Abstract Aims Risk stratification for sudden cardiac death in patients with Brugada syndrome remains a major challenge. Contemporary risk prediction models have only modest predictive value. The aim of this study was to assess the role of micro-RNAs from peripheral blood as candidate biomarkers in Brugada syndrome. Methods and results In this prospective study, Brugada patients and unaffected control individuals were enrolled for analysis of leucocyte-derived microRNAs (miRNAs) levels. Expression levels of 798 different circulating miRNAs were analysed on the NanoString® nCounter platform. All results were cross-validated by using a quantitative polymerase chain reaction. Micro-RNA expression levels of Brugada patients were compared with clinical data. A total of 21 definite Brugada patients (38% with a history of ventricular arrhythmia or cardiac arrest) and 30 unaffected control individuals were included in the study. Micro-RNA analysis showed a distinct expression profile in Brugada patients with 42 differentially expressed markers (38 up-regulated, 4 down-regulated miRNAs). The symptom status of Brugada patients was associated with a distinct miRNA signature. Micro-RNAs 145-5p and 585-3p were significantly up-regulated in symptomatic Brugada patients (P = 0.04). Incorporating miRNAs 145-5p and 585-3p into a multivariable model demonstrated significantly increased symptom prediction (area under the curve = 0.96; 95% confidence interval: 0.88–1.00). Conclusion Brugada patients display a distinct miRNA expression profile compared with unaffected control individuals. There is also evidence that certain miRNAs (miR-145-5p and miR-585-3p) are associated with the symptom status of Brugada patients. The results suggest the principal utility of leucocyte-derived miRNAs as prognostic biomarkers for Brugada syndrome.

Background: Regulatory authorities of most industrialized countries recommend 6 months of private driving restriction after implantation of a secondary prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. This study aimed to assess the incidence rate of appropriate device therapies in contemporary recipients of a secondary prevention ICD. Methods: This retrospective study at 3 Canadian tertiary care centers enrolled consecutive patients with new secondary prevention ICD implants between 2016 and 2020. Results: For a median of 760 days (324, 1190 days), 721 patients were followed up. The risk of recurrent ventricular arrhythmia was highest during the first 3 months after device insertion (34.4%) and decreased over time (10.6% between 3 and 6 months, 11.7% between 6 and 12 months). The corresponding incidence rate per 100 patient-days was 0.48 (95% CI, 0.35-0.64) at 90 days, 0.28 (95% CI, 0.17-0.45) at 180 days, and 0.21 (95% CI, 0.13-0.33) between 181 and 365 days after ICD insertion (P<0.001). The cumulative incidence of arrhythmic syncope resulting in sudden cardiac incapacitation was 1.8% within the first 90 days and subsequently dropped to 0.4% between 91 and 180 days (P<0.001) after ICD insertion. Conclusions: The incidence rate of appropriate therapies resulting in sudden cardiac incapacitation in contemporary recipients of a secondary prevention ICD is much lower than previously reported and declines significantly after the first 3 months. Lowering driving restrictions to 3 months after the index cardiac event seems safe, and revision of existing guidelines should be considered in countries still adhering to a 6-month period. Existing restrictions for private driving after implantation of a secondary prevention ICD should be reconsidered.

Background:Cephalosporins are the cornerstone of cardiac device infection prophylaxis. Owing to fears of cross-reactivity, penicillin-allergic patients are exposed to potentially more-toxic drugs, with decreased efficacy. We evaluated the safety of a cefazolin test dose (CTD) in self-reported penicillin-allergic patients.Methods:In this single-centre study, we evaluated consecutive patients with chart documentation of penicillin allergy undergoing cardiac device implantation, over a 2-year period. A CTD was performed if no cephalosporin allergy or severe anaphylactic reaction to penicillin had been documented. Patients were given 2 doses of 100 mg IV cefazolin, and if no allergic reaction occurred after 5 minutes, the full dose (1800 mg) was administered in the electrophysiology laboratory just before the implantation procedure.Results:A total of 2200 patients were included. The frequency of reported penicillin allergy was 9.3% (n = 204). In 80% of cases, the type of allergic reaction was not reported in medical notes or was unknown by the patient. A CTD was performed in 67.6% of patients with a penicillin allergy (n = 138). A total of 5 adverse events occurred (3.6% of patients [95% confidence interval, 1.1%-6.1%]) - 4 skin rashes and 1 tongue edema. These 5 patients became asymptomatic after antihistaminic and corticosteroid IV treatment. Even if the test dose was negative, 79% of patients also were administered vancomycin before the procedure, as it requires a 1-hour infusion prior to the CTD in the implantation procedure room.Conclusion:A CTD in most penicillin-allergic patients appears to be safe and allows its use per recommended guidelines.

