Redefining Sudden Cardiac Death: Insights from the Comprehensive UCSF SCD Study

Transcription

1 Redefining Sudden Cardiac Death: Insights from the Comprehensive UCSF SCD Study 8 September 2012 California Heart Rhythm Symposium Zian H. Tseng, M.D., M.A.S. Associate Professor of Medicine in Residence Cardiac Electrophysiology Section University of California, San Francisco

2 Disclosures Major Research grant: K12 RR (NIH) Research grant: R01 HL (NIH / NHLBI ) Minor Biotronik: Honorarium

3 Outline 1. What do we know (or think we know) about SCD 2. Gaps in SCD knowledge 3. Preliminary findings of Comprehensive UCSF SCD Study 4. Early study insights 5. Interesting case studies

4 Etiology of Sudden Cardiac Death Huikuri et al. N Engl J Med, Vol

5 Magnitude of Sudden Cardiac Death in the U.S. 500,000 # deaths/year 400, , , ,000 0 AIDS Breast Cancer Lung Cancer Stroke SCD 1 U.S. Census Bureau, Statistical Abstract of the United States: American Cancer Society, Inc., Surveillance Research, Cancer Facts and Figures Heart and Stroke Statistical Update, American Heart Association. 4 Circulation. 2001;104:

6 Sudden Cardiac Death: Definitions 2006 ACC/AHA/HRS standardized definition: SCA is the sudden cessation of cardiac activity so that the victim becomes unresponsive, with no normal breathing and no signs of circulation. If corrective measures are not taken rapidly, this condition progresses to sudden cardiac death. Cardiac arrest should be used to signify an event as described above, that is reversed, usually by CPR and/or defibrillation or cardioversion, or cardiac pacing. SCD should not be used to describe events that are not fatal.

7 Sudden Cardiac Death: Definitions VALIANT trial: Valsartan after acute MI and HF The cause of death was considered as SCD if death occurred suddenly and unexpectedly in a patient in otherwise stable condition, with no premonitory HF, MI, or another clear cause of death. These could have been witnessed deaths (with or without documentation of arrhythmias) or unwitnessed deaths if the patient had been seen within 24 hours before death. MERIT-HF trial: Metoprolol for Heart Failure SCD: Witnessed instantaneous death in the absence of progressive circulatory failure lasting for 60 min or more, unwitnessed death in the absence of pre-existence progressive circulatory failure or other causes of death

8 Sudden Cardiac Death: Definitions Criteria focus on the out-of-hospital occurrence of a presumed sudden pulseless condition and the absence of evidence of a noncardiac condition (e.g., central airway obstruction, intracranial hemorrhage, PE) as the cause of SCA. Adjudicated review of all available records (paramedic reports, rhythm strips, past medical records, etc.) World Health Organization (WHO) definition of SCD: Unexpected death within 1 h of symptom onset if witnessed Unexpected death within 24 h of having been observed alive and sx-free if unwitnessed

9 Methodological Issues in Population Studies of SCD Estimates in the US range from 184, ,000 annually due to subjective/ inconsistent methods of data collection Most data predates modern cardiac era Derived from homogenous (white) populations Where does the data come from? Death record review of listed COD Paramedic/ER narratives Which deaths can be counted as SCD? WHO criteria Documented VF Subjective interpretation of presentation narrative

10 Comprehensive Surveillance of SCD Oregon SUDS (Chugh, JACC, 2004) WHO criteria Portland, OR: population 1,000,000 Track dozens of ambulance companies and area hospitals Review of all available records SCA: 53/100,000

11 Sudden Arrhythmic Death vs. Sudden Cardiac Death The most relevant SD phenotype from an EP and public health standpoint (and the only one treated with ICD) is sudden arrhythmic death How many SCDs nationwide are caused by treatable arrhythmias? How do we know that presumed SCDs are even truly cardiac? Gold standard test is needed to rule out noncardiac and nonarrhythmic causes Pulmonary embolus Tamponade Aortic valve rupture

12 Comprehensive UCSF SCD Study By CA state law, all deaths occurring outside of the hospital (including ER deaths) have to be reported to the ME Office Nearly all sudden deaths are investigated ME Office is thus a robust surveillance method for all OOH SCDs Typical autopsy rates of prior case studies of SCD (from which paradigms have been derived): 10-15% The more likely a death is natural, the less likely autopsy is performed

