Environmental Exposome and Atrial Fibrillation: Emerging Evidence and Future Directions.

There has been increased awareness of the linkage between environmental exposures and cardiovascular health and disease. Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting millions of people worldwide and contributing to substantial morbidity and mortality. Although numerous studies have explored the role of genetic and lifestyle factors in the development and progression of atrial fibrillation, the potential impact of environmental determinants on this prevalent condition has received comparatively less attention. This review aims to provide a comprehensive overview of the current evidence on environmental determinants of atrial fibrillation, encompassing factors such as air pollution, temperature, humidity, and other meteorologic conditions, noise pollution, greenspace, and the social environment. We discuss the existing evidence from epidemiological and mechanistic studies, critically evaluating the strengths and limitations of these investigations and the potential underlying biological mechanisms through which environmental exposures may affect atrial fibrillation risk. Furthermore, we address the potential implications of these findings for public health and clinical practice and identify knowledge gaps and future research directions in this emerging field.

Treatment-related adverse events, including fatal toxicities, in patients with solid tumours receiving neoadjuvant and adjuvant immune checkpoint blockade: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Incorporating immune checkpoint blockade into perioperative cancer therapy has improved clinical outcomes. However, the safety of immune checkpoint blockade needs better evaluation, given the chances of more prolonged disease-free survival. We aimed to assess how adding immune checkpoint blockade to perioperative therapy affects treatment-related adverse events. METHODS: For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library from database inception until Aug 8, 2023, for randomised controlled trials that assessed the addition of immune checkpoint blockade to neoadjuvant or adjuvant therapy for cancer, reported treatment-related deaths, and had a design in which the experimental group assessed immune checkpoint blockade in combination with the therapy used in the control group. Meta-analysis was done to pool odds ratios (ORs) of treatment-related deaths, any grade and grade 3-4 treatment-related adverse events, serious adverse events, and adverse events leading to treatment discontinuation. The protocol is registered with PROSPERO, CRD42022343741. FINDINGS: 28 randomised controlled trials with 16 976 patients were included. The addition of immune checkpoint blockade was not significantly associated with increased treatment-related deaths (OR 1·76, 95% CI 0·95-3·25; p=0·073), consistent across immune checkpoint blockade subtype (I2=0%). 40 fatal toxicities were identified across 9864 patients treated with immune checkpoint blockade, with pneumonitis being the most common (six [15·0%]); 13 fatal toxicities occurred among 7112 patients who were not treated with immune checkpoint blockade. The addition of immune checkpoint blockade increased the incidence of grade 3-4 treatment-related adverse events (OR 2·73, 95% CI 1·98-3·76; p<0·0001), adverse events leading to treatment discontinuation (3·67, 2·45-5·51; p<0·0001), and treatment-related adverse events of any grade (2·60 [1·88-3·61], p<0·0001). The immune checkpoint blockade versus placebo design primarily used as adjuvant therapy was associated with increased incidence of treatment-related deaths (4·02, 1·04-15·63; p=0·044) and grade 3-4 adverse events (5·31, 3·08-9·15; p<0·0001), whereas the addition of immune checkpoint blockade in the neoadjuvant setting was not associated with increased incidence of treatment-related death (1·11, 95% CI 0·38-3·29; p=0·84) or grade 3-4 adverse events (1·17, 0·90-1·51; p=0·23). INTERPRETATION: The addition of immune checkpoint blockade to perioperative therapy was associated with an increase in grade 3-4 treatment-related adverse events and adverse events leading to treatment discontinuation. These findings provide safety insights for further clinical trials assessing neoadjuvant or adjuvant immune checkpoint blockade therapy. Clinicians should closely monitor patients for treatment-related adverse events to prevent treatment discontinuations and morbidity from these therapies in earlier-stage settings. FUNDING: None.

Association between atrial fibrillation and heart failure patient reported outcomes across the ejection fraction spectrum.

