TY - JOUR
T1 - Role of endothelin in microvascular dysfunction following percutaneous coronary intervention for non-ST elevation acute coronary syndromes
T2 - A single-centre randomised controlled trial
AU - Guddeti, Raviteja R.
AU - Prasad, Abhiram
AU - Matsuzawa, Yasushi
AU - Aoki, Tatsuo
AU - Rihal, Charanjit
AU - Holmes, David
AU - Best, Patricia
AU - Lennon, Ryan J.
AU - Lerman, Lilach O.
AU - Lerman, Amir
N1 - Funding Information:
The authors sincerely thank Ms Rebecca E. Nelson for study coordination and Ms Jonella M. Tilford and Ms Lynn E. Polk for imaging technical support. This study was funded by Department of Cardiology, Mayo Clinic and Mayo Foundation.
Publisher Copyright:
© 2016, BMJ Publishing Group. All rights reserved.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
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U2 - 10.1136/openhrt-2016-000428
DO - 10.1136/openhrt-2016-000428
M3 - Article
AN - SCOPUS:84981313211
SN - 2053-3624
VL - 3
JO - Open Heart
JF - Open Heart
IS - 2
M1 - e000428
ER -