These included associations with incident HF reported elsewhere such as Gal-3, HGF, and Resistin,59–61 proteins such as CXCL16 with reported associations with prognosis in HF,62 and with cardiac fibrosis on cardiac magnetic resonance imaging in HF including MMP3.63 Among the novel associations to highlight, CTSL1 is a potent endoprotease linked to the development of dilated cardiomyopathy and HF in mouse models.64,65 We used cis-MR to estimate whether the observational protein-HF associations reflected an underlying causal relationship. This evidence concerns the gene CXCL16 and hydrops fetalis.