Abstract 12035: Higher Numbers of Circulating CD34+ Cells Are Associated With More Pronounced Effects of Neprilysin Inhibitors in Patients With Chronic Heart Failure

Introduction:Preliminary evidence suggests that neprilysin inhibitors (ARNI) may affect angiogenesis in heart failure with reduced ejection fraction (HFrEF).Hypothesis:Since CD34+ cells represent one of the key determinants of vasculogenesis and angiogenesis, we investigated a potential association between clinical effects of ARNI and circulating CD34+ cell count in HFrEF.Methods:We performed a prospective single center pilot cohort study in 27 HFrEF patients. After enrollment, all patients received standard heart failure therapy including ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARB) for 3 months. At this point, ACE-I/ARB were switched to ARNI. At the time of switch, we measured circulating CD34+ cell count using Beckman-Coulter Navios EX flow cytometry with standard antibodies according to ISAGE protocol. All patients were followed for 6 months after the switch. Favorable response to ARNI therapy was defined as an increase in left ventricular ejection fraction (LVEF) ≥5% at 6-month follow-up.Results:At 6 months we found a favorable response to ARNI in 18 patients (64%, Group A), and 10 had less favorable response (36%, Group B). Before ARNI introduction the groups did not differ in gender (male: 94% in Group A vs. 78% in Group B, P=0.21), heart failure etiology (ischemic: 35% vs. 23%, P=0.49), diabetes (11% vs. 22%, P=0.46), renal dysfunction (22% vs. 43%, P=0.25), hypertension (28% vs. 55%, P=0.17), LVEF (36±5% vs. 34±7%, P=0.41), LVEDV (181±57 mL vs. 185±36 mL, P=0.83), TAPSE (1.8±0.8 vs. 1.9±0.4, P=0.91) or NT-proBNP (980±1438 pg/mL vs. 780±603 pg/mL, P=0.70). Compared to Group B, patients in Group A were younger (52±13 years vs. 64±9 years, P=0.03) and had a higher CD34+ cell count (2.9±2.0x106/L vs. 1.2±0.5x106/L, P=0.02). When compared to the remainig cohort, patients with CD34+ cell count above the median displayed a significantly higher increase in LVEF (+8.1±3.2% vs. +4.7±3.7%, P=0.03), and a trend of increase in TAPSE (+0.4±0.4 cm vs. -0.1±0.7 cm, P=0.06).Conclusion:Higher numbers of circulating CD34+ cells appear to be associated with more pronounced beneficial effects of ARNI therapy in HFrEF patients. Thus, the effects or ARNI in heart failure may be partly mediated through modulation of vascular homeostasis.