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF) and is associated with worse clinical outcomes. We evaluated the relationship between AF and longitudinal changes in health-related quality of life (HRQoL) measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) in both HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). METHODS: This is a post-hoc analysis of the TOPCAT and HF-ACTION trials. The effect of AF on KCCQ overall summary scores (OSS), in both trials, was examined using a mixed effects regression model. Patients were divided into 3 groups according to AF status at baseline: patients with a history of AF but no AF detected on ECG at enrollment (Hx AF group), patients with history of AF and AF detected on ECG at enrollment (ECG AF group) and patients with post-randomization new-onset AF (New AF group). RESULTS: In TOPCAT, among 1,710 patients with KCCQ data available, AF was associated with a significantly lower KCCQ-OSS (-3.98; 95% CI -7.21: -0.74) at 48 months, with a significant AF status by time interaction (P = .03). In HF-ACTION, among 1,814 patients with available KCCQ data, AF was associated with a significantly lower KCCQ-OSS (-3.67; 95% CI -6.21: -1.41) at 24 months but there was no significant AF status by time interaction. In both trials, the type of AF was not associated with significant changes in KCCQ-OSS score. CONCLUSION: Ιn patients with both HFpEF and HFrEF, AF was independently associated with worse HRQoL measured by KCCQ.

Trends and disparities in cardiac implantable electronic device infection-related mortality in the United States.

INTRODUCTION: We performed a cross-sectional study using the Centers for Disease Control and Prevention's (CDC's) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database to analyze the trends in cardiac implantable electronic device (CIED) infection-related mortality from 1999 to 2020. METHODS: We analyzed the death certificate data from the CDC WONDER database from 1999 to 2020 for CIED infections in the US population aged ≥25 years using International Classification of Diseases, Tenth Revision (ICD-10) codes, listed as the underlying or contributing cause of death. Age-adjusted mortality rates (AAMR) and 95% confidence intervals (CIs) were computed per 1 million population by standardizing crude mortality rates to the 2000 US census population. To assess annual mortality trends, we employed the Joinpoint regression model, calculating the annual percent change (APC) in AAMR and corresponding 95% CIs. RESULTS: Overall, there was an observed declining trend in AAMRs related to CIED infection-related mortality. Males accounted for 55% of the total deaths, with persistently higher AAMRs compared to females over the study duration. Both males and females had an overall decreasing trend in AAMRs throughout the study duration. On race/ethnicity stratified analysis, non-Hispanic (NH) Blacks exhibited the highest overall AAMR, followed by NH American Indians or Alaska Natives, NH Whites, Hispanic or Latinos, and NH Asian or Pacific Islanders. On a stratified analysis based on region, the South region had the highest overall AAMR, followed by the Midwest, West, and Northeast regions. CONCLUSION: Our study demonstrates a significant decline in CIED infection-related mortality in patients over the last two decades. Notable gender, racial/ethnic, and regional differences exist in the rates of mortality related to CIED infections.

Contemporary trends of leadless pacemaker implantation in the United States.

INTRODUCTION: Leadless pacemakers (LPM) have established themselves as the important therapeutic modality in management of selected patients with symptomatic bradycardia. To determine real-world utilization and in-hospital outcomes of LPM implantation since its approval by the Food and Drug Administration in 2016. METHODS: For this retrospective cohort study, data were extracted from the National Inpatient Sample database from the years 2016-2020. The outcomes analyzed in our study included implantation trends of LPM over study years, mortality, major complications (defined as pericardial effusion requiring intervention, any vascular complication, or acute kidney injury), length of stay, and cost of hospitalization. Implantation trends of LPM were assessed using linear regression. Using years 2016-2017 as a reference, adjusted outcomes of mortality, major complications, prolonged length of stay (defined as >6 days), and increased hospitalization cost (defined as median cost >34 098$) were analyzed for subsequent years using a multivariable logistic regression model. RESULTS: There was a gradual increased trend of LPM implantation over our study years (3230 devices in years 2016-2017 to 11 815 devices in year 2020, p for trend <.01). The adjusted mortality improved significantly after LPM implantation in subsequent years compared to the reference years 2016-2017 (aOR for the year 2018: 0.61, 95% CI: 0.51-0.73; aOR for the year 2019: 0.49, 95% CI: 0.41-0.59; and aOR for the year 2020: 0.52, 95% CI: 0.44-0.62). No differences in adjusted rates of major complications were demonstrated over the subsequent years. The adjusted cost of hospitalization was higher for the years 2019 (aOR: 1.33, 95% CI: 1.22-1.46) and 2020 (aOR: 1.69, 95% CI: 1.55-1.84). CONCLUSION: The contemporary US practice has shown significantly increased implantation rates of LPM since its approval with reduced rates of inpatient mortality.

