Concomitant elevated serum levels of tenascin, MMP-9 and YKL-40, suggest ongoing remodeling of the heart up to 3 months after cardiac surgery after normalization of the revascularization markers

Abstract

Abstract Background The recovery from cardiac surgery involves resolving inflammation and remodeling with significant connective tissue turnover. Dynamics of smoldering inflammation and injury (white blood cells, platelets, CRP, IL-8, IL-6), vascular inflammation (IL-15, VEGF, RANTES), connective tissue remodeling (tenascin, MMP-9), cardiac injury and remodeling (YKL-40), and vascular remodeling (epiregulin, MCP-1, VEGF) were assessed up to 3 months after cardiac surgery. We hypothesize that at 3 months, studied markers will return to pre-surgical levels. Methods Patients (n = 139) scheduled for non-emergent heart surgery were included, except for patients with pre-existing immunological aberrancies. Blood was collected before surgery(tbaseline), 24 h later(t24h) after the first sample, 7 days(t7d), and 3 months(t3m) after tbaseline. Serum markers were measured via multiplex or ELISA. Electronic medical records (EMR) were used to extract demographical, pre-existing conditions and clinical data. Disposition (discharge home, discharge to facility, death, re-admission) was determined at 28 days and 3 months from admission. Results Not all inflammatory markers returned to baseline (CRP↑↑, leukocytosis, thrombocytosis, IL-8↓, IL-6↓). Tenascin and YKL-40 levels remained elevated even at t3m. YKL-40 serum levels were significantly elevated at t24h and t7d while normalized at t3m. VEGF returned to the baseline, yet MCP-1 remained elevated at 3 months. CCL28 increased at 3 months, while RANTES and IL-15 declined at the same time. Disposition at discharge was determined by serum MMP-9, while YKL-40 correlated with duration of surgery and APACHE II24h. Conclusions The data demonstrated an ongoing extracellular matrix turnover at 3 months, while acute inflammation and vascular remodeling resolved only partially.