Abstract 17998: Impairment of Vascular Bone Marrow Niche Predicts Death in Patients With Chronic Heart Failure

Abstract

Background: The bone marrow vascular niche is essential for hematopoietic regeneration. Patients with chronic heart failure are characterized by myelosuppresion and anemia. Therefore, in order to investigate whether chronic heart failure is associated with an impairment in the vascular niche of the bone marrow, we measured in bone marrow plasma levels of the prototypical angiogenic factor PlGF (placental growth factor), as well as, its soluble inhibitor, sFlt-1 (Fms-like tyrosine kinase 1), which acts as a decoy receptor for PlGF, as a measure of the functional integrity of the vascular bone marrow niche. Methods and Results: Bone marrow plasma levels of sFlt-1 and PlGF were determined by ELISA in 187 patients (mean age: 62.2±11.3years) with chronic heart failure, who were enrolled in the Frankfurt Bone Marrow-Derived Mononuclear Cell Therapy Registry. Fifty-one patients died within the 5-year follow-up period. Patients with increased bone marrow-derived sFlt-1/PlGF ratio had a 1.35-fold increased risk for death (95%CI: 1.08 to 1.68, p=0.007). This association was robust after adjustment for age, gender, left ventricular ejection fraction (LVEF), eGFR and NT-proBNP serum levels (HR:1.3, 95%CI: 1.014 to 1.678, p=0.038) or the Seattle Heart Failure score (HR:1.38, 95%CI: 1.112 to 1.723, p=0.004). Importantly, this association remained significant even after adjustment for colony-forming unit capacity (HR:1.33, 95%CI: 1.051 to 1.675, p=0.018) and SDF-1-induced migratory capacity of bone marrow-derived cells (HR:1.35, 95%CI: 1.087 to 1.678, p=0.007). Conclusions: The present study for the first time discloses that an impairment of the angiogenic potential of the bone marrow microenvironment, defined as increased sFlt-1 to PlGF ratio in the bone marrow plasma, is independently associated with mortality in patients with chronic heart failure. These data further corroborate the importance of the bone marrow-heart axis to predict clinical outcome in patients with chronic heart failure.