Rationale and design of the NODE-303 study: evaluating the safety of symptom-prompted, self-administered etripamil for paroxysmal supraventricular tachycardia episodes in real-world settings.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common episodic arrhythmia characterized by unpredictable onset and burdensome symptoms including palpitations, dizziness, chest pain, distress, and shortness of breath. Treatment of acute episodes of PSVT in the clinical setting consists of intravenous adenosine, beta-blockers, and calcium channel blockers (CCBs). Etripamil is an intranasally self-administered L-type CCB in development for acute treatment of AV-nodal dependent PSVT in a nonmedical supervised setting. METHODS: This paper summarizes the rationale and study design of NODE-303 that will assess the efficacy and safety of etripamil. In the randomized, double-blinded, placebo-controlled, Phase 3 RAPID trial, etripamil was superior to placebo in the conversion of single PSVT episodes by 30 minutes post initial dose when administered in the nonhealthcare setting; this study required a mandatory and observed test dosing prior to randomization. The primary objective of NODE-303 is to evaluate the safety of symptom-prompted, self-administered etripamil for multiple PSVT episodes in real-world settings, without the need for test dosing prior to first use during PSVT. Secondary endpoints include efficacy and disease burden. Upon perceiving a PSVT episode, the patient applies an electrocardiographic monitor, performs a vagal maneuver, and, if the vagal maneuver is unsuccessful, self-administers etripamil 70 mg, with an optional repeat dose if symptoms do not resolve within 10 minutes after the first dose. A patient may treat up to four PSVT episodes during the study. Adverse events are recorded as treatment-emergent if they occur within 24 hours after the administration of etripamil. RESULTS: Efficacy endpoints include time to conversion to sinus rhythm within 30 and 60 minutes after etripamil administration, and the proportion of patients who convert at 3, 5, 10, 20, 30, and 60 minutes. Patient-reported outcomes are captured by the Brief Illness Perception Questionnaire, the Cardiac Anxiety Questionnaire, the Short Form Health Survey 36, the Treatment Satisfaction Questionnaire for Medication and a PSVT survey. CONCLUSIONS: Overall, these data will support the development of a potentially paradigm-changing long-term management strategy for recurrent PSVT.

Etripamil Nasal Spray for Conversion of Repeated Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia During Long-Term Follow-Up: Results From the NODE-302 Study.

Background Self-administration of investigational intranasal L-type calcium channel blocker etripamil during paroxysmal supraventricular tachycardia (PSVT) appeared safe and well-tolerated in the phase 3 NODE-301 (Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Efficacy, and Safety Study of Etripamil Nasal Spray for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia) trial of adults with sustained atrioventricular nodal-dependent PSVT. The NODE-302 open-label extension further characterized etripamil safety and efficacy. Methods and Results Eligible patients were monitored via self-applied cardiac monitoring system for 5 hours after etripamil self-administration. The primary end point was time-to-conversion of positively adjudicated PSVT to sinus rhythm after etripamil treatment. Probability of conversion to sinus rhythm was reported via Kaplan-Meier plot. Adverse events were based on self-reported symptoms and clinical evaluations. Among 169 patients enrolled, 105 self-administered etripamil ≥1 time for perceived PSVT (median [range], 232 [8-584] days' follow-up). Probability of conversion within 30 minutes of etripamil was 60.2% (median time to conversion, 15.5 minutes) among 188 PSVT episodes (92 patients) positively adjudicated as atrioventricular nodal dependent by independent ECG analysis. Among 40 patients who self-treated 2 episodes, 75% had a significantly consistent response by 30 minutes; 9 did not convert on either episode, and 21 converted on both episodes (χ2=8.09; P=0.0045). Forty-five of 105 patients (42.9%) had ≥1 treatment-emergent adverse event, generally transient and mild-to-moderate, including nasal congestion (14.3%), nasal discomfort (14.3%), or rhinorrhea (12.4%). No serious cardiac safety events were observed within 24 hours of etripamil. Conclusions In this extension study, investigational etripamil nasal spray was well tolerated for self-treating recurrent episodes of PSVT without medical supervision. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03635996.

Association of the Timing and Extent of Cardiac Implantable Electronic Device Infections With Mortality.

