Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry.

BACKGROUND: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. METHODS: From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. RESULTS: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively). CONCLUSIONS: Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.

Cardiovascular Events According to Inhaler Therapy and Comorbidities in Chronic Obstructive Pulmonary Disease.

Background: COPD coexists with many concurrent comorbidities. Cardiovascular complications are deemed to be major causes of death in COPD. Although inhaler therapy is the main therapeutic intervention in COPD, cardiovascular events accompanying inhaler therapy require further investigation. Therefore, this study aimed to investigate new development of cardiovascular events according to each inhaler therapy and comorbidities. Methods: This study analyzed COPD patients (age ≥ 40 years, N = 199,772) from the Health Insurance Review and Assessment Service (HIRA) database in Korea. The development of cardiovascular events, from the index date to December 31, 2020, was investigated. The cohort was eventually divided into three arms: the LAMA/LABA group (N = 28,322), the ICS/LABA group (N = 11,812), and the triple group (LAMA/ICS/LABA therapy, N = 6174). Results: Multivariable Cox analyses demonstrated that, compared to ICS/LABA therapy, triple therapy was independently associated with the development of ischemic heart disease (HR: 1.22, 95% CI: 1.04-1.43), heart failure (HR: 1.45, 95% CI: 1.14-1.84), arrhythmia (HR: 1.72, 95% CI: 1.41-2.09), and atrial fibrillation/flutter (HR: 2.31, 95% CI: 1.64-3.25), whereas the LAMA/LABA therapy did not show a significant association. Furthermore, emergency room visit during covariate assessment window was independently associated with the development of ischemic heart disease, heart failure, arrhythmia, and atrial fibrillation/flutter (p < 0.05). Conclusion: Our data suggest that cardiovascular risk should be considered in COPD patients receiving triple therapy, despite the confounding bias resulting from disparities in each group.

Economic analyses in cardiac electrophysiology: from clinical efficacy to cost utility.

Cardiac electrophysiology is an evolving field that relies heavily on costly device- and catheter-based technologies. An increasing number of patients with heart rhythm disorders are becoming eligible for cardiac interventions, not least due to the rising prevalence of atrial fibrillation and increased longevity in the population. Meanwhile, the expansive costs of healthcare face finite societal resources, and a cost-conscious approach to new technologies is critical. Cost-effectiveness analyses support rational decision-making in healthcare by evaluating the ratio of healthcare costs to health benefits for competing therapies. They may, however, be subject to significant uncertainty and bias. This paper aims to introduce the basic concepts, framework, and limitations of cost-effectiveness analyses to clinicians including recent examples from clinical electrophysiology and device therapy.

Identification of recurrent atrial fibrillation using natural language processing applied to electronic health records.

AIMS: This study aimed to develop and apply natural language processing (NLP) algorithms to identify recurrent atrial fibrillation (AF) episodes following rhythm control therapy initiation using electronic health records (EHRs). METHODS AND RESULTS: We included adults with new-onset AF who initiated rhythm control therapies (ablation, cardioversion, or antiarrhythmic medication) within two US integrated healthcare delivery systems. A code-based algorithm identified potential AF recurrence using diagnosis and procedure codes. An automated NLP algorithm was developed and validated to capture AF recurrence from electrocardiograms, cardiac monitor reports, and clinical notes. Compared with the reference standard cases confirmed by physicians' adjudication, the F-scores, sensitivity, and specificity were all above 0.90 for the NLP algorithms at both sites. We applied the NLP and code-based algorithms to patients with incident AF (n = 22 970) during the 12 months after initiating rhythm control therapy. Applying the NLP algorithms, the percentages of patients with AF recurrence for sites 1 and 2 were 60.7% and 69.9% (ablation), 64.5% and 73.7% (cardioversion), and 49.6% and 55.5% (antiarrhythmic medication), respectively. In comparison, the percentages of patients with code-identified AF recurrence for sites 1 and 2 were 20.2% and 23.7% for ablation, 25.6% and 28.4% for cardioversion, and 20.0% and 27.5% for antiarrhythmic medication, respectively. CONCLUSION: When compared with a code-based approach alone, this study's high-performing automated NLP method identified significantly more patients with recurrent AF. The NLP algorithms could enable efficient evaluation of treatment effectiveness of AF therapies in large populations and help develop tailored interventions.

