Characterizing atrial fibrillation in patients with and without heart failure across the ejection fraction spectrum: Incidence, prevalence, and treatment strategies.

AIMS: Heart failure (HF) and atrial fibrillation (AF) often coexist. We explored AF incidence, prevalence, and treatment strategies in patients with versus without HF across the ejection fraction (EF) spectrum. METHODS AND RESULTS: We analysed patients with HF from the Swedish HF Registry (1 December 2005-31 December 2021), matched 1:1 by sex, age, and county of residence to patients without HF from Statistics Sweden. Two study cohorts were derived (i) to assess AF prevalence and treatments, and (ii) to evaluate AF incidence and related predictors. Overall, 195 106 patients were considered, 50% of them with HF (of whom 54% with HF with reduced [HFrEF], 23% mildly reduced [HFmrEF], and 23% with preserved EF [HFpEF]). From 2006 to 2021, AF prevalence increased in both patients with (57% to 58%) and without HF (8% to 11%). HF patients, particularly if with HFrEF, were more likely receiving AF treatments than those without HF. Over time, antiarrhythmic use decreased, while rate control drugs and oral anticoagulant use, and AF-related procedures increased, regardless of HF and EF. During a median follow-up of 3.7 years, in 86 210 patients without AF, incident AF risk was two-fold higher in HF versus non-HF (hazard ratio [HR] 2.76, 95% confidence interval [CI] 2.45-3.12), highest in HFpEF (HR 3.12, 95% CI 2.65-3.67) versus HFrEF (HR 2.68, 95% CI 2.34-3.06) and HFmrEF (HR 2.53, 95% CI 2.17-2.94). CONCLUSIONS: Atrial fibrillation prevalence, anticoagulant use, and AF-related procedures increased over time regardless of HF, with HF patients more likely receiving AF treatments. In HF, despite higher AF prevalence and incidence in HFpEF, AF treatment use remained modest, calling for further implementation.

Impact of Catheter Ablation of Electrical Storm on Survival: A Propensity Score-Matched Analysis.

BACKGROUND: Electrical storm (ES) is a life-threatening condition, associated with substantial early and subacute mortality. Catheter ablation (CA) is a well-established therapy for ES. However, data regarding the impact of CA on the short-term and midterm survival of patients admitted for ES remain unclear. OBJECTIVES: This multicenter study aimed to investigate the impact of CA of ES on survival outcomes, while accounting for key patient characteristics associated with treatment selection. METHODS: A propensity score-matching (PSM) analysis was performed on 780 consecutive patients admitted for ES in 4 tertiary centers. PSM (1:1) based on the main characteristics associated with the use of CA or medical therapy alone was performed, resulting in 2 groups of 288 patients. RESULTS: After PSM, patients who underwent CA (n = 288) and those treated with medical therapy alone (n = 288) did not present any significant differences in the main demographic characteristics, ES presentation, and management. Compared with medical therapy alone, CA was associated with a significantly lower rate of ES recurrence at 1 year (5% vs 26%; P < 0.001). Similarly, CA was associated with a higher 1-year (91% vs 81%; P < 0.001) and 3-year (78% vs 71%; P = 0.017) survival after discharge. In subgroup analyses, effect of ablation therapy remained consistent in patients older than 70 years of age (HR: 0.39; 95% CI: 0.24-0.66), with substantial efficacy in patients with a LVEF <35% (HR: 0.39; 95% CI: 0.27-0.59). CONCLUSIONS: In propensity-matched analyses, this large study shows that CA-based management of patients admitted for ES is associated with a reduction in mortality compared with medical treatment, particularly in patients with a low ejection fraction.