Twiddler syndrome is an uncommon yet dangerous phenomenon usually resulting in lead displacement with loss of capture of cardiac implantable electronic devices. In this case report, we present an interesting case of Twiddler syndrome without lead dislodgment which was detected by an alert triggered by an increase in impedance on remote monitoring.

Introduction: Implantation of epicardial pacing leads remains a well-known alternative to the standard transvenous approach in several situations. However, long-term data on the performance and safety of epicardial pacing leads remain scarce. Methods: We conducted a retrospective cohort study at a single tertiary center including all patients with right or left ventricular epicardial lead implantation between 1996 to 2018; n=255. Electrophysiological lead parameters at implantation and during follow-up were analyzed and compared with clinical data from the electronic medical records. Results: 230 patients were included in the analysis. Implanted lead models included the Medtronic 4968 (n=202) and Medtronic 5071 (n=28). Indications for epicardial lead implantation included upgrade to CRT in 153/230 (67%) individuals and standard right or left ventricular pacing only in 76/230 (33%). Of the 153 epicardial CRT patients, 50 had a history of failed transvenous CRT and 103 had concomitant cardiac surgery for other indications and were thought to have a likely indication for CRT in the nearby future. Mean follow-up time was 4,7years±4,2. Lead impedances were significantly higher in the 4968 model compared to the 5071. Pacing thresholds for both lead models were similar at implantation but were subsequently significant higher in the 5071 model. Higher pacing thresholds in the 5071 model did not result in premature battery depletion. Periprocedural complications related to the epicardial lead insertion occurred in 3/230 patients. Epicardial lead related complications at follow-up remained low (8/230; 3 dysfunctions, 2 dislodgments, 1 impending skin erosion). There were only 2 cases of epicardial lead infections at follow-up requiring surgical extraction. 4,3% of all implanted leads remained unconnected at follow-up. Conclusions: Epicardial lead implantation for either CRT or pacing indications is a durable and safe alternative to transvenous lead insertion.

Background: Current guidelines recommend 4 weeks of private driving restriction after implantation of a primary-prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. Advances in medical treatment and ICD programming have lowered the overall rate of device therapies. The objective of this study was to assess the incidence of ICD therapies at 30, 60, and 180 days after implantation. Methods: Driving Restrictions and Early Arrhythmias in Patients Receiving a Primary-Prevention Implantable Cardioverter-Defibrillator (DREAM-ICD) was a retrospective cohort study conducted at 2 Canadian university centres enrolling patients with new implantation of a primary-prevention ICD. Device programming was standardised according to current guidelines. A total of 803 patients were enrolled. Results: The cumulative rates of appropriate ICD therapies at 30, 60, and 180 days were 0.12%, 0.50%, and 0.75%, respectively. There was no syncope during the first 6 months. The median duration to the first appropriate ICD therapy was 208 (range 23-1109) days after implantation. The rate of inappropriate ICD therapies at 30 days was only 0.2%. Overall, < 13.6% of all appropriate ICD therapies occurred within the first 6 months after implantation. Conclusions: The rate of appropriate ICD therapies within the first 30 days after device insertion is extremely low in contemporary primary prevention cohorts with guideline-concordant device programming. There was no increased risk for ventricular arrhythmia early after ICD insertion. The results of DREAM-ICD suggest the need for a revision of the existing driving restrictions for primary-prevention ICD recipients.

