Antiarrhythmic Drugs In Patients Research Articles

Long-term anti-arrhythmic is effective than no anti-arrhythmic in patients with first developed paroxysmal atrial fibrillation

Abstract Background There is no detailed guideline recommendation of AAD treatment for the firstly developed paroxysmal atrial fibrillation (AF). Anti-arrhythmic drugs (AAD) prevent recurrence of AF and short-term AAD treatment would increase drug safety by reducing treatment duration. Introduction We designed the prospective, randomized trial to evaluate the efficacy of short- and long-term AAD (flecainide) compared with no treatment in maintaining sinus rhythm in patients with firstly developed paroxysmal atrial fibrillation (PAF). Methods Definition of the firstly developed PAF was the patients with firstly developed symptomatic PAF without history of palpitation. Sixty patients were randomly assigned into no AAD treatment (Group I; N=21), short-term AAD treatment (flecainide 100mg bid for 4 weeks, Group II; N=20) or long-term AAD treatment (flecainide 100mg bid for 6 months, Group III; N=19). All patients were in sinus rhythm at randomization. Patients received clinical follow up with serial evaluation of rhythm status. Results There were no significant differences in age, gender, cardiovascular comorbidities and echocardiographic parameters. Among the total population, AF recurred in 16 patients (26.7%) during the follow up period. AF free survival was significantly different among groups (p=0.038) (Fig 1). Conclusions Long-term AAD at least 6 months is beneficial in maintaining sinus rhythm than no or shot-term AAD in patients with firstly developed PAF.

Class 1C Antiarrhythmics for Premature Ventricular Complex Suppression in Nonischemic Cardiomyopathy With Implantable Cardioverter-Defibrillators

BackgroundPremature ventricular complexes (PVCs) are common and associated with worse outcomes in patients with heart failure. Class 1C antiarrhythmic drugs (AADs) effectively suppress PVCs, but guidelines currently restrict their use in structural heart disease. ObjectivesThis study aimed to assess the safety and efficacy of class 1C AADs in patients with nonischemic cardiomyopathy (NICM) and implantable cardioverter-defibrillators (ICDs). MethodsAll patients with NICM and an ICD treated with flecainide or propafenone at the Hospital of the University of Pennsylvania between 2014 and 2022 were identified. PVC burden, left ventricular ejection fraction (LVEF), and biventricular pacing percentage were compared before and during class 1C AAD treatment. Safety outcomes included sustained atrial and ventricular arrhythmias, heart failure admissions, and death. ResultsWe identified 34 patients, 23 receiving flecainide and 11 propafenone. Most patients (62%) had failed other AADs or catheter ablation (68%) prior to class 1C AAD initiation. PVC burden decreased from 20% ± 13% to 6% ± 7% (P < 0.001), LVEF increased from 33% ± 9% to 37% ± 10% (P = 0.01), and biventricular pacing percentage increased from 85% ± 9% to 93% ± 7% (P = 0.01). Sustained ventricular tachycardia (2 vs 9 patients) and admissions for decompensated heart failure (2 vs 3 patients) decreased compared with the 12 months prior to class 1C AAD initiation. ConclusionsClass 1C AADs effectively suppressed PVCs in patients with NICM and ICDs, leading to increases in LVEF and biventricular pacing percentage. In this limited sample, their use was safe. Larger studies are needed to confirm the safety of this approach.

Abstract 12194: Clinical Application of Virtual Antiarrhythmic Drug Test Using Digital Twins in Patients Who Recurred Atrial Fibrillation After Catheter Ablation

Introduction: We previously reported that a computational modeling-guided antiarrhythmic drug (AAD) test was feasible for assessing diverse AADs in patients with atrial fibrillation (AF). In this study, we took the virtual AAD test (V-AAD) in patients who took AADs after AF catheter ablation (AFCA). Hypothesis: Patients using an effective drug in the VAAD test will have fewer AF recurrences than patients using an ineffective drug. Methods: This single-center retrospective study included 246 patients (72.8% male, 60.7±10.2 years of age, 38.6% paroxysmal AF) prescribed AADs within 3 months after AFCA. Using realistic computational modeling, we evaluated the effects of five AADs (amiodarone, sotalol, dronedarone, flecainide, and propafenone; 2 doses for each drug). Clinical AADs (C-AAD) were chosen at the discretion of the physicians blinded to the V-AAD test. We defined the effective V-AAD as the V-AAD that terminated AF or converted AF to atrial tachycardia (AT) and the best V-AAD as the V-AAD that ended virtual AF the fastest. We compared AF recurrence rates after the AAD prescription depending on the results of the V-AAD test. Results: The ineffective and best V-AAD were administered in 64 (26.0 %) and 70 patients (28.5%). The recurrence rate within a year after using the ineffective, effective, and best V-AAD were 46.9%, 35.7%, and 25.7%, respectively (log-rank p=0.013). The recurrence rate within a year in patients with at least one V-AAD terminating AF and those without was 33.9% and 50.0%, respectively (log-rank p=0.034). The use of best V-AAD (OR 0.43, 95% CI [0.18-0.96]; p=0.042, vs. ineffective V-AAD) is an independent predictor of AF recurrence within a year of using AAD after AFCA. Conclusions: The digital twins-guided V-AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF who had a high chance of recurrence after AFCA. We need a prospective randomization study to assess the prediction power of the V-AAD test.

