BMC Cardiovascular Disorders

AimsTo establish the extent and impact of symptoms in patients with atrial fibrillation (AF), the importance of different aspects of quality of life (QoL), and how we should assess wellbeing. MethodsFocus groups of patients with symptomatic permanent AF in a trial of heart rate control; the RATE-AF trial randomised 160 patients aged [≥]60 years with permanent AF and at least NYHA class II dyspnoea to either digoxin or beta-blockers. Patient and public representatives led the focus groups and performed all data acquisition and analysis, using thematic approaches to interpret patient views about QoL and its measurement. ResultsSubstantial impairment of health-related QoL was noted in 160 trial patients, with impact on all domains apart from mental health. Eight women and 11 men aged 61-87 years participated in the focus groups. Common themes were a lack of information from healthcare professionals about AF, a lack of focus on QoL in consultations, and a sense of frustration, isolation and reduced confidence. There was marked variability in symptoms in individual patients, with some describing severe impact on activities of daily living, and profound interaction with comorbidities such as arthritis. Day-to-day variation in QoL and difficulty in attributing symptom burden to AF or other comorbidities led to challenges in questionnaire completion. Consensus was reached that collecting both general and AF-specific QoL would be useful in routine practice, along with participation in peer support, which was empowering for the patients. ConclusionsThe impact of comorbidities is poorly appreciated in the context of AF, with considerable variability in QoL that requires both generic and AF-specific assessment. Improvement in QoL should direct the appraisal, and reappraisal, of treatment decisions for patients with permanent AF.

BackgroundHeart failure (HF) and atrial fibrillation (AF) are closely linked, each exacerbating the other. While sodium-glucose cotransporter-2 inhibitors (SGLT2i) are known to provide substantial benefits in HF management, their effect on AF incidence in this population is not well-defined. ObjectiveThis study aims to assess the effect of SGLT2i therapy on the development of new-onset AF in patients with HF. MethodsThis retrospective analysis included all patients hospitalized with a primary diagnosis of HF and no prior diagnosis of AF over a 3-year period. The primary outcome was the occurrence of new-onset AF within 12 months following HF hospitalization. ResultsOf 3,953 patients 720 (18.2%) developed AF within one year. SGLT2i use was associated with significantly lower risk of AF (HR 0.69, 95% CI:0.55-0.87; p=0.002) across all HF types-reduced, mid-range, and preserved ejection fraction. Kaplan-Meier survival analysis revealed significantly reduced AF-free survival in patients not on SGLT2i therapy, compared to patients on SGLT2i therapy, across subgroups categorized by diabetes, hypertension, coronary artery disease, age [&ge;]65 years, and BMI [&ge;]30Kg/m2 (p <0.05 for all). Among those who developed AF, SGLT2i use had significantly lower incidence of AF during follow-up as compared to when not used (12.1% vs. 19.5%, p<0.001). SGLT2 use also delayed onset of AF compared to those not treated with an SGLT2i (339 {+/-} 80 days vs. 317 {+/-} 106 days; p<0.001). ConclusionsThe use of SGLT2i therapy is associated with a significantly lower risk of the developing AF following hospitalization for HF.

IntroductionWith the improvement of long-term survival of patients with congenital heart disease (CHD), complications such as atrial fibrillation (AF) have become a concern. This study aimed to determine the epidemiology data and risk factors of AF in adult CHD (ACHD) patients and evaluate the impact of AF on late outcomes using a large ACHD cohort in Asia. MethodThis study enrolled all CHD patients older than 18 years of age diagnosed with CHD at National Taiwan University Hospital between 2007 and 2018. Data on patients clinical characteristics, electrocardiogram, Holter reports, and follow-up information were collected. AF status was classified as sustained AF, paroxysmal AF, or intra-atrial reentry tachycardia (IART). CHD was categorized as simple, severe, or complex CHD (single ventricle). Primary endpoint was defined as cerebrovascular accidents (CVA) or death. ResultThe study included 4403 patients (55.9% women), with 16.4% having severe and 2.9% having complex CHD. The cumulative incidence of AF was 6.9% (54.8% paroxysmal AF, 26.9% sustained AF, and 18.4% IART), which is comparable to the Western countries. The incidence increased with age and was higher in patients with pulmonary hypertension (PH, 27%), complex CHD (12.7%), and metabolic syndrome. The mean onset age of IART, paroxysmal, and sustained AF was 35.7{+/-}15.8, 48.4{+/-}19.3, and 56.9{+/-}14.2 years, respectively. Multivariate Cox regression analysis revealed that male sex, PH, and severe and complex CHD were the most critical risk factors for AF (odds ratio 1.67, 1.91, 3.55, and 12.6, respectively). The 70-year CVA-free survival rate was 67.1% in patients with AF (vs. 80.5% in those without AF, p<0.001). However, multivariate Cox regression analysis identified male sex, PH, severe and complex CHD, and genetic syndrome as the most significant risk factors of the primary endpoint (odds ratio 1.76, 3.38, 2.62 and 19.3, and 8.91, respectively). ConclusionsThis large ACHD cohort showed a high cumulative incidence of AF, similar to the Western countries, which increased with age, PH, and CHD severity. CVA-free survival was more closely associated with these factors than with AF.

