Sudden death in the young

BACKGROUND: Sudden death is rare in young people, but it has a disproportionate impact on the community. OBJECTIVES: The purpose of this study was to determine the causes of sudden, natural death in persons aged 5-35 years. METHODS: All autopsies conducted at a forensic medicine facility in the years 1995-2004 (inclusive) were reviewed. This facility serves more than 2.5 million people in the eastern part of Sydney, Australia. Data collected included subject age, height, weight, gender, circumstances of death, and pathologic findings at autopsy. Deaths caused by trauma, accidental causes, drowning, and drug toxicity were excluded from analysis. RESULTS: There were 427 nontraumatic, sudden deaths in the 10-year period (70.7% male). Cardiac causes accounted for 56.4%, noncardiac causes 39.3%, and undetermined cause 4.3%. The most common cardiac cause of sudden death was presumed arrhythmia in those with no or minimal structural heart disease (29.0%). Other cardiac causes were acute myocardial infarction (24.5%), myocarditis (11.6%), hypertrophic cardiomyopathy (5.8%), aortic dissection (5.4%), and dilated cardiomyopathy (5.4%). More than two thirds of deaths caused by acute myocardial infarction occurred in the age group from 30-35 years. Sudden cardiac death occurred during physical activity in 10.8% of cases. Sudden cardiac death was reported in a first-degree relative in 4.5% of decedents. The most common noncardiac causes of sudden death were epilepsy (23.8%), intracerebral hemorrhage (23.8%), asthma (16.1%), and pulmonary embolism (12.5%). CONCLUSION: Presumed cardiac arrhythmia is the most common cause of sudden, natural death in the young. There was no reported history of sudden death among the relatives of most decedents.     

Arrhythmic sudden death in children

Sudden death (SD) in childhood is rare, representing only 10% of paediatric mortality after one year of age. The individual risk is estimated between 1 in 20.000 and 1 in 50.000 per year. In case of a negative autopsy for cardiac morphologic anomalies, the most presumable cause remains a genetically-determined malignant primary ventricular arrhythmia. Rhythmic sudden cardiac death can be categorized as a complication of a cardiomyopathy (dilated or hypertrophic), or as a primary channelopathy without any structural heart disease. Primary ventricular arrhythmias include long QT syndrome, Brugada syndrome, short QT syndrome and Polymorphic Ventricular Tachycardia. The diagnosis of such syndromes relies upon specific ECG anomalies, personal history of family members, eventually echocardiography and drug challenge. For some of these diseases, morbid genes have been identified thus rendering possible the management of pre symptomatic or undiagnosed family members within specialized multidisciplinary teams. In case of sudden arrhythmic death in children, the parents and siblings must be examined Rescued sudden death exposes to a high risk of recurrence. In such patients, the automatic implantable defibrillator has dramatically improved survival.     

Sudden unexpected death in persons less than 40 years of age

This study retrospectively assesses the underlying causes of sudden unexpected death and the occurrence of prodromal symptoms in 162 subjects (aged 9 to 39 years) over a 10-year period (1976 to 1985). Underlying cardiac diseases accounted for sudden death in 73% and noncardiac causes in 15% of subjects. In 12% of subjects, the causes were unidentifiable. Myocarditis (22%), hypertrophic cardiomyopathy (22%) and conduction system abnormalities (13%) were the major causes in 32 subjects aged less than 20 years. Major causes of 46 deaths in subjects 20 to 29 years were atherosclerotic coronary artery disease (24%), myocarditis (22%) and hypertrophic cardiomyopathy (13%). The largest number of deaths in 84 subjects aged greater than or equal to 30 years was attributed to coronary artery disease (58%), followed by myocarditis (11%). Among noncardiac causes of sudden death, intracranial hemorrhage was the most frequent (5%), followed by infectious disease (4%). Prodromal symptoms were reported by 54% of subjects; most frequent were chest pain (25%) in subjects aged greater than or equal to 20 years, and dizziness (16%) in those aged less than 20. Sudden death, which occurred during routine daily activity in 49% and during sleep in 23% of subjects, was related to physical exercise in 23% and emotional upset in 6%. Sudden unexpected death in the young is still an unresolved medical problem. The early recognition of prodromal symptoms could be crucial in the prevention of sudden death, specifically when exercise-related.     

