Abstract
Background: Cardiomyopathies are a group of diseases of the heart that can lead to heart failure, cardiac arrhythmia, and sudden death. They typically manifest as an enlarged heart or a normal heart with microscopic anomalies (fibrosis, inflammation, etc.). The aim of the study is to investigate the prevalence of deaths due to cardiomyopathies of unknown etiology in young subjects in a forensic pathology setting.
Materials and Methods: Deaths due to cardiomyopathy in decedents less than 40 years old evaluated at the Cook County Medical Examiner’s Office in Chicago from January 2013 to June 2018 were studied.
Results: In total, 140 cases of cardiomyopathies were identified in the study period: among these, in 20 cases (14%), no underlying etiology could be found through medical history and autopsy investigation. The demographics and the macroscopic and microscopic findings of these cases are described, highlighting the importance of medical history review and adequate histological sampling of hearts in cases of sudden, unexpected death in children and young adults.
Conclusion: This study highlights the importance of medical history review and adequate histological sampling of hearts in cases of sudden, unexpected death in children and young adults to identify possible cardiomyopathies of unknown etiology.
Keywords: Forensic science, cardiomyopathies, children, young adults, heart diseases, histology, genetic testing.
[1]
Hughes SE, McKenna WJ. New insights into the pathology of inherited cardiomyopathy. Heart 2005; 91(2): 257-64.
[http://dx.doi.org/10.1136/hrt.2004.040337] [PMID: 15657260]
[http://dx.doi.org/10.1136/hrt.2004.040337] [PMID: 15657260]
[2]
Maron BJ, Thiene G. Classification of cardiomyopathiesHurst’s the Heart 13e. New York, NY: McGraw Hill 2011.
[3]
Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies: An American heart association scientific statement from the council on clinical cardiology, heart failure and transplantation committee; quality of care and outcomes research and functional genomics and translational biology interdisciplinary working groups; and council on epidemiology and prevention. Circulation 2006; 113(14): 1807-16.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.174287] [PMID: 16567565]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.174287] [PMID: 16567565]
[4]
Rizzo S, Carturan E, De Gaspari M, Pilichou K, Thiene G, Basso C. Update on cardiomyopathies and sudden cardiac death. Forensic Sci Res 2019; 4(3): 202-10.
[http://dx.doi.org/10.1080/20961790.2019.1631957] [PMID: 31489386]
[http://dx.doi.org/10.1080/20961790.2019.1631957] [PMID: 31489386]
[5]
Thiene G, Corrado D, Basso C. Cardiomyopathies: Is it time for a molecular classification? Eur Heart J 2004; 25(20): 1772-5.
[http://dx.doi.org/10.1016/j.ehj.2004.07.026] [PMID: 15474691]
[http://dx.doi.org/10.1016/j.ehj.2004.07.026] [PMID: 15474691]
[6]
Pediatric cardiomyopathy. available from: https://rarediseases.org/rare-diseases/pediatric-cardiomyopathy/ (Accessed on 12.28.2021).
[7]
Afzal S, Kristensen IB. Characterization of cardiomyopathy cases at a forensic institute in the period 1992-2006 and perspectives for screening. Forensic Sci Med Pathol 2008; 4(2): 108-12.
[http://dx.doi.org/10.1007/s12024-007-9022-8] [PMID: 19291480]
[http://dx.doi.org/10.1007/s12024-007-9022-8] [PMID: 19291480]
[8]
Papadakis M, Raju H, Behr ER, et al. Sudden cardiac death with autopsy findings of uncertain significance: Potential for erroneous interpretation. Circ Arrhythm Electrophysiol 2013; 6(3): 588-96.
[http://dx.doi.org/10.1161/CIRCEP.113.000111] [PMID: 23671135]
[http://dx.doi.org/10.1161/CIRCEP.113.000111] [PMID: 23671135]
[9]
Roberts SE, Pryce JW, Weber MA, Malone M, Ashworth MT, Sebire NJ. Clinicopathological features of fatal cardiomyopathy in childhood: An autopsy series. J Paediatr Child Health 2012; 48(8): 675-80.
[http://dx.doi.org/10.1111/j.1440-1754.2012.02450.x] [PMID: 22515160]
[http://dx.doi.org/10.1111/j.1440-1754.2012.02450.x] [PMID: 22515160]
[10]
Cardiomyopathy. Available from: https://www.cdc.gov/heartdisease/cardiomyopathy.htm (Accessed on 02.09.2021).
