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26 Grenville Street Toronto, ON. M7A 2G9 Telephone: (416) 314-4000 Facsimile: (416) 314-4030 26, rue Grenville Toronto, ON. M7A 2G9 Telephone: (416) 314-4000 Telecopieur: (416) 314-4030 Bonita M.B. Porter, B.Sc., Phm., B.Sc., M.D., CCFP Chief Coroner for Ontario Coroners insert this memo into Section 3 Reference - "Investigations General" of the Coroners Investigation Manual Attached are guidelines (Appendix A) developed by a working group of cardiologists, geneticists, genetic counsellors, laboratory directors, coroners and pathologists. Please use it during the investigation of sudden premature cardiac death, where it is thought that surviving relatives might be affected by the same lethal condition as the decedent. Negotiations are continuing with the Ministry of Health and Long-Term Care with regard to the final determination of administrative re§>ponsibilityfor the extraction, cataloguing and storage of DNA samples. However, pathologists and the regional genetics laboratories are free to make their own arrangements pending this final agreement. Questions regarding these guidelines should be directed to your Regional Supervising Coroner. Bonita M.B. Porter B.Sc., Phm., M.Sc., M.D., CCFP Chief Coroner for Ontario BMBP:ks Attachment Guidelines for the Investigation of Sudden Cardiac Death: Coroner's Investigation and Medicolegal Autopsy Sudden unexpected cardiac death of persons under the age of 40 is not rare. The incidence is estimated at 3.5 to 5.5 per million population per year, with significant loss of years of potential life. Many causes of death can be ascertained following scene investigation and complete autopsy, as well as ancillary testing. In a small portion of medico-legal cases, however, a cause of death may not be found. Recent molecular research has found that in such deaths, with negative findings at autopsy, many of the decedents, or their firstdegree relatives tested positive for cardiac channel mutations or other heritable cardiac conditions. The purpose of these guidelines is to assist coroners and forensic pathologists in the appropriate investigation of cases of sudden death in young individuals. These guidelines apply to decedents greater than two years of age. They have been written to aid in: i. Standardizing autopsy practice for "negative" autopsies in medicolegal cases in sudden cardiac death in young individuals. ii. Ensuring that appropriate ancillary testing is performed to exclude other possible causes of death in these cases. iii. Ensuring adequate material is retained should the family/next of kin consent to genetic analysis of this material. a. All previously asymptomatic or symptomatic· but undiagnosed individuals under the age of forty years who suffer a sudden witnessed collapse followed by death and where the scene and circumstantial evaluation are negative for obvious causes of death (e.g. drug overdose, etc.). * Symptoms = syncope, exercise-related pre-syncope, palpitations, seizure of unknown origin especially with familial pattern of seizures b. Previously asymptomatic or undiagnosed symptomatic individuals, who drown while swimming without phenomena such as poor swimming skills, fatigue, boating accident, intoxication, etc. A. Obtain all available medical records, including but not limited to, cardiac investigations, and especially EKGs. B. Obtain a detailed family history of any sudden unexplained or cardiac death in first- or second-degree relatives (parents, grandparents, siblings, cousins, etc.). C. Complete a history of the events surrounding the death (including but not limited to, antecedent symptoms of chest pain, dyspnea, palpitations, pre-syncope), if available. D. Carefully assess the circumstances and scene for the presence or possibility of positional asphyxia, sudden unexpected death in epilepsy (with established seizure diagnosis - see above), cardiac arrest during exercise, sudden cardiac death during sleep, hypothermia, hyperthermia, commotio cordis, or electrocution. E. Issue a warrant for a forensic autopsy. a. An external examination should be performed according to the standard practice of forensic pathology. b. These cases should be arriving within autopsy facilities as "sudden and unexpected natural deaths". If however, there is concern that the death may actually be an undifferentiated, criminally suspicious death, the pathologist should refer to those guidelines and perform the procedures as outlined for those types of deaths (see Guidelines on autopsy practice for forensic pathologists, Oct. 2007, second edition). c. External examination (along with history) should exclude the possibility of commotio cordis. a. An internal examination of the head, neck, chest, abdomen and pelvis should be performed according to the standard of practice of forensic pathology. b. In all cases, special attention should be paid to the heart with the cardiac examination to include: I. III. Examination of the Pericardium to exclude hemopericardium. Examination of the great arteries to assess their location and to rule out the possibility of aortic dissection. iv. Opening of the aorta and great vessels with inspection of the valves for thrombi, as well as evidence of valvular stenosis or regurgitation. v. vi. Examination of the coronary arteries to include: 1. Cross sectioning through the main coronary arteries to exclude atherosclerotic stenosis as well as, coronary dissection. 