Antiarrhythmic Research Articles

Body Surface Potential Mapping during Atrial Depolarization in Rats with Post-Infarction Chronic Heart Failure against the Background of Fabomotizole Therapy.

Cardiac remodeling in rats with post-infarction chronic heart failure caused by anterior transmural myocardial infarction leads to an atypical location of areas of positive and negative cardioelectric potentials on the body surface before the onset of the PII-wave on the ECG in the limb leads, which is a sign of increased heterogeneity of atrial depolarization associated with the appearance of additional excitation focus in the left atrium. A course of therapy with fabomotizole leads to a decrease in the heterogeneity of atrial depolarization at the initial stages of the formation of the cardioelectric field of the atria on the body surface before the onset of the PII-wave, thereby producing an antiarrhythmic effect.

A conflict choice of treatment during defibrillation in cardiopulmonary resuscitation: Lidocaine, amiodarone or both? A retrospective study

Objective: Cardiopulmonary arrest is considered to be an unpredicted event leading to sudden death. The primary purpose of the study is to investigate the effects of antiarrhythmic drugs during defibrillation within cardiopulmonary resuscitation (d-CPR) on survival outcomes. Materials and Methods: The antiarrhythmic drug treatment during d-CPR management in our hospital from 2015 to 2022 were evaluated retrospectively. Demographic information, and details related to resuscitation were obtained from the “Cardiopulmonary Resuscitation and Code Blue Forms”. According to inclusion criteria, from 898 patient data 135 were included. The treatment of anti-arrhythmic drugs administered during d-CPR management were lidocaine, amiodarone, or amiodarone&lidocaine together. Data recorded related to the present study were evaluated primarily according to the return of spontaneous circulation (ROSC) and survival outcomes. Results: The mean cardiopulmonary resuscitation duration was 31.82±22.37 minutes in patients with ROSC and 42.40±9.28 minutes in non-ROSC, p<0.01. Amiodarone administration during d-CPR was the highest preffered treatment from 2015 to 2022, when compared with the usage of amiodarone&lidocaine together (14.1%), p<0.01. However the administration of lidocaine during d-CPR (39.3% of all) appered to be performed before 2020 in our hospital. Additionally amiodarone revealed a positive effect on systolic blood pressure and mean arterial pressure in ROSC patients (p=0.02, p=0.04 respectively), while the choice of antiarrhythmic drug treatment during d-CPR management showed no significant difference on survival status. Conclusion: The observed ROSC was 42.2%. The choice of antiarrhythmic drug treatment during d-CPR management showed no significant difference on survival status, although amiodarone revealed a positive effect on systolic blood pressure and mean arterial pressure in the patients with ROSC.

Ventricular Tachycardia and Fibrillation: Amiodarone as a Safety and Prophylactic

Background: The best antiarrhythmic drug on the market right now for treating both atrial and ventricular arrhythmias is amiodarone. This is a derivative of iodinated benzofuran that has shown promise in treating a variety of cardiac arrhythmias, such as life-threatening ventricular arrhythmias, paroxysmal supraventricular tachycardias, and atrial fibrillation. Objective: To assess the status of amiodarone with therapeutic doses in the Bangladeshi population. Materials and Method: The quasi experimental study was conducted in the Department of Cardiology, Northeast Medical College, Sylhet during April, 2022 to March, 2023 patients got admitted in the Department of Cardiology, NMCH, Sylhet, consecutive patients who had been treated with amiodarone for arrhythmia were included in this study. Patients without an amiodarone prescription were assumed and patients who will not give informed written consent were excluded in this study. Result: In multivariable logistic regression, bradycardia or conduction disturbance, amiodarone daily dose (≥300 mg), and duration of amiodarone (>4 month) were substantially (p<0.05) linked with deleterious effects of amiodarone. Conclusion: The most common adverse event was bradycardia or conduction disturbance followed by thyroid toxicity, hepatic toxicity, eye toxicity and pulmonary toxicity. Bradycardia or conduction disturbance, amiodarone daily dose (≥300 mg) and duration of amiodarone (>4 month) was found to be significantly associated with adverse effects of amiodarone.

