Coronary aspirate TNFα reflects saphenous vein bypass graft restenosis risk in diabetic patients

Theodor Baars, Thomas Konorza, Philipp Kahlert, Stefan Möhlenkamp, Raimund Erbel, Gerd Heusch, Petra Kleinbongard, Theodor Baars, Thomas Konorza, Philipp Kahlert, Stefan Möhlenkamp, Raimund Erbel, Gerd Heusch, Petra Kleinbongard

Abstract

Background: Patients with diabetes mellitus (DM) have an increased risk for periprocedural complications and adverse cardiac events after percutaneous coronary intervention. We addressed the potential for coronary microvascular obstruction and restenosis in patients with and without DM undergoing stenting for saphenous vein bypass graft (SVG) stenosis under protection with a distal occlusion/aspiration device.

Methods: SVG plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Percent diameter stenosis was determined from quantitative coronary angiography before, immediately after and 6 months after stent implantation. Coronary aspirate was retrieved during stent implantation and divided into particulate debris and plasma. Total calcium, several vasoconstrictors, and tumor necrosis factor (TNF)α in particulate debris and coronary aspirate plasma were determined.

Results: Patients with and without DM had similar plaque volume, but larger necrotic core and greater particulate debris release in patients with than without DM (20.3±2.7 vs. 12.7±2.6% and 143.9±19.3 vs. 75.1±10.4 mg, P<0.05). The TNFα concentration in particulate debris and coronary aspirate plasma was higher in patients with than without DM (15.9±6.6 vs. 5.1±2.4 pmol/mg and 2.2±0.7 vs. 1.1±0.2 pmol/L, P<0.05), whereas total calcium and vasoconstrictors were not different. Patients with DM had a greater percent diameter stenosis 6 months after stent implantation than those without DM (22.17±5.22 vs. 6.34±1.11%, P<0.05). The increase in TNFα immediately after stent implantation correlated with restenosis 6 months later (r=0.69, P<0.05).

Conclusion: In diabetics, particulate debris and coronary aspirate plasma contained more TNFα, which might reflect the activity of the underlying atherosclerotic process.

Trial registration: URL: http://www.clinicaltrials.gov/ct2/results?term=NCT01430884; unique identifier: NCT01430884.

Figures

Figure 1
Figure 1
SVG plaque volume (A) and composition (B) - Data are mean±SEM, comparison between patients with and without DM by unpairedt tests. DM = diabetes mellitus.
Figure 2
Figure 2
Amount of released particulate debris (A) and calcium concentration per amount of particulate debris (B) – The normalized amount of released particulate debris to stent volume in numbers in inserts; data are mean±SEM, comparison between patients with and without DM by unpairedttests. DM = diabetes mellitus.
Figure 3
Figure 3
Concentrations of serotonin (A), TxB2(B), and TNFα (C) per amount of particulate debris- Data are mean±SEM, comparison between patients with and without DM by unpairedt tests. DM = diabetes mellitus; TxB2 = thromboxane B2, TNFα = tumor necrosis factor α.
Figure 4
Figure 4
Vasoconstrictor responses to coronary arterial plasma before and to coronary aspirate plasma after stent implantation – Detected on rat mesenteric arteries with intact endothelium (+E) and denuded -E, respectively. Data are mean±SEM, comparison between patients with and without DM and before and after stent implantation by 2-way repeated measures ANOVA with Bonferroni’s correction. DM = diabetes mellitus.
Figure 5
Figure 5
Correlation between TNFα increase immediately after stent implantation and percent diameter stenosis 6 months later – Linear regression (black line) between the increase in TNFα and percent diameter stenosis in patients with (filled circle) and without (open circle) DM. TNFα = tumor necrosis factor α.

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