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

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.

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© 2024 The Authors.

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This work was supported by grants from the SENSHIN Medical Research Foundation (to Dr Nomura), the Japan Foundation for Applied Enzymology (to Drs Ko, Nomura, and Dai), the Kanae Foundation for the Promotion of Medical Science (to Dr Nomura), the MSD Life Science Foundation (to Dr Nomura), the Sakakibara Heart Foundation Cardiovascular Research Program 2023 (to Dr Ko), the Tokyo Biomedical Research Foundation (to Dr Nomura), the Astellas Foundation for Research on Metabolic Disorders (to Dr Nomura), the Novartis Foundation (Japan) for the Promotion of Science (to Dr Nomura), the Japanese Circulation Society (to Drs Ko and Nomura), the Takeda Science Foundation (to Drs Ko and Nomura), the Cell Science Research Foundation (to Dr Nomura), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Dr Nomura), the Japan Heart Foundation (to Dr Ko), and the Daiichi-Sankyo Foundation of Life Science (to Dr Nomura); a Grant-in-Aid for Scientific Research (A) (to Dr Nomura); a Grant-in-Aid for Scientific Research (S) (to Dr Komuro); the UTEC-UTokyo FSI Research Grant Program (to Dr Nomura); the JST FOREST Program (grant JPMJFR210U) (to Dr Nomura); a Japan Society for the Promotion of Science Grant-in-Aid for Japan Society for the Promotion of Science fellow (23KJ0434) (to Dr Dai) and AMED JP23ek0109600h0002 (to Dr Ko); and JP20ek0109487, JP18km0405209, JP21ek0109543, JP21tm0724601, JP22ama121016, JP22ek0210172, JP22ek0210167, JP22bm1123011, JP23tm0724607, JP23gm4010020, JP23tm0524009, JP23tm0524004, JP23jf0126003, and JP24ek0109755 (to Drs Nomura and Komuro). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.