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.

Association Between Concurrent Use of Amiodarone and DOACs and Risk of Bleeding in Patients With Atrial Fibrillation.

Amiodarone is a commonly used pharmacotherapy in patients with atrial fibrillation (AF), with a potential for drug-drug interactions with direct oral anticoagulants (DOACs). We aimed to assess the bleeding risk after co-prescription of amiodarone and DOACs among adults with AF. We conducted a population-based, nested case-control study in Ontario, Canada. The study population included all patients with AF aged >66 years on a DOAC between April 1, 2011 and March 31, 2018. Cases were patients admitted with major bleeding (index date). Controls were matched in a 2:1 ratio to cases. We categorized exposure to amiodarone before the index date as: (1) current users (amiodarone within 60 days), (2) past users (amiodarone within 61 to 140 days), and (3) unexposed (no amiodarone prescription or amiodarone prescription >140 days before index date). Conditional logistic regression models were used to examine the association between bleeding and amiodarone co-prescription. Among 86,679 patients with AF on a DOAC, we identified 2,766 cases (3.2%) admitted with major bleeding. The median age of patients with AF was 80 years (interquartile range 75 to 85); 48.3% were women. After multivariable adjustment, there was a significant association between major bleeding and current use of amiodarone (adjusted odds ratio 1.53; 95% confidence interval 1.24 to 1.89, p <0.001) but no significant association between major bleeding and past use of amiodarone (adjusted odds ratio 1.13, 95% confidence interval 0.76 to 1.68, p = 0.545) compared with the unexposed group. In conclusion, among older patients with AF on a DOAC, there was 53% increased odds of major bleeding with the current use of amiodarone.

Perioperative Safety and Early Patient and Device Outcomes Among Subcutaneous Versus Transvenous Implantable Cardioverter Defibrillator Implantations : A Randomized, Multicenter Trial.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) improve survival in patients at risk for cardiac arrest, but are associated with intravascular lead-related complications. The subcutaneous ICD (S-ICD), with no intravascular components, was developed to minimize lead-related complications. OBJECTIVE: To assess key ICD performance measures related to delivery of ICD therapy, including inappropriate ICD shocks (delivered in absence of life-threatening arrhythmia) and failed ICD shocks (which did not terminate ventricular arrhythmia). DESIGN: Randomized, multicenter trial. (ClinicalTrials.gov: NCT02881255). SETTING: The ATLAS trial. PATIENTS: 544 eligible patients (141 female) with a primary or secondary prevention indication for an ICD who were younger than age 60 years, had a cardiogenetic phenotype, or had prespecified risk factors for lead complications were electrocardiographically screened and 503 randomly assigned to S-ICD (251 patients) or transvenous ICD (TV-ICD) (252 patients). Mean follow-up was 2.5 years (SD, 1.1). Mean age was 49.0 years (SD, 11.5). MEASUREMENTS: The primary outcome was perioperative major lead-related complications. RESULTS: There was a statistically significant reduction in perioperative, lead-related complications, which occurred in 1 patient (0.4%) with an S-ICD and in 12 patients (4.8%) with TV-ICD (-4.4%; 95% CI, -6.9 to -1.9; P = 0.001). There was a trend for more inappropriate shocks with the S-ICD (hazard ratio [HR], 2.37; 95% CI, 0.98 to 5.77), but no increase in failed appropriate ICD shocks (HR, 0.61 (0.15 to 2.57). Patients in the S-ICD group had more ICD site pain, measured on a 10-point numeric rating scale, on the day of implant (4.2 ± 2.8 vs. 2.9 ± 2.2; P < 0.001) and 1 month later (1.3 ± 1.8 vs. 0.9 ± 1.5; P = 0.035). LIMITATION: At present, the ATLAS trial is underpowered to detect differences in clinical shock outcomes; however, extended follow-up is ongoing. CONCLUSION: The S-ICD reduces perioperative, lead-related complications without significantly compromising the effectiveness of ICD shocks, but with more early postoperative pain and a trend for more inappropriate shocks. PRIMARY FUNDING SOURCE: Boston Scientific.

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.

Intra-His bundle block with Wenckebach phenomenon.

