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      Comparison of Intracoronary Epinephrine and Adenosine for No-Reflow in Normotensive Patients With Acute Coronary Syndrome (COAR Trial)

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          Abstract

          Background:

          Intracoronary epinephrine has been effectively used in treating refractory no-reflow, but there is a dearth of data on its use as a first-line drug in normotensive patients in comparison to the widely used adenosine.

          Methods:

          In this open-labeled randomized clinical trial, 201 patients with no-reflow were randomized 1:1 into intracoronary epinephrine as the treatment group and intracoronary adenosine as the control group and followed for 1 month. The primary end points were improvement in coronary flow, as assessed by TIMI (Thrombolysis in Myocardial Infarction) flow, frame counts, and myocardial blush. Secondary end points were in-hospital and short-term mortality and major adverse cardiac events.

          Results:

          In all, 101 patients received intracoronary epinephrine and 100 patients received adenosine. Epinephrine was generally well tolerated with no immediate table death or ventricular fibrillation. No-reflow was more effectively improved with epinephrine with final TIMI III flow (90.1% versus 78%, P=0.019) and final corrected TIMI frame count (24±8.43 versus 26.63±9.22, P=0.036). However, no significant difference was observed in final grade III myocardial blush (55.4% versus 45%, P=0.139), mean reduction of corrected TIMI frame count (−25.71±11.79 versus −26.08±11.71, P=0.825), in-hospital and short-term mortality, and major adverse cardiac events.

          Conclusions:

          Epinephrine is relatively safe to use in no-reflow in normotensive patients. A significantly higher frequency of post-treatment TIMI III flow grade and lower final corrected TIMI frame count with relatively better achievement of myocardial blush grade III translate into it displaying relatively better efficacy than adenosine.

          Registration:

          URL: https://www.clinicaltrials.gov; Unique identifier: NCT04699110.

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          Most cited references22

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          TIMI frame count: a quantitative method of assessing coronary artery flow.

          Although the Thrombolysis in Myocardial Infarction (TIMI) flow grade is valuable and widely used qualitative measure in angiographic trials, it is limited by its subjective and categorical nature. In normal patients and patients with acute myocardial infarction (MI) (TIMI 4), the number of cineframes needed for dye to reach standardized distal landmarks was counted to objectively assess an index of coronary blood flow as a continuous variable. The TIMI frame-counting method was reproducible (mean absolute difference between two injections, 4.7 +/- 3.9 frames, n=85). In 78 consecutive normal arteries, the left anterior descending coronary artery (LAD) TIMI frame count (36.2 +/- 2.6 frames) was 1.7 times longer than the mean of the right coronary artery (20.4 +/- 3.0) and circumflex counts (22.2 +/- 4.1, P < .001 for either versus LAD). Therefore, the longer LAD frame counts were corrected by dividing by 1.7 to derive the corrected TIMI frame count (CTFC). The mean CTFC in culprit arteries 90 minutes after thrombolytic administration followed a continuous unimodal distribution (there were not subpopulations of slow and fast flow) with a mean value of 39.2 +/- 20.0 frames, which improved to 31.7 +/- 12.9 frames by 18 to 36 hours (P < .001). No correlation existed between improvements in CTFCs and changes in minimum lumen diameter (r=-.05, P=.59). The mean 90-minute CTFC among nonculprit arteries (25.5 +/- 9.8) was significantly higher (flow was slower) compared with arteries with normal flow in the absence of acute MI (21.0 +/- 3.1, P < .001) but improved to that of normal arteries by 1 day after thrombolysis (21.7 +/- 7.1, P=NS). The CTFC is a simple, reproducible, objective and quantitative index of coronary flow that allows standardization of TIMI flow grades and facilitates comparisons of angiographic end points between trials. Disordered resistance vessel function may account in part for reductions in flow in the early hours after thrombolysis.
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            ACC/AHA Guidelines for the Clinical Application of Echocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography). Developed in collaboration with the American Society of Echocardiography.

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              No-reflow phenomenon following percutaneous coronary intervention for acute myocardial infarction: incidence, outcome, and effect of pharmacologic therapy.

              No-reflow (NR) phenomenon is a well-known problem, often accompanying percutaneous coronary intervention for acute ST elevation myocardial infarction (STEMI). There are little data on effects of pharmacologic therapy on the resolution, outcome, and long-term natural history of NR. Retrospectively assess incidence, management, and prognosis of NR in a tertiary referral hospital. Study included patients with STEMI, treated with percutaneous coronary intervention (PCI). Effect of pharmacologic therapy and long-term outcome were assessed. NR was defined by thrombolysis in myocardial infarction (TIMI) < 3 or myocardial blush grade (MBG) < 3. Of 347 identified subjects, NR occurred in 110 (32%) by TIMI and 198 (57%) by MBG. Higher incidence was identified in men versus women (34% vs. 25% by TIMI, P = 0.08; and 60% vs. 48% by MBG, P = 0.04). Pharmacologic therapy was equally effective in restoring normal flow, increasing TIMI score from 1.62 ± 0.07 to 2.78 ± 0.06 (P < 0.0001) and MBG score from 0.43 ± 0.08 to 2.09 ± 0.11 (P < 0.0001). Twenty-three percent who did not receive pharmacologic therapy developed clinical composite of congestive heart failure, cardiogenic shock, and/or death; only 9% of patients who received pharmacologic therapy developed this composite. Patients with severe NR despite treatment had poorer prognosis. Sixty-five percent of patients who survived and had repeat angiogram about 1.5 years later had spontaneous improvement in coronary flow by MBG. NR is common in STEMI. Treatment with nicardipine, nitroprusside, and verapamil are equally effective in improving flow. If not treated, prognosis is poor. ©2010, Wiley Periodicals, Inc.
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                Author and article information

                Contributors
                Journal
                Circ Cardiovasc Interv
                Circ Cardiovasc Interv
                HCV
                Circulation. Cardiovascular Interventions
                Lippincott Williams & Wilkins (Hagerstown, MD )
                1941-7640
                1941-7632
                10 January 2022
                February 2022
                : 15
                : 2
                : e011408
                Affiliations
                [1]Department of Adult Cardiology (K.A.K., N.Q., T.S., J.A.S., D.K., R.K., D.Q., U.Y., J.J.), National Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan.
                [2]Department of Clinical Research (M.K.), National Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan.
                Author notes
                Correspondence to: Kamran Ahmed Khan, FCPS(Card), Assistant Professor & Interventional Cardiologist at National Institute of Cardiovascular Diseases (NICVD), Rafiqui (H.J.) Shaheed Rd, Karachi-75510, Sindh, Pakistan. Email kamran00480@ 123456yahoo.com
                Article
                00008
                10.1161/CIRCINTERVENTIONS.121.011408
                8843359
                35000456
                e142ca1e-2abd-4878-a435-219b289fb7c9
                © 2022 The Authors.

                Circulation: Cardiovascular Interventions is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

                History
                : 24 August 2021
                : 8 November 2021
                Categories
                10007
                10021
                10029
                10033
                Original Articles
                Coronary Interventions
                Custom metadata
                TRUE

                acute coronary syndrome,adenosine,epinephrine,myocardial infarction,percutaneous coronary intervention

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