BackgroundIn the CAP-AF trial, injection of calcium chloride (CaCl2) into the four major atrial ganglionated plexi (GP) reduced the relative risk of postoperative atrial fibrillation (POAF) by 63% in patients undergoing coronary artery bypass surgery (CABG). ObjectiveThe CAP-AF2 trial intended to investigate if similar autonomic denervation could prevent POAF in patients with mitral regurgitation (MR) but without persistent AF who underwent surgery for MR. MethodsThe CAP-AF-2 trial was an investigator-initiated, single center, double-blind, randomized clinical trial. This trial planned to 1:1 randomize 320 adult patients to CaCl2 vs. sodium chloride (NaCl, sham) injection into the four GP during surgery. The primary outcome was incidence of POAF ([&ge;]30 seconds) in 7 days. Secondary outcomes included length of hospitalization, POAF burden, actionable antiarrhythmic therapy for POAF, heart rate variability changes and plasma inflammatory markers. ResultsThis trial was terminated after midterm analysis showing that the cumulative POAF incidence was higher in the CaCl2 group (43/78, 55.13%) than the NaCl group (31/82, 37.80%; confidence interval of difference 1.01%-32.48%, P= 0.028). In the CaCl2 group, more patients were hospitalized over 7 days (69.8% vs. 45.2%; p=0.033) and more patients required amiodarone therapy (p=0.039). AF burden, plasma inflammatory markers and heart rate variability were not different between the two groups. Frequent atrial bigeminy or nonsustained atrial tachycardia immediately preceded POAF in 76.7% (CaCl2) and 29.0% (NaCl) patients, respectively (P<0.001), consistent with triggers caused by higher sympathetic activity. Immunohistochemistry study obtained from GP and left atrium during surgery revealed parasympathetic dominance in patients receiving MV surgery but sympathetic dominance in patients undergoing CABG. ConclusionsUnlike patients undergoing CABG, autonomic denervation increased the risk of POAF in patients receiving MR surgery, indicating distinct AF substrate in different cardiovascular diseases. Calcium-mediated autonomic denervation may have tipped the tissue autonomic balance toward sympathetic dominance and provided triggers for POAF. While autonomic denervation has emerged as a novel therapy to treat various cardiovascular diseases, it should only be performed with evidence supported by randomized clinical trials. The Chinese Clinical Trial Registry registration number: ChiCTR2000029314. website: http://www.chictr.org.cn/showproj.aspx?proj=48587 CLINICAL PERSPECTIVES What is new- Calcium-mediated autonomic denervation increased the incidence of post-operative atrial fibrillation (AF) in patient undergoing mitral valve surgery for severe mitral regurgitation, contradictory to the beneficial effects it exerted on patients undergoing coronary artery bypass surgery. Clinical implications- Each cardiovascular disease may have its distinct autonomic balance at the tissue level. - Mechanisms underlying the initiation and maintenance of AF vary greatly among cardiovascular diseases; autonomic denervation therefore can be beneficial or harmful. - Autonomic denervation for each cardiovascular disease should only be performed with evidence from randomized clinical trials to demonstrate its efficacy and safety.

BackgroundObesity is considered a significant risk factor for numerous cardiovascular conditions. The prevalence of atrial fibrillation (AF) is elevated among patients with obesity. Weight loss has been shown to reverse cardiac remodelling, leading to lower recurrence of AF despite the better prognosis in obese patients. MethodsWe utilized the National Inpatient Sample 2016-2019 to extract patients [&ge;]18 years of age admitted with AF as the primary diagnosis based on ICD 10 codes. We performed univariate and multivariate regression analysis for known coronary risk factors. We divided patients based on their body mass index (BMI), and our primary outcomes were determining the odds of electrical cardioversion (ECV) and cardiac ablation (CA) due to AF. ResultsThe analysis included 1,625,809 weighted patients. Patients include underweight (6.66%), normal BMI (4.03), overweight (6.51%), obesity class I (20.65%), obesity class II (21.45%), and obesity class III (40.7). After multivariate regression analysis, patients with obesity class I, II, or III had higher odds of ECV, irrespectively of coronary risk factors (OR 1.3, 95% CI 1.25-1.37, OR 1.3, 95% CI 1.32-1.43, OR 1.3, 95% CI1.29-1.38, respectively, with statistically significant P values). However, underweight or normal BMI patients had fewer odds of ECV (OR 0.5 95%CI 0.49-0.61 and OR 0.6 95%CI 0.58-0.74, respectively, with P values <0.001). Meanwhile, there was no statistical significance between a BMI and the odds of CA. ConclusionOur study highlights the significant impact of BMI on managing AF, particularly regarding ECV. Patients in higher BMI categories (obesity class I to III) had increased odds of undergoing ECV, suggesting obesity influences treatment approaches and outcomes in AF management. Interestingly, BMI did not affect the likelihood of CA, indicating a complex relationship between body weight and AF treatment modalities warranting further investigation.

