A Mechanistic Clinical Trial Using (R)- Versus (S)-Propafenone to Test RyR2 (Ryanodine Receptor) Inhibition for the Prevention of Atrial Fibrillation Induction.

BACKGROUND: Experimental data suggest ryanodine receptor-mediated intracellular calcium leak is a mechanism for atrial fibrillation (AF), but evidence in humans is still needed. Propafenone is composed of two enantiomers that are equally potent sodium-channel blockers; however, (R)-propafenone is an ryanodine receptor inhibitor whereas (S)-propafenone is not. This study tested the hypothesis that ryanodine receptor inhibition with (R)-propafenone prevents induction of AF compared to (S)-propafenone or placebo in patients referred for AF ablation. METHODS: Participants were randomized 4:4:1 to a one-time intravenous dose of (R)-propafenone, (S)-propafenone, or placebo. The study drug was given at the start of the procedure and an AF induction protocol using rapid atrial pacing was performed before ablation. The primary endpoint was 30 s of AF or atrial flutter. RESULTS: A total of 193 participants were enrolled and 165 (85%) completed the study protocol (median age: 63 years, 58% male, 95% paroxysmal AF). Sustained AF and/or atrial flutter was induced in 60 participants (84.5%) receiving (R)-propafenone, 60 (80.0%) receiving (S)-propafenone group, and 12 (63.2%) receiving placebo. Atrial flutter occurred significantly more often in the (R)-propafenone (N=23, 32.4%) and (S)-propafenone (N=26, 34.7%) groups compared to placebo (N=1, 5.3%, P=0.029). There was no significant difference between (R)-propafenone and (S)-propafenone for the primary outcome of AF and/or atrial flutter induction in univariable (P=0.522) or multivariable analysis (P=0.199, adjusted for age and serum drug level). CONCLUSIONS: There is no difference in AF inducibility between (R)-propafenone and (S)-propafenone at clinically relevant concentrations. These results are confounded by a high rate of inducible atrial flutter due to sodium-channel blockade. REGISTRATION: https://clinicaltrials.gov; Unique Identifier: NCT02710669.

Is prophylactic ablation of the cavotricuspid and peri-incisional isthmus justified in patients with postoperative atrial flutter after right atriotomy?

BACKGROUND: The two most common postoperative atrial flutter (AFL) circuits after right atriotomy are the cavotricuspid isthmus (CTI) dependent and the lateral, peri-incisional. We investigated whether radiofrequency ablation (RFA) of both circuits results in more favorable long-term outcomes. METHODS: Single-center retrospective cohort study of consecutive patients who underwent RFA of AFL after open-heart surgery. The effect of surgery type and RFA strategy on AFL recurrence was evaluated. RESULTS: One hundred and forty-two patients (mean age 64.5 ± 12.7 years, 65.% male) were enrolled. Patients with right atrial (RA) flutter (n = 124) were divided into two groups based on the index RFA procedure: only one RA circuit was ablated (Group 1, n = 84, 67.7%) or both the CTI and the peri-incisional circuit ablated (Group 2, n = 40, 32.3%). The previous open-heart surgery was categorized based on the extension of the RA incision: limited (Type A) or extended (Type B) atriotomy. After a mean follow-up of 36 ± 28 months, flutter recurrence was not different among patients with limited RA atriotomy (25% vs. 22% in Groups 1A and 2A, respectively, p = 1.0). However, after type B surgery, ablation of both AFL circuits was associated with a reduced recurrence rate (63% vs. 26% in Groups 1B and 2B, respectively, p = .002). CONCLUSIONS: In patients with postoperative RA flutter after extended right atriotomy, ablation of both the CTI and the peri-incisional isthmus significantly reduces the AFL recurrence rate. Prophylactic ablation of both isthmi, even if not proven to support reentry, is reasonable in this population.

Meta-analysis of patent foramen ovale closure versus medical therapy for prevention of recurrent ischemic neurological events: Impact of medication type.

