This study aims at identifying processes that are deregulated in blood cells by Clonal Hematopoiesis of Indeterminate Potential (CHIP) which are involved in the development of heart failure with preserved ejection fraction (HEpEF).
Heart failure is responsible of 70,000 deaths every year in France. Heart failure can be divided into 2 categories depend on whether the ejection fraction is reduced (HFrEF) or preserved (HFpEF). Most of the treatments efficient in HFrEF are unable to prevent decompensating or reduce mortality associated with HFpEF. HFpEF pathophysiology remains poorly understood, which represents an obstacle to their management and to reduce cardiovascular events they are associated with. Currently, it is admitted that cardiovascular risk factors (CVRF such as aging, female gender, diabetes mellitus, high blood pressure, hypercholesterolemia, obesity) are responsible of a low grade chronic inflammatory state that causes an endothelial dysfunction that contributes to the development of HFpEF. However, not all patients with these CVRF develop HFpEF. Moreover, the mechanisms linking CVRF to inflammation or alteration of cardiomyocyte function by endothelial dysfunction remain unknown. This suggests that it exists a role for another factor that remains to be identified. Clonal Hematopoiesis of Indeterminate Potential (CHIP) result from the acquisition in hematopoietic stem cells of mutations associated with hematological malignancies, in the absence of any hematological disease. This situation initially described with a frequency of \<5% before 60 years and \>20% after 80 years old appears to be more frequent (\>40% of people over 65 years). CHIP are mainly associated with the occurrence of cardiovascular events such as atherothrombosis and heart failure, possibly due to the induction of a chronic inflammation. Because CHIP are very frequent in the elderly and because CHIP are associated with inflammation and cardiovascular events, they could represent the missing link in the pathophysiology sequence that leads to the appearance of endothelial dysfunction and HFpEF development.
Study Type
OBSERVATIONAL
Enrollment
80
Presence of clonal hematopoiesis indeterminate potential (CHIP)
Presence of CHIP defined as the presence of a mutation with an allele frequency greater than 2%.
Time frame: Inclusion Visit
Diagnosis of heart failure with preserved ejection fraction
Diagnosis based on the European Society of Cardiology diagnostic sequence
Time frame: Inclusion Visit
scRNA-seq analysis
Sixteen patients will be selected for scRNA-seq analysis: * 3 patients with HFpEF and TET2 mutation * 3 patients with HFpEF and DNMT3A mutation * 2 patients with HFpEF but without CHIP * 3 patients with TET2 mutation but without HFpEF * 3 patients with DNMT3A mutation but without HFpEF * 2 patients without HFpEF nor CHIP
Time frame: 6 months (+/- 3 months)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.