Ischemic Sudden Cardiac Death Research Articles

Age-related trends of ischemic sudden cardiac death in women

Age-related trends of ischemic sudden cardiac death in women

Proportion of ischemic and nonischemic sudden cardiac death by age and sex

Abstract Background Among women the incidence of sudden cardiac death (SCD) is significant, but lower than in men. During the last decades the proportion of nonischemic SCD seems to have increased in both sexes. Coronary artery disease (CAD) have changed to be sickness of elderly women rather than middle-aged men as in women the prevalence and incidence of CAD starts to increase after the menopause. Purpose The aim of this study was to illustrate how the amount and the proportions of ischemic and nonischemic SCD vary between women and men in different age groups. Methods The Fingesture study has systematically collected clinical and autopsy data from SCD victims in Northern Finland between 1998 and 2017. The cohort consists of 5,869 SCD victims. Results Approximately one fifth of the SCD victims were women (21.1%; P<0.001). Three out of four SCDs were ischemic (74.8%; P<0.001) and majority of the ischemic SCD victims were men (79.8%; P=0.005). The mean age of female victims was 70.1±13.1 years and 63.5±11.8 years among male victims (P<0.001). Amongst women one SCD out of 15 occurred to the subject under 50 years of age (6.7%; P<0.001) whereas in men one SCD victim out of nine was under 50 years old (11.4%; P<0.001). A nonischemic SCD was observed in 350 women and in 1,127 men (P<0.001). The proportion of nonischemic death was higher among women than in men in every age group from under 30 years of age to subjects of 84 years old studied in five year periods (Figure 1). Only age group of 65-69 years in women and 60-64 years in men were not statistically significant, otherwise all the P-values were ≤0.003. The difference in proportion of ischemic and non-ischemic SCD was the smallest among subjects of 40-49 years of age amongst the proportion of ischemic SCD increased rapidly both in women and in men as the prevalence of non-ischemic SCD started to decrease (Figure 1). Amongst SCD victims aged 40-44 years 47.9% of the deaths of men (P<0.001) and 41.7% of the deaths of women (P<0.001) were ischemic etiology. Among women aged 50-54 years over half of the SCDs were ischemic (53.1%; P<0.001). The gender difference in proportion of ischemic SCD was actually the smallest in age groups 40-49 years and after 70 years of age, and its largest in the middle in favor of men. (Figure 1). After the age of 70 years the total amount of SCDs started to plateau in men and decrease in the amount of SCDs was seen in men after the age of 75 years as in women the plateau phase was not reached until the age of 80 years (Figure 2). Conclusion Minority of the SCDs occur under the age of 50 years, especially among women. The proportion of nonischemic SCD was higher in women than in men despite the age. However, already in pre- and perimenopausal age the proportion of ischemic SCD in women was remarkable and the amount of ischemic SCD increased until the age of 80 years emphasizing the need of early primary and secondary prevention of CAD also in women not only in men.Figure 1.Figure 2.

Conventional cardiovascular risk factors in young individuals with three-vessel coronary artery disease experiencing sudden cardiac death

Abstract Background Coronary artery disease (CAD) is a major cause of sudden cardiac death (SCD) in young victims under 50 years of age. Despite the young age, highly advanced CAD is a common finding at autopsies. Purpose We aimed to determine the prevalence of conventional cardiovascular risk factors in ischemic SCD victims under the age of 50 years with a three-vessel CAD detected at autopsy. Methods The study population was derived from the Fingesture study, consisting of consecutive victims of SCD in Northern Finland between years 1998-2017 (n=5,869). All victims underwent medico-legal autopsy with histological examinations, and toxicology investigations was performed if necessary. Pre-mortem clinical history was obtained from available medical records and medication, questionnaires to closest family members and police reports about the conditions of the death. Results In the Fingesture study, a total of 266 SCDs caused by CAD were observed in victims under 50 years of age. Three-vessel disease was detected in 118 victims (44%). The victims with three-vessel disease had more commonly a history of diabetes (26% vs. 14%, p=0.017) compared with victims with fewer major coronary arteries affected. No statistically significant difference was detected in the prevalence of known dyslipidemia (16% vs. 9%, p=0.134), hypertension (29% vs. 19%, p=0.103), male gender (88% vs. 91%, p=0.552), family history of SCD (33% vs. 36%, p=0.841), smoking (81% vs. 72%, p=0.371), or mean age (45 years vs. 44 years, p=0.120). Conclusions The history of diabetes was the only conventional risk factor associated with three-vessel disease in young individuals who experienced SCD determined to be caused by CAD. Along with previous studies, these results highlight the role of diabetes in the development of CAD and adverse outcomes in young people.

