Scope and Nature of Sudden Cardiac Death before age 40 in Ontario: A Report from the Cardiac Death Advisory Committee of the Office of the Chief Coroner
Caileigh M. Pilmer B.Sc., Bonita Porter MD, Joel A. Kirsh MD, Audrey L. Hicks Ph.D., Norman Gledhill Ph.D., Veronica Jamnik Ph.D., Brent E. Faught Ph.D., Doris Hildebrandt B.A., Neil McCartney Ph.D., Robert M Gow MBBS, Jack Goodman Ph.D., Andrew D. Krahn MD.
Author Affiliation:
Caileigh M. Pilmer, Andrew D. Krahn: University of Western Ontario, London, ON, Canada
Bonita Porter, Doris Hildebrandt: Office of the Chief Coroner, Toronto, ON, Canada
Joel A. Kirsh: The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
Audrey L. Hicks: McMaster University, Hamilton, ON, Canada
Norman Gledhill, Veronica Jamnik: York University, Toronto, ON, Canada
Brent E. Faught, Neil McCartney: Brock University, St. Catharines, ON, Canada
Robert M Gow: Children's Hospital of Eastern Ontario, Ottawa, ON, Canada
Jack Goodman: University of Toronto, Mt. Sinai Hospital, Toronto, ON, Canada
Address for Correspondence:
Dr. Andrew Krahn
Arrhythmia Service
London Health Sciences Centre
339 Windermere Rd
London, Ontario CANADA
N6A 5A5
Tel: 1-519-663-3746
Fax: 1-519-663-3782
Email:
Short Title: Sudden cardiac death before age 40 in Ontario
Word count: 3647
The authors have no conflict of interest to declare.
Abstract
Background: Understanding sudden cardiac death in the young may inform prevention strategies.
Objectives: To determine the scope and nature of sudden death in a geographically defined population.
Methods: We performed a retrospective population-based cohort study in Ontario, Canada of all sudden cardiac death cases involving persons aged 2-40 years identified from the 2008 comprehensive Coroner database. Of 1,741 coroner’s cases, 376 were considered potential sudden cardiac death cases and underwent review.
Results: There were 174 cases of adjudicated sudden cardiac death from a population of 6,602,680 persons aged 2-40 years. Structural heart disease was present in 126 cases (72%), 78% of which was unrecognized. There was no identifiable cause of death in 48 cases (28%), representing primary arrhythmia syndromes. The majority of decedents were male (76%) over the age of 18 (90%). The overall incidence of sudden cardiac death increased with age from 0.7/100,000 (2-18 years) to 2.4/100,000 (19-29 years) to 5.3/100,000 person-years (30-40 years). Persons experiencing sudden cardiac death under age 30 were more likely to have a primary arrhythmia syndrome (OR=2.97, p<0.001). The majority of events occurred in the home (72%); 33% of events in children/adolescents and 9% of events in adults occurred during reported moderate or vigorous exercise (p=0.002). There were no pediatric deaths during organized competitive sports.
Conclusion: The incidence of sudden cardiac death increases with age, typically occurring in a male at rest in the home with unrecognized underlying heart disease or a primary arrhythmia syndrome. Prevention strategies should consider targeting identification of unrecognized structural heart disease and primary arrhythmia syndromes.
Key words: sudden death, autopsy, heart disease, genetics
Introduction
Sudden cardiac death in the young is a tragic and devastating event for families and communities. It is currently not known how best to prevent or limit sudden cardiac death in the younger age group1-5. Characterization of the population that suffers sudden cardiac death would assist in understanding the scope and nature of the problem, and could potentially inform strategies targeting prevention 6,7,8,9. Ontario is Canada’s most populous province, with an ethnically, culturally, and socioeconomically diverse population of thirteen million inhabitants. In this province, coroners are mandated to investigate any and all deaths that are sudden, unexpected, or from non-natural causes. In 2008, of the 2864 deaths that occurred in the 2-40 age group, 1741 were investigated by the coroner’s office. These death investigations were obliged to answer the following five questions: who was the deceased, how, when and where the death occurred, and by what means the death occurred. Coroners in Ontario have the legal right to perform an autopsy to assist in their investigation of the death, and have access to additional services such as general and specialist pathologists and toxicology screening. Individual coroners also have the support of the Office of the Chief Coroner of Ontario (OCCO) for assistance and collaboration on complicated cases. The OCCO maintains a centralized, comprehensive database and death investigation files on all deaths investigated in Ontario. We sought to understand sudden cardiac death in persons aged 2-40 using this comprehensive provincial registry to enable accurate determination of incidence and cause of sudden cardiac death.
