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

Area of Science:

• Cardiovascular Medicine
• Genetics
• Hematology

Background:

• Clonal hematopoiesis of indeterminate potential (CHIP) is a known risk factor for atherosclerotic disease.
• The prognostic significance of CHIP in nonischemic dilated cardiomyopathy (DCM) remains unclear.

Purpose of the Study:

• To investigate the impact of CHIP on the prognosis and clinical course of patients with nonischemic dilated cardiomyopathy.
• To explore the association between CHIP, germline mutations, and cardiac remodeling in DCM.

Main Methods:

• Whole-exome sequencing and deep target sequencing were performed on 198 DCM patients.
• Analysis included detection of germline mutations in cardiomyopathy genes and somatic mutations in CHIP driver genes.
• A DCM murine model was used to assess the effects of CHIP on cardiac function and fibrosis.

Main Results:

• CHIP driver mutations were identified in 22 patients (11.1%).
• CHIP was found to be an independent risk factor for left ventricular reverse remodeling in DCM patients.
• CHIP exacerbated cardiac systolic dysfunction and fibrosis in the DCM murine model.

Conclusions:

• The presence of CHIP in DCM patients is associated with adverse left ventricular remodeling.
• Somatic mutations in CHIP and germline mutations in cardiomyopathy genes can predict clinical prognosis in DCM.
• CHIP may represent a novel therapeutic target for improving outcomes in nonischemic dilated cardiomyopathy.