Current status and future directions in the study of experimental chagasic cardiomyopathy

Chagasic cardiomyopathy (CCM) is the most severe manifestation of Chagas disease (CD), caused by infection with Trypanosoma cruzi. Current treatments rely on antiparasitic drugs, which have limited efficacy and significant side effects, or symptomatic management adapted from other cardiomyopathies—often insufficient to address CCM's unique features, such as severe arrhythmias, heart failure, and microvascular dysfunction. Despite over a century of research, critical gaps remain in understanding the pathogenesis of CCM, and no therapy effectively prevents parasite persistence or disease progression. Here, we summarize our group's key findings on the development and characterization of experimental CCM. We detail how murine models of T. cruzi infection have been instrumental in describing electrocontractile remodeling, isolating cardiomyocytes, and elucidating the cellular mechanisms and signaling pathways—particularly involving oxidative stress and calcium handling—that underlie disease pathogenesis. Our data support the hypothesis that targeting CaMKII, a central regulator of calcium and redox signaling in both host and parasite, may offer dual therapeutic benefits by reducing T. cruzi infectivity and preventing CCM onset. Finally, we discuss future directions for leveraging experimental models to develop more effective and specific therapies for Chagas disease.