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Background Postoperative atrial fibrillation (POAF) is a frequent adverse event after thoracic surgery with associated morbidity, mortality, and healthcare costs. It has been shown to be preventable with prophylactic amiodarone, which is only recommended in high-risk individuals due to the potential associated side effects. Risk factors for POAF have been identified and incorporated into a prediction model to identify high-risk patients. Further evaluation in the form of a multicenter clinical trial is required to assess the effectiveness of prophylaxis specifically in this high-risk population. The feasibility of such a trial first needs to be assessed. Methods The PREP-AF trial is a double-blind randomized controlled feasibility trial. Individuals undergoing major thoracic surgery who are identified to be high-risk by the POAF prediction model will be randomized 1:1 to receive a short course of amiodarone vs. placebo in the immediate postoperative period. The primary outcome is feasibility, which will be measured by the number of eligible patients identified, consented, and randomized; intervention adherence; and measurement of future outcomes of a full trial. Discussion This study will determine the feasibility of a randomized controlled trial to assess the effectiveness of prophylactic amiodarone, in high-risk patients undergoing major thoracic surgery. This will inform the development of a multi-center trial to establish if prophylactic amiodarone is safe and effective at reducing the incidence of POAF. Preventing this adverse event will not only improve outcomes for patients but also reduce the associated health resource utilization and costs. Trial registration ClinicalTrials.gov NCT04392921. Registered on 19 May 2020.

The Medical Assistance in Dying (MAiD) program has been steadily expanding in Canada, and is expected to continue to do so. There are a substantial number of Canadians with pacemakers and defibrillators, many of whom are potential MAiD recipients. There is a need for review and reflection of standardisation of cardiac device management in MAiD patients, not only because of ethical concerns, but also because of the complexity of management at end of life. This document examines the status and role of cardiac devices (pacemakers and intracardiac defibrillators) and their physiologic interactions and influences during the MAiD process, and provides recommendations for their management.

Background: Multiple studies have examined the prevalence of left atrial appendage thrombus (LAAT) in patients anticoagulated with direct oral anticoagulants (DOACs) and have reported conflicting results. Methods: Studies reporting the prevalence of LAAT on transesophageal echocardiography (TEE) after 3 or more weeks of DOAC therapy were identified. The proportions of anticoagulated patients diagnosed with LAAT were pooled using random-effects models. Prespecified subgroup analyses by the indication of TEE (pre–atrial fibrillation [AF] ablation vs cardioversion) and TEE strategy (routine use vs selective) were conducted via stratification. Results: Forty studies were identified: 22 full manuscripts and 18 abstracts. Only 11 studies performed TEE routinely. Most studies included patients with paroxysmal AF and low thromboembolic risk. The pooled prevalence of LAAT was 2.5% (95% confidence interval [1.6%-3.4%]). The prevalence of LAAT is lower in the pre-AF ablation group compared with pre-cardioversion (1.1% vs 4.0%, P = 0.033). Routine TEE strategy yielded a lower LAAT prevalence in both groups (0.1% vs 2.3%, P = 0.002 and 3.2% vs 5.8%, P = 0.432, respectively). Conclusion: The reported prevalence of LAAT on TEE in patients treated with DOACs is highly variable. Factors associated with a high LAAT prevalence were pre-cardioversion indication and selective TEE strategy. Routine use of TEE before AF ablation may not be warranted. Résumé: Introduction: De nombreuses études ont porté sur la prévalence des thrombi se formant dans l’appendice auriculaire gauche (TAAG) chez les patients qui reçoivent des anticoagulants oraux directs (AOD) et ont révélé des résultats contradictoires. Méthodes: Nous avons recensé les études qui ont fait état de la prévalence des TAAG à l’échocardiographie transœsophagienne (ETO) trois semaines ou plus après le traitement par AOD. Les modèles à effets aléatoires ont permis de regrouper les patients qui prenaient des anticoagulants et avaient reçu un diagnostic de TAAG. Nous avons réalisé les analyses de sous-groupes prédéterminés par l’indication d’ETO (fibrillation auriculaire [FA] avant l’ablation vs FA avant la cardioversion) et la stratégie d’utilisation de l’ETO (systématique vs sélective) grâce à la stratification. Résultats: Nous avons recensé 40 études : 22 manuscrits complets et 18 résumés. Seules 11 études portaient sur l’utilisation systématique de l’ETO. La plupart des études portaient sur des patients qui étaient atteints de FA paroxystique et exposés à un faible risque thromboembolique. La prévalence groupée de TAAG était de 2,5 % (intervalle de confiance à 95 % [1,6 %-3,4 %]). La prévalence de TAAG était plus faible dans le groupe de FA avant l’ablation que dans le groupe de FA avant la cardioversion (1,1 % vs 4,0 %, P = 0,033). La stratégie d’utilisation systématique de l’ETO a permis d’obtenir une prévalence plus faible de TAAG dans les deux groupes (0,1 % vs 2,3 %, P = 0,002 et 3,2 % vs 5,8 %, P = 0,432, respectivement). Conclusion: La prévalence de TAAG à l’ETO chez les patients traités par AOD varie beaucoup. Les facteurs associés à une prévalence élevée de TAAG étaient l’indication avant la cardioversion et la stratégie d’utilisation sélective de l’ETO. L’utilisation systématique de l’ETO avant l’ablation peut ne pas être justifiée.

Background High-power short-duration (HPSD) ablation has been explored for pulmonary vein isolation. Early data suggest similar efficacy with shorter procedure times and perhaps greater safety. Data are lacking on the use of this ablation strategy for other arrhythmias. Objective The purpose of this study was to evaluate the safety, efficacy, and clinical outcomes of HPSD ablation in patients with typical atrial flutter compared to those undergoing ablation with conventional settings. Methods Consecutive patients undergoing cavotricuspid isthmus (CTI) ablation using standard power settings were compared to those performed after transitioning to HPSD ablation. Demographics, procedural details, and ablation outcomes were prospectively collected. The primary endpoint was duration of radiofrequency energy delivery. Secondary endpoints were radiation duration and analgesia requirements. Results A total of 114 consecutive subjects undergoing CTI ablation (57 standard power, 57 HPSD) were included. HPSD ablation and electroanatomic mapping/contact force (EAM/CF) use were associated with 66% (95% confidence interval [CI] 58%–73%) and 50% (95% CI 37%–60%) shorter ablation times compared to standard power and not using EAM/CF, respectively. Patients in the HPSD group required 50 mcg less fentanyl relative to the standard ablation arm after adjusting for sex, age, and comorbidities (P = .048). At a median follow-up of 6 months, 4 patients (7%) in the standard arm had recurrence of atrial flutter, compared to none in HPSD group (P = .057). Conclusion HPSD is a safe and effective approach to CTI ablation. This strategy may reduce ablation time and analgesia requirements. Larger studies and longer follow-up are needed to further evaluate this strategy., Graphical abstract

