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Importance The safety and efficacy of leadless VVI pacemakers have been demonstrated in multiple clinical trials, but the comparative performance of the device in a large, real-world population has not been examined. Objective To compare patient characteristics and complications among patients implanted with leadless VVI and transvenous VVI pacemakers. Design, Setting, Participants The Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers (Micra CED) is a continuously enrolling observational cohort study evaluating complications, utilization, and outcomes of leadless VVI pacemakers in the US Medicare fee-for-service population. Patients implanted between March 9, 2017, and December 1, 2018, were identified and included. All Medicare patients implanted with leadless VVI and transvenous VVI pacemakers during the study period were enrolled. Patients with less than 12 months of continuous enrollment in Medicare prior to leadless VVI or transvenous VVI implant and with evidence of a prior cardiovascular implantable electronic device were excluded, leaving 5746 patients with leadless VVI pacemakers and 9662 patients with transvenous VVI pacemakers. Data were analyzed from May 2018 to April 2021. Exposures Medicare patients implanted with leadless VVI pacemakers or transvenous VVI pacemakers. Main Outcomes and Measures The main outcomes were acute (30-day) complications and 6-month complications. Results Of 15 408 patients, 6701 (43.5%) were female, and the mean (SD) age was 81.0 (8.7) years. Compared with patients with transvenous VVI pacemakers, patients with leadless VVI pacemakers were more likely to have end-stage kidney disease (690 [12.0%] vs 226 [2.3%]; P

Importance Bleeding and thrombotic events (eg, stroke and systemic embolism) are common in patients with atrial fibrillation (AF) taking warfarin sodium despite a well-established therapeutic range. Objective To evaluate whether history of therapeutic warfarin control in patients with AF is independently associated with subsequent bleeding or thrombotic events. Design, Setting, and Participants In this multicenter cohort study of 176 primary care, cardiology, and electrophysiology clinics in the United States, data were obtained during 51 830 visits among 10 137 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry; 5545 patients treated with warfarin were included in the bleeding analysis, and 5635 patients were included in the thrombotic event analysis. Patient follow-up was performed from June 29, 2010, to November 30, 2014. Data analysis was performed from August 4, 2016, to February 15, 2019. Exposures Multiple measures of warfarin control within the preceding 6 months were analyzed: time in therapeutic range of 2.0 to 3.0, most recent international normalized ratio (INR), percentage of time that a patient had interpolated INR values less than 2.0 or greater than 3.0, INR variance, INR range, and percentage of INR values in therapeutic range. Main Outcomes and Measures Association of INR measures, alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the subsequent 6 months was assessed post hoc using logistic regression models. Results A total of 5545 patients (mean [SD] age, 74.5 [9.8] years; 3184 [57.4%] male) with AF were included in the major bleeding analysis and 5635 patients (mean [SD] age, 74.5 [9.8] years; 3236 [57.4%] male) in the thrombotic event analysis. During a median follow-up of 1.5 years (interquartile range, 1.0-2.5 years), there were 339 major bleeds (6.1%) and 51 strokes (0.9%). Multiple metrics of warfarin control were individually associated with subsequent bleeding. After adjustment for clinical bleeding risk, 3 measures—time in therapeutic range (per 1-SD increase ≤55: adjusted odds ratio [aOR], 1.16; 95% CI, 1.02-1.32), variation in INR values (aOR, 1.32; 95% CI, 1.19-1.47), and maximum INR (aOR, 1.20; 95% CI, 1.10-1.31)—remained associated with bleeding risk. Adding INR variance to a clinical risk model slightly increased the C statistic from 0.68 to 0.69 and had a net reclassification improvement index of 0.028 (95% CI, −0.029 to 0.067). No INR measures were associated with subsequent stroke risk. Conclusions and Relevance Three metrics of prior warfarin control were associated with bleeding risk but only marginally more so than traditional clinical factors. This study did not identify any measures of INR control that were significantly associated with stroke risk.

