1. San Antonio Medical BRAC Integration Office, 916-1000 Incidence of Sudden Cardiac Death Associated with Physical Exertion in the United States Military Samuel O. Jones, MD, MPH, FACC, FHRS Colonel, US Air Force Associate Professor, USUHS Arrhythmia Service, Cardiology Division San Antonio Military Medical Center

2. San Antonio Medical BRAC Integration Office, 916-1000 Conflicts: None The information and opinions expressed in this document are solely those of the authors and do not represent an endorsement by or the views of the Uniformed Services University of the Health Sciences, the United States Air Force, the Department of Defense, or the United States Government.

3. San Antonio Medical BRAC Integration Office, 916-1000 Background Sudden Cardiac Death (SCD) is a tragic and devastating event – SCD which occurs to an athlete during sports or physical exertion generates immense public attention Increasingly recognized, a significant percentage of cases occur during physical exertion, due to the inherent elevated risk. Incidence rates vary and precise data may be difficult – Varying definitions, incomplete ability to identify cases, and different populations studied. 3

4. San Antonio Medical BRAC Integration Office, 916-1000 Background Relative risk of SCD is elevated during or immediately post exertion – Physicians Health Study 16.9 x RR – Police officers 40.6 x (during restraints) – Firefighters 12.1 to 136 times greater during fire suppression as compared to non-emergency duty Pathophysiology – wall stress, double product, ischemia – Acute events, plaque disruption, thrombogenicity – Electrolyte shift, volume changes 4 Albert CM. NEJM 2000;343:1355 Varvarigou V. BMJ 2014;349: 6534 Kales SN. NEJM 2007;235:1207

5. San Antonio Medical BRAC Integration Office, 916-1000 Incidence of SCD w/ Exertion Young patients 12-35 in Denmark 1.2 per 100,000 General population of sports related deaths in France 0.46 per 100,000 (? as high as 1.7 ?) Marathon runners 2005-2010 rate of 1.25 per 100,000 Triathlon 1.5 per 100,000 5 Marijon E. Circ 2011;124:672 Holst AG.. Heart Rhythm.2010; 7: 1365 Kim JH. NEJM 2012; 366:130 Harris K JAMA 2010;303:1255

6. San Antonio Medical BRAC Integration Office, 916-1000 Background U.S. military records provide excellent data for analysis given – complete capture of all deaths – well-defined population – comprehensive electronic medical record – accessible surveillance systems Study aimed to calculate the incidence rate of SCD related to exertion in the U.S. military – Secondarily, determine etiologies, classify according to activities, and characterize demographic and risk profiles of decedents. 6

7. San Antonio Medical BRAC Integration Office, 916-1000 SCD in the Athlete Earliest case report of SCD in the athlete? Pheidippides (530 BC- 490 BC) Ran from battlefield near Marathon to Athens to announce Greek victory over Persians Upon giving the message, he collapsed and died 7

8. San Antonio Medical BRAC Integration Office, 916-10008

9. The Problem Definition of “athlete” may be broad – In total, there are estimated 5 million HS athletes – 500,000 collegiate – 5,000 professional – Extend to firefighters? 1.2 million AD military? Young, vigorous, represent healthy lifestyle – Sudden death does not fit our beliefs Each event is a high profile case, generating public outcry to prevent these conditions

10. San Antonio Medical BRAC Integration Office, 916-1000 Incidence of SCD Organized High School/College Athletes – 1:134,000/Year (Male) (7.47:million/Year) – 1:750,000/Year (Female) (1.33/million/Year) Air Force Recruits – 1:735,000/Year Marathon Runners – 1:50,000 Race Finishers (Mean Age 37yo) In brief, ~ 300 deaths/year

11. San Antonio Medical BRAC Integration Office, 916-1000 Causes of SCD in the young HCM ARVC Coronary artery anomalies Premature CAD LQTS/ Brugada Myocarditis Preexcitation syndromes

12. San Antonio Medical BRAC Integration Office, 916-1000 Methods AF Medical Examiner Tracking System Surveillance system Autopsy reports Death certificates Official investigations Military EHR Clinical Laboratory Radiographic Prescription data 12 All decedents meeting the case definition from Jan 1, 2005 to Dec 31, 2010 were included

13. San Antonio Medical BRAC Integration Office, 916-1000 Criteria Sudden Cardiac Death Autopsy-confirmed heart disease with clinical circumstances c/w cardiac etiology Circumstances were c/w cardiac arrhythmia in absence of other conditions that could explain death Exertion-related A death or initiation of terminal life support within 1 hr of physical exertion. Un-witnessed but unexpected death where individual had been exercising prior to death. 13

