External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy to restore normal/sinus rhythm, and can be achieved through drugs (pharmacological) or a synchronised electric shock (electrical cardioversion). OBJECTIVES: To assess the efficacy and safety of pharmacological and electrical cardioversion for atrial fibrillation (AF), atrial flutter and atrial tachycardias. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) and three trials registers (ClinicalTrials.gov, WHO ICTRP and ISRCTN) on 14 February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) at the individual patient level. Patient populations were aged ≥ 18 years with AF of any type and duration, atrial flutter or other sustained related atrial arrhythmias, not occurring as a result of reversible causes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology to collect data and performed a network meta-analysis using the standard frequentist graph-theoretical approach using the netmeta package in R. We used GRADE to assess the quality of the evidence which we presented in our summary of findings with a judgement on certainty. We calculated differences using risk ratios (RR) and 95% confidence intervals (CI) as well as ranking treatments using a P value. We assessed clinical and statistical heterogeneity and split the networks for the primary outcome and acute procedural success, due to concerns about violating the transitivity assumption. MAIN RESULTS: We included 112 RCTs (139 records), from which we pooled data from 15,968 patients. The average age ranged from 47 to 72 years and the proportion of male patients ranged from 38% to 92%. Seventy-nine trials were considered to be at high risk of bias for at least one domain, 32 had no high risk of bias domains, but had at least one domain classified as uncertain risk, and one study was considered at low risk for all domains. For paroxysmal AF (35 trials), when compared to placebo, anteroapical (AA)/anteroposterior (AP) biphasic truncated exponential waveform (BTE) cardioversion (RR: 2.42; 95% CI 1.65 to 3.56), quinidine (RR: 2.23; 95% CI 1.49 to 3.34), ibutilide (RR: 2.00; 95% CI 1.28 to 3.12), propafenone (RR: 1.98; 95% CI 1.67 to 2.34), amiodarone (RR: 1.69; 95% CI 1.42 to 2.02), sotalol (RR: 1.58; 95% CI 1.08 to 2.31) and procainamide (RR: 1.49; 95% CI 1.13 to 1.97) likely result in a large increase in maintenance of sinus rhythm until hospital discharge or end of study follow-up (certainty of evidence: moderate). The effect size was larger for AA/AP incremental and was progressively smaller for the subsequent interventions. Despite low certainty of evidence, antazoline may result in a large increase (RR: 28.60; 95% CI 1.77 to 461.30) in this outcome. Similarly, low-certainty evidence suggests a large increase in this outcome for flecainide (RR: 2.17; 95% CI 1.68 to 2.79), vernakalant (RR: 2.13; 95% CI 1.52 to 2.99), and magnesium (RR: 1.73; 95% CI 0.79 to 3.79). For persistent AF (26 trials), one network was created for electrical cardioversion and showed that, when compared to AP BTE incremental energy with patches, AP BTE maximum energy with patches (RR 1.35, 95% CI 1.17 to 1.55) likely results in a large increase, and active compression AP BTE incremental energy with patches (RR: 1.14, 95% CI 1.00 to 1.131) likely results in an increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: high). Use of AP BTE incremental with paddles (RR: 1.03, 95% CI 0.98 to 1.09; certainty of evidence: low) may lead to a slight increase, and AP MDS Incremental paddles (RR: 0.95, 95% CI 0.86 to 1.05; certainty of evidence: low) may lead to a slight decrease in efficacy. On the other hand, AP MDS incremental energy using patches (RR: 0.78, 95% CI 0.70 to 0.87), AA RBW incremental energy with patches (RR: 0.76, 95% CI 0.66 to 0.88), AP RBW incremental energy with patches (RR: 0.76, 95% CI 0.68 to 0.86), AA MDS incremental energy with patches (RR: 0.76, 95% CI 0.67 to 0.86) and AA MDS incremental energy with paddles (RR: 0.68, 95% CI 0.53 to 0.83) probably result in a decrease in this outcome when compared to AP BTE incremental energy with patches (certainty of evidence: moderate). The network for pharmacological cardioversion showed that bepridil (RR: 2.29, 95% CI 1.26 to 4.17) and quindine (RR: 1.53, (95% CI 1.01 to 2.32) probably result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up when compared to amiodarone (certainty of evidence: moderate). Dofetilide (RR: 0.79, 95% CI 0.56 to 1.44), sotalol (RR: 0.89, 95% CI 0.67 to 1.18), propafenone (RR: 0.79, 95% CI 0.50 to 1.25) and pilsicainide (RR: 0.39, 95% CI 0.02 to 7.01) may result in a reduction in this outcome when compared to amiodarone, but the certainty of evidence is low. For atrial flutter (14 trials), a network could be created only for antiarrhythmic drugs. Using placebo as the common comparator, ibutilide (RR: 21.45, 95% CI 4.41 to 104.37), propafenone (RR: 7.15, 95% CI 1.27 to 40.10), dofetilide (RR: 6.43, 95% CI 1.38 to 29.91), and sotalol (RR: 6.39, 95% CI 1.03 to 39.78) probably result in a large increase in the maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: moderate), and procainamide (RR: 4.29, 95% CI 0.63 to 29.03), flecainide (RR 3.57, 95% CI 0.24 to 52.30) and vernakalant (RR: 1.18, 95% CI 0.05 to 27.37) may result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: low). All tested electrical cardioversion strategies for atrial flutter had very high efficacy (97.9% to 100%). The rate of mortality (14 deaths) and stroke or systemic embolism (3 events) at 30 days was extremely low. Data on quality of life were scarce and of uncertain clinical significance. No information was available regarding heart failure readmissions. Data on duration of hospitalisation was scarce, of low quality, and could not be pooled. AUTHORS' CONCLUSIONS: Despite the low quality of evidence, this systematic review provides important information on electrical and pharmacological strategies to help patients and physicians deal with AF and atrial flutter. In the assessment of the patient comorbidity profile, antiarrhythmic drug onset of action and side effect profile versus the need for a physician with experience in sedation, or anaesthetics support for electrical cardioversion are key aspects when choosing the cardioversion method.

