Distinct Substrates of Idiopathic Ventricular Fibrillation Revealed by Arrhythmia Characteristics on Implantable Cardioverter-Defibrillator.

BACKGROUND: Idiopathic ventricular fibrillation (IVF) can be associated with undetected distinct conditions such as microstructural cardiomyopathic alterations (MiCM) or Purkinje (Purk) activities with structurally normal hearts. OBJECTIVE: This study sought to evaluate the characteristics of recurrent VF recorded on implantable defibrillator electrograms, associated with these substrates. METHODS: This was a multicenter collaboration study. At 32 centers, we selected patients with an initial diagnosis of IVF and recurrent arrhythmia at follow-up without antiarrhythmic drugs, in whom mapping demonstrated Purk or MiCM substrate. We analyzed variables related to previous ectopy, sinus rate preceding VF, trigger, and initial VF cycle lengths. Logistic regression with cross validation was used to evaluate the performance of criteria to discriminate Purk or MiCM substrates. RESULTS: Among 95 patients (35 women, age 35 ± 11 years) meeting the inclusion criteria, IVF was associated with MiCM in 41 and Purk in 54 patients. A total of 117 arrhythmia recurrences including 91% VF were recorded on defibrillator. Three variables were mostly discriminant. Sinus tachycardia (≤570 ms) was more frequent in MiCM (35.9% vs 13.4%, P = 0.014) whereas short-coupled (<350 ms) triggers were most frequent in Purk-related VF (95.5% vs 23.1%, P = 0.001), which also had shorter VFCLs (182 ± 15 ms vs 215 ± 24 ms, P < 0.001).The multivariable combination provided the highest prediction (accuracy = 0.93 ± 0.05, range 0.833-1.000), discriminating 81% of IVF substrates with a high probability (>80%). Ectopy were inconsistently present before VF. CONCLUSIONS: Characteristics of arrhythmia recurrences on implantable cardioverter- defibrillator provide phenotypic markers of the distinct and hidden substrates underlying IVF. These findings have significant clinical and genetic implications.

Result of the left bundle branch area pacing data collection registry, an international multicenter study of conduction system pacing with a Tendril STS 2088 stylet-driven lead.

INTRODUCTION: Left bundle branch area (LBBA) pacing (LBBAP) has been proposed as an alternative therapy option in patients indicated for cardiac pacing to treat bradycardia or heart failure. The aim of the study was to evaluate the safety and effectiveness of LBBAP in patients implanted with a Tendril 2088 stylet-driven lead. METHODS: The international retrospective data collection registry included 11 sites from 5 countries globally. Patients with attempted implants of the Tendril lead in the LBBA were followed for at least 6 months post the implant attempt. The primary safety and efficacy endpoints were freedom from LBBAP lead-related serious adverse events and the composite of LBBA capture threshold of ≤2.0 V and R-wave amplitudes ≥5 mV (or ≥value at implant), respectively. RESULTS: Of 221 patients with attempted implants of the Tendril 2088 lead in the LBBA, 91.4% (202/221) had successful implants for LBBAP. Regardless of the LBBAP implant success, all patients were followed for at least 6 months (8.7 ± 7.3 months). Baseline characteristics: 44% female, 84% ≥65 years old, 34% coronary artery disease, and 86% of primary indications for pacemaker implant. Both primary safety and effectiveness endpoints were met (freedom from LBBAP lead-related serious adverse device effects of 99.5% and electrical performance composite success rate of 93%). The capture thresholds in LBBAP at implant and 6 months were 0.8 ± 0.3 V@0.4 ± 0.1 ms and 0.8 ± 0.3 V@0.4 ± 0.1 ms. The rate of patients with capture threshold rise ≥1 V was 1.5% through 6 months. The R-wave amplitudes in LBBAP at implant and 6 months were 9.3 ± 3.2 mV and 10.6 ± 3.0 mV. CONCLUSIONS: This large multicenter study demonstrates that the stylet-driven Tendril™ STS 2088 lead is safe and effective for LBBAP with high success and low complication rates.

Atrioventricular conduction disorders in aortic valve infective endocarditis.

