Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation.

BACKGROUND: Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit. METHODS: We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason). RESULTS: We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group. CONCLUSIONS: Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.).

Ability to remotely monitor atrial high-rate episodes using a single-chamber implantable cardioverter-defibrillator with a floating atrial sensing dipole.

AIMS: To allow timely initiation of anticoagulation therapy for the prevention of stroke, the European guidelines on atrial fibrillation (AF) recommend remote monitoring (RM) of device-detected atrial high-rate episodes (AHREs) and progression of arrhythmia duration along pre-specified strata (6 min…<1 h, 1 h…<24 h, ≥ 24 h). We used the MATRIX registry data to assess the capability of a single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (DX ICD system) to follow this recommendation in patients with standard indication for single-chamber ICD. METHODS AND RESULTS: In 1841 DX ICD patients with daily automatic RM transmissions, electrograms of first device-detected AHREs per patient in each duration stratum were adjudicated, and the corresponding positive predictive values (PPVs) for the detections to be true atrial arrhythmia were calculated. Moreover, the incidence and progression of new-onset AF was assessed in 1451 patients with no AF history. A total of 610 AHREs ≥6 min were adjudicated. The PPV was 95.1% (271 of 285) for episodes 6min…<1 h, 99.6% (253/254) for episodes 1 h…<24 h, 100% (71/71) for episodes ≥24 h, or 97.5% for all episodes (595/610). The incidence of new-onset AF was 8.2% (119/1451), and in 31.1% of them (37/119), new-onset AF progressed to a higher duration stratum. Nearly 80% of new-onset AF patients had high CHA2DS2-VASc stroke risk, and 70% were not on anticoagulation therapy. Age was the only significant predictor of new-onset AF. CONCLUSION: A 99.7% detection accuracy for AHRE ≥1 h in patients with DX ICD systems in combination with daily RM allows a reliable guideline-recommended screening for subclinical AF and monitoring of AF-duration progression.

Midodrine for the Prevention of Vasovagal Syncope : A Randomized Clinical Trial.

BACKGROUND: Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope. OBJECTIVE: To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481). SETTING: 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom. PATIENTS: Patients with recurrent vasovagal syncope and no serious comorbid conditions. INTERVENTION: Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months. MEASUREMENTS: The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up. RESULTS: The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups. LIMITATION: Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center. CONCLUSION: Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden. PRIMARY FUNDING SOURCE: The Canadian Institutes of Health Research.

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.

A proof of principle study of atomoxetine for the prevention of vasovagal syncope: the Prevention of Syncope Trial VI.

AIMS: There are few effective therapies for vasovagal syncope (VVS). Pharmacological norepinephrine transporter (NET) inhibition increases sympathetic tone and decreases tilt-induced syncope in healthy subjects. Atomoxetine is a potent and highly selective NET inhibitor. We tested the hypothesis that atomoxetine prevents tilt-induced syncope. METHODS AND RESULTS: Vasovagal syncope patients were given two doses of study drug [randomized to atomoxetine 40 mg (n = 27) or matched placebo (n = 29)] 12 h apart, followed by a 60-min drug-free head-up tilt table test. Beat-to-beat heart rate (HR), blood pressure (BP), and cardiac haemodynamics were recorded using non-invasive techniques and stroke volume modelling. Patients were 35 ± 14 years (73% female) with medians of 12 lifetime and 3 prior year faints. Fewer subjects fainted with atomoxetine than with placebo [10/29 vs. 19/27; P = 0.003; risk ratio 0.49 (confidence interval 0.28-0.86)], but equal numbers of patients developed presyncope or syncope (23/29 vs. 21/27). Of patients who developed only presyncope, 87% (13/15) had received atomoxetine. Patients with syncope had lower nadir mean arterial pressure than subjects with only presyncope (39 ± 18 vs. 69 ± 18 mmHg, P < 0.0001), and this was due to lower trough HRs in subjects with syncope (67 ± 30 vs. 103 ± 32 b.p.m., P = 0.006) and insignificantly lower cardiac index (2.20 ± 1.36 vs. 2.84 ± 1.05 L/min/m2, P = 0.075). There were no significant differences in stroke volume index (32 ± 6 vs. 35 ± 5 mL/m2, P = 0.29) or systemic vascular resistance index (2156 ± 602 vs. 1790 ± 793 dynes*s/cm5*m2, P = 0.72). CONCLUSION: Norepinephrine transporter inhibition significantly decreased the risk of tilt-induced syncope in VVS subjects, mainly by blunting reflex bradycardia, thereby preventing final falls in cardiac index and BP.