Design and deployment of the STEEER-AF trial to evaluate and improve guideline adherence: a cluster-randomized trial by the European Society of Cardiology and European Heart Rhythm Association.

The aim is to describe the rationale, design, delivery, and baseline characteristics of the Stroke prevention and rhythm control Treatment: Evaluation of an Educational programme of the European society of cardiology in a cluster-Randomized trial in patients with Atrial Fibrillation (STEEER-AF) trial. STEEER-AF is a pragmatic trial designed to objectively and robustly determine whether guidelines are adhered to in routine practice and evaluate a targeted educational programme for healthcare professionals. Seventy centres were randomized in six countries (France, Germany, Italy, Poland, Spain, and UK; 2022-23). The STEEER-AF centres recruited 1732 patients with a diagnosis of atrial fibrillation (AF), with a mean age of 68.9 years (SD 11.7), CHA2DS2-VASc score of 3.2 (SD 1.8), and 647 (37%) women. Eight hundred and forty-three patients (49%) were in AF at enrolment and 760 (44%) in sinus rhythm. Oral anticoagulant therapy was prescribed in 1543 patients (89%), with the majority receiving direct oral anticoagulants (1378; 89%). Previous cardioversion, antiarrhythmic drug therapy, or ablation was recorded in 836 patients (48.3%). Five hundred fifty-one patients (31.8%) were currently receiving an antiarrhythmic drug, and 446 (25.8%) were scheduled to receive a future cardioversion or ablation. The educational programme engaged 195 healthcare professionals across centres randomized to the intervention group, consisting of bespoke interactive online learning and reinforcement activities, supported by national expert trainers. The STEEER-AF trial was successfully deployed across six European countries to investigate guideline adherence in real-world practice and evaluate if a structured educational programme for healthcare professionals can improve patient-level care. Clinicaltrials.gov, NCT04396418.

Mineralocorticoid receptor antagonists in atrial fibrillation: a new class of antiarrhythmic drugs?

Mineralocorticoid receptor antagonists in atrial fibrillation: a new class of antiarrhythmic drugs?

Inhibition of Clostridioides difficile toxins TcdA and TcdB by the amiodarone derivative dronedarone.

The dreaded nosocomial pathogen Clostridioides difficile causes diarrhea and severe inflammation of the colon, especially after the use of certain antibiotics. The bacterium releases two deleterious toxins, TcdA and TcdB, into the gut, which are mainly responsible for the symptoms of C.difficile-associated diseases (CDADs). Both toxins are capable of entering independently into various host cells, e.g., intestinal epithelial cells, where they mono-O-glucosylate and inactivate Rho and/or Ras GTPases, important molecular switches for various cellular functions. We have shown recently that the cellular uptake of the Clostridioides difficile toxins TcdA and TcdB (TcdA/B) is inhibited by the licensed class III antiarrhythmic drug amiodarone (Schumacher et al. in Gut Microbes 15(2):2256695, 2023). Mechanistically, amiodarone delays the cellular uptake of both toxins into target cells most likely by lowering membrane cholesterol levels and by interfering with membrane insertion and/or pore formation of TcdA/B. However, serious side effects, such as thyroid dysfunction and severe pulmonary fibrosis, limit the clinical use of amiodarone in patients with C. difficile infection (CDI). For that reason, we aimed to test whether dronedarone, an amiodarone derivative with a more favorable side effect profile, is also capable of inhibiting TcdA/B. To this end, we tested in vitro with various methods the impact of dronedarone on the intoxication of Vero and CaCo-2 cells with TcdA/B. Importantly, preincubation of both cell lines with dronedarone for 1h at concentrations in the low micromolar range rendered the cells less sensitive toward TcdA/B-induced Rac1 glucosylation, collapse of the actin cytoskeleton, cell rounding, and cytopathic effects, respectively. Our study points toward the possibility of repurposing the already approved drug dronedarone as the preferable safer-to-use alternative to amiodarone for inhibiting TcdA/B in the (supportive) therapy of CDADs.

