Antiarrhythmic Drug Therapy In Patients Research Articles

Bleeding Associated With Antiarrhythmic Drugs in Patients With Atrial Fibrillation Using Direct Oral Anticoagulants: A Nationwide Population Cohort Study.

This study investigated drug-drug interactions in patients with atrial fibrillation taking both a direct oral anticoagulant (DOAC) and an antiarrhythmic drug. Using data from the National Health Insurance database (2012-2018), we identified 78 805 patients with atrial fibrillation on DOACs, with 24 142 taking amiodarone, 8631 taking propafenone, 2784 taking dronedarone, 297 taking flecainide, 177 taking sotalol, and 42 772 on DOACs alone. Patients with bradycardia, heart block, heart failure, mitral stenosis, prosthetic valves, or incomplete data were excluded. Propensity score matching compared those taking both DOACs and antiarrhythmic drugs with those on DOACs alone. There was an increased risk of major bleeding in patients concomitantly taking DOACs with amiodarone when compared with matched patients taking DOACs alone (hazard ratio [HR],1.13 [95% CI, 1.04-1.23]; P=0.0044), particularly in patients taking dabigatran (HR, 1.19 [95% CI, 1.03-1.38]; P=0.0175). No significant difference in bleeding risk was found for propafenone, dronedarone, flecainide, or sotalol. The small sample sizes in the flecainide and sotalol groups limit interpretation. Notably, intracranial bleeding risk was higher in patients on DOACs and amiodarone, regardless of age. Additionally, patients <80 years old taking dabigatran with amiodarone or propafenone had a higher risk of gastrointestinal bleeding. Concomitant use of DOACs with amiodarone, but not dronedarone or propafenone, increases the risk of major bleeding, particularly intracranial bleeding. This study provides new evidence to guide clinicians to tailor concomitant anticoagulation and antiarrhythmic therapy for patients with atrial fibrillation.

Percutaneous stellate ganglion blockade as an add-on therapy for the treatment of arrhythmic storm

Abstract Introduction Arrhythmic storm (AS) due to repetitive ventricular arrhythmias (VA) is a life-threatening condition that can be resistant to antiarrhythmic therapy. Sympathetic nervous system plays an important role in triggering and maintaining VA. Reducing sympathetic activity by percutaneous stellate ganglion blockade (SBG) may improve outcomes in treating AS. Purpose To evaluate the effect of SBG on outcomes of AS. Methods In this retrospective study, we analyzed 18 patients treated with SBG for AS from August 2017 to May 2022. All patient experienced VA while on antiarrhythmic drug therapy. SBG was performed under ultrasound guidance to avoid vascular structures. Either 0.75% levobupivacaine or 0.5% ropivacaine were applied to block the stellate ganglion after negative aspiration. The decision to perform unilateral or bilateral SBG was left to the operator. Results The majority of patients were male (17/18, 94.4%), mean age was 61.8 ± 13.4 years, mean BMI 28.1 ± 5.39 kg/m2, mean LVEF was 34.4 ± 12.2%, majority had an ischemic cardiomyopathy (12/18, 66.7%). Half of the patients had monomorphic VA (9/18, 50.0%), the other half had polymorphic VA (9/18, 50.0%). Majority of patients were hemodynamically unstable (13/18, 72.2%) and more than a third had a cardiac arrest (7/18, 38.9%). Half of the patients had unilateral SBG (9/18, 50.0%), and the other half bilateral SBG (9/18, 50.0%). SBG was repeated in two patients (2/18, 11.1%). On the repeat procedure, both had bilateral SBG. There were 4 minor complications (4/18, 22.2%) and no major complications. Two patients had intermittent Horner’s syndrome, one had a small hematoma on the puncture site, and one had small hematoma in the mediastinum. All complications resolved on their own and did not require an intervention. In the 72 hours after SBG, 5 patients had a recurrence of VA (5/18, 27.8%). After the discharge, 6 patients also had a recurrence of VA (6/18, 44.4%). SBG significantly reduced mean number of VA episodes in the next 72 hours (12.3 ± 11.1 vs 4.3 ± 10.6; P=0.007) with a mean difference of 8.0 VA episodes (95% CI, 4.5 - 14.0; P=0.007) (Figure 1). One patient died due to recurrent VA leading to ischemic brain damage (1/18, 5.6%). Four patients died due to non-VA related causes (4/18, 22.2%). Two deaths were due to septic shock, the other two due to cardiogenic shock. Details of baseline characteristics and outcomes are in the Figure 2. Conclusion SBG significantly reduces episodes of VA after failed antiarrhythmic drug therapy in patients presenting with AS.A before-after graph of VA after SBG.Baseline and outcomes table.

Wound incidence and outcomes in atrial fibrillation: Comparing catheter ablation and anti-arrhythmic drug therapy.

