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 austomal 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 showsarrhythmias 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 integrety 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.
Our reseach 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.
Department of Medical Genetics
Department of Cardiology
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