Importance Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15];P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21];P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93];P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60];P Conclusions and Relevance Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial. Trial Registration ClinicalTrials.gov Identifier:NCT00911508

Catheter ablation is more effective than drug therapy in restoring sinus rhythm in patients with atrial fibrillation (AF), but its incremental effect on long-term quality of life (QOL) is uncertain.To determine whether catheter ablation is more beneficial than conventional drug therapy for improving QOL in patients with AF.An open-label randomized clinical trial of catheter ablation vs drug therapy in 2204 symptomatic patients with AF older than 65 years or 65 years or younger with at least 1 risk factor for stroke. Patients were enrolled from November 2009 to April 2016 from 126 centers in 10 countries. Follow-up ended in December 2017.Pulmonary vein isolation, with additional ablation procedures at the discretion of the investigators, for the catheter ablation group (n = 1108) and standard rhythm and/or rate-control drugs selected and managed by investigators for the drug therapy group (n = 1096).Prespecified co-primary QOL end points at 12 months, including the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary score (range, 0-100; 0 indicates complete disability and 100 indicates no disability; patient-level clinically important difference, ≥5 points) and the Mayo AF-Specific Symptom Inventory (MAFSI) frequency score (range, 0-40; 0 indicates no symptoms and 40 indicates the most severe symptoms; patient-level clinically important difference, ≤-1.6 points) and severity score (range, 0-30; 0 indicates no symptoms and 30 indicates the most severe symptoms; patient-level clinically important difference, ≤-1.3 points).Among 2204 randomized patients (median age, 68 years; 1385 patients [63%] were men, 946 [43%] had paroxysmal AF, and 1256 [57%] had persistent AF), the median follow-up was 48.5 months, and 1968 (89%) completed the trial. The mean AFEQT summary score was more favorable in the catheter ablation group than the drug therapy group at 12 months (86.4 points vs 80.9 points) (adjusted difference, 5.3 points [95% CI, 3.7-6.9]; P .001). The mean MAFSI frequency score was more favorable for the catheter ablation group than the drug therapy group at 12 months (6.4 points vs 8.1 points) (adjusted difference, -1.7 points [95% CI, -2.3 to -1.2]; P .001) and the mean MAFSI severity score was more favorable for the catheter ablation group than the drug therapy group at 12 months (5.0 points vs 6.5 points) (adjusted difference, -1.5 points [95% CI, -2.0 to -1.1]; P .001).Among patients with symptomatic atrial fibrillation, catheter ablation, compared with medical therapy, led to clinically important and significant improvements in quality of life at 12 months. These findings can help guide decisions regarding management of atrial fibrillation.ClinicalTrials.gov Identifier: NCT00911508.