Importance: Cardiac implantable electronic device (CIED) infection is a potentially devastating complication with an estimated 12-month mortality of 15% to 30%. The association of the extent (localized or systemic) and timing of infection with all-cause mortality has not been established. Objective: To evaluate the association of the extent and timing of CIED infection with all-cause mortality. Design, Setting, and Participants: This prospective observational cohort study was conducted between December 1, 2012, and September 30, 2016, in 28 centers across Canada and the Netherlands. The study included 19 559 patients undergoing CIED procedures, 177 of whom developed an infection. Data were analyzed from April 5, 2021, to January 14, 2023. Exposures: Prospectively identified CIED infections. Main Outcomes and Measures: Time-dependent analysis of the timing (early [≤3 months] or delayed [3-12 months]) and extent (localized or systemic) of infection was performed to determine the risk of all-cause mortality associated with CIED infections. Results: Of 19 559 patients undergoing CIED procedures, 177 developed a CIED infection. The mean (SD) age was 68.7 (12.7) years, and 132 patients were male (74.6%). The cumulative incidence of infection was 0.6%, 0.7%, and 0.9% within 3, 6, and 12 months, respectively. Infection rates were highest in the first 3 months (0.21% per month), reducing significantly thereafter. Compared with patients who did not develop CIED infection, those with early localized infections were not at higher risk for all-cause mortality (no deaths at 30 days [0 of 74 patients]: adjusted hazard ratio [aHR], 0.64 [95% CI, 0.20-1.98]; P = .43). However, patients with early systemic and delayed localized infections had an approximately 3-fold increase in mortality (8.9% 30-day mortality [4 of 45 patients]: aHR, 2.88 [95% CI, 1.48-5.61]; P = .002; 8.8% 30-day mortality [3 of 34 patients]: aHR, 3.57 [95% CI, 1.33-9.57]; P = .01), increasing to a 9.3-fold risk of death for those with delayed systemic infections (21.7% 30-day mortality [5 of 23 patients]: aHR, 9.30 [95% CI, 3.82-22.65]; P < .001). Conclusions and Relevance: Findings suggest that CIED infections are most common within 3 months after the procedure. Early systemic infections and delayed localized infections are associated with increased mortality, with the highest risk for patients with delayed systemic infections. Early detection and treatment of CIED infections may be important in reducing mortality associated with this complication.

First Randomized, Multicenter, Placebo-Controlled Study of Self-Administered Intranasal Etripamil for Acute Conversion of Spontaneous Paroxysmal Supraventricular Tachycardia (NODE-301).

BACKGROUND: Pharmacologic termination of paroxysmal supraventricular tachycardia (PSVT) often requires medically supervised intervention. Intranasal etripamil, is an investigational fast-acting, nondihydropyridine, L-type calcium channel blocker, designed for unsupervised self-administration to terminate atrioventricular nodal-dependent PSVT. Phase 2 results showed potential safety and efficacy of etripamil in 104 patients with PSVT. METHODS: NODE-301, a phase 3, multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of etripamil nasal spray administered, unsupervised in patients with symptomatic sustained PSVT. After a medically supervised etripamil test dose while in sinus rhythm, patients were randomized 2:1 to receive etripamil 70 mg or placebo. When PSVT symptoms developed, patients applied a cardiac monitor and attempted a vagal maneuver; if symptoms persisted, they self-administered blinded treatment. An independent Adjudication Committee reviewed continuous electrocardiogram recordings. The primary efficacy endpoint was termination of adjudicated PSVT within 5 hours after study drug administration. RESULTS: NODE-301 accrued 156 positively adjudicated PSVT events treated with etripamil (n=107) or placebo (n=49). The hazard ratio for the primary endpoint, time-to-conversion to sinus rhythm during the 5-hour observation period, was 1.086 (95% CI, 0.726-1.623; P=0.12). In predefined sensitivity analyses, etripamil effects (compared with placebo) occurred at 3, 5, 10, 20, and 30 minutes (P<0.05). For example, at 30 minutes, there was a 53.7% of SVT conversion in the treatment arm compared to 34.7% in the placebo arm (hazard ratio, 1.87 [95% CI, 1.09-3.22]; P=0.02). Etripamil was well tolerated; adverse events were mainly related to transient nasal discomfort and congestion (19.6% and 8.0%, respectively, of randomized treatment-emergent adverse events. CONCLUSIONS: Although the primary 5-hour efficacy endpoint was not met, analyses at earlier time points indicated an etripamil treatment effect in terminating PSVT. Etripamil self-administration during PSVT was safe and well tolerated. These results support continued clinical development of etripamil nasal spray for self-administration during PSVT in a medically unsupervised setting. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03464019.

