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Ventricular arrhythmias in cardiac channelopathies are linked to autonomic triggers, which are sub-optimally targeted in current management strategies. Improved molecular understanding of cardiac channelopathies and cellular autonomic signalling could refine autonomic therapies to target the specific signalling pathways relevant to the specific aetiologies as well as the central nervous system centres involved in the cardiac autonomic regulation. This review summarizes key anatomical and physiological aspects of the cardiac autonomic nervous system and its impact on ventricular arrhythmias in primary inherited arrhythmia syndromes. Proarrhythmogenic autonomic effects and potential therapeutic targets in defined conditions including the Brugada syndrome, early repolarization syndrome, long QT syndrome, and catecholaminergic polymorphic ventricular tachycardia will be examined. Pharmacological and interventional neuromodulation options for these cardiac channelopathies are discussed. Promising new targets for cardiac neuromodulation include inhibitory and excitatory G-protein coupled receptors, neuropeptides, chemorepellents/attractants as well as the vagal and sympathetic nuclei in the central nervous system. Novel therapeutic strategies utilizing invasive and non-invasive deep brain/brain stem stimulation as well as the rapidly growing field of chemo-, opto-, or sonogenetics allowing cell-specific targeting to reduce ventricular arrhythmias are presented. [ABSTRACT FROM AUTHOR]

Accessing the pericardial space safely and efficiently is an important skill for interventional cardiac electrophysiologist. With the increased recognition of the complexity of the 3‐dimensional arrhythmogenic substrate due to advances in imaging and mapping technologies there has been an expansion of epicardial procedures in recent years. Equally, minimally invasive implantation of epicardial pacing, cardiac resynchronization, or defibrillation leads is expanding in specific patients where transvenous systems are contraindicated or their long term sequelae should be ideally avoided. Selective delivery of intrapericardial pharmacological antiarrhythmic therapy is yet another potential indication, albeit still investigational. The expanding indications for percutaneous epicardial procedures is contrasted by the still substantial risk and challenges associated with accessing the pericardial space. Myocardial perforation, coronary artery laceration, and damage to the surrounding organs are all recognized and feared complications. A number of innovative epicardial access techniques have been proposed to overcome the difficulties and risks of traditional dry subxiphoid punctures and may allow for more widespread use of epicardial access in the future. We review 10 different established and novel subxiphoidal epicardial access techniques describing procedural success rates, safety profile and overall experience. The technical aspects as well as access times and costs for extra equipment will be reviewed. Finally, an outlook of reported preclinical techniques awaiting in‐human feasibility studies is provided. [ABSTRACT FROM AUTHOR]

This document is a response by Lambiase and van Duijvenboden to a letter regarding their article titled "Prognostic Significance of Different Ventricular Ectopic Burdens During Submaximal Exercise in Asymptomatic UK Biobank Subjects." The authors appreciate the interest in their publication and acknowledge the limitation of not having continuous blood pressure measurements during exercise in the UK Biobank. However, they did explore the associations between resting blood pressure and PVC burden in more detail. They found that higher resting systolic blood pressure and pulse pressure were associated with an increased risk of high PVC burden. The authors also discuss the potential link between hypertension, autonomic dysfunction, impaired vagal reactivation, and increased PVC burden during recovery. They suggest that future studies with simultaneous measurements of blood pressure and cardiac rhythm during exercise would be of great interest. [Extracted from the article]

Background: The subcutaneous (S) implantable cardioverter-defibrillator (ICD) is safe and effective for sudden cardiac death prevention. However, patients in previous S-ICD studies had fewer comorbidities, had less left ventricular dysfunction, and received more inappropriate shocks (IAS) than in typical transvenous ICD trials. The UNTOUCHED trial (Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction) was designed to evaluate the IAS rate in a more typical, contemporary ICD patient population implanted with the S-ICD using standardized programming and enhanced discrimination algorithms.Methods: Primary prevention patients with left ventricular ejection fraction ≤35% and no pacing indications were included. Generation 2 or 3 S-ICD devices were implanted and programmed with rate-based therapy delivery for rates ≥250 beats per minute and morphology discrimination for rates ≥200 and <250 beats per minute. Patients were followed for 18 months. The primary end point was the IAS-free rate compared with a 91.6% performance goal, derived from the results for the ICD-only patients in the MADIT-RIT study (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy). Kaplan-Meier analyses were performed to evaluate event-free rates for IAS, all-cause shock, and complications. Multivariable proportional hazard analysis was performed to determine predictors of end points.Results: S-ICD implant was attempted in 1116 patients, and 1111 patients were included in postimplant follow-up analysis. The cohort had a mean age of 55.8±12.4 years, 25.6% were women, 23.4% were Black, 53.5% had ischemic heart disease, 87.7% had symptomatic heart failure, and the mean left ventricular ejection fraction was 26.4±5.8%. Eighteen-month freedom from IAS was 95.9% (lower confidence limit, 94.8%). Predictors of reduced incidence of IAS were implanting the most recent generation of device, using the 3-incision technique, no history of atrial fibrillation, and ischemic cause. The 18-month all-cause shock-free rate was 90.6% (lower confidence limit, 89.0%), meeting the prespecified performance goal of 85.8%. Conversion success rate for appropriate, discrete episodes was 98.4%. Complication-free rate at 18 months was 92.7%.Conclusions: This study demonstrates high efficacy and safety with contemporary S-ICD devices and programming despite the relatively high incidence of comorbidities in comparison with earlier S-ICD trials. The inappropriate shock rate (3.1% at 1 year) is the lowest reported for the S-ICD and lower than many transvenous ICD studies using contemporary programming to reduce IAS. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02433379. [ABSTRACT FROM AUTHOR]

Aims A significant proportion of patients implanted with biventricular (BiV) devices fail to respond. Clinical response may be improved by additional ventricular stimulation sites. This single-centre, double-blinded randomized crossover trial aimed to determine whether long-term multisite ventricular pacing is superior to conventional BiV pacing in heart failure patients. Methods and results A total of 43 patients referred for cardiac resynchronization therapy (CRT) underwent transvenous implantation of a triventricular (TriV) device. Pacing leads were positioned in the right ventricular (RV) apex and a lateral coronary sinus (CS) branch, with a third ventricular lead implanted in a further lateral CS branch in 23 patients (group A) and on the high RV septum in 20 patients (group B). Devices were programmed in a randomized order to four pre-determined pacing configurations: conventional BiV, TriV, and dual-site and single-site left bentricular (LV) or RV pacing for 3-month periods with clinical and echo assessment at the end of each period. The primary endpoint was the comparison of 6 min walk distance (6MW) after 3 months of BiV vs. TriV pacing; secondary endpoints were Minnesota Living With Heart Failure (MLWHF) scores, and LV dimensions and function. The 12-month follow-up period was completed by 37 patients. Compared with BiV pacing, TriV pacing resulted in significant improvements in 6MW (451 ± 112 m vs. 425 ± 119 m, P = 0.008), MLWHF (32 ± 19 vs. 38 ± 24, P = 0.036), LV end-systolic volume (158 ± 79mL vs. 168 ± 76 mL, P < 0.05), and ejection fraction (30 ± 8% vs. 27 ± 8%, P < 0.05). Conclusions TriV pacing was associated with significant improvements in clinical and echocardiographic parameters compared with BiV pacing. [ABSTRACT FROM PUBLISHER]

Objective Implantable cardioverter defibrillators (ICDs) are routinely used to prevent sudden cardiac death (SCD) in selected hypertrophic cardiomyopathy (HCM) patients, but the determinants of device-related complications, therapies and long-term cardiovascular mortality in ICD recipients are not known. Design Retrospective observational cohort study. Setting Single-centre tertiary referral cardiomyopathy clinic. Patients 334 consecutively evaluated HCM patients (median age 40 years, 62% male, 92% primary prevention) at risk of SCD treated with ICD. Thirty-six patients (11%) received concurrent cardiac resynchronisation therapy for heart failure symptoms. Results During the 1286 patient-years of follow-up, cardiovascular mortality (including transplantation) occurred in 22 (7%) patients (1.7%/year) and was associated with New York Heart Association (NYHA) class III/IV (adjusted HR=9.38, 95% CI 3.31 to 26.55, p≤0.001), percentage fractional shortening (HR=0.92, 95% CI 0.87 to 0.96, p=0.001) and implantation for secondary prevention (HR=0.07, 95% CI 0.01 to 0.86, p=0.04). There were no SCD. Twenty-eight (8%) patients received appropriate shocks (2.3%/year), which were predicted by baseline fractional shortening (HR=0.96, 95% CI 0.92 to 0.99, p=0.04). Fifty-five (16%) patients received inappropriate shocks (4.6%/ year). Sixty (18%) patients experienced implant-related complications (5.1%/year), including two deaths. Adverse ICD-related events (inappropriate shocks and/or implant complications) were seen in 101 (30%) patients (8.6%/year). Patients with cardiac resynchronisation therapy were more likely to develop implant complications than those with single-chamber ICDs (HR=4.39, 95% CI 1.44 to 13.35, p=0.009) and had a higher 5-year cardiovascular mortality than did the rest of the cohort (21% vs 6%, p<0.001). Conclusions HCM patients with an ICD have a significant cardiovascular mortality and are exposed to frequent inappropriate shocks and implant complications. These data suggest that new strategies are required to improve patient selection for ICDs and to prevent disease progression in those that receive a device. [ABSTRACT FROM AUTHOR]

