1 EMS: Out of Hospital Cardiac Arrest ACC/AHA/HRS: Sudden Cardiac - - PDF document

1

Redefining Sudden Cardiac Death: Insights from the San Francisco POstmortem Systematic invesTigation of Sudden Cardiac Death Study

17 December 2016 33rd Annual Advances in Heart Disease Park Central Hotel, San Francisco

Zian H. Tseng, M.D., M.A.S. Associate Professor of Medicine in Residence Murray Davis Endowed Professor Cardiac Electrophysiology Section University of California, San Francisco

U.S. Mortality by Death Certificates

100,000 200,000 300,000 400,000 500,000 AIDS Breast Cancer Lung Cancer Stroke SCD # deaths/year

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.

Etiology of Sudden Cardiac Death

Huikuri et al. N Engl J Med, Vol. 345 2001

RCTs, Registries: Sudden Cardiac Death

• 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 h before death.”

• MERIT-HF trial: Metoprolol for Heart Failure

– “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”

• Hinkle-Thaler, 1982:

– “No evidence of circulatory impairment until they collapsed and the pulse disappeared”

• SCD-HeFT and MADIT 2

– No definition of SCD

2

ACC/AHA/HRS, 2006:

“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.”

ACC/AHA/HRS: Sudden Cardiac Death

2004: CDC established Cardiac Arrest Registry to Enhance Survival (CARES) to precisely define OHCA

• utcomes in the continuum of emergency cardiac care:

911 dispatch centers, EMS providers, and receiving hospitals “OHCA is a cardiac arrest that occurred in the pre- hospital setting, had a presumed cardiac etiology, and involved a person who received resuscitative efforts, including CPR or defibrillation.”

EMS: Out of Hospital Cardiac Arrest

World Health Organization (WHO), 1969:

– 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

• Out-of-hospital
• Absence of obvious noncardiac condition
• Presumed sudden pulseless condition

Sudden Cardiac Death: Definition Methodological Issues in Population Studies of SCD

§ US incidence estimates: 184,000 - 450,000 annually (2.5-fold range) § Where does the data come from?

§ Death certificate review of listed COD § Retrospective review of paramedic/ER narratives § Incomplete medical records

§ Which definition should we use for SCD?

§ WHO (Hinkle-Thaler) criteria? § Documented VF? § CARES? § Witnessed cases only?

3

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
• practice. Autopsy rates:
• OOH deaths: ~10% (U.S.),2 23% (Finland)3
• Hinkle-Thaler: 27%4
• Exemplar autopsy studies demonstrating CAD as cause
• f > 80% of SCDs5,6 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 NEJM1997

14 February 2016

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+SCD: 53/100,000

Chugh SS et al JACC 2004

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+SCD: 53/100,000

Chugh SS et al JACC 2004

Autopsy rate: 11%

4

Sudden Cardiac Arrest vs. Sudden Cardiac Death

SCA SCD

Sudden Cardiac Arrest vs. Sudden Cardiac Death

SCA SCD?

Sudden “Cardiac” Death

SCA Valvular CAD DCM HCM 1o electrical disease Tamponade Neurologic Ao Dissection Hemorrhage

Sudden Arrhythmic Death

SCA

Valvular

CAD DCM HCM 1o electrical disease

Tamponade Neurologic Hemorrhage Ao Dissection

5

San Francisco POST SCD Study

POstmortem Systematic InvesTigation of Sudden Cardiac Death SF Medical Examiner SF Cardiology UC

All out of hospital and ER deaths reported by law to ME Every Incident SCD 2011-

San Francisco County

• Single ME Office serving 49 mi2, pop

864,000 (~1.5M business hrs)

• Racially/Ethnically diverse:

33% Asian, 6.1% Black, 15% Hispanic, 48% White

• 8 Hospitals, 3 ambulance companies

(SFFD responds to ~85% of 911 calls)

