New-onset Atrial Fibrillation Research Articles

Semaglutide and atrial fibrillation: a systematic review and meta-analysis of randomized clinical trials

Abstract Introduction Semaglutide is a glucagon-like peptide-1 receptor agonist that has been highly recommended for glycemic controland weight reduction. Obesity can also increase the risk of developing atrial fibrillation (AF). Aims To assess the association of semaglutide with cardiac arrhythmias, primarily AF. Methods We performed a systematic searched Pubmed, Embase and Cochrane database, between November and December 2023, to identify semaglutide’s randomized controlled trials (RCTs) with or without diabetic patients that reported new-onset cardiac arrythmias. A Mantel-Haenszel method and a random-effects model was used to calculate the odds ratio (OR) and 95% confidence interval (CI). Results 16 RCTs were included, 6 with oral semaglutide and 11 with subcutaneous semaglutide. A total of 19892 patients were included, providing 137 new-onset AF. Our meta-analysis revealed a lower incidence of new-onset AF in semaglutide patients (pooled odds ratio [OR], 0.54; 95% confidence interval [CI] 0.39, 0.77, P < 0.01; I2 = 0%). Sub-analysis of oral and subcutaneous showed similar significant reduction (pooled OR 0.44; 95% CI [0.22, 0.87], P = 0.02, I2 = 0% and pooled OR 0.59; 95% CI [0.39, 0.88], P < 0.01, I2 = 0%, respectively). Significant reduction was also observed, regardless diabetic status. However, semaglutide revealed similar atrial flutter incidence (pooled OR 0.78; 95% CI [0.30, 2.05], P = 0.62, I2 = 0%), ventricular arrhythmias (pooled OR 1.68; 95% CI [0.77, 3.6], P = 0.19, I2 = 0%) and sudden cardiac death (pooled OR 1.68; 95% CI [0.77, 3.66], P = 0.19, I2 = 0%). Conclusion Our study suggests that in patients with or without diabetes, semaglutide reduces the risk of new-onset atrial fibrillation. This analysis provides an additionalcardiovascular benefit of this drug besides the major adverse cardiovascular events.

Long-term risk of heart failure and postoperative atrial fibrillation following noncardiac surgery: not so different from non-surgical atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with the development of heart failure (HF). However, it is unclear if postoperative AF (POAF) after noncardiac surgery differs from non-surgical AF in terms of the risk of HF. Objectives To investigate the long-term rate of incident HF in patients developing new-onset POAF after noncardiac surgery relative to patients with non-surgical nonvalvular AF (NVAF). Methods Using Danish nationwide registries, all patients aged ≥30 years who developed POAF following noncardiac, nonobstetric surgery from 1996 to 2020 were identified. These patients were matched in a 1:3 ratio by age, sex, selected comorbidities, and year of inclusion with patients with non-surgical NVAF. The primary outcome was incident HF. Secondary outcomes were HF hospitalization and all-cause mortality. Results A total of 1,846 patients with POAF were matched with 5,538 patients with non-surgical NVAF (median age: 76 years [25th-75th percentile: 67-83 years]; 53.1% females). The median follow-up was 7.6 years. Compared with patients with non-surgical NVAF, patients with POAF did not have a significantly different rate of incident HF (2.7 versus 3.0 events per 100 person-years; HR 0.89 [95% CI, 0.78-1.03]) or HF hospitalization (2.2 versus 2.4 per 100 person-years; HR 0.88 [95% CI, 0.76-1.03]), but they had a higher rate of all-cause mortality (10.0 versus 8.7 per 100 person-years; HR 1.27 [95% CI, 1.18-1.37]) (Figure 1). Conclusions Patients with new-onset postoperative atrial fibrillation did not have a significantly different rate of incident heart failure or heart failure hospitalization, but they had a higher associated rate of all-cause mortality compared to patients with non-surgical atrial fibrillation. This finding suggests that postoperative atrial fibrillation may be regarded as non-surgical atrial fibrillation in terms of the long-term risk of heart failure. This highlights the importance of increased awareness among physicians of the risk of adverse outcomes, including heart failure, in patients with postoperative atrial fibrillation after noncardiac surgery. Closer postoperative follow-up and monitoring, as well as aggressive treatment of cardiovascular risk factors, may be warranted to reduce the risk of adverse outcomes in these patients.

Postoperative atrial fibrillation following noncardiac surgery is associated with long-term heart failure: insights from a nationwide cohort

Abstract Background Atrial fibrillation (AF) is associated with the development of heart failure (HF). Whether postoperative AF (POAF) also confers a greater risk of HF is unclear. Purpose To investigate the long-term rate of incident HF in patients developing new-onset POAF after noncardiac surgery relative to patients who did not develop POAF after noncardiac surgery. Methods In this cohort study, the Danish nationwide registries were used to identify all patients aged ≥30 years who developed POAF following noncardiac, nonobstetric surgery from 1996 to 2020. These patients were matched in a 1:3 ratio by age, sex, type of surgery, selected comorbidities, and year of inclusion with patients without POAF after noncardiac surgery. The primary outcome was incident HF. Secondary outcomes were HF hospitalization and all-cause mortality. Results A total of 2,270 patients with POAF were matched with 6,810 patients without POAF (median age: 75 years [25th-75th percentile: 67-82 years]; 53.5% females). The median follow-up was 7.2 years. Compared with patients without POAF, those with POAF had a higher associated long-term rate of incident HF (2.6 versus 1.2 events per 100 person-years; HR 2.39 [95% CI 2.06-2.78]]), HF hospitalization (2.2 versus 1.0 events per 100 person-years; HR 2.33 [95% CI 1.97-2.74]), and all-cause mortality (9.8 versus 7.4 events per 100-person-years; HR 1.55 [95% CI 1.45-1.66]) (Figure 1). Conclusions Patients with new-onset postoperative atrial fibrillation following noncardiac surgery had a higher associated long-term rate of incident heart failure compared to those without postoperative atrial fibrillation following noncardiac surgery. These findings highlight the importance of increased awareness among physicians of the risk of adverse outcomes, including heart failure, in patients with postoperative atrial fibrillation after noncardiac surgery. Closer postoperative follow-up and monitoring, as well as aggressive treatment of cardiovascular risk factors, may be warranted to reduce the risk of adverse outcomes in these patients.

