scholarly journals Familial Dilated Cardiomyopathy: Risk Stratification for Sudden Cardiac Death

2020 ◽  
Author(s):  
Gustav Mattsson ◽  
Peter Magnusson
Keyword(s):  
Heart Failure ◽  
Health Care ◽  
Sudden Cardiac Death ◽  
Risk Stratification ◽  
Dilated Cardiomyopathy ◽  
Health Care Providers ◽  
Cardiac Death ◽  
Reduced Ejection Fraction ◽  
Improve Risk Stratification ◽  
Familial Dilated Cardiomyopathy

Heart failure implies a considerable burden for patients and resources for the health care system. Dilated cardiomyopathy is defined as left ventricular dilation and reduced systolic function, not solely explained by ischemic heart disease or abnormal loading conditions. Numerous genes have been identified in familial cases of dilated cardiomyopathy. Heart failure with reduced ejection fraction increases the risk for sudden cardiac death. Implantable cardioverter defibrillator therapy can provide a means of preventing sudden cardiac death in those deemed to be at high risk. Health care providers are in need of better tools in order to improve risk stratification. This chapter aims to provide an overview of the current knowledge about risk of arrhythmia and sudden death in patients with familial dilated cardiomyopathy, in particular for those patients with a specific mutation.

scholarly journals Risk stratification and subclinical phenotyping of dilated and/or arrhythmogenic cardiomyopathy mutation-positive relatives: CVON eDETECT consortium

2021 ◽  
Author(s):  
R. W. Roudijk ◽  
K. Taha ◽  
M. Bourfiss ◽  
P. Loh ◽  
L. van den Heuvel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Early Detection ◽  
Risk Stratification ◽  
Dilated Cardiomyopathy ◽  
Cardiac Death ◽  
Diagnostic Techniques ◽  
Arrhythmogenic Cardiomyopathy ◽  
Early Detection Of Disease ◽  
Non Invasive

AbstractIn relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy, early detection of disease onset is essential to prevent sudden cardiac death and facilitate early treatment of heart failure. However, the optimal screening interval and combination of diagnostic techniques are unknown. The clinical course of disease in index patients and their relatives is variable due to incomplete and age-dependent penetrance. Several biomarkers, electrocardiographic and imaging (echocardiographic deformation imaging and cardiac magnetic resonance imaging) techniques are promising non-invasive methods for detection of subclinical cardiomyopathy. However, these techniques need optimisation and integration into clinical practice. Furthermore, determining the optimal interval and intensity of cascade screening may require a personalised approach. To address this, the CVON-eDETECT (early detection of disease in cardiomyopathy mutation carriers) consortium aims to integrate electronic health record data from long-term follow-up, diagnostic data sets, tissue and plasma samples in a multidisciplinary biobank environment to provide personalised risk stratification for heart failure and sudden cardiac death. Adequate risk stratification may lead to personalised screening, treatment and optimal timing of implantable cardioverter defibrillator implantation. In this article, we describe non-invasive diagnostic techniques used for detection of subclinical disease in relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy.

scholarly journals Risk Stratification of Sudden Cardiac Death in Patients with Heart Failure: An update

2018 ◽  
Vol 7 (11) ◽  
pp. 436 ◽  
Author(s):  
Daniele Masarone ◽  
Giuseppe Limongelli ◽  
Ernesto Ammendola ◽  
Marina Verrengia ◽  
Rita Gravino ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Risk Stratification ◽  
Cardiac Death ◽  
Clinical Syndrome ◽  
Pump Failure ◽  
Reduced Ejection Fraction ◽  
Clinical Challenge ◽  
Patients With Heart Failure ◽  
Symptoms And Signs

Heart failure (HF) is a complex clinical syndrome in which structural/functional myocardial abnormalities result in symptoms and signs of hypoperfusion and/or pulmonary or systemic congestion at rest or during exercise. More than 80% of deaths in patients with HF recognize a cardiovascular cause, with most being either sudden cardiac death (SCD) or death caused by progressive pump failure. Risk stratification of SCD in patients with HF and preserved (HFpEF) or reduced ejection fraction (HFrEF) represents a clinical challenge. This review will give an update of current strategies for SCD risk stratification in both HFrEF and HFpEF.

scholarly journals Prognostic implications of troponin T variations in inherited cardiomyopathies using systems biology

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Rameen Shakur ◽  
Juan Pablo Ochoa ◽  
Alan J. Robinson ◽  
Abhishek Niroula ◽  
Aneesh Chandran ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systems Biology ◽  
Sudden Cardiac Death ◽  
Risk Stratification ◽  
Clinical Data ◽  
Cardiac Death ◽  
Troponin T ◽  
Management Options ◽  
Familial Cardiomyopathy ◽  
The Impact