• By CA state law, all OOH or ER

deaths are reported to the ME

Methods

• Daily AM review of all OOH deaths reported to ME

to determine WHO SCDs ages 18-90 y for full autopsy, histology, tox

• All county death certificates retrieved and reviewed

quarterly from DPH to cross-check for missed SCDs

• IRBs with all county hospitals and ambulance

companies

• Outside medical records obtainable via ME

medicolegal authority

Case Adjudication

Data reviewed at adjudication

• PMH (active problems, prescriptions, recent visits)
• Medications (Rx, QT-prolonging, methadone)
• EMS runsheets and rhythms
• Witness/family interviews
• Autopsy, tox, histology findings

Adjudication panel

• Dr. Phil Ursell

Chief Cardiac Pathologist UCSF

• Dr. Ellen Moffatt

Medical Examiner, City and County of San Francisco

• Dr. Zian H. Tseng

Study PI Cardiac Electrophysiologist, UCSF

• Dr. Jeff Olgin

Chief of Cardiology, UCSF

• Dr. Anthony Kim

Neurologist Director of UCSF Stroke Center

6

Deaths in San Francisco 2/1/2011-3/1/2014 N=20441 Not Reported to ME N= 7769 Deaths Reported to ME: all ER, OOH, Unexpected Inpatient Death N= 12672 Non-Natural Deaths N= 2021 Natural Deaths N= 10651 Excluded- Age <18 or >90 N= 1998 Excluded- Inpatient/Hospice N= 3843 OOH Natural Deaths, 18- 90 yo, N= 4810 OOH Deaths, Eligible for Autopsy N= 3690 Under MD Care < 3 weeks Signed Death Certificate, Ineligible for Autopsy N= 1120 WHO SCD w/o Autopsy N= 89 Non-Sudden Deaths N= 1031 Excluded at Initial Presentation (Non-Sudden or Ineligible) N= 2776 EMS SCD Refused Autopsy N= 16 Autopsied EMS SCDs N= 898 Excluded after comprehensive records review (Non-Sudden Death) N= 268 Adjudicated Autopsied Potential SCDs N= 630 Excluded at Adjudication (Non-Sudden Death) N= 105 Adjudicated Autopsied WHO SCDs N= 525 SCD by EMS referred for autopsy N= 914 (See Table 1A) (See Table 1B) Accidental OD Deaths N=815 (See Table 1C) (See Table 1C) (See Table 1C) (See Table 1C and 2B) Key for Case Review: Death Certif. (DC) Only EMS + Initial ME Investig. All Records (all medical records, EMS run sheets and ME records) Adjudication SCD Criteria Witnessed: Symptoms <1 hour of death Unwitnessed: Observed well within 24 hours of death Excluded: Known metastatic CA, ESRD on HD, Hospice, Hospitalization <1 mo

POstmortem Systematic InvesTigation of Sudden Cardiac Death…….. February 1, 2011 – March 1, 2014

(See Table 1C and 2A)

ME POST SCD Autopsy Rate = 97% Overall WHO SCD Autopsy Rate = 83%

Tseng, ZH….Moffatt E. AHA Late-breaking 2016 SCD with Autopsy SCD without Autopsy p* SCD with Autopsy vs. without Autopsy SF Adult Population 2011 US Adult Population 2011 N 525 105

• 690,689

232,556,019 Age, mean ±SD 62.8 ± 14.5 73.1 ± 11.6

• 18-90

37-89

• Male, n (%)

362 (69%) 74 (70%) 0.82 350,179 (51%) 112,848,136 (49%) Race (%) White 279 (53%) 44 (42%) 0.001 290,089 (42%) 149,300,964 (64%) Black 81 (15%) 8 (8%) 40,751 (6%) 28,371,834 (12%) Hispanic 40 (8%) 8 (8%) 102,913 (15%) 37,441,519 (16%) Asian 110 (21%) 37 (35%) 232762 (34%) 11,395,245 (5%) Other 15 (3%) 8 (8%) 24,174 (3%) 6,046,457 (3%) Median Income Tertile 1 248 (50%) 43 (45%) 0.3446 266,642 (39%) 184,288,905 (79%) Tertile 2 82 (16%) 14 (13%) 230,900 (33%) 16,631,720 (7%) Tertile 3 171 (34%) 43 (42%) 193,147 (28%) 31,635,394 (14%)

• for age, t-test assuming unequal variance; for categorical, Fisher's exact test
• Population data from American Community Survey 2011

