L-Arginine Enhances the Effects of Cardiac Rehabilitation on Physical Performance: New Insights for Managing Cardiovascular Patients During the COVID-19 Pandemic

: Cardiac rehabilitation (CR) following acute myocardial infarction (AMI) improves physical capacities and decreases hospitalizations and cardiovascular mortality. L-Arginine is the substrate used by nitric oxide (NO) synthase (NOS) to generate NO and it has been shown to exert its beneficial effects on endothelium driving vasodilatation, reducing inflammation, and ameliorating physical function. We hypothesized that L-Arginine could enhance physical capacities in patients who underwent CR after AMI. We designed a study aimed to assess the effects of L-arginine administration on the physical capacity of patients who underwent coronary revascularization after AMI. The trial was carried out amid the COVID-19 pandemic. Patients were assigned, with a 2:1 ratio, to add to their standard therapy 1 bottle containing 1.66 g of L-arginine or 1 bottle of identical aspect apart from not containing L-arginine, twice a day orally for 3 weeks. Patients performed a 6-minute walking test (6MWT) and were assessed their Borg modified 0-10 rating of perceived exertion (BRPE) before starting and at the end of the treatment. Seventy-five patients receiving L-Arginine, and thirty-five receiving placebo successfully completed the study. The 6MWT distance increased significantly in the L-Arginine group compared to both baseline and placebo (p<0.0001). Additionally, we observed a significant improvement in the BRPE in patients treated with L-arginine but not in the placebo group. Taken together, our data indicate that L-arginine potentiates the response to CR, independently of age, sex, baseline functional capacity, and comorbid conditions. Significance Statement This study shows for the first time that oral supplementation of L-arginine potentiates the response to cardiac rehabilitation after myocardial infarction and cardiac revascularization. Indeed, we observed a significant improvement in two fundamental parameters, namely, the 6-minute walking test and the Borg modified 0-10 rating of perceived exertion. Strikingly, the beneficial effects of L-arginine were independent from age, sex, comorbid conditions, and baseline functional capacity.