REStoring mIcrovaScular inTegrity in acute Heart Failure – RESIST-HF

Acute HF represents a huge financial burden on global healthcare systems due to the resources and costs associated with the hospitalization of a patient. Moreover, post-discharge readmission rates are extremely high in acute HF patients. Despite the number of people affected worldwide by acute HF, no evidence-based therapy exists for this condition.

Acute decompensated heart failure (ADHF) therefore represents a major therapeutic challenge. Although numerous well-established therapies are available in the clinic for chronic HF, the acute HF market has considerable unmet needs.

Cardiac edema may be a key-player in this pathophysiological situation, and we hypothesize that loss of microvascular integrity in blood vessels and lymphatics contributes to cardiac edema in ADHF. We have previously shown that prevention of vascular hyperpermeability reduces cardiac edema acutely post-MI.

Here, we will investigate, in our novel rodent and pig ADHF models, the contribution of microvascular leakage and/or lymphatic dysfunction to cardiac edema; and further determine if restoration of vascular integrity (Patent, Partner 1; Project coordinator) may reduce blood microvascular hyperpermeability, lymphatic dysfunction as well as cardiac edema and lead to improved cardiac functional recovery.

Our RESIST-HF project, focused on restoring microvascular integrity, will improve the understanding of ADHF mechanisms and may reveal new and efficient pharmacological strategies to improve patient outcome.