BACKGROUND There are discrepancies in the quantitative echocardiographic criteria for the right ventricle (RV) between the revised task force criteria (TFC) for Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) and the guidelines for RV assessment endorsed by American Society of Echocardiography (ASE). Importantly, these criteria do not take into account potential adaptation of the RV to exercise. The goal of this study was to compare the revised TFC quantitative echocardiographic parameters in patients with ARVC/D, athletes and matched controls. METHODS Echocardiographic parameters of the RV were retrospectively collected in patients who fulfilled the TFC for ARVC/D, an age- matched, sex-matched, and body surface area-matched control population, and athletes (defined as individuals who exercised for more than 7 hours per week). Patients with structural heart disease were excluded in the control and athlete groups. RESULTS Twenty patients with ARVC/D, 11 athletes and 20 matched controls were included. There was no significant difference between ARVC/D patients and athletes with the exception of the parasternal long axis right ventricular outflow tract diameter. All parameters were significantly different between ARVC/D patients and the control group. Furthermore, when subjects were categorized into meeting 1 major revised TFC/abnormal ASE criteria or not, only ASE criteria were able to differentiate ARVC/D from control population. Both were unable to differentiate ARVC/D from athletes. CONCLUSIONS Right ventricle quantitative echocardiographic criteria in the revised TFC are not specific for ARVC/D. Care should be taken in applying these criteria in athletes.

BACKGROUND The effectiveness, safety, and pulmonary vein (PV) reconnection patterns of point-by-point high-power, short-duration (HPSD) ablation relative to conventional force-time integral (FTI)-guided strategies for atrial fibrillation (AF) ablation are unknown. OBJECTIVES To compare 1-year freedom from atrial arrhythmia (AA), complication rates, procedural times, and PV reconnection patterns with HPSD AF AF ablation versus an FTI-guided low-power, long-duration (LPLD) strategy. METHODS We compared consecutive patients undergoing a first ablation procedure for paroxysmal or persistent AF. The HPSD protocol utilized a power of 50 W and durations of 6-8 s posteriorly and 8-10 s anteriorly. The LPLD protocol was FTI-guided with a power of ≤25 W posteriorly (FTI ≥ 300g·s) and ≤35 W anteriorly (FTI ≥ 400g·s). RESULTS In total, 214 patients were prospectively included (107 HPSD, 107 LPLD). Freedom from AA at 1 year was achieved in 79% in the HPSD group versus 73% in the LPLD group (p = .339; adjusted hazard ratio with HPSD, 0.67; 95% confidence interval, 0.36-1.23; p

AIMS: Electrical cardioversion is commonly performed to restore sinus rhythm in patients with atrial fibrillation (AF), but it is unsuccessful in 10–12% of attempts. We sought to evaluate the effectiveness and safety of a novel cardioversion protocol for this arrhythmia. METHODS AND RESULTS: Consecutive elective cardioversion attempts for AF between October 2012 and July 2017 at a tertiary cardiovascular centre before (Phase I) and after (Phase II) implementing the Ottawa AF cardioversion protocol (OAFCP) as an institutional initiative in July 2015 were evaluated. The primary outcome was cardioversion success, defined as ≥2 consecutive sinus beats or atrial-paced beats in patients with implanted cardiac devices. Secondary outcomes were first shock success, sustained success (sinus or atrial-paced rhythm on 12-lead electrocardiogram prior to discharge from hospital), and procedural complications. Cardioversion was successful in 459/500 (91.8%) in Phase I compared with 386/389 (99.2%) in Phase II (P

Introduction Fluoroscopy use during catheter ablation procedures increases the cumulative lifetime radiation exposure of patients and operators, potentially leading to a higher risk of cancer and radiation-related injuries. Nonfluoroscopic ablation (NFA) has been described for supraventricular tachycardia, typical atrial flutter, paroxysmal atrial fibrillation (AF), and outflow-tract ventricular tachycardia (VT). Complete transition to NFA of more complex arrhythmias, including persistent AF, left atrial (LA) flutter, and structural VT, has not been previously described. We describe the transition to completely NFA of complex arrhythmias, including LA flutter and structural VT. The techniques, challenges, limitations, and results are described. Methods and results Complex ablation procedures were performed using intracardiac echocardiography (ICE) and a three-dimensional mapping system without fluoroscopy or lead protection. Eighty consecutive patients underwent NFA (mean age, 60.1 ± 9.9 years, 70 with LA arrhythmias, 10 with VT). All cases were performed without the need for rescue fluoroscopy. There was an initial increase in procedural time for ablation of LA arrhythmias upon transitioning to NFA. However, after excluding the first 20 NFA cases to allow for operator learning, the transition to NFA was not associated with an increase in mean procedural time (229 ± 38 vs 225 ± 32 minutes; P = 0.002 for noninferiority). All procedures were completed successfully with no complications. Conclusions NFA of most complex arrhythmias (persistent AF, LA flutter, and structural VT) is feasible, with a modest learning curve and no increase in procedural times.

Background There is limited data on the scar burden in patients with atrial fibrillation (AF). In this study, we sought to evaluate the presence and extent of an abnormal left atrial (LA) substrate in patients with paroxysmal or persistent AF. Methods Consecutive patients who underwent initial AF catheter ablation were prospectively enrolled. Endocardial voltage mapping was acquired in sinus rhythm using multipolar mapping catheters. Automated software was used to ensure homogeneous data collection. Assessment of low-voltage area (LVA) was performed by a reviewer blinded to clinical details. Results One hundred and four patients were prospectively enrolled; 69 had paroxysmal and 35 persistent AF. The mean LA volume was 159 ± 48 mL, and the average number of LA points collected was 1308 ± 1065. Atrial LVAs were present in 23 of 69 (33%) subjects with paroxysmal and 20 of 35 (57%) with persistent AF ( P = 0.02). Amongst 43 of 104 patients with scar, the average extent of LVA was 19.4 ± 21.6 cm 2 and the mean percentage area was 7.6 ± 8.8%. Univariate analysis showed that age, LA volume, and persistent AF were associated with the presence of LVA. Multivariable analysis showed that age (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.00-1.11; P = 0.046) and LA volume (OR 1.02; 95% CI 1.01-1.04; P P = 0.56). Conclusions There is wide variability in the presence and extent of LVA in patients with paroxysmal or persistent AF. Age and LA volume were predictors of LVA. There was no correlation between AF classification and the presence of LVA.