BackgroundGLP-1 receptor agonists (GLP-1RAs), initially developed for glycemic control in type 2 diabetes, have shown cardiometabolic benefits including weight loss, improved endothelial function, and reduced inflammation. Recent data suggest potential anti-arrhythmic effects via modulation of atrial substrate and autonomic tone. Their impact in obese, non-diabetic patients remains underexplored. This study examines whether GLP-1RA use is associated with reduced AF recurrence after catheter ablation in obese patients, using real-world data from a large multicenter database. MethodsWe conducted a retrospective cohort study using the TriNetX research network, which contains de-identified electronic health records from more than 100 million patients. Adult patients (age [&ge;]18 years) with obesity (BMI >30 kg/m2) who underwent AF ablation between January 2005 and January 2025 were eligible. The cohort was divided into GLP-1RA users (n = 2,867) and non-users (n = 2,867), with 1:1 propensity score matching performed across 82 clinical and demographic variables including age, sex, race, AF subtype, cardiovascular comorbidities, and baseline medications. ResultsDuring a median follow-up of 1.6 years (IQR: 2.6): AF recurrence was significantly lower in GLP-1RA users (7.43% vs. 8.40%, HR 0.843, 95%CI 0.780-0.911, p<0.0001) Progression to permanent AF occurred less frequently in GLP-1RA users (3.15% vs. 4.35%, HR 0.743, 95%CI 0.610-0.905, p=0.003). Risk of all-cause mortality was lower in the GLP-1RA group (HR 0.700, 95%CI 0.553-0.887, p=0.003) HF hospitalization (HR 0.819, 95%CI 0.722-0.929, p=0.002) and cardiovascular hospitalizations (HR 0.856, 95%CI 0.773-0.947, p=0.003) were also significantly lower with GLP-1RA use. No significant difference was found for redo ablation. ConclusionIn a large real-world cohort of obese patients undergoing catheter ablation for AF, GLP-1RA therapy was associated with lower risks of AF recurrence, progression to permanent AF, cardiovascular hospitalizations, and mortality.

BackgroundBy means of echocardiographic assessment and deformation analysis we sought to evaluate the effect of spironolactone versus placebo in addition to standard treatment in patients with paroxysmal or persistent atrial fibrillation (AF) and preserved ejection fraction regarding the performance of the left atrium (LA) and the left ventricle (LV), and quality of life (QOL). MethodsPresent double-blind, placebo-controlled study enrolled 125 patients with a history of paroxysmal (n=58) and persistent (n=67) non-valvular AF and LVEF [&ge;]45% that were randomized to spironolactone 25 mg (n=63) or placebo (n=62) once daily in addition to optimal standard treatment. Comprehensive echocardiography and QOL were obtained at inclusion and after 12 months. The primary outcome was 12-month change in LA reservoir function as assessed by peak atrial longitudinal strain (PALS) and peak strain rate (SR-s). Secondary outcomes included LA phasic volumes, global longitudinal strain of left ventricle (GLS), E/e ratio, QOL, and recurrent documented episodes of AF. ResultsSpironolactone improved the LA reservoir function documented by PALS and SR-s (P =0.03 and P =0.02 for adjusted treatment effect, respectively) but only when adjusting for the parallel changes in blood pressure. Blood pressure significantly reduced in the spironolactone-treated subjects and affected primary outcomes, but not diastolic indices of LV. Transmitral E velocity and E/e ratio reduced significantly by spironolactone (P=0.009 for adjusted treatment effect). No differences in secondary outcome parameters were found across treatment groups including volumes, LA geometry, GLS, total number AF recurrences, time-to-first AF recurrence or QOL. ConclusionSpironolactone improved left atrial reservoir function by lowering blood pressure and decrease E/e ratio but did not affect left atrial volumes or geometry, quality of life or recurrent episodes of atrial fibrillation. Trial registration: ClinicalTrials.org identifier NCT02764619 and EudraCT identifier 2013-000797-30.