Putative druggable targets to selectively enhance cardiac conduction can be considered from the level of the ion channels determining the initiation and duration of the cardiac action potential to the gap junction proteins responsible for optimal cellular electrical coupling. Nature has provided a number of inherited disorders of conduction, the pathophysiology of which offer novel insights into future therapeutic targets. This review will focus upon the potential cellular and molecular targets for drug development based upon our knowledge of their pathophysiological impact. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to examine if exercise-induced ischemia initiated late preconditioning in humans that becomes manifest during subsequent exercise and serial balloon occlusion of the left anterior descending coronary artery (LAD).: BackgroundThe existence of late preconditioning in humans is controversial. We therefore compared myocardial responses to exercise-induced and intracoronary balloon inflation–induced ischemia in two groups of patients subjected to different temporal patterns of ischemia.: MethodsThirty patients with stable angina secondary to single-vessel LAD disease underwent percutaneous coronary intervention (PCI) after two separate exercise tolerance test (ETT) protocols designed to investigate isolated early preconditioning (IEP) alone or the second window of protection (SWOP). The IEP subjects underwent three sequential ETTs at least two weeks before PCI. The SWOP subjects underwent five sequential ETTs commencing 24 h before PCI.: ResultsDuring PCI there was no significant difference in intracoronary pressure–derived collateral flow index (CFI) between groups (IEP = 0.15 ± 0.13, SWOP = 0.19 ± 0.15). In SWOP patients, compared with the initial ETT, the ETT performed 24 h later had a 40% (p < 0.001) increase in time to 0.1-mV ST depression and a 60% (p < 0.05) decrease in ventricular ectopic frequency. During the first balloon inflation, peak ST elevation was reduced by 49% (p < 0.05) in the SWOP versus the IEP group, and the dependence on CFI observed in the IEP group was abolished (analysis of covariance, p < 0.05). The significant attenuation of ST elevation (47%, p < 0.005) seen at the time of the second inflation in the IEP patients was not seen in the SWOP patients.: ConclusionsExercise-induced ischemia triggers late preconditioning in humans, which becomes manifest during exercise and PCI. This is the first evidence that ischemia induced by coronary occlusion is attenuated in humans by a late preconditioning effect induced by exercise. [Copyright &y& Elsevier]

Key Points: Question: Is antitachycardia pacing followed by shock clinically equivalent to a shock-only strategy in primary prevention implantable cardioverter-defibrillator recipients when programmed with long detection to therapy delays? Findings: In this randomized clinical trial that included 2626 patients and was designed as an equivalence trial with sequential superiority analysis of each group, anti-tachycardia pacing prior to shock reduced the relative risk of time to first all-cause shock by 28%, a significant difference. Meaning: Antitachycardia pacing is effective as a first-line therapy in prolonging time to first all-cause shock, although the shock burden was not significantly different between the groups during follow-up. Importance: The emergence of novel programming guidelines that reduce premature and inappropriate therapies along with the availability of new implantable cardioverter-defibrillator (ICD) technologies lacking traditional endocardial antitachycardia pacing (ATP) capabilities requires the reevaluation of ATP as a first strategy in terminating fast ventricular tachycardias (VTs) in primary prevention ICD recipients. Objective: To assess the role of ATP in terminating fast VTs in primary prevention ICD recipients with contemporary programming. Design, Setting, and Participants: This global, prospective, double-blind, randomized clinical trial had an equivalence design with a relative margin of 35%. Superiority tests were performed at interim analyses and the final analysis if equivalence was not proven. Patients were enrolled between September 2016 and April 2021 at 134 sites in 8 countries, with the last date of follow-up on July 6, 2023. Patients were required to have an indication for a primary prevention ICD, including left ventricular ejection fraction less than or equal to 35%. Interventions: Patients were randomized in a 1:1 ratio to receive ATP plus shock vs shock only. Main Outcomes and Measures: The primary end point was time to first all-cause shock. Secondary end points included time to first appropriate shock, time to first inappropriate shock, all-cause mortality, and the composite of time to first all-cause shock plus all-cause mortality. Results: A total of 2595 patients were randomized (mean age, 63.9 years; 22.4% were females). At a mean follow-up of 38 months, first all-cause shock occurred in 129 participants in the ATP plus shock group and 178 participants in the shock only group. The hazard ratio (HR) for the primary end point was 0.72 (95.9% CI, 0.57-0.92), with P =.005 for superiority of the ATP plus shock group over the shock only group. During follow-up in an intention-to-treat analysis, the total shock burden per 100 patient-years was not statistically different, at 12.3 and 14.9, respectively (P =.70). Conclusions and Relevance: The use of a single burst of ATP prior to shock in primary prevention ICD recipients with modern ICD detection programming prolonged the time to first all-cause ICD shock. Trial Registration: ClinicalTrials.gov Identifier: NCT02923726 This randomized clinical trial assesses the role of antitachycardia pacing in terminating fast ventricular tachycardia in primary prevention patients with implantable cardioverter-defibrillators with contemporary programming. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does pulmonary vein isolation have a placebo effect in treatment of atrial fibrillation? Findings: In this double-blind randomized trial of 126 patients with symptomatic atrial fibrillation, pulmonary vein isolation resulted in a significant and clinically important decrease in atrial fibrillation burden, with substantial improvements in symptoms and quality of life, compared with a sham procedure. Meaning: Pulmonary vein isolation significantly reduced atrial fibrillation burden compared with a sham control, providing evidence that the benefit of pulmonary vein isolation in symptomatic atrial fibrillation is not because of a placebo effect. Importance: There are concerns that pulmonary vein isolation for atrial fibrillation may have a profound placebo effect, but no double-blind randomized clinical trials have been conducted. Objective: To determine whether pulmonary vein isolation is more effective than a sham procedure for improving outcomes in atrial fibrillation. Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 2 tertiary centers in the UK between January 2020 and March 2024 among patients with symptomatic paroxysmal or persistent atrial fibrillation. Major exclusion criteria included long-standing persistent atrial fibrillation, prior left atrium ablation, other arrhythmias requiring ablative therapy, a left atrium of 5.5 cm or larger, and ejection fraction of less than 35%. Intervention: Participants were randomly assigned to receive pulmonary vein isolation with cryoablation (n = 64) or a sham procedure with phrenic nerve pacing (n = 62). Main Outcomes and Measures: The primary end point was atrial fibrillation burden at 6 months, excluding a 3-month blanking period. Secondary outcomes included quality-of-life measures, time to events, and safety. Atrial fibrillation burden was measured by an implantable loop recorder. Results: A total of 126 participants were randomized (mean age, 66.8 years; 89 men [70.63%]; 20.63% with paroxysmal atrial fibrillation). The absolute mean atrial fibrillation burden change from baseline to 6 months was 60.31% in the ablation group and 35.0% in the sham group (geometric mean difference, 0.25; 95% CI, 0.15-0.42; P <.001). The estimated difference in the overall Atrial Fibrillation Effect on Quality of Life score at 6 months, favoring catheter ablation, was 18.39 points (95% CI, 11.48-25.30 points). The Short Form 36 general health score also improved substantially more with ablation, with an estimated difference of 9.27 points at 6 months (95% CI, 3.78-14.76 points). Conclusions and Relevance: Pulmonary vein isolation resulted in a statistically significant and clinically important decrease in atrial fibrillation burden at 6 months, with substantial improvements in symptoms and quality of life, compared with a sham procedure. Trial Registration: ClinicalTrials.gov Identifier: NCT04272762 This randomized clinical trial assesses the effect of pulmonary vein isolation vs a sham procedure on atrial fibrillation burden at 6 months in patients with symptomatic paroxysmal or persistent atrial fibrillation. [ABSTRACT FROM AUTHOR]

