While for TNF-α such a model is to the best of our knowlegde still missing an elegant experiment has proven the causal role of oxidative stress in mediating diaphragm dysfunction in HF (Ahn et al., 2015): therein it was shown that in a knock out model of p47phox-dependent Nox2 isoform of NAD(P)H oxidase (a putative source of diaphragm oxidants) experimentally induced HFrEF diaphragm isometric force, shortening velocity, and peak power were decreased by 20–50% in HF wild-type mice whereas p47phox knockout mice were protected from impairments in diaphragm contractile function elicited by HF. The gene discussed is FMO5; the disease is hydrops fetalis.