Long-Term Changes in Atrial Arrhythmia Burden After Renal Denervation Combined With Pulmonary Vein Isolation: SYMPLICITY-AF

BackgroundThe autonomic nervous system plays an important role in atrial fibrillation (AF) and hypertension. Renal denervation (RDN) lowers blood pressure (BP), but its role in AF is poorly understood. ObjectivesThe purpose of this study was to investigate whether RDN reduces AF recurrence after pulmonary vein isolation (PVI). MethodsThis study randomized patients from 8 centers (United States, Germany) with drug-refractory AF for treatment with PVI+RDN vs PVI alone. A multielectrode radiofrequency Spyral catheter system was used for RDN. Insertable cardiac monitors were used for continuous rhythm monitoring. The primary efficacy endpoint was ≥2 minutes of AF recurrence or repeat ablation during all follow-up. The secondary endpoints included atrial arrhythmia (AA) burden, discontinuation of class I/III antiarrhythmic drugs, and BP changes from baseline. ResultsA total of 70 patients with AF (52 paroxysmal, 18 persistent) and uncontrolled hypertension were randomized (RDN+PVI, n = 34; PVI, n = 36). At 3.5 years, 26.2% and 21.4% of patients in RDN+PVI and PVI groups, respectively, were free from the primary efficacy endpoint (log rank P = 0.73). Patients with mean ≥1 h/d AA had less daily AA burden after RDN+PVI vs PVI (4.1 hours vs 9.2 hours; P = 0.016). More patients discontinued class I/III antiarrhythmic drugs after RDN+PVI vs PVI (45% vs 14%; P = 0.040). At 1 year, systolic BP changed by −17.8 ± 12.8 mm Hg and −13.7 ± 18.8 mm Hg after RDN+PVI and PVI, respectively (P = 0.43). The composite safety endpoint was not significantly different between groups. ConclusionsIn patients with AF and uncontrolled BP, RDN+PVI did not prevent AF recurrence more than PVI alone. However, RDN+PVI may reduce AF burden and antiarrhythmic drug usage, but this needs further prospective validation.

Development and characterization of the mode-of-action of inhibitory and agonist peptides targeting the voltage-gated sodium channel SCN1B beta-subunit

Cardiac arrhythmia treatment is a clinical challenge necessitating safer and more effective therapies. Recent studies have highlighted the role of the perinexus, an intercalated disc nanodomain enriched in voltage-gated sodium channels including both Nav1.5 and β1 subunits, adjacent to gap junctions. These findings offer insights into action potential conduction in the heart. A 19-amino acid SCN1B (β1/β1B) mimetic peptide, βadp1, disrupts VGSC beta subunit-mediated adhesion in cardiac perinexii, inducing arrhythmogenic changes. We aimed to explore βadp1's mechanism and develop novel SCN1B mimetic peptides affecting β1-mediated adhesion. Using patch clamp assays in neonatal rat cardiomyocytes and electric cell substrate impedance sensing (ECIS) in β1-expressing cells, we observed βadp1 maintained inhibitory effects for up to 5 h. A shorter peptide (LQLEED) based on the carboxyl-terminus of βadp1 mimicked this inhibitory effect, while dimeric peptides containing repeated LQLEED sequences paradoxically promoted intercellular adhesion over longer time courses. Moreover, we found a link between these peptides and β1-regulated intramembrane proteolysis (RIP) - a signaling pathway effecting gene transcription including that of VGSC subunits. βadp1 increased RIP continuously over 48 h, while dimeric agonists acutely boosted RIP for up to 6 h. In the presence of DAPT, an RIP inhibitor, βadp1's effects on ECIS-measured intercellular adhesion was reduced, suggesting a relationship between RIP and the peptide's inhibitory action. In conclusion, novel SCN1B (β1/β1B) mimetic peptides are reported with the potential to modulate intercellular VGSC β1-mediated adhesion, potentially through β1 RIP. These findings suggest a path towards the development of anti-arrhythmic drugs targeting the perinexus.

A simulation study on the antiarrhythmic mechanisms of established agents in myocardial ischemia and infarction.

Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed reduction in recurrent arrhythmias through antiarrhythmic drug therapy, the precise mechanisms underlying their effectiveness in treating ischemic heart disease remain unclear. Moreover, there is a lack of specialized drugs designed explicitly for the treatment of myocardial ischemic arrhythmia. This study employs an electrophysiological simulation approach to investigate the potential antiarrhythmic effects and underlying mechanisms of various pharmacological agents in the context of ischemia and myocardial infarction (MI). Based on physiological experimental data, computational models are developed to simulate the effects of a series of pharmacological agents (amiodarone, telmisartan, E-4031, chromanol 293B, and glibenclamide) on cellular electrophysiology and utilized to further evaluate their antiarrhythmic effectiveness during ischemia. On 2D and 3D tissues with multiple pathological conditions, the simulation results indicate that the antiarrhythmic effect of glibenclamide is primarily attributed to the suppression of efflux of potassium ion to facilitate the restitution of [K+]o, as opposed to recovery of IKATP during myocardial ischemia. This discovery implies that, during acute cardiac ischemia, pro-arrhythmogenic alterations in cardiac tissue's excitability and conduction properties are more significantly influenced by electrophysiological changes in the depolarization rate, as opposed to variations in the action potential duration (APD). These findings offer specific insights into potentially effective targets for investigating ischemic arrhythmias, providing significant guidance for clinical interventions in acute coronary syndrome.

Association of Regression from Sustained to Paroxysmal Atrial Fibrillation with Clinical Outcomes: The Fushimi AF Registry

BackgroundSome patients with atrial fibrillation (AF), albeit less frequently, may regress from sustained to paroxysmal type. ObjectivesWe sought to investigate how the regression of AF is associated with outcomes. MethodsAmong the AF patients enrolled in the Fushimi AF Registry who were identified as having sustained AF at baseline, conversion of sustained to paroxysmal AF during follow-up was defined as AF regression. Major adverse cardiovascular events (MACE) were defined as a composite of cardiac death, myocardial infarction, ischemic stroke, systemic embolism, or hospitalization due to heart failure. ResultsAmong 2,261 patients with sustained AF at baseline, AF regression was observed in 214 (9.5%) patients over a median follow-up period of 5.8 years (1.78% per patient-year). The annual incidence of MACE in patients with AF regression was significantly lower than those without (3.47% vs. 6.59% per patient-year, P < 0.001; adjusted hazard ratio [HR], 0.53, 95% confidence interval [CI], 0.38-0.72). Furthermore, AF regression was significantly associated with reduced risk of MACE during and after the regression period from sustained to paroxysmal forms (during regression period: adjusted HR, 0.45; 95% CI, 0.22-0.90; after regression period: adjusted HR, 0.43; 95% CI, 0.26-0.67). The incidence of MACE was comparable between spontaneous regression (35/178: 19.7%) and therapy-associated regression (either receiving catheter ablation or antiarrhythmic drugs before the regression) (7/36: 19.4%) (P=0.98). ConclusionRegression of AF was associated with a lower incidence of adverse cardiovascular events. The risk of adverse events decreased significantly during the regression period and its reduction level persisted after regression.Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000005834.

Antiarrhythmic drug therapy and catheter ablation in patients with paroxysmal or persistent atrial fibrillation: a systematic review and meta-analysis

BackgroundCatheter ablation and antiarrhythmic drug therapy are utilized for rhythm control in atrial fibrillation (AF), but their comparative effectiveness, especially with contemporary treatment modalities, remains undefined. We conducted a systematic review and meta-analysis contrasting current ablation techniques against antiarrhythmic medications for AF.MethodsWe searched PubMed, SCOPUS, Cochrane CENTRAL, and Web of Science until November 2023 for randomized trials comparing AF catheter ablation with antiarrhythmics, against antiarrhythmic drug therapy alone, reporting outcomes for > 6 months. Four investigators extracted data and appraised risk of bias (ROB) with ROB 2 tool. Meta-analyses estimated pooled efficacy and safety outcomes using R software.ResultsTwelve trials (n = 3977) met the inclusion criteria. Catheter ablation was associated with lower AF recurrence (relative risk (RR) = 0.44, 95%CI (0.33, 0.59), P ˂ 0.0001) and hospitalizations (RR = 0.44, 95%CI (0.23, 0.82), P = 0.009) than antiarrhythmic medications. Catheter ablation also improved the physical quality of life component score (assessed by a 36-item Short Form survey) by 7.61 points (95%CI -0.70-15.92, P = 0.07); but, due to high heterogeneity, it was not statistically significant. Ablation was significantly associated with higher procedural-related complications [RR = 15.70, 95%CI (4.53, 54.38), P < 0.0001] and cardiac tamponade [RR = 9.22, 95%CI (2.16, 39.40), P = 0.0027]. All-cause mortality was similar between the two groups.ConclusionsFor symptomatic AF, upfront catheter ablation reduces arrhythmia and hospitalizations better than continued medical therapy alone, albeit with moderately more adverse events. Careful patient selection and risk-benefit assessment are warranted regarding the timing of ablation.