The most prevalent form of cardiac arrhythmia is atrial fibrillation (AF), which is typically managed through catheter ablation or anti-arrhythmic drug therapy. We compared the incidence and outcomes of wound complications in patients with atrial fibrillation who were treated with catheter ablation as opposed to anti-arrhythmic drug therapy. From May to November 2023, 240 adult AF patients who were treated with catheter ablation or anti-arrhythmic medications participated in a 6-month retrospective cohort study at Sir Run Run Shaw Hospital in Hangzhou, China. An observation was made regarding 29 wound complications out of 240 patients. In comparison to drug therapy group, incidence of minor (8 vs. 11) and total complications (18 vs. 11) was greater in catheter ablation group. Significant adverse events occurred at higher rate in the catheter ablation group (6 versus 1) (p < 0.05). However, despite these patterns, there was no statistically significant difference in the rates of complications (total: p = 0.245; minor: p = 0.217; major: p = 0.128). Comparable treatment efficacy was observed across groups. In contrast to drug therapy, catheter ablation was associated with decreased probability of complications (odds ratio: 0.86), as determined by logistic regression; cardiac failure was a significant predictor of adverse outcomes. The study concluded that the risks of wound complications associated with catheter ablation and anti-arrhythmic drug therapy in patients with atrial fibrillation are comparable. Notwithstanding an elevated propensity for complications in ablation group, the statistical analysis indicated comparable safety profiles.

Single beta-blocker or combined amiodarone therapy in ICD and CRT-D patients - Insights from the German DEVICE-registry

Abstract Background Because of its antiarrhythmic potency and due to the lack of alternatives, amiodarone is often used for antiarrhythmic therapy in patients with ICD or CRT-D systems. To date, robust data on the safety and clinical benefit of amiodarone therapy in these patients are missing. Objective This study was designed to assess the periprocedural and post-procedural outcome of combined therapy with beta-blockers plus amiodarone compared to treatment with single beta-blockers in this "real life" cohort of ICD recipients of the German DEVICE registry. Methods 4,499 patients who underwent ICD implantation, revision, or upgrade in 49 centers participating in the German DEVICE Registry were enrolled 03/2007-02/2014. Patients' characteristics, procedural data, periprocedural complications, and post-procedural clinical outcome, were analyzed. Results 12.7 % (572 patients) received amiodarone in addition to beta-blocker therapy. These patients were slightly older and more frequently male than the 3,927 patients with sole betablocker therapy. The two cohorts of patients had no relevant differences in terms of underlying cardiomyopathy. Stroke, and chronic kidney disease were more often present in the patient group receiving amiodarone. Early implantation-associated complications were similar between the groups. One-year overall mortality was, however, significantly higher in the beta-blocker plus amiodarone cohort (adjusted HR 2.09; p&amp;lt;0.001). This was particularly pronounced in the subgroups of patients with sinus rhythm or severely reduced left ventricular function. Interestingly, amongst the surviving patients, amiodarone was not associated with a significantly reduced risk of ICD discharges, syncopal events. Further, the occurrence of VT storm or incessant VTs and the number of patients scheduled for intracardiac ablation did not differ among both groups while the rate of rehospitalization was lower in the cohort with sole beta-blockers. Conclusions Taken together, these retrospective "real-word" data suggest an increased all-cause mortality under amiodarone therapy, particularly in the subgroups of patients with sinus rhythm or severely reduced left ventricular function. In surviving patients, rates of arrhythmic events were comparable.Abstract Figure

Abstract 14263: Comparison of Catheter Ablation versus Antiarrhythmic Therapy in Patients With Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction

Introduction: The differences in outcomes between catheter ablation (CA) versus antiarrhythmic drugs (AAD) for atrial fibrillation (AF) in the setting of heart failure with preserved ejection fraction (HFpEF) are not known. Hypothesis: We hypothesize that patients with AF and HFpEF who undergo CA will have lower morality, stroke/TIA, and acute HF compared to those treated with AAD. Methods: TriNetX, a national retrospective electronic database, was used to identify patients aged 18-80 years with AF and HFpEF from 2017-2023. Patients with a prior diagnosis of systolic HF or cross overs from AAD to CA were excluded. Patients who underwent CA were compared to those treated with AAD (amiodarone, flecainide, dronedarone, dofetilide, propafenone, sotalol). Baseline group comparison was performed using student’s t-test. Age, sex, chronic kidney disease, COPD, hypertension, type 2 diabetes mellitus, obstructive sleep apnea, and stroke/TIA were used for 1:1 propensity matching. Kaplan Meier curves were calculated to compare all-cause mortality, stroke/TIA, acute diastolic and systolic HF. Results: Patients who received CA (n=1468) and AAD (n=7426) were propensity matched yielding 1008 patients per cohort. Compared to AAD, CA demonstrated significantly lower all-cause mortality (9.13% vs. 23.7%; HR=2.6; 95% CI [2.038,3.315]; log-rank p&lt;0.0001), lower stroke/TIA risk (5.12% vs. 7.69%; HR=1.6; 95% CI [1.056,2.28]; log-rank p=0.02), and less frequent hospitalization for acute diastolic HF (12.1% vs. 18.8%; HR=1.6; 95% CI [1.185,2.152]; log-rank p=0.0018). Rate of acute systolic HF was similar for both cohorts with 7.76% for CA and 6.90% for AAD (HR=0.88; 95% CI [0.63,1.222]; log-rank p=0.4395). Conclusions: Patients with AF and HFpEF had lower mortality, risk of stroke and acute diastolic HF when they received CA versus AAD. Randomized clinical trials are needed to better understand their short and long-term outcomes.

