Analysis of drug-induced and spontaneous cardioversions reveals similar patterns leading to termination of atrial fibrillation.

Introduction: The mechanisms leading to the conversion of atrial fibrillation (AF) to sinus rhythm are poorly understood. This study describes the dynamic behavior of electrophysiological parameters and conduction patterns leading to spontaneous and pharmacological AF termination. Methods: Five independent groups of goats were investigated: (1) spontaneous termination of AF, and drug-induced terminations of AF by various potassium channel inhibitors: (2) AP14145, (3) PA-6, (4) XAF-1407, and (5) vernakalant. Bi-atrial contact mapping was performed during an open chest surgery and intervals with continuous and discrete atrial activity were determined. AF cycle length (AFCL), conduction velocity and path length were calculated for each interval, and the final conduction pattern preceding AF termination was evaluated. Results: AF termination was preceded by a sudden episode of discrete activity both in the presence and absence of an antiarrhythmic drug. This episode was accompanied by substantial increases in AFCL and conduction velocity, resulting in prolongation of path length. In 77% ± 4% of all terminations the conduction pattern preceding AF termination involved medial to lateral conduction along Bachmann's bundle into both atria, followed by anterior to posterior conduction. This finding suggests conduction block in the interatrial septum and/or pulmonary vein area as final step of AF termination. Conclusion: AF termination is preceded by an increased organization of fibrillatory conduction. The termination itself is a sudden process with a critical role for the interplay between spatiotemporal organization and anatomical structure.

Investigative agents for atrial fibrillation: agonists and stimulants, progress and expectations.

INTRODUCTION: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Its prevalence has increased due to worldwide populations that are aging in combination with the growing incidence of risk factors associated. Recent advances in our understanding of AF pathophysiology and the identification of nodal players involved in AF-promoting atrial remodeling highlights potential opportunities for new therapeutic approaches. AREAS COVERED: This detailed review summarizes recent developments in the field antiarrhythmic drugs in the field AF. EXPERT OPINION: The current situation is far than optimal. Despite clear unmet needs in drug development in the field of AF treatment, the current development of new drugs is absent. The need for a molecule with absence of cardiac and non-cardiac toxicity in the short and long term is a limitation in the field. Improvement in the understanding of AF genetics, pathophysiology, molecular alterations, big data and artificial intelligence with the objective to provide a personalized AF treatment will be the cornerstone of AF treatment in the coming years.

Antiarrhythmic Drug Use in Pregnancy: Considerations and Safety Profiles.

Pregnancy entails notable physiological alterations and hormonal fluctuations that affect the well-being of both the fetus and the mother. Cardiovascular events and arrhythmias are a major concern during pregnancy, especially in women with comorbidities or a history of arrhythmias. This paper provides an overview of the prevalence, therapies, and prognoses of different types of arrhythmias during pregnancy. The administration of antiarrhythmic drugs (AADs) during pregnancy demands careful consideration because of their possible effect on the mother and fetus. AADs can cross the placenta or be present in breast milk, potentially leading to adverse effects such as teratogenicity, growth restriction, or premature birth. The safety profiles of different classes of AADs are discussed. Individualized treatment approaches and close monitoring of pregnant women prescribed AADs are essential to ensure optimal maternal and fetal outcomes.

Atrial Fibrillation and Heart Failure With Reduced Ejection Fraction: New Assessment of an Old Problem.

Atrial fibrillation (AF) and heart failure (HF)-specifically, heart failure with reduced ejection fraction (HFrEF)-often coexist, and each contributes to the propagation of the other. This relationship extends from the mechanistic and physiological to clinical syndromes, quality of life, and long-term cardiovascular outcomes. The risk factors for AF and HF overlap and create a critical opportunity to prevent adverse outcomes among patients at greatest risk for either condition. Increasing recognition of the linkages between AF and HF have led to widespread interest in designing diagnostic, predictive, and interventional strategies targeting all aspects of disease, from identifying genetic predisposition to addressing social determinants of health. Advances across this spectrum culminated in updated multisociety guidelines for management of AF, which includes specific consideration of comorbid AF and HF. This review expands on these guidelines by further highlighting relevant clinical trial findings and providing additional context for the evolving recommendations for management in this important and growing population.

Safety of different therapies for atrial fibrillation: a network meta-analysis.

