Comparative Effectiveness of Left Atrial Appendage Occlusion Versus Oral Anticoagulation by Sex.

BACKGROUND: The comparative real-world outcomes of older patients with atrial fibrillation (AF) treated with anticoagulation compared with left atrial appendage occlusion (LAAO) may be different from those in clinical trials because of differences in anticoagulation strategies and patient demographics, including a greater proportion of women. We sought to compare real-world outcomes between older patients with AF treated with anticoagulation and those treated with LAAO by sex. METHODS: Using Medicare claims data from 2015 to 2019, we identified LAAO-eligible beneficiaries and divided them into sex subgroups. Patients receiving LAAO were matched 1:1 to those receiving anticoagulation alone through propensity score matching. The risks of mortality, stroke or systemic embolism, and bleeding were compared between matched groups with adjustment for potential confounding characteristics in Cox proportional hazards models. RESULTS: Among women, 4085 LAAO recipients were matched 1:1 to those receiving anticoagulation; among men, 5378 LAAO recipients were similarly matched. LAAO was associated with a significant reduction in the risk of mortality for women and men (hazard ratio [HR], 0.509 [95% CI, 0.447-0.580]; and HR, 0.541 [95% CI, 0.487-0.601], respectively; P<0.0001), with a similar finding for stroke or systemic embolism (HR, 0.655 [95% CI, 0.555-0.772]; and HR, 0.649 [95% CI, 0.552-0.762], respectively; P<0.0001). Bleeding risk was significantly greater in LAAO recipients early after implantation but lower after the 6-week periprocedural period for women and men (HR, 0.772 [95% CI, 0.676-0.882]; and HR, 0.881 [95% CI, 0.784-0.989], respectively; P<0.05). CONCLUSIONS: In a real-world population of older Medicare beneficiaries with AF, compared with anticoagulation, LAAO was associated with a reduction in the risk of death, stroke, and long-term bleeding among women and men. These findings should be incorporated into shared decision-making with patients considering strategies for reduction in AF-related stroke.

Cardiac Resynchronization Therapy Improves Outcomes in Patients With Intraventricular Conduction Delay But Not Right Bundle Branch Block: A Patient-Level Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Benefit from cardiac resynchronization therapy (CRT) varies by QRS characteristics; individual randomized trials are underpowered to assess benefit for relatively small subgroups. METHODS: The authors analyzed patient-level data from pivotal CRT trials (MIRACLE [Multicenter InSync Randomized Clinical Evaluation], MIRACLE-ICD [Multicenter InSync ICD Randomized Clinical Evaluation], MIRACLE-ICD II [Multicenter InSync ICD Randomized Clinical Evaluation II], REVERSE [Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction], RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure], BLOCK-HF [Biventricular Versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block], COMPANION [Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure], and MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy]) using Bayesian Hierarchical Weibull survival regression models to assess CRT benefit by QRS morphology (left bundle branch block [LBBB], n=4549; right bundle branch block [RBBB], n=691; and intraventricular conduction delay [IVCD], n=1024) and duration (with 150-ms partition). The continuous relationship between QRS duration and CRT benefit was also examined within subgroups defined by QRS morphology. The primary end point was time to heart failure hospitalization (HFH) or death; a secondary end point was time to all-cause death. RESULTS: Of 6264 patients included, 25% were women, the median age was 66 [interquartile range, 58 to 73] years, and 61% received CRT (with or without an implantable cardioverter defibrillator). CRT was associated with an overall lower risk of HFH or death (hazard ratio [HR], 0.73 [credible interval (CrI), 0.65 to 0.84]), and in subgroups of patients with QRS ≥150 ms and either LBBB (HR, 0.56 [CrI, 0.48 to 0.66]) or IVCD (HR, 0.59 [CrI, 0.39 to 0.89]), but not RBBB (HR 0.97 [CrI, 0.68 to 1.34]; Pinteraction <0.001). No significant association for CRT with HFH or death was observed when QRS was <150 ms (regardless of QRS morphology) or in the presence of RBBB. Similar relationships were observed for all-cause death. CONCLUSIONS: CRT is associated with reduced HFH or death in patients with QRS ≥150 ms and LBBB or IVCD, but not for those with RBBB. Aggregating RBBB and IVCD into a single "non-LBBB" category when selecting patients for CRT should be reconsidered. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT00271154, NCT00251251, NCT00267098, and NCT00180271.