POST SCD Demographics

Tseng, ZH….Moffatt E. AHA Late-breaking 2016

SCD Case Study #1

• 74 yo Filipino gentleman

– 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

SCD Case Study #1

• 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

7

“Non-Cardiac SCD”

• Referring MD
• 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

Acute CAD N=52 (10%, 18%) Chronic CAD N=117 (22%, 40%) Cardiomyopathy N=53 (10%, 18%) Hypertrophy N=44 (8%, 15%) Primary Electrical Disease N=7 (1%, 2%) Other Cardiac, Arrhythmic N=20 (4%, 7%) Cardiac, Non Arrythmic N=22 (4%, 100%) Acute Renal Failure N=6 (1%, 3%) Aortic Dissection N=14 (3%, 7%) Aspiration/Asphyxia N=5 (1%, 2%) Chemical Overdose N=71 (14%, 34%) GI Hemorrhage/Other GI N=14 (3%, 7%) Hypo/Hyperglycemia/DKA N=9 (2%, 4%) Infection N=23 (4%, 11%) Neurological N=29 (6%, 14%) Pulmonary Embolism N=19 (4%, 9%) Other Non-Cardiac N=20 (4%, 10%)

Adjudicated Etiologies of SCD

Cardiac, Arrhythmic N=293 (56%) Cardiac, Non-Arrhythmic N=22 (4%) Non-Cardiac N=210 (40%)

N=525 SAD: no extra- cardiac (PE, SAH, lethal tox) or non-arrhythmic (tamponade, acute HF) COD

Tseng, ZH….Moffatt E. AHA Late-breaking 2016 SCD SAD Non-SAD P value SAD vs. non- SAD N 525 293 232

• Medical Records Unobtainable

33 (6%) 15 (5%) 18 (8%) Confirmed No Medical History 24 (5%) 15 (5%) 9 (4%) History of: HTN 290 (55%) 175 (60%) 116 (50%) 0.0260 DM 117 (22%) 72 (24%) 46 (20%) 0.20 Dyslipidemia 157 (30%) 108 (37%) 50 (22%) 0.0001 Any cardiac history 224 (43%) 131 (45%) 93 (40%) 0.29 CHF 68 (13%) 47 (16%) 21 (9%) 0.0179 AF/AFL 54 (10%) 27 (9%) 24 (10%) 0.66 Aortic stenosis (mod or severe) 6 (1%) 2 (1%) 3 (1%) 0.47 Mitral valve prolapse 8 (2%) 5 (2%) 3 (1%) 0.70 CKD (non ESRD) 58 (11%) 33 (11%) 25 (10%) 0.86 Seizures 39 (7%) 14 (5%) 25 (11%) 0.0093 CVA 33 (6%) 18 (6%) 16 (7%) 0.73 Depression 93 (18%) 37 (13%) 56 (24%) 0.0006 COPD 64 (12%) 32 (11%) 32 (14%) 0.32 Non-Metastatic Cancer 63 (12%) 40 (14%) 23 (10%) 0.18 Tobacco Use 211 (40%) 115 (39%) 96 (42%) 0.62 Alcohol Abuse 122 (23%) 57 (19%) 65 (28%) 0.0210 Illicit Drug Use 79 (15%) 27 (9%) 52 (22%) <0.0001

Pre-Mortem Conditions

Tseng, ZH….Moffatt E. AHA Late-breaking 2016 57.1% 62.5% 44.6% 58.1% 54.2% 62.0% 45.0% 60.7% 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80

Total Male Female White Hispanic Asian Black Other

Adjusted Incidence Rates

SCD and SAD Incidence Rates per 100,000 person-years

All SCD Weighted SAD IRR P-value IRR P-value Male vs. Female 2.4 <0.0001 3.32 <0.0001 Hispanic vs. White 0.46 <0.0001 0.42 <0.0001 Asian vs. White 0.55 0.002 0.57 0.0014 Black vs. White 2.15 0.0006 1.66 0.0168 Other vs. White 1.13 0.28 1.12 0.66

Key:

SAD Weighted SCD Observed SAD Unweighted Other: American Indian/Alaskan Native, Native Hawaiian or Other Pacific Islander N=630

