VANISH Trial Research Articles

Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being. VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied. Metrics correlating with baseline HRQOL and CPET performance were identified. The impact of valsartan treatment on these measures was analyzed in the early stage cohort. Two hundred participants were included: 166 with early stage HCM (mean age, 23±10 years; 40% female; 97% White; and 92% New York Heart Association class I) and 34 subclinical sarcomere variant carriers (mean age, 16±5 years; 50% female; and 100% White). Baseline HRQOL was good in both cohorts, although slightly better in subclinical HCM (composite pediatric quality of life score 84.6±10.6 versus 90.2±9.8; P=0.005). Both cohorts demonstrated mildly reduced functional status (mean percent predicted peak oxygen uptake 73±16 versus 78±12 mL/kg per minute; P=0.18). Percent predicted peak oxygen uptake and peak oxygen pulse correlated with HRQOL. Valsartan improved physical HRQOL in early stage HCM (adjusted mean change in pediatric quality of life score +4.1 versus placebo; P=0.01) but did not significantly impact CPET performance. Functional capacity can be impaired in young, healthy people with early stage HCM, despite New York Heart Association class I status and good HRQOL. Peak oxygen uptake was similarly decreased in subclinical HCM despite normal left ventricular wall thickness and excellent HRQOL. Valsartan improved physical pediatric quality of life scores but did not significantly impact CPET performance. Further studies are needed for validation and to understand how to improve patient experience. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01912534.

Host and Microbe Blood Metagenomics Reveals Key Pathways Characterizing Critical Illness Phenotypes.

Rationale: Two molecular phenotypes of sepsis and acute respiratory distress syndrome, termed hyperinflammatory and hypoinflammatory, have been consistently identified by latent class analysis in numerous cohorts, with widely divergent clinical outcomes and differential responses to some treatments; however, the key biological differences between these phenotypes remain poorly understood.Objectives: We used host and microbe metagenomic sequencing data from blood to deepen our understanding of biological differences between latent class analysis-derived phenotypes and to assess concordance between the latent class analysis-derived phenotypes and phenotypes reported by other investigative groups (e.g., Sepsis Response Signature [SRS1-2], molecular diagnosis and risk stratification of sepsis [MARS1-4], reactive and uninflamed).Methods: We analyzed data from 113 patients with hypoinflammatory sepsis and 76 patients with hyperinflammatory sepsis enrolled in a two-hospital prospective cohort study. Molecular phenotypes had been previously assigned using latent class analysis.Measurements and Main Results: The hyperinflammatory and hypoinflammatory phenotypes of sepsis had distinct gene expression signatures, with 5,755 genes (31%) differentially expressed. The hyperinflammatory phenotype was associated with elevated expression of innate immune response genes, whereas the hypoinflammatory phenotype was associated with elevated expression of adaptive immune response genes and, notably, T cell response genes. Plasma metagenomic analysis identified differences in prevalence of bacteremia, bacterial DNA abundance, and composition between the phenotypes, with an increased presence and abundance of Enterobacteriaceae in the hyperinflammatory phenotype. Significant overlap was observed between these phenotypes and previously identified transcriptional subtypes of acute respiratory distress syndrome (reactive and uninflamed) and sepsis (SRS1-2). Analysis of data from the VANISH trial indicated that corticosteroids might have a detrimental effect in patients with the hypoinflammatory phenotype.Conclusions: The hyperinflammatory and hypoinflammatory phenotypes have distinct transcriptional and metagenomic features that could be leveraged for precision treatment strategies.

