Association of arterial hypertension gene polymorphisms with the risk of sudden cardiac death in young people

2020 ◽  
Vol 22 (3) ◽  
pp. 18-22
Author(s):  
V. A. Kachnov ◽  
V. V. Tyrenko ◽  
S. N. Kolubaeva ◽  
D. V. Cherkashin ◽  
G. G. Kutelev ◽  
...  
Keyword(s):  
At Risk ◽  
Sudden Cardiac Death ◽  
Young People ◽  
Arterial Hypertension ◽  
Mathematical Models ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Risk Variants ◽  
Close Relatives ◽  
The Relationship

Abstract. The frequency of occurrence of arterial hypertension genes in individuals at risk of sudden cardiac death was studied. The relationship between risk factors for sudden cardiac death and the presence of polymorphisms of arterial hypertension genes was revealed. There was a high incidence of homozygous risk variants AGTR2 AA and CYP11B2 TT-polymorphisms responsible for the development of left ventricular hypertrophy, including in young individuals. A correlation was found between deaths in close relatives under 50 years of age and the presence of polymorphisms in the CYP11B2 344 CT gene in young people at risk of sudden cardiac death. We have obtained data indicating the feasibility of conducting a study of the polymorphism of the CYP11B2 gene in the presence of a risk of sudden cardiac death. A direct correlation was found between the presence of fatal outcomes in relatives under 50 years of age by the mechanism of sudden cardiac death and the number of homozygous variants of arterial hypertension genes. Mathematical models for predicting the presence of polymorphisms in genes responsible for the possibility of arterial hypertension are constructed. Among the constructed mathematical models, the most informative were models for detecting carriers of mutations in the genes ADD1 1378 GT, CYP11B2 344 CT and NOS3 894 GT. The expediency of the analysis to search for mutations of arterial hypertension genes, especially in the CYP11B2 344 CT gene, for the possibility of earlier and more intensive preventive measures in young people is shown. The data obtained indicate that there are relationships between the risk of sudden cardiac death, some known predictors of its occurrence, and the genes for arterial hypertension.

scholarly journals Gene polymorphisms associated with lipid metabolism disorders in young adults with risk of ­sudden cardiac death

2021 ◽  
Vol 102 (6) ◽  
pp. 805-814
Author(s):  
V A Kachnov ◽  
E V Kryukov ◽  
S N Kolyubaeva ◽  
G G Kutelev ◽  
V V Tyrenko
Keyword(s):  
At Risk ◽  
Lipid Metabolism ◽  
Sudden Cardiac Death ◽  
Young People ◽  
Mathematical Models ◽  
Cardiac Death ◽  
Gene Polymorphisms ◽  
Pon1 Gene ◽  
Lipid Metabolism Disorders ◽  
Increased Risk

Aim. To study the frequency of polymorphisms in genes associated with lipid metabolism disorders in young people with risk of sudden cardiac death, to identify the relationships between gene polymorphisms and risk factors of sudden cardiac death, and to develop mathematical models to identify the probability of carrying mutations in these genes. Methods. The study included 436 young people (mean age 19.81.6 years). A standard examination and survey by questionnaire specially developed by us were conducted to identify an increased risk of sudden cardiac death. 59 individuals with a risk of sudden cardiac death were selected. The control group was 65 people, which was comparable to the study group. A blood test was performed to determine lipid profile and polymorphisms: Leu28Pro (rs 429358) in gene APOE, C3238G (rs 5128) in gene APOC3, Gln192Arg (rs 662) in gene PON1, Ser447Ter (rs 328) in gene LPL, G250A (rs 1800588) in gene LIPC. Statistical analysis was performed using the statistical package SPSS 17.0 and Statistica 6.0. The parametric KruskalWallis test, the MannWhitney U-test, the Pearsons chi-squared test, the Spearman rank correlation coefficient, and logistic regression analysis were used. Results. We revealed a high frequency of Gln192Arg (rs 662) polymorphism in the PON1 gene in the group of individuals at risk of sudden cardiac death and its correlation with the deaths in relatives under age 50 years. Mathematical models for predicting the presence of polymorphisms in genes associated with lipid metabolism disorders have been developed. Among the developed mathematical models, the models for identifying carriers of the minor allele of Gln192Arg polymorphism in the PON1 gene, Ser447Ter in the LPL gene, and 250 GA in the LIPC gene had the highest sensitivity, specificity, and accuracy. Conclusion. In persons at risk for sudden cardiac death, it is advisable to conduct a screening for mutations in genes associated with lipid metabolism disorders, especially in Gln192Arg polymorphism in gene PON1.