Impact of Choice of Prophylaxis on the Microbiology of Cardiac Implantable Electronic Device Infections: Insights From the Prevention of Arrhythmia Device Infection Trial (PADIT).

BACKGROUND: The Prevention of Arrhythmia Device Infection Trial (PADIT) investigated whether intensification of perioperative prophylaxis could prevent cardiac implantable electronic device (CIED) infections. Compared with a single dose of cefazolin, the perioperative administration of cefazolin, vancomycin, bacitracin, and cephalexin did not significantly decrease the risk of infection. Our objective was to compare the microbiology of infections between study arms in PADIT. METHODS: This was a post hoc analysis. Differences between study arms in the microbiology of infections were assessed at the level of individual patients and at the level of microorganisms using the Fisher exact test. RESULTS: Overall, 209 microorganisms were reported from 177 patients. The most common microorganisms were coagulase-negative staphylococci (CoNS; 82/209 [39.2%]) and S. aureus (75/209 [35.9%]). There was a significantly lower proportion of CoNS in the incremental arm compared with the standard arm (30.1% vs 46.6%; P = .04). However, there was no significant difference between study arms in the frequency of recovery of other microorganisms. In terms of antimicrobial susceptibility, 26.5% of microorganisms were resistant to cefazolin. CoNS were more likely to be cefazolin-resistant in the incremental arm (52.2% vs 26.8%, respectively; P = .05). However, there was no difference between study arms in terms of infections in which the main pathogen was sensitive to cefazolin (77.8% vs 64.3%; P = .10) or vancomycin (90.8% vs 90.2%; P = .90). CONCLUSIONS: Intensification of the prophylaxis led to significant changes in the microbiology of infections, despite the absence of a decrease in the overall risk of infections. These findings provide important insight on the physiopathology of CIED infections. TRIAL REGISTRATION: NCT01002911.

Canadian Registry of Electronic Device Outcomes: remote monitoring outcomes in the Abbott battery performance alert-a multicentre cohort.

AIMS: Cardiac implantable electronic devices with device advisories have the potential of device malfunction. Remote monitoring (RM) of devices has been suggested to allow the identification of abnormal device performance and permit early intervention. We sought to describe the outcomes of patients with and without RM in devices subject to the Abbott Premature Battery Depletion (PBD) advisory with data from a Canadian registry. METHODS AND RESULTS: Patients with an Abbott device subject to the PBD advisory from nine implantable cardioverter defibrillator (ICD) implanting centres in Canada were included in the registry. The use of RM was identified from baseline and follow-up data in the registry. The primary outcome was detection of PBD and all-cause mortality. A total of 2666 patients were identified with a device subject to the advisory. In all, 1687 patients (63.2%) had RM at baseline. There were 487 deaths during follow-up. At a mean follow-up of 5.7 ± 0.7 years, mortality was higher in those without a remote monitor compared with RM at baseline (24.7% vs. 14.5%; P < 0.001). Pre-mature battery depletion was identified in 36 patients (2.1%) with RM vs. 7 (0.7%) without RM (P = 0.004). Time to battery replacement was significantly reduced in patients on RM (median 5 vs. 13 days, P = 0.001). CONCLUSION: The use of RM in patients with ICD and cardiac resynchronization therapy under advisory improved detection of PBD, time to device replacement, and was associated with a reduction in all-cause mortality. The factors influencing the association with mortality are unknown and deserve further study.

Canadian Registry of Electronic Device Outcomes (CREDO): The Abbott ICD Premature Battery Depletion Advisory, a Multicentre Cohort Study.

BACKGROUND: Premature or rapid battery depletion may compromise the performance and reliability of an implantable cardioverter defibrillator (ICD), potentially resulting in harm or death to patients. We sought to describe the outcomes and clinical management of devices included in the Abbott ICD Premature Battery Depletion Advisory, using data from a Canadian registry. METHODS: This prospective observational study includes patients with an Abbott device subject to the advisory, from 9 centres in Canada. The incidence and outcomes related to device revision owing to premature battery depletion were identified and adjudicated by a committee. RESULTS: There were 2678 patients enrolled with a device subject to the advisory. Devices were implanted between 2010 and 2017; follow-up time was 5.7 ± 0.7 years. Device revision occurred in 222 patients (8.3%). Revision for premature battery depletion occurred in 43 patients (1.6%). Devices were revised at physician discretion on notice of the advisory in 16 patients (0.6%), and at patient request in 5 patients (0.2%). A total of 63 (2.4%) devices reached routine end of battery life. A further 95 (3.5%) patients underwent revision for other reasons. There were no reported major complications or adverse events with device revision owing to the advisory. There were no deaths attributed to premature battery depletion. CONCLUSIONS: The rate of premature battery depletion associated with the Abbott ICD Premature Battery Depletion Advisory is low. There were no clinically adverse events identified that were associated with the battery performance of devices under advisory.