Risk of atrial fibrillation recurrence after new-onset transient episode during ST-elevation myocardial infarction

Abstract Background Atrial fibrillation (AF) often complicates ST-elevation myocardial infarction (STEMI) and is associated with major in-hospital complications and increased mortality. The data on AF recurrence after new-onset transient STEMI-associated AF is scarce, and electrocardiographic (ECG) predictors of AF recurrence are unknown. Purpose Our aim was to assess the risk of AF recurrence and to find out the predictors of AF recurrence after transient STEMI-associated AF. Methods STEMI patients admitted during 2007-2010 for primary percutaneous coronary interventions (PCI) were followed up until 2018. All ECGs ever recorded before, during or after STEMI (n=58907) were exported from regional database in digital format and processed using Glasgow algorithm. Clinical characteristics and mortality status were retrieved from the Swedish national registries. Information regarding AF was obtained from the national registries and the regional ECG database. STEMI-associated AF was defined as first-ever AF episode occurring between symptom onset and hospital discharge. Patients with pre-existing AF, AF after acute coronary artery bypass surgery and patients discharged with ongoing AF were excluded from analysis. P-wave indexes were assessed from the latest sinus rhythm ECG before discharge. The primary endpoint was the first documented AF episode after discharge. The secondary endpoints were total mortality and ischemic stroke. Cox regression analysis was adjusted for relevant clinical covariates. Results 1) 1956 patients who were discharged alive on sinus rhythm were included in the analysis (age 65±12, 70% males), 127(6.5%) of them had transient STEMI-associated AF. 2) Patients with STEMI-associated AF were more likely to develop AF during follow-up (n=74 [58.3%]) than patients without AF before or during STEMI (No AF) (n=56 [3.1%], HR=4.80 95%CI 3.93-5.97) (Figure 1). 3) None of the clinical and demographic characteristics was associated with AF recurrence. P-wave duration, P-terminal force in V1 and P-voltage in lead I were associated with AF recurrence, however only reduced P-wave voltage in lead I <93 µV (75th percentile) (HR=2.29 95% CI 1.21-4.35, p=0.011) remained independently associated with AF recurrence in adjusted analysis (Figure 2). 4) During follow-up, 134 patients had an ischemic stroke and 522 died. STEMI-associated AF was associated with higher long-term mortality risk comparing to No AF (HR=1.18 95%CI 1.02-1.36). The risk of stroke was not associated with STEMI-associated AF (HR=1.08 95%CI 0.79-1.49). In patients with STEMI-associated AF, occurrence of stroke did not differ between patients with and without AF recurrence (5[7%] vs 8 [15%] respectively, p=0.147). Conclusion STEMI-associated transient AF is associated with a 4.8-fold increased risk of AF after discharge, reaching 28% by 1 year after discharge. ECG-based P-wave indexes reflecting atrial remodeling can be used for the prediction of AF recurrence after discharge.

Impact of the underlying rhythm during cavotricuspid isthmus ablation on the incidence of future new-onset atrial fibrillation: insights from an international multi-centre registry

Abstract Background Radiofrequency catheter ablation of the cavotricuspid isthmus (RF-CTI) is the estabslished treatment of typical atrial flutter (AFL). After RF-CTI for AFL patients without previously documented atrial fibrillation (AF) may also develop AF. It is unknown whether the presence or absence of AFL at the time of ablation can predict the future occurence of AF. Purpose To compare baseline characteristics, procedural data, and long-term follow-up (FU) of patients with AFL. Methods Consecutive patients with documented AFL undergoing RF-CTI were enrolled in a multi-center registry in five centers in two countries between February 2017 and July 2023. For patients with AFL, entrainment mapping was performed for confirming CTI dependent AFL. Patients were categorized into two groups, those with AFL and those with sinus rhythm (SR) during RF-CTI. FU data were collected, including clinical assessments, 12-lead electrocardiogram (ECG) and 24-hour Holter-ECGs during each visit. Results Of the 949 subjects, 36% were excluded from the analysis due to a history of AF. A total of 574 patients were included (mean age 68 +/- 11 yrs, 14% females), 62% presented in AFL group and 38 % SR group during CTI. Median FU was 364 days. Patients in AFL group were older (P < 0.029), more likely to have diabetes (P = 0.026), and were less frequently treated with antiarrhythmic drugs (P < 0.001). In the first 12 months of FU, 40% of the patients underwent three FU examinations, while 77% of the patients underwent at least one 24-hour Holter-ECGs during FU. In the Kaplan-Meier analysis patients in AFL group significantly less often developed AF during FU (log-rank, P < 0.016, central ). In the multivariate Cox regression analysis, sinus rhythm during ablation (hazard ratio 1.474; 95% CI 1.043-2.084; P = 0.028), male gender (hazard ratio 1.722; 95% CI 1.116-2.658; P = 0.014) and coronary artery disease (hazard ratio 1.711; 95% CI 1.145-2.555; P = 0.009) were identified as predictors for the occurence of AF during FU. Conclusion Over a one year follow-up, new onset AF occurs significantly less frequently in patients with ongoing atrial flutter during RF-CTI ablation.