Methods
Data Collection
This epidemiologic study incorporated a retrospective cohort design. Cases of potential relevance were identified from the comprehensive database of the Office of the Chief Coroner of Ontario (OCCO), which contains data on all cases reported to and investigated by coroners in Ontario. All files contained a coroner’s report (the Coroner’s Investigation Statement Form 3), and an autopsy report (Report of Post Mortem Examination) if an autopsy was conducted. Other information, such as police reports and reports from other investigating bodies including the Children’s Aid Society and Workplace Safety and Insurance Board, was available depending on circumstances of death. In the case of inquest, a full inquest file including all hearings and final recommendations was available. The coroner’s report included personal information and findings of the death investigation – date of death, environment and manner of death, involvements, reported medical cause of death, as well as a narrative section that included other relevant information such as past medical history that was obtained from medical records and interviews of family members, friends and eyewitnesses. Further detail regarding the structure and definitions used in the Ontario Coroner system is presented in the online Appendix (Tables 1 and 2), in conjunction with a sample Coroner Investigation report.
Sudden death was defined as an event resulting in death or terminal life support within one hour of collapse, or an unwitnessed, but unexpected death in the absence of known or suspected condition that may predispose to terminal illness 10. Deaths were further defined as cardiac in origin if there was autopsy-confirmed heart disease with clinical circumstances consistent with a potential cardiac etiology of death. Sudden unexplained death (SUD) was defined as any sudden death unexplained by pre-existing disease and without identifiable cause on post-mortem examination. Sudden unexpected death below the age of two years was considered a separate entity and was not included.
Using the OCC database, all files that satisfied the following three inclusion criteria were reviewed: 1) date of death in 2008 (the most recent calendar year for which comprehensive electronically-searchable data were available), 2) age at death for selection of patients aged 2-40 inclusive, and 3) manner of death listed as “natural–cardiac”, “natural–other”, “accidental”, or “undetermined”. This yielded 978 potential cases (Figure 1). These cases were reviewed for relevance, and cases that were not sudden, not unexpected, or not of possible cardiac etiology were excluded. This was accomplished in two steps – the first by examining headings such as cause of death and excluding those that were clearly non-cardiac, which excluded 354 files. The second step involved reviewing the remaining 624 files in their entirety, which excluded a further 248 files. Because of the breadth of the inclusion criteria in terms of manner of death, many deaths were readily excluded based solely on cause of death (including deaths classified as undetermined in which the cause of death was gunshot wound, and natural deaths in which the cause of death was clearly non-cardiac such as pneumonia or sepsis). Accidental deaths in which the cause of death was attributed to acute drug toxicity were excluded, but those in which alcohol and/or drugs were contributing factors were reviewed individually for relevance. Similarly, passengers in motor vehicle accidents were excluded without review of the chart, but the drivers were reviewed individually.
Data were collected on the remaining 376 cases, which were considered possible sudden cardiac deaths. These data included demographic information such as date of birth, sex, death information including date, location, cause, and manner of death. Autopsy findings, especially related to cardiac conditions, were noted as was any known history of cardiac or other disease. Cardiac pathology discovered on autopsy was listed separately from any known pre-existing cardiac conditions, as documented in the coroner’s report. Since the death files did not contain copies of the individual’s medical charts, previous medical conditions were noted at the discretion of the investigating coroner and abstracted by a single investigator (CP).
Additional data that were collected included premonitory symptoms, nature of physical activity and/or intensity at time of death, medication or substance use, cardiac risk factors, and narrative details about the circumstances of death from the available evidence. Premonitory symptoms included potential cardiac symptoms such as chest pain, shortness of breath, palpitations and syncope. Further investigations such as requests for additional medical records or personal interviews were not obtained because of the retrospective nature of the study. Physical activity level at time of death was determined from the coroner’s narrative, and was classified as during sleep, at rest, during light to moderate activities of daily living (ADLs), during moderate to vigorous exercise (estimated workload ≥3 metabolic equivalents), or unknown. Decedents were classified as dying at rest if the event was described as such by an eyewitness, or if the decedent was found in a position suggesting rest, such as supine or seated. Light to moderate ADLs included activities such as housework, and other non-physically strenuous activities such as driving. Moderate to vigorous exercise included any sporting or fitness activities such as swimming, running, and team sports, as well as any strenuous physical work or chores such as shoveling snow.