Aims There is ongoing controversy about the need for routine transoesophageal echocardiography (TOE) prior to atrial fibrillation (AF) ablation. Recently, the debate was reignited by the publication of a large series of patients showing a prevalence of left atrial appendage thrombus (LAAT) on TOE of 4.4%. We sought to assess the prevalence of LAAT on TOE before AF ablation at our institution. Methods and results Consecutive patients scheduled for AF ablation at our institution between January 2009 and December 2016 were included. All patients were on oral anticoagulation for at least 4 weeks prior to TOE. Transoesophageal echocardiographies were performed 3-5 days prior to scheduled AF ablation. Data were collected utilizing a prospective database. In all, 668 patients and 943 AF ablation procedures were included. Mean age was 64 ± 11 years, 72% were male, average CHADS2 score was 1.0 ± 1.0, and 72% of the patients had paroxysmal AF. At the time of ablation, 496 (53%) were on non-vitamin K antagonist oral anticoagulants (NOACs) and 447 (47%) were on Warfarin. There were three cases with LAAT (3/943, 0.3%), all of whom had persistent AF and were on Warfarin. Two patients underwent surgical ablation and the third patient did not undergo ablation. Conclusion In our experience, the prevalence of LAAT in patients on anticoagulation therapy undergoing TOE before catheter ablation of AF is 0.3%, which was much lower than recently reported. None of the patients with paroxysmal AF or on NOACs were found to have LAAT. Rather than routine use of TOE prior to AF ablation, a risk-based approach should be considered.

BACKGROUND Recurrence of atrial fibrillation (AF) post-ablation occurs in 30-50% of patients. The approach to a repeat ablation, beyond isolation of reconnected pulmonary veins (PVs), is not well established. We sought to prospectively assess outcomes and determine predictors of recurrence among consecutive patients who underwent repeat AF ablation with a standardized approach. METHODS AND RESULTS This was a single-center prospective study of consecutive patients who underwent repeat AF ablation. Our ablation protocol consisted of six steps: PV re-isolation, ablation of left atrial low-voltage areas (LVAs), ablation of isoprenaline induced non-PV triggers, electrophysiology study (EPS), and ablation of all clinical and induced atrial flutters. Between February 2017 and January 2020, 725 AF ablations were performed at our center. Of these, 74 were repeat AF ablation using the new protocol. The average age was 62.5 ± 9.2 years; 18% were female; 51% had paroxysmal AF at time of initial ablation. The indication for repeat ablation was paroxysmal AF in 39 (53%) patients, persistent AF in 24 (32%) patients. Among the study cohort of 74 patients undergoing repeat AF ablation, 53 (72%) had PV reconnection; 30 (41%) had LVA; 7 (10%) had non-PV triggers; five (7%) had AVNRT, and five (7%) had typical atrial flutter. Arrhythmia-free survival was 65% at one year. The absence of PV reconnection was the only factor independently associated with recurrence (overall rate 71%, adjusted OR 7.91, 95% CI 2.31-27.16, p=0.001). The arrhythmia-free survival was 29% in those without PV reconnection; meanwhile it was 88% in those with all PVs reconnected. Those with absence of reconnection had more LVA (67% vs 30%, p=0.004) and hypertension (67% vs 30%, p=0.004), suggesting more atrial myopathy. CONCLUSION We describe a comprehensive approach to repeat AF ablation using a standardized protocol that included isolation of reconnected PVs, targeting all areas of low-voltage, ablating all non-PV triggers, inducible SVT, and atrial flutters. Finding reconnected PVs at repeat procedure was a strong predictor of arrhythmia-free survival. Recurrence rates were high among those with absence of PV reconnection, potentially suggesting advanced atrial substrate as the underlying etiology. Our findings demonstrate that PV re-isolation remains the most important treatable cause of atrial arrhythmia recurrence after AF ablation; however further research is needed to investigate therapies beyond PV re-isolation.

Introduction Targeting localized drivers (electrical rotors or focal impulses) during catheter ablation for atrial fibrillation (AF) has been proposed as a strategy to improve procedural success. However, the strength and quality of the evidence to support this approach is unclear. Methods and results Clinical studies reporting efficacy or safety outcomes of driver-guided ablation for AF were identified in Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, Pubmed, and conference abstracts from major scientific meetings. Random-effects meta-analysis of efficacy outcomes from controlled studies was performed. Thirty-one reports from 30 studies were included: two randomized controlled trials, five nonrandomized controlled studies, and 23 uncontrolled studies. In controlled studies, driver-guided ablation has been associated with higher rates of acute AF termination (RR 2.08, 95% CI 1.43–3.05; P < 0.001) and increased freedom from AF/atrial tachycardia (AT) at ≥1 year (RR 1.34, 95% CI 1.05–1.70; P = 0.02). Similar rates of procedural complications have been reported between ablation strategies. Overall, current data on driver-guided ablation are predominantly from nonrandomized studies with considerable heterogeneity in mapping and ablation strategies used and in clinical outcomes reported. Conclusion Pooled data on the efficacy of AF driver-guided catheter ablation suggest increased freedom from AF/AT relative to conventional strategies. However, most studies are nonrandomized and of moderate quality. Though promising data exist, there remains no conclusive evidence for the efficacy of AF driver ablation. Robust data from randomized trials are needed.