Eicosapentaenoic Acid: between Cardiovascular Benefits and the Risk of Atrial Fibrillation.

In recent years, scientific research has increasingly focused on the cardiovascular benefits of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements. The most promising results emerged from the new trials on a high-dose eicosapentaenoic acid (EPA)-only approach, instead of the previously prescribed therapy with EPA + docosahexaenoic acid (DHA). The evidence of the reduction of cardiovascular events in patients at high cardiovascular risk with EPA is intriguing. However, physicians have expressed concern about the potential high risk of atrial fibrillation (AF) occurrence due to such an approach. This study aims to investigate the current evidence on the cardiovascular benefits of EPA and its association with atrial arrhythmogenesis. Current guidelines consider EPA (as IPE) treatment for selected patients but with no specific indication regarding AF risk evaluation. We propose a flowchart that could be a starting point for the future development of an algorithm to help clinicians to prescribe EPA safely and effectively, especially in patients at high risk of incipient AF.

Association Between Atrial Fibrillation and Diabetes-Related Complications: A Nationwide Cohort Study.

OBJECTIVE: This study aimed to investigate the associations between concurrent atrial fibrillation and diabetes-related complications among patients with diabetes. RESEARCH DESIGN AND METHODS: This nationwide observational cohort study used the health checkup database from the Korean National Health Insurance Service. Patients diagnosed with diabetes who underwent health checkups between 2009 and 2012 were investigated. The patients with atrial fibrillation were matched in a 1:5 ratio with those without atrial fibrillation using propensity scores. Study outcomes included macrovascular, microvascular (diabetic retinopathy and diabetic nephropathy), and diabetic foot complications. The risks of clinical outcomes were measured using hazard ratios (HRs) with 95% CIs. RESULTS: A total of 65,760 patients with diabetes were analyzed (54,800 without atrial fibrillation and 10,960 with atrial fibrillation). After well-balanced propensity score matching, atrial fibrillation was associated with significantly higher risks of macrovascular complications (HR 1.12, 95% CI 1.09-1.16), diabetic nephropathy (HR 1.23, 95% CI 1.16-1.30), and diabetic foot complications (HR 1.13, 95% CI 1.09-1.17) compared with no atrial fibrillation, while the risk of diabetic retinopathy was comparable (HR 0.99, 95% CI 0.96-1.03). Patients with atrial fibrillation had a significantly higher risk of diabetic foot amputation (HR 4.12, 95% CI 1.98-8.56). CONCLUSIONS: Among patients with diabetes, concurrent atrial fibrillation was associated with increased risks for diabetes-related macrovascular complications, diabetic nephropathy, and diabetic foot. Such patients require holistic management to reduce the risk of adverse outcomes.

Global Burden of Atrial Fibrillation and Flutter by National Income: Results From the Global Burden of Disease 2019 Database.

Background Atrial fibrillation (AF) and atrial flutter (AFL) are common conditions that can lead to significant morbidity and death. We aimed to understand the distribution and disparities of the global burden of AF/AFL as well as the underlying risk factors. Methods and Results Data on the AF/AFL burden from the Global Burden of Disease data set were analyzed for the years 1990 to 2019, with countries grouped into low, lower-middle, upper-middle, and high national income classes according to World Bank categories. Data were supplemented with World Health Organization and World Bank information. The prevalence of AF/AFL has more than doubled (+120.7%) since 1990 in all income groups, though with a larger increment in middle-income countries (+146.6% in lower-middle- and +145.2% in upper-middle-income countries). In absolute numbers, 63.4% of AF/AFL cases originate from upper-middle-income countries, although the relative prevalence is highest in high-income countries. Prevalence of AF/AFL appears to be correlated with medical doctor rate and life expectancy. The most relevant AF/AFL risk factors are unevenly distributed among income classes, with elevated blood pressure as the only risk factor that becomes less common with increasing income. The development of these risk factors differed over time. Conclusions The global burden of AF/AFL is increasing in all income groups and is more pronounced in middle-income countries, with further growth to be expected. Underdiagnosis of AF/AFL in low- and middle-income countries may contribute to lower reported prevalence. The risk factor distribution varies between income groups.

Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation.

BACKGROUND: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial. OBJECTIVES: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF. METHODS: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS: Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively. CONCLUSIONS: In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.

The efficacy of direct oral anticoagulants in patients on concomitant treatment with levetiracetam.