A 66-year-old lady presented with shortness of breath and a Wenckebach atrioventricular (AV) conduction pattern on the ECG. The electrophysiologic study showed split-His potentials and intra-Hisian Wenckebach. The case highlights the interesting finding of Wenckebach conduction in the His bundle.

Association of Cardiology Billing Amounts With Health Care Utilization and Clinical Outcomes in Patients With Atrial Fibrillation.

Background The relationship between health care utilization and outcomes in patients with atrial fibrillation is unknown. The objective of this study was to investigate whether cardiologists' billing amounts in a fee-for-service environment are associated with better patient-level clinical outcomes. Methods and Results A retrospective cohort study was conducted using administrative claims data of cardiologists in Ontario, Canada between April 1, 2011 and March 31, 2016. The cardiologists were stratified into quintiles based on their median billing patterns per patient over the observation period. The primary outcomes were patient-level receipt of repeat visits, cardiac diagnostic tests, and medications ≤1 year of index date. The secondary clinical outcomes were death, emergency department visits, and all-cause hospitalization 1-year post-index visit. The patient cohort comprised 182 572 patients with atrial fibrillation (median age 74 years, 58% male) from 467 cardiologists. Patients with atrial fibrillation seen by higher-billing cardiologists were 26% more likely to have an echocardiogram (adjusted odds ratio [aOR], 1.26 [95% CI, 1.10-1.43] for quintile 5 versus 2), 28% a stress test (aOR, 1.28 [1.12-1.46] for quintile 5 versus 2), 25% continuous electrocardiographic monitoring (aOR, 1.25 [1.08-1.46] for quintile 4 versus 2), and 79% more likely to get a stress echocardiogram (aOR, 1.79 [1.32-2.42] for quintile 5 versus 2). They also had a higher rate of all-cause hospitalization (aOR, 1.13 [1.07-1.20]). Mortality rates were similar across cardiologists billing quintiles (eg, aOR, 0.98 [0.87-1.11] for quintile 4 versus 2). Conclusions Higher-billing cardiologists ordered more diagnostic tests per patient with atrial fibrillation but these are not associated with improvements in outcomes.

Age-Related Changes in the Anatomy of the Triangle of Koch: Implications for Catheter Ablation of Atrioventricular Nodal Re-entry Tachycardia.

BACKGROUND: Atrioventricular nodal re-entrant tachycardia is the most common type of paroxysmal supraventricular tachycardia. We sought to assess whether important anatomic factors, such as the location of the slow pathway, proximity to the bundle of His, and coronary sinus ostium dimensions, varied with patient age, and whether these factors had an impact on procedural duration, acute success, and complications. METHODS: Baseline demographic and procedural data were collected, and the maps were analyzed. Linear regression models were performed to evaluate the associations between age and these anatomic variations. Associations were also assessed, with age categorized as being ≥ 60 years or < 60 years. RESULTS: The slow pathway was more commonly located in a superior location relative to the coronary sinus ostium in older patients. The location of the slow pathway moved in a superior direction by 1 mm for every increase in 2 years from the mean estimate of age. Additionally the slow pathway tended to be closer to the coronary sinus ostium in older patients, and the diameter of the ostium was larger in older patients. This resulted in longer procedure time, longer ablation times, and a greater need for long sheaths for stability. CONCLUSIONS: The location of the slow pathway becomes more superior and closer to the coronary sinus ostium with increasing age. Additionally, the coronary sinus diameter increases with age. These factors result in longer ablation and procedural times in older patients.

