Abstract
Background
Adverse left ventricular (LV) remodelling is associated with development of heart failure and poor outcomes in patients with acute myocardial infarction (AMI). Understanding the immunomodulatory mechanisms of LV remodelling is an essential step for the development of novel therapies. Interferon-γ-inducible protein-10 (IP-10)/CXCL10 is a chemokine involved in the recruitment of activated T cells into sites of tissue inflammation. Although IP-10 was reported to reduce adverse LV remodeling in a preclinical myocardial infarction model, its role in LV remodeling in humans with AMI remains unknown.
Purpose
To determine the clinical predictive value of serum IP-10 in LV remodeling in patients with ST-segment elevation myocardial infarction (STEMI).
Methods
This is a substudy of the double-blind, randomised controlled trial “Evaluating the effectiveness of intravenous ciclosporin on reducing reperfusion injury in patients undergoing primary percutaneous coronary intervention” (CAPRI; ClinicalTrials.gov registry number NCT02390674), which enrolled 52 acute STEMI patients. LV remodeling was assessed by cardiovascular magnetic resonance (CMR) imaging and was defined as the 12-week vs. the 3-day post-myocardial infarction change of the left ventricular ejection fraction (ΔLVEF), LV end-diastolic volume (ΔEDV) or LV end-systolic volume (ΔESV). Serum IP-10 was measured before and 5min, 15min, 30min, 90min and 24h after reperfusion by ELISA. Linear regression analysis was used to determine the independent association of IP-10 with the endpoints of the study.
Results
Serum IP-10 concentration peaked at 30min after reperfusion followed by a 2-fold decrease at the 24h post reperfusion compared to pre-reperfusion levels (P<0.001 for all). Comparison of the 12-week CMR to the baseline CMR imaging revealed that baseline pre-reperfusion as well as 5min, 15min, 30min and 90min, but not 24h, post-reperfusion IP-10 serum levels associated with increased LVEF and decreased ESV at 12-weeks (range correlation coefficient r=[0.35–0.41], P<0.05 with ΔLVEF and r=[−0.33 to −0.44], P<0.05 with ΔESV) indicating that the increase of IP-10 at the acute phase of myocardial infarction confers a cardioprotective role. Multivariable linear regression analysis for ΔLVEF showed that in a model including baseline pre-reperfusion or 5min or 15min or 30min or 90min post-reperfusion IP-10 and age, gender, traditional risk factors (arterial hypertension, body-mass index, hyperlipoproteinemia, diabetes mellitus, smoking, family history of CAD), infarct location, admission high-sensitivity troponin T, door-to-balloon time and ciclosporin treatment, only IP-10 was the independent determinant of ΔLVEF.
Conclusions
Increased serum IP-10 levels early after reperfusion are associated with reverse LV remodeling in patients with STEMI undergoing primary PCI. The clinical application of IP-10 as a novel biomarker of LV remodeling post-AMI should be further explored and validated.
Funding Acknowledgement
Type of funding source: None
Dynamic changes in injured myocardium, very early after acute myocardial infarction, quantified using T1 mapping cardiovascular magnetic resonance
