OM, a selective, small-molecule cardiac myosin activator is the most advanced exemplar of this novel mechanistic class and, after extensive preclinical and clinical study, is now being tested in a large Phase 3 cardiovascular outcomes trial in patients with HF-rEF (GALACTIC-HF, www.clinicaltrials.gov identifier, NCT02929329). This evidence concerns the gene ALYREF and hydrops fetalis.