Blood alcohol in victims of sudden cardiac death in northern Finland.

AIMS: Momentary intake of large quantity of alcohol provokes ventricular ectopic activity increasing electrical instability. The present study was aimed to assess the prevalence of alcohol intake prior to a sudden cardiac death (SCD) event. METHODS AND RESULTS: Victims of unexpected SCD [n = 2363, age 61 ± 12 years, males 1940 (82%)] included in the Finnish study of genotype and phenotype profiles of SCD (FINGESTURE) had a thorough interview of family members, medico-legal autopsy, and determination of blood alcohol concentration. Because of the Finnish law, all unexpected deaths undergo medico-legal autopsy. Patients who were admitted to a hospital due to an acute myocardial infarction [n = 128, age 63 ± 10 years, males 100 (78%)] served as controls. Based on autopsy findings, 1691 of these victims had ischaemic heart disease (IHD) and were included in the present analysis. A total of 646 (38%) SCD victims with IHD had a blood ethanol concentration above 0‰. Of these victims with blood alcohol test positive, 41% (n = 264) had blood ethanol concentration ≥1.5‰ and 56% (n = 362) ≥1‰. Male SCD victims had more frequently alcohol in blood than the females (40 vs. 27%, P < 0.001, respectively). None of the controls, who gave a consent for the blood ethanol concentration determination (n = 88), had alcohol in blood. Of the controls, 40 (31%) declined to participate in the study and give the consent for blood alcohol testing. CONCLUSION: Almost 4 of 10 of the victims of unexpected SCD have evidence of alcohol intake before the fatal event in the northern Finland autopsy population.

Psychotropic medications and the risk of sudden cardiac death during an acute coronary event.

AIMS: Psychotropic medication increases cardiac mortality, but the reasons for this association are not clear. We studied the role of psychotropic drugs as a triggering factor of sudden cardiac death (SCD) during an acute coronary event. METHODS AND RESULTS: The use of medication was compared between victims of SCD and survivors of an acute coronary event in a case-control study including a consecutive series of victims of SCD (n= 1814, mean age 65 ± 11 years) verified to be due to an acute coronary event at medico-legal autopsy and consecutive series of patients surviving an acute myocardial infarction (AMI; n= 1171, mean age 66 ± 12 years). The medication history was obtained from autopsy/hospital records and interviews with relatives of SCD victims and AMI patients. The use of antipsychotics [9.7 vs. 2.4%, odds ratio (OR) 4.4, 95% confidence interval (CI) 2.9-6.6; P< 0.001] and antidepressants (8.6 vs. 5.5%, OR: 1.6, 95% CI: 1.2-2.2; P= 0.003) was more common in the SCD than AMI group, but the use of benzodiazepines did not differ between the groups (11.7 vs. 13.2%; P= 0.270). The use of antipsychotics remained as a significant risk factor for SCD after adjustment for confounding variables (OR: 3.4, 95% CI: 1.8-6.5; P< 0.001). Combined use of phenothiazines and any antidepressant was associated with a very high risk of SCD (OR: 18.3, 95% CI: 2.5-135.3; P< 0.001). CONCLUSION: The use of psychotropic drugs, especially combined use of antipsychotic and antidepressant drugs, is strongly associated with an increased risk of SCD at the time of an acute coronary event.

Cardiac arrest and left ventricular fibrosis in a Finnish family with the lamin A/C mutation.

INTRODUCTION: We screened the candidate genes from a Finnish family in which the mother was resuscitated from ventricular fibrillation and the daughter died suddenly without any prior cardiac symptoms. METHODS AND RESULTS: In addition to screening of potential structural gene mutations, phenotyping of the proband and medico-legal autopsy of the victim of the sudden death, including histopathological examinations, were performed. Genetic screening revealed an R541C mutation in the lamin A/C gene both in the proband and her daughter. None of the 16 first- or second-degree relatives, or 96 unrelated healthy subjects, carried the same mutation. In the proband, the size and the global function of the left ventricle (LV) were normal, but a local hypokinesia and thinning of inferoposterior area of the LV were seen in 2D echocardiography and magnetic resonance imaging. Coronary angiogram and the results of the electrophysiological study were normal. Autopsy of the victim of sudden death showed localized thinning and fibrosis in the inferoposterior area of the LV, with only minimal fibrosis in the right ventricle and no abnormalities in the interventricular septum. CONCLUSION: These observations indicate that a fatal or near-fatal cardiac arrhythmia can be the first clinical manifestation of a "de novo" mutation R541C of the lamin A/C gene. Replacement of cardiac myocytes by fibrosis seems to be the predominant pathologic-anatomic finding.