CONTEXTE: La tachycardie par réentrée nodale auriculoventriculaire est le type le plus fréquent de tachycardie supraventriculaire paroxystique. Nous avons voulu évaluer si des facteurs anatomiques importants, tels que l'emplacement de la voie lente, la proximité du faisceau de His et les dimensions de l'orifice du sinus coronaire (ostium), variaient avec l'âge, et si ces facteurs avaient un effet sur la durée de l'intervention, le succès à court terme et les complications. MÉTHODOLOGIE: Des données sur les caractéristiques démographiques initiales et l'intervention ont été recueillies, et les cartes obtenues ont été analysées. Des modèles de régression linéaire ont servi à déterminer les corrélations entre l'âge et ces variations anatomiques. Les corrélations ont aussi été évaluées selon des catégories d'âge, soit ≥ 60 ans et < 60 ans. RÉSULTATS: La voie lente a été repérée plus souvent dans un emplacement supérieur par rapport à l'orifice du sinus coronaire chez les patients plus âgés. L'emplacement de la voie lente s'était déplacé de 1 mm vers le haut pour chaque augmentation de 2 ans de l'estimation moyenne de l'âge. Par ailleurs, chez les patients plus âgés, la voie lente était généralement plus proche de l'orifice du sinus coronaire et le diamètre de l'orifice était élargi. Ces variations se sont traduites par une augmentation du temps d'intervention et d'ablation et par un besoin accru de longues gaines pour la stabilité. CONCLUSIONS: L'emplacement de la voie lente devient plus éloigné vers le haut et plus proche de l'orifice du sinus coronaire avec le vieillissement. De plus, le diamètre du sinus coronaire augmente avec l'âge. Ces facteurs entraînent des temps d'ablation et d'intervention plus longs chez les patients plus âgés.

Canadian national electrophysiology ablation registry report 2011-2016.

BACKGROUND/PURPOSE: Interventional cardiac electrophysiology (EP) is a rapidly evolving field in Canada; a nationwide registry was established in 2011 to conduct a periodic review of resource allocation. METHODS: The registry collects annual data on EP lab infrastructure, imaging, tools, human resources, procedural volumes, success rates, and wait times. Leading physicians from each EP lab were contacted electronically; participation was voluntary. RESULTS: All Canadian EP centres were identified (n = 30); 50 and 45 % of active centres participated in the last 2 instalments of the registry. A mean of 508 ± 270 standard and complex catheter ablation procedures were reported annually for 2015-2016 by all responding centres. The most frequently performed ablation targets atrial fibrillation (PVI) arrhythmia accounting for 36 % of all procedures (mean = 164 ± 85). The number of full time physicians ranges between 1 and 7 per centre, (mean = 4). The mean wait time to see an electrophysiologist for an initial non-urgent consult is 23 weeks. The wait time between an EP consult and ablation date is 17.8 weeks for simple ablation, and 30.1 weeks for AF ablation. On average centres have 2 (range: 1-4) rooms equipped for ablations; each centre uses the EP lab an average of 7 shifts per week. While diagnostic studies and radiofrequency ablations are performed in all centres, point-by-point cryoablation is available in 85 % centres; 38 % of the respondents use circular ablation techniques. CONCLUSIONS: This initiative provides contemporary data on invasive electrophysiology lab practices. The EP registry provides activity benchmarks on national trends and practices.

Assessment of Radiation-Induced Malfunction in Cardiac Implantable Electronic Devices.

BACKGROUND: Radiation therapy (RT) is a standard cancer treatment modality, and an increasing number of patients with cardiac implantable electronic devices (CIEDs) are being referred for RT. The goals of this study were as follows: (i) to determine the incidence of CIED malfunction following RT; (ii) to characterize the various types of malfunctions that occur; and (iii) to identify risk factors associated with CIED malfunction following RT. METHODS: A retrospective study of patients with CIEDs who received RT between 2007 and 2018 at 4 Canadian centres (Sunnybrook Health Sciences Centre, Kingston General Hospital, Hamilton Health Sciences Centre, and University of Ottawa Heart Institute) was conducted. Patients underwent CIED interrogation after completion of RT, to assess for late damage to the CIEDs. Data on demographics, devices, and RT were compared for the primary outcome of device malfunction. RESULTS: Of 1041 patients with CIEDs who received RT, 811 patients with complete data were included. Device malfunctions occurred in 32 of 811 patients (4%). The most common device malfunctions were reduced ventricular/atrial sensing (in 13 of 32 [41%]), an increase in lead threshold (in 9 of 32 [22%]), lead noise (in 5 of 32 [16%]), and electrical reset (in 2 of 32 [6%]). Higher beam energy (≥ 10 MV) was associated with malfunction (P < 0.0001). Radiation dose was not significantly different between the malfunction and non-malfunction groups (58.3 cGy vs 65 cGy, respectively, P = 0.71). CONCLUSIONS: Although RT-induced CIED malfunctions are rare (occurring in 4% of patients with a CIED who undergo RT), collaborative efforts between radiation oncologists and cardiac rhythm device clinics to optimize CIED monitoring are needed, to detect and manage CIED malfunctions. Malfunctions are more common in patients receiving higher-beam energy ( ≥ 10 MV ) RT.

