Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Although various therapies developed over the last two decades have shown improved long term outcomes in patients with established HF, there has been little progress in preventing the adverse cardiac remodeling that initiates HF. To fill the gap in treatment, current research efforts are focused on understanding novel mechanisms and signaling pathways. Immune activation, inflammation, oxidative stress, alterations in mitochondrial bioenergetics, and autophagy have been postulated as important pathophysiological events in this process. An improved understanding of these complex processes could facilitate a therapeutic shift toward molecular targets that can potentially alter the course of HF.

In this review, we address the role of immunity, inflammation, and oxidative stress as well as other novel emerging concepts in the pathophysiology of HF that may have therapeutic implications.

Based on the experimental and clinical studies presented here, we anticipate that a better understanding of the pathophysiology of HF will open the door for new therapeutic targets. A one-size-fits-all approach may not be appropriate for all patients with HF, and further clinical trials utilizing molecular targeting in HF may result in improved outcomes.