BackgroundAtrial fibrillation (AF) recurrence is common in patients after catheter ablation. Previous studies have demonstrated a lower risk of AF recurrence after ablation with the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients with diabetes or heart failure. However, the effects of SGLT2i in AF patients after catheter ablation without current indications for SGLT2i were uncertain. ObjectiveThis trial aims to evaluate the effect of dapagliflozin on AF burden after ablation in persistent atrial fibrillation (PeAF) patients. Study DesignEfficacy of DApagliflozin on REcurrence after catheter ablation for Atrial Fibrillation (DARE-AF) is a parallel-group, randomized, open-label randomized controlled trial. We aim to enroll 200 patients with de novo atrial fibrillation (AF) undergoing catheter ablation, and patients with class I indications for SGLT2 Inh (diabetes, heart failure, or chronic kidney disease) are excluded. PeAF patients will be randomized in a 1:1 ratio to intervention or control group. Patients in the intervention group will receive dapagliflozin 10mg once daily for three months. The primary outcome is AF burden accessed by 7-day single-lead electrocardiogram patches at three months after ablation. ConclusionsDARE-AF is the first clinical trial, aiming to evaluate the effect of 3-month treatment with dapagliflozin on AF burden after catheter ablation in PeAF patients without current indications.

BackgroundThe aim of this single-center retrospective study is to evaluate the long-term outcome after convergent procedure (CP) for patients with paroxysmal atrial fibrillation (AF), persistent AF and long-standing persistent AF. Methods and resultsWe analyzed outcomes of patients that underwent CP from January 2009 until July 2020. 119 patients with paroxysmal AF (23.5%), persistent AF (5.9%) or long-standing persistent AF (70.6%) that attended long-term follow up were included. The outcome was assessed at 1-year after CP and at long-term follow up. At 1-year follow up rhythm and daily AF burden were assessed for patients with implantable loop recorder (61.2%). For others rhythm was assessed by clinical presentation and 12-lead ECG recording. At long-term follow up patients having sinus rhythm or unclear history of AF were monitored with 7-day ECG Holter and AF burden was determined. Long-term success was defined as freedom from AF/atrial flutter (AFL) with sinus rhythm on 12-lead ECG recording and AF/AFL burden <1% on 7-day Holter ECG. Repeat catheter ablations (RFA) prior to long-term follow up were documented. At 1-year follow up 91.4% of patients had sinus rhythm and 76.1% of patients had AF/AFL burden <1%. At long-term follow up (8.3 {+/-} 2.8 years) 65.5% of patients had sinus rhythm and 53.8% patients had AF/AFL burden <1% on 7-day holter ECG. Additional RFAs were performed in 32.8% of patients who had AF or AFL burden <1%. At long-term follow up age, body mass index and left atrial volume index were associated with increased risk of AF recurrence. ConclusionsCP resulted in high long-term probability of sinus rhythm maintenance. During long-term follow-up additional RFAs were required to maintain sinus rhythm in a substantial number of patients.

BackgroundAmong very elderly patients with atrial fibrillation, the frequency of inappropriate direct oral anticoagulant (DOAC) dosing, associated factors, and temporal trends in practice are unknown. ObjectiveTo investigate the frequency of inappropriate DOAC dosing, associated factors, and temporal trends in very elderly patients with atrial fibrillation. MethodsWe retrospectively enrolled consecutive very elderly inpatients ([&ge;]80 years of age) diagnosed with atrial fibrillation at Beijing Hospital from January 2018 to August 2023, and discharged on DOACs were stratified according to receipt of underdosing, overdosing, or recommended dosing. Risk factors associated with underdosing or overdosing were identified using logistic regression. Cochran-Mantel-Haenszel analyses were used to assess temporal trends. ResultsWe included 676 inpatients aged [&ge;]80 years with atrial fibrillation (mean age 84.4{+/-}3.5 years, 53.1% female) prescribed a DOAC at hospital discharge (22.9% dabigatran, 62.3% rivaroxaban, 14.8% edoxaban). Recommended dosing occurred in 338 (50.6%) patients, underdosing in 308 (45.6%), and overdosing in 30 (4.4%). The overall rate of inappropriate dosing was 49.4%. Risk factors associated with underdosing included older age (OR = 1.98, 95% CI: 1.52-2.60, p < 0.001), lower CrCl (OR = 0.98, 95% CI: 0.97-0.99, p = 0.01), and non-internal medicine ward (OR = 2.15, 95% CI: 1.33-3.45, p = 0.002). The risk factor associated with overdosing was younger age (OR = 0.38, 95% CI: 0.19-0.75, p = 0.005). Over the study period, recommended dosing increased over time with a corresponding decline in inappropriate dosing, but these changes were not statistically significant. ConclusionsInappropriate DOAC dosing, especially underdosing, remains common in very elderly AF inpatients. This issue persists despite years passing, emphasizing the need for patient-focused, collaborative AF management and thorough prognostic studies. What Is New?Among AF patients aged 80 and above, nearly half experienced inappropriate NOAC dosing, with 92.3% of these cases being underdosed. This situation has not shown significant improvement over the years. Risk factors associated with underdosing included older age, compromised renal function, and hospitalization in non-internal medicine wards. Risk factor associated with overdosing was younger age. What Are the Clinical Implications?There is an urgent need for patient-centered, multidisciplinary AF management and shared decision-making, coupled with robust prognostic research focusing on very elderly AF patients.