The efficacy and safety of intraoperative intravenous amiodarone in patients undergoing on-pump coronary artery bypass grafting surgery: a systemic review and PRISMA-compliant meta-analysis.

BACKGROUND: To evaluate the clinical efficacy and safety of intraoperative intravenous amiodarone for arrhythmia prevention in on-pump coronary artery bypass grafting (CABG) patients. METHODS: A meta-analysis of randomized controlled trials was conducted. Pubmed, Embase, Cochrane Library, Ovid, China National Knowledge Infrastructure, and the Wan Fang database until July 1th, 2023. The primary outcomes of interest included the incidences of intra- and post-operative atrial fibrillation (POAF), ventricular fibrillation, or any arrhythmia, including atrial fibrillation, ventricular fibrillation, ventricular tachycardia, premature ventricular contraction, and sinus bradycardia. For continuous and dichotomous variables, treatment effects were calculated as the weighted mean difference (WMD)/risk ratio (RR) and 95% confidence interval (CI). RESULTS: A database search yielded 7 randomized controlled trials including 608 patients, where three studies, including three treatments (amiodarone, lidocaine, and saline), contributed to the clinical outcome of atrial fibrillation, ventricular fibrillation, or any arrhythmia. Meta-analysis demonstrated that amiodarone can significantly reduce the incidence of POAF (RR, 0.39; 95%CI: 0.20, 0.77; P = 0.007, I2 = 0%) in patients undergoing on-pump CABG; there was no statistically significant influence on intra-operative atrial fibrillation, intra- and post-operative ventricular fibrillation, or any arrhythmia. CONCLUSIONS: The current study suggests that intraoperative administration of intravenous amiodarone may be safe and effective in preventing POAF in patients undergoing on-pump CABG. More well-designed clinical trials are needed to validate this result.

Catheter ablation versus antiarrhythmic drug therapy for sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM. METHODS: A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up. RESULTS: Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10-0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12-0.95]; P = 0.029). CONCLUSIONS: In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD.

[Rhythm management in patients with heart failure].

INTRODUCTION: Arrhythmias manifest frequently in individuals with heart failure, posing a notable threat of mortality and morbidity. While the prevention of sudden cardiac death through ICD therapy remains pivotal, accurate risk stratification remains a challenging task even in 2024. Recent data underscore the early consideration of catheter ablation for ventricular tachycardias. Although antiarrhythmic drug therapy serves as an ancillary measure for symptomatic patients, it does not confer prognostic advantages. The holistic management of arrhythmias in heart failure necessitates a systematic, multidimensional approach that initiates with evidence-based medical therapy for heart failure and integrates device-based and interventional therapies. Noteworthy clinical studies have illustrated the positive prognostic impact of early rhythm control strategies, particularly catheter ablation, in individuals managing heart failure and atrial fibrillation.

A review regarding the article 'Multidisciplinary management strategies for atrial fibrillation.'