Same-day discharge for left atrial appendage occlusion procedure: A systematic review and meta-analysis.

INTRODUCTION: Most patients undergoing a left atrial appendage occlusion (LAAO) procedure are admitted for overnight observation. A same-day discharge strategy offers the opportunity to improve resource utilization without compromising patient safety. We compared the patient safety outcomes and post-discharge complications between same-day discharge versus hospital admission (HA) (>1 day) in patients undergoing LAAO procedure. METHODS: A systematic search of MEDLINE and Embase was conducted. Outcomes of interest included peri-procedural complications, re-admissions, discharge complications including major bleeding and vascular complications, ischemic stroke, all-cause mortality, and peri-device leak >5 mm. Mantel-Haenszel risk ratios (RRs) with 95% CIs were calculated. RESULTS: A total of seven observational studies met the inclusion criteria. There was no statistically significant difference between same-day discharge versus HA regarding readmission (RR: 0.61; 95% confidence interval [CI]: [0.29-1.31]; p = .21), ischemic stroke after discharge (RR: 1.16; 95% CI: [0.49-2.73]), peri-device leak >5 mm (RR: 1.27; 95% CI: [0.42-3.85], and all-cause mortality (RR: 0.60; 95% CI: [0.36-1.02]). The same-day discharge study group had significantly lower major bleeding or vascular complications (RR: 0.71; 95% CI: [0.54-0.94]). CONCLUSIONS: This meta-analysis of seven observational studies showed no significant difference in patient safety outcomes and post-discharge complications between same-day discharge versus HA. These findings provide a solid basis to perform a randomized control trial to eliminate any potential confounders.

The effect of weight loss on recurrence of atrial fibrillation after catheter ablation: A systematic review and meta-analysis.

BACKGROUND: Obesity is associated with an increased risk of developing recurrent atrial fibrillation (AF) after catheter ablation (CA). However, the current data on weight loss interventions show inconsistent results in preventing the recurrence of AF after CA. METHODS: We conducted a systematic search in MEDLINE and EMBASE to identify studies that reported the outcome of recurrence of AF after CA in obese patients undergoing weight interventions. The subgroup analysis included: (1) Weight loss versus no weight loss, (2) >10% weight loss versus <10% weight loss, (3) <10% weight loss versus no weight loss, (4) Follow-up <12 months, and (5) Follow-up >12 months after CA. Mantel-Haenszel risk ratios with a 95% confidence interval (CI) were calculated using a random effects model and for heterogeneity, I2 statistics were reported. RESULTS: A total of 10 studies (one randomized controlled trial and nine observational studies) comprising 1851 patients were included. The recurrence of AF was numerically reduced in the weight loss group (34.5%) versus no weight loss group (58.2%), but no statistically significant difference was observed (risk ratio [RR] = 0.76; 95% CI: 0.49-1.18, p = .22). However, there was a statistically significant reduction in recurrence of AF with weight loss versus no weight loss at follow-up >12 months after CA (RR = 0.47; 95% CI: 0.32-0.68, p < .0001). At follow-up >12 months after CA, both >10% weight loss versus <10% weight loss (RR = 0.49; 95% CI: 0.31-0.80, p = .004) and <10% weight loss versus no weight loss (RR = 0.39; 95% CI: 0.31-0.49, p < .00001) were associated with a statistically significant reduction in recurrent AF. CONCLUSION: In patients with AF undergoing CA, weight loss is associated with reducing recurrent AF at > 12 months after ablation and these benefits are consistently seen with both >10% and <10% weight loss. The benefits of weight loss in preventing recurrent AF after CA should be examined in larger studies with extended follow-up duration.

Outcomes of percutaneous left atrial appendage occlusion device implantation in atrial fibrillation patients based on underlying stroke risk.

