Systematic review and meta-analysis of mortality and digoxin use in atrial fibrillation

Background: There is growing controversy regarding the association between digoxin and mortality in atrial fibrillation (AF). The aim of this analysis was to systematically review digoxin use and risk of mortality in patients with AF. Methods: MEDLINE, EMBASE, GoogleScholar, CINAHL, meeting abstracts, presentations, and Cochrane central databases were searched from inception through December 2014, without language restrictions. For a study to be selected, it had to report the risk of mortality associated with digoxin use in AF patients as an outcome measure. Data were extracted by 2 independent authors. Evidence tables were created. Results: A total of 16 studies (6 post hoc analyses of randomized controlled trials) with 111,978 digoxin users and 389,643 non-digoxin users were included. In a random effects model, patients treated with digoxin had a 27% increased risk of all-cause mortality (pooled HR 1.27; 95% CI 1.19–1.36) and 21% increased risk of cardiovascular mortality (pooled HR 1.21; 95% CI 1.12–1.30) compared with those who did not use digoxin. In a random effects model, the association of digoxin with all-cause mortality was stronger for AF patients without heart failure (pooled HR 1.47; 95% CI 1.25–1.73) than AF patients with heart failure (pooled HR 1.21; 95% CI 1.07–1.36, interaction p = 0.06). Conclusions: Digoxin use in AF is associated with increased risk of all-cause and cardiovascular mortalities. The effect size was larger for AF patients without heart failure than AF patients with heart failure. The study suggests further directed analyses to study the effect that is suggested by this meta-analysis, especially in AF without heart failure.

Brachial Flow-Mediated Dilation and Incident Atrial Fibrillation The Multi-Ethnic Study of Atherosclerosis

Objective—It is unknown whether endothelial dysfunction precedes atrial fibrillation (AF) development. The objective of this study was to examine the association of brachial flow-mediated dilation (FMD) with incident AF. Approach and Results—A total of 2936 participants (mean age, 61±9.9 years; 50% women; 66% nonwhites) from the Multi-Ethnic Study of Atherosclerosis with available ultrasound brachial FMD measurements who were free of baseline AF were included in this analysis. Baseline (2000–2002) FMD was computed from the percentage difference (%FMD) in brachial artery diameter and maximum diameter during measured vasodilator response. AF was ascertained from hospitalization data including Medicare claims during a median follow-up of 8.5 years. Probability-weighted Cox proportional-hazards regression was used to compute hazard ratios and 95% confidence intervals for the association between FMD as a continuous variable (%FMD values per 1-SD increase) and incident AF. Incident AF was detected in 137 (4.7%) participants. Those with %FMD values below the sex-specific median value (median %FMD; men, 3.6%; women, 4.2%; incidence rate per 1000 person-years, 7.3; 95% confidence interval, 5.9–9.0) were more likely to develop AF than people whose %FMD values were above the median value (incidence rate per 1000 person-years, 4.5; 95% confidence interval, 3.4–5.8; log-rank P=0.0043). In a multivariable Cox regression analysis, each 1-SD increase in %FMD values (SD, 2.8%) was associated with less incident AF (hazard ratio, 0.84; 95% confidence interval, 0.70–0.99). These results were consistent across subgroups stratified by age, sex, and race/ethnicity. Conclusions—Smaller brachial FMD values are associated with higher rates of AF, sugge

Racial Differences in Survival among Hemodialysis Patients after Coronary Artery Bypass Grafting

The aim of this study was to examine racial differences in long-term survival among hemodialysis patients after coronary artery bypass grafting (CABG). To our knowledge this has not been previously addressed in the literature. Black and white hemodialysis patients undergoing first-time, isolated CABG procedures between 1992 and 2011 were compared. Survival probabilities were computed using the Kaplan-Meier product-limit method and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. A total of 207 (2%) patients were on hemodialysis at the time of CABG. White (n = 80) hemodialysis patients had significantly decreased 5-year survival compared with black (n = 127) patients (adjusted HR = 1.9, 95% CI = 1.2–2.8). Our finding provides useful outcome information for surgeons, primary care providers, and their patients

Electrocardiographic Advanced Interatrial Block and Atrial Fibrillation Risk in the General Population

Although advanced inter-atrial block (aIAB) is an established electrocardiographic phenotype, its prevalence, incidence, and prognostic significance in the general population are unclear. We examined the prevalence, incidence, and prognostic significance of aIAB in 14,625 (mean age=54±5.8 years; 26% black; 55% female) participants from the Atherosclerosis Risk In Communities (ARIC) study. aIAB was detected from digital electrocardiograms recorded during 4 study visits (1987–1989, 1990–1992, 1993–1995, and 1996–1998). Risk factors for the development of aIAB were examined using multivariable Poisson regression models with robust variance estimates. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between aIAB, as a time-dependent variable, and atrial fibrillation (AF). AF was ascertained from study electrocardiogram data, hospital discharge records, and death certificates thorough 2010. A total of 69 (0.5%) participants had aIAB at baseline and 193 (1.3%) developed aIAB during follow-up. The incidence rate for aIAB was 2.27 (95%CI=1.97, 2.61) per 1000 person-years. Risk factors for aIAB development included age, male sex, white race, antihypertensive medication use, low-density lipoprotein cholesterol, body mass index, and systolic blood pressure. In a Cox regression analysis adjusted for socio-demographics, cardiovascular risk factors, and potential confounders, aIAB was associated with an increased risk for AF (HR=3.09, 95%CI=2.51, 3.79). In conclusion, aIAB is not uncommon in the general population. Risk factors for developing aIAB are similar to those for AF and the presence of aIAB is associated with an increased risk for AF