Benefit of cardiac resynchronization therapy among older patients: A patient-level meta-analysis.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces heart failure hospitalizations (HFH) and mortality for guideline-indicated patients with heart failure (HF). Most patients with HF are aged ≥70 years but such patients are often under-represented in randomized trials. METHODS: Patient-level data were combined from 8 randomized trials published 2002-2013 comparing CRT to no CRT (n = 6,369). The effect of CRT was estimated using an adjusted Bayesian survival model. Using age as a categorical (<70 vs ≥70 years) or continuous variable, the interaction between age and CRT on the composite end point of HFH or all-cause mortality or all-cause mortality alone was assessed. RESULTS: The median age was 67 years with 2436 (38%) being 70+; 1,554 (24%) were women; 2,586 (41%) had nonischemic cardiomyopathy and median QRS duration was 160 ms. Overall, CRT was associated with a delay in time to the composite end point (adjusted hazard ratio [aHR] 0.75, 95% credible interval [CI] 0.66-0.85, P = .002) and all-cause mortality alone (aHR of 0.80, 95% CI 0.69-0.96, P = .017). When age was treated as a categorical variable, there was no interaction between age and the effect of CRT for either end point (P > .1). When age was treated as a continuous variable, older patients appeared to obtain greater benefit with CRT for the composite end point (P for interaction = .027) with a similar but nonsignificant trend for mortality (P for interaction = .35). CONCLUSION: Reductions in HFH and mortality with CRT are as great or greater in appropriately indicated older patients. Age should not be a limiting factor for the provision of CRT.

Arrhythmias in Female Patients: Incidence, Presentation and Management.

There is a growing appreciation for differences in epidemiology, treatment, and outcomes of cardiovascular conditions by sex. Historically, cardiovascular clinical trials have under-represented females, but findings have nonetheless been applied to clinical care in a sex-agnostic manner. Thus, much of the collective knowledge about sex-specific cardiovascular outcomes result from post hoc and secondary analyses. In some cases, these investigations have revealed important sex-based differences with implications for optimizing care for female patients with arrhythmias. This review explores the available evidence related to cardiac arrhythmia care among females, with emphasis on areas in which important sex differences are known or suggested. Considerations related to improving female enrollment in clinical trials as a way to establish more robust clinical evidence for the treatment of females are discussed. Areas of remaining evidence gaps are provided, and recommendations for areas of future research and specific action items are suggested. The overarching goal is to improve appreciation for sex-based differences in cardiac arrhythmia care as 1 component of a comprehensive plan to optimize arrhythmia care for all patients.

Atrial Fibrillation.

Evidence for diagnosis and treatment of atrial fibrillation (AF) has expanded substantially since 2017, when In the Clinic last considered this subject. Direct oral anticoagulants have become the predominant therapy for thromboembolic disease, and antidotes for these drugs are now available. Device-based left atrial appendage occlusion is frequently used in patients who cannot tolerate systemic anticoagulation, and growing evidence suggests that early rhythm control improves outcomes. Catheter ablation is now frequently performed to prevent recurrent AF. Managing risk factors for AF, such as hypertension, diabetes, and obesity, remains paramount in prevention of this condition.

Facilitating Shared Decision Making Among Black Patients at Risk for Sudden Cardiac Arrest : A Randomized Clinical Trial.