The left atrial appendage is a key site of thrombus formation in atrial fibrillation (AF) and can be occluded or removed at the time of cardiac surgery. There is limited evidence regarding the effectiveness of surgical left atrial appendage occlusion (S-LAAO) for reducing the risk of thromboembolism.To evaluate the association of S-LAAO vs no receipt of S-LAAO with the risk of thromboembolism among older patients undergoing cardiac surgery.Retrospective cohort study of a nationally representative Medicare-linked cohort from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (2011-2012). Patients aged 65 years and older with AF undergoing cardiac surgery (coronary artery bypass grafting [CABG], mitral valve surgery with or without CABG, or aortic valve surgery with or without CABG) with and without concomitant S-LAAO were followed up until December 31, 2014.S-LAAO vs no S-LAAO.The primary outcome was readmission for thromboembolism (stroke, transient ischemic attack, or systemic embolism) at up to 3 years of follow-up, as defined by Medicare claims data. Secondary end points included hemorrhagic stroke, all-cause mortality, and a composite end point (thromboembolism, hemorrhagic stroke, or all-cause mortality).Among 10 524 patients undergoing surgery (median age, 76 years; 39% female; median CHA2DS2-VASc score, 4), 3892 (37%) underwent S-LAAO. Overall, at a mean follow-up of 2.6 years, thromboembolism occurred in 5.4%, hemorrhagic stroke in 0.9%, all-cause mortality in 21.5%, and the composite end point in 25.7%. S-LAAO, compared with no S-LAAO, was associated with lower unadjusted rates of thromboembolism (4.2% vs 6.2%), all-cause mortality (17.3% vs 23.9%), and the composite end point (20.5% vs 28.7%) but no significant difference in rates of hemorrhagic stroke (0.9% vs 0.9%). After inverse probability-weighted adjustment, S-LAAO was associated with a significantly lower rate of thromboembolism (subdistribution hazard ratio [HR], 0.67; 95% CI, 0.56-0.81; P .001), all-cause mortality (HR, 0.88; 95% CI, 0.79-0.97; P = .001), and the composite end point (HR, 0.83; 95% CI, 0.76-0.91; P .001) but not hemorrhagic stroke (subdistribution HR, 0.84; 95% CI, 0.53-1.32; P = .44). S-LAAO, compared with no S-LAAO, was associated with a lower risk of thromboembolism among patients discharged without anticoagulation (unadjusted rate, 4.2% vs 6.0%; adjusted subdistribution HR, 0.26; 95% CI, 0.17-0.40; P .001), but not among patients discharged with anticoagulation (unadjusted rate, 4.1% vs 6.3%; adjusted subdistribution HR, 0.88; 95% CI, 0.56-1.39; P = .59).Among older patients with AF undergoing concomitant cardiac surgery, S-LAAO, compared with no S-LAAO, was associated with a lower risk of readmission for thromboembolism over 3 years. These findings support the use of S-LAAO, but randomized trials are necessary to provide definitive evidence.

Importance The joint American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) guidelines on the management of atrial fibrillation (AF) are used extensively to guide patient care. Objective To describe the evidence base and changes over time in the AHA/ACC/HRS guidelines on AF with respect to the distribution of recommendations across classes of recommendations and levels of evidence. Data Sources Data from the AHA/ACC/HRS guidelines on AF from 2001, 2006, 2011, and 2014 were abstracted. A total of 437 recommendations were included. Data Extraction and Synthesis The number of recommendations and distribution of classes of recommendation (I, II, and III) and levels of evidence (A, B, and C) were determined for each guideline edition. Changes in recommendation class and level of evidence were analyzed using the 2001 and 2014 guidelines. Results From 2001 to 2014, the total number of AF recommendations increased from 95 to 113. Numerically, there was a nonsignificant increase in the use of level of evidence B (30.5% to 39.8%; P = .17) and a nonsignificant decrease in the use of level of evidence C (60.0% to 51.3%; P = .21), with limited changes in the use of level A evidence (8.4% to 8.8%; P = .92). In the 2014 guideline document, 10 of 113 (8.8%) recommendations were supported by level of evidence A, whereas 58 of 113 (51.3%) were supported by level of evidence C. Most recommendations were equally split among class I (49/113; 43.4%) and class IIa/IIb (49/113; 43.4%), with the minority (15/113; 13.3%) assigned as class III. Most class I recommendations were supported by level of evidence C (29/49; 59.2%), whereas only 6 of 49 (12.2%) were supported by level of evidence A. No rate control category recommendations were supported by level of evidence A. Conclusions and Relevance Some aspects of the quality of evidence underlying AHA/ACC/HRS AF guidelines have improved over time. However, the use of level of evidence A remains low and has not increased since 2001. These findings highlight the need for focused and pragmatic randomized studies on the clinical management of AF.