BACKGROUND: Aortic valve infective endocarditis may be complicated by high-degree atrioventricular block in up to 10-20% of cases. AIM: To assess high-degree atrioventricular block occurrence, contributing factors, prognosis and evolution in patients referred for aortic infective endocarditis. METHODS: Two hundred and five patients referred for aortic valve infective endocarditis between January 2018 and March 2021 were included in this study. A comprehensive assessment of clinical, electrocardiographic, biological, microbiological and imaging data was conducted, with a follow-up carried out over 1 year. RESULTS: High-degree atrioventricular block occurred in 22 (11%) patients. In univariate analysis, high-degree atrioventricular block was associated with first-degree heart block at admission (odds ratio 3.1; P=0.015), periannular complication on echocardiography (odds ratio 6.9; P<0.001) and severe biological inflammatory syndrome, notably C-reactive protein (127 vs 90mg/L; P=0.011). In-hospital mortality (12.7%) was higher in patients with high-degree atrioventricular block (odds ratio 4.0; P=0.011) in univariate analysis. Of the 16 patients implanted with a permanent pacemaker for high-degree atrioventricular block and interrogated, only four (25%) were dependent on the pacing function at 1-year follow-up. CONCLUSIONS: High-degree atrioventricular block is associated with high inflammation markers and periannular complications, especially if first-degree heart block is identified at admission. High-degree atrioventricular block is a marker of infectious severity, and tends to raise the in-hospital mortality rate. Systematic assessment of patients admitted for infective endocarditis suspicion, considering these contributing factors, could indicate intensive care unit monitoring or even temporary pacemaker implantation in those at highest risk.

Cardiovascular Safety of Hydroxychloroquine-Azithromycin in 424 COVID-19 Patients.

Background and Objectives: Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular, the potential of prolong cardiac repolarization when using this combination has been discussed. Materials and Methods: We report a pragmatic and simple safety approach which we implemented among the first patients treated for COVID-19 in our center in early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) > 500 ms, hypokalemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 h of the initial prescription. Results: Among the 424 consecutive adult patients (mean age 46.3 ± 16.1 years; 216 women), 21.5% patients were followed in conventional wards and 78.5% in a day-care unit. A total of 11 patients (2.6%) had contraindications to the HCQ-AZ combination. In the remaining 413 treated patients, there were no arrhythmic events in any patient during the 10-day treatment regimen. QTc was slightly but statistically significantly prolonged by 3.75 ± 25.4 ms after 2 days of treatment (p = 0.003). QTc prolongation was particularly observed in female outpatients <65 years old without cardiovascular disease. Ten patients (2.4%) developed QTc prolongation > 60 ms, and none had QTc > 500 ms. Conclusions: This report does not aim to contribute to knowledge of the efficacy of treating COVID-19 with HCQ-AZ. However, it shows that a simple initial assessment of patient medical history, electrocardiogram (ECG), and kalemia identifies contraindicated patients and enables the safe treatment of COVID-19 patients with HCQ-AZ. QT-prolonging anti-infective drugs can be used safely in acute life-threatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists are applied.

SCN5A Variants as Genetic Arrhythmias Triggers for Familial Bileaflet Mitral Valve Prolapse.

Mitral valve prolapse (MVP) is a common valvular heart defect with variable outcomes. Several studies reported MVP as an underestimated cause of life-threatening arrhythmias and sudden cardiac death (SCD), mostly in young adult women. Herein, we report a clinical and genetic investigation of a family with bileaflet MVP and a history of syncopes and resuscitated sudden cardiac death. Using family based whole exome sequencing, we identified two missense variants in the SCN5A gene. A rare variant SCN5A:p.Ala572Asp and the well-known functional SCN5A:p.His558Arg polymorphism. Both variants are shared between the mother and her daughter with a history of resuscitated SCD and syncopes, respectively. The second daughter with prodromal MVP as well as her healthy father and sister carried only the SCN5A:p.His558Arg polymorphism. Our study is highly suggestive of the contribution of SCN5A mutations as the potential genetic cause of the electric instability leading to ventricular arrhythmias in familial MVP cases with syncope and/or SCD history.

Diaphragmatic CMAP Monitoring During Cryoballoon Procedures: Surface vs. Hepatic Recording Comparison and Limitations of This Approach.

