Sudden Cardiac Death (Scd) in Young Athletes

SUDDEN CARDIAC DEATH (SCD) IN YOUNG ATHLETES

Mehrdad Salamat, MD, FAAP, FACC Clinical Associate Professor of Pediatrics Texas A & M University; Health Science Center SCD in Young Athletes

I have no relevant financial relationship(s) to disclose

SCD in Young Athletes - 2021 History/Myth The earliest documented case of SCD occurred in 490 BC. Pheidippides (fīdĬp´Ĭdēz), a Greek soldier, conditioned runner, ran from Marathon to Athens to announce military victory over Persia, only to deliver his message, “Rejoice! We conquer!”, then to collapse and die.

Rich BS. Sudden death screening. Med Clin North Am 1994;78(2):267-88

SCD in Young Athletes - 2021 Definition Sudden cardiac death (SCD) / arrest (SCA) – Non-traumatic and unexpected sudden cardiac arrest that occurs within 1 hour of a previously normal state of health Competitive athlete – Someone who participates in an organized team or individual sport that requires regular competitions against others as a central component, places a high premium on excellence and achievement, and requires vigorous and intense training in a systematic fashion

SCD in Young Athletes - 2021 Objectives To know the incidence of SCD To learn the mechanism of SCD To understand the conditions that may lead to SCD To recognize the warning signs

SCD in Young Athletes - 2021 Incidence Documentation? – No nationwide registry – Different sources National Collegiate Athletic Association (NCAA) Media database Insurance companies – During sleep or at rest – SCD vs SCA (emergence of AED)

SCD in Young Athletes - 2021 Incidence Overall incidence of SCD

– Not clear – Estimates 1:900,000 to 3,000 (AY) – More realistic 1:80,000 to 40,000 (AY)

*(AY) = Athlete-year

SCD in Young Athletes - 2021 Incidence

Annual incidence of Annual Death Rate SCD/SCA in athletes MVA 14,700 – Higher in males (3:1) – Higher in blacks (3:1) Suicide 5,000 – Higher in basketball players Abuse 1,600 Drowning 1,500 Accidents by guns 500 Abuse (Texas) 150 SCD in HS & college 25-50 students (US)

SCD in Young Athletes - 2021 Incidence

SCD in Young Athletes - 2021 Deaths in High-Level Athletes

M (15) Soccer playing soccer with his dad M (16) Soccer during a game M (18) Tennis after a coaching session F (13) Swimming warming up at a swimming gala M (17) Soccer after sledging in snow with friends

M (17) Rowing watching TV M (16) Soccer while resting

SCD in Young Athletes - 2021

www.c-r-y.org.uk Sudden Cardiac Death - Pathophysiology V-fib as the final event Susceptibility to V-fib may be enhanced by – Increased ventricular mass – Relative bradycardia – Non-uniformity of refractoriness – Acidosis – Increased sympathetic nervous system activity 10x rise in norepinephrine, 3x rise in epinephrine during exercise – Dehydration, electrolyte imbalance SCD in young athletes (< 35 y) is rarely secondary to atherosclerotic coronary artery disease

SCD in Young Athletes - 2021 Sudden Death in Young Competitive Athletes: Clinical, Demographic and Pathologic Profiles Maron BJ, et al. JAMA 1996;276:199-208 Lesion No. (%) of Athletes HCM + Possible HCM 48 (36) + 14 (10) CA abnormalities 31 (24) Ruptured aortic aneurysm 6 (5) Aortic valve stenosis 5 (4) Myocarditis 4 (3) Idiopathic myocardial scarring 4 (3) Idiopathic DCM 4 (3) ARVD 4 (3) MVP 3 (2) Atherosclerotic CA disease 3 (2) Other CHD 2 (1.5) Long QT syndrome 1 (0.5) Sarcoidosis 1 (0.5) Sickle cell trait 1 (0.5) “Normal” heart 3 (2) SCD in Young Athletes - 2021 Incidence, Etiology, and Comparative Frequency of Sudden Cardiac Death in NCAA Athletes: A Decade in Review Harmon KG, et al. Circulation 2015, 132: 10/2/2019