Abstract 16362: Does Extra-Pulmonary Triggers or Autonomic Neural Activity Affect the Rhythm Control by Anti-Arrhythmic Drugs in Patients With Post-Ablation Atrial Fibrillation Recurrence?

Introduction: Although the EAST-AFNET trial demonstrated the usefulness of atrial fibrillation (AF) rhythm control, including antiarrhythmic drugs (AADs), little is known about their effect on recurred AF after catheter ablation (CA). Hypothesis: We explored the effect of AADs depending on the presence of extra-pulmonary vein triggers (ExPVT) or post-ablation heart rate variability (HRV) in patients who recurred after AFCA. Methods: In this retrospective analysis of a single-center cohort, we analyzed 2,036 patients who underwent de-novo AFCA, and 486 of them had recurrent AF and subsequently underwent rhythm control with AADs. We investigated the effects of the extra-pulmonary vein (PV) triggers and post-procedural 3 rd month HRV (rMSSD; cut-off determined by Youden index) on the AAD responsiveness. Results: The post-AFCA recurrence was significantly higher in patients with ExPVT (Log-rank p&lt;0.001, HR 1.45 [1.16-1.83], p=0.001) or higher 3 rd month post procedure HRV-rMSSD (Log-rank p&lt;0.001, HR 1.36 [1.11-1.65], p=0.003) than their counterparts. Patients with ExPVT at de novo procedure had significantly higher 3 rd month rMSSD (15.0 [11.0-23.0] vs. 17.0 [11.0-28.0], p=0.022) and patients with high 3 rd month rMSSD showed a higher rate of ExPVT identified at the 2 nd repeat procedure (n=160, 41.0% vs. 22.2%, p=0.019). Among those patients how recurred AF after AFCA, post-AAD recurrence did not differ depending on ExPVT (Log-rank p=0.455, HR 1.12 [0.78-1.69], p=0.436) or rMSSD (Log-rank p=0.457, HR 1.16 [0.87-1.55], p=0.300). Post-AAD recurrence did not differ between class IC and III AADs (p for interaction = 0.311). Conclusion: ExPVT and post-procedural high rMSSD are independent risk factors for post-AFCA recurrences but not for AAD response in recurred AF patients. Whether AADs may suppress ExPVT and modulate cardiac autonomic activity after post-AFCA recurrences need further investigation.

The Cost-Effectiveness of First-Line Cryoablation vs First-Line Antiarrhythmic Drugs in Canadian Patients With Paroxysmal Atrial Fibrillation

BackgroundThe EARLY-AF (NCT02825979), STOP AF First (NCT03118518), and Cryo-FIRST (NCT01803438) randomised controlled trials (RCTs) demonstrated that cryoballoon pulmonary vein isolation reduces atrial fibrillation (AF) recurrence compared with antiarrhythmic drugs (AADs) in patients with symptomatic paroxysmal atrial fibrillation (PAF). The present study developed a cost-effectiveness model (CEM) of first-line cryoablation compared with first-line AADs for PAF, from the Canadian health care payer’s perspective. MethodsData from the 3 RCTs were analysed to estimate key CEM parameters. The model structure used a decision tree for the first 12 months and a Markov model with a 3-month cycle length for the remaining lifetime time horizon. Costs were set at 2023 Canadian dollars, health benefits were expressed as quality-adjusted life years (QALYs), and both were discounted 3% annually. Probabilistic sensitivity analysis (PSA) considered parameter uncertainty. ResultsThe statistical analysis estimated that first-line cryoablation generates a 47% reduction (P < 0.001) in the rate of AF recurrence, a 73% reduction in the rate of subsequent ablation (P < 0.001), and a 4.3% (P = 0.025) increase in health-related quality of life, compared with first-line AADs. The PSA indicates that an individual treated with first-line cryoablation accrues less costs (−$3,862) and more QALYs (0.19) compared with first-line AADs. Cryoablation is cost-saving in 98.4% of PSA iterations and has a 99.9% probability of being cost-effective at a cost-effectiveness threshold of $50,000 per QALY gained. Cost-effectiveness results were robust to changes in key model parameters. ConclusionsFirst-line cryoballoon ablation is cost-effective when compared with AADs for patients with symptomatic PAF.

