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01-01-2015 | Case Report

Genetic and toxicologic investigation of Sudden Cardiac Death in a patient with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) under cocaine and alcohol effects

Authors: Francesca Cittadini, Nadia De Giovanni, Mireia Alcalde, Sara Partemi, Oscar Campuzano, Ramon Brugada, Antonio Oliva

Published in: International Journal of Legal Medicine | Issue 1/2015

Abstract

Cocaine and alcohol toxicity is well known, especially when simultaneously abused. These drugs perform both acute and chronic harmfulness, with significant cardiac events such as ventricular arrhythmias, tachycardia, systemic hypertension, acute myocardial infarction, ventricular hypertrophy, and acute coronary syndrome. The present report refers about a patient who died after a documented episode of psychomotor agitation followed by cardiac arrest. At the autopsy investigation, arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed and confirmed by postmortem molecular analysis revealing a mutation in the DSG2 gene. Postmortem toxicological analysis demonstrated a recent intake of cocaine, and the death was attributed to cardiac arrhythmias. The detection of cocaine and cocaethylene in hair samples proved chronic simultaneous intake of cocaine and alcohol at least in the last month. The authors discuss the role of these drugs and genetic predisposition of the ARVC in causing the death of the patient.

Kauferstein S, Kiehne N, Jenewein T, Biel S, Kopp M, König R, Erkapic D, Rothschild M, Neumann T (2013) Genetic analysis of sudden unexplained death: a multidisciplinary approach. Forensic Sci Int 229(1–3):122–127. doi:10.1016/j.forsciint.2013.03.050 CrossRef

Campuzano O, Allegue C, Partemi S, Iglesias A, Oliva A, Brugada R (2014) Negative autopsy and sudden cardiac death. Int J Legal Med 128(4):599–606CrossRef

Madea B, Saukko P, Oliva A, Musshoff F (2010) Molecular pathology in forensic medicine—introduction. Forensic Sci Int 203(1–3):3–14. doi:10.1016/j.forsciint.2010.07.017 CrossRef

Michaud K, Mangin P, Elger BS (2011) Genetic analysis of sudden cardiac death victims: a survey of current forensic autopsy practices. Int J Legal Med 125(3):359–366CrossRef

Herren T, Gerber PA, Duru F (2009) Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare "disease of the desmosome" with multiple clinical presentations. Clin Res Cardiol 98:141–158CrossRef

Battipaglia I et al (2012) Association of heart rate variability with arrhythmic events in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circ J 76:618–623CrossRef

Sen-Chowdhry S et al (2007) Clinical and genetic characterization of families with arrhythmogenic right ventricular dysplasia/cardiomyopathy provides novel insights into patterns of disease expression. Circulation 115:1710–1720CrossRef

Corrado D et al (2000) Arrhythmogenic right ventricular dysplasia/cardiomyopathy: need for an international registry. Study Group on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy of the Working Groups on Myocardial and Pericardial Disease and Arrhythmias of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the World Heart Federation. Circulation 101:E101–E106CrossRef

Marcus FI et al (2010) Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Eur Heart J 31:806–814CrossRef

10.

Cox MG et al (2011) Arrhythmogenic right ventricular dysplasia/cardiomyopathy: pathogenic desmosome mutations in index-patients predict outcome of family screening: Dutch arrhythmogenic right ventricular dysplasia/cardiomyopathy genotype-phenotype follow-up study. Circulation 123:2690–2700CrossRef

11.

Campuzano O, Alcalde M, Allegue C, Iglesias A, García-Pavía P, Partemi S, Oliva A, Pascali VL, Berne P, Sarquella-Brugada G, Brugada J, Brugada P, Brugada R (2013) Genetics of arrhythmogenic right ventricular cardiomyopathy. J Med Genet 50(5):280–289. doi:10.1136/jmedgenet-2013-101523 CrossRef

12.

Campuzano O, Alcalde M, Iglesias A, Barahona-Dussault C, Sarquella-Brugada G, Benito B, Arzamendi D, Flores J, Leung TK, Talajic M, Oliva A, Brugada R (2012) Arrhythmogenic right ventricular cardiomyopathy: severe structural alterations are associated with inflammation. J Clin Pathol 65(12):1077–1083. doi:10.1136/jclinpath-2012-201022 CrossRef

13.

Schwartz BG, Rezkalla S, Kloner RA (2010) Cardiovascular effects of cocaine. Circulation 122(24):2558–2569. doi:10.1161/CIRCULATIONAHA.110.940569.] CrossRef

14.