Abstract 12135: Quality of Life in Early-Stage Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial

Background: The VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) showed valsartan improves LV remodeling in early-stage HCM, but its effects on quality of life (QOL) are unknown. A better understanding of QOL may impact patient wellness. Aims: Describe baseline QOL in early-stage HCM. Assess the impact of valsartan on QOL in early-stage HCM. Methods: We evaluated QOL using age-adjusted versions of the Pediatric Quality of Life Inventory in VANISH participants (ages 8-45): 166 with early-stage HCM, 34 with subclinical HCM (sarcomere variant present but normal LV wall thickness/no HCM diagnosis). Demographic, imaging, CPET, and biomarker correlates of baseline QOL were studied. The impact of valsartan on QOL was analyzed in the early-stage HCM cohort. Results: Participants with early-stage HCM reported good baseline QOL, better than an earlier published healthy validation cohort but diminished compared to subclinical participants (mean overall/physical/psychosocial scores 85/87/84 for early-stage, 90/92/89 subclinical, 82/84/81 earlier validation cohort). Race and ethnicity influenced QOL, with non-white and Hispanic participants reporting lower scores (Table 1). Valsartan improved physical QOL (p=0.03), with suggestion of differential effect by sex and pubertal status, but limited power to detect effect modification (Figure 1). Conclusion: Baseline QOL is lower in patients with early-stage HCM compared to subclinical participants despite NYHA I status. Non-white and Hispanic participants and those with lower baseline peak VO 2 may have lower quality of life. Valsartan treatment improved physical QOL.

Angiotensin receptor blockers in patients with hypertrophic cardiomyopathy: A comparison of VANISH and INHERIT randomized trials

To identify the cause of discrepancy between the INHERIT trial and VANISH trial in regards to disease modification of angiotensin receptor II blockers in hypertrophic cardiomyopathy (HCM). We replicated the data analysis used in VANISH, converting individual change in each component of the composite endpoint into a z-score and applying this z-score to the INHERIT results. No significant improvement was identified in the composite z-score between the 2 groups at 12-month follow-up (P=.4). With the exception of tissue Doppler systolic (s') velocity, we found no significant benefit or harm from losartan compared to placebo for any of the individual components of the composite score at 12-month follow-up. Results were similar in analyses without imputed data or when restricted to patients with sarcomeric HCM. Despite applying the potentially more sensitive composite z-score endpoint as in the VANISH trial, no statistically significant benefits from the use of losartan compared to placebo could be detected at 12-month follow-up in patients with overt HCM participating in the INHERIT trial.

Reduction in shock burden with catheter ablation versus escalated antiarrhythmic drug therapy: Insights from the VANISH trial

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 1. Canadian Institutes of Health Research (CIHR) 2. Additional financial support from St. Jude Medical and Biosense Webster Background Recurrent shocks for ventricular tachycardia (VT) are associated with an increased risk of heart failure and mortality and have a negative influence on quality of life. Catheter ablation has been shown to improve VT event-free survival in patients with antiarrhythmic drug (AAD)-refractory VT and prior myocardial infarction (MI); however, the effects of ablation on shock burden has yet to be investigated. Purpose Our primary objectives were to compare the shock-treated VT event burden and appropriate shock burden following randomization to treatment with either catheter ablation or escalated AAD therapy among VT patients with prior MI in the Ventricular tachycardia AblatioN versus escalated antiarrhythmic drug therapy in Ischemic Heart disease (VANISH) randomized trial. Methods Recurrent event analyses were performed using the intention-to-treat population of the VANISH trial. Shock-treated VT event burden was defined as the total number of VT events treated with ≥1 appropriate internal or external shocks. Appropriate shock burden was defined as the total number of appropriate internal and external shocks delivered, regardless of the number of VT events. All VT events and implantable cardioverter defibrillator (ICD) therapies were adjudicated by reviewers blinded to the treatment allocation. Three recurrent event models were used to compare the shock burden between treatment arms (Anderson-Gill (AG), Frailty, and Prentice, Williams, and Peterson Total Time (PWP-TT). Each model clustered by patient and accounted for competing risk of death with the Fine and Gray sub-distributions hazards model. Results Of the 259 patients enrolled in the VANISH trial [median age 69.8 (IQR 63.0-74.2) years, 7.0% women], 132 patients were randomized to ablation and 129 patients to escalated AAD therapy. Over a median follow-up of 23.4 (IQR 14.7-40.4) months, there were 138 shock-treated VT events [39.07 (95% CI 33.14-46.07) shock-treated VT events per 100 person-years] in the ablation arm and 218 shock-treated VT events [64.60 (95% CI 56.49–73.84) shock-treated VT events per 100 person-years] in the escalated AAD therapy arm (Figure 1). Ablation patients had a 40% lower shock-treated VT event burden (ie. number of shock-treated VT events) compared to patients randomized to escalated AAD therapy [Figure 1; AG HR 0.60 (95% 0.38-0.95)]. Further, there was also a statistically significant reduction in the appropriate shock burden (i.e. number of appropriate shocks) among ablation patients (169 appropriate shocks) compared to escalated AAD therapy patients (266 appropriate shocks) [Figure 1; AG HR 0.61 (95% CI 0.37-0.96)]. All results were consistent between the 3 recurrent event models. Conclusion Among patients with AAD-refractory VT and a prior MI, catheter ablation reduced shock-treated VT event burden and appropriate shock burden compared to escalated AAD therapy.