Catheter ablation has become an accepted first line therapy for paroxysmal atrial fibrillation (PAF), with pulmonary vein isolation (PVI) being the key element of ablation strategies. Catheter ablation of AF has been proven to be superior to antiarrhythmic drug (AAD) therapy regarding efficacy and improvement of survival in patients with heart failure. PVI has become a routine treatment procedure in recent decades especially for patients with symptomatic PAF. Recent research investigations have shown that AF recurrence still occurs in a significant number of patients after ablation. AF recurrence leads to a decrease in patients' quality of life and is related to an increased risk of cardiovascular events and mortality. As most arrhythmia recurrences take place within the first 3 months after the initial procedure, this time period is seen as a so-called "blanking period", in which ablation is not recommended, since up to 50 % of patients can become arrhythmia free in the long run. Ablation therapy, however, is less successful in patients suffering from long standing persistent AF, with a 20.3 % success rate after a single procedure and a 45 % success rate after multiple RFA procedures. Several scores have been established and validated to predict cardiac rhythm outcomes after catheter ablation. However, due to the lack of external validation of most of the scores, their efficacy in predicting recurrence of atrial fibrillation needs to be further evaluated in independent external studies.

Definition and management of arrhythmia-induced cardiomyopathy: findings from the European Heart Rhythm Association survey.

AIMS: Arrhythmia-induced cardiomyopathy (AiCM) represents a subtype of acute heart failure (HF) in the context of sustained arrhythmia. Clear definitions and management recommendations for AiCM are lacking. The European Heart Rhythm Association Scientific Initiatives Committee (EHRA SIC) conducted a survey to explore the current definitions and management of patients with AiCM among European and non-European electrophysiologists. METHODS AND RESULTS: A 25-item online questionnaire was developed and distributed among EP specialists on the EHRA SIC website and on social media between 4 September and 5 October 2023. Of the 206 respondents, 16% were female and 61% were between 30 and 49 years old. Most of the respondents were EP specialists (81%) working at university hospitals (47%). While most participants (67%) agreed that AiCM should be defined as a left ventricular ejection fraction (LVEF) impairment after new onset of an arrhythmia, only 35% identified a specific LVEF drop to diagnose AiCM with a wide range of values (5-20% LVEF drop). Most respondents considered all available therapies: catheter ablation (93%), electrical cardioversion (83%), antiarrhythmic drugs (76%), and adjuvant HF treatment (76%). A total of 83% of respondents indicated that adjuvant HF treatment should be started at first HF diagnosis prior to antiarrhythmic treatment, and 84% agreed it should be stopped within six months after LVEF normalization. Responses for the optimal time point for the first LVEF reassessment during follow-up varied markedly (1 day-6 months after antiarrhythmic treatment). CONCLUSION: This EHRA Survey reveals varying practices regarding AiCM among physicians, highlighting a lack of consensus and heterogenous care of these patients.

Pharmacological Approach for Symptomatic Nonsustained Ventricular Tachycardia.

Nonsustained ventricular tachycardia (NSVT) is a common arrhythmia associated with heart failure, cardiomyopathy, coronary artery disease, electrolyte imbalances, and congenital heart disorders (Foth et al., 2023). NSVT is often asymptomatic depending on its burden percentage. However, typical NSVT presentation in the emergency department (ED) includes palpitations, near-syncope, dizziness, skipped beats, chest pain, and/or dyspnea (Katritsis et al., 2012). In some instances, NSVT can present with elevated or slightly elevated troponin from demand ischemia. A definite diagnosis of NSVT is not of high complexity; nevertheless, it is not always identified on electrocardiogram (ECG) by the time the patient arrives to the ED. Identification of NSVT usually requires prolonged cardiac monitoring, mobile cardiac telemetry (MCT), and in some instances internal loop recorder placement. The purpose of this case is to discuss the typical presentation and pharmacological approach of patients with stable NSVT.

Atrial Fibrillation: Common Questions and Answers About Diagnosis and Treatment.