Background and objective Contact force (CF) sensing is a novel technology used for catheter ablation of atrial fibrillation (AF). We compared the single procedure success of CF-guided pulmonary vein isolation (PVI) with that of non-CF guided PVI during a 3-year (1,095 days) follow up period and analyzed the pattern of pulmonary vein (PV) reconnection. Methods A cohort of 167 subjects (68 CF vs. 99 non-CF) with paroxysmal AF were included in the study. Atrial arrhythmia (AA) recurrence was defined as documented AF, atrial flutter, or atrial tachycardia lasting >30 seconds and occurring after 90 days. Results Subjects in the CF group showed a statistically nonsignificant improvement in AA free survival compared to those in the non-CF group (66.2% vs. 51.5%; P value: 0.06). A greater propensity for reconnection was noted around the right-sided PVs compared to left-sided PVs related in both catheter ablation groups. For example, in the CF group 36% of right-sided segments reconnected compared to 16% of left-sided segments (P value

Pulmonary vein reconnection leading to recurrence of atrial arrhythmias after pulmonary vein isolation (PVI) for atrial fibrillation remains a significant challenge. A number of adjunctive measures during PVI have been used to attempt to reduce pulmonary vein reconnection and recurrence of atrial arrhythmias. We performed a systematic review of the literature and meta-analysis of studies evaluating the efficacy of adjunctive measures used during PVI in reducing recurrent atrial arrhythmias.Our literature search found four interventions that met the prespecified definition of adjunctive measure: adenosine testing post-PVI, contact force-guided PVI, pacing inexcitability of the ablation line during PVI and additional ablation based on the computed tomography thickness of the pulmonary vein-left atrial appendage ridge. Sixteen studies enrolling 3507 patients met all inclusion and exclusion criteria. PVI performed with adjunctive measures was shown to reduce the 1-year recurrence rate of atrial arrhythmias. The point estimate for the combined relative risk of atrial arrhythmia recurrence was 0.56 [95% confidence interval (CI): 0.43-0.73; P value0.001] in the PVI with adjunctive measures group.PVI for atrial fibrillation assisted by adjunctive measures results in clinically significant reduction of recurrent atrial arrhythmias. Additional research is required to assess the relative efficacy of individual or combined adjunctive strategies used during PVI for atrial fibrillation.

Background Defibrillator placement carries an inherent risk to the patient. Traditionally, major adverse events defined as cardiac arrest, tamponnade, pneumothorax, infection requiring re-operation, MI and CVA within 30 days are reported to occur between 3 and 4%. Minor complications such as heamatomae or lead dislodgement are reported between 8 and 13%. Novel lead technologies, protocolised programming and reduced use of Heparin bridging have been reported to reduce adverse outcomes. However, patients are still typically monitored in hospital for 24 hours to mitigate these risks. There is little evidence that discharge delay is effective yet incurs significant additional costs. Purpose We sought to evaluate the frequency and timing of adverse events relating to defibrillator surgery (ICD and CRT-D) at a large Canadian tertiary care center (UOHI). Methods We retrospectively reviewed all patients who received a defibrillator placed from 1st April 2013 to 31st March 2018 inclusive. Patient comorbidities were extracted from the hospital electronic medical record (EMR) system. Device related information and complications were extracted from UOHI PaceartTM system and EMR and cross referenced with physician remuneration databases. Results A total of 2221 procedures were performed on 2153 patients (78% male, mean age 65 years). The majority (60%) of defibrillator implants were de novo, with 884 (40%) pulse generator replacements/ upgrades and 868 (39%) defibrillators had CRT capability. Patients were routinely discharged within 24 hours of ICD surgery. Post-operative follow up ≥30 days was complete in 97% patients. Major adverse events occurred within 30 days in 9 patients (0.4%); 9 (100%) were infection requiring re-operation. An additional 32 patients (1.5%) required repeat interventions or readmission within 30 days of implant, most commonly due to lead dislodgement. Only 2 patients required readmission within 24 hours of surgery (0.1%). All procedure-related adverse events during clinical follow up (≤5 years) were 131 (5.9%) occurring in 122 patients. There were no apparent predictors of adverse events in this cohort. Conclusion(s) Contemporary risks to patients undergoing defibrillator surgery are considerably lower than that reported in 2010. The risk of infection appears constant despite increased antibiosis. Patients receiving an ICD or CRT-D can safely be discharged within 24 hours if no complications are apparent. Acknowledgement/Funding None

Background Current LBBB definitions cannot always distinguish LBBB from left ventricular conduction delay. Only patients with LBBB are expected to normalize with His bundle pacing. Patients who develop new LBBB immediately post transcatheter aortic valve replacement (TAVR) provide an excellent model to define electrocardiogram (ECG) features of LBBB. We sought to describe their ECG features and develop a new ECG definition of LBBB. Methods We screened ECGs from 264 consecutive patients who underwent TAVR at the University of Ottawa Heart Institute. Patients with a baseline QRS of ≤100 ms who developed QRS ≥120 ms immediately after TAVR were included. Two electrocardiologists reviewed all ECG independently. Baseline demographics and echocardiographic data were retrospectively collected. Results 36 patients were included in the analysis. The median age was 85.5 years (IQR, 81.8–89 years) and 52.8% were males. The minimum QRS duration was 126 ms. The median QRS axis was −18° (IQR, −40–4.5°), which is 18.5° leftward compared to the median QRS axis before TAVR. Fourteen patients (38.9%) had left axis deviation. All patients had a notched/slurred R wave in at least one lateral lead and an R wave duration of ≤20 ms in V1 when present. Conclusion We developed a new ECG definition of LBBB that includes 2 novel findings: notching/slurring of the R wave in at least one lateral lead and an R wave ≤20 ms in V1. Further larger studies are warranted to confirm these findings.

Objectives This study systematically reviewed the prevalence of pulmonary vein (PV) reconnection in subjects with and without AF recurrence and assessed the relationship between PV reconnection and freedom from atrial fibrillation (AF). Background Pulmonary vein reconnection is frequently observed in patients experiencing recurrent AF post catheter ablation. However, its prevalence in AF-free patients has not been well studied. Methods An electronic search was performed for studies describing PV electrical conduction in subjects with and without AF recurrence post PV isolation (PVI). Results Eleven of 5,665 articles met selection criteria. A total of 683 subjects were included in the meta-analysis; 379 had AF recurrence, and 304 were AF-free. Among patients with AF recurrence, 324 of 379 patients (85.5%) had at least 1 pulmonary vein reconnected. Among AF-free patients, 178 of 304 patients (58.6%) had at least 1 PV electrically reconnected, and 126 of 304 (41.4%) had durable PVI. The relative risk (RR) of recurrent AF was significantly lower with durable PVI than with PV reconnection (RR: 0.57; 95% confidence interval [CI]: 0.37 to 0.86; p = 0.008). Analysis of 7 studies including exclusively paroxysmal AF patients (n = 470) showed RR of 0.69 (95% CI: 0.45 to 1.05; p = 0.09). Conclusions This meta-analysis shows that durable PVI is associated with a lower risk of AF recurrence after catheter ablation. However, the association was modest, and PV electrical reconnection is common, affecting 58% of AF-free patients. Analysis of studies that included exclusively patients with paroxysmal AF showed a weaker relationship. Additional research is warranted to better understand the mechanism(s) of benefit of catheter ablation for AF and investigate whether PVI should be the primary goal.