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

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. 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). 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.

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

Abstract 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.

Evolution of coronary artery calcium and absolute myocardial perfusion after percutaneous revascularization: a 3-year serial hybrid [15O]H2O PET/CT imaging study

Abstract Funding Acknowledgements Type of funding sources: None. Background. The value of serial coronary artery calcium (CAC) scores to predict changes in absolute myocardial perfusion and epicardial vasomotor function is poorly documented. Purpose. This study explored the association between progression of CAC score and changes in absolute myocardial perfusion. Methods. Fifty-three patients with single-vessel coronary artery disease (CAD) underwent [15O]H2O Positron Emission Tomography/Computed Tomography at 1 month (baseline), 1 year, and 3 years after percutaneous coronary intervention (PCI) to assess CAC scores, hyperemic myocardial blood flow (hMBF), coronary flow reserve (CFR) and cold pressor test MBF (CPT-MBF), within the context of the VANISH (Impact of Vascular Reparative Therapy on Vasomotor Function and Myocardial Perfusion) trial. Relationships between baseline CAC score and evolution of perfusion indices were explored with a mixed model-analysis. Results. Baseline CAC score was 0 in 9%, 0.1-99.9 in 40%, 100-399.9 in 36% and ≥400 in 15% of patients, respectively. In higher baseline CAC groups, scores increased more over time (overall p < 0.01). Mixed model-analysis allowed for averaging perfusion indices over all time points: hMBF (3.74 ± 0.83; 3.33 ± 0.79; 3.08 ± 0.78 and 2.44 ± 0.74 mL·min-1·g-1) and CFR (3.82 ± 1.12; 3.17 ± 0.80; 3.19 ± 0.81; 2.63 ± 0.92) were lower among higher baseline CAC groups (p < 0.01; p = 0.03). However, no significant interaction was found between baseline CAC groups and time after PCI for all perfusion indices, denoting that evolution of perfusion indices over time were not significantly different between CAC groups. Furthermore, CAC progression was not correlated with evolution of hMBF (r = 0.08, p = 0.57), CFR (r = 0.09, p = 0.53) or CPT-MBF (r = 0.03, p = 0.82) during 3 years follow-up. Conclusions. Higher baseline CAC was associated with lower hMBF and CFR. However, both baseline CAC and its progression were not associated with evolution of absolute hMBF, CFR and CPT-MBF over time, suggesting that CAC score and progression of CAC are poor indicators of change in absolute myocardial perfusion.

