The emerging role of clonal haematopoiesis in the pathogenesis of dilated cardiomyopathy.

Abstract

The increased sensitivity of novel DNA sequencing techniques has made it possible to identify somatic mutations in small circulating clones of haematopoietic stem cells. When the mutation affects a 'driver' gene, the mutant clone gains a competitive advantage and has the potential to expand over time, a phenomenon referred to as clonal haematopoiesis (CH), which is emerging as a new risk factor for various non-haematological conditions, most notably cardiovascular disease (e.g. heart failure). Dilated cardiomyopathy (DCM) is a form of non-ischaemic heart failure that is characterized by a heterogeneous aetiology. The first evidence is arising that CH plays an important role in the disease course in patients with DCM, and a strong association of CH with multiple aetiologies of DCM has been described (e.g. inflammation, chemotherapy, and atrial fibrillation). The myocardial inflammation induced by CH may be an important trigger for DCM development for an already susceptible heart, e.g. in the presence of genetic variants, environmental triggers, and comorbidities. Studies investigating the role of CH in the pathogenesis of DCM are expected to increase rapidly. To move the field forward, it will be important to report the methodology and results in a standardized manner, so results can be combined and compared. The accurate measurement of CH in patients with DCM can provide guidance of specific (anti-inflammatory) therapies, as mutations in the CH driver genes prime the inflammasome pathway.