Repositioning of antiarrhythmics for prostate cancer treatment: a novel strategy to reprogram cancer-associated fibroblasts towards a tumor-suppressive phenotype.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a significant role in fueling prostate cancer (PCa) progression by interacting with tumor cells. A previous gene expression analysis revealed that CAFs up-regulate genes coding for voltage-gated cation channels, as compared to normal prostate fibroblasts (NPFs). In this study, we explored the impact of antiarrhythmic drugs, known cation channel inhibitors, on the activated state of CAFs and their interaction with PCa cells. METHODS: The effect of antiarrhythmic treatment on CAF activated phenotype was assessed in terms of cell morphology and fibroblast activation markers. CAF contractility and migration were evaluated by 3D gel collagen contraction and scratch assays, respectively. The ability of antiarrhythmics to impair CAF-PCa cell interplay was investigated in CAF-PCa cell co-cultures by assessing tumor cell growth and expression of epithelial-to-mesenchymal transition (EMT) markers. The effect on in vivo tumor growth was assessed by subcutaneously injecting PCa cells in SCID mice and intratumorally administering the medium of antiarrhythmic-treated CAFs or in co-injection experiments, where antiarrhythmic-treated CAFs were co-injected with PCa cells. RESULTS: Activated fibroblasts show increased membrane conductance for potassium, sodium and calcium, consistently with the mRNA and protein content analysis. Antiarrhythmics modulate the expression of fibroblast activation markers. Although to a variable extent, these drugs also reduce CAF motility and hinder their ability to remodel the extracellular matrix, for example by reducing MMP-2 release. Furthermore, conditioned medium and co-culture experiments showed that antiarrhythmics can, at least in part, reverse the protumor effects exerted by CAFs on PCa cell growth and plasticity, both in androgen-sensitive and castration-resistant cell lines. Consistently, the transcriptome of antiarrhythmic-treated CAFs resembles that of tumor-suppressive NPFs. In vivo experiments confirmed that the conditioned medium or the direct coinjection of antiarrhythmic-treated CAFs reduced the tumor growth rate of PCa xenografts. CONCLUSIONS: Collectively, such data suggest a new therapeutic strategy for PCa based on the repositioning of antiarrhythmic drugs with the aim of normalizing CAF phenotype and creating a less permissive tumor microenvironment.

Navigating the Incidence of Postoperative Arrhythmia and Hospitalization Length: The Role of Amiodarone and Other Antiarrhythmics in Prophylaxis.

Antiarrhythmic drugs play a pivotal role in managing and preventing arrhythmias. Amiodarone, classified as a class III antiarrhythmic, has been used prophylactically to effectively prevent atrial fibrillation postoperatively in cardiac surgeries. However, there is a lack of consensus on the use of amiodarone and other antiarrhythmic drugs as prophylaxis to reduce the occurrence of all types of postoperative arrhythmias in cardiac and non-cardiac surgeries. A comprehensive PubMed query yielded 614 relevant papers, of which 52 clinical trials were analyzed. The data collection included the class of antiarrhythmics, timing or method of drug administration, surgery type, type of arrhythmia and its incidence, and hospitalization length. Statistical analyses focused on prophylactic antiarrhythmics and their respective reductions in postoperative arrhythmias and hospitalization length. Prophylactic amiodarone alone compared to placebo demonstrated a significant reduction in postoperative arrhythmia incidence in cardiac and non-cardiac surgeries (24.01%, p<0.0001), and it was the only treatment group to significantly reduce hospitalization length versus placebo (p = 0.0441). Prophylactic use of class 4 antiarrhythmics versus placebo also demonstrated a significant reduction in postoperative arrhythmia incidence (28.01%, p<0.0001), and while there was no significant statistical reduction compared to amiodarone (4%, p=0.9941), a lack of abundant data provides a case for further research on the prophylactic use of class 4 antiarrhythmics for this indication. Amiodarone prophylaxis remains a prime cornerstone of therapy in reducing postoperative arrhythmia incidence and hospitalization length. Emerging data suggests a need for a broader exploration of alternative antiarrhythmic agents and combination therapies, particularly class 4 antiarrhythmics, in both cardiac and non-cardiac surgeries. This meta-analysis depicts the effectiveness of amiodarone, among other antiarrhythmics, in postoperative arrhythmia incidence and hospitalization length reduction in cardiac and non-cardiac surgeries.

Sex differences in clinical features, utilization of oral anticoagulant agents, and 1-year outcome in Middle Eastern patients with atrial fibrillation.

