Sex- and age-specific differences in the use of antiarrhythmic therapies among atrial fibrillation patients: a nationwide cohort study.

BACKGROUND AND AIMS: Atrial fibrillation (AF) patients frequently require active rhythm control therapy to maintain sinus rhythm and reduce symptom burden. Our study assessed whether antiarrhythmic therapies (AATs) are used disproportionately between men and women after new-onset AF. METHODS: The nationwide Finnish anticoagulation in atrial fibrillation (FinACAF) registry-based linkage study covers all patients with new-onset AF in Finland during 2007-2018. Study outcomes included initiation of AATs in the form of antiarrhythmic drugs (AAD), cardioversion, or catheter ablation. RESULTS: The study population constituted of 229 565 patients (50% females). Women were older than men (76.6 ± 11.8 vs. 68.9 ± 13.4 years) and had higher prevalence of hypertension or hyperthyroidism, but lower prevalence of vascular disease, diabetes, renal disease, and cardiomyopathies than men. Overall, 17.6% of women and 25.1% of men were treated with any AAT. Women were treated with AADs more often than men in all age groups (adjusted subdistribution hazard ratio (aSHR) 1.223, 95%-CI 1.187-1.261). Cardioversions were also performed less often on women than on men aged <65 years (aSHR 0.722, 95%-CI 0.695-0.749), more often in patients ≥75 years (aSHR 1.166, 95%-CI 1.108-1.227), while no difference between the sexes existed in patients aged 65-74 years. Ablations were performed less often in women aged <65 years (aSHR 0.908, 95%-CI 0.826-0.998) and ≥75 years (aSHR 0.521, 95%-CI 0.354-0.766), whereas there was no difference in patients aged 65-74 years. CONCLUSION: Women used more AAD than men in all age groups but underwent fewer cardioversion and ablation procedures when aged <65 years.

Safety observation of antiarrhythmic drug use in a patient with sinus bradycardia following atrial fibrillation radiofrequency ablation combined with cardiac neural ablation: a case report.

This study assessed the safety of Antiarrhythmic Drug (AAD) administration in a patient experiencing sinus bradycardia following radiofrequency ablation for Atrial Fibrillation (AF), followed by cardiac ganglion ablation. Post-AF radiofrequency ablation, the employment of AADs is a prevalent clinical practice; however, these drugs may exacerbate bradycardia, leading to increased patient discomfort and treatment complexity. The decision to employ AADs in patients with sinus bradycardia post-AF ablation poses a significant clinical challenge. This investigation aimed to ascertain the safety of AADs in such patients. The study encompassed a single case, wherein a patient with pre- and post-procedure sinus bradycardia was treated with AADs following AF radiofrequency ablation and cardiac ganglion ablation, with a subsequent safety assessment. The findings indicate that AADs can be safely administered to patients with sinus bradycardia after these procedures, offering valuable insights for clinical decision-making. This case report underscores the intricacies of post-AF ablation management in patients with sinus bradycardia and advocates for personalized therapeutic strategies. The results enhance the clinical knowledge regarding the safety of AADs in this patient subset and may guide future treatment protocols. Nonetheless, the study's conclusions are drawn from a single case, and further research with larger cohorts is essential to substantiate these findings and elucidate the long-term safety and efficacy of this therapeutic approach.

Effectiveness of a Triple Antiarrhythmic Drug Strategy for Arrhythmia Recurrence after Persistent Atrial Fibrillation Ablation.

