Disclosures Redefining Sudden Cardiac Death: Insights from the San - PDF document

Disclosures Redefining Sudden Cardiac Death: Insights from the San Francisco • Industry PO stmortem S ystematic • None inves T igation of • Grants S udden C ardiac D eath Study • NIH/NHLBI: R01 HL 102090 • NIH/NHLBI: R01 HL 126555 14 September 2019 • CDC: 6 NU38DP000019-01-01 10 th Annual California Heart Rhythm Symposium • CDC: 1 NU38DP000019-01-00 Zian H. Tseng, M.D., M.A.S. Professor of Medicine in Residence Murray Davis Endowed Professor Cardiac Electrophysiology Section University of California, San Francisco U.S. Mortality by Death Certificates Etiology of Sudden Cardiac Death 500,000 400,000 # deaths/year 300,000 200,000 100,000 0 AIDS Breast Lung Stroke SCD Cancer Cancer 1 U.S. Census Bureau, Statistical Abstract of the United States : 2001. 2 American Cancer Society, Inc., Surveillance Research, Cancer Facts and Figures 2001. 3 2002 Heart and Stroke Statistical Update , American Heart Association. 4 Circulation . 2001;104:2158-2163. Huikuri et al. N Engl J Med , Vol. 345 2001 1

Background RCTs, Cohorts: Sudden Cardiac Death • ARIC, CHS: • Traditional SCD definitions are based on: – “ A sudden pulseless condition from a cardiac origin in a previously • Death certificates stable individual occurring OOH or in the ED. For unwitnessed deaths, the participant must have been seen within 24h of arrest in • EMS records (CARES) a stable condition and without evidence of a noncardiac cause.” • Epidemiologic criteria (ACC/AHA/HRS, WHO, • MERIT-HF trial: Metoprolol for Heart Failure Hinkle-Thaler) which all presume cardiac cause – “Witnessed instantaneous death in the absence of progressive • Therefore, incidence of SCD estimates vary widely circulatory failure lasting for 60 min or more, unwitnessed death in the absence of pre-existence progressive circulatory failure or other causes of death” • Hinkle-Thaler, 1982: • WHO criteria: – “No evidence of circulatory impairment until they collapsed and the • Witnessed: unexpected death within 1 h symptom pulse disappeared” onset • SCD-HeFT and MADIT 2 • Unwitnessed: unexpected death within 24 h of – No definition of SCD having been observed alive and free of symptoms Emperor’s New Clothes? • ~ 90% of SCDs occur out of hospital (OOH) 1 in jurisdiction of coroner or medical examiner (ME) • Investigation after such natural deaths is not routine ME 14 February 2016 practice. Autopsy rates • OOH deaths: ~10% (U.S.), 2 23% (Finland) 3 • Hinkle-Thaler: 27% 4 • Exemplar autopsy studies demonstrating CAD as cause of > 80% of SCDs 5,6 therefore limited by referral bias 1. Nichol JAMA 2008 2. Shojania NEJM 2008 3. Lunetta Inj Prev 2007 4. Hinkle, Thaler Circulation 65,1982. 5. Davies Circulation 85, 1992 6. Burke…. Virmani NEJM 1997 2

Comprehensive Surveillance of SCD Comprehensive Surveillance of SCD ▪ Oregon – SUDS (Chugh, JACC , 2004) ▪ Oregon – SUDS (Chugh, JACC , 2004) ▪ WHO criteria ▪ WHO criteria ▪ ▪ Portland, OR: population 1,000,000 Portland, OR: population 1,000,000 ▪ ▪ Track dozens of ambulance companies and area Track dozens of ambulance companies and area hospitals hospitals ▪ ▪ Review of all available records Review of all available records ▪ ▪ SCA+SCD: 53/100,000 SCA+SCD: 53/100,000 Autopsy rate: 11% Chugh SS et al J ACC 2004 Chugh SS et al J ACC 2004 Sudden Cardiac Arrest vs. Sudden “Cardiac” Death Sudden Cardiac Death SCA SCA CAD Tamponade SCD? Valvular Neurologic DCM HCM Ao Dissection Hemorrhage 1 o electrical disease 3

