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

2022 ◽  
Vol 8 ◽  
Author(s):  
Juha H. Vähätalo ◽  
Lauri T. A. Holmström ◽  
Katri Pylkäs ◽  
Sini Skarp ◽  
Katja Porvari ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Sudden Cardiac Death ◽  
Cardiac Hypertrophy ◽  
Cardiac Death ◽  
Rare Variants ◽  
Left Ventricular ◽  
Single Vessel ◽  
Myocardial Structure ◽  
Artery Disease

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.

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

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
J H Vahatalo ◽  
L T A Holmstrom ◽  
K Pylkas ◽  
K Porvari ◽  
L Pakanen ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiac Hypertrophy ◽  
Genetic Background ◽  
Myocardial Hypertrophy ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Single Vessel ◽  
Myocardial Structure ◽  
Artery Disease

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.

scholarly journals Biomarkers as predictors of sudden cardiac death in coronary artery disease patients with preserved left ventricular function (ARTEMIS study)

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0203363 ◽  
Author(s):  
E. Samuli Lepojärvi ◽  
Heikki V. Huikuri ◽  
Olli-Pekka Piira ◽  
Antti M. Kiviniemi ◽  
Johanna A. Miettinen ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Sudden Cardiac Death ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Artery Disease

scholarly journals Obesity and sudden cardiac death in the young: Clinical and pathological insights from a large national registry

2018 ◽  
Vol 25 (4) ◽  
pp. 395-401 ◽  
Author(s):  
Gherardo Finocchiaro ◽  
Michael Papadakis ◽  
Harshil Dhutia ◽  
Della Cole ◽  
Elijah R Behr ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Sudden Cardiac Death ◽  
Left Ventricular Hypertrophy ◽  
Cardiac Death ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Arrhythmic Death ◽  
Sudden Arrhythmic Death Syndrome ◽  
Artery Disease

Aims Obesity is an increasing public health problem and a risk factor for cardiovascular diseases. The aim of the study was to determine the main features and aetiologies in a large cohort of sudden cardiac deaths that occurred in obese subjects. Methods Between 1994 and 2014, 3684 consecutive cases of unexpected sudden cardiac death were referred to our cardiac pathology centre. This study was confined to young individuals (age ≤ 35 years) for whom information about body mass index was available and consisted of 1033 cases. Results Two-hundred and twelve individuals (20%) were obese. In obese sudden cardiac death victims the main post-mortem findings were: normal heart (sudden arrhythmic death syndrome) ( n = 108; 50%), unexplained left ventricular hypertrophy ( n = 25; 12%) and critical coronary artery disease ( n = 25; 12%). Less common were hypertrophic cardiomyopathy ( n = 4; 2%) and arrhythmogenic right ventricular cardiomyopathy ( n = 4;2%). When compared with non-obese sudden cardiac death victims, sudden arrhythmic death syndrome was less common (50% vs. 60%, P < 0.01), whereas left ventricular hypertrophy and critical coronary artery disease were more frequent (12% vs. 2%, P < 0.001 and 12% vs. 3%, P < 0.001, respectively). The prevalence of critical and non-critical coronary artery disease was significantly higher in obese individuals (23% vs. 10% in non-obese individuals, P < 0.001). Conclusions Various conditions underlie sudden cardiac death in obesity, with a prevalence of sudden arrhythmic death syndrome, left ventricular hypertrophy and coronary artery disease. The degree of left ventricular hypertrophy measured by heart weight is excessive even after correction for body size. Almost one in four young obese sudden death patients show some degree of coronary artery disease, underscoring the need for primary prevention in this particular subgroup.

P5647Temporal variability of T-wave morphology and risk of sudden cardiac death in patients with coronary artery disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J T Rahola ◽  
A M Kiviniemi ◽  
O H Ukkola ◽  
M P Tulppo ◽  
M J Junttila ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Sudden Cardiac Death ◽  
Spatial Heterogeneity ◽  
Temporal Variability ◽  
Cardiac Death ◽  
T Wave ◽  
Clinical Risk ◽  
Wave Morphology ◽  
Artery Disease

