scholarly journals Next generation sequencing in sudden cardiac death (pilot study)

2020 ◽  
Vol 25 (10) ◽  
pp. 3880
Author(s):  
V. N. Maksimov ◽  
D. E. Ivanoshchuk ◽  
P. S. Orlov ◽  
A. A. Ivanova ◽  
S. K. Malyutina ◽  
...  
Keyword(s):  
Pilot Study ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Morphological Changes ◽  
World Health ◽  
Missense Mutations ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
Health Organization ◽  
European Society Of Cardiology

Aim. To search for causal mutations in candidate genes responsible for the development of sudden cardiac death (SCD) in men who died under the age of 45.Material and methods. The SCD group (n=37) was formed using the criteria the World Health Organization and the European Society of Cardiology. Autopsy material was collected from men who died suddenly outside medical institutions and underwent forensic medical examination according to the standard protocol. Autopsy revealed no morphological changes that could explain sudden death. The mean age was 32,4±6,4 years. Genomic DNA was isolated from myocardial tissue using phenol-chloroform extraction. Clinical exome sequencing was performed. At first, we analyzed the results of sequencing of 24 genes, mutations in which lead to cardiovascular diseases associated with an increased risk of SCD: KCNQ1, KCNH2, SCN5A, AKAP9, ANK2, CACNA1C, CALM1, CALM2, CAV3, KCNE1, KNCJNE2, KCNE2, SCN4B, SNTA1, MYH2, APOB, KCNA5, TGFB3, NEB, PDX1, FLNC, PLEC, KCND3.Results. Of 37 samples, we revealed 13 probable pathogenic missense mutations in 9 samples (24,3%). Of 13 probable pathogenic variants, 5 were new.Conclusion. This pilot study provides following conclusions: it is necessary to continue molecular autopsy research in Russia; to increase the effectiveness of detecting causal mutations, it is necessary to reduce the age of patients with SCD included in the study; studying the families of deceased; cooperation of experienced specialists — forensic pathologist, laboratory geneticist, cardiologist.

scholarly journals The first results of gene panel sequencing in sudden cardiac death in young men

2020 ◽  
pp. 36-38
Author(s):  
В.Н. Максимов ◽  
Д.Е. Иванощук ◽  
П.С. Орлов ◽  
А.А. Иванова ◽  
С.К. Малютина ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Myocardial Tissue ◽  
Missense Mutations ◽  
Molecular Autopsy ◽  
Increased Risk ◽  
First Results ◽  
Continue Research ◽  
European Society Of Cardiology ◽  
Gene Panel Sequencing

Цель исследования: поиск причинных мутаций в генах-кандидатах внезапной сердечной смерти (ВСС) у мужчин, умерших в возрасте до 45 лет. Группа ВСС (30 образцов) была сформирована c использованием критериев ВСС ВОЗ и Европейского общества кардиологов. Средний возраст 31,3±5,3 года. Геномную ДНК выделяли из ткани миокарда методом фенол-хлороформной экстракции. Выполнили секвенирование клинического экзома. На первом этапе проанализировали результаты секевнирования 16 генов, мутации в которых приводят к ССЗ, ассоциированным с повышенным риском ВСС: KCNQ1, KCNH2, SCN5A, AKAP9, ANK2, CACNA1C, CALM1, CALM2, CAV3, KCNE1, KCNE2, KCNJ2, KCNJ5, SCN4B, SNTA1, SCN10A. Из 30 образцов с ВСС при анализе результатов секвенирования 16 генов было обнаружено 6 вероятно патогенных миссенс-мутаций в 7 образцах (23,3 %). В гене SCN10A обнаружено 2 мутации, в KCNH2, KCNE1, AKAP9, SNTA1 - по одной мутации. Подводя первые итоги пилотного исследования ВСС можно сделать следующие предварительные выводы: необходимо продолжение исследований в области молекулярной аутопсии в России, для повышения результативности поиска причинных мутаций, желательны снижение возраста случаев ВСС включаемых в исследование, а также работа с семьями умерших ВСС. Objective: Search for causal mutations in candidate genes for sudden cardiac death (SCD) in men who die before the age of 45. Materials and methods. The SCD group (30 samples) was formed using the criteria for sudden cardiac death of the WHO and the European Society of Cardiology. The average age is 31,3±5,3 years. Genomic DNA was isolated from myocardial tissue using phenol-chloroform extraction. Clinical exome sequencing was performed. At the first stage, the results of sequencing of 16 genes were analyzed, mutations in which result in CVD associated with an increased risk of SCD: KCNQ1, KCNH2, SCN5A, AKAP9, ANK2, CACNA1C, CALM1, CALM2, CAV3, KCNE1, KCNE2, KCNJ5, KCNJ5, SNTA1, SCN10A. Results. Of 30 samples with SCD, when analyzing the results of sequencing 16 genes, 6 probably pathogenic missense mutations were found in 7 samples (23.3%). 2 mutations were found in the SCN10A gene, one mutation in KCNH2, KCNE1, AKAP9, SNTA1. Findings. Summing up the first results of a pilot SCD study, the following preliminary conclusions can be drawn: it is necessary to continue research in the field of molecular autopsy in Russia, in order to increase the effectiveness of the search for causative mutations, it is desirable to reduce the age of SCD cases included in the study, as well as work with families of deceased SCD.