An elevated resting heart rate (RHR) is associated with increased cardiovascular mortality. Genome-wide association studies (GWAS) have identified > 350 loci. Uniquely, in this study we applied genetic fine-mapping leveraging tissue specific chromatin segmentation and colocalization analyses to identify causal variants and candidate effector genes for RHR. We used RHR GWAS summary statistics from 388,237 individuals of European ancestry from UK Biobank and performed fine mapping using publicly available genomic annotation datasets. High-confidence causal variants (accounting for > 75% posterior probability) were identified, and we collated candidate effector genes using a multi-omics approach that combined evidence from colocalisation with molecular quantitative trait loci (QTLs), and long-range chromatin interaction analyses. Finally, we performed druggability analyses to investigate drug repurposing opportunities. The fine mapping pipeline indicated 442 distinct RHR signals. For 90 signals, a single variant was identified as a high-confidence causal variant, of which 22 were annotated as missense. In trait-relevant tissues, 39 signals colocalised with cis-expression QTLs (eQTLs), 3 with cis-protein QTLs (pQTLs), and 75 had promoter interactions via Hi-C. In total, 262 candidate genes were highlighted (79% had promoter interactions, 15% had a colocalised eQTL, 8% had a missense variant and 1% had a colocalised pQTL), and, for the first time, enrichment in nervous system pathways. Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets. Our genetic fine-mapping pipeline prioritised 262 candidate genes for RHR that warrant further investigation in functional studies, and we provide potential therapeutic targets to reduce RHR and cardiovascular mortality. [ABSTRACT FROM AUTHOR]

A letter commenting on new standard for assessment of bleeding risk in patients with atrial fibrillation and supporting the role of biomarkers in the field of arrhythmic disorders as discussed by researcher Ziad Hijazi and colleagues is presented.

A letter to the editor is presented in response to the article "Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation" by Karl-Heinz Kuck, and colleagues in the June 9, 2016 issue.

A letter to the editor is presented in response to the article "Atrial fibrillation begets heart failure and vice versa: temporal associations and differences in preserved versus reduced ejection fraction," by Rajalakshmi Santhanakrishnan and colleagues in the 206 issue.

A letter to the editor is presented in response to the article "Arrhythmic mitral valve prolapse and sudden cardiac death," by Cristina Basso and colleagues in the 2015 issue.

BACKGROUND: The consequences of exercise-induced premature ventricular contractions (PVCs) in asymptomatic individuals remain unclear. This study aimed to assess the association between PVC burdens during submaximal exercise and major adverse cardiovascular events (MI/HF/LTVA: myocardial infarction [MI], heart failure [HF], and life-threatening ventricular arrhythmia [LTVA]), and all-cause mortality. Additional end points were MI, LTVA, HF, and cardiovascular mortality. METHODS: A neural network was developed to count PVCs from ECGs recorded during exercise (6 minutes) and recovery (1 minute) in 48 315 asymptomatic participants from UK Biobank. Associations were estimated using multivariable Cox proportional hazard models. Explorative studies were conducted in subgroups with cardiovascular magnetic resonance imaging data (n=6290) and NT-proBNP (N-terminal Pro-B-type natriuretic peptide) levels (n=4607) to examine whether PVC burden was associated with subclinical cardiomyopathy. RESULTS: Mean age was 56.8±8.2 years; 51.1% of the participants were female; and median follow-up was 12.6 years. Low PVC counts during exercise and recovery were both associated with MI/HF/LTVA risk, independently of clinical factors: adjusted hazard ratio (HR), 1.2 (1–5 exercise PVCs, P <0.001) and HR, 1.3 (1–5 recovery PVCs, P <0.001). Risks were higher with increasing PVC count: HR, 1.8 (>20 exercise PVCs, P <0.001) and HR, 1.6 (>5 recovery PVCs, P <0.001). A similar trend was observed for all-cause mortality, although associations were only significant for high PVC burdens: HRs, 1.6 (>20 exercise PVCs, P <0.001) and 1.5 (>5 recovery PVCs, P <0.001). Complex PVC rhythms were associated with higher risk compared with PVC count alone. PVCs were also associated with incident HF, LTVA, and cardiovascular mortality, but not MI. In the explorative studies, high PVC burden was associated with larger left ventricular volumes, lower ejection fraction, and higher levels of NT-proBNP compared with participants without PVCs. CONCLUSIONS: In this cohort of middle-aged and older adults, PVC count during submaximal exercise and recovery were both associated with MI/HF/LTVA, all-cause mortality, HF, LTVAs, and cardiovascular mortality, independent of clinical and exercise test factors, indicating an incremental increase in risk as PVC count rises. Complex PVC rhythms were associated with higher risk compared with PVC count alone. Underlying mechanisms may include the presence of subclinical cardiomyopathy. [ABSTRACT FROM AUTHOR]

Heart rate variability (HRV) is a cardiac autonomic marker with predictive value in cardiac patients. Ultra-short HRV (usHRV) can be measured at scale using standard and wearable ECGs, but its association with cardiovascular events in the general population is undetermined. We aimed to validate usHRV measured using ≤ 15-s ECGs (using RMSSD, SDSD and PHF indices) and investigate its association with atrial fibrillation, major adverse cardiac events, stroke and mortality in individuals without cardiovascular disease. In the National Survey for Health and Development (n = 1337 participants), agreement between 15-s and 6-min HRV, assessed with correlation analysis and Bland–Altman plots, was very good for RMSSD and SDSD and good for PHF. In the UK Biobank (n = 51,628 participants, 64% male, median age 58), after a median follow-up of 11.5 (11.4–11.7) years, incidence of outcomes ranged between 1.7% and 4.3%. Non-linear Cox regression analysis showed that reduced usHRV from 15-, 10- and 5-s ECGs was associated with all outcomes. Individuals with low usHRV (< 20th percentile) had hazard ratios for outcomes between 1.16 and 1.29, p < 0.05, with respect to the reference group. In conclusion, usHRV from ≤ 15-s ECGs correlates with standard short-term HRV and predicts increased risk of cardiovascular events in a large population-representative cohort. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The unipolar electrogram (UEG) provides local measures of cardiac activation and repolarization and is an important translational link between patient and laboratory. A simple theoretical model of the UEG was previously proposed and tested in silico. Method and results: The aim of this study was to use epicardial sock‐mapping data to validate the simple model's predictions of unipolar electrogram morphology in the in vivo human heart. The simple model conceptualizes the UEG as the difference between a local cardiac action potential and a position‐independent component representing remote activity, which is defined as the average of all action potentials. UEGs were recorded in 18 patients using a multielectrode sock containing 240 electrodes and activation (AT) and repolarization time (RT) were measured using standard definitions. For each cardiac site, a simulated local action potential was generated by adjusting a stylized action potential to fit AT and RT measured in vivo. The correlation coefficient (cc) measuring the morphological similarity between 13,637 recorded and simulated UEGs was cc  =  0.89 (0.72–0.95), median (Q1–Q3), for the entire UEG, cc  =  0.90 (0.76–0.95) for QRS complexes, and cc  =  0.83 (0.58–0.92) for T‐waves. QRS and T‐wave areas from recorded and simulated UEGs showed cc> 0.89 and cc> 0.84, respectively, indicating good agreement between voltage isochrones maps. Simulated UEGs accurately reproduced the interaction between AT and QRS morphology and between RT and T‐wave morphology observed in vivo. Conclusions: Human in vivo whole heart data support the validity of the simple model, which provides a framework for improving the understanding of the UEG and its clinical utility. [ABSTRACT FROM AUTHOR]

