Sudden Cardiac Arrest: Increasing Survival

1. Sudden Cardiac Arrest: Increasing Survival Cynthia M. Tracy, M.D. George Washington University Medical Center Speaker has no relationships with any proprietary entity producing health care goods or services consumed by or used on patients

2. Objectives Upon completion of this activity, participants will be able to: • Describe current trends in cardiac vascular disease (CVD) and SCA. • Assess the risk of SCA in heart failure (HF) and post-myocardial infarction (MI) patients. • Describe 2008 ACC/AHA/HRS Class I guidelines for the use of implantable cardiac defibrillator (ICD) and cardiac resynchronization therapy with defibrillation (CRT-D) therapies in patients at risk of SCA, and the evidence supporting these guidelines. • Describe current utilization of device therapy and assess current use of these devices in your practice.

3. Agenda • CVD Epidemiology and SCA Facts • SCA Risk Factors • ICD and CRT-D Therapies • Secondary Prevention of SCA • Primary Prevention of SCA • Implications in Real-World Practice • Device Treatment Algorithms • Summary

4. CVD Epidemiology and SCA Facts

5. Prevalence of Cardiovascular Diseases in Adults Age 20 and Older by Age and Sex NHANES: 1999-2004

6. Deaths from Cardiovascular DiseaseUnited States: 1900-2004

7. Percentage Breakdown of Deaths fromCardiovascular DiseasesUnited States: 2004 (Final) • About 50% of CHD deaths are due to SCA. This is the largest cause of CV death.

8. Underlying Arrhythmias of SCA Polymorphic VT 13% Bradycardia17% Monomorphic VT62% Primary VF8% Bayés de Luna A, et al. Am Heart J. 1989;117:151-159.

9. Magnitude of Deaths from SCA in the United States * Range: 166,200 to 310,000 1 Vital Statistics of the U.S., Data Warehouse, National Center for Health Statistics. 4 Department of Health and Human Services. Centers for Disease Control and Prevention. 2 Chugh SS, et al. J Am Coll Cardiol. 2004;44:1268-1275. 5 Avert Organization: www.avert.org 3 Nichol G, et al. JAMA. 2008;300:1423-1431. 6 2008 Heart and Stroke Statistics Update. American Heart Association.

10. SCD Rates for Gender and Ethnicity White 600 Black 502.7 American Indian/Alaska Native 500 Asian/Pacific Islander 407.1 400 336.1 Per 100,000 Standard US Population 270.5 258.8 300 212.6 200 130.0 100 153.4 0 Males Females Zheng ZJ, et al. Circulation. 2001;104(18):2158-2163.

11. Incidence of SCD by Age and Gender 4500 Men 4000 Women 3500 3000 2500 SCD Rate Per 100,000 2000 1500 1000 500 0 35 - 54 55 - 64 65 - 74 75 - 84 > 84 Age Group Zheng ZJ, et al. Circulation. 2001;104:2158-2163.

12. SCA Resuscitation Success versus Time* 100 Chance of success reduced 7-10% each minute 90 80 70 % Success *Non-linear 60 50 40 30 20 10 0 1 2 3 4 5 6 7 8 9 Time (minutes) Cummins RO. Annals Emerg Med. 1989;18:1269-1275.

13. SCA Chain of Survival Statistics Even in the best EMS/early defibrillation programs, it is difficult to achieve high survival times due to any SCA events not being witnessed and the difficulty of reaching victims within 6-8 minutes. • 48% to 58% SCAs not witnessed1,2 • 85% SCAs occur at home/non-public1 • 4.6% to 8% estimated SCA out-of-hospital survival1,2 1 Nichol G, et al. JAMA. 2008;300:1423-1431. 2 Chugh SS, et al. J Am Coll Cardiol. 2004;44:1268-1275.