Ryanodine receptor inhibition with acute dantrolene treatment reduces arrhythmia susceptibility in human hearts.

Ryanodine receptor 2 (RyR2) hyperactivity is observed in structural heart diseases that are a result of ischemia or heart failure. It causes abnormal calcium handling and calcium leaks that cause metabolic, electrical, and mechanical dysfunction, which can trigger arrhythmias. Here, we tested the antiarrhythmic potential of dantrolene (RyR inhibitor) in human hearts. Human hearts not used in transplantation were obtained, and right ventricular outflow tract (RVOT) wedges and left ventricular (LV) slices were prepared. Pseudo-ECGs were recorded to determine premature ventricular contraction (PVC) incidences. Optical mapping was performed to determine arrhythmogenic substrates. After baseline optical recordings, tissues were treated with 1) isoproterenol (250 nM), 2) caffeine (200 mM), and 3) dantrolene (2 or 10 mM). Optical recordings were obtained after each treatment. Isoproterenol and caffeine treatment increased PVC incidence, whereas dantrolene reduced the PVC burden. Isoproterenol shortened action potential duration (APD) in the RV, RVOT, and LV regions and shortened calcium transient duration (CaTD) in the LV. Caffeine further shortened APD in the RV, did not modulate APD in the RVOT, and prolonged APD in the LV. In addition, in the LV, CaTD prolongation was also observed. More importantly, adding dantrolene did not alter APD in the RV or RVOT regions but produced a trend toward APD prolongation and significant CaTD prolongation in the LV, restoring these parameters to baseline values. In conclusions, dantrolene treatment suppresses triggers and reverses arrhythmogenic substrates in the human heart and could be a novel antiarrhythmic therapy in patients with structural heart disease.NEW & NOTEWORTHY Ryanodine receptor 2 hyperactivity is observed in structural heart diseases caused by ischemia or heart failure. It causes abnormal calcium leaks, which can trigger arrhythmias. To prevent arrhythmias, we applied dantrolene in human hearts ex vivo. Isoproterenol and caffeine treatment increased PVC incidence, whereas dantrolene reduced the PVC burden. Dantrolene treatment suppresses triggers and reverses arrhythmogenic substrates and could be a novel antiarrhythmic therapy in patients with structural heart disease.

Current practice and attitudes of stroke physicians towards rhythm-control therapy for stroke prevention: results of an international survey

BackgroundPatients with ischemic stroke and atrial fibrillation (AF) are at particularly high risk for recurrent stroke and cardiovascular events. Early rhythm control has been shown to be superior to usual care for the prevention of stroke and cardiovascular events for people with early AF. There are no data on the willingness to use rhythm control for patients with AF and acute ischemic stroke in clinical practice.MethodsAn online survey was carried out among stroke physicians to assess current practice and attitudes toward rhythm control in patients with AF and acute ischemic stroke between December 22nd 2021 and March 24th 2022.ResultsThe survey was completed by 277 physicians including 237 from 15 known countries and 40 from unspecified countries. 79% (210/266) reported that they do not regularly apply treatment for rhythm control by ablation or antiarrhythmic drugs at all or only in small numbers (≤ 10%) of patients with AF and acute ischemic stroke. In those patients treated with rhythm-control therapy, antiarrhythmic drugs were used by the majority of respondents (89%), while only a minority reported using AF ablation (11%). 88% of respondents (221/250) stated that they would be willing to randomize patients with AF after acute ischemic stroke to either early rhythm control or usual care in a clinical trial.ConclusionDespite its potential benefit, few patients with AF and acute ischemic stroke appear to be treated with rhythm control, which may result from uncertainty regarding potential complications of antiarrhythmic therapy in patients with acute stroke. Together with recent data on the effectiveness of early rhythm control in patients with a history of stroke, these results call for a randomized clinical trial to assess the efficacy of early rhythm control in patients with acute ischemic stroke and AF.

Early initiation of anti-relapse antiarrhythmic therapy in patients with atrial fibrillation and flutter after pharmacological cardioversion with refralon.