Evolution of coronary artery calcium and absolute myocardial perfusion after percutaneous revascularization: A 3-year serial hybrid [15O]H2O PET/CT imaging study

Background and aimsThe value of serial coronary artery calcium (CAC) scores to predict changes in absolute myocardial perfusion and epicardial vasomotor function is poorly documented. This study explored the association between progression of CAC score and changes in absolute myocardial perfusion. MethodsFifty-three patients (26% female) with de novo single-vessel coronary artery disease underwent [15O]H2O positron emission tomography/computed tomography at 1 month (baseline), 1 year, and 3 years after complete revascularization with percutaneous coronary intervention (PCI) to assess CAC scores, hyperemic myocardial blood flow (hMBF), coronary flow reserve (CFR) and cold pressor test MBF (CPT-MBF), within the context of the VANISH trial. ResultsBaseline CAC score was 0 in 9%, 0.1–99.9 in 40%, 100–399.9 in 36% and ≥400 in 15% of patients, respectively. Mixed model-analysis allowed for averaging perfusion indices over all time points: hMBF (3.74 ± 0.83; 3.33 ± 0.79; 3.08 ± 0.78 and 2.44 ± 0.74 mL min−1·g−1) and CFR (3.82 ± 1.12; 3.17 ± 0.80; 3.19 ± 0.81; 2.63 ± 0.92) were lower among higher baseline CAC groups (p < 0.01; p = 0.03). However, no significant interaction was found between baseline CAC groups and time after PCI for all perfusion indices, denoting that evolution of perfusion indices over time was not significantly different between CAC groups. Furthermore, CAC progression was not correlated with evolution of hMBF (r = 0.08, p = 0.57), CFR (r = 0.09, p = 0.53) or CPT-MBF (r = 0.03, p = 0.82) during 3 years of follow-up. ConclusionsHigher baseline CAC was associated with lower hMBF and CFR. However, both baseline CAC and its progression were not associated with evolution of absolute hMBF, CFR and CPT-MBF over time, suggesting that CAC score and progression of CAC are poor indicators of change in absolute myocardial perfusion.

Baseline Characteristics of the VANISH Cohort.

The VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) targeted young sarcomeric gene mutation carriers with early-stage hypertrophic cardiomyopathy (HCM) to test whether valsartan can modify disease progression. We describe the baseline characteristics of the VANISH cohort and compare to previous trials evaluating angiotensin receptor blockers. Applying a randomized, double-blinded, placebo-controlled design, 178 participants with nonobstructive HCM (age, 23.3±10.1 years; 61% men) were randomized in the primary cohort and 34 (age, 16.5±4.9 years; 50% men) in the exploratory cohort of sarcomeric mutation carriers without left ventricular hypertrophy. In the primary cohort, maximal left ventricular wall thickness was 17±4 mm for adults and Z score 7.0±4.5 for children. Nineteen percent had late gadolinium enhancement on cardiac magnetic resonance. Mean peak oxygen consumption was 33 mL/kg per minute, and 92% of participants were New York Heart Association functional class I. New York Heart Association class II was associated with older age, MYH7 variants, and more prominent imaging abnormalities. Six previous trials of angiotensin receptor blockers in HCM enrolled a median of 24 patients (range, 19-133) with mean age of 51.2 years; 42% of patients were in New York Heart Association class ≥II, and sarcomeric mutations were not required. The VANISH cohort is much larger, younger, less heterogeneous, and has less advanced disease than prior angiotensin receptor blocker trials in HCM. Participants had relatively normal functional capacity and mild HCM features. New York Heart Association functional class II symptoms were associated with older age, more prominent imaging abnormalities, and MYH7 variants, suggesting both phenotype and genotype contribute to disease manifestations. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01912534.

Myocardial Blood Flow and Coronary Flow Reserve During 3 Years Following Bioresorbable Vascular Scaffold Versus Metallic Drug-Eluting Stent Implantation: The VANISH Trial