14. Time Dependent Risk • Risk of SCD after a clinical event is not linear • Risk of SCD and total cardiac death highest within 6-18 months after index event • Survival curves show similar characteristics after: • Survival of CA • Diagnosis of heart failure • Unstable angina • Recent MI • Mortality is highest in the 1st month post MI in patients with <30% EF

15. Substrates for Sudden Cardiac Arrest • 3/4 pts with SCD have CHD • Hypertrophic cardiomyopathy (HCM) • Dilated cardiomyopathy (DCM) • RV cardiomyopathy • Long QT Syndrome/short QT Syndrome/Brugada, etc... • Other (AS, MVP, WPW)

16. Substrates for Sudden Cardiac Arrest:Sudden Cardiac Arrest Survivors • Highest risk factor for Sudden Cardiac Arrest is prior SCA event • 30 to 50% of SCA survivors will experience another SCA event within one year • First-degree relatives of SCA patients have a 50% higher risk of MI or primary cardiac arrest Myerburg RJ. Heart Disease, 5th ed, Vol 1. Philadelphia: WB Saunders Co;1997:ch 24. Fogoros RN. Practical Cardiac Diagnosis: EP Testing, 2nd ed. Blackwell Science, pp 172. The AVID Investigators. N Engl J Med. 1997;337:1576-1583. Myerburg RJ. Ann Intern Med.. 1993;119:1187-1197. Demirovic J. Progr Cardiovasc Dis. 1994;37:39-48. Friedlander Y. Circulation. 1998;97:155-160.

17. Substrates for Sudden Cardiac Arrest:Prior Episode of VT • VT in combination with syncope or a low ejection fraction (LVEF < 40%) leads to an increased risk of Sudden Cardiac Arrest • One-year risk of SCA - 20 to 50% Myerburg RJ. Heart Disease, 5th ed, Vol 1. Philadelphia: WB Saunders Co;1997:ch 24. Fogoros RN. Practical Cardiac Diagnosis: EP, 2nd ed. Blackwell Science, pp 172. The AVID Investigators. N Engl J Med. 1997;337:1576-1583.

18. Substrates for Sudden Cardiac Arrest: Prior MI • Prior MI identified in as many as 75% of SCA patients • Prior MI raises the one-year risk of SCA by 5% as a single risk factor • Five-year risk of SCA is 32% for patients with all 3 risk factors: • Prior MI • Non-sustained, inducible, nonsuppressible VT • LVEF < 40% Myerburg RJ. Heart Disease, 5th ed,Vol 1. Philadelphia: WB Saunders Co;1997:ch 24. De Vreede-Swagemakers JJ. J Am Coll Cardiol. 1997;30:1500-1505. Kannel WB. Circulation. 1975;51:606-613. Shen WK. Mayo Clin Proc. 1991;66:950-962. Bigger JT. Circulation. 1984;69:250-258. Ruberman W. Circulation. 1981;64:297-305. Buxton AE. N Engl J Med. 1999;341:1882-1890.

19. Substrates for Sudden Cardiac Arrest:Coronary Artery Disease • Extensive CAD is seen in approx 75% SCA patients • 3-4 vessel disease • Autopsies have shown acute changes e.g. thrombus, plaque disruption in >50% • Over 50% of SCA victims had no manifestations of CAD prior to the sudden death episode • SCA is the first sign of heart disease in 20-50% of cases Futterman LG. Am J Crit Care. 1997;6:472-482. Demirovic J. Progr Cardiovasc Dis. 1994;37:39-48. Moss AJ. N Engl J Med. 1996;335:1933-1940. Friedlander Y. Circulation. 1998;97:155-160.

20. Substrates for Sudden Cardiac Arrest:Heart Failure • About one-half of all deaths in heart failure patients are characterized as sudden due to arrhythmias • The risk of SCA increases as left ventricular function deteriorates (low LVEF) • Unexplained syncope has predicted SCA in patients in functional NYHA Class II - IV Myerburg RJ. Heart Disease. 5th ed, Vol 1. Philadelphia: WB Saunders Co; 1997:ch 24. Middlekauf HR. J Am Coll Cardiol. 1993;21:110-116. Stevenson WE. Circulation. 1993;88:2953-2961.