Background/Purpose: Lyme disease (LD) is an emerging problem in the Canadian province of Nova Scotia with a sharp rise in reported cases over the past 2 years, including cases referred to the pediatric rheumatology clinic in Halifax, the sole pediatric rheumatology referral centre in the province. This increase is likely related to an increase in the number and size of endemic areas in the province; it is expected that cases will continue to rise. We sought to characterize the demographics, clinical presentation, treatment course and musculoskeletal outcome of children with LD in our clinic. Methods: Subjects with a diagnosis of LD since 2008 were identified in the pediatric rheumatology clinic database. The medical records of patients with LD were reviewed for demographic variables, referral patterns, clinical presentation, investigations, treatment course, and outcome. Results: Seventeen patients were identified; all patients were referred for evaluation of arthritis. 76% of patients presented in 2012 and 2013. Median age was 11.5 years (2.6-15.8), 16 were male. All lived in known endemic areas with Lunenburg county being most common (59%); 76% did not recall a tick bite. Subjects were referred by their family physician (7), emergency department (4), orthopedic surgery (4), and infectious diseases (2). The median number of physician visits for MSK symptoms prior to rheumatology consult was 2 (range 1 to >5). Only one patient was referred with a known diagnosis of LD; LD was suspected in 37.5% of the remaining cases based on referral information. Six patients had prior joint aspiration, 2 of whom were treated for septic arthritis. Pain and/or swelling were reported by all patients; in those with swelling 47% were persistent/53% episodic. The median number of joints involved was 1, with 94% having knee involvement. Patients reported MSK-symptoms for a median of 2 months (range 0.1-11) prior to referral to rheumatology. Four patients had a history of neurologic manifestations of LD prior to MSK presentation, none of which were recognized as LD. ECG was done in 13 cases and was normal. Three patients had a history of erythema migrans. 14/17 patients have completed antibiotic treatment. Arthritis resolved in 50% of patients after 1 course of antibiotics and 29% after 2 courses. A third course of antibiotics was required in 21% of patients for persistent arthritis. Two patients continued to have arthritis following completion of antibiotic therapy. At a median of 5 months (range 0-50) following treatment, there are 2 patients with persistent synovitis and functional limitations; one having evidence of joint damage despite extensive arthritis treatment (NSAID, steroid injection, DMARDs and a biologic). Conclusion: Increasing numbers of children with Lyme arthritis are being seen in the pediatric rheumatology clinic in Nova Scotia. LD was not considered as a diagnosis in the majority of cases by the referring physician. A quarter of patients also had a history of unrecognized neurologic manifestations of LD. In keeping with published North American reports, most patients had an excellent outcome however a proportion continued to have arthritis and disability following antibiotic therapy. [ABSTRACT FROM AUTHOR]

Commotio cordis is a rare phenomenon when ventricular fibrillation and sudden death occurs with a blunt, nonpenetrating blow to the chest. Individual susceptibility to commotio cordis has been demonstrated in swine models, and might be present in humans as well. We report a case of commotio cordis in an adolescent with a heterozygous mutation on the gene CACNA1C, encoding for an L‐type calcium channel expressed in the heart. This genetic mutation has been previously associated with a phenotype of long‐QT syndrome; however, this was not demonstrated in our patient despite extensive investigations. To the best of our knowledge, this is the first report of commotio cordis in which an ion‐channel gene mutation involved in repolarization abnormalities has been documented. This finding might corroborate the hypothesis that a genetic predisposition plays a role in the individual susceptibility to this rare cause of cardiac arrest. [ABSTRACT FROM AUTHOR]

Introduction: Preliminary data suggest that high power short duration (HPSD) ablation for pulmonary vein isolation (PVI) are safe. Limited data are available on its effectiveness. Aim was to evaluate HPSD ablation in atrial fibrillation ablation using a novel Qdot Micro catheter. Methods and Results: Prospective multicenter study evaluating safety and efficacy of PVI with HPSD ablation. First pass isolation (FPI) and sustained PVI was assessed. If FPI was not achieved additional ablation index (AI)‐guided ablation with 45 W was performed and metrics predictive of this were determined. Sixty‐five patients and 260 veins were treated. Procedural and LA dwell time was 93.9 ± 30.4 and 60.5 ± 23.1 min, respectively. FPI was achieved in 47 (72.3%) patients and 231 veins (88.8%) with an ablation duration of 4.6 ± 1.0 min. Twenty‐nine veins required additional AI‐guided ablation to achieve initial PVI with 24 anatomical sites ablated with the right posterior carina being the most common site (37.5%). A contact force of ≥8 g (area under the curve [AUC]: 0.81; p < 0.001) and catheter position variation of ≤1.2 mm (AUC: 0.79; p < 0.001) with HPSD were strongly predictive of not requiring additional AI‐guided ablation. Out of the 260 veins, only 5 (1.9%) veins showed acute reconnection. HPSD ablation was associated with shorter procedure times (93.9 vs. 159.4 min; p < 0.001), ablation times (6.1 vs. 27.7 min; p < 0.001), and lower rates of PV reconnection (9.2% vs. 30.8%; p = 0.004) compared to moderate power cohort. Conclusions: HPSD ablation is an effective ablation modality which results in effective PVI whilst maintaining a safety profile. Its superiority needs to be evaluated in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: This prospective trial sought to phenotype persistent atrial fibrillation (AF) based on AF mechanisms using electrocardiographic imaging (ECGI) mapping to determine whether this would predict long‐term freedom from arrhythmia after pulmonary vein isolation (PVI). Methods: Patients with persistent AF of <2 years duration underwent cryoballoon PVI. ECGI mapping was performed before PVI to determine potential drivers (PDs) defined as rotational activations completing ≥1.5 revolutions or focal activations. The coprimary endpoint was the association between (1) PD burden (defined as the number of PD occurrences) and (2) PD distribution (defined as the number of segments on an 18‐segment model of the atria harboring PDs) with freedom from arrhythmia at 1‐year follow up. Results: Of 100 patients, 97 completed follow up and 52 (53.6%) remained in sinus rhythm off antiarrhythmic drugs. Neither PD burden nor PD distribution predicted freedom from arrhythmia (hazard ratio [HR]: 1.01, 95% confidence interval [CI]: 0.99–1.03, p =.164; and HR: 1.04, 95% CI: 0.91–1.17, p =.591, respectively). Otherwise, the burden of rotational PDs, rotational stability, and the burden of PDs occurring at the pulmonary veins and posterior wall all failed to predict arrhythmia recurrence (all p >.10). Conclusions: AF mechanisms as determined using ECGI mapping do not predict outcomes after PVI for persistent AF. Further studies using different methodologies to characterize AF mechanisms are warranted (NCT03394404). [ABSTRACT FROM AUTHOR]

Introduction: We assessed the prevalence of non‐type 1 Brugada pattern (T1BrP) in children and young adults from the Sudden Cardiac Death‐Screening Of risk factorS cohort and the diagnostic yield of nonexpert manual and automatic algorithm electrocardiogram (ECG) measurements. Methods: Cross‐sectional study. We reviewed 14 662 ECGs and identified 2226 with a rSr′‐pattern in V1‐V2. Among these, 115 were classified by experts in hereditary arrhythmic‐syndromes as having or not non‐T1BrP, and were compared with measurements of 5 ECG‐derived parameters based on a triangle formed by r′ ‐wave (d(A), d(B), d(B)/h, β‐angle) and ST‐ascent, assessed both automatically and manually by nonexperts. We estimated intra‐ and interobserver concordance for each criterion, calculated diagnostic accuracy and defined the most appropriate cut‐off values. Results: A rSr′‐pattern in V1‐V2 was associated with higher PQ interval and QRS duration, male gender, and lower body mass index (BMI). The manual measurements of non‐T1BrP criteria were moderately reproducible with high intraobserver and moderate interobserver concordance coefficients (ICC: 0.72–0.98, and 0.63–0.76). Criteria with higher discriminatory capacity were: distance d(B) (0.72; 95% confidence interval [CI]: 0.65−0.80) and ST‐ascent (0.87; 95% CI: 0.82–0.92), which was superior to the 4 r′‐wave criteria together (area under curve [AUC: 0.74]). We suggest new cut‐offs with improved combination of sensitivity and specificity: d(B) ≥ 1.4 mm and ST‐ascent ≥ 0.7 mm (sensitivity: 1%–82%; specificity: 71%–84%), that can be automatically measured to allow classification in four morphologies with increasing non‐T1BrP probability. Conclusion: rSr′‐pattern in precordial leads V1‐V2 is a frequent finding and the detection of non‐T1BrP by using the aforementioned five measurements is reproducible and accurate. In this study, we describe new cut‐off values that may help untrained clinicians to identify young individuals who may require further work‐up for a potential Brugada Syndrome diagnosis. [ABSTRACT FROM AUTHOR]

