Sudden Cardiac Death in Women.

BACKGROUND: Despite recent progress in profiling of risk for sudden cardiac death (SCD) and prevention and intervention of cardiac diseases, SCD remains a major cause of death. Among women, the incidence of SCD is significant, but lower than in men, particularly in the premenopausal and early postmenopausal years. Possibly, as a consequence of the difference in population burden, the mechanisms and risk markers of SCD are not as well defined for women. The aim of this study was to determine the autopsy findings and causes of death among women in a large SCD population. Additionally, we sought to classify prior ECG characteristics in male and female subjects with SCD. METHODS: The Fingesture study has systematically collected clinical and autopsy data from subjects with SCD in Northern Finland between 1998 and 2017. The cohort consists of 5869 subjects with SCD. Previously recorded ECGs were available and analyzed in 1101 subjects (18.8% of total population; and in 25.3% of women). RESULTS: Female subjects with SCD were significantly older than men: 70.1±13.1 years versus 63.5±11.8 years (mean ± standard deviation, P<0.001). The most frequently identified cause of death was ischemic heart disease in both sexes: 71.7% among women versus 75.7% among men, P=0.005. In contrast, women were more likely to have nonischemic cause of SCD than men (28.3% versus 24.3%, P=0.005). The prevalence of primary myocardial fibrosis was higher among women (5.2%, n=64) than in men (2.6%, n=120; P<0.001). Female subjects with SCD were more likely to have normal prior ECG tracings (22.2% versus 15.3% in men, P<0.001). A normal ECG was even more common among nonischemic female subjects with SCD (27.8% versus 16.2% in men, P=0.009). However, ECG markers of left ventricular hypertrophy, with or without repolarization abnormalities, were more common among women (8.2%; 17.9%) than in men (4.9%; 10.6%, P=0.036; P<0.001, respectively). CONCLUSIONS: Women were considerably older at the time of SCD and more commonly had nonischemic causes. Women were also more likely to have a prior normal ECG than men, but an increased marker for SCD risk based on ECG criteria for left ventricular hypertrophy with repolarization abnormalities was more commonly observed in women.

Primary Myocardial Fibrosis as an Alternative Phenotype Pathway of Inherited Cardiac Structural Disorders.

BACKGROUND: Myocardial fibrosis is a common postmortem finding among young individuals with sudden cardiac death. Because there is no known single cause, we tested the hypothesis that some cases of myocardial fibrosis in the absence of identifiable causes (primary myocardial fibrosis [PMF]) are associated with genetic variants. METHODS: Tissue was obtained at autopsy from 4031 consecutive individuals with sudden cardiac death in Northern Finland, among whom PMF was the only structural finding in 145 subjects with sudden cardiac death. We performed targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function when autopsies did not identify a secondary basis for myocardial fibrosis. All variants with an effect on protein and with a minor allele frequency <0.01 were classified as pathogenic or variants of uncertain significance on the basis of American College of Medical Genetics consensus guidelines. RESULTS: Among the 96 specimens with DNA passing quality control (66%), postmortem genetic tests identified 24 variants of known or uncertain significance in 26 subjects (27%). Ten were pathogenic/likely pathogenic variants in 10 subjects (10%), and 14 were variants of uncertain significance in 11 genes among 16 subjects (17%). Five variants were in genes associated with arrhythmogenic right ventricular cardiomyopathy, 6 in hypertrophic cardiomyopathy-associated genes, and 11 in dilated cardiomyopathy-associated genes; 2 were not associated with these disorders. Four unique variants of uncertain significance cosegregated among multiple unrelated subjects with PMF. No pathogenic/likely pathogenic variants were detected in ion channel-encoding genes. CONCLUSIONS: A large proportion of subjects with PMF at autopsy had variants in genes associated with arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy without autopsy findings of those diseases, suggesting that PMF can be an alternative phenotypic expression of structural disease-associated genetic variants or that risk-associated fibrosis was expressing before the primary disease. These findings have clinical implications for postmortem genetic testing and family risk profiling.

