Antiarrhythmic drug therapy after catheter ablation for atrial fibrillation has no impact on recurrences, cardiovascular events and mortality – insights from the German Ablation Registry

Background Data on the optimal treatment strategy for antiarrhythmic drug therapy (AAD) after atrial fibrillation (AF) catheter ablation are inconsistent. While AAD potentially stabilizes sinus rhythm, it also increases the patients' treatment burden. Methods Patients from the prospective German Ablation Registry (n=3275) discharged with or without AAD after AF catheter ablation were compared regarding long-term success, cardiovascular events and patient reported outcome. Results In patients with paroxysmal AF (n=2138) recurrence and rehospitalization rates did not differ when discharged with (n=1051) or without (n=1087) AAD (recurrence: adjusted odds ratio (OR) 1.13, 95% confidence interval (CI) [0.95–1.35]; rehospitalization: OR 1.08, 95% CI [0.90–1.30]). The reablation rate was higher and reduced treatment satisfaction was reported more often in those discharged with AAD (reablation: OR 1.30, 95% CI [1.05–1.61]; reduced treatment satisfaction: OR 1.76, 95% CI [1.20–2.58]). Similar rates of recurrences, rehospitalisations, reablations and treatment satisfaction were found in patients with persistent AF (n=1137) discharged with (n=641) or without (n=496) AAD (recurrence: OR 1.22, 95% CI [0.95–1.56]; rehospitalization: OR 1.16, 95% CI [0.90–1.50]; reablation: OR 1.21, 95% CI [0.91–1.61]; treatment satisfaction: OR 1.24, 95% CI [0.74–2.08]). The incidence of cardiovascular events and mortality did not differ at follow-up in paroxysmal and persistent AF patients discharged with or without AAD. Conclusion The rates of recurrences, cardiovascular events and mortality did not differ between patients discharged with or without AAD after AF catheter ablation. However, AAD should be considered carefully in patients with paroxysmal AF, in whom it was associated with a higher reablation rate and reduced treatment satisfaction. FUNDunding Acknowledgement Type of funding sources: None.

Amiodarone and amplitude spectral area of ventricular fibrillation in patients with out-of-hospital cardiac arrest

Background Ventricular fibrillation is the most common cause of out-of-hospital cardiac arrest (OHCA) and the use of antiarrhythmic drug therapy is usually recommended in addition to defibrillation. The role of the amplitude spectral area (AMSA) of ventricular fibrillation as a predictor of defibrillation efficacy has been established, while the existing data in favour of the use of amiodarone has been assessed with poor evidence and controversy. Purpose The aim of our study is to evaluate whether the administration of amiodarone during resuscitation could affect AMSA values. Materials All the OHCAs with a shockable presenting rhythm and attempted resuscitation which occurred from January 2015 to June 2019 in the province of Pavia were considered. Both the end-tidal CO2 (ETCO2) and AMSA values were calculated by retrospectively analyzing the data collected by the Corpuls 3 monitors/defibrillators (Corpuls, Kaufering, Germany) used in the territory and by considering a pre-shock interval of 2 seconds. Results Among a total of 3413 OHCAs, resuscitation was attempted in 2195 cases (64%), 377 (17%) had a shockable presenting rhythm and in 112 cases (3.4%) it was possible to obtain the values of ETCO2 and AMSA for a total of 391 shocks. Among these, 301 shocks (77%) were delivered to patients who received amiodarone during resuscitation. The success rate of each single shock was similar in the two groups but with an unfavorable trend for amiodarone (amiodarone 43.5% vs no amiodarone 54.4%, p=0.07). AMSA was significantly lower in patients treated with amiodarone (7.9 mV·Hz, IQR 5.4–12.2 vs 10.6 mV·Hz, IQR 7.1–14.1; p<0.001). According to a multivariate analysis, the administration of amiodarone and the time to shock were independent predictors of AMSA values. Lastly, on a sample of 124 shocks, homogeneous for age, sex, ETCO2, outcome of resuscitation and randomly matched, the AMSA of patients who received amiodarone was significantly lower (7.2 mV·Hz, IQR 7.2–11.7 vs 9.7 mV·Hz, IQR 6.7–12.5; p=0.02). Conclusions Our results indicate that amiodarone administration is associated with lower values of AMSA. Since higher AMSA values are known to be associated with a higher probability of shock rate success, this could help to better clarify the controversial role of amiodarone administration in patients with OHCA. FUNDunding Acknowledgement Type of funding sources: None.