BACKGROUND: Compound motor action potential (CMAP) monitoring is a common method used to prevent right phrenic nerve palsy during cryoballoon ablation for atrial fibrillation. OBJECTIVE: We compared recordings simultaneously obtained with surface and hepatic electrodes. METHODS: We included 114 consecutive patients (mean age 61.7 ± 10.9 years) admitted to our department for cryoballoon ablation. CMAP was monitored simultaneously with a hepatic catheter and a modified lead I ECG, whilst right phrenic nerve was paced before (stage 1) and during (stage 2) the right-sided freezes. If phrenic threat was detected with hepatic recordings (CMAP amplitude drop >30%) the application was discontinued with forced deflation. RESULTS: The ratio of CMAP/QRS was 4.63 (2.67-9.46) for hepatic and 0.76 (0.55-1.14) for surface (p < 0.0001). Signal coefficients of variation during stage 1 were 3.92% (2.48-6.74) and 4.10% (2.85-5.96) (p = 0.2177), respectively. Uninterpretable signals were more frequent on surface (median 10 vs. 0; p < 0.0001). For the 14 phrenic threats, the CMAP amplitude dropped by 35.61 ± 8.27% on hepatic signal and by 33.42 ± 11.58% concomitantly on surface (p = 0.5417). Our main limitation was to achieve to obtain stable phrenic capture (57%). CMAP monitoring was not reliable because of pacing instability in 15 patients (13.16%). A palsy occurred in 4 patients (3.51%) because cryoapplication was halted too late. CONCLUSION: Both methods are feasible with the same signal stability and amplitude drop precocity during phrenic threats. Clarity and legibility are significantly better with hepatic recording (sharper signals, less far-field QRS). The two main limitations were pacing instability and delay between 30% CMAP decrease and cryoapplication discontinuation.

Advantages and disadvantages of drug challenge during electrophysiological study in patients with new left bundle branch block after transaortic valve implantation.

AIMS: Electrophysiological study (EPS) is recommended in case of new-onset persistent left bundle branch block (NOP-LBBB) after transaortic valve implantation (TAVI) to identify patients at high risk of delayed atrioventricular block (D-AVB). We evaluated the added value of drug challenge, after normal baseline EPS, to predict D-AVB in such patients. METHODS: We conducted a comparative single-centre study of two successive periods, during which we used baseline EPS alone (first period) or drug challenge in case of normal baseline EPS (second period), for patients with NOP-LBBB after TAVI. The primary endpoint was a composite of pacemaker use, documented D-AVB, cardiac syncope, sudden death, or delayed pacemaker implantation. RESULTS: Among 736 patients with TAVI implantation between January 2016 and September 2019, 64 with NOP-LBBB were included. During the first period, 4/22 (18.2%) presented with a positive baseline EPS. After a mean (standard deviation [SD]) of 15.6 (8.3) months, 7/22 (31.8%) reached the primary endpoint. During the second period, 19/42 (45.2%) presented with a positive EPS. After a mean (SD) of 12.8 (3.5) months, 8/42 (19.0%) reached the primary endpoint. There was a tendency to increased sensitivity (42.9-87.5%; P = 0.12) and negative predictive value (77.8-95.7%; P = 0.15) of the EPS, respectively during the first to the second period. However, the specificity decreased (93.3-64.7%; P = 0.04). CONCLUSION: Diagnostic yield improved with drug challenge in case of normal baseline EPS. However, the decrease in specificity led to a high rate of unnecessary pacemaker implantation.

Anomalous Left Coronary Artery Connected to the Pulmonary Artery in a 15-Year-Old Girl: Case Report and Discussion on Secondary Prevention of Sudden Death.