Artificial intelligence-enabled electrocardiogram for left ventricular diastolic dysfunction and long-term risk of new-onset atrial fibrillation

Abstract Background Heart failure (HF) and atrial fibrillation (AF) are intertwined, sharing common risk factors and influencing each other in a reciprocal manner. While left ventricular diastolic dysfunction (LVDD) stands as a hallmark of HF's hemodynamic profile, its direct correlation with heightened AF risk remains uncertain. Our recent validation of an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm for LVDD detection has opened new avenues. Yet, whether AI-ECG-detected LVDD correlates with long-term AF risk remains unexplored. Methods We performed a retrospective study among all patients with a comprehensive LVDD assessment from the test population of the AI-ECG LVDD study between September 2001 and June 2022. Patients with prior documented AF according to health records or previous ECG were excluded. Patients were classified by AI-ECG as normal diastolic function (DF), grade 1 (G1), grade 2 (G2), or grade 3 (G3) LVDD. We assessed the risk of AF across AI-ECG LVDD grade, with normal DF as reference, with competing risk models. Results Of 97,023 patients free of AF at baseline, 63,533 (65.4%), 10,776 (11.1%), 18,940 (19.5%), and 3,774 (3.9%) were classified as normal DF, G1-LVDD, G2-LVDD, and G3-LVDD, respectively. Worse AI-ECG LVDD was associated with older age, lower left ventricular ejection fraction (LVEF), and higher rates of HF, diabetes, hypertension, chronic pulmonary disease, renal failure, and cardiovascular disease (p-of-trend<0.001 for all). Over a median follow-up of 4.8 years (interquartile range 1.8-9.2 years), new-onset AF occurred in 6,795 (7.0%) patients. In multivariable survival analysis, adjusted to multiple risk factors including LVEF and clinical HF, G2 and G3 LVDD, representing patients with high filling pressures, were independently associated with a higher AF-risk [G2-LVDD: adjusted hazard ratio (aHR) 1.64 (95% confidence interval (95%CI) 1.52-1.73), G3-LVDD: aHR 2.24 (95%CI 2.02-2.48)]. Conclusion The AI-ECG LVDD algorithm independently predicts long-term AF risk, regardless of LVEF and clinical HF status, highlighting its potential for identifying high-risk populations and guiding proactive monitoring and management.

Predicting atrial fibrillation from ECG characteristics

Abstract Background/Introduction Atrial fibrillation (AF) is the most common cardiac arrythmia, and demographic shifts in age continues to increase the prevalence of atrial fibrillation on a global scale. With manifestations of short and intermittent duration, identifying and diagnosing AF often proves to be a challenge. As a consequence, patients who develop AF are at risk of experiencing stroke and other cardiac diseases such as heart failure (HF) before appropriate treatment is initialized. Despite the potential benefits of early AF detection, risk profiling based on electrocardiographic (ECG) findings is currently lacking. Several smaller studies have identified ECG characteristics associated with increased risk of AF, but these characteristics have not been individually evaluated in large-scale nationwide cohorts, and no evidence exists on the additive effect of these ECG characteristics. Purpose We aimed to evaluate the risk of new-onset AF, HF, and stroke according to five ECG characteristics previously linked to AF, in order to identify potential predictors of AF. Methods We used national registers and the Danish Nationwide ECG Cohort to include patients with ECG measurements taken between 2010 and 2022. Patients were grouped according to how many of the following ECG characteristics were present in their baseline ECG: Elevated heart rate (>80), prolonged PR-interval (≥196 ms for women and ≥204 ms for men), biphasic P-waves (positive and negative amplitude within same p-wave), abnormal P terminal force (≥ 6000 mV×ms), and prolonged P-wave duration(≥120 ms). Patients were followed for 2 years to evaluate the risk of atrial fibrillation, heart failure (HF), and stroke, according to baseline ECG characteristics. Results We included 1,505,474 patients of whom 594,702 had exactly one ECG characteristic, 197,367 had two characteristics, 44,983 had three characteristics, 6,390 had four characteristics, and 451 had all five characteristics on their baseline ECG. The risk of developing AF or HF increased with the number of ECG characteristics present on the baseline ECG. Patients with two ECG characteristics had a 2-fold increased risk of AF or HF compared to patients with no ECG characteristics (HR: 2.11 95%CI: 2.05-2.16). Patients with two or more ECG characteristics present on their baseline ECG exceeded a 5% 2-year absolute risk of developing either AF or HF. Among patients with only one ECG characteristic on their baseline ECG, elevated heart rate and prolonged PR interval were the factors most associated with an increased risk of AF compared to patients with none of the ECG characteristics on their baseline ECG. Conclusions The absolute and relative risk of atrial fibrillation, heart failure, and stroke increased with the number of ECG characteristics present on the baseline ECG. We suggest that the ECG characteristics evaluated in this study could be used in screening scenarios for atrial fibrillation to identify high risk patients.Absolute and relative 2-year risksRisk acc. to specific ECG characteristic

Cost differences between oral anticoagulation therapies in atrial fibrillation patients

