Venous congestion and endothelial cell activation in acute decompensated heart failure

Abstract

Despite accumulating clinical evidence supporting a key role for venous congestion in the development of acute decompensated heart failure (ADHF), there remain several gaps in our knowledge of the pathophysiology of ADHF. Specifically, the biomechanically driven effects of venous congestion on the vascular endothelium (the largest endocrine/paracrine organ of the body), on neurohormonal activation, and on renal and cardiac dysfunction remain largely unexplored. We propose that venous congestion is a fundamental, hemodynamic stimulus for vascular inflammation, which plays a key role in the development and possibly the resolution of ADHF through vascular, humoral, renal, and cardiac mechanisms. A better understanding of the role of venous congestion and endothelial activation in the pathophysiology of ADHF may provide a strong rationale for near-future testing of treatment strategies that target biomechanically driven inflammation. Targeting vascular and systemic inflammation before symptoms arise may prevent progression to overt clinical decompensation in the ADHF syndrome.

Fig. 1

Proposed relationship between venous congestion, endothelial activation, and decompensation in CHF: venous congestion ↔ inflammation. ECs sense both biochemical stimuli and biomechanical forces, and translate both types of signals into genetic regulatory events. When exposed to biomechanical stress (circumferential stretch associated with venous congestion), ECs release pro-oxidant, proinflammatory, and vasoconstricting mediators, which contribute to the development of ADHF. Antioxidant enzymes are the primary defense mechanism against oxidative and inflammatory damage. ADHF—acute decompensated heart failure; CHF—chronic heart failure; COX—cyclo-oxygenase; CuZnSOD—copper-zinc superoxide dismutase; EC—endothelial cell; eNOS—endothelial nitric oxide synthase; ET—endothelin; GPx1—glutathione peroxidase; ICAM—intercellular adhesion molecule; iNOS—inducible nitric oxide synthase; MnSOD—manganese superoxide dismutase; TNF—tumor necrosis factor

Fig. 2

The active role of venous congestion in the pathophysiology of ADHF. Although venous congestion represents the effect rather than the cause, once initiated and sustained, it may cause additional fluid retention through endothelial, neurohormonal, renal, and cardiac mechanisms. ADHF—acute decompensated heart failure