14. San Antonio Medical BRAC Integration Office, 916-1000 Methods Full time active duty service members along with National Guard and Reserves Analysis of environmental heat load at time of exertion via wet bulb globe temperature (WBGT) Physical activities and clinical history preceding SCD were obtained via witness interviews Clinical data from EHR – BMI, lipids, blood pressure, smoking – Recent clinical history to including symptoms within prior 6 months 14

15. San Antonio Medical BRAC Integration Office, 916-1000 Case Determination 15 Personnel

16. 16 All Cases Active Component Cases Reserve/Guard Cases n =200%n=135%n=65% Age <35 years7537.56346.71218.5 ≥35 years12562.57253.35381.5 Sex Male19597.513398.56295.3 Female52.521.534.6 Race White11758.57757.04061.5 Black6331.54331.92030.8 Other2010.01511.157.7 Demographic Characteristics of Cases of Sudden Cardiac Death with Exertion

17. 17 All Cases Active Component Cases Reserve/Guard Cases n =200%n=135%n=65% Age <35 years7537.56346.71218.5 ≥35 years12562.57253.35381.5 Sex Male19597.513398.56295.3 Female52.521.534.6 Race White11758.57757.04061.5 Black6331.54331.92030.8 Other2010.01511.157.7 Demographic Characteristics of Cases of Sudden Cardiac Death with Exertion

18. 18 All Cases Active Component Cases Reserve/Guard Cases n =200%n=135%n=65% Age <35 years7537.56346.71218.5 ≥35 years12562.57253.35381.5 Sex Male19597.513398.56295.3 Female52.521.534.6 Race White11758.57757.04061.5 Black6331.54331.92030.8 Other2010.01511.157.7 Demographic Characteristics of Cases of Sudden Cardiac Death with Exertion

19. 19 DeathsPerson-Years Incidence Rate Per 100,000 Person Years (95% Confidence Interval) * Incidence Rate Ratio (95% Confidence Interval) † Total1358,298,6601.63 (1.37-1.92) Age <35 years636,425,4210.98 (0.76-1.25)1.00 [reference] ≥35 years721,873,1843.84 (3.03-4.81)3.70 (2.66-5.14) Race White775,763,9671.34 (1.06-1.66) 1.00 [reference] Black431,433,2903.00 (2.20-4.00) 2.60 (1.81-3.72) Other151,101,3461.36 (0.79-2.20)1.30 (0.78-2.18) Sex Male1337,103,6461.87 (1.57-2.21) 1.00 [reference] Female2662,3980.30 (0.51-1.00)5.28 (2.16-12.93) Race and Sex White Male775,101,5691.51 (1.20-1.88) Black Male411,093,0163.75 (2.73-5.04) Other Male15909,0371.65 (0.96-2.66)

20. 20 DeathsPerson-Years Incidence Rate Per 100,000 Person Years (95% Confidence Interval) * Incidence Rate Ratio (95% Confidence Interval) † Total1358,298,6601.63 (1.37-1.92) Age <35 years636,425,4210.98 (0.76-1.25)1.00 [reference] ≥35 years721,873,1843.84 (3.03-4.81)3.70 (2.66-5.14) Race White775,763,9671.34 (1.06-1.66) 1.00 [reference] Black431,433,2903.00 (2.20-4.00) 2.60 (1.81-3.72) Other151,101,3461.36 (0.79-2.20)1.30 (0.78-2.18) Sex Male1337,103,6461.87 (1.57-2.21) 1.00 [reference] Female2662,3980.30 (0.51-1.00)5.28 (2.16-12.93) Race and Sex White Male775,101,5691.51 (1.20-1.88) Black Male411,093,0163.75 (2.73-5.04) Other Male15909,0371.65 (0.96-2.66)

21. 21 DeathsPerson-Years Incidence Rate Per 100,000 Person Years (95% Confidence Interval) * Incidence Rate Ratio (95% Confidence Interval) † Total1358,298,6601.63 (1.37-1.92) Age <35 years636,425,4210.98 (0.76-1.25)1.00 [reference] ≥35 years721,873,1843.84 (3.03-4.81)3.70 (2.66-5.14) Race White775,763,9671.34 (1.06-1.66) 1.00 [reference] Black431,433,2903.00 (2.20-4.00) 2.60 (1.81-3.72) Other151,101,3461.36 (0.79-2.20)1.30 (0.78-2.18) Sex Male1337,103,6461.87 (1.57-2.21) 1.00 [reference] Female2662,3980.30 (0.51-1.00)5.28 (2.16-12.93) Race and Sex White Male775,101,5691.51 (1.20-1.88) Black Male411,093,0163.75 (2.73-5.04) Other Male15909,0371.65 (0.96-2.66)

