A randomized clinical trial of catheter ablation and antiarrhythmic drug therapy for suppression of ventricular tachycardia in ischemic cardiomyopathy: The VANISH2 trial.

BACKGROUND: Recurrent ventricular tachycardia (VT) in patients with prior myocardial infarction is associated with adverse quality of life and clinical outcomes, despite the presence of implanted defibrillators (ICDs). Suppression of recurrent VT can be accomplished with antiarrhythmic drug therapy or catheter ablation. The Ventricular Tachycardia Antiarrhythmics or Ablation In Structural Heart Disease 2 (VANISH2) trial is designed to determine whether ablation is superior to antiarrhythmic drug therapy as first line therapy for patients with ischemic cardiomyopathy and VT. METHODS: The VANISH2 trial enrolls patients with prior myocardial infarction and VT (with one of: ≥1 ICD shock; ≥3 episodes treated with antitachycardia pacing (ATP) and symptoms; ≥5 episodes treated with ATP regardless of symptoms; ≥3 episodes within 24 hours; or sustained VT treated with electrical cardioversion or pharmacologic conversion). Enrolled patients are classified as either sotalol-eligible, or amiodarone-eligible, and then are randomized to either catheter ablation or to that antiarrhythmic drug therapy, with randomization stratified by drug-eligibility group. Drug therapy, catheter ablation procedures and ICD programming are standardized. All patients will be followed until two years after randomization. The primary endpoint is a composite of mortality at any time, appropriate ICD shock after 14 days, VT storm after 14 days, and treated sustained VT below detection of the ICD after 14 days. The outcomes will be analyzed according to the intention-to-treat principle using survival analysis techniques RESULTS: The results of the VANISH2 trial are intended to provide data to support clinical decisions on how to suppress VT for patients with prior myocardial infarction. CLINICALTRIALS: gov registration NCT02830360.

Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results from the RAFT-AF trial.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) frequently coexist and can be challenging to treat. Pharmacologically based rhythm control of AF has not proven to be superior to rate control. Ablation-based rhythm control was compared with rate control to evaluate if clinical outcomes in patients with HF and AF could be improved. METHODS: This was a multicenter, open-label trial with blinded outcome evaluation using a central adjudication committee. Patients with high-burden paroxysmal (>4 episodes in 6 months) or persistent (duration <3 years) AF, New York Heart Association class II to III HF, and elevated NT-proBNP (N-terminal pro brain natriuretic peptide) were randomly assigned to ablation-based rhythm control or rate control. The primary outcome was a composite of all-cause mortality and all HF events, with a minimum follow-up of 2 years. Secondary outcomes included left ventricular ejection fraction, 6-minute walk test, and NT-proBNP. Quality of life was measured using the Minnesota Living With Heart Failure Questionnaire and the AF Effect on Quality of Life. The primary analysis was time-to-event using Cox proportional hazards modeling. The trial was stopped early because of a determination of apparent futility by the Data Safety Monitoring Committee. RESULTS: From December 1, 2011, to January 20, 2018, 411 patients were randomly assigned to ablation-based rhythm control (n=214) or rate control (n=197). The primary outcome occurred in 50 (23.4%) patients in the ablation-based rhythm-control group and 64 (32.5%) patients in the rate-control group (hazard ratio, 0.71 [95% CI, 0.49-1.03]; P=0.066). Left ventricular ejection fraction increased in the ablation-based group (10.1±1.2% versus 3.8±1.2%, P=0.017), 6-minute walk distance improved (44.9±9.1 m versus 27.5±9.7 m, P=0.025), and NT-proBNP demonstrated a decrease (mean change -77.1% versus -39.2%, P<0.0001). Minnesota Living With Heart Failure Questionnaire demonstrated greater improvement in the ablation-based rhythm-control group (least-squares mean difference of -5.4 [95% CI, -10.5 to -0.3]; P=0.0036), as did the AF Effect on Quality of Life score (least-squares mean difference of 6.2 [95% CI, 1.7-10.7]; P=0.0005). Serious adverse events were observed in 50% of patients in both treatment groups. CONCLUSIONS: In patients with high-burden AF and HF, there was no statistical difference in all-cause mortality or HF events with ablation-based rhythm control versus rate control; however, there was a nonsignificant trend for improved outcomes with ablation-based rhythm control over rate control. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01420393.