21. Severity of Heart FailureModes of Death NYHA II NYHA III CHF CHF 12% Other 26% Other 59% Sudden 24% Sudden Death 64% 15% Death n = 103 n = 103 NYHA IV CHF Other 33% 56% Sudden Death 11% n = 27 MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). LANCET. 1999;353:2001-07.

22. Substrates for Sudden Cardiac Arrest: Hypertrophic Cardiomyopathy • Sudden cardiac death is the most common cause of death in patients with HCM • Prevalence of HCM is about 0.2% of the general population and about 10% of HCM patients are considered to be at high risk of SCA • Recent study showed that over a ten year period > 50% of high-risk patients would experience SCA • HCM is the most common cause of SCA in athletes under 35 years of age • EP testing of limited utility Myerburg RJ. Heart Disease, A Textbook of Cardiovascular Medicine. 5th ed, Vol 1. Philadelphia: WB Saunders Co; 1997:ch 24. Maron BJ. New Engl J Med. 2000;342:365-373.

23. Substrates for Sudden Cardiac Arrest: Arrhythmogenic Right Ventricular Cardiomyopathy • ARVC suspected in young pts (usually men) with RV arrhythmias • Syncope, presyncope, less frequently biventricular failure seen • VA typically LBBB morphology and ranges from NSVT, VT to VF • ECG typically shows precordial T wave inversion- v1-v3 and QRS >110 ms • Low voltage potentials (epsilon waves) following QRS are characteristic but rare • >50% have abnormal SAECG

24. Substrates for Sudden Cardiac Arrest: Arrhythmogenic Right Ventricular Cardiomyopathy • SCD is frequently the first manifestation 0.08% to 9% • SCD occurs relatively frequently during exercise or stress • SCD more common in those with gross RV abnormalities but can occur in those with only microscopic abnormalities • Certain genetic types may be associated with increased risk • Current state of knowledge- genetic testing does not contribute to risk stratification • May be increased risk if > 1 family member with SCD • EP testing of limited utility

25. Substrates for Sudden Cardiac Arrest: Long QT Syndrome • Idiopathic LQTS is a congenital disorder that may lead to unexplained syncope, seizures, and SCA • Patients either remain asymptomatic or are prone to symptomatic and potentially lethal arrhythmias • A positive family history of LQTS or SCA is present in 60% of LQTS patients • Due to the hereditary linkage, it is necessary to identify other family members at risk Schwartz PJ. Curr Probl Cardiol. 1997;22:297-351. Smith WM. Ann Intern Med. 1980;93:578-584. Garson A Jr. Circulation. 1993;87:1866-1872.

26. Secondary Prevention ofSudden Cardiac Arrest

27. Patient Case #1 History • 54 y.o. African-American female • Ischemic cardiomyopathy • NYHA Class I • LVEF 45% per echo at your institution • Long-time heavy smoker; has COPD • Compliant and stable on optimal medical therapy • Syncopal episodes; with documented episodes of VT

28. Patient Case #1 Clinical Decisions • Should this patient be referred for an ICD evaluation? • What factors enter into your decision? • Is there anything else you’d want to know before making the decision?

29. Arrhythmic Death in VT/VF PatientsAVID Results in Non-ICD Arm 20 18% 18 16 14 11% 12 10 % Arrhythmic Death 8% 8 6 4 2 0 1 Year 2 Years 3 Years Pratt CM. Circulation. 1998;98(suppl I):1494-1495.

30. AVID Registry Study Survival by Arrhythmia Type Unexplained syncope Non - syncopal VT w/symptoms 1.00 VF Transient correctable VT/VF Asymptomatic VT .90 VT w/syncope Cumulative Survival (%) .80 .70 P = 0.007 .65 0 1 2 3 Years Anderson JL, et al. Circulation. 1999;99:1692-1699.

31. Randomized Clinical Trials ICD Therapy for the Secondary Prevention of SCA 1 The AVID Investigators. N Engl J Med. 1997;337:1576-1583. 2 Kuck KH, et al. Circulation. 2000;102:748-754. 3 Connolly SJ, et al. Circulation. 2000;101:1297-1302.

