Risk Stratification of Sudden Cardiac Death

Transcription

1 Risk Stratification of Sudden Cardiac Death Michael R Gold, MD, PhD Medical University of South Carolina Charleston, SC USA Disclosures: None

2 Sudden Cardiac Death A Major Public Health Problem > 1/2 of all cardiac deaths 1/6 of all deaths > 400,000 SCD annually in US

3 Sudden Death Can Result From a Variety of Processes Sustained Monomorphic VT VF Asystole

4 Sudden Death Can Result From a Variety of Processes Acute Ischemia Causing Ventricular Fibrillation

5 Sudden Death Can Result From a Variety of Processes Complete Heart Block Ventricular Fibrillation

6 Sudden Death Can Result From a Variety of Processes Pause Dependent Torsade de Pointes Associated with Antifungal Drug

7 40 Years of ICD Technology Engineering Tour de Force

8 ICDs in the Prevention of Death from Tachyarrhythmia Cardiac Arrest AVID Secondary Prevention 80% CAD 20% other The AVID Investigators NEJM 1997;337:1576

9 Secondary Prevention of SCD AVID/CIDS/CASH Metaanalysis EVENTS AT 2 YEARS ICD N=934 AMIO N=932 H.R. Deaths p<0.001 Arrhythmic p<0.001 Non - Arr

10 Survival From Out-of-Hospital Cardiac Arrest 19% Seattle % AED Seattle % (Blacks) 2.6% (Whites) Chicago % Miami % AED Miami

11 HAT Study Primary Endpoint

12 PAD Trial 993 Units 157 Residential (16%) 836 Public (84%) Recreational facilities (28%) Shopping centers (28%) Entertainment complexes (10%) Community centers (8%) Large office buildings (8%) Other (hotels, factories, transit centers) (17%) Hallstrom A, et al. N Engl J Med. 2004;351:637.

13 PAD Trial Hallstrom A, et al. N Engl J Med. 2004;351:637.

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16 Septadian Variability of SCD

17 Subpopulation on Beta Blockers

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20 Influence of Race on SCD Per 100,000 Standard US Population African-American White American Indian Asian Years Age-adjusted death rates (per 100,000 US population) for sudden cardiac death Zheng Z. Circulation 2001

21 Risk Stratification for SCD Risk stratification of SCD has been studied for 40 years The rule of 80 emerged 80% Male 80% VT/VF 80% CAD 80% LV dysfunction More recent epidemiological studies have questioned these assumptions which are the foundation of preventative strategies

22 Sudden Cardiac Death The Maastricht Prospective Registry : 492 cases Hx of CHF 59 pts (12%) In 54% (224 pts) cardiac arrest was the first manifestation of cardiac disease! Gorgels et al. European Heart J, 2003; 24:1204

23 Sudden Cardiac Death The Maastricht Prospective Registry Patients with Cardiac History: n=224 CAD (77%) New MI 10 (6%) Prior MI 113 (66%) Time first MI to SCA 9.7 ± 7.5 yrs Prior Ant. MI 37% Inf. MI 53% Gorgels et al. European Heart J, 2003; 24:1204

24 The Oregon Sudden Unexpected Death Study : 714 cases-multnomah County, Oregon (pop.: 660,486) EF measured prior to event in only 121 cases (17%) Stecker et al. JACC, 2006; 47:1161

25 Sudden Death-The Oregon Sudden Unexpected Death Study Patients with Known EF (121) LV Ejection Fraction % 35% % 22 55% 48 Stecker et al. JACC, 2006; 47:1161

26 LVEF and SCA Incidence % SCA Victims % 5.1% 2.8% 1.4% 0-30% 31-40% 41-50% >50% LVEF devreede-swagemakers JJ. J Am Coll Cardiol. 1997;30:

27 Why is there a paradox between SCD and post MI Risk? Gusto Study (n=2400) Angiographic substudy Cardiac Cath 5-7 days post MI EF < 30% 4.3% EF 30-40% 10.1% EF > 40% 85.6% Equivalent sudden deaths in EF <30% and EF > 40% groups even if 20-fold greater risk!

