Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation.

BACKGROUND: Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit. METHODS: We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason). RESULTS: We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group. CONCLUSIONS: Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.).

Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis of clinical trials.

BACKGROUND AND AIMS: Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in a variety of settings. This study aimed to assess whether cardioprotective effects of MRAs are modified by heart failure (HF) and atrial fibrillation (AF) status and to study their impact on AF events. METHODS: MEDLINE, Embase, and Cochrane Central databases were searched to 24 March 2023 for randomized controlled trials evaluating the efficacy of MRAs as compared with placebo or usual care in reducing cardiovascular outcomes and AF events in patients with or at risk for cardiovascular diseases. Random-effects models and interaction analyses were used to test for effect modification. RESULTS: Meta-analysis of seven trials (20 741 participants, mean age: 65.6 years, 32% women) showed that the efficacy of MRAs, as compared with placebo, in reducing a composite of cardiovascular death or HF hospitalization remains consistent across patients with HF [risk ratio = 0.81; 95% confidence interval (CI): 0.67-0.98] and without HF (risk ratio = 0.84; 95% CI: 0.75-0.93; interaction P = .77). Among patients with HF, MRAs reduced cardiovascular death or HF hospitalization in patients with AF (hazard ratio = 0.95; 95% CI: 0.54-1.66) to a similar extent as in those without AF (hazard ratio = 0.82; 95% CI: 0.63-1.07; interaction P = .65). Pooled data from 20 trials (21 791 participants, mean age: 65.2 years, 31.3% women) showed that MRAs reduce AF events (risk ratio = 0.76; 95% CI: 0.67-0.87) in both patients with and without prior AF. CONCLUSIONS: Mineralocorticoid receptor antagonists are similarly effective in preventing cardiovascular events in patients with and without HF and most likely retain their efficacy regardless of AF status. Mineralocorticoid receptor antagonists may also be moderately effective in preventing incident or recurrent AF events.

Atrial Fibrillation Recurrence in Patients With Transient New-Onset Atrial Fibrillation Detected During Hospitalization for Noncardiac Surgery or Medical Illness : A Matched Cohort Study.

BACKGROUND: Atrial fibrillation (AF) is often detected for the first time in patients who are hospitalized for another reason. Long-term risks for AF recurrence in these patients are unclear. OBJECTIVE: To estimate risk for AF recurrence in patients with new-onset AF during a hospitalization for noncardiac surgery or medical illness compared with a matched population without AF. DESIGN: Matched cohort study. (ClinicalTrials.gov: NCT03221777). SETTING: Three academic hospitals in Hamilton, Ontario, Canada. PARTICIPANTS: The study enrolled patients hospitalized for noncardiac surgery or medical illness who had transient new-onset AF. For each participant, an age- and sex-matched control participant with no history of AF from the same hospital ward was recruited. All participants left the hospital in sinus rhythm. MEASUREMENTS: 14-day electrocardiographic (ECG) monitor at 1 and 6 months and telephone assessment at 1, 6, and 12 months. The primary outcome was AF lasting at least 30 seconds on the monitor or captured by ECG 12-lead during routine care at 12 months. RESULTS: Among 139 participants with transient new-onset AF (70 patients with medical illness and 69 surgical patients) and 139 matched control participants, the mean age was 71 years (SD, 10), the mean CHA2DS2-VASc score was 3.0 (SD, 1.5), and 59% were male. The median duration of AF during the index hospitalization was 15.8 hours (IQR, 6.4 to 49.6 hours). After 1 year, recurrent AF was detected in 33.1% (95% CI, 25.3% to 40.9%) of participants in the transient new-onset AF group and 5.0% (CI, 1.4% to 8.7%) of matched control participants; after adjustment for the number of ECG monitors worn and for baseline clinical differences, the adjusted relative risk was 6.6 (CI, 3.2 to 13.7). After exclusion of participants who had electrical or pharmacologic cardioversion during the index hospitalization (n = 40) and their matched control participants and limiting to AF events detected by the patch ECG monitor, recurrent AF was detected in 32.3% (CI, 23.1% to 41.5%) of participants with transient new-onset AF and 3.0% (CI, 0% to 6.4%) of matched control participants. LIMITATIONS: Generalizability is limited, and the study was underpowered to evaluate subgroups and clinical predictors. CONCLUSION: Among patients who have transient new-onset AF during a hospitalization for noncardiac surgery or medical illness, approximately 1 in 3 will have recurrent AF within 1 year. PRIMARY FUNDING SOURCE: Peer-reviewed grants.