Transvenous implantation of a left ventricular (LV) pacing lead is the standard approach to deliver cardiac resynchronization therapy (CRT) but fails in 5-10% of procedures. Surgical implantation of a LV epicardial lead represents an alternative approach to deliver CRT to patients with failed transvenous lead insertion or to individuals with other indications for cardiac surgery and anticipated need for CRT or pacing in the future. Long-term data on the performance and safety of epicardial pacing leads remain scarce.

Background Monitoring of cardiac implantable electronic devices was highly impacted by the COVID-19 pandemic considering the high volume of in-person visits for regular follow-up. Recent recommendations highlight the important role of remote monitoring to prevent exposure to the virus. This study compared remote monitoring of implantable cardioverter defibrillators (ICDs) in patients whose in-person annual visit was substituted for a remote monitoring session with patients who were already scheduled for a remote monitoring session. Methods This was a cross-sectional observational study of 329 consecutive patients between 20 March and 24 April 2020. Group 1 included 131 patients whose in-person annual visit was substituted for a remote monitoring session. Group 2 included 198 patients who underwent a remote monitoring session as scheduled in their usual device follow-up. The time interval since the last in-person visit was 13.3 +/- 3.2 months in group 1 and 5.9 +/- 1.7 months in group 2 (P < .01). Results In group 1, 15 patients (11.5%) experienced a clinical event compared to 15 patients (7.6%) in group 2 (P = .25). Nineteen patients (14.5%) required a physician intervention in group 1 compared to 19 patients (9.6%) in group 2 (P = .22). Two patients (1.5%) in group 1 and four patients (2.0%) in group 2 required an early in-person follow-up visit during the pandemic (P > .99). Conclusion Remote monitoring of ICDs is useful to identify clinical events and allows physicians to treat patients appropriately during the COVID-19 pandemic regardless of the time interval since their last in-person visit. It reduces significantly in-person visit for regular follow-up.

Background: Apical hypertrophic cardiomyopathy (aHCM) is thought to have a more benign clinical course compared to septal HCM (sHCM), but most data have been derived from Asian cohorts. Comparative data on clinical outcome in Caucasian aHCM cohorts are scarce, and the results are conflicting. The aim of this study was to estimate the prevalence and outcome of aHCM in French-Canadians of Caucasian descent. Methods and results: We conducted a retrospective, single-center cohort study. The primary endpoint was a composite of documented sustained ventricular arrhythmia (VA), appropriate ICD therapy, arrhythmogenic syncope, cardiac arrest, or all-cause mortality. A total of 301 HCM patients (65% males) were enrolled including 80/301 (27%) with aHCM and 221/301 (73%) with sHCM. Maximal wall thickness was similar in both groups. Left ventricular apical aneurysm was significantly more common in aHCM (10 vs. 0.5%; p < 0.001). The proportion of patients with myocardial fibrosis ≥ 15% of the left ventricular mass was similar between aHCM and sHCM (21 vs. 24%; p = 0.68). Secondary prevention ICDs were more often implanted in aHCM patients (16 vs. 7%; p = 0.02). The primary endpoint occurred in 26% of aHCM and 10.4% of sHCM patients (p = 0.001) and was driven by an increased incidence of sustained VA (10 vs. 2.3%; p = 0.01). Multivariate analysis identified apical aneurysm and a phenotype of aHCM as independent predictors of the primary endpoint and the occurrence of sustained ventricular tachycardia. Unexplained syncope and a family history of sudden cardiac death were additional predictors for sustained VA. Apical HCM was associated with an increased risk of ventricular arrhythmia even when excluding patients with apical aneurysm. Conclusions: The phenotype of apical HCM is much more common in French-Canadians (27%) of Caucasian descent compared to other Caucasian HCM populations. Apical HCM in French-Canadians is associated with an increased risk for ventricular arrhythmia.

