Systolic heart failure with reduced ejection fraction has long been regarded as a heart with an irreversible depression in myocardial contractility. Improvements in ventricular function with recovery of contractility, however, have occurred during a period of cardiac unloading provided by a continuous-flow left ventricular assist device. The authors briefly review subcellular remodelling involved in the appearance of depressed cardiomyocyte work. Redox-sensitive deiodinase 3 (Dio3) is held responsible for a reduction of intracellular thyroid hormone signalling with the re-expression of a fetal gene program that includes slow β-myosin heavy chain. The attendant reduction in contractile work is an adaptation that preserves myocyte efficiency (work/energy consumed) and viability. Neutralizing oxidative stress and Dio3 is integral to the reversal of subcellular remodelling and rescue of depressed contractility.
