Prevention Of Atrial Fibrillation Research Articles

Potassium Supplementation and Prevention of Atrial Fibrillation After Cardiac Surgery: The TIGHT K Randomized Clinical Trial.

Supplementing potassium in an effort to maintain high-normal serum concentrations is a widespread strategy used to prevent atrial fibrillation after cardiac surgery (AFACS), but is not evidence-based, carries risks, and is costly. To determine whether a lower serum potassium concentration trigger for supplementation is noninferior to a high-normal trigger. This open-label, noninferiority, randomized clinical trial was conducted at 23 cardiac surgical centers in the United Kingdom and Germany. Between October 20, 2020, and November 16, 2023, patients with no history of atrial dysrhythmias scheduled for isolated coronary artery bypass grafting (CABG) surgery were enrolled. The last study patient was discharged from the hospital on December 11, 2023. Patients were randomly assigned to a strategy of tight or relaxed potassium control (only supplementing if serum potassium concentration fell below 4.5 mEq/L or 3.6 mEq/L, respectively). Patients wore an ambulatory heart rhythm monitor, which was analyzed by a core laboratory masked to treatment assignment. The prespecified primary end point was clinically detected and electrocardiographically confirmed new-onset AFACS in the first 120 hours after CABG surgery or until hospital discharge, whichever occurred first. All primary outcome events were validated by an event validation committee, which was masked to treatment assignment. Noninferiority of relaxed potassium control was defined as a risk difference for new-onset AFACS with associated upper bound of a 1-sided 97.5% CI of less than 10%. Secondary outcomes included other heart rhythm-related events, clinical outcomes, and cost related to the intervention. A total of 1690 patients (mean age, 65 years; 256 [15%] females) were randomized. The primary end point occurred in 26.2% of patients (n = 219) in the tight group and 27.8% of patients (n = 231) in the relaxed group, which is a risk difference of 1.7% (95% CI, -2.6% to 5.9%). There was no difference between the groups in the incidence of at least 1 AFACS episode detected by any means or by ambulatory heart rhythm monitor alone, non-AFACS dysrhythmias, in-patient mortality, or length of stay. Per-patient cost for purchasing and administering potassium was significantly lower in the relaxed group (mean difference, $111.89 [95% CI, $103.60-$120.19]; P <.001). For AFACS prophylaxis, supplementation only when serum potassium concentration fell below 3.6 mEq/L was noninferior to the current widespread practice of supplementing potassium to maintain a serum potassium concentration greater than or equal to 4.5 mEq/L. The lower threshold of supplementation was not associated with any increase in dysrhythmias or adverse clinical outcomes. ClinicalTrials.gov Identifier: NCT04053816.

Milvexian vs apixaban for stroke prevention in atrial fibrillation: The LIBREXIA atrial fibrillation trial rationale and design

Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk. LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years. The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter. ClinicalTrials.gov NCT05757869.

Associations of ambient air pollution with incidence and dynamic progression of atrial fibrillation

The influence of air pollution on dynamic changes in clinical state from healthy to atrial fibrillation (AF), further AF-related complications and ultimately, death are unclear. We aimed to investigate the relationships between air pollution and the occurrence and progression trajectories of AF. We retrieved 442,150 participants free of heart failure (HF), myocardial infarction (MI), stroke and dementia at baseline from UK Biobank. Exposures to air pollution for each transition stage were estimated at the geocoded residential address of each participant using the bilinear interpolation approach. The outcomes were incident AF, complications, and death. Multi-stage models were used to evaluate the associations between air pollution and dynamic progression of AF. Over a 12.6-year median follow-up, a total of 21,670 incident AF patients were identified, of whom, 4103 developed complications and 1331 died. PM2.5, PM10, NOx and NO2 were differentially positively associated, while O3 was negatively associated with risks of progression trajectories of AF. PM2.5 exposure was significantly associated with an increased risk of progression. The associations of PM2.5, PM10, NOx, and NO2 on incident AF were generally more pronounced compared to other transitions. The cumulative transition probabilities were generally higher in individuals with higher exposure levels of PM2.5, PM10, NOx, and NO2 and lower exposure to O3. Air pollution could potentially have a role in increasing the risk of both the occurrence and progression of AF, emphasizing the significance of air pollution interventions in both the primary prevention of AF and the management of AF-related outcomes.

