Non-Pulsatile Flow is Associated with Lower Levels of Circulating CD34+ Cells in LVAD-Supported Patients

Abstract

The lack of pulsatility may be associated with altered angiogensis in LVAD patients. Since CD34+ cells represent an important regulator of angiogenesis in heart failure, we sought to investigate a potential correlation between flow pulsatility and circulating CD34+ cell levels in this patient population. In a single-center prospective cohort study we measured peripheral CD34+ cell numbers in patients undergoing LVAD support for at least 3 months. Patients with active infection, active hematologic disorders and history of chemotherapy were excluded. Pulsatile flow was defined as aortic valve opening in each cardiac cycle in the setting of optimized left ventricular unloading. Peripheral CD34+ cells were quantified by flow cytometry using the International Society of Hemotherapy and Graft Engineering protocol. Of 12 patients, pulsatile flow was established in 6 patients (Group A) and 6 patients failed to demonstrate flow pulsatility (Group B). The two groups did not differ in age (60±9 years in Group A vs. 59±6 years in Group B, P=0.97), gender (male; 83% vs. 83%, P=1.00), heart failure etiology (ischemic: 50% vs. 52%, P=0.84), serum creatinine (1.10±0.19 mg/dL vs. 0.97±0.17 μmol/L, P=0.35), NT-proBNP (926±587 pg/mL vs. 1562±1190 pg/mL, P=0.35), LDH levels (3.2±0.5 μmol/L vs. 3.4±3.2 μmol/L, P=0.79), length of LVAD support (932±369 days vs. 462±298 days, P=0.10), mean blood pressure (86±9 mmHg vs. 83±4 mmHg, P=0.43) or estimated pump flow (4.8±0.9 L/min vs. 4.3±0.6 L/min, P=0.32). Pulsatility index was higher in Group A than in Group B (5.6±1.2 vs. 3.6±0.6, P=0.006). Despite similar leukocyte counts (6.7±0.9x109/L in Group A vs. 7.3±0.8 x109/L in Group B, P=0.52), hemoglobin (12.6±7.3 g/dL vs. 13.5±1.6 g/dL, P=0.28) and serum iron (16±10 μmol/L vs. 14±5 μmol/L, P=0.66) we found significantly higher peripheral CD34+ cell count in Group A than in Group B (2.4±0.7x106/L vs. 1.6±0.8 x106/L, P=0.03). Overall, CD34+ cell count was inversely related to red cell distribution width (R2=0.-58 , P=0.05). Non-pulsatile flow appears to be associated with lower numbers of peripheral CD34+ cells in LVAD-supported patients. This suggests that hemodynamic changes after prolonged LVAD support may significantly alter angiogenesis and vasculogenesis pathways in chronic heart failure.