AIMS: To determine outcomes in atrial fibrillation patients undergoing percutaneous left atrial appendage occlusion (LAAO) based on the underlying stroke risk (defined by the CHA2DS2-VASc score). METHODS AND RESULTS: Data were extracted from the National Inpatient Sample for calendar years 2016-20. Left atrial appendage occlusion implantations were identified on the basis of the International Classification of Diseases, 10th Revision, Clinical Modification code of 02L73DK. The study sample was stratified on the basis of the CHA2DS2-VASc score into three groups (scores of 3, 4, and ≥5). The outcomes assessed in our study included complications and resource utilization. A total of 73 795 LAAO device implantations were studied. Approximately 63% of LAAO device implantations occurred in patients with CHA2DS2-VASc scores of 4 and ≥5. The crude prevalence of pericardial effusion requiring intervention was higher with increased CHA2DS2-VASc score (1.4% in patients with a score of ≥5 vs. 1.1% in patients with a score of 4 vs. 0.8% in patients with a score of 3, P < 0.01). In the multivariable model adjusted for potential confounders, CHA2DS2-VASc scores of 4 and ≥5 were found to be independently associated with overall complications [adjusted odds ratio (aOR) 1.26, 95% confidence interval (CI) 1.18-1.35, and aOR 1.88, 95% CI 1.73-2.04, respectively] and prolonged length of stay (aOR 1.18, 95% CI 1.11-1.25, and aOR 1.54, 95% CI 1.44-1.66, respectively). CONCLUSION: A higher CHA2DS2-VASc score was associated with an increased risk of peri-procedural complications and resource utilization after LAAO. These findings highlight the importance of patient selection for the LAAO procedure and need validation in future studies.

Association of atrial fibrillation and outcomes in patients undergoing bone marrow transplantation.

AIMS: Haematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for several malignant and non-malignant haematologic conditions. Patients undergoing HSCT are at an increased risk of developing atrial fibrillation (AF). We hypothesized that a diagnosis of AF would be associated with poor outcomes in patients undergoing HSCT. METHODS AND RESULTS: The National Inpatient Sample (2016-19) was queried with ICD-10 codes to identify patients aged >50 years undergoing HSCT. Clinical outcomes were compared between patients with and without AF. A multivariable regression model adjusting for demographics and comorbidities was used to calculate the adjusted odds ratio (aOR) and regression coefficients with corresponding 95% confidence intervals and P-values. A total of 50 570 weighted hospitalizations for HSCT were identified, out of which 5820 (11.5%) had AF. Atrial fibrillation was found to be independently associated with higher inpatient mortality (aOR 2.75; 1.9-3.98; P < 0.001), cardiac arrest (aOR 2.86; 1.55-5.26; P = 0.001), acute kidney injury (aOR 1.89; 1.6-2.23; P < 0.001), acute heart failure exacerbation (aOR 5.01; 3.54-7.1; P < 0.001), cardiogenic shock (aOR 7.73; 3.17-18.8; P < 0.001), and acute respiratory failure (aOR 3.24; 2.56-4.1; P < 0.001) as well as higher mean length of stay (LOS) (+2.67; 1.79-3.55; P < 0.001) and cost of care (+67 529; 36 630-98 427; P < 0.001). CONCLUSION: Among patients undergoing HSCT, AF was independently associated with poor in-hospital outcomes, higher LOS, and cost of care.

Safety and efficacy of colchicine for the prevention of post-operative atrial fibrillation in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Colchicine is an anti-inflammatory drug that may prevent post-operative atrial fibrillation (POAF). The effect of this drug has been inconsistently shown in previous clinical trials. We aimed to compare the efficacy and safety of colchicine vs. placebo to prevent POAF in patients undergoing cardiac surgery. METHODS AND RESULTS: A systematic search of EMBASE, MEDLINE, SCOPUS, ClinicalTrials.gov, and the Cochrane Library for randomized controlled trials (RCTs) was conducted from inception till April 2023. The primary outcome was the incidence of POAF after any cardiac surgery. The secondary outcome was the rate of drug discontinuation due to adverse events and adverse gastrointestinal events. Risk ratios (RR) were reported using the Mantel Haenszel method. A total of eight RCTs comprising 1885 patients were included. There was a statistically significant lower risk of developing POAF with colchicine vs. placebo (RR: 0.70; 95% CI: 0.59-0.82; P < 0.01, I2 = 0%), and this effect persisted across different subgroups. There was a significantly higher risk of adverse gastrointestinal events (RR: 2.20; 95% CI: 1.38-3.51; P < 0.01, I2 = 55%) with no difference in the risk of drug discontinuation in patients receiving colchicine vs. placebo (RR: 1.33; 95% CI: 0.93-1.89; P = 0.11, I2 = 0%). CONCLUSION: This meta-analysis of eight RCTs shows that colchicine is effective at preventing POAF, with a significantly higher risk of adverse gastrointestinal events but no difference in the rate of drug discontinuation. Future studies are required to define the optimal duration and dose of colchicine for the prevention of POAF.