Detecting QT prolongation from a single-lead ECG with deep learning.

For a number of antiarrhythmics, drug loading requires a 3-day hospitalization with continuous monitoring for QT-prolongation. Automated QT monitoring with wearable ECG monitors would enable out-of-hospital care. We therefore develop a deep learning model that infers QT intervals from ECG Lead-I-the lead that is often available in ambulatory ECG monitors-and use this model to detect clinically meaningful QT-prolongation episodes during Dofetilide drug loading. QTNet-a deep neural network that infers QT intervals from Lead-I ECG-was trained using over 3 million ECGs from 653 thousand patients at the Massachusetts General Hospital and tested on an internal-test set consisting of 633 thousand ECGs from 135 thousand patients. QTNet is further evaluated on an external-validation set containing 3.1 million ECGs from 667 thousand patients at another healthcare institution. On both evaluations, the model achieves mean absolute errors of 12.63ms (internal-test) and 12.30ms (external-validation) for estimating absolute QT intervals. The associated Pearson correlation coefficients are 0.91 (internal-test) and 0.92 (external-validation). Finally, QTNet was used to detect Dofetilide-induced QT prolongation in a publicly available database (ECGRDVQ-dataset) containing ECGs from subjects enrolled in a clinical trial evaluating the effects of antiarrhythmic drugs. QTNet detects Dofetilide-induced QTc prolongation with 87% sensitivity and 77% specificity. The negative predictive value of the model is greater than 95% when the pre-test probability of drug-induced QTc prolongation is below 25%. These results show that drug-induced QT prolongation risk can be tracked from ECG Lead-I using deep learning.

Bradycardic peri-arrest after electrical cardioversion for atrial fibrillation: a case report

Electrical cardioversion can precipitate prolonged bradycardia and cardiac arrest when the sinoatrial node is dysfunctional, and the escape rhythms from the atrioventricular node and ventricles fail to take over. We report the case of an elderly male who rapidly progressed into bradycardic peri-arrest after electrical cardioversion for persistent atrial fibrillation. Despite the immediate initiation of intravenous atropine and transcutaneous pacing, 2 minutes of cardiopulmonary resuscitation with further boluses of atropine and adrenaline were required before the return of spontaneous circulation. The patient was transferred to the intensive care unit, and a permanent pacemaker was implanted before discharge. Advanced age, long duration of atrial fibrillation, previous aortic valve replacement, use of anti-arrhythmic drugs, and intravenous propofol bolus were all contributing factors to this event. We summarise the relevant clinical features, risk factors, and management considerations, in the hope of promoting awareness of this rare complication of a common procedure.

Integrative approach for improved dofetilide solubility using β-cyclodextrin and two its substituted derivatives: Solutions and solid dispersions

