scholarly journals Genetic contributions to the expression of acquired causes of cardiac hypertrophy in non-ischemic sudden cardiac death victims

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lauri Holmström ◽  
Katri Pylkäs ◽  
Anna Tervasmäki ◽  
Juha Vähätalo ◽  
Katja Porvari ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Cardiac Death ◽  
Heart Weight ◽  
Gene Variants ◽  
Myocardial Disease ◽  
Myocardial Diseases ◽  
Pathogenic Variants ◽  
Uncertain Significance ◽  
Genetic Contributions

AbstractThe contribution of genetic variants to non-ischemic sudden cardiac death (SCD) due to acquired myocardial diseases is unclear. We studied whether SCD victims with hypertension/obesity related hypertrophic myocardial disease harbor potentially disease associated gene variants. The Fingesture study has collected data from 5869 autopsy-verified SCD victims in Northern Finland. Among SCD victims, 740 (13%) had hypertension and/or obesity as the most likely explanation for myocardial disease with hypertrophy and fibrosis. We performed next generation sequencing using a panel of 174 cardiac genes for 151 such victims with the best quality of DNA. We used 48 patients with hypertension and hypertrophic heart as controls. Likely pathogenic variants were identified in 15 SCD victims (10%) and variants of uncertain significance (VUS) were observed in additional 43 SCD victims (28%). In controls, likely pathogenic variants were present in two subjects (4%; p = 0.21) and VUSs in 12 subjects (25%; p = 0.64). Among SCD victims, presence of potentially disease-related variants was associated with lower mean BMI and heart weight. Potentially disease related gene variants are common in non-ischemic SCD but further studies are required to determine specific contribution of rare genetic variants to the extent of acquired myocardial diseases leading to SCD.

P1392Next generation sequencing in lone atrial fibrillation patients

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
I Rudaka ◽  
D Rots ◽  
O Kalejs ◽  
L Gailite
Keyword(s):  
Atrial Fibrillation ◽  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Cardiac Death ◽  
Structural Heart Disease ◽  
Missense Variant ◽  
Lone Atrial Fibrillation ◽  
Excessive Alcohol Consumption ◽  
Pathogenic Variants ◽  
Rare Genetic Variants

Abstract Background. Minor part of atrial fibrillation (AF) patients develops the disease without any well-known risk factors, which is a particular form of the disease, known as a lone AF. Rare genetic variants were described as causative for lone AF. The aim of this study was to investigate occurrence of rare genetic variants in lone AF patients. Material and Methods. We performed Mendeliome sequencing for 21 lone AF patients. Lone AF was defined as AF in individuals younger than 65 years in the absence of cardiovascular or structural heart disease, endocrinologic or pulmonary disease, chronic kidney disease, obesity and excessive alcohol consumption. Data analysis was performed by current laboratory pipeline. We analyzed 453 cardiomyopathy, arrhythmias and sudden cardiac death related genes. Results. In eight out of 21 (38%) lone AF patients rare likely pathogenic variants were found (Table 1.). Seven rare truncating TTN variants and one LMNA missense variant were observed. Four unrelated patients were positive for the same TTN variant c.13696 C > T; p.(Gln4566Ter). The same variant was previously found in ARVC patient in our laboratory. Segregation analysis and phenotyping of relatives is ongoing. Conclusions. Rare genetic variants are common causes of the lone atrial fibrillation. TTN gene variant c.13696C > T; p.(Gln4566Ter) is a potential founder variant in the Baltic population. Table 1. Genetic variants in lone AF Gender Age of AF onset Genetic variant Family history Male 53 LMNA: p.(Ser326Thr) AF in mother Male 11 TTN: p.(Trp31854Ter) AF in father Male 30 TTN: p.(GLn4566Ter) AF in uncle Female 45 TTN: p.(GLn4566Ter) Negative Male 37 TTN: p.(GLn4566Ter) AF in father Male 25 TTN: p.(GLn4566Ter) AF in father, maternal and paternal grandmother Female 60 TTN: p.(Arg27414Ter) Sudden cardiac death at the age of 50 in grand father Female 52 TTN: p.(Arg1012Ter) AF in mother