Forensically confirmed SCD in National Collegiate Athletic Association (NCAA) 2003-2013 ~ 4,200,000 (AY) 514 deaths – SCD 79 (15%) Most common cause – Structurally normal heart

*SUD = Sudden unexplained death *SCT = Sickle Cell Trait

SCD in Young Athletes - 2021 Sudden Cardiac Death Genetic/ Electrical abnormalities structural abnormalities – LQTS – Cardiomyopathies – SQTS HCM – Brugada syndrome DCM – CPVT ARVD/C – WPW Non-compaction Acquired abnormalities – Congenital coronary artery (CA) abnormalities – Infection > myocarditis > DCM LCA from right sinus of Valsalva – Acquired CA disease – Aortopathies Kawasaki Marfan syndrome – Drug abuse Familial TAAD – Trauma (commotio cordis) – AS, MVP

SCD in Young Athletes - 2021 Sudden Cardiac Death Cardiomyopathy – Hypertrophic cardiomyopathy (HCM) Hypertrophic obstructive cardiomyopathy (HOCM) – Dilated cardiomyopathy (DCM) – Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) – Non-compaction cardiomyopathy

SCD in Young Athletes - 2021 Hypertrophic Cardiomyopathy Hank Gathers

Loyola Marymont University basketball star – SCD while playing basketball – Symptomatic months before his death – FHx HCM

SCD in Young Athletes - 2021 Hypertrophic Cardiomyopathy Historically “most common cause of SCD in US adolescent” Most commonly autosomal dominant (AD) inheritance – Wide variability of expression – Mitochondrial transmission Obstructive or non-obstructive

SCD in Young Athletes - 2021 Hypertrophic Cardiomyopathy

SCD in Young Athletes - 2021

www.nlm.nih.gov Hypertrophic Cardiomyopathy

Disarray and disorganization of myocardial fibers, showing abnormal branching, overlapping and hypertrophy, with interstitial plexiform fibrosis.

members.aol.com/drhasegawa/hcm.htm

SCD in Young Athletes - 2021 Hypertrophic Cardiomyopathy History (symptoms mostly with exercise) – Syncope – Near-syncope – Chest pain – Palpitations Significant FHx – Early SCD – Unexplained sudden death – Known FHx of HCM

SCD in Young Athletes - 2021 Hypertrophic Cardiomyopathy Physical exam (“dynamic” auscultation) – ± SEM, depending on LVOTO – ± SRM, depending on MR ECG – LAD, LVH, ST-abnormalities – Prolonged QTc Echo – Diagnostic

SCD in Young Athletes - 2021 Hypertrophic Cardiomyopathy

SCD in Young Athletes - 2021 Arrhythmogenic “Right Ventricular” Dysplasia Apoptosis, inflammation, fatty replacement of myocardium – Triangular of dysplasia - RV RV apex, outflow tract, posterior wall – LV could be involved as well Ventricular tachycardia – LBBB pattern – Originating from RV outflow tract Syncope or SCD Accounting for up to 22% of SCD among Italian athletes – Corrado D, et al. NEJM 1998

SCD in Young Athletes - 2021 Arrhythmogenic “Right Ventricular” Dysplasia

Physical examination unrevealing 30-50% positive FHx – Major cause of SCD in athletes in the Veneto Region of Northeastern Italy – Mostly autosomal dominant (AD) – Different mutations on multiple chromosome Desmosomal proteins ECG, Holter, EST, echo, MRI, “biopsy”

SCD in Young Athletes - 2021 Arrhythmogenic “Right Ventricular” Dysplasia

Inverted T waves (V1-V3; 87% of pts) • > 14 years • Absence of CRBBB ε-waves (V1-V3; 33% of pts) • Late potentials; post excitation • Slow depolarization • Signal averaged ECG

SCD in Young Athletes - 2021 Arrhythmogenic “Right Ventricular” Dysplasia

Patchy replacement of myocardium by fatty or fibro-fatty tissue

Hein W. et al. Diagnosis of Arrhythmogenic Right Ventricular Dysplasia: A Review Radiographics. 2002;22:639-648