Clinical application of virtual antiarrhythmic drug test using digital twins in patients who recurred atrial fibrillation after catheter ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background We previously reported a proof-of-concept study that digital twins can test antiarrhythmic drug (AAD) effects on atrial fibrillation (AF) after integrating the patients’ cardiac CT imaging and electroanatomical map (EAM). In this study, we evaluated the reproducibility of the virtual AAD test (V-AAD) in the clinical setting in patients who recurred after AF catheter ablation (AFCA) and took AADs. Methods This single-center retrospective study included 232 patients (71.6% male, 60.5±10.2 years of age, 40.9% paroxysmal AF) who were prescribed AADs after AFCA due to real or high chance of recurrence. Clinical AADs (C-AAD) were chosen at the discretion of the primary care physician blinded to V-AAD test. All those included patients underwent V-AAD test using digital twins reflecting the patients’ atrial anatomy, histology, and electrophysiology by integrating cardiac CT and EAM. The ion currents for each AAD (amiodarone, sotalol, dronedarone, flecainide, and propafenone; 2 doses for each drug) were defined based on previous publications. We defined the most efficient V-AAD as the V-AAD that terminated virtual AF the fastest. We evaluated the association between AF recurrence rate while using C-AAD and the most efficient V-AAD, which showed excellent termination/ defragmentation of AF in the digital twins. Results In the clinical setting, the most effective V-AAD was administered in 72 patients (31.0%), and not effective V-AADs in 61 patients (26.3%). During the median 782 (IQR 582-1047) days follow-up, AF recurrence was observed in 132 patients (56.9%) (under the class IC 44.4% and class III 57.4%). The recurrence rate within a year after using the effective V-AAD was 40.9%, and that of using the ineffective V-AAD was 54.1%, respectively (log-rank p=0.046). The recurrence rate within a year in patients with ≥2 effective V-AADs and those with 0 or 1 were 42.4% and 59.3%, respectively (log-rank p=0.056). Conclusions The digital twins-guided V-AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF who recurred after AFCA. We need a prospective randomization study to evaluate the prediction power of the V-AAD test.

Prevalence and bleeding risk associated with the concomitant use of direct oral anticoagulants and antiarrhythmic drugs in patients with atrial fibrillation, based on the French healthcare insurance database.

Pharmacokinetic interactions exist between apixaban or rivaroxaban, and CYP3A4 and P-glycoprotein inhibitors such as amiodarone, verapamil and diltiazem. We aimed to estimate the prevalence of exposure to this drug-drug association (DDA) and to assess the bleeding risk associated in patients with atrial fibrillation (AF). We conducted a cohort study using a representative 1/97th sample of the French healthcare insurance database between 2014 and 2019. Patients with AF receiving apixaban or rivaroxaban were included and followed-up until hospitalization for bleeding, death, discontinuation of apixaban or rivaroxaban, exposure to strong CYP3A4 inhibitor, or until December 31st 2019, whichever came first. Primary outcome was hospitalization for bleeding registered as primary diagnosis. The association between the exposure to the DDA and hospitalization for bleeding was evaluated as a time-dependent variable in Cox model. Between 2014 and 2019, the AF population under apixaban or rivaroxaban represented 10,392 patients. During the study period, the annual average prevalence of DDA exposure in this population was 38.9%. Among the 10,392 patients, 223 (2.1%) were hospitalized for bleeding, of which 75 (33.6%) received the association and 148 (66.4%) received apixaban or rivaroxaban alone. There was no association between DDA exposure and risk of hospitalization for bleeding (aHR = 1.19, [95% CI: 0.90, 1.58]). Age (HR 1.03 [1.02, 1.05]) and male gender (HR 1.72 [1.28, 2.30]) were associated with an increased risk of hospitalization for bleeding. Exposure to antiarrhythmic drugs was not associated with an increased risk of hospitalization for bleeding in patients with AF under rivaroxaban or apixaban.

The Effectiveness of Catheter Ablation in the Management of Ventricular Tachycardia in Comparison With Antiarrhythmic Drugs in Patients With Structural Heart Disease: A Meta-Analysis.

The aim of this meta-analysis is to compare the safety and efficacy of catheter ablation versus antiarrhythmic drugs (AADs) in the management of ventricular tachycardia (VT) in patients with structural heart diseases. Two independent investigators searched electronic databases including PubMed, Cochrane, and Excerpta Medica database (EMBASE) using keywordcombinations (Medical Subject Headings (MeSH) terms and free terms)such as "catheter ablation," "ventricular tachycardia," "escalation," and "antiarrhythmic drugs" from inception to November 30, 2022. The primary efficacy outcomes included recurrence of VT at follow-up, all-cause mortality, and cardiovascular mortality. The secondary efficacy outcomes assessed in the current meta-analysis included implantable cardioverter-defibrillator (ICD) shock and hospitalization due to cardiac reasons. Safety outcomes included treatment-related adverse events and serious adverse events. A total of three studies were included in this meta-analysis. Therewas no significant difference in the risk of recurrence of VT (RR: 0.94, 95% CI: 0.72-1.24, p-value: 0.67), all-cause mortality (RR: 0.99, 95% CI: 0.67, 1.46, p-value: 0.98), cardiovascular mortality (risk ratio (RR): 0.90, 95% confidence interval (CI): 0.56-1.45, p-value: 0.67),incidence of ICD shocks (RR: 0.99, 95% CI: 0.76-1.29, p-value: 0.93, I-square: 0%), and hospitalization due to cardiac reasons in follow-up (RR: 0.77, 95% CI: 0.55-1.07, p-value: 0.12) between the catheter ablation group and the antiarrhythmic druggroup. However, the risk of treatment-related adverse events was lower in the ablation group compared to the antiarrhythmic medicine (AAM) group (RR: 0.44, 95% CI: 0.29-0.67, p-value: 0.0001). In this meta-analysis of three randomized controlled trials (RCTs) among patients with structural heart disease who had ventricular tachycardia, the incidence of the recurrence of VT, all-cause mortality, cardiovascular mortality, and ICD shock was not significantly different between patients who received catheter ablation and antiarrhythmic drugs. However, regarding safety, catheter ablation is a safe procedure with a low risk of treatment-related events compared to antiarrhythmic drugs.