ObjectivesThe randomized clinical VANISH (Impact of Vascular Reparative Therapy on Vasomotor Function and Myocardial Perfusion: A Randomized [15O]H2O PET/CT Study) trial was conducted to assess quantitative myocardial blood flow (MBF) during resting, hyperemia, and cold pressor testing (CPT) with positron emission tomographic perfusion imaging after the implantation of a bioresorbable everolimus-eluting scaffold compared with a drug-eluting stent. BackgroundLong-term resorption of the bioresorbable everolimus-eluting scaffold reinstates normal vessel geometry, allowing natural regeneration of the newly formed endothelium with revival of vasomotor function. MethodsSixty patients (18 to 65 years of age) with single-vessel disease and type A or B1 lesions were randomized in a 1-to-1 fashion. Approximately 1 month, 1 year, and 3 years after device implantation, patients underwent [15O]H2O cardiac positron emission tomography. The primary endpoint was the interaction of device type and evolution over time of hyperemic MBF, coronary flow reserve, or CPT reserve. At 3-year follow-up, control invasive coronary angiography with optical coherence tomography was performed. ResultsFifty-nine (98%), 56 (93%), and 51 (85%) patients successfully completed 1-month, 1-year, and 3-year follow-up positron emission tomography, respectively, and no culprit vessel events were registered during follow-up time. The primary study endpoint (i.e., interaction between device type and time) was nonsignificant for hyperemic MBF, CPT reserve, and coronary flow reserve (p > 0.05 for all). In all patients, hyperemic MBF decreased from 1 to 3 years (p = 0.02), while coronary flow reserve was lower at 3-year follow-up compared with 1-month and 1-year follow-up (p = 0.03 for both). After 3 years, percentage area stenosis measured with optical coherence tomography was higher within the bioresorbable everolimus-eluting scaffold compared with the drug-eluting stent (p = 0.03). ConclusionsThe hypothesized beneficial effects of scaffold resorption did not translate to improved MBF during maximal hyperemia or endothelium-dependent vasodilation by CPT.

New Trends in High Risk Ventricular Tachycardia Catheter Ablation

Ventricular tachycardia (VT) is one of the major causes of sudden cardiac death (SCD). In general, VT could be managed with antiarrhythmic drugs (AADs) therapy, catheter ablation and implantable cardioverter defibrillators (ICD). While the AADs therapy and catheter ablation have been shown to reduce the recurrence of VT, only the ICD therapy is effective in aborting SCD. The recently published VANISH trial reveals that VT catheter ablation significantly decreases the rate of death, VT storm and appropriate ICD shock comparing with an escalation of AADs therapy for ischemic cardiomyopathy (ICM). However, the mapping strategies and feasibility of VT catheter ablation are often limited by the hemodynamically intolerant VT. Substrate modification strategy and percutaneous left ventricular assist device (pLVAD) are often used to overcome the hemodynamic intolerance. So far there are no large-scale randomized clinical trials comparing different mapping strategies in the setting of hemodynamically unstable VT, specifically when it comes to risk stratification for patients with hemodynamic instability. The aim of the present article is to systemically review different VT mapping strategies, the role of pLVAD in hemodynamically intolerant VT ablation with a special consideration of high risk VT.

P4197Evolution of vasomotor function and myocardial perfusion during three years follow-up after randomization between bioresorbable vascular scaffold and metal drug eluting stent: the VANISH trial

P4197Evolution of vasomotor function and myocardial perfusion during three years follow-up after randomization between bioresorbable vascular scaffold and metal drug eluting stent: the VANISH trial

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

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. 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. 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 ± 7.6vs 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. 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.

Prognostic Value of Noninducibility on Outcomes of Ventricular TachycardiaAblation: A VANISH Substudy.