Risk of sudden cardiac death in relation to season-specific cold spells: a case-crossover study in Finland.

OBJECTIVE: To test a priori hypothesis of an association between season-specific cold spells and sudden cardiac death (SCD). METHODS: We conducted a case-crossover study of 3614 autopsy-verified cases of SCD in the Province of Oulu, Finland (1998-2011). Cold spell was statistically defined by applying an individual frequency distribution of daily temperatures at the home address during the hazard period (7 days preceding death) and 50 reference periods (same calendar days of other years) for each case using the home coordinates. Conditional logistic regression was applied to estimate ORs for the association between the occurrence of cold spells and the risk of SCD after controlling for temporal trends. RESULTS: The risk of SCD was associated with a preceding cold spell (OR 1.33; 95% CI 1.00, 1.78). A greater number of cold days preceding death increased the risk of SCD approximately 19% per day (OR 1.19; 95% CI 1.07 to 1.32). The association was strongest during autumn (OR 2.51; 95% CI 1.27 to 4.96) and winter (OR 1.70; 95% CI 1.13 to 2.55) and lowest during summer (OR 0.42; 95% CI 0.15 to 1.18) and spring (OR 0.89; 95% CI 0.45 to 1.79). The association was stronger for ischaemic (OR 1.55; 95% CI 1.12 to 2.13) than for non-ischaemic SCD (OR 0.68; 95% CI 0.32 to 1.45) verified by medicolegal autopsy. CONCLUSIONS: Our results indicate that there is an association between cold spells and SCD, that this association is strongest during autumn, when the weather event is prolonged, and with cases suffering ischaemic SCD. These findings are subsumed with potential prevention via weather forecasting, medical advice and protective behaviour.

Cold spells and ischaemic sudden cardiac death: effect modification by prior diagnosis of ischaemic heart disease and cardioprotective medication.

Sudden cardiac death (SCD) is the leading cause of death. The current paradigm in SCD requires the presence of an abnormal myocardial substrate and an internal or external transient factor that triggers cardiac arrest. Based on prior mechanistic evidence, we hypothesized that an unusually cold weather event (a cold spell) could act as an external factor triggering SCD. We tested potential effect modification of prior diagnoses and select pharmacological agents disrupting pathological pathways between cold exposure and death. The home coordinates of 2572 autopsy-verified cases of ischaemic SCD aged ≥35 in the Province of Oulu, Finland, were linked to 51 years of home-specific weather data. Based on conditional logistic regression, an increased risk of ischaemic SCD associated with a cold spell preceding death (OR 1.49; 95% CI: 1.06-2.09). Cases without a prior diagnosis of ischaemic heart disease seemed more susceptible to the effects of cold spells (OR 1.70; 95% CI: 1.13-2.56) than cases who had been diagnosed during lifetime (OR 1.14; 95% CI: 0.61-2.10). The use of aspirin, ß-blockers, and/or nitrates, independently and in combinations decreased the risk of ischaemic SCD during cold spells. The findings open up new lines of research in mitigating the adverse health effects of weather.

Temporal Trends in the Clinical and Pathological Characteristics of Victims of Sudden Cardiac Death in the Absence of Previously Identified Heart Disease.

BACKGROUND: Coronary artery disease is identified in ≈80% of victims of sudden cardiac death (SCD). Because the prevention strategies and public awareness have changed during the past decades, we studied the temporal trends in the pathogenesis of SCD. METHODS AND RESULTS: FinGesture (n=4031) is a prospective study designed to classify the phenotype and genotype profiles of SCD in a consecutive series of victims of SCD in Northern Finland. On the basis of Finnish law, all subjects who die suddenly undergo autopsy. We analyzed the characteristics of SCD victims and autopsy findings in 1998 to 2002, 2003 to 2007, and 2008 to 2012. Among victims of SCD as a first cardiac event (n=2697), the proportion with coronary artery disease decreased during the 2008 to 2012 time period, compared with the 2 preceding 5-year periods: 74.0% in 1998 to 2002, 73.1% in 2003 to 2007, and 66.4% in 2008 to 2012 (P<0.001). Proportion of SCDs associated with hypertensive heart disease with left ventricular hypertrophy in the absence of coronary artery disease increased from 1.7% in 1998 to 2002 to 5.8% in 2003 to 2007 and 8.9% in 2008 to 2012 (P<0.001). Similarly, myocardial fibrosis in the absence of myocarditis or left ventricular hypertrophy, or other known pathogeneses, was 6.7% in the past 5-year period compared with 2 previous 5-year periods (3.7% and 4.0%; P<0.001 between 1998-2002 and 2008-2012 and between 2003-2007 and 2008-2012). CONCLUSIONS: The proportion of SCDs attributable to coronary artery disease, in the absence of a history of heart disease, has decreased, whereas the proportion associated with hypertensive heart disease and idiopathic fibrosis has increased during the past 15 years.