28 Non-Antiarrhythmic Drugs that Reduce Mortality and SCD Beta Blockers ACE Inhibitors ARBs Statins Aldosterone Antagonists ASA

29 Antiarrhythmic Drugs that Reduce Mortality and SCD

30 MADIT I- Inclusion Criteria CAD LVEF < 35% Nonsustained VT Inducible VT (+ EPS)

31 Probability of survival MADIT I - Survival p=.009 at termination 2 yr mortality 39% v 16% HR Defibrillator Conventional therapy Year Moss AJ. N Engl J Med. 1996;335:

32 MUSTT Randomized Patient Results Total Mortality EP-Guided Rx, No ICD No EP-Guided AA Rx EP-Guided Rx, ICD Event Rate p < Time after Enrollment (Years) Buxton AE. N Engl J Med. 1999;341:

33 MADIT II - Eligibility Criteria Inclusion LVEF < 30% > 1 prior MI No arrhythmia req. Exclusion NYHA Class IV < 1 month from acute MI CABG or PTCA < 3 months Patients meeting MADIT I criteria

34 MADIT-II Survival 1.0 Probability of Survival Conventional Defibrillator 0.6 P = No. At Risk Year Defibrillator (0.91) 274 (0.94) 110 (0.78) 9 Conventional (0.90) 170 (0.78) 65 (0.69) 3 Moss AJ. N Engl J Med. 2002;346:

35 MADIT II 8 Year Long Term Follow-up Number Needed to Treat to save one life (NNT) and Life Years Saved (LYS) for all MADIT II patients month NNT 17 6 LYS Death 31% 37%

36 2521 patients with either ischemic or NIDCM NYHA Class II or III EF < 35% Single chamber ICDs VVI 35/50bpm. Shock only 188 bpm Amio/placebo drug or ICD/placebo drug

37 Sudden Cardiac Death SCD-HeFT Heart Failure Trial Mortality by Intention to treat N = 2,521 HR 97.5% CI P-Value Amiodarone vs. Placebo , ICD Therapy vs. Placebo , % 34.0% 28.9 % Mortality 0.2 Follow-up: 45.5 months Vital status: 100% known 0.1 Bardy, NEJM 2005 Amiodarone ICD Therapy Placebo Months of follow-up

38 DINAMIT 674 Patients s/p Acute MI Single lead ICD EF ~ 28% 70% Q wave MI Time to ICD from MI -18 dy Hohnloser, S. et al. N Engl J Med 2004;351:

39 Immediate Risk-Stratification Improves Survival (IRIS) Study N=902 patients Randomized comparison of ICDs vs. OMT 5-31 days after MI LVEF 40%, HR > 90 +/- NSVT No survival benefit with prophylactic ICD therapy Steinbeck G, et al. N Engl J Med 2009;361:

40 Incremental Benefits with HF Therapies (Cumulative % Reduction in Odds of Death at 24 Months) -28% to -49% P< % to -71% P< % to -81% P< % to -86% P< % to -88% P< % to -87% P< Fonarow GC, Yancy, CW. J Am Heart Assoc 2012;1:16-26.

41 Primary Prevention ICDs in Nonischemic Cardiomyopathy The role of ICDs among patients with ischemic cardiomyopathy was is well established, provided that it is not implanted early post MI Further expansion of ICD indications for patients with nonischemic cardiomyopathy was evaluated in a series of trials This included both narrow and wide QRS patients using conventional ICDs or CRT devices

42 DEFINITE NIDCM Age 58 71% men 23% DM 25% AF QRS 115 ms LBBB 20% HR 0.65 [95% CI, 0.40 to 1.06] ACE/ARB 97% -blockers 85% P=0.08 ICD 229 pts Standard pts Kadish A et al NEJM 2004;350:2151 Follow up 29 +/- 14 months

43 DEFINITE Sudden Death Mortality All-Cause Mortality in NYHA Class III P=0.006 P=0.02 Kadish A et al NEJM 2004;350:2151

44 DEFINITE: ICDs in NIDCM No required time from HF diagnosis to enrollment Early ICD Implants <3 mo (150) Control 17.6% ICD 7.3% HR = 0.37 ( ) p = % RR Kadish et al JACC 2006