SCD in Young Athletes - 2021 Arrhythmogenic “Right Ventricular” Dysplasia

www.ipej.org/0303/indik.htm

SCD in Young Athletes - 2021 Left Ventricular Non-Compaction Failure of myocardial development during embryogenesis – Trabeculated myocardium > myocardial compaction – Failure of compaction of the myocardium > LVNC 8 to 12 per 1,000,000 (underestimated) Autosomal dominant – Mutations in the MYH7 (14q11.2) and MYBPC3 (11011.2) genes have been estimated to cause up to 30% of cases ghr.nlm.nih.gov/condition/left-ventricular-noncompaction#genes

SCD in Young Athletes - 2021 Left Ventricular Non-Compaction Clinical presentation – Asymptomatic, CHF, arrhythmias, SCD – Association with Barth syndrome, sickle cell disease Imaging – Comparison of non-compacted to compacted layer of myocardium (NC/C >2) – “Spongy” heart

SCD in Young Athletes - 2021 Left Ventricular Non-Compaction

SCD in Young Athletes - 2021 Sudden Cardiac Death Congenital anomalies of the coronary artery – Left coronary artery (LCA) arising from the right sinus of Valsalva – Single coronary artery – Intramural coronary artery

SCD in Young Athletes - 2021 Congenital Coronary Artery Abnormality Pete Maravich “Pistol Pete”

Famous LSU and N.O. Jazz 70’s basketball star – Died at 40 years of age while playing a 3 on 3 game in a California gym – Autopsy showed single right coronary artery

SCD in Young Athletes - 2021 LCA off the Right Sinus of Valsalva

AAOC: ANOMALOUS AORTIC ORIGIN of CORONARY ARTERY

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SCD in Young Athletes - 2021 LCA off the Right Sinus of Valsalva

AAOC: ANOMALOUS AORTIC ORIGIN of CORONARY

https://thoracickey.com/wp- content/uploads/2016/06/B97814377 0637600057X_f1.jpg

SCD in Young Athletes - 2021 Congenital Coronary Artery Abnormality

Ostial anomalies – Intramural coronary artery

SCD in Young Athletes - 2021 Congenital Coronary Artery Abnormality Presentation (with exertion) – SCD – Syncope – Pre-syncope – Chest pain Diagnosis – ECG, Echo, CTA, MRI, coronary-angiography Treatment – Surgery Re-implantation of the CA

SCD in Young Athletes - 2021 Sudden Cardiac Death Arrhythmia – Channelopathies Long QT syndrome (LQTS) Short QT syndrome (SQTS) Brugada syndrome Catecholaminergic polymorphic ventricular tachycardia (CPVT) – Wolff-Parkinson-White syndrome (WPW)

SCD in Young Athletes - 2021 Long QT Syndrome

Abnormality of the ventricular repolarization Defect in cardiac ion-channels’ structure and function – Mutations in proteins forming Na+, K+, Ca2+ channels

SCD in Young Athletes - 2021 Long QT Syndrome Increased risk of ventricular arrhythmias – Polymorphic ventricular tachycardia – Torsade de pointes Degenerates to ventricular fibrillation Sympathetic nerve function is an important modulator – Can further delay repolarization – Induce early after-depolarization – Trigger sudden arrhythmic death

SCD in Young Athletes - 2021 Long QT Syndrome Meanwhile – ~ 200 different mutations – At least 15 different subtypes – Phenotype does not always follow genotype – Clinical variability among members of a family with the same gene mutation, suggesting presence of modifier genes

SCD in Young Athletes - 2021 Long QT Syndrome

Clinical features ECG findings – Recurrent syncope – QT prolongation Strong emotional stress – Bradycardia Physical activity – T wave changes Sudden awakening from sleep – T wave alternans – Seizure – QT dispersion Family history – U wave – LQTS – SCD – Seizures – Congenital deafness

SCD in Young Athletes - 2021 Long QT Syndrome - T wave alternans

SCD in Young Athletes - 2021 Long QT Syndrome

Bazett’s formula – Corrected QT for HR

< 0.450 in infants < 0.440 in children Acquired long QTc  Electrolytes (K, Ca, Mg)  HIV  Increased intracranial pressure The longer the QT, the higher the likelihood of VT (> 0.500)