Postmortem Specificity of Troponin for Acute Miocard Infarction Diagnosis throug Qualitative Dosing from Pericardial Fluid

2018 ◽  
Vol 69 (9) ◽  
pp. 2482-2486
Author(s):  
Iuliana Hunea ◽  
Simona Irina Damian ◽  
Carmen Corina Radu ◽  
Sorin Moldoveanu ◽  
Tatiana Iov
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Disease ◽  
Cardiac Death ◽  
Troponin I ◽  
Troponin T ◽  
Morphological Changes ◽  
Pericardial Fluid ◽  
Histological Changes ◽  
Lethal Arrhythmia ◽  
Myocardial Lesions

Cardiac disease is the leading cause of death, and sudden cardiac death occupies the first place in sudden deaths of natural causes. Sudden cardiac death due to lethal arrhythmia may be the first manifestation of a cardiac disease, such cases becoming suspect dead, thus forensic cases. The autopsy performed in such cases may reveal important cardiovascular disease but not obvious macroscopic or histological changes of acute myocardial infarction (IMA), except for cases of survival for several hours after the onset of the symptomatology. Biochemical markers were used to test for myocardial lesions in the absence of morphological changes. Methods for determining myoglobin, CK-MB, troponin T (cTn T), troponin I (cTn I) were introduced to the clinic to diagnose the condition of patients with chest pain as early as the 1990s. The lack of pathognomonic elements in corps investigations, where part of the analysis cannot be carried out, requires verification of the value of the investigations that can be carried out, with reference to the biochemical in the present case, in establishing the diagnosis with certainty.

Antidiabetics: Structural Diversity of Molecules with a Common Aim

2018 ◽  
Vol 25 (18) ◽  
pp. 2140-2165 ◽  
Author(s):  
Jelena B. Popovic-Djordjevic ◽  
Ivana I. Jevtic ◽  
Tatjana P. Stanojkovic
Keyword(s):  
Structural Diversity ◽  
World Health ◽  
Common Disease ◽  
Peroxisome Proliferator ◽  
Epidemic Disease ◽  
Peroxisome Proliferator Activated Receptor ◽  
Increased Risk ◽  
Dipeptidyl Peptidase Iv Inhibitors ◽  
Glucagon Like Peptide 1 ◽  
Health Organization