OBJECTIVE: Most published studies have aimed to compare the effectiveness of different treatment strategies for atrial fibrillation (AF), while few articles have comprehensively compared the safety of therapeutic measures.The aim of the article was to assess the safety of different therapeutic measures (different ablation techniques, antiarrhythmic drugs and surgery) in patients with AF. METHOD: A comprehensive and systematic search was undertaken across various databases, namely PubMed, Embase, Cochrane Library, and Web of Science, with the aim of identifying pertinent randomized controlled trials (RCTs) that delve into the safety aspects of diverse atrial fibrillation treatment strategies. The search was conducted up until December 1st, 2023. R4.2.3 software gemtc package was used for data analysis, Review Manager 5.3 was used for quality assessment of included studies, and stata15.0 was used for publication bias.Safety is defined as the adverse outcomes that occur in different treatment strategies for atrial fibrillation, with specific adverse events as described below. RESULT: 22 RCTs (involving 5073 subjects) with interventions including cryoballoon ablation (CA), radiofrequency ablation (RF), laser balloon ablation (LB), pulmonary vein ablation catheter (PVAC), antiarrhythmic drugs (AADS), and surgery (SA) were included in this study. In this article, medication and surgery were combined into the same intervention (non-traditional treatment measure, UT). UT was not associated with pericardial effusion (OR:4.27e-10, 95%CI:4.91e-30-0.0663), infections (OR:0.248, 95%CI:0.0584-0.89), arrhythmias (OR:0.609,95%CI:0.393-0.936), pseudoaneurysms (OR:5.57e-10, 95%CI:1.16e-31-0.934) and pulmonary vein stenosis (OR:1.16e-09, 95%CI:6.56e-24-0.194). Complications of the procedure were mainly mechanical injuries. Among the various ablation strategies, radiofrequency ablation had a lower incidence of phrenic nerve palsy and pain (OR:4.01e-06, 95%CI:1.18e-17-0.710) than cryoballoon ablation, which was superior to radiofrequency ablation in terms of infection rates. Finally, there were no significant differences between the various ablation techniques in terms of other complication rates. CONCLUSION: Because the interventions in the UT group were predominantly AADS and antiarrhythmic drug therapy didn't have some of the common aggressive complications of ablation strategies, the UT group had a low rate of complications such as pericardial effusion, postprocedural arrhythmia, pseudoaneurysm, and pulmonary vein stenosis compared with various catheter ablation strategies. Additionally, we also discovered between the various ablation technology groups, there was no significant difference in the incidence of major adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registry number:CRD42024566530.

[Antiarrhythmic drugs in the present day]. / Antiarrhythmika in der heutigen Zeit.

Cardiac arrhythmias cause a significant proportion of hospitalizations and physician contacts worldwide. By using antiarrhythmic drugs, cardiac arrhythmias can be effectively treated and the frequency of recurrences reduced. Atrial fibrillation and heart failure represent diseases in which antiarrhythmic drugs are more often used on a long-term basis. The aim of this article is to provide an overview of the most common antiarrhythmic drugs and their uses as well as to provide recommendations for adequate handling and use, especially in the outpatient setting. In addition to long-term use, some antiarrhythmic drugs are also administered for the acute management of supraventricular or ventricular tachycardia. Relevant contraindications, side effects and interactions must be considered, meaning that patients should be followed up when using these potent drugs. This article shows in detail what to consider when using antiarrhythmic drugs in order to ensure not only effective but also safe treatment.

Wide Spectrum of Flecainide Toxicity: A Case Report and Literature Review.

Flecainide toxicity is a rare but serious condition that can present with a wide range of clinical symptoms. We report the case of a 79-year-old female with paroxysmal atrial fibrillation on flecainide therapy who developed altered mental status, visual hallucinations, and bradycardia. Laboratory results revealed an acute kidney injury, which contributed to elevated flecainide levels. Discontinuation of flecainide led to a rapid resolution of symptoms and normalization of ECG findings. This case underscores the critical need for careful monitoring of renal function and potential drug interactions in patients receiving flecainide to prevent toxicity, highlighting the wide range of flecainide toxicity, including rare manifestations such as encephalopathy and visual hallucinations.

A danish healthcare-focused economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation.

INTRODUCTION: Three randomised controlled trials (RCTs) have demonstrated that first-line cryoballoon pulmonary vein isolation decreases atrial tachycardia in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drugs (AADs). The aim of this study was to develop a cost-effectiveness model (CEM) for first-line cryoablation compared with first-line AADs for the treatment of PAF. The model used a Danish healthcare perspective. METHODS: Individual patient-level data from the Cryo-FIRST, STOP AF and EARLY-AF RCTs were used to parameterise the CEM. The model structure consisted of a hybrid decision tree (one-year time horizon) and a Markov model (40-year time horizon, with a three-month cycle length). Health-related quality of life was expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year. Model outcomes were produced using probabilistic sensitivity analysis. RESULTS: First-line cryoablation is dominant, meaning it results in lower costs (-€2,663) and more QALYs (0.18) when compared to first-line AADs. First-line cryoablation also has a 99.96% probability of being cost-effective, at a cost-effectiveness threshold of €23,200 per QALY gained. Regardless of initial treatment, patients were expected to receive ∼ 1.2 ablation procedures over a lifetime horizon. CONCLUSION: First-line cryoablation is both more effective and less costly (i.e. dominant), when compared with AADs for patients with symptomatic PAF in a Danish healthcare system.

