Clinical outcomes in patients with atrial fibrillation treated with digoxin, according to the presence of heart failure: Insights from the MISOAC-AF trial.

BACKGROUND: Digoxin is widely used in atrial fibrillation (AF) and heart failure (HF). However, current evidence regarding its association with clinical outcomes is conflicting. AIM: To investigate the relationship between digoxin therapy and adverse outcomes in patients with AF, with or without HF, in a contemporary AF cohort. METHODS: We performed a retrospective analysis of data from 698 patients, who were followed over a median of 2.5 years. The primary outcome was all-cause mortality and the secondary outcome was all-cause hospitalization, in a time-to-event analysis. Propensity scores were used to derive matched populations, balanced on key baseline covariates. To limit potential confounding, inverse probability of treatment weighting (IPTW) analysis was performed. RESULTS: Among patients with HF, 39 (10.5%) were administered digoxin at baseline, whereas 331 (89.5%) were not. Digoxin administration was not associated with an increased risk of death (hazard ratio (HR) in the digoxin group, 1.21; 95% Confidence Interval (CI), 0.69 to 2.13, p = 0.50) or hospitalization of any cause (HR 1.15; 95% CI, 0.67 to 1.96; p = 0.60). Among patients without HF, 11 (3.5%) were administered digoxin, with neutral effects on all-cause mortality (HR: 3.25; 95% CI, 0.98 to 10.70), p = 0.06) and all-cause hospitalization (HR, 1.15; 95% CI, 0.67 to 1.96, p = 0.60). Qualitatively, consistent results were observed using IPTW. CONCLUSIONS: Among patients with AF, digoxin administration was not associated with an increased risk of death and hospitalization for any cause, irrespective of HF status.

Renal function and mortality in patients with atrial fibrillation.

AIM: The aim of this study is to examine the association of the presence of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) values with mortality in patients with atrial fibrillation. METHODS: This posthoc analysis of a randomized controlled trial consisted of hospitalized patients with atrial fibrillation who were followed up for a median of 2.7 years after discharge. Kaplan-Meier curves, multivariate Cox-regression and spline curves were utilized to assess the association of CKD, CKD stages 2-5 according to the KDOQI guidelines, and the continuum of eGFR values with the primary outcome of all-cause death, and the secondary outcome of cardiovascular mortality. RESULTS: Out of 1064 hospitalized patients with atrial fibrillation, 465 (43.7%) had comorbid CKD. The presence of CKD was associated with an increased risk for both all-cause and cardiovascular mortality following hospitalization [adjusted hazard ratio (aHR): 1.60; 95% confidence intervals (95% CIs): 1.25-2.05 and aHR: 1.74; 95% CI: 1.30-2.33, respectively]. The aHRs for all-cause mortality in CKD stages 2-5, as compared with CKD stage 1 were 2.18, 2.62, 4.20 and 3.38, respectively (all P < 0.05). In spline curve analyses, eGFR values lower than 50 ml/min/1.73 m2 were independent predictors of higher all-cause and cardiovascular mortality. CONCLUSION: In recently hospitalized patients with atrial fibrillation, the presence of CKD was independently associated with decreased survival, which was significant across CKD stages 2-5, as compared with CKD stage 1. Values of eGFR lower than 50 ml/min/1.73 m2 were incrementally associated with worse prognosis.

Education level predicts mortality and morbidity in hospitalised patients with atrial fibrillation.

AIM: Education level has been long considered a life-quality modifier, but little is known about its relation to life expectancy in patients with cardiovascular disease. This study aims to assess possible correlations between education level and survival in patients with atrial fibrillation (AF). METHODS: This retrospective cohort study used data from a randomised trial of 1082 hospitalised patients with AF (mean age of 75 ± 11 years) who were followed up after discharge. Patients were divided into three groups based on their education level: i) none or primary (NPEL), ii) secondary (SEL), and iii) tertiary education level (TEL). Kaplan-Meier curves and multivariable-adjusted hazard ratios (aHRs) were used to compare survival rates between groups. The primary outcome was all-cause mortality. The composite secondary outcome was cardiovascular mortality or any hospitalisation. RESULTS: After a median 31-month follow-up period, 289 (41.9%) patients died in the NPEL group, 75 (31.1%) in the SEL group, and 29 (19.1%) in the TEL group. The aHRs for all-cause mortality were 0.42 (95% CI, 0.27 to 0.66; p < 0.001) for the TEL group compared with the NPEL group, 0.55 (95% CI, 0.33 to 0.93; p = 0.02) for the TEL group compared with the SEL group, and 0.68 (95% CI, 0.50 to 0.93; p = 0.01) for the SEL group compared with the NPEL group. The corresponding aHRs for the composite secondary outcome were 0.36 (95% CI, 0.23 to 0.52; p < 0.001), 0.49 (95% CI, 0.29 to 0.80; p < 0.001), and 0.67 (95% CI, 0.50 to 9.91; p = 0.01). CONCLUSION: Higher education levels were independently associated with fewer fatal and non-fatal outcomes in recently hospitalised patients with AF.