BACKGROUND: The optimal treatment strategy for patent foramen ovale (PFO) patients with cryptic stroke remains controversial. We performed this meta-analysis to evaluate the effect of PFO closure versus different types of medical therapy. METHODS: We searched PubMed, Embase, and Cochrane databases. The primary efficacy endpoints were the composite outcome of recurrent stroke and/or transient ischemic attack (TIA). Secondary efficacy endpoints included separate stroke and TIA. Safety endpoints included new-onset atrial fibrillation (AF)/atrial flutter and bleeding. RESULTS: Compared with antiplatelet therapy, PFO closure significantly reduced the risk of composite outcome (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.27-0.51), stroke (OR 0.22, 95% CI 0.13-0.36], and TIA (OR 0.57, 95% CI 0.34-0.98); Compared with the mixed medical therapy group (consist of antiplatelet therapy, anticoagulant therapy, or both), PFO closure still showed some benefits, but the effect was not as significant as that of antiplatelet therapy (composite outcome: OR 0.53, 95% CI 0.41-0.69; stroke: OR 0.48, 95% CI 0.34-0.68; TIA: OR 0.69, 95% CI 0.50-0.96); Compared with anticoagulant therapy, PFO closure showed no benefit (composite outcome: OR 0.77, 95% CI 0.46-1.28; stroke: OR 0.59, 95% CI 0.28-1.25; TIA: OR 1.01, 95% CI 0.50-2.04). In terms of safe endpoints, compared with antiplatelet therapy and anticoagulant therapy, PFO closure increased the risk of AF/atrial flutter (OR 9.56, 95% CI 2.85-32.06; OR 18.96, 95% CI 1.11-323.8, respectively) and reduced the risk of bleeding (OR 0.50, 95% CI 0.24-1.05; OR 0.13, 95% CI 0.04-0.46, respectively); compared with mixed medical therapy, PFO closure increased the risk of AF/atrial flutter (OR 4.40,95% CI 2.24-8.67), but there was no difference in bleeding (OR 0.97, 95% CI 0.56-1.68). CONCLUSIONS: With the addition of anticoagulants, the benefit of PFO closure decreased gradually. Patient groups that adopt individualized medical therapy strategies may benefit more.

Protective Effects of Sodium-Glucose Transporter 2 Inhibitors on Atrial Fibrillation and Atrial Flutter: A Systematic Review and Meta- Analysis of Randomized Placebo-Controlled Trials.

Background: Hyperglycemia is associated with an increased risk of developing atrial fibrillation (AF) and atrial flutter (AFL). Sodium-glucose transporter 2 inhibitors (SGLT2i) have been reported to prevent AF/AFL in some studies, but not others. Therefore, a meta-analysis was performed to investigate whether SGLT2i use is associated with lower risks of AF/AFL. Methods: PubMed, Scopus, Web of Science, Cochrane library databases were searched for randomized placebo-controlled trials comparing SGLT2i and placebo. Results: A total of 33 trials involving 66,685 patients were included. The serious adverse events (SAEs) of AF/AFL occurrence were significantly lower in the SGLT2i group than the placebo group (0.96% vs. 1.19%; RR 0.83; 95% CI 0.71-0.96; P = 0.01; I2 25.5%). Similarly, the SAEs of AF occurrence was significantly lower in the SGLT2i group (0.82% vs. 1.06%; RR 0.81; 95% CI 0.69-0.95; P = 0.01; I2 10.2%). The subgroup analysis showed that the reduction in AF/AFL was significant only for dapagliflozin (1.02% vs. 1.49%; RR 0.73; 95% CI 0.59-0.89; P = 0.002; I2 0%), but not for canagliflozin (1.00% vs 1.08%; RR 0.83; 95% CI 0.62-1.12; P = 0.23; I2 0%), empagliflozin (0.88% vs 0.70%; RR 1.20; 95% CI 0.76-1.90; P = 0.43; I2 0%), ertugliflozin (1.01% vs 0.96%; RR 1.08; 95% CI 0.66-1.75; P = 0.76; I2 0%), and sotagliflozin (0.16% vs 0.10%; RR 1.09; 95% CI 0.13-8.86; P = 0.93; I2 0%). Conclusions: SGLT2i use is associated with a 19.33% lower SAEs of AF/AFL compared with the placebo. Dapagliflozin users had the lowest SAEs of AF/AFL incidence. Further studies are needed to determine whether canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin similarly exert protective effects against AF/AFL development.

SGLT2 inhibitors and atrial fibrillation in type 2 diabetes: a systematic review with meta-analysis of 16 randomized controlled trials.

