Pei-Hsun Sung1,2,3, Wei-Chun Huang4, Ting-Hsing Chao5, Cheng-Han Lee5, Teng-Yao Yang6, Yu-Sheng Lin6, Rei-Yeuh Chang7, Jun-Ted Chong8, Cheng-Hsu Yang1, Chieh-Jen Chen1, Sheng-Ying Chung1, Shu-Kai Hsueh1, Chiung-Jen Wu1, Hon-Kan Yip1,2,3,9,10. 1. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine. 2. Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine. 3. Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung. 4. Department of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung. 5. Division of Cardiology, Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan. 6. Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi. 7. Division of Cardiology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City. 8. Division of Cardiology, Department of Internal Medicine, Pingtung Christian Hospital, Pingtung. 9. Department of Medical Research, China Medical University Hospital, China Medical University. 10. Department of Nursing, Asia University, Taichung, Taiwan.
Abstract
BACKGROUND: Ischemia-reperfusion injury following acute ST-segment elevation myocardial infarction (STEMI) is strongly related to inflammation. However, whether intracoronary (IC) tacrolimus, an immunosuppressant, can improve myocardial perfusion is uncertain. METHODS: A multicenter double-blind randomized controlled trial was conducted in Taiwan from 2014 to 2017. Among 316 STEMI patients with Killip class ≤ 3 undergoing primary percutaneous coronary intervention (PCI), 151 were assigned to the study group treated with IC tacrolimus 2.5 mg to the culprit vessel before first balloon inflation, and the remaining 165 were assigned to the placebo group receiving IC saline only. The primary endpoint was percentage of post-PCI TIMI-3 flow. The primary composite endpoints included achievement of TIMI-3 flow, TIMI- myocardial perfusion (TMP) grade, or 90-min ST-segment resolution (STR). The secondary endpoints were left ventricular ejection fraction (LVEF) and 1-month/1-year major adverse cardio-cerebral vascular events (MACCEs) (defined as death, myocardial infarction, stroke, target-vessel revascularization or re-hospitalization for heart failure). RESULTS: Although post-PCI TIMI-3 epicardial flow and MACCE rate at 1 month and 1 year did not differ between the two groups, TMP grade (2.54 vs. 2.23, p < 0.001) and 90-min STR (67% vs. 61%, p < 0.001) were significantly higher in the tacrolimus-treated group than in the placebo group. The STEMI patients treated with tacrolimus also had significantly higher 3D LVEF and less grade 2 or 3 LV diastolic dysfunction at 9 months compared to those without. CONCLUSIONS: IC tacrolimus for STEMI improved coronary microcirculation and 9-month LV systolic and diastolic functions. However, the benefit of tacrolimus on clinical outcomes remains inconclusive due to insufficient patient enrollment.
BACKGROUND: Ischemia-reperfusion injury following acute ST-segment elevation myocardial infarction (STEMI) is strongly related to inflammation. However, whether intracoronary (IC) tacrolimus, an immunosuppressant, can improve myocardial perfusion is uncertain. METHODS: A multicenter double-blind randomized controlled trial was conducted in Taiwan from 2014 to 2017. Among 316 STEMI patients with Killip class ≤ 3 undergoing primary percutaneous coronary intervention (PCI), 151 were assigned to the study group treated with IC tacrolimus 2.5 mg to the culprit vessel before first balloon inflation, and the remaining 165 were assigned to the placebo group receiving IC saline only. The primary endpoint was percentage of post-PCI TIMI-3 flow. The primary composite endpoints included achievement of TIMI-3 flow, TIMI- myocardial perfusion (TMP) grade, or 90-min ST-segment resolution (STR). The secondary endpoints were left ventricular ejection fraction (LVEF) and 1-month/1-year major adverse cardio-cerebral vascular events (MACCEs) (defined as death, myocardial infarction, stroke, target-vessel revascularization or re-hospitalization for heart failure). RESULTS: Although post-PCI TIMI-3 epicardial flow and MACCE rate at 1 month and 1 year did not differ between the two groups, TMP grade (2.54 vs. 2.23, p < 0.001) and 90-min STR (67% vs. 61%, p < 0.001) were significantly higher in the tacrolimus-treated group than in the placebo group. The STEMI patients treated with tacrolimus also had significantly higher 3D LVEF and less grade 2 or 3 LV diastolic dysfunction at 9 months compared to those without. CONCLUSIONS: IC tacrolimus for STEMI improved coronary microcirculation and 9-month LV systolic and diastolic functions. However, the benefit of tacrolimus on clinical outcomes remains inconclusive due to insufficient patient enrollment.
Entities:
Keywords:
Left ventricular systolic and diastolic function; Microcirculation; Myocardial perfusion; ST-segment elevation myocardial infarction; Tacrolimus
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