Fragmented QRS complex as a predictor of exercise-related sudden cardiac death.

INTRODUCTION: Little is known about the association between electrocardiographic abnormalities and exercise-related sudden cardiac death. Therefore, our aim was to identify possible electrocardiographic findings related to exercise-induced sudden cardiac death. METHODS AND RESULTS: The FinGesture study includes 3,989 consecutive sudden cardiac deaths in northern Finland between 1998 and 2012, out of whom a total of 647 subjects had a previously recorded electrocardiography acquired from the archives of Oulu University Hospital. In 276 of these cases the death was witnessed, and the activity at the time of death was either rest or physical exercise (PE); in 40 (14%) cases sudden cardiac death was exercise-related and in 236 (86%) cases death took place at rest. Fragmented QRS complex in at least two consecutive leads within anterior leads (V1-V3) was more common in the exercise-group compared to rest-group (17 of 40, 43% vs. 51 of 236, 22%, P  =  0.005). Pathologic Q wave in anterior leads was more common in the PE group (9 of 40, 23% vs. 26 of 236, 11%; P  =  0.044). Median QRS duration was prolonged in the exercise-group compared to the rest-group (100 milliseconds vs. 94 milliseconds, P = 0.047). QTc interval, the prevalence of inverted T-waves, or other electrocardiographic abnormalities did not differ significantly between the two groups. CONCLUSIONS: As a conclusion, fragmented QRS complex in the anterior leads is associated with an increased risk of sudden cardiac death during PE.

Inferolateral early repolarization among non-ischaemic sudden cardiac death victims.

Aim: Inferolateral early repolarization (ER) has been associated with an increased risk of sudden cardiac death (SCD). However, this association is thought to be mainly due to ischaemic SCD. The association of ER and non-ischaemic SCD has not been studied. The aim was to evaluate whether inferolateral ER is associated with non-ischaemic SCD. Methods and results: Study population consists of 275 consecutive victims of non-ischaemic SCD with 12-lead ECG and control group of general population cohort with 10 864 subjects. Sudden cardiac deaths were verified as non-ischaemic by medicolegal autopsy. Hypertensive cardiomyopathy (HTCMP) (25%), alcohol related dilated cardiomyopathy (ACMP) (24%), obesity associated cardiomyopathy (OCMP) (23%), and idiopathic myocardial fibrosis (IMF) (15%) were the most common causes of non-ischaemic SCD. A structurally normal heart was seen in only 1.5%. The prevalence of inferolateral ER was 20.7% among patients with non-ischaemic SCD compared to 5.3% in the general population (P < 0.001). The ECG pattern was accompanied with a horizontal/descending ST segment in 95% of the cases. The prevalence of inferolateral ER was slightly higher in the HTCMP group (26%) and the ACMP group (24%) than in the IMF group (20%) and the OCMP group (13%). The history of previously diagnosed cardiac diseases was not higher among subjects with ER (55%) than those without (59%, P = 0.59). Conclusion: The prevalence of inferolateral ER among non-ischaemic SCD victims is high. Almost all ER patterns are accompanied with the malignant horizontal/descending ST segment morphology suggesting that inferolateral ER is not only associated with an ischaemic SCD but also a non-ischaemic SCD.

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.

Victims of lethal hypothermia have decreased levels of thrombomodulin in myocardium and urine.

