Myoflame-19 Trial: Cardioprotection with Losartan/Prednisolone in Post-COVID Cardiac Inflammation

Prof. Dr. Valentina Puntmann presented, for the first time, the results of the randomised, placebo-controlled clinical trial MYOFLAME-19. She first outlined post-infectious diseases from the perspective of cardiologists, raising the issue of myocarditis in young people as an immediate infection-associated health concern. One of her main aims is to advance the integration of cardiac magnetic resonance imaging (MRI) in diagnosing heart disease to guide therapeutic interventions. The use of cardiac MRI can be extended to map out dynamic disease processes, including chronic disease activity and remission. The COVID-19 pandemic served as a validation of her and colleague's previous work, with the influx of COVID-19 patients highlighting the role of chronic persistent immune-mediated inflammation affecting the vascular system following infectious disease. Endothelial dysfunction has been identified as a key pathomechanism, which may be positioned at the intersection of immune dysregulation, autoimmunity, and autonomic dysfunction, even leading to downstream effects like a dysbalance in metabolites, including lactate. As such, stabilising the endothelium may be a key target for therapeutic intervention. The MYOFLAME-19 trial was thus designed to apply losartan — an angiotensin II receptor type 1 (AT1) receptor blocker — in combination with prednisone — as a means to address low grade inflammation by drawing upon evidence on low cortisol levels found in post-COVID patients. Patients included in the 16-week long trial did not have any pre-existing heart conditions. After undergoing imaging diagnostics to look for inflammation markers, patients were randomised in groups receiving either losartan or losartan in combination with prednisone, or respective placebo control groups. 832 patients were screened in total, with 302 undergoing cardiac imaging and 279 subsequently randomised into the intervention or placebo groups. The median age was 39 years with enrolled patients being mostly female and showing post-COVID fatigue syndrome symptoms for at least 12 months. The results of the trial, pointing to an increase in ejection fraction and a reduction in inflammation markers as well as atrium pressure, support the central hypothesis of treatable vascular dysfunction given that symptoms in the treated patients improved alongside markers. While the study did not meet its primary endpoint, the results provide directional proof of concept. The obtained methodological and mechanistic biological insides can form the foundation for subsequent investigations and clincial trials, including a future extension of MYOFLAME-19.