13 Comprehensive Surveillance of SCD Oregon SUDS (Chugh, JACC, 2004) WHO criteria Portland, OR: population 1,000,000 Track dozens of ambulance companies and area hospitals Review of all available records SCA: 53/100,000 Autopsy rate: 11%

14 Comprehensive Surveillance of SCD in San Francisco All out of hospital and ER deaths are reported by law San Francisco Medical Examiner

15 Metropolitan San Francisco Population: ~750,000 residents (49 mi 2 ) ~1.5 million during business day Racially/ethnically diverse: 48% White 33% Asian-American 15% Hispanic 6.1% African-American By 2050, population of U.S. will closely reflect that of S.F. (US Census Bureau)

16 UCSF-ME SCD Study Design 3-year autopsy study of all sudden deaths in San Francisco (WHO criteria), including detailed cardiac evaluation: Heart weight/cmi LV septal thickness (origin of papillary muscles) Coronary vessels sectioned every 5mm to grade stenosis severity Trichrome histology to evaluate myocardial fibrosis All reported deaths reviewed every morning to screen for WHO criteria Cardiac, skin, and blood specimens for future studies (with NOK consent)

17 Study Eligibility Criteria Deaths reported to the MEO are preliminarily enrolled as SCDs if: 1. Age Death occurred within city and county of SF 3. Initial presentation meets WHO criteria Exclusion criteria: 1. Documented end-stage disease (e.g., ESRD on dialysis, metastatic cancer, COPD on home O2) 2. Current or very recent SNF/hospice care 3. Specific and significant recent-onset complaints 4. Significant evidence of suicide or overdose at time of presentation

18 Study Workflow Enrollment Autopsy PMH Record Review Adjudication Eligibility criteria are applied between each step as PMH and post-mortem data are collected

19 Case Adjudication Each case is determined to be arrhythmic, nonarrhythmic, or non-cardiac based on: - Past medical history (active problems, prescriptions, recent visits) - Medications (e.g., QT-prolonging, methadone) - Narratives and rhythm at death presentation - Autopsy findings (including toxicology and histology) Adjudication panel 2 Electrophysiologists Cardiac pathologist Medical Examiner Neurologist

20 Surveillance of WHO SCDs (2/1/2011-9/3/2012) Natural Deaths (Possible SCD) Non-Case, SCD SCD-Missed (External Only) SCD (Full Autopsy) SCD-Excluded Non-Arrhythmic Arrhythmic Non-Cardiac

21 Sudden Arrhythmic Deaths vs. Control (Trauma) Deaths SF ME Deaths N=1420 WHO SCDs Accidental Trauma deaths N=376 Autopsy Autopsy Arrhythmic Cardiac Non- Cardiac Non-arrhythmic Comparison to an appropriate control group, randomly sampled from the same population at risk for SCD, already receiving autopsy Steinhaus DA.Tseng ZH. Am Heart J Jan;163(1):

22 Study Cohort Demographics (2/2/11 8/15/12) * *

23 Relative SCD Incidence by Demographic Group (2/2/11 12/23/11) 3.2-fold higher incidence of arrhythmic SCD in males vs. females 1.6-fold higher incidence of arrhythmic SCD in black vs. white

24 SCD Rates in San Francisco, Rates of SCD per 100, SF 2007 WHO SCD SF 2007 SAD Chugh et al. (2004) de Vreede- Swagemakers et al. (1997) Low Rate Becker et al. (1993) High Rate Becker et al. (1993) 1. Chugh SS, Jui J, Gunson K, Stecker EC, John BT, Thompson B, Ilias N, Vickers C, Dogra V, Daya M, Kron J, Zheng ZJ, Mensah G, McAnulty J. Current burden of sudden cardiac death: mul\ple source surveillance versus retrospec\ve death cer\ficate- based review in a large U.S. community. J Am Coll Cardiol. 2004;44(6): de Vreede- Swagemakers JJ, Gorgels AP, Dubois- Arbouw WI, van Ree JW, et al. Out- of- hospital cardiac arrest in the 1990s " a popula\on- based study in the Maastricht area on incidence, characteris\cs and survival. J Am Coll Cardiol 1997;30(6): Becker, LB, Smith DW, Rhodes KV. Incidence of cardiac arrest: a neglected factor in evalua\ng survival rates. Ann Emerg Med 1993;22(1): Steinhaus DA.Tseng ZH. Am Heart J Jan;163(1):

