Mechanisms of current therapeutic strategies for heart failure: more questions than answers?

Abstract

Heart failure (HF) is a complex, multifactorial and heterogeneous syndrome with substantial mortality and morbidity. Over the last few decades, numerous attempts have been made to develop targeted therapies which may attenuate the known pathophysiological pathways responsible for causing progression of HF. However, therapies developed with this objective have sometimes failed to show benefit. The pathophysiological construct of HF with numerous etiologies suggests that interventions with broad mechanisms of action which simultaneously target more than one pathway maybe more effective in improving outcomes of patients with HF. Indeed, current therapeutics with clinical benefit in HF have targeted a wider range of intermediate phenotypes. Despite extensive scientific breakthroughs in HF research recently, questions persist regarding the ideal therapeutic targets which may help achieve maximum benefit. In this review, we evaluate the mechanism of action of current therapeutic strategies, the pathophysiological pathways they target and highlight remaining knowledge gaps regarding the mode of action of these interventions.