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.

Intracardiac echo-facilitated 3D electroanatomical mapping of ventricular arrhythmias from the papillary muscles: assessing the 'fourth dimension' during ablation.

AIMS: Ventricular arrhythmias (VA) originating from a papillary muscle (PM) have recently been described as a distinct clinical entity with peculiar features that make its treatment with catheter ablation challenging. Here, we report our experience using an intracardiac echo-facilitated 3D electroanatomical mapping approach in a case series of patients undergoing ablation for PM VA. METHODS AND RESULTS: Sixteen patients who underwent catheter ablation for ventricular tachycardia (VT) or symptomatic premature ventricular contractions originating from left ventricular PMs were included in the study. A total of 24 procedures (mean 1.5 per patient) were performed: 15 using a retrograde aortic approach and 9 using a transseptal approach. Integrated intracardiac ultrasound for 3D electroanatomical mapping was used in 15 of the 24 procedures. The posteromedial PM was the most frequent culprit for the clinical arrhythmia, and the body was the part of the PM most likely to be the successful site for ablation. The site of ablation was identified based on the best pace map matching the clinical arrhythmia and the site of earliest the activation. At a mean follow-up of 10.5 ± 7 months, only two patients had recurrent arrhythmias following a repeat ablation procedure. CONCLUSION: An echo-facilitated 3D electroanatomical mapping allows for real-time creation of precise geometries of cardiac chambers and endocavitary structures. This is useful during procedures such as catheter ablation of VAs originating from PMs, which require detailed representation of anatomical landmarks. Routine adoption of this technique should be considered to improve outcomes of PM VA ablation.

Pacemaker or defibrillator surgery without interruption of anticoagulation.

BACKGROUND: Many patients requiring pacemaker or implantable cardioverter-defibrillator (ICD) surgery are taking warfarin. For patients at high risk for thromboembolic events, guidelines recommend bridging therapy with heparin; however, case series suggest that it may be safe to perform surgery without interrupting warfarin treatment. There have been few results from clinical trials to support the safety and efficacy of this approach. METHODS: We randomly assigned patients with an annual risk of thromboembolic events of 5% or more to continued warfarin treatment or to bridging therapy with heparin. The primary outcome was clinically significant device-pocket hematoma, which was defined as device-pocket hematoma that necessitated prolonged hospitalization, interruption of anticoagulation therapy, or further surgery (e.g., hematoma evacuation). RESULTS: The data and safety monitoring board recommended termination of the trial after the second prespecified interim analysis. Clinically significant device-pocket hematoma occurred in 12 of 343 patients (3.5%) in the continued-warfarin group, as compared with 54 of 338 (16.0%) in the heparin-bridging group (relative risk, 0.19; 95% confidence interval, 0.10 to 0.36; P<0.001). Major surgical and thromboembolic complications were rare and did not differ significantly between the study groups. They included one episode of cardiac tamponade and one myocardial infarction in the heparin-bridging group and one stroke and one transient ischemic attack in the continued-warfarin group. CONCLUSIONS: As compared with bridging therapy with heparin, a strategy of continued warfarin treatment at the time of pacemaker or ICD surgery markedly reduced the incidence of clinically significant device-pocket hematoma. (Funded by the Canadian Institutes of Health Research and the Ministry of Health and Long-Term Care of Ontario; BRUISE CONTROL ClinicalTrials.gov number, NCT00800137.).

Strategy of continued vs interrupted novel oral anticoagulant at time of device surgery in patients with moderate to high risk of arterial thromboembolic events: The BRUISE CONTROL-2 trial.