Aim Evaluating the efficacy and safety of early administration of antirecurrence antiarrhythmic therapy (AAT) following restoration of sinus rhythm (SR) with refralon.Aim Evaluating the efficacy and safety of early administration of antirecurrence antiarrhythmic therapy (AAT) following restoration of sinus rhythm (SR) with refralon.Material and methods The study included 247 patients with atrial fibrillation/atrial flutter (AF/AFL) (142 men) who underwent pharmacological cardioversion (PCV) with refralon. A 4-step schedule of drug administration was used (successive intravenous infusions at doses of 5, 5, 10, and 10 µg/kg; maximum total dose was 30 µg/kg). Patients who recovered SR and had no contraindications were prescribed antirecurrence AAT in the early (≤24 h; n=101) or delayed (≥24 h; n=95) period. Lappaconitine hydrobromide, propafenone, and sotalol were administered orally as the antirecurrence therapy. The decision on the time of initiating ATT and the choice of the drug and its dose was taken by the attending physician individually. The safety criteria included a prolonged PQ interval &gt;200 ms; second- or third-degree atrioventricular block; QRS complex duration &gt;120 ms; QT prolongation &gt;500 ms; and heartbeat pauses &gt;3 s. The efficacy criteria included the absence of sustained recurrence of AF/AFL after initiation of AAT and the duration of hospitalization after PCV. Patients were followed up during the study until they were discharged from the hospital.Results SR was recovered in 229 (92.7 %) patients. In the group of early AAT initiation, a PQ duration &gt;200 ms was observed in 8 (7.9 %) patients, whereas in the group of delayed AAT initiation, in 7 patients (7.4 %; p=1.000). A wide QRS complex &gt;120 ms was recorded in 1 (1.1 %) patient of the delayed AAT initiation group and in none of the patients of the early AAT initiation group (p=0.485). Ventricular arrhythmogenic effects and QT prolongation &gt;500 ms were not detected in any patient. Numbers of early AF recurrence did not differ in the groups of early and delayed AAT initiation: 6 (5.9 %) vs. 5 (5.3 %), respectively (p=1.000). Median duration of hospitalization after PCV was 4 days in the group of early AAT initiation and 5 days in the group of delayed AAT initiation (р=0.009).Conclusion Early initiation of the refralon AAT does not increase the risk of drug adverse effects and reduces the duration of stay in the hospital.

Antiarrhythmic Drugs vs. Ablation for Atrial Fibrillation

Summary:&#x0D; Atrial fibrillation (AF) is a common and potentially life-threatening cardiac arrhythmia that affects millions of individuals worldwide. The treatment landscape for AF has traditionally comprised antiarrhythmic drugs (AADs), which aim to restore and maintain normal heart rhythm. However, over the past two decades, catheter ablation has emerged as an alternative therapeutic approach in the management of AF. This article systematically compares the effectiveness, safety, and long-term outcomes of AADs and catheter ablation as treatment strategies for atrial fibrillation.&#x0D; Introduction:&#x0D; Atrial fibrillation (AF) is characterized by disorganized electrical activity in the atria, causing irregular and often rapid heart rhythm. Over the years, pharmacological therapy with antiarrhythmic drugs (AADs) has been the mainstay of AF treatment. Nonetheless, catheter ablation has gained significant momentum due to its ability to directly target the arrhythmogenic substrate within the heart.1&#x0D; Efficacy:&#x0D; &#x0D; Antiarrhythmic Drugs: Various classes of AADs inhibit specific ion channels or receptors to normalize cardiac electrical conduction. While AADs can effectively restore sinus rhythm in many patients, their long-term success in maintaining sinus rhythm is modest, with recurrence rates ranging from 40% to 60% within one year.2&#x0D; Catheter Ablation: Ablation procedures selectively target and destroy the abnormal electrical pathways contributing to AF. In well-selected patients, catheter ablation has demonstrated higher efficacy rates than AADs, particularly in paroxysmal AF, with success rates reaching 70-80% or more after a single procedure.2&#x0D; &#x0D; Safety Profile:&#x0D; &#x0D; Antiarrhythmic Drugs: Although generally well-tolerated, AADs have notable adverse effects, including pro-arrhythmia, organ toxicity, and drug-drug interactions. These side effects often limit their usage or require careful patient monitoring.3&#x0D; Catheter Ablation: While catheter ablation is generally safe, it has a finite risk of procedural complications, such as vascular injury, cardiac perforation, and stroke. Nonetheless, the overall complication rate is low, ranging from 1% to 5%, and is further decreasing with advancements in technology and operator experience.3&#x0D; &#x0D; Quality of Life and Symptom Control:&#x0D; &#x0D; Antiarrhythmic Drugs: Effective rate control with AADs can significantly improve symptom burden and quality of life in patients with persistent or permanent AF.4&#x0D; Catheter Ablation: Successful ablation procedures can offer long-term freedom from AF symptoms, eliminating or reducing the dependence on AADs and their associated side effects.4&#x0D; &#x0D; Long-Term Outcomes:&#x0D; &#x0D; Antiarrhythmic Drugs: AAD therapy is often lifelong, and patients may require multiple medication adjustments due to loss of efficacy or intolerable side effects. However, AADs remain a treatment option for patients with contraindications for ablation or in those who prefer medical management.4&#x0D; Catheter Ablation: Successful ablation procedures have been associated with excellent long-term outcomes, with sustained freedom from AF achieved in approximately 60-70% of patients at 1-5 years of follow-up. Repeat ablations may be necessary in some cases.4&#x0D; &#x0D; Conclusion:&#x0D; While both antiarrhythmic drugs and catheter ablation have their advantages and disadvantages in the management of atrial fibrillation, catheter ablation has emerged as a promising treatment strategy, offering higher success rates and long-term symptom control compared to AADs. However, individual patient characteristics, preferences, and comorbidities should guide the selection of the optimal treatment approach, ensuring personalized and comprehensive management of atrial fibrillation. Further research is needed to refine patient selection criteria, improve ablation techniques, and optimize the use of antiarrhythmic drugs to enhance treatment outcomes for AF patients.&#x0D; References&#x0D; &#x0D; Asad ZUA, Yousif A, Khan MS, Al-Khatib SM, Stavrakis S. Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Circ Arrhythm Electrophysiol. 2019;12(9):e007414.&#x0D; Andrade JG, Deyell MW, Macle L, Wells GA, Bennett M, Essebag V, et al. EARLY-AF Investigators. Progression of Atrial Fibrillation after Cryoablation or Drug Therapy. N Engl J Med. 2023;388(2):105-16.&#x0D; Charitakis E, Metelli S, Karlsson LO, Antoniadis AP, Rizas KD, Liuba I, et al. Comparing efficacy and safety in catheter ablation strategies for atrial fibrillation: a network meta-analysis. BMC Med. 2022;20(1):1-3.&#x0D; Deshpande R, AlKhadra Y, Singanallur P, Botchway A, Labedi M. Outcomes of catheter ablation versus antiarrhythmic therapy in patients with atrial fibrillation: a systematic review and meta-analysis. J Interv Card Electrophysiol. 2022;65(3):773-802.&#x0D;