Abstract 12857: Electrocardiographic Findings in Women With Ischemic Sudden Cardiac Death and Anatomic Left Ventricular Hypertrophy

Background: Sudden cardiac death (SCD) is a major mode of death worldwide. Previous SCD studies have shown that left ventricular hypertrophy (LVH) is a risk factor for SCD, especially in the presence of myocardial scarring or ischemia. Due to the lower incidence, women are often underrepresented in SCD studies and therefore, most recognized SCD risk factors are biased towards men. Aim: The aim of this study was to investigate sex-specific ECG findings in subjects with ischemic SCD and LVH. Methods: The study population was derived from the FinGesture study, which has collected all SCD cases from Northern Finland 1998-2017. All SCD cases underwent medicolegal autopsy to determine the cause of death. In the present study, we selected SCD cases with coronary artery disease (CAD) and anatomic LVH at autopsy, of whom antemortem electrocardiogram (ECG) was available for 483 subjects (24.4 % women; 75.6 % men). Antemortem recorded ECGs were obtained from medical records and independently analyzed by two investigators. Results: The prevalence of pathological Q-waves (11.9 % vs. 22.1 %, p = 0.016) and fragmented QRS (fQRS) (43.9 % vs. 56.4 %, p = 0.033) was lower in women compared to men. In addition, women were less likely to have prolonged QTc duration (17.8 % in women vs. 32.3 % in men, p = 0.003). The only ECG finding that appeared as more prevalent in women with anatomic LVH was ECG-LVH by Cornell’s criteria (26.4 % vs. 12.4 %, p = 0.002). The prevalence of having abnormal ECG was slightly lower in women (82.2 %) compared to men (89.2 %), p = 0.054. There were no significant differences between sexes when comparing the prevalence of anatomic LVH in subjects with ECG-LVH and ischemic SCD (90.6 % in women vs. 84.9 % in men, p = 0.524). Conclusions: Except for ECG-LVH by Cornell’s criteria, women with ischemic SCD and anatomic LVH were less likely than men to have ECG findings that are often associated with an increased risk of SCD.

Abstract 15206: Prevalence of Myocardial Adipose Tissue in Non-Ischemic and Ischemic Victims of Sudden Cardiac Death

Background: Recent imaging studies have shown that patients with myocardial infarction scar who have ventricular arrhythmias show more adipose tissue around the scar. Similar changes are seen in ARVC. Purpose: The aim of this study was to determine the prevalence of myocardial adipose tissue that co-localize with fibrosis in non-ischemic and ischemic sudden cardiac death (SCD) victims. Methods: The ischemic and non-ischemic subjects were derived from the FinGesture cohort, consisting of autopsy verified consecutive victims of SCD in Northern Finland between years 1998-2017 (n=5,869). Total of 48 non-ischemic, 47 ischemic and 37 accidental/intoxication related death subjects were included in the study. Hematoxylin-eosin-stained slides were digitized and fibrofatty deposits was determined using virtual microscopy software. Results: Myocardial adipose tissue was present in 51% of ischemic cases, 29% of non-ischemic cases and 14% of controls (p< 0.001). In ischemic cases, BMI seems to be associated with the presence of myocardial adipose tissue. Mean BMI was higher in subjects with myocardial adipose tissue versus subjects without (29.2 vs 24.9. p=0.022). Conclusions: The findings suggest that adipose tissue might have an influence in creation of fatal arrhythmias in SCD as it does in scar related ventricular arrhythmias. In addition, it seems that obesity is associated with ischemic scar related adipose tissue metaplasia.