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.

Pre-treatment with antiarrhythmic drugs for elective electrical cardioversion of atrial fibrillation: a systematic review and network meta-analysis.

Our objective was to compare the efficacy of pre-treatment with different classes of anti-arrhythmic drugs (AADs) in patients with atrial fibrillation (AF) undergoing electrical cardioversion. We performed a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing different AADs in patients with AF undergoing electrical cardioversion. We grouped AADs into five network nodes: no treatment or rate control, Class Ia, Class Ic, Class III, and amiodarone. Outcomes were (i) acute restoration and (ii) maintenance of sinus rhythm. We searched MEDLINE and EMBASE from inception until June 2020. We used Python 3.8.3 and R 3.6.2 for data analysis. We evaluated the overall certainty of evidence with the GRADE framework. We included 28 RCTs. Compared with no treatment or rate control, Class III AADs [odds ratio (OR): 2.41; 95% credible interval (CrI): 1.37 to 4.62, high certainty] and amiodarone (OR: 2.58; 95% CrI: 1.54 to 4.37, high certainty) improved restoration of sinus rhythm. Amiodarone improved long-term maintenance of sinus rhythm when compared with no treatment or rate control (OR: 5.37; 95% CrI: 4.00-7.39, high certainty), Class Ic (OR: 1.89; 95% CrI: 1.05-3.45, moderate certainty) and Class III AADs (OR: 2.19; 95% CrI: 1.39-3.26, high certainty). Before electrical cardioversion of AF, treatment with Class III AADs or amiodarone improves the acute restoration of sinus rhythm. Amiodarone is most likely to improve the maintenance of sinus rhythm after electrical cardioversion, but Class Ic and Class III AADs are also effective.

PO-717-08 UNUSUAL LETHAL COMPLICATION DURING SCAR-RELATED VT ABLATION: A CASE OF DRY TAMPONADE

Scar related ventricular tachycardia (VT) ablation has been shown to be more effective than anti-arrhythmic drugs in patients with ischemic cardiomyopathy (ICMP) and recurrent VT. In this particular population, complication rate can be as high as 10%, the most common ones being vascular damage, and pericardial complications. To identify a rare but severe complication of scar related VT ablation NA A 78 yo male with an old inferior and a recent anterior myocardial infarction (LVEF= 25%) was referred to our institution for VT ablation due to arrhythmic storm. Cardiac CT scan revealed inferior and anterior wall thinning (Inheart technology; figure panel A). Procedure was performed under conscious sedation in a stable patient. RF energy was delivered at 40 to 50W using a Smarttouch ST/SF catheter and the Carto 3 navigation system (Biosense Webster). After CT-channel ablation, a non clinical VT was induced. During ablation of this VT on the inferior wall, ST segment elevation in inferior leads became apparent, and arterial pressure dropped from 90 to 70mmHg. The patient was asymptomatic. Per-procedure coronary angiography showed no acute lesion and transthoracic echo demonstrated a dry pericardium. Ablation was continued and the patient was transferred to the ICU 1 hour later, with arterial pressure stabilized at 70 mm Hg. In the ICU, hemodynamic suddenly deteriorated 20 minutes after arrival and the patient went into cardiac arrest. After resuscitation, minimal pericardial effusion and clots were seen on TTE. Percutaneous pericardial drainage was attempted but failed to restore hemodynamics. The patient was then transferred to the operating room for surgical drainage. The diagnosis of circumferential intramyocardial hematoma contained by the epicardial layer (dry tamponade) was made (Figure panel B). Due to the extent of the hematoma, dilaceration of the myocardium and the clinical context, no further resuscitation was attempted and the patient finally died. This diagnosis of dry tamponade is rare in electrophysiology but well known by cardiologists performing chronic total occlusion angioplasty. It needs to be recognized by electrophysiologists at its early phase to avoid lethal outcome using hemodynamic support during the healing process.