BACKGROUND: Racial disparities in implantable cardioverter-defibrillator (ICD) implantation are multifactorial and are partly explained by higher refusal rates. OBJECTIVE: To assess the effectiveness of a video decision support tool for Black patients eligible for an ICD. DESIGN: Multicenter, randomized clinical trial conducted between September 2016 and April 2020. (ClinicalTrials.gov: NCT02819973). SETTING: Fourteen academic and community-based electrophysiology clinics in the United States. PARTICIPANTS: Black adults with heart failure who were eligible for a primary prevention ICD. INTERVENTION: An encounter-based video decision support tool or usual care. MEASUREMENTS: The primary outcome was the decision regarding ICD implantation. Additional outcomes included patient knowledge, decisional conflict, ICD implantation within 90 days, the effect of racial concordance on outcomes, and the time patients spent with clinicians. RESULTS: Of the 330 randomly assigned patients, 311 contributed data for the primary outcome. Among those randomly assigned to the video group, assent to ICD implantation was 58.6% compared with 59.4% in the usual care group (difference, -0.8 percentage point [95% CI, -13.2 to 11.1 percentage points]). Compared with usual care, participants in the video group had a higher mean knowledge score (difference, 0.7 [CI, 0.2 to 1.1]) and a similar decisional conflict score (difference, -2.6 [CI, -5.7 to 0.4]). The ICD implantation rate within 90 days was 65.7%, with no differences by intervention. Participants randomly assigned to the video group spent less time with their clinician than those in the usual care group (mean, 22.1 vs. 27.0 minutes; difference, -4.9 minutes [CI, -9.4 to -0.3 minutes]). Racial concordance between video and study participants did not affect study outcomes. LIMITATION: The Centers for Medicare & Medicaid Services implemented a requirement for shared decision making for ICD implantation during the study. CONCLUSION: A video-based decision support tool increased patient knowledge but did not increase assent to ICD implantation. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute.

Research Opportunities in Stroke Prevention for Atrial Fibrillation: A Report From a National Heart, Lung, and Blood Institute Virtual Workshop.

Atrial fibrillation (AF) is one of the strongest risk factors for ischemic stroke, which is a leading cause of disability and death. Given the aging population, increasing prevalence of AF risk factors, and improved survival in those with cardiovascular disease, the number of individuals affected by AF will continue increasing over time. While multiple proven stroke prevention therapies exist, important questions remain about the optimal approach to stroke prevention at the population and individual patient levels. Our report summarizes the National Heart, Lung, and Blood Institute virtual workshop focused on identifying key research opportunities related to stroke prevention in AF. The workshop reviewed major knowledge gaps and identified targeted research opportunities to advance stroke prevention in AF in the following areas: (1) improving risk stratification tools for stroke and intracranial hemorrhage; (2) addressing challenges with oral anticoagulants; and (3) delineating the optimal roles of percutaneous left atrial appendage occlusion and surgical left atrial appendage closure/excision. This report aims to promote innovative, impactful research that will lead to more personalized, effective use of stroke prevention strategies in people with AF.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection History and Antibody Response to 3 Coronavirus Disease 2019 Messenger RNA Vaccine Doses.

BACKGROUND: Data on antibody kinetics are limited among individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From a cohort of healthcare personnel and other frontline workers in 6 US states, we assessed antibody waning after messenger RNA (mRNA) dose 2 and response to dose 3 according to SARS-CoV-2 infection history. METHODS: Participants submitted sera every 3 months, after SARS-CoV-2 infection, and after each mRNA vaccine dose. Sera were tested for antibodies and reported as area under the serial dilution curve (AUC). Changes in AUC values over time were compared using a linear mixed model. RESULTS: Analysis included 388 participants who received dose 3 by November 2021. There were 3 comparison groups: vaccine only with no known prior SARS-CoV-2 infection (n = 224); infection prior to dose 1 (n = 123); and infection after dose 2 and before dose 3 (n = 41). The interval from dose 2 and dose 3 was approximately 8 months. After dose 3, antibody levels rose 2.5-fold (95% confidence interval [CI] = 2.2-3.0) in group 2 and 2.9-fold (95% CI = 2.6-3.3) in group 1. Those infected within 90 days before dose 3 (and median 233 days [interquartile range, 213-246] after dose 2) did not increase significantly after dose 3. CONCLUSIONS: A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection <3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster.

Risk Factors for Reinfection with SARS-CoV-2 Omicron Variant among Previously Infected Frontline Workers.

In a cohort of essential workers in the United States previously infected with SARS-CoV-2, risk factors for reinfection included being unvaccinated, infrequent mask use, time since first infection, and being non-Hispanic Black. Protecting workers from reinfection requires a multipronged approach including up-to-date vaccination, mask use as recommended, and reduction in underlying health disparities.