Guidelines do not support the combination of direct oral anticoagulants (DOACs) and the antiepileptic drug levetiracetam, due to potential relevant P-glycoprotein (P-gp) mediated interaction that might result in decreased DOACs concentrations and increased thromboembolic risk. However, there is no systematic data on the safety of this combination. The aim of this study was to find patients concurrently treated with levetiracetam and DOAC, assess their plasma concentrations of DOAC, and the incidence of thromboembolic events. From our registry of patients on anticoagulation drugs we identified 21 patients concomitantly treated with levetiracetam and DOAC, 19 patients with atrial fibrillation and two patients with venous thromboembolism. Eight patients received dabigatran, 9 apixaban and 4 rivaroxaban. For each subject blood samples were collected for determination of trough DOAC and trough levetiracetam concentrations. The average age was 75 ± 9 years, 84% were males, HAS-BLED score was 1.8 ± 0.8, and in patients with atrial fibrillation CHA2DS2-VASc score was 4.6 ± 2.0. The average trough concentration level of levetiracetam was 31.0 ± 34.5 mg/L. Median trough concentrations of DOACs were for dabigatran 72 (range 25-386) ng/mL, for rivaroxaban 47 (range 19-75) ng/mL, and for apixaban 139 (range 36-302) ng/mL. During the observation period of 1388 ± 994 days none of the patients suffered a thromboembolic event. Our results did not demonstrate a reduction in DOACs plasma levels during levetiracetam treatment, suggesting that levetiracetam could not be an important P-gp inducer in humans. DOAC in combination with levetiracetam remained effective therapy to protect against thromboembolic events.

ORal anticoaGulants in diAbetic and Nondiabetic patients with nOn-valvular atrial fibrillatioN (ORGANON).

BACKGROUND: Diabetes represents a pro-thrombotic condition. OBJECTIVES: The primary objective was to evaluate the effects of Vitamin K Antagonist (VKA) compared to direct oral anticoagulants (DOACs) in diabetic and nondiabetic patients with non-valvular atrial fibrillation, newly diagnosed. The secondary objective was to evaluate the effects on the risk of bleeding. METHODS: We enrolled 300 patients with newly diagnosed atrial fibrillation. One hundred and sixteen patients were taking warfarin, 31 acenocumarol, 22 dabigatran, 80 rivaroxaban, 34 apixaban, and 17 edoxaban. We evaluated: anthropometric parameters, glycated hemoglobin (HbA1c), fasting and post-prandial glucose (FPG, and PPG), lipid profile, Lp(a), small and dense low-density lipoprotein (SD-LDL), oxidized LDL (Ox-LDL), I-troponin (I-Tn), creatinine, transaminases, iron, red blood cells (RBC); hemoglobin (Hb), platelets (PLT), fibrinogen, D-dimer, anti-thrombin III, C-reactive protein (Hs-CRP), Metalloproteinases-2 (MMP-2), Metalloproteinases-9 (MMP-9), and incidence of bleeding. RESULTS: We did not record any differences among nondiabetic patients between VKA and DOACs. However, when we considered diabetic patients, we found a slight, but significant improvement of triglycerides and SD-LDL. As regards incidence of bleeding, minor bleeding was more frequent in VKA diabetic group compared to DOACs diabetic group; furthermore, the incidence of major bleeding was higher with VKA in nondiabetic and diabetic group, compared to patients with DOACs. Among DOACs, we recorded a higher incidence of bleeding (minor and major) with dabigatran compared to rivaroxaban, apixaban and edoxaban in nondiabetic and diabetic patients. CONCLUSION: DOACs seem to be metabolically favourable in diabetic patients. Regarding incidence of bleeding, DOACs with the exception of dabigatran, seem better than VKA in diabetic patients.

The effect of vitamin D3 supplementation on atrial fibrillation in generally healthy men and women: The Finnish Vitamin D Trial.

Atrial fibrillation is a common cardiac arrhythmia with high morbidity risk. Observational studies suggest that vitamin D deficiency is associated with higher atrial fibrillation risk but there is limited evidence whether vitamin D supplementation could affect the risk. In these post hoc analyses from the Finnish Vitamin D Trial, we compared the incidence of atrial fibrillation with 5-year supplementation of vitamin D3 (1600 IU/d or 3200 IU/d) vs placebo. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813.

Dietary ω-3 fatty acids and the incidence of atrial fibrillation in the Million Veteran Program.