A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome.

Importance: Sudden death and cardiac arrest frequently occur without explanation, even after a thorough clinical evaluation. Calcium release deficiency syndrome (CRDS), a life-threatening genetic arrhythmia syndrome, is undetectable with standard testing and leads to unexplained cardiac arrest. Objective: To explore the cardiac repolarization response on an electrocardiogram after brief tachycardia and a pause as a clinical diagnostic test for CRDS. Design, Setting, and Participants: An international, multicenter, case-control study including individual cases of CRDS, 3 patient control groups (individuals with suspected supraventricular tachycardia; survivors of unexplained cardiac arrest [UCA]; and individuals with genotype-positive catecholaminergic polymorphic ventricular tachycardia [CPVT]), and genetic mouse models (CRDS, wild type, and CPVT were used to define the cellular mechanism) conducted at 10 centers in 7 countries. Patient tracings were recorded between June 2005 and December 2023, and the analyses were performed from April 2023 to December 2023. Intervention: Brief tachycardia and a subsequent pause (either spontaneous or mediated through cardiac pacing). Main Outcomes and Measures: Change in QT interval and change in T-wave amplitude (defined as the difference between their absolute values on the postpause sinus beat and the last beat prior to tachycardia). Results: Among 10 case patients with CRDS, 45 control patients with suspected supraventricular tachycardia, 10 control patients who experienced UCA, and 3 control patients with genotype-positive CPVT, the median change in T-wave amplitude on the postpause sinus beat (after brief ventricular tachycardia at ≥150 beats/min) was higher in patients with CRDS (P < .001). The smallest change in T-wave amplitude was 0.250 mV for a CRDS case patient compared with the largest change in T-wave amplitude of 0.160 mV for a control patient, indicating 100% discrimination. Although the median change in QT interval was longer in CRDS cases (P = .002), an overlap between the cases and controls was present. The genetic mouse models recapitulated the findings observed in humans and suggested the repolarization response was secondary to a pathologically large systolic release of calcium from the sarcoplasmic reticulum. Conclusions and Relevance: There is a unique repolarization response on an electrocardiogram after provocation with brief tachycardia and a subsequent pause in CRDS cases and mouse models, which is absent from the controls. If these findings are confirmed in larger studies, this easy to perform maneuver may serve as an effective clinical diagnostic test for CRDS and become an important part of the evaluation of cardiac arrest.

Bariatric Surgery and Cardiovascular Outcomes in Patients With Obesity and Cardiovascular Disease:: A Population-Based Retrospective Cohort Study.

BACKGROUND: Bariatric surgery has been shown to significantly reduce cardiovascular risk factors. However, whether surgery can reduce major adverse cardiovascular events (MACE), especially in patients with established cardiovascular disease, remains poorly understood. The present study aims to determine the association between bariatric surgery and MACE among patients with cardiovascular disease and severe obesity. METHODS: This was a propensity score-matched cohort study using province-wide multiple-linked administrative databases in Ontario, Canada. Patients with previous ischemic heart disease or heart failure who received bariatric surgery were matched on age, sex, heart failure history, and a propensity score to similar controls from a primary care medical record database in a 1:1 ratio. The primary outcome was the incidence of extended MACE (first occurrence of all-cause mortality, myocardial infarction, coronary revascularization, cerebrovascular events, and heart failure hospitalization). Secondary outcome included 3-component MACE (myocardial infarction, ischemic stroke, and all-cause mortality). Outcomes were evaluated through a combination of matching via propensity score and subsequent multivariable adjustment. RESULTS: A total of 2638 patients (n=1319 in each group) were included, with a median follow-up time of 4.6 years. The primary outcome occurred in 11.5% (151/1319) of the surgery group and 19.6% (259/1319) of the controls (adjusted hazard ratio [HR], 0.58 [95% CI, 0.48-0.71]; P<0.001). The association was notable for those with heart failure (HR, 0.44 [95% CI, 0.31-0.62]; P<0.001; absolute risk difference, 19.3% [95% CI, 12.0%-26.7%]) and in those with ischemic heart disease (HR, 0.60 [95% CI, 0.48-0.74]; P<0.001; absolute risk difference, 7.5% [95% CI, 4.7%-10.5%]). Surgery was also associated with a lower incidence of the secondary outcome (HR, 0.66 [95% CI, 0.52-0.84]; P=0.001) and cardiovascular mortality (HR, 0.35 [95% CI, 0.15-0.80]; P=0.001). CONCLUSIONS: Bariatric surgery was associated with a lower incidence of MACE in patients with cardiovascular disease and obesity. These findings require confirmation by a large-scale randomized trial.