Heart rate and death and hospitalization for heart failure in patients with persistent or permanent atrial fibrillation: Insights from the ARISTOTLE trial.

Rate control is fundamental in the treatment of patients with atrial fibrillation (AF). The independent association of heart rate with outcomes and range of heart rate associated with best outcomes remains uncertain. We assessed the relationship between heart rate and clinical outcomes in patients with persistent or permanent AF enrolled in the randomized, double-blind ARISTOTLE trial. In patients with persistent or permanent AF, a faster heart rate is associated with a modest, but statistically significant increase in death and heart failure hospitalizations. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00412984).

Pre-existing conditions associated with post-acute sequelae of COVID-19.

Post-acute sequelae of COVID-19 (PASC) are conditions that occur or remain at least 28 days after SARS-CoV-2 infection. While some risk factors for PASC have been identified, little is known about pre-existing conditions that render one susceptible to developing PASC. Data from participants (n = 1224) in a longitudinal COVID-19 cohort study in Arizona were used to investigate comorbid conditions associated with PASC. After adjustment of the models for age, BMI, gender, race, and smoking, the following pre-existing conditions were statistically significantly associated with the development of PASC: asthma (OR = 1.54; 95% CI = 1.10-2.15); chronic constipation (OR = 4.29; 95% CI = 1.15-16.00); reflux (OR = 1.54; 95% CI = 1.01-2.34); rheumatoid arthritis (OR = 3.69; 95%CI = 1.15-11.82); seasonal allergies (OR = 1.56; 95% CI = 1.22-1.98); and depression/anxiety (OR = 1.72; 95% CI = 1.17-2.52). When grouping conditions together, statistically significant associations with PASC were observed for respiratory (OR = 1.47; 95% CI = 1.06-2.14); gastrointestinal (OR = 1.62; 95% CI = 1.16-2.26), and autoimmune conditions (OR = 4.38; 95% CI = 1.59-12.06). After adjustment for severity of acute SARS-CoV-2 infection and depression/anxiety, seasonal allergies (OR = 1.48; 95% CI 1.15-1.91) and autoimmune disease (OR = 3.78; 95% CI - 1.31-10.91) remained significantly associated with risk for PASC. These findings indicate that numerous pre-existing conditions may be associated with an increased risk for the development of PASC. Patients with these conditions should consider taking extra steps to avoid infection.

Association of leadless pacing with ventricular and valvular function.

BACKGROUND: Traditional transvenous pacemakers are associated with worsening tricuspid valve function due to lead-related leaflet impingement, as well as ventricular dysfunction related to electromechanical dyssynchrony from chronic right ventricular (RV) pacing. The association of leadless pacing with ventricular and valvular function has not been well established. We aimed to assess the association of leadless pacemaker placement with changes in valvular regurgitation and ventricular function. METHODS AND RESULTS: Echocardiographic features before and after leadless pacemaker implant were analyzed in consecutive patients who received a leadless pacemaker with pre- and postprocedure echocardiography at Duke University Hospital between November 2014 and November 2019. Valvular regurgitation was graded ordinally from 0 (none) to 3 (severe). Among 54 patients, the mean age was mean age was 70.1 ± 14.3 years, 24 (44%) were women, and the most frequent primary pacing indication was complete heart block in 24 (44%). The median RV pacing burden was 45.4 (interquartile range [IQR] 3.5-97.0). On echocardiogram performed 8.9 months (IQR 4.5-14.5) after implant, there was no change in the average severity of tricuspid regurgitation (mean change 0.07 ± 1.15, p = .64) from pre-procedure echocardiogram. We observed a decrease in the average left ventricular ejection fraction (LVEF) (52.3 ± 9.3 to 47.9 ± 12.1, p = .0019) and tricuspid annular plane systolic excursion (TAPSE) (1.8 ± 0.6 to 1.6 ± 0.4, p = .0437). Thirteen patients (24%) had absolute drop in LVEF of ≥10%. CONCLUSION: We did not observe short term worsening valvular function in patients with leadless pacemakers. However, consistent with the pathophysiologic impact of RV pacing, leadless pacing was associated with a reduction in biventricular function.

Cardiac resynchronization therapy in patients with a prior history of atrial fibrillation: Insights from four major clinical trials.