BackgroundAtrial fibrillation (AF) is considered the most common supraventricular arrhythmia in patients undergoing coronary artery bypass graft (CABG). The predictive value of the SYNTAX score for post-CABG new-onset AF incidence has not been clearly evaluated. This study aimed to assess this association in patients undergoing isolated on-pump CABG. MethodThis study was done in a single-center, randomized, and observational setting. A total of 133 patients undergoing on-pump isolated CABG who were older than 18 years and had sinus rhythm were enrolled. Demographic variables of patients were recorded, and the SYNTAX score was measured for the participants. The multivariate logistic regression model was applied to identify the predictors of post-CABG new-onset AF. ResultsThe logistic regression model showed that SYNTAX score of more than 28.25 (p-value= 0.001; OR= 14.25, 95% CI= 2.90_70.11), hypertension (p-value=0.02; OR = 6.59, 95% CI = 1.23_34.57), and calcium channel blocker consumption (p-value=0.02; OR = 8.05, 95% CI = 1.43_45.42) are predictors of new-onset AF after on-pump CABG. ConclusionThis study demonstrated that patients with higher SYNTAX scores in coronary angiography are more likely to develop new-onset AF after isolated on-pump CABG.

BackgroundThe Endothelial Activation and Stress Index (EASIX) reflects endothelial dysfunction and has prognostic value in cardiovascular diseases. This study investigates the association between EASIX and all-cause mortality in critically ill atrial fibrillation (AF) patients. MethodsUsing MIMIC-IV (v3.1) data, 4722 AF patients were stratified by EASIX quartiles. Cox regression, Kaplan-Meier curves, and restricted cubic spline (RCS) models assessed mortality risk at 7, 30, 180, and 365 days. Subgroup analyses evaluated consistency. ResultsEASIX was significantly associated with increased mortality at all time points. The Kaplan-Meier survival curve shows that as the EASIX quartile increases, the 7-day, 30-day, 180-day, and 365-day mortality rates of AF patients significantly increase. RCS analyses showed that there was a significant non-linear relationship between EASIX and the 7-day, 30-day, 180-day, and 365-day mortality rates of patients with AF. The Cox analysis before and after adjusting for confounding factors showed that EASIX was an independent risk factor for 7-day, 30-day, 180-day, and 365-day all-cause mortality in AF patients. Subgroup analyses further indicated the robustness of these results. ConclusionsEASIX levels are significantly correlated with all-cause mortality at 7, 30, 180, and 365 days in patients with AF, and endothelial dysfunction plays an important role in poor prognosis in AF patients.

ImportanceObservational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF. ObjectiveThe primary objective of this study was to investigate the relationship between blood pressure and risk of AF using genetic proxies for blood pressure within a Mendelian randomization (MR) framework. We secondarily explored the relationship between genetically proxied use of anti-hypertensive drugs and risk of AF. DesignTwo-sample MR was performed using an inverse-variance weighted meta-analysis with weighted median MR and Egger intercept tests performed as sensitivity analyses. Genetic proxies for the anti-hypertensive drug classes were used to investigate the impact of these therapies on the risk of AF. SettingInternational Consortium of Blood Pressure, UK Biobank and Atrial Fibrillation Genetics Consortium. ParticipantsSummary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) were obtained from the International Consortium of Blood Pressure and the UK Biobank discovery analysis (>750,000 individuals of European ancestry). Summary statistics for AF were obtained from the 2018 Atrial Fibrillation Genetics Consortium multi-ethnic GWAS (>65,000 AF cases and >522,000 referents). ExposureGenetically predicted SBP, DBP and PP as quantified by risk scores. Main OutcomeOdds ratio for AF per 10 mmHg increase in genetically proxied blood pressure. ResultsTen mmHg increases in genetically proxied SBP, DBP or PP were associated with increased odds of AF (SBP: OR 1.17, 95% CI 1.11-1.22, p=1[x] 10-11; DBP: OR 1.25, 95% CI 1.16-1.35, p=3[x] 10-8; PP: OR 1.1, 95% CI 1.0-1.2, p=0.05). Ten mmHg decreases in SBP estimated by genetic proxies of anti-hypertensive medications showed calcium channel blockers (OR 0.66, 95% CI 0.57-0.76, p=8[x] 10-9) and beta-blockers (OR 0.61, 95% CI 0.46-0.81, p=6[x] 10-4) decreased the risk of AF. Conclusions and RelevanceBlood pressure-increasing genetic variants were associated with increased risk of AF, consistent with a causal relationship between blood pressure and AF. These data support the concept that blood pressure reduction through pharmacologic intervention, and specifically calcium channel blockade or beta blockade could reduce the risk of AF.

