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Circulation Nov 2023Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM) with clinical and subclinical episodes occurring in nearly one-half... (Review)
Review
Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM) with clinical and subclinical episodes occurring in nearly one-half of patients. AF in HCM historically has been characterized as a decisive disease complication associated with substantial risk for thromboembolic stroke and increased morbidity and mortality. However, there have been many advances in treatment strategy resulting in improved outcomes for this patient group. For example, stroke risk in HCM has been greatly reduced by using systemic oral anticoagulation initiated after the first clinical (symptomatic) AF episode, usually with preference given to direct anticoagulants over warfarin. In contrast, stroke risk scoring systems (such as CHADS-VASc score) are not informative in HCM given the substantial potential for stroke events in patients with low scores, and therefore should not be used for anticoagulation decisions in this disease. A novel risk score specifically designed for HCM (HCM-AF score) can reliably identify most patients with HCM at risk for future AF. Although a strategy focused on controlling ventricular rate is effective in asymptomatic (or minimally symptomatic) patients with AF, restoring and maintaining sinus rhythm is required for most patients with marked AF symptom burden and impaired quality of life. Several antiarrhythmic drugs such as sotalol, disopyramide, and amiodarone, can be effective in suppressing AF episodes; albeit safe, long-term efficacy is supported by only limited data. Catheter AF ablation has emerged as an important treatment option for some patients, although freedom from AF after a single ablation is relatively low (35% at 3 years), multiple ablations and the concomitant use of antiarrhythmic drugs can control AF with more than two-thirds of patients maintaining sinus rhythm at 5 years. Surgical AF ablation with biatrial Cox-Maze IV performed as an adjunctive procedure during myectomy can reduce symptomatic AF episodes (70% of patients free from AF at 5 years). For the vast majority of patients who have HCM with AF, the implementation of contemporary therapies has allowed for improved quality of life and low HCM-related mortality.
Topics: Humans; Atrial Fibrillation; Anti-Arrhythmia Agents; Quality of Life; Risk Factors; Anticoagulants; Stroke; Cardiomyopathy, Hypertrophic; Catheter Ablation; Treatment Outcome
PubMed: 38011245
DOI: 10.1161/CIRCULATIONAHA.123.065037 -
Heart (British Cardiac Society) Jan 2024Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease characterised by fibrofatty replacement of the ventricular myocardium due to specific mutations,... (Review)
Review
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease characterised by fibrofatty replacement of the ventricular myocardium due to specific mutations, leading to ventricular arrhythmias and sudden cardiac death. Treating this condition can be challenging due to progressive fibrosis, phenotypic variations and small patient cohorts limiting the feasibility of conducting meaningful clinical trials. Although widely used, the evidence base for anti-arrhythmic drugs is limited. Beta-blockers are theoretically sound, yet their efficacy in reducing arrhythmic risk is not robust. Additionally, the impact of sotalol and amiodarone is inconsistent with studies reporting contradictory results. Emerging evidence suggests that combining flecainide and bisoprolol may be efficacious.Radiofrequency ablation has shown some potential in disrupting ventricular tachycardia circuits, with combined endo and epicardial ablation yielding better results which could be considered at the index procedure. In addition, stereotactic radiotherapy may be a future option that can decrease arrhythmias beyond simple scar formation by altering levels of Nav1.5 channels, Connexin 43 and Wnt signalling, potentially modifying myocardial fibrosis.Future therapies, such as adenoviruses and GSk3b modulation, are still in early-stage research. While implantable cardioverter-defibrillator implantation is a key intervention for reducing arrhythmic death, the risks of inappropriate shocks and device complications must be carefully considered.
Topics: Humans; Arrhythmogenic Right Ventricular Dysplasia; Arrhythmias, Cardiac; Anti-Arrhythmia Agents; Death, Sudden, Cardiac; Sotalol; Tachycardia, Ventricular; Defibrillators, Implantable
PubMed: 37433658
DOI: 10.1136/heartjnl-2023-322612 -
Primary Care Mar 2024Ventricular tachyarrhythmias remain a major cause of sudden cardiac arrest (SCA) that leads to sudden cardiac death (SCD). Primary prevention strategies to prevent SCD... (Review)
Review
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).
Topics: Humans; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Heart Arrest; Defibrillators, Implantable; Sotalol
PubMed: 38278568
DOI: 10.1016/j.pop.2023.07.008 -
Circulation. Arrhythmia and... Aug 2023Sotalol and dronedarone are both used for maintenance of sinus rhythm for patients with atrial fibrillation. However, while sotalol requires initial monitoring for QT...