Pre-Excited Atrial Fibrillation in Wolff-Parkinson-White (WPW) Syndrome: A Case Report and a Review of the Literature.

Wolff-Parkinson-White (WPW) syndrome is defined by specific electrocardiogram (ECG) changes resulting in ventricular pre-excitation (the so-called WPW pattern), related to the presence of an accessory pathway (AP), combined with recurrent tachyarrhythmias. WPW syndrome is characterized by different supraventricular tachyarrhythmias (SVT), including atrioventricular re-entry tachycardia (AVRT) and atrial fibrillation (AF) with rapid ventricular response, with AVRT being the most common arrhythmia associated with WPW, and AF occurring in up to 50% of patients with WPW. Several mechanisms might be responsible for AF development in the WPW syndrome, and a proper electrocardiographic interpretation is of pivotal importance since misdiagnosing pre-excited AF could lead to the administration of incorrect treatment, potentially inducing ventricular fibrillation (VF). Great awareness of pre-excited AF's common ECG characteristics as well as associated causes and its treatment is needed to increase diagnostic performance and improve patients' outcomes. In the present review, starting from a paradigmatic case, we discuss the characteristics of pre-excited AF in the emergency department and its management, focusing on the most common ECG abnormalities, pharmacological and invasive treatment of this rhythm disorder.

Efficacy of cryoablation in atrial fibrillation: comparison with antiarrhythmic therapy.

Atrial fibrillation (AF) represents the most common arrhythmia in clinical practice, characterized by irregular atrial electrical activity originating mainly in and around the pulmonary veins. This condition can manifest itself symptomatically or silently but still dangerously. Complications associated with AF include stroke, heart failure, worst clinical outcome in patients with underlying conditions, increased emergency room visits, hospitalizations, and cardiovascular mortality. Currently, according to the main international guidelines, antiarrhythmic therapy is considered the first choice for rhythm control in patients with AF despite modest efficacy and non-negligible side effects. In recent decades, radiofrequency catheter ablation has emerged as an alternative to antiarrhythmic drugs for rhythm control. Cryoablation was developed with the aim of reducing procedural times and reducing complications related to the ablative procedure with radiofrequency without losing efficacy. Recent studies conducted with rigour and scientific solidity have demonstrated on the one hand that the results of this technique are not inferior compare with radiofrequency. This study aims to compare data on the safety and efficacy of cryoablation with those obtained from antiarrhythmic drugs through a review of the most recent scientific evidence.

Impact of an Organized Treatment Pathway on Management of Atrial Fibrillation: The ER2EP Study.

Background: Atrial fibrillation (AF) is the most common arrhythmia reported worldwide. There is significant heterogeneity in AF care pathways for a patient seen in the emergency room, impacting access to guideline-driven therapies. Objectives: The purpose of this study was to compare the difference in AF outcomes between those treated with an organized treatment pathway vs routine-care approach. Methods: The emergency room to electrophysiology service study (ER2EP) is a multicenter, prospective observational registry (NCT04476524) enrolling patients with AF from sites where a pathway for management of AF was put in place compared to sites where a pathway was not in place within the same health system and the same physicians providing services at all sites. Multivariable regression modeling was performed to identify predictors of clinical outcomes. Beta coefficient or odds ratio was reported as appropriate. Results: A total of 500 patients (ER2EP group, n = 250; control group, n = 250) were included in the study. The mean age was 73.4 ± 12.9 years, and 52.2% were males. There was a statistically significant difference in primary endpoint [time to ablation (56 ± 50.9 days vs 183.3 ± 109.5 days; P < 0.001), time to anticoagulation initiation (2.1 ± 1.6 days vs 19.7 ± 35 days, P < 0.001), antiarrhythmic drug initiation (4.8 ± 7.1 days vs 24.7 ± 44.4 days, P < 0.001) compared to the control group, respectively. As such, this resulted in reduced length of stay in the ER2EP group compared to the control group (2.4 ± 1.4 days vs 3.23 ± 2.5 days, P = 0.002). Conclusions: This study provides evidence that having an organized pathway from the emergency department for AF patients involving electrophysiology services can improve early access to definitive therapies and clinical outcomes.

