Association Between Clonal Hematopoiesis and Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy

[Display omitted] •Study investigators analyzed simultaneously germline variants in cardiomyopathy-related genes and somatic mutations in CHIP driver genes from blood samples in nonischemic patients with DCM.•DCM patients with CHIP had a decreased probability of achieving LVRR, serving as a potent surrogate marker for adverse events in DCM. This effect was independent of established risk factors, including germline cardiomyopathy-related gene variants.•CHIP caused by Asxl1 mutation exacerbated cardiac dysfunction and myocardial fibrosis in DCM murine model with the germline truncating variant in the Ttn gene. Although clonal hematopoiesis of indeterminate potential (CHIP) is an adverse prognostic factor for atherosclerotic disease, its impact on nonischemic dilated cardiomyopathy (DCM) is elusive. The authors performed whole-exome sequencing and deep target sequencing among 198 patients with DCM and detected germline mutations in cardiomyopathy-related genes and somatic mutations in CHIP driver genes. Twenty-five CHIP driver mutations were detected in 22 patients with DCM. Ninety-two patients had cardiomyopathy-related pathogenic mutations. Multivariable analysis revealed that CHIP was an independent risk factor of left ventricular reverse remodeling, irrespective of known prognostic factors. CHIP exacerbated cardiac systolic dysfunction and fibrosis in a DCM murine model. The identification of germline and somatic mutations in patients with DCM predicts clinical prognosis.