The complexation an anti-arrhythmia drug dofetilide (DFT) with β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) were studied using two main approaches: phase solubility diagrams and solid dispersions technique. The phase solubility diagrams were constructed in buffer solutions with physiological values рН 2.0 и 7.4. In accordance with the protolytic properties of the drug, the solubilizing effect of cyclodextrins turned out to be more effective in a neutral environment (buffer pH 7.4): the solubility improvement of DFT in the presence of β-CD, HP-β-CD and SBE-β-CD was 3.6, 11.8 and 18.1 times, respectively. In buffer pH 2.0, the tendency for an increase in the solubilizing effect, depending on the chemical nature of the CDs used, is maintained, but the solubility of the drug almost does not grow. The binding constants for the DFT/HP-β-CD and DFT/SBE-β-CD complexes equal to 344 L·mol−1 and 429 L·mol−1 in buffer pH 7.4 indicate the formation of stable inclusion complexes and belong to the optimal range for refinement bioavailability and stability of hydrophobic drugs. Amorphous solid dispersions DFT/β-CD, DFT/HP-β-CD and DFT/SBE-β-CD with stoichiometry 1:1 were obtained by grinding method. The combination FTIR, PXRD, DSC, TGA and SEM methods confirmed the inclusion complexes formation of the drug with cyclodextrins used. Dissolution profiles of solid dispersions DFT/β-CD, DFT/HP-β-CD and DFT/SBE-β-CD were graphing in buffer solutions рН 2.0 and 7.4. Enlargement factor of DFT solubility in the composition of solid dispersions DFT/β-CD, DFT/HP-β-CD and DFT/SBE-β-CD in the neutral medium are 3.4, 4.1 and 5.2, respectively. Whereas the formation of solid inclusion complexes DFT/CDs in an acidic buffer has virtually no effect on the increase in the equilibrium concentration of the active substance in the solution. Findings have demonstrated that the use of SBE-β-CD shows the best solubilization potential for DFT both in solution and as a solid dispersion.

Monomorphic premature ventricular contractions in patients without cardiac structural changes: clinical and prognostic significance and evaluation of therapy effectiveness (clinical and experimental study)

Aim. To determine the individualized choice of therapy for monomorphic premature ventricular contractions (PVCs) in patients without structural cardiac changes by assessing the predictors of arrhythmogenic cardiomyopathy (ACM) and the clinical and prognostic significance of its course.Material and methods. Experimental study. Animals were used to model PVCs by the mechanism of early post-depolarization (EPD) (aconitine), re-entry (peroxide or H2O2 arrhythmia). In addition to the generally accepted parameters, the following ACMs were analyzed during electrocardiography (ECG): pre-ectopic interval, its variability, maximum index of internal deviation of PVCs, the QRS complex of PVC (QRSpvc), QRS of sinus rhythm (QRSsr), their ratio (QRSpvc/QRSsr), etc. Clinical study. A total of 343 patients with class IV-V PVCs aged 16 to 34 years were observed (B. Rayn, 1984). The same parameters were determined by ECG as in experimental arrhythmias. The follow-up duration was up to 10 years. The end point was the detection or absence of cardiovascular pathology.Results. Experimental study. When modeling ventricular arrhythmias using the EPD mechanism, early (R/T) monotopic PVCs were recorded, and re-entry — early and late monomorphic PVCs. ACM predictors were recorded only when modeling arrhythmia by the re-entry mechanism. Clinical study. In patients without structural cardiac changes, early (R/T) monotopic PVC highly correlated with ventricular ectopy induced by the EPD mechanism (aconitine) (r=0,92). These patients did not have cardiovascular diseases, and the most effective antiarrhythmic drugs for eliminating ventricular ectopy were class I drugs. In patients without structural cardiac changes, early and late monomorphic PVCs highly correlated with experimental ventricular ectopy caused by the re-entry mechanism (H2O2 arrhythmia). In these patients, on average, 7,2±0,5 years after inclusion in the study, various clinical forms of coronary artery disease were detected, and the positive clinical effect of PVC treatment was achieved mainly with the use of class III antiarrhythmic drugs.Conclusion. In patients with early monotopic ventricular ectopia, without detection of ACM predictors, the most effective were class I antiarrhythmic drugs. In other patients with early and late monomorphic ventricular ectopia and detected ACM predictors, class III agents were found to be effective.

Real-world evidence demonstrates an appropriate atrial fibrillation population for hybrid convergent approach versus stand-alone cryoballoon ablation: A long-term safety and efficacy study.