436 194 323 48 147 89 23 Tseng, ZH….Moffatt E. AHA Late-breaking 2016

8

57.1% 62.5% 44.6% 58.1% 54.2% 62.0% 45.0% 60.7% 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80

Total Male Female White Hispanic Asian Black Other

Adjusted Incidence Rates

SCD and SAD Incidence Rates per 100,000 person-years

All SCD Weighted SAD IRR P-value IRR P-value Male vs. Female 2.4 <0.0001 3.32 <0.0001 Hispanic vs. White 0.46 <0.0001 0.42 <0.0001 Asian vs. White 0.55 0.002 0.57 0.0014 Black vs. White 2.15 0.0006 1.66 0.0168 Other vs. White 1.13 0.28 1.12 0.66

Key:

SAD Weighted SCD Observed SAD Other: American Indian/Alaskan Native, Native Hawaiian or Other Pacific Islander

N = 1003

N=630

436 194 323 48 147 89 23 Excluded EMS SCDs

Key:

SAD Weighted SCD Observed SAD Unweighted

Tseng, ZH….Moffatt E. AHA Late-breaking 2016

SCD Case Study #2

• 78 yo Asian man

– Dilated cardiomyopathy, stable EF 25% – 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

ICD Interrogation

x 30

VF ≠ Sudden Arrhythmic Death

• 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

9

Acute CAD N=54 (10%, 18%) Chronic CAD N=115 (22%, 39%) Cardiomyopathy N=53 (10%, 18%) Hypertrophy N=45 (9%, 15%) Primary Electrical Disease N=7 (1%, 2%) Other Cardiac, Arrhythmic N=20 (4%, 7%) Cardiac, Non Arrythmic N=22* (4%, 100%) Acute Renal Failure N=6 (1%, 3%) Aortic Dissection N=14 (3%, 7%) Aspiration/Asphyxia N=5 (1%, 2%) Chemical Overdose N=71 (14%, 34%) GI Hemorrhage/Other GI N=11 (2%, 5%) Hypo/Hyperglycemia/DKA N=9 (2%, 4%) Infection N=24 (2%, 11%)

Neurologic N=28 (5%, 13%)

Pulmonary Embolism N=19 (4%, 9%) Other Non-Cardiac N=22 (4%, 11%)

Sudden Neurologic Death: 2nd largest Non-cardiac Cause

Cardiac, Arrhythmic N=294 (56%) Cardiac, Non-Arrhythmic N=22 (4%) Non-Cardiac N=209 (40%)

N=525

Kim AS….Tseng ZH. Neurology 2016

Sudden Neurologic Death Masquerading as SCD

• Risk of SND higher in women and non-whites

(p<0.01)

• Mostly intracranial hemorrhages but also stroke

and SUDEP

• Antiplatelet or AC associated with ICH among

noncardiac deaths (OR 6.0 [95% CI 1.5–24.8], p = 0.01) and overall (OR 3.9 [95% CI 1.01–15.5, p = 0.05)

• Up to 25,000 SNDs missed annually in U.S.
• 50% increase in fatal ICH incidence in U.S.

annually

Kim AS….Tseng ZH. Neurology 2016

Other 2% Agonal/Idioventricular 0.2% Asystole 94% PEA 2% VF 2%

Unwitnessed N=405

*Other: NSR (STEMI), AF/L (STEMI), Sinus Brady (STEMI and NSTEMI)

Other 13% Agonal/Idioventri cular 4% Asystole 34% PEA 13% VF 33% VT 3%

Witnessed N=120

Initial Rhythms at EMS Arrival Time to Initial Rhythm

Witnessed SCDs

5 10 15 20 Time to EKG (minutes) Other Agonal/Idioventricular Asystole VT/VF PEA P = .34

10

COD by Initial Rhythm

Witnessed SCDs

Initial Rhythm Arrhythmic COD N=78 Non- Arrhythmic COD N=42 P value Fisher’s Exact Total Agonal/Idioventricul ar 3 (60%) 2 (40%) 1.0 5 Asystole 26 (63%) 15 (37%) 0.84 41 NSR 3 (60%) 2 (40%) 1.0 5 PEA 2 (13%) 13 (87%) <0.0001 15 Sinus Brady 2 (40%) 3 (60%) 0.34 5 VT/VF 39 (91%) 4 (9%) <0.0001 43 Other 2 (67%) 1 (33%) 1.0 3 Unknown 1 (33%) 2 (67%) 0.61 3