Sudden death after radiofrequency ablation of the atrioventricular node in patients with atrial fibrillation

OBJECTIVES: We evaluated the incidence and predictors of sudden death after atrioventricular (AV) node ablation and pacemaker implantation. BACKGROUND: Sudden death may occur after radiofrequency catheter ablation of the AV node and pacemaker implantation in patients with atrial fibrillation (AF). Whether it is related to the procedure or to pre-existing heart disease remains unclear. METHODS: All patients who had radiofrequency catheter ablation of the AV node and pacemaker implantation for rate control of medically refractory AF were identified retrospectively and observed prospectively. All patients with sudden death after ablation were identified. The relationship between the procedure and sudden death was defined on the basis of the time between the two as "likely," "possibly" or "unlikely." RESULTS: Of 334 consecutive patients with AF who underwent AV node ablation, nine had sudden death after the ablation. Four patients (1.2%) had sudden death likely related to the procedure: in 3 patients, arrest occurred within 48 h after the procedure; in one patient, arrest occurred four days after the procedure. In three other patients (0.9%), sudden death was possibly related to the procedure because the event occurred within three months afterward. The remaining two deaths were unrelated to the procedure. Diabetes, New York Heart Association functional class (>or=II), preprocedure ventricular arrhythmia, mitral or aortic stenosis, aortic regurgitation and chronic obstructive pulmonary disease were independent predictors for sudden death. CONCLUSIONS: Sudden death likely or possibly related to catheter ablation occurred in 7 of 334 patients (2.1%). Risk of sudden death is highest within two days after the procedure.     

Sudden death of school children in Japan

The autopsy findings of sudden deaths of school children revealed that the main causes of death were latent myocarditis and arrhythmia, followed by idiopathic cardiomyopathy. The incidence of sudden death of school children in recent years is gradually increasing and 150 cases of sudden death occurred during the 1983 school year. A high incidence of sudden death in senior high school students was found. Sudden cardiac death accounted for approximately 80% of total deaths. The incidence of sudden cardiac death revealed prominent regional differences in Japan. The average for deaths was 0.40/100,000 children/5 years and the highest prefecture revealed 0.70 and the lowest 0.07. The cause of such differences is not clear and requires further analysis.     

Sudden death associated with anomalous coronary origin and obstructive coronary disease in the young

Sudden cardiac death in a young patient is a catastrophic occurrence. Anomalous coronary origin (ACO) is a significant cause of sudden cardiac death among individuals under the age of 35 years. We sought to define the premortem clinical and postmortem histopathologic findings in victims of sudden cardiac death resulting from either ACO or obstructive atherosclerotic coronary artery disease (CAD) among U.S. military recruits (ages 17-35 years). The autopsy records of all sudden cardiac deaths occurring among recruits during their basic military training period from 1977 through 2001 were reviewed. Twenty-one deaths were associated with ACO and 10 with CAD. Recruits with ACO were more likely to have prodromal symptoms of exertional syncope and/or chest pain (48% vs. 0%, P = 0.011). All sudden cardiac deaths resulting from ACO involved a left main coronary artery takeoff from the right coronary sinus with a course between the aorta and the right ventricular outflow tract and an otherwise normal distribution of the major epicardial coronary arteries. Myocardial fibrosis was seen equally in those with both CAD and ACO (30% vs. 20%, P = 0.66), but the finding of necrosis tended to be more common among recruits with CAD (50% vs. 15%, P = 0.08). In conclusion, review of autopsy data of sudden cardiac deaths among U.S. military recruits reveals myocardial fibrosis or necrosis occurred in 70% of cases with CAD and 35% of cases with ACO. Sudden cardiac deaths resulting from ACO were more likely to be associated with premortem exertional chest discomfort and/or syncope compared with deaths resulting from CAD.     

Genetics and cardiovascular disease--causes and prevention of unexpected sudden adult death: the role of the SADS clinic

Sudden arrhythmic death syndrome (SADS) accounts for approximately 500 deaths in England and Wales per year. Clinical screening of the surviving first-degree relatives can identify an inherited cardiovascular condition in up to half of families, permitting lifestyle modification and confirmed effective prophylactic therapies to prevent further sudden deaths. Mechanisms for molecular autopsy are available to improve the diagnostic yield but practical barriers to its successful implementation exist. This article reviews the clinical screening of the first-degree relatives of SADS patients, molecular autopsy of probands and the broader implications of national recommendations for the investigation of sudden cardiac death.     