Case definition
Cases were defined by incorporating information from across the file, including death factor, medical cause of death, underlying pathology, description of the environment and circumstances, and contributing factors and co-morbidities. The review adopted an inclusive approach to ensure that unrecognized circumstances such as drowning or single vehicle accidents would be reviewed to detect possible syncope or sudden death while swimming or driving. Cases were included following adjudication by three of the authors - the primary author, an experienced expert in cardiac arrhythmia and sudden cardiac death (AK) and an experienced expert in cardiac pathology and the provincial death investigation system (BP, Deputy Chief Coroner, Province of Ontario). In total, this review excluded a further 202 cases leaving 174 of the possible 376 cases. Cases were included when sudden cardiac death occurred without the identification of any additional factors that could have contributed to death, including toxicology, alcohol or hazardous conditions. Also included were cases when sudden cardiac death occurred with a single potentially contributory factor (other than cardiac disease or primary arrhythmia), but which was not of sufficient gravity that it was expected to cause sudden cardiac death. For example, a patient with unrecognized hypertrophic cardiomyopathy (HCM) who was involved in a fatal single vehicle accident with significant trauma that was unlikely to be fatal, where there was no evidence of attempt to avoid collision, was presumed to represent a fatal arrhythmia resulting in loss of consciousness while driving.
The adjudicated cases were further sub-classified into either sudden cardiac death with no anatomical cause, or sudden cardiac death with underlying structural heart disease. Structural heart disease was deemed either ischemic or non-ischemic, and recognized or unrecognized prior to death based on the narrative in the coroner’s investigation report.
Statistic Analysis
The authors had full access to the data at the OCCO and take full responsibility for its integrity. Statistical analysis was conducted using Graphpad Prism version 5.0d (La Jolla, CA) by one of the authors (CP). Descriptive statistics between those with SCD and SUD, as well as across age groups were compared using one-way ANOVA for continuous variables (means and standard deviations) as appropriate. The chi-square test was used for categorical variables (proportional rates and confidence intervals). Non-parametric multiple comparison analysis was used to determine simultaneous proportional group differences. Overall and age related incidence rates were calculated using the reported sudden cardiac death cases relative to appropriate at risk population size for Ontario in 2008 with 95% confidence intervals derived from the Poisson distribution. Level of statistical significance was set at p0.05.
Results
In 2008, there were 174 cases adjudicated to have sudden cardiac death from an estimated population of 6,602,680 persons aged 2-40 11. Based on this information, the incidence of sudden cardiac death in the overall population was 2.6/100,000 person-years. The incidence of sudden cardiac death increased with age, from 0.7/100,000 person-years in those aged 2-18 to 2.4/100,000 person-years in those aged 19-29 to 5.3/100,000 person-years in those aged 30-40. The majority of decedents were male (76%), and over the age of 18 (90%, Table 1).
Attributed Cause of Death
Of the 174 cases of sudden cardiac death, 126 cases had underlying structural heart disease (72%, 95% CI=60-85), while 48 (28%, 95% CI=20-35) had no identifiable anatomic or toxicological cause of death; sudden unexplained death likely representing primary arrhythmia syndromes. Of the 126 cases with structural heart disease, 104 cases were acquired (ischemic or non-ischemic cardiomyopathy etc., 83%), 20 were congenital or developmental (inherited cardiomyopathy, congenital anomalies, 16%) and two were both. Persons under age 30 were more likely than those aged 30-40 to have a primary arrhythmia syndrome (42% versus 19%; OR=2.97, 95% CI= 1.60-6.28; p<0.001, Figure 2). There was no difference in frequency of a primary arrhythmia syndrome between those less than 18 years and those 19 years to 29 years (44% vs. 37%, p= 0.59). Most structural heart disease was unrecognized (78% of structural heart disease, Table 2). The most common structural heart disease pathology was coronary artery disease, which was found in 36% of all sudden cardiac deaths, and in 49% of those with structural heart disease (Table 1). The non-ischemic causes of structural heart disease are listed in Figure 3, with the most common cause being dilated cardiomyopathy (DCM). Of note, all the included aortic dissections were non-traumatic. Details regarding age specific causes of death are summarized in Table 3.
Overall, 16% of cases had previously recognized heart disease (95% CI, 11-22%). There was no difference in proportion of recognition of underlying heart disease between ischemic and non-ischemic disease (16% vs. 28%, p=0.13), and no difference in proportion of recognition of underlying heart disease between adults and children (22% recognized vs. 30% recognized, p=0.69). Overall, unrecognized underlying heart disease and primary arrhythmia syndromes accounted for 84% of deaths (n=146).