Omega-3 Fatty Acids and Arrhythmias.

The pro- and antiarrhythmic effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been extensively studied in preclinical and human trials. Despite early evidence of an antiarrhythmic role of n-3 PUFA in the prevention of sudden cardiac death and postoperative and persistent atrial fibrillation (AF), subsequent well-designed randomized trials have largely not shown an antiarrhythmic benefit. Two trials that tested moderate and high-dose n-3 PUFA demonstrated a reduction in sudden cardiac death, but these findings have not been widely replicated, and the potential of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to reduce arrhythmic death in combination, or as monotherapy, remains uncertain. The accumulated clinical evidence does not support supplementation of n-3 PUFA for postoperative AF or secondary prevention of AF. Several large, contemporary, randomized controlled trials of high-dose n-3 PUFA for primary or secondary cardiovascular prevention have demonstrated a small, significant, dose-dependent increased risk of incident AF compared with mineral oil or corn oil comparator. These findings were reproduced with both icosapent ethyl monotherapy and a mixed EPA+DHA formulation. The proarrhythmic mechanism of increased AF in contemporary cohorts exposed to high-dose n-3 PUFA is unknown. EPA and DHA and their metabolites have pleiotropic cardiometabolic and pro- and antiarrhythmic effects, including modification of the lipid raft microenvironment; alteration of cell membrane structure and fluidity; modulation of sodium, potassium, and calcium currents; and regulation of gene transcription, cell proliferation, and inflammation. Further characterization of the complex association between EPA, EPA+DHA, and DHA and AF is needed. Which formulations, dose ranges, and patient subgroups are at highest risk, remain unclear.

Comparison of oral anticoagulants for stroke prevention in atrial fibrillation using the UK clinical practice research Datalink Aurum: A reference trial (ARISTOTLE) emulation study.

Stroke prevention guidance for patients with atrial fibrillation (AF) uses evidence generated from randomised controlled trials (RCTs). However, applicability to patient groups excluded from trials remains unknown. Real-world patient data provide an opportunity to evaluate outcomes in a trial analogous population of direct oral anticoagulants (DOACs) users and in patients otherwise excluded from RCTs; however, there remains uncertainty on the validity of methods and suitability of the data. Successful reference trial emulation can support the generation of evidence around treatment effects in groups excluded or underrepresented in trials. We used linked United Kingdom primary care data to investigate whether we could emulate the pivotal ARISTOTLE trial (apixaban versus warfarin) and extend the analysis to investigate the impact of warfarin time in therapeutic range (TTR) on results. Patients with AF in the UK Clinical Practice Research Datalink (CPRD Aurum) prescribed apixaban or warfarin from 1 January 2013 to 31 July 2019 were selected. ARISTOTLE eligibility criteria were applied to this population and matched to the RCT apixaban arm on baseline characteristics creating a trial-analogous apixaban cohort; this was propensity-score matched to warfarin users in the CPRD Aurum. ARISTOTLE outcomes were assessed using Cox proportional hazards regression stratified by prior warfarin exposure status during 2.5 years of patient follow-up and results benchmarked against the trial results before treatment effectiveness was further evaluated based on (warfarin) TTR. The dataset comprised 8,734 apixaban users and propensity-score matched 8,734 warfarin users. Results [hazard ratio (95% confidence interval)] confirmed apixaban noninferiority for stroke or systemic embolism (SE) [CPRD 0.98 (0.82,1.19) versus trial 0.79 (0.66,0.95)] and death from any cause [CPRD 1.03 (0.93,1.14) versus trial 0.89 (0.80,0.998)] but did not indicate apixaban superiority. Absolute event rates for stroke/SE were similar for apixaban in CPRD Aurum and ARISTOTLE (1.27%/year), whereas a lower event rate was observed for warfarin (CPRD Aurum 1.29%/year, ARISTOTLE 1.60%/year). Analysis by TTR suggested similar effectiveness of apixaban compared with poorly controlled warfarin (TTR < 0.75) for stroke/SE [0.91 (0.73, 1.14)], all-cause death [0.94 (0.84, 1.06)], and superiority for major bleeding [0.74 (0.63, 0.86)]. However, when compared with well-controlled warfarin (TTR ≥ 0.75), apixaban was associated with an increased hazard for all-cause death [1.20 (1.04, 1.37)], and there was no significant benefit for major bleeding [1.08 (0.90, 1.30)]. The main limitation of the study's methodology are the risk of residual confounding, channelling bias and attrition bias in the warfarin arm, and selection bias and misclassification in the analysis by TTR. Analysis of noninterventional data generated results demonstrating noninferiority of apixaban versus warfarin consistent with prespecified benchmarking criteria. Unlike in ARISTOTLE, superiority of apixaban versus warfarin was not seen, possible due to the lower proportion of Asian patients and higher proportion of patients with well-controlled warfarin compared to ARISTOTLE. This methodological template can be used to investigate treatment effects of oral anticoagulants in patient groups excluded from or underrepresented in trials and provides a framework that can be adapted to investigate treatment effects for other conditions.