BACKGROUND
Sotalol and dronedarone are both used for maintenance of sinus rhythm for patients with atrial fibrillation. However, while sotalol requires initial monitoring for QT prolongation and proarrhythmia, dronedarone does not. These treatments can be used in comparable patients, but their safety and effectiveness have not been compared head to head. Therefore, we retrospectively evaluated the effectiveness and safety using data from a large health care system.
METHODS
Using Veterans Health Administration data, we identified 11 296 antiarrhythmic drug-naive patients with atrial fibrillation prescribed dronedarone or sotalol in 2012 or later. We excluded patients with prior conduction disease, pacemakers or implantable cardioverter-defibrillators, ventricular arrhythmia, cancer, renal failure, liver disease, or heart failure. We used natural language processing to identify and compare baseline left ventricular ejection fraction between treatment arms. We used 1:1 propensity score matching, based on patient demographics, comorbidities, and medications, and Cox regression to compare strategies. To evaluate residual confounding, we performed falsification analysis with nonplausible outcomes.
RESULTS
The matched cohort comprised 6212 patients (3106 dronedarone and 3106 sotalol; mean [±SD] age, 71±10 years; 2.5% female; mean [±SD] CHADS-VASC, 2±1.3). The mean (±SD) left ventricular ejection fraction was 55±11 and 58±10 for dronedarone and sotalol users, correspondingly. Dronedarone, compared with sotalol, did not demonstrate a significant association with risk of cardiovascular hospitalization (hazard ratio, 1.03 [95% CI, 0.88-1.21]) or all-cause mortality (hazard ratio, 0.89 [95% CI, 0.68-1.16]). However, dronedarone was associated with significantly lower risk of ventricular proarrhythmic events (hazard ratio, 0.53 [95% CI, 0.38-0.74]) and symptomatic bradycardia (hazard ratio, 0.56 [95% CI, 0.37-0.87]). The primary findings were stable across sensitivity analyses. Falsification analyses were not significant.
CONCLUSIONS
Dronedarone, compared with sotalol, was associated with a lower risk of ventricular proarrhythmic events and conduction disorders while having no difference in risk of incident cardiovascular hospitalization and mortality. These observational data provide the basis for prospective efficacy and safety trials.
Topics: Female; Humans; Middle Aged; Aged; Aged, 80 and over; Male; Anti-Arrhythmia Agents; Dronedarone; Sotalol; Atrial Fibrillation; Retrospective Studies; Prospective Studies; Stroke Volume; Veterans; Ventricular Function, Left; Amiodarone
PubMed: 37485722
DOI: 10.1161/CIRCEP.123.011893 -
Communications Medicine Jul 2023Professional society practice guidelines conflict regarding their recommendations of dofetilide (DOF) and sotalol (STL) for treatment of arrhythmias in hypertrophic...
BACKGROUND
Professional society practice guidelines conflict regarding their recommendations of dofetilide (DOF) and sotalol (STL) for treatment of arrhythmias in hypertrophic cardiomyopathy (HCM), and supporting data is sparse. We aim to assess safety and efficacy of DOF and STL on arrhythmias in HCM.
METHODS
This was an observational study of HCM patients treated with DOF or STL for atrial fibrillation (AF) and ventricular arrhythmias (VA). Outcomes of drug discontinuation and arrhythmia recurrence were compared at 1 year and latest follow-up by Kaplan-Meier analysis. Predictors of drug failure were studied using uni- and multi-variable analyses. Drug-related adverse events were quantitated.
RESULTS
Here we show that of our cohort of 72 patients (54 ± 14 years old, 75% male), 21 were prescribed DOF for AF, 52 STL for AF, and 18 STL for VA. At 1 year, discontinuation and recurrence rates were similar for DOF-AF (38% and 43%) and STL-AF (29% and 44%) groups. Efficacy data was similar at long-term follow-up of 1603 (IQR 994-4131) days, and for STL-VA. Drug inefficacy was the most common reason for discontinuation (28%) followed by side-effects (13%). Incidences of heart failure hospitalization (5%) and mortality (3%) were low. One STL-AF patient developed non-sustained torsades de pointes in the setting of severe pneumonia and acute kidney injury, but there were no other drug-related serious adverse events.
CONCLUSIONS
DOF and STL demonstrate modest efficacy and satisfactory safety when used for AF and VA in HCM patients.
