Sudden Cardiac Death Among Adolescents in the United Kingdom

Gherardo Finocchiaro, MD, PHD; Davide Radaelli, MD; Stefano D'Errico, MD; Michael Papadakis, MBBS, MD; Elijah R. Behr, MA, MBBS, MD; Sanjay Sharma, BSC, MBCHB, MD; Joseph Westaby, BM BS, PHD; Mary N. Sheppard, MBBCH, BAO, BSC, MD

Disclosures

J Am Coll Cardiol. 2023;81(11):1007-1017.

Abstract and Introduction

Abstract

Background: Causes and precipitating factors of sudden cardiac death (SCD) in adolescents are poorly understood.

Objectives: The authors sought to investigate the etiologies of SCD and their association with physical activity in a large cohort of adolescents.

Methods: Between 1994 and June 2022, 7,675 cases of SCD were consecutively referred to our national cardiac pathology center; 756 (10%) were adolescents. All cases underwent detailed autopsy evaluation by expert cardiac pathologists. Clinical information was obtained from referring coroners.

Results: A structurally normal heart, indicative of sudden arrhythmic death syndrome was the most common autopsy finding (n = 474; 63%). Myocardial diseases were detected in 163 cases (22%), including arrhythmogenic cardiomyopathy (n = 36; 5%), hypertrophic cardiomyopathy (n = 31; 4%), idiopathic left ventricular hypertrophy (n = 31; 4%), and myocarditis (n = 30; 4%). Coronary artery anomalies were identified in 17 cases (2%). Decedents were competitive athletes in 128 cases (17%), and 159 decedents (21%) died during exercise. Arrhythmogenic cardiomyopathy was diagnosed in 8% of athletes compared with 4% of nonathletes (P = 0.05); coronary artery anomalies were significantly more common in athletes (9% vs 1%; P < 0.001), as well as commotio cordis (5% compared with 1% in nonathletes; P = 0.001). The 3 main comorbidities were asthma (n = 58; 8%), epilepsy (n = 44; 6%), and obesity (n = 40; 5%).

Conclusions: Sudden arrhythmic death syndrome and myocardial diseases are the most common conditions diagnosed at autopsy in adolescent victims of SCD. Among causes of SCD, arrhythmogenic cardiomyopathy, coronary artery anomalies, and commotio cordis are more common in young athletes than in similar age sedentary individuals.

Introduction

Sudden cardiac death (SCD) is a tragic event that occasionally affects young individuals. A spectrum of cardiac conditions may cause SCD with variable prevalence depending on the age and other demographics of the cohort. Inherited cardiac diseases, such as cardiomyopathies and channelopathies, are the predominant cardiac causes in individuals <35 years of age.^[1] Autopsy is an essential first diagnostic step that guides clinical evaluation of surviving relatives toward inherited structural diseases or primary arrhythmogenic syndromes.

Adolescence is the period of life between childhood and adulthood, from ages 10 to 19 years. It is an important phase of development with rapid physical and psychological growth. Genetic conditions that cause SCD may express during the peripuberal phase transitioning from a preclinical state to overt phenotype.^[2,3] Therefore, knowledge regarding the precise causes and precipitating factors for SCD in this specific subgroup is required to implement prevention through screening methods and widespread availability of automated external defibrillators (AEDs). Screening with electrocardiograms (ECGs) may facilitate the early diagnosis of cardiomyopathies and channelopathies,^[4–6] but has limited value in detecting coronary artery disease (CAD).^[4] Conversely, the AED appears to be more effective in the termination of arrhythmias in individuals with CAD or coronary artery anomalies than in athletes with cardiomyopathy.^[7]

The objective of this study was to investigate the causes and circumstances of SCD in a large cohort of adolescents whose heart was referred following a SCD to our cardiovascular pathology center and examined by expert cardiac pathologists.