Background: Clinical decision-making is influenced by many factors, including clinicians' perceptions of the certainty around what is the best course of action to pursue. Objective: To characterise the documentation of working diagnoses and the associated level of real-time certainty expressed by clinicians and to gauge patient opinion about the importance of research into clinician decision certainty. Method: This was a single-centre retrospective cohort study of non-consultant grade clinicians and their assessments of patients admitted from the emergency department between 01 March 2019 and 31 March 2019. De-identified electronic health record proformas were extracted that included the type of diagnosis documented and the certainty adjective used. Patient opinion was canvassed from a focus group. Results: During the study period, 850 clerking proformas were analysed; 420 presented a single diagnosis, while 430 presented multiple diagnoses. Of the 420 single diagnoses, 67 (16%) were documented as either a symptom or physical sign and 16 (4%) were laboratory-result-defined diagnoses. No uncertainty was expressed in 309 (74%) of the diagnoses. Of 430 multiple diagnoses, uncertainty was expressed in 346 (80%) compared to 84 (20%) in which no uncertainty was expressed. The patient focus group were unanimous in their support of this research. Conclusion: The documentation of working diagnoses is highly variable among non-consultant grade clinicians. In nearly three quarters of assessments with single diagnoses, no element of uncertainty was implied or quantified. More uncertainty was expressed in multiple diagnoses than single diagnoses. Implications: Increased standardisation of documentation will help future studies to better analyse and quantify diagnostic certainty in both single and multiple working diagnoses. This could lead to subsequent examination of their association with important process or clinical outcome measures. [ABSTRACT FROM AUTHOR]

Background: Infection remains a major complication of cardiac implantable electronic devices and can lead to significant morbidity and mortality. Implantable devices that avoid transvenous leads, such as the subcutaneous implantable cardioverter‐defibrillator (S‐ICD), can reduce the risk of serious infection‐related complications, such as bloodstream infection and infective endocarditis. While the 2017 AHA/ACC/HRS guidelines include recommendations for S‐ICD use for patients at high risk of infection, currently, there are no clinical trial data that address best practices for the prevention of S‐ICD infections. Therefore, an expert panel was convened to develop a consensus on these topics. Methods: An expert process mapping methodology was used to achieve consensus on the appropriate steps to minimize or prevent S‐ICD infections. Two face‐to‐face meetings of high‐volume S‐ICD implanters and an infectious diseases specialist, with expertise in cardiovascular implantable electronic device infections, were conducted to develop consensus on useful strategies pre‐, peri‐, and postimplant to reduce S‐ICD infection risk. Results: Expert panel consensus on recommended steps for patient preparation, S‐ICD implantation, and postoperative management was developed to provide guidance in individual patient management. Conclusion: Achieving expert panel consensus by process mapping methodology for S‐ICD infection prevention was attainable, and the results should be helpful to clinicians in adopting interventions to minimize risks of S‐ICD infection. [ABSTRACT FROM AUTHOR]

Introduction: Transvenous implantable cardioverter‐defibrillators (TV‐ICD) infection is a serious complication that frequently requires complete device removal for attempted cure, which can be associated with patient morbidity and mortality. The objective of this study is to assess mortality risk associated with TV‐ICD infection in a large Medicare population with de novo TV‐ICD implants. Methods: A survival analysis was conducted using 100% fee‐for‐service Medicare facility‐level claims data to identify patients who underwent de novo TV‐ICD implantation between 7/2016 and 1/2018. TV‐ICD infection within 2 years of implantation was identified using International Classification of Disease, 10th Edition and current procedural terminology codes. Baseline patient risk factors associated with mortality were identified using the Charlson Comorbidity Index categories. Infection was treated as a time‐dependent variable in a multivariate Cox proportional hazards model to account for immortal time bias. Results: Among 26,742 Medicare patients with de novo TV‐ICD, 518 (1.9%) had a device‐related infection. The overall number of decedents was 4721 (17.7%) over 2 years, with 4555 (17%) in the noninfection group and 166 (32%) in the infection group. After adjusting for baseline patient demographic characteristics and various comorbidities, the presence of TV‐ICD infection was associated with an increase of 2.4 (95% CI: 2.08–2.85) times in the mortality hazard ratio. Conclusion: The rate of TV‐ICD infection and associated mortality in a large, real‐world Medicare population is noteworthy. The positive association between device‐related infection and risk of mortality further highlights the need to reduce infections [ABSTRACT FROM AUTHOR]

Aims Sudden cardiac death (SCD) is a common mode of death in hypertrophic cardiomyopathy (HCM), but identification of patients who are at a high risk of SCD is challenging as current risk stratification guidelines have never been formally validated. The objective of this study was to assess the power of the 2003 American College of Cardiology (ACC)/European Society of Cardiology (ESC) and 2011 ACC Foundation (ACCF)/American Heart Association (AHA) SCD risk stratification algorithms to distinguish high risk patients who might be eligible for an implantable cardioverter defibrillator (ICD) from low risk individuals. Methods and results We studied 1606 consecutively evaluated HCM patients in an observational, retrospective cohort study. Five risk factors (RF) for SCD were assessed: non-sustained ventricular tachycardia, severe left ventricular hypertrophy, family history of SCD, unexplained syncope and abnormal blood pressure response to exercise. During a follow-up period of 11 712 patient years (median 6.6 years), SCD/appropriate ICD shock occurred in 20 (3%) of 660 patients without RF (annual rate 0.45%), 31 (4.8%) of 636 patients with 1 RF (annual rate 0.65%), 27 (10.8%) of 249 patients with 2 RF (annual rate 1.3%), 7 (13.7%) of 51 patients with 3 RF (annual rate 1.9%) and 4 (40%) of 10 patients with ⩾4 RF (annual rate 5.0%). The risk of SCD increased with multiple RF (2 RF: HR 2.87, p⩽0.001; 3 RF: HR 4.32, p=0.001; ⩾4 RF: HR 11.37, p<0.0001), but not with a single RF (HR 1.43 p=0.21). The area under time-dependent receiver operating characteristic curves (representing the probability of correctly identifying a patient at risk of SCD on the basis of RF profile) was 0.63 at 1 year and 0.64 at 5 years for the 2003 ACC/ESC algorithm and 0.61 at 1 year and 0.63 at 5 years for the 2011 ACCF/AHA algorithm. Conclusions The risk of SCD increases with the aggregation of RF. The 2003 ACC/ESC and 2011 ACCF/AHA guidelines distinguish high from low risk individuals with limited power. [ABSTRACT FROM AUTHOR]

Introduction: Ethanol ablation (EA) is an alternative option for subjects with ventricular arrhythmias (VAs) refractory to conventional medical and ablative treatment. However, data on the efficacy and safety of EA remain sparse. Methods: A systematic literature search was conducted. The primary outcomes were 1) freedom from the targeted VA and 2) freedom from any VAs post‐EA. Additional safety outcomes were also analyzed. Results: Ten studies were selected accounting for a population of 174 patients (62.3 ± 12.5 years, 94% male) undergoing 185 procedures. The overall acute success rate of EA was 72.4% (confidence interval [CI95%]: 65.6–78.4). After a mean follow‐up of 11.3 ± 5.5 months, the incidence of relapse of the targeted VA was 24.4% (CI95%: 17.1–32.8), while any VAs post‐EA occurred in 41.3% (CI95%: 33.7–49.1). The overall incidence of procedural complications was 14.1% (CI95%: 9.8–19.8), with pericardial complications and complete atrioventricular block being the most frequent. An anterograde transarterial approach was associated with a higher rate of VA recurrences and complications compared to a retrograde transvenous route; however, differences in the baseline population characteristics and in the targeted ventricular areas should be accounted. Conclusion: EA is a valuable therapeutic option for VAs refractory to conventional treatment and can result in 1‐year freedom from VA recurrence in 60%–75% of the patients. However, anatomical or technical challenges preclude acute success in almost 30% of the candidates and the rate of complication is not insignificant, highlighting the importance of well‐informed patient selection. The certainty of the evidence is low, and further research is necessary. [ABSTRACT FROM AUTHOR]

Background: The risk factors for developing pacing induced left ventricular dysfunction (LVD) in patients with high burden of right ventricular pacing (RVP) is poorly understood. Therefore, in the present study, we aimed to assess the determinants of pacing induced LVD. Methods: Our data were retrospectively collected from 146 patients with RVP > 40% who underwent generator change (GC) or cardiac resynchronization therapy (CRT) upgrade between 2016 and 2019 who had left ventricular ejection fraction (EF) ≥50% at initial implant. Results: A total of 75 patients had CRT upgrade due to pacing induced LVD (EF < 50%) and 71 patients with preserved LV function (EF ≥ 50%) had a GC. Primary indication for pacing in both groups was complete heart block. Male predominance (p =.008), prior myocardial infarction (MI) (p =.001), atrial fibrillation (AF) (p =.009), chronic kidney disease (CKD) (p =.005), and borderline low systolic function (BLSF) (EF 50%–55%) (p =.04) were more prevalent in the CRT upgrade group. Presence of AF (odds ratio [OR] = 3.05, 95% confidence interval [CI] 1.42–6.58; p =.004), BLSF (OR = 3.8, 95% CI 1.22–11.8; p =.02), and male gender (OR = 2.41, 95% CI 1.14–5.08; p =.02) were independent predictors for RVP induced LVD. Age (OR = 1.08, 95% CI 1.02–1.14; p =.005) and BLSF (OR = 5.33, 95% CI 1.26–22.5; p =.023) were independent predictors of earlier development of LVD after implant. Conclusions: Our results suggested that AF, BLSF, and male gender are predictors for development of pacing induced LVD in patients with high RVP burden. LVD can occur at any time after pacemaker implant with BLSF and increasing age associated with earlier development of LVD. [ABSTRACT FROM AUTHOR]

