Novel Approaches to VT Management Glenn M Polin MD

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Novel Approaches to VT Management Glenn M Polin MD Medical Director, Electrophysiology Laboratory John Ochsner Heart and Vascular Institute New Orleans, LA

Disclosures Pfizer Speaker Bureau Bristol Myers Squibb Speaker Bureau

What Options Are Available to Reduce Risk of VT and ICD Shocks? 1) General Medical and Cardiac Care a) Heart failure management (meds, euvolemia) b) Prevent ischemia c) Prevent electrolyte abnormalities 2) Appropriate ICD Programming - MADIT-RIT 3) Antiarrhythmics 4) Catheter Ablation 5) Emerging Therapies - Neuraxial modulation

Appropriate ICD Programming

1500 patients with primary prevention ICDs randomized to three treatment arms Conventional Programming 170-199 bpm = 2.5 s delay to therapy >200 bpm = 1 s delay to therapy High-Rate Therapy >200 bpm = 2.5 s delay to therapy Delayed Therapy 170-199 bpm = 60 s delay to therapy 200-249 bpm = 12 s delay to therapy >250 bpm = 2 s delay to therapy Primary Endpoint = Time to first inappropriate shock Moss, EJ, et al. N Engl J Med 2012;367:2275-83.

25% Reductions in Appropriate and Inappropriate Therapy Based on ICD Programming 22% 20% >3x reduction in treated VT 15% Appropriate Rx 10% 9% 6% Inappropriate Rx Mortality at 2.5y 5% 0% 170/m 200/m 170/mDelayed Average f/u 1.4y Moss, EJ, et al. N Engl J Med 2012;367:2275-83.

Total Occurrence of Appropriate and Inappropriate Device Therapy Conclusions: High Rate Therapy was associated with a 79% reduction in occurrence of first inappropriate shock, and a 55% reduction in all-cause mortality, with similar rates of syncope. Moss, EJ, et al. N Engl J Med 2012367:2275-83.

Antiarrhythmics

Antiarrhythmic Drugs for VT Stevenson, WG. Heart Rhythm 2013;10:1919-1926.

Catheter Ablation for VT

VT Ablation: Rationale Healthy Myocardium QRS Myocardial Scar from Infarction Photo courtesy of William Stevenson

Josephson MJ, et al. Circulation 1979;60:1430-1439.

Surgical Experience with VT Ablation 88% 52% 69% 56% 10-15% surgical mortality Miller JM, et al. J Am Coll Cardiol 1988;11:112A.

How Do Electrophysiologists Ablate VT? Activation Mapping Electrode catheter moved point by point through multiple ventricular sites during VT and recording EGM at each site Site of earliest activation (ie. earliest onset of electrical depolarization) identifies origin of tachycardia/exit site Entrainment Mapping Pace from catheter at rate faster than tachycardia, from site thought to be within VT circuit Examining change in QRS morphology during pacing and post-pacing timing of resumption of VT helps determine whether paced site is in reentry circuit Pace Mapping Site where paced QRS matches clinical VT likely exit site for scar VT Substrate Mapping Identify areas of myocardium likely to sustain reentry based on anatomic features or EP characteristics, with ablation targeted to these areas

Clinical VT Ablation Approach

Substrate-Based VT Ablation Approach

Study population: 118 pts with ischemic cardiomyopathy and hemodynamically stable VT Randomized to either a) clinical ablation, or b) substrate-based ablation targeting all abnormal EGMs within scar Primary Endpoint: Recurrence of VT over 12 months Di Biase L, et al. J Am Coll Cardiol 2015;66(25):2872-2882.

VISTA: VT Ablation Strategies

VISTA: Primary Endpoint

VISTA: Conclusions Substrate-based ablation reduces recurrence of any VT at follow-up compared with ablation limited to clinical and mappable VTs in pts with ischemic cardiomyopathy Combined reduction in rehospitalization and mortality seen in substrate-based ablation group Larger % of pts able to discontinue AADs in substrate-based ablation group vs standard ablation arm

259 patients with ICM who had VT despite AAD use Randomized to ablation vs escalation of therapy No Amiodarone Amiodarone Amiodarone < 300mg Amiodarone > 300mg Amiodarone > 300 mg Amio/Mexilitine Primary outcome Composite of death, 3 or more VT episodes within 24 hours (VT storm), appropriate ICD shock Mean follow-up: 27.9±17.1 months Sapp J, et al. N Engl J Med 2016;375;111-121.

Trial Conclusions: It is appropriate to offer catheter ablation to patients with ischemic cardiomyopathy, an ICD, and recurrent ventricular tachycardia while taking amiodarone. For patients who have ventricular tachycardia while taking another antiarrhythmic drug or no antiarrhythmic drug, catheter ablation does not appear to be superior to treatment with amiodarone. Amiodarone

Frankel D, et al. J Cardiovasc Electrophysiol 2011;22:1123-1128. Benefits of Catheter Ablation: Reduction in VT Episodes AND Reduction in Antiarrhythmic Drugs Amiodarone: 559 mg (mean)/400 mg (median) 98 mg (mean)/0 mg (median) VT Episodes: 17 (mean)/6 (median) 1 (mean)/0 (median)

VT Ablation: Safety Considerations Possible need for mechanical support peri-ablation procedure No Likely transplant candidate? Yes RV function good? No No durable support options Yes Option of LVAD as destination therapy Options of LVAD OR: Biventricular VAD OR: Total artificial heart as bridge to transplant

VT Ablation in Nonischemic Cardiomyopathy Compared to ischemic cardiomyopathy... Fewer endocardial low amplitude fractionated EGMs or late potentials Smaller endocardial scar area, often patchy, with preferential localization at basal sites, adjacent to valve annuli Epicardial scar areas> Endocardial scar areas Greater incidence of focal nonreentrant and intramural VT origin

VT Ablation Outcomes in Ischemic Cardiomyopathy vs Dilated Cardiomyopathy Dinov et al. Circulation 2014;129:728-736. Ischemic Cardiomyopathy Nonischemic Cardiomyopathy

Devotions Upon Emergent Occasions, John Donne, 1623 Neuromodulation for VT No man is an island, Entire of itself, Management Every man is a piece of the continent, A part of the main.

Cardiac Injury Results in Extracardiac/Neural Remodeling: A VT Circuit with Extracardiac Components! Ajijola OA, et al. J Am Col Cardiol 59;10:962-964.

Nerve Stimulation Can Induce Lethal Arrhythmias in a Normal Heart Vaseghi M, et al. Heart Rhythm 2012;9:1303 1309

Cervical Sympathetic Denervation Bourke T, et al. Circulation. 2010;121:2255-2262.

41 patients (14 LCSD, 27 BSCD) ICD shocks were reduced from mean of 19.6±19 pre-procedure to 2.3±2.9 post-procedure (P <.001), with 90% experiencing a reduction in shock burden Vaseghi M, et al. Heart Rhythm 2014;11:360 366.

Complications Related to CSD Procedure Vaseghi M, et al. Heart Rhythm 2014;11:360 366.

Autonomic Modulation Therapy An Ongoing Area of Investigation

Conclusions ICDs treat but do not prevent VT VT and VT shocks are associated with significant morbidity and mortality Intelligent device programming can reduce inappropriate AND appropriate ICD shocks Antiarrhythmic options are limited, and efficacy for preventing arrhythmias has overall been disappointing Catheter ablation plays an important role in reducing VT/VF shocks in patients with ICDs and is a key aspect of 21 st century VT management Neuromodulation is an emerging area of investigation and holds promise in reducing VT in our sickest patients

Thank You