San Francisco POST SCD Study Sudden Arrhythmic Death PO stmortem S ystematic Inves T igation of S udden C ardiac D eath SCA CAD Tamponade Valvular All out of hospital and ER deaths reported Neurologic by law to ME DCM Every Incident HCM SCD Hemorrhage 2011- Ao Dissection 1 o electrical disease UC SF Medical Examiner SF Cardiology Deaths in San Francisco County 2/1/2011-3/1/2014 N = 20,440 Case Adjudication Death Certificate Review Not Reported to ME Inpatient/Hospice Deaths N = 7,769 Data reviewed at adjudication Reported to ME Non-Natural Deaths All OOH, ED, Unexpected N = 2,021 Inpatient Deaths - PMH (active problems, prescriptions, recent visits) N = 12,671 Age <18 or >90 - Medications (Rx, QT-prolonging, methadone) N = 2,012 - EMS runsheets and rhythms Inpatient / Nursing Home / EMS + ME Scene Hospice Deaths Investigation Review - Witness/family interviews N = 3,862 Attended Deaths Ineligible for Autopsy N = 2,744 Active MD care < 3 wk, MD Signed DC - Autopsy, tox, histology findings N = 1,120 OHCA Deaths N = 89 Referred for Autopsy N = 912 Adjudication panel WHO-Defined SCDs Non-Sudden Comprehensive w/o Autopsy Deaths Non-Sudden Deaths Medical Records N = 105 N = 1,031 N = 3,115 Review Declined Autopsy N = 16 Autopsied OHCA Deaths N = 896 Adjudication OHCA Deaths N = 371 Dr. Anthony Kim Dr. Phil Ursell Dr. Ellen Moffatt Dr. Zian H. Tseng Dr. Jeff Olgin Excluded Deaths (Suppl Table I) Chief Cardiac Medical Examiner, Study PI Chief of Cardiology, Neurologist Adjudicated Autopsied WHO-Defined SCDs (Suppl Table II) Pathologist City and County of Cardiac UCSF Director of UCSF WHO-Defined SCDs UCSF San Francisco Electrophysiologist, Stroke Center N = 525 Tseng ZH…Moffatt E Circulation 2018 UCSF 4

SCD Case Study #1 SCD Case Study #1 • 74 yo Filipino gentleman • Recommended uptitration of ß blocker, ICD – 4 V CABG 2002 implant as an outpatient after completing – EF 22%, fixed defect anterior, inferior walls antibiotic treatment – Diabetes • ICD scheduled for 1 month after discharge • Admitted for fever and bronchitis, receiving IV • 2 weeks later patient found dead in the antibiotics morning by wife • Troponin negative, slightly fluid overloaded • Pt had returned to usual state of health, no • Called to consult on several asymptomatic complaints the night before runs of NSVT (5-7 beats) and to consider primary prevention ICD Adjudicated Etiologies of SCD “Non - Cardiac SCD” • 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 Tseng, ZH….Moffatt E . AHA Late-breaking 2016 5

SCD and SAD Incidence Rates per 100,000 person-years 75 4 89 Person-Years 70 Key: Trauma Death SAD� Weighted 65 3 SCD� Observed Non-SAD 60 SAD� Unweighted Autopsy-Defined SAD 55 100,000� 2 50 Z-Score N� =� 1001 45 per� 436 23 40 1 Rates� 323 35 45% 630 Incidence� 30 0 63.1% 25 56.7% 147 59.6% 20 194 57.4% 48 -1 Adjusted� 15 61.8% 54.6% 10 45% -2 5 0 h m c c e c e e D D n M c e M t a i s i s s o i r m g A A m Total Total Female Male Asian Black Hispanic White Other a s C u C i a a o i e i d o C C t l l h e e d c D h i H o r l a D a t s o s r e t WHO-Defined� SCDs b y c e / y OHCA� r e c F C i i s a m h D u D v i t i h n u s m Deaths m - r e r l E n r O o c i r a t l D WHO-Defined� SCD Weighted� Autopsy-Defined� SAD A r N a r e A n u o A Median y a c t h h e a N - l c n e u C r r i i c e R IRR P-value IRR P-value r a H r t T o t c s n r c r h e N c o I e - t o e O O Male� vs.� Female 2.37 <.0001 3.33 <.0001 h A n m , v l t E o O c i s l a N Asian� vs.� White 0.48 <.0001 0.44 <.0001 u y i n IQR P d r e a r t Black� vs.� White 2.04 <.0001 1.52 .05 a m r e C i p r Hispanic� vs.� White 0.48 <.0001 0.44 <.0001 P y Tseng, ZH….Moffatt E . H Other� vs.White 1.11 .34 1.03 .91 In review SAD in Women vs. Men SCD Case Study #2 • 78 yo Asian man – Dilated cardiomyopathy, stable EF 25% P=0.0006 – Paroxysmal AF, on warfarin – Primary prevention ICD implanted 3 years ago, no shocks • In usual state of health when wife went shopping • 3 hours later wife found him unresponsive • Paramedics called, asystole on arrival, no resuscitation attempted Tseng, ZH….Moffatt E . In review 6