CONTEXTE: L'épuisement prématuré ou rapide de la pile pourrait compromettre le rendement et la fiabilité d'un défibrillateur cardioverteur implantable (DCI), et risque d'être dommageable ou mortel pour les patients. Nous avons voulu décrire les issues et la gestion clinique des dispositifs mentionnés dans l'avis d'Abbott sur l'épuisement prématuré de la pile de DCI, en utilisant des données tirées d'un registre canadien. MÉTHODOLOGIE: L'étude observationnelle prospective a été menée auprès de patients porteurs d'un dispositif Abbott faisant l'objet de l'avis, dans neuf établissements au Canada. La fréquence des révisions de dispositif dues à l'épuisement prématuré de la pile et les issues qui y sont associées ont été recensées et évaluées par un comité. RÉSULTATS: Ont été inscrits à l'étude 2 678 patients porteurs d'un dispositif faisant l'objet de l'avis. Les dispositifs avaient été mis en place entre 2010 et 2017; la durée du suivi avait été de 5,7 ± 0,7 ans. Une révision de dispositif a été effectuée chez 222 patients (8,3 %). Elle a été motivée par un épuisement prématuré de la pile chez 43 patients (1,6 %). Une révision de dispositif a été faite à la discrétion du médecin, après réception de l'avis, chez 16 patients (0,6 %) et à la demande de cinq patients (0,2 %). Au total, la pile de 63 (2,4 %) dispositifs avait atteint la fin de sa durée de vie habituelle. D'autres raisons ont entraîné une révision chez 95 autres patients (3,5 %). Aucune complication majeure et aucun effet indésirable n'ont été signalés avec les dispositifs révisés par suite de l'avis. Il n'y a eu aucun décès attribué à un épuisement prématuré de la pile. CONCLUSIONS: Le taux d'épuisement prématuré de la pile de DCI associé à l'avis d'Abbott est faible. Il n'y a pas eu d'incidents cliniques jugés liés au rendement de la pile des dispositifs faisant l'objet de l'avis.

Post-operative pain following cardiac implantable electronic device implantation: insights from the BRUISE CONTROL trials.

AIMS: Post-operative pain following cardiac implantable electronic device (CIED) insertion is associated with patient dissatisfaction, emotional distress, and emergency department visits. We sought to identify factors associated with post-operative pain and develop a prediction score for post-operative pain. METHODS AND RESULTS: All patients from the BRUISE CONTROL-1 and 2 trials were included in this analysis. A validated Visual Analogue Scale (VAS) was used to assess the severity of pain related to CIED implant procedures. Patients were asked to grade the most severe post-operative pain, average post-operative pain, and pain on the day of the first post-operative clinic. Multivariable regression analyses were performed to identify predictors of significant post-operative pain and to develop a pain-prediction score. A total of 1308 patients were included. Multivariable regression analysis found that the presence of post-operative clinically significant haematoma {CSH; P value < 0.001; odds ratio (OR) 3.82 [95% confidence interval (CI): 2.37-6.16]}, de novo CIED implantation [P value < 0.001; OR 1.90 (95% CI: 1.47-2.46)], female sex [P value < 0.001; OR 1.61 (95% CI: 1.22-2.12)], younger age [<65 years; P value < 0.001; OR 1.54 (95% CI: 1.14-2.10)], and lower body mass index [<20 kg/m2; P value < 0.05; OR 2.05 (95% CI: 0.98-4.28)] demonstrated strong and independent associations with increased post-operative pain. An 11-point post-operative pain prediction score was developed using the data. CONCLUSION: Our study has identified multiple predictors of post-operative pain after CIED insertion. We have developed a prediction score for post-operative pain that can be used to identify individuals at risk of experiencing significant post-operative pain.

Risk Factors for Infections Involving Cardiac Implanted Electronic Devices.