Characteristics of women with ischemic sudden cardiac death

Background Sudden cardiac death (SCD) is a significant mode of death causing 15-20% of all deaths in high-income countries. Coronary artery disease (CAD) is the most common cause of SCD in both sexes, and SCD is often the first manifestation of underlying CAD in women. This case-control study aimed to determine the factors associated with SCD due to CAD in women. Methods The study group consisted of women with CAD-related SCD (N = 888) derived from the Fingesture study conducted in Northern Finland from 1998 to 2017. All SCDs underwent medicolegal autopsy. The control group consisted of women with angiographically verified CAD without SCD occurring during the 5-year-follow-up (N = 610). To compare these groups, we used medical records, autopsy findings, echocardiograms, and electrocardiograms (ECGs). Results Subjects with SCD were older (73.2 ± 11.3 vs. 68.8 ± 8.0, p < 0.001) and were more likely to be smokers or ex-smokers (37.1% vs. 27.6%, p = 0.045) compared to control patients. The proportion of subjects with prior myocardial infarction (MI) was higher in controls (46.9% vs. 41.4% in SCD subjects, p = 0.037), but in contrast, SCD subjects were more likely to have underlying silent MI (25.6% vs. 2.4% in CAD controls, p < 0.001). Left ventricular hypertrophy (LVH) was more common finding in SCD subjects (70.9% vs. 55.1% in controls, p < 0.001). Various electrocardiographic abnormalities were more common in subjects with SCD, including higher heart rate, atrial fibrillation, prolonged QTc interval, wide or fragmented QRS complex and early repolarization. The prevalence of Q waves and T inversions did not differ between the groups. Conclusions Underlying LVH and previous MI with myocardial scarring are common and often undiagnosed in women with CAD-related SCD. These results suggest that untreated CAD with concomitant myocardial disease is an important factor in SCD in women.

PO-03-230 LEFT VENTRICULAR FUNCTION IN SUDDEN CARDIAC DEATH DUE TO ISCHEMIC AND NONISCHEMIC HEART DISEASE

Sudden cardiac death (SCD) remains a major public health problem. Severe left ventricular (LV) dysfunction (EF ≤ 35%) increases the risk of SCD and is the most important indication for prophylactic implantable cardioverter defibrillator (ICD). Previous studies have shown that subjects with EF ≤ 35% represent a minority of all SCD cases. However, it has been unclear whether ischemic and nonischemic cardiac diseases present with different LVEF prior to SCD. We sought to evaluate the spectrum of LVEF among SCD victims with ischemic and nonischemic etiologies. Our study population is drawn from the Fingesture study, which has prospectively collected autopsy and clinical data from consecutive SCD victims from Northern Finland between 1998 and 2017. The cause of death was verified to be of cardiac origin in a medicolegal autopsy in all cases. Cases with ischemic SCD had evidence of coronary artery disease and ischemic cardiomyopathy at autopsy. Electronic health records were examined to identify subjects who underwent evaluation for LV function before SCD. LV function was categorized by quantitative assessment of LVEF as normal (EF ≥ 50%), reduced (50% > EF > 35%), and severely reduced (EF ≤ 35%). In all cases, echocardiography was unrelated to the SCD event. Left ventricular assessment was available in 717 SCD victims. The majority of subjects (n=449, 62.7%) had normal LVEF prior to SCD. The prevalence of reduced LVEF was 21.9%, while severely reduced LVEF was found only in 110 subjects (15.4%). Men were more likely to have LV dysfunction than women (45.9% vs 29.6%; p<0.001). In addition, LVEF was found to be severely reduced more commonly in men compared to women (17.4% vs 10.9% respectively; p<0.001). In SCD victims with ischemic and nonischemic heart disease, LV dysfunction was equally common (37.7% vs 36% respectively; p=0.72). The prevalence of severely reduced LVEF was also similar between ischemic SCD and nonischemic SCD (15.1% vs. 16.3%, respectively; p=0.72). Only one third of SCD cases had ventricular dysfunction and only one in seven had severely reduced LVEF prior to their SCD event, suggesting that only a minority of SCD victims meet the current criteria for primary prevention ICD. We found no difference in the spectrum of LVEF between ischemic and nonischemic heart diseases. However, women were found to have preserved LV function more often than men, highlighting the importance of developing novel SCD risk stratification tools beyond LVEF.