[11]
Tin LL, Beevers DG, Lip GY. Hypertension, left ventricular hypertrophy, and sudden death. Curr Cardiol Rep 2002; 4(6): 449-57.
[http://dx.doi.org/10.1007/s11886-002-0105-6] [PMID: 12379162]
[http://dx.doi.org/10.1007/s11886-002-0105-6] [PMID: 12379162]
[12]
Stevens SM, Reinier K, Chugh SS. Increased left ventricular mass as a predictor of sudden cardiac death: Is it time to put it to the test? Circ Arrhythm Electrophysiol 2013; 6(1): 212-7.
[http://dx.doi.org/10.1161/CIRCEP.112.974931] [PMID: 23424223]
[http://dx.doi.org/10.1161/CIRCEP.112.974931] [PMID: 23424223]
[13]
Hsia HH, Marchlinski FE. Characterization of the electroanatomic substrate for monomorphic ventricular tachycardia in patients with nonischemic cardiomyopathy. Pacing Clin Electrophysiol 2002; 25(7): 1114-27.
[http://dx.doi.org/10.1046/j.1460-9592.2002.01114.x] [PMID: 12164454]
[http://dx.doi.org/10.1046/j.1460-9592.2002.01114.x] [PMID: 12164454]
[14]
Grimm W, Maisch B. Sudden cardiac death in dilated cardiomyopathy - therapeutic options. Herz 2002; 27(8): 750-9.
[http://dx.doi.org/10.1007/s00059-002-2425-0] [PMID: 12574892]
[http://dx.doi.org/10.1007/s00059-002-2425-0] [PMID: 12574892]
[15]
Wettrell G. Dilated cardiomyopathy of unknown cause in young patients: Risk evaluation, possible etiologies, and treatment. Libyan J Med 2007; 2(4): 157-8.
[http://dx.doi.org/10.3402/ljm.v2i4.4720] [PMID: 21503233]
[http://dx.doi.org/10.3402/ljm.v2i4.4720] [PMID: 21503233]
[16]
Coronel R, Baartscheer A, Rademaker JME, Vermeulen JT, de Bakker JMT. The Arrhythmogenic Substrate in Ischemic and Non-ischemic Cardiomyopathies. Progress in Catheter Ablation Developments in Cardiovascular MedicineDordrecht. Springer 2001; p. 241.
[http://dx.doi.org/10.1007/978-94-015-9791-3_1]
[http://dx.doi.org/10.1007/978-94-015-9791-3_1]
[17]
Samanta R, Pouliopoulos J, Thiagalingam A, Kovoor P. Role of adipose tissue in the pathogenesis of cardiac arrhythmias. Heart Rhythm 2016; 13(1): 311-20.
[http://dx.doi.org/10.1016/j.hrthm.2015.08.016] [PMID: 26277495]
[http://dx.doi.org/10.1016/j.hrthm.2015.08.016] [PMID: 26277495]
[18]
Alpert MA. Obesity cardiomyopathy: Pathophysiology and evolution of the clinical syndrome. Am J Med Sci 2001; 321(4): 225-36.
[http://dx.doi.org/10.1097/00000441-200104000-00003] [PMID: 11307864]
[http://dx.doi.org/10.1097/00000441-200104000-00003] [PMID: 11307864]
[19]
Poirier P, Cornier MA, Mazzone T, et al. Bariatric surgery and cardiovascular risk factors: A scientific statement from the American Heart Association. Circulation 2011; 123(15): 1683-701.
[http://dx.doi.org/10.1161/CIR.0b013e3182149099] [PMID: 21403092]
[http://dx.doi.org/10.1161/CIR.0b013e3182149099] [PMID: 21403092]
[20]
American Diabetes Association. Standards of medical care in diabetes-2013. Diabetes Care 2013; 36 (Suppl. 1): S11-66.
[http://dx.doi.org/10.2337/dc13-S011] [PMID: 23264422]
[http://dx.doi.org/10.2337/dc13-S011] [PMID: 23264422]
[21]
Albakri A. Obesity cardiomyopathy: A review of literature on clinical status and meta-analysis of diagnostic and clinical management. Med Clin Arch 2018; 2(3): 1-13.
[http://dx.doi.org/10.15761/MCA.1000134]
[http://dx.doi.org/10.15761/MCA.1000134]
[22]
Arbustini E, Narula N, Tavazzi L, et al. The MOGE(S) classification of cardiomyopathy for clinicians. J Am Coll Cardiol 2014; 64(3): 304-18.