BACKGROUND: Type 2 diabetes is closely related to an increased risk of atrial fibrillation (AF) and atrial flutter (AFL). Whether sodium-glucose cotransporter 2 (SGLT2) inhibitors can attenuate AF/AFL progression remains unclear. METHODS: We searched electronic databases (PubMed, Embase and ClinicalTrials.gov) from their inception to January 2020 for trials evaluating the AF outcomes of SGLT2 inhibitors in patients with type 2 diabetes. The data search and extraction were conducted with a standardized data form and any conflicts were resolved by consensus. Relative risks (RRs) with 95% confidence intervals (CIs) were used for binary variables, and the weighed mean differences (WMDs) with the standard deviation (SDs) were applied for continuous variables. RESULTS: We included data from 16 identified trials consisting of 38,335 patients with type 2 diabetes. Incorporated data demonstrated that compared to placebo, SGLT2 inhibitors significantly reduced AF/AFL (RR: 0.76; 95% CI 0.65-0.90; p = 0.001) and all-cause mortality (RR: 0.91; 95% CI 0.83-0.99; p = 0.03). AF/AFL reductions were not modified by age, body weight, glycated haemoglobin (HbA1c), or systolic blood pressure (SBP) at baseline (all p-interactions > 0.3). SGLT2 inhibitors also significantly reduced heart failure events (RR: 0.73; 95% CI 0.64-0.84; p < 0.00001), HbA1c (WMD: - 0.62%; 95% CI - 0.89 to - 0.34; p < 0.00001), body weight (WMD: - 2.12 kg; 95% CI - 2.91 to - 1.34; p < 0.00001), SBP (WMD: - 3.34 mmHg; 95% CI - 4.12 to - 2.56; p < 0.00001), and diastolic blood pressure (DBP) (WMD: - 1.11 mmHg; 95% CI - 1.62 to - 0.60; p < 0.0001). Of note, cerebrovascular events and myocardial infarction did not increase in patients taking SGLT2 inhibitors. CONCLUSION: SGLT2 inhibitors may confer a specific AF/AFL-reduction benefit in the susceptible type 2 diabetes population, regardless of age, body weight, HbA1c, and systolic blood pressure at baseline. Such an AF/AFL-reduction benefit may be partly attributed to pharmacological effects on reductions in HbA1c, body weight, blood pressure, and the occurrence of heart failure.

Use and Outcomes Associated With Perioperative Amiodarone in Cardiac Surgery.

Background In randomized controlled trials, perioperative administration of amiodarone has been shown to reduce the incidence of postoperative atrial arrhythmias and length of stay (LOS) among patients undergoing coronary bypass surgery. However, little is known about the use or effectiveness of perioperative amiodarone in routine clinical practice. Methods and Results We studied patients ≥18 years old without a previous history of atrial or ventricular arrhythmias who underwent elective coronary bypass surgery between 2013 and 2014 within a network of 235 US hospitals. Perioperative amiodarone was defined as receipt of amiodarone either on the day of or the day preceding surgery. We used covariate-adjusted modeling and instrumental variable methods to examine the association between receipt of amiodarone and the development of atrial arrhythmias, in-hospital mortality, readmission, LOS, and cost. Of 12 758 patients, 2195 (17.2%) received perioperative amiodarone, 3330 (26.1%) developed atrial arrhythmias postoperatively, and the average LOS was 6.4 days (±2.6 days). Instrumental variable analysis showed that receipt of perioperative amiodarone was associated with lower risk of atrial arrhythmias (risk difference -11 percentage points, 95% CI -19 to -4 percentage points; P=0.002) and a shorter LOS (-0.7 day, 95% CI -1.39 to -0.01 days; P=0.048). There was no association between receipt of perioperative amiodarone and in-hospital mortality, cost, or readmission. Conclusions Among patients undergoing coronary bypass surgery without previous arrhythmias, perioperative amiodarone is associated with a lower risk of atrial arrhythmias and shorter LOS. These findings are consistent with previous randomized trials and lend support to current guideline recommendations.

Dabigatran and warfarin in nonvalvular atrial fibrillation or atrial flutter in outpatient clinic practice in Brazil.