Symptoms Prior to Arrest

GI 1% Vomit 2% Syncope 3% CP 5% Shortness of Breath 7% Other 10% Multiple symptoms 24% None Known 48%

Witnessed N=120

Syncope 0.2% Vomit 0.2% Cough 2% GI 2% CP 2% Shortness of Breath 2% Fatigue 3% Other 9% Multiple Symptoms 8% None Known 72%

Unwitnessed N=405

COD by Presenting Symptom

Witnessed SCDs

Symptom Arrhythmic COD N=78 Non- Arrhythmic COD N=42 P value Fisher’s Exact Total None Known 40 (69%) 18 (31%) 0.38 58 Multiple 18 (62%) 11 (38%) 0.70 29 Other 10 (83%) 2 (17%) 0.16 12 Shortness of Breath 3 (37%) 5 (63%) 0.09 8 Chest Pain 2 (33%) 4 (67%) 0.10 6 Syncope 2 (50%) 2 (50%) 0.52 4 Vomiting / Nausea 2 (100%) 0 (0%) 0.30 2 GI 1 (100%) 0 (0%) 0.46 1 Fatigue 0 (0%) 0 (0%)

• Cough

0 (0%) 0 (0%)

• Total

78 (65%) 42 (35%) 120

SCD Case Study #3

• 46 yo Hispanic man with well-controlled HIV

disease (CD4 1000, VL <50)

• Compliant with HAART and statins
• Without complaint, found dead by his

roommate 1 hour after last seen well

11

HIV Increases Risk of Fibrosis and SCD

• 760 g heart
• Pulmonary edema
• 2V CAD
• 50% LAD, 60% LCx
• Dense transmural and

interstitial fibrosis

Sudden Cardiac Death in Patients with HIV Infection Mortality Rates by Cause and Year

• 230 deaths over 3.7 median years’ follow-up
• 13% SCDs, 86% (30/35) of all cardiac deaths
• Mean HIV SCD rate: 2.6/1,000 PY (95% CI 1.8-3.8), 4.5-fold

higher than background HIV- SCD rate

Tseng ZH et al. JACC 2012 59(21):1891-6

HIV is Associated with Higher Risk of SCD:

Veterans Aging Cohort Study Virtual Cohort

Moyers B…Tseng ZH. AHA Scientific Sessions 2013;128:A16770

P <0.001

(years)

Time to SCD by HIV Status

• +

Adjusted for age, gender, Framingham RF, comorbidities, substance use:

• HIV+ had 1.5x risk of SCD (HR 1.45, 95% CI 1.29-1.64, p<0.001).
• Age, HTN, DM, smoking, HCV, CKD, anemia, and EtOH abuse associated with increased SCD risk

12

SCD Case Study #4

• 74 yo Caucasian man with CAD, PPM for

CHB

• Gen change scheduled for 5 weeks after ERI
• Did not show up to UCSF EP lab morning of

procedure: died in sleep

SCD Case Study #4

• Autopsy negative (no acute MI, PE, or bleed)

Current Postmarket Surveillance of CIEDs

• >3 million in U.S. alone have a PPM or ICD
• Manufacturer and User Facility Device

Experience (MAUDE) is mandatory for manufacturers, voluntary for healthcare providers

• Major limitation is that it generally captures patients under

active care who by definition are alive

• No mandatory surveillance of devices exists for patients who

die to determine the role of CIED failure

• Vast majority of SCDs with CIEDs do not get investigated

Tseng ZH, Hayward R, Clark N et al JAMA-IM 2015

Sudden Death in Patients with CIEDs

SCD with CIED (22, 4.3%)

Tseng ZH, Hayward R, Clark N et al JAMA-IM 2015

13

ICD Lead Fracture During Shock

• Improper device selection
• VT programming: delayed VF detection, ATP in VF zone
• Opportunities for MD practice improvement: device

selection, programming

Tseng ZH, Hayward R, Clark N et al JAMA-IM 2015

Sudden Death in Patients with CIEDs

SCD with CIED (22, 4.3%)

