A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease

Circulation. 2024 Nov 21. doi: 10.1161/CIRCULATIONAHA.123.067156. Online ahead of print.

Abstract

Background: Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate of ≈0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial.

Methods: We determined cardiomyocyte renewal in 52 patients with advanced heart failure, 28 of whom received left ventricular assist device support. We measured the concentration of nuclear bomb test-derived 14C in cardiomyocyte genomic DNA and performed mathematical modeling to establish cardiomyocyte renewal in heart failure with and without LVAD unloading.

Results: We show that cardiomyocyte generation is minimal in end-stage heart failure patients at rates 18 to 50× lower compared with the healthy heart. However, patients receiving left ventricle support device therapy, who showed significant functional and structural cardiac improvement, had a >6-fold increase in cardiomyocyte renewal relative to the healthy heart.

Conclusions: Our findings reveal a substantial cardiomyocyte regeneration potential in human heart disease, which could be exploited therapeutically.

Keywords: heart failure; heart-assist device; myocytes, cardiac.