CONTEXTE: La radiothérapie (RT) est une modalité standard de traitement du cancer, et un nombre croissant de patients porteurs de dispositifs cardiaques électroniques implantables (DCEI) doivent recevoir un traitement de RT. Les objectifs de cette étude étaient les suivants : (i) déterminer l'incidence d'une défaillance du DCEI après une RT; (ii) caractériser les différents types de défaillances qui se produisent; (iii) déterminer les facteurs de risque associés à la défaillance du DCEI après une RT. MÉTHODOLOGIE: Une étude rétrospective des patients avec un DCEI ayant reçu une RT entre 2007 et 2018 dans quatre centres canadiens (Sunnybrook Health Sciences Centre, Kingston General Hospital, Hamilton Health Sciences Centre et Institut de cardiologie de l'Université d'Ottawa) a été menée. Le DCEI des patients a été interrogé après la fin de la RT, pour en évaluer les dommages tardifs. Les données sur les caractéristiques démographiques, les dispositifs et la RT ont été comparées pour le paramètre d'évaluation principal, soit la défaillance du dispositif. RÉSULTATS: Sur les 1 041 patients avec un DCEI ayant reçu une RT, 811 patients avec des données complètes ont été inclus. Des défaillances du dispositif sont survenues chez 32 des 811 patients (4 %). Les défaillances les plus fréquentes du dispositif étaient une détection ventriculaire/atriale réduite (chez 13 des 32 patients [41 %]), une augmentation du seuil de la sonde (chez 9 des 32 patients [22 %]), un bruit provenant de la sonde (chez 5 des 32 patients [16 %]) et une réinitialisation électrique (chez 2 des 32 patients [6 %]). Une énergie de faisceau plus élevée (≥ 10 MV) était associée à une défaillance (p < 0,0001). La dose de rayonnement ne présentait pas de différence significative entre le groupe où une défaillance a été constatée et l'autre groupe (58,3 cGy vs 65 cGy, respectivement, p = 0,71). CONCLUSIONS: Bien que les défaillances du DCEI causées par la RT soient rares (survenant chez 4 % des patients avec un DCEI qui subissent une RT), une collaboration est nécessaire entre les radio-oncologues et les cliniques de dispositifs de gestion du rythme cardiaque, afin d'optimiser la surveillance du DCEI et de détecter et de gérer ces défaillances. Les défaillances sont plus fréquentes chez les patients recevant une énergie de faisceau plus élevée au moment de la RT ( ≥ 10 MV ) .

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.

Differences in Healthcare Use Between Patients With Persistent and Paroxysmal Atrial Fibrillation Undergoing Catheter-Based Atrial Fibrillation Ablation: A Population-Based Cohort Study From Ontario, Canada.

Background Patients with persistent atrial fibrillation (AF) undergoing catheter-based AF ablation have lower success rates than those with paroxysmal AF. We compared healthcare use and clinical outcomes between patients according to their AF subtypes. Methods and Results Consecutive patients undergoing AF ablation were prospectively identified from a population-based registry in Ontario, Canada. Via linkage with administrative databases, we performed a retrospective analysis comparing the following outcomes between patients with persistent and paroxysmal AF: healthcare use (defined as AF-related hospitalizations/emergency room visits), periprocedural complications, and mortality. Multivariable Poisson modeling was performed to compare the rates of AF-related and all-cause hospitalizations/emergency room visits in the year before versus after ablation. Between April 2012 and March 2016, there were 3768 consecutive patients who underwent first-time AF ablation, of whom 1040 (27.6%) had persistent AF. The mean follow-up was 1329 days. Patients with persistent AF had higher risk of AF-related hospitalization/emergency room visits (hazard ratio [HR], 1.21; 95% CI, 1.09-1.34), mortality (HR, 1.74; 95% CI, 1.15-2.63), and periprocedural complications (odds ratio, 1.36; 95% CI, 1.02-1.75) than those with paroxysmal AF. In the overall cohort, there was a 48% reduction in the rate of AF-related hospitalization/emergency room visits in the year after versus before ablation (rate ratio [RR], 0.52; 95% CI, 0.48-0.56). This reduction was observed for patients with paroxysmal (RR, 0.45; 95% CI, 0.41-0.50) and persistent (RR, 0.74; 95% CI, 0.63-0.87) AF. Conclusions Although patients with persistent AF had higher risk of adverse outcomes than those with paroxysmal AF, ablation was associated with a favorable reduction in downstream AF-related healthcare use, irrespective of AF type.