~1% SCDs w/ device malfunction

Tseng ZH, Hayward R, Clark N et al JAMA-IM 2015

SCD in Patients with CIEDs

• Only 1 of 11 cases reported to MAUDE
• Current calculated rates of device malfunctions may

be substantial underestimates

• JAMA-IM Editor’s Note: “The system by which the US

FDA engages in medical device postmarket safety surveillance needs strengthening. These findings of previously unsuspected device malfunction and ineffectiveness are critical to the accurate understanding of the benefits and risks of these implanted devices.”

Ross J. JAMA IM 2015;175(8):1350-135

Magnitude of Sudden Cardiac Death in the U.S.

100,000 200,000 300,000 400,000 500,000 AIDS Breast Cancer Lung Cancer Stroke SCD # deaths/year

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.

> 2-3 fold

• verestimate

30-50% underestimate

14

SCA ≠ SCD

SCA Valvular CAD DCM HCM

1o electrical disease

Tamponade Neurologic HIV CIEDs

Etiology of Sudden Cardiac Death

Adapted from Huikuri et al. N Engl J Med, Vol. 345 2001

2-fold

• verestimate

2-fold underestimate

Implications

• Reliance on EMS records and/or death certificates is

insufficient for accurate determination of SCD incidence

• Further investigation in minority groups and women
• To reduce overall public health burden of SCD, in

addition to CAD, efforts also should be directed towards screening, treating and preventing OD, neurologic diseases, hypertrophy, cardiomyopathy

• SCD cohorts for genetic and molecular association

studies will need refinement of phenotype

Early and Anticipated Insights

• SAD only account for just over half of all “SCDs”
• Men, blacks have 2-fold higher incidence of SAD than reference
• SCD rates are up to 4-fold higher in HIV+
• CIED problems underestimated: postmortem surveillance

necessary

• Sudden neurologic death most common non-cardiac cause after

OD, higher risk in Asians and women

• Precise phenotypes for future genetic association studies
• Evaluation of imyocardial fibrosis, cardiac mass, CAD, valvular

disease as risk factors

• Precision EMS protocols
• Prediction modeling for true arrhythmic causes in existing SCD

cohorts

• Hemorrhage risk with anticoagulants, antiplatelets

15

Acknowledgements

• SF Medical Examiner’s Office

– Ellen Moffatt

– Amy Hart

• UCSF Pathology

– Phil Ursell

• POST SCD Team

– Jeff Olgin – Robert Hayward – Brian Moyers – Annie Narla – Alefiyah Rajabali – Satvik Ramakrishna – Ben Colburn – Nina Clark – Rana Khan – Annie Bedigian – Joanne Probert – Santo Ricceri – Alan Iwahashi

• UCSF Epidemiology/Biostatistics

– Eric Vittinghoff

• ZSFG

– Priscilla Hsue – Diane Havlir

• UCSF Pediatrics

– Ronn Tanel

• SF VAMC

– Joseph Wong – Edmund Keung

• UCSF Cardiology

– Elyse Foster – Francesca Delling – Saptarsi Haldar – Rahul Deo

• UCSF Neurology

– Anthony Kim – Michael Wilson

• SFFD/SFGH Emergency Medicine

– Karl Sporer – Clement Yeh – Robert Rodriguez R01 HL102090 (NIH) R01 HL126555 (NIH) DP14-1403 (CDC) R56 1067039 (NIH)