Catheter ablation of atrial fibrillation versus antiarrhythmic therapy in patients with left ventricular systolic dysfunction

Aim. To evaluate the efficacy of catheter ablation (CA) of atrial fibrillation (AF) in patients with left ventricular systolic dysfunction and the effect of the procedure on the course of chronic heart failure (CHF) compared with the use of antiarrhythmic therapy (AAT). Materials and methods. The study included patients (n=80) with left ventricular ejection fraction (LVEF) less than 50% and AF, who were divided into 2 groups: the first group (n=40) underwent CA, the second group included patients on AAT. At baseline and after 6 months of follow-up, transthoracic echocardiography, determination of NT-proBNP concentration, 6-minute walk test and The Minnesota Living With Heart Failure Questionnaire were performed. Results. After 6 months of follow-up, the absence of documented AF paroxysms was observed in 80% in the CA group versus 45% in the AAT group (p=0,001). A significant increase in LV EF was revealed in both groups, however, in CA group it was more significant (57% [50,5; 60] in the CA group versus 46% [40; 50] in the AAT group (p=0,0001)). There was a decrease in the left ventricle ESD and the left atrial size and volume in the CA group, while in the AAT group the dynamics of these parameters did not change within six months (p=0.0001). An improvement in the clinical course of CHF was observed in both groups: the level of NT-proBNP was 196,6 [116,5; 327,1] pg/ml and 540.5 [382,8; 861,2] pg/ml (0,0001), the 6-minute walk distance increased to 470 m [400; 500] and 368 [330; 400] m (p=0,0001), respectively, the improvement of the functional class (1,15±0,67 and 2,05±0,55 (p=0,0001)) and the quality of life (p=0,0001) were observed. Conclusion . CA is an effective method for patients with AF and CHF. The use of CA in patients with CHF promotes reverse remodeling, a decrease in the level of NT-proBNP, as well as an improvement in the quality of life and an increase in exercise tolerance.