25 Adjudicated Causes of WHO SCDs 33% of All 57% of WHO SCD Arrhythmic SCD (n=127) (n=74)

26 Nearly half of WHO SCDs are Non-Cardiac 47 of 127 (40%) WHO SCDs were non-cardiac

27 Presenting Rhythms for Witnessed SCDs

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32 Morbidity Prevalence: Arrhythmic SCD vs. Trauma Deaths

33 Cardiac Parameters in Arrhythmic SCDs vs. Trauma Deaths Cardiac mass predicts arrhythmic SCD Higher degree of CAD in arrhythmic SCD LAD (46%) and RCA (35%) most commonly affected vessels Higher incidence of previous MI (23%) for arrhythmic SCD 12 (41%) of arrhythmic SCDs had microscopic replacement fibrosis without a grossly visible scar

34 Interstitial Fibrosis in SADs vs. Trauma Controls 40x LV septum, trichrome stain 75 yo AM trauma victim, minimal CAD 77 yo AM SAD victim, minimal CAD Global interstitial fibrosis score 1.5-fold higher in SADs than controls, adjusted for age, sex, ethnicity, CAD level

35 Sudden Cardiac Death in Patients with HIV Infection 2860 consecutive patients in a public HIV clinic (SFGH) April August deaths over 3.7 median years follow-up 13% SCDs, 86% (30/35) of all cardiac deaths Mean HIV+ SCD rate was 4.5-fold higher than background HIV- SCD rate

36 Magnitude of Sudden Cardiac Death in the U.S. 500,000 >2-fold overestimate # deaths/year 400, , , ,000 0 AIDS Breast Cancer Lung Cancer Stroke SCD 1 U.S. Census Bureau, Statistical Abstract of the United States: American Cancer Society, Inc., Surveillance Research, Cancer Facts and Figures Heart and Stroke Statistical Update, American Heart Association. 4 Circulation. 2001;104:

37 Etiology of Sudden Cardiac Death 2-fold overestimate Adapted from Huikuri et al. N Engl J Med, Vol

38 Early Insights WHO SCD criteria have a low PPV (60%) for SAD Men, blacks have 2-fold higher incidence of SAD than reference Active coronary lesion and CAD as the cause of SAD is far lower than previous estimates Interstitial myocardial fibrosis is associated with SAD and may serve a useful risk stratifier High rates of SCD in HIV: risk factors? Sudden neurologic death Vast underestimation of device/lead failures

39 Interesting Case Studies 78 yo Caucasian man Nonischemic dilated cardiomyopathy, stable EF 25% Paroxysmal AF Primary prevention ICD implanted 3 years ago, no shocks In usual state of health when wife left for shopping 3 hours later wife found him unresponsive Paramedics called, asystole on arrival, no resuscitation attempted

40 ICD Interrogation x 30

41 Interesting Case Studies At autopsy Massive subarachnoid hemorrhage (requires perfusing rhythm) Heart 760 g Neurocardiogenic injury VF due to acute adrenergic surge Despite rhythm documentation of VF, cause of death was neurologic

42 Interesting Case Studies 74 yo Filipino man 4 V CABG 2002 EF 22%, fixed defect anterior, inferior walls Diabetes Admitted for fever and bronchitis, receiving IV antibiotics Troponin negative, slightly fluid overloaded Called to consult on several asymptomatic runs of NSVT (5-7 beats) and to consider primary prevention ICD

43 Interesting Case Studies Recommended uptitration of ß blocker, ICD implant as an outpatient after completing antibiotic treatment ICD scheduled for 1 month after discharge 2 weeks later patient found dead in the morning by wife Pt had returned to usual state of health, no complaints the night before

44 Interesting Case Studies Referring MD At autopsy, 2.5 L fresh blood in stomach and duodenum Heart: no acute coronary lesions Cause of death: exsanguination ICD would not have prevented SCD, pt may not have survived procedure

45 Acknowledgements SF Medical Examiner s Office Ellen Moffatt Amy Hart UCSF Pathology Phil Ursell UCSF EP Section Jeff Olgin Brian Moyers Ben Colburn Lauren McGuire Dean Whiteman UCSF Epidemiology Eric Vittinghoff UCSF Neurology Anthony Kim SFFD/ SFGH Emergency Medicine Karl Sporer Clement Yeh UCSF Program in Human Genetics Brad Aouizerat Massachusetts General Hospital Dan Steinhaus

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