Will Factor XI Inhibitors Replace Current Anticoagulants for Stroke Prevention in Atrial Fibrillation?

This review provides an overview of the factor XI (FXI) inhibitor hypothesis for the development of novel anticoagulants which may be safer to those currently used in clinical practice and describes preliminary clinical data from phase 2 dose-ranging studies of patients with atrial fibrillation. Recent data from phase 2 dose ranging studies demonstrate substantial reductions in bleeding with FXI pathway inhibition compared with currently approved anticoagulants. However, larger studies are necessary to demonstrate efficacy of FXI inhibition for stroke prevention in atrial fibrillation. FXI pathway inhibition holds great promise for revolutionizing the landscape of anticoagulation for atrial fibrillation, primarily by reducing bleeding risk; however, further data are necessary to demonstrate efficacy.

Left atrial appendage closure for stroke prevention in atrial fibrillation: current status and perspectives.

Atrial fibrillation (AF) is associated with an increased risk of stroke and systemic embolism, and the left atrial appendage (LAA) has been identified as a principal source of thromboembolism in these patients. While oral anticoagulation is the current standard of care, LAA closure (LAAC) emerges as an alternative or complementary treatment approach to reduce the risk of stroke or systemic embolism in patients with AF. Moderate-sized randomized clinical studies have provided data for the efficacy and safety of catheter-based LAAC, largely compared with vitamin K antagonists. LAA device iterations, advances in pre- and peri-procedural imaging, and implantation techniques continue to increase the efficacy and safety of LAAC. More data about efficacy and safety of LAAC have been collected, and several randomized clinical trials are currently underway to compare LAAC with best medical care (including non-vitamin K antagonist oral anticoagulants) in different clinical settings. Surgical LAAC in patients with AF undergoing cardiac surgery reduced the risk of stroke on background of anticoagulation therapy in the LAAOS III study. In this review, we describe the rapidly evolving field of LAAC and discuss recent clinical data, ongoing studies, open questions, and current limitations of LAAC.

