PIK3C3 and heart failure: In addition, Class III PI3K’s role in the transition of cardiac hypertrophy to heart failure might suggest inhibition of VPS34 to be of clinical value in this context [203], but demonstration that VPS34 prevents hypertrophic cardiomyopathy by regulating myofibril proteostasis, and that its loss leads to cardiomegaly and decreased contractility, suggests this is unlikely to be a beneficial therapeutic approach [139, 140].