ObjectivesWomen with heart failure (HF) with reduced ejection fraction receiving submaximal doses of beta-blockers and renin-angiotensin system (RAS) inhibitors have a lower risk of mortality or hospitalizations for heart failure. However, optimal doses of beta-blockers or RAS inhibitors in women with atrial fibrillation (AF) with and without HF are unclear. We investigated sex-specific associations of beta-blocker and RAS inhibitor doses with cardiovascular outcomes in patients with AF with and without HF. MethodsWe used data from the prospective BEAT-AF and Swiss-AF cohorts on patients with AF. The outcome was major adverse cardiovascular events (MACE), including death, myocardial infarction, stroke, systemic embolization, and HF-related hospitalization. Predictors of interest were spline (primary analysis) or quartiles (secondary analysis) of beta-blocker or RAS inhibitor dose in percent of the maximum dose (reference), in interaction with sex. Cox models were adjusted for demographics, comorbidities and co-medication. ResultsAmong 3,961 patients (28% women), MACE occurred in 1,113 (28%) patients over 5-year median follow-up. Distributions of RAS inhibitor and beta-blocker doses were similar in women and men. Cox models revealed no association between beta-blocker dose or RAS inhibitor dose and MACE. In a subgroup of patients with AF and HF, the lowest hazard of MACE was observed in women prescribed 100% of RAS inhibitor dose. However, there was no association between RAS dose quartiles and MACE. ConclusionsIn these two cohorts of patients with AF, doses of beta-blockers and RAS inhibitors did not differ by sex and were overall not associated with MACE. What is already known on the subjectSex-specific analyses of beta-blocker and renin angiotensin system (RAS) inhibitor doses in patients with heart failure with reduced ejection fraction have revealed a lower hazard of death or heart failure-related hospitalisation in women receiving low doses compared to maximum doses. The pathophysiology and pharmacotherapy of atrial fibrillation show sex differences, but the potential sex-specific associations of different drug doses with cardiovascular outcomes are unknown in this population. What this study addsThis study identifies no associations between beta-blocker doses and major adverse cardiovascular events in patients with atrial fibrillation. How this study might affect research, practice or policyThe findings of the present study reassure that the recommended maximum doses of beta-blockers and RAS inhibitors appeared safe among patients of both sexes with atrial fibrillation.

IntroductionAtrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and is a significant risk factor for ischemic stroke and death. Digitalis has been used for more than 200 years to treat heart conditions, including AF, and its use remains controversial due to uncertain long-term morbidity and mortality. MethodsWe conducted a cohort study of hospitalized patients with AF assessing the effects of digoxin on longterm all-cause mortality. Patients were divided into two groups: with and without heart failure (HF). We performed multivariable Cox regression analysis to assess hazard ratios (HR) for all-cause mortality depending on digoxin treatment and used propensity score matching to adjust for differences in background characteristics between treatment groups. ResultsAmong 2179 consecutive patients hospitalized with AF, the median age was 73 {+/-} 14, and 52.5% of patients were male, 49% had HF, and 18.8% were discharged on digoxin. Median left ventricular ejection fraction in the whole cohort was 60 (IQR 40-65). Among patients with HF, 34.5% had preserved, 17.3% had mid-range and 48.1% had reduced left ventricular ejection fraction. The mean follow-up time was 3 {+/-} 2.05 years. In patients without HF there was a statistically significant increased mortality in the digoxin subgroup after propensity score matching (HR = 2.23, 95% CI 1.42-3.51, p < 0.001). In contrast, in patients with HF, there was no difference in mortality between the treatment groups (p = 0.92). ConclusionsDigoxin use in our study was associated with increased mortality in patients with AF and without concomitant HF.