Pro‐arrhythmia with antiarrhythmic drugs in patients with idiopathic ventricular arrhythmia: A common problem with vague definitions and complex interactions

Journal of Cardiovascular ElectrophysiologyVolume 33, Issue 7 p. 1636-1636 LETTER TO THE EDITOR Pro-arrhythmia with antiarrhythmic drugs in patients with idiopathic ventricular arrhythmia: A common problem with vague definitions and complex interactions Can Hasdemir MD, Corresponding Author Can Hasdemir MD [email protected] orcid.org/0000-0002-4755-9165 Department of Cardiology, Ege University School of Medicine, Izmir, Turkey Correspondence Can Hasdemir, Ege University School of Medicine, Department of Cardiology, Izmir, Turkey. Email: [email protected]Search for more papers by this authorSerdar Payzin MD, Serdar Payzin MD Department of Cardiology, Ege University School of Medicine, Izmir, TurkeySearch for more papers by this author Can Hasdemir MD, Corresponding Author Can Hasdemir MD [email protected] orcid.org/0000-0002-4755-9165 Department of Cardiology, Ege University School of Medicine, Izmir, Turkey Correspondence Can Hasdemir, Ege University School of Medicine, Department of Cardiology, Izmir, Turkey. Email: [email protected]Search for more papers by this authorSerdar Payzin MD, Serdar Payzin MD Department of Cardiology, Ege University School of Medicine, Izmir, TurkeySearch for more papers by this author First published: 21 April 2022 https://doi.org/10.1111/jce.15507 Disclosures: None. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume33, Issue7July 2022Pages 1636-1636 RelatedInformation

Long-Term Cost-Effectiveness Comparison of Catheter Ablation and Antiarrhythmic Drugs in Atrial Fibrillation Treatment Using Discrete Event Simulation

ObjectivesTo evaluate the lifetime cost-effectiveness of 3 widely used atrial fibrillation (AF) treatments from the perspectives of Chinese healthcare system: antiarrhythmic drugs (AADs), ThermoCool SmartTouch guided by ablation index (STAI), and second-generation cryoballoon (CB2). MethodsA discrete event simulation (DES) model was implemented to compare the lifetime cost-effectiveness of AADs, STAI, and CB2. AF disease progression was explicitly modeled based on the Atrial Fibrillation Progression Trial clinical study results. The base-case analysis assumed that patients with paroxysmal AF (PAF) entered the model at the age of 55 years and had a CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ( > 65 = 1 point, > 75 = 2 points), Diabetes, previous Stroke/transient ischemic attack (2 points)-Vascular disease (peripheral arterial disease, previous myocardial infarction, aortic atheroma), Age 65 to 74 years, and Sex category) score of 2 for males and 3 for females. Model parameter uncertainties were incorporated throughout the DES simulation with full probabilistic model parameterization. ResultsThe lifetime cost-effectiveness evaluations showed that patients treated with AADs gained an average of 4.98 quality-adjusted life-years (QALYs) and 9.63 life-years (LYs) at an average cost of US dollar (USD) 15 374. Patients treated with CB2 gained 5.92 QALYs and 10.74 LYs at an average cost of USD 26 811. The STAI group gained an average of 6.55 QALYs and 11.57 LYs at an average cost of USD 24 722. The incremental cost-effectiveness ratios was USD 5927 and USD 12 167 per QALY for STAI versus AADs and CB2 versus AADs, respectively. Assuming the willingness-to-pay threshold for China is USD 30 390 per QALY, both ablation treatments will be cost-effective compared with AADs for patients with PAF. ConclusionsThe DES model demonstrated that catheter ablations are more cost-effective than AADs for patients with PAF under the healthcare system in China. Among catheter ablation technologies, STAI provides better outcomes at lower costs.

Abstract 12074: Rhythm Control Strategy in Recent Atrial Fibrillation: An Online Educational Intervention Improved Physician Knowledge, Competence, and Confidence

Background: In clinical practice, rhythm control strategies, including antiarrhythmic drugs (AAD), are currently used for the management of patients with arrhythmias. Despite latest guideline updates and randomized trials on early rhythm control strategies, physicians remain uncertain on the selection of a good strategy for these patients. Purpose: To determine if an online continuing medical education intervention could improve knowledge, competence, and confidence of cardiologists and surgeons related to latest data on rhythm control strategies and the use of AAD in patients with recent AF. Methods: Cardiologists and surgeons electively participated in a video-based, 3-faculty educational panel discussion on earlier rhythm control strategies in recent AF. A repeated pairs pre-/post-assessment study design was used and a paired samples t-test for overall and McNemar’s test at the question level ( P &lt;.05 is considered significant) assessed statistical significance. Data were collected March 3, 2021 through June 1, 2021. Results: Overall significant improvements were seen after education for both cardiologists (N = 525) and surgeons (N = 2180). Pre-assessment, the average correct response rate was 55% for cardiologists and 51% for surgeons, while post-assessment average correct response rates increased to 66% and 64%, respectively. Significant improvements were observed in cardiologists’ and surgeons’ knowledge and competence related to the use of rhythm control strategies in recent AF (Table). As a result of the education, 39% of cardiologists and 48% of surgeons had a measurable improvement in their confidence on rhythm control strategies choice in recent AF. Conclusion: The statistically significant improvements observed in this intervention demonstrate that participation in a video-based panel discussion to increase knowledge, competence, and confidence of cardiologists regarding the selection of rhythm control strategies in recent AF.