45 Sudden Cardiac Death SCD-HeFT Heart Failure Trial Mortality by Intention to treat N = 2,521 HR 97.5% CI P-Value Amiodarone vs. Placebo , ICD Therapy vs. Placebo , % 34.0% 28.9 % Mortality 0.2 Follow-up: 45.5 months Vital status: 100% known 0.1 Bardy, NEJM 2005 Amiodarone ICD Therapy Placebo Months of follow-up

46 Sudden Cardiac Death SCD HeFT Heart Failure Trial Mortality by NYHA Class: ICD vs. Placebo Class II ICD Therapy Placebo Class III HR 97.5% CI , % 46% Mortality HR 97.5% CI , % 20% Months of follow-up Months of follow-up NYHA Class II - NNT = 8

47 Sudden Cardiac Death SCD HeFT Heart Failure Trial Mortality by CHF Etiology Mortality Ischemic Etiology ICD Therapy Placebo HR 97.5% CI , % 36% Non Ischemic Etiology HR 97.5% CI , % 21% Months of follow-up Months of follow-up

48 Sudden Cardiac Death SCD HeFT Heart Failure Trial Mode of Death in SCD HeFT: ICD Placebo % Deaths % % % % % % 83 Total Deaths: ICD = 182 Placebo = 244 ICD Placebo 0 Arrhythmic Heart Failure Other p <0.001 *45.5 mo median f/u Adapted from Packer D, et al HRS 2005

49 Class and etiology of CHF: VT/VF shocks # of Pts % 21% 24% 25% II III Isch. N-Isch. ICD implanted VT/VF shock

50 Classification of Recommendations for Device-Based Therapy SIZE OF TREATMENT EFFECT Class I Benefit > > > Risk Procedure/Treatment SHOULD be performed/administered Class IIa Benefit > > Risk Additional studies with focused objectives needed IT IS REASONABLE to perform procedure/ administer treatment Class IIB Benefit > Risk Additional studies with broad objectives needed; additional registry data would be helpful Procedure/Treatment MAY BE CONSIDERED Class III Risk > Benefit Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL From: ACC/AHA/HRS Guideline Committee JACC 2008; 51:

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52 Danish NIDCM Trial NYHA class II or III, or NYHA class IV if CRT LVEF 35%, > 200 pg/ml of NT probnp GDMT target doses of ACE/ARB and blockers PM or CRT P was not an exclusion AF with HR resting over 100 bpm excluded Dialysis excluded

53 Danish NIDCM Trial 1116 patients Randomized to ICD or usual clinical care Mean QRS: 146 ms (ICD); 145 ms (control) CRT: 58% (ICD); 58% (control)

54 Outcomes All Cause Mortality

55 Outcomes Cardiovascular Death Sudden Cardiac Death

56 Comparisons: DEFINITE, SCD HeFT, DANISH DEFINITE SCD HeFT DANISH ACE/ARB 96.7% 89% 97% blockers 85% 78% 92% Mineralocorticoid? 30% 58%

57 Mortality: DEFINITE DANISH DEFINITE CONTROL DEFINITE ICD

58 Mortality Comparisons SCD-HeFT CONTROL SCD-HeFT ICD

59 COMPARISON OF REPORTED SCD RATES DANISH: Unusually low SCD rate: 1.5% per year, only 35% of all deaths were sudden PARADIGM DANISH Blue Dots

60 DANISH TRIAL CONSIDERATIONS Selection Bias: Enrolled unusually low risk NIDCM patients were the more ill already offered ICDs? Well treated on GDMT Outcome adulterated by CRT Much higher % of CRT eligible patients enrolled than found in usual outpatient clinics (20 25% v 60% in DANISH)

61 CARE-HF Hazard Ratio 0.60 (95% CI 0.47 to 0.77; P<0.0001) CRT Survival 0.50 Medical Therapy 0.25 Number at risk CRT Medical therapy Time (days)

62 COMPANION: All-Cause Mortality

63 All-cause Mortality in NICM Patients with Primary Prevention ICD or CRT From: Golwala H et al. Circulation 2017; 135:

64 SUMMARY SCD remains a major cause of mortality in the US and Asia Treatment and Prevention of CAD and CHF are important, including PCI and Medications ICDs are the most effective therapy to prevent SCD, but utililaztion remains low ICDs should be considered in ischemic cardiomyopathy as well as dilated cardiomyopathy which persist with GDMT, despite the recent Danish Trial