Objectives Type 2 diabetes mellitus is a chronic progressive disease that is associated with increased risk for cardiovascular diseases and with impaired mitochondrial metabolism in cardiac and skeletal muscles. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with significant morbidity and mortality. Type 2 diabetes is also one of the prevalent concomitant diseases in patients with AF. During AF, myocardial energy demand is high due to electrical activity. To date, however, very little is known about the effects of AF on atrial muscle mitochondrial energetics. We hypothesized that preexisting fibrillation or type 2 diabetes impacts atrial mitochondrial energetics and electron transport chain supercomplexes. Methods Atrial appendages were collected from patients who had consented and who had and did not have preexisting AF and were undergoing coronary artery bypass graft surgery. Mitochondrial functional analyses were conducted in permeabilized myofibers using high-resolution respirometry. Results Results show impaired complex I and II function in addition to impaired electron transport chain supercomplex assembly in patients with diabetes and AF compared to patients with diabetes but without AF. There were no differences in mitochondrial content in atrial muscle between the groups. There was a strong trend for increased oxidative damage (protein carbonyls) in patients with diabetes and AF compared to patients with diabetes but without AF. Conclusions Overall, findings suggest impaired mitochondrial function in AF and type 2 diabetes.

The purpose of this review is to understand the epidemiology, clinical features, etiopathogenesis, and management of atrioesophageal fistula (AEF) after atrial fibrillation (AF) ablation. The incidence of AEF after AF ablation is 0.015%-0.04%. The principal clinical features include fever, dysphagia, upper gastrointestinal bleeding, sepsis, and embolic strokes. The close proximity of the esophagus to the posterior left atrial wall is responsible for esophageal injury during ablation. Prophylactic proton pump inhibitors, esophageal temperature monitoring, visualization of the esophagus during catheter ablation, esophageal protection devices, and avoidance of energy delivery in close proximity to the esophagus play an important role in preventing esophageal injury. Early surgical repair or esophageal stenting are the mainstay of treatment. Eliminating esophageal injury during AF ablation is of utmost importance in preventing AEF. A high index of suspicion and early intervention is necessary to prevent fatal outcomes.

Introduction Sarcoidosis is a granulomatous disease of unknown etiology, which involves the heart in 5–25% of cases. Although ventricular tachycardia (VT) has been reported as the first presentation of sarcoidosis, its prevalence has not previously been investigated. In this prospective study, we sought to systematically investigate the prevalence of cardiac sarcoidosis (CS) in patients presenting with monomorphic VT (MMVT) and no previous history of sarcoidosis. Methods Consecutive patients presenting with MMVT to a tertiary care center were screened for inclusion. Patients with idiopathic VT, VT secondary to coronary artery disease, or prior diagnosis of sarcoidosis were excluded. Included patients underwent F-18-fluorodeoxyglucose positron emission tomography (PET) scan. In subjects with PET scanning suggestive of active myocardial inflammation, histological diagnosis was confirmed through extracardiac or endomyocardial biopsy (EMB). Results A total of 182 patients presented to our institution with VT between February 2010 and September 2012 and 14 subjects met inclusion criteria. Within this group, six of 14 (42%) patients had abnormal PET scans suggesting active myocardial inflammation. Four of the six patients had tissue biopsies that were diagnostic of sarcoidosis; the remaining two patients had guided EMB indicating nonspecific myocarditis. Atrioventricular block was observed in three of four (75%) patients with CS and none in 10 of the others (P = 0.022). Three of the four patients had pulmonary sarcoidosis and one patient had isolated CS. All four patients were treated with corticosteroids. Conclusion In this prospective study, four of 14 (28%) patients presenting with MMVT (without idiopathic VT, ischemic VT, or known sarcoidosis) had CS as the underlying etiology. Clinicians should consider screening for CS in patients with unexplained MMVT.

Background Patients who receive appropriate implantable cardioverter defibrillator (ICD) shocks have a subsequent adverse prognosis. Most data suggest that patients with inappropriate ICD shocks also have a subsequent adverse prognosis, although this is more controversial. The shocks may be an epiphenomenon, that is, a marker of underlying disease progression; however, it cannot be excluded that shocks cause direct myocardial damage. This latter question is difficult to clarify as the arrhythmia provoking the shock can also cause troponin release. Inappropriate shocks secondary to lead fracture are an ideal situation to examine this question; any troponin release in an otherwise well and hemodynamically stable patient, is likely due directly to the shocks. Methods All patients with Fidelis lead fracture admitted to our institution with inappropriate shocks were included in this study. Troponin (I or T) was considered positive if the level was above the 99th percentile reference cutoff. Results Elevated troponin levels were recorded in 16 of 22 patients (73%). Patients with elevated troponin received a higher number of shocks (20.3 ± 30.1 vs 5.3 ± 4.8, P = 0.07) compared with patients with normal troponin. Very elevated troponin levels (>0.8 mcg/L) were seen in five of 22 (22%) patients. The mean peak troponin level for these five patients was 7.06 ± 8.56 mcg/L; two patients had troponin levels that would be expected from a medium-sized myocardial infarction or severe myocarditis. Conclusion Troponin elevation occurred in the majority of our patients after inappropriate ICD discharges secondary to lead fracture. This indicates that ICD shocks can cause myocardial injury.

Premature ventricular contraction (PVC)-induced cardiomyopathy is increasingly being recognized as a reversible cause of left ventricular (LV) systolic dysfunction (LVSD). The diagnosis of PVC-induced cardiomyopathy is considered in subjects with high PVC burdens (> 10,000 per 24 hours) after excluding other known causes of LVSD. PVC suppression is the mainstay of the management of PVC-induced cardiomyopathy, in addition to proven evidence-based medical therapy recommended for subjects with LVSD. Management strategies for PVC-induced cardiomyopathy include medical therapy and/or catheter ablation, with an increasing role for catheter ablation as a first-line therapy in view of the potential for permanent suppression of PVCs. Recovery of LVSD is typically a gradual process over months after effective suppression of PVCs. Last, asymptomatic patients with high PVC burdens and preserved LV systolic function appear to be at low risk over the intermediate term for developing LVSD. However, it is prudent to monitor LV function periodically because of the potential for deterioration of LV function observed during long-term follow-up in some subjects.