Psychosocial risk factors and outcomes in patients undergoing catheter ablation for atrial fibrillation.

The association of psychosocial risk factors with cardiovascular disease is well-established, and there is a growing recognition of their influence on atrial fibrillation (AF) . A recent National Heart, Lung, and Blood Institute workshop called for transforming AF research to integrate social determinants of health. There is limited data examining the impact of psychosocial risk factors (PSRFs) on outcomes in patients with an established diagnosis of AF. Catheter ablation for AF has been shown to improve arrhythmia burden and quality of life compared with medical treatment alone. It is unknown how PSRFs affect clinical outcomes in patients undergoing AF ablation. It is important to understand this relationship, especially given the increasing adoption of catheter ablation in clinical practice.

Association of heart failure with procedural complications and in-hospital outcomes from left atrial appendage occlusion device implantation in patients with atrial fibrillation: insights from the national inpatient sample of 62 980 procedures.

AIMS: To determine outcomes in atrial fibrillation (AF) patients undergoing percutaneous left atrial appendage occlusion (LAAO) with concomitant heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Data were extracted from National Inpatient Sample for calendar years 2015-2019. LAAO device implantations were identified on the basis of ICD-10-CM code of 02L73DK. The outcomes assessed in our study included complications, in-patient mortality, and resource utilization. A total of 62 980 LAAO device implantations were studied. HFpEF (14.4%, n = 9040) and HFrEF (11.2%, n = 7100) were associated with a higher prevalence of major complications and in-patient mortality in crude analysis. In the multivariate model adjusted for potential confounders, HFpEF and HFrEF were not associated with major complications [adjusted odds ratio (aOR) 1.04, 95% confidence interval (CI) 0.93-1.16 and aOR 1.07, 95% CI 0.95-1.21] or in-patient mortality (aOR 1.48, 95% CI 0.85-2.55 and aOR 1.26, 95% CI 0.67-2.38). HFpEF and HFrEF were associated with prolonged length of stay (LOS) > 1 day (aOR 1.41, 95% CI 1.31-1.53 and aOR 1.66, 95% CI 1.53-1.80) and increased hospitalization costs > median cost 24 752$ (aOR 1.26, 95% CI 1.19-1.34 and aOR 1.21, 95% CI 1.13-1.29). CONCLUSION: The prevalence of HF in AF patients undergoing percutaneous LAAO was approximately 26%. HF was not independently associated with major complications and in-patient mortality but was associated with prolonged LOS and higher hospitalization costs.

Uninterrupted versus interrupted direct oral anticoagulation for catheter ablation of atrial fibrillation: A systematic review and meta-analysis.

INTRODUCTION: To evaluate the safety of uninterrupted versus interrupted direct oral anticoagulation (DOAC) for patients undergoing catheter ablation (CA) of atrial fibrillation (AF). METHODS: We conducted a systematic search of MEDLINE and EMBASE for randomized controlled trials (RCT) and observational studies comparing uninterrupted versus interrupted DOAC for patients undergoing CA of AF. Primary outcome was major bleeding. Secondary outcomes included minor bleeding, stroke or transient ischemic attack (TIA) or thromboembolism (TE), silent cerebral ischemic events, and cardiac tamponade. Meta-analysis was stratified by study design. Risk ratios (RR) with 95% confidence intervals were calculated using random effects model and Mantel-Haenszel method was used to pool RR. RESULTS: A total of 13 studies (7 randomized, 6 observational) comprising 3595 patients were included. The RCT restricted analysis did not show any difference in terms of major bleeding (risk ratio [RR] = 0.79; [0.35-1.79]), minor bleeding (RR = 0.99 [0.68-1.43]), stroke or TIA or TE (RR = 0.80 [0.19-3.32]), silent cerebral ischemic events (RR = 0.64 [0.32-1.28]), and cardiac tamponade (RR = 0.61 [0.20-1.92]). Observational study restricted analysis showed a protective effect of uninterrupted DOAC on silent cerebral ischemic events (RR = 0.45 [0.31-0.67]) and no difference in other outcomes. CONCLUSIONS: There is no difference in bleeding and thromboembolic outcomes with uninterrupted versus interrupted DOAC for CA of AF and observational data suggests that uninterrupted DOACs are protective against silent cerebral ischemic lesions.