UCSF Human Genetics

Pui-Yan Kwok Bob Nussbaum

UCSF Medical Ethics

Bernie Lo

Kaiser San Francisco

Jon Zaroff

NYU

Orrin Devinsky Brad Aouizerat

Stanford

Joseph Wu

Table 1: Non-Sudden Deaths

Table 1: Non-Sudden Deaths 1A: Deaths not Reported to ME Total (%) Inpatient Death 5462 (70.3%) SNF/Hospice Death 2094 (27.0%) Death OOH – Under Physician Care 197 (2.5%) ER/OP Death – Under Physician Care 16 (0.2%) 1B: Non-Natural Deaths Total (%) Accidental Overdose 818 (40.5%) Trauma Death 572 (28.3%) Suicide 355 (17.6%) Homicide 228 (11.3%) Other Accidental Death 48 (2.4%) 1C: Excluded Natural Deaths Total (%) Nursing Home/Hospice 3861 (38.5%) ES Disease/Metastatic CA 2249 (22.4%) Age (<18, >90) 2012 (20.1%) Non-sudden presentation (includes OD at scene) 1009 (10.1%) Recent Complaints 427 (4.2%) Recent Major Procedure/Hospitalization(<1month) 395 (3.9%) DNR/Refused Treatment 39 (0.4%) Arrested Out of County 29 (0.3%) Tseng, ZH….Moffatt E. AHA Late-breaking 2016

Table 2: Cause of Sudden Deaths without Autopsy

Table 2: Cause of Sudden Deaths without Autopsy 2A: Sudden Deaths without Autopsy Total (%) Cardiac Causes 85 (95%) Complications of Diabetes Mellitus 1 (1%) Complications of Stroke 2 (2%) Respiratory Failure 1 (1%) 2B: Sudden Deaths Refused Autopsy Total (%) Cardiac Causes 16 (100%) Tseng, ZH….Moffatt E. AHA Late-breaking 2016

16

Etiologies of Excluded EMS SCDs

Acute CAD N=7 2% Chronic CAD N=77 21% Cardiomyopathy N=14 4% Other Cardiac, Arrhythmic N=20 5% Cardiac, Non Arrhythmic N=17 5% Aortic Dissection N=2 0% Aspiration/Asphyxia N=8 2% Chemical Overdose N=81 22% GI Hemorrhage/Other GI N=8 2% Hypo/Hyperglycemia/DKA N=6 2% Infection N=10 3% Neurological N=9 2% Pulmonary Embolism N=15 4% Other Non-Cardiac N=27 7% Pending N=72 19%

Cardiac, Arrhythmic N=118 (32%) Cardiac, Non-Arrhythmic N=17 (5%) Non-Cardiac N=166 (45%) Pending N=72 (19%)

N=373

Etiologies of Excluded EMS SCDs

Acute CAD N=3 3% Chronic CAD N=12 11% Cardiomyopathy N=6 5% Other Cardiac, Arrhythmic N=11 10% Cardiac, Non Arrhythmic N=6 6% Aortic Dissection N=1 1% Chemical Overdose N=24 23% GI Hemorrhage/Othe r GI N=3 3% Hypo/Hyperglyce mia/DKA N=2 2% Infection N=2 2% Neurological N=4 4% Pulmonary Embolism N=5 5% Other Non-Cardiac N=5 5% Pending N=21 20%

Cardiac, Arrhythmic N=32 (30%) Cardiac, Non-Arrhythmic N=6 (6%)

N=105

Acute CAD N=4 2% Chronic CAD N=65 24% Cardiomyopathy N=8 3% Other Cardiac, Arrhythmic N=9 3% Cardiac, Non Arrhythmic N=11 4% Aortic Dissection N=1 0% Aspiration/Asphyxia N=8 3% Chemical Overdose N=57 21% GI Hemorrhage/Other GI N=5 2% Hypo/Hyperglycemia/ DKA N=4 2% Infection N=8 3% Neurological N=5 2% Pulmonary Embolism N=10 4% Other Non-Cardiac N=22 8% Pending N=51 19%

Cardiac, Arrhythmic N=86 (32%) Cardiac, Non- Arrhythmic N=11 (4%)