A preliminary study into the signal quality of the Empatica's E4 portable photoplethysmogram device as validation for further research on using the device to detect the heart arrhythmia atrial fibrillation. In order to pursue this research, it was necessary to verify the quality of the data produced by the E4 device against a device currently used by clinicians to detect atrial fibrillation. This was done by having healthy volunteers wear both the Empatica E4 and the clinician standard device while following standard clinician procedure for atrial fibrillation diagnosis. The device was compared qualitatively against General Electric's SEER Light Extend Recorder holter portable electrocardiogram. The analysis was done by non-experts at varying academic levels. The primary reviewer's results showed similar data quality between both devices 85% of the time and the holter performed better 5% of the time.

Objectives: We aimed to develop diagnostic criteria for the short QT syndrome (SQTS) to facilitate clinical evaluation of suspected cases.Background: The SQTS is a cardiac channelopathy associated ...

Left ventricular systolic dysfunction (LVSD) is a risk factor for atrial fibrillation (AF), but the atrial cellular electrophysiological mechanisms in humans are unclear.This study sought to investigate whether LVSD in patients who are in sinus rhythm (SR) is associated with atrial cellular electrophysiological changes that could predispose to AF.Right atrial myocytes were obtained from 214 consenting patients in SR who were undergoing cardiac surgery. Action potentials or ion currents were measured using the whole-cell-patch clamp technique.The presence of moderate or severe LVSD was associated with a shortened atrial cellular effective refractory period (ERP) (209 +/- 8 ms; 52 cells, 18 patients vs 233 +/- 7 ms; 134 cells, 49 patients; P0.05); confirmed by multiple linear regression analysis. The left ventricular ejection fraction (LVEF) was markedly lower in patients with moderate or severe LVSD (36% +/- 4%, n = 15) than in those without LVSD (62% +/- 2%, n = 31; P0.05). In cells from patients with LVEFor= 45%, the ERP and action potential duration at 90% repolarization were shorter than in those from patients with LVEF45%, by 24% and 18%, respectively. The LVEF and ERP were positively correlated (r = 0.65, P0.05). The L-type calcium ion current, inward rectifier potassium ion current, and sustained outward ion current were unaffected by LVSD. The transient outward potassium ion current was decreased by 34%, with a positive shift in its activation voltage, and no change in its decay kinetics.LVSD in patients in SR is independently associated with a shortening of the atrial cellular ERP, which may be expected to contribute to a predisposition to AF.

Background Cholinesterase inhibitors are used to treat the symptoms of dementia and can theoretically cause bradycardia. Previous studies suggest that patients taking these medications have an increased risk of undergoing pacemaker insertion. Since these drugs have a marginal impact on patient outcomes, it might be preferable to change drug treatment rather than implant a pacemaker. This population-based study determined the association of people with dementia exposed to cholinesterase inhibitor medication and pacemaker insertion. Methods We used data from the Ontario health administrative databases from January 1, 1993 to June 30, 2012. We included all community-dwelling seniors who had a code for dementia and were exposed to cholinesterase inhibitors (donezepil, galantamine, and rivastigmine) and/or drugs used to treat co-morbidities of hypertension, diabetes, depression and hypothyroidism. We controlled for exposure to anti-arrhythmic drugs. Observation started at first exposure to any medication and continued until the earliest of pacemaker insertion, death, or end of study. Results 2,353,909 people were included with 96,000 (4.1%) undergoing pacemaker insertion during the observation period. Case–control analysis showed that pacemaker patients were less likely to be coded with dementia (unadjusted OR 0.42 [95%CI 0.41-0.42]) or exposed to cholinesterase inhibitors (unadjusted OR 0.39 [95%CI 0.37-0.41]). That Cohort analysis showed patients with dementia taking cholinesterase inhibitors had a decreased risk of pacemaker insertion (unadj-HR 0.58 [0.55-0.61]). Adjustment for patient age, sex, and other medications did not notably change results, as did restricting the analysis to incident users. Conclusions Patients taking cholinesterase inhibitors rarely undergo, and have a significantly reduced risk of, cardiac pacemaker insertion.

Endothelin-1 (ET-1) is elevated in patients with atrial fibrillation (AF) and heart failure. We investigated effects of ET-1 on human atrial cellular electrophysiological measurements expected to influence the genesis and maintenance of AF. Action potential characteristics and L-type Ca(2+) current (I(CaL)) were recorded by whole cell patch clamp, in atrial isolated myocytes obtained from patients in sinus rhythm. Isoproterenol (ISO) at 0.05 muM prolonged the action potential duration at 50% repolarisation (APD(50): 54 +/- 10 vs. 28 +/- 5 ms; P < 0.05, N = 15 cells, 10 patients), but neither late repolarisation nor cellular effective refractory period (ERP) were affected. ET-1 (10 nM) reversed the effect of ISO on APD(50), and had no basal effect (in the absence of ISO) on repolarisation or ERP. During repetitive stimulation, ISO (0.05 microM) produced arrhythmic depolarisations (P < 0.05). Each was abolished by ET-1 at 10 nM (P < 0.05). ISO (0.05 microM) increased peak I(CaL) from -5.5 +/- 0.4 to -14.6 +/- 0.9 pA/pF (P < 0.05; N = 79 cells, 34 patients). ET-1 (10 nM) reversed this effect by 98 +/- 10% (P < 0.05), with no effect on basal I(CaL). Chronic treatment of patients with a beta-blocker did not significantly alter basal APD(50) or I(CaL), the increase in APD(50) or I(CaL) by 0.05 microM ISO, nor the subsequent reversal of this effect on APD(50) by 10 nM ET-1. The marked anti-adrenergic effects of ET-1 on human atrial cellular action potential plateau, arrhythmic depolarisations and I(CaL), without affecting ERP and independently of beta-blocker treatment, may be expected to contribute a potentially anti-arrhythmic influence in the atria of patients with AF and heart failure.

Introduction: Persistent left superior vena cava (PLSVC) is a rare congenital anomaly of the superior venous system that may be discovered at the time of cardiac implantable electronic device (CIED) implantation. Methods and Results: We present a subject who needed cardiac resynchronization therapy (CRT)-CIED implantation and was discovered to have PLSVC with absent innominate vein during the implant procedure. We were able to successfully implant a CRT-CIED using a right-sided approach via the right superior vena cava (SVC). We present a description of our implant technique and a brief review of the different aspects of CIED implantation in subjects with variants of PLSVC. Conclusions: Superior venous anomalies such as PLSVC can make CIED implantation technically challenging. However, with increasing operator experience, cardiac imaging and appropriate tools successful CIED implantation is possible in almost all cases.

