Abstract 17537: Myocardial Dysfunction is Associated With Impaired Angiogenesis in Patients With Heart Failure With Preserved Ejection Fraction

Abstract

Background: Recent evidence suggests that myocardial microvascular damage may represent a key parameter in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Aim: We sought to investigate a potential correlation between parameters of angiogenesis and myocardial dysfunction in HFpEF patients. Methods: We enrolled 30 consecutive HFpEF patients with NYHA class III, left ventricular ejection fraction (LVEF) >50%, E/e' >15, and NT-proBNP >300 pg/ml. In all patients endothelial progenitor cells (EPCs) were mobilized by granulocyte-colony stimulating factor (G-CSF; 10 mcg/kg, 5 days) and collected via apheresis. Before EPC mobilisation we performed echocardiography and measured plasma levels of biomarkers of angiogenesis. All patients underwent electroanatomical mapping for the measurement of myocardial viability; preserved viability was defined as mean unipolar voltage> 8.3 mV. Results: Myocardial viability was preserved in 11 patients (37%; Group A) and decreased in 19 patients (63%; Group B). The groups did not differ in age (63±10 years in Group A vs. 61±8 years in Group B, P=0.78), gender (male: 73% vs. 79%, P=0.70), serum creatinine (1.07±0.34 mg/dL vs. 1.04±0.40 mg/dL, P=0.43), or LVEF (60±7% vs. 57±4%, P=0.32). In Group B we found higher levels of NT-proBNP (2370±1020 pg/mL vs. 920±455 pg/mL in Group A, P=0.04) and E/e’ (23.2±3.1 vs. 17.4±1.8 pg/ in Group A, P=0.02). After G-CSF stimulation, we found significantly lower numbers of EPCs in Group B (53±42 x10 6 cells/L) than in Group A (102±52 x10 6 cells/L, P=0.001). Similarly, apheresis yielded lower numbers of EPCs in Group B (85±82 x10 6 cells vs. 200±93 x10 6 cells in Group A, P=0.003). When compared to Group A, patients in Group B displayed lower levels of pro-angiogenic biomarkers (agiopoietin-1: 7.4±2.8 ng/mL vs. 12.4±5.1 ng/mL, P=0.02; vascular endothelial growth factor: 27.5±20.1 pg/mL vs. 51.6±24.2 pg/mL, P=0.01), and higher levels of anti-angiogenic biomarkers (endostatin: 56.5±19.1 ng/mL vs. 33.2±14.3 ng/mL, P=0.01; thrombospondin-2: 16.4±4.3 ng/mL vs. 9.2±5.0 ng/mL, P=0.03). Conclusion: In patients with HFpEF, myocardial dysfunction appears to correlate with reduced mobilisation of endothelial progenitor cells and impaired angiogenesis.