First, although pharmacological activation of BCKDH by the BCKDK inhibitor BT2 has consistently shown to decrease cardiac BCAA levels and improve cardiac function in several models of heart failure (Chen et al., 2019; Li et al., 2017; Sun et al., 2016; Uddin et al., 2019; Wang et al., 2016), an in vivo isotopic tracing study in mice after [U‐13C]‐isoleucine infusion showed that BT2 treatment led to only modest increases in the levels of labeled tricarboxylic acid cycle intermediates in the heart (Neinast, Jang, et al., 2019). This evidence concerns the gene PPM1K and heart failure.