A hybrid convergent approach (endocardial and epicardial ablation) demonstrated superior effectiveness in a recent randomized study for long-standing persistent atrial fibrillation (LSPAF). Yet, there is a lack of real-world, long-term evidence as to which patients are best candidates for a hybrid convergent approach compared to standard endocardial cryoballoon pulmonary vein isolation (CB PVI). This single-center, retrospective analysis spanning from 2010 to 2015 compared two distinctly different atrial fibrillation (AF) cohorts; one treated with stand-alone cryoablation and one treated with a hybrid convergent approach. Baseline characteristics described candidates for each approach. The following criteria were utilized to determine CB PVI candidacy: (1) paroxysmal AF (PAF) (stage 3A) with failed class I/III antiarrhythmic drug (AAD) or (2) persistent/LSPAF (stage 3B/3C/3D) with failed class I/III AAD unwilling to undergo hybrid procedure. Selection criteria for the hybrid procedure included: (1) PAF refractory to both class I/III AAD and prior CB PVI (stage 3D) or (2) persistent/LSPAF (stage 3B/3C/3D) with failed class I/III AAD agreeable to hybrid procedure. Prior sternotomy was excluded. Serial electrocardiograms and continuous monitoring evaluated primary efficacy outcome of time-to-first recurrence of atrial arrhythmia after a 90-day blanking period. Secondary outcomes were procedure-related complications and AAD use (at discharge, 12, and 36 months). Kaplan-Meier methods evaluated arrhythmia recurrence. Of 276 patients, 197 (64.2 ± 10.6 years old; 66.5% male; 74.1% 3A-PAF; 18.3% 3B/3D-persistent AF; 1.0% 3C-LSPAF; 6.6% undetermined) underwent CB PVI and 79 (61.4 ± 8.1 years old; 83.5% male; 41.8% 3D-PAF; 45.5% 3B/3D-persistent AF; 12.7% 3C/3D-LSPAF) underwent hybrid procedure. Arrhythmia freedom through 36 months was 55.2% for CB PVI and 50.4% for hybrid (p = .32). Class I AAD utilization at discharge occurred in 38 (19.3%) patients in the CB PVI group and 5 (6.3%) patients in the hybrid group (p = .01). CB PVI class I AAD utilization at 12 months occurred in 14 (9.0) patients versus 0 patients for hybrid convergent (p = .004). Patients with one or more adverse event were as follows: two (1.0%) in the CB PVI group (both transient phrenic nerve palsy) and three (3.7%) in the hybrid group (two with significant bleeding and one with wound infection) (p = .14). This study demonstrated that patients with more complex forms of AF (3D-PAF or 3B/3C/3D-persistent/LSPAF) could be well managed with a convergent approach. In a real-world evaluation, outcomes match safety and efficacy thresholds achieved for patients with earlier, less complex AF etiologies treated by CB PVI alone.

Ablation Compared to Pharmacological Treatment for the Reduction of Atrial Fibrillation Recurrence: A Meta-Analysis.

Atrial fibrillation (AF) is one of the most common heart arrhythmias, and due to its variable presentation, detecting and treating AF appropriately can reduce some of its serious complications. Among treatment options, surgical ablation and antiarrhythmic drug therapy are two of the most widely used choices. A systematic review and meta-analysis were conducted to examine the rates of AF recurrence in those treated with ablationcompared to pharmacological treatment. Google Scholar and PubMed were searched for study trials published within the last decade that calculated the recurrence of AF symptoms in patient groups that received ablation or pharmacological treatment. Selected studies were analyzed in RevMan 5.4 software (The Cochrane Collaboration, London, England, UK), and each study's odds ratio and overall odds ratio were calculated using a 95% confidence interval. A total of seven studies with 2324 patients were analyzed for the meta-analysis, with 1162 patients receiving ablation and 1162 patients receiving pharmacological treatment. There was a statistically significant decrease in the recurrence of AF in the ablation group compared to the pharmacological treatment group, with a pooled odds ratio of 0.24 (CI 95% 0.14-0.39). AF treated with ablation was more effective in reducing AF recurrence than general pharmacological treatment.