Severe cold stress has been shown to cause changes in the expression and secretion of thrombomodulin (TM), an endothelial protein regulating haemostasis and inflammation. To further evaluate TM as a cold stress indicator, relative TM mRNA and TM protein levels in the myocardium and the concentrations of TM in serum and urine were analysed in different causes of death (hypothermia main cause, n = 80; hypothermia contributory cause, n = 26; cardiovascular disease (CVD) main cause, n = 94; trauma main cause, n = 45; other main cause, n = 25). Urinary catecholamine concentrations and myocardial heat shock factor 1 (HSF1) transcript levels were also studied. The TM mRNA and the TM protein levels in myocardium and urine were significantly lower in hypothermia deaths than those in the controls. Post-mortem interval did not correlate with urinary TM concentration. The sensitivity and specificity of urinary TM assay to detect hypothermia deaths were 70.8 and 70.3 %, respectively. Catecholamine concentrations in urine correlated significantly with TM concentration in urine and TM mRNA levels in all groups excluding CVD deaths. There were no differences in the HSF1 transcript levels and no correlation to TM levels. These findings provide further evidence that cold stress and hypothermia affect TM expression and secretion and that they are possibly linked to catecholamine action. Thus, measuring post-mortem TM levels may provide additional support to diagnosing hypothermia in medico-legal examination. The results may also provide additional knowledge for the treatment of hypothermic patients and the use of hypothermia for medical purposes.

Changes in cardiac thrombomodulin and heat shock transcription factor 1 expression and peripheral thrombomodulin and catecholamines during hypothermia in rats.

Effects of hypothermia and rewarming on thrombomodulin, catecholamines and heat shock transcription factor 1 (HSF1) were studied in rats. The aims of this study were to clarify whether cold stress, under anesthesia, is sufficient to change levels of thrombomodulin in healthy endothelium and in the circulation and whether adrenaline, noradrenaline and HSF1 could act as regulators in the process. Rats were divided into control, mild hypothermia (2 and 4.5 hours at + 21 °C; MH1, MH2), severe hypothermia (2 and 4.5 h at + 10 °C; SH1, SH2) and two rewarming groups (2 h at + 10 °C followed by 2 h at + 21 °C or 3 h at + 28 °C; SHW1, SHW2) (n = 15/group, except n = 6 in MH1). Fentanyl-fluanisone-midazolam was used as anesthetic. Low levels of thrombomodulin in plasma and myocardial arterioles/venules measured by ELISA and immunohistochemistry were associated with significant increase of thrombomodulin transcript level in SH1 rats analyzed by quantitative PCR. Plasma adrenaline correlated negatively with the relative amount of myocardial thrombomodulin transcripts and positively with plasma thrombomodulin in SH. Transcript levels of thrombomodulin and HSF1 correlated strongly (r = 0.83; p < 0.001) in SH. Plasma/urine ratio of thrombomodulin and plasma adrenaline (r = 0.87; p = 0.005) or noradrenaline (r = 0.78; p = 0.023) were strongly correlated in SHW1 rats. Hence, cellular and soluble levels of thrombomodulin are modified by cold stress in healthy rats, possibly via catecholamines and HSF1.

Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals.

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10(-10)). The risk allele, while ancestral, has a frequency of ~1.4%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95% CI 1.57-2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006).

Mortality from traumatic brain injury after reduction of alcohol prices: a population-based study from northern Finland.

AIMS: Traumatic brain injury (TBI) is the leading cause of death after trauma, and alcohol is a major risk factor for TBI. In Finland, alcohol taxes were cut by one third in 2004. This resulted in a marked increase of alcohol consumption. We investigated whether increased alcohol consumption influenced the number of fatal TBIs. METHODS: All (n = 318) fatal TBIs were identified from medico-legal reports during the years 1999, 2006 and 2007 among the residents of Oulu Province, Finland. Mortality rates were compared before and after alcohol price reduction. Alcohol involvement based on the presence of alcohol in body fluids and/or alcohol-related diseases recorded in death certificates. RESULTS: The proportion of alcohol-related TBI deaths of all TBI deaths increased (from 1999 to 2007) among middle-aged people from 48% to 91% (p = 0.001) but decreased among young adults from 74% to 41% (p = 0.015). The overall TBI mortality rate did not increase. Fatal TBIs due to falls were significantly more commonly alcohol-related in 2006-2007 than in 1999 (p = 0.003) and accumulated among middle-aged people. CONCLUSIONS: After the price reduction, alcohol-related fatal TBIs increased most among middle-aged people, and they were frequently caused by fall accidents. The reduction of alcohol prices did not increase the total number of fatal TBIs. Middle-aged and elderly subjects with TBI should be routinely asked for alcohol drinking and those with hazardous drinking habits should be guided for alcohol intervention.