BACKGROUND: Cardiac implantable electronic device infection is a major complication that usually requires device removal. PADIT (Prevention of Arrhythmia Device Infection Trial) was a large cluster crossover trial of conventional versus incremental antibiotics. OBJECTIVES: This study sought to investigate independent predictors of device infection in PADIT and develop a novel infection risk score. METHODS: In brief, over 4 6-month periods, 28 centers used either conventional or incremental prophylactic antibiotic treatment in all patients. The primary outcome was hospitalization for device infection within 1 year (blinded endpoint adjudication). Multivariable logistic prediction modeling was used to identify the independent predictors and develop a risk score for device infection. The prediction models were internally validated with bootstrap methods. RESULTS: Device procedures were performed in 19,603 patients, and hospitalization for infection occurred in 177 (0.90%) within 1 year of follow-up. The final prediction model identified 5 independent predictors of device infection (prior procedures [P], age [A], depressed renal function [D], immunocompromised [I], and procedure type [T]) with an optimism-corrected C-statistic of 0.704 (95% confidence interval: 0.660 to 0.744). A PADIT risk score ranging from 0 to 15 points classified patients into low (0 to 4), intermediate (5 to 6) and high (≥7) risk groups with rates of hospitalization for infection of 0.51%, 1.42%, and 3.41%, respectively. CONCLUSIONS: This study identified 5 independent predictors of device infection and developed a novel infection risk score in the largest cardiac implantable electronic device trial to date, warranting validation in an independent cohort. The 5 independent predictors in the PADIT score are readily adopted into clinical practice. (Prevention of Arrhythmia Device Infection Trial [PADIT Pilot]; NCT01002911).

Effect of Direct Oral Anticoagulants, Warfarin, and Antiplatelet Agents on Risk of Device Pocket Hematoma: Combined Analysis of BRUISE CONTROL 1 and 2.

BACKGROUND: Oral anticoagulant use is common among patients undergoing pacemaker or defibrillator surgery. BRUISE CONTROL (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial; NCT00800137) demonstrated that perioperative warfarin continuation reduced clinically significant hematomas (CSH) by 80% compared with heparin bridging (3.5% versus 16%). BRUISE-CONTROL-2 (NCT01675076) observed a similarly low risk of CSH when comparing continued versus interrupted direct oral anticoagulant (2.1% in both groups). Using patient level data from both trials, the current study aims to: (1) evaluate the effect of concomitant antiplatelet therapy on CSH, and (2) understand the relative risk of CSH in patients treated with direct oral anticoagulant versus continued warfarin. METHODS: We analyzed 1343 patients included in BRUISE-CONTROL-1 and BRUISE-CONTROL-2. The primary outcome for both trials was CSH. There were 408 patients identified as having continued either a single or dual antiplatelet agent at the time of device surgery. RESULTS: Antiplatelet use (versus nonuse) was associated with CSH in 9.8% versus 4.3% of patients (P<0.001), and remained a strong independent predictor after multivariable adjustment (odds ratio, 1.965; 95% CI, 1.202-3.213; P=0.0071). In multivariable analysis, adjusting for antiplatelet use, there was no significant difference in CSH observed between direct oral anticoagulant use compared with continued warfarin (odds ratio, 0.858; 95% CI, 0.375-1.963; P=0.717). CONCLUSIONS: Concomitant antiplatelet therapy doubled the risk of CSH during device surgery. No difference in CSH was found between direct oral anticoagulant versus continued warfarin. In anticoagulated patients undergoing elective or semi-urgent device surgery, the patient specific benefit/risk of holding an antiplatelet should be carefully considered. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00800137, NCT01675076.

Concomitant anti-platelet therapy in warfarin-treated patients undergoing cardiac rhythm device implantation: A secondary analysis of the BRUISE CONTROL trial.

