Infants with heart disease generate new cardiomyocytes rapidly early in life, producing 0.74 billion new cells within the first 4 months, but this regenerative capacity declines 3.4-fold after 4 months (P = 0.0417). Data presented at the American Heart Association (AHA) 2025 Scientific Sessions highlight that congenital and acquired heart disease alters this critical developmental phase.

The evaluation included 18 infants: 13 with ToF, 5 with HF awaiting transplantation, and one ToF infant receiving propranolol therapy. All infants received nitrogen-15-labeled thymidine (15N-thymidine) to identify dividing cardiomyocytes. Myocardial samples were collected during surgical repair of ToF, placement or removal of LVADs, or heart transplantation. Multi-Isotope Imaging Mass Spectrometry (MIMS) quantified DNA replication and polyploidy to assess cardiomyocyte division versus post-mitotic status.

Diseased hearts demonstrated increased formation of post-mitotic polyploid cardiomyocytes, reflected by 1.38-fold higher average per-nucleus DNA content vs. 11 non-diseased individuals (P = 0.0358). The HF infant on LVAD support improved clinically but continued to show reduced cardiomyocyte proliferation. In contrast, beta-blockade with propranolol reduced the incidence of polyploid nuclei in the ToF infant, suggesting a favorable impact on cardiomyocyte division.

These findings highlight a brief early-life period for cardiomyocyte regeneration and suggest beta-blockade as a promising strategy in infant heart disease.