Dennis M McNamara, Leslie Cooper, Matthias G. Friedrich, Yaron Arbel, Arvind Bhimaraj, Edimar Bocchi, A. J. Hamer, Artur Haddad Herdy, Mathieu Kerneis, Peter P. Liu, Andrea B. Parker, Stuart Pocock, Eldon R. Smith, W H Wilson Tang, Guillermo Torre-Amione, Carsten Tschöpe, ARCHER Study Group, Artur Haddad Herdy, Paulo Caramori, Edimar Bocch, Lídia Zytynski Moura, Ariane Vieira Scarlatelli Macedo, Maria da Consolação Vieira Moreira, Denilson Campos de Albuquerque, Eduardo Dytz, Fernando Carvalho Neuenschwander, Luís Beck da Silva, Benoît Lattuca, Claire Bouleti, Theo Pezel, Mathieu Kerneis, Jeremie Abtan, Étienne Puymirat, Clément Delmas, Florent Huang, François Roubille, Thomas Bochaton, Gil Moravsky, Xavier Alejandro Piltz, Yaron Arbel, Amir Orlev, Pavan Bhat, Daniel A. Zlotoff, Georgia Thomas, Mark Hofmeyer, David Lin, Brittany Palmer, Dennis M McNamara, Leslie Cooper, Matthias G. Friedrich, Yaron Arbel, Arvind Bhimaraj, Edimar Bocchi, Mathieu Kerneis, Peter P. Liu, W H Wilson Tang, Guillermo Torre-Amione, Carsten Tschöpe, A. J. Hamer, Andrea B. Parker, Eldon R. Smith, Stuart Pocock
INTRODUCTION: Cannabidiol has been shown to exert significant anti-inflammatory effects and has demonstrated efficacy in murine models of autoimmune myocarditis, pericarditis, and heart failure. The ARCHER Study assessed whether a pharmaceutically produced cannabidiol formulation showed beneficial effects on cardiac magnetic resonance (CMR) endpoints known to predict prognosis in this patient population. METHODS: In a multicentre international double-blind placebo-controlled phase 2 study, we randomly assigned 109 patients within 10 days of CMR confirmed diagnosis of acute myocarditis to 12 weeks of pharmaceutically produced oral cannabidiol (active) or placebo. Dose was titrated up to 10 mg/kg of body weight twice daily. Primary endpoints were the difference in extracellular volume (ECV) and global longitudinal strain (GLS) measured by CMR at week 12. Other CMR endpoints included left-ventricular ejection fraction (LVEF), LV mass, intracellular volume (ICV), LV end-diastolic and end-systolic volumes (LVEDV, LVESV), and left-atrial end-systolic volume (LAESV). RESULTS: All randomized patients (56 active/53 placebo) completed the study with no loss to follow-up. Study drug appeared safe and well tolerated. Baseline mean ECV 38.9 ± 10.9 ml, GLS -15.3 ± 3.6%, and LVEF 60.6 ± 9.9% were consistent with mild to moderate myocarditis and predominantly intact LV function. Week 12 mean ECV was 33.6 ml in the active group and 37.3 ml in the placebo group, a difference of -3.7 ml, confidence interval (CI): -7.4 to 0.1; P = .0538; GLS was -16.0% in the active group and -15.9% in the placebo group, difference of -0.1, CI: -1.2 to 1.1; P = .90. Left ventricular mass was significantly reduced in the active group at 121.1 g compared to placebo 130.3 g, a difference of -9.2, CI: -16.4 to -2.1; P = .0117. In terms of remodelling, LAESV was significantly reduced in the active group (-8.1 ml; P = .0376) while the reduction in LVEDV failed to reach significance (-7.4 ml; P = .098). CONCLUSION: In mild-to-moderate acute myocarditis, treatment with pharmaceutically manufactured cannabidiol was not associated with a statistically significant change in myocardial ECV or GLS, although a trend towards reduction in ECV was observed. In addition, improvement in other potential markers of myocardial recovery, including a significant reduction in LV mass, was seen in the active treatment group. Further investigation of the therapeutic potential of this therapy in inflammatory cardiac conditions is warranted.