32. Secondary Prevention Trials:Reduction in Mortality with ICD Therapy 58% 56% % Mortality Reduction w/ ICD Rx 33% 31% 23%* 20%* 1 2 3 • Non-significant results. • 1 The AVID Investigators. N Engl J Med. 1997;337:1576-1583. • 2 Kuck Kh, et al. Circulation. 2000;102:748-754. • 3 Connolly SJ, et al. Circulation. 2000;101:1297-1302.

33. 2008 ACC/AHA/HRS Class I ICDSecondary Prevention Guidelines for the Management of Ventricular Arrhythmias • History of SCA, VF, hemodynamically unstable sustained VT (exclude reversible causes) • Structural heart disease and spontaneous sustained VT, whether hemodynamically stable or unstable • Syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at EP study • Non-sustained VT due to prior MI, LVEF < 40% and inducible VT at EP study Epstein AE, et al. Circulation 2008;117:e350-408.

34. Primary Prevention of Sudden Cardiac Arrest

35. Patient Case #2 History • 52 y.o. woman • Moderate alcohol consumption, has stopped since MI • Lives alone in rural community • NYHA Class III • PMHX: MI one year ago, echo on discharge was 35% • Medications: BB, ACE-I, lipid-lowering agent, clopidorgrel, omega-3

36. Patient Case #2 Clinical Decisions • Should this patient be referred for an ICD evaluation? • What factors enter into your decision? • Is there anything else you’d want to know before making the decision?

37. SCA Relationship to HF and Reduced LVEF • Reduced left ventricular ejection fraction (LVEF) remains the single most important risk factor for overall mortality and SCD1 • As HF progresses, pump failure (rather than SCA) becomes relatively more likely as the cause of death2 • 25% overall death in 2.5 years in HF patients and 50% die of SCA3 1 Prior SG, et al. Eur Heart J. 2001;22:1374-1450. 2 MERIT-HF Study Group. Lancet. 1999;353:2001-2007. 3Sweeney MO, PACE. 2001;24:871-888.

38. SCD Risks in HF Patients with LV Dysfunction 50 Total Mortality 44 42 41 Sudden Cardiac Death 39.7 40 30 Control Group Mortality % 20 19 20 17 15 11 9 8 10 7 6 4 0 CHF-STAT GESICA SOLVD V-HeFT I MERIT-HF CIBIS-II CARVEDILOL-US 45 months 13 months 41.4 months 27 months 12 months 16 months 6 months Total Mortality ~15 to 40%; SCD accounts for ~50% of Total Deaths

39. Relation of LVEF to Risk of SCA Note: 56.5% of all SCA victims had an LVEF > 30% 7.5% 8 7 6 5.1% 5 % Sudden Cardiac Deaths 4 2.8% 3 1.4% 2 1 0 0-30% 31-40% 41-50% > 50% LVEF deVreede-Swagemakers JJ, et al. J Am Coll Cardiol. 1997;30:1500-1505.

40. Severity of Heart FailureModes of Death NYHA II NYHA III CHF CHF 12% Other 26% Other 24% 59% Sudden 64% Sudden 15% Death Death (N = 103) (N = 103) NYHA IV CHF Other 33% 56% Sudden Death 11% (N = 27) MERIT-HF Study Group. Lancet.1999;353:2001-2007.

41. SCA Relationship to MI In people who’ve had an MI and have HF, SCD occurs at 4 times the rate of the general population. Adabag AS, et al. JAMA. 2008;300:2022-2029.

42. Time Dependence of Mortality Risk Post-MIPrediction of Sudden Cardiac Death After Myocardial Infarction in the Beta-Blocking Era1 • 700 post-MI patients; ~ 95% on beta blockers 2 years after discharge. • The epidemiologic pattern of SCD was different from that reported in previous studies. • Arrhythmia events did not concentrate early after the index event; most occurred > 18 months post-MI. TotalMortality 18 18 15 15 CardiacMortality 12 12 Cumulative Events (%) 9 9 Non-SCD 6 6 SCD 3 3 20 40 60 20 40 60 Follow-Up (months) Follow-Up (months) 1 Huikuri HV, et al. J Am Coll Cardiol. 2003;42:652-658.

