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

Preventing Sudden Death Current & Future Role of ICD Therapy

Canada Research Chairs

ACC – March 2013

Derek V Exner, MD, MPH, FRCPC, FACC, FAHA, FHRS

Professor, Libin Cardiovascular Institute of Alberta Canada Research Chair, Cardiovascular Clinical Trials

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

Derek V. Exner - Disclosures

March 2013

Overview

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

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Sudden Death / Sudden Cardiac Arrest

Cardiovascular death < 1 hour of symptoms

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More deaths than others combined

Magnitude

100,000 200,000 300,000 400,000 500,000 Deaths per year

Breast Lung Stroke Sudden Cancer Cancer Death

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What Proportion of Sudden Deaths are Arrhythmic?

• 1. 20%
• 2. 40%
• 3. 60%
• 4. 80%

Sudden Death: Diverse Mechanisms

VF Rapid VT Brady/EM D Other

Am J Cardiol 1989;117:151-9

Ambulatory VT/VF Brady/EMD

Circulation 1989;80:1675-80

Awaiting Transplant

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Population Subgroups

Rea AJC 2004;93:1455-60.

25 50 75

Heart Failure Prior MI

Population Attributable Risk % of events (prevalence) Individual risk (incidence)

0% 25% 50% 75%

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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

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

Exner Randomized Trials of ICD Therapy 2011

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Recommend for history of hemodynamically significant or sustained ventricular arrhythmia (secondary prevention). For ALL: Strong Recommendation High Quality Evidence Consider for primary prevention:

• i. Ischemic LVD, NYHA II-III, EF ≤

35%, measured > 1 m post MI, & > 3 m post revascularization ;

• 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

• ptimal medical therapy.

Recommendations - Chronic Heart Failure

Implantable cardioverter-defibrillator (ICD)

Primary Prevention ICD Therapy Use Is:

• 1. Too High
• 2. About Right
• 3. To Low

ON 152

AB 120 Atlantic 186

QC 170

SK 105 MB 185 BC 122 Territories 125

New ICD Implants per Million

Crysler Industry Data 2010

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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

25 50 75 100 Proportion (%)

Relying Solely On Low LVEF

Most Identified Are Not At High Risk Fails to Identify Most of Those at Risk

• Exner. Curr Opin Cardiol 2009, 24:61–7

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Clinical Risk Stratification: MADIT II

Predictors of ICD benefit

• age > 70,
• NYHA 3 or 4,
• Elevated urea

(> 26 mg/dl / (> 9.3 mmol/ L)

• QRSd > 120 ms,
• Atrial fibrillation.

Goldenberg et al., JACC 2008;51:288-96 None of the 5 risk factors (n = 345; 31%) HR for ICD therapy 0.96 (95% CI 0.44, 2.07); p = 0.91 > 1 risk factor (n = 786; 69%) HR for ICD therapy 0.51 (95% CI 0.37, 0.70); p < 0.001

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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 ?

VT / VF 65% OS 12% SVT 20% NSVT 3%

Poole et al. N Engl J Med 2008;359:1009-17

• 1 in 3 ICD recipients

in SCD-HeFT received shocks

• Inappropriate

2-fold higher risk of death

• Appropriate

5-fold higher risk of death

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Shock Reduction Algorithms

Time to Development of Shocks for VT/VF Time to Development of Inappropriate Shocks Reduced from 30.7% to 26.1% Reduced from 23.5% to 8.4% 99.2% of all VT/VF episodes detected without delay

Volosin, Exner, et al. JCE 2011;22:280-9

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Range of NID Settings

Original NID = 18/24 Virtual ICD NID = 18/24 NID = 24/32 NID = 30/40

Time to Development of Inappropriate shocks

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Volosin, Exner, et al. JCE 2011;22:280-9

MADIT-RIT: Shock Reduction

NEJM 2012;367(24):2275-83

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~ 80% reduction in inappropriate ICD therapies

MADIT-RIT: Reduced Mortality

NEJM 2012;367(24):2275-83

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~ 50% reduction in mortality (6.6% vs. 3.2%)

ICD Therapy: Recent MI

Exner Randomized Trials of ICD Therapy 2011

DINAMIT (n = 674) BEST-ICD (n = 138) IRIS (n = 898) Odds ratio (95% confidence interval) 1.12 (0.76, 1.67) 1.17 (0.39, 3.48) 1.01 (0.75, 1.36) 0.5 1 2 Favors ICD

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Hohnloser et al,

DINAMIT

• N = 674
• EF < 0.35 (6-40 d post-MI)
• Impaired HR variability

Steinbeck et al,

IRIS

• N = 898
• EF < 0.40 (5-31 d post-MI)
• Elevated HR +/- NSVT
• Hohnloser. NEJM 2004;351:2481-8.
• Steinbeck. NEJM 2009;361:1427-36.

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• Hohnloser. NEJM 2004;351:2481-8.
• Steinbeck. NEJM 2009;361:1427-36.

DINAMIT IRIS

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Development of a Cardiac Arrest

Moss & Zareba J Electrocardiol 2003;36:101-8

Autonomic Nervous System Underlying Fixed Substrate Dynamic Substrate

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Holter, Modified Moving Average TWA

J Appl Physiol 2002;92:541-9 J Am Coll Cardiol 2011;58;1309-24

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Heart Rate Turbulence (HRT)

# of RR interval RR interval (ms) PVC

Schmidt et al. Lancet 1999;353:1390-6. Bauer et al. JACC 2008;52:1353-65.

Reflex response to perturbation 1 291 pts (post-MI)  Holter < 14 d > 3-fold higher risk of death (indep’t) Validation in multiple studies. Consistent utility.

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HRT

• nset

HRT

slope

# of RR interval RR interval (ms) PVC

Heart Rate Turbulence (HRT)

Reflex response to perturbation 1 291 pts (post-MI)  Holter < 14 d > 3-fold higher risk of death (indep’t) Validation in multiple studies. Consistent utility.

Schmidt et al. Lancet 1999;353:1390-6. Bauer et al. JACC 2008;52:1353-65.

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Combined Parameter Assessment

Cardiac Death or Cardiac Arrest

Remaining HRT + TWA & EF < 0.50

322 post-MI patients serial assessment (2-4 & 10-14 weeks) Later testing more accurate 6-fold higher risk with abnormal HRT + TWA

Sensitivity: 55% Positive PV: 27% Negative PV: 96%

Exner et al. JACC 2007;50:2275-84.

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Risk Estimation Following Infarction Noninvasive Evaluation: ICD efficacy

EF 0.36 to 0.50 2-15 mo. post-MI > 3 mo. post-revasc. < 80 years & without dialysis, perm AF or AAD

Holter

Abnormal TWA + HRT Registry Usual Care Alone Usual Care + ICD Minimum follow-up: 2 years Mean follow-up: 5 years 1° outcome: mortality 2° outcomes: cost & QoL

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Summary

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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)