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

AIMS: Complexity of the ventricular tachycardia (VT) substrate and the size and thickness of infarction area border zones differ based on location of myocardial infarctions (MIs). These differences may translate into heterogeneity in the effectiveness of treatments. This study aims to examine the influence of infarct location on the effectiveness of VT ablation in comparison with escalated pharmacological therapy in patients with prior MI and antiarrhythmic drug (AAD)-refractory VT. METHODS AND RESULTS: VANISH trial participants were categorized based on the presence or absence of an inferior MI scar. Inverse probability of treatment weighted Cox models were calculated for each subgroup. Of 259 randomized patients (median age 69.8 years, 7.0% women), 135 had an inferior MI and 124 had a non-inferior MI. Among patients with an inferior MI, no statistically significant difference in the composite primary outcome of all-cause mortality, appropriate implantable cardioverter-defibrillator (ICD) shock, and VT storm was detected between treatment arms [adjusted hazard ratio (aHR) 0.80, 95% confidence interval (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). In a sensitivity analysis of anterior MI patients (n = 83), a trend towards a reduction in the primary outcome with ablation was detected (aHR 0.50, 95% CI 0.23-1.09). CONCLUSION: The effectiveness of VT ablation versus escalated AADs 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 comparison to escalation of AADs in reducing VT-related events.

Ventricular tachycardia characteristics and outcomes with catheter ablation vs. antiarrhythmic therapy: insights from the VANISH trial.

AIMS: Catheter ablation is superior to escalated antiarrhythmic drugs among patients with ventricular tachycardia (VT) and prior myocardial infarction (MI). However, it is uncertain whether clinical VT characteristics, should influence choice of therapy. The purpose of this study was to evaluate whether presentation with electrical storm and the clinical VT cycle length predicted response to ablation vs. escalated antiarrhythmic therapy. METHODS AND RESULTS: All patients enrolled in the Ventricular Tachycardia Ablation vs. Escalated Antiarrhythmic Drug Therapy in Ischaemic Heart Disease (VANISH) trial were included. The association between VT cycle length and presentation with electrical storm and the primary outcome of death, subsequent VT storm or appropriate ICD shock was evaluated. Among the study population of 259 patients, escalated antiarrhythmic drug therapy had worse outcomes for those presenting with a VT cycle length >400 ms [<150 b.p.m., 89/259, hazard ratio (HR) 1.7 (1.02-3.13)]. This effect was more pronounced among those taking amiodarone at baseline [HR of 2.22 (1.19-4.16)]. Presentation with VT storm (32/259) did not affect the primary outcome between groups. However, those presenting with VT storm on amiodarone had a trend towards worse outcomes with escalated antiarrhythmic therapy [HR 4.31 (0.55-33.93)]. CONCLUSION: The VT cycle length can influence response to either ablation or escalated drug therapy in patients with VT and prior MI. Those with slow VT had improved outcomes with ablation. Patients presenting with electrical storm demonstrated similar outcomes to the overall trial population, with a trend to benefit of catheter ablation, particularly in those on amiodarone.

Effect of coronary revascularization on long-term clinical outcomes in patients with ischemic cardiomyopathy and recurrent ventricular arrhythmia.