Background: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 in 12 adults in the world, with still increasing prevalence. World Health Organization (WHO) declared this worldwide health problem, as an epidemic disease, to be the only non-infectious disease with such categorization. People with DMT2 are at increased risk of various complications and have shorter life expectancy. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability. Methods: A systematic search of peer-reviewed scientific literature and public databases has been conducted. We included the most recent relevant research papers and data in respect to the focus of the present review. The quality of retrieved papers was assessed using standard tools. Results: The review highlights the chemical structural diversity of the molecules that have the common target-DMT2. So-called traditional antidiabetics as well as the newest and the least explored drugs include polypeptides and amino acid derivatives (insulin, glucagon-like peptide 1, dipeptidyl peptidase-IV inhibitors, amylin), sulfonylurea derivatives, benzylthiazolidine- 2,4-diones (peroxisome proliferator activated receptor-γ agonists/glitazones), condensed guanido core (metformin) and sugar-like molecules (α-glucosidase and sodium/ glucose co-transporter 2 inhibitors). Conclusion: As diabetes becomes a more common disease, interest in new pharmacological targets is on the rise.

scholarly journals Newborns at risk of Covid-19 ― lessons from the last year

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Malika D. Shah ◽  
Ola Didrik Saugstad
Keyword(s):  
Horizontal Transmission ◽  
Mode Of Delivery ◽  
Newborn Infants ◽  
World Health ◽  
Premature Delivery ◽  
Mortality And Morbidity ◽  
Skin Contact ◽  
Cord Clamping ◽  
Increased Risk ◽  
Health Organization

Abstract After more than 1 year of the SARS-CoV-2 pandemic, a great deal of knowledge on how this virus affects pregnant women, the fetus and the newborn has accumulated. The gap between different guidelines how to handle newborn infants during this pandemic has been minimized, and the American Academy of Pediatrics (AAP)’s recommendations are now more in accordance with those of the World Health Organization (WHO). In this article we summarize present knowledge regarding transmission from mother to the fetus/newborn. Although both vertical and horizontal transmission are rare, SARS-CoV-2 positivity is associated with an increased risk of premature delivery and higher neonatal mortality and morbidity. Mode of delivery and cord clamping routines should not be affected by the mother’s SARS-CoV-2 status. Skin to skin contact, rooming in and breastfeeding are recommended with necessary hygiene precautions. Antibodies of infected or vaccinated women seem to cross both the placenta and into breast milk and likely provide protection for the newborn.

Association between digoxin use and sudden cardiac death in individuals with the rs10494366 variant of the NOS1AP gene

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Soroush ◽  
A Aarnoudse ◽  
F Shokri ◽  
M Van Den Berg ◽  
F Ahmadizar ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Smoking Status ◽  
Adaptor Protein ◽  
Therapeutic Window ◽  
P Value ◽  
Qtc Interval ◽  
Total Study Population ◽  
Increased Risk

Abstract Background Digoxin is one of the oldest cardiovascular medications still used to treat heart failure and atrial fibrillation. Due to its narrow therapeutic window, it is associated with life threatening intoxication and arrhythmias, and with QTc-shortening. Common genetic variation in the nitric oxide synthase-1 adaptor protein (NOS1AP) has been associated with QTc interval prolongation. Purpose We investigated whether the rs10494366 variant of the NOS1AP gene modified the risk of SCD in patients using digoxin. Methods In a prospective population-based cohort study, we included data of the three cohorts, started as of January 1st, 1991 until January 1st 2014. Digoxin current use on the date of cardiac death in cases and the same day of follow-up in the remainder of the cohort was a time-dependent exposure. The main outcome was SCD defined as sudden and unexpected death as a result of cardiac causes, according to international criteria. Identification and adjudication of SCD was performed independently, before the start of this study. We used Cox proportional hazard regression analysis to investigate the associations between NOS1AP rs10494366 variant and incident SCD among digoxin users compared to non-users. Associations were adjusted for age, sex (model 1) in addition to BMI, prevalent diabetes, myocardial infarction, baseline hypertension and smoking status (past, current, never) (model 2). Results We included 14,594 individuals, with a mean age of 65.3 (SD 10.3) years. Almost 59% were female. The cumulative incidence of SCD was 9.5% (609 cases) by the end of follow up. Among them, 98 (16%) individuals were exposed to digoxin at the time of death. In model 1, NOS1AP rs10494366 variant was not associated with SCD in the total study population. However, an interaction term of the gene with the daily dose of digoxin was significantly associated with increased risk of SCD (p-value 0.0001). In model 2, the risk of SCD in current users of digoxin was 4.2 [95% CI 1.3–13.8] for the GG genotype; 2.1 [95% CI 1.1–4.2] for the GT genotype, and 1.5 [95% CI 0.7–3.2] for the TT genotype. Conclusion NOS1AP rs10494366 variant modified the risk of sudden cardiac death in users of digoxin. Our study suggests that individuals with the homozygous minor GG allele have a fourfold increased risk of sudden cardiac death. Funding Acknowledgement Type of funding source: None