SCD in Young Athletes - 2021 Long QT Syndrome

SCD in Young Athletes - 2021 1993 LQTS Diagnostic Criteria Schwartz PJ et al. Circulation 1993;88:782-784

Variable Points Variable Points ECG Findings Clinical History QTc ≥ 480 ms 3 Syncope with stress 2 QTc 460-470 ms 2 Syncope without stress 1 QTc 450 ms (males) 1 Congenital deafness 0.5 Torsade de pointes 2 Family history T-wave alternans 1 Definite LQTS 1 Notched T-wave in 3 leads 1 Unexplained SCD < age 30 0.5 Low heart rate for age 0.5 (immediate family members)

Low probability ≤ 1 point Intermediate probability 2-3 points High probability ≥ 4 points

SCD in Young Athletes - 2021 Long QT Syndrome 287 children were reviewed – Presentation Syncope 26% Seizures 10% Cardiac arrest 9% Pre-syncope or palpitations 6%

– Exercise-related symptoms 88% – Congenital deafness 4.5%

Garson et al.: The long QT syndrome in children. A international study of 287 patients. Circulation 1993;87:1866-1872

SCD in Young Athletes - 2021 Long QT Syndrome Torsade de Pointes (“Twisting of the Points”)

From “Heart disease” 6th edition. Braunwald E, Zipes DP, Libby P; editors

SCD in Young Athletes - 2021 Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

Prevalence estimated ~ 1: 10,000 Mean age of presentation 6 to 10 y of age; 75% before 20 y of age Absence of structural heart disease FHx and EST Classically at a HR threshold >100-120, isolated PVC develop first, followed by short runs of non-sustained VT – Exertion, stress (physical, emotional) Estimated cause of >10% of SCD??

SCD in Young Athletes - 2021 Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Genes involved in release of Ca2+ from the sarcoplasmic reticulum Mutations in 2 genes (both on chrom. 1): RYR2 (AD), CASQ2 (AR) – RYR2 gene mutations cause ~50% of cases – CASQ2 gene mutations cause ~1 to 2% of cases Treatment similar to LQTS treatment – Avoid QT-prolonging drugs – β-receptor blockade – Flecainide – Left cervicothoracic sympathetic ganglionectomy – AICD

SCD in Young Athletes - 2021 Commotio Cordis Precordial blow during a period of electrically vulnerable ventricular repolarization leading to ventricular fibrillation

Maron (1995)-NEJM – 25 cases of SCD (3-19 years of age) secondary to blunt chest trauma – Baseball/softball, lacrosse, hockey, karate, football – 16 during competitive, 9 during recreational sports – Impact was not judged to be extraordinary – 7 (28 percent) had protective chest padding

SCD in Young Athletes - 2021 Upper and lower limits of vulnerability to sudden arrhythmic death with chest-wall impact (commotio cordis). Link MS, et al. JACC 2003;41:99-104

SCD in Young Athletes - 2021 Covid-19 A few points about COVID-19 – Any viral infection can cause myocarditis – Myocarditis with or without cardiomyopathy is associated with SCD – Data about COVID-19 and SCD/SCA or scarce

SCD in Young Athletes - 2021 Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19 Infection Rajpal S, et al. JAMA Cardiol 2021;6:116-8 26 athletes (15 male; Mean age 19.5) No hospitalizations No antiviral therapy 12 reported mild symptoms No diagnostic ST/T wave changes Normal function on echo and CMR No troponin I elevation 4 athletes with CMR findings c/w with myocarditis

SCD in Young Athletes - 2021 Coronavirus Disease 2019 and the Athletic Heart Emerging Perspectives on Pathology, Risks, and Return to Play Jonathan H. Kim, JAMA Cardiol 2021;6(2):219-27

Coronavirus Disease 2019 and the Athletic Heart Emerging Perspectives on Pathology, Risks, and Return to Play Jonathan H. Kim, JAMA Cardiol 2021;6(2):219-27

Red Flags - History Exertion related symptoms – Chest pain – Dizziness – Near-syncope – Syncope – Palpitation??? Myocarditis Drug abuse

SCD in Young Athletes - 2021 Red Flags - Family History Cardiomyopathy Early sudden cardiac death Unexplained sudden death Connective tissue disorder – Marfan Arrhythmia – LQTS – CVPT