OBJECTIVES: To compare warfarin and dabigatran for thromboembolic event prevention in patients with nonvalvular atrial fibrillation or atrial flutter. METHODS: This was a retrospective cohort of participants with nonvalvular atrial fibrillation or atrial flutter using either warfarin or dabigatran in a reference center in Brazil. RESULTS: There were 112 patients (mean age 65.5 years), with 55.3% using warfarin. The median duration of follow-up was 1.9 years for warfarin and 1.6 years for dabigatran (p = 0.167). Warfarin patients had a higher median of medical appointments per year (8.3 [6.8-10.4] vs 3.1 [2.3-4.2], p < 0.001) and the frequency of minor bleeding was more than four times higher (17.7% vs 4.0%, p = 0.035). Among patients with prior stroke, those using warfarin had 2.6 times more medical appointments for person-years of follow-up (8.5 vs 3.3). There was no major bleeding or embolic event during follow-up period. CONCLUSION: The dabigatran group had a lower frequency of minor bleeding and number of medical appointments than the warfarin group, without more embolic events or major bleeding.

Dabigatran and warfarin in nonvalvular atrial fibrillation or atrial flutter in outpatient clinic practice in Brazil / Dabigatrana e varfarina em pacientes com fibrilação atrial não valvar ou flutter em ambulatório especializado no Brasil

ABSTRACT Objectives: To compare warfarin and dabigatran for thromboembolic event prevention in patients with nonvalvular atrial fibrillation or atrial flutter. Methods: This was a retrospective cohort of participants with nonvalvular atrial fibrillation or atrial flutter using either warfarin or dabigatran in a reference center in Brazil. Results: There were 112 patients (mean age 65.5 years), with 55.3% using warfarin. The median duration of follow-up was 1.9 years for warfarin and 1.6 years for dabigatran (p = 0.167). Warfarin patients had a higher median of medical appointments per year (8.3 [6.8-10.4] vs 3.1 [2.3-4.2], p < 0.001) and the frequency of minor bleeding was more than four times higher (17.7% vs 4.0%, p = 0.035). Among patients with prior stroke, those using warfarin had 2.6 times more medical appointments for person-years of follow-up (8.5 vs 3.3). There was no major bleeding or embolic event during follow-up period. Conclusion: The dabigatran group had a lower frequency of minor bleeding and number of medical appointments than the warfarin group, without more embolic events or major bleeding.

RESUMO Objetivos: Comparar varfarina e dabigatrana para prevenção de eventos tromboembólicos em pacientes com fibrilação atrial não valvar ou flutter (FA). Métodos: Coorte retrospectiva de pacientes com FA em uso de varfarina ou dabigatrana em serviço especializado no Brasil. Resultados: Foram avaliados 112 pacientes (média idade 65,5), com 55,3% no grupo varfarina. A mediana do tempo de seguimento foi de 1,9 anos para o grupo varfarina e 1,6 para dabigatrana (p = 0,167). No grupo varfarina houve maior mediana de consultas médicas (CM) por ano (8,3[6,8-10,4] vs. 3,1[2,3-4,2], p < 0,001), com frequência de sangramento menor quatro vezes maior (17,7% vs. 4,0%, p = 0,035). Nos pacientes com acidente vascular cerebral isquêmico prévio, o grupo varfarina teve 2,6 vezes mais CM por pessoas-ano de seguimento (8,5 vs. 3,3). Não houve sangramento maior ou eventos embólicos no período de seguimento. Conclusão: Pacientes em uso de dabigatrana tiveram menor número de sangramento menor e CM que aqueles em uso de varfarina, sem aumentar eventos embólicos ou sangramentos maiores.

A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial.

BACKGROUND: Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. METHODS/DESIGN: The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded "seamless" phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. CONCLUSIONS: GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. (ClinicalTrials.govNCT01970501).

Pharmacologic Prevention of Incident Atrial Fibrillation: Long-Term Results From the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

BACKGROUND: Although atrial fibrillation (AF) guidelines indicate that pharmacological blockade of the renin-angiotensin system may be considered for primary AF prevention in hypertensive patients, previous studies have yielded conflicting results. We sought to determine whether randomization to lisinopril reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a large clinical trial cohort with extended post-trial surveillance. METHODS AND RESULTS: We performed a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double-blind, active-controlled clinical trial that enrolled hypertensive individuals ≥55 years of age with at least one other cardiovascular risk factor. Participants were randomly assigned to receive amlodipine, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin versus usual care. The primary outcome was the development of either AF or AFL as diagnosed by serial study ECGs or by Medicare claims data. Among 14 837 participants without prevalent AF or AFL, 2514 developed AF/AFL during a mean 7.5±3.2 years of follow-up. Compared with chlorthalidone, randomization to either lisinopril (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15; P=0.46) or amlodipine (hazard ratio, 0.93; 95% confidence interval, 0.84-1.03; P=0.16) was not associated with a significant reduction in incident AF/AFL. CONCLUSIONS: Compared with chlorthalidone, treatment with lisinopril is not associated with a meaningful reduction in incident AF or AFL among older adults with a history of hypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

The Analog Blanking Period of Implantable Cardiac Rhythm Devices.