N-terminal pro-brain natriuretic peptide and sudden cardiac death in hypertrophic cardiomyopathy

Heart ◽  
2020 ◽  
pp. heartjnl-2020-317701
Author(s):  
Guixin Wu ◽  
Jie Liu ◽  
Shuiyun Wang ◽  
Shiqin Yu ◽  
Ce Zhang ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Sudden Cardiac Death ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Cardiac Death ◽  
Cardiac Fibrosis ◽  
Discrimination Performance ◽  
Net Reclassification Improvement ◽  
C Statistic ◽  
Increased Risk

ObjectiveElevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.MethodsThe study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell’s C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson’s staining was analysed.ResultsDuring follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson’s trichrome staining in the myocardium (r=0.198, p<0.05).ConclusionNT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease.

scholarly journals Iodine Excretion and Intake in Women of Reproductive Age in South Australia Eating Plant-Based and Omnivore Diets: A Pilot Study

2021 ◽  
Vol 18 (7) ◽  
pp. 3547
Author(s):  
Jane S. Whitbread ◽  
Karen J. Murphy ◽  
Peter M. Clifton ◽  
Jennifer B. Keogh
Keyword(s):  
Pilot Study ◽  
Urinary Iodine ◽  
Group Versus ◽  
Iodine Intake ◽  
Reproductive Age ◽  
World Health ◽  
Urinary Iodine Concentration ◽  
Women Of Reproductive Age ◽  
Increased Risk ◽  
Iodine Excretion

Women consuming a strictly vegan/plant-based diet may be at increased risk of low iodine intake due to avoidance of animal products containing iodine. The aim of this pilot study was to determine the iodine excretion and intake in women consuming vegan/plant based diets compared with women consuming omnivore diets. Fifty-seven women (n = 31 plant-based, n = 26 omnivores), provided two spot urine samples to assess urinary iodine concentration (UIC). Two days of dietary intake were also recorded by participants. As the data were not normally distributed results are reported as median (IQR). UIC was significantly different between groups, 44 (26–66) µg/L in the vegan/plant-based group versus 64 (40–88) µg/L in omnivores (p < 0.05). UIC did not meet the >100 µg/L level recommended by the World Health Organization. Iodine intake was also significantly different, 78 (62–91) µg/day in the vegan/plant-based group and 125 (86–175) µg/day in the omnivores (p = 0.000). Iodine intake and bread intake were correlated with iodine excretion (CC 0.410–4.11, p = 0.003). These data indicate iodine insufficiency in both groups of women as the median values were below the minimum WHO recommendation. A larger study assessing iodine excretion in the Australian women of reproductive age who are not pregnant or breastfeeding is needed to confirm these findings.

scholarly journals Vital exhaustion and sudden cardiac death in the Atherosclerosis Risk in Communities Study

Heart ◽  
2017 ◽  
Vol 104 (5) ◽  
pp. 423-429 ◽  
Author(s):  
Brittany M Bogle ◽  
Nona Sotoodehnia ◽  
Anna M Kucharska-Newton ◽  
Wayne D Rosamond
Keyword(s):  
Risk Factors ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Disease Risk ◽  
Ventricular Tachyarrhythmia ◽  
Atherosclerosis Risk In Communities ◽  
Vital Exhaustion ◽  
Increased Risk ◽  
Atherosclerosis Risk ◽  
Aric Study