Abstract Background Direct oral anticoagulants (DOACs) have largely replaced warfarin as the primary choice of oral anticoagulation (OAC) in atrial fibrillation (AF) patients. This study uses a nationwide registry data set to compare the health and social care costs of AF patients using different OAC therapies. We studied how these costs were distributed among different care services in the year following AF onset and how the costs develop in time before and after AF diagnosis. Methods This study is a part of the Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) research project, which includes data on patients with AF, combining registry data on primary and secondary care services as well as social services, drug purchases and laboratory data. We included all new-onset AF patients from 2011 to 2017 in Finland with an indication for OAC treatment. Patients were divided based on their first OAC purchase. Time in therapeutic range (TTR) values were assessed for warfarin patients, and they were divided into quartiles based on their TTR value. Standardized costs were determined for different health and social care contacts, accounting for hospital care, primary and ambulatory care, and long-term care. Drug costs were acquired from the Reimbursement for Prescription Medicines registry. Results A total of 130,745 patients (66,610 on warfarin, 32,996 on DOACs) were included. First-year total costs after onset of AF were €10,412 for rivaroxaban (n=13,320), €12,631 for apixaban (n=11,886), €10,706 for dabigatran (n=7,514) and €10,689 for edoxaban (n=366). Costs of care clustered near the diagnosis of AF (Figure 1). Costs for warfarin patients increased inversely with TTR, ranging from €10,945 in the highest TTR quartile (TTR over 82%) to €21,387 in the lowest (TTR under 57%). Average first-year costs for warfarin patients were €15,689, higher than DOAC patients by €3,058-€5,277 (Figure 2). Patients without any OAC had the highest first-year costs, €17,898. Patients with high risk of stroke had higher total costs both in patients using DOACS (€7,271 for patients with a CHA2DS2VA score of 1 vs €11,947 for patients with CHA2DS2VA 2+) and warfarin (€9,933 for CHA2DS2VA 1 vs €16,354 for CHA2DS2VA 2+). Drug costs averaged €1,541 for rivaroxaban, €1,659 for apixaban, €1,495 for dabigatran and €1,540 for edoxaban, and €986 warfarin users. Hospital care was the largest cost driver with 64% of total costs across the whole cohort, followed by primary care (19%), drug purchases (7%), social service costs (6%) and reimbursements for travel and private care (4%). Conclusions DOACs were superior to warfarin in a broad range of social and healthcare cost measures despite higher drug expenses. Patients on warfarin with low TTR and patients without any OAC had the highest cost of care.

Circadian rhythm in atrial fibrillation detected by implantable loop recorder: a post-hoc analysis of a randomized clinical trial

Abstract Introduction Previous studies suggest the existence of circadian, weekly, and seasonal rhythms in the occurrence of atrial fibrillation (AF), which may be utilized to improve the yield of screening. The heterogeneity of AF natural history also necessitates better phenotyping to overcome the challenges of identifying candidates for screening and treatment. Purpose To explore the potential circadian rhythm in AF occurrence in persons without known arrhythmia but at high risk of AF and stroke. Methods Post-hoc analysis of the LOOP study (Atrial Fibrillation Detected by Continuous Electrocardiogram Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals), which randomized 6004 AF naïve participants (≥70 years old with additional stroke risk factors) 1:3 to receive implantable loop recorder screening or usual care. All loop recorder data was extracted to obtain the date and time of AF episode onset, AF duration, mean and max heart rate (HR) during AF, and symptom annotations. New-onset AF episodes lasting ≥6 minutes were adjudicated, and all subsequent episodes were included in the analysis. Results A total of 41,713 AF episodes (median duration 18 (8-64) minutes) were identified among 430 participants (Table 1). The median number of episodes for each participant with AF was 21 (4-82) and the median AF burden was 0.17% (0.04%-0.83%) of time from debut to end of monitoring. The most and least frequent days of AF onset were Sunday (15.3%) and Friday (13.6%), respectively, while AF occurred slightly more often during spring (26%) than in other seasons. The median time of onset was 09:57:15 AM (05:15:30 AM – 03:33:00 PM). The most frequent time of onset was at 09:00 AM (rounded to the nearest hour), which was two times more likely than at 09:00 PM, and 22% of all episodes occurred between 08:00 and 11:00 AM (Figure 1). A total of 25,329 (61%) episodes occurred between midnight and noon (AM). Nocturnal episodes, defined as episodes with onset between 10:00 PM and 07:00 AM, occurred in 368 (86%) AF participants and constituted a median of 40% of all episodes and 37% (14%-63%) of each participant’s episodes. The median duration of nocturnal episodes was 28 (10-104) minutes compared to 14 (8-44) minutes for daytime episodes. The averaged heart rate during AF was 81 (71-96) beats per minute (BPM), while 330 (77%) participants had AF episodes with heart rates equal to or above 100 BPM, and the duration of these episodes was 50 (15-201) minutes compared to 30 (21-85) minutes for slower episodes (below 100 BPM). Conclusion A circadian pattern was observed for screening-detected AF. AF onset occurred predominantly between 08:00 and 11:00 AM, representing more than one in five episodes. Nocturnal AF occurred in most participants with AF and accounted for almost half of all episodes, while these episodes also lasted longer than daytime episodes. This may warrant future studies investigating the timing of AF screening.