PURPOSE OF REVIEW Endurance exercise, despite a plethora of proven health benefits, is increasingly recognized as a potential cause of lone atrial fibrillation. Moderate exercise reduces all-cause mortality and protects against developing atrial fibrillation. However, more intense exercise regimes confer modest incremental health benefits, induce cardiac remodelling and negate some of the cardiovascular benefits of exercise. The implications of endurance exercise and athletic heart are becoming increasingly relevant as the popularity of endurance exercise has increased 20-fold within a generation. RECENT FINDINGS An apparent dose-response relationship exists between endurance exercise and left atrial dilatation. Repeated strenuous endurance exercise overloads atria, resulting in stretch-induced 'microtears', inflammation and endocardial scarring. Although these findings are observational in humans, similar mechanisms have recently been confirmed in animal models suggesting causation. SUMMARY Currently, it is not known whether a ceiling for endurance exercise exists, and, if so, what factors determine the threshold of harm. Although preliminary research is promising, much work remains if we are to understand the mechanisms underpinning atrial fibrillation in athletes.

To review the management of ventricular arrhythmias in patients with heart failure secondary to reduced ejection fraction (HFrEF).Recurrent ventricular arrhythmias and automatic implantable cardioverter defibrillator (AICD) shocks are responsible for significant mortality and morbidity in patients with HFrEF. Antiarrhythmic drugs and catheter ablation are the main treatment options. Frequent premature ventricular contractions (PVCs;10,000-20,000/24-h period) are being recognized as a cause of cardiomyopathy and suboptimal response to cardiac resynchronization therapy (CRT). Patients with ventricular assist devices (VADs) have frequent ventricular tachyarrhythmias resulting in increased morbidity and mortality. Such patients may need continuation of active ICD therapy and adjunctive catheter ablation.There is a pressing need to develop new antiarrhythmic drugs to treat patients with recurrent AICD shocks. The effectiveness of catheter ablation as first-line therapy for preventing ventricular arrhythmias and recurrent AICD shocks needs to be directly compared with amiodarone. Ventricular tachyarrhythmias are common in CRT patients and patients with VADs. Frequent PVCs may result in a reversible form of HFrEF.

Short QT syndrome (SQTS) is a rare genetic disease with a risk of sudden cardiac death. The present report describes syncope in a young man that resulted in a motor vehicle accident. An electrocardiogram and initial investigations were unremarkable, but treadmill testing showed a lack of adaptation of the QT interval, which has been described in SQTS. To evaluate the possible diagnosis of SQTS, DNA sequencing of genes known to be associated with SQTS was performed and identified a novel mutation in the KCNH2 gene. Consequently, the patient was diagnosed with SQTS and the recommendation of implantable cardioverter defibrillator implantation was accepted by the patient before discharge from the hospital.

Aims Cardiac resynchronization therapy (CRT) benefits patients with heart failure and a wide QRS complex. Still, one-third derive no clinical benefit and a majority of patients demonstrate no objective improvement of left ventricular (LV) function. Left bundle branch block (LBBB) is a strong predictor of response to CRT. We evaluated whether absence of electrocardiogram (ECG) markers of residual left bundle (LB) conduction in guideline-defined LBBB predicted a greater response to CRT. Methods and results An r wave ≥1 mm in lead V1 (r-V1) and/or a q wave ≥1 mm in lead aVL (q-aVL) was used to identify patients with residual LB conduction. Forty patients with a wide QRS were prospectively enrolled and subdivided into three groups: complete LBBB (cLBBB), LBBB without r-V1 or q-aVL ( n = 12); LBBB with residual LB conduction (rLBBB), LBBB with r-V1 and/or q-aVL ( n = 15); and non-specific intraventricular conduction delay (IVCD), ( n = 13). Following CRT: mean change in left ventricular ejection fraction was 11.9 ± 11.9% in cLBBB, 3.8 ± 5.4% in rLBBB ( P = 0.045), and 2.5 ± 4.4% in IVCD ( P = 0.02 cLBBB vs. IVCD); mean reduction in left ventricular end-systolic volume was 26.4 ± 39.2% in cLBBB, 14.3 ± 22.9% in rLBBB ( P = 0.35), and 5.6 ± 17.3% in IVCD ( P = 0.11 cLBBB vs. IVCD); mean change in native QRS duration was −8.0 ± 11.0 ms in cLBBB, −0.8 ± 8.24 ms in rLBBB ( P = 0.07), and 0.15 ± 8.0 ms in IVCD ( P = 0.048 cLBBB vs. IVCD). Conclusion In patients with guideline-defined LBBB, the absence of ECG markers of residual LB conduction was predictive of a greater improvement in LV function with CRT.

Aims An increasing number of transseptal punctures (TSPs) are performed worldwide for atrial ablations. Transseptal punctures can be complex and can be associated with potentially life threatening complications. The purpose of the study was to evaluate the safety and efficacy of a novel transseptal guidewire (TSGW) designed to facilitate TSPs. Methods and results Transseptal punctures were performed using a SafeSept™ TSGW passed through a standard TSP apparatus. Transseptal punctures were performed by standard technique with additional use of a TSGW allowing probing of the interatrial septum without needle exposure and penetration of the fossa into the left atrium (LA). Transseptal puncture using the TSGW was performed in 210 patients. Left atrial access was achieved successfully in 205 of 210 patients (97.6%) and in 96.3% of patients undergoing repeat TSP. Left atrial access was achieved with the first pass in 81.2% (mean 1.4 ± 0.9 passes, range 1–6) using the TSGW. No serious complications were attributable to the use of the TSGW, even in cases of failed TSP. Conclusions The TSGW is associated with a high success rate for TSP and may be a useful alternative to transoesophageal or intracardiac echocardiogram-guided TSP.

There is a substantial mortality rate in patients admitted alive after out-of-hospital cardiac arrest. The primary objective of our study was to examine trends in in-hospital survival in out-of-hospital cardiac arrest survivors in Canada between 1994 and 2004. The secondary objective was to examine predictors of in-hospital survival in these patients.Data on hospital admissions from April 1, 1994, to March 31, 2004, were obtained from the Health Person-oriented Information Database, maintained by Statistics Canada. We included all patients with a primary diagnosis of cardiac arrest who survived to hospital admission. We assessed survival to hospital discharge in all patients admitted alive.In Canada, 13,263 patients survived community arrest between 1994 and 2004. The annual incidence of hospital admission after out-of-hospital cardiac arrest decreased by 33%, from 5.37 per 100,000 in 1994 to 3.63 per 100,000 in 2004 (P.0001 for trend). Subsequently, 5,045 patients (38.03%) survived to hospital discharge. The survival rate did not change during the duration of the study. Invasive coronary artery disease management was associated with a greatly increased chance of survival (odds ratio 21.98, 95% CI 17.62-27.42). Also male gender, heart failure, and acute myocardial ischemia were independent positive predictors of survival to hospital discharge; greater age and comorbidities were negative predictors of survival. Finally, there were significant interprovincial variations in survival rates.Our study, the largest of its kind, has 4 main findings. Firstly, between 1993 and 2004, there was a significant and steady decline in admission rates after community cardiac arrest. Second, there was no change in the in-hospital survival rates. Thirdly, invasive management of coronary artery disease was associated with a greatly improved chance of survival, and finally, there were important regional variations in survival rates.