ObjectiveVital exhaustion (VE), a construct defined as lack of energy, increased fatigue and irritability, and feelings of demoralisation, has been associated with cardiovascular events. We sought to examine the relation between VE and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) Study.MethodsThe ARIC Study is a predominately biracial cohort of men and women, aged 45–64 at baseline, initiated in 1987 through random sampling in four US communities. VE was measured using the Maastricht questionnaire between 1990 and 1992 among 13 923 individuals. Cox proportional hazards models were used to examine the hazard of out-of-hospital SCD across tertiles of VE scores.ResultsThrough 2012, 457 SCD cases, defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual, were identified in ARIC by physician record review. Adjusting for age, sex and race/centre, participants in the highest VE tertile had an increased risk of SCD (HR 1.48, 95% CI 1.17 to 1.87), but these findings did not remain significant after adjustment for established cardiovascular disease risk factors (HR 0.94, 95% CI 0.73 to 1.20).ConclusionsAmong participants of the ARIC study, VE was not associated with an increased risk for SCD after adjustment for cardiovascular risk factors.

Abstract 2415: Long-Term Baroreflex Activation Therapy Increases the Threshold for the Induction of Lethal Ventricular Arrhythmias in Dogs with Chronic Advanced Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mengjun Wang ◽  
Valerio Zaca ◽  
Alice Jiang ◽  
Itamar Ilsar ◽  
Matthew Ebinger ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Lv Function ◽  
Baroreflex Activation Therapy ◽  
Increased Risk ◽  
Lv Remodeling ◽  
Activation Therapy

Heart failure (HF) is associated with a high incidence of ventricular tachycardia (VT) and fibrillation (VF). Patients with HF in whom these lethal arrhythmias can be induced by electrophysiological (EP) testing carry a high risk of sudden cardiac death. We showed that chronic electrical carotid baroreflex activation therapy (BAT) with the Rheos® System (CVRx, Inc.) improves LV function, attenuates LV remodeling and restores autonomic sympathetic-parasympathetic balance in dogs with HF. This study examined the effects of long-term therapy with BAT on the induction of VT or VF in dogs with coronary microembolization-induced HF (LV ejection fraction ~20%). Eleven dogs with HF underwent EP testing at baseline prior to therapy and after 3 and 6 months of therapy with BAT and again 6 weeks after withdrawal of BAT therapy (n = 7) or no therapy at all (Control, n = 4). Programmed ventricular stimulation was performed from the right ventricular apex and included delivery of up to 4 extrastimuli at progressively shorter coupling intervals (in steps of 10 msec). The extrastimuli were delivered following 8 ventricular paced beats with a drive cycle length between 600 and 200 msec. If a sustained monomorphic VT or VF could not be induced, isoproterenol infusion was initiated to increase the sinus rate by ~30% and the EP stimulation protocol was repeated. At baseline, a sustained VT or VF was induced in all 11 dogs (100%). After 3 and 6 months of follow-up, all Control dogs (100%) were induced into sustained VT or VF. After 3 months of BAT, only 3 of 7 dogs (43%) were induced into sustained VT or VF. After 6 months of BAT, only 2 of 7 dogs (29%) were induced into sustained VT or VF. Finally after withdrawal of BAT therapy, all dogs (100%) were again induced into systained VT or VF. In addition to improving LV function and attenuating LV remodeling, long-term monotherapy with BAT markedly increases the threshold for lethal ventricular arrhythmias in dogs with chronic HF. This is a marked improvement over inducibility of lethal arrhythmias seen in historical untreated controls. This benefit of BAT supports the continued exploration of this device as a therapeutic modality for treating patients with chronic HF and increased risk of sudden cardiac death.

Sign in / Sign up

Export Citation Format

Share Document