22. 22 DeathsPerson-Years Incidence Rate Per 100,000 Person Years (95% Confidence Interval) * Incidence Rate Ratio (95% Confidence Interval) † Total1358,298,6601.63 (1.37-1.92) Age <35 years636,425,4210.98 (0.76-1.25)1.00 [reference] ≥35 years721,873,1843.84 (3.03-4.81)3.70 (2.66-5.14) Race White775,763,9671.34 (1.06-1.66) 1.00 [reference] Black431,433,2903.00 (2.20-4.00) 2.60 (1.81-3.72) Other151,101,3461.36 (0.79-2.20)1.30 (0.78-2.18) Sex Male1337,103,6461.87 (1.57-2.21) 1.00 [reference] Female2662,3980.30 (0.51-1.00)5.28 (2.16-12.93) Race and Sex White Male775,101,5691.51 (1.20-1.88) Black Male411,093,0163.75 (2.73-5.04) Other Male15909,0371.65 (0.96-2.66)

23. 23 All Cases CasesBy Age Group n = 200% <35 years≥35 years n = 75%n =125% Atherosclerotic CVD11055.01216.09878.4 Idiopathic3015.02330.775.6 Anomalous Coronary Arteries 199.51621.332.4 Cardiomegaly/ Cardiomyopathy (excluding HCM) 189.01216.064.8 HCM73.545.332.4 Hypertensive CV Disease52.522.732.4 Myocarditis52.534.021.6 Valvular Disorder31.522.710.8 ARVC31.511.321.6

24. 24 All Cases CasesBy Age Group n = 200% <35 years≥35 years n = 75%n =125% Atherosclerotic CVD11055.01216.09878.4 Idiopathic3015.02330.775.6 Anomalous Coronary Arteries 199.51621.332.4 Cardiomegaly/ Cardiomyopathy (excluding HCM) 189.01216.064.8 HCM73.545.332.4 Hypertensive CV Disease52.522.732.4 Myocarditis52.534.021.6 Valvular Disorder31.522.710.8 ARVC31.511.321.6

25. 25 All Cases CasesBy Age Group n = 200% <35 years≥35 years n = 75%n =125% Atherosclerotic CVD11055.01216.09878.4 Idiopathic3015.02330.775.6 Anomalous Coronary Arteries 199.51621.332.4 Cardiomegaly/ Cardiomyopathy (excluding HCM) 189.01216.064.8 HCM73.545.332.4 Hypertensive CV Disease52.522.732.4 Myocarditis52.534.021.6 Valvular Disorder31.522.710.8 ARVC31.511.321.6

26. San Antonio Medical BRAC Integration Office, 916-1000 Results In age ≥35 years, cardiac risk factors present – 80% had BMI > 25, 32% hyperlipidemia, 24% hypertension, 15% smoking No deaths occurred at extremes of temperature – WBGT<85 degrees or indoors Predominant activity was running or elliptical use in 60%. 20% of all events occurred during mandatory run of physical fitness test – Of these, 2/3 occurred after the test completed

27. San Antonio Medical BRAC Integration Office, 916-1000 Limitations Information was obtained retrospectively and from case materials that were not collected systematically Missing data points Population of predominantly young males who voluntarily joined the service may not translate to other populations 27

28. San Antonio Medical BRAC Integration Office, 916-1000 Conclusions From 2005-2010, the overall incidence in U.S. military members (1.63 per 100,000) was similar to most reported corresponding civilian SCD rates. Compared within groups, higher incidence rates were present in age ≥35 years, African-Americans, and males. The most common diagnosis depended on age – Age ≥35 years CAD – Age <35 years idiopathic and anomalous coronary arteries 28

29. San Antonio Medical BRAC Integration Office, 916-1000 Thank You 29

30. Physical Activity Preceding SCD 30 All Cases CasesBy Age Group n = 200%<35 years≥35 years n = 75%n =125% Running/Elliptical11959.55472.06552.0 Other * 2010.045.31612.8 PT † /Unit PT 178.511.31612.8 Walking ‡ 136.545.397.2 Swimming84.068.021.6 Basketball73.534.043.2 Weight Lifting, etc § 73.522.754.0 Bicycling42.011.332.4 Football10.500.010.8 Soccer10.500.010.8 Tennis10.500.010.8 Unknown21.000.021.6

31. Cardiac Risk Factors 31 All Cases CasesBy Age Group n =200% <35 years≥35 years n =75%n =125% Hyperlipidemia4221.022.74032.0 Smoker3316.51418.71915.2 Hypertension3115.511.33024.0 Family Hx of CAD2512.568.01915.2 Family Hx of SCD73.545.332.4 Previous Hx CAD42.000.0415.2 Diabetes21.000.022.0 * Prevalence values represent the minimum burden of these factors, due to missing data.