The diagnostic value of cardiac magnetic resonance in athletes with suspected structural myocardial diseases

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Vago ◽  
L Szabo ◽  
D Balla ◽  
Z.S Dohy ◽  
C.S Czimbalmos ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Sudden Cardiac Death ◽  
Magnetic Resonance ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Funding Source ◽  
Research Development ◽  
Myocardial Disease ◽  
Myocardial Diseases

Abstract Introduction Sudden cardiac death (SCD) is the leading cause of death in athletes occurring usually during intensive training. Cardiac magnetic resonance (CMR) is a reliable technique to assess ventricular volumes and function. Furthermore, it provides tissue-specific information and has a crucial role in detecting structural myocardial diseases. Aim We aimed to investigate the prevalence of myocardial structural heart diseases and the etiology of sudden cardiac death in highly trained athletes and their outcome during follow-up. Method We examined athletes (training ≥6 hours/week) who underwent CMR due to suspected structural myocardial disease at Semmelweis University Heart and Vascular Center between 2009 and 2019. Cine movie images and late gadolinium enhanced (LGE) images were performed. Athletes with structural myocardial alterations were followed for the endpoint of all-cause-mortality. Results CMR was performed on a total of 338 athletes (280 male, 24±11 age). The indications for CMR were as follows: aborted sudden cardiac death/sustained ventricular tachycardia (SVT) (4%), ECG alterations (36%), echocardiographic alterations (32%), positive family history of SCD or cardiomyopathies (CMP) (3%), and patients' complaints, e.g. palpitation, syncope, dyspnoea, chest complaints (25%). CMR confirmed structural myocardial disease in 82 athletes with the following distribution: 20 hypertrophic (HCM), 10 arrhythmogenic (AC), 8 dilated (DCM), and 7 non-compact (NCCMP) CMP. The CMR images of three patients indicated Fabry disease. We found post-myocardial infarction scars in 7 cases, and atypical non-ischemic scars in 28 athletes. Besides pathological conditions, we identified minor alterations in 58 patients (51 male, 25±12 age) such as: increased trabeculation, nonspecific LGE in left ventricular insertion point and myocardial crypts. Among athletes examined after aborted sudden cardiac death or SVT we found structural heart disease in 11 males and one female: AC (n=7), HCM (n=1), NCCMP (n=1) and atypical non-ischemic scars (n=3, in two patients the localisation was lateral subepicardial) were diagnosed. During the median follow up of five years one patient died in whom CMR showed lateral scar formation and only mildly reduced left ventricular ejection fraction (50%). Conclusions The most common structural alteration was non-ischaemic scar, the most common CMP was HCM, and the leading cause of sudden cardiac death or SVT in our competitive athletes was AC and lateral subepicardial scar formation. LGE pattern in various cardiomyopathies Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Project no. NVKP_16-1-2016-0017 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the NVKP_16 funding scheme. This project was supported by a grant from the National Research, Development and Innovation Office (NKFIH) of Hungary (K 120277).

scholarly journals Genetic variants of uncertain significance: How to match scientific rigour and standard of proof in sudden cardiac death?

2020 ◽  
Vol 45 ◽  
pp. 101712 ◽  
Author(s):  
Simone Grassi ◽  
Oscar Campuzano ◽  
Mònica Coll ◽  
María Brión ◽  
Vincenzo Arena ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Cardiac Death ◽  
Standard Of Proof ◽  
Variants Of Uncertain Significance ◽  
Scientific Rigour ◽  
Uncertain Significance

Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals

2021 ◽  
Author(s):  
Liang Guo ◽  
Sho Torii ◽  
Raquel Fernandez ◽  
Ryan E. Braumann ◽  
Daniela T. Fuller ◽  
...  
Keyword(s):  
African American ◽  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Cardiac Death

scholarly journals Genotype-Related Clinical Characteristics and Myocardial Fibrosis and Their Association with Prognosis in Hypertrophic Cardiomyopathy

2020 ◽  
Vol 9 (6) ◽  
pp. 1671 ◽  
Author(s):  
Hyung Yoon Kim ◽  
Jong Eun Park ◽  
Sang-Chol Lee ◽  
Eun-Seok Jeon ◽  
Young Keun On ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Myocardial Fibrosis ◽  
Genetic Variants ◽  
Asian Patients ◽  
Pathogenic Variants ◽  
Clinical Events ◽  
Cerebrovascular Events ◽  
Genotypic Analysis ◽  
Uncertain Significance