Antiepileptic medications and the risk for sudden cardiac death caused by an acute coronary event: a prospective case-control study.

BACKGROUND: Epilepsy is associated with sudden death, but the reasons for this association are not well known. Objective We studied the role of antiepileptic drugs (AEDs) as a factor contributing to sudden cardiac death (SCD) in The Finnish Study of the Genotype and Phenotype Characteristics of Sudden Cardiac Death (FinGesture). METHODS AND RESULTS: The FinGesture study compares the characteristics of victims of SCD caused by an autopsy-verified acute coronary event (cases) vs. survivors of an acute coronary event (ACS) (controls). The study population comprised 3737 cases (mean age 64 ± 12 y) and 3081 controls (mean age 66 ± 12 y). The use of AED was obtained from death certificates, autopsy/hospital records, national drug imbursement register, and interviews with the relatives. AEDs were more commonly used by the victims of SCD vs. controls (5.5% vs. 2.2%, adjusted odds ratio 2.7, 95% CI; 1.9-3.9; p < 0001). The use of AED for non-epilepsy indications was also more common in the cases than in controls (1.5% vs. 1.0%, p = 0.005). CONCLUSION: A higher rate of AED was observed in victims of SCD than in a control group of ACS patients. Concomitant use of AED could be responsible for a small fraction of deaths due to acute coronary events. Key message Epilepsy has been associated with sudden cardiac death. The use of antiepileptic drugs seems to be associated with an increased risk of sudden cardiac death during a coronary event. Physicians should be aware of the risk related to antiepileptic drugs especially when used for other reasons than epilepsy.

Sudden cardiac death during physical exercise: Characteristics of victims and autopsy findings.

OBJECTIVE: To provide data on the risk factors and characteristics of subjects who experience sudden cardiac death (SCD) during physical exercise. METHODS AND RESULTS: We assessed the characteristics and the medico-legal autopsy findings of SCD victims who had experienced a witnessed fatal cardiac arrest at rest (n = 876) or in relation to physical exercise (n = 328) in the Finnish Study of Genotype and Phenotype Characteristics of SCD (FinGesture). A total of 876 (73%) witnessed SCDs occurred at rest (R group) and 328 (27%) during or immediately after physical exercise (PE group). Male gender was more common in the PE group compared to the R group (309/328, 94% versus 678/876, 77%, P < 0.001). Coronary artery disease was a more common structural heart disease than non-ischemic disease at autopsy when SCD was exercise-triggered (299/328, 91% versus 657/876, 75%, P < 0.001). Myocardial scarring and cardiac hypertrophy were more commonly found at autopsy in the PE group (194/328, 59% versus 370/876, 42%, P < 0.001; 243/328, 74% versus 585/876, 67%, P = 0.012, respectively). Skiing, cycling, and snow shoveling were the most common modes of exercise at the time of SCD. CONCLUSIONS: SCD during or immediately after exercise is related to male gender, ischemic heart disease, cardiac hypertrophy, and myocardial scarring.

Increased type I collagen synthesis in victims of sudden cardiac death due to idiopathic myocardial fibrosis.

AIMS: Idiopathic myocardial fibrosis (IMF) was observed to be the most prevalent autopsy finding in the victims of sudden cardiac death (SCD) under the age of 40 years in the FinGesture cohort. To elucidate further the mechanisms of IMF, we examined the collagen composition from the myocardial samples taken from the victims of IMF-associated SCD. METHODS: Eighteen cases with IMF as a cause of death, confirmed by autopsy, were selected for the analysis. Controls (n = 27) included were cases in whom no cardiac or non-cardiac disease could be found as a cause of unexpected death at autopsy. In addition to conventional histological examination, immunohistochemical staining of procollagens I and III (PINP and PIINP), mature collagen III (IIINTP), and the cross-linked collagen I degradation product (ICTP) were performed. RESULTS: Increased accumulation of PINP was observed in the fibrotic tissue of the IMF cases in comparison with control samples. In contrast, type III collagen was not as frequently expressed in the fibrotic areas. CONCLUSION: Myocardial accumulation of PINP in the victims of IMF-associated SCD indicates increased type I collagen synthesis. Future studies on the role of circulating type I collagen biomarkers are needed to study further the implications of the described association.