OBJECTIVE: Studies have revealed that sex can predict differences in multiple aspects of atrial fibrillation (AF). These differences are underreported in the Middle East. This study aims to describe sex-specific differences in risk factors, symptomatology, management, and outcomes in Middle Eastern patients with AF. METHODS: The JoFib (Jordan-Atrial-Fibrillation) study is an observational, prospective, multicenter, nationwide registry in AF. Comparisons were made between female and male patients using Pearson chi-square and Mann-Whitney U tests. Multivariable regression models were constructed to investigate whether the female sex was predictive of any AF-related outcomes (all-cause death, cardiovascular death, ischemic stroke or systemic embolism [IS/SE], major bleeding, and clinically relevant non-major bleeding). RESULTS: Of 2,020 patients with AF, 54% (n = 1091) were females. Females with AF were older (median age 71 vs. 69, p <.001), but had less heart failure (20.9% vs. 27.2%, p = .001) and coronary artery disease (7.5% vs. 14.7%, p <.001). Females with AF were more symptomatic (74.7% vs. 66.5%, p <.001) and frequently received anticoagulant therapy (84.4% vs. 78.9%, p = .001). Rhythm control was pursued less frequently in females (23.4% vs. 27.3%, p = .04). All studied outcomes occurred with similar frequencies in females and males, and sex was not significantly predictive of any outcome. CONCLUSION: Females with AF are more symptomatic, yet they are treated less with rhythm control. Despite higher risk, females have similar risk-adjusted all-cause cardiovascular death and stroke rates compared to males. Future studies should explore how treatments and interventions can influence quality-of-life and cardiovascular outcomes in females with AF.

Direct oral anticoagulant use in hospitalized patients with atrial fibrillation across body mass index categories: design and rationale for a retrospective cohort study.

Background: Atrial fibrillation (AF) and obesity are common conditions globally; yet, there remains suboptimal pharmacological management contributing to high rates of hospitalization in patients with AF. The altered pathophysiology of both obese and underweight individuals may influence the pharmacology of medications, including those used to manage AF. This, in turn, increases the risk of adverse events and impacts patient risk for stroke and rehospitalization. Despite the well-established complications of obesity, research investigating the relationship between obesity and AF is scant. Objectives: The primary aim of this study is to describe cardiovascular-related hospitalization in AF patients according to BMI categories. A secondary aim is to describe anticoagulant and antiarrhythmic prescribing practice patterns in patients with AF, according to the BMI category. Design: A retrospective, exploratory descriptive observational cohort study, using routinely collected electronic medical record data from five public hospitals within a single health district, with a population dominantly that is culturally and linguistically diverse, and has a low socioeconomic status. Methods and analysis: Data extraction will include a 24-month period (January 2017 to December 2018) with a 12-month follow-up. All adult (⩾18 years) patients at discharge diagnosed with AF, prescribed any oral anticoagulant and/or oral rate/rhythm control agent, will be eligible for inclusion. Ethics and dissemination: Ethics approval from the health district and the University of Wollongong has been granted. Findings will seek to demonstrate associations between management strategies and patient outcomes, as well as describe patterns of acute care management from prescribers. These data will be used to inform and generate hypotheses for large-scale studies examining the impact of body weight on anticoagulation prescribing at national and global scales.

Background: Across the world, two of the most common conditions include obesity and a heart disease that causes irregular heartbeat which is known as Atrial Fibrillation (AF). As a result of the excessive over or underweight of an individual with AF, can affect how some of the medications used manage AF work, in turn potentially affecting their health. Purpose: The main purpose of this study is to describe how often people with AF end up in the hospital because of heart-related problems based on their weight category. We also want to describe how doctors prescribe blood thinners and medicines that control the heart rhythm, in patients with AF based on their body weight. Design and method: To do this we will examine old electronic medical records over a two-year period, from January 2017 to December 2018 from five public hospitals, and we will see what happens after one year if they were hospitalised. These hospitals serve a diverse population with a mix of languages and cultures and are low-income earning households. We will only examine the electronic medical records of adults (18 years and over) who were diagnosed with AF and were prescribed blood thinners and/or heart rate or rhythm-controlling medications at the time of leaving the hospital. All adult (⩾18 years) patients at discharge diagnosed with AF, prescribed any oral anticoagulant and/or oral rate/rhythm control agent, will be eligible for inclusion. We have already gotten approval from the hospital and the University of Wollongong to conduct this study ethically. We anticipate that the results from this study will help us understand how different treatments and body weights are connected, and this knowledge can be used to plan bigger studies on a national and global scale to improve how we care for people with irregular heartbeats.