N=268

Excluded After Comprehensive Records Review Excluded At Adjudication

Non-Cardiac N=120 (45%) Pending N=51 (19%) Non-Cardiac N=46 (44%) Pending N=21 (20%) SFFD CARES Cases 1/1/2011-12/31/12 N=649 Non-Cardiac Etiology N= 196 Trauma= 53, Respiratory/Drowning= 57, Other= 48, Unk= 38 EMS defined OCHAs N=453 Age <18 N=1 EMS defined OCHAs >18 y/o N= 452 Survived to Admission N=77 Non-Sudden Arrests (not meeting WHO criteria) N=100 Died OOH/ED N= 147 Unknown outcome N=1 Not-unexpected Arrests (known end stage disease, SNF/Hospice, OD) N= 127 Inpatient Death N= 35 Survived to Hospital Discharge N= 42 Confirmed Sudden Cardiac Arrests N= 225 UCSF/SFGH Inpatient Deaths N= 13 UCSF/SFGH Survival to Hospital Discharge N= 14 Non-UCSF/SFGH cases N=28 Non-UCSF/SFGH cases N=22 Race Asian (N=110) Black (81) Hispanic (40) Other (15) White (279) Cardiac, Arrhythmic 68 (62%) p* = 0.42 35 (43%) p* = 0.0246 21 (53%) p* = 0.56 9 (60%) p* = 0.84 160 (57%) Acute CAD 14 (13%) 0.65 5 (6%) 0.19 2 (5%) 0.24 0 (0%) 0.17 31 (11%) Chronic CAD 24 (22%) 0.65 10 (12%) 0.0242 9 (23%) 0.83 6 (40%) 0.16 67 (24%) Cardiomyopathy 9 (8%) 0.65 12 (15%) 0.19 3 (8%) 0.66 2 (13%) 0.64 27 (10%) Hypertrophy 11 (10%) 0.58 7 (9%) 0.91 3 (8%) 0.87 0 (0%) 0.25 23 (8%) Primary Electrical Disease 1 (1%) 0.88 0 (0%) 0.35 3 (8%) 0.0052 0 (0%) 0.69 3 (1%) Other 9 (8%) 0.0361 1 (1%) 0.34 1 (3%) 0.81 1 (7%) 0.47 9 (3%) Cardiac, Non-Arrhythmic 6 (5%) 0.63 1 (1%) 0.19 0 (0%) 0.18 3 (20%) 0.0071 12 (4%) Acute MI w/ Rupture 6 (5%) 0.09 0 (0%) 0.18 0 (0%) 0.34 0 (0%) 0.57 6 (2%) Acute MI w/ Pump Failure 0 (0%) 0.53 1 (1%) 0.35 0 (0%) 0.70 2 (13%) p < 0.0001 1 (0.4%) Chronic Heart Failure 0 (0%) 0.21 0 (0%) 0.28 0 (0%) 0.45 1 (7%) 0.13 4 (1%) Pericarditis 0 (0%) 0.53 0 (0%) 0.59 0 (0%) 0.70 0 (0%) 0.82 1 (0.4%) Non-Cardiac 36 (33%) 0.30 45 (56%) 0.0058 19 (48%) 0.27 3 (20%) 0.15 107 (38%) Acute Renal Failure 0 (0%) 0.27 1 (1%) 0.90 1 (3%) 0.45 1 (7%) 0.07 3 (1%) Aortic Dissection 4 (4%) 0.69 0 (0%) 0.12 2 (5%) 0.47 0 (0%) 0.51 8 (3%) Aspiration/Asphyxia 2 (2%) 0.33 0 (0%) 0.44 1 (3%) 0.27 0 (0%) 0.74 2 (1%) Chemical Overdose 5 (5%) 0.0027 18 (22%) 0.18 4 (10%) 0.34 0 (0%) 0.10 44 (16%) GI Hemorrhage/Other GI 2 (2%) 0.84 3 (4%) 0.43 3 (8%) 0.06 0 (0%) 0.57 6 (2%) Hypo/Hyperglycemia/DK A 1 (1%) 0.88 5 (6%) 0.0061 0 (0%) 0.51 0 (0%) 0.69 3 (1%) Infection 5 (5%) 0.53 5 (6%) 0.23 3 (8%) 0.18 1 (7%) 0.47 9 (3%) Neuro 11 (10%) 0.0117 5 (6%) 0.30 3 (8%) 0.24 0 (0%) 0.46 10 (4%) Pulmonary Embolism 1 (1%) 0.09 6 (7%) 0.26 0 (0%) 0.18 0 (0%) 0.41 12 (4%) Other Non-Cardiac 5 (5%) 0.66 2 (2%) 0.62 0 (0%) 0.22 1 (7%) 0.54 10 (4%)