Background. Anomalous left coronary artery connected to the pulmonary artery (ALCAPA) is a rare congenital heart disease. Adaptive development of sufficient heterocoronary collaterality in the newborn may allow survival to a later age. In older children or adults, malignant ventricular arrhythmias can reveal the disease. Case Report. A 15-year-old girl was referred to the local hospital after a resuscitated out-of-hospital cardiac arrest. CT scan and coronary angiography revealed an ALCAPA. Direct aortic reimplantation of the left coronary artery was performed. Postoperative ECG monitoring showed short episodes of nonsustained ventricular tachycardia. Transthoracic echocardiography and cardiac MRI revealed subendocardial fibrosis of the anterolateral papillary muscle. Beta-blockade therapy was initiated at first intention. After hospital discharge, the patient reported several fainting without loss of consciousness. Considering sudden death nonrelated to effort, episodes of nonsustained ventricular tachycardia, and areas of myocardial fibrosis, the patient underwent subcutaneous cardioverter-defibrillator implantation. 6-month follow-up is satisfactory without clinical or rhythmic abnormalities. Discussion. Indication for surgical correction of ALCAPA is well defined, but rhythmic secondary prevention after resuscitated cardiac arrest is less consensual. Cardiac MRI is an essential tool in the identification of a potential rhythmic substrate and should be taken into account in the discussion of a preventive cardioverter-defibrillator implantation.

Smartwatch Electrocardiogram and Artificial Intelligence for Assessing Cardiac-Rhythm Safety of Drug Therapy in the COVID-19 Pandemic. The QT-logs study.

BACKGROUND: QTc interval monitoring, for the prevention of drug-induced arrhythmias is necessary, especially in the context of coronavirus disease 2019 (COVID-19). For the provision of widespread use, surrogates for 12­lead ECG QTc assessment may be useful. This prospective observational study compared QTc duration assessed by artificial intelligence (AI-QTc) (Cardiologs®, Paris, France) on smartwatch single­lead electrocardiograms (SW-ECGs) with those measured on 12­lead ECGs, in patients with early stage COVID-19 treated with a hydroxychloroquine-azithromycin regimen. METHODS: Consecutive patients with COVID-19 who needed hydroxychloroquine-azithromycin therapy, received a smartwatch (Withings Move ECG®, Withings, France). At baseline, day-6 and day-10, a 12­lead ECG was recorded, and a SW-ECG was transmitted thereafter. Throughout the drug regimen, a SW-ECG was transmitted every morning at rest. Agreement between manual QTc measurement on a 12­lead ECG and AI-QTc on the corresponding SW-ECG was assessed by the Bland-Altman method. RESULTS: 85 patients (30 men, mean age 38.3 ± 12.2 years) were included in the study. Fair agreement between manual and AI-QTc values was observed, particularly at day-10, where the delay between the 12­lead ECG and the SW-ECG was the shortest (-2.6 ± 64.7 min): 407 ± 26 ms on the 12­lead ECG vs 407 ± 22 ms on SW-ECG, bias -1 ms, limits of agreement -46 ms to +45 ms; the difference between the two measures was <50 ms in 98.2% of patients. CONCLUSION: In real-world epidemic conditions, AI-QTc duration measured by SW-ECG is in fair agreement with manual measurements on 12­lead ECGs. Following further validation, AI-assisted SW-ECGs may be suitable for QTc interval monitoring. REGISTRATION: ClinicalTrial.govNCT04371744.

Seasonal variations in cardiac implantable electronic device infections.

Infections of cardiac implantable electronic devices (CIEDs) have increased over the past decade. However, the impact of the climate on CIED infections is unknown. To determine whether there is a seasonal variation in CIED infections. In this single-center observational study, retrospective analysis of prospectively collected data was performed. Timone Hospital in Marseille (south-east France) is a tertiary care institution and the regional reference center for management of CIED infections. All consecutive patients with CIED extractions for infectious reasons were included over a 12-year period. We noted the mean temperature (°C), precipitation (mm) and the incidence of CIED infections over this period. Among 612 patients [mean (standard deviation) age, 72.4 (13.0) years; 74.0% male], 238 had endocarditis alone (38.9%), 249 had pocket infection alone (40.7%), and 125 had both (20.4%). We found bacterial documentation in 428 patients (70.0%), commensal in 245 (40.0%). The incidence of CIED infections was positively associated with high temperature (regression coefficient = 0.075; P = 0.01) and precipitation (regression coefficient = 0.022; P < 0.01). Seasonal variation was specific of pocket infections, whether they were associated with endocarditis or not. Subgroups with infection seasonality were: women, elderly people (> 75 years), late CIED infection and skin commensal bacterial infections. We found a seasonal variation in pocket infections, whether associated with endocarditis or not. Infections were associated with elevated temperatures and precipitation. Therefore, specific prevention strategy should be discussed in high-risk patients.