BACKGROUND: Patients who require perioperative anticoagulation during cardiac implantable electronic device surgery are at increased risk for bleeding complications. The BRUISE CONTROL trial demonstrated that continuing warfarin was safer than heparin bridging, reducing the incidence of clinically significant pocket hematoma. Novel oral anticoagulants are being increasingly prescribed in place of warfarin. The best perioperative management of these new anticoagulants is unknown. METHODS/DESIGN: A randomized controlled trial to investigate whether a strategy of continued vs interrupted novel oral anticoagulant (dabigatran, rivaroxaban, or apixaban) at the time of device surgery, in patients with moderate to high risk of arterial thromboembolic events, reduces the incidence of clinically significant hematoma (defined as a hematoma requiring reoperation and/or resulting in prolongation of hospitalization, and/or requiring interruption of anticoagulation). The secondary outcomes include components of the primary outcome, composite of all other major perioperative bleeding events, thromboembolic events, all-cause mortality, cost-effectiveness, patient quality of life, perioperative pain, and satisfaction. Planned analyses include descriptive statistics of all baseline variables. For the primary outcome, interrupted vs continued novel oral anticoagulant arms will be compared using the χ(2) test. If any clinically significant differences are identified, a logistic regression analysis will be conducted. Quality of life will be assessed using EuroQol-5D, and perioperative pain using a visual analog scale. DISCUSSION: BRUISE CONTROL-2 is a randomized trial evaluating the best strategy to manage novel oral anticoagulants at the time of device surgery. We hypothesize that device surgery can be performed safely without interruption of these medications.

Arrhythmic Risk Following Recovery of Left Ventricular Ejection Fraction in Patients with Primary Prevention ICD.

BACKGROUND: Left ventricular ejection fraction (LVEF) recovers during follow-up in a significant proportion of patients implanted with a cardioverter defibrillator (ICD) for primary prevention. Little is known about the midterm arrhythmic risk in this population, particularly in relation to the presence or absence of ischemic cardiomyopathy. METHODS AND RESULTS: We retrospectively analyzed 286 patients with an ICD implanted for primary prevention between 2002 and 2010. Patients were divided into two groups based on their last LVEF assessment: (1) Recovery, defined as an LVEF > 35%; and (2) No-Recovery, defined as an LVEF ≤ 35%. Kaplan-Meir curves and multivariate Cox regression analysis were performed separately for patients with ischemic (211 patients) and nonischemic (75 patients) cardiomyopathy. Forty-nine patients (17.1%) had LVEF recovery to >35% at last follow-up. Overall, 72 patients (25.2%) experienced ventricular arrhythmias requiring ICD therapy during a median follow-up of 4.4 years. With multivariate Cox regression, LVEF recovery was associated with a lower arrhythmic risk in the whole cohort (hazard ratio [HR]: 0.38 [0.13-0.85]; P = 0.02) and in the nonischemic cardiomyopathy cohort (HR: 0.10 [0.005-0.55]; P = 0.005), but not in the ischemic cardiomyopathy cohort (HR: 0.84 [0.25-2.10]; P = 0.74). CONCLUSION: In conclusion, patients with nonischemic cardiomyopathy who improved their LVEF to >35% after primary prevention ICD implantation were at very low absolute arrhythmic risk. Our study raises the possibility that the LVEF cutoff to safely withhold ICD replacement might be higher in patients with ischemic compared to nonischemic cardiomyopathy. This will need to be confirmed in prospective studies.

Real-life experience with a new anticoagulation regimen for patients undergoing left-sided ablation procedures.

BACKGROUND: Current guidelines for anticoagulation during left-sided procedures recommend the administration of unfractionated heparin (UFH) with an initial bolus of 50-100 U/kg, followed by continuous infusion to maintain an activated clotting time (ACT) ≥ 300 s. Our objective was to compare the effectiveness of this standard regimen (100 U/kg bolus) to a more aggressive approach (200 U/kg bolus). METHODS: We collected data on a series of consecutive patients undergoing left sided ablation procedures. Patients with an INR ≥2.0 on the day of the procedure were excluded. Procedural anticoagulation was performed using one of two UFH regimens: 1) 100 U/kg bolus, followed by 10 U/kg/hour infusion or 2) 200 U/kg bolus, followed by 20 U/kg/hour infusion. ACT was measured 10 min after the second bolus and then controlled every 20 min. Heparin was titrated throughout the procedure to maintain an ACT 300-400 s. RESULTS: 145 consecutive patients were included in the study: 34 received an initial bolus of 100 U/kg and 111 received 200 U/kg. The mean time required to reach an ACT ≥300 s was 15.25 min (95% CI 12.97-17.03) in the 200 U/kg group and 51.23 min (95% CI 40.65-61.81) in the 100 U/kg group (p < 0.001). There was no difference between groups with regard to thromboembolic or hemorrhagic complications. CONCLUSION: Current anticoagulation guidelines for left-sided ablation procedures almost universally fail to achieve an initial ACT ≥300 s. A 200 U/kg heparin bolus is much more effective to promptly reach the target ACT, with a low rate of overshoot.