Characterization of arrhythmia substrate to ablate persistent atrial fibrillation (COAST-AF): Randomized controlled trial design and rationale.

BACKGROUND: Atrial low voltage area (LVA) catheter ablation has emerged as a promising strategy for ablation of persistent atrial fibrillation (AF). It is unclear if catheter ablation of atrial LVA increases treatment success rates in patients with persistent AF. OBJECTIVE: The primary aim of this trial is to assess the potential benefit of adjunctive catheter ablation of atrial LVA in addition to pulmonary vein isolation (PVI) in patients with persistent AF, when compared to PVI alone. The secondary aims are to evaluate safety outcomes, the quality of life and the healthcare resource utilization. METHODS/DESIGN: A multicenter, prospective, parallel-group, 2-arm, single-blinded randomized controlled trial is under way (NCT03347227). Patients who are candidates for catheter ablation for persistent AF will be randomly assigned (1:1) to either PVI alone or PVI + atrial LVA ablation. The primary outcome is 18-month documented event rate of atrial arrhythmia (AF, atrial tachycardia or atrial flutter) post catheter ablation. Secondary outcomes include procedure-related complications, freedom from atrial arrhythmia at 12 months, AF burden, need for emergency department visits/hospitalization, need for repeat ablation for atrial arrhythmia, quality of life at 12 and 18 months, ablation time, and procedure duration. DISCUSSION: Characterization of Arrhythmia Mechanism to Ablate Atrial Fibrillation (COAST-AF) is a multicenter randomized trial evaluating ablation strategies for catheter ablation. We hypothesize that catheter ablation of atrial LVA in addition to PVI will result in higher procedural success rates when compared to PVI alone in patients with persistent AF.

Estimated incidence of previously undetected atrial fibrillation on a 14-day continuous electrocardiographic monitor and associated risk of stroke.

AIMS: There is uncertainty about whether and how to perform screening for atrial fibrillation (AF). To estimate the incidence of previously undetected AF that would be captured using a continuous 14-day ECG monitor and the associated risk of stroke. METHODS AND RESULTS: We analysed data from a cohort of patients >65 years old with hypertension and a pacemaker, but without known AF. For each participant, we simulated 1000 ECG monitors by randomly selecting 14-day windows in the 6 months following enrolment and calculated the average AF burden (total time in AF). We used Cox proportional hazards models adjusted for CHA2DS2-VASc score to estimate the risk of subsequent ischaemic stroke or systemic embolism (SSE) associated with burdens of AF > and <6 min. Among 2470 participants, the median CHA2DS2-VASc score was 4.0, and 44 patients experienced SSE after 6 months following enrolment. The proportion of participants with an AF burden >6 min was 3.10% (95% CI 2.53-3.72). This was consistent across strata of age and CHA2DS2-VASc scores. Over a mean follow-up of 2.4 years, the rate of SSE among patients with <6 min of AF was 0.70%/year, compared to 2.18%/year (adjusted HR 3.02; 95% CI 1.39-6.56) in those with >6 min of AF. CONCLUSIONS: Approximately 3% of individuals aged >65 years with hypertension may have more than 6 min of AF detected by a 14-day ECG monitor. This is associated with a stroke risk of over 2% per year. Whether oral anticoagulation will reduce stroke in these patients is unknown.

Remote ECG monitoring to reduce complications following transcatheter aortic valve implantations: the Redirect TAVI study.