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.

Stress-specific responses of p21 expression: implication of transcript variant p21 alt-a in long-term hypoxia.

p21 (CDKN1A, Cip1, Waf1) is a cyclin-dependent kinase inhibitor capable of causing cell cycle arrest or promoting cell cycle transit as well as acting as a regulator of apoptosis. In this study, we analyzed the effects of various antemortem conditions on p21 protein level and expression profiles of known p21 transcript variants in human heart tissue. The selected death cause groups were: non-cardiac, hypothermia, acute ischemia, and chronic hypoxia. Immunohistochemical staining of p21 in cardiac myocytes could be observed only in hypothermia death cases, in which the mRNA expression of the most abundant variant, p21V1, also exceeded that in other death cause groups. Cytoplasmic localization of p21 protein in vascular smooth muscle cells together with substantially increased expression of cardioprotective Pim-1 especially in chronic hypoxia, but in acute ischemia and hypothermia as well, indicate change of p21 function from cell cycle arrest to promotion of proliferation and cell survival in these cases. In chronic hypoxia deaths the expression of variant p21 alt-a was highly pronounced whereas the expression of variant p21B was low. In chronic hypoxia deaths the expression of p53 was substantially higher compared to the other groups, being a potential regulator of p21 alt-a expression. In acute ischemia deaths increased expression of variant p21B, suggested to be proapoptotic in several cell lines, was observed. Our results suggest a role for variant p21 alt-a in hypoxia and for variant p21B in acute myocardial ischemia. The known cardioprotective aspect of hypothermia might come from an increased p21 protein level.

Extreme obesity and associated cardiovascular disease verified at autopsy: time trends over 3 decades.

Extreme obesity is a strong predictor of premature death, but the prevalence of cardiovascular disease in morbidly obese populations is largely unknown. The aim of the present study was to find out whether there has been an increase in extreme obesity with body mass index 40.0 kg/m(2) or greater in medicolegal autopsy material in a known geographical area in Finland during a period of 3 decades and to examine the prevalence and time trends of associated cardiovascular disease in this obesity category. Autopsy reports of 235 cases examined in 1975 to 2006 were analyzed. The number of extremely obese individuals increased from 0.6% of the yearly amount of autopsies in the 1970s and 1980s to 2.8% and 2.5% in 2005 and 2006, respectively. The most frequent cause of death was cardiomyopathy or cardiomegaly (28.9%), followed by coronary heart disease (24.3%). Either coronary arteries were lesion-free, or only fatty streaks had been observed in 46.8% of the women and in 43.1% of the men. No significant changes in the average body mass index or severity of coronary atherosclerosis were observed. Younger individuals younger than 40 years began to appear more often after 1995. An increased trend of extreme obesity in a region where autopsy frequency is high may refer to a general increase of this obesity category. A large number of extremely obese people are resistant to coronary atherosclerosis, but cardiac hypertrophy may be accompanied by several mechanisms leading to sudden death even among the youngest extremely obese individuals.

Gln27Glu variant of Beta2-adrenoceptor gene affects male type fat accumulation in women.