Recurrence of new-onset post-operative AF after cardiac surgery: detected by implantable loop recorders: A systematic review and Meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is one of the most common complications after cardiac surgery. New-onset post-operative AF may signal an elevated risk of AF and associated outcomes in long-term follow-up. We aimed to estimate the rate of AF recurrence as detected by an implantable loop recorder (ILR) in patients experiencing post-operative AF within 30 days after cardiac surgery. METHODS: We searched MEDLINE, Embase and Cochrane CENTRAL to April 2023 for studies of adults who did not have known AF, experienced new-onset AF within 30 days of cardiac surgery and received an ILR. We pooled individual participant data on timing of AF recurrence using a random-effects model with a frailty model applied to a Cox proportional hazard analysis. RESULTS: From 8671 citations, 8 single-centre prospective cohort studies met eligibility criteria. Data were available from 185 participants in 7 studies, with a median follow-up of 1.7 (IQR: 1.3-2.8) years. All included studies were at a low risk of bias. Pooled AF recurrence rates following 30 post-operative days were 17.8% (95% CI 11.9%-23.2%) at 3 months, 24.4% (17.7%-30.6%) at 6 months, 30.1% (22.8%-36.7%) at 12 months and 35.3% (27.6%-42.2%) at 18 months. CONCLUSIONS: In patients who experience new-onset post-operative AF after cardiac surgery, AF recurrence lasting at least 30 s occurs in approximately 1 in 3 in the first year after surgery. The optimal frequency and modality to use for monitoring for AF recurrence in this population remain uncertain.

Clinical predictors of Fidelis lead failure: report from the Canadian Heart Rhythm Society Device Committee.

BACKGROUND: Approximately 268,000 Fidelis leads were implanted worldwide until distribution was suspended because of a high rate of early failure. Careful analyses of predictors of increased lead failure hazard are required to help direct future lead design and also to inform decision making on lead replacement. We sought to perform a comprehensive analysis of all potential predictors in a multicenter study. METHODS AND RESULTS: A total of 3169 Sprint Fidelis leads were implanted in 11 centers with a total of 251 failures. Lead failure rates at 3, 4, and 5 years were 5.3%, 10.6%, and 16.8%, respectively. The rate of lead failure continues to accelerate (P<0.001). There were 4 independent predictors of failure: center, sex, access vein, and previous lead failure. Women had a higher hazard of failure (hazard ratio 1.51; 95% confidence interval, 1.14-2.04; P=0.005). Both axillary and subclavian access increased the hazard of failure (P=0.007); hazard ratio for axillary was 1.94, (95% confidence interval, 1.23-3.04) and for subclavian 1.63 (95% confidence interval, 1.08-2.46). Previous lead failure increased the hazard of a subsequent Fidelis failure with a hazard ratio of 3.12 (95% confidence interval, 1.80-5.41; P<0.001). CONCLUSIONS: The rate of Fidelis failure continues to increase over time, with failures approaching 17% at 5 years. Women, patients with leads inserted via the subclavian or axillary vein, and those with a previous lead fracture were at greatest risk of Fidelis failure. Our data suggest that Fidelis replacement should be strongly considered at the time of generator replacement.

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.

Complications associated with revision of Sprint Fidelis leads: report from the Canadian Heart Rhythm Society Device Advisory Committee.