Microvolt QRS Alternans Without Microvolt T-Wave Alternans in Human Cardiomyopathy: A Novel Risk Marker of Late Ventricular Arrhythmias.

Background Action potential alternans can induce ventricular tachyarrhythmias and manifest on the surface ECG as T-wave alternans (TWA) and QRS alternans (QRSA). We sought to evaluate microvolt QRSA in cardiomyopathy patients in relation to TWA and ventricular tachyarrhythmia outcomes. Methods and Results Prospectively enrolled cardiomyopathy patients (n=100) with prophylactic defibrillators had 12-lead ECGs recorded during ventricular pacing from 100 to 120 beats/min. QRSA and TWA were quantified in moving 128-beat segments using the spectral method. Segments were categorized as QRSA positive (QRSA+) and/or TWA positive (TWA+) based on ≥2 precordial leads having alternans magnitude >0 and signal:noise >3. Patients were similarly categorized based on having ≥3 consecutive segments with alternans. TWA+ and QRSA+ occurred together in 31% of patients and alone in 18% and 14% of patients, respectively. Although TWA magnitude (1.4±0.4 versus 4.7±1.0 µV, P<0.01) and proportion of TWA+ studies (16% versus 46%, P<0.01) increased with rate, QRSA did not change. QRS duration was longer in QRSA+ than QRSA-negative patients (138±23 versus 113±26 ms, P<0.01). At 3.5 years follow-up, appropriate defibrillator therapy or sustained ventricular tachyarrhythmia was greater in QRSA+ than QRSA-negative patients (30% versus 8%, P=0.02) but similar in TWA+ and TWA-negative patients. Among QRSA+ patients, the event rate was greater in those without TWA (62% versus 21%, P=0.02). Multivariable Cox analysis revealed QRSA+ (hazard ratio [HR], 4.6; 95% CI, 1.5-14; P=0.009) and QRS duration >120 ms (HR, 4.1; 95% CI, 1.3-12; P=0.014) to predict events. Conclusions Microvolt QRSA is novel phenomenon in cardiomyopathy patients that can exist without TWA and is associated with QRS prolongation. QRSA increases the risk of ventricular tachyarrhythmia 4-fold, which merits further study as a risk stratifier.

Dual-Antithrombotic Therapy With DOACs After Acute Coronary Syndrome or Percutaneous Coronary Intervention in Atrial Fibrillation: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The choice of antithrombotic therapy for atrial fibrillation (AF) patients who have an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is challenging. We aimed to assess outcomes between dual-antithrombotic therapy with the use of direct-acting oral anticoagulants (DOACs) plus an antiplatelet agent (dual therapy) compared with warfarin plus 2 antiplatelet agents (triple therapy) for AF patients after PCI or with ACS. METHODS: Systematic searches of multiple major databases were performed from their inception through September 2019. We included only randomized controlled trials. Odds ratios (ORs) were pooled with the use of a random-effects model. RESULTS: We identified 4 randomized controlled trials, which included 7168 patients. Compared with triple-antithrombotic therapy with warfarin, dual-antithrombotic therapy with DOACs was associated with a significant reduction in major bleeding (OR 0.56, 95% confidence interval [CI] 0.38-0.82; P = 0.003) as well as major bleeding or clinically relevant nonmajor bleeding (OR 0.53, 95% CI 0.38-0.75; P < 0.001). The rate of composite of death and ischemic events (stroke and myocardial infarction) was not statistically different between groups (OR 1.21, 95% CI 0.99-1.49; P = 0.06). There was no significant difference between groups in the rate of death (OR 1.20, 95% CI 0.95-1.53; P = 0.13). CONCLUSIONS: In patients with AF and recent ACS or PCI, the use of dual-antithrombotic therapy with DOACs was associated with less major bleeding and less major bleeding or clinically relevant nonmajor bleeding compared with triple therapy. The use of dual therapy also showed nonsignificantly higher composite of death and ischemic events but no difference in mortality.