We present two patients with fractures within the pace–sense circuit of their Medtronic Sprint Fidelis leads who received inappropriate shocks from their Medtronic defibrillators during device interrogation. This was not simply a coincidence, but due to electromagnetic interference induced within the Sprint Fidelis lead by the device programmer during two-way communication with the defibrillator. Our subsequent investigations have uncovered at least two other similar incidents in Canada. We have also discovered that the Medtronic ‘Auto-resume’ feature may leave future patients uniquely vulnerable to such inappropriate shocks in the future.

Introduction We investigated whether post-cardiac surgery (CS) new-onset atrial fibrillation (AF) is predicted by pre-CS atrial cellular electrophysiology, and whether the antiarrhythmic effect of beta-blocker therapy may involve pre-CS pharmacological remodeling. Methods and results Atrial myocytes were obtained from consenting patients in sinus rhythm, just prior to CS. Action potentials and ion currents were recorded using whole-cell patch-clamp technique. Post-CS AF occurred in 53 of 212 patients (25%). Those with post-CS AF were older than those without (67 +/- 2 vs 62 +/- 1 years, P = 0.005). In cells from patients with post-CS AF, the action potential duration at 50% and 90% repolarization, maximum upstroke velocity, and effective refractory period (ERP) were 13 +/- 4 ms, 217 +/- 16 ms, 185 +/- 10 V/s, and 216 +/- 14 ms, respectively (n = 30 cells, 11 patients). Peak L-type Ca(2+) current, transient outward and inward rectifier K(+) currents, and the sustained outward current were -5.0 +/- 0.5, 12.9 +/- 2.4, -4.1 +/- 0.4, and 9.7 +/- 1.0 pA/pF, respectively (13-62 cells, 7-19 patients). None of these values were significantly different in cells from patients without post-CS AF (P > 0.05 for each, 60-279 cells, 29-86 patients), confirmed by multiple and logistic regression. In patients treated >7 days with a beta-blocker pre-CS, the incidence of post-CS AF was lower than in non-beta-blocked patients (13% vs 27%, P = 0.038). Pre-CS beta-blockade was associated with a prolonged pre-CS atrial cellular ERP (P = 0.001), by a similar degree (approximately 20%) in those with and without post-CS AF. Conclusion Pre-CS human atrial cellular electrophysiology does not predict post-CS AF. Chronic beta-blocker therapy is associated with a reduced incidence of post-CS AF, unrelated to a pre-CS ERP-prolonging effect of this treatment.

BACKGROUND: Sarcoidosis is a systemic inflammatory disorder of unknown etiology. Cardiac involvement occurs in 5-25 % of patients, and may present with any or combination of AV block, ventricular tachycardia, or heart failure. Pathological diagnosis is usually pursued prior to treatment with immunosuppressant medications, and requires the identification of characteristic non-caseating granulomatous inflammation. A cardiac biopsy is often required when there are no other more accessible sites, or where the disease is limited to the heart. However, sarcoidosis is a patchy disease and cardiac biopsy has a low yield. Recently we published a report of using electroanatomical voltage mapping to guide a positive biopsy in a patient with isolated CS. We report our additional experience with this technique. Our aim was to assess the relative yield of voltage-guided and non-guided biopsies at our institution for the diagnosis of cardiac sarcoidosis. METHODS: Patients with A-V block, ventricular tachycardia, or congestive heart failure undergoing endomyocardial right ventriular biopsy for the suspicion of cardiac sarcoidosis (CS) were included. If the biopsy directly led to the diagnosis or confirmation of cardiac sarcoidosis it was considered diagnostic. Non-guided biopsies were performed in the usual manner, targeting the right ventricular septum. Three dimensional electroanatomical mapping was used in guided RV biopsies, and ideally the “border zone” between normal tissue (> 1.5 mV) and scar (< 0.5 mV) was targeted. RESULTS: Eleven patients (mean age 53 yrs, 6 male) who underwent a total of 14 biopsies (5 guided and 9 nonguided) were included. Ventricular tachycardia was present in 7 patients (63%), A-V block in 7 (63%), and CHF in 3 (27%) patients. The yield for a definite diagnosis of CS was 3/5 for guided procedures (60 %), and 2/9 (22%) for nonguided procedures. A final pathological diagnosis of cardiac sarcoidosis was made in 5 patients based on the cardiac biopsy. CONCLUSION: Using 3D electro-anatomical mapping to guide endomyocardial biopsy for the diagnosis of cardiac sarcoidosis has a high yield, although the numbers in this report are small. Due to the patchy nature of the disease, and the importance of obtaining an early diagnosis, routine use of 3D mapping to guide endomyocardial RV biopsy sites holds promise, and may in future become standard for this indication. 464 PACEMAKER IMPLANT RATES: A NATIONAL PERSPECTIVE

In Clopidogrel in Unstable angina to prevent Recurrent Events (CURE), addition of clopidogrel to aspirin therapy reduced the primary composite outcome (death from cardiovascular causes, non-fatal myocardial infarction or stroke) in patients with acute coronary syndrome without ST-segment elevation. However, a significant excess of major bleeding in those randomised to clopidogrel versus placebo was also detected. Aims/purpose Clopidogrel is a thienopyridine derivative which irreversibly binds to platelet adenosine diphosphate (ADP) receptors. ADP receptor inhibition prevents formation of the platelet fibrinogen plug via the glycoprotein IIB/IIIA receptor-complex. At the time of the design of CURE, existing data suggested that clopidogrel was at least as effective as aspirin in preventing myocardial infarction, stroke and vascular death in those at risk of ischaemic events. 1 Moreover the combination of clopidogrel and aspirin in the short term had been shown to reduce myocardial infarction following percutaneous coronary revascularisation. 2