BACKGROUND: Although recent large randomized clinical trials have reported an increased risk of atrial fibrillation (AF) with marine ω-3 fatty acid supplements, it is unclear whether dietary marine ω-3 fatty acids assessed through food frequency questionnaires are associated with AF risk. OBJECTIVES: We sought to test the hypothesis that dietary eicosapentaenoic acid/docosahexaenoic acid/docosapentaecnoic acid (EPA/DHA/DPA) is associated with a higher risk of AF in a large prospective cohort of US Veterans. METHODS: We analyzed data from Million Veteran Program participants who completed self-reported food frequency questionnaires. We used multivariable Cox regression to estimate the HRs of AF across quintiles of ω-3 fatty acid consumption and a cubic spline analysis to assess the dose-response relations between ω-3 fatty acids and AF. RESULTS: Of the 301,294 veterans studied, the median intake of ω-3 fatty acids (EPA/DHA/DPA) was 219 mg/d (IQR: 144-575), and the mean age was 64.9 y (SD: 12.0); 91% were men, and 84% were White. Consumption of EPA/DHA/DPA exhibited a nonlinear inverse relation with incident AF characterized by an initial decline to 11% at 750 mg/d of marine ω-3 fatty acid intake followed by a plateau. CONCLUSIONS: Contrary to our hypothesis, dietary EPA/DHA/DPA was not associated with a higher risk of AF but was inversely related to AF risk in a nonlinear manner.

Effect of vitamin D on postoperative atrial fibrillation in patients who underwent coronary artery bypass grafting: A systematic review and meta-analysis.

BACKGROUND: Vitamin D insufficiency/deficiency has been identified as a risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). This is associated with significantly increased morbidity and mortality leading to not only prolonged hospital and intensive care unit (ICU) stay, but increased risk of stroke, heart failure, dementia, and long-term atrial fibrillation. This analysis aims to evaluate the efficacy of vitamin D supplementation in preventing POAF in patients undergoing CABG. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials and SCOPUS from inception to June 2022 for randomized controlled trials (RCTs). The outcome of interest was the incidence of POAF. Secondarily, we analyzed the length of ICU stay, length of hospital stay, cardiac arrest, cardiac tamponade, and blood transfusion. Results were pooled using a random-effect model. Three RCTs consisting of 448 patients were included. RESULTS: Our results suggest that vitamin D significantly reduced the incidence of POAF (RR: 0.60; 95 % CI: 0.40, 0.90; p = 0.01; I2 = 8 %). It was also observed that vitamin D significantly reduced the duration of ICU stay (WMD: -1.639; 95 % CI: -1.857, -1.420; p < 0.00001). Furthermore, the length of hospital stay (WMD: -0.85; 95 % CI: -2.14, 0.43; p = 0.19; I2 = 87 %) was also reduced, however, the result was not significant. CONCLUSION: Our pooled analysis suggests that vitamin D prevents POAF. Future large-scale randomized trials are needed to confirm our results.

Mobile health technology integrated care in atrial fibrillation patients with diabetes mellitus in China: A subgroup analysis of the mAFA-II cluster randomized clinical trial.

BACKGROUND: The Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) prospective randomized trial showed the efficacy of a mobile health (mHealth) implemented 'Atrial fibrillation Better Care' (ABC) pathway for the integrated care management of patients with atrial fibrillation (AF). In this ancillary analysis, we evaluated the effect of mAFA intervention according to the history of diabetes mellitus (DM). METHODS: The mAFA-II trial enrolled 3324 AF patients across 40 centres in China, between June 2018 and August 2019. In this analysis, we assessed the interaction between history of DM and the effect of mAFA intervention on the risk of the primary composite outcome of stroke, thromboembolism, all-cause death and rehospitalizations. Results were expressed as adjusted hazard ratio (aHR) and 95% confidence intervals (95%CI). The effect of mAFA intervention on exploratory secondary outcomes was also assessed. RESULTS: Overall, 747 (22.5%) patients had DM (mean age: 72.7 ± 12.3, 39.6% females; 381 allocated to mAFA intervention). mAFA intervention was associated with a significant risk reduction for the primary composite outcome both in patients with and without DM (aHR [95%CI]: .36 [.18-.73] and .37 [.23-.61], respectively, p for interaction = .941). A significant interaction was found only for the composite of recurrent AF, heart failure and acute coronary syndromes (pint =.025), with lower effect of mAFA intervention in patients with DM. CONCLUSIONS: A mHealth-technology implemented ABC pathway showed a consistent effect in reducing the risk of the primary composite outcome in AF patients with and without DM. TRIAL REGISTRATION: WHO International Clinical Trials Registry Platform (ICTRP) Registration number: ChiCTR-OOC-17014138.