Comparison of family history of sudden cardiac death in nonischemic and ischemic heart disease.

BACKGROUND: Recent studies have identified the presence of familial clustering of ischemic sudden cardiac death (SCD) as a clinical expression of coronary artery disease. The purpose of this study was to determine whether nonischemic SCD has a similar familial background, which would be evidence of a genetic predisposition. METHODS AND RESULTS: The retrospective case-control study included (1) consecutive victims of nonischemic SCD (n=223), (2) consecutive victims of ischemic SCD (n=596), whose deaths and diagnosis were verified at medicolegal autopsy, and (3) control subjects without heart disease (n=475). In each study group, the family history of SCD among the first-degree relatives was determined and verified from death certificates. The prevalence of SCD in ≥1 first-degree relative was significantly higher in victims of ischemic (34.2%) than nonischemic SCD (13.4%; P<0.001) or controls (17.6%; P<0.001). The history of SCD in first-degree relatives did not differ from controls in nonischemic SCD victims (P=0.155). In a subgroup analysis of victims of ischemic SCD, the prevalence of family history of SCD in first-degree relatives did not differ between those with or without a prior infarct scar at autopsy (33.1% versus 29.9%, respectively; P=0.222). CONCLUSIONS: Ischemic SCD has a strong familial background both in cases with and without a prior myocardial infarction. The family history of SCD is not significantly increased in victims of nonischemic SCD, suggesting a larger role of sporadic occurrence than inherited traits as the cause of nonischemic SCD.

Association of early repolarization and sudden cardiac death during an acute coronary event.

BACKGROUND: Electrocardiographic early repolarization (ER) pattern has been previously associated with arrhythmic mortality and with an increased risk of ventricular fibrillation. We hypothesized that there is an association between ER and sudden cardiac death (SCD) during an acute coronary event. METHODS AND RESULTS: The present study included 432 consecutive victims of SCD because of acute coronary event and 532 survivors of such an event, in whom 12-lead ECGs recorded before and unrelated to the event could be evaluated. SCDs were verified by medicolegal autopsy to be because of acute coronary event. ER was defined as an elevation of the QRS-ST junction in at least 2 inferior or lateral leads, manifested as QRS notching or slurring. The prevalence of ER pattern ≥0.1 mV was more common in cases (62/432; 14.4%) than controls (42/532; 7.9%) (P=0.001). The victims of SCD were younger, were more commonly men and smokers, had lower body mass index, had elevated heart rate, had prolonged QRS complex, and had lower prevalence of history of prior cardiovascular disease than controls. After adjustments for baseline differences, the odds ratio for J waves without ST-segment elevation in the SCD group was 2.15 (95% CI, 1.20-3.85; P=0.01). CONCLUSIONS: Higher prevalence of ER in a standard 12-lead ECG in victims of SCD than in survivors of an acute coronary event suggests that the presence of ER increases the vulnerability to fatal arrhythmia during acute myocardial ischemia and provides a plausible mechanistic link between this ECG pattern and higher arrhythmic mortality of middle-aged/elderly subjects.

Causes of nonischemic sudden cardiac death in the current era.

BACKGROUND: Previous data have shown that various nonischemic cardiac diseases account for about 20% of sudden cardiac deaths (SCDs) and that dilated and hypertrophic cardiomyopathy (CM) are major causes of nonischemic SCD. OBJECTIVE: The purpose of this study was to define the prevalence and causes of SCD due to nonischemic CM in the current era given the substantial change in the diagnosis and treatment of cardiac diseases and in lifestyle patterns. METHODS: A total of 2661 consecutive victims of SCD from among a population of approximately 470,000 inhabitants in the Province of Oulu, Northern Finland, were included in the study. The causes of deaths were determined from the uniformly required autopsies of SCD victims in Finland, plus available medical records and standardized questionnaires. RESULTS: Nonischemic cause of SCD was found in 579 victims (21.8% of all the SCDs). Mean age (± SD) was 55 (±12) years; 78% were males. After subgrouping the nonischemic SCDs into various categories, SCDs associated most closely with obesity (23.7%), followed by alcoholic CM (19.0%), hypertensive CM (15.5%), and fibrotic CM (13.6%). Fibrotic CM was the most common association with SCD in subjects younger than 40 years (28.3%), whereas alcoholic CM was the most common cause of death in subjects between 40 and 59 years of age (25.8%). CONCLUSION: CM related to obesity, fibrotic CM, and alcoholic CM are commonly associated with nonischemic SCD in the current era. The association of SCD with fibrotic CM is notably frequent among victims younger than 40 years.