Exploring the therapeutic utility of the factor XIa inhibitor asundexian.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Factor XIa inhibitors are a promising novel class of anticoagulants that attenuate pathological thrombosis with minimal interference with hemostasis. These effects contrast with those of conventional anticoagulants, which may exhibit adverse events of untoward bleeding precluding treatment in some patients. A variety of investigational pharmacological modalities have been developed and studied to target factor XIa. Asundexian is a small molecule inhibitor of factor XIa that has been evaluated in several clinical studies. It has been studied as an oral, once-daily medication and found to inhibit approximately 90% of factor XIa activity at doses of 20 to 50mg. Phase 2 trials have demonstrated the potential for improved safety compared to standard of care in certain treatment settings, such as in atrial fibrillation. For other indications, such as noncardioembolic stroke and acute myocardial infarction, asundexian has been used in addition to background antiplatelet therapy. In these instances, asundexian did not show a difference in the incidence of bleeding events compared to placebo. Phase 3 trials have recently been launched; however, the OCEANIC-AF trial was prematurely discontinued due to inefficacy of asundexian vs apixaban for stroke prevention in atrial fibrillation. Another phase 3 trial, OCEANIC-AFINA, is planned to compare asundexian to placebo in patients with atrial fibrillation at high risk for stroke who are deemed ineligible for anticoagulation.

Uncovering the Role of Direct Oral Anticoagulants in Stroke Prevention for Atrial Fibrillation: A Review of the Literature.

Atrial fibrillation (AF) is a predominant contributor to morbidity and mortality, and stroke prevention remains the mainstay for the management of AF. The precise mechanism involved in thrombus formation remains unknown. However, factors such as stretch-induced fibrosis, endothelial dysfunction, disordered atrial contractions, and pro-thrombotic states have been postulated for the development of AF. Various risk assessment strategies have been acknowledged for determining the risk of stroke in AF, of which the congestive heart failure, hypertension, age ≥75, diabetes, stroke, vascular disease, age between 65-74, and female sex (CHA2DS2-VASc) score remains the ultimate risk stratification tool. For the longest time, vitamin K antagonists (VKA) were the only oral anticoagulants available but were associated with an increased risk of bleeding. Recently, direct oral anticoagulants (DOACs) were approved and considered more efficient and safer than or as secure as warfarin in stroke prevention and lowering intra-cranial bleeding events. The pharmacodynamics and pharmacokinetics of DOACs were also clarified in this article. This review article compiles current evidence-based data on the role of DOACs, uncovering their underlying mechanisms, and comparing their efficacy with warfarin in stroke prevention in AF.

Evaluation of the effect of empagliflozin on prevention of atrial fibrillation after coronary artery bypass grafting: a double-blind, randomized, placebo-controlled trial.

This study is aimed at evaluating the effect of empagliflozin in preventing atrial fibrillation after coronary artery bypass grafting (CABG). Eighty-two patients who fulfilled the inclusion criteria were allocated to the empagliflozin group (n = 43) or placebo group (n = 39). In two groups, patients received empagliflozin or placebo tablets 3days before surgery and on the first three postoperative days (for 6days) in addition to the standard regimen during hospitalization. During the first 3days after surgery, types of arrhythmias after cardiac surgery, including supraventricular arrhythmias, especially postoperative atrial fibrillation (POAF), ventricular arrhythmias, and heart blocks, were assessed by electrocardiogram monitoring. C-reactive protein (CRP) levels were evaluated pre-operatively and postoperative on the third day. The incidence of POAF in the treatment group was lower compared to the control group; however, this reduction was statistically non-significant (p = 0.09). The frequency of ventricular tachycardia was reduced significantly in the treatment group versus patients in the control (p = 0.02). Also, a significant reduction in the frequency of premature ventricular contractions (PVCs) was seen in the treatment group in comparison with the control group (p = 0.001). After the intervention, CRP levels were significantly less in the empagliflozin group compared to the control group in the third postoperative day (p = 0.04). The prophylactic use of empagliflozin effectively reduced the incidence of ventricular arrhythmia in patients undergoing CABG surgery.

Effects of Heart Failure Therapies on Atrial Fibrillation: Biological and Clinical Perspectives.

Heart failure (HF) and atrial fibrillation (AF) are prevalent cardiovascular diseases that contribute significantly to morbidity, mortality, hospitalisation, and healthcare costs. It is not uncommon for these conditions to coexist and have mutually reinforcing effects. A critical factor in the aetiology of these conditions is oxidative stress, driven by reactive oxygen species (ROS), which contributes to atrial remodelling and fibrosis. The recent introduction of new drugs for the treatment of heart failure has also had an impact on the management of atrial fibrillation due to their influence on oxidative stress. The objective of this review is to analyse the effects of these therapies, including their role in mitigating ROS, on the prevention and treatment of AF in HF patients.