Identifying treatment heterogeneity in atrial fibrillation using a novel causal machine learning method.

BACKGROUND: Lifelong oral anticoagulation is recommended in patients with atrial fibrillation (AF) to prevent stroke. Over the last decade, multiple new oral anticoagulants (OACs) have expanded the number of treatment options for these patients. While population-level effectiveness of OACs has been compared, it is unclear if there is variability in benefit and risk across patient subgroups. METHODS: We analyzed claims and medical data for 34,569 patients who initiated a nonvitamin K antagonist oral anticoagulant (non-vitamin K antagonist oral anticoagulant (NOAC); apixaban, dabigatran, and rivaroxaban) or warfarin for nonvalvular AF between 08/01/2010 and 11/29/2017 from the OptumLabs Data Warehouse. A machine learning (ML) method was applied to match different OAC groups on several baseline variables including, age, sex, race, renal function, and CHA2DS2 -VASC score. A causal ML method was then used to discover patient subgroups characterizing the head-to-head treatment effects of the OACs on a primary composite outcome of ischemic stroke, intracranial hemorrhage, and all-cause mortality. RESULTS: The mean age, number of females and white race in the entire cohort of 34,569 patients were 71.2 (SD, 10.7) years, 14,916 (43.1%), and 25,051 (72.5%) respectively. During a mean follow-up of 8.3 (SD, 9.0) months, 2,110 (6.1%) of patients experienced the composite outcome, of whom 1,675 (4.8%) died. The causal ML method identified 5 subgroups with variables favoring apixaban over dabigatran; 2 subgroups favoring apixaban over rivaroxaban; 1 subgroup favoring dabigatran over rivaroxaban; and 1 subgroup favoring rivaroxaban over dabigatran in terms of risk reduction of the primary endpoint. No subgroup favored warfarin and most dabigatran vs warfarin users favored neither drug. The variables that most influenced favoring one subgroup over another included Age, history of ischemic stroke, thromboembolism, estimated glomerular filtration rate, Race, and myocardial infarction. CONCLUSIONS: Among patients with AF treated with a NOAC or warfarin, a causal ML method identified patient subgroups with differences in outcomes associated with OAC use. The findings suggest that the effects of OACs are heterogeneous across subgroups of AF patients, which could help personalize the choice of OAC. Future prospective studies are needed to better understand the clinical impact of the subgroups with respect to OAC selection.

Real-World Evaluation of Anticoagulant Treatment Patterns in Patients with Atrial Fibrillation: Data from Multicenter ROTA Study.

OBJECTIVE: Oral anticoagulant therapy is the cornerstone of atrial fibrillation management to prevent stroke and systemic embolism. However, there is limited real-world information regarding stroke and systemic embolism prevention strategies in patients with atrial fibrillation. The aim of the ROTA study is to obtain the real-world data of anticoagulant treatment patterns in patients with atrial fibrillation. METHODS: The ROTA study is a prospective, multicenter, and observational study that included 2597 patients with atrial fibrillation. The study population was recruited from 41 cardiology outpatient clinics between January 2021 and May 2021. RESULTS: The median age of the study population was 72 years (range: 22-98 years) and 57.4% were female. The median CHA2DS2-VASc and HAS-BLED scores were 4 (range: 0-9) and 1 (range: 0-6), respectively. Vitamin K antagonists and direct oral anticoagulants were used in 15.9% and 79.4% of patients, respectively. The mean time in therapeutic range was 52.9% for patients receiving vitamin K antagonists, and 76% of those patients had an inadequate time in therapeutic range with <70%. The most common prescribed direct oral anticoagulants were rivaroxaban (38.1%), apixaban (25.5%), and edoxaban (11.2%). The rate of overuse of vitamin K antagonists and direct oral anticoagulants was high (76.1%) in patients with low stroke risk, and more than one-fourth of patients on direct oral anticoagulant therapy were receiving a reduced dose of direct oral anticoagulants. Among patients who were on direct oral anticoagulant treatment, patients with apixaban treatment were older, had higher CHA2DS2-VASc and HAS-BLED scores, and had lower creatinine clearance than the patients receiving other direct oral anticoagulants. CONCLUSIONS: The ROTA study provides important real-world information about anticoagulant treatment patterns in patients with atrial fibrillation.time in therapeutic range with <70%.