AIMS: The optimal strategy of monitoring for conduction disturbances in patients undergoing transcatheter aortic valve implantation (TAVI) is uncertain. We evaluated a pre- and post-TAVI remote ambulatory cardiac monitoring (rACM) strategy for identification of conduction disturbances and to reduce unplanned pre-discharge post-TAVI permanent pacemaker implantation (PPMI). METHODS AND RESULTS: REdireCT TAVI (NCT0381820) was a prospective cohort study of patients referred for outpatient TAVI. Patients with prior PPMI were excluded. Remote ambulatory cardiac monitoring consisted of 2 weeks of continuous electrocardiogram (ECG) monitoring (Pocket-ECGTM) both before and after TAVI. Compliance to monitoring, frequency of notifications, unplanned PPMI post-TAVI, and length of hospitalization were measured. Between June 2018 and March 2020, in 192 undergoing TAVI (mean age: 81.8 years; female sex 46%; balloon-expandable valve 95.3%), compliance to rACM was 91.7% pre-TAVI (mean duration: 12.8 days), and 87.5% post-TAVI (mean duration: 12.9 days). There were 24 (12.5%) rACM notifications (13 pre-TAVI; 11 post-TAVI) resulting in 14 (7.3%) planned PPMI: seven pre-TAVI [due to sinus pauses n = 2 or atrio-ventricular block (AVB) n = 5] and seven post-TAVI [due to sinus pauses n = 1 or AVB n = 5 or ventricular tachycardia (VT) n = 1]. In addition, nine (4.7%) patients received pre-TAVI PPMI due to high-risk baseline ECG (right bundle branch block with hemi-block or prolonged PR interval). Unplanned PPMI post-TAVI during index hospitalization occurred in six (3.1%) patients due to AVB and in one patient readmitted with AVB. The median length of stay post-TAVI was 1 day. CONCLUSION: A strategy of routine rACM was feasible and frequently led to PPMI. Our approach of 2-week rACM both pre- and post-TAVI achieves both high patient compliance and sufficient surveillance. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03810820.

Characteristics and outcomes of atrial fibrillation in patients without traditional risk factors: an RE-LY AF registry analysis.

AIMS: Data on patient characteristics, prevalence, and outcomes of atrial fibrillation (AF) patients without traditional risk factors, often labelled 'lone AF', are sparse. METHODS AND RESULTS: The RE-LY AF registry included 15 400 individuals who presented to emergency departments with AF in 47 countries. This analysis focused on patients without traditional risk factors, including age ≥60 years, hypertension, coronary artery disease, heart failure, left ventricular hypertrophy, congenital heart disease, pulmonary disease, valve heart disease, hyperthyroidism, and prior cardiac surgery. Patients without traditional risk factors were compared with age- and region-matched controls with traditional risk factors (1:3 fashion). In 796 (5%) patients, no traditional risk factors were present. However, 98% (779/796) had less-established or borderline risk factors, including borderline hypertension (130-140/80-90 mmHg; 47%), chronic kidney disease (eGFR < 60 mL/min; 57%), obesity (body mass index > 30; 19%), diabetes (5%), excessive alcohol intake (>14 units/week; 4%), and smoking (25%). Compared with patients with traditional risk factors (n = 2388), patients without traditional risk factors were more often men (74% vs. 59%, P < 0.001) had paroxysmal AF (55% vs. 37%, P < 0.001) and less AF persistence after 1 year (21% vs. 49%, P < 0.001). Furthermore, 1-year stroke occurrence rate (0.6% vs. 2.0%, P = 0.013) and heart failure hospitalizations (0.9% vs. 12.5%, P < 0.001) were lower. However, risk of AF-related re-hospitalization was similar (18% vs. 21%, P = 0.09). CONCLUSION: Almost all patients without traditionally defined AF risk factors have less-established or borderline risk factors. These patients have a favourable 1-year prognosis, but risk of AF-related re-hospitalization remains high. Greater emphasis should be placed on recognition and management of less-established or borderline risk factors.

Thromboembolic events around the time of cardioversion for atrial fibrillation in patients receiving antiplatelet treatment in the ACTIVE trials.

