Role of endothelin in microvascular dysfunction following percutaneous coronary intervention for non-ST elevation acute coronary syndromes: a single-centre randomised controlled trial

Raviteja R Guddeti, Abhiram Prasad, Yasushi Matsuzawa, Tatsuo Aoki, Charanjit Rihal, David Holmes, Patricia Best, Ryan J Lennon, Lilach O Lerman, Amir Lerman, Raviteja R Guddeti, Abhiram Prasad, Yasushi Matsuzawa, Tatsuo Aoki, Charanjit Rihal, David Holmes, Patricia Best, Ryan J Lennon, Lilach O Lerman, Amir Lerman

Abstract

Objectives: Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor, and its expression is increased in atherosclerosis and after PCI. In this study, we aim to define the role of endothelin in regulating coronary microvascular blood flow and myocardial perfusion following PCI in patients with non-ST elevation acute coronary syndromes (NSTACS), by assessing whether adjunctive therapy with a selective endothelin A (ETA) receptor antagonist acutely improves postprocedural coronary microvascular blood flow.

Methods: In a randomised, double-blinded, placebo-controlled trial, 23 NSTACS patients were enrolled to receive an intracoronary infusion of placebo (n=11) or BQ-123 (n=12) immediately before PCI. Post-PCI coronary microvascular blood flow and myocardial perfusion were assessed by measuring Doppler-derived average peak velocity (APV), and cardiac biomarker levels were quantified.

Results: Compared with the placebo group, APV was significantly higher in the drug group immediately after PCI (30 (20, 37) vs 19 (9, 26) cm/s; p=0.03). Hyperaemic APV, measured post-adenosine administration, was higher in the BQ-123 group, but the difference did not achieve statistical significance (56 (48, 72) vs 46 (34, 64) cm/s; p=0.090). Maximum coronary flow reserve postprocedure was not different between the two groups (2.1 (1.6, 2.3) vs 2.5 (1.8, 3.0)). Per cent change in creatine kinase isoenzyme MB from the time of PCI to 8 and 16 hours post-PCI was significantly lower in the drug group compared with the placebo group (-17 (-26, -10) vs 26 (-15, 134); p=0.02 and -17 (-38, 14) vs 107 (2, 446); p=0.007, respectively).

Conclusions: Endothelin is a mediator of microvascular dysfunction during PCI in NSTACS, and adjunctive selective ETA antagonist may augment myocardial perfusion during PCI.

Trial registration number: NCT00586820; Results.

Figures

Figure 1
Figure 1
Study design. Patient enrolment, randomisation and study protocol. NSTEMI, non-ST elevation myocardial infarction; PCI, percutaneous coronary intervention.
Figure 2
Figure 2
Average peak velocity. APV (cm/s) in drug and placebo groups immediately post-PCI and after intracoronary adenosine infusions.
Figure 3
Figure 3
(A) Percentage change in CK-MB levels. Percentage change in CK-MB levels from the time of PCI to 8 and 16 hours post-PCI. (B) Percentage change in cTnT levels. Percentage change in cTnT from the time of PCI to 8 and 16 hours after PCI.

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