A matter of inflammation: CAR T-cell therapy and atrial fibrillation

Abstract Background Chimeric antigen receptor (CAR) T-cell therapy has been revolutionary in the treatment of blood cancers, but has been associated with arrhythmias such as atrial fibrillation (AF). Whether the incidence of AF has changed over time and if contributing risk factors are present remains to be defined. Methods Leveraging the Mayo Electronic Medical Record, we extracted a cohort of patients who underwent CAR T-cell therapy between 2016 and 2022. From this cohort, we identified those who had a diagnosis of AF at any point. We then defined the endpoint of interest as the first episode of new or recurrent AF during or after CAR T-cell infusion. Fine and Gray subdistribution hazard modeling was used to calculate the association of patient characteristics to the endpoint of interest. Variables with P<0.20 in univariate modeling were chosen for the multivariate model. Significance was defined as P<0.05. Results There were 328 patients who underwent CAR T-cell therapy between 2016 and 2022. Of this cohort, 27 (8.2%) patients had a pre-existing diagnosis of AF, of which 6 had recurrence of AF after CAR T (22.2%), while 21 (77.8%) did not. Of the 301 patients without a prior history of AF, 8 (2.7%) patients developed new-onset AF after CAR T. The majority of the 14 new or recurrent AF events (4.3% overall incidence) occurred within 30 days of receiving CAR T (N=10, 71.4%), the remainder after 180 days (Figure 1). No trend in declining incidence over time was noted. Prior AF, neurotoxicity, and inflammation (cytokine release syndrome and macrophage activating syndrome-like (MAS-L)) were strongly associated with the risk of developing new or recurrent AF (Table 1). Only presence of MAS-L remained an independent predictor in the multivariate model (HR 15.4, 95% CI 3.9-61.2, P<0.001). Conclusion AF is mainly seen early following CAR T-cell therapy, and mainly in association with severe inflammatory responses. Early and aggressive treatment of CRS and MAS-L may be recommendable for patients undergoing CAR-T therapy, especially for those with a prior history of AF.

The incidence of atrial fibrillation in patients with interatrial shunt: is it reduced after surgical or transcatheter closure of the shunt?

Abstract Background Atrial fibrillation (AF) is a prevalent diagnosis among individuals with interatrial shunts, and the prevalence increases with age (1). Since the 1990s, interventionists have introduced transcatheter techniques, to close interatrial shunts, while surgical procedures reserved in cases of technical complexity (2). Despite the potential reduction in AF incidence post interatrial shunt closure, discernible modifications in the cardiac conduction system may persist (3). Notwithstanding, reports indicate an incidence of new-onset AF in approximately 10-25% of patients after interatrial shunt closure, with a pronounced prevalence among elderly (4). This study aims to delineate the incidence of AF subsequent to interatrial shunt, surgical och transcatheter, closure within a national cohort in Sweden. Methods The study includes all patients diagnosed with an interatrial shunt, atrial septal defect and patent foramen ovale, classified using the International Classification of Diseases, 10th edition (ICD-10), as documented in the Swedish National Patient Register, along with data sourced from the Cause of Death Register. Patients with multiple diagnoses of other congenital heart diseases are excluded, and interventions performed between 1997 and 2017 are identified using the NOMESCO surgical classification. Comorbidities such as chronic ischemic heart disease, myocardial infarction, heart failure, hypertension, and diabetes are considered, with the primary endpoint being the incidence of AF post-intervention. Results A total of 3,426 patients with interatrial shunts underwent intervention between 1997 and 2017, with a mean follow-up duration of 6.2 years. Among these, 49% (n=1,725) underwent transcatheter closure, while 41 patients underwent both transcatheter and surgical procedures. The mean age was 36 years, with 9% presenting with heart failure at baseline. Before the intervention, 14% (n=483) had AF, increasing to 22% (n=755) post-intervention. Of those developing AF post-intervention, 16% (n=119) experienced the AF event within 60 days, evenly distributed between transcatheter and surgical procedures. Over 40% of patients with post-intervention AF had an average age of 62. The incidence of AF post-intervention was 1.6 per 100 patient-years (see Figure). Stroke incidence was 3.6 per 100 patient-years and the mortality rate was 7% (n=257) during follow up (see Table). Conclusions Patients with interatrial shunts exhibit a high incidence of AF, which further escalates following closure of the interatrial shunt, not only within the first few days post-intervention, particularly among the elderly population. This can relate to high incidence of ischemic stroke.Figure

Long-term changes in frailty and incident atrial fibrillation: multicenter prospective cohort study

