Clonal haematopoiesis of indeterminate potential in cardiovascular medicine: is it time for selective testing?

Clonal haematopoiesis of indeterminate potential (CHIP), a recently recognized, age-related cardiovascular risk factor, results from acquired, somatic mutations in a subset of known leukaemia driver genes in haematopoietic stem or progenitor cells. While prior work suggested that screening for these somatic mutations, which requires DNA sequencing, was premature due to lack of actionable evidence-based interventions, this review proposes that in light of the rapidly accumulating knowledge regarding CHIP, selective clinical testing by cardiovascular clinicians is now justified for specific high-risk individuals to improve cardiovascular risk stratification and inform preventive care. By identifying distinct mutations and estimating their burden (variant allele fraction), clinicians can understand better an individual's CHIP-related cardiovascular risk and tailor surveillance and management strategies, even before validation of targeted therapies. This review advocates a biologically driven approach to selective assessment of CHIP that leverages the advances in understanding this condition and its clinical consequences.