Background: The spectrum of genetic variants and their clinical significance of Hypertrophic cardiomyopathy (HCM) have been poorly studied in Asian patients. The objectives of this study were to assess the spectrum of genetic variants and genotype–phenotype relationships within a Korean HCM population. Methods: Eighty-nine consecutive unrelated HCM patients were included. All patients underwent genotypic analysis for 23 HCM-associated genes. Clinical parameters including echocardiographic and cardiac magnetic resonance (CMR) parameters were evaluated. A composite of major adverse cardiac and cerebrovascular events was assessed. Results: Genetic variants were detected in 55 of 89 subjects. Pathogenic variants or likely pathogenic variants were identified in 27 of HCM patients in MYBPC3, TNNI3, MYH7, and MYL7. Variants of uncertain significance were identified in 28 patients. There were significant differences in the presence of non-sustained ventricular tachycardia (p = 0.030) and myocardial fibrosis on CMR (p = 0.029) in the detected compared to the not-detected groups. Event-free survival was superior in the not-detected group (p = 0.006). Conclusion: Genetic variants in patients with HCM are relatively common and are associated with adverse clinical events and myocardial fibrosis on CMR. Genotypic analysis may add important information to clinical variables in the assessment of long-term risk for HCM patients.

scholarly journals Contribution of electrocardiography to the diagnosis of cardiomyopathies and athletic heart syndrome

2020 ◽  
Vol 25 ◽  
pp. 4023
Author(s):  
O. S. Chumakova ◽  
M. Yu. Isaeva ◽  
O. S. Koroleva ◽  
D. A. Zateyshchikov
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Youth Sports ◽  
Myocardial Diseases ◽  
Increased Risk

The review describes the role of electrocardiography in the diagnosis of the most common nonischemic myocardial diseases associated with an increased risk of sudden cardiac death, especially in youth sports.

P1247FLNC pathogenic variants in patients with various cardiomyopathies:prevalence and genotype-phenotype correlations

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Ader ◽  
P De Groote ◽  
P Reant ◽  
D Dupin-Deguine ◽  
C Rambaud ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Pathogenic Variant ◽  
Pathogenic Variants ◽  
History Of ◽  
Custom Panel ◽  
Few Data ◽  
First Time

Abstract Background/Introduction Pathogenic variants FLNC encoding filamin C have been firstly reported to cause myopathies, and were recently linked to isolated cardiac phenotypes.However, few data on phenotype-genotype correlation are available. Purpose Our aim was to estimate the prevalence of FLNC pathogenic variants in cardiomyopathies and to study the relations between phenotype and genotype. Methods DNAs from a cohort of 1150 unrelated index-patients with an isolated cardiomyopathy (700 hypertrophic, 300 dilated, 50 restrictive cardiomyopathies, and 100 left ventricle non-compactions) have been sequenced on a custom panel of 52 cardiomyopathy disease-causing genes. Results A FLNC pathogenic variant was identified in 28 patients corresponding to a prevalence ranging from 1 to 8% depending on the cardiomyopathy subtypes. Truncating variants were always identified in patients with dilated cardiomyopathy, while missense or in-frame variants were found in other phenotypes. This work reported for the first time a left ventricular non-compaction associated with FLNC pathogenic variant. In the cohort, nine patients (32%) were implanted with an automatic defibrillator. In 7 families (25%), history of sudden cardiac death (SCD) before 50 years was reported. A personal or family history of sudden cardiac death (SCD) was significantly higher in patients with truncating variants than in patients carrying missense variants (p=0.01). Four patients died of cardiac cause including 3 from SCD and 1 from heart failure. Conclusion This work highlights the role of FLNC in cardiomyopathies. A correlation between the type of the variant and the cardiomyopathy subtype was observed as well as with SCD risk. These new data should be taken into consideration for patient's management and primary prevention of sudden cardiac death. Acknowledgement/Funding La ligue contre la Cardiomyopathie

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