Background: The PRAETORIAN trial (A Prospective, Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy) showed noninferiority of subcutaneous implantable cardioverter defibrillator (S-ICD) compared with transvenous implantable cardioverter defibrillator (TV-ICD) with regard to inappropriate shocks and complications. In contrast to TV-ICD, S-ICD cannot provide antitachycardia pacing for monomorphic ventricular tachycardia. This prespecified secondary analysis evaluates appropriate therapy and whether antitachycardia pacing reduces the number of appropriate shocks.Methods: The PRAETORIAN trial was an international, investigator-initiated randomized trial that included patients with an indication for implantable cardioverter defibrillator (ICD) therapy. Patients with previous ventricular tachycardia <170 bpm or refractory recurrent monomorphic ventricular tachycardia were excluded. In 39 centers, 849 patients were randomized to receive an S-ICD (n=426) or TV-ICD (n=423) and were followed for a median of 49.1 months. ICD programming was mandated by protocol. Appropriate ICD therapy was defined as therapy for ventricular arrhythmias. Arrhythmias were classified as discrete episodes and storm episodes (≥3 episodes within 24 hours). Analyses were performed in the modified intention-to-treat population.Results: In the S-ICD group, 86 of 426 patients received appropriate therapy, versus 78 of 423 patients in the TV-ICD group, during a median follow-up of 52 months (48-month Kaplan-Meier estimates 19.4% and 17.5%; P=0.45). In the S-ICD group, 83 patients received at least 1 shock, versus 57 patients in the TV-ICD group (48-month Kaplan-Meier estimates 19.2% and 11.5%; P=0.02). Patients in the S-ICD group had a total of 254 shocks, compared with 228 shocks in the TV-ICD group (P=0.68). First shock efficacy was 93.8% in the S-ICD group and 91.6% in the TV-ICD group (P=0.40). The first antitachycardia pacing attempt successfully terminated 46% of all monomorphic ventricular tachycardias, but accelerated the arrhythmia in 9.4%. Ten patients with S-ICD experienced 13 electrical storms, versus 18 patients with TV-ICD with 19 electrical storms. Patients with appropriate therapy had an almost 2-fold increased relative risk of electrical storms in the TV-ICD group compared with the S-ICD group (P=0.05).Conclusions: In this trial, no difference was observed in shock efficacy of S-ICD compared with TV-ICD. Although patients in the S-ICD group were more likely to receive an ICD shock, the total number of appropriate shocks was not different between the 2 groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022. [ABSTRACT FROM AUTHOR]

: ObjectivesWe investigated whether the source of the acute phase response in unstable angina (UA) lay within the culprit coronary plaque or distal myocardium.: BackroundAn inflammatory response is an important component of the acute coronary syndromes. However, its origin and mechanism remain unclear.: MethodsIn 94 stable patients undergoing coronary angiography, the relationship between systemic levels of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6) and C-reactive protein (CRP) and extent of atherosclerosis was studied. The temporal relationship between these markers and troponin T (TnT) was determined in 91 patients with UA. Cytokine levels were measured in the aortic root and coronary sinus of 36 unstable patients.: ResultsThere was no relationship found between stable coronary atherosclerosis and inflammatory marker levels. Compared with this group, admission levels of IL-6 (3.6 ± 0.3 ng/ml vs. 10.7 ± 1.7 ng/ml, p < 0.05) and CRP (2.3 ± 0.1 mg/l vs. 4.6 ± 0.6 mg/l, p < 0.05) were elevated in patients with UA. In this group, IL-6 and CRP remained elevated in those who subsequently experienced major adverse cardiac events. This inflammatory response occurred in parallel to the appearance of TnT. Both TNF-alpha (19.2 ± 3.4 ng/ml vs. 17.1 ± 3.3 ng/ml, p < 0.001) and IL-6 (10.3 ± 1.4 ng/ml vs. 7.7 ± 1.1 ng/ml, p < 0.01) were elevated in the coronary sinus compared with aortic root in patients with UA. This was principally observed in those who were TnT positive. There was no cytokine gradient across the culprit plaque.: ConclusionsThere is an intracardiac inflammatory response in UA that appears to be the result of low-grade myocardial necrosis. The ruptured plaque does not appear to contribute to the acute phase response. [Copyright &y& Elsevier]

The electrocardiogram (ECG) is a commonly used clinical tool that reflects cardiac excitability and disease. Many parameters are can be measured and with the improvement of methodology can now be quantified in an automated fashion, with accuracy and at scale. Furthermore, these measurements can be heritable and thus genome wide association studies inform the underpinning biological mechanisms. In this review we describe how we have used the resources in UK Biobank to undertake such work. In particular, we focus on a substudy uniquely describing the response to exercise performed at scale with accompanying genetic information. [ABSTRACT FROM AUTHOR]

Background: Anatomical studies demonstrate significant variation in cavotricuspid isthmus (CTI) architecture. Methods: Thirty‐eight patients underwent CTI ablation at two tertiary centers. Operators delivered 682 lesions with a target ablation index (AI) of 600 Wgs. Ablation parameters were recorded every 10–20 ms. Post hoc, Visitags were trisected according to CTI position: inferior vena cava (IVC), middle (Mid), or ventricular (V) lesions. Results: There were no complications. 92.1% of patients (n = 35) remained in sinus rhythm after 14.6 ± 3.4 months. For the whole CTI, peak AI correlated with mean impedance drop (ID) (R2 = 0.89, p <.0001). However, analysis by anatomical site demonstrated a non‐linear relationship Mid CTI (R2 = 0.15, p =.21). Accordingly, while mean AI was highest Mid CTI (IVC: 473.1 ± 122.1 Wgs, Mid: 539.6 ± 103.5 Wgs, V: 486.2 ± 111.8 Wgs, ANOVA p <.0001), mean ID was lower (IVC: 10.7 ± 7.5Ω, Mid: 9.0 ± 6.5Ω, V: 10.9 ± 7.3Ω, p =.011), and rate of ID was slower (IVC: 0.37 ± 0.05 Ω/s, Mid: 0.18 ± 0.08 Ω/s, V: 0.29 ± 0.06 Ω/s, p <.0001). Mean contact force was similar at all sites; however, temporal fluctuations in contact force (IVC: 19.3 ± 12.0 mg/s, Mid: 188.8 ± 92.1 mg/s, V: 102.8 ± 32.3 mg/s, p <.0001) and catheter angle (IVC: 0.42°/s, Mid: 3.4°/s, V: 0.28°/s, p <.0001) were greatest Mid CTI. Use of a long sheath attenuated these fluctuations and improved energy delivery. Conclusions: Ablation characteristics vary across the CTI. At the Mid CTI, higher AI values do not necessarily deliver more effective ablation; this may reflect localized fluctuations in catheter angle and contact force. [ABSTRACT FROM AUTHOR]

Background: We evaluated the effect of adenosine upon mechanisms sustaining persistent AF through analysis of contact electrograms and ECGI mapping. Methods: Persistent AF patients undergoing catheter ablation were included. ECGI maps and cycle length (CL) measurements were recorded in the left and right atrial appendages and repeated following boluses of 18 mg of intravenous adenosine. Potential drivers (PDs) were defined as focal or rotational activations completing ≥ 1.5 revolutions. Distribution of PDs was assessed using an 18 segment biatrial model. Results: 46 patients were enrolled. Mean age was 63.4 ± 9.8 years with 33 (72%) being male. There was no significant difference in the number of PDs recorded at baseline compared to adenosine (42.1 ± 15.2 vs 40.4 ± 13.0; p = 0.417), nor in the number of segments harbouring PDs, (13 (11–14) vs 12 (10–14); p = 0.169). There was a significantly higher percentage of PDs that were focal in the adenosine maps (36.2 ± 15.2 vs 32.2 ± 14.4; p < 0.001). There was a significant shortening of CL in the adenosine maps compared to baseline which was more marked in the right atrium than left atrium (176.7 ± 34.7 vs 149.9 ± 27.7 ms; p < 0.001 and 165.6 ± 31.7 vs 148.3 ± 28.4 ms; p = 0.003). Conclusion: Adenosine led to a small but significant shortening of CL which was more marked in the right than left atrium and may relate to shortening of refractory periods rather than an increase in driver burden or distribution. Registered on Clinicaltrials.gov: NCT03394404. [ABSTRACT FROM AUTHOR]