BACKGROUND AND OBJECTIVE: Treating recurrent atrial arrhythmias after persistent atrial fibrillation (PeAF) ablation is often challenging. This single-center, prospective study aimed to observe the effectiveness of different combinations of oral antiarrhythmic drugs (AADs) in reverting to sinus rhythm (SR) in patients with recurrent atrial arrhythmias after PeAF ablation. METHODS: Forty-five patients who experienced recurrent atrial arrhythmias after PeAF ablation were included. Based on their medication regimens, patients were divided into two groups, with the study group being a triple-drug group (digoxin combined with amiodarone/ propafenone and ß-blocker), and the control group being a non-triple-drug group. RESULTS: The rate of reversion to SR was significantly higher in the study group (n = 29) than in the control group (n = 16) at 3 weeks (34.48% vs. 0%, p < 0.01) and 1 month (44.84% vs. 6.25%, p = 0.02) after initiating AADs. No patients with asymptomatic bradycardia were observed in either group. CONCLUSIONS: For patients with recurrent atrial arrhythmias after PeAF ablation, a regimen of low-dose digoxin combined with amiodarone/propafenone and ß-blocker may effectively improve short-term reversion rates.

The Properties of the Transient Outward, Inward Rectifier and Acetylcholine-Sensitive Potassium Currents in Atrial Myocytes from Dogs in Sinus Rhythm and Experimentally Induced Atrial Fibrillation Dog Models.

AIMS: Atrial fibrillation (AF) is the most common chronic/recurrent arrhythmia, which significantly impairs quality of life and increases cardiovascular morbidity and mortality. Therefore, the aim of the present study was to investigate the properties of three repolarizing potassium currents which were shown to contribute to AF-induced electrical remodeling, i.e., the transient outward (Ito), inward rectifier (IK1) and acetylcholine-sensitive (IK,ACh) potassium currents in isolated atrial myocytes obtained from dogs either with sinus rhythm (SR) or following chronic atrial tachypacing (400/min)-induced AF. METHODS: Atrial remodeling and AF were induced by chronic (4-6 weeks of) right atrial tachypacing (400/min) in dogs. Transmembrane ionic currents were measured by applying the whole-cell patch-clamp technique at 37 °C. RESULTS: The Ito current was slightly downregulated in AF cells when compared with that recorded in SR cells. This downregulation was also associated with slowed inactivation kinetics. The IK1 current was found to be larger in AF cells; however, this upregulation was not statistically significant in the voltage range corresponding with atrial action potential (-80 mV to 0 mV). IK,ACh was activated by the cholinergic agonist carbachol (CCh; 2 µM). In SR, CCh activated a large current either in inward or outward directions. The selective IK,ACh inhibitor tertiapin (10 nM) blocked the outward CCh-induced current by 61%. In atrial cardiomyocytes isolated from dogs with AF, the presence of a constitutively active IK,ACh was observed, blocked by 59% with 10 nM tertiapin. However, in "AF atrial myocytes", CCh activated an additional, significant ligand-dependent and tertiapin-sensitive IK,ACh current. CONCLUSIONS: In our dog AF model, Ito unlike in humans was downregulated only in a slight manner. Due to its slow inactivation kinetics, it seems that Ito may play a more significant role in atrial repolarization than in ventricular working muscle myocytes. The presence of the constitutively active IK,ACh in atrial myocytes from AF dogs shows that electrical remodeling truly developed in this model. The IK,ACh current (both ligand-dependent and constitutively active) seems to play a significant role in canine atrial electrical remodeling and may be a promising atrial selective drug target for suppressing AF.

Ketamine Terminating Persistent Ventricular Tachycardia.

Ventricular tachycardia (VT) is an arrhythmia associated with sudden cardiac death. VT storm is a complication of persistent VT requiring immediate antiarrhythmic therapy. In refractory cases, adjunctive therapy includes sedation/mechanical ventilation or catheter ablation. This case highlights a patient with ischemic cardiomyopathy in refractory VT storm terminated by administration of ketamine.

Long-term Health-related Quality of Life and Rhythm-Outcomes of Catheter Ablation versus Antiarrhythmic Drugs in Patients with Atrial Fibrillation.