BACKGROUND: It has been observed that replacement of an implantable cardioverter-defibrillator generator in response to a device advisory may be associated with a substantial rate of complications, including death. The risk of lead revision in response to a lead advisory has not been determined previously. METHODS AND RESULTS: Twenty-five implantable cardioverter-defibrillator implantation and follow-up centers from the Canadian Heart Rhythm Society Device Advisory Committee were surveyed to assess complication rates as a result of lead revisions due to the Sprint Fidelis advisory issued in October 2007. As of June 1, 2009, there had been 310 lead failures found in 6237 Sprint Fidelis leads in Canada (4.97%) over a follow-up of 40 months. There were 469 leads to be revised, 66% for confirmed fracture. Of the patients who underwent revision, 95% had a new lead inserted, whereas 4% had a pace/sense lead added. The lead was removed in 248 cases (53%), by simple traction in 61% and by laser lead extraction in 33%. Complications were encountered in 14.5% of the lead revisions; 7.25% of these were major, whereas 7.25% were minor. There were 2 deaths (0.43%). The overall risk of complications (19.8%) was greater in those who underwent lead removal at the time of revision than in those whose leads were abandoned (8.6%; P=0.0008). CONCLUSIONS: The overall rate of major complications that arose from lead revision due to the Sprint Fidelis advisory was significant. This must be taken into account when lead revision is planned in those patients who have not yet demonstrated an abnormality in lead performance.

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.

Non-fluoroscopic catheter ablation of arrhythmias with origin at the summit of the left ventricle.

BACKGROUND: Catheter ablation of ventricular arrhythmias (VAs) arising from the left ventricular Summit (LVS) is challenging and requires high-dose fluoroscopy to limit vascular damage of the coronary arteries. Ionizing radiation can increase the incidence of malignancies to both patient and operator. This study describes outcomes of catheter ablation of LVS VAs using intracardiac echo-facilitated 3D electroanatomical mapping (ICE-3D) to avoid fluoroscopy. METHODS: Twenty-six patients (47 ± 17 years old; 52% males; median ejection fraction 55 ± 13%) with premature ventricular contractions or ventricular tachycardia underwent catheter ablation. VAs were localized using ICE-3D with arrhythmia foci being mapped at the LVS. Focal ablation was performed using a 3.5-mm open-irrigated, contact force sensing radiofrequency catheter. RESULTS: Acute success and recurrence rates were 84% and 24%, respectively. Holter burden was significantly reduced (24 ± 15% to 1.5 ± 2%; P = 0.01) after ablation. The use of zero fluoroscopy was achieved in 100% of cases. No major complications were observed. CONCLUSIONS: Zero fluoroscopy catheter ablation of LVS VAs using ICE-3D mapping is feasible and effective.

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).

Challenge and Impact of Quinidine Access in Sudden Death Syndromes: A National Experience.

OBJECTIVES: This study sought to determine the nature of quinidine use and accessibility in a national network of inherited arrhythmia clinics. BACKGROUND: Quinidine is an antiarrhythmic medication that has been shown to be beneficial in select patients with Brugada syndrome, early repolarization syndrome, and idiopathic ventricular fibrillation. Because of the low prevalence of these conditions and restricted access to quinidine through a single regulatory process, quinidine use is rare in Canada. METHODS: Subjects prescribed quinidine were identified through the Hearts in Rhythm Organization that connects the network of inherited arrhythmia clinics across Canada. Cases were retrospectively reviewed for patient characteristics, indications for quinidine use, rate of recurrent ventricular arrhythmia, and issues with quinidine accessibility. RESULTS: In a population of 36 million, 46 patients are currently prescribed quinidine (0.0000013%, age 48.1 ± 16.1 years, 25 are male). Brugada syndrome, early repolarization syndrome, and idiopathic ventricular fibrillation constituted a diagnosis in 13 subjects (28%), 6 (13%), and 21 (46%), respectively. Overall, 37 subjects (81%) had cardiac arrest as an index event. After initial presentation, subjects experienced 7.47 ± 12.3 implantable cardioverter-defibrillator shocks prior to quinidine use over 34.3 ± 45.9 months, versus 0.86 ± 1.69 implantable cardioverter-defibrillator shocks in 43.8 ± 41.8 months while on quinidine (risk ratio: 8.7, p < 0.001). Twenty-two patients access quinidine through routes external to Health Canada's Special Access Program. CONCLUSIONS: Quinidine use is rare in Canada, but it is associated with a reduction in recurrent ventricular arrhythmias in patients with Brugada syndrome, early repolarization syndrome, and idiopathic ventricular fibrillation, with minimal toxicity necessitating discontinuation. Drug interruption is associated with frequent breakthrough events. Access to quinidine is important to deliver this potentially lifesaving therapy.