With the expansion in catheter-based treatments for atrial fibrillation the number of transseptal punctures being performed by cardiac electrophysiologists has increased significantly. Although in general transseptal puncture is successful, in a small percentage of cases it cannot be achieved due to complex intraatrial anatomy. We report the case of a difficult transseptal puncture (TSP), performed where the conventional approach using a Brockenbrough needle sheath was unable to perforate the septum. TSP was only achieved using a novel technique assisted by an angioplasty wire. (PACE 2010; 33:243–245) [ABSTRACT FROM AUTHOR]

Introduction: The frequency of catheter ablation for atrial fibrillation (AF) has increased dramatically, stretching resources. Discharge on the same day as treatment may increase the efficiency and throughput. There are limited data regarding the safety of this strategy. Methods: We performed a retrospective analysis of consecutive patients undergoing AF ablation in a tertiary center and in a district general hospital, and identified those discharged on the same day of treatment. The safety endpoint was any complication and/or presentation to hospital in the 48‐h and at 30 days postdischarge. We performed an economic analysis to calculate potential cost saving. Results: Among a total population of 2628 patients, we identified 727 subjects (61.1 ± 12.5 years, 69.6% male) undergoing day‐case AF ablation. Cryoballoon technique was used in 79.2% of the day‐cases, and 91.6% of the procedures were performed under conscious sedation. 1.8% (13) of the participants met the safety composite endpoint at 48‐h, however only 0.7% (5) required at least 1 day of hospitalization. Bleeding or hematoma at the femoral access site (0.5%) and pericarditic chest pain (0.5%) were the main reasons for readmission. None experienced cardiac tamponade or other life‐threatening complications in the 48‐h postdischarge. Overall rate of complication and/or presentation to hospital at 30 days was 3.7%. Our day‐case policy resulted in an annual cost‐saving of approximately of £83 927 for our hospital. Conclusion: In this large multicentre cohort, same‐day discharge in selected patients following AF ablation appears to be safe and cost‐effective, with a very low rate of early readmission or post‐discharge complication. [ABSTRACT FROM AUTHOR]

The long-term effect of tricuspid regurgitation (TR) after device implantation on long-term mortality remains unknown. In the present study, we sought to examine whether patients undergoing an implantable cardiac device procedure (pacemaker, cardiac defibrillator or cardiac resynchronisation therapy) have an increased risk of TR and to determine the effect of this on long-term survival. A total of 304 patients who underwent device implant and had pre- and post-implant transthoracic echocardiogram were included in the analysis. All-cause mortality was the study endpoint over a follow-up period of median 11.6 years. New ≥ moderate tricuspid regurgitation post-device implantation developed in 66/304 (21.7%) patients. New right ventricular dysfunction post-device implantation occurred in 59/304 (19.4%) patients. Independent predictors of new RV dysfunction were ischaemic heart disease (OR 4.23, 95% CI 1.58 – 11.33, p = 0.004), left ventricular impairment (OR 2.74, 95% CI 5.41 – 30.00, p < 0.0001) and new ≥ moderate TR (OR 7.72, 95% CI 3.27 – 18.23, p < 0.001). Independent predictors of mortality were new ≥ moderate TR [HR: 3.14 (95% CI 1.29 – 7.63) p = 0.01] and new RV impairment [HR: 2.82 (95% CI 1.33 – 5.98) p = 0.01. Worsening TR and RV dysfunction post-device implantation is common. New post-implant ≥ moderate TR is associated with increased risk of new RV impairment and poor long term (>10 years) survival. • Worsening TR and RV dysfunction post-device implantation is common. • Post-implant ≥ moderate TR is associated with increased risk of new RV impairment. • Post-implant ≥ moderate TR is associated with poor long-term survival. [ABSTRACT FROM AUTHOR]

Introduction: Patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) require chronic anticoagulation due to high thromboembolic risk. Evidence supporting the use of non–vitamin K oral anticoagulants (NOACs) in patients with HCM remains sparse, and there are no data regarding the use of NOACs in patients with HCM undergoing catheter ablation of AF. Methods: Observational nonrandomized study in four European centers. We aimed to investigate the safety and efficacy of NOACs compared with vitamin K antagonists (VKAs) in patients with HCM undergoing catheter ablation for AF. Results: A total of 137 patients with HCM (mean age: 55.0 ± 13.4, 29.1% female) underwent 230 catheter ablations for AF (1.7 ± 1.0 per patient). A total of 55 patients (39.4%) underwent 70 procedures (30.4%) on NOAC, while the remaining were on VKA. Warfarin (97.6%) and rivaroxaban (56.4%) were the most frequently used agents in the respective groups. No procedure‐related deaths were reported. We observed no significant difference in the rate of thromboembolism (VKA: 0.6%; NOAC: 0%; p = 1.0) or minor bleeding (VKA: 0.6%; NOAC: 1.4%; p =.54). There was a nonsignificant trend towards a lower incidence of major bleeding (VKA: 6.9%; NOAC: 1.4%; p =.09). Conclusion: These preliminary data suggest that NOACs are at least as safe and effective as VKAs in patients with HCM undergoing catheter ablation for AF. [ABSTRACT FROM AUTHOR]

Background: Infection is a well‐recognized complication of cardiovascular implantable electronic device (CIED) implantation, including the more recently available subcutaneous implantable cardioverter‐defibrillator (S‐ICD). Although the AHA/ACC/HRS guidelines include recommendations for S‐ICD use, currently there are no clinical trial data that address the diagnosis and management of S‐ICD infections. Therefore, an expert panel was convened to develop consensus on these topics. Methods: A process mapping methodology was used to achieve a primary goal – the development of consensus on the diagnosis and management of S‐ICD infections. Two face‐to‐face meetings of panel experts were conducted to recommend useful information to clinicians in individual patient management of S‐ICD infections. Results: Panel consensus of a stepwise approach in the diagnosis and management was developed to provide guidance in individual patient management. Conclusion: Achieving expert panel consensus by process mapping methodology in S‐ICD infection diagnosis and management was attainable, and the results should be helpful in individual patient management. [ABSTRACT FROM AUTHOR]

Sudden cardiac death is responsible for half of all deaths from cardiovascular disease. The analysis of the electrophysiological substrate for arrhythmias is crucial for optimal risk stratification. A prolonged T-peak-to-Tend (Tpe) interval on the electrocardiogram is an independent predictor of increased arrhythmic risk, and Tpe changes with heart rate are even stronger predictors. However, our understanding of the electrophysiological mechanisms supporting these risk factors is limited. We conducted genome-wide association studies (GWASs) for resting Tpe and Tpe response to exercise and recovery in ∼30,000 individuals, followed by replication in independent samples (∼42,000 for resting Tpe and ∼22,000 for Tpe response to exercise and recovery), all from UK Biobank. Fifteen and one single-nucleotide variants for resting Tpe and Tpe response to exercise, respectively, were formally replicated. In a full dataset GWAS, 13 further loci for resting Tpe, 1 for Tpe response to exercise and 1 for Tpe response to exercise were genome-wide significant (p ≤ 5 × 10−8). Sex-specific analyses indicated seven additional loci. In total, we identify 32 loci for resting Tpe, 3 for Tpe response to exercise and 3 for Tpe response to recovery modulating ventricular repolarization, as well as cardiac conduction and contraction. Our findings shed light on the genetic basis of resting Tpe and Tpe response to exercise and recovery, unveiling plausible candidate genes and biological mechanisms underlying ventricular excitability. [ABSTRACT FROM AUTHOR]