BACKGROUND: Anti-platelet therapy is commonly used in patients receiving oral anticoagulation and may increase bleeding risk among patients undergoing cardiac implantable electronic device (CIED) surgery. We sought to determine the proportion of anticoagulated patients who are concomitantly receiving anti-platelet therapy, the associated risk of clinically significant hematoma (CSH), and the proportion of patients in whom anti-platelet usage is guideline-indicated. METHODS: A secondary analysis of the Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial (BRUISE CONTROL). Patients who were receiving warfarin, had an annual predicted risk of thromboembolism of ≥5% and were scheduled to undergo non-emergent CIED surgery were randomized to continued warfarin versus heparin bridging. In the current analysis, patients were divided into those receiving anti-platelet therapy and those not receiving anti-platelet therapy. The incidence of CSH was compared in both groups. The proportion of patients on potentially inappropriate and potentially interruptible antiplatelet therapy was estimated. RESULTS: All 681 patients enrolled in BRUISE CONTROL were included, of whom 280 received and 401 did not receive anti-platelet therapy. Anti-platelet therapy increased the risk of CSH (relative risk, 1.72; 95% confidence interval (CI), 1.09 to 2.72; P = 0.02). Of the 280 patients receiving anti-platelet therapy, 97 (34.6%) had no guideline indication for concomitant anti-platelet therapy and an additional 146 (52.1%) were on anti-platelet therapy that could potentially have been interrupted around CIED surgery. CONCLUSIONS: Concomitant anti-platelet therapy in patients receiving anticoagulation is associated with a significant risk of CSH. The majority of concomitant anti-platelet therapy is potentially inappropriate or interruptible. TRIAL REGISTRATION: clinicaltrials.gov Identifier: (NCT00800137).

Prevention of Arrhythmia Device Infection Trial: The PADIT Trial.

BACKGROUND: Infection of implanted medical devices has catastrophic consequences. For cardiac rhythm devices, pre-procedural cefazolin is standard prophylaxis but does not protect against methicillin-resistant gram-positive organisms, which are common pathogens in device infections. OBJECTIVE: This study tested the clinical effectiveness of incremental perioperative antibiotics to reduce device infection. METHODS: The authors performed a cluster randomized crossover trial with 4 randomly assigned 6-month periods, during which centers used either conventional or incremental periprocedural antibiotics for all cardiac implantable electronic device procedures as standard procedure. Conventional treatment was pre-procedural cefazolin infusion. Incremental treatment was pre-procedural cefazolin plus vancomycin, intraprocedural bacitracin pocket wash, and 2-day post-procedural oral cephalexin. The primary outcome was 1-year hospitalization for device infection in the high-risk group, analyzed by hierarchical logistic regression modeling, adjusting for random cluster and cluster-period effects. RESULTS: Device procedures were performed in 28 centers in 19,603 patients, of whom 12,842 were high risk. Infection occurred in 99 patients (1.03%) receiving conventional treatment, and in 78 (0.78%) receiving incremental treatment (odds ratio: 0.77; 95% confidence interval: 0.56 to 1.05; p = 0.10). In high-risk patients, hospitalization for infection occurred in 77 patients (1.23%) receiving conventional antibiotics and in 66 (1.01%) receiving incremental antibiotics (odds ratio: 0.82; 95% confidence interval: 0.59 to 1.15; p = 0.26). Subgroup analysis did not identify relevant patient or site characteristics with significant benefit from incremental therapy. CONCLUSIONS: The cluster crossover design efficiently tested clinical effectiveness of incremental antibiotics to reduce device infection. Device infection rates were low. The observed difference in infection rates was not statistically significant. (Prevention of Arrhythmia Device Infection Trial [PADIT Pilot] [PADIT]; NCT01002911).

Continued vs. interrupted direct oral anticoagulants at the time of device surgery, in patients with moderate to high risk of arterial thrombo-embolic events (BRUISE CONTROL-2).

Aims: Guidelines recommend warfarin continuation rather than heparin bridging for pacemaker and defibrillator surgery, after the BRUISE CONTROL trial demonstrated an 80% reduction in device pocket haematoma with this approach. However, direct oral anticoagulants (DOACs) are now used to treat the majority of patients with atrial fibrillation. We sought to understand the best strategy to manage the DOACs at the time of device surgery and specifically hypothesized that performing device surgery without DOAC interruption would result in a reduced haematoma rate. Methods and results: We randomly assigned patients with atrial fibrillation and CHA2DS2-VASc score ≥2, to continued vs. interrupted DOAC (dabigatran, rivaroxaban, or apixaban). The primary outcome was blindly evaluated, clinically significant device pocket haematoma: resulting in re-operation, interruption of anticoagulation, or prolonging hospital stay. In the continued arm, the median time between pre- and post-operative DOAC doses was 12 h; in the interrupted arm the median time was 72 h. Clinically significant haematoma occurred in of 7 of 328 (2.1%; 95% CI 0.9-4.3) patients in the continued DOAC arm and 7 of 334 (2.1%; 95% CI 0.9-4.3) patients in the interrupted DOAC arm (P = 0.97). Complications were uncommon, and included one stroke and one symptomatic pericardial effusion in each arm. Conclusions: These results suggest that, dependent on the clinical scenario, either management strategy (continued DOAC or interrupted DOAC) might be reasonable, at least for patients similar to those enrolled in our trial.

