Usefulness of neurohormonal markers in the diagnosis and prognosis of heart failure
Institut Clínic del Torax, Hospital Clínic, IDIBAPS – Institut D'Investigacions Biomèdiques August Pi I Sunyer, C/Villarroel 170, Barcelona University, Barcelona 08036, Spain
Corresponding author. Tel: +34 3 2275400 ext. 2035; fax: +34 3 2275454. E-mail address: eroig{at}clinic.ub.es
The recent insights into the pathophysiology of heart failure drawn from studies of mechanisms that lead to ventricular remodelling will be briefly reviewed. Neurohormonal activation has been considered to be an adaptative process activated in response to a fall in cardiac output. Its main goal is to maintain perfusion to the vital organs and assure peripheral perfusion. This activated mechanism is generally adaptive in the short-term and maladaptive over the long-term. There are a number of regulatory peptides and hormones activated in heart failure causing vasoconstriction, water retention and cell growth, and proliferation. There are also counter-regulatory peptides that are released in an attempt to offset the maladaptative actions previously described; their effects being vasodilation, reduction of fluid retention, and inhibition of cell growth and proliferation. Although, a balance between these two opposite hormones and peptides will lead to the stabilization of heart failure, there is now direct evidence that chronic neurohormonal activation makes an important contribution to the progression of heart failure.
The circulating inflammatory cytokines are increased in patients with heart failure. On the basis of a growing body of experimental evidence, cytokines have been associated with negative inotropic effect and left ventricular (LV) remodelling. Expression of the iNOS has been found in myocytes of explanted hearts of patients undergoing heart transplantation. The increased NO within the myocardium can also promote cytotoxic actions inducing myocardial damage, apoptosis, and further disease progression. Moreover, cytokine activation contributes to endothelial dysfunction present in heart failure.
The equilibrium between MMP and TIMP plays an important role preserving the stability of collagen that forms the ECM. It has been pointed out that an imbalance between MMP/TIMP, favouring ECM degradation may facilitate the remodelling process. Supporting this hypothesis, increased expression of enzymes that can contribute to collagen breakdown has been found in myocardial tissue of terminal heart failure patients.
Heart failure is a complex disorder that is still poorly understood. Only a better understanding of the process that mediates LV remodelling will bring new therapeutic approaches.
Key Words: Heart failure • NH activation • LV remodeling