Abstract 15714: Prediction of Sudden Cardiac Death With Automated High-Throughput Analysis of T-Wave Heterogeneity in Standard 12-Lead Electrocardiogram

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tuomas Kenttä ◽  
Bruce D Nearing ◽  
Kimmo Porthan ◽  
Jani T Tikkanen ◽  
Matti Viitasalo ◽  
...  
Keyword(s):  
At Risk ◽  
Relative Risk ◽  
Sudden Cardiac Death ◽  
General Population ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Adjusted Relative Risk ◽  
T Wave ◽  
Increased Risk ◽  
Patients At Risk

Introduction: Noninvasive identification of patients at risk for sudden cardiac death (SCD) remains a major clinical challenge. Abnormal ventricular repolarization is associated with increased risk of lethal ventricular arrhythmias and SCD. Hypothesis: We investigated the hypothesis that spatial repolarization heterogeneity can identify patients at risk for SCD in general population. Methods: Spatial R-, J- and T-wave heterogeneities (RWH, JWH and TWH, respectively) were automatically analyzed with second central moment technique from standard digital 12-lead ECGs in 5618 adults (46% men; age 50.9±12.5 yrs.) who took part in Health 2000 Study, an epidemiological survey representative of the entire Finnish adult population. During average follow-up of 7.7±1.4 years, a total of 72 SCDs occurred. Thresholds of RWH, JWH and TWH were based on optimal cutoff points from ROC curves. Results: Increased RWH, JWH and TWH (Fig.1) in left precordial leads (V4-V6) were univariately associated with SCD (P<0.001, each). When adjusted with clinical risk markers (age, gender, BMI, systolic blood pressure, cholesterol, heart rate, left ventricular hypertrophy, QRS duration, arterial hypertension, diabetes, coronary heart disease and previous myocardial infarction) JWH and TWH remained as independent predictors of SCD. Increased TWH (≥102μV) was associated with a 1.9-fold adjusted relative risk (95% confidence interval [CI]: 1.2 - 3.1; P=0.011) and increased JWH (≥123μV) with a 2.0-fold adjusted relative risk for SCD (95% CI: 1.2 - 3.3; P=0.004). When both TWH and JWH were above threshold, the adjusted relative risk for SCD was 3.2-fold (95% CI: 1.7 - 6.2; P<0.001). When all heterogeneity measures (RWH, JWH and TWH) were above threshold, the risk for SCD was 3.7-fold (95% CI: 1.6 - 8.6; P=0.003). Conclusions: Automated measurement of spatial J- and T-wave heterogeneity enables analysis of high patient volumes and is able to stratify SCD risk in general population.

Sudden cardiac death associated with premature atheroma in the young: an autopsy study emphasising single-vessel lesions

2015 ◽  
Vol 26 (4) ◽  
pp. 743-748 ◽  
Author(s):  
Anna C. Green ◽  
Mary N. Sheppard
Keyword(s):  
Sudden Cardiac Death ◽  
Young People ◽  
Cardiac Death ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Autopsy Study ◽  
Dual Pathology ◽  
Single Vessel ◽  
Acute Infarction ◽  
Ischaemic Damage