BACKGROUND: Analog blanking periods (BPs) that hold down the display of electrograms (EGMs) in cardiac rhythm devices have received much less attention than the well-known digital BPs which do not influence the EGM display. In Biotronik devices (Biotronik GmbH, Berlin, Germany), when a paced event initiates an analog BP in one chamber (right atrium, right ventricle [RV], or left ventricle [LV]), an identical cross-chamber analog BP starts in the other two chambers. METHODS: All clinical observations were recorded from patients with Biotronik devices. The effect of the atrial cross-chamber analog BP initiated by a ventricular paced event on the atrial EGM was studied in the records of seven patients with frequent paroxysmal atrial flutter to determine the effect of critically timed RV paced event (RVp) or LV paced event (LVp) upon the atrial EGM. The effect of atrial pacing triggering cross-chamber analog BPs in the RV and LV channels on the RV and LV EGMs was also investigated in cases of conducted supraventricular beats and ventricular premature complexes. The effect of a triggered LVp initiating a cross-chamber analog BP in the RV channel on the EGM of a sensed RV sensed event was evaluated in 10 cases. Simulation studies were also performed to verify the clinical observations. RESULTS: Patients with atrial flutter showed intermittent truncation or deformity and even disappearance of the atrial signals due to an atrial cross-chamber analog BP initiated by RVp and/or LVp. Three patients demonstrated deformity of the signal shape of ventricular premature beats falling within a ventricular cross-chamber analog BP initiated by right atrial paced event (RAp). We found only one case of a supraventricular QRS complex trapped in a ventricular cross-chamber analog BP initiated by RAp. All the recordings of LVp triggering upon RVs revealed a variety of RV signal deformities occasionally with preservation of the terminal part of the RV signal. Simulation studies confirmed the effect of the analog BP on the atrial and the ventricular EGMs. CONCLUSION: The analog BP of Biotronik devices may cause truncation or deformity of atrial and ventricular signals and the occasional disappearance of an atrial signal during atrial flutter. These effects must not be interpreted as device malfunction. In the clinical evaluation of the EGM curves, the effects of the analog BPs have to be carefully considered in order to avoid possible misinterpretation.

Characteristics and Outcomes of Concurrently Diagnosed New Rapid Atrial Fibrillation or Flutter and New Reduced Ejection Fraction.

BACKGROUND: Characteristics and outcomes of concurrently diagnosed new rapid atrial fibrillation (AF) or atrial flutter (AFL) and new heart failure with reduced left ventricular ejection fraction (LVEF) are not well described. METHODS: A retrospective cohort study of subjects referred for expedited transesophageal echocardiography-guided rhythm-control strategies for concurrent new rapid AF/AFL and new LVEF ≤ 40% diagnosed during the same admission was analyzed. RESULTS: Twenty-five subjects (median age 57 years; 96% male; 96% Caucasian; median CHA2 DS2 -VASc = 2) presented with new AF (n = 18) or AFL (n = 7) with rapid ventricular rate (median 135 beats/min) and new reduced LVEF (median 27%; range, 10-37.5%). Seven (28%) subjects had left atrial appendage thrombi (LAAT) and five (20%) subjects had heavy or binge alcohol use. Baseline characteristics were similar between those with and without LAAT. Thirteen subjects with AF and without LAAT underwent direct-current cardioversion (DCCV) and 10 (77%) had AF recurrence within 90 days. Improvement of long-term LVEF to >40% was comparable for subjects with and without initial LAAT (83% vs 94%; P = 0.46). Three of four subjects who received primary prophylaxis implantable cardioverter-defibrillators improved their LVEF to >35% after sinus rhythm maintenance. The median long-term follow-up time was 3.0 years. CONCLUSIONS: Subjects with concurrently diagnosed new rapid AF/AFL and new reduced LVEF are characterized by a high prevalence of LAAT and significant alcohol use. AF subjects without initial LAAT who underwent DCCV had a high 90-day AF recurrence rate. The presence of LAAT did not have a prognosticative effect on eventual LVEF improvement, which was observed in almost all subjects.