The new global pandemic related to COVID-19 (SARS-CoV-2 virus) significantly impacted healthcare systems and the management of several heart diseases since its outbreak in December 2019. Monitoring of cardiac implantable electronic devices (CIED) was highly impacted considering the high volume of in-person visits for regular follow-up. Recent recommendations insist on the reduction of in-person visits for CIED monitoring and on the important role of remote device monitoring in the pandemic context. Nevertheless, these recommendations are mainly supported by expert consensus. Thus, the aim of this study was to evaluate the relevance and usefulness of remote device monitoring to identify clinical events and device anomalies in patients with cardiac implantable defibrillators whose in-person visit was cancelled because of the COVID 19 pandemic restrictions. This cross-sectional descriptive study included all patients whose in-person visit was cancelled during the COVID-19 pandemic and who underwent remote device monitoring of their cardiac implantable defibrillator between March 20th and April 24th 2020 at our institution. We recorded clinical events identified with remote device monitoring as well as physicians' interventions. 129 consecutive patients (77.5% male) with a mean age of 65.5 years (± 11.7 years) were included in the study. Patients were mainly non-dependent (95.3%) and treated for primary prevention (60.5%). 40.7% of patients had dual-chamber defibrillators, 29.4% single-chamber defibrillators, 30.2% biventricular defibrillators and 1.6% sub-cutaneous defibrillators. Clinically significant arrhythmias (atrial fibrillation, atrial flutter, ventricular tachycardia or any arrhythmia leading to a therapeutic change) were observed in 9 patients, antitachycardia pacing in 1 patient, battery issues in 3 patients, and lead dysfunction in 3 patients. 114 patients (88.4%) had no clinical event. No shock or inappropriate therapy was reported. A total of 21 physicians' interventions were observed. A phone call to the patient was performed in 4 patients to enquire about symptoms, medication change in 2 patients, recommendations to the treating physician concerning medication changes in 3 patients, early in-patient follow-up in 2 patients, early remote device monitoring follow-up in 2 patients, and suggested non-urgent programming change at the next visit in 8 patients. Remote device monitoring is relevant and useful to identify clinical events and device anomalies in patients with cardiac implantable defibrillators whose in-person visit was cancelled during the COVID-19 pandemic. This approach allows physicians' to modify patients' treatment appropriately, except for programming changes. Thus, we should feel confident to use remote device monitoring for patients with cardiac implantable defibrillators during the COVID-19 pandemic.

Diagnosis of arrhythmic disorders is challenging because of their short-lasting, intermittent character. Conventional technologies of noninvasive ambulatory rhythm monitoring are limited by modest sensitivity. We present a novel form of wearable electrocardiogram (ECG) sensors providing an alternative tool for long-term rhythm monitoring with the potential of increased sensitivity to detect intermittent or subclinical arrhythmia. The objective was to assess the signal quality and R-R coverage of a wearable ECG sensor system compared to a standard 3-lead Holter. In this phase-1 trial, healthy individuals underwent 24-h simultaneous rhythm monitoring using the OMsignal system together with a 3-lead Holter recording. The OMsignal system consists of a garment (bra or shirt) with integrated sensors recording a single-lead ECG and an acquisition module for data storage and processing. Head-to-head signal quality was assessed regarding adequate P-QRS-T distinction and was performed by three electrophysiologists blinded to the recording technology. The accuracy of signal coverage was assessed using Bland-Altman analysis. Fifteen individuals underwent simultaneous 24-h recording. Signal quality and accuracy of the OMgaments was equivalent to Holter-monitoring (84% vs 93% electrophysiologists rating, p = 0.06). Signal coverage of R-R intervals showed a very close overlay between the OMsignal system and Holter signals, mean difference in heart rate of 2 5 bpm. The noise level of OMgarments was comparable to Holter recording. OMgarments provide high signal quality for adequate rhythm analysis, representing a promising novel technology for long-term non-invasive ECG monitoring.