Abstract 10184: The Risk Factors for Ischemic Sudden Cardiac Death in Women

Background: Sudden cardiac death (SCD) is a significant cause of death accounting for 15-20 % of all deaths in Western countries. Coronary artery disease (CAD) is the most common cause of SCD. Even though women are at a lower risk for SCD &amp; CAD, the decline in mortality of these conditions has been slower in women than in men. Previous studies have shown that CAD is more challenging to detect in women, hence SCD is often the first manifestation of underlying CAD among women. The aim of this case-control study was to determine factors associated to SCD due to CAD in women. Methods: The study group consists of women with ischemic SCD (N=888) derived from the Fingesture study conducted in Northern Finland from 1998 to 2017 and all SCDs were autopsy verified. The control group consisted of women with angiographically verified CAD without SCD occurring during the 5-year-follow-up (N=610) from Artemis study. To perform comparison between these groups, we utilized medical records, autopsy findings, echocardiograms and ECGs. Results: Subjects with SCD were older (73.2±11.3 vs. 68.8±8.0 p &lt; 0.001) and were more likely to be smokers or ex-smokers (37.1% vs. 27.6 %, p = 0.045). The proportion of subjects with prior myocardial infarction (MI) was higher in controls (46.9 % vs. 41.4 % in SCD subjects, p = 0.037), but in contrast, SCD subjects were more likely to have underlying silent MI (25.6 % vs. 2.4 % in CAD controls, p &lt; 0.001). Decreased left ventricular ejection fraction (LVEF 35-55 %) was more common finding in SCD subjects than in CAD controls (33.1% vs. 8.7 %, p &lt; 0.001, respectively) as well as LV hypertrophy (70.9 % vs. 55.1 %, p &lt; 0.001, respectively). Various ECG-abnormalities were more common in SCD subjects including higher heart rate, prolonged QTc- and JTc-intervals, wide or fragmented QRS-complex, short PR-interval and early repolarization. The prevalence of Q-waves and T-inversions did not differ between these groups. Conclusions: Underlying CAD and MI are often underdiagnosed in women with ischemic SCD considering the high proportion of silent myocardial infarctions and the number of subjects without prior CAD diagnosis. LV hypertrophy as well as decreased LVEF were more frequent findings in SCD subjects. Several ECG abnormalities were more common among subjects with SCD.

Genetic Variants Associated With Sudden Cardiac Death in Victims With Single Vessel Coronary Artery Disease and Left Ventricular Hypertrophy With or Without Fibrosis