Designing a study that examines the use of blood thinners in hospitalised patients with irregular heartbeat at different body weights.

Amiodarone and Dronedarone Causes Liver Injury with Distinctly Different Clinical Presentations.

OBJECTIVE: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database. METHODS: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020. RESULTS: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes. CONCLUSION: Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity.

Pediatric antiarrhythmics and toxicity: A clinical review.

Antiarrhythmic medications are fundamental in the acute and chronic management of pediatric arrhythmias. Particularly in the pediatric patient population, associated antiarrhythmic toxicities represent important potential adverse effects. Emergency medicine clinicians must be skilled in the detection, workup, and management of antiarrhythmic toxicity. This is a clinical review of the indications, pharmacology, adverse effects, and toxicologic treatment of antiarrhythmics commonly used in the pediatric patient population.

Assessment of Dofetilide or Sotalol Tolerability in the Elderly.

Background: Dofetilide and sotalol are potassium channel antagonists that require inpatient QTc monitoring during initiation, due to increased risk of fatal arrhythmias. Elderly patients are especially subject to an increased risk of fatal arrhythmias due to polypharmacy, comorbidities, and physiologic cardiac changes with aging. This study will describe the tolerability and risk factors associated with the initiation of sotalol or dofetilide in patients ≥80 years of age. Methodology: This is a multicenter, retrospective, descriptive study of patients ≥80 years old who were initiated on either dofetilide or sotalol between May 8, 2018 and July 31, 2021 at institutions within the Mayo Clinic Health System. The percentage of patients who received nonpackage insert recommended doses was identified. Incidence of and reasons for dose reductions or discontinuations due to safety-related events or clinical concerns during the initial loading period were collected. Results: The final analysis included 104 patients. The majority of patients (75%) received nonstandard initial doses of dofetilide or sotalol based on baseline estimated creatinine clearance or QTc. Overall, 39% (N = 41) of patients experienced a dose reduction or discontinuation due to a safety-related event or concern. Patients who received nonstandard initial doses of dofetilide or sotalol had 4.7 times greater odds of experiencing a safety-related event requiring dose reduction or discontinuation. Conclusion: Following package insert dosing in elderly patients increases safety and tolerability relative to more aggressive dosing of dofetilide or sotalol.

Arrhythmias and Sudden Cardiac Death.

Ventricular tachyarrhythmias remain a major cause of sudden cardiac arrest (SCA) that leads to sudden cardiac death (SCD). Primary prevention strategies to prevent SCD include promoting a healthy lifestyle, following United States Preventive Service Task Force recommendations related to cardiovascular disease, and controlling comorbid conditions. For a patient experiencing SCA, early cardiopulmonary resuscitation and defibrillation should be performed. Implantable cardioverter defibrillators are more effective at secondary prevention compared with drug therapy but medications such as amiodarone, beta-blockers, and sotalol may be helpful adjuncts to reduce the risk of SCD or improve a patient's symptoms (eg, palpitations and inappropriate defibrillator shocks).

State-independent inhibition of the oncogenic Kv10.1 channel by desethylamiodarone, a comparison with amiodarone.