Abstract Background Atrial fibrillation is the most common sustained cardiac arrhythmia and is prevalent among the elderly. Previous findings indicated a higher prevalence of AF in frail adults and frailty prevalent in AF patients. However, the association between dynamic changes of frailty and risk of new-onset AF is unclear. Purpose We aimed to investigate the associations of long-term changes in frailty with incident AF. Its associations with heart failure (HF), coronary heart disease (CHD), and stroke were also evaluated as a secondary aim. Methods Over 50,000 participants from UK Biobank cohort were included, with available frailty index (FI) data and free of AF, HF, CHD or stroke in both baseline and final follow-up assessments. Participants were categorized into nonfrailty, prefrailty and frailty based on their FI scores. Changes of frailty status from baseline to final follow-up assessment included alleviation, maintenance, and aggravation. Thus, transitions of frailty status included 7 categories: nonfrailty maintenance, nonfrailty aggravation (nonfrailty to prefrailty or frailty), prefrailty alleviation (prefrailty to nonfrailty), prefrailty maintenance, prefrailty aggravation (prefrailty to frailty), frailty alleviation (frailty to prefrailty or nonfrailty), and frailty maintenance. FI in baseline and follow-ups are used to calculate the trajectories of frailty (ΔFI). Cox proportional hazard models were used. Results Compared with nonfrailty at baseline, the HRs (95% CI) of AF for prefrailty and frailty were 1.32 (1.29, 1.36) and 1.89 (1.83, 1.96) in the multivariable-adjusted model. During a median of 5.1 years of follow-up from the final assessment, 1729 cases of AF were recorded. Frailty trajectory analysis showed that even a 0.01 point/year increase in ΔFI was associated with 14% (95% CI 1.08-1.20) higher risk of AF, independent of baseline FI and the risk rose to 1.89 (1.45, 2.46) with per 0.05 point/year increase in ΔFI. This association was strengthened in low genetic risk of AF, but sex, age, smoking status, alcohol intake, obesity, hypertension, diabetes and cancer did not materially modify the associations. Moreover, compared with nonfrailty maintenance, sustained frailty had the highest risk of AF (HR 1.95, 1.61-2.36). Alleviation from frailty reduced the risk of AF by 30% (95%CI 0.53-0.94), compared to sustained frailty. These associations were similar in HF and CHD, however, not significant in stroke. Conclusions Middle aged and elderly people, including those with diabetes, obesity and hypertension, may gain substantial benefits in risk of AF, HF and CHD by becoming less frail or maintaining nonfrailty, irrespective of past frailty status and established risk factors, delivering public health implications for the necessity of early identification and timely interventions of frailty in heart health management.

Stroke recurrence after transcatheter PFO closure in patients with cryptogenic stroke.

Patent foramen ovale (PFO) closure is recommended for secondary prevention of cryptogenic stroke. However, data on long-term results are limited. We aimed to evaluate safety and efficacy of transcatheter PFO closure and predict neurologic recurrence. Data from patients undergoing PFO closure between 2010 and 2015 was collected to assess the combined endpoint of transient ischemic attack (TIA), stroke, or death from stroke at short- and long-term follow-up. 330 patients were included, mean age was 49 (±12) years and 55.5% were male. Before PFO closure, 86% experienced a stroke and 19% multiple neurological events. Procedure-related complications occurred in 2.4% of patients. Over a median follow-up of 10 years, the combined endpoint occurred in 3.6%, with a recurrence rate of 0.38 per 100 patient-years. Freedom from the combined endpoint at 5 and 10 years was 97.5% and 96.2%, respectively. New-onset atrial fibrillation was detected in 3%. The Risk of Paradoxical Embolism (RoPE) score (adjHR: 0.68; p=0.032), the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system (adjHR: 0.37; p=0.042), and a history of prior neurological events (adjHR: 9.94; p<0.001) were independent predictors of future recurrent neurologic events. Age, sex, and cardiovascular risk factors did not influence outcomes. In this real-world cohort, transcatheter PFO closure was associated with low long-term recurrence of neurologic events, especially cryptogenic strokes. The RoPE score, the PASCAL score and history of previous neurological events were predictive of recurrent events. This study supports the safety and efficacy of PFO closure for secondary prevention of cryptogenic strokes, and underscores the importance of patient selection.

Impact of atrial high-rate episodes on new onset of atrial fibrillation and all-cause mortality in elderly patients over 90 years old with dual-chamber pacemaker implantation

Objective: To investigate the impacts of atrial high-rate episodes (AHRE) on the risks of new onset of atrial fibrillation and all-cause mortality in elderly patients over 90 years old after cardiac dual-chamber pacemaker implantation. Methods: This study was a retrospective study. Patients aged 90 years and above who were implanted with cardiac dual-chamber pacemakers and followed up in the People's Liberation Army General Hospital from January 2017 to June 2022 were enrolled and divided into AHRE≥6 h group and AHRE<6 h group according to the onset time of AHRE. The primary endpoint was new onset of atrial fibrillation, and the secondary endpoints were all-cause mortality and cardiovascular mortality. Kaplan-Meier survival curve was poltted, and log-rank test was used to compare the differences in the incidence of new onset of atrial fibrillation, all-cause death and cardiovascular death between AHRE≥6 h and AHRE<6 h groups. Multivariate Cox survival analysis was used to investigate the factors affecting new onset of atrial fibrillation, all-cause death and cardiovascular death in elderly patients aged 90 years and above with dual-chamber pacemaker implantation. Results: A total of 169 patients were enrolled, aged (93.95±3.28) years, including 18 females (11%). The median follow-up time was 28.9 months. There were 87 and 82 patients in AHRE≥6 h group and AHRE<6 h group, respectively. Kaplan-Meier survival curve analysis showed that the incidence of new onset of atrial fibrillation (log-rank P<0.001), all-cause death (log-rank P=0.004) and cardiovascular death (log-rank P=0.026) in AHRE≥6 h group was significantly higher than that in AHRE<6 h group.After adjusting for traditional risk factors, multivariate Cox survival analysis showed that AHRE≥6 h was an independent risk factor for new onset of atrial fibrillation (HR=4.046, 95%CI 2.402-6.814, P<0.001) and all-cause mortality (HR=1.668, 95%CI 1.119-2.487, P=0.012) in elderly patients over 90 years old with cardiac dual-chamber pacemaker implantation. However, AHRE≥6 h had no effect on cardiovascular mortality (P>0.05). Anemia (HR=3.098, 95%CI 1.342-7.153, P=0.008) and heart failure with reduced ejection fraction (HR=3.028, 95%CI 1.181-7.763, P=0.021) were both independently associated with cardiovascular mortality. Conclusions: AHRE is common in cardiac dual-chamber pacemakers recipients aged 90 years and above, and AHRE≥6 h can be used as a predictor of new onset of atrial fibrillation or all-cause mortality in these patients.