AIMS: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF). METHODS: Individual-patient-data from four randomized trials investigating CRT-Defibrillators (COMPANION, MADIT-CRT, REVERSE) or CRT-Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all-cause mortality or to all-cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian-Weibull survival regression model adjusting for baseline characteristics. RESULTS: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56-0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55-1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55-0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66-1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70-1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60-0.97). CONCLUSION: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF.

Serum per- and polyfluoroalkyl substance concentrations and longitudinal change in post-infection and post-vaccination SARS-CoV-2 antibodies.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.

Implementing Psychological First Aid for Healthcare Workers During the COVID-19 Pandemic: A Feasibility Study of the ICARE Model.

Maintaining the resilience of healthcare workers (HCWs) during the protracted COVID-19 pandemic is critical as chronic stress is associated with burnout, inability to provide high-quality care, and decreased attentiveness to infection prevention protocols. Between May and July 2020, we implemented the ICARE model of psychological first aid (PFA) in a novel online (i.e., telehealth) format to address the psychological support needs of HCWs during the COVID-19 pandemic. We found that HCWs needed psychological support related to obtaining clear information about pandemic policies and guidelines, navigating new rules and responsibilities, and processing overwhelming and conflicting emotions. The HCWs in our program repeatedly expressed appreciation for the support we provided. Future directions include establishing online discussion forums, increasing opportunities for individual support, and training HCWs to provide peer support using PFA. This program has far-reaching potential benefit to HCWs and to society at large in the context of a pandemic.

Polypharmacy in chronic liver disease patients: Implications for disease severity, drug-drug interaction, and quality of life.

Multiple prescriptions for different medications may be needed for chronic conditions, increasing the risk of polypharmacy. The WHO defined polypharmacy as "the administration of many drugs at the same time or the administration of an excessive number of drugs". The primary goal of this study was to evaluate polypharmacy in patients with chronic liver disease and to identify potential drug-drug interactions associated with it. A cross-sectional study was conducted at a tertiary care hospital in Mangalore, Karnataka, for six months, from November 2020 to April 2021. The study involved 118 patients with chronic liver disease from various age groups. Data was gathered by analyzing patients' medical records kept on the ward and interviewing them individually. In admission and discharge prescriptions, polypharmacy was examined. Online interaction checkers from Drugs.com and Medscape were used to interpret potential drug-drug interactions. The SF-36 and Chronic Liver Disease Questionnaire were used to measure the quality of life. The data obtained were analyzed statistically to determine the significant correlation. The number of prescribed drugs was significantly correlated (P = 0.018) with the severity of liver disease in Child-Pugh categories B and C. Additionally, moderate polypharmacy reduced quality of life (P < 0.05), and the physical health category was significantly associated with disease severity (P < 0.05). Drug-drug interactions were found in 108 out of the 118 examined prescriptions, totaling 586 interactions in the admission list and 405 interactions in the discharge list. If the potentially serious main drug interaction identified in this study is not well monitored, it could lead to a serious, potentially fatal health condition. Despite being advised, safety is not always guaranteed by liver enzyme monitoring. Therefore, healthcare providers must take additional precautions to avoid inappropriate prescribing, minimize side effects, and ensure drug safety.

Research Priorities in Atrial Fibrillation Screening: A Report From a National Heart, Lung, and Blood Institute Virtual Workshop.

Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized that AF frequently is undetected until complications such as stroke or heart failure occur. Hence, the public and clinicians have an intense interest in detecting AF earlier. However, the most appropriate strategies to detect undiagnosed AF (sometimes referred to as subclinical AF) and the prognostic and therapeutic implications of AF detected by screening are uncertain. Our report summarizes the National Heart, Lung, and Blood Institute's virtual workshop focused on identifying key research priorities related to AF screening. Global experts reviewed major knowledge gaps and identified critical research priorities in the following areas: (1) role of opportunistic screening; (2) AF as a risk factor, risk marker, or both; (3) relationship between AF burden detected with long-term monitoring and outcomes/treatments; (4) designs of potential randomized trials of systematic AF screening with clinically relevant outcomes; and (5) role of AF screening after ischemic stroke. Our report aims to inform and catalyze AF screening research that will advance innovative, resource-efficient, and clinically relevant studies in diverse populations to improve the diagnosis, management, and prognosis of patients with undiagnosed AF.