Alcohol as a risk factor for sudden infant death syndrome (SIDS)

Aim To test whether alcohol is a risk factor for sudden infant death syndrome (SIDS). Design and setting US epidemiological study using computerized death certificates, linked birth and infant death dataset, and Fatality Analysis Reporting System. Participants All SIDS cases (n = 129 090) and other infant deaths (n = 295 151) from 1973–2006; all persons involved in late‐night alcohol‐related crashes (n = 135 946) from 1994–2008. Measurements Three measures were used: the expected number of deaths on New Year versus the observed number (expected values were determined using a locally weighted scatterplot smoothing polynomial), the average number of weekend deaths versus the average number of weekday deaths, and the SIDS death rate for children of alcohol‐consuming versus non‐alcohol‐consuming mothers. Findings These measures indicate that the largest spikes in alcohol consumption and in SIDS (33%) occur on New Year, alcohol consumption and SIDS increase significantly on weekends, and children of alcohol‐consuming mothers are much more likely to die from SIDS than are children of non‐alcohol‐consuming mothers. Conclusions Alcohol consumption appears to be a risk factor for sudden infant death syndrome, although it is unclear whether alcohol is an independent risk factor, a risk factor only in conjunction with other known risk factors (like co‐sleeping), or a proxy for other risk factors associated with occasions when alcohol consumption increases (like smoking). Our findings suggest that caretakers and authorities should be informed that alcohol impairs parental capacity and might be a risk factor for sudden infant death syndrome; in addition, future research should further explore possible connections between sudden infant death syndrome and alcohol.     

Sudden death (VI). The Brugada syndrome and right myocardiopathies as a cause of sudden death. The differences and similarities

In 1992 we described a new syndrome characterized by syncopal or sudden death episodes in patients with a structurally normal heart and a characteristic electrocardiogram 9 showing a pattern of right bundle branch block and ST segment elevation in right precordial leads V1 to V3. The disease is genetically determined with and autosomic dominant pattern of transmission. Until now three mutations and one polymorphism in the sodium cardiac channel gene have been identified in two families and one sporadic patient. As in many other genetically determined diseases, the disease is heterogeneous, caused by more than one gene. The syndrome has been identified in almost all countries in the world. Its incidence is difficult to evaluate, but it seems to be responsible for 4 to 10 sudden deaths per year per 10,000 inhabitants in areas like Laos or Thailand, and it represents the most frequent cause of death in young male adults in these countries. Up to 50% of all sudden deaths in patients with structurally normal heart are caused by the disease. The diagnosis can be easily made thanks to the characteristic electrocardiographic pattern. In some patients, the presence of concealed and intermittent forms might make the diagnosis more difficult. The electrocardiogram can be modulated by autonomic changes and administration of antiarrhythmic drugs. Beta-adrenergic stimulation normalizes the electrocardiogram, whereas ajmaline, flecainide or procainamide administration increase ST segment elevation. These drugs allow the unmasking of concealed or intermittent forms of the disease. Prognosis of patients with the syndrome is poor without an implantable defibrillator and antiarrhythmic drugs like amiodarone or betablockers do not protect against sudden death. The poor prognosis is similar in patients with a history of aborted sudden death or syncope and in asymptomatic patients in whom the abnormal electrocardiogram characteristic of the syndrome, was identified during a routine examination.     

Sudden death in the general population in Okinawa: incidence and causes of death

Sudden unexpected death is generally considered to be caused by acute myocardial infarction and/or arrhythmia. To document the incidence and causes of sudden death in Japan, where the incidence of myocardial infarction is low, the present study examined death certificates, hospital records, the forensic medical records, and the police records of residents of the southern part of Okinawa island who died at the age of 20-74 years during a 3-year period from January 1, 1992 to December 31, 1994. Sudden death was defined as death within 24 h from the onset of unexpected symptoms. The study documented 126 (87 men and 39 women) sudden deaths. The crude incidence rate was 0.37/1,000 person per year (0.51 in men and 0.23 in women). According to the death certificates, 78 cases died of heart diseases. However, the cause of death could be determined by examination of all available records in only 64 cases: myocardial infarction in 10, non-ischemic heart diseases in 13, and stroke in 23 cases. Even when the analysis was limited to the cases who died within 1 h from the onset of symptoms, heart disease was the cause of death in only 22% of the cases while the cause of death could not be determined in 53% of the cases. Only 13% of those diagnosed as heart diseases on the death certificate were verified. The agreement rate between the diagnosis reached by the re-evaluation of the records and that on the death certificate was 82% for stroke and 33% for other diseases. In Okinawa, Japan, the frequencies of heart disease and stroke as the cause of sudden death may be similar. Except for stroke, the diagnosis appearing on the death certificate has substantial inaccuracy.     