BACKGROUND: The beta2-adrenergic receptor (BAR2) is the main lipolytic receptor in white human adipose tissue. There is a functional glutamine 27 glutamic acid (Gln27Glu, rs 1042714) polymorphism in its gene, which has been variably associated with body mass index. This gene variant may be associated with male-type adiposity in women and thus increased cardiovascular risk. We investigated whether the BAR2 Gln27Glu polymorphism is associated with visceral fat and coronary intima thickness in women. METHODS: The amount of mesenteric and omental fat was directly measured and anthropometric measurements were done from 112 forensic autopsy cases of women aged 15 to 49 years. The thickness of the coronary intima, which reflects the severity of atherosclerosis, was measured by computerized image analysis. The BAR2 Gln27Glu polymorphism was determined by polymerase chain reaction. RESULTS: We found that the amount of visceral fat was significantly higher in women with the Glu allele (689 +/- 555 g) compared to Gln/Gln homozygotes (481 +/- 392 g, P = 0.023). The waist-hip ratio also tended to be higher in women with the Glu allele compared to Gln/Gln homozygotes (p = 0.050). There were no statistically significant differences between the genotype groups in BMI or the thickness of coronary intima. CONCLUSION: The Glu allele of the BAR2 gene may be a risk factor for visceral fat accumulation in young to middle-aged women. However, this polymorphism was not associated with preclinical atherosclerosis.

Characteristics and Prognosis of Exercise-Related Sudden Cardiac Arrest.

Introduction: The previous studies about exercise-related sudden cardiac arrest (SCA) have mainly focused on sports activity, but information related to SCA in other forms of physical exercise is lacking. Our aim was to identify characteristics and prognosis of SCA victims in the general population who suffered SCA during physical activity. Methods and results: We collected retrospectively all cases of attempted resuscitation in Oulu University Hospital Area between 2007 and 2012. A total of 300 cases were of cardiac origin. We only included witnessed cases with Emergency Medical System arrival time ≤15 min. Cases of low-intensity physical activity were excluded. A total of 47 SCAs occurred during moderate-to-vigorous physical activity (exercise-group) and 43 cases took place at rest (rest-group). The subjects in exercise-group were younger compared to the rest-group (60 ± 14 years vs. 67 ± 14 years, p = 0.016). The initial rhythm recorded was more often ventricular fibrillation (VF) in exercise-group compared to the rest-group (77 vs. 50%, p = 0.010). Pulseless electrical activity (PEA) was rare in exercise-group compared to the rest -group (2.1 vs. 14%, p = 0.033, respectively). Bystander cardiopulmonary resuscitation (CPR) was more often performed when SCA took place during physical exercise (47 vs. 23 %, p = 0.020). Survival rates to hospital discharge were higher in the exercise-group compared to the rest -group (49 vs. 9.3%, p < 0.0001). Conclusions: SCA occurring during physical activity is more frequently a result of VF and bystander CPR is more often performed. There is also a notably better survival rate to hospital discharge.

Coronary stenosis as a modifier of the effect of cold spells on the risk of sudden cardiac death: a case-crossover study in Finland.

OBJECTIVE: To test the a priori hypothesis that the association between cold spells and ischaemic sudden cardiac death (SCD) is modified by the severity of coronary stenosis. METHODS: 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 weather data. Cold spell was statistically defined for each home address as unusually cold weather pertinent to the location and time of year. We estimated the occurrence of cold spells during the hazard period (7 days preceding death) and reference periods (the same calendar days over 51 years) in a case-crossover setting applying conditional logistic regression, controlling for temporal trends and stratifying by severity of coronary stenosis. RESULTS: The association between cold spells and ischaemic SCD was stronger among patients with 75%-95% stenosis (OR 2.03; 95% CI 1.31 to 3.17), and weaker to non-existent among patients with <75% stenosis (OR 0.97; 95% CI 0.37 to 2.55) or coronary total occlusion (100% stenosis) (OR 1.01; 95% CI 0.52 to 1.96). Lack of calcium-channel blockers and statin therapy seemed to accentuate the role of stenosis during cold spells. CONCLUSIONS: We provide evidence that the association between cold spells and ischaemic SCD is modified by the severity of coronary stenosis. The findings suggest that disturbances in coronary circulation play part in the pathogenesis of SCD during cold weather.