Impact of High-Intensity Statin on Atrial Fibrillation After Off-Pump Coronary Artery Bypass.

There is uncertainty regarding the impact of high-intensity statins on postoperative outcomes in patients undergoing surgical myocardial revascularization. This study was conducted to evaluate the impact of high-intensity statin treatment on the occurrence rate of new-onset postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass grafting (OPCAB). Six hundred thirteen patients (66.8±9.8 years, male:female = 476:137) who underwent isolated OPCAB were retrospectively enrolled. Hypertension (n = 409, 66.7%), diabetes mellitus (n = 343, 59.6%) and chronic kidney disease (n = 138, 22.5%) were common comorbidities. Statins and beta-blockers were administered to all patients until the day of surgery and resumed within 6 hours after surgery. Risk factors associated with POAF were analyzed, including the use of high-intensity statins (atorvastatin 40 mg-80 mg or rosuvastatin 20 mg), as well as baseline characteristics and preoperative risk factors. High-intensity statins were used in 158 patients (25.8%). POAF occurred in 184 patients (30.0%). The use of high-intensity statins was not correlated with preoperative levels of low-density lipoprotein (P = 0.135) or high sensitivity C-reactive protein (P = 0.365). Multivariate logistic regression analysis revealed that the use of high-intensity statins was significantly associated with a reduced occurrence of POAF (P = 0.022, odds ratio [95% confidence interval] = 0.592 [0.378-0.926]). Age, acute coronary syndrome, insulin-dependent diabetes mellitus and chronic kidney disease were also significantly associated with POAF. Preoperative administration of high-intensity statins was associated with a 41% reduction in the occurrence rate of POAF in patients who underwent OPCAB.

Prediction of New-onset Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy Using Plasma Proteomics Profiling.

Atrial fibrillation (AF) is the most common sustained arrhythmia among patients with hypertrophic cardiomyopathy (HCM), increasing symptom burden and stroke risk. We aimed to construct a plasma proteomics-based model to predict new-onset AF in patients with HCM and determine dysregulated signaling pathways. In this prospective, multi-center cohort study, we conducted plasma proteomics profiling of 4,986 proteins at enrollment. We developed a proteomics-based machine learning (ML) model to predict new-onset AF using samples from one institution (training set) and tested its predictive ability using independent samples from another institution (test set). We performed a survival analysis to compare the risk of new-onset AF among high- and low-risk groups in the test set. We performed pathway analysis of proteins significantly (univariable p<0.05) associated with new-onset AF using a false discovery rate (FDR) threshold of 0.001. The study included 284 patients with HCM (training set: 193, test set: 91). Thirty-seven (13%) patients developed AF during median follow-up of 3.2 years [25-75 percentile: 1.8-5.2]. Using the proteomics-based prediction model developed in the training set, the area under the receiver-operating-characteristic curve (AUC) was 0.89 (95% confidence interval 0.78-0.99) in the test set. In the test set, patients categorized as high-risk had a higher rate of developing new-onset AF (log-rank p=0.002). The Ras-MAPK pathway was dysregulated in patients who developed incident AF during follow-up (FDR<1.0×10-6). This is the first study to demonstrate the ability of plasma proteomics to predict new-onset AF in HCM and identify dysregulated signaling pathways.

Comparative Effectiveness of Devices for Interventional Patent Foramen Ovale Closure: Insights from a 23-Year Monocentric Analysis

Background/Objectives: Patent foramen ovale (PFO) is a congenital heart defect affecting up to 25% of the population, associated with an increased risk of cryptogenic stroke. Percutaneous PFO closure is a minimally invasive procedure aimed at reducing stroke risk by eliminating the right-to-left shunt. Methods: This monocentric, retrospective study analyzed 716 patients who underwent PFO closure between January 2000 and February 2023. Data collected included demographics, indications for closure, procedural details, and outcomes. Key endpoints were complications at the puncture site, pericardial effusion, recurrent stroke or transient ischemic attack (TIA), thrombi on the device, new-onset atrial fibrillation, and death. Results: The cohort had a mean age of 50.6 ± 12.6 years, with 60.8% female. Four devices were used: Occlutech PFO occluder (n = 106), Amplatzer PFO occluder (n = 227), Gore septal occluder (n = 296), and Cardia PFO-Star (n = 87). The initial procedural success rate was 98.9%, with no significant differences between devices. Complication rates were low across all devices. Residual shunt incidence decreased from 17.9% in 1 month to 3.4% in 12 months. Device-specific complications included late-onset pericardial effusion (p = 0.01), erosions (Cardia PFO-Star), and device thrombus formation (Gore septal occluder). Conclusions: PFO closure is a safe and effective method for preventing recurrent strokes, with high success rates and varying specific complication profiles, depending on the device. Further long-term studies are needed to evaluate newer devices and optimize patient outcomes.

Trends in Transcatheter Versus Surgical Aortic Valve Replacement Outcomes in Patients With Low-Surgical Risk: A Systematic Review and Meta-Analysis of Randomized Trials.