32. San Antonio Medical BRAC Integration Office, 916-1000 SCD- US military DoD registry 1998-2008 – AD members, 15 million pt-yrs (~1.5 million/yr) – Over 14,000 sudden deaths 902 due to likely SCD with full records (~90/yr) – Mean age 38, predominantly males – 79% definitely cardiac – 21% sudden unexplained death (autopsy did not clearly reveal a cause Significant percentage occurred during exertion

33. San Antonio Medical BRAC Integration Office, 916-1000 JACC 2011 Incidence of SCD in Athletes

34. San Antonio Medical BRAC Integration Office, 916-1000 Incidence of SCD Organized High School/College Athletes – 1:134,000/Year (Male) (7.47:million/Year) – 1:750,000/Year (Female) (1.33/million/Year) Marathon Runners – 1:50,000 Race Finishers (Mean Age 37yo)

35. San Antonio Medical BRAC Integration Office, 916-1000 ACC/AHA Recommendations (2007) Personal history 1. Exertional chest pain/discomfort 2. Unexplained syncope/near-syncope not clearly attributable to neurocardiogenic mechanism 3. Excessive and unexplained dyspnea/fatigue, associated with exercise 4. Prior recognition of a heart murmur 5. Elevated systemic blood pressure Family history 6. Premature death (sudden and unexpected) before age 50 years in ≥ 1 relative 7. Disability from heart disease in a close relative ≤ 50 years of age 8. Knowledge of heritable CV disease: (HCM/DCM, long-QT syndrome, Marfan syndrome, or clinically important arrhythmias) Circulation 2007; 115:1643-1655 Prevention: AHA Guidelines Electrophysiologist’s view of the world “Syncope and sudden death are really the same thing… except in one case you wake up”

36. San Antonio Medical BRAC Integration Office, 916-1000 ACC/AHA Recommendations (2007) Circulation 2007; 115:1643-1655 Physical examination 9. Heart murmur 10. Diminished or asymmetric femoral pulses (to exclude aortic coarctation) 11. Physical stigmata of Marfan syndrome 12. Asymmetric or elevated (>140/90 mmHg) brachial artery blood pressure Prevention: AHA Guidelines What about ECG?

37. San Antonio Medical BRAC Integration Office, 916-1000 Sudden Death in the Young MaronCorradoUS Military n=286n=277n=108 Age17 (9-40)23 (12-35)21 (18-35) RegionRegistryItalyUS military Hypertrophic cardiomyopathy 102 (35.7%) 23 ( 8.3%) 8 ( 7.4%) Anomalous coronary artery37 (12.9%) 8 ( 2.9%) 21 (19.4%) Atherosclerotic CAD10 ( 3.5%) 58 (20.9%) 10 ( 9.3%) Right ventricular dysplasia11 ( 3.8%) 37 (13.4%) 1 ( 0.9%) Structurally normal hearts71 (25.6%)44 (40.7%) Incidence per 10 5 person- years 1.011.1 Maron BJ, et al. J Am Coll Cardiol 2003;41:974–80 Corrado D, et al. J Am Coll Cardiol 2003;42:1959–63 Eckart RE, et al. Ann Int Med 2004;141:829– 834

38. San Antonio Medical BRAC Integration Office, 916-1000 Screening- US perspective Multiple issues with Italian data – Association does not prove causality US different than Italy – Population 5 x as great, different disease prevalence ECG is an imperfect test – 5-20% chance of abnormal ECG with many false pos Follow-up testing more of an issue in US Cost prohibitive (estimated over $2 Billion annual costs for US)

39. San Antonio Medical BRAC Integration Office, 916-1000 Legal / Ethical Issues Nay-sayers of screening: – Inherent risk is understood and accepted – Impossible to achieve zero-risk – In the big public health picture- low prevalence Assuming a limited pot of money, should we spend this on other items? – Societal double standard for competitive athletes Who is responsible? – Individual/ physician? – Team/school/government?

40. San Antonio Medical BRAC Integration Office, 916-1000 Lesson from Jim Fixx High profile author who popularized running in the 1980’s – Preached jogging made people live longer Had sudden death while running along road at age 52 Autopsy revealed severe diffuse 3 vv CAD 40

41. San Antonio Medical BRAC Integration Office, 916-1000 I want to die like my father did, peacefully in his sleep Not screaming like the passengers in his car.

42. San Antonio Medical BRAC Integration Office, 916-1000 Case A 27 yo male -syncopal episode while playing basketball. Did have LH prior to attack. Completely oriented afterwards; no incontinence. PMH, Meds, ROS: unremarkable Questionable family history

43. San Antonio Medical BRAC Integration Office, 916-1000 Anomalous Coronaries