Rituximab as a novel treatment for heart failure: evidence from a case series

摘要

As part of the quest for novel therapies for heart failure (HF) with reduced ejection fraction, inflammation has been considered with interest as a potential target for treatment. Indeed, both myocardial damage and tissue hypoperfusion may induce the production of cytokines that can promote the progression of cardiac dysfunction. Nonetheless, clinical trials on tumour necrosis factor-α (TNFα) or interleukin-1β (IL-1β) inhibitors have yielded modest or negative results, possibly because the activation of inflammatory pathways is limited and inflammation does not become a crucial disease determinant in the majority of patients.Conversely, modulation of the immune response is particularly promising in the 30% of cases of myocarditis where inflammation does not resolve and there is a progression to chronic inflammatory dilated cardiomyopathy (DCMi). Among 202 patients with DCM from ≥6?months, as many as 42% displayed myocardial inflammation on endomyocardial biopsy (EMB).5 Among them, those randomized to steroids and azathioprine developed decrease in left ventricular (LV) volumes, function recovery, and improvement in New York Heart Association (NYHA) class during the first 3?months of treatment. These effects were sustained over 2?years, although no differences in survival were noted. Another study evaluated 85 patients with DCMi randomized to prednisone and azathioprine or placebo for 6?months.6 A positive effect of immunosuppression on cardiac remodelling was reported, with a mean LV ejection fraction (LVEF) increase from 26% to 46%; HF symptoms improved as well, and no major adverse effects were found. Nonetheless, both steroids and azathioprine have a large spectrum of activity and an unfavourable safety profile, prompting a search for more selective therapeutic approaches.