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Table 1. Pathological Macroscopic and Microscopic Criteria Defining Main Underlying Diseases
	Macroscopic	Microscopic
Hypertrophic cardiomyopathy	Increased left ventricular wall thickness (globally or focally) and/or increased heart weight	Myocyte hypertrophy, myocyte disarray (>20% of myocardial disarray in at least 2 tissue blocks of 4 cm²) and interstitial fibrosis
Idiopathic left ventricular hypertrophy	Increase left ventricular wall thickness and increased heart weight	Myocyte hypertrophy ± fibrosis in the absence of myocyte disarray
Idiopathic left ventricular fibrosis	Normal heart weight and wall thickness with/without scarring macroscopically	Fibrosis (>20% in at least 2 tissue blocks of 4 cm²) with no myocyte disarray
Arrhythmogenic cardiomyopathy	Right or left ventricular thinning, fatty replacement, fibrosis on the epicardial surface or outer wall	Fat and fibrosis (>20% in at least 2 tissue blocks of 4 cm²) in the wall of the right and/or left ventricle, particularly in outer wall, with degenerative changes in the myocytes
Myocarditis	Normal or dilated ventricles	Inflammation (>20% in at least 2 tissue blocks of 4 cm²) with myocyte Necrosis
Anomalous coronary artery	Anomalous origin of the coronary artery, coronary artery atresia, stenosis	Fibrosis/acute/chronic infarction in the left ventricle
Coronary atherosclerosis	Atherosclerosis with estimated luminal narrowing >75%	Acute or chronic infarction in the left ventricle
Dilated cardiomyopathy	Increase in heart weight with dilated left ventricle (>4 cm) and thin wall (<10 mm). Absence of coronary artery disease.	Diffuse interstitial and replacement fibrosis (>20% in at least 2 tissue blocks of 4 cm²) in the left ventricle with degenerative changes in the myocytes
Mitral valve prolapse	Prolapse of mitral valve above the atrioventricular junction with ballooning between chordae in 1 or both leaflets	Myxoid degeneration with expansion in spongiosa of leaflets and destruction of fibrosa layer
Bicuspid aortic valve	Fusion of 2 aortic cusps, with or without presence of a raphe often with significant valve stenosis
Morphologically normal heart	Normal	Normal

Table 2. Characteristics of the Population According to Circumstances of Death
	Total (N = 756)	Died During Exercise (n = 159)	Died at Rest (n = 597)	P Value
Age, y	16 ± 2	16 ± 2	16 ± 2	1.00
Male	521 (69)	136 (85)	385 (64)	<0.001
FH of SD	116 (15)	26 (16)	90 (15)	0.755
Athletes	128 (17)	86 (67)	42 (33)	<0.001
Heart weight, g	330 ± 106	350 ± 107	325 ± 106	0.597
LV fibrosis	115 (15)	35 (22)	80 (13)	0.005
SADS	474 (63)	81 (51)	393 (66)	0.001
HCM	32 (4)	14 (9)	18 (3)	<0.001
AC	36 (5)	14 (9)	22 (4)	<0.001
ILVH	31 (4)	9 (6)	22 (4)	0.276
ILVF	18 (2)	3 (2)	15 (3)	0.496
Coronary anomalies	17 (2)	12 (7)	5 (1)	<0.001
CHD and/or VHD	44 (6)	7 (4)	37 (6)	0.329
Myocarditis	30 (4)	1 (1)	29 (5)	0.02
Comorbidities	225 (30)	36 (4)	189 (32)	<0.001
Asthma	58 (8)	16 (10)	42 (7)	0.205
Epilepsy	44 (6)	5 (3)	39 (7)	0.06
Obesity	40 (5)	6 (4)	34 (6)	0.329
Autism	23 (3)	4 (3)	19 (3)	1.00
Depression	17 (2)	0 (0)	17 (3)	0.027
Medications	168 (22)	27 (17)	141 (24)	0.06
Antiasthmatic agents	45 (6)	12 (8)	33 (6)	0.36
Antiepileptic agents	34 (5)	4 (3)	30 (5)	0.284
Antidepressants	13 (2)	0 (0)	13 (2)	0.07
Antiarrhythmics	13 (2)	2 (1)	11 (2)	0.398
Antidiabetics	8 (1)	1 (1)	7 (1)	1.00

Values are mean ± SD or n (%),
AC = arrhythmogenic right ventricular cardiomyopathy; CHD = congenital heart disease; DCM = dilated cardiomyopathy; FH = family history; HCM = hypertrophic cardiomyopathy; ILVF = idiopathic left ventricular fibrosis; ILVH = idiopathic left ventricular hypertrophy; LV = left ventricular; SADS = sudden arrhythmic death syndrome; SD = sudden death; VHD = valvular heart disease.