This study sought to evaluate the predictive value of noninducibility on long-term outcomes. The traditional endpoint for catheter ablation of ventricular tachycardia (VT) is noninducibility of VT by programmed stimulation; however, the definition of inducibility remains variable and its prognostic value limited by nonstandardized periprocedural antiarrhythmic drug therapy and implantable cardioverter-defibrillator programming in prior observational studies. The VANISH trial randomized patients with prior myocardial infarction and VT to ablation (with an endpoint of noninducibility of VT≥300 ms after ablation) versus antiarrhythmic drug escalation. Patients enrolled in the VANISH study randomized to catheter ablation were included. The relationship between post-ablation inducibility and the primary composite endpoint (death, VT storm >30 days, or appropriate implantable cardioverter-defibrillator shock >30 days) was assessed using a time-to-event analysis, adjusting for other clinical and procedural characteristics. A total of 129 patients from the ablation arm were included in the primary analysis, of which 51 were noninducible post-ablation compared with 78 who had inducible VT or in whom inducibility testing was not performed. There were no significant baseline characteristic or procedural differences except for increased implantable cardioverter-defibrillator shocks before randomization in the noninducible group. In multivariate analysis, inducibility significantly increased the risk of death, appropriate shock, or VT storm after 30 days (HR: 1.87; p= 0.017). Inducibility of any VT post-ablation was associated with an increased risk of the composite endpoint in the VANISH trial. A randomized trial is required to confirm whether more aggressive ablation targeting faster induced VTs (<300 ms) can improve outcomes.

Effect of Baseline Antiarrhythmic Drug on Outcomes With Ablation in Ischemic Ventricular Tachycardia: A VANISH Substudy (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease).

The VANISH trial (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) compared the effectiveness of escalated antiarrhythmic drug therapy to catheter ablation in patients with prior myocardial infarction, an implanted defibrillator, and ventricular tachycardia (VT). The effectiveness of these interventions in patients on sotalol versus amiodarone was compared. Analysis was conducted based on whether patients had recurrent VT, despite amiodarone (amio-refractory) or nonamiodarone drugs (sotalol-refractory). Outcomes included death, VT storm, appropriate implantable cardioverter defibrillator shock, and any ventricular arrhythmia. At baseline, 169 (65.2%) were amio-refractory, and 90 (34.7%) were sotalol-refractory (1 patient on procainamide rather than sotalol). Amio-refractory patients had more renal insufficiency (23.7% versus 10%; P=0.0008), worse New York Heart Association class (82.3% II/III versus 65.5%; P=0.0003), and lower ejection fraction (29±9.7% versus 35.2±11%; P<0.0001). Within the amio-refractory group, ablation resulted in reduction of any ventricular arrhythmia compared with escalated drug therapy (hazard ratio, 0.53; 95% confidence interval, 0.31-0.9), P=0.020). Sotalol-refractory patients had trends toward higher mortality and VT storm with ablation, with no effect on implantable cardioverter defibrillator shocks. Within the escalated drug therapy arm, amio-refractory patients had a higher rate of the composite outcome (hazard ratio, 1.94; 95% confidence interval, 1.14-3.29; P=0.0144) and a trend to higher mortality (hazard ratio, 2.40; 95% confidence interval, 0.93-6.22; P=0.07), whereas mortality was not different between amio- and sotalol-refractory patients within the ablation treatment group. Patients with amio-refractory VT have a higher rate of ventricular arrhythmia and mortality than those with sotalol-refractory VT and derive greater benefit of catheter ablation than for patients with sotalol-refractory VT who are switched to amiodarone. URL: https://clinicaltrials.gov. Unique identifier: NCT00905853.

Abstract 21033: Effect of Baseline Antiarrhythmic Drug on Outcomes With Ablation in Ischemic Ventricular Tachycardia: A Vanish Substudy