Prevention of venous thrombosis after electrophysiology procedures: a survey of national practice.

PURPOSE: Femoral venous access is required for most electrophysiology procedures. Limited data are available regarding post-procedure venous thromboembolism (VTE), specifically deep vein thrombosis (DVT) and pulmonary embolism (PE). Potential preventative strategies are unclear. We aimed to survey Canadian centers regarding incidence of VTE and strategies for prevention of VTE after procedures that do not require post-procedure anticoagulation. METHODS: An online survey was distributed to electrophysiologists representing major Canadian EP centers. Participants responded regarding procedural volume, incidence of VTE post-procedure, and their practice regarding pharmacological and non-pharmacological peri-procedural VTE prophylaxis. RESULTS: The survey included 17 centers that performed a total of 6062 procedures in 2016. Ten patients (0.16%) had VTE (including 9 DVTs and 6 PEs) after diagnostic electrophysiology studies and right-sided ablation procedures excluding atrial flutter. Five centers (41.6%) administered systemic intravenous heparin during both diagnostic electrophysiology studies and right-sided ablation procedures. For patients taking oral anticoagulants, 10 centers (58.8%) suspend therapy prior to the procedure. Two centers (11.8%) routinely prescribed post-procedure pharmacologic prophylaxis for VTE. Four centers (23.5%) used compression dressings post-procedure and all prescribed bed rest for a maximum of 6 h. Of the variables collected in the survey, none were found to be predictive of VTE. CONCLUSIONS: VTE is not a common complication of EP procedures. There is significant variability in the strategies used to prevent VTE events. Future research is required to evaluate strategies to reduce the risk of VTE that may be incorporated into EP practice guidelines.

Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia to Sinus Rhythm.

BACKGROUND: There is no nonparenteral medication for the rapid termination of paroxysmal supraventricular tachycardia. OBJECTIVES: The purpose of this study was to assess the efficacy and safety of etripamil nasal spray, a short-acting calcium-channel blocker, for the rapid termination of paroxysmal supraventricular tachycardia (SVT). METHODS: This phase 2 study was performed during electrophysiological testing in patients with previously documented SVT who were induced into SVT prior to undergoing a catheter ablation. Patients in sustained SVT for 5 min received either placebo or 1 of 4 doses of active compound. The primary endpoint was the SVT conversion rate within 15 min of study drug administration. Secondary endpoints included time to conversion and adverse events. RESULTS: One hundred four patients were dosed. Conversion rates from SVT to sinus rhythm were between 65% and 95% in the etripamil nasal spray groups and 35% in the placebo group; the differences were statistically significant (Pearson chi-square test) in the 3 highest active compound dose groups versus placebo. In patients who converted, the median time to conversion with etripamil was <3 min. Adverse events were mostly related to the intranasal route of administration or local irritation. Reductions in blood pressure occurred predominantly in the highest etripamil dose. CONCLUSIONS: Etripamil nasal spray rapidly terminated induced SVT with a high conversion rate. The safety and efficacy results of this study provide guidance for etripamil dose selection for future studies involving self-administration of this new intranasal calcium-channel blocker in a real-world setting for the termination of SVT. (Efficacy and Safety of Intranasal MSP-2017 [Etripamil] for the Conversion of PSVT to Sinus Rhythm [NODE-1]; NCT02296190).

Canadian Registry of Implantable Electronic Device Outcomes: Longer-term follow-up of the Riata lead under advisory.