Sodium Intake and Incident Atrial Fibrillation in Individuals With Vascular Disease

Numerous prospective cohort studies have reported a J-shaped association of urinary sodium excretion with cardiovascular events and mortality. To study the association between sodium intake and incident atrial fibrillation (AF). This cohort study included participants in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomised Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) multicenter, randomized clinical trials comparing the effect of ramipril 10 mg daily with telmisartan 80 mg daily, or their combination (ONTARGET) or 80 mg telmisartan daily with placebo (TRANSCEND) for the outcome of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. ONTARGET and TRANSCEND included 31 546 participants with vascular disease or high-risk diabetes, and this study excluded participants without a urine sample for sodium measurement, missing data for key covariates, a history of AF, or AF detected in the first year after enrollment. Analyses were performed in July 2023 to May 2024. Estimated sodium intake from a morning fasting urine sample (Kawasaki formula). The main outcome was incident AF. The association between estimated sodium intake and incident AF was modeled using multivariable adjusted Cox regression and cubic splines. A total of 27 391 participants (mean [SD] age, 66.3 [7.2] years; 19 310 [70.5%] male) were included. Mean (SD) estimated sodium intake was 4.8 (1.6) g/d. During a mean (SD) follow-up of 4.6 (1.0) years, 1562 participants (5.7%) had incident AF. After multivariable adjustment, a J-shaped association between sodium intake and AF risk was observed (P for nonlinearity = .03). Sodium intake of 8 g/d or greater (3% of participants) was associated with incident AF (hazard ratio, 1.32; 95% CI, 1.01-1.74) compared with sodium intake of 4 to 5.99 g/d. Cubic splines showed that sodium intake greater than 6 g/d (19% of participants) was associated with a 10% increased AF risk per additional 1-g/d sodium intake (hazard ratio, 1.10; 95% CI, 1.03-1.18), but with no further lowering of AF risk at lower levels of sodium intake. In this cohort study of sodium intake and AF risk, there was a J-shaped association between sodium intakes and AF risk in patients with cardiovascular disease or diabetes. Lowering sodium intake for AF prevention is best targeted at individuals who consume high sodium diets.

Use of digital patient decision-support tools for atrial fibrillation treatments: a systematic review and meta-analysis

ObjectivesTo assess the effects of digital patient decision-support tools for atrial fibrillation (AF) treatment decisions in adults with AF.Study designSystematic review and meta-analysis.Eligibility criteriaEligible randomised controlled trials (RCTs) evaluated digital...

Antihypertensive Drugs for the Prevention of Atrial Fibrillation: A Drug Target Mendelian Randomization Study.

We investigated the potential impact of antihypertensive drugs for atrial fibrillation (AF) prevention through a drug target Mendelian randomization study to avoid the potential limitations of clinical studies. Validated published single-nucleotide polymorphisms (SNPs) that mimic the action of 12 antihypertensive drug classes, including alpha-adrenoceptor blockers, adrenergic neuron blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, beta-adrenoceptor blockers, centrally acting antihypertensive drugs, calcium channel blockers, loop diuretics, potassium-sparing diuretics and mineralocorticoid receptor antagonists, renin inhibitors, thiazides and related diuretic agents, and vasodilators were used. We estimated, via their corresponding gene and protein targets, the downstream effect of these drug classes to prevent AF via systolic blood pressure using 2-sample Mendelian randomization analyses. The SNPs were extracted from 2 European genome-wide association studies for the drug classes (n=317 754; n=757 601) and 1 European genome-wide association study for AF (n=1 030 836). Drug target Mendelian randomization analyses supported the significant preventive causal effects of lowering systolic blood pressure per 10 mm Hg via alpha-adrenoceptor blockers (n=11 SNPs; odds ratio [OR], 0.34 [95% CI, 0.21-0.56]; P=2.74×10-05), beta-adrenoceptor blockers (n=17 SNPs; OR, 0.52 [95% CI, 0.35-0.78]; P=1.62×10-03), calcium channel blockers (n=49 SNPs; OR, 0.50 [95% CI, 0.36-0.70]; P=4.51×10-05), vasodilators (n=19 SNPs; OR, 0.53 [95% CI, 0.34-0.84]; P=7.03×10-03), and all 12 antihypertensive drug classes combined (n=158 SNPs; OR, 0.64 [95% CI, 0.54-0.77]; P=8.50×10-07) on AF risk. Our results indicated that lowering systolic blood pressure via protein targets of various antihypertensive drugs seems promising for AF prevention. Our findings inform future clinical trials and have implications for repurposing antihypertensive drugs for AF prevention.