Azithromycin use increases the risk of sudden cardiac death in patients with hemodialysis-dependent kidney failure.

Azithromycin is an antibiotic with QT-prolonging potential commonly prescribed to individuals receiving hemodialysis. Hemodialysis patients have a high prevalence of clinical conditions, such as structural heart disease, that can enhance the pro-arrhythmic effects azithromycin, but were excluded from prior investigations evaluating the cardiac safety of azithromycin. Using data from the United States Renal Data System (2007-2017), we conducted two cohort studies to examine the cardiac safety of azithromycin relative to amoxicillin-based antibiotics (amoxicillin, amoxicillin/clavulanic acid) and levofloxacin (a fluoroquinolone antibiotic known to prolong the QT-interval) in the hemodialysis population. The primary outcome was five-day sudden cardiac death. Using inverse probability of treatment weighted survival models, we estimated hazard ratios, risk differences, and 95% confidence intervals. The azithromycin vs. amoxicillin-based antibiotic cohort included 282,899 patients and 725,431 treatment episodes (381,306 azithromycin and 344,125 amoxicillin-based episodes). Azithromycin vs. amoxicillin-based antibiotic treatment was associated with higher relative and absolute risks of sudden cardiac death, weighted hazard ratio of 1.70 (95% Confidence Interval, 1.36 to 2.11) and weighted risk difference per 100,000 treatment episodes of 25.0 (15.5 to 36.5). The azithromycin vs. levofloxacin cohort included 245,143 patients and 554,557 treatment episodes (387,382 azithromycin and 167,175 levofloxacin episodes). Azithromycin vs. levofloxacin treatment was associated with lower relative and absolute risks of sudden cardiac death, weighted hazard ratio of 0.79 (0.64 to 0.96) and weighted risk difference per 100,000 treatment episodes of -18.9 (-35.5 to -3.8). Thus, when selecting among azithromycin, levofloxacin, and amoxicillin-based antibiotics, clinicians should weigh the relative antimicrobial benefits of these drugs against their potential cardiac risks.

Leadless pacemaker implantation after lead extraction for cardiac implanted electronic device infection.

BACKGROUND: Cardiac implanted electronic device (CIED) pocket and systemic infection remain common complications with traditional CIEDs and are associated with high morbidity and mortality. Leadless pacemakers may be an attractive pacing alternative for many patients following complete hardware removal for a CIED infection by eliminating surgical pocket-related complications as well as lower risk of recurrent complications. OBJECTIVE: To describe use and outcomes associated with leadless pacemaker implantation following extraction of a CIED system due to infection. METHODS: Patient characteristics and postprocedural outcomes were described in patients who underwent leadless pacemaker implantation at Duke University Hospital between November 11, 2014 and November 18, 2019, following CIED infection and device extraction. Outcomes of interest included procedural complications, pacemaker syndrome, need for system revision, and recurrent infection. RESULTS: Among 39 patients, the mean age was 71 ± 17 years, 31% were women, and the most frequent primary pacing indication was complete heart block (64.1%) with 9 (23.1%) patients being pacemaker dependent at the time of Micra implantation. The primary organism implicated in the CIED infection was Staphylococcus aureus (43.6%). Nine of the 39 patients had a leadless pacemaker implanted before or on the same day as their extraction procedure, and the remaining 30 patients had a leadless pacemaker implanted after their extraction procedure. During follow-up (mean 24.8 ± 14.7 months) after leadless pacemaker implantation, there were a total of 3 major complications: 1 groin hematoma, 1 femoral arteriovenous fistula, and 1 case of pacemaker syndrome. No patients had evidence of recurrent CIED infection after leadless pacemaker implantation. CONCLUSIONS: Despite a prior CIED infection and an elevated risk of recurrent infection, there was no evidence of CIED infection with a mean follow up of over 2 years following leadless pacemaker implantation at or after CIED system removal. Larger studies with longer follow-up are required to determine if there is a long-term advantage to implanting a leadless pacemaker versus a traditional pacemaker following temporary pacing when needed during the periextraction period in patients with a prior CIED infection.