Atrial fibrillation is a supraventricular arrhythmia that increases the risk of stroke and all-cause mortality. It is the most common cardiac dysrhythmia in adults in the primary care setting, and its prevalence increases with age. The U.S. Preventive Services Task Force concluded that there is insufficient evidence to assess the benefits and harms of screening asymptomatic adults older than 50 years for atrial fibrillation. Many patients with atrial fibrillation are asymptomatic, but symptoms can include palpitations, exertional dyspnea, fatigue, and chest pain. Diagnosis is based on history and physical examination findings and should be confirmed with 12-lead electrocardiography or other recording device. The initial evaluation should include transthoracic echocardiography; serum electrolyte levels; complete blood count; and thyroid, kidney, and liver function tests. Stroke risk should be assessed in patients with atrial fibrillation using the CHA2DS2-VASc score. Warfarin and direct oral anticoagulants reduce the risk of stroke by preventing atrial thrombus formation and subsequent cerebral or systemic emboli. Hemodynamically unstable patients, including those with decompensated heart failure, should be evaluated and treated emergently. Most hemodynamically stable patients should be treated initially with rate control and anticoagulation. Rhythm control, using medications or procedures, should be considered in patients with hemodynamic instability or in some patients based on risk factors and shared decision-making. Electrical cardioversion may be appropriate as first-line rhythm control. Conversion to sinus rhythm with catheter ablation may be considered in patients who are unable or unwilling to take rate or rhythm control medications long-term or if medications have been ineffective.

Vericiguat suppresses ventricular tachyarrhythmias inducibility in a rabbit myocardial infarction model.

BACKGROUND: The VICTORIA trial demonstrated a significant decrease in cardiovascular events through vericiguat therapy. This study aimed to assess the potential mechanisms responsible for the reduction of cardiovascular events with vericiguat therapy in a rabbit model of myocardial infarction (MI). METHODS: A chronic MI rabbit model was created through coronary artery ligation. Following 4 weeks, the hearts were harvested and Langendorff perfused. Subsequently, electrophysiological examinations and dual voltage-calcium optical mapping studies were conducted at baseline and after administration of vericiguat at a dose of 5 µmol/L. RESULTS: Acute vericiguat therapy demonstrated a significant reduction in premature ventricular beat burden and effectively suppressed ventricular arrhythmic inducibility. The electrophysiological influences of vericiguat therapy included an increased ventricular effective refractory period, prolonged action potential duration, and accelerated intracellular calcium (Cai) homeostasis, leading to the suppression of action potential and Cai alternans. The pacing-induced ventricular arrhythmias exhibited a reentrant pattern, attributed to fixed or functional conduction block in the peri-infarct zone. Vericiguat therapy effectively mitigated the formation of cardiac alternans as well as the development of reentrant impulses, providing additional anti-arrhythmic benefits. CONCLUSIONS: In the MI rabbit model, vericiguat therapy demonstrates anti-ventricular arrhythmia effects. The vericiguat therapy reduces ventricular ectopic beats, inhibiting the initiation of ventricular arrhythmias. Furthermore, the therapy successfully suppresses cardiac alternans, preventing conduction block and, consequently, the formation of reentry circuits.

Dronedarone for the Treatment of Atrial Arrhythmias in Adults With Congenital Heart Disease.

BACKGROUND: Atrial tachyarrhythmias are common and difficult to treat in adults with congenital heart disease. Dronedarone has proven effective in patients without congenital heart disease, but data are limited about its use in adults with congenital heart disease of moderate to great complexity. METHODS: A single-center, retrospective chart review of 21 adults with congenital heart disease of moderate to great complexity who were treated with dronedarone for atrial tachyarrhythmias was performed. RESULTS: The median (IQR) age at dronedarone initiation was 35 (27.5-39) years. Eleven patients (52%) were male. Ten patients (48%) had New York Heart Association class I disease, 10 (48%) had class II disease, and 1 (5%) had class III disease. Ejection fraction at initiation was greater than 55% in 11 patients (52%), 35% to 55% in 9 patients (43%), and less than 35% in 1 patient (5%). Prior treatments included ß-blockers (71%), sotalol (38%), amiodarone (24%), digoxin (24%), and catheter ablation (38%). Rhythm control was complete in 5 patients (24%), partial in 6 (29%), and inadequate in 10 (48%). Two patients (10%) experienced adverse events, including nausea in 1 (5%) and cardiac arrest in 1 (5%), which occurred 48 months after initiation of treatment. There were no deaths during the follow-up period. The median (IQR) follow-up time for patients with complete or partial rhythm control was 20 (1-54) months. CONCLUSION: Dronedarone can be effective for adult patients with congenital heart disease and atrial arrhythmias for whom more established therapies have failed, and with close monitoring it can be safely tolerated.

Non-paroxysmal junctional tachycardia complicating disseminated intravascular coagulation during massive surgical hemorrhage: A case report.