Toxicologic analysis of 35 drugs in post mortem human blood samples with focus on antihypertensive and antiarrhythmic drugs.

Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in therapeutic doses, and if they were taken in accidental, intentional, or suicidal overdose scenarios. Therefore, a novel analytical method was developed and validated for the quantification of 35 drugs with toxicological relevance, including antihypertensive and antiarrhythmic drugs (ajmaline, amlodipine, amiodarone, atenolol, bisoprolol, carvedilol, clonidine, desethylamiodarone, diltiazem, donepezil, doxazosin, dronedarone, esmolol, flecainide, lercanidipine, lidocaine, metoprolol, nebivolol, nimodipine, pindolol, prajmaline, propafenone, propranolol, sotalol, urapidil, and verapamil), as well as other medications commonly found in combination (sildenafil, tadalafil, atorvastatin, clopidogrel, dapoxetine, memantine, pentoxifylline, rivastigmine, and ivabradine). The method enables simultaneous identification and quantification in blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Validation exhibited excellent linearity across the concentration range for all analytes. Precision and accuracy were within acceptable limits, with bias and relative standard deviation (RSD) values consistently below 9 % and 10 %, respectively. Selectivity and specificity assessments confirmed the absence of any interference from contaminants or co-extracted drugs. The method demonstrated very high sensitivity, with limits of detection (LOD) as low as 0.01 ng/ml and limits of quantification (LOQ) as low as 0.04 ng/ml. Extraction recovery exceeded 57.5 % for all analytes except atenolol, and matrix effects were <17 % for all analytes except pindolol. Processed sample stability evaluations revealed consistent results with acceptable deviations for all analytes. In addition, the method was specifically tested for the use in post mortem analysis. The applicability of our method was demonstrated by the analysis of two authentic human autopsy blood samples.

Catheter Ablation as First-Line Therapy in Persistent Atrial Fibrillation: Patient Characteristics and Clinical Outcomes.

BACKGROUND: In patients with persistent atrial fibrillation (PerAF), antiarrhythmic drugs (AADs) are considered a first-line rhythm-control strategy, whereas catheter ablation is a reasonable alternative. OBJECTIVES: This study sought to examine the prevalence, patient characteristics, and clinical outcomes of patients with PerAF who underwent catheter ablation as a first or second-line strategy. METHODS: This multicenter observational study included consecutive patients with PerAF who underwent first-time ablation between January 2020 and September 2021 in 9 medical centers in the United States. Patients were divided into those who underwent ablation as first-line therapy and those who had ablation as second-line therapy. Patient characteristics and clinical outcomes were compared between the groups. RESULTS: A total of 2,083 patients underwent first-time ablation for PerAF. Of these, 1,086 (52%) underwent ablation as a first-line rhythm-control treatment. Compared with patients treated with AADs as first-line therapy, these patients were predominantly male (72.6% vs 68.1%; P = 0.03), with a lower frequency of hypertension (64.0% vs 73.4%; P < 0.001) and heart failure (19.1% vs 30.5%; P < 0.001). During a mean follow-up of 325.9 ± 81.6 days, arrhythmia-free survival was similar between the groups (HR: 1.13; 95% CI: 0.92-1.41); however, patients in the second-line ablation strategy were more likely to continue receiving AAD therapy (41.5% vs 15.9%; P < 0.001). CONCLUSIONS: A first-line ablation strategy for PerAF is prevalent in the United States, particularly in men with fewer comorbidities. More data are needed to identify patients with PerAF who derive benefit from an early intervention strategy.

Programmed Ventricular Stimulation: Risk Stratification and Guiding Antiarrhythmic Therapies.

Electrophysiologic testing with programmed ventricular stimulation (PVS) has been utilized to induce ventricular tachycardia (VT), thereby improving risk stratification for patients with ischemic and nonischemic cardiomyopathies and determining the effectiveness of antiarrhythmic therapies, especially catheter ablation. A variety of procedural aspects can be modified during PVS in order to alter the sensitivity and specificity of the test including the addition of multiple baseline pacing cycle lengths, extrastimuli, and pacing locations. The definition of a positive result is also critically important, which has varied from exclusively sustained monomorphic VT (>30 seconds) to any ventricular arrhythmia regardless of morphology. In this review, we discuss the history of PVS and evaluate its role in sudden cardiac death risk stratification in a variety of patient populations. We propose an approach to future investigations that will capitalize on the unique ability to vary the sensitivity and specificity of this test. We then discuss the application of PVS during and following catheter ablation. The strategies that have been utilized to improve the efficacy of intraprocedural PVS are highlighted during a discussion of the limitations of this probabilistic strategy. The role of noninvasive programmed stimulation is also reviewed in predicting recurrent VT and informing management decisions including repeat ablations, modifications in antiarrhythmic drugs, and implantable cardioverter-defibrillator programming. Based on the available evidence and guidelines, we propose an approach to future investigations that will allow clinicians to optimize the use of PVS for risk stratification and assessment of therapeutic efficacy.