Background: Noninvasive mapping identifies potential drivers (PDs) in atrial fibrillation (AF). We analyzed the impact of pulmonary vein isolation (PVI) on PDs and whether baseline PD pattern predicted termination of AF. Methods: Patients with persistent AF less than 2 years underwent electrocardiographic imaging mapping before and after cryoballoon PVI. We recorded the number of PD occurrences, characteristics (rotational wavefronts ≥ 1.5 revolutions or focal activations), and distribution using an 18‐segment atrial model. Results: Of 100 patients recruited, PVI terminated AF in 15 patients; 21.3% ± 9.1% (8.7 ± 4.8) of PDs occurred at the pulmonary veins (PVs) and posterior wall. PVI had no impact on PD occurrences outside the PVs and posterior wall (33.2 ± 12.9 vs 31.6 ± 12.5; P =.164), distribution over the remaining 13 segments (9 [8‐11] vs 9 [8‐10]; P =.634), the proportion of PDs that was rotational (82.9% ± 9.7% vs 83.6% ± 10.1%; P =.496), or temporal stability (2.4 ± 0.4 vs 2.4 ± 0.5 rotations; P =.541). Fewer focal PDs (area under the curve, 0.683; 95% CI, 0.528‐0.839; P =.024) but not rotational PDs (P =.626) predicted AF termination with PVI. Conclusions: PVI did not have a global impact on PDs outside the PVs and posterior wall. Although fewer focal PDs predicted termination of AF with PVI, the burden of rotational PDs did not. It is accepted though not all PDs are necessarily real or important. Outcome data are needed to confirm whether noninvasive mapping can predict patients likely to respond to PVI. [ABSTRACT FROM AUTHOR]

Use of non-vitamin K oral anticoagulants (NOACs) has rapidly increased worldwide. We aimed to systematically assess the available evidence regarding the safety and efficacy of NOACs in patients undergoing cardiac implantable electronic device (CIED) surgery. We performed a systematic literature search. Eligible randomised controlled trials and cohort studies were included. The primary outcome measures were clinically significant device-pocket haematoma and thromboembolic events. A total of 12 studies were included, equating to 2120 patients. The separate pooling of rate of events showed a low incidence of clinically significant device-pocket haematoma, although numerically higher in patients on continued (1.5%; CI 95% 0.8–3.0) versus interrupted NOAC (0.9%; CI 95% 0.5–1.7). The rate of any device-pocket haematoma was numerically higher in the continued versus interrupted NOAC group (5.4%; CI 95% 3.8–7.7 versus 2.4%; CI 95% 1.8–3.3). The incidence of thromboembolic events (0.4%; CI 95% 0.2–0.8) was low and comparable. From a meta-analysis of 3 studies (equating to 773 subjects) allowing for a comparison of continued versus interrupted NOAC, we found no significant difference between the 2 strategies in terms of clinically significant pocket haematoma (RR1.14; CI 95% 0.43–3.06, p = 0.79), thromboembolic complications (RR1.03; CI 95% 0.06–16.37, p = 0.98), and any pocket haematoma (RR1.19; CI 95% 0.65–2.20, p = 0.57). Use of NOACs at the time of CIEDs surgery appears to be safe, and either strategy of peri-procedure continuation or interruption might be reasonable. However, continuation of NOAC seems to be associated with a numerically higher rate of bleeding complications. Certainty of the evidence is low, and further studies are required to confirm these findings. • Non-vitamin K oral anticoagulants (NOAC) during pacemaker or defibrillator surgery are safe. • Either NOAC continuation or interruption appears reasonable for atrial fibrillation. • Incidence of bleeding and thromboembolism is low. • Incidence of pocket haematoma appears numerically higher with NOAC continuation. [ABSTRACT FROM AUTHOR]

Introduction: Implantable loop recorders (ILR) are predominantly implanted by cardiologists in the catheter laboratory. We developed a nurse‐delivered service for the implantation of LINQ (Medtronic; Minnesota) ILRs in the outpatient setting. This study compared the safety and cost‐effectiveness of the introduction of this nurse‐delivered ILR service with contemporaneous physician‐led procedures. Methods: Consecutive patients undergoing an ILR at our institution between 1st July 2016 and 4th June 2018 were included. Data were prospectively entered into a computerized database, which was retrospectively analyzed. Results: A total of 475 patients underwent ILR implantation, 271 (57%) of these were implanted by physicians in the catheter laboratory and 204 (43%) by nurses in the outpatient setting. Six complications occurred in physician‐implants and two in nurse‐implants (P = .3). Procedural time for physician‐implants (13.4 ± 8.0 minutes) and nurse‐implants (14.2 ± 10.1 minutes) were comparable (P = .98). The procedural cost was estimated as £576.02 for physician‐implants against £279.95 with nurse‐implants, equating to a 57.3% cost reduction. In our center, the total cost of ILR implantation in the catheter laboratory by physicians was £10 513.13 p.a. vs £6661.55 p.a. with a nurse‐delivered model. When overheads for running, cleaning, and maintaining were accounted for, we estimated a saving of £68 685.75 was performed by moving to a nurse‐delivered model for ILR implants. Over 133 catheter laboratory and implanting physician hours were saved and utilized for other more complex procedures. Conclusion: ILR implantation in the outpatient setting by suitably trained nurses is safe and leads to significant financial savings. [ABSTRACT FROM AUTHOR]

The patterns and prevalence of early repolarization pattern (ER) in pediatric populations from ethnic backgrounds other than Caucasian have not been determined. Black African children (ages 4–12) from north-west Madagascar were prospectively recruited and their ECGs compared with those of age- and sex-matched Caucasian ethnicity individuals. ER was defined by ≥ 0.1 mV J-point elevation in at least two contiguous inferior and/or lateral ECG leads. A total of 616 children were included. There was a trend toward a higher frequency of ER in the Africans compared to the Caucasians (23.3% vs. 17.1%, respectively, p = 0.053). The subtype (slurred vs. notched) and location of ER (lateral, inferior, or inferior-lateral) were significantly different in the two groups (p < 0.001 and p = 0.020, respectively). There was no significant difference in the number of high-risk ECG features of ERP (i.e., horizontal/descendent pattern, inferior or inferior-lateral location or J-waves ≥ 2 mm) between African and Caucasian children. On the multivariate analysis, African ethnicity was an independent predictive factor of ER (OR 3.57, 95% CI 2.04–6.25, p < 0.001). African children have an increased risk of ER compared to Caucasian counterparts. Future studies should clarify the clinical and prognostic significance of ER in the pediatric population, and whether ethnicity has an impact on the outcomes. [ABSTRACT FROM AUTHOR]

Background: Use of the subcutaneous implantable defibrillator (S‐ICD) has increased because the device received US Food and Drug Administration approval in 2012, but we still know little about whether the quality of life (QoL) of patients with an S‐ICD versus a transvenous ICD (TV‐ICD) is comparable. We compared S‐ICD patients with TV‐ICD patients on QoL, depression, and anxiety up to 12 months' follow‐up. Methods: A matched cohort of S‐ICD (N = 167) and TV‐ICD patients (N = 167) completed measures on QoL, depression, anxiety, and personality at baseline, 3, 6, and 12 months post implant. Data were analyzed using multivariable modeling with repeated measures. Results: In adjusted analyses, we found no statistically significant differences between cohorts on physical and mental QoL and depression (all Ps > .05), while S‐ICD patients reported lower anxiety than TV‐ICD patients (P = 0.0007). Both cohorts experienced improvements in physical and mental QoL and symptoms of depression and anxiety over time (all Ps < .001), primarily between implant and 3 months. These improvements were similar for both cohorts with respect to physical and mental QoL and anxiety (Ps > .05), while S‐ICD patients experienced greater reductions in depressive symptoms (P = .0317). Conclusion: The QoL and depression levels were similar in patients with an S‐ICD and a TV‐ICD up to 12 months' follow‐up, while S‐ICD patients reported lower anxiety levels and a greater reduction in depression over time as compared to TV‐ICD patients. This knowledge may be important for patients and clinicians, if the indication for implantation allows both the S‐ICD and the TV‐ICD, making a choice possible. [ABSTRACT FROM AUTHOR]

A murine line haploinsufficient in the cardiac sodium channel has been used to model human Brugada syndrome: a disease causing sudden cardiac death due to lethal ventricular arrhythmias. We explored the effects of cholinergic tone on electrophysiological parameters in wild-type and genetically modified, heterozygous, Scn5a+/- knockout mice. Scn5a+/- ventricular slices showed longer refractory periods than wild-type both at baseline and during isoprenaline challenge. Scn5a+/- hearts also showed lower conduction velocities and increased mean increase in delay than did littermate controls at baseline and blunted responses to isoprenaline challenge. Carbachol exerted limited effects but reversed the effects of isoprenaline with coapplication. Scn5a+/- mice showed a reduction in conduction reserve in that isoprenaline no longer increased conduction velocity, and this was not antagonized by muscarinic agonists. [ABSTRACT FROM AUTHOR]