BACKGROUND: Patients with ventricular tachycardia (VT) postmyocardial infarction (MI) are a higher risk group with significant morbidity and mortality. We examined the impact of prior coronary revascularization on clinical outcomes in patients with ischemic cardiomyopathy and VT. METHODS: The VANISH trial randomized 259 patients with prior MI and antiarrhythmic drug-refractory VT to receive escalated medical therapy or catheter ablation. Clinical outcomes were compared according to whether patients have undergone prior revascularization procedures. The primary outcome was a composite of death, appropriate implantable cardiac defibrillator (ICD) shock, or VT storm. The secondary outcomes included elements of the primary outcome, hospitalization, and any ventricular arrhythmia. RESULTS: 190 patients (73%) had prior coronary revascularization. Revascularization group had more men (97% vs 83%; P  =  0.0003) and patients in that group were older (mean age 69.3 ± 7.6 vs 66.7 ± 9.2; P  =  0.04), had more renal insufficiency (22.6% vs 8.7%; P  =  0.01), and were more likely to have an implanted cardiac resynchronization device (23% vs 10%, P  =  0.03) as compared with the nonrevascularized patients. There were no significant differences in baseline medication use. There was a trend toward fewer hospitalizations in the revascularization group (64% vs 77%; P  =  0.07); there were no differences in the individual outcomes of mortality, VT storm, ICD shocks, recurrent MI, or cardiac failure. CONCLUSIONS: In this cohort of patients with an ischemic cause for VT, a history of prior coronary revascularization was not associated with a reduction in ventricular arrhythmia or mortality.

Recent Insights Into Mechanisms and Clinical Approaches to Electrical Storm.

Electrical storm, characterized by repetitive ventricular tachycardia/ventricular fibrillation over a short period, is becoming more common with widespread use of implantable cardioverter defibrillator (ICD) therapy. Electrical storm, sometimes called "arrhythmic storm" or "ventricular tachycardia storm," is usually a medical emergency requiring hospitalization and expert management, and significantly affects short- and long-term outcomes. This syndrome typically occurs in patients with underlying structural heart disease (ischemic or nonischemic cardiomyopathy) or inherited channelopathies. Triggers for electrical storm should be sought but are often unidentifiable. Initial management is dictated by the hemodynamic status, whereas subsequent management typically involves ICD interrogation and reprogramming to reduce recurrent shocks, identification and management of triggers like electrolyte abnormalities, myocardial ischemia, or decompensated heart failure, and antiarrhythmic drug therapy or catheter ablation. Sympathetic nervous system activation is central to the initiation and maintenance of arrhythmic storm, so autonomic modulation is a cornerstone of management. Sympathetic inhibition can be achieved with medications (particularly ß-adrenoreceptor blockers), deep sedation, or cardiac sympathetic denervation. More definitive management targets the underlying ventricular arrhythmia substrate to terminate and prevent recurrent arrhythmia. Arrhythmia targeting can be achieved with antiarrhythmic medications, catheter ablation, or more novel therapies, such as stereotactic radiation therapy, that target the arrhythmic substrate. Mechanistic studies point to adrenergic activation and other direct consequences of ICD shocks in promoting further arrhythmogenesis and hypocontractility. In this report, we review the pathophysiologic mechanisms, clinical features, prognosis, and therapeutic options for electrical storm. We also outline a clinical approach to this challenging and complex condition, along with its mechanistic basis.

Responding to Cardiac Arrest in the Community in the Digital Age.

Sudden cardiac arrest (SCA) is a common event, affecting almost 400,000 individuals annually in North America. Initiation of cardiopulmonary resuscitation (CPR) and early defibrillation using an automated external defibrillator (AED) are critical for survival, yet many bystanders are reluctant to intervene. Digital technologies, including mobile devices, social media, and crowdsourcing might help play a role to improve survival from SCA. In this article we review the current digital tools and strategies available to increase rates of bystander recognition of SCA, prompt immediate activation of emergency medical services (EMS), initiate high-quality CPR, and to locate, retrieve, and operate AEDs. Smartphones can help to educate and connect bystanders with EMS dispatchers, through text messaging or video calling, to encourage the initiation of CPR and retrieval of the closest AED. Wearable devices and household smart speakers could play a future role in continuous vital signs monitoring in individuals at risk of lethal arrhythmias and send an alert to either chosen contacts or EMS. Machine learning algorithms and mathematical modelling might aid EMS dispatchers with better recognition of SCA as well as policymakers with where to best place AEDs for optimal accessibility. There are challenges with the use of digital tech, including the need for government regulation and issues with data ownership, accessibility, and interoperability. Future research will include smart cities, e-linkages, new technologies, and using social media for mass education. Together or in combination, these emerging digital technologies might represent the next leap forward in SCA survival.

