Whether the regenerative capacity of human cardiomyocytes is used in pathologically challenged hearts has been unknown. Using retrospective 14C birth dating we have analyzed cardiomyocyte renewal in patients with and without left ventricular support device (LVAD) therapy for end-stage heart failure. We show that cardiomyocyte generation is minimal in patients without LVAD therapy at rates 25-50 times lower compared to pre-onset of the disease, respectively. However, in a subset of mechanically unloaded hearts, which show a partial reversal in cardiac function, we found an increase in cardiomyocyte renewal to 3.1% per year. Our findings reveal a regenerative potential in LVAD patients with partial heart failure reversal, which could be exploited therapeutically. Files: Multi_Ploidy_Analysis_20x_local thresholding.cppipe: CellProfiler pipeline for multinucleation and Ploidy Analysis WGA CM-CSA pipeline with selection.cppipe: CellProfiler pipeline for WGA Analysis pyC14-master.zip: Snapshot from the module https://github.com/rodjul42/pyC14. Need for most scripts. chains.zip: Raw results from the sampling. Needed to run the overview.ipynb. damage.zip: Raw results from the sampling. Needed to run the damage.ipynb. calc_healty.ipynb : Calculate the interpolated healthy state for disease subjects. overview.ipynb: Scripts get the point estimates and prior plots. plots_and_genomic_age.ipynb: Plots of ploidy nucleation and genomic age. dnadamage.ipynb: DNA Damage analysis nuclei.csv: Nuclei Data Supp_Table1_Derks_24FEB.xlsx: C14 and ploidy data ploidy_children.csv and data_healthy.csv: Used data from Bergmann et al 2015. The names for model scenarios are different in the code and in the paper. The mapping is listed in this table: POP8P_D_h_exp_c SCENARIO I POP8P_h_exp_c SCENARIO II POP8P_H2_d_exp_Hcalc_c_agediag 2-phase model