Peripheral reflex feedbacks in chronic heart failure: Is it time for a direct treatment?

Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF), no single conceptual paradigm for HF has withstood the test of time. The last model that has been developed, the neurohormonal model, has the great virtue of highlighting the role of the heart as an endocrine organ, as well as to shed some light on the key role on HF progression of neurohormones and peripheral organs and tissues beyond the heart itself. However, while survival in clinical trials based on neurohormonal antagonist drugs has improved, HF currently remains a lethal condition. At the borders of the neurohormonal model of HF, a partially unexplored path trough the maze of HF pathophysiology is represented by the feedback systems. There are several evidences, from both animal studies and humans reports, that the deregulation of baro-, ergo- and chemo-reflexes in HF patients elicits autonomic imbalance associated with parasympathetic withdrawal and increased adrenergic drive to the heart, thus fundamentally contributing to the evolution of the disease. Hence, on top of guideline-recommended medical therapy, mainly based on neurohormonal antagonisms, all visceral feedbacks have been recently considered in HF patients as additional potential therapeutic targets.