Risk-Adjusted Survival after Coronary Artery Bypass Grafting: Implications for Quality Improvement

Mortality represents an important outcome measure following coronary artery bypass grafting. Shorter survival times may reflect poor surgical quality and an increased number of costly postoperative complications. Quality control efforts aimed at increasing survival times may be misleading if not properly adjusted for case-mix severity. This paper demonstrates how to construct and cross-validate efficiency-outcome plots for a specified time (e.g., 6-month and 1-year survival) after coronary artery bypass grafting, accounting for baseline cardiovascular risk factors. The application of this approach to regional centers allows for the localization of risk stratification rather than applying overly broad and non-specific models to their patient populations

Peripheral Arterial Disease and Risk of Atrial Fibrillation and Stroke: The Multi�Ethnic Study of Atherosclerosis

Background Peripheral arterial disease (PAD) shares several risk factors with atrial fibrillation (AF), and persons with PAD have an increased risk of stroke. It is unclear if PAD is associated with an increased risk for AF and whether this potential association explains the increased risk of stroke observed in those with PAD. Methods and Results We examined the association between PAD, measured by ankle�brachial index (ABI), and incident AF and incident stroke, separately, in 6568 participants (mean age 62±10 years, 53% women, 62% nonwhite) from the Multi�Ethnic Study of Atherosclerosis (MESA). ABI values 1.4 defined PAD. AF was ascertained through review of hospital discharge records and from Medicare claims data until December 31, 2010. An independent adjudication committee ascertained stroke events. Cox regression was used to estimate hazard ratios and 95% CIs for the association between PAD and AF and stroke. Over a median follow�up of 8.5 years, 301 (4.6%) participants developed AF and 140 (2.1%) developed stroke. In a model adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, PAD was associated with an increased risk of AF (hazard ratio 1.5, 95% CI 1.1 to 2.0). In a similar model, PAD was associated with incident stroke (hazard ratio 1.7, 95% CI 1.1 to 2.5), and the magnitude of risk was not different after inclusion of AF as a time�dependent covariate (hazard ratio 1.7, 95% CI 1.1 to 2.5). Conclusions PAD is associated with an increased risk of AF and stroke in MESA. Potentially, the relationship between PAD and stroke is not mediated by AF

Electrocardiographic left atrial abnormality and stroke subtype in the atherosclerosis risk in communities study: Left Atrial Abnormality and Stroke Subtype

To assess the relationship between abnormally increased P-wave terminal force in lead V1 (PTFV1), an electrocardiographic (ECG) marker of left atrial abnormality, and incident ischemic stroke subtypes. We hypothesized that associations would be stronger with non-lacunar stroke, since we expected left atrial abnormality to reflect the risk of thromboembolism rather than in-situ cerebral small-vessel occlusion

Monoamine Oxidase is a Major Determinant of Redox Balance in Human Atrial Myocardium and is Associated With Postoperative Atrial Fibrillation

BACKGROUND: Onset of postoperative atrial fibrillation (POAF) is a common and costly complication of heart surgery despite major improvements in surgical technique and quality of patient care. The etiology of POAF, and the ability of clinicians to identify and therapeutically target high-risk patients, remains elusive. METHODS AND RESULTS: Myocardial tissue dissected from right atrial appendage (RAA) was obtained from 244 patients undergoing cardiac surgery. Reactive oxygen species (ROS) generation from multiple sources was assessed in this tissue, along with total glutathione (GSHt) and its related enzymes GSH-peroxidase (GPx) and GSH-reductase (GR). Monoamine oxidase (MAO) and NADPH oxidase were observed to generate ROS at rates 10-fold greater than intact, coupled mitochondria. POAF risk was significantly associated with MAO activity (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=1.8, 95% confidence interval [CI]=0.84 to 4.0; Q3: ARR=2.1, 95% CI=0.99 to 4.3; Q4: ARR=3.8, 95% CI=1.9 to 7.5; adjusted Ptrend=0.009). In contrast, myocardial GSHt was inversely associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=0.93, 95% confidence interval [CI]=0.60 to 1.4; Q3: ARR=0.62, 95% CI=0.36 to 1.1; Q4: ARR=0.56, 95% CI=0.34 to 0.93; adjusted Ptrend=0.014). GPx also was significantly associated with POAF; however, a linear trend for risk was not observed across increasing levels of the enzyme. GR was not associated with POAF risk. CONCLUSIONS: Our results show that MAO is an important determinant of redox balance in human atrial myocardium, and that this enzyme, in addition to GSHt and GPx, is associated with an increased risk for POAF. Further investigation is needed to validate MAO as a predictive biomarker for POAF, and to explore this enzyme's potential role in arrhythmogenesis

Atrial Fibrillation and Risk of ST-Segment-Elevation Versus Non-ST-Segment-Elevation Myocardial Infarction: The Atherosclerosis Risk in Communities (ARIC) Study

It has recently been reported that atrial fibrillation [AF] is associated with an increased risk of myocardial infarction [MI]. However, the mechanism underlying this association is currently unknown. Further study of the relationship of AF with type of MI [ST elevation MI (STEMI) vs. non-ST elevation MI [NSTEMI] might shed light on the potential mechanisms