High-density mapping for catheter ablation of premature ventricular complexes originating from left ventricular papillary muscles: A case series.

PURPOSE: Ablation of premature ventricular complexes (PVCs) originating from left-sided papillary muscles is challenging. We tested a new approach by performing high-density mapping of PVC. METHODS AND RESULTS: We used a 20-pole deflectable spiral catheter during ablation procedures in four consecutive patients. Three presented with mitral valve prolapse, one with dilated cardiomyopathy. PVC burden was 24 ± 13%. The procedures lasted 182 ± 55.4 minutes, including 10 ± 3.2 minutes of radiofrequency. In all patients, mapping evidenced internal primary activation relative to the left ventricle shell (mean distance 21.3 ± 5.1 mm). Endocavitary prematurity was -38.3 ± 4.8 ms. Primary ablation success was achieved for all patients. CONCLUSIONS: High-density mapping of the papillary muscles in the left ventricle using a spiral catheter may be feasible. We identified the PVC foci away from the left ventricular shell. This consolidates the assumption for the origin of these ectopic beats at the junction between the chordae tendineae and the papillary muscles.

Endo-/Epicardial Catheter Ablation of Atrial Fibrillation: Feasibility, Outcome, and Insights Into Arrhythmia Mechanisms.

BACKGROUND: Until today, catheter interventional mapping and ablation of atrial fibrillation (AF) has been limited to the right and left atrial endocardium. We report feasibility, electrophysiological findings, and clinical outcome using a combined endo-/epicardial catheter approach for mapping and ablation of AF. METHODS AND RESULTS: Fifty-nine patients with permanence of pulmonary vein isolation and further symptomatic recurrences of paroxysmal AF, persistent AF, or atrial tachycardia underwent reablation using biatrial endo-/epicardial mapping and ablation. Identification of arrhythmia substrates and selection of ablation strategy were based on sinus rhythm voltage mapping. Using continuous monitoring and a 3-month blanking period, freedom from AF/atrial tachycardia ≥2 minutes was defined as primary end point. In all patients, endo-/epicardial mapping and ablation was feasible using standard technologies of catheter access, 3-dimensional mapping, and radiofrequency ablation. Epicardial mapping and ablation did not add procedural risks. Exclusively epicardial low voltage substrates were found in 14% of the patients. For the first time, novel epicardial conduction abnormalities located in the epicardial fiber network were described in human AF patients (19% of the cohort). Epicardial ablation was needed in 80% of the patients. Over 23±10 months of follow-up freedom from arrhythmia recurrences measured 73%. CONCLUSIONS: Catheter-based endo-/epicardial mapping and ablation of AF was feasible and safe. Epicardial mapping provided new insights into AF mechanisms. Epicardial ablation increased transmurality of ablation lesions. Clinical outcome in this cohort of complex AF patients was favorable, indicating potential further development of current AF treatment.

Comparison of epicardial vs. endocardial reimplantation in pacemaker-dependent patients with device infection.

Aims: Reimplantation of cardiac implantable electronic devices (CIEDs) after extraction due to device infection is a major issue in pacemaker-dependent patients. We compared in-hospital and long-term outcomes with two techniques: epicardial reimplantation (EPI) before CIED extraction and temporary pacing (TP) with a view to delayed endocardial reimplantation. Methods and results: Two cohorts of consecutive pacemaker-dependent patients who underwent transvenous lead extraction at our tertiary centre were included in this retrospective cohort study. According to successive policies, either the EPI or the TP approach was used. In-hospital complications occurred at similar rates in the EPI (n = 59) and TP (n = 52) cohorts (37.3% vs. 32.7%, respectively; P = 0.61). Thirteen (25.0%) patients in the TP cohort eventually were reimplanted epicardially, mainly because of infection of the temporary lead. Finally, 65 patients were discharged with an epicardial device and 37 with an endocardial device. Median follow-up was 41.7 (interquartile range 34.1-51.5) months. No difference was observed in long-term mortality according to the reimplantation strategy, but use of TP was associated with a reduced risk of late endocarditis and device reintervention (hazard ratio (HR) 0.25, 95% confidence interval (CI) 0.09-0.069, P = 0.01), whereas epicardial device reimplantation was associated with an increased risk (HR 3.62, 95% CI 1.07-12.21, P = 0.04). Conclusion: We observed similar in-hospital outcomes in our EPI and TP cohorts. Twenty-five percent of the patients initially paced by a TP strategy finally needed an epicardial device, mainly because of infection of their TP lead. Use of TP resulted in lower rates of late endocarditis and device reintervention.