IntroductionImplantable cardioverter-defibrillator (ICD) DF-4 connectors have been introduced to facilitate defibrillator lead connection and to reduce the size of device header. There are limited data regarding the overall performance of those leads and no comparison between different ICD DF-4 leads. MethodsThis is a cohort study of consecutive patients implanted with ICD DF-4 lead system at one University Centre between October 2010 and February 2015. A historical control group of patients with ICD DF-1 lead implantation was used for comparison. The following ICD DF-4 leads were evaluated: St. Jude Medical Durata 7122Q (St. Jude Medical, St. Paul, MN, USA), Medtronic Sprint Quattro Secure 6935M (Medtronic Inc., Minneapolis, MN, USA), Boston Scientific Endotak Reliance 4-Site 0293 (Boston Scientific, Marlborough, MA, USA), and Boston Scientific Reliance 4-Front 0693. This study evaluated the acute and mid-term performances of those leads as well as complications. ResultsA total of 812 patients (age 6312 years, 80% male, left ventricular ejection fraction 31 +/- 12%) underwent implantation of an ICD DF-4 lead. Acute and follow-up R-wave sensing and threshold were excellent. Compared to implantation, intrinsic R waves were higher at follow-up for Boston Scientific and Medtronic leads, and pacing lead impedances were lower for all leads at first follow-up (P<0.001). The number of lead dislodgement or failure was similar between all leads. The estimated lead survival rates at 3 years were 95.6% for Boston Scientific Endotak 4-Site, 97.1% for Boston Scientific 4-Front, 97.7% for Medtronic Sprint Quattro, and 97.5% for St. Jude Durata (P=0.553). ConclusionAll ICD DF-4 leads had excellent acute and mid-term electrical performances. Longer follow-up will be necessary to confirm their sustained performance.

BACKGROUND:Cardiostat™ is a single lead ambulatory ECG monitor. Recording is made through 2 electrodes positioned in a lead 1-like configuration. We first validated its accuracy for atrial fibrillation detection compared to a 12-lead ECG. In the second phase of the study, arrhythmia detection accuracy was compared between Cardiostat™ ambulatory ECG and a standard 24 h Holter ECG monitoring. METHOD/RESULTS:Phase one of the study included patients undergoing cardioversion for atrial fibrillation (AF) or atrial flutter. Cardiostat™ tracings were compared with standard 12-lead ECG. In the second phase, patients undergoing 24 h ambulatory Holter ECG monitoring for control or suspicion of atrial fibrillation (AF) were included. Simultaneous Holter monitoring and Cardiostat™ ECG recordings were performed. Tracings were analysed and compared. Two hundred twelve monitoring were compared. AF was diagnosed in 73 patients. Agreement between Cardiostat™ ECG and standard Holter monitoring was 99% for AF detection with kappa = 0.99. Kappa correlation for atrial flutter detection was only moderate at 0.51. AF burden was similar in both recordings. Noise hindered analysis in a greater proportion with Cardiostat™ compared to Holter ambulatory ECG (8.5 vs 3.8%). CONCLUSION:Cardiostat™ ambulatory ECG device showed excellent correlation with the standard Holter ECG monitoring for AF detection. Holter monitoring was however superior to discriminate premature atrial and ventricular beats and to qualify the morphology of PVCs since it has more vectors for analysis. Added value of Cardiostat™ includes longer monitoring duration, less cumbersome installation and water resistance.

