Risk of arterial thromboembolism, bleeding and mortality in atrial fibrillation patients with comorbid cancer: A systematic review and meta-analysis.

AIMS: Atrial fibrillation (AF) and cancer often co-exist. Each has been associated with an increased risk of morbidity and mortality. The aim of this meta-analysis was to synthesize available data regarding the incidence of arterial thromboembolism (TE), bleeding, and all-cause mortality in patients with AF with or without cancer. METHODS: Literature search was conducted in PubMed, Ovid MEDLINE, WebOfScience, Scopus, CENTRAL, OpenGrey, and EThOS databases to identify studies that included patients with AF and accounted for cancer status with the incidence of TE (ischemic stroke, transient ischemic attack, or arterial thrombosis), major or clinically relevant non-major bleeding, and all-cause mortality. A random-effects meta-analysis was used. RESULTS: Overall, 17 studies were included (3,149,547 patients). The risk of TE was similar in patients with AF with comorbid cancer compared with that in AF alone (pooled odds ratio [pOR] 0.97, 95% Confidence Interval [CI] 0.85-1.11, I2 = 87%). Major or clinically relevant non-major bleeding (pOR 1.65, 95% CI 1.35-2.02, I2 = 98%) and all-cause death (pOR 2.17, 95% CI 1.83-2.56, I2 = 98%) were significantly higher in patients with AF with cancer than in patients with AF only. The history of TE and hypertension and mean age were significant moderators of TE risk. CONCLUSION: In patients with AF, the presence of cancer is associated with a similar risk of TE as well as an increased risk of bleeding and all-cause death compared with the absence of cancer.

Cardioselective versus Non-Cardioselective Beta-Blockers and Outcomes in Patients with Atrial Fibrillation and Chronic Obstructive Pulmonary Disease.

Background: Atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) have been independently associated with increased mortality; however, there is no evidence regarding beta-blocker cardioselectivity and long-term outcomes in patients with AF and concurrent COPD. Methods: This post hoc analysis of the MISOAC-AF randomized trial (NCT02941978) included patients hospitalized with comorbid AF. At discharge, all patients were classified according to the presence of COPD; patients with COPD on beta-blockers were classified according to beta-blocker cardioselectivity. Adjusted hazard ratios (aHRs) were calculated by using multivariable Cox regression models. The primary outcome was all-cause mortality, and the secondary outcomes were cardiovascular mortality and hospitalizations. Results: Of 1103 patients with AF, 145 (13%) had comorbid COPD. Comorbid COPD was associated with an increased risk of all-cause (aHR, 1.33; 95% confidence interval (CI), 1.02 to 1.73) and cardiovascular mortality (aHR 1.47; 95% CI, 1.10 to 1.99), but not with increased risk of hospitalizations (aHR 1.10; 95% CI, 0.82 to 1.48). The use of cardioselective versus non-cardioselective beta-blockers was associated with similar all-cause mortality (aHR 1.10; 95% CI, 0.63 to 1.94), cardiovascular mortality (aHR 1.33; 95% CI, 0.71 to 2.51), and hospitalizations (aHR 1.65; 95% CI 0.80 to 3.38). Conclusions: In recently hospitalized patients with AF, the presence of COPD was independently associated with increased risk of all-cause and cardiovascular mortality. No difference between cardioselective and non-cardioselective beta-blockers, regarding clinical outcomes, was identified.

Polypharmacy and Major Adverse Events in Atrial Fibrillation.

ABSTRACT: Patients with atrial fibrillation (AF) often receive multiple medications daily. The purpose of this study was to examine the prognostic implications of polypharmacy in patients with AF. This is a retrospective post hoc analysis of 1113 AF patients, enrolled in a randomized trial during an acute hospitalization (MISOAC-AF, NCT02941978). The presence of polypharmacy (use of >4 drugs daily) was assessed at hospital discharge. Regression analyses were performed to identify clinical predictors of polypharmacy and compare the outcomes of patients with or without confirmed polypharmacy. The coprimary outcomes were all-cause and cardiovascular (CV) mortality. Among patients with polypharmacy, the difference in the risk of mortality was also assessed per each added drug as a numeric variable. Polypharmacy was found in 36.9% of participants. Dyslipidemia, coronary artery disease, lower left ventricular ejection fraction, and higher glomerular filtration rates were independent predictors of polypharmacy. Polypharmacy was an independent predictor for all-cause death (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI]: 1.01-1.64) and CV death (aHR: 1.39, 95% CI: 1.05-1.84). Among patients with polypharmacy, each additional concomitant medication was independently associated with a 4% increased risk of all-cause mortality (aHR = 1.04, 95% CI: 1.00-1.08) and a 5% increased risk of CV mortality (aHR = 1.05, 95% CI: 1.00-1.10). Polypharmacy was common among patients with AF hospitalized in a tertiary hospital and was incrementally associated with higher rates of mortality.

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.

Impact of religious fasting on metabolic and hematological profile in both dyslipidemic and non-dyslipidemic fasters.