BACKGROUND: Data on long-term effects of catheter ablation versus antiarrhythmic drugs (AAD) on health-related quality of life (HRQoL) and atrial fibrillation (AF) burden are limited. OBJECTIVE: The study aimed to assess long-term HRQoL and rhythm data in symptomatic AF patients. METHODS: The 75 patients who underwent ablation and 74 receiving AAD in the Catheter Ablation compared with Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial were followed for 48 months. General Health using 36-Item Short-Form Health Survey, time to first AF-episode ≥1 hour, and AF burden, recorded by implantable cardiac monitors, were compared. RESULTS: 147 patients completed follow-up, with seven crossovers in the ablation group and 34 crossovers in the AAD group. General Health improved by ablation, median 62 points at baseline to 79.2 points at follow-up (p<0.001), and by AAD from median 67 to 77 points (p<0.001), without treatment differences (p=0.77). Time to first AF-episode ≥1 hour was longer, median 257 days (ablation group) versus 180 days (AAD group), p=0.025. The cumulative AF burden during follow-up was lower in the ablation (median 0.3% [interquartile range 0, 1.4]) versus the AAD group (1.6% [0.1, 11.0]), p=0.01. The cumulative reduction in AF burden compared with baseline was greater in the ablation (median -89.5% [-98.4, -51.3]) versus the AAD group (-52.7% [-92.6, 263.6]), p<0.001). CONCLUSIONS: HRQoL improvement at long-term did not differ between ablation and AAD group despite a larger reduction in AF burden after ablation. The results should be interpreted in the light of a high crossover rate in the AAD group.

Cardiac Arrhythmias and Their Management: An In-Depth Review of Current Practices and Emerging Therapies.

Cardiac arrhythmias encompass a range of conditions characterized by abnormal heart rhythms, affecting millions globally and significantly contributing to morbidity and mortality. This review provides a comprehensive analysis of the current practices and emerging therapies in managing cardiac arrhythmias, covering their definition, classification, epidemiology, and the critical importance of effective management. It explores the pathophysiology underlying various arrhythmias, including the mechanisms of arrhythmogenesis, such as re-entry, automaticity, and triggered activity. The review details the latest diagnostic tools, including ECG, Holter monitoring, and electrophysiological studies, and discusses the clinical presentation of different arrhythmias, from supraventricular to ventricular types and bradyarrhythmias. We examine current pharmacological and non-pharmacological treatment strategies, such as antiarrhythmic drugs, catheter ablation, and device therapy, highlighting their efficacy and limitations. Furthermore, the review delves into emerging therapies, including advanced catheter ablation techniques, novel antiarrhythmic agents, gene therapy, and innovative device technologies like leadless pacemakers and subcutaneous implantable cardioverter-defibrillators (ICDs). Special considerations for managing arrhythmias in diverse populations, including pediatrics, the elderly, and pregnant women, are discussed. Additionally, the review explores future directions in arrhythmia management, emphasizing personalized medicine, artificial intelligence applications, and the integration of advanced technologies in diagnosis and treatment. By synthesizing current knowledge and prospects, this review aims to enhance understanding and promote advancements in the field, ultimately improving patient outcomes with cardiac arrhythmias.

Efficacy of prescribing Inderal for polymorphic ventricular tachycardia in a young patient with the normal QT interval: A case report study.

Polymorphic ventricular tachycardia (PVT) is a group of life-threatening heart rhythm disorders. These arrhythmias share similar electrocardiographic characteristics but require different modes of therapy for effective treatment. It is important to note that the medications that are considered the first-line treatment for one type of PVT may not be appropriate for another type, and may worsen the condition. Therefore, it is crucial to accurately diagnose the type of PVT before initiating treatment to provide the most effective therapy for the patient. A 42-year-old man was admitted to the emergency department with dyspnea, Levine sign, and severe chest pain. His electrocardiogram showed ST elevation, and the QT interval was normal. The patient was sent to the cath lab based on the treatment protocols. According to the results of angiography, three coronary arteries were severely obstructed. His coronary arteries did not open during percutaneous coronary intervention; thus, the healthcare team decided on open heart surgery. He suffered from recurrent PVT following open heart surgery and did not respond to any of the drugs suitable for this type of tachycardia. Inderal prevented the recurrence of ventricular tachycardia (VT) in a patient with polymorphic VT without QT prolongation, contrary to the healthcare team's expectations. Inderal was used as the last line of treatment because this patient's arrhythmia was polymorphic VT without QT prolongation. Inderal is typically used for treating VT in patients with long QT syndromes and heart structural disorders. This case report aims to highlight the impact of Inderal on polymorphic tachycardia, specifically in cases where the QT interval is not elongated. In this particular case, the standard treatment approaches were ineffective in preventing reversibility, but Inderal proved to be successful. Therefore, we feel it is important to document and share this case.