Concomitant atrial fibrillation surgery for people undergoing cardiac surgery.

BACKGROUND: People with atrial fibrillation (AF) often undergo cardiac surgery for other underlying reasons and are frequently offered concomitant AF surgery to reduce the frequency of short- and long-term AF and improve short- and long-term outcomes. OBJECTIVES: To assess the effects of concomitant AF surgery among people with AF who are undergoing cardiac surgery on short-term and long-term (12 months or greater) health-related outcomes, health-related quality of life, and costs. SEARCH METHODS: Starting from the year when the first "maze" AF surgery was reported (1987), we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (March 2016), MEDLINE Ovid (March 2016), Embase Ovid (March 2016), Web of Science (March 2016), the Database of Abstracts of Reviews of Effects (DARE, April 2015), and Health Technology Assessment Database (HTA, March 2016). We searched trial registers in April 2016. We used no language restrictions. SELECTION CRITERIA: We included randomised controlled trials evaluating the effect of any concomitant AF surgery compared with no AF surgery among adults with preoperative AF, regardless of symptoms, who were undergoing cardiac surgery for another indication. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. We evaluated the risk of bias using the Cochrane 'Risk of bias' tool. We included outcome data on all-cause and cardiovascular-specific mortality, freedom from atrial fibrillation, flutter, or tachycardia off antiarrhythmic medications, as measured by patient electrocardiographic monitoring greater than three months after the procedure, procedural safety, 30-day rehospitalisation, need for post-discharge direct current cardioversion, health-related quality of life, and direct costs. We calculated risk ratios (RR) for dichotomous data with 95% confidence intervals (CI) using a fixed-effect model when heterogeneity was low (I² ≤ 50%) and random-effects model when heterogeneity was high (I² > 50%). We evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to create a 'Summary of findings' table. MAIN RESULTS: We found 34 reports of 22 trials (1899 participants) with five additional ongoing studies and three studies awaiting classification. All included studies were assessed as having high risk of bias across at least one domain. The effect of concomitant AF surgery on all-cause mortality was uncertain when compared with no concomitant AF surgery (7.0% versus 6.6%, RR 1.14, 95% CI 0.81 to 1.59, I² = 0%, 20 trials, 1829 participants, low-quality evidence), but the intervention increased freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off antiarrhythmic medications > three months (51.0% versus 24.1%, RR 2.04, 95% CI 1.63 to 2.55, I² = 0%, eight trials, 649 participants, moderate-quality evidence). The effect of concomitant AF surgery on 30-day mortality was uncertain (2.3% versus 3.1%, RR 1.25 95% CI 0.71 to 2.20, I² = 0%, 18 trials, 1566 participants, low-quality evidence), but the intervention increased the risk of permanent pacemaker implantation (6.0% versus 4.1%, RR 1.69, 95% CI 1.12 to 2.54, I² = 0%, 18 trials, 1726 participants, moderate-quality evidence). Investigator-defined adverse events, including but limited to, need for surgical re-exploration or mediastinitis, were not routinely reported but were not different between the two groups (other adverse events: 24.8% versus 23.6%, RR 1.07, 95% CI 0.85 to 1.34, I² = 45%, nine trials, 858 participants), but the quality of this evidence was very low. AUTHORS' CONCLUSIONS: For patients with AF undergoing cardiac surgery, there is moderate-quality evidence that concomitant AF surgery approximately doubles the risk of freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off anti-arrhythmic drugs while increasing the risk of permanent pacemaker implantation. The effects on mortality are uncertain. Future, high-quality and adequately powered trials will likely affect the confidence on the effect estimates of AF surgery on clinical outcomes.

Computer-guided normal-low versus normal-high potassium control after cardiac surgery: No impact on atrial fibrillation or atrial flutter.