AIMS: It is unknown whether cardioversion of atrial fibrillation causes thromboembolic events or is a risk marker. To assess causality, we examined the temporal pattern of thromboembolism in patients having cardioversion. METHODS AND RESULTS: We studied patients randomized to aspirin or aspirin plus clopidogrel in the ACTIVE trials, comparing the thromboembolic rate in the peri-cardioversion period (30 days before until 30 days after) to the rate during follow-up, remote from cardioversion. Among 962 patients, the 30-day thromboembolic rate remote from cardioversion was 0.16%; while it was 0.73% in the peri-cardioversion period [hazard ratio (HR) 4.1, 95% confidence interval (CI) 2.1-7.9]. The 30-day thromboembolic rates in the periods immediately before and after cardioversion were 0.47% and 0.96%, respectively (HR 2.2, 95% CI 0.7-7.1). Heart failure (HF) hospitalization increased in the peri-cardioversion period (HR 11.5, 95% CI 6.8-19.4). Compared to baseline, the thromboembolic rate in the 30 days following cardioversion was increased both in patients who received oral anticoagulation or a transoesophageal echocardiogram prior to cardioversion (HR 7.9, 95% CI 2.8-22.4) and in those who did not (HR 4.8, 95% CI 1.6-14.9) (interaction P = 0.2); the risk was also increased with successful (HR 4.5; 95% CI 2.0-10.5) and unsuccessful (HR 10.2; 95% CI 2.3-44.9) cardioversion. CONCLUSIONS: Thromboembolic risk increased in the 30 days before cardioversion and persisted until 30 days post-cardioversion, in a pattern similar to HF hospitalization. These data suggest that the increased thromboembolic risk around the time of cardioversion may not be entirely causal, but confounded by the overall clinical deterioration of patients requiring cardioversion.

Wearable and implantable diagnostic monitors in early assessment of atrial tachyarrhythmia burden.

Atrial fibrillation (AF) is the cause of substantial direct patient morbidity and a frequent cause of emergency room visits. Even when asymptomatic, AF remains a major cause of stroke, particularly among the elderly. As the risk of both AF and stroke increase with age, the importance of AF-related stroke is growing as a result of demographic shifts in many countries. Oral anticoagulation is highly effective at preventing stroke due to AF; however, AF remains undetected in a large number of individuals. The last decade has witnessed the development of many new technologies to detect AF. Screening studies using single-time point or repeated discrete screening methods have uncovered previously undiagnosed AF in 1-3% of asymptomatic individuals. However, continuous monitoring with implanted devices demonstrates short-lasting AF in over one-third of older individuals with cardiovascular risk factors. Debate remains regarding the minimum burden of AF that is associated with an increase in stroke risk, and the threshold for using oral anticoagulation. Over the next 5 years, ongoing studies will help clarify how wearable and implantable technology can be used to improve outcomes in patients with previously unrecognized AF.

Programmable Bio-nanochip Platform: A Point-of-Care Biosensor System with the Capacity To Learn.

The combination of point-of-care (POC) medical microdevices and machine learning has the potential transform the practice of medicine. In this area, scalable lab-on-a-chip (LOC) devices have many advantages over standard laboratory methods, including faster analysis, reduced cost, lower power consumption, and higher levels of integration and automation. Despite significant advances in LOC technologies over the years, several remaining obstacles are preventing clinical implementation and market penetration of these novel medical microdevices. Similarly, while machine learning has seen explosive growth in recent years and promises to shift the practice of medicine toward data-intensive and evidence-based decision making, its uptake has been hindered due to the lack of integration between clinical measurements and disease determinations. In this Account, we describe recent developments in the programmable bio-nanochip (p-BNC) system, a biosensor platform with the capacity for learning. The p-BNC is a "platform to digitize biology" in which small quantities of patient sample generate immunofluorescent signal on agarose bead sensors that is optically extracted and converted to antigen concentrations. The platform comprises disposable microfluidic cartridges, a portable analyzer, automated data analysis software, and intuitive mobile health interfaces. The single-use cartridges are fully integrated, self-contained microfluidic devices containing aqueous buffers conveniently embedded for POC use. A novel fluid delivery method was developed to provide accurate and repeatable flow rates via actuation of the cartridge's blister packs. A portable analyzer instrument was designed to integrate fluid delivery, optical detection, image analysis, and user interface, representing a universal system for acquiring, processing, and managing clinical data while overcoming many of the challenges facing the widespread clinical adoption of LOC technologies. We demonstrate the p-BNC's flexibility through the completion of multiplex assays within the single-use disposable cartridges for three clinical applications: prostate cancer, ovarian cancer, and acute myocardial infarction. Toward the goal of creating "sensors that learn", we have developed and describe here the Cardiac ScoreCard, a clinical decision support system for a spectrum of cardiovascular disease. The Cardiac ScoreCard approach comprises a comprehensive biomarker panel and risk factor information in a predictive model capable of assessing early risk and late-stage disease progression for heart attack and heart failure patients. These marker-driven tests have the potential to radically reduce costs, decrease wait times, and introduce new options for patients needing regular health monitoring. Further, these efforts demonstrate the clinical utility of fusing data from information-rich biomarkers and the Internet of Things (IoT) using predictive analytics to generate single-index assessments for wellness/illness status. By promoting disease prevention and personalized wellness management, tools of this nature have the potential to improve health care exponentially.