Multi-day telemonitoring is the optimum control method in the medicational treatment of arrhythmias

Background. The use of antiarrhythmic (AA) drugs requires constant monitoring due to the risk of arrhythmic and side effects. It is impossible to quickly identify and respond to emerging adverse events using 24-hour monitoring of the electrocardiogram (ECG), due to the method technical features. The introduction into practice of multi-day telemonitoring (MTM) of ECG contributes to an increase in the detection of rare and asymptomatic arrhythmias, and improves control over the AA therapy effectiveness.Objective. To study the possibilities and advantages of MTM in the selection of AA therapy and the prevention of its complications in patients with ventricular arrhythmias (VA).Design and methods. The study included 73 patients with frequent symptomatic high-grade VA (44 women and 29 men) aged 28 to 86 years (56.6 ± 28.3 years), in whom MTM ECG was performed for the purpose of individual selection of AA therapy.Results. In 19 % patients using MTM, the psychogenic nature of VA and a necessity to avoid prescribing was suspected. In 63 % patients with VA the optimal AA therapy in the minimum effective doses was selected using MTM, in 18 % patients the futility of drug therapy was proven and radiofrequency ablation was recommended.Conclusion. MTM ECG is justified for the selecting AA therapy in patients with VA. MTM has undoubted advantages over daily monitoring and helps to reduce the time for AA agent choosing.

Single beta-blocker or combined amiodarone therapy in implantable cardioverter-defibrillator and cardiac resynchronization therapy—defibrillator patients: Insights from the German DEVICE registry

Because of its antiarrhythmic potency and due to the lack of alternatives, amiodarone is often used for antiarrhythmic therapy in patients with implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator systems. To date, robust data on the safety and clinical benefit of amiodarone therapy in these patients are missing. The purpose of this study was to assess the periprocedural and postprocedural outcomes of combined therapy with beta-blockers plus amiodarone compared to treatment with single beta-blockers in the "real-life" cohort of ICD recipients of the German DEVICE registry. A total of 4499 patients who underwent ICD implantation, revision, or upgrade in 49 centers participating in the German DEVICE registry were enrolled from March 2007 to February2014. Amiodarone had no significant effect on the success of defibrillation testing. Early implantation-associated complications were similar between the groups. However, 1-year overall mortality was significantly higher in the beta-blocker plus amiodarone cohort (adjusted hazard ratio 2.09; P <.001). Interestingly, among the surviving patients, amiodarone was not associated with a significantly reduced risk of ICD discharges or syncopal events. Furthermore, the occurrence of ventricular tachycardia (VT) storm or incessant VTs and the number of patients scheduled for intracardiac ablation did not differ among both groups, whereas the rate of rehospitalization was lower in the cohort with only beta-blockers. Although amiodarone has no adverse effect on the success of defibrillation testing, our data suggest an increased all-cause mortality under amiodarone therapy, especially in the subgroups of patients with sinus rhythm or severely reduced left ventricular function. In surviving patients, rates of arrhythmic events were comparable.

Abstract 15591: Acute Dantrolene Treatment Reverses Arrhythmogenic Substrate and Reduces Triggers Induced by Ryanodine Receptor 2 Hyperactivity in Human Hearts

Introduction: Ryanodine receptor 2 (RyR2) hyperactivity is commonly observed in structural heart diseases that are a result of ischemia or heart failure. It results in abnormal calcium handling and calcium leak that can trigger arrhythmias. Dantrolene, a RyR inhibitor, is used to prevent calcium leak from RyR1 in skeletal muscles. Hypothesis: Suppressing RyR2 hyperactivity with acute dantrolene treatment can reduce arrhythmia burden in human hearts. Methods: Human donor hearts that were not used in transplantation were obtained and 1 cm 3 cubes were isolated from the left ventricle. Slices at 400 μm thickness were generated from these cubes, pinned and perfused with Tyrode’s solution in a recording tissue chamber. Pseudo-ECGs were recorded with ECG electrodes and the slices were optically mapped to measure conduction velocity (CV), action potential duration (APD) and calcium transient duration (CaTD). After an initial 30 min equilibration period, baseline optical recordings were obtained. Slices were then treated with 1) Isoproterenol (Iso, 250 nM) to stimulate β-adrenergic receptors, 2) Caffeine (200 μM) for RyR2 receptor activation and 3) Dantrolene (10 μM), sequentially. Dual optical recordings, Vm and Ca, were obtained after each treatment. Results: Substrate: Iso reduced APD (425±36 vs 394±43, p=0.03), as expected, and addition of Caffeine restored APD to baseline. More importantly, addition of Dantrolene prolonged APD even further (460±90, p=0.04). CaTD was also similarly reduced by Iso (445±48 vs 387±25, p=0.04) and restored to baseline by Caffeine+Iso. No significant changes in CV were measured under any condition. Trigger: In slices where PVCs were inducible, Caffeine+Iso increased occurrence of PVCs (20 vs 53 PVCs/min) while addition of Dantrolene reduced PVC incidence (18 PVCs/min). Conclusions: Dantrolene treatment, acutely reversed proarrhythmogenic substrate and reduced triggers and could therefore be a suitable approach for anti-arrhythmic therapy in patients with structural heart disease. Additionally, human LV slice preparation is useful in antiarrhythmic drug studies.