Incidence of Post-Heart Transplant Chronic Thyroiditis and Its Association With Pretransplant Amiodarone Use

Chronic thyroiditis (CT) is a common cause of thyroid dysfunction and could therefore adversely affect outcomes in patients undergoing heart transplant (HT). The incidence of post-HT CT and whether amiodarone, a commonly used anti-arrhythmic drug in patients with heart failure during pre-HT period, is associated with the development of post-HT CT are unknown. A retrospective review of HT recipients from February 2, 2010 to October 16, 2018 was performed. Patients who lacked relevant pre-/post-HT records, underwent thyroidectomy, had pre-HT thyroid dysfunction or thyroiditis within 15 days post-HT, and those on amiodarone during the post-HT period were excluded, yielding a final cohort of 75 patients. Patients had a mean age of 63.3 ± 1.4 years and were predominantly male (90.7%) and white (80%). The incidence of post-HT CT was 32% with the majority (83.3%) manifesting as hypothyroidism. Median time to diagnosis of CT after transplant was 10.2 months (interquartile range, 4-27.4). Additionally, the CT group had higher pre-HT use of amiodarone (non-CT vs CT: 21.6% vs 50%, P=.01), higher prevalence of atrial fibrillation (non-CT vs CT: 23.5% vs 45.8%; P=.05), and more stage IV/V chronic kidney disease (non-CT vs CT: 2% vs 16.7%, P=.02). On multivariate analysis, pre-HT amiodarone use was associated with the development of post-HT CT after adjustment for age, sex, and chronic kidney disease (odds ratio, 3.65; 95% CI, 1.17-11.44; P=.03). The incidence of post-HT CT is high and is strongly associated with pre-HT amiodarone use underpinning the importance of closely following the post-HT thyroid profile in these patients.

Spatial Changes in the Atrial Fibrillation Wave-Dynamics After Using Antiarrhythmic Drugs: A Computational Modeling Study.

Background: We previously reported that a computational modeling-guided antiarrhythmic drug (AAD) test was feasible for evaluating multiple AADs in patients with atrial fibrillation (AF). We explored the anti-AF mechanisms of AADs and spatial change in the AF wave-dynamics by a realistic computational model.Methods: We used realistic computational modeling of 25 AF patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal AF) reflecting the anatomy, histology, and electrophysiology of the left atrium (LA) to characterize the effects of five AADs (amiodarone, sotalol, dronedarone, flecainide, and propafenone). We evaluated the spatial change in the AF wave-dynamics by measuring the mean dominant frequency (DF) and its coefficient of variation [dominant frequency-coefficient of variation (DF-COV)] in 10 segments of the LA. The mean DF and DF-COV were compared according to the pulmonary vein (PV) vs. extra-PV, maximal slope of the restitution curves (Smax), and defragmentation of AF.Results: The mean DF decreased after the administration of AADs in the dose dependent manner (p < 0.001). Under AADs, the DF was significantly lower (p < 0.001) and COV-DF higher (p = 0.003) in the PV than extra-PV region. The mean DF was significantly lower at a high Smax (≥1.4) than a lower Smax condition under AADs. During the episodes of AF defragmentation, the mean DF was lower (p < 0.001), but the COV-DF was higher (p < 0.001) than that in those without defragmentation.Conclusions: The DF reduction with AADs is predominant in the PVs and during a high Smax condition and causes AF termination or defragmentation during a lower DF and spatially unstable (higher DF-COV) condition.

Computational modeling for antiarrhythmic drugs for atrial fibrillation according to the genotypes