Kv10.1 is a voltage-dependent K channel whose ectopic expression is associated with several human cancers. Additionally, Kv10.1 has structure-function properties which are not yet well understood. We are using drugs of clinical importance in an attempt to gain insight on the relationship between pharmacology and characteristic functional properties of this channel. Herein, we report the interaction of desethylamiodarone (desAd), the active metabolic product of the antiarrhythmic amiodarone with Kv10.1: desAd binds to both closed and open channels, with most inhibition taking place from the open state, with affinity ~ 5 times smaller than that of amiodarone. Current inhibition by desAd and amiodarone is not synergistic. Upon repolarization desAd becomes trapped in Kv10.1 and thereafter dissociates slowly from closed-and-blocked channels. The addition of the Cole-Moore shift plus desAd open-pore-block time courses yields an increasing phase on the steady-state inhibition curve (H∞) at hyperpolarized holding potentials. In contrast to amiodarone, desAd does not inhibit the Kv10.1 Cole-Moore shift, suggesting that a relevant hydrophobic interaction between amiodarone and Kv10.1 participates in the inhibition of the Cole-Moore shift, which is lost with desAd.

Ablation Versus Antiarrhythmic Drugs as First-Line Therapy for Treatment-Naive Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Evidence on the relative safety and efficacy of atrial fibrillation catheter ablation and antiarrhythmic drugs (AADs) as the first-line therapy for patients with treatment-naive atrial fibrillation (AF) remains disputed. Digital databases were queried to identify relevant randomized controlled trials. The incidence of recurrent AF, major adverse cardiovascular events, and its components (all-cause death, nonfatal stroke, and bleeding) were compared using the DerSimonian and Laird method under the random-effects model to calculate pooled unadjusted risk ratio (RR) with 95% confidence intervals (CIs). A total of 6 randomized controlled trials consisting of 1,120 patients (574 ablation and 549 AADs) were included in the final analysis. Over a median follow-up of 1 year, the risk of any AF recurrence (RR 0.54, 95% CI 0.39 to 0.75) was significantly lower in patients receiving ablation than in patients receiving AADs. However, there was similar risk of major adverse cardiovascular events (RR 2.65, 95% CI 0.61 to 11.46), trial-defined composite end point of adverse events (RR 0.71, 95% CI 0.28 to 1.80), stroke (RR 2.42, 95% CI 0.22 to 26.51), all-cause mortality (RR 1.98, 95% CI 0.28 to 13.90), and procedure/medication failure (RR 2.65, 95% CI 0.61 to 11.46) with both therapies. In conclusion, in patients presenting with treatment-naive AF, ablation as a first-line therapy lowers the risk of AF recurrence with no associated increase in major adverse events, stroke, and mortality compared with AADs.

Novel pyridyl-substituted nitronyl nitroxides as potential antiarrhythmic and hypotensive agents with low toxicity and enhanced stability in aqueous solutions.

This study explores the antiarrhythmic and hypotensive potential of pyridyl-substituted nitronyl nitroxides derivatives, uncovering the crucial role of a single carbon moiety of the pyridine cycle alongside radical and charged oxygen centers of the imidazoline fragment. Notably, the introduction of fluorine atoms diminished the antiarrhythmic effect, while the most potent derivatives featured the nitronyl nitroxide pattern positioned at the third site of the pyridine cycle. Gender-dependent responses were observed in lead compounds LCF3 and LMe, with LMe inducing temporary bradycardia and hypotension specifically in female rats, and LCF3 causing significant blood pressure reduction followed by rebound in females compared to milder effects in males. Mechanistic insights point towards ß1 adrenoceptor blockade as an underlying mechanism, supported by experiments on isolated rat atria. This research underscores the interplay between structure, cardiovascular effects and gender-specific responses, offering insights for therapeutic strategies for treating free radical-associated cardiovascular disorders.

Blocking channels to metastasis: targeting sodium transport in breast cancer.