Intramural Needle Ablation for Refractory Premature Ventricular Contractions.

BACKGROUND: Frequent premature ventricular contractions (PVCs) are often amenable to catheter ablation. However, a deep intramural focus may lead to failure due to inability of standard ablation techniques to penetrate the focus. We sought to assess the efficacy and safety of infusion needle ablation (INA) for PVCs that are refractory to standard radiofrequency ablation. METHODS: Under 2 Food and Drug Administration approved protocols, INA was evaluated in patients with frequent PVCs that were refractory to standard ablation. Initial targets for ablation were selected by standard mapping techniques. INA was performed with a deflectable catheter equipped with an extendable/retractable needle at the tip that can be extended up to 12 mm into the myocardium and is capable of pacing and recording. After contrast injection for location assessment, radiofrequency ablation was performed with the needle tip using a temperature-controlled mode (maximum temperature 60 °C) with saline infusion from the needle. The primary end point was a decrease in PVC burden to <5000/24 hours at 6 months. The primary safety end point was incidence of procedure- or device-related serious adverse events. RESULTS: At 4 centers, 35 patients (age 55.3±16.9 years, 74.2% male) underwent INA. The baseline median PVC burden was 25.4% (interquartile range, 18.4%-33.9%) and mean left ventricular ejection fraction was 37.7±12.3%. Delivering 10.3±8.0 INA lesions/patient (91% had adjunctive standard radiofrequency ablation also) resulted in acute PVC elimination in 71.4%. After a mean follow-up of 156±109 days, the primary efficacy end point was met in 73.3%. The median PVC burden decreased to 0.8% (interquartile range, 0.1%-6.0%; P<0.001). The primary safety end point occurred in 14.3% consisting of 1 (2.9%) heart block, 1 (2.9%) femoral artery dissection, and 3 (8.6%) pericardial effusions (all treated percutaneously). CONCLUSIONS: INA is effective for the elimination of frequent PVCs that are refractory to conventional ablation and is associated with an acceptable safety profile. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01791543 and NCT03204981.

The role of catheter ablation for ventricular tachycardia in patients with ischemic heart disease.

PURPOSE OF REVIEW: Catheter ablation has evolved remarkably over the last 2 decades, bringing nonpharmacologic therapy to complex arrhythmias like atrial fibrillation and scar-related ventricular tachycardia. As our therapeutic options have increased for patients with ventricular tachycardia, choosing the right therapy for the right patient has become more complex. Ablation carries acute and perhaps longer-term procedural risk and variable success, whereas drug therapy likewise is limited by both side-effects and efficacy. RECENT FINDINGS: Early randomized trials of catheter ablation for ventricular tachycardia and multicenter experiences have recently been published, and further studies are underway to define the appropriate application of this therapy. Randomized trials have demonstrated that catheter ablation can reduce ventricular tachycardia episodes with relatively low risk. Multicenter experience has demonstrated a moderate risk of serious procedural adverse events in this very sick population, but ablation has never been compared directly with antiarrhythmic drug therapy. SUMMARY: There is still little evidence to clarify the relative merits of antiarrhythmic drug therapy in comparison with ablation. The optimal role of either therapy will remain uncertain until the completion of trials currently in progress. Until further evidence is available, most clinicians advocate first-line antiarrhythmic drug therapy, and reserve catheter ablation for when this fails or is not tolerated.

Guidance on Minimizing Risk of Drug-Induced Ventricular Arrhythmia During Treatment of COVID-19: A Statement from the Canadian Heart Rhythm Society.