Association of initial recorded rhythm and underlying cardiac disease in sudden cardiac arrest.

BACKGROUND: Asystole (ASY) and pulseless electrical activity (PEA) are increasing and ventricular fibrillation (VF) or ventricular tachycardia (VT) declining as presenting rhythms of sudden cardiac arrest (SCA). Since there is limited information on possible differences in the etiology of underlying structural heart disease, we analyzed the clinical and/or autopsy findings of victims with ASY, PEA or VT/VF. METHODS: All SCA cases with recorded ASY, PEA or VT/VF occurring after onset of witnessed collapse were analyzed by the emergency personnel between the years 2007-2012 within the Oulu University Hospital area. Underlying structural heart disease was diagnosed by medico-legal autopsy or by clinical investigation (echocardiography, angiography). Of a total number of 659 subjects with a documented rhythm at the time of SCA, 300 were determined to be due to cardiac disease at autopsy or as a result of clinical investigation. Delay was less than 30min from collapse to rhythm recording in 274 subjects (mean age 65±14 yrs; 214 males, 78.1%). RESULTS: The presenting rhythm was ASY in 87 (31.8%) PEA in 38 (13.9%) and VT/VF in 149 subjects (54.4%). There was no significant difference in the delay from the onset of collapse to the rhythm recording between ASY (11±8min) and VT/VF (9±6min, p=0.06) or PEA (6±8min) and VT/VF (p=0.334). The majority of SCA subjects had an ischemic cause for the event (n=216, 78.8%). Non-ischemic cause for SCA was associated with non-shockable rhythm (Non-ischemic: ASY 46.6% PEA 17.2% VT/VF 36.2% v. Ischemic: ASY 27.8% PEA 13.0% VT/VF 59.3%) even when adjusted for gender, age and delay from collapse to rhythm recording (ASY/PEA v. VT/VF, OR 3.2 95%CI: 1.67-6.50, p=0.001). CONCLUSIONS: Asystole and PEA are a more common presenting rhythm than VT/VF at the time of SCA in non-ischemic cardiac disease. The decreasing trend of ischemic heart disease as a cause of SCA may partly explain the increasing trend of ASY/PEA.

Family history and the risk of sudden cardiac death as a manifestation of an acute coronary event.

BACKGROUND: Observational studies have suggested that a parental history of sudden death increases one's risk of dying suddenly. This study tested the hypothesis that a family history of sudden cardiac death (SCD) is a risk factor for SCD caused by an acute coronary event. METHODS AND RESULTS: A retrospective case-control study included (1) consecutive victims of SCD (n=138) whose deaths were verified to be due to an acute coronary event without a history of prior myocardial infarction at medicolegal autopsy, (2) consecutive patients surviving an acute myocardial infarction (AMI; n=254), and (3) healthy control subjects (n=470). Family history of AMI and SCD among the first-degree relatives was ascertained in each study group. The incidence of SCD in the 1223 first-degree relatives of SCD victims was higher (5.2%) than that in the 2326 relatives of AMI survivors (3.3%; odds ration [OR] 1.6, 95% confidence interval [CI] 1.2 to 2.2, P<0.01) or the 3748 relatives of controls (OR 2.2; 95% CI 1.6 to 3.0, P<0.001). The history of SCD in 2 or more first-degree relatives was also higher (10.9%) among SCD victims than among AMI survivors (3.5%; OR 3.3, 95% CI 1.4 to 7.8, P<0.01) or controls (1.1%; OR 11.3, 95% CI 4.0 to 31.8, P<0.001). The family history of AMI did not differ between the SCD and AMI groups. Male gender and current smoking were the only coronary risk factors that were more prevalent among SCD victims than among AMI survivors (P<0.001 for both). CONCLUSIONS: Subjects with a family history of SCD have an increased risk of dying suddenly during an acute coronary event.

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.