OBJECTIVES This analysis uses the data from the randomized controlled trial to assess the cost effectiveness of catheter ablation (n = 132) versus escalated antiarrhythmic therapy (n = 127). BACKGROUND For survivors of myocardial infarction with implantable cardioverter-defibrillator shocks despite antiarrhythmic drugs, the VANISH (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) trial demonstrated improved clinical outcomes with catheter ablation compared with more aggressive antiarrhythmic pharmacotherapy. METHODS Health care resource use and quality-of-life data were used to determine the cost effectiveness of catheter ablation. Published references were used to estimate costs (in 2015 Canadian dollars). The analysis was over 3 years, with a 5% discount rate. Adjustment was made for censoring and baseline utilities. RESULTS Ablation resulted in greater quality-adjusted life-years (QALYs) than escalated drug therapy did (1.63 vs. 1.49; difference: 0.14; 95% confidence interval [CI]: -0.20 to 0.46) and higher cost ($65,126 vs. $60,269; difference: $4,857; 95% CI: -$19,757 to $27,106); with an incremental cost per QALY gained for ablation versus escalated drug therapy of $34,057 primarily due to the initial costs of ablation, which were partially offset by the costs of subsequent ablations and adverse outcomes in the escalated drug therapy arm. For patients with amiodarone-refractory ventricular tachycardia, ablation dominated escalated drug therapy, with greater QALYs (1.48 vs. 1.26; difference: 0.22; 95% CI: -0.19 to 0.59) and lower costs ($67,614 vs. $68,383; difference: -$769; 95% CI: -$35,330 to $27,092). For those with sotalol-refractory ventricular tachycardia, ablation resulted in similar QALYs (1.90 vs. 1.90; difference: -0.00; 95% CI: -0.59 to 0.62) and higher costs ($60,455 vs. $45,033; difference: $15,422; 95% CI: -$10,968 to $48,555). CONCLUSIONS For the total trial population, results are suggestive that ablation is cost effective compared with escalation of drug therapy. This result was only manifest for the subgroup of patients whose qualifying arrhythmia occurred despite amiodarone. (c) 2018 by the American College of Cardiology Foundation.

Hypertrophic cardiomyopathy (HCM) is among the leading causes of unexplained sudden cardiac death in younger individuals and competitive athletes. Phenotypic variants include septal-HCM (sHCM) and apical-HCM (aHCM) with the latter being labeled to have a more benign course. Most data on aHCM are derived from Asian populations and there is a lack of contemporary data in predominantly Caucasian populations. We conducted a retrospective cohort study at a single tertiary university hospital. Patients with HCM were identified from electronic medical records and implantable cardiac defibrillator (ICD)-clinic databases. Classification into aHCM and sHCM was based on cardiac imaging (echocardiogram, cardiac magnetic resonance imaging) according to current guidelines. Clinical and genetic data of consecutive HCM patients were collected and correlated with the occurrence of ventricular arrhythmias. The primary endpoint was a composite of appropriate ICD-therapy (ATP or shock) and/or documentation of sustained ventricular arrhythmias. A total of 128 individuals with HCM were included (mean age at diagnosis, 50±17 years; male sex, 70% [89/128]; Caucasians, 98% [125/128]). Apical-HCM was diagnosed in 27% (35/128) and sHCM in 73% (93/128) individuals. Left ventricular mass index was similar (84±25 g/m2 vs. 91±32 g/m2;p=0.40), but maximal wall thickness was less pronounced in aHCM compared to sHCM (18±4 mm vs. 21±6 mm;p=0.02). Presence of late gadolinium enhancement was found in 70% of aHCM and 76% of sHCM individuals (p=0.77). Left ventricular apical aneurysm was significantly more common in aHCM compared to sHCM (17% vs. 0%;p=0.004). Familial HCM was present in 21% in both groups. Overall, 73% (94/128) of individuals were ICD carriers (76% primary and 24% secondary prevention) with similar proportions in both groups. Median follow-up duration was similar for aHCM and sHCM (58 months [IQR 75] vs. 88 months [IQR 125];p=0.34). The primary endpoint occurred twice as often in aHCM individuals (26% vs 12%;p=0.06), mainly driven by the occurrence of sustained ventricular arrhythmias, predominantly monomorphic ventricular tachycardia (23% vs. 9%;p=0.04). Presence of apical aneurysm was an independent predictor of the primary outcome (hazard ratio, 3.2; 95% confidence interval, 0.35-6.08;p=0.03). Genetic test results were available in 38% (49/128) of all individuals. There was a trend towards a higher yield of pathogenic variants in sHCM (21% vs. 0%;p=0.08). Apical-HCM is relatively common in the French-Canadian population, accounting for 27% of cases, and is associated with more frequent ventricular arrhythmias compared to sHCM. Apical aneurysm is an independent predictor of ventricular tachycardia.