Rhythm control versus rate control in patients with atrial fibrillation and heart failure across the left ventricular ejection fraction spectrum.

BACKGROUND: Rhythm control and rate control are both employed commonly in patients with atrial fibrillation (AF) and heart failure (HF), but limited real-world data exist on them. We aimed to compare outcomes between these two strategies across the left ventricular ejection fraction (LVEF) spectrum. MATERIALS AND METHODS: This retrospective cohort study used data from the randomized MISOAC-AF trial, including from patients with AF and coexistent HF who were hospitalized and followed up after discharge. At baseline, the patients were classified into pharmaceutical (or electrical cardioversion) rhythm control strategy or rate control treatment (b-blocker, digoxin, calcium channel blockers) groups. The primary outcome was all-cause mortality. Kaplan-Meier curves and multivariable-adjusted Cox regression were utilized to compare the two strategies. Spline curve models were used to demonstrate the results across the LVEF stratified spectrum. RESULTS: In total, 199 AF patients with HF were studied (mean age, 77 years). At discharge, 73 (36.7%) patients received rhythm control and 126 (63.3%) rate control treatment. After a median follow-up period of 31 months, 26 (35.6%) patients in the rhythm-control group died, as compared to 43 (33.3%) in the rate-control group (aHR: 1.29; 95% CI: 0.78-2.14; p = 0.31). The spline curves also revealed no difference in all-cause mortality favoring either strategy in any HF subtype across the nominally classified LVEF. CONCLUSION: The use of a pharmacological rhythm-control strategy was not associated with a survival advantage compared to the rate control strategy in recently hospitalized patients with AF and comorbid HF. More randomized trials and large studies are needed in the future to explore these results in each subgroup of HF patients.

Associations of Atrial Fibrillation Patterns With Mortality and Cardiovascular Events: Implications of the MISOAC-AF Trial.

AIM: This retrospective cohort study aimed to evaluate the prognostic implications of the distinct atrial fibrillation (AF) temporal patterns: first diagnosed, paroxysmal, and persistent or permanent AF. METHODS: In this post hoc analysis of the MISOAC-AF trial (NCT02941978), a total of 1052 patients with AF (median age 76 years), discharged from the cardiology ward between 2015 and 2018, were analyzed. Kaplan-Meier and Cox-regression analyses were performed to compare the primary outcome of all-cause mortality, the secondary outcomes of stroke, major bleeding and the composite outcome of cardiovascular (CV) mortality or hospitalization among AF patterns. RESULTS: Of patients, 121 (11.2%) had first diagnosed, 356 (33%) paroxysmal, and 575 (53.2%) persistent or permanent AF. During a median follow-up of 31 months (interquartile range 10 to 52 months), 37.3% of patients died. Compared with paroxysmal AF, patients with persistent or permanent AF had higher mortality rates (adjusted hazard ratio (aHR), 1.37; 95% confidence interval [CI], 1.08-1.74, P = .009), but similar CV mortality or hospitalization rates (aHR, 1.09; 95% CI, 0.91-1.31, P = .35). Compared with first diagnosed AF, patients with persistent or permanent AF had similar mortality (aHR, 1.26; 95% CI, 0.87-1.82, P = .24), but higher CV mortality or hospitalization rates (aHR, 1.35; 95% CI, 1.01-1.8, P = .04). Stroke and major bleeding events did not differ across AF patterns (all P > .05). CONCLUSIONS: In conclusion, in recently hospitalized patients with comorbid AF, the presence of persistent or permanent AF was associated with a higher incidence of mortality and morbidity compared with paroxysmal and first diagnosed AF.

Indications for percutaneous left atrial appendage occlusion in hospitalized patients with atrial fibrillation.

