Acute heart failure as “acute endothelitis” — Interaction of fluid overload and endothelial dysfunction

Acute heart failure (AHF) is defined as a change in heart failure (HF) symptoms (i.e. dyspnoea, abdominal bloating, and fatigue) and signs (i.e. pulmonary crackles, jugular vein distension, and peripheral oedema) resulting in a need for urgent therapy. Symptoms and signs of HF are due to elevated left and right ventricular filling pressures with or without low cardiac output [1]. Heart failure symptoms typically worsen a few days (3±2.5 days) before hospital admission [2]. However, recent studies, based on continuous monitoring of intracardiac pressures (i.e. Chronicle, Medtronic Inc.) and of intrathoracic impedance (i.e. OptiVol, Medtronic Inc.), have substantially moved back the clock for the onset of AHF. Congestion (high filling pressures) progressively increases and intrathoracic fluid accumulates, starting 7–14 days before HF signs and symptoms worsen, eventually requiring urgent intravenous therapy [2,3]. What happens during the days that precede overt clinical decompensation? Can congestion itself cause progressive fluid overload, and, if so, is it possible to break this vicious cycle? Our hypothesis is that “systemic endothelitis”, characterized by a boost in endothelial oxidative stress and activation with induction of vasoactive and pro-inflammatory genes,