Exploring the interplay between extracellular pH and Dronedarone's pharmacological effects on cardiac function.

Dronedarone (DRN) is a clinically used drug to mitigate arrhythmias with multichannel block properties, including the sodium channel Nav1.5. Extracellular acidification is known to change the pharmacological properties of several antiarrhythmic drugs. Here, we explore how modification in extracellular pH (pHe) shapes the pharmacological profile of DRN upon Nav1.5 sodium current (INa) and in the ex vivo heart preparation. Embryonic human kidney cells (HEK293T/17) were used to transiently express the human isoform of Nav1.5 α-subunit. Patch-Clamp technique was employed to study INa. Neurotoxin-II (ATX-II) was used to induce the late sodium current (INaLate). Additionally, ex vivo Wistar male rat preparations in the Langendorff system were utilized to study electrocardiogram (ECG) waves. DRN preferentially binds to the closed state inactivation mode of Nav1.5 at pHe 7.0. The recovery from INa inactivation was delayed in the presence of DRN in both pHe 7.0 and 7.4, and the use-dependent properties were distinct at pHe 7.0 and 7.4. However, the potency of DRN upon the peak INa, the voltage dependence for activation, and the steady-state inactivation curves were not altered in both pHe tested. Also, the pHe did not change the ability of DRN to block INaLate. Lastly, DRN in a concentration and pH dependent manner modulated the QRS complex, QT and RR interval in clinically relevant concentration. Thus, the pharmacological properties of DRN upon Nav1.5 and ex vivo heart preparation partially depend on the pHe. The pHe changed the biological effect of DRN in the heart electrical function in relevant clinical concentration.

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.

A Comparative Study of the Rapid (IKr) and Slow (IKs) Delayed Rectifier Potassium Currents in Undiseased Human, Dog, Rabbit, and Guinea Pig Cardiac Ventricular Preparations.

To understand the large inter-species variations in drug effects on repolarization, the properties of the rapid (IKr) and the slow (IKs) components of the delayed rectifier potassium currents were compared in myocytes isolated from undiseased human donor (HM), dog (DM), rabbit (RM) and guinea pig (GM) ventricles by applying the patch clamp and conventional microelectrode techniques at 37 °C. The amplitude of the E-4031-sensitive IKr tail current measured at -40 mV after a 1 s long test pulse of 20 mV, which was very similar in HM and DM but significant larger in RM and GM. The L-735,821-sensitive IKs tail current was considerably larger in GM than in RM. In HM, the IKs tail was even smaller than in DM. At 30 mV, the IKr component was activated extremely rapidly and monoexponentially in each studied species. The deactivation of the IKr component in HM, DM, and RM measured at -40 mV. After a 30 mV pulse, it was slow and biexponential, while in GM, the IKr tail current was best fitted triexponentially. At 30 mV, the IKs component activated slowly and had an apparent monoxponential time course in HM, DM, and RM. In contrast, in GM, the activation was clearly biexponential. In HM, DM, and RM, IKs component deactivation measured at -40 mV was fast and monoexponential, while in GM, in addition to the fast component, another slower component was also revealed. These results suggest that the IK in HM resembles that measured in DM and RM and considerably differs from that observed in GM. These findings suggest that the dog and rabbit are more appropriate species than the guinea pig for preclinical evaluation of new potential drugs expected to affect cardiac repolarization.

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.

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.

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.

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.

[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.