Most importantly, our preclinical trials show that sapropterin dihydrochloride (an orally active synthetic form of BH4, the major component of the clinically used drug, KUVAN®) can rescue heart failure in cardiomyocyte-specific Ythdf2 conditional knockout mice (Supplementary Fig. 7G and H), suggesting a feasible therapeutic strategy for dealing with BHPF-induced cardiac defects. This evidence concerns the gene YTHDF2 and heart failure.