Objective: Cardiac hypertrophy with varying degrees of myocardial fibrosis is commonly associated with coronary artery disease (CAD) related sudden cardiac death (SCD), especially in young victims among whom patterns of coronary artery lesions do not entirely appear to explain the cause of SCD. Our aim was to study the genetic background of hypertrophy, with or without fibrosis, among ischemic SCD victims with single vessel CAD.Methods: The study population was derived from the Fingesture study, consisting of all autopsy-verified SCDs in Northern Finland between the years 1998 and 2017 (n = 5,869). We carried out targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function in 95 ischemic-SCD victims (mean age 63.6 ± 10.3 years; 88.4% males) with single-vessel CAD in the absence of previously diagnosed CAD and cardiac hypertrophy with or without myocardial fibrosis at autopsy.Results: A total of 42 rare variants were detected in 43 subjects (45.3% of the study subjects). Five variants in eight subjects (8.4%) were classified as pathogenic or likely pathogenic. We observed 37 variants of uncertain significance in 39 subjects (40.6%). Variants were detected in myocardial structure protein coding genes, associated with arrhythmogenic right ventricular, dilated, hypertrophic and left ventricular non-compaction cardiomyopathies. Also, variants were detected in ryanodine receptor 2 (RYR2), a gene associated with both cardiomyopathies and catecholaminergic polymorphic ventricular tachycardias.Conclusions: Rare variants associated with cardiomyopathies, in the absence of anatomic evidence of the specific inherited cardiomyopathies, were common findings among CAD-related SCD victims with single vessel disease and myocardial hypertrophy found at autopsies, suggesting that these variants may modulate the risk for fatal arrhythmias and SCD in ischemic disease.

HISTOMORPHOLOGICAL SPECTRUM OF VARIOUS CARDIAC CHANGES IN SUDDEN DEATH: AN AUTOPSYSTUDY

INTRODUCTION : Cardiovascular disease (including coronary artery disease, stroke and peripheral vascular disease) is no.1 cause of worldwide mortality, with about 80% of burden occurring in developing countries. Sudden cardiac death is dened as unexpected death from cardiac causes either without symptoms or within 1-24 hours of onset of symptoms(1). The common cause of sudden cardiac death is ischaemic heart disease. Non ischaemic sudden cardiac death occurs in hypertrophic obstructive cardiomyopathy and in severe left ventricular hypertrophy(2). The purpose of this study will be to determine the causes of sudden death and observe the spectrum of morphological and histopathological changes in heart after sudden death. MATERIALS AND METHODS: This autopsy study was conducted on 121 cases of sudden death over a period extending from January 2019 to August 2020 in autopsy section of Pathology department of BJGMC, Pune. In this autopsy study hearts of patients with a history of sudden death were evaluated for histological and morphological changes. Each heart was grossed adopting the inow outow method and short axis method. Staining solutions used were Solution A: Alum Hematoxylin and Solution B: 1% Eosin Y. OBSERVATIONS : 50 (41.32%) cases out of 121 cases had coronary artery disease along with myocardial infarction of which 43 cases were males and 7 cases were females. No cardiac aetiology was found in 23.96% cases. Coronary artery disease was independently seen in 14.87% cases. Left ventricular concentric hypertrophy was noted in 4.13% cases. Myocardial infarction independently was noted in 3.30%cases, Myocarditis in 2.47% cases, myocarditis with pericarditis in 1.65% cases, HOCM, lipoma, mitral stenosis, pericarditis, septic infarct, secondaries of adenocarcinoma, early vegetation and small vessel disease in 0.82% cases. Calcic aortic stenosis was demonstrated in 1 case. Brown atrophy was demonstrated in 1 case. DISCUSSION : Out of 69 cases of coronary artery disease calcication was commonly seen in 34(49.27%) cases. 47(82.45%) (M-39,l F-8) out of 57 cases of myocardial infarction demonstrated chronic or old infarct. Single vessel involvement was most common in which left anterior descending coronary artery was signicantly involved in 68.75 % cases. Posterior wall was most commonly involved by myocardial infarction which included posterior, posteroseptal, and posterolateral infarcts.