Limited data exist on long-term outcomes after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). This meta-analysis aims to elucidate outcome trends following TAVR versus SAVR in patients with severe aortic stenosis and low-surgical risk. A systematic search was conducted in PubMed, Embase, Scopus, and the Cochrane Library databases from inception until May 2024, to identify studies comparing TAVR versus SAVR in patients with low-surgical risk (Society of Thoracic Surgeons predicted risk of mortality score <4%). The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, stroke, disabling stroke, rehospitalization, myocardial infarction, aortic valve reintervention, permanent pacemaker implantation, and new-onset atrial fibrillation. Binary random-effects models were used to compare the risk of each outcome across various follow-up intervals and the risk of bias was assessed using the Cochrane Collaboration's Risk of Bias-2 tool. The meta-analysis included 6 randomized trials including 4682 patients. TAVR was associated with a lower risk of all-cause mortality than SAVR in the 30-day (hazard ratio [HR: 0.45] [95% CI: 0.26-0.77], I2: 0%) and 30-day to 1-year (HR: 0.55 [95% CI: 0.37-0.81], I2: 16%) follow-ups. However, the risk of all-cause mortality was similar during >1-year follow-ups. TAVR was associated with a significantly lower risk of cardiovascular mortality, disabling stroke, rehospitalization, new-onset atrial fibrillation, and a higher risk of permanent pacemaker implantation compared with SAVR during the 30-day follow-up. TAVR was associated with a lower risk of all-cause mortality within the first year of post-procedural follow-up compared with SAVR. However, the risk of all-cause mortality was similar in >1-year follow-ups.

Acute amiodarone-induced pulmonary toxicity in adult ICU patients with new-onset atrial fibrillation-A systematic review.

New-onset atrial fibrillation or flutter (NOAF) is a common arrhythmia in adult intensive care unit (ICU) patients. Intravenous amiodarone is one of the most used anti-arrhythmic drugs, despite its risk of inducing acute amiodarone-induced pulmonary toxicity (APT). We aimed to outline the body of evidence on acute APT in ICU patients with NOAF. We performed a systematic search using the population, intervention, comparison, and outcome (PICO) approach. We included studies of adults admitted to the ICU, who developed NOAF during their ICU stay, were treated with amiodarone, and reported on acute APT, irrespective of research design. The CASE guidelines were applied to evaluate the quality of the included studies, and study results are reported in accordance with the preferred reporting items for systematic reviews and meta-analyses. No randomised controlled trials or observational studies were identified. Nine case reports and one retrospective case series of fatal outcomes in ICU patients treated with amiodarone for NOAF constituted the evidence base. The quality of the included studies was high with a mean of 10 (range 8-12) of the 13 CASE guideline criteria fulfilled. The studies included a total of 16 critically ill adults who was diagnosed with acute APT after a mean of 9 days (range 2-20 days) following initiation of amiodarone with a mean total dose of amiodarone of 4553 mg (range 1100-13,500 mg) predominantly administrated intravenously. Three out of nine patients in the case reports died in the ICU during the amiodarone treatment. No long-term follow-up was conducted for the survivors. Acute APT in adult ICU patients treated with amiodarone for NOAF is poorly described and is based on a total of 16 reported cases. Additional studies assessing the safety of amiodarone in critically ill adults with NOAF in the ICU is warranted.

A pooled analysis of the incidence and mortality risk of atrial fibrillation in patients with COVID-19.

There exist serious cardiovascular complications subsequent to SARS-Cov2 infection (COVID-19); however, the association between COVID-19 and atrial fibrillation (AF) remains to be elucidated. We aimed to assess the prevalence of AF among COVID-19 patients and its associated risk of death. The present systematic review was performed in accordance with the PRISMA guidelines. The protocol was registered with CRD42022306523. A comprehensive literature search was performed across PubMed, Embase, and Cochrane databases to identify studies reporting on the prevalence of pre-existing or new-onset fibrillation (AF), and/or the associated clinical outcomes in patients with COVID-19 from January 2020 to December 2023. The random-effect model was used to estimate the prevalence of AF and its related mortality. A total of 80 studies, including 39,062,868 COVID-19 patients, were identified in the present investigation. The prevalence rates of pre-existing AF or new-onset AF were 10.5% (95% CI [9.3-11.7%]) or 10.3% (95% CI [6.2-14.5%]), respectively. Subgroup analysis revealed a two fold higher incidence of AF in older patients (≥65 years) compared to younger patients (<65 years) (14.4% vs. 6.4%). The highest rate of AF was observed in Europeans (10.7%, 95% CI [10.2-11.2%]), followed by Northern Americans (10.0%, 95% CI [8.2-11.7%]), while Asians demonstrated a lower prevalence (2.7%, 95% CI [2.2-3.3%]). Notably, severe COVID-19 patients displayed a significantly elevated prevalence of AF at 14.l% (95% CI [13.3-14.9%]), which was approximately 2.5-fold higher than that in non-severe patients (5.2%, 95% CI [4.8-5.5%]). Both pre-existing (HR: 1.83, 95% CI [1.49-2.17]) and new-onset AF (HR: 3.47, 95% CI [2.26-5.33]) were associated with an increased mortality risk among COVID-19 patients. Furthermore, the effect on mortality risk was more significant in Asians (HR: 5.33, 95% CI [1.62-9.04]), compared to Europeans (HR: 1.68, 95% CI [1.24-2.13]) and North Americans (HR: 2.01, 95% CI [1.18-2.83]). This study comprehensively investigated the association between AF and COVID-19 in a real-world setting. Notably, a high prevalence of AF was observed among older individuals, severe COVID-19 patients, and in Europe and Northern America. Moreover, co-existing AF was found to be associated with an increased risk for mortality. Further investigations are warranted to improve the management and outcomes of COVID-19 patients with AF.