Introduction: The VANISH trial enrolled patients with prior myocardial infarction, an implanted defibrillator and ventricular tachycardia (VT) despite antiarrhythmic (AAD) drugs and compared the effectiveness of escalated AAD therapy to catheter ablation. We sought to compare the effectiveness of these interventions in patients with sotalol-refractory VT versus amiodarone-refractory VT. Methods: All patients enrolled in the VANISH study were included (n=259). VT recurrence was compared in patients despite amiodarone (amio-refractory) as compared to non-amiodarone drugs (sotalol-refractory). Outcomes were a composite of death, VT storm, appropriate ICD shock, each of these components and any ventricular arrhythmia. Results: At baseline, 169 (65.2%) were amio-refractory and 90 (34.7%) were sotalol-refractory (1 patient was enrolled with VT despite procainamide). Amio-refractory patients had more renal insufficiency (23.7% vs 10%, p=0.0008), worse NYHA class (82.3% II/III vs 65.5%, p=0.0003), and lower ejection fraction (29 ± 9.7% vs 35.2 ± 11%, p&lt;0.0001). After adjusting for these baseline differences, there was no difference in mortality between the two groups. When examined within the escalated drug therapy arm, amio-refractory patients had a higher incidence of the composite outcome (HR 1.94, 95%CI (1.14, 3.29), p=0.0144), and a trend to higher mortality (HR 2.40, 95%CI (0.93, 6.22), p=0.07), while no difference in outcomes were observed within the ablation treatment group. Within the amio-refractory group, ablation resulted in significant reduction of any ventricular arrhythmia (HR 0.53, 95%CI (0.31, 0.9), p=0.020). Sotalol-refractory patients had trends towards higher mortality and VT storm with ablation, with no effect on ICD shocks. Conclusions: The benefit of catheter ablation is greater for patients with amio-refractory VT than for patients with sotalol-refractory VT who are then switched to amiodarone.

PROGNOSTIC VALUE OF NON-INDUCIBILITY ON OUTCOMES OF VENTRICULAR TACHYCARDIA ABLATION: A VENTRICULAR TACHYCARDIA ABLATION VS. ENHANCED DRUG THERAPY IN STRUCTURAL HEART DISEASE (VANISH) SUBSTUDY

The traditional endpoint of VT ablation is non-inducibility of VT by programmed electrical stimulation (PES); however, the definition of inducibility remains variable and its prognostic value has been muddied by alterations in peri-ablation antiarrhythmic drug (AAD) therapy or non-standardized ICD programming in prior observational studies. The VANISH trial randomized ischemic VT patients to VT ablation (with endpoint of non-inducibility of VT >=300ms after ablation) vs. AAD escalation. We proposed to determine the predictive value of non-inducibility on long-term clinical outcomes, adjusting for other clinical and procedural characteristics. The relationship of inducibility on the primary composite endpoint of death, VT storm > 30 days, or appropriate ICD shock > 30 days, was assessed using a time-to-event analysis. Survival rates were summarized between inducibility groups using Kaplan-Meier product-limit estimates. Results were analyzed according to presence of inducible VT (defined as inducibility post ablation of any VT – including those < 300ms) vs. non-inducible or inducibility not performed. Polymorphic VT or VF were not considered to be inducible. 129 patients from the ablation arm were included in the primary analysis of which 51 were non-inducible post ablation as compared to 78 who were inducible or where inducibility was not performed. At baseline, there was no significant characteristic or procedural differences between the non-inducible vs inducible/not performed cohorts except for an increased number of ICD shocks within 3 months observed in the latter group. There were no baseline characteristics that were shown to be significantly predictive of inducibility. In multivariate analysis, inducibility was associated with an increase in the primary endpoint of death, appropriate shock or VT storm after 30 days (HR 1.87, 95% CI 1.12, 3.11, P = 0.017). Inducibility of any VT post ablation was associated with an increased risk of the composite outcome in the VANISH Trial. No patient or procedural characteristics were shown to be significantly predictive of inducibility. A randomized trial targeting faster induced VTs may determine whether a more aggressive strategy can improve outcomes.

COST EFFECTIVENESS OF VENTRICULAR TACHYCARDIA ABLATION VERSUS ESCALATION OF ANTIARRHYTHMIC DRUG THERAPY IN THE VANISH TRIAL

