Preventing Sudden Death Current & Future Role of ICD Therapy - PowerPoint PPT Presentation

Preventing Sudden Death Current & Future Role of ICD Therapy Derek V Exner , MD, MPH, FRCPC, FACC, FAHA, FHRS Professor, Libin Cardiovascular Institute of Alberta Canada Research Chair, Cardiovascular Clinical Trials Canada Research Chairs ACC – March 2013

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Derek V. Exner - Disclosures Consulting & Boehringer Ingelheim, GE Healthcare, Honoraria Medtronic, Sanofi-Aventis, St Jude Medical Speakers ’ Biotronik, Boston Scientific, GE Healthcare, Bureau Medtronic, St Jude Medical Equipment AudiCor, Cambridge Heart, GE Healthcare, donations Roche Diagnostics, Sorin / ELA Research Cambridge Heart, Heart Force Medical, GE Support Healthcare, Medtronic, St Jude Medical Investor Analytics4Life Salary & Alberta AET, CIHR, CRC, HSF Alberta, JC Grants Anderson Legacy Foundation, WED. March 2013

Overview Sudden death Epidemiology Risk quantification ICD Therapy in 2013 Indications Expectations Unanswered questions March 2013

Sudden Death / Sudden Cardiac Arrest Cardiovascular death < 1 hour of symptoms March 2013

Magnitude 500,000 400,000 Deaths per year 300,000 200,000 100,000 0 Breast Lung Stroke Sudden Cancer Cancer Death More deaths than others combined March 2013

What Proportion of Sudden Deaths are Arrhythmic? 1. 20% 2. 40% 3. 60% 4. 80%

Sudden Death: Diverse Mechanisms Ambulatory Awaiting Transplant Brady/EM Brady/EMD VT/VF D VF Other Rapid VT Am J Cardiol 1989 ;117:151-9 Circulation 1989 ;80:1675-80 March 2013

Population Subgroups Prior MI Population Attributable Risk % of events (prevalence) Heart Individual risk (incidence) Failure 0% 25% 50% 75% 0 25 50 75 Rea AJC 2004 ;93:1455-60. March 2013

Who is Indicated for an ICD? 1. Prior cardiac arrest / sustained VT 2. CAD & EF < 35% 3. CAD & EF < 30% 4. 1 & 2 5. 1 & 3

Odds ratio (95% confidence interval) Risk Groups AVID (n = 1,016) 0.59 (0.43, 0.81) CIDS (n = 659) 0.81 (0.57, 1.14) Spontaneous or Inducible CASH (n = 288) 0.71 (0.43, 1.18) Ventricular Arrhythmias MADIT I (n = 196) 0.30 (0.15, 0.59) 0.34 (0.22, 0.53) MUSTT (n = 514) MADIT II (n = 1,232) 0.68 (0.50, 0.92) AMIOVIRT (n = 103) 0.86 (0.27, 2.75) Heart Failure or LV CAT (n = 104) 0.76 (0.33, 1.80) Dysfunction Alone COMPANION (n = 903) 0.64 (0.46, 0.90) SCD-HEFT (n = 1,676) 0.70 (0.56, 0.87) DEFINITE (n = 458) 0.66 (0.39, 1.11) CABG-Patch (n = 900) 1.11 (0.81, 1.52) LV dysfunction in DINAMIT (n = 674) 1.12 (0.76, 1.67) Specific Circumstances BEST-ICD (n = 138) 1.17 (0.39, 3.48) IRIS (n = 898) 1.01 (0.75, 1.36) Overall 0.72 (0.60, 0.86) 1 2 0.2 0.5 Favors ICD Exner Randomized Trials of ICD Therapy 2011 March 2013

Recommendations - Chronic Heart Failure Implantable cardioverter-defibrillator (ICD) Recommend for history of hemodynamically significant or sustained ventricular arrhythmia For ALL: ( secondary prevention ). Strong Consider for primary prevention : Recommendation i. Ischemic LVD, NYHA II- III, EF ≤ 35%, measured > 1 m post MI, & > High Quality 3 m post revascularization ; Evidence ii. Ischemic LVD, NYHA class I, & EF ≤ 30% > 1 m post MI, & < 3 m post revascularization ; iii. Nonischemic LVD, NYHA class II-III, EF ≤ 35%, measured > 9 m after optimal medical therapy.

Primary Prevention ICD Therapy Use Is: 1. Too High 2. About Right 3. To Low

New ICD Implants per Million Territories 125 QC AB SK MB BC ON 120 170 105 185 122 152 Atlantic 186 Crysler Industry Data 2010 March 2013

Regarding My Enthusiasm for Primary Prevention ICD Therapy: 1. I am keen 2. I am not keen due to the risk of shocks 3. I am not keen due to an inability to predict who will benefit 4. I am not keen due to the risk of long-term complications (leads, redo procedures) 5. I am not keen due to poor accessibility

Relying Solely On Low LVEF 100 Most Identified Fails to Identify Are Not At High Most of Those 75 Risk Proportion (%) at Risk 50 25 0 Exner. Curr Opin Cardiol 2009 , 24:61 – 7 March 2013

