Right Ventricular Dysfunction Correlates With Decreased Endothelial Progenitor Cell Mobilisation And Impaired Angiogenesis In Patients With Dilated Cardiomyopathy

Aim: Although we have previously demonstrated that CD34 + cell therapy may improve right ventricular (RV) function in non-ischemic dilated cardiomyopathy (NICM), the underlying mechanisms remain poorly defined. We sought to investigate a potential correlation between RV function and alterations in angiogenesis in this patient population. Methods: . We enrolled 43 consecutive patients with NICM, NYHA class III, and LVEF<40%. 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. The presence of RV dysfunction was defined as TAPSE<17 mm, pulsed Doppler S wave< 9.5 cm/s and RV fractional area change< 35%. Results: . RV dysfunction was present in 25/43 patients (58%, RVD Group), and 18/43 patients had preserved RV function (42%, No-RVD Group). The groups did not differ in age, gender, serum creatinine, bilirubin, left ventricular ejection fraction, or NT-proBNP levels. After G-CSF stimulation, we found significantly lower numbers of EPCs in RVD Group (44±43 x10 6 cells/L) than in No-RVD Group (92±53 x10 6 cells/L, P=0.001). Similarly, apheresis yielded significantly lower numbers of EPCs in RVD Group (81±82 x10 6 cells vs. 205±100 x10 6 cells in No-RVD Group, P=0.001). When compared to No-RVD Group, patients in RVD Group displayed lower levels of vascular endothelial growth factor (32±23 pg/mL vs. 51±24 pg/mL, P=0.01), and higher levels of agiopoietin-2 (61±33 ng/mL vs. 21±18 ng/mL, P=0.01), endostatin (86±30 pg/mL vs. 63±27 ng/mL, P=0.01), and thrombospondin (180±74 pg/mL vs. 93±84 ng/mL, P=0.01), implicating a more pronounced impairment of angiogenetic pathway. Conclusion: In patients with NICM, RV dysfunction appears to correlate with reduced mobilisation of endothelial progenitor cells and impaired angiogenesis.