Clinical characteristics of sudden death victims in heritable (chromosome 1p1-1q1) conduction and myocardial disease

Objectives. The purpose of this study was to identify the clinical characteristics of family members at risk of sudden death.Background. The significance of sudden death in heritable cardiac disorders with delayed expression is incompletely understood. Additional insights come from a four-decade experience of seven generations of a family of German origin with autosomal dominant (chromosome 1p1-1q1) cardiac conduction and myocardial disease.Methods and Results. A total of 38 family members (20 males; 18 females) were identified with sudden death. Twenty-eight family members (mean age 48 ± 8 years) from earlier generations had no pacemaker at the time of sudden death. In this group, 15 subjects were asymptomatic prior to sudden death. Ten family members with sudden death, from later generations, had chronically implanted pacemakers for high grade atrioventricular block. This group was older (mean age 57 ± 2 years), with decreased functional status (New York Heart Association class II to IV), enlarged left atria, dilated left ventricles with reduced systolic function and documented ventricular fibrillation in three members. Twenty-eight family members with sudden death were descendants of sib lineages 2 or 6; 21 family members with sudden death were offspring of a parent who also suffered sudden death.Conclusion. Sudden death is an important late outcome in heritable (chromosome 1p1-1q1) cardiac conduction and myocardial disease. Pacemaker therapy is important for the treatment of symptomatic bradycardia, but it does not prevent sudden death. Family members who are beyond the third decade of life with reduced functional capacity, left ventricular dysfunction, pacemakers and who are the offspring of a parent with sudden death appear to be at greatest risk.     

Sudden death in type 1 diabetes: the mystery of the 'dead in bed' syndrome

Sudden cardiac death is an unpredictable and devastating event, particularly in the young. A significant proportion of sudden deaths in the young are unexplained-no cause is identified either during life or at post-mortem. This is seen in a subgroup of young patients with type 1 diabetes who have dead in bed syndrome, where these victims are in good health, retire to bed, only to be found dead the following morning in a bed which is undisturbed, suggesting no terminal struggle or seizure. The underlying cause of dead in bed syndrome remains unknown, but is likely to be due to a terminal malignant arrhythmia. A plausible hypothesis is that it may be secondary to QT interval prolongation (followed by a degenerate ventricular tachycardia), caused by a number of factors including acute hypoglycaemia, on a background of cardiac autonomic neuropathy, and possible genetic influences. It is envisaged that understanding the causes and triggers of dead in bed syndrome will allow appropriate therapeutic interventions to be initiated in high-risk patients with type 1 diabetes, with the ultimate goal to prevent sudden death.     

Timing of sudden death in patients with heart failure

Objectives. The purpose of this study was to determine the timing of sudden death in patients with advanced heart failure.Background. The frequency of sudden cardiac death and myocardial infarction is greatest in the morning hours, suggesting that physiologic processes associated with morning activities may trigger these events. In patients with advanced heart failure, a variety of mechanisms may cause sudden death, and the frequency of their occurrence may differ from that in other patient groups, perhaps altering the timing of sudden death in heart failure.Methods. Deaths among 566 consecutive patients followed up after treatment for advanced heart failure were prospectively categorized as sudden death, death due to heart failure or noncardiac death. For 72 sudden deaths the time of death was determined from witnesses to the event and from death certificates.Results. Sudden death occurred 2.5 times more frequently between 6:01 amand 12 noon than in the three other 6-h intervals, with 46% of deaths occurring during this period (p < 0.005). The morning peak occurred both in patients with coronary artery disease and in those with nonischemic causes of heart failure.Conclusions. Despite a variety of potential mechanisms of sudden death and underlying causes of heart disease in patients with heart failure, the 24-h distribution of sudden death in these patients is similar to that observed in other patient groups. Morning surges in sympathetic nervous system activity may promote a variety of sudden death mechanisms, including ischemic and nonischemic arrhythmias.     