BackgroundPatients with atrial fibrillation (AF), the most common sustained cardiac arrhythmia, often have a low cardiorespiratory fitness (CRF) and poor physical and mental health due to disabling AF symptoms. This is more pronounced in females, who also report worse AF symptoms and quality of life (QoL) than males. Improving CRF through exercise training is an important AF management target associated with lower hospitalization and mortality rates. Emerging research suggests smaller CRF improvements in females than males following the same exercise training program. Yet, this has not been systematically reviewed in the AF population. The primary purpose of this systematic review is to compare changes in CRF following exercise training between females and males with AF. Secondary aims will compare changes in AF symptoms, QoL and additional physical and mental health outcomes between sexes. MethodsWe will adhere to the reporting guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Five electronic bibliographic databases are being searched to identify studies with prospective cohort and experimental designs, implementing exercise training of any form (e.g. aerobic, strength) for at least 4 weeks, in adults ([&ge;]18 years old) with an AF diagnosis. Eligible studies must report a baseline and follow-up measure of at least one primary or secondary outcome. CRF (primary outcome) can be estimated or directly measured as peak oxygen consumption (VO2peak). When eligible results are not segregated by sex, authors will be contacted to obtain sex-specific data. Study quality and risk of bias will be assessed using the Tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEX) scale and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Meta-analyses will be conducted to synthesize the measures of effect in studies with sufficient homogeneity. DiscussionThis review will address the lack of sex-based analyses in exercise studies in the AF population. By using a sex lens, we will provide evidence on the physical and mental health effects of exercise training in females and males with AF. Our findings will be of value to patients with AF, researchers and healthcare providers involved in AF management. Systematic review registrationPROSPERO #CRD42022302310

BackgroundThere are few myocardial damage markers that could be used to diagnose acute myocardial infarction(AMI) or assess its severity, especially glycosylated apolipoprotein J(ApoJ-Glyc) has demonstrated superiority in cardiomyocytes and animal STEMI models in the early stages of myocardial ischemia(MI). We aimed to excavate the potential role of ApoJ-Glyc as a protein marker in the pathogenesis of AMI in humans and its added value in the evolution of the disease. Methods and ResultsELISA was used to determine the serum concentration of ApoJ-Glyc in 163 patients enrolled by the criteria. Statistical analysis could used to discuss the relationship between ApoJ-Glyc and AMI. Compared to control groups, serum ApoJ-Glyc levels decreased by 36% and 37% in early AMI patients and AMI patients, respectively (P<0.0001), showing a higher discriminant value for early diagnosis and diagnosis of AMI [area under the curve (AUC) : 0.871 and 0.886, P< 0.0001]. For the first time, we demonstrated that ApoJ-Glyc was not statistically significant in the comparative difference between NSTEMI and STEMI groups (P> 0.05). Patients with gradually declining ApoJ-Glyc had a higher Grace Risk Scores. Subsequent studies have also demonstrated that more MACCE did occur with a 6-month follow-up(P<0.05). ConclusionsApoJ-Glyc which serve as an alarm bell for the detection of early ischaemia, may be a new biomarker for AMI. ApoJ-Glyc can assess the severity of myocardial infarction. The continuous decrease of serum ApoJ-Glyc suggests an increase in the risk of post-AMI ischaemia and the onset of unpredictable MACCE. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/23291631v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1d3b996org.highwire.dtl.DTLVardef@13d4482org.highwire.dtl.DTLVardef@15cf203org.highwire.dtl.DTLVardef@114de20_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundDespite the recognized risk of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) in patients with obstructive sleep apnea (OSA), the effect of continuous positive airway pressure (CPAP) remains inconsistent across studies, necessitating further examination. MethodsUtilizing databases encompassing Web of Science, Pubmed and OVID, we implemented a meta-analysis dedicated to investigating the role of OSA in post-PVI AF recurrence and the preventative properties of CPAP. ResultsOur meta-analysis of OSA patients undergoing PVI suggests an AF recurrence risk with a RR (risk ratio) of 1.67 (95% CI: 1.52-1.83). For patients with no atrial size difference, the risk is RR=2.13 (95% CI: 1.63-2.79), and with size difference, its RR=1.78 (95% CI: 1.46-2.17). Diagnoses from the Berlin questionnaire and polysomnography yielded RRs of 1.71 (95% CI: 1.37-2.14) and 1.75 (95% CI: 1.40-2.18), respectively. Non-CPAP usage increases AF recurrence risk by 67% and especially in cases of significant atrial size difference (RR=1.63, 95%CI:1.32-2.03). Conversely, when atrial size difference is absent, the impact of CPAP appears to be insignificant (RR=1.22, 95%CI: 0.98-3.02). Co-existence of paroxysmal and non-paroxysmal AF indicates a significant CPAP effect (RR=1.78, 95% CI: 1.50-2.09), contrary to one study on paroxysmal AF patients (RR=1.3, 95%CI: 0.71-1.50). ConclusionOur meta-analysis found a significant risk of AF recurrence in patients with OSA following PVI. However, OSA had an insignificant impact on AF recurrence in paroxysmal AF patients. Non-CPAP usage generally increased recurrence risk. Yet, in subgroups without prominent atrial size difference and paroxysmal AF, CPAPs influence was not significant. Keywords: CPAP; Atrial Fibrillation; Obstructive Sleep Apnea; Pulmonary vein isolation