Cardiac Sympathetic Activity and Rhythm Control Following Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation—A Prospective 123I-mIBG-SPECT/CT Imaging Study

Background: Pulmonary vein isolation (PVI) and antiarrhythmic drug therapy are established treatment strategies to preserve sinus rhythm in atrial fibrillation (AF). However, the efficacy of both interventional and pharmaceutical therapy is still limited. Solid evidence suggests an important role of the cardiac sympathetic nervous system in AF. In this blinded, prospective observational study, we studied left ventricular cardiac sympathetic activity in patients treated with PVI and with antiarrhythmic drugs. Prospectively, Iodine-123-benzyl-guanidine single photon emission computer tomography (123I-mIBG-SPECT) was performed in a total of 23 patients with paroxysmal AF, who underwent PVI (n = 20) or received antiarrhythmic drug therapy only (n = 3), respectively. 123I-mIBG planar and SPECT/CT scans were performed before and 4 to 8 weeks after PVI (or initiation of drug therapy, respectively). For semiquantitative SPECT image analysis, attenuation-corrected early/late images were analyzed. Quantitative SPECT analysis was performed using the AHA 17-segment model of the left ventricle. Results: PVI with point-by-point radiofrequency ablation led to a significantly (p < 0.05) higher visual sympathetic innervation defect score when comparing pre-and post PVI. Newly emerging innervation deficits post PVI were localized predominantly in the inferior lateral wall. These findings were corroborated by semiquantitative SPECT analysis identifying inferolateral segments with a reduced tracer uptake in comparison to SPECT before PVI. Following PVI, patients with an AF relapse showed a different sympathetic innervation pattern compared to patients with sufficient rhythm control. Conclusions: PVI results in novel defects of cardiac sympathetic innervation. Differences in cardiac sympathetic innervation remodelling following PVI suggest an important role of the cardiac autonomous nervous system in the maintenance of sinus rhythm following PVI.

Comparative effectiveness of ventricular tachycardia ablation versus escalated antiarrhythmic drug therapy by location of myocardial infarction: A sub-study of the VANISH trial

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Fonds de recherché du Québec-Santé (FRQS) [post doctoral award for Dr. Samuel) BACKGROUND Complexity of ventricular tachycardia (VT) substrate, efficiency of lesion formation, and the size and thickness of infarction area border zones differ based on location of myocardial infarctions (MI). These differences may translate into heterogeneity in risk of events and effectiveness of treatments for VT. Small observational studies suggest that VT from inferior infarctions have higher risk of early recurrence despite smaller infarct areas. However, differential effectiveness of VT treatments based on location of MI not been definitively established. PURPOSE The objective of this sub-study of the Ventricular tachycardia AblatioN versus escalated antiarrhythmic drug therapy in ISchemic Heart disease (VANISH) randomized trial was to compare the effectiveness of VT ablation by location of MI in reducing the composite endpoint of all-cause mortality, VT storm, or appropriate ICD therapy when compared to escalated pharmacological therapy in VT patients with a prior MI. METHODS VANISH participants were categorized into 3 subgroups based on MI location: 1. Inferior (may also have MI in other locations); 2. Non-inferior (no inferior MI, all patients not in group 1); and 3. Anterior (may also have MI in other locations). Inverse probability of treatment weighting was used to balance baseline characteristics (ie. age, sex, comorbidities, medications, and the location of additional infarctions) between patients randomized to ablation or escalated therapy within each subgroup. Weighted Cox proportional hazards models were calculated separately for each subgroup. RESULTS Of 259 patients enrolled in the VANISH trial [median age 69.8 (IQR 63.0-74.2) years, 7.0% women], 135 had an inferior MI, 124 a non-inferior MI, and 83 an anterior MI. Among patients with an inferior MI, no statistically significant difference in the primary outcome was detected between patients randomized to ablation or escalated therapy [aHR 0.78 (95% CI 0.51-1.20)]. In contrast, patients with non-inferior MIs had a statistically significant reduction in the incidence of the primary outcome with ablation [aHR 0.48 (95% CI 0.27-0.86)]; which was of greater magnitude than the reduction observed in the overall results of the VANISH trial [HR 0.72 (95% CI 0.53-0.98)]. In addition, a trend towards a reduction in the primary outcome with ablation was detected in patients with anterior MIs [aHR 0.50 (95% CI 0.23-1.09)]. CONCLUSION The effectiveness of VT ablation versus escalated pharmacological therapy varies based on the location of the MI. Patients with MI scars located only in non-inferior regions of the ventricles derive greater benefit from VT ablation in reducing VT-related events. Further studies are required to explore reasons for this finding and to assess the impact of VT treatment strategies based on MI location in optimizing outcomes.