Representation of women, older patients, ethnic, and racial minorities in trials of atrial fibrillation.

BACKGROUND: Representation trends of women, older adults, and ethnic/racial minorities in randomized controlled trials (RCTs) of atrial fibrillation (AF) are uncertain. METHODS: We systematically reviewed 134 AF related RCTs (phase II and III) encompassing 149,162 participants using Medline and ClinicalTrials.gov through April 2019 to determine representation trends of women, older patients (≥75 years), and ethnic/racial minorities. Weighted data on the prevalence of AF from epidemiological studies were used to compare the representation of the studied groups of interest in AF RCTs to their expected burden of the disease. RESULTS: Only 18.7% of the RCTs reported proportion of older patients, and 12.7% RCTs reported ethnic/racial minorities. The proportions of women in RCTs versus general population were 35.2% and 35.1%, of Hispanics were 11.9% and 5.2%, of Blacks were 1.2% and 5.7%, of American Indian/Alaskans were 0.2% and 0.2%, of Asians were 14.2% and 2.4%, of native Hawaiian/Pacific Islanders were 0.05% and 0.1% and of non-Whites were 19.5% and 22.5%, respectively. The weighted mean age (SD) across the trials was 65.3 (3.2) years which was less than the corresponding weighted mean age of 71.1 (4.5) years in the comparative epidemiological data. CONCLUSION: The reporting of older patients and ethnic/racial minorities was poor in RCTs of AF. The representation of women and American Indian/Alaskan natives matched their expected population share of disease burden. Hispanics and Asians were over-represented and Blacks, native Hawaiian/Pacific Islanders and non-Whites were under-represented in RCTs of AF.

Efficacy and safety of low dose rivaroxaban in patients with coronary heart disease: a systematic review and meta-analysis.

The mortality effects and risk-benefit profile of low dose rivaroxaban (2.5 mg twice daily) in patients with coronary heart disease are not completely understood. Five randomized controlled trials (26,110 patients) were selected using PubMed and Cochrane library till April 2019. The background antiplatelet therapy was aspirin in 3 trials, P2Y12 inhibitor in 1 trial, and in 1 trial 65% patients received aspirin and 35% were on dual antiplatelet therapy (DAPT). The outcomes of interest were cardiovascular mortality, all-cause mortality, myocardial infarction (MI), stroke and major bleeding events. Random effects hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Low dose rivaroxaban did not reduce the risk of cardiovascular mortality (HR 0.90, 95% CI 0.73-1.11, P = 0.34) or all-cause mortality (HR 0.91, 95% CI 0.74-1.12, P = 0.38) compared with control. However, low dose rivaroxaban was associated with reduction in MI (HR 0.85, 95% CI 0.73-0.99, P = 0.04), and stroke (HR 0.59, 95%CI 0.48-0.73, P < 0.001) at the expense of major bleeding (HR 1.64, 95% CI 1.39-1.94, P < 0.001) compared with control. These effects did not vary according to acute coronary syndrome or stable coronary heart disease (P-interaction > 0.05). The use of low dose rivaroxaban in patients with coronary heart disease predominantly receiving antiplatelet monotherapy did not reduce cardiovascular or all-cause mortality. The benefits of preventing MI and stroke were balanced by increased risk of major bleeding.

Obesity is associated with incident atrial fibrillation independent of gender: A meta-analysis.