AbstractAimsThis is the first autopsy study in the United Kingdom to analyse the demographic and pathological characteristics of atheroma associated with sudden cardiac death in young people.MethodsAn observational retrospective study of referred cases of sudden cardiac death in the young (⩽35 years) associated with premature atheroma was carried out.ResultsIn total, 46 cases were referred, with a median age of 30 years (27, 32); 72% of the referred cases were male, with a mean body mass index of 30 kg/m2. Circumstances of death were as follows: at rest (n=21), exertion (n=7), in bed (n=7), related to drugs/alcohol (n=4), and unknown (n=7). A previous cardiac history was provided in 10 cases. A history of class A/B drug use was found in eight cases. There was macroscopic evidence of infarction in 10 cases (acute, n=3 and chronic, n=7). Microscopically, 10 cases demonstrated contraction band necrosis, 11 acute infarction, and 11 chronic infarction. Single-vessel disease predominated (n=28). The left anterior descending coronary artery was involved in 39/46 cases. Thrombosis was seen in 16 cases, mainly due to erosion; one case showed dual pathology with arrhythmogenic right ventricular cardiomyopathy and another showed left ventricular hypertrophy.ConclusionsThis study highlights premature atheroma mainly in a single vessel in young people with or without evidence of ischaemic damage in the ventricle. Dual pathology may occur. The role of arrhythmias and channelopathies are important considerations. Premature atheroma should prompt investigation for dyslipidaemias in family members.

The relationship between left ventricular outflow tract gradient and sudden cardiac death in childhood hypertrophic cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Norrish ◽  
T Ding ◽  
E Field ◽  
C O'Mahony ◽  
P.M Elliott ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Inverse Relationship ◽  
Left Ventricular Outflow Tract ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Funding Source ◽  
Left Ventricular Outflow ◽  
The Relationship

Abstract Background The most common mode of death in childhood hypertrophic cardiomyopathy (HCM) is sudden cardiac death (SCD). Left ventricular outflow tract obstruction (LVOTO) is an established risk factor for SCD in adults with the disease. In contrast, the prognostic implications of LVOTO in childhood disease is unclear, with recent studies suggesting that it may have an inverse relationship with the risk of SCD. Purpose The aim of this study was to explore the role of LVOTO and the risk of SCD in childhood HCM. Methods A multi-centre, retrospective, longitudinal cohort of 871 children (diagnosed with HCM &lt;16 years of age) was used to explore the relationship between SCD and LVOTO (LVOT gradient ≥30mmHg). Results 189 patients (23%) had LVOTO, which was mild (30–50mmHg), moderate (50–100mmHg) or severe (&gt;100mmHg) in 58 (6.7%), 98 (11.3%) and 33 (3.8%), respectively. The risk of SCD showed an inverse relation to LVOT gradient severity compared to those with no obstruction: mild HR 1.75 (95% CI 0.89–3.44), moderate HR 1.04 (95% 0.55–1.98), and severe HR 0.7 (0.36–1.35) [figure].On univariable analysis [table] LVOTO was associated with heart failure symptoms (NYHA&gt;1) [p &lt;0.001], maximal wall thickness (MWT) [p &lt;0.001], left atrial (LA) diameter [p &lt;0.001], and future myectomy occurring during follow up [p &lt;0.001]. The inverse relationship observed was not altered by the presence or absence of other traditional risk factors. Conclusions LVOTO appears to have a complex relationship with the risk of SCD in childhood HCM, with multiple contributing factors. The pathophysiological mechanisms behind this observation need further exploration, which may be limited by low patient numbers Cummulative incidence of SCD by LVOTO Funding Acknowledgement Type of funding source: Other. Main funding source(s): British Heart Foundation

scholarly journals Screening young athletes for diseases at risk of sudden cardiac death: role of stress testing for ventricular arrhythmias

2019 ◽  
Vol 27 (3) ◽  
pp. 311-320 ◽  
Author(s):  
Alessandro Zorzi ◽  
Teresina Vessella ◽  
Manuel De Lazzari ◽  
Alberto Cipriani ◽  
Vittoria Menegon ◽  
...  
Keyword(s):  
At Risk ◽  
Sudden Cardiac Death ◽  
Physical Examination ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Stress Testing ◽  
Diagnostic Yield ◽  
Holter Monitoring ◽  
Left Ventricular ◽  
Young Athletes