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant [HI19C0114] from the Ministry of Health and Welfare. Additionally, the work was funded by grants [NRF-2019R1C1C100907512], and [NRF-2020R1A2B01001695] from the Basic Science Research Program run by the National Research Foundation of Korea (NRF) under the Ministry of Science, ICT &amp; Future Planning (MSIP). Background The efficacy of antiarrhythmic drugs (AAD) can vary in patients with atrial fibrillation (AF) and the PITX2 gene affects the responsiveness of AADs. We explored the virtual AAD (V-AAD) responses between wild-type and PITX2+/- deficient AF conditions by realistic in-silico AF modeling. Methods We tested the V-AADs in AF modeling integrated with patients’ 3D-computed tomography and 3D-electroanatomical mapping, acquired in 25 patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal type). The ion currents for the PITX2+/- deficiency and each AAD (amiodarone, sotalol, dronedarone, flecainide, and propafenone) were defined based on previous publications. Results We compared the wild-type and PITX2+/- deficiency in terms of the action potential duration (APD90), conduction velocity (CV), maximal slope of restitution (Smax), and wave-dynamic parameters, such as the dominant frequency (DF), phase singularities (PS), and AF termination rates according to the V-AADs. The PITX2+/- deficient model exhibited a shorter APD90 (p &amp;lt; 0.001), a lower Smax (p &amp;lt; 0.001), mean DF (p = 0.012), PS number (p &amp;lt; 0.001), and a longer AF cycle length (AFCL, p = 0.011). Five V-AADs changed the electrophysiology in a dose dependent manner. AAD-induced AFCL lengthening (p &amp;lt; 0.001) and reductions in the CV (p = 0.033), peak DF (p &amp;lt; 0.001) and PS number (p &amp;lt; 0.001) were more significant in PITX2+/- deficient than wild-type AF. PITX2+/- deficient AF was easier to terminate with class IC AADs than the wild-type AF (p = 0.018). Conclusions The computational modeling-guided AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF. AF wave-dynamics and electrophysiological characteristics are different among the PITX2 deficient and the wild-type genotype models. BaselineChanges after AADClass ICClass IIIWild-typePITX2+/-p-valueWild-typePITX2+/-p-valueWild-typePITX2+/-p-valueWild-typePITX2+/-p-valueAPD90, (ms)243.7 ± 33.8184.4 ± 15.5&amp;lt;0.00138.2 ± 37.343.4 ± 56.20.223275.9 ± 43.5219.0 ± 39.2&amp;lt;0.001284.9 ± 32.8233.8 ± 71.4&amp;lt;0.001CV, (m/s)0.78 ± 0.320.70 ± 0.210.347-0.15 ± 0.18-0.20 ± 0.260.0330.63 ± 0.320.53 ± 0.300.0270.60 ± 0.360.43 ± 0.33&amp;lt;0.001Mean Smax0.787 ± 0.280.531 ± 0.18&amp;lt;0.0010.005 ± 0.260.115 ± 0.24&amp;lt;0.0010.828 ± 0.310.694 ± 0.320.0030.768 ± 0.320.608 ± 0.27&amp;lt;0.001Mean AFCL, (ms)146.96 ± 24.61164.78 ± 22.730.01122.62 ± 24.5537.92 ± 32.72&amp;lt;0.001165.44 ± 36.96190.85 ± 35.61&amp;lt;0.001169.05 ± 25.26203.35 ± 34.78&amp;lt;0.001Peak DF, (Hz)10.68 ± 2.9711.82 ± 3.340.211-2.98 ± 4.94-5.46 ± 4.66&amp;lt;0.00110.01 ± 4.397.23 ± 4.20&amp;lt;0.0016.30 ± 4.325.80 ± 4.070.301Mean DF, (Hz)6.80 ± 0.886.22 ± 0.710.012-1.95 ± 2.44-2.20 ± 1.990.2065.75 ± 1.784.53 ± 2.00&amp;lt;0.0014.14 ± 2.393.69 ± 2.000.077PS Number, (N)101086 ± 9608814150 ± 24778&amp;lt;0.001-59322 ± 99288-7409 ± 27856&amp;lt;0.00150579 ± 6523611568 ± 21868&amp;lt;0.00132951 ± 558643524 ± 8302&amp;lt;0.001PS Life Span, (ms)109.36 ± 113.90102.24 ± 226.640.889-24.87 ± 72.06-41.38 ± 126.350.073103.36 ± 180.6868.05 ± 162.790.14871.91 ± 141.8655.99 ± 217.970.454Table. Effects of AADs in the Wild-type and PITX2+/- Deficiency groupAbstract Figure. Wild-type vs. PITX2+/- baseline model

Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype.

Background: The efficacy of antiarrhythmic drugs (AAD) can vary in patients with atrial fibrillation (AF), and the PITX2 gene affects the responsiveness of AADs. We explored the virtual AAD (V-AAD) responses between wild-type and PITX2+/−-deficient AF conditions by realistic in silico AF modeling.Methods: We tested the V-AADs in AF modeling integrated with patients' 3D-computed tomography and 3D-electroanatomical mapping, acquired in 25 patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal type). The ion currents for the PITX2+/− deficiency and each AAD (amiodarone, sotalol, dronedarone, flecainide, and propafenone) were defined based on previous publications.Results: We compared the wild-type and PITX2+/− deficiency in terms of the action potential duration (APD90), conduction velocity (CV), maximal slope of restitution (Smax), and wave-dynamic parameters, such as the dominant frequency (DF), phase singularities (PS), and AF termination rates according to the V-AADs. The PITX2+/−-deficient model exhibited a shorter APD90 (p < 0.001), a lower Smax (p < 0.001), mean DF (p = 0.012), PS number (p < 0.001), and a longer AF cycle length (AFCL, p = 0.011). Five V-AADs changed the electrophysiology in a dose-dependent manner. AAD-induced AFCL lengthening (p < 0.001) and reductions in the CV (p = 0.033), peak DF (p < 0.001), and PS number (p < 0.001) were more significant in PITX2+/−-deficient than wild-type AF. PITX2+/−-deficient AF was easier to terminate with class IC AADs than the wild-type AF (p = 0.018).Conclusions: The computational modeling-guided AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF. AF wave-dynamic and electrophysiological characteristics are different among the PITX2-deficient and the wild-type genotype models.