The RACE to the EAST. In pursuit of rhythm control therapy for atrial fibrillation—a dedication to Harry Crijns

The RACE trial was one of the first landmark trials to establish whether restoring and maintaining sinus rhythm could reduce morbidity and mortality in patients with atrial fibrillation (AF). Its neutral outcome shaped clinical decision-making for almost 20 years. However, there were two important treatment-related factors associated with mortality of rhythm control therapy at that time: One was safety of antiarrhythmic drug therapy, and the other one withdrawal of anticoagulation after restoration of sinus rhythm. Both concerns have been overcome, and, moreover, important knowledge considering the importance of time for the treatment of AF has been gained. These insights led to the concept of the EAST-AFNET 4 trial, and after more than two decades in the pursuit of ongoing therapeutic improvement, early rhythm control therapy has demonstrated to reduce a composite of cardiovascular death, stroke, and hospitalization for worsening of HF or acute coronary syndrome, by 21% (first primary outcome, absolute reduction 1.1 per 100 patient-years). For this entire period, Harry Crijns characterized the treatment of AF patients, and contributed decisively to realizing the benefit of rhythm control therapy. It is almost easier to list the clinical trials without Harry's involvement than to list those which he co-designed and led.

Whole Food Plant-Based Diet as a Treatment of Recurrent Atrial Fibrillation Following Catheter Ablation

Atrial fibrillation (af) may recur despite antiarrhythmic drug therapy or catheter ablation. is case reports such a scenario of a patient with recurrent paroxysms of af following catheter ablation that resolved following institution of a whole-food, plant-based diet. us, a change to a whole-food, plant-based diet may be an effective intervention for reducing or eliminating af recurrence.

Electrical Substrate Ablation for Refractory Ventricular Fibrillation: Results of the AVATAR Study

Background - Refractory ventricular fibrillation (VF) is a challenging clinical entity, for which ablation of triggering premature ventricular complexes (PVCs) is described. When PVCs are infrequent and multifocal, the optimal treatment strategy is uncertain. Methods - We prospectively enrolled consecutive patients presenting with multiple ICD shocks for VF refractory to antiarrhythmic drug therapy, exhibiting infrequent (≤3%), multifocal PVCs (≥3 morphologies). Procedurally, VF was induced with rapid pacing and mapped, identifying sites of conduction slowing and rotation or rapid focal activation. VF electrical substrate ablation (VESA) was then performed. Outcomes were compared against reference patients with VF who were unable or unwilling to undergo catheter ablation. The primary outcome was a composite of ICD shock, electrical storm, or all-cause mortality. Results - VF was induced and mapped in 6 patients (60±10 y, LVEF 46±19%) with ischemic (n=3) and nonischemic cardiomyopathy. An average of 3.3±0.5 sites of localized reentry during VF were targeted for radiofrequency ablation (38.3±10.9 minutes) during sinus rhythm, rendering VF non-inducible with pacing. Freedom from the primary outcome was 83% in the VF ablation group versus 17% in 6 non-ablation reference patients at a median of 1.0 years (IQR 0.5-1.5 years, p=0.046) follow-up. Conclusions - VESA is associated with a reduction in the combined endpoint compared with the non-ablation reference group. Additional work is required to understand the precise pathophysiologic changes which promote VF in order to improve preventative and therapeutic strategies.