Consider this a WARNing

Atrial fibrillation (AF) prediction can be valuable at many timescales and in many populations. In this issue of Patterns, Gavidia etal. train a model called WARN for short-term prediction of AF in the timescale of minutes in patients wearing 24-h continuous Holter electrocardiograms. The ability to predict near-term (e.g., 30 min) AF has the potential to enable preventive therapies with rapid mechanisms of action (e.g., oral anticoagulation, anti-arrhythmic drugs). In this way, efficient, continuous, and algorithmic monitoring of AF risk could reduce burden on healthcare workers and represents a valuable clinical pursuit.

New Perspectives in The Management of Paroxysmal Atrial Fibrillation: Dual AntiArrhythmic Medications.

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice projected to affect 12.1 million individuals by the year 2030. Patients who are diagnosed with AF have an increased risk of morbidity and mortality. Although catheter ablation is a class I treatment recommendation in patients with symptomatic paroxysmal AF, antiarrhythmic medications (AAM) continue to be the mainstay of treatment in limited resource settings not offering ablation procedures. Currently, the most used AAMs are those which block either the sodium or potassium channels. We hypothesized that the use of selective dual AAM (sodium and potassium channel blockers) (DAAM) improves the chance of maintaining sinus rhythm and decreases the need for catheter ablation when compared with single AAM (SAAM). This retrospective observational study was conducted in 150 patients with paroxysmal AF over 5 years at Richmond University Medical Center in Staten Island, New York. The following data were collected: age, sex, comorbidities, electrocardiogram findings, ejection fraction by echocardiography, classes of AAM, duration, and response to treatments. The primary endpoint included the absence of symptoms and maintenance of sinus rhythm. The secondary endpoint included the requirement of electrical cardioversion or catheter ablation. A total of 86 patients met the inclusion criteria in our analysis. The average age of the patients was 71.06 years (SD = 7.66). About 45 patients were given DAAM of either amiodarone + flecainide or dronedarone + flecainide and were treated for an average of 15.4 months, followed by catheter ablation, if needed. Also, 41 patients received a SAAM followed by catheter ablation, if needed. A Mann-Whitney test indicated that electrical cardioversion and catheter ablation were greater for the SAAM group (Md = 1) than for the DAAM group (Md = 0) (U = 294.00, P value <0.001; U = 507.00, P value <0.001, respectively). No pro-arrhythmic side effects or death were encountered in either group. Treatment of paroxysmal AF with DAAM is effective compared with SAAM and is less likely to need catheter ablation or electrical cardioversion. Well-designed prospective studies are needed to further explore the use of DAAM in the management of paroxysmal AF and its clinical impact in limited resource settings.

Percutaneous left stellate ganglion block for refractory ventricular tachycardia in structural heart disease: our single-centre experience.

When electrical storm (ES) is amenable to neither antiarrhythmic drugs, nor deep sedation or catheter ablation, autonomic modulation may be considered. We report our experience with percutaneous left stellate ganglion block (PSGB) to temporarily suppress refractory ventricular arrhythmia (VA) in patients with structural heart disease. Aretrospective analysis was performed at our institution of patients with structural heart disease and an implantable cardioverter defibrillator (ICD) who had undergone PSGB for refractory VA between January 2018 and October 2021. The number of times antitachycardia pacing (ATP) was delivered and the number of ICD shocks/external cardioversions performed in the week before and after PSGB were evaluated. Charts were checked for potential complications. Twelve patients were identified who underwent acombined total of 15PSGB and 5surgical left cardiac sympathetic denervation procedures. Mean age was 73 ± 5.8years and all patients were male. Nine of 12 (75%) had ischaemic cardiomyopathy, with the remainder having non-ischaemic dilated cardiomyopathy. Mean left ventricular ejection fraction was 35% (± 12.2%). Eight of 12 (66.7%) patients were already being treated with both amiodarone and beta-blockers. The reduction in ATP did not reach statistical significance (p = 0.066); however, ICD shocks (p = 0.028) and ATP/shocks combined were significantly reduced (p = 0.04). At our follow-up electrophysiology meetings PSGB was deemed ineffective in 4of 12patients (33%). Temporary anisocoria was seen in 2 of12 (17%) patients, and temporary hypotension and hoarseness were reported in asingle patient. In this limited series, PSGB showed promise as amethod for temporarily stabilising refractory VA and ES in acohort of male patients with structural heart disease. The side effects observed were mild and temporary.