Coronary Artery Disease as the Cause of Sudden Cardiac Death Among Victims < 50 Years of Age

Coronary artery disease (CAD) is the most common cause of sudden cardiac death (SCD). Atherosclerosis increases with age, but also many victims of SCD in young and middle-aged population have CAD at autopsy. The purpose of this study was to determine the characteristics and autopsy findings of SCD due to CAD among victims of SCD under the age of 50. Fingesture is a population-based study consisting of consecutive series of victims of autopsy verified SCD in Northern Finland between the years 1998 to 2017 (n = 5,869). Histological examinations were part of all autopsies and a toxicology investigation was performed if needed. Analyses included information accumulated from death certificates, medical records, autopsy data, standardized questionnaire to the closest family members of the victims of SCD and police reports of the conditions of the death. Overall, 10.4% of all SCDs occurred among victims under the age of 50 years (610 victims). Most common underlying cause of SCD among these younger SCD victims was CAD (43.6%). The prevalence of CAD as the cause of SCD became more common in young SCD victims after the age of 35 years. The mean age of ischemic SCD victims was 44±5 years and most were men (89.5%). Most victims (90.2%) had no clinical diagnosis of CAD, however 33.8% had an autopsy evidence of silent myocardial infarction. SCD occurred during physical activity in 24.1%. Three-vessel disease was detected in 44.4% of the study victims. Cardiac hypertrophy (58.3%) and myocardial fibrosis (82.6%) were also common. At least 1 cardiovascular risk factor was present in 64.7% of SCD victims. In conclusion, most SCDs among victims < 50 years of age are due to CAD.

Association of isolated T inversion and sudden cardiac death – etiology and gender differences

Abstract Background Inferolateral T wave inversion has been associated with increased risk of mortality and sudden cardiac death (SCD) in general population. However, the association between isolated T inversion and SCD is still unclear. Purpose The purpose of this study was to examine whether isolated T inversion associates with SCD, and find out possible gender differences. Methods FinGesture Study has systematically collected clinical data and medico-legal autopsy data from 5,869 consecutive SCD victims (mean age 64.9±12.4 yrs.) in Northern of Finland between years 1998 and 2017. Previously recorded electrocardiograms (ECG) were available and analyzed in 1,101 subjects. The control group consisted of 7,217 subjects representative of Finnish general population (mean age 51.5±12.4 yrs.). T inversion was interpreted isolated if there was at least two T inversions ≥−0.1 mV in at least two contiguous leads, and there were no ECG signs of left ventricular hypertrophy (LVH) defined by Sokolow-Lyon criteria or bunchle brand block (BBB) attached to it. Results In a current study, isolated T inversion was more common finding among SCD victims compared to general population: isolated T inversion in any leads 10.9% vs. 0.9% (SCD vs. general population, p&amp;lt;0.001), laterally 7.7% vs. 0.1% (p&amp;lt;0.001), inferiorly 3.2% vs. 0.5% (p&amp;lt;0.001) and anteriorly 2.9% vs. 0.4% (p&amp;lt;0.001). Particularly, isolated T inversion seemed to assoaciate with ischemic SCD taking into account that 61.5% of the total isolated T inversions were seen in ischemic SCD victims (p=0.018). In addition, 62.1% of the inferior isolated T inversions (p=0.023) and 61.7% of the lateral isolated T inversions (p=0.031) were in ischemic SCD victims versus 37.9% and 38.3% in non-ischemic SCD victims, respectively. The prevalence of isolated T inversion in any lead was also higher among male SCD victims compared to female victims (12.8% vs. 8.2%, p&amp;lt;0.001, respectively). There was no statistically significant difference in the prevalence of LVH and strain changes between the populations. Among bundle branch blocks left BBB was predictably more typical in SCD victims (5.8% vs. 0.5%, p&amp;lt;0.001). Conclusion We noticed an association between isolated T inversion and SCD. The association was most prominent in males and in those with ischemic etiology of SCD. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Finnish Medical Foundation, Finnish Foundation for Cardiovascular Research

P481The genetic background of sudden cardiac deaths caused by single vessel coronary artery disease and myocardial hypertrophy with fibrosis