Atrial Fibrillation Ablation in Heart Failure With Reduced vs Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

Importance: Catheter ablation is associated with reduced heart failure (HF) hospitalization and death in select patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). However, the benefit in patients with HF with preserved ejection fraction (HFpEF) is uncertain. Objective: To investigate whether catheter ablation for AF is associated with reduced HF-related outcomes according to HF phenotype. Data Source: A systematic search of MEDLINE, Embase, and Cochrane Central was conducted among studies published from inception to September 2023. Study Selection: Parallel-group randomized clinical trials (RCTs) comparing catheter ablation with conventional rate or rhythm control therapies in patients with HF, New York Heart Association functional class II or greater, and a history of paroxysmal or persistent AF were included. Pairs of independent reviewers screened 7531 titles and abstracts, of which 12 RCTs and 4 substudies met selection criteria. Data Extraction and Synthesis: Data were abstracted in duplicate according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Pooled effect estimates were calculated using random-effects Mantel-Haenszel models. Interaction P values were used to test for subgroup differences. Main Outcomes and Measures: The primary outcome was HF events, defined as HF hospitalization, clinically significant worsening of HF, or unscheduled visits to a clinician for treatment intensification. Secondary outcomes included cardiovascular and all-cause mortality. Results: A total of 12 RCTs with 2465 participants (mean [SD] age, 65.3 [9.7] years; 658 females [26.7%]) were included; there were 1552 participants with HFrEF and 913 participants with HFpEF. Compared with conventional rate or rhythm control, catheter ablation was associated with reduced risk of HF events in HFrEF (risk ratio [RR], 0.59; 95% CI, 0.48-0.72), while there was no benefit in patients with HFpEF (RR, 0.93; 95% CI, 0.65-1.32) (P for interaction = .03). Catheter ablation was associated with reduced risk of cardiovascular death compared with conventional therapies in HFrEF (RR, 0.49; 95% CI, 0.34-0.70) but a differential association was not detected in HFpEF (RR, 0.91; 95% CI, 0.46-1.79) (P for interaction = .12). Similarly, no difference in the association of catheter ablation with all-cause mortality was found between HFrEF (RR vs conventional therapies, 0.63; 95% CI, 0.47-0.86) and HFpEF (RR vs conventional therapies, 0.95; 95% CI, 0.39-2.30) groups (P for interaction = .39). Conclusions and Relevance: This study found that catheter ablation for AF was associated with reduced risk of HF events in patients with HFrEF but had limited or no benefit in HFpEF. Results from ongoing trials may further elucidate the role of catheter ablation for AF in HFpEF.