Pacemaker-induced atrial fibrillation reconsidered-associations with different pacing sites and prevention approaches.

The incidence of atrial fibrillation (AF) is significantly higher in patients with pacemakers than in the general population, which could be due to patient characteristics and the diagnostic tool of the pacemaker in detecting atrial high-rate episodes and subclinical AF, but also to the pacemaker itself providing AF-promoting conditions. It is well known that high ventricular pacemaker burden increases the likelihood of AF occurrence. However, the sites of atrial and ventricular pacing may also influence the risk for AF. The conventional sites for atrial and ventricular pacing are in the right atrial appendage and in the right ventricular apex. However, growing evidence suggests that alternative pacing sites may be superior for the prevention of AF. Bachmann bundle pacing, for example, promotes interatrial excitation conduction, resulting in atrial synchronicity and a shorter total atrial activation time, which may be preventive for the occurrence of AF. Moreover, in recent years, new ventricular pacing sites have come into focus with His bundle and left bundle branch pacing. In addition to the hemodynamic and electrophysiological cardiac benefits, these new options may also offer benefits in the prevention of AF. This review provides an overview of pacing-induced AF mechanisms and the association with different pacing sites, as well as approaches for prevention of pacing-induced AF, highlighting different sites and modes of atrial pacing and the newer sites of ventricular pacing.

Healthy-aging conditions might promote the prevention of aging-induced atrial inflammation and atrial fibrillation

Healthy-aging conditions might promote the prevention of aging-induced atrial inflammation and atrial fibrillation

Semaglutide for the prevention of atrial fibrillation: A systematic review and meta-analysis

BackgroundSemaglutide, a glucagon-like peptide-1 receptor agonist, is reported to have cardiac benefits, but its effects on preventing atrial fibrillation (AF) remain inconclusive. This study aimed to investigate whether semaglutide can prevent AF occurrence in patients with type 2 diabetes mellitus (T2DM), obesity, or overweight. MethodsWe searched MEDLINE, EMBASE, the Cochrane CENTRAL database, and clinicaltrials.gov from inception to December 29, 2023. Randomized controlled trials of semaglutide in patients with T2DM, obesity, or overweight were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for the overall population and subgroups. ResultsTwenty-one trials comprising 25957 patients were included. In the overall pooled analysis, semaglutide decreased AF occurrence compared to control drugs (RR 0.70, 95 % CI 0.52–0.95). This result was consistent in trials using other antihyperglycemic medications as controls (RR 0.43, 95 % CI 0.21–0.89), but not in placebo-controlled trials (RR 0.77, 95 % CI 0.56–1.07). The outcome was favorable for patients with T2DM (RR 0.71, 95 % CI 0.52–0.97), but not for patients with overweight or obesity (RR 0.56, 95 % CI 0.18–1.73). Results varied by type of semaglutide, with oral semaglutide showing an RR of 0.49 (95 % CI 0.25–0.97) and subcutaneous semaglutide showing an RR of 0.77 (95 % CI 0.55–1.07). ConclusionSemaglutide was associated with a reduced risk of AF occurrence in the overall analysis. Favorable outcomes were observed in subsets using other antihyperglycemic medications as controls, in patients with T2DM, and with oral semaglutide.

