Genetics of Heart Failure

Heart Failure (HF) is one of the most important causes for morbidity and mortality in the aging western population. The prevalence in the population aged 75-80 is 25%, the mortality in severely symptomatic patients is 15-15% per year. Due to improved (acute-) therapy of ischemic heart diseases which often leads to heart failure, the number of younger HF patients increases continuously. In spite of this strong epidemiologic importance of HF, only 30% of HF patients are diagnosed correctly in early stages of HF because of lacking early diagnostic criteria. Early diagnosis is of critical importance to prevent fast progression by early state of the art clinical HF therapy. Besides extrinsic risk factors (environmental causes and live style) also the genetic background of the patients seems to affect the individual risk of HF. In contrast to ischemic heart diseases where large genome wide association studies (GWAS) have been performed, those studies are not available for HF until now.
The initiative “Genetics of Heart Failure” within the Program of Medical Genome Research has targeted the exploration of genetic causes, modifiers and molecular pathway mechanisms of HF.

In a unique interdisciplinary network approach the results of genome wide association studies with 6.000 patients of four HF subphenotpyes are utilized:

1.) Dilated Cardiomyopathy (DCM),
2.) Left ventricular Hypertrophy (LVH),
3.) Diastolic Dysfunction (DD), and
4.) Atrial Fibrillation (AF)

Common as well as subphenotype-specific disease relevant polymorphic markers (SNP`s) of HF will be analyzed.

Moreover, significant SNPs of the four subphenotypes will be correlated with clinical progression and clinical end points of HF patients. New candidate genes and candidate regions will be identified and signal transduction pathways will be functionally analyzed in (transgenic) animal models (Zebra fish, mouse and rat) and in vitro systems. Methodological platforms and bioinformatics methods are used to get detailed information about genetic function and molecular interactions. The final goal is to develop an innovative, clinically applicable risk score for HF, integrating proven clinical risk assessment and new genetic and molecular data.

Latest results can be found in detail in the descriptions of the subprojects