Embed Size (px)
Citation preview
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
Disclosures
• Major – Research grant: K12 RR024130 (NIH)
– Research grant: R01 HL102090 (NIH / NHLBI )
• Minor – Biotronik: Honorarium
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
Etiology of Sudden Cardiac Death
Huikuri et al. N Engl J Med, Vol. 345 2001
Magnitude of Sudden Cardiac Death in the U.S.
0
100,000
200,000
300,000
400,000
500,000
AIDS BreastCancer
LungCancer
Stroke SCD
# d
eath
s/ye
ar
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.
• 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.”
Sudden Cardiac Death: Definitions
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”
• 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
Sudden Cardiac Death: Definitions
Methodological Issues in Population Studies of SCD
§ Estimates in the US range from 184,000-450,000 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
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
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
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
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%
Comprehensive Surveillance of SCD in San Francisco
San Francisco Medical Examiner
All out of hospital and ER deaths are reported
by law
Metropolitan San Francisco • Population: ~750,000 residents (49 mi2)
– ~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)
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)
Study Eligibility Criteria Deaths reported to the MEO are preliminarily enrolled as SCDs if: 1. Age 18-90 2. 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
Study Workflow
Enrollment Autopsy PMH
Record Review
Adjudication
Eligibility criteria are applied between each step as PMH and post-mortem data are collected
Case Adjudication Each case is determined to be arrhythmic, non-arrhythmic, 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
Surveillance of WHO SCDs (2/1/2011-9/3/2012)
Natural Deaths (Possible SCD)
Non-Case, SCD
SCD-Missed (External Only) SCD
(Full Autopsy)
Non-Arrhythmic Arrhythmic Non-Cardiac
SCD-Excluded
Sudden Arrhythmic Deaths vs. Control (Trauma) Deaths
SF ME Deaths N=1420
WHO SCDs
Cardiac Non-Cardiac
Arrhythmic Non-arrhythmic
Autopsy
Accidental Trauma deaths
N=376
Autopsy
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. 2012 Jan;163(1):125-31.
Study Cohort Demographics (2/2/11 – 8/15/12)
*http://quickfacts.census.gov/qfd/states/06/06075.html
*
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
SCD Rates in San Francisco, 2007
34.6
19.4
53
95
36
128
0
20
40
60
80
100
120
140
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)
Rates of SCD per 100,000
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):1268-‐1275. 2. 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):1500-‐5. 3. Becker, LB, Smith DW, Rhodes KV. Incidence of cardiac arrest: a neglected factor in evalua\ng survival rates. Ann Emerg Med 1993;22(1):86-‐91.
Steinhaus DA….Tseng ZH. Am Heart J. 2012 Jan;163(1):125-31.
Adjudicated Causes of WHO SCDs
57% of Arrhythmic SCD
(n=74)
33% of All WHO SCD
(n=127)
Nearly half of WHO SCDs are Non-Cardiac
47 of 127 (40%) WHO SCDs were non-cardiac
Presenting Rhythms for Witnessed SCDs
Morbidity Prevalence: Arrhythmic SCD vs. Trauma Deaths
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
Interstitial Fibrosis in SADs vs. Trauma Controls
• Global interstitial fibrosis score 1.5-fold higher in SADs than controls, adjusted for age, sex, ethnicity, CAD level
75 yo AM trauma victim, minimal CAD
77 yo AM SAD victim, minimal CAD
40x LV septum, trichrome stain
• 2860 consecutive patients in a public HIV clinic (SFGH) April 2000 - August 2009
• 230 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
Sudden Cardiac Death in Patients with HIV Infection
Magnitude of Sudden Cardiac Death in the U.S.
0
100,000
200,000
300,000
400,000
500,000
AIDS BreastCancer
LungCancer
Stroke SCD
# d
eath
s/ye
ar
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-fold overestimate
Etiology of Sudden Cardiac Death
Adapted from Huikuri et al. N Engl J Med, Vol. 345 2001
2-fold overestimate
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
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
ICD Interrogation
x 30
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
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
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
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
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