[http://dx.doi.org/10.1016/j.jacc.2014.05.027] [PMID: 25034069]
[http://dx.doi.org/10.1016/j.jacc.2014.05.027] [PMID: 25034069]
[23]
Marian AJ, Braunwald E. Hypertrophic cardiomyopathy: Genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res 2017; 121(7): 749-70.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311059] [PMID: 28912181]
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311059] [PMID: 28912181]
[24]
Musunuru K, Hershberger RE, Day SM, et al. Genetic testing for inherited cardiovascular diseases: A scientific statement from the american heart association. Circ Genom Precis Med 2020; 13(4): e000067.
[http://dx.doi.org/10.1161/HCG.0000000000000067] [PMID: 32698598]
[http://dx.doi.org/10.1161/HCG.0000000000000067] [PMID: 32698598]
[25]
Hershberger RE, Givertz MM, Ho CY, et al. Genetic evaluation of cardiomyopathy-a heart failure society of America practice guideline. J Card Fail 2018; 24(5): 281-302.
[http://dx.doi.org/10.1016/j.cardfail.2018.03.004] [PMID: 29567486]
[http://dx.doi.org/10.1016/j.cardfail.2018.03.004] [PMID: 29567486]
[26]
Basso C, Carturan E, Pilichou K, Rizzo S, Corrado D, Thiene G. Sudden cardiac death with normal heart: Molecular autopsy. Cardiovasc Pathol 2010; 19(6): 321-5.
[http://dx.doi.org/10.1016/j.carpath.2010.02.003] [PMID: 20381381]
[http://dx.doi.org/10.1016/j.carpath.2010.02.003] [PMID: 20381381]
[27]
Semsarian C, Ingles J, Wilde AA. Sudden cardiac death in the young: The molecular autopsy and a practical approach to surviving relatives. Eur Heart J 2015; 36(21): 1290-6.
[http://dx.doi.org/10.1093/eurheartj/ehv063] [PMID: 25765769]
[http://dx.doi.org/10.1093/eurheartj/ehv063] [PMID: 25765769]
[28]
Scheiper S, Ramos-Luis E, Blanco-Verea A, et al. Sudden unexpected death in the young - Value of massive parallel sequencing in postmortem genetic analyses. Forensic Sci Int 2018; 293: 70-6.
[http://dx.doi.org/10.1016/j.forsciint.2018.09.034] [PMID: 30415094]
[http://dx.doi.org/10.1016/j.forsciint.2018.09.034] [PMID: 30415094]
[29]
Sanchez O, Campuzano O, Fernández-Falgueras A, et al. Natural and undetermined sudden death: Value of post-mortem genetic investigation. PLoS One 2016; 11(12): e0167358.
[http://dx.doi.org/10.1371/journal.pone.0167358] [PMID: 27930701]
[http://dx.doi.org/10.1371/journal.pone.0167358] [PMID: 27930701]
[30]
Larsen MK, Nissen PH, Berge KE, et al. Molecular autopsy in young sudden cardiac death victims with suspected cardiomyopathy. Forensic Sci Int 2012; 219(1-3): 33-8.
[http://dx.doi.org/10.1016/j.forsciint.2011.11.020] [PMID: 22177269]
[http://dx.doi.org/10.1016/j.forsciint.2011.11.020] [PMID: 22177269]
[31]
Marey I, Fressart V, Rambaud C, et al. Clinical impact of post-mortem genetic testing in cardiac death and cardiomyopathy. Open Med (Wars) 2020; 15(1): 435-46.
[http://dx.doi.org/10.1515/med-2020-0150] [PMID: 33336002]
[http://dx.doi.org/10.1515/med-2020-0150] [PMID: 33336002]
[32]
Hertz CL, Christiansen SL, Ferrero-Miliani L, et al. Next-generation sequencing of 100 candidate genes in young victims of suspected sudden cardiac death with structural abnormalities of the heart. Int J Legal Med 2016; 130(1): 91-102.
[http://dx.doi.org/10.1007/s00414-015-1261-8] [PMID: 26383259]
[http://dx.doi.org/10.1007/s00414-015-1261-8] [PMID: 26383259]
[33]
Lahrouchi N, Raju H, Lodder EM, et al. The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy. Eur J Hum Genet 2020; 28(1): 17-22.
[http://dx.doi.org/10.1038/s41431-019-0500-8] [PMID: 31534214]
[http://dx.doi.org/10.1038/s41431-019-0500-8] [PMID: 31534214]
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