2. Check for abnormal insertions, take-off and specifically to examine if the coronary artery is located between the great vessels 3. Examination of the proximal coronary ostia to exclude an occlusive atherosclerotic plaque at the level of the ostia. Gross inspection and transillumination thinning, fat infiltration, etc. of the RV for RV c. Cross-sections through the ventricles to assess for myocardial infarcts, scars, hypertrophy and mural thrombi. d. Obtaining the weight of the heart following removal of blood and postmortem clot. a. Representative samples of major organs and tissues should be collected and retained in formalin. b. Sections of the heart in cases of unexplained sudden death should include the right ventricle (the section of the right ventricle should include the anterior wall and the outflow tract so that arrhythmogenic right ventricular dysplasia may be excluded), the interventricular septum, the anterior and posterior left ventricles, sections of the lung and kidneys (to evaluate for vascular disease). c. To rule out myocarditis (which if detected may influence the need for genetic testing) a minimum of 10 blocks of myocardium should be examined histologically. Pathological criteria for arrhythmogenic right ventricular dysplasia are still evolving and the diagnosis may not be excluded based on one histological section of the RV outflow tract. One of the tissue blocks should include the AV node. d. Consideration should be given to obtaining a cardiac pathology consu Itation. a. In all cases, in addition to histology, vitreous fluid should be obtained and submitted for biochemical analysis including electrolytes, urea, creatinine, ketones and glucose. b. Comprehensive toxicological testing should be performed by the Centre of Forensic Sciences in all cases. Collection of the following samples is required: i. Blood from the heart Blood from the femoral vessels iii. Stomach contents iv. Urine v. Sample of liver II. 5. Genetic studies for arrhythmogenic and other lethal heritable cardiac disorders: If the history and initial coroner investigation (see sections 1 - External Examination and Section 2- Internal Examination) indicate there is a reasonable suspicion that the death may be attributable to a cardiac channel mutation, the pathologist should acquire appropriate tissue samples. Pathologists should collect and retain the usual tissue samples in formalin and/or paraffin, but also are encouraged to explore more ideal samples for DNA extraction (e.g. frozen highly cellular tissue such as 1cm3 of skeletal muscle stored at -20°C). Samples should be overnight couriered to the regional clinical genetics laboratory for DNA extraction, cataloguing and storage (prior agreement with the laboratory and notification on a case-bycase basis of the laboratory is required). If no cause of death is evident at the time of postmortem examination, or if the heart appears to demonstrate congenital heart disease, consideration should be given regarding retention of the heart and submission to a cardiac pathologist. Retention of tissues (whole organs), however, should only be made in consultation with the Investigating Coroner who in turn will discuss this with the next of kin. In conjunction with the Investigating Coroner, in cases where a genetic cause of sudden cardiac death is either likely or found at autopsy, establish contact with the next of kin and provide information regarding avenues for clinical follow-up as per prior regional arrangement. ii. Advise the next of kin that tissues have been retained, and will be made available on authorized request to the appropriate genetic testing facility. iii. Establish regional referral patterns for genetic assessment, and provide information on these to the next of kin. J. Puranik R, Chow CK, Ouflou JA et al. Sudden death in the young. Heart Rhythm 2005;2:1277 Morentin B, Aguilera B et al. Sudden unexpected non-violent death between 1 and 19 years in north Spain. Arch Ois Child 2000;82:456 Wren C, O'Sullivan JJ, Wright C. Sudden death in children and adolescents. Heart. 2000 Apr;83( 4 ):410-3 Pollanen MS. Guidelines on autopsy practice for forensic pathologists. Criminally suspicious cases and homicides. 2nd edition. 2007. Office of the Chief Coroner, Ontario Liberthson RR. Sudden death from cardiac causes in children and young adults. N Engl J Med 1996; 334(16): 1039-1044 Behr E, Wood OA, Wright M et al.Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome. Lancet 2003; 362 (9394): 1457-9 Tan HL, Hofman N, Van Langen 1Met al. Sudden unexplain death: heritability and diagnostic yield of cardiological and genetic examination in surviving relatives. Circulation 2005; 112 (2): 207-13 Tester OJ, Ackerman MJ. Postmortem Long QT syndrome genetic testing for sudden unexplained death in the young. J Am Call Cardiol 2007; 49(2): 240-6