For survivors of myocardial infarction with implantable cardioverter-defibrillator (ICD) shocks despite antiarrhythmic drugs, the VANISH trial demonstrated improved clinical outcomes with catheter ablation compared to additional pharmacotherapy. This analysis uses the data from the randomised controlled trial to assess the cost effectiveness of catheter ablation (n=132) versus escalated antiarrhythmic therapy (escalated drug therapy) (n=127). Healthcare resource use and quality of life data was collected in the trial, and used to determine the cost-effectiveness of catheter ablation. Published references were used to estimate costs (2015 CAN $). Analysis was stratified by amiodarone therapy at baseline. The analysis was over 3 years, with a 5% discount rate. Adjustment was made for censoring and baseline utilities. Overall, ablation resulted in greater quality adjusted life years (QALYs) than escalated drug therapy (1.63 vs 1.49; difference: 0.14, 95% CI -0.20 to 0.47) and a higher cost ($64,728 vs $60,937; difference $3,790, 95% CI - $17,848 to $23,105); with an incremental cost per QALY gained for ablation versus escalated drug therapy of $26,575. The higher costs in the ablation arm were primarily due to the initial costs of ablation which were partially offset by the costs of subsequent ablations and adverse outcomes in the escalated drug therapy arm. Amiodarone use at baseline significantly impacted cost-effectiveness. For those on amiodarone at baseline, ablation dominated escalated drug therapy, with greater QALYs (1.48 vs 1.26, difference: 0.22 (95% CI -0.16 to 0.62)) and lower costs ($67,307 vs $68,959, difference: -$1,652 (95% CI -$33,230 to $22,268)). For patients not on amiodarone at baseline, ablation resulted in similar QALYs (1.90 vs 1.90, difference: -0.00 (95% CI -0.62 to 0.60)) and higher costs ($59,883 vs $45,874, difference: $14 009 (95% CI -$9,948 to $43,412)). For the total trial population, ablation was cost effective compared with escalation of drug therapy. This result was manifest for the subgroup of patients who were receiving amiodarone at baseline but not for those not receiving amiodarone.

Ventricular Tachycardia with ICD Shocks: When to Medicate and When to Ablate.

Ventricular tachycardia occurrence in implantable cardioverter defibrillator (ICD) patients may result in shock delivery and is associated with increased morbidity and mortality. In addition, shocks may have deleterious mechanical and psychological effects. Prevention of ventricular tachycardia (VT) recurrence with the use of antiarrhythmic drugs or catheter ablation may be warranted. Antiarrhythmic drugs are limited by incomplete efficacy and an unfavorable adverse effect profile. Catheter ablation can be effective but acute complications and long-term VT recurrence risk necessitating repeat ablation should be recognized. A shared clinical decision process accounting for patients' cardiac status, comorbidities, and goals of care is often required. There are four published randomized trials of catheter ablation for sustained monomorphic VT (SMVT) in the setting of ischemic heart disease; there are no randomized studies for non-ischemic ventricular substrates. The most recent trial is the VANISH trial which randomly allocated patients with ICD, prior infarction, and SMVT despite first-line antiarrhythmic drug therapy to catheter ablation or more aggressive antiarrhythmic drug therapy. During 28months of follow-up, catheter ablation resulted in a 28% relative risk reduction in the composite endpoint of death, VT storm, and appropriate ICD shock (p=0.04). In a subgroup analysis, patients having VT despite amiodarone had better outcomes with ablation as compared to increasing amiodarone dose or adding mexiletine. There is evidence for the effectiveness of both catheter ablation and antiarrhythmic drug therapy for patients with myocardial infarction, an implantable defibrillator, and VT. If sotalol is ineffective in suppressing VT, either catheter ablation or initiation of amiodarone is a reasonable option. If VT occurs despite amiodarone therapy, there is evidence that catheter ablation is superior to administration of more aggressive antiarrhythmic drug therapy. Early catheter ablation may be appropriate in some clinical situations such as patients presenting with relatively slow VT below ICD detection, electrical storms, hemodynamically stable VT, or in very selected patients with left ventricular assist devices. The optimal first-line suppressive therapy for VT, after ICD implantation and appropriate programming, remains to be determined. Thus far, there has not been a randomized controlled trial to compare catheter ablation to antiarrhythmic drug therapy as a first-line treatment; the VANISH-2 study has been initiated as a pilot to examine this question.