Colchicine to Prevent Atrial Fibrillation Recurrence After Catheter Ablation: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Inflammation may promote atrial fibrillation (AF) recurrence after catheter ablation. This study aimed to evaluate a short-term anti-inflammatory treatment with colchicine following ablation of AF. METHODS: Patients scheduled for ablation were randomized to receive colchicine 0.6 mg twice daily or placebo for 10 days. The first dose of the study drug was administered within 4 hours before ablation. Atrial arrhythmia recurrence was defined as AF, atrial flutter, or atrial tachycardia >30 s on two 14-day Holters performed immediately and at 3 months following ablation. RESULTS: The modified intention-to-treat population included 199 patients (median age, 61 years; 22% female; 70% first procedure) who underwent radiofrequency (79%) or cryoballoon ablation (21%) of AF. Antiarrhythmic drugs were prescribed at discharge in 149 (75%) patients. Colchicine did not prevent atrial arrhythmia recurrence at 2 weeks (31% versus 32%; hazard ratio [HR], 0.98 [95% CI, 0.59-1.61]; P=0.92) or at 3 months following ablation (14% versus 15%; HR, 0.95 [95% CI, 0.45-2.02]; P=0.89). Postablation chest pain consistent with pericarditis was reduced with colchicine (4% versus 15%; HR, 0.26 [95% CI, 0.09-0.77]; P=0.02) and colchicine increased diarrhea (26% versus 7%; HR, 4.74 [95% CI, 1.95-11.53]; P<0.001). During a median follow-up of 1.3 years, colchicine did not reduce a composite of emergency department visit, cardiovascular hospitalization, cardioversion, or repeat ablation (29 versus 25 per 100 patient-years; HR, 1.18 [95% CI, 0.69-1.99]; P=0.55). CONCLUSIONS: Colchicine administered for 10 days following catheter ablation did not reduce atrial arrhythmia recurrence or AF-associated clinical events, but did reduce postablation chest pain and increase diarrhea.

Alcohol Consumption and Atrial Arrhythmia Recurrence After Atrial Fibrillation Ablation: A Systematic Review and Meta-analysis.

BACKGROUND: Although alcohol consumption is associated with an increased risk of atrial fibrillation (AF), it is unclear whether alcohol is associated with AF recurrences after catheter ablation for AF. We aimed to systematically review the medical literature to assess the impact of alcohol consumption on the recurrence of AF after AF ablation. METHODS: A structured electronic database search of the scientific literature (Medline, Embase, and Central from inceptions to December 2021) was performed for studies reporting rates of AF recurrence after catheter ablation stratified by patients' level of alcohol consumption according to study-specific definitions. Unadjusted study-specific odds ratios (ORs) were meta-analysed with the use of random-effects models. Risk of bias was evaluated by means of the ROBINS-I tool. RESULTS: We identified 9 observational studies which included 5436 patients who underwent catheter ablation for AF. Compared with patients consuming little or no alcohol, patients consuming moderate to high amounts of alcohol had a greater risk of AF recurrence (summary OR 1.45, 95% confidence interval [CI] 1.06-1.99; P = 0.02; I2 = 79%). Results remained robust when we excluded studies with < 100 participants (OR 1.40, 95% CI 1.03-1.9) or abstract-only publications (OR 1.84, 95% CI 1.21-2.8). All included studies were found to be at serious risk of bias, primarily due to confounding. CONCLUSIONS: Increased alcohol consumption is associated with an increased risk of AF recurrence after catheter ablation for AF. Reduction of alcohol consumption may be beneficial in this context.

Rhythm vs. Rate Control in Patients with Postoperative Atrial Fibrillation after Cardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; it is associated with morbidity and mortality. We undertook this review to compare the effects of rhythm vs. rate control in this population. METHODS: We searched MEDLINE, Embase and CENTRAL to March 2023. We included randomized trials and observational studies comparing rhythm to rate control in cardiac surgery patients with POAF. We used a random-effects model to meta-analyze data and rated the quality of evidence using GRADE. RESULTS: From 8,110 citations, we identified 8 randomized trials (990 patients). Drug regimens used for rhythm control included amiodarone in four trials, other class III anti-arrhythmics in one trial, class I anti-arrhythmics in four trials and either a class I or III anti-arrhythmic in one trial. Rhythm control compared to rate control did not result in a significant difference in length of stay (mean difference -0.8 days; 95% CI -3.0 to +1.4, I2 = 97%), AF recurrence within 1 week (130 events; risk ratio [RR] 1.1; 95%CI 0.6-1.9, I2 = 54%), AF recurrence up to 1 month (37 events; RR 0.9; 95%CI 0.5-1.8, I2 = 0%), AF recurrence up to 3 months (10 events; RR 1.0; 95%CI 0.3-3.4, I2 = 0%) or mortality (25 events; RR 1.6; 95%CI 0.7-3.5, I2 = 0%). Effect measures from seven observational studies (1428 patients) did not differ appreciably from those in randomized trials. CONCLUSIONS: Although atrial fibrillation is common after cardiac surgery, limited low-quality data guide its management. Limited available evidence suggests no clear advantage to either rhythm or rate control. A large-scale randomized trial is needed to inform this important clinical question.