BackgroundCatheter ablation (CA) is the leading rhythm control strategy for atrial fibrillation (AF). Despite its effectiveness, AF recurrences, driven by underlying structural and electrical remodeling in both the atria and the ventricle, remain prevalent. Cardiac magnetic resonance (CMR) imaging has emerged as a key modality for assessing myocardial remodeling and potentially identifying predictors of AF recurrence. This study aimed to investigate atrial and biventricular remodeling following CA of AF and its impact on AF recurrence. Methods and ResultsFifty patients with AF (52% male, age 68{+/-}10 years) and twenty healthy controls (45% male, age 68{+/-}10 years) underwent CMR at least three months following CA. Recurrence of AF was evaluated over 1-year follow-up and defined as at least two unsuccessful attempts to restore SR. Atrial function was measured using phasic volumetric and strain parameters. Ventricular function was evaluated through volumetry, global left ventricular (LV) and right ventricular (RV) strain and LV structure through parametric mapping (native T1/T2 mapping and extracellular volume (ECV)). Patients with AF recurrence at 1 year showed significantly impaired LA active emptying function (14{+/-}12% vs 26{+/-}14%, P=0.009) and strain (-4.5{+/-}4.3% vs -10.6{+/-}6.8%, P=0.004), prolongation of both LV T1 (1040{+/-}55ms vs 985{+/-}43ms, P=0.007) and T2 (53.6{+/-}1.6ms vs 50.6{+/-}2.5ms, P=0.002) times and elevated LV ECV (28.0{+/-}3.0% vs 26.2{+/-}1.7%, P=0.027) compared with those without recurrence. A combined model incorporating LA active strain, LV T1 native, ECV and T2 further improved prediction of AF recurrence at 1-year follow-up (HR: 17.70, 95% CI=3.89 - 80.61, log-rank P value <0.001 for cut-off values of LA Active Strain > -8%, T1 > 1017.3ms, ECV > 27% and T2 > 52.4ms). RV free wall longitudinal strain was more negative in AF non-recurrence group compared with controls but not in the AF recurrence group, suggesting the compensatory importance of RV function in post-procedural hemodynamic recovery. ConclusionAF recurrence after CA appears linked to persistent atrial dysfunction and ventricular remodelling, potentially fostering a pro-arrhythmic milieu. Incorporating CMR-derived measures into AF care might help improve personalized risk stratification for CA outcomes.

ObjectivesThis study aimed to explore the linkage between intra-left ventricular (LV) diastolic hemodynamics and coronary endothelial function, utilizing four-dimensional (4D) flow magnetic resonance imaging (MR) and myocardial flow reserve (MFR) through simultaneous acquisition using hybrid PETMR system in patients with ischemic heart disease (IHD). MethodsSixty-eight patients (mean 66 {+/-} 15 years, male 55) with IHD who underwent rest-pharmacological stress 13N-ammonia PET/MR were included. MFR and summed defect score (SSS and SRS for stress and rest) were obtained thorough rest-stress PET images. MR acquisition was performed simultaneously during PET scan to obtain rest-stress 4D flow datasets and followed by cine-MRI for the LV volume measurement. LV diastolic inflow(mL/s), peak velocity(cm/s), and averaged diastolic kinetic energy (KE)(J/mL) indexed with endo-diastolic volume were computed. ResultsDiastolic LV inflow parameters and KE significantly increased in stress scan compared to the rest (74.8 {+/-} 17.5 cm/s vs. 64.5 {+/-} 14.4 cm/s, p<0.0001; 10.1 {+/-} 5.2 vs. 13.3 {+/-} 7.8, p=0.0004 for peak velocity and KE, respectively). Stress KE showed a significant and weak correlation to MFR and SSS (r = 0.3, p=0.004; r=-0.4, p=0.002 for MFR and SSS, respectively). In patients with MFR above median value (1.76), stress KE significantly elevated from rest KE, while no significant change was observed for the patients with MFR below median (11.0 {+/-} 4.6 vs. 16.2 {+/-} 8.8, p=0.0002; 9.7 {+/-} 5.4 vs. 10.3 {+/-} 5.1 for rest vs. stress, respectively). ConclusionNon-invasive assessment of intra-LV diastolic hemodynamics derived from 4D flow MRI demonstrated significant alterations under stress, and was found to have a notable association with the extent of ischemia and coronary endothelial dysfunction.