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TP 5 Etiology of Heart Failure


Illnesses originating primarily in cardiac muscle tissue – the cardiomyopathies – are the third most common cause of heart failure in western industrialized nations after coronary artery disease and hypertension. The most common form of cardiomyopathy is dilated cardiomyopathy (DCM), in which the cardiac cavities are enlarged and there is a loss of function. The second most common form is hypertrophic cardiomyopathy (HCM), in which the myocardial tissue thickens abnormally.

The enormous progress in the identification of disease genes have fundamentally changed our understanding of cardiomyopathies. It is well-known that mutations lead to different forms and variations in the progression of the illness. However, genetic examinations have been reserved for scientific research up to now, and thus limited to very few patients and families. For this reason, we do not have enough experience with a sufficient number of precisely genotyped patients in estimating the significance of individual mutations for the highly variable clinical progression of cardiomyopathies.


Subproject 5 has two primary goals: on the one hand, cross-linked research should enable us to offer patients with hypertrophic and dilated cardiomyopathy (HCM and DCM) molecular diagnoses. The primary focus here is on the development and validation of a molecular genetic diagnostic procedure that meets the requirements of timely, cost-effective and accurate human genetic examinations. On the other hand, these examinations should be representative and record the frequency of mutations in the known disease genes as well as their correlation to the clinical forms of heart failure. 

Main result

Two genes that are important for the initiation of cardiomyopathic disease, i.e. MYH7 and MYBPC3, were sequenced using DNA biosamples of 236 patients with hypertrophic and 652 patients with dilative cardiomyopathy. This approach yielded a new and profound insight into the relation between mutations and subsequent dysfunctions of cardiac structure and morphology.


  • Waldmüller S et al. Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure. Eur J Heart Fail. 2011;13:1185-92.
  • Budde BS et al. Noncompaction of the ventricular myocardium is associated with a de novo mutation in the beta-myosin heavy chain gene. PLoS One. 2007;2:e1362.


All subjects are followed long-term. DNA samples for cooperative research (e.g., next generation sequencing to investigate genotype-phentype associations) with academic and industrial partners are available.


PD Dr. Thomas Scheffold
Celenus Fachklinik Freiburg
Tel.: +49 (0)761 888595945
E-Mail: ed.grubierf-kinilkhcafnull@dloffehcs.t