Kitzman DW, Scholz DG, Hagen PT, Ilstrup DM, Edwards WD (1988) Age-related changes in normal human hearts during the first decades of life. Part II (Maturity). A quantitative anatomic study of 765 specimens from subjects 20 to 99 years old. Mayo Clin Proc 63(2):137–146CrossRef

15.

Basso C, Burke M, Fornes P, Gallagher PJ, de Gouveia RH, Sheppard M, Thiene G, van der Wal A (2008) Guidelines for autopsy investigation of sudden cardiac death. Association for European Cardiovascular Pathology. Virchows Arch 452(1):11–18CrossRef

16.

Oliva A, Brugada R, D’Aloja E, Boschi I, Partemi S, Brugada J, Pascali VL (2011) State of the art in forensic investigation of sudden cardiac death. Am J Forensic Med Pathol 32(1):1–16CrossRef

17.

Flanagan RJ, Connally G, Evans JM (2005) Analytical toxicology: guidelines for sample collection postmortem. Toxicol Rev 24(1):63–71CrossRef

18.

Cooper GA, Kronstrand R, Kintz P (2012) Society of Hair Testing guidelines for drug testing in hair. Forensic Sci Int 218(1–3):20–24CrossRef

19.

De Giovanni N, Strano Rossi S (1994) Simultaneous detection of cocaine and heroin metabolites in urine by solid-phase extraction and gas chromatography–mass spectrometry. J Chromatogr B Biomed Appl 658(1):69–73CrossRef

20.

Desmet FO, Hamroun D, Lalande M, Collod-Béroud G, Claustres M, Béroud C (2009) Human splicing finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res 37(9):e67CrossRef

21.

1000 Genomes Project Consortium, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA (2010) A map of human genome variation from population-scale sequencing. Nature 467(7319):1061–1073CrossRef

22.

Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29(1):308–311CrossRef

23.

Andreasen C, Nielsen JB, Refsgaard L, Holst AG, Christensen AH, Andreasen L, Sajadieh A, Haunsø S, Svendsen JH, Olesen MS (2013) New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. Eur J Hum Genet 21(9):918–928CrossRef

24.

Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, Abeysinghe S, Krawczak M, Cooper DN (2003) Human Gene Mutation Database (HGMD): 2003 update. Hum Mutat 21(6):577–581CrossRef

25.

Syrris P, Ward D, Asimaki A, Evans A, Sen-Chowdhry S, Hughes SE, McKenna WJ (2007) Desmoglein-2 mutations in arrhythmogenic right ventricular cardiomyopathy: a genotype-phenotype characterization of familial disease. Eur Heart J 28(5):581–588CrossRef

26.

Berg JS, Adams M, Nassar N, Bizon C, Lee K, Schmitt CP, Wilhelmsen KC, Evans JP (2013) An informatics approach to analyzing the incidentalome. Genet Med 15(1):36–44CrossRef

27.

Pennings EJ, Leccese AP, Wolff FA (2002) Effects of concurrent use of alcohol and cocaine. Addiction 97(7):773–783CrossRef

28.

Cami J, Farré M, González ML, Segura J, De La Torre R (1998) Cocaine metabolism in humans after use of alcohol. Clinical and research implications. Recent Dev Alcohol 14:437–455CrossRef

29.

Bortolotti F, Gottardo R, Pascali J, Tagliaro F (2012) Toxicokinetics of cocaine and metabolites: the forensic toxicological approach Curr. Med Chem 19(33):5658–5663

30.

Pilgrim JL (2013) Cocaine in sudden and unexpected death: a review of 49 post-mortem cases. Forensic Sci Int 227(1–3):52–59CrossRef

31.

Kozor R, Grieve SM, Buchholz S, Kaye S, Darke S, Bhindi R, Figtree GA (2014) Regular cocaine use is associated with increased systolic blood pressure, aortic stiffness and left ventricular mass in young otherwise healthy individuals. PLoS ONE 9(4):e89710. doi:10.1371/journal.pone.0089710 CrossRef

32.

Liaudet L, Calderari B, Pacher P. Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity. Heart Fail Rev. 2014 Jan 8.

Title: Genetic and toxicologic investigation of Sudden Cardiac Death in a patient with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) under cocaine and alcohol effects
Authors: Francesca Cittadini
Nadia De Giovanni
Mireia Alcalde
Sara Partemi
Oscar Campuzano
Ramon Brugada
Antonio Oliva
Publication date: 01-01-2015
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Legal Medicine / Issue 1/2015
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-014-1119-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Genetic and toxicologic investigation of Sudden Cardiac Death in a patient with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) under cocaine and alcohol effects

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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