BACKGROUND: The Riata lead advisory was announced in 2011 and has posed unique management challenges because of cable externalization and insulation abrasion, in some cases leading to sudden loss of defibrillation. OBJECTIVE: The purpose of this study was to provide further data on the rate of electrical failure in a population of patients with a Riata lead under advisory. METHODS: Using the Canadian Registry of Electronic Device Outcomes, prospective follow-up data were collected on 1352 Riata leads under advisory in 17 implantable cardioverter-defibrillator (ICD) implantation centers in Canada. Data on electrical and structural failure were collected, as well as periprocedural complications related to lead revision (abandonment or extraction). RESULTS: Of the 1352 leads included in this 12-month follow-up cohort, 110 leads were revised. Mean follow-up time was 10.4 ± 1.5 years. The 12-year rate of electrical failure for the 8Fr lead was 9.45%, whereas the 10-year failure rate for the 7Fr lead was 7.25% and was not found to be accelerating. Of the leads revised because of advisory only (patient preference, advisory related, electrical or structural failure), the majority were abandoned (n = 54 [76.0%]), whereas 17 (24.0%) were extracted using power tools. The rate of major complications in each group was 5.6% and 5.9%, respectively. CONCLUSION: This report provides further data on the risk of electrical lead failure over a long lead dwell time. The risk of failure exceeds the risk of periprocedural major complications, indicating that the risk-to-benefit ratio is favorable to revise the lead in appropriate clinical scenarios.

Short-term dabigatran interruption before cardiac rhythm device implantation: multi-centre experience from the RE-LY trial.

AIMS: Cardiac implantable electronic device (CIED) surgery is commonly performed in patients with atrial fibrillation (AF). The current analysis was undertaken to compare peri-operative anticoagulation management, bleeding, and thrombotic events in AF patients treated with dabigatran vs. warfarin. METHODS AND RESULTS: This study included 611 patients treated with dabigatran vs. warfarin who underwent CIED surgery during the RE-LY trial. Among 201 warfarin-treated patients, warfarin was interrupted a median of 144 (inter-quartile range, IQR: 120-216) h, and 37 (18.4%) patients underwent heparin bridging. In dabigatran-treated patients (216 on 110 mg bid and 194 on 150 mg bid), the duration of dabigatran interruption was a median of 96 (IQR: 61-158) h. Pocket hematomas occurred in 9 (2.20%) patients on dabigatran and 8 (3.98%) patients on warfarin (P = 0.218). The occurrence of pocket hematomas was lower with dabigatran compared with warfarin with heparin bridging (RD: -8.62%, 95% CI: -24.15 to - 0.51%, P = 0.034) but not when compared with warfarin with no bridging (P = 0.880). Ischemic stroke occurred in 2 (0.3%) patients; one in the warfarin group (without bridging) and one in the dabigatran 150 mg bid group (P = 0.735). CONCLUSION: In patients treated with dabigatran undergoing CIED surgery, interruption of dabigatran is associated with similar or lower incidence of pocket hematoma, when compared with warfarin interruption without or with heparin bridging, respectively. Whether uninterrupted dabigatran can reduce pocket hematoma or ischemic stroke remains to be evaluated.

Bipolar radiofrequency ablation of aneurysm remnants after coil embolization can improve endovascular treatment of experimental bifurcation aneurysms.

OBJECTIVE Endovascular treatment of aneurysms may result in incomplete initial occlusion and aneurysm recurrence at angiographic follow-up studies. This study aimed to assess the feasibility and efficacy of bipolar radiofrequency ablation (RFA) of aneurysm remnants after coil embolization. METHODS Bipolar RFA was accomplished using the coil mass as 1 electrode, while the second electrode was a stent placed across the aneurysmal neck. After preliminary experiments and protocol approval from the Animal Care committee, wide-necked bifurcation aneurysms were constructed in 24 animals. Aneurysms were allocated to 1 of 3 groups: partial intraoperative coil embolization, followed by RFA (n = 12; treated group) or without RFA (n = 6; control group 1); or attempted complete endovascular coil embolization 2-4 weeks later (n = 6; control group 2). Angiographic results were compared at baseline, immediately after RFA, and at 12 weeks, using an ordinal scale. Pathological results and neointima formation at the neck were compared using a semiquantitative grading scale. RESULTS Bipolar RFA was able to reliably target the aneurysm neck when the coil mass and stent were used as electrodes. RFA improved angiographic results immediately after partial coiling (p = 0.0024). Two RFA-related complications occurred, involving transient occlusion of 1 carotid artery and 1 hemorrhage from an adventitial arterial blister. At 12 weeks, angiographic results were improved with RFA (median score of 0), when compared with controls (median score of 2; p = 0.0013). Neointimal closure of the aneurysm neck was better with RFA compared with controls (p = 0.0003). CONCLUSIONS Bipolar RFA can improve results of embolization in experimental models by selectively ablating residual lesions after coil embolization.