Outcomes of catheter ablation versus antiarrhythmic therapy in patients with atrial fibrillation: a systematic review and meta-analysis.

Recent data have shown an advantage of rhythm control over rate control for the treatment of atrial fibrillation (AF). Nevertheless, the data regarding efficacy of catheter ablation (CA) compared with antiarrhythmic drugs (AADs) in patients with AF is lacking. Therefore, we sought to evaluate recurrence of arrhythmia, all-cause mortality, cardiovascular deaths, stroke/TIA, and all-cause readmissions of CA compared with AAD in patients with AF. Systematically searched through PubMed, Google Scholar, EMBASE, and Cochrane for randomized control trials that compared CA and AAD in atrial fibrillation patients. Review Manager 5.4 and OpenMetaAnalyst were used to analyze the data. Data was pooled for the outcomes using random-effect models (DerSimonian and Laird) and reported as pooled odds ratio (OR). A total of 4822 patients were included. The CA group had 2417 patients while the AAD group included 2405 patients. Pooled data demonstrated that the CA arm had a statistically significant decrease in risk for recurrence of arrhythmia as compared to AAD (OR 0.25; [95% CI, 0.18-0.36]; p < 0.001). All-cause readmission was statistically significantly lower in CA as compared to AAD (OR 0.33; [95%CI, 0.17-0.63]; p < 0.001). For other secondary outcomes, there was no statistically significant difference between CA and AAD with regard to all-cause mortality (OR 0.75; [95% CI, 0.55-1.03]), cardiovascular death (OR 0.76; [95% CI, 0.22-2.54]), bleeding (OR 1.09, [95% CI 0.74, 1.61]), or stroke/TIA outcome (OR 0.90, [95% CI, 0.59-1.37]). In this study of pooled data from 16 RCTs, CA utilization for atrial fibrillation had improved freedom from arrhythmia as well as reduced all-cause readmission compared with AAD.

Predicting Heart Failure in Arrhythmogenic Right Ventricular Cardiomyopathy

Predicting Heart Failure in Arrhythmogenic Right Ventricular Cardiomyopathy

Management of ventricular tachycardia in patients with ischaemic cardiomyopathy: contemporary armamentarium.

Worldwide, ∼4 million people die from sudden cardiac death every year caused in more than half of the cases by ischaemic cardiomyopathy (ICM). Prevention of sudden cardiac death after myocardial infarction by implantation of a cardioverter-defibrillator (ICD) is the most common, even though not curative, therapy to date. Optimized ICD programming should be strived for in order to decrease the incidence of ICD interventions. Catheter ablation reduces the recurrence of ventricular tachycardias (VTs) and is an important adjunct to sole ICD-based treatment or pharmacological antiarrhythmic therapy in patients with ICM, as conclusively demonstrated by seven randomized controlled trials (RCTs) in the last two decades. However, none of the conducted trials was powered to reveal a survival benefit for ablated patients as compared to controls. Whereas thorough consideration of an early approach is necessary following two recent RCTs (PAUSE-SCD, BERLIN VT), catheter ablation is particularly recommended in patients with recurrent VT after ICD therapy. In this context, novel, pathophysiologically driven ablation strategies referring to deep morphological and functional substrate phenotyping based on high-resolution mapping and three-dimensional visualization of scars appear promising. Emerging concepts like sympathetic cardiac denervation as well as radioablation might expand the therapeutical armamentarium especially in patients with therapy-refractory VT. Randomized controlled trials are warranted and on the way to investigate how these translate into improved patient outcome. This review summarizes therapeutic strategies currently available for the prevention of VT recurrences, the optimal timing of applicability, and highlights future perspectives after a PAUSE in BERLIN.

Clinical features and antiarrhythmic therapy in patients with catecholaminergic polymorphic ventricular tachycardia

Aims. To evaluate the long-term efficacy of antiarrhythmic therapy in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT).Methods. CPVT was diagnosed in 11 patients between the ages of 3-12 years with a minimum follow-up of 10 years. The data analyzed was obtained from existing medical records that included symptoms, family screenings, treadmill tests, electrocardiography, echocardiography, implanted cardioverter-defibrillator data (ICD), and medical treatments.Results. Cardiac events were registered in 75% of patients on beta-blocker therapy. Supraventricular arrhythmias such as atrial and atrioventicular nodal tachycardia, atrial fibrillation and atrial flutter were detected using various ECG diagnostic methods in all patients, which is significantly higher than reported in similar studies. A combination of anti-arrhythmic therapy and beta-blocker treatment reduced the number of cardiac events by 50% as compared to only beta-blocker treatment.Conclusion. Multiple supraventricular arrhythmias have a high prevalence in patients with CPVT and can trigger ventricular arrhythmia. Combined antiarrhythmic therapy is effective because it prevents cardiac events in patients with CPVT. Combined antiarrhythmic therapy improves the prognosis of patients with CPVT and may help to avoid or postpone ICD implantation.