New-onset atrial fibrillation, cardiovascular outcomes and all-cause mortality in patients with newly diagnosed cancer: A large population-based matched cohort study.

11184 Background: Studies have shown an association between atrial fibrillation (AF) and cancer, but the relationship is incompletely studied. there is also a paucity of data regarding the specific association between cancer type and AF risk . Notably, the longitudinal associations of new-onset AF with adverse cardiovascular (ACV) outcomes in Newly Diagnosed Cancer Patients remain unclear. Thus, through a comprehensive nationwide population-based study, we assessed the associations between new-onset AF and subsequent risks of ACV events and all-cause mortality. Methods: This large retrospective cohort study was conducted using the TriNetX database and included adults (&gt;18 years) with any new cancer diagnoses. We performed 1:1 propensity score matching (PSM) for demographics, BMI, nicotine dependence, comorbidities, cancer type, and medications to similar controls as cancer patients without AF. The primary outcome was new ACV events like heart failure (HF), major adverse cardiovascular events (MACE; coronary artery intervention myocardial infarction, or unstable angina), ischemic heart disease (IHD), and cerebrovascular events (CVE; cerebral infarction, carotid intervention, stroke, transient ischemic attack. The secondary outcome was all-cause mortality. Sensitivity analysis assessed statistical robustness. Hazard ratios (HR) were calculated to compare group outcomes. Results: Among the new diagnoses, 52,606 developed AF, and 374,959 remained AF free during the follow-up. After PSM, both cohorts (51,567 each) were well-matched. The mean follow-up duration was 4.8 (± 2.7) years. Among newly diagnosed cancer patients, those with incident AF had higher risk of MACE (HR 1.56; 95% CI 1.49–2.16), HF (HR 3.10; 95% CI 2.76–4.36), IHD (HR 1.68; 95% CI 1.41–2.01), CVE (HR 2.93; 95% CI 2.13–4.04), and all-cause mortality (HR 2.56; 95% CI 1.89–3.78) compared with those without incident AF. We noted a higher incidence rate during the initial months after the diagnosis of AF for both sexes. During the first year, the association with any ACV events (men: HR 2.78, 95% CI, 1.85–3.20; women: HR 1.81, 95% CI, 1.31–2.67) was more substantial than that following AF diagnosis for both sexes. New ‐onset AF was strongly associated with metastatic cancer. In sensitivity analysis, we excluded individuals with &lt;1 year of follow-up results were consistent, and all statistically significant associations remained unchanged. Conclusions: cancer patients who developed AF had significantly higher risks of subsequent adverse cardiovascular events and greater all-cause mortality. AF was strongly associated with metastatic disease. Our findings highlight the importance of strategies for AF prevention to mitigate macrovascular complications in all newly diagnosed cancer patients.

2-Aminoethoxydiphenyl borate prolongs atrial and shortens ventricular action potential duration through modulation of ion channels in the sarcolemma

