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University Medical Center Groningen

Research Lines

Cardiogenetics

Chronic heart failure (CHF) is a growing health problem in industrialized countries and is sometimes even referred to as an epidemic. As the incidence of CHF is age dependent its prevalence will only increase with the increasing average population age. In the Netherlands only already 200,000 people are suffering from CHF and each year 50,000 new patients are being diagnosed. Mortality rate is high and patients experience many adverse effects both from the disease and the treatment. Many studies, therefore, are undertaken to evaluate and improve disease management of CHF.

Distinct CHF subforms

Patients with heart failure can roughly be divided into two groups: those with ventricular dysfunction due to ischaemia and those with a non-ischaemic heart disease. Most of the different forms of cardiomyopathy in the last group can have a distinct cause like hypertension or a valvular heart disease. However in an important subset of these no such cause is identified thereby obtaining the classification "idiopathic" cardiomyopathy. The familial character of these different forms of idiopathic cardiomyopathy has been recognized in many studies.

Four categories of disease are distinghuised and the basis of haemodynamical and morphological characteristics: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC).

HCM is characterised by (usually asymmetric) left ventricular hypertrophy. In myocardial biopsies, myofibrillar disarray and myocyte hypertrophy is seen. Arrhythmias and premature sudden death are common. It is the most frequent with 1 in 500 people being affected and familial disease with an autosomal dominant inheritance predominates. So far more than 10 genes have been identified, most of them encoding cardiac sarcomere proteins.

DCM is characterized by dilatation and impaired systolic function of one or both ventricles. In more than 50% of patients no cause is identified and of this idiopathic subgroup more than 30% is familial with a prevailing dominant mode of inheritance as well. The (autosomal) genes identified so far partly overlap those identified in HCM (table) however also mutations in genes involved in the nuclear envelope and cytoskeleton/intermediate filaments and intracellular calcium homeostasis were identified.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterised by progressive fibrofatty replacement of the right ventricular myocardium. The clinical presentation shows arrhythmias of right ventricular origin. ARVC presents in at least 30% of patients as a familial disorder. Genetic defects only have been identified in a few patients. The genes involved either play a role in electromechanical coupling by release of calcium from the sarcoplasmatic reticulum into the cytosol (ryanodine receptor gene) or integrity of cell-junction (plakoglobin/desmoplakin).

Restrictive cardiomyopathy (RCM) is characterized by impaired ventricular filling and reduced diastolic volume in the presence of normal systolic function and (near-) normal myocardial thickness. Several disorders are known to cause RCM, but many cases remain idiopathic. Very recently mutations in the cardiac Troponin I gene were identified.

Research projects

Our research projects all aim at finding genes/loci explaining chronic heart failure. Finding the genetic components contributing to CHF will give more insight in the development of the disease, which might eventually might lead to better management in CHF patients and even prevention of CHF in mutation carriers.

Our research is embedded in a strong collaboration set up between the Department of Medical Genetics and the Department of Cardiology. The research projects are embedded in the CardioVascular Centre Groningen, (CVC-1) subtheme heart failure.

Contact persons

Department of Medical Genetics
Robert MW Hofstra

UMCG Medical Genetics

r.m.w.hofstra@medgen.umcg.nl

Peter van Tintelen UMCG Medical Genetics 

J.P.van.Tintelen@medgen.umcg.nl

 

Department of Cardiology
Dirk Jan van Veldhuisen UMCG  Cardiology

d.j.vanveldhuisen@thorax.umcg.nl

 

Projects

 

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