Abstract 12131: Improved Knowledge and Confidence of Antiarrhythmic Drugs in Atrial Fibrillation via Online Educational Intervention

Background: Antiarrhythmic drugs (AAD) are currently used for the management of patients with arrhythmias. Despite randomized trial and real-world data many physicians remain hesitant to select an AAD in the daily-life routine. Purpose: To determine if an online continuing professional development intervention could improve knowledge and confidence of cardiologists and primary care physicians (PCPs) related to real-world data for AAD. Methods: Cardiologists and PCPs electively participated in a video-based, 2-faculty educational panel discussion on AAD management of arrhythmias, including real-world data. Educational effect was assessed using a repeated pair, pre-assessment/post-assessment study design and a chi-square test assessed differences from pre- to post-assessment. P -values &lt; .05 are statistically significant. Cramer’s V assessed level of educational effect using the range of &lt; 0.06 (modest), 0.06-0.15 (noticeable), 0.16-0.26 (considerable), and &gt; 0.26 (extensive). Data were collected June 5, 2020 through July 20, 2020. Results: Overall significant improvements were seen after education for cardiologists (N = 367; P &lt; .0001; V = .359) and PCPs (N = 760; P &lt; .0001; V = .359). Pre-assessment, the average correct response rate was 32% for cardiologists and 29% for PCPs, while post-assessment average correct response rates increased to 68% and 61%, respectively. Significant improvements were observed in cardiologists’ and PCPs’ knowledge related to the effect of AAD on outcomes (Table). As a result of the education, 36% of cardiologists and 45% of PCPs had a measurable improvement in confidence regarding selection of appropriate antiarrhythmic therapy for patients with AF. Conclusion: The statistically significant improvements observed in this intervention demonstrate that participation in a video-based panel discussion improved the knowledge and confidence regarding real-world data for AAD regarding their effects on outcomes.

Cryoablation versus anti-arrhythmic therapy for initial treatment of atrial fibrillation: a systematic review and meta-analysis

Abstract Introduction Atrial fibrillation is a common cardiac arrhythmia that affects approximately 2% of the overall population. Guidelines suggest the use of anti-arrhythmic agents as initial therapy in patients with symptomatic atrial fibrillation, however using cryoablation as a first line therapy might have increased efficacy. The safety and efficacy of cryoablation as initial therapy has not yet been established. Purpose We performed a systematic review and meta-analysis of randomized controlled trials to investigate the use of cryoballoon catheter ablation compared to anti-arrhythmic therapy as an initial intervention to prevent recurrence of atrial tachyarrhythmias in patients with atrial fibrillation. We also wanted to determine if using this initial ablative approach did not present increased adverse events. Methods A comprehensive search of multiple databases was performed to find randomized control trials that directly compared cryoablation therapy versus anti-arrhythmic therapy as initial treatment for patients with atrial fibrillation. A total of three RCTs met the inclusion criteria (724 patients) and were used in the meta-analysis. The primary outcome of our meta-analysis was recurrence of atrial tachyarrhythmias. The secondary outcome evaluated serious adverse events of each therapy. Results The results showed a statistically significant reduction of recurrence of atrial tachyarrhythmic events in patients receiving cryoablation compared to anti-arrhythmic therapy [Risk Ratio (RR): 0.60, 95% CI (0.49, 0.72), P&amp;lt;0.ehab724.03521, I2=0%]. There was no significant difference in serious adverse events between patients receiving cryoablation compared to patients receiving anti-arrhythmic therapy. [Risk Ratio (RR): 1.19, 95% CI (0.71, 2.00), P=0.52, I2=0%]. Conclusion Our meta-analysis showed that cryoablation therapy as an initial therapy is more efficacious than anti-arrhythmic therapy in patients with atrial fibrillation without an increased risk of serious adverse events. Funding Acknowledgement Type of funding sources: None.

Safety and interaction of direct oral anticoagulants with antiarrhythmic drugs

The use of direct oral anticoagulants minimized the risks associated with vitamin K antagonist (warfarin) therapy. Currently, direct oral anticoagulants have priority over warfarin for the prevention of thromboembolic events in patients with atrial fibrillation and a number of other conditions requiring anticoagulant therapy. Direct oral anticoagulants along with antiarrhythmic therapy are the accepted strategy for atrial fibrillation treatment. At the same time, the effect of drug-drug interactions (DDI) between direct oral anticoagulants and antiarrhythmic drugs, which have common points of metabolic application, has not been fully elucidated. In order to provide effective and safe anticoagulant and antiarrhythmic therapy in patients with AF, it is important to understand the mechanisms and severity of DDI of direct oral anticoagulants and antiarrhythmic agents. This review discusses the issues of DDI of direct oral anticoagulants and antiarrhythmic drugs used to treat atrial fibrillation.