BACKGROUND/OBJECTIVES: Religious fasting (RF) is practiced annually by millions of Christian and Muslim followers worldwide. Scarce data exist on the impact of RF on the metabolic and hematological profile of individuals with or without dyslipidemia. SUBJECTS/METHODS: The present study included: (i) 60 Greek Orthodox participants, 30 with dyslipidemia and 30 without dyslipidemia, who abstained from meat, fish and dairy products for seven consecutive weeks, and (ii) 15 young, non-dyslipidemic Muslim participants abstaining totally from food and liquid from dawn till sunset during 30 days. Biochemical (iron, ferritin, vitamin B12, calcium, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglyceride and fasting glucose) and hematological (hemoglobin, hematocrit) serum blood test results of study participants were measured pre- and post- RF (at weeks 0 and 7 for Orthodox participants and at weeks 0 and 4 for Muslim participants). RESULTS: In dyslipidemic and non-dyslipidemic Orthodox participants, a significant reduction of fasting glucose, HDL, LDL and TC levels was found post-RF. Hemoglobin, hematocrit, iron and ferritin levels were significantly increased, while post-RF vitamin B12 and calcium levels were substantially decreased. Subanalysis between dyslipidemic and non-dyslipidemic Orthodox participants revealed a greater decrease of cholesterol levels in the former. In Muslim participants, triglyceride, LDL and total cholesterol levels were increased post-RF (all p values < 0.05). CONCLUSIONS: Our study adds to the existing literature evidence about the significant impact of RF on metabolic and hematological profiles of Orthodox and Muslim followers. The prevention of calcium and B12 deficiency during Orthodox RF by supplement consumption as well as the protection from dehydration and dysregulation of lipid metabolism during Ramadan RF should concern both clinicians and dietician nutritionists. Nevertheless, studies with larger sample size and/or long-term follow-up are warranted before reaching definite conclusions about the effects of RF on human health.

Oral anticoagulation patterns and prognosis in octogenarian patients with atrial fibrillation.

The relationship between oral anticoagulants (OACs) and prognosis in elderly patients with atrial fibrillation (AF) has not been adequately explored. In this retrospective cohort study, we identified subjects aged over 80 from a database of 1140 AF patients discharged from the cardiology ward of a single tertiary center between 2015 and 2018. We examined the OAC treatment of octogenarian patients at discharge [VKA (vitamin K antagonist), NOAC (non-vitamin K antagonist oral anticoagulant), no OAC treatment]. We analyzed follow-up data of patients on OAC at discharge. The primary endpoint was all-cause death. The secondary endpoint was the incidence of stroke and major bleeding. The association of NOAC versus VKA treatment with these endpoints was assessed with multivariable Cox regression, using the VKA group as reference. A total of 330 octogenarian patients with AF were included with a mean (± SD) age of 83.9 ± 3.5 years. At discharge, 53.3% received a NOAC, 30% a VKA, and 16.7% no OAC. Patients on OAC were followed-up over a median of 2.6-years . The adjusted risk of all-cause death was not different in the NOAC group, compared with the VKA group (hazard ratio [HR], 0.72; 95% confidence intervals [CI] 0.50-1.03; P = 0.07). The risk of stroke or major bleeding was not different either (all P > 0.05). In conclusion, in this cohort of post-discharge octogenarian patients with AF, the risk for all-cause death was similar in NOAC versus VKA users, after adjustment for baseline covariates. No differences in stroke and major bleeding events among these treatment groups were revealed.

"Maternal diabetes mellitus and its impact on the risk of delivering a child with congenital heart disease: a systematic review and meta-analysis".

AIM: Maternal pregestational diabetes mellitus (PGDM), type 1 or type 2, has been established as a potential risk factor for congenital heart disease (CHD). At the same time, the correlation between gestational diabetes mellitus (GDM) and increased risk of CHD has not been yet fully elucidated. The objective of this systematic review and meta-analysis (PROSPERO number: CRD42020182390) was to analyze the existing evidence on PGDM and to attempt to fill, to the best of our ability, the remaining knowledge gap in the association of GDM with CHD. MATERIALS AND METHODS: Two authors have independently searched the Pubmed/Medline, Scopus, Cochrane, Web of Science, and Theses Global databases with keywords and Boolean operators. The search yielded 9333 relevant articles, which were later screened for eligibility. Original peer-reviewed (case-control or cohort) studies were included if they were published in English between 1997 and 2020. Thirteen studies on mothers with PGDM and seven studies on mothers with GDM were finally included in our meta-analysis to investigate the association of maternal diabetes with the risk of delivering a child with CHD. The selected studies were all assessed for their methodological quality using the Newcastle-Ottawa scale. Associations with p < .05 were considered statistically significant. RESULTS: Our meta-analysis (I2 > 75%, total population: n = 12,461,586) of 79,476 women with PGDM and 160,893 with GDM produced an odds ratio of 3.48 (2.36-4.61) and 1.55 (1.48-1.61), respectively. Additionally, we did not find any noticeable difference in the risk for CHD among diabetic women living in the USA and Europe. Nevertheless, it still needs to be clarified, whether or not the gestational diabetic population includes undiagnosed women with preexisting diabetes, which might account for the increased risk of delivering a child with CHD in women classified as suffering from GDM. CONCLUSION: While both GDM and PGDM seem to significantly increase the risk of CHD in comparison with the general population, PDGM appears to have a greater association with CHD, being correlated with a 3.5-fold increase in the risk of malformation. Preconceptional and gestational diabetes care are, therefore, essential to mitigate the adverse effect of hyperglycemia on fetal heart formation during pregnancy.

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.