Causes of sudden death in young female military recruits

This study sought to examine the incidence of sudden death in a large, multiethnic cohort of young women. Approximately 852,300 women entered basic military training from 1977 to 2001. During this period, there were 15 sudden deaths in female recruits (median age 19 years, 73% African-American), occurring at a median of 25 days after arrival for training. Of the sudden deaths, 13 (81%) were due to reasons that may have been cardiac in origin. Presumed arrhythmic sudden death in the setting of a structurally normal heart was seen in 8 recruits (53%), and anomalous coronary origins were found in 2 recruits (13%). The mortality rate was 11.4 deaths per 100,000 recruit-years (95% confidence interval 6.9 to 18.9). The rate was significantly higher for African-American female recruits (risk ratio 10.2, p <0.001). Sudden death with a structurally normal heart was the leading cause of death in female recruits during military training.     

The role of molecular autopsy in unexplained sudden cardiac death

PURPOSE OF REVIEW: Sudden cardiac death (SCD) is one of the most common causes of death, with many attributable to cardiac/coronary abnormalities evident at autopsy. A significant number of SCDs, however, particularly in young people, remain unexplained following a medico-legal investigation, including autopsy, and are referred to as autopsy-negative sudden unexplained death (SUD). Due to molecular advances, however, a cardiac channel molecular autopsy may potentially provide a pathogenic basis for SUD and establish cause and manner of death. RECENT FINDINGS: Over the past decade, five population-based investigations of sudden death in young people elucidated the frequency of and causes responsible for these tragic events. The most inclusive epidemiologic study concluded that nearly 30% of SCDs in young people are autopsy-negative (i.e. SUD) and most likely secondary to cardiac channelopathies. Case reports on the post-mortem molecular diagnosis of cardiac channelopathies through the use of a molecular autopsy have been presented. Recently, a molecular autopsy series of SUD identified pathogenic mutations in long QT syndrome and catecholaminergic polymorphic ventricular tachycardia-associated genes in over one-third of cases. Similar post-mortem cardiac channel genetic testing in a large population-based cohort of sudden infant death syndrome has elucidated mutations in 5-10% of cases. SUMMARY: With autopsy-negative SUD accounting for a significant number of sudden deaths in young people, a new role for the medical examiner is emerging. An accurate diagnosis, derived from a molecular autopsy, will guide the appropriate initiation of pre-emptive strategies in hopes of preventing future tragedies among those left behind.     

Sudden cardiac death: an update

Sudden cardiac death (SCD) is a devastating and all too common result of both acquired and genetic heart diseases. The profound sadness endured by families is compounded by the risk many of these deaths confer upon surviving relatives. For those with known cardiac disease, disease‐specific therapy and risk stratification are key to reducing sudden death. For families of a SCD victim, uncovering a definitive cause of death can help relieve the agonising uncertainty and is a vital first step in screening surviving relatives and instituting therapy to reduce SCD risk. Increasing knowledge about the molecular mechanisms and genetic drivers of malignant arrhythmias in the diverse clinical entities that can cause SCD is vital if we are to optimise risk stratification and personalise patient care. Advances in diagnostic tools, disease‐specific therapy and defibrillator technology are improving outcomes for patients and their families but there is still much progress to be made.     

Sudden cardiac death in athletes

Sudden cardiac death in athletes is an uncommon but extremely visible event because of the high profile of amateur and professional athletes and the expected excellent health of these athletes. However, paradoxically, athletic performance may immediately increase the risk of ventricular arrhythmias and sudden cardiac death while run reducing atherosclerosis, which thus improves cardiovascular health and longevity. In athletes younger than 30 years, the most common underlying causes are due to inherited heart disease. In the older athletes, sudden death is generally due to arrhythmias in the context of coronary artery disease. Many athletes with aborted sudden death, arrhythmia-related syncope, or high-risk genetic disorders benefit from therapy with implanted cardioverter/defibrillators (ICDs) . Although ICD therapy can effectively abort sudden death, implantation of an ICD generally prohibits an individual from all competitive athletics except low-intensity sports. The screening of athletes has been notoriously inadequate; however, the optimal screening strategies have yet to be determined. Recommendations for participation in competitive athletics generally follow the recently published 36th Bethesda Conference Eligibility Recommendations for Competitive Athletes with Cardiovascular Abnormalities.     

