library_construction_protocol: The myocardial tissues from the LV apex were extracted at LVAD implantation, being divided into several blocks. One block was immediately sealed in a polypropylene tube and stored at -80°C for preservation. Nuclei were isolated and extracted from frozen myocardial tissue samples from selected cases using the Miltenyi Gentle MACS Kit (Miltenyi Biotec, Bergisch Gladbach, Germany). This kit has been validated for nuclear isolation from frozen mouse myocardial tissues and subsequent single-nucleus RNA sequencing following the same protocol. 14,15 Lysis buffer was prepared using nuclei extraction buffer and RNase inhibitor, whereas resuspension buffer was prepared using phosphate-buffered saline, bovine serum albumin, and RNase inhibitor. Tissue fragments were incubated with lysis buffer, and the nuclei were isolated using the gentleMACS Dissociator (Miltenyi Biotec). The protocol included filtering the lysate through strainers and centrifuging, after which the nuclei were extracted. DAPI staining was used to assess the nuclear morphology and count. The isolated nuclei were preserved in a resuspension buffer and promptly processed for library preparation. The library preparation was performed using the 10x Genomics Chromium Single Cell Multiome ATAC + Gene Expression Kit (10X Genomics, CA, USA).