Incident Atrial Fibrillation and Risk of Dementia in a Diverse, Community-Based Population.

Background Atrial fibrillation (AF) is the most common, clinically relevant arrhythmia in adults and associated with ischemic stroke and premature death. However, data are conflicting on whether AF is independently associated with risk of dementia, particularly in diverse populations. Methods and Results We identified all adults from 2 large integrated health care delivery systems between 2010 and 2017 and performed a 1:1 match of incident AF: no AF by age at index date, sex, estimated glomerular filtration rate category, and study site. Subsequent dementia was identified through previously validated diagnosis codes. Fine-Gray subdistribution hazard models were used to examine the association of incident AF (versus no AF) with risk of incident dementia, adjusting for sociodemographics and comorbidity and accounting for competing risk of death. Subgroup analyses by age, sex, race, ethnicity, and chronic kidney disease status were also performed. Among 196 968 matched adults, mean (SD) age was 73.6 (11.3) years, with 44.8% women, and 72.3% White. Incidence rates (per 100 person-years) for dementia over a median follow-up of 3.3 (interquartile range, 1.7-5.4) years were 2.79 (95% CI, 2.72-2.85) and 2.04 (95% CI, 1.99-2.08) per 100 person-years in persons with versus without incident AF, respectively. In adjusted models, incident AF was associated with a significantly greater risk of diagnosed dementia (subdistribution hazard ratio [sHR], 1.13 [95% CI, 1.09-1.16]). With additional adjustment for interim stroke events, the association of incident AF with dementia remained statistically significant (sHR, 1.10 [95% CI, 1.07-1.15]). Associations were stronger for age <65 (sHR, 1.65 [95% CI, 1.29-2.12]) versus ≥65 (sHR, 1.07 [95% CI, 1.03-1.10]) years (interaction P<0.001); and those without (sHR, 1.20 [95% CI, 1.14-1.26]) versus with chronic kidney disease (sHR, 1.06 [95% CI, 1.01-1.11]; interaction P<0.001). No meaningful differences were seen by sex, race, or ethnicity. Conclusions In a large, diverse community-based cohort, incident AF was associated with a modestly increased risk of dementia that was more prominent in younger patients and those without chronic kidney disease but did not substantially vary across sex, race, or ethnicity. Further studies should delineate mechanisms underpinning these findings, which may inform use of AF therapies.

Heart failure with preserved ejection fraction and atrial fibrillation: recent advances and open questions.

Atrial fibrillation (AF) and heart failure (HF) are frequently associated and can be caused or exacerbated by each other through different mechanisms. AF is particularly common in patients with heart failure with preserved ejection fraction (HFpEF) defined as left ventricular ejection fraction (LVEF) ≥ 50%, with a prevalence ranging around 40-60%.In two recent trials, treatment with SGLT2 inhibitors resulted in a lower risk of worsening heart failure or cardiovascular death than placebo in patients with HFpEF, and SGLT2 inhibitors similarly improved prognosis whether patients had AF or not at enrolment. Analyses for subgroups of interest of patients with HFpEF likely to be at higher risk of AF (particularly those with older age or obesity) similarly indicated a consistent benefit with SGLT2 inhibitors. That subgroup in patients with HFpEF is those with a history of previous HF with LVEF ≤ 40%. The EAST-AFNET 4 trial indicated that early rhythm-control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with recent AF and cardiovascular conditions, including those with HF. In patients with AF and HF included in the CABANA trial, catheter ablation produced marked improvements in survival, freedom from AF recurrence, and quality of life compared to drug therapy. When strategies aiming at rhythm control eventually fail in patients with AF and HFpEF, a strategy of rate control with atrioventricular junction ablation and cardiac resynchronisation should be discussed since it may also reduce all-cause mortality.Finally, and in conclusion, considering that patients with AF and HFpEF may have a variety of cardiovascular and non-cardiovascular additional comorbidities, they are among those likely to have the highest clinical benefit being adherent to a holistic and integrated care management of AF following the ABC (Atrial Fibrillation Better Care) pathway.