Fig. 1.

The vicious cycle of right ventricular failure (RVF). The reduced right coronary artery (RCA) flow and RCA systolic perfusion pressure in RVH ultimately cannot support the increased oxygen demand in increased RV mass. This causes RV hypoxia and ischemia. The transcriptional factors HIF-1α and Myc are activated by RV ischemia. This transcriptional reprogramming contributes to a switch from mitochondrial metabolism (glucose oxidation) to glycolysis. RV function is then further reduced by the depressed ATP production and myocardial acidosis and eventually RVF develops. Interrupting this cycle, by enhancing blood supply, inhibiting transcription factors, or restoring glucose oxidation (by inhibiting PDKs or FAO) is postulated to be therapeutic