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.

Quantification of abnormal QRS peaks predicts response to cardiac resynchronization therapy and tracks structural remodeling.

BACKGROUND: Although QRS duration (QRSd) is an important determinant of cardiac resynchronization therapy (CRT) response, non-responder rates remain high. QRS fragmentation can also reflect electrical dyssynchrony. We hypothesized that quantification of abnormal QRS peaks (QRSp) would predict CRT response. METHODS: Forty-seven CRT patients (left ventricular ejection fraction = 23±7%) were prospectively studied. Digital 12-lead ECGs were recorded during native rhythm at baseline and 6 months post-CRT. For each precordial lead, QRSp was defined as the total number of peaks detected on the unfiltered QRS minus those detected on a smoothed moving average template QRS. CRT response was defined as >5% increase in left ventricular ejection fraction post-CRT. RESULTS: Sixty-percent of patients responded to CRT. Baseline QRSd was similar in CRT responders and non-responders, and did not change post-CRT regardless of response. Baseline QRSp was greater in responders than non-responders (9.1±3.5 vs. 5.9±2.2, p = 0.001) and decreased in responders (9.2±3.6 vs. 7.9±2.8, p = 0.03) but increased in non-responders (5.5±2.3 vs. 7.5±2.8, p = 0.049) post-CRT. In multivariable analysis, QRSp was the only independent predictor of CRT response (Odds Ratio [95% Confidence Interval]: 1.5 [1.1-2.1], p = 0.01). ROC analysis revealed QRSp (area under curve = 0.80) to better discriminate response than QRSd (area under curve = 0.67). Compared to QRSd ≥150ms, QRSp ≥7 identified response with similar sensitivity but greater specificity (74 vs. 32%, p<0.05). Amongst patients with QRSd <150ms, more patients with QRSp ≥7 responded than those with QRSp <7 (75 vs. 0%, p<0.05). CONCLUSIONS: Our novel automated QRSp metric independently predicts CRT response and decreases in responders. Electrical dyssynchrony assessed by QRSp may improve CRT selection and track structural remodeling, especially in those with QRSd <150ms.

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).

Identifying Factors That Predict the Prescription of Non-vitamin K Antagonist Oral Anticoagulants in Older Individuals With Atrial Fibrillation.

OBJECTIVES: Factors that influence decision of non-vitamin K antagonist oral anticoagulants (NOACs) use among older atrial fibrillation (AF) patients in long-term care (LTC) facilities have not been well studied. The aim of this study was to assess whether increased frailty influenced physicians to prescribe NOACs over warfarin. DESIGN: We retrospectively reviewed the electronic medical record (EMR) and pharmacy data of 25 LTC facilities in Ontario, Canada, in May 2015. The diagnosis of AF was ascertained from EMR and confirmed by complete chart review of a random sample of the cohort. A score of ≥2 on the Changes in Health, End-stage disease, Signs, and Symptoms (CHESS) scale was used as a surrogate marker of frailty. MEASURES: Multivariable logistic regression model was used to assess whether a higher frailty score is associated with the use of NOACs in comparison to warfarin, independent of potential patient-level confounders. SETTING AND PARTICIPANTS: In total, 3378 active residents were assessed in 25 LTC facilities. All the residents were ≥65 years old. We identified 433 residents with AF; 273 (63%) AF residents were on anticoagulation therapy and included in the analysis. RESULTS: Residents were more often treated with NOACs (n = 159; 58%) in comparison to warfarin (n = 114; 42%). A CHESS score of ≥2 increased the odds of prescribing NOACs by 2.46 times [95% confidence interval (CI) 1.11, 5.49; P = .03] when adjusted for important patient-level factors. Patients with hypertension had a trend of increased NOAC prescriptions but did not reach statistical significance [odds ratio 2.1 (95% CI 0.91, 4.81), P = .08]. None of the patient-level factors were associated with NOAC prescriptions. CONCLUSIONS AND IMPLICATIONS: In this real world cohort of AF patients in LTC who are prescribed an oral anticoagulation therapy, a higher CHESS score (≥2) is associated with increased use of NOACs in comparison to warfarin.