Study of Microvascular Dysfunction, CFR and Cardioprotective Effect of Early Administration of Esmolol in MI

Summary

Study rationale: to evaluate clinical and prognostic relevance of microvascular dysfunction, coronary flow reserve and cardioprotective effects of iv administration of esmolol in patients with myocardial infarction. First substudy is an open randomized trial evaluating the efficacy and safety of early intravenous administration of esmolol in patients with acute ST-segment elevation myocardial infarction (MI) and relative contraindications to administration of other intravenous β1-adrenergic blocker (metoprolol etс.). Сomparison group will include patients who have not received intravenous β1-adrenergic blocker. Secondary outcome in this substudy is the degree of microvascular obstruction and infarct size according to MRI with gadolinium delayed enhancement. Second substudy examines the quantitative parameters of coronary physiology in patients with MI and multivessel disease. Changes of coronary physiology measurements over time ((iFR, Pd/Pa, FFR, delta FFR, gradient FFR per time unit (dFFR(t)/dt), pullback pressure gradient (PPG)) measured in the infarct-related artery and in non-infarct-related arteries with diameter stenosis of 50-85% immediately after the completion of a primary percutaneous coronary intervention and during a second hospitalization (30-45 days after STEMI) will be evaluated. The comparison changes of coronary physiology over time with presence of an MVO and infarct size determined by MRI. The model of calculating coronary flow reserve (CFR) based on tridimensional reconstruction of coronary arteries and coronary physiology parameters as measured during coronary angiography will be developed. The influence of coronary physiology parameters measured after complete myocardial revascularization by PCI, and derived CFR in patients with MI on long-term clinical outcomes will be evaluated, based on prospective data collection. Primary composite outcome in all substudies will be the sum of adverse cardiac outcomes (congestive heart failure, episodes of recurrent congestive heart failure worsening resulting in hospitalizations, cardiac mortality, MI recurrences, unstable angina, urgent myocardial revascularization) within \> 12 months post-infarction. Secondary composite outcome in all substudies is the degree of microvascular obstruction and infarct size evaluated by MRI with gadolinium delayed enhancement.

Timeline

Start

2024-01-29

Primary completion

2029-01-29

Completion

2030-01-29

Publications

• Background Sun B, Wang CY, Chen RR. Clinical Efficacy and Safety of Early Intravenous Administration of Beta-Blockers in Patients Suffering from Acute ST-Segment Elevation Myocardial Infarction Without Heart Failure Undergoing Primary Percutaneous Coronary Intervention: A Study-Level Meta-Analysis of Randomized Clinical Trials. Cardiovasc Drugs Ther. 2024 Aug;38(4):833-846. doi: 10.1007/s10557-023-07448-x. Epub 2023 Apr 1.
• Background Garcia-Ruiz JM, Fernandez-Jimenez R, Garcia-Alvarez A, Pizarro G, Galan-Arriola C, Fernandez-