INTRODUCTION: This study was designed to determine the effect of 2 different potassium regulation strategies with different targets (within the reference range) on atrial fibrillation (AF) or atrial flutter (AFL) in a cohort of intensive care unit patients after cardiac surgery. METHODS: The GRIP-COMPASS study was a prospective double-blinded interventional study in 910 patients after cardiac surgery (coronary artery bypass grafting and/or valvular surgery). Patients were assigned to either the normal-low potassium target (nLP group, 4.0 mmol/L) or the normal-high potassium target (nHP group, 4.5 mmol/L) in alternating blocks of 50 patients. Potassium levels were regulated using a validated computer-assisted potassium replacement protocol (GRIP-II). The primary end point was the incidence of AF/AFL on a 12-lead electrocardiogram during the first postoperative week. RESULTS: Of the 910 patients, 447 were assigned to the nLP group; and 463, to the nHP group, with no baseline differences between the 2 groups. The mean daily administered dose of potassium was 30 ± 23 mmol (nLP) versus 52 ± 27 mmol (nHP) (P < .001), which resulted in mean intensive care unit potassium concentration of 4.22 ± 0.36 mmol/L and 4.33 ± 0.34 mmol/L, respectively (P < .001). The incidence of AF/AFL after cardiac surgery did not differ: 38% in the nLP group and 41% in the nHP group. Also in several subgroups (eg, patients not known with prior AF/AFL or with valve surgery), there were no differences. CONCLUSIONS: There were no differences in incidence of AF/AFL with 2 potassium regulation strategies with different potassium targets and different amounts of potassium administered in patients after cardiac surgery.

Association of left atrial function with incident atypical atrial flutter after atrial fibrillation ablation.

BACKGROUND: Symptomatic left atrial (LA) flutter (LAFL) is common after atrial fibrillation (AF) ablation. OBJECTIVE: The purpose of this study was to examine the association of baseline LA function with incident LAFL after AF ablation. METHODS: The source cohort included 216 patients with cardiac magnetic resonance (CMR) before initial AF ablation between 2010 and 2013. Patients who underwent cryoballoon or laser ablation, patients with AF during CMR, and those with suboptimal CMR, or missing follow-up data were excluded. Baseline LA volume and function were assessed by feature-tracking CMR analysis. RESULTS: The final cohort included 119 patients (mean age 58.9 ± 11 years; 76.5% men; 70.6% patients with paroxysmal AF). During a median follow-up of 421 days (interquartile range 235-751 days), 22 patients (18.5%) had incident LAFL. Baseline LA volume was similar between the 2 groups. In contrast, baseline reservoir, conduit, and contractile function of the LA were significantly impaired in patients with incident LAFL. Baseline global peak longitudinal atrial strain (PLAS) <22.65% predicted incident LAFL with 86% sensitivity and 68% specificity (C statistic 0.76). In a multivariable model adjusting for age, heart failure, and LA volume, PLAS (hazard ratio 0.9 per % increase in PLAS; P = .003) and LA linear lesions (hazard ratio 2.94; P = .020) were independently associated with incident LAFL. The coexistence of PLAS <22.65% and linear lesions was associated with 9-fold increased hazard of incident LAFL. CONCLUSION: Baseline LA function and linear lesions were independently associated with incident LAFL after AF ablation. Linear lesions should be limited to selected cases, especially in patients with impaired LA function.

Comparison of Left Atrial and Biatrial Maze Procedure in the Treatment of Atrial Fibrillation: A Meta-Analysis of Clinical Studies.

Background The outcomes of atrial fibrillation (AF) between biatrial maze (BAM) and left atrial maze (LAM) are still controversial. The purpose of this study was to compare the clinical and rhythm outcomes between BAM and LAM in patients with AF. Methods Electronic databases and article references were systematically searched (1990-2014) to access relevant studies. Odds ratio (OR) and weight mean difference (WMD) with 95% confidence interval (CI) were reported. Results Fourteen studies with 2,075 patients were finally involved in the present meta-analysis. The rate of restored sinus rhythm (SR) was similar in BAM and LAM groups (OR: 1.25, 95% CI: 0.91-1.72, p = 0.163). BAM reduced the prevalence of atrial flutter during follow-up (OR: 0.12, 95% CI: 0.01-0.96, p = 0.046). Compared with BAM, LAM shorten aortic cross-clamping time (WMD = 9.05 minutes, 95% CI: 1.28-16.82, p = 0.023) and cardiopulmonary bypass time (WMD = 20.21 minutes, 95% CI: 7.40-33.03, p = 0.002). No significant difference was found between groups in the risk of death (OR: 1.22, 95% CI: 0.70-2.14, p = 0.233), cerebrovascular events (OR: 1.44, 95% CI: 0.51-4.06, p = 0.493), and reoperation for bleeding (OR: 1.34, 95% CI: 0.70-2.55, p = 0.374). However, the risk for implantation of permanent pacemaker was significantly higher in BAM group (OR: 2.60, 95% CI: 1.09-6.20, p = 0.031). Conclusion No significant difference was found between BAM and LAM in the rate of restored SR, the risk of death, cerebrovascular events, and reoperation for bleeding. BAM is superior to LAM in reducing the prevalence of atrial flutter during follow-up, but LAM shortens the aortic cross-clamping time and cardiopulmonary bypass time, and decreases the risk of permanent pacemaker implantation.