RATIONALE: Non-paroxysmal junctional tachycardia (NPJT) is a self-limiting supraventricular tachycardia associated with primary heart disease, cardiac surgery, digitalis toxicity, and metabolic or electrolyte imbalances. However, NPJT caused enhanced normal automaticity even in the absence of structural heart disease can be fatal if not managed properly. PATIENT CONCERNS: A 74-year-old hypertensive female patient was scheduled for transureteroureterostomy and right ureteroneocystostomy under general anesthesia. DIAGNOSIS: The patient developed NPJT without visible P wave and severe hypotension due to adrenergic stimulation in response to massive hemorrhage during surgery. INTERVENTIONS: NPJT with hypotension was initially converted to sinus rhythm with normotension with administration of adenosine and esmolol. However uncontrolled surgical hemorrhage and administration of large dose of vasopressors eventually perpetuated NPJT refractory to antiarrhythmic drugs. OUTCOMES: Despite intravenous fluid resuscitation and massive transfusion, the patient was deteriorated hemodynamically due to uncontrolled bleeding and persistent NPJT, which resulted in hypovolemic shock and fatal disseminated intravascular coagulation (DIC). LESSONS: NPJT can occur by enhanced automaticity due to increased catecholamine during severe surgical hemorrhage. Although NPJT is generally self-limiting, it can be refractory to antiarrhythmic agents and accelerate hypotension if the surgical bleeding is uncontrolled. Therefore, aggressive management of the primary pathologic condition is crucial for the management of NPJT and hemodynamic collapse even in the absence of structural heart disease.

Impacts of gene variants on drug effects-the foundation of genotype-guided pharmacologic therapy for long QT syndrome and short QT syndrome.

The clinical significance of optimal pharmacotherapy for inherited arrhythmias such as short QT syndrome (SQTS) and long QT syndrome (LQTS) has been increasingly recognised. The advancement of gene technology has opened up new possibilities for identifying genetic variations and investigating the pathophysiological roles and mechanisms of genetic arrhythmias. Numerous variants in various genes have been proven to be causative in genetic arrhythmias. Studies have demonstrated that the effectiveness of certain drugs is specific to the patient or genotype, indicating the important role of gene-variants in drug response. This review aims to summarize the reported data on the impact of different gene-variants on drug response in SQTS and LQTS, as well as discuss the potential mechanisms by which gene-variants alter drug response. These findings may provide valuable information for future studies on the influence of gene variants on drug efficacy and the development of genotype-guided or precision treatment for these diseases.

Prognostic Impact of Sinus Rhythm in Atrial Fibrillation Patients: Separating Rhythm Outcomes From Randomized Strategy Findings From the CABANA Trial.

BACKGROUND: Clinically detected atrial fibrillation (AF) is associated with a significant increase in mortality and other adverse cardiovascular events. Since the advent of effective methods for AF rhythm control, investigators have attempted to determine how much these adverse prognostic AF effects could be mitigated by the restoration of sinus rhythm (SR) and whether the method used mattered. METHODS: The CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) randomized 2204 AF patients to ablation versus drug therapy, of which 1240 patients were monitored in follow-up using the CABANA ECG rhythm monitoring system. To assess the prognostic benefits of SR, we performed a prespecified analysis using Cox survival modeling with heart rhythm as a time-dependent variable and randomized treatment group as a stratification factor. RESULTS: In the 1240 patient study cohort, 883 (71.2%) had documented AF at some point during their postblanking follow-up. Among the 883 patients, 671 (76.0%) experienced AF within the first year of postblanking follow-up, and 212 (24.0%) experienced their first AF after ≥1 year of postblanking follow-up. The primary CABANA end point (death, disabling stroke, serious bleeding, or cardiac arrest) occurred in 95 (10.8%) of the 883 patients with documented AF and in 29 (8.1%) of the 357 patients with no AF recorded during follow-up. In multivariable time-dependent analysis, the presence of SR (compared with non-SR) was associated with a significantly reduced risk of the primary end point (adjusted hazard ratio, 0.57 [95% CI, 0.38-0.85]; P=0.006; independent of treatment strategy [ablation versus drugs]). Corresponding results for all-cause mortality were adjusted hazard ratio of 0.59 [95% CI, 0.35-1.01]; P=0.053). CONCLUSIONS: In patients in the CABANA trial with detailed long-term rhythm follow-up, increased time in SR was associated with a clinically consequential decrease in mortality and other adverse prognostic events. The predictive value of SR was independent of the therapeutic approach responsible for reducing the burden of detectable AF. REGISTRATION: URL: https://clinicaltrials.gov; Unique Identifier: NCT00911508.