Abstract Body (Do not enter title and authors here): Introduction: B cells infiltrate the heart in a CXC chemokine receptor type 5 (CXCR5)-dependent manner and influence inflammation and remodeling. Yet whether CXCR5 expression on circulating B cells can be used as a marker to identify patients more likely to respond to pacing therapies for heart failure (HF) like cardiac resynchronization therapy (CRT) is unknown
Research Question: Is the amount of CXCR5 expression on circulating B cells in humans prior to CRT associated with measures of left ventricular (LV) functional and neurohormonal response to CRT?
Hypothesis: We hypothesized that lower B cell expression of CXCR5 pre-CRT is associated with greater improvements in LV function and neurohormonal activation (B-type natriuretic peptide [BNP]) after CRT.
Methods: Protein expression in cryopreserved peripheral blood mononuclear cells (PBMCs) was measured with cytometry by time of flight (CyTOF). CXCR5 expression in B cell subsets was evaluated before and six months after CRT in 24 patients. Cardiac magnetic resonance (CMR) was performed prior to CRT, and the LV end-systolic volume index (LVESVI) before and after CRT was assessed by echocardiography. Response was defined as a 15% reduction in the LVESVI six months after CRT.
Results: In 24 patients with HF undergoing CRT, the median age was 68 years (IQR 61 to 75 years), 38% were female, and 15 were responders (R). The median pre-CRT serum BNP concentration was 178 pg/mL (IQR 94-251 pg/mL) in R and 430 (IQR 272-757 pg/mL) in non-responders (NR) (p=0.07). The median pre-CRT LVESVI was 74 mL/m² (IQR 60 to 103 mL/m²) in R and 90 mL/m² (IQR 83 to 110 mL/m²) in NR (p=0.19). Pre-CRT CXCR5 expression in naive B cells (CD27- IgDhiCD196lo IgMlo) was lower in R v. NR (p=0.0016) (Figure 1). The area under the receiver operating characteristic curve (AUROC) for response was 0.80 (p=0.0026) with B cell CXCR5 as the only predictor and 0.89 (p=0.0015) with both B cell CXCR5 and the pre-CRT CMR LV ejection fraction (LVEF) as predictors (Figure 2). The odds ratio for response per unit increase of B cell CXCR5 was 0.18 (p=0.027) in the latter model. Pre-CRT B cell CXCR5 expression was also correlated with the change in BNP six months after CRT (r=0.45, p=0.027) (Figure 3).
Conclusions: B cell CXCR5 may be an important predictor of CRT response based on LV function and neurohormones even after adjustment for known predictors. Further investigation of B-cell CXCR5 for prognosis in HF patients undergoing CRT is of great interest.