Prevention of postsurgical atrial tachycardia with a modified right atrial free wall incision.

BACKGROUND: Most postsurgical macroreentry atrial tachycardias (PS-MATs) are atriotomy related; however, underlying mechanisms and prevention remain undefined. OBJECTIVE: The purpose of the present study was to investigate the electrophysiological and histologic bases of right atriotomy incision arrhythmogenicity and whether a modified atriotomy that extends the incisional line to the tricuspid annulus (TA) and inferior vena cava (IVC) prevents PS-MAT. METHODS: Atrial arrhythmia induction and electrophysiological and histologic characteristics were studied 8 weeks after right atriotomy in 30 adult swine according to incision distance to TA or IVC (groups A, B, and C: broad, narrow, and closed corridors, respectively; group D, no-incision sham; n = 6 per group, except n = 12 for group B). RESULTS: Sustained PS-MATs were induced and mapped in the broad- and narrow-corridor groups (A, 1 of 6 [16.7%] vs B, 5 of 12 [41.7%]) but not in the closed-corridor (C) or sham (D) groups (P = .087). With 20-ms pacing cycle-length decrements (from 350 to 270 ms), mean conduction time over 20 mm at the atriotomy-to-TA corridor was 29.2 ± 2.2, 31.0 ± 4.2, 26.0 ± 1.9, and 17.0 ± 1.4 ms for 5 and 10 mm (both group B), 15 mm (group A), and sham incision (P = .017), respectively. Conduction properties correlated with histologic findings: the wider the corridor, the healthier its tissue. In group C (modified atriotomy), both corridors were replaced by dense scar with complete conduction block. CONCLUSION: Atriotomy corridor width determines conduction properties and contributes to arrhythmogenicity. A modified right atriotomy that extends to the TA and IVC prevents PS-MAT.

Effects of enhanced pacing modalities on health care resource utilization and costs in bradycardia patients: An analysis of the randomized MINERVA trial.

BACKGROUND: Many patients who suffer from bradycardia and need cardiac pacing also have atrial fibrillation (AF). New pacemaker algorithms, such as atrial preventive pacing and atrial antitachycardia pacing (DDDRP) and managed ventricular pacing (MVP), have been specifically designed to reduce AF occurrence and duration and to minimize the detrimental effects of right ventricular pacing. The randomized MINimizE Right Ventricular pacing to prevent Atrial fibrillation and heart failure trial established that DDDRP + MVP pacing modality reduced permanent AF in bradycardia patients as compared with standard dual-chamber pacing (DDDR). OBJECTIVE: The aim of this study was to estimate the cost savings due to lower AF-related health care utilization events based on health care costs from the United States and the European Union. METHODS: Dual-chamber pacemaker patients with a history of paroxysmal or persistent AF were randomly assigned to receive DDDR (n = 385) or the advanced features (DDDRP + MVP; n = 383). We used published health care costs from the United States and the European Union (Italy, Spain, and the United Kingdom) to estimate the costs associated with AF-related hospitalizations and emergency visits. RESULTS: The rate of AF-related hospitalizations was significantly lower in the DDDRP + MVP group than in the conventional pacemaker group (DDDR group; 42% reduction; incidence rate ratio 0.58). Similarly, a significant reduction of 68% was observed for AF-related emergency department visits (incidence rate ratio 0.32; P < .001). As a consequence, DDDRP + MVP could potentially reduce health care costs by 40%-44%. Over a ten-year period, the cost savings per 100 patients ranged from $35,702 in the United Kingdom to $121,831 in the United States. CONCLUSION: New pacing algorithms such as DDDRP + MVP used in the MINimizE Right Ventricular pacing to prevent Atrial fibrillation and heart failure trial successfully reduced AF-related health care utilization, resulting in significant cost savings to payers.