm) and safety endpoints (bleeding, mortality). Thromboembolism was defined as ischemic stroke, transient ischemic attack, or systemic embolism. We included 10 cohort studies with 2,440 patients, of whom 1,397 (57.3%) received DOAC. Concerning periprocedural outcomes (within 7 days following implantation), DOAC was associated with a reduction in major bleeding (Risk ratio [RR] 0.32; 95% confidence interval [CI] 0.11-0.92) compared with warfarin, without significant differences in all bleeding (RR 0.46; 95% CI 0.15-1.42) and thromboembolism (RR 0.93; 95% CI 0.21-4.16). On first follow-up transesophageal echocardiography, DRT (RR 0.79; 95% CI 0.39-1.60) and PDL>5 mm (RR 0.44; 95% CI 0.16-1.20) were comparable among groups. With a mean follow-up of 1.5-12 months, DOAC was associated with reductions in major bleeding (RR 0.52; 95% CI 0.30-0.89) and all bleeding (RR 0.38; 95% CI 0.25-0.58) compared with warfarin. The outcomes of thromboembolism (RR 0.79; 95% CI 0.36-1.73) and all-cause mortality (RR 0.49; 95% CI 0.19-1.28) were not significantly different between the 2 groups. Following WATCHMAN implantation, DOAC was associated with reductions in major bleeding and all bleeding compared with warfarin at mid-term follow-up. The outcomes of thromboembolism, all-cause mortality, DRT, and PDL >5 mm were comparable among groups.

Ventricular nanosecond pulsed electric field delivery using active fixation leads: a proof-of-concept preclinical study.

BACKGROUND: Mid-myocardial ventricular arrhythmias are challenging to treat. Cardiac electroporation via pulsed electric fields (PEFs) offers significant promise. We therefore tested PEF delivery using screw-in pacemaker leads as proof-of-concept. METHODS: In 5 canine models, we applied nanosecond PEF (pulse width 300 ns) across the right ventricular (RV) septum using a single lead bipolar configuration (n = 2) and between two leads (n = 3). We recorded electrograms (EGMs) prior to, immediately post, and 5 min after PEF. Cardiac magnetic resonance imaging (cMRI) and histopathology were performed at 2 weeks and 1 month. RESULTS: Nanosecond PEF induced minimal extracardiac stimulation and frequent ventricular ectopy that terminated post-treatment; no canines died with PEF delivery. With 1 lead, energy delivery ranged from 0.64 to 7.28 J. Transient ST elevations were seen post-PEF. No myocardial delayed enhancement (MDE) was seen on cMRI. No lesions were noted on the RV septum at autopsy. With 2 leads, energy delivery ranged from 56.3 to 144.9 J. Persistent ST elevations and marked EGM amplitude decreases developed post-PEF. MDE was seen along the septum 2 weeks and 1 month post-PEF. There were discrete fibrotic lesions along the septum; pathology revealed dense connective tissue with < 5% residual cardiomyocytes. CONCLUSIONS: Ventricular electroporation is feasible and safe with an active fixation device. Reversible changes were seen with lower energy PEF delivery, whereas durable lesions were created at higher energies. Central illustration: pulsed electric field delivery into ventricular myocardium with active fixation leads.