Abstract Background The possible relationship between temporal variability of electrocardiographic spatial heterogeneity of repolarisation and the risk of sudden cardiac death (SCD) in patients with coronary artery disease (CAD) is not completely understood. Purpose To investigate the prognostic value of temporal variability of T-wave spatial heterogeneity in SCD in patients with CAD. Methods The Innovation to reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study population consisted of 1,946 patients with angiographically verified CAD. T-wave morphology dispersion (TMD), which estimates the average angle between all reconstruction vector pairs in T-wave loop based on leads I-II and V2-V6, was analysed on beat-to-beat basis from 10 minutes period of the baseline electrocardiographic recording in 1,678 study subjects. The temporal variability of TMD was evaluated by standard deviation of TMD (TMD-SD). Results After on average of 7.4±2.0 years of follow-up, a total of 47 of the 1,678 study subjects (2.8%) had experienced SCD or were resuscitated from sudden cardiac arrest (SCA). TMD-SD was significantly higher in patients who had experienced SCD/SCA compared with those who remained alive (3.64±2.57 vs. 2.65±2.54, p<0.01, respectively), but did not differ significantly between the patients who had experienced non-sudden cardiac death (n=40, 2.4%) and those who remained alive (2.98±2.43 vs. 2.67±2.55, p=0.45, respectively) or between the patients who succumbed to non-cardiac death (n=88, 5,2%) and those who stayed alive (2.74±2.44 vs. 2.67±2.55, p=0.81). After adjustments with relevant clinical risk indicators of SCD/SCA, such as left ventricular ejection fraction, diabetes, left bundle branch block and Canadian Cardiac Society class, TMD-SD still predicted SCD/SCA (HR 1.113, 95% CIs 1.028–1.206, p<0.01). The discrimination and reclassification accuracy increased significantly (p=0.02, p=0.033) and the C-index increased from 0.733 to 0.741 when TMD-SD was added to the clinical risk model of SCD/SCA. The Kaplan-Meier survival curves show proportional probabilities of event-free survival for different modes of death for patients classified according to the optimised TMD-SD cut-off point (Figure). Figure 1 Conclusions Temporal variability of electrocardiographic spatial heterogeneity of repolarisation represented by TMD-SD independently predicts long-term risk of SCD/SCA in patients with CAD. Acknowledgement/Funding Sigrid Juselius Foundation and Finnish Foundation for Cardiovascular Research

scholarly journals Sudden Cardiac Death in the Young

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Francis J. Ha ◽  
Hui-Chen Han ◽  
Prashanthan Sanders ◽  
Kim Fendel ◽  
Andrew W. Teh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Body Mass Index ◽  
Coronary Artery ◽  
Sudden Cardiac Death ◽  
Odds Ratio ◽  
Cardiac Death ◽  
Arrhythmic Death ◽  
Sudden Arrhythmic Death Syndrome ◽  
Artery Disease

Background: Sudden cardiac death (SCD) in the young is devastating. Contemporary incidence remains unclear with few recent nationwide studies and limited data addressing risk factors for causes. We aimed to determine incidence, trends, causes, and risk factors for SCD in the young. Methods and Results: The National Coronial Information System registry was reviewed for SCD in people aged 1 to 35 years from 2000 to 2016 in Australia. Subjects were identified by the International Classification of Diseases , Tenth Revision code relating to circulatory system diseases (I00–I99) from coronial reports. Baseline demographics, circumstances, and cause of SCD were obtained from coronial and police reports, alongside autopsy and toxicology analyses where available. During the study period, 2006 cases were identified (median age, 28±7 years; men, 75%; mean body mass index, 29±8 kg/m 2 ). Annual incidence ranged from 0.91 to 1.48 per 100 000 age-specific person-years, which was the lowest in 2013 to 2015 compared with previous 3-year intervals on Poisson regression model ( P =0.001). SCD incidence was higher in nonmetropolitan versus metropolitan areas (0.99 versus 0.53 per 100 000 person-years; P <0.001). The most common cause of SCD was coronary artery disease (40%), followed by sudden arrhythmic death syndrome (14%). Incidence of coronary artery disease–related SCD decreased from 2001–2003 to 2013–2015 ( P <0.001). Proportion of SCD related to sudden arrhythmic death syndrome increased during the study period ( P =0.02) although overall incidence was stable ( P =0.22). Residential remoteness was associated with coronary artery disease–related SCD (odds ratio, 1.44 [95% CI, 1.24–1.67]; P <0.001). For every 1-unit increase, body mass index was associated with increased likelihood of SCD from cardiomegaly (odds ratio, 1.08 [95% CI, 1.05–1.11]; P <0.001) and dilated cardiomyopathy (odds ratio, 1.04 [95% CI, 1.01–1.06]; P =0.005). Conclusions: Incidence of SCD in the young and specifically coronary artery disease–related SCD has declined in recent years. Proportion of SCD related to sudden arrhythmic death syndrome increased over the study period. Geographic remoteness and obesity are risk factors for specific causes of SCD in the young.

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