Assessment of Catheter Ablation or Antiarrhythmic Drugs for First-line Therapy of Atrial Fibrillation

Early rhythm control of atrial fibrillation (AF) with either antiarrhythmic drugs (AADs) or catheter ablation has been reported to improve cardiovascular outcomes compared with usual care; however, the optimal therapeutic modality to achieve early rhythm control is unclear. To assess the safety and efficacy of AF ablation as first-line therapy when compared with AADs in patients with paroxysmal AF. PubMed/MEDLINE, Scopus, Google Scholar, and various major scientific conference sessions from January 1, 2000, through November 23, 2020. Randomized clinical trials (RCTs) published in English that had at least 12 months of follow-up and compared clinical outcomes of ablation vs AADs as first-line therapy in adults with AF. The quality of individual studies was assessed using the Cochrane risk of bias tool. Six RCTs met inclusion criteria, including 1212 patients. Two investigators independently extracted data. Reporting was performed in compliance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines. Analysis was performed using a random-effects model with the Mantel-Haenszel method, and results are presented as 95% CIs. Main outcomes were safety and efficacy of AF ablation as first-line therapy when compared with AADs. Trials were evaluated as having low risk of selection and attrition biases, high risk of performance bias, and with unclear risk for detection biases due to unblinding and open-label designs. A total of 6 RCTs involving 1212 patients with AF were included (609 were randomized to AF ablation and 603 to drug therapy; mean [SD] age, 56 [11] years). Compared with AADs, catheter ablation use was associated with reductions in recurrent atrial arrhythmia (32.3% vs 53%; risk ratio [RR], 0.62; 95% CI, 0.51-0.74; P < .001; I2 = 40%), with a number needed to treat with ablation to prevent 1 arrhythmia of 5. Use of ablation was also associated with reduced symptomatic atrial arrhythmia (11.8% vs 26.4%; RR, 0.44; 95% CI, 0.27-0.72; P = .001; I2 = 54%) and hospitalization (5.6% vs 18.7%; RR, 0.32; 95% CI, 0.19-0.53; P < .001) with no significant difference in serious adverse events between the groups (4.2% vs 2.8%; RR, 1.52; 95% CI, 0.81-2.85; P = .19). In this meta-analysis of randomized clinical trials including first-line therapy of patients with paroxysmal AF, catheter ablation compared with antiarrhythmic drugs was associated with reductions in recurrence of atrial arrhythmias and hospitalizations, with no difference in major adverse events.

Antiarrhythmic drugs in patients with early persistent atrial fibrillation and heart failure: results of the RACE 3 study.

AimsMaintaining sinus rhythm in patients with persistent atrial fibrillation (AF) is challenging. We explored the efficacy of class I and III antiarrhythmic drugs (AADs) in patients with persistent AF and mild to moderate heart failure (HF).Methods and resultsIn the RACE 3 trial, patients with early persistent symptomatic AF and short history of mild to moderate HF with preserved or reduced left ventricular ejection fraction (LVEF) were randomized to targeted or conventional therapy. Both groups received AF and HF guideline-driven treatment. Additionally, the targeted-group received mineralocorticoid receptor antagonists, statins, angiotensin-converting enzyme inhibitors and/or receptor blockers, and cardiac rehabilitation. Class I and III AADs could be instituted in case of symptomatic recurrent AF. Eventually, pulmonary vein isolation could be performed. Primary endpoint was sinus rhythm on 7-day Holter after 1-year. Included were 245 patients, age 65 ± 9 years, 193 (79%) men, AF history was 3 (2–6) months, HF history 2 (1–4) months, 72 (29.4%) had HF with reduced LVEF. After baseline electrical cardioversion (ECV), 190 (77.6%) had AF recurrences; 108 (56.8%) received class I/III AADs; 19 (17.6%) flecainide, 36 (33.3%) sotalol, 3 (2.8%) dronedarone, 50 (46.3%) amiodarone. At 1-year 73 of 108 (68.0%) patients were in sinus rhythm, 44 (40.7%) without new AF recurrences. Maintenance of sinus rhythm was significantly better with amiodarone [n = 29/50 (58%)] compared with flecainide [n = 6/19 (32%)] and sotalol/dronedarone [n = 9/39 (23%)], P = 0.0064. Adverse events occurred in 27 (25.0%) patients, were all minor and reversible.ConclusionIn stable HF patients with early persistent AF, AAD treatment was effective in nearly half of patients, with no serious adverse effects reported.