The development of therapies that can suppress invasion and prevent metastasis, 'anti-metastatic drugs', is an important area of unmet therapeutic need. The new results of a recent open-label, multicentre randomised trial published in J Clin Oncol showed a significant disease-free survival (DFS) benefit for breast cancer patients receiving presurgical, peritumoral injection of lidocaine, an amide local anaesthetic, which blocks voltage-gated sodium channels (VGSCs). VGSCs are expressed on electrically excitable cells, including neurons and cardiomyocytes, where they sustain rapid membrane depolarisation during action potential firing. As a result of this key biophysical function, VGSCs are important drug targets for excitability-related disorders, including epilepsy, neuropathic pain, affective disorders and cardiac arrhythmia. A growing body of preclinical evidence highlights VGSCs as key protagonists in regulating altered sodium influx in breast cancer cells, thus driving invasion and metastasis. Furthermore, prescription of certain VGSC-inhibiting medications has been associated with reduced cancer incidence and improved survival in several observational studies. Thus, VGSC-inhibiting drugs already in clinical use may be ideal candidates for repurposing as possible anti-metastatic therapies. While these results are promising, further work is required to establish whether other VGSC inhibitors may afford superior metastasis suppression. Finally, increasing preclinical evidence suggests that several other ion channels are also key drivers of cancer hallmarks; thus, there are undoubtedly further opportunities to harness ion transport inhibition that should also be explored.

Experimental drugs for supraventricular tachycardia: an analysis of early phase clinical trials.

INTRODUCTION: Supraventricular tachycardias (SVT) are a diverse group of commonly encountered arrhythmias arising at or above the atrioventricular (AV) node. Conventional anti-arrhythmic medications are restricted by extensive side-effect profiles and limited efficacy. Catheter ablation has emerged as a first-line therapy for many arrhythmias but is not a suitable option for all patients. This has prompted the exploration of novel pharmacological approaches targeting specific molecular mechanisms of SVT. AREAS COVERED: This review article aims to summarize recent advancements in pharmacological therapeutics for SVT and their clinical implications. The understanding of molecular mechanisms underlying these arrhythmias, particularly atrial fibrillation, has opened up new possibilities for targeted interventions. Beyond the manipulation of ion channels and membrane potentials, pharmacotherapy now focuses on upstream targets such as inflammation, oxidative stress, and structural remodeling. This review strives to provide a comprehensive overview of recent advancements in pharmacological therapeutics directed at the management of SVT. We begin by providing a brief summary of the mechanisms and management of commonly encountered SVT before delving into individual agents, which in turn are stratified based on their molecular treatment targets. EXPERT OPINION: The evolving landscape of pharmacologic therapy offers hope for more personalized and tailored interventions in the management of SVT.

Selective Inhibition of Cardiac Late Na+ Current Is Based on Fast Offset Kinetics of the Inhibitor.

The present study was designed to test the hypothesis that the selectivity of blocking the late Na+ current (INaL) over the peak Na+ current (INaP) is related to the fast offset kinetics of the Na+ channel inhibitor. Therefore, the effects of 1 µM GS967 (INaL inhibitor), 20 µM mexiletine (I/B antiarrhythmic) and 10 µM quinidine (I/A antiarrhythmic) on INaL and INaP were compared in canine ventricular myocardium. INaP was estimated as the maximum velocity of action potential upstroke (V+max). Equal amounts of INaL were dissected by the applied drug concentrations under APVC conditions. The inhibition of INaL by mexiletine and quinidine was comparable under a conventional voltage clamp, while both were smaller than the inhibitory effect of GS967. Under steady-state conditions, the V+max block at the physiological cycle length of 700 ms was 2.3% for GS967, 11.4% for mexiletine and 26.2% for quinidine. The respective offset time constants were 110 ± 6 ms, 456 ± 284 ms and 7.2 ± 0.9 s. These results reveal an inverse relationship between the offset time constant and the selectivity of INaL over INaP inhibition without any influence of the onset rate constant. It is concluded that the selective inhibition of INaL over INaP is related to the fast offset kinetics of the Na+ channel inhibitor.

Keeping It "Current": A Review of Treatment Options for the Management of Supraventricular Tachycardia.