Clinical Risk Stratification: MADIT II Predictors of ICD benefit • age > 70 , None of the 5 risk factors (n = 345; 31%) • NYHA 3 or 4 , HR for ICD therapy 0.96 (95% CI 0.44, 2.07); p = 0.91 • Elevated urea (> 26 mg/dl / (> 9.3 mmol/ L) • QRS d > 120 ms , > 1 risk factor (n = 786; 69%) • Atrial fibrillation . HR for ICD therapy 0.51 (95% CI 0.37, 0.70); p < 0.001 Goldenberg et al., JACC 2008 ;51:288-96 March 2013

Based on data from SCD-HeFT, over the initial 5 years, patients receiving a primary prevention ICD should expect ? 1. 10% risk of shocks; 95% for VT/VF 2. 25% risk of shocks; 80% for VT/VF 3. 33% risk of shocks; 65% for VT/VF 4. 50% risk of shocks; 50% for VT/VF

Shocks: Necessary & Appropriate ? - 1 in 3 ICD recipients in SCD-HeFT received shocks VT / VF 65% - Inappropriate 2-fold higher risk of death OS - Appropriate SVT 12% 5-fold higher NSVT 20% 3% risk of death Poole et al. N Engl J Med 2008 ;359:1009-17 March 2013

Shock Reduction Algorithms 99.2% of all VT/VF episodes detected without delay Time to Development of Time to Development of Shocks for VT/VF Inappropriate Shocks Reduced from Reduced from 30.7% to 26.1% 23.5% to 8.4% Volosin, Exner, et al. JCE 2011 ;22:280-9 March 2013

Range of NID Settings Time to Development of Inappropriate shocks Original NID = 18/24 Virtual ICD NID = 18/24 NID = 24/32 NID = 30/40 Volosin, Exner, et al. JCE 2011 ;22:280-9 March 2013

MADIT-RIT: Shock Reduction ~ 80% reduction in inappropriate ICD therapies NEJM 2012 ;367(24):2275-83 March 2013

MADIT-RIT: Reduced Mortality ~ 50% reduction in mortality (6.6% vs. 3.2%) NEJM 2012 ;367(24):2275-83 March 2013

ICD Therapy: Recent MI Odds ratio (95% confidence interval) DINAMIT (n = 674) 1.12 (0.76, 1.67) BEST-ICD (n = 138) 1.17 (0.39, 3.48) IRIS (n = 898) 1.01 (0.75, 1.36) 1 2 0.5 Favors ICD Exner Randomized Trials of ICD Therapy 2011 March 2013

DINAMIT IRIS • N = 674 • N = 898 • EF < 0.35 (6-40 d post-MI) • EF < 0.40 (5-31 d post-MI) • Impaired HR variability • Elevated HR +/- NSVT Steinbeck. NEJM 2009 ;361:1427-36. Hohnloser. NEJM 2004 ;351:2481-8. Steinbeck et al, Hohnloser et al, March 2013

DINAMIT IRIS Steinbeck. NEJM 2009 ;361:1427-36. Hohnloser. NEJM 2004 ;351:2481-8. March 2013

Development of a Cardiac Arrest Autonomic Nervous System Underlying Dynamic Fixed Substrate Substrate Moss & Zareba J Electrocardiol 2003 ;36:101-8 March 2013

Holter, Modified Moving Average TWA J Appl Physiol 2002 ;92:541-9 J Am Coll Cardiol 2011 ;58;1309-24 March 2013

Heart Rate Turbulence (HRT) Reflex response to perturbation RR interval (ms) 1 291 pts (post-MI)  Holter < 14 d > 3-fold higher risk of death ( indep’ t) Validation in multiple PVC studies. Consistent utility. # of RR interval Schmidt et al. Lancet 1999 ;353:1390-6. Bauer et al. JACC 2008 ;52:1353-65. March 2013

Heart Rate Turbulence (HRT) Reflex response to perturbation RR interval (ms) 1 291 pts (post-MI)  Holter < 14 d HRT slope > 3-fold higher risk of HRT death ( indep’ t) onset Validation in multiple PVC studies. Consistent utility. # of RR interval Schmidt et al. Lancet 1999 ;353:1390-6. Bauer et al. JACC 2008 ;52:1353-65. March 2013

Combined Parameter Assessment 322 post-MI patients HRT + TWA & EF < 0.50 serial assessment (2-4 & 10-14 weeks) Later testing more accurate 6-fold higher risk with Remaining abnormal HRT + TWA Sensitivity: 55% Positive PV: 27 % Negative PV: 96% Cardiac Death or Cardiac Arrest Exner et al. JACC 2007 ;50:2275-84. March 2013

Risk Estimation Following Infarction Noninvasive Evaluation: ICD efficacy EF 0.36 to 0.50 Minimum follow-up: 2 years 2-15 mo. post-MI Mean follow-up: 5 years > 3 mo. post-revasc. 1° outcome: mortality < 80 years & without 2° outcomes: cost & QoL dialysis, perm AF or AAD Usual Care Alone Abnormal TWA + HRT Holter Usual Care + ICD Registry March 2013

Summary Sudden death remains an important issue Post-MI patients are at risk EF alone is a poor discriminator The recommendations for ICD therapy are based on many large randomized trials Clinical risk scores exist to maximize benefit Shock reduction is here to stay Unanswered questions persist (post-MI) March 2013