PubMed: 37468544
DOI: 10.1038/s43856-023-00315-8 -
Journal of Cardiovascular Pharmacology Aug 2023According to the American Heart Association, approximately 6 million adults have been afflicted with heart failure in the United States in 2020 and are more likely to... (Review)
Review
According to the American Heart Association, approximately 6 million adults have been afflicted with heart failure in the United States in 2020 and are more likely to have sudden cardiac death accounting for approximately 50% of the cause of mortality. Sotalol is a nonselective β-adrenergic receptor antagonist with class III antiarrhythmic properties that has been mostly used for atrial fibrillation treatment and suppressing recurrent ventricular tachyarrhythmias. The use of sotalol in patients with left ventricular dysfunction is not recommended by the American College of Cardiology or American Heart Association because studies are inconclusive with conflicting results regarding safety. This article aims to review the mechanism of action of sotalol, the β-blocking effects on heart failure, and provide an overview of clinical trials on sotalol use and its effects in patients with heart failure. Small- and large-scale clinical trials have been controversial and inconclusive about the use of sotalol in heart failure. Sotalol has been shown to reduce defibrillation energy requirements and reduce shocks from implantable cardioverter-defibrillators. Torsades de Pointes is the most life-threatening arrhythmia that has been documented with sotalol use and occurs more commonly in women and heart failure patients. Thus far, mortality benefits have not been demonstrated with sotalol use and larger multicenter studies are required going forward.
Topics: Humans; Female; Sotalol; Anti-Arrhythmia Agents; Adrenergic beta-Antagonists; Heart Failure; Atrial Fibrillation
PubMed: 37229640
DOI: 10.1097/FJC.0000000000001439 -
The Medical Letter on Drugs and... Jan 2024
Topics: Humans; Atrial Fibrillation
PubMed: 38180321
DOI: 10.58347/tml.2024.1693a -
EBioMedicine Sep 2023Brugada syndrome (BrS) is a cardiac channelopathy that can result in sudden cardiac death (SCD). SCN5A is the most frequent gene linked to BrS, but the...
BACKGROUND
Brugada syndrome (BrS) is a cardiac channelopathy that can result in sudden cardiac death (SCD). SCN5A is the most frequent gene linked to BrS, but the genotype-phenotype correlations are not completely matched. Clinical phenotypes of a particular SCN5A variant may range from asymptomatic to SCD. Here, we used comparison of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) derived from a SCN5A mutation-positive (D356Y) BrS family with severely affected proband, asymptomatic mutation carriers (AMCs) and healthy controls to investigate this variation.
METHODS
26 iPSC lines were generated from skin fibroblasts using nonintegrated Sendai virus. The generated iPSCs were differentiated into cardiomyocytes using a monolayer-based differentiation protocol.
FINDINGS
D356Y iPSC-CMs exhibited increased beat interval variability, slower depolarization, cardiac arrhythmias, defects of Na channel function and irregular Ca signaling, when compared to controls. Importantly, the phenotype severity observed in AMC iPSC-CMs was milder than that of proband iPSC-CMs, an observation exacerbated by flecainide. Interestingly, the iPSC-CMs of the proband exhibited markedly decreased Ca currents in comparison with control and AMC iPSC-CMs. CRISPR/Cas9-mediated genome editing to correct D356Y in proband iPSC-CMs effectively rescued the arrhythmic phenotype and restored Na and Ca currents. Moreover, drug screening using established BrS iPSC-CM models demonstrated that quinidine and sotalol possessed antiarrhythmic effects in an individual-dependent manner. Clinically, venous and oral administration of calcium partially reduced the malignant arrhythmic events of the proband in mid-term follow-up.
INTERPRETATION
Patient-specific and genome-edited iPSC-CMs can recapitulate the varying phenotypic severity of BrS. Our findings suggest that preservation of the Ca currents might be a compensatory mechanism to resist arrhythmogenesis in BrS AMCs.
FUNDING
National Key R&D Program of China (2017YFA0103700), National Natural Science Foundation of China (81922006, 81870175), Natural Science Foundation of Zhejiang Province (LD21H020001, LR15H020001), National Natural Science Foundation of China (81970269), Key Research and Development Program of Zhejiang Province (2019C03022) and Natural Science Foundation of Zhejiang Province (LY16H020002).
Topics: Humans; Brugada Syndrome; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Arrhythmias, Cardiac; Mutation; Death, Sudden, Cardiac
PubMed: 37544203
DOI: 10.1016/j.ebiom.2023.104741