OBJECTIVE: To review treatment options and updates that exist for the management of paroxysmal supraventricular tachycardia (PSVT). DATA SOURCES: A literature search of PubMed was performed including articles from 1974 to June 2023 using the terms: arrhythmias, adenosine, verapamil, diltiazem, esmolol, propranolol, metoprolol, beta-blockers, amiodarone, PSVT, synchronized cardioversion, methylxanthines, dipyridamole, pediatrics, heart transplant, and pregnancy. Primary literature and guidelines were reviewed. STUDY SELECTION AND DATA EXTRACTION: Studies were considered if they were available in English and conducted in humans. DATA SYNTHESIS: PSVT is a subset of supraventricular tachycardia (SVT) that presents as a rapid, regular tachycardia with an abrupt onset and termination. Due to frequent emergency department (ED) visits annually with symptoms of PSVT, appropriate and efficient management of these patients is vital. This review provides an overview of the pathophysiology of PSVT, while also describing the literature behind nonpharmacologic and pharmacologic management of PSVT. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review describes new literature regarding the improved success of the modified Valsalva maneuver as a nonpharmacologic therapy in PSVT. In addition, it describes a new technique in administration of adenosine that has improved outcomes, defines dose adjustments needed for drug interactions with adenosine, compares the utilization of nondihydropyridine calcium channel blockers with adenosine, and provides management recommendations for patients in special populations. CONCLUSIONS: With high annual rates of ED visits for SVT, providers should be aware of the data behind management and modifications of therapy based on patient-specific factors (ie, patient preference, pharmacokinetics/pharmacodynamics, drug interactions, and special populations).

Blanking period antiarrhythmic drugs after catheter ablation for atrial fibrillation: a meta-analysis of randomized controlled trials.

Background: Antiarrhythmic drugs (AADs) are frequently prescribed following catheter ablation (CA) for atrial fibrillation (AF). However, to date, there is a lack of large-scale, multicenter controlled studies that have confirmed the efficacy of AADs in reducing the incidence of late recurrence of AF after CA. Furthermore, the optimal duration of short-term use of AADs after CA remains a controversial topic. Methods: PubMed, Embase, Cochrane Library, CNKI, and ClinicalTrials.gov were searched until April 25, 2022. We conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of blanking period AADs in predicting both early and late recurrence of AF. In addition, Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the quality of evidence in this meta-analysis. Results: 12 RCTs with 3,625 patients were included in this meta-analysis. Short-term use of AADs after AF ablation reduced the risk of early recurrence of AF compared with the no-AADs group. In the subgroup analysis of AADs use time, it was found that only using AADs for more than 2 months can reduce the early recurrence of AF after CA. However, when compared with the no-AADs group, short-term use of AADs after CA did not reduce the incidence of late recurrence of AF. Conclusions: Short-term use of AADs (more than 2 months) can reduce the early recurrence but not the late recurrence of AF after CA.

The Feasibility and Safety of Flecainide Use Among Patients With Varying Degrees of Coronary Disease.

BACKGROUND: Class IC antiarrhythmic agents are effective for treating atrial tachyarrhythmias, but their use is restricted in patients with coronary artery disease (CAD). Data on the safety of the use of IC agents in patients with CAD in the absence of recent acute coronary syndromes are lacking. OBJECTIVES: This study sought to evaluate the safety and feasibility of treatment with IC agents in patients with varying degrees of CAD in a large serial, real-world cohort. METHODS: We retrospectively identified all patients at our institution from January 2005 to February 2021 on a IC agent (n = 3,445) and those on sotalol or dofetilide (n = 2,216) as controls, excluding those with a prior history of ventricular tachycardia, implantable cardioverter-defibrillator placement, or nonrevascularized myocardial infarction. Baseline clinical characteristics included degree of CAD (categorized as none, nonobstructive, or obstructive), other comorbid illness, and medication use. Clinical outcomes, including survival, were ascertained. We performed Cox regression analysis to evaluate the effect of IC use on event-free survival across varying degrees of CAD. RESULTS: After adjustment for baseline characteristics, there was an independent association between IC use and improved mortality. However, there was an interaction between IC use and degree of CAD (compared to sotalol) demonstrating poorer event-free survival among those with obstructive coronary disease (HR: 3.80; 95% CI: 1.67-8.67; P = 0.002). CONCLUSIONS: Among select patients with nonobstructive CAD and without a history of ventricular tachycardia, IC agents are not associated with increased mortality. Therefore, these agents may be an option for some patients in whom they are frequently restricted. Further prospective studies are warranted.