AIMS: Percutaneous left atrial appendage occlusion (LAAO) is an alternative nonpharmacological therapeutic option for stroke prevention in patients with NVAF. However, no data exist on potential LAAO candidates' prevalence among 'real-world' NVAF patients. This study aimed to investigate the indications for LAAO in hospitalized patients with comorbid nonvalvular atrial fibrillation (NVAF). METHODS: This is a post-hoc analysis of the MISOAC-AF (Motivational Interviewing to Support OAC-AF, ClinicalTrials.gov: NCT02941978), randomized controlled trial, which enrolled NVAF patients hospitalized for any reason in a tertiary cardiology department. In this analysis, patients with a history of major bleeding or stroke under OAC therapy were considered to have a strong indication for LAAO. RESULTS: A total of 980 patients with NVAF were studied (mean age 73.9 ±â€Š10.9 years, 54.7% men). Prior major bleeding occurred in 134 (13.7%) patients (intracranial bleeding in 1%, upper and lower gastrointestinal bleeding in 6.4 and 8.9%, respectively). A total of 58 (5.9%) patients experienced an embolic stroke while being treated using OAC. Overall, either of these events was prevalent in 173 (17.7%) patients, denoting a strong indication for LAAO. CONCLUSION: Almost one out of six patients hospitalized with comorbid NVAF may be considered eligible for percutaneous LAAO for stroke prevention.Trial Identification: NCT02941978, https://clinicaltrials.gov/ct2/show/NCT02941978.

Τhe association of heart failure across left ventricular ejection fraction with mortality in atrial fibrillation.

AIMS: The aim of this study is to investigate the prognostic implications of the presence of heart failure (HF) across the range of left ventricular ejection fraction (LVEF) in patients with comorbid atrial fibrillation (AF). METHODS AND RESULTS: We conducted a retrospective cohort study of 1063 patients (median age 76 years), discharged from the cardiology ward with a primary or secondary diagnosis of AF between 2015 and 2018. We used Cox proportional-hazards and spline models to examine the association of the presence of HF, across the range of LVEF, with the primary outcome of all-cause mortality. HF was documented in 52.9% of patients at baseline. During a median follow-up of 31 months (interquartile range 10 to 52 months), 37.3% of patients died. The presence of HF was associated with a significantly higher risk of mortality [adjusted hazard ratio (aHR) 2.17; 95% confidence interval (CI), 1.70 to 2.77; P < 0.001], which was evident across HF with reduced (aHR 3.03; 95% CI 2.41 to 4.52), mid-range (aHR 2.08; 95% CI 1.47 to 2.94), and preserved LVEF (aHR 1.94; 95% CI 1.47 to 2.55). Among patients with HF, the spline curve depicted a non-linear association between LVEF and the risk of death, in which there was a steep and progressive increase in mortality for every 5% reduction in LVEF below 25% (aHR 1.97, 95% CI 1.04 to 3.73, P = 0.04). CONCLUSIONS: In patients with AF who were discharged from the hospital, the presence of HF at baseline was independently associated with a twofold risk of death, which was significant across LVEF-classified HF subtypes. Among patients with AF and HF, the risk of death rose significantly as LVEF was reduced below 25%.

Prognostic significance of diabetes mellitus in patients with atrial fibrillation.

BACKGROUND: There are limited data on the association of diabetes mellitus (DM) and levels of glycated hemoglobin (HbA1c) with outcomes in patients with atrial fibrillation (AF). METHODS: This retrospective cohort study included patients who were recently hospitalized with a primary or secondary diagnosis of AF from December 2015 through June 2018. Kaplan-Meier curves and Cox-regression adjusted hazard ratios (aHR) were calculated for the primary outcome of all-cause mortality and for the secondary outcomes of cardiovascular (CV) mortality and the composite outcome of CV death or hospitalization. Competing-risk regression analyses were performed to calculate the cumulative risk of stroke, major bleeding, AF- or HF-hospitalizations adjusted for the competing risk of all-cause death. Spline curve models were fitted to investigate associations of HbA1c values and mortality among patients with AF and DM. RESULTS: In total 1109 AF patients were included, of whom 373 (33.6%) had DM. During a median follow-up of 2.6 years, 414 (37.3%) patients died. The presence of DM was associated with a higher risk of all-cause mortality (aHR = 1.40 95% confidence intervals [CI] 1.11-1.75), CV mortality (aHR = 1.39, 95% CI 1.07-1.81), sudden cardiac death (aHR = 1.73, 95% CI 1.19-2.52), stroke (aHR = 1.87, 95% CI 1.01-3.45) and the composite outcome of hospitalization or CV death (aHR = 1.27, 95% CI 1.06-1.53). In AF patients with comorbid DM, the spline curves showed a positive linear association between HbA1c levels and outcomes, with values 7.6-8.2% being independent predictors of increased all-cause mortality, and values < 6.2% predicting significantly decreased all-cause and CV mortality. CONCLUSIONS: The presence of DM on top of AF was associated with substantially increased risk for all-cause or CV mortality, sudden cardiac death and excess morbidity. HbA1c levels lower than 6.2% were independently related to better survival rates suggesting that optimal DM control could be associated with better clinical outcomes in AF patients with DM.