Right ventricular and tricuspid valve function in patients chronically implanted with leadless pacemakers.

Aims: Leadless cardiac pacing has recently been proposed as alternative to conventional right ventricular (RV) pacing. With this approach, devices are directly screwed or fixed with tines in the RV wall, but the possible consequences on RV and tricuspid valve (TV) structure and function remain unknown. We thus conducted a study to evaluate this potential impact in chronically implanted patients. Methods and results: Repeated echocardiographic studies were performed prior to implantation, at discharge, and 2 months thereafter on all consecutive patients implanted with a leadless pacemaker at our centre between October 2014 and end-December 2015. Whenever possible, patients were evaluated in non-paced rhythm. Anatomical and functional parameters of RV, TV, and left cardiac structures were assessed. Overall, 23 patients (12 females, aged 85.2 ± 6.3 years) were included, with 14 implanted using Nanostim™ (Saint Jude Medical) and 9 with Micra™ (Medtronic). Indications for pacing were paroxysmal atrio-ventricular block in 12 patients, intermittent sinus bradycardia in 5, unexplained syncope in 3, and atrial fibrillation with slow ventricular rate in the remaining 3. The pacing percentage was 34 ± 42% at the last visit. Most devices were implanted in the septo-apical or mid-septal region. There were no significant changes in echocardiographic parameters observed. One patient developed significantly increased TV regurgitation, without abnormal leaflet motion or TV annulus size changes, suggesting it to be due to RV pressure changes. Conclusion: In patients chronically implanted with leadless pacemakers, there were no significant changes in heart structure and function observed, especially concerning the RV and TV.

Theophylline as an adjunct to control malignant ventricular arrhythmia associated with early repolarization.

Early repolarization (ER) has been associated with an increased risk of sudden cardiac arrest. Interestingly, ventricular arrhythmias seem to be triggered by parasympathetic stimulation. In the present case report, we describe complete control of highly frequent malignant ventricular arrhythmias after adding theophylline to ineffective oral hydroquinidine and high-rate pacing in a patient suffering from malignant ER. We hypothesize that the theophylline-mediated enhanced beta-adrenergic stimulation could reduce the transmural myocardial voltage discrepancy by increasing the inward ICa,L current.

Electromyographic monitoring for prevention of phrenic nerve palsy in second-generation cryoballoon procedures.

BACKGROUND: Electromyography-guided phrenic nerve (PN) monitoring using a catheter positioned in a hepatic vein can aid in preventing phrenic nerve palsy (PNP) during cryoballoon ablation for atrial fibrillation. We wanted to evaluate the feasibility and efficacy of PN monitoring during procedures using second-generation cryoballoons. METHODS AND RESULTS: This study included 140 patients (43 women) in whom pulmonary vein isolation was performed using a second-generation cryoballoon. Electromyography-guided PN monitoring was performed by pacing the right PN at 60 per minute and recording diaphragmatic compound motor action potential (CMAP) via a quadripolar catheter positioned in a hepatic vein. If a 30% decrease in CMAP amplitude was observed, cryoapplication was discontinued with forced deflation to avoid a PNP. Monitoring was unfeasible in 8 of 140 patients (5.7%), PNP occurred in 1. Stable CMAP amplitudes were achieved before ablation in 132 of 140 patients (94.3%). In 18 of 132 patients (13.6%), a 30% decrease in CMAP amplitude occurred and cryoablation was discontinued. Each time, recovery of CMAP amplitude took <60 s. In 9 of 18 cases, a second cryoapplication in the same pulmonary vein was safely performed. We observed no PNP or complication related to electromyography-guided PN monitoring. CONCLUSIONS: Electromyography-guided PN monitoring using a catheter positioned in a hepatic vein seems feasible and effective to prevent PNP during cryoballoon ablation using second-generation cryoballoon.