ECMO for drug-refractory electrical storm without a reversible trigger: a retrospective multicentric observational study.

AIMS: Drug-refractory electrical storm (ES) is a life-threatening medical emergency. We describe the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in drug-refractory ES without a reversible trigger, for which specific guideline recommendations are still lacking. METHODS AND RESULTS: Retrospective observational study in four Iberian centres on the indications, treatment, complications, and outcome of drug-refractory ES not associated with acute coronary syndromes, decompensated heart failure, drug toxicity, electrolyte disturbances, endocrine emergencies, concomitant acute illness with fever, or poor compliance with anti-arrhythmic drugs, requiring VA-ECMO for circulatory support. Thirty-four (6%) out of 552 patients with VA-ECMO for cardiogenic shock were included [71% men; 57 (44-62) years], 65% underwent cardiopulmonary resuscitation before VA-ECMO implantation, and 26% during cannulation. Left ventricular unloading during VA-ECMO was used in 8 (24%) patients: 3 (9%) with intraaortic balloon pump, 3 (9%) with LV vent, and 2 (6%) with Impella. Thirty (88%) had structural heart disease and 8 (24%) had an implantable cardioverter-defibrillator. The drug-refractory ES was mostly due to monomorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) (59%), isolated monomorphic VT (26%), polymorphic VT (9%), or VF (6%). Thirty-one (91%) required deep sedation, 44% overdrive pacing, 36% catheter ablation, and 26% acute autonomic modulation. The main complications were nosocomial infection (47%), bleeding (24%), and limb ischaemia (21%). Eighteen (53%) were weaned from VA-ECMO, and 29% had heart transplantation. Twenty-seven (79%) survived to hospital discharge (48 (33-82) days). Non-survivors were older [62 (58-67) vs. 54 (43-58); P < 0.01] and had a higher first rhythm disorder-to-ECMO interval [0 (0-2) vs. 2 (1-11) days; P = 0.02]. Seven (20%) had rehospitalization during follow-up [29 (12-48) months], with ES recurrence in 6%. CONCLUSIONS: VA-ECMO bridged drug-refractory ES without a reversible trigger with a high success rate. This required prolonged hospital stays and coordination between the ECMO centre, the electrophysiology laboratory, and the heart transplant programme.

Class 1C Antiarrhythmics for Premature Ventricular Complex Suppression in Nonischemic Cardiomyopathy With Implantable Cardioverter-Defibrillators.

BACKGROUND: Premature ventricular complexes (PVCs) are common and associated with worse outcomes in patients with heart failure. Class 1C antiarrhythmic drugs (AADs) effectively suppress PVCs, but guidelines currently restrict their use in structural heart disease. OBJECTIVES: This study aimed to assess the safety and efficacy of class 1C AADs in patients with nonischemic cardiomyopathy (NICM) and implantable cardioverter-defibrillators (ICDs). METHODS: All patients with NICM and an ICD treated with flecainide or propafenone at the Hospital of the University of Pennsylvania between 2014 and 2022 were identified. PVC burden, left ventricular ejection fraction (LVEF), and biventricular pacing percentage were compared before and during class 1C AAD treatment. Safety outcomes included sustained atrial and ventricular arrhythmias, heart failure admissions, and death. RESULTS: We identified 34 patients, 23 receiving flecainide and 11 propafenone. Most patients (62%) had failed other AADs or catheter ablation (68%) prior to class 1C AAD initiation. PVC burden decreased from 20% ± 13% to 6% ± 7% (P < 0.001), LVEF increased from 33% ± 9% to 37% ± 10% (P = 0.01), and biventricular pacing percentage increased from 85% ± 9% to 93% ± 7% (P = 0.01). Sustained ventricular tachycardia (2 vs 9 patients) and admissions for decompensated heart failure (2 vs 3 patients) decreased compared with the 12 months prior to class 1C AAD initiation. CONCLUSIONS: Class 1C AADs effectively suppressed PVCs in patients with NICM and ICDs, leading to increases in LVEF and biventricular pacing percentage. In this limited sample, their use was safe. Larger studies are needed to confirm the safety of this approach.