Background Homoarginine ( hA rg) has been shown to be cardioprotective in a model of ischemic heart failure; however, the mechanism remains unknown. hA rg can inhibit tissue‐nonspecific alkaline phosphatase ( TNAP ), an enzyme that promotes vascular calcification. We hypothesized that hA rg will exert beneficial effects by reducing calcification in a mouse model of coronary artery disease associated with TNAP overexpression and hypercholesterolemia. Methods and Results TNAP was overexpressed in the endothelium in mice homozygous for a low‐density lipoprotein receptor mutation (wicked high cholesterol [ WHC ] allele). WHC and WHC –endothelial TNAP mice received placebo or hA rg supplementation (14 mg/L in drinking water) starting at 6 weeks of age simultaneously with an atherogenic diet. Outcomes were compared between the groups after 4 to 5 weeks on treatment. Experiments were performed in males, which presented a study limitation. As expected, WHC –endothelial TNAP mice on the placebo had increased mortality (median survival 27 days, P <0.0001), increased coronary calcium and lipids ( P <0.01), increased left ventricular end‐diastolic diameter ( P <0.0001), reduced ejection fraction ( P <0.05), and increased myocardial fibrosis ( P <0.0001) compared with WHC mice. Contrary to our hypothesis, hA rg neither inhibited TNAP activity in vivo nor reduced coronary artery calcification and atherosclerosis in WHC –endothelial TNAP mice; however, compared with the placebo, hA rg prevented left ventricular dilatation ( P <0.01), preserved ejection fraction ( P <0.05), and reduced myocardial fibrosis ( P <0.001). Conclusions The beneficial effect of hA rg supplementation in the setting of calcified coronary artery disease is likely due to its direct protective actions on the myocardial response to the ischemic injury and not to the inhibition of TNAP activity and calcification.

Kawasaki disease (KD) and multisystem inflammatory syndrome (MIS) are rare conditions that occur predominately in children. Recent reports document KD and MIS in adult patients following infection with SARS-CoV-2. Rarely, MIS is observed following vaccination against SARS-CoV-2, mostly in patients with prior SARS-CoV-2 infection. We report a case of KD in a man after a second SARS-CoV-2 vaccine dose, in absence of concurrent or prior SARS-CoV-2 infection. This patient also met criteria for probable MIS associated with vaccination. He tested negative for SARS-CoV-2 RNA via reverse transcriptase PCR, negative for SARS-CoV-2 nucleocapsid antibodies and demonstrated high levels SARS-CoV-2 spike protein antibodies, commonly used to assess vaccine response. Symptom improvement followed treatment with intravenous immunoglobulin, including desquamation of the hands and feet. As widespread vaccination against SARS-CoV-2 continues, increased vigilance and prompt intervention is necessary to limit the effects of postvaccination inflammatory syndromes.