The COVID-19 pandemic has led to efforts at rapid investigation and application of drugs which may improve prognosis but for which safety and efficacy are not yet established. This document attempts to provide reasonable guidance for the use of antimicrobials which have uncertain benefit but may increase risk of QT interval prolongation and ventricular proarrhythmia, notably, chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir. During the pandemic, efforts to reduce spread and minimize effects on health care resources mandate minimization of unnecessary medical procedures and testing. We recommend that the risk of drug proarrhythmia be minimized by 1) discontinuing unnecessary medications that may also increase the QT interval, 2) identifying outpatients who are likely to be at low risk and do not need further testing (no history of prolonged QT interval, unexplained syncope, or family history of premature sudden cardiac death, no medications that may prolong the QT interval, and/or a previous known normal corrected QT interval [QTc]), and 3) performing baseline testing in hospitalized patients or those who may be at higher risk. If baseline electrocardiographic testing reveals a moderately prolonged QTc, optimization of medications and electrolytes may permit therapy. If the QTc is markedly prolonged, drugs that further prolong it should be avoided, or expert consultation may permit administration with mitigating precautions. These recommendations are made while there are no known effective treatments for COVID-19 and should be revisited when further data on efficacy and safety become available.

Mapping and ablation of multiple atrial arrhythmias in a patient with persistent atrial standstill after remote viral myocarditis.

This is a case of multiple atrial arrhythmias (atrioventricular node reentry and two different focal atrial tachycardias) originating from the remaining atrial myocardium after global scarring of both atria following a remote viral myocarditis. All the induced arrhythmias were successfully treated with catheter ablation.

Body-surface potential mapping to aid ablation of scar-related ventricular tachycardia.

We investigated whether body-surface potential mapping (BSPM) during catheter ablation of scar-related ventricular tachycardia (VT) could assist with the identification of VT exit sites. The study population consisted of 9 patients who underwent catheter ablation for VT, among whom 12 induced VTs with known exit sites were identified by entrainment criteria, pace mapping, or site of successful ablation. Paced activation was initiated at various intracardiac sites (20 +/- 4 sites per patient, a total of 180) documented by nonfluoroscopic electroanatomic mapping. During all episodes of VT and pacing, patients had a 120-lead electrocardiogram recorded, and we analyzed these electrocardiographic data--by means of a similarity coefficient (SC) calculated over 100 milliseconds after the initiation of depolarization--to assess the similarity between the BSPM sequences occurring during VTs and those induced by pacing. Based on 245 observations, the relationship between the SC and the distance of the pacing site from the VT exit site was then obtained for each individual VT by linear regression analysis: the distance D (in millimeters) from the VT exit site was related to SC by the regression equation D = slope (1 - SC2) + intercept. The parameters in this equation varied widely for the 12 VTs, but, in general, the nearer the pacing site was to the exit site, the better the goodness of match. This suggests that, although there is no universally applicable relationship between D and SC, BSPM could provide a useful adjunct to standard pace mapping, although additional processing--namely, an inverse calculation of epicardial potentials/isochrones--may be needed to reliably identify VT exit sites from body-surface electrocardiograms.

Catheter ablation for ventricular tachycardia in structural heart disease.

The management of ventricular tachyarrhythmias has changed significantly over the past several decades. The advent of readily available implantable cardioverter defibrillators (ICDs) has had the greatest effect, with important mortality effects in patients with ventricular tachycardia and structural heart disease. ICDs have been shown to reduce sudden death in patients with ischemic and nonischemic cardiomyopathies; evidence of adverse consequences of ICD shocks, however, is mounting. In addition to the negative effects on patient-reported quality of life, anxiety, and depression, frequent ventricular arrhythmias and ICD shocks have also been associated with increased mortality. It is therefore important to identify and implement effective ventricular tachycardia-suppressive strategies. Antiarrhythmic drugs represent one such method, but are challenged by unfavourable side effect profiles and proarrhythmic risk. Catheter ablation of ventricular tachycardia is now a well-accepted intervention, which has been demonstrated to reduce recurrent arrhythmias. Questions persist regarding the optimal role for ablation compared with drug therapy.