Aims The athletic preparticipation evaluation (PPE) protocol proposed by the European Society of Cardiology includes history, physical examination and resting electrocardiogram (ECG). The aim of this study was to assess the results of adding constant-load ECG stress testing (EST) to the protocol for the evaluation of ventricular arrhythmias (VA) inducibility. Methods We evaluated a consecutive cohort of young athletes with history, physical examination, resting ECG and EST. Athletes with VA induced by EST underwent 24-hour 12-lead Holter monitoring and echocardiography. Cardiac magnetic resonance (CMR) was reserved for those with frequent, repetitive or exercise-worsened VA, and for athletes with echocardiographic abnormalities. Results Of 10,985 athletes (median age 15 years, 66% males), 451 (4.1%) had an abnormal history, physical examination or resting ECG and 31 (0.28%) were diagnosed with a cardiac disease and were at risk of sudden cardiac death. Among the remaining 10,534 athletes, VA at EST occurred in 524 (5.0%) and a previously missed at-risk condition was identified in 23 (0.22%); the most common ( N = 10) was an echocardiographically silent non-ischaemic left-ventricular fibrosis evidenced by CMR. The addition of EST increased the diagnostic yield of PPE by 75% (from 0.28% to 0.49%) and decreased the positive predictive value by 20% (from 6.9% to 5.5%). During a 32 ± 21 months follow-up, no cardiac arrests occurred among either eligible athletes or non-eligible athletes with cardiovascular disease. Conclusions The addition of exercise testing for the evaluation of VA inducibility to history, physical examination and ECG resulted in an increase of the diagnostic yield of PPE at the expense of an increase in false-positive findings.

scholarly journals Comparison of variant detection rate in genes between two cohorts of Czech living patients versus victims of sudden cardiac death with clinical / post mortem diagnosis of non-ischemic cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Borisincova ◽  
P Votypka ◽  
K Rucklova ◽  
A Pilin ◽  
M Kulvajtova ◽  
...  
Keyword(s):  
At Risk ◽  
Czech Republic ◽  
Primary Prevention ◽  
Sudden Cardiac Death ◽  
Genetic Counselling ◽  
Cardiac Death ◽  
Detection Rate ◽  
Funding Source ◽  
Post Mortem ◽  
Custom Made

Abstract Introduction Hereditary cardiomyopathy is associated with an increased risk of ventricular arrhythmia and sudden cardiac death (SCD). Genetic stratification substantiates risk assessment and enables the primary prevention of SCD in relatives at risk. We have analyzed the genetic aetiology of SCD in a representative Czech cohort with post mortem diagnosis of various forms of cardiomyopathy and compared it to living cases with these cardiac disorders. Patients and methods Between 2018 and 2019, altogether 47 victims of SCD with post mortem diagnosis of hypertrophic- (HCM; 18/47), arrhythmogenic- (ACM; 19/47) and dilated cardiomyopathy (DCM; 10/47) were identified. Concurrently, genetic testing was performed in 114 living patients (HCM 54/114, ACM 22/114, DCM 38/114). Genetic counselling and cardiologic examination had been carried out in first-degree relatives in all patients/SCD victims. Massively parallel sequencing (MiSeq platform; Illumina.com) was utilized for a custom-made panel comprising 100 candidate genes (Sophia Genetics, Switzerland). The presence of pathogenic variants was validated by Sanger DNA sequencing and through family segregation analyses. Results The causative detection rate (according to ACMG.net classes 4 or 5) in SCD victims with DCM was 60% (6/10) and in living patients with DCM 47.4% (18/38). Variants in TTN, RBM20, DES and FLNC (mainly truncating variants) prevailed in both groups. The detection rate in ACM was 5% (1/19 in SCN5A gene) in SCD victims and 31.8% (7/22) in living patients. Interestingly, the most prevalent mutated gene PKP2 in living patients was not detected in SCD victims. The detection rate in SCD victims with post mortem diagnosis of HCM was 16% (3/18) and in living patients 35% (19/54). The most prevalent gene was MYBPC3 in both groups, while PRKAG2 was detected in one SCD victim and in one living case who survived cardiac arrest. Conclusion Post-mortem genetic analysis in DCM yields a high detection rate and allows potentially effective primary prevention of SCD in relatives at risk. In contrast, the molecular autopsy of HCM and ACM renders a much lower yield which is below the mutation detection rate in living phenotype positive individuals. The results help to improve the genetic counselling in affected families in Czech Republic. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic

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