Urinary proteomic signatures associated with β-blockade and heart rate in heart transplant recipients.

Abstract

Heart transplant (HTx) recipients have a high heart rate (HR), because of graft denervation and are frequently started on β-blockade (BB). We assessed whether BB and HR post HTx are associated with a specific urinary proteomic signature. In 336 HTx patients (mean age, 56.8 years; 22.3% women), we analyzed cross-sectional data obtained 7.3 years (median) after HTx. We recorded medication use, measured HR during right heart catheterization, and applied capillary electrophoresis coupled with mass spectrometry to determine the multidimensional urinary classifiers HF1 and HF2 (known to be associated with left ventricular dysfunction), ACSP75 (acute coronary syndrome) and CKD273 (renal dysfunction) and 48 sequenced urinary peptides revealing the parental proteins. In adjusted analyses, HF1, HF2 and CKD273 (p ≤ 0.024) were higher in BB users than non-users with a similar trend for ACSP75 (p = 0.06). Patients started on BB within 1 year after HTx and non-users had similar HF1 and HF2 levels (p ≥ 0.098), whereas starting BB later was associated with higher HF1 and HF2 compared with non-users (p ≤ 0.014). There were no differences in the urinary biomarkers (p ≥ 0.27) according to HR. BB use was associated with higher urinary levels of collagen II and III fragments and non-use with higher levels of collagen I fragments. BB use, but not HR, is associated with a urinary proteomic signature that is usually associated with worse outcome, because unhealthier conditions probably lead to initiation of BB. Starting BB early after HTx surgery might be beneficial.