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): PPP allowance, Health holland ZonmW Background 2-Aminoethoxydiphenyl Borate (2-APB) has been shown to prevent atrial fibrillation in animal models, supposedly through its inhibitory action on the intracellular IP3 receptor and subsequent calcium regulation. However, 2-APB may modulate other ion channels or transporters and the cellular mechanisms associated with the prevention of atrial fibrillation are not well established. We aimed at unravelling the cellular effects of 2-APB on atrial and ventricular action potential and currents. Methods Rabbit (New Zealand White) left atrial and ventricular cardiomyocytes were isolated from Langendorff-perfused hearts by enzymatic dissociation. Adult human atrial cardiomyocytes were obtained by enzymatic dissociation from left atrial appendages (LAA) routinely removed from AF patients undergoing minimally invasive surgical pulmonary vein isolation. Action potentials (APs) and K+ currents were recorded at 36.5 °C with the amphotericin-B-perforated or whole cell patch clamp technique. RNA was isolated from left atrial and ventricular tissue and sequenced on an Illumina HiSeq4000 platform. Results In rabbit atrial cardiomyocytes, extracellular application of 5 uM 2-APB had no effect on action potential duration (APD), but extracellular application of 50 uM 2-APB prolonged the APD by 40% and inhibited an outward K+-current. Inversely, extracellular application of 5 uM 2-APB shortened the APD of rabbit left ventricular cardiomyocytes by 20% while extracellular application 50 uM 2-APB did not prolong the APD. Additionally, 2-APB did not modulate K+ currents in ventricular rabbit cardiomyocytes. Intracellular application (in the patch pipet) of 50 uM 2-APB did not have any effects on atrial APD, suggesting that IP3 receptor inhibition is not involved. However, subsequent application of 50 uM 2-APB in the bath prolonged the APD by 40% indicating that 2-APB prolongs atrial APD by inhibiting one or more K+ channel types in the sarcolemmal membrane from the extracellular site. RNA sequencing analysis revealed potential targets channel including TRP and Kv channels differentially expressed in atria versus ventricle. In human atrial cardiomyocytes from AF patients, application of 50 uM 2-APB prolonged APD by 25%. Conclusions 2-APB prolongs rabbit and human atrial APD and shortens rabbit ventricular APD in a concentration dependent manner, most likely due to modulation of sarcolemmal K+ channels, differentially expressed in the two cell types. Pharmacological studies with 2-APB may reveal novel cellular mechanisms identifying potential new targets for the treatment of atrial fibrillation.

Direct oral anticoagulants versus vitamin K antagonists as stroke prevention in atrial fibrillation after cardiac surgery: a systematic review and meta-analysis

Abstract Background Cardiothoracic surgery guidelines advocate the use of vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) in the first days to months after major cardiac surgery. No recommendations on choice of anticoagulant in the first months after cardiac surgery have been issued since 2008, before the use of direct oral anticoagulants (DOACs). The basis for this is a lack of data on the safety and efficacy of DOACs after cardiac surgery. Purpose To systematically assess and meta-analyze the existing evidence on the effect of DOACs compared with VKAs on efficacy and safety after cardic surgery. We hypothesized that DOACs are non-inferior to VKAs in the setting of AF after cardiac surgery. Methods We searched Ovid MEDLINE, Ovid EMBASE, the Cochrane Central Register of Controlled trials and Clinicaltrials.gov from inception till 20 June 2023 and screened references in relevant reviews as grey literature search. Observational studies and randomized controlled trials comparing DOACs with VKAs for stroke prevention in patients with (postoperative) atrial fibrillation after cardiac surgery were included, focusing on procedures through thoracoscopy or thoracotomy. Outcomes of interest included thromboembolic events, all-cause stroke, major bleeding and mortality up to 6 months after cardiac surgery and admission duration. A random effects model was used to determine pooled treatment effects. The level of evidence was rated following the GRADE recommendations. Results We identified 4,146 records of which ten were included, together reporting on &amp;gt; 30,000 patients. There were no significant differences in thromboembolic events (OR 0.98; 95% CI 0.61-1.58; I^2 0%; GRADE: very low), all-cause stroke (OR 1.14; 95% CI 0.51-2.54; I^2 0%; GRADE: very low), major bleeding (OR 0.91; 95% CI 0.51-1.62; I^2 53%; GRADE: very low), all-cause mortality (OR 1.00; 95% CI 0.73-1.37; I^2 0%; GRADE: low), admission duration (MD -0.33; 95% CI -1.16 – 0.49; I^2 0%; GRADE: very low) between DOACs and VKAs in the first 6 months after cardiac surgery. Conclusion Efficacy and safety of DOACs as stroke prevention in AF following cardiac surgery were similar to that of VKAs in ten studies comprising more than 30,000 patients. Based on the existing literature, there is insufficient evidence to recommend one class of oral anticoagulants over another in the first months after cardiac surgery.Forest plot of primary outcomes