LAUSR

Despite significant advances in treatment options, heart failure remains a devastating disease with significant morbidity/mortality and economic burden. In this context, new therapeutic approaches are eagerly needed. The paper by Bundgaard in this issue of the journal1 proposes a treatment target, the third isotype of beta-adrenergic receptors (β3 AR) that was identified in the human myocardium >15 years ago,2 but only recently tested in the clinical arena thanks to the availability of a specific agonist, mirabegron. The molecule is available for clinical use in urology for the treatment of overactive bladder disease, a painful condition of frequent micturition, based on its well-established relaxing effect on the bladder smooth muscle that expresses β3 AR.3 Bundgaard et al. now present the results of a first pilot trial of mirabegron in patients suffering from heart failure with reduced ejection fraction (HFrEF), the rationale of which was based on pre-clinical data pointing to beneficial effects of β3 AR activation in the failing myocardium. Although the trial did not meet its primary endpoint (increase in LVEF over placebo), a non-pre-specified, subgroup analysis in patients with the lowest EF suggests potential benefits in subjects with more severe LV dysfunction.