BACKGROUND: The prevalence of obesity is increasing among the general population. Obesity is associated with increased risk of several cardiovascular conditions, which in turn may increase the risk for atrial fibrillation (AF). We performed a meta-analysis of cohort studies that examined the effect of obesity on the incidence of AF. In addition, we examined the effect of obesity on the incidence of AF stratified by gender. METHODS AND RESULTS: We searched the MEDLINE and EMBASE databases for studies evaluating the effect of obesity on AF. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model. Sixteen trials involving 587,372 subjects were included in the analysis. Obesity was defined as body mass index >30 kg/m2 . AF during follow-up developed in 5,751 of 91,031 (6.3%) obese subjects and in 15,346 of 496,341 (3.1%) nonobese subjects (RR = 1.51, 95% CI 1.35 to 1.68; P < 0.00001). Based on the pooled estimate across the studies, the effect of obesity on incident AF was similar in men (RR = 1.41, 95% 1.24 to 1.62; P < 0.00001) and women (RR = 1.53, 95% CI 1.19 to 1.97; P < 0.00001). CONCLUSION: Obesity is associated with an increased risk of new-onset AF in susceptible individuals. This effect appears to be consistent in both genders. Further studies are warranted to examine the impact of weight loss interventions on the risk of developing AF.

Implantable Cardioverter Defibrillators for Primary Prevention of Mortality in Patients With Nonischemic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) improve survival in patients with heart failure due to ischemic cardiomyopathy, but their benefit in nonischemic cardiomyopathy (NICM) has been recently questioned. We performed a meta-analysis of randomized clinical trials to examine the effect of ICDs on total mortality and arrhythmic death in patients with NICM. We also examined the impact of age and cardiac resynchronization therapy (CRT) on the relative effect of ICD compared to control. METHODS AND RESULTS: We searched the MEDLINE and EMBASE databases for randomized trials evaluating the effect of ICD versus control in patients with NICM. Hazard ratios (HR) with 95% confidence interval (CI) were calculated using a random effects model. Six trials involving 2,967 patients were included (ICD, n = 1,553; control, n = 1,414). Based on the pooled estimate across the six studies, the use of ICD was associated with a significant reduction in total mortality (HR = 0.78, 95% CI 0.66-0.92; P = 0.003), as well as arrhythmic death (HR = 0.46, 95% CI 0.29-0.71; P = 0.0005) compared to control. ICD decreased total mortality in younger patients compared to control (HR = 0.63, 95% CI 0.46-0.86; P = 0.004), but not in older patients (HR = 0.97, 95% CI 0.56-1.68; P = 0.92). In patients with CRT, ICD reduced total mortality compared to control (HR = 0.78, 95% CI 0.65-0.95; P = 0.02), but not in patients with CRT (HR = 0.71, 95% CI 0.40-1.26). CONCLUSIONS: ICDs decrease total mortality and arrhythmic deaths in patients with NICM. The benefit of ICD appears to be dependent on age and concomitant use of CRT.

Effect of implantable loop recorder-based continuous rhythm monitoring on incident atrial fibrillation and stroke: An updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: In patients with a history of stroke or those at high risk for developing stroke, a continuous rhythm monitoring strategy using an implantable loop recorder (ILR) is often performed to screen for atrial fibrillation (AF). OBJECTIVES: The purpose of this study was to perform a systematic review (MEDLINE and EMBASE) including randomized controlled trials comparing ILR-based continuous rhythm monitoring vs usual care in patients with a history of stroke or patients at high risk for developing stroke. METHODS: A meta-analysis was performed, and aggregate risk ratio (RR) and risk difference (RD) with 95% confidence interval (CI) were calculated. RESULTS: Four randomized controlled trials with 7237 patients (ILR 2114, non-ILR 5123) were included. ILR vs non-ILR was associated with increased detection of incident AF (RR 3.88; 95% CI 2.23-6.75; P <.00001; number needed to treat [NNT] = 7.7; I2 = 61%), increased appropriate initiation of anticoagulation (RR 2.29; 95% CI 2.07-2.55; P <.00001; NNT = 6.7; I2 = 0), and a 25% lower risk of developing stroke (RR 0.75; 95% CI 0.59-0.95]; P = .02; NNT = 100; I2 = 0%). In patients with history of stroke there was no difference in the risk of developing incident stroke (RR 0.83; 95% CI 0.61-1.14]; P = .25; I2 = 0%). CONCLUSION: Our meta-analysis showed that screening for AF with ILR is associated with increased detection of AF and increased initiation of appropriate anticoagulation therapy in patients with a history of stroke or those with risk factors for stroke. The benefit of stroke risk reduction with ILR remains unclear, and future studies focused on the inclusion of patients without a history of stroke are needed to elucidate this uncertainty.