Abstract Funding Acknowledgements Sigrid Juselius Foundation, Finnish Foundation for Cardiovascular Research, Aarne Koskelo Foundation, The Finnish Medical Foundation Background Coronary artery disease (CAD) is the most common underlying cause of sudden cardiac death (SCD). Cardiac hypertrophy with varying amount of myocardial fibrosis is a common risk factor for CAD related SCD especially in young SCD victims where severity of CAD seems not to entirely explain the cause of SCD. Purpose The aim was to study the genetic background of hypertrophy and fibrosis among young, ischemic SCD victims with single vessel CAD. Methods The study population was derived from the Fingesture study consisting of all autopsy-verified sudden cardiac deaths in Northern Finland between years 1998-2017 (n = 5,869). CAD was determined to be the cause of SCD in 4,392 victims (74.8%). We carried out targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function in 95 ischemic-SCD victims (mean [standard error] age, 63.6 [1.06] years; 88.4% males) with single-vessel CAD and cardiac hypertrophy in the absence of previously diagnosed CAD, and whose DNA passed the quality control for further analysis. Assessment for pathogenicity of detected variants was based on American College of Medical Genetics consensus guidelines. Results A total of 43 variants were detected in 43 of the study subjects (45.3 %). Five variants in eight subjects (8.4%) were classified as pathogenic or likely pathogenic. We observed 38 variants of uncertain significance in 39 victims (40.6 %). Variants were detected in myocardial structure protein coding genes, associated with arrhythmogenic right ventricular cardiomyopathy (13 variants), dilated cardiomyopathy (16 variants), hypertrophic cardiomyopathy (6 variants) and left ventricular non-compaction cardiomyopathy (3 variants). Five variants were detected in RYR2 associated with both cardiomyopathies and catecholaminergic polymorphic ventricular tachycardias. Seven variants were detected in multiple unrelated subjects. None of the subjects presented characteristic autopsy findings related to cardiomyopathies. Conclusions Variants associated with cardiomyopathies were common findings among CAD related SCD victims with single vessel disease and myocardial hypertrophy found at autopsies, suggesting that these variants may modulate the risk for fatal arrhythmias and sudden death in ischemic disease.

Electrocardiographic associations with myocardial fibrosis among sudden cardiac death victims

ObjectiveA major challenge in reducing the incidence of sudden cardiac death (SCD) is the identification of patients at risk. Myocardial fibrosis has a substantial association with SCD risk but is...

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

ObjectiveTo 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.MethodsThe home coordinates of 2572...

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

ObjectiveTo test a priori hypothesis of an association between season-specific cold spells and sudden cardiac death (SCD).MethodsWe conducted a case–crossover study of 3614 autopsy-verified cases of SCD in the Province...

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

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. 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). 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.

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, β-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.

Postmortem mRNA expression patterns in left ventricular myocardial tissues and their implications for forensic diagnosis of sudden cardiac death.

Sudden cardiac death (SCD), which is primarily caused by lethal heart disorders resulting in structural and arrhythmogenic abnormalities, is one of the prevalent modes of death in most developed countries. Myocardial ischemia, mainly due to coronary artery disease, is the most common type of heart disease leading to SCD. However, postmortem diagnosis of SCD is frequently complicated by obscure histological evidence. Here, we show that certain mRNA species, namely those encoding hemoglobin A1/2 and B (Hba1/2 and Hbb, respectively) as well as pyruvate dehydrogenase kinase 4 (Pdk4), exhibit distinct postmortem expression patterns in the left ventricular free wall of SCD subjects when compared with their expression patterns in the corresponding tissues from control subjects with non-cardiac causes of death. Hba1/2 and Hbb mRNA expression levels were higher in ischemic SCD cases with acute myocardial infarction or ischemic heart disease without recent infarction, and even in cardiac death subjects without apparent pathological signs of heart injuries, than control subjects. By contrast, Pdk4 mRNA was expressed at lower levels in SCD subjects. In conclusion, we found that altered myocardial Hba1/2, Hbb, and Pdk4 mRNA expression patterns can be employed as molecular signatures of fatal cardiac dysfunction to forensically implicate SCD as the primary cause of death.

Comparison of Family History of Sudden Cardiac Death in Nonischemic and Ischemic Heart Disease

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. 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). 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.