Circadian variability in the occurrence of sudden cardiac death in patients with hypertrophic cardiomyopathy

Objectives. The present study examined whether sudden death in patients with hypertrophic cardiomyopathy occurred with a particular pattern of frequency throughout the day.Background. Previous investigators have shown a circadian distribution in the occurrence of sudden death and other cardiovascular events in patients with atherosclerotic coronary artery disease. Sudden death is also an important feature of the natural history of patients with hypertrophic cardiomyopathy.Methods. The study group comprised 94 patients with a time of death (or cardiac arrest) that could be ascertained accurately to the nearest hour. This hourly distribution was analyzed by harmonic regression.Results. Sudden death did not occur uniformly or randomly throughout the day. Rather, it was distributed in a bimodal pattern that conformed to a two-harmonic regression model. A disproportionate number of sudden deaths (43 [46%] of 94) occurred in the first peak in midmorning between 7 amand 1 pm. The second peak of sudden death was less distinct but was in the early evening, between 8 pmand 10 pm. This periodicity in occurnace of sudden cardiac death was not evident for the days of the week or months of the year and, furthermore, did not appear to be influenced by other clinical variables, such as age, gender, severity of symptoms, subaortic gradient or left ventricular wall thickness. Sudden death occurred most commonly during periods of severe exertion (37 [39%] of 94).Conclusions. Sudden death in hypertrophic cardiomyopathy demonstrates a bimodal pattern of circadian variability over the 24-h day, with a prominent midmorning peak similar to that described in patients with coronary artery disease, and a less striking early-evening peak of occurrence. These findings suggest that temporally related physiologic changes, possibly in the electrical vulnerability of the myocardial substrate, may play a role in the sudden death of patients with hypertrophic cardiomyopathy.     

A survey of sudden death among school children in Osaka Prefecture

For 2 years, from January 1985 to December 1986, we carried out a thorough investigation of sudden death or apparent sudden death in a population between 5 and 19 years of age in Osaka Prefecture. Sudden death (unexpected death caused by intrinsic factors within 24 h after the onset of symptoms) occurred in 62 boys and 30 girls, with an annual sudden death rate of 3.0 per 100,000 for boys and 1.5 per 100,000 for girls. Of these 92 deaths, 64 occurred among school children (elementary or high school students), and it was these that were subjected to further analyses. Of the school children deaths, 29.7% seemed to be apparent sudden cardiac death (based on circumstances immediately before death, although there was no definite evidence for sudden cardiac death), and 29.7% were sudden death clearly attributable to underlying heart diseases (hence, sudden cardiac death in the usual meaning of this term accounted for about 60% of the 64 sudden deaths). In addition, 17.2% of the 64 cases were sudden death from bronchial asthma. Analysis of seasonal variation in the incidence of sudden death showed that apparent sudden cardiac death frequently occurred in summer, while sudden death clearly attributable to underlying cardiac diseases often took place in winter, sudden death from bronchial asthma occurred chiefly in summer and fall. Of the total number of sudden deaths, death occurred during exercise in 29.7%, and during sleep in 18.8% of individuals. The percentage of sudden deaths occurring during school hours was as low as 23.4% (15/64). Analysis of the physical condition of the 64 sudden death cases immediately before death disclosed the presence of respiratory infection in 10.9%, fatigue in 21.9%, lack of sleep in 4.7% and other conditions in 4.7%. Thus, the percentage of sudden deaths which occurred under ordinary physical conditions was 57.8% (37/64), of which 14 deaths (21.9% of the total) were associated with exercise.     

Sudden cardiac death (part 1

Sudden cardiac death is a sudden unexpected non-violent death for cardiac reasons which according to the majority of authors occurs within one hour after the development of symptoms of acute impairment of health. This syndrome is a major problem of contemporary medicine with a very adverse prognosis. The authors analyze the epidemiology, causes, influence of the external environment, basic arrhythmogenic mechanisms and prognosis of sudden death. Examination methods of this clinical condition are evaluated from the aspect of their application in the risk stratification of patients.