Single-nucleus multi-omics reveals reversible molecular signatures in skeletal muscle of patients with heart failure with preserved ejection fraction
Single-nucleus multiome profiling of 140 skeletal muscle biopsies from 95 individuals (25 healthy controls, 70 HFpEF patients) maps molecular signatures of skeletal muscle remodeling in HFpEF, including type 1 fiber and pericyte depletion and type 2x fiber enrichment. Paired biopsies from 45 HFpEF patients before and after a supervised diet and exercise intervention show the chromatin accessibility and transcriptional changes were partially reversible. HFpEF-linked chromatin was enriched for heart failure and cardiometabolic GWAS signals.