Despite the frequency of atrial fibrillation (AF) in clinical practice, relatively little is known about sex differences in symptoms and quality of life and how they may affect treatment and outcomes.To determine whether symptoms, quality of life, treatment, and outcomes differ between women and men with AF.This observational cohort study included 10 135 patients with AF. The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation is a prospective, nationwide, multicenter outpatient registry of patients with incident and prevalent AF enrolled at 176 sites between June 2010 and August 2011.Symptoms, quality of life as measured by Atrial Fibrillation Effects on Quality of Life scores, AF treatment, cardiovascular outcomes, stroke or non-central nervous system embolism, and all-cause mortality.Overall, 4293 of the cohort (42%) were female. Compared with men, women were older (77 years; interquartile range [IQR], 69-83, vs 73 years; IQR, 65-80; P .001) and had higher median CHA2DS2-VASc scores (5; IQR, 4-6, vs 3; IQR, 2-5; P .001), but less sleep apnea (578 [13.5%] vs 1264 [21.6%]; P .001). Only 32.1% of women (n = 1378) were asymptomatic (European Heart Rhythm Association class I) compared with 42.5% of men (n = 2483) in unadjusted analyses (P .001). Women had lower (more severe) unadjusted baseline overall Atrial Fibrillation Effects on Quality of Life scores (n = 2007; 80; IQR, 62-92 vs 83; IQR, 69-94; P .001). Women had similar rates of anticoagulation and similar time in therapeutic range. In follow-up, women experienced lower risk-adjusted all-cause mortality (adjusted hazard ratio, 0.57; 95% CI, 0.49-0.67) and cardiovascular death (adjusted hazard ratio, 0.56; 95% CI, 0.44-0.72); however, they had a higher risk for stroke or non-central nervous system embolism (adjusted hazard ratio, 1.39; 95% CI, 1.05-1.84; P = .02) compared with men.Women with AF have more symptoms and worse quality of life. Despite higher risk, women have lower risk-adjusted all-cause and cardiovascular death compared with men, but higher stroke rates. Future studies should focus on how treatment and interventions specifically affect AF-related quality of life and cardiovascular outcomes in women.clinicaltrials.gov Identifier: NCT01165710.

In the current therapeutic era, the risk for sudden cardiac death (SCD) after non-ST-segment elevation acute coronary syndrome (NSTE ACS) has not been characterized completely.To determine the cumulative incidence of SCD during long-term follow-up after NSTE ACS, to develop a risk model and risk score for SCD after NSTE ACS, and to assess the association between recurrent events after the initial ACS presentation and the risk for SCD.This pooled cohort analysis merged individual data from 48 286 participants in 4 trials: the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2), Study of Platelet Inhibition and Patient Outcomes (PLATO), Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER), and Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trials. The cumulative incidence of SCD and cardiovascular death was examined according to time after NSTE ACS. Using competing risk and Cox proportional hazards models, clinical factors at baseline and after the index event that were associated with SCD after NSTE ACS were identified. Baseline factors were used to develop a risk model. Data were analyzed from January 2, 2014, to December 11, 2015.Sudden cardiac death.Of the initial 48 286 patients, 37 555 patients were enrolled after NSTE ACS (67.4% men; 32.6% women; median [interquartile range] age, 65 [57-72] years). Among these, 2109 deaths occurred after a median follow-up of 12.1 months. Of 1640 cardiovascular deaths, 513 (31.3%) were SCD. At 6, 18, and 30 months, the cumulative incidence estimates of SCD were 0.79%, 1.65%, and 2.37%, respectively. Reduced left ventricular ejection fraction, older age, diabetes mellitus, lower estimated glomerular filtration rate, higher heart rate, prior myocardial infarction, peripheral artery disease, Asian race, male sex, and high Killip class were significantly associated with SCD. A model developed to calculate the risk for SCD in trials with systematic collection of left ventricular ejection fraction had a C index of 0.77. An integer-based score was developed from this model and yielded a calculated SCD probability ranging from 0.1% to 56.7% (C statistic, 0.75). In a multivariable model that included time-dependent clinical events occurring after the index hospitalization for ACS, SCD was associated with recurrent myocardial infarction (hazard ratio [HR], 2.95; 95% CI, 2.29-3.80; P .001) and any hospitalization (HR, 2.45; 95% CI, 1.98-3.03; P .001), whereas coronary revascularization had a negative relationship with SCD (HR, 0.75; 95% CI, 0.58-0.98; P = .03).In the current therapeutic era, SCD accounts for about one-third of cardiovascular deaths after NSTE ACS. Risk stratification can be performed with good accuracy using commonly collected clinical variables. Clinical events occurring after the index hospitalization are underappreciated but important risk factors.