Acute
heart failure (AHF) is defined by a constellation of signs and symptoms that manifest when new or decompensated
ventricular dysfunction is triggered by an acute precipitant such as excessive preload, afterload, or
myocardial ischemia. Despite being one of the most frequent causes of hospitalization and cardiovascular mortality, little to no progress has been made over the last few decades to advance the treatment of AHF. Current mainstays of
pharmacotherapy for AHF including
diuretics,
vasodilators, and inotropes can improve symptoms; however, no currently approved agent has been shown to provide lasting outcome benefit for patients with AHF. First discovered in pregnant women where it is known to help with growth of the cervix and assist with the maternal cardiovascular and renovascular responses to pregnancy,
relaxin is an endogenous
neurohormone that has novel vasoactive properties. In particular,
relaxin is a potent
vasodilator with a number of pleiotropic effects that may affect cardiac remodeling, making
relaxin an attractive compound for use in the management of AHF. Indeed, in two randomized controlled trials, a single 48-hour infusion of
relaxin relieved symptoms of AHF with no evidence of major adverse effects. A signal of mortality benefit at 180 days was noted in both trials, prompting a third trial of
relaxin powered for 180-day mortality that is currently under way. The pharmacology that underscores the potential benefit of
relaxin is discussed and insight is provided into future clinical application of this novel
drug should it prove to be the first
therapy capable of reducing mortality in AHF.