SCD in Young Athletes - 2021 Red Flags - Physical Exam Heart murmurs – Especially when increases with Valsalva maneuvers or in standing position Men taller than 6’, women taller than 5’10” – Who have ≥ 2 physical features or family history of Marfan syndrome

SCD in Young Athletes - 2021 Dilemma First “symptom” – Sudden cardiac death Pre-participation screening – Noninvasive methods is not sufficient to guarantee detection of many critical cardiovascular abnormalities – Cost-effectiveness Ethical consideration Legal consideration

SCD in Young Athletes - 2021 Screening Epstein and Maron (1986) – It would require Screening of 200,000 To detect CHD in 1000 10 would have a defect capable of SCD 1 would actually die Maron et al. (1987) – Screened 501 college athletes – 90% had echocardiogram 1 had LVH secondary to systemic HTN 14 had mild MVP

SCD in Young Athletes - 2021 The effectiveness of screening Hx, PE, and ECG to detect potentially lethal cardiac disorders in athletes: a systematic review/meta-analysis. Harmon KG, et al. J Electrocardiol 2015;48(3):329-38

Articles reporting on ~ 47,000 athletes analyzed

Mode Sensitivity Specificity History 20% 94% Physical 9% 97% ECG 94% 93%

SCD in Young Athletes - 2021 Pre-participation screening of young competitive athletes for prevention of SCD. Corrado D et al., JACC 2008;52: 1981-9

SCD in Young Athletes - 2021 Screening - Normal ECG in Athletes Sinus bradycardia Early repolarization >30 BPM Isolated voltage criteria for Ectopic atrial rhythm LVH without: Junctional escape – LAD AVB Iº – ST depression – T wave inversion AVB IIº: Mobitz type I – Pathologic Q waves (Wenckebach) Isolated IRBBB

SCD in Young Athletes - 2021 Screening - Abnormal ECG in Athletes T wave inversion beyond RVH V1 and V2 LVH with ST depression in ≥ 2 leads – LAE Pathologic Q waves – ST depression LBBB – T inversion LAD Preexcitation LAE SVT RAE with IRBBB Frequent PVC’s Non-sustained VT

SCD in Young Athletes - 2021 SCD in Young Athletes - 2021 Automated External Defibrillator (AED)

SCD in Young Athletes - 2021 SCD in Young Athletes - 2021 Question #1

What is the most common autopsy finding as the etiology of sudden cardiac death (SCD) in NCAA athletes?

A) Hypertrophic cardiomyopathy B) Anomalous left coronary artery from the right sinus of Valsalva C) Anomalous right coronary artery from the left sinus of Valsalva D) Structurally normal heart E) Aortic dissection

SCD in Young Athletes - 2021 Question #2

Which of the following athletes is at highest risk for sudden cardiac death/arrest (SCD/A)?

A) 17-year-old male black basketball player B) 14-year-old female black soccer player C) 16-year-old male white football player D) 17-year-old female white swimmer E) 16-year-old female black swimmer

SCD in Young Athletes - 2021 Question #3

Which of the following statements about commotio cordis is TRUE?

A) It can always be prevented by appropriate protective chest padding B) It does not occur during recreational sports C) It is the result of the precordial blow during a period of ventricular repolarization (T wave) D) It does not occur during softball E) It is the result of precordial blow during a period of ventricular depolarization (QRS deflection)

SCD in Young Athletes - 2021 Question #4

As per recommendation of Kim et al., published in 2021, a 14-year-old young athlete diagnosed with COVID-19 infection and history of mild symptoms with meanwhile full resolution of symptoms, should undergo the following studies before being cleared for “return to play (RTP)”?

A) ECG B) 24-hour Holter C) Echocardiogram D) Cardiac exercise stress testing E) No testing is necessary

SCD in Young Athletes - 2021 Question #5

Which of the following is NOT a red flag during pre-participation physical evaluation in an otherwise asymptomatic athlete with a 50percentile height?

A) A heart murmur which is louder in standing position B) Paternal history of long QT syndrome C) Resting heart rate of 43 bpm D) Maternal grandfather with long QT syndrome E) Family history of Marfan syndrome

SCD in Young Athletes - 2021