43. Relation of Time from MI to ICD Benefitin the MADIT-II Trial % Mortality for Each Time Period Time from MI (n = 300) (n = 283) (n = 284) (n = 292) Hazard Ratio .98 (p = 0.92) 0.52 (p = 0.07) 0.50 (p = 0.02) 0.62 (p = 0.09) Wilber, D. Circulation. 2004;109:1082-1084.

44. SCD Rates in Post-MI Patients with LV Dysfunction 32 Total Mortality 30 28 Arrhythmic Mortality 28 21 19.8 20 20 18 16 16 14 Control Group Mortality % at 2 years 12 10 9.4 10 7 0 TRACE CAPRICORN EMIAT MADIT MUSTT MUSTT MADIT II Registry Inducible Total Mortality ~20 to 30%; SCD accounts for ~50% of Total Deaths

45. Randomized Clinical Trials Supporting Device Therapy ICD and CRT-D for the Primary Prevention of SCA 1Bardy GH, et al. N Engl J Med. 2005;352:225-237. 2 Packer DL. Heart Rhythm. 2005;2:S38-S39 3 Bristow MR, et al. N Engl J Med. 2004;350:2140-2150. 4Buxton AE, et al. N Engl J Med. 1999;341:1882-1890. 5 Moss AJ, et al. N Engl J Med. 2002;346:877-883.

46. Primary Prevention Post-MI and HF Trials Reduction in Mortality with ICD or CRT-D Therapy Overall Death 80 73 Arrhythmic Death 64 62 56 55 60 36 % Mortality Reduction w/ ICD Rx 40 31 23 20 0 1,2 3 4 5 SCD-HeFT COMPANION MUSTT MADIT-II 1Bardy GH, et al. N Engl J Med. 2005;352:225-237. 2 Packer DL. Heart Rhythm. 2005;2:S38-S39 3 Bristow MR, et al. N Engl J Med. 2004;350:2140-2150. 4Buxton AE, et al. N Engl J Med. 1999;341:1882-1890. 5 Moss AJ, et al. N Engl J Med. 2002;346:877-883.

47. Patient Case #3 History • 68 y.o. male • NYHA Class III • LVEF measured in 2006 was 37% • QRS 130 ms • PMHX: MI 12 years ago • Medications: BB, ACE-I, lipid-lowering agent • Just completed last round of chemotherapy for Pancreatic CA

48. Patient Case #3 Clinical Decisions • Should this patient be referred for a CRT-D evaluation? • What factors enter into your decision? • Is there anything else you’d want to know before making the decision?

49. 2008 ACC/AHA/HRS Class I Primary Prevention Guidelines for Management of Ventricular Arrhythmias: ICD and CRT-D • ICD Class I Guidelines • LVEF < 35% due to prior MI; who are at least 40 days post-MI; and are in NHYA Class II or III • Nonischemic DCM who have an LVEF < 35% and who are in NYHA Class II or III • LV dysfunction due to prior MI how are at least 40 days post-MI; have an LVEF < 30%; and are in NHYA Class I • CRT-D Class I Guideline • LVEF < 35%; a QRS duration > 0.12 seconds; and sinus rhythm; and NHYA Class III or ambulatory IV and on optimal medical therapy Epstein AE, et al. Circulation 2008;117:e350-e408.

50. ICD Contraindications • Patient Class III contraindications for ICD or CRT-D: • Not expected to survive with an acceptable functional status for at least one year • Incessant VT or VF • Significant psychiatric illness that may be aggravated by device transplant or preclude systematic follow-up • NYHA Class IV with drug-refractory HF, who are not candidates for cardiac transplantation or CRT-D • Syncope of undetermined cause without inducible VT and without structural heart disease • VT or VF that is amenable to surgical or catheter ablation • Patients whose VTs due to a completely reversible cause in the absence of structural heart disease • Questions • Are there patients who are indicated but who should not get an ICD? • Who makes the decision on whether or not an ICD is offered? Epstein AE, et al. Circulation. 2008;117:e350-e408.