AbstractThe cardiac troponin T variations have often been used as an example of the application of clinical genotyping for prognostication and risk stratification measures for the management of patients with a family history of sudden cardiac death or familial cardiomyopathy. Given the disparity in patient outcomes and therapy options, we investigated the impact of variations on the intermolecular interactions across the thin filament complex as an example of an unbiased systems biology method to better define clinical prognosis to aid future management options. We present a novel unbiased dynamic model to define and analyse the functional, structural and physico-chemical consequences of genetic variations among the troponins. This was subsequently integrated with clinical data from accessible global multi-centre systematic reviews of familial cardiomyopathy cases from 106 articles of the literature: 136 disease-causing variations pertaining to 981 global clinical cases. Troponin T variations showed distinct pathogenic hotspots for dilated and hypertrophic cardiomyopathies; considering the causes of cardiovascular death separately, there was a worse survival in terms of sudden cardiac death for patients with a variation at regions 90–129 and 130–179 when compared to amino acids 1–89 and 200–288. Our data support variations among 90–130 as being a hotspot for sudden cardiac death and the region 131–179 for heart failure death/transplantation outcomes wherein the most common phenotype was dilated cardiomyopathy. Survival analysis into regions of high risk (regions 90–129 and 130–180) and low risk (regions 1–89 and 200–288) was significant for sudden cardiac death (p = 0.011) and for heart failure death/transplant (p = 0.028). Our integrative genomic, structural, model from genotype to clinical data integration has implications for enhancing clinical genomics methodologies to improve risk stratification.

scholarly journals Sudden Cardiac Death in Hereditary Dilated Cardiomyopathy

2020 ◽  
Author(s):  
Marianna Leopoulou ◽  
Jo Ann LeQuang ◽  
Joseph V. Pergolizzi ◽  
Peter Magnusson
Keyword(s):  
Sudden Cardiac Death ◽  
Left Ventricle ◽  
Sudden Death ◽  
Risk Stratification ◽  
Dilated Cardiomyopathy ◽  
Cardiac Death ◽  
Disease Risk ◽  
Systolic Dysfunction ◽  
Preventive Strategies ◽  
Genetic Origin

Dilated cardiomyopathy (DCM) is characterized by the phenotype of a dilated left ventricle with systolic dysfunction. It is classified as hereditary when it is deemed of genetic origin; more than 50 genes are reported to be related to the condition. Symptoms include, among others, dyspnea, fatigue, arrhythmias, and syncope. Unfortunately, sudden cardiac death may be the first manifestation of the disease. Risk stratification regarding sudden death in hereditary DCM as well as preventive management poses a challenge due to the heterogeneity of the disease. The purpose of this chapter is to present the epidemiology, risk stratification, and preventive strategies of sudden cardiac death in hereditary DCM.

Abstract 395: A Synonymous Coding SNP Alters SCN5A Regulation by miR-24 and Associates With Non-Arrhythmic Death in Heart Failure

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Xiaoming Zhang ◽  
Jin-Young Yoon ◽  
Michael Morley ◽  
Patrick Breheny ◽  
Heather Bloom ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Clinical Signs ◽  
Heart Rhythm ◽  
Coding Sequence ◽  
Reduced Ejection Fraction ◽  
Arrhythmic Death ◽  
And Function ◽  
Myocardial Gene Expression

Mutations disrupting SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and SNPs linked to SCN5A splicing, localization and function associate with heart failure-related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. Recently, we generated a transcriptome-wide map of microRNA (miR) binding sites in human heart and evaluated their interface with polymorphisms. Among >500 common SNPs residing within miR target regions, we identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within SCN5A coding sequence. This SNP is known to reproducibly associate with heart rhythm measurements, but is not considered to be “causal”. Here, we show that miR-24 potently suppresses SCN5A and that rs1805126 modulates this regulation. In further exploring the clinical significance of this, we found that rs1805126 minor allele homozygosity associates with decreased cardiac SCN5A expression and increased mortality in heart failure patients. Unexpectedly, this risk was not linked with arrhythmic sudden cardiac death, but rather, with clinical signs of worsening heart failure (e.g. reduced ejection fraction) and myocardial gene expression changes related to bioenergetics, inflammation and extracellular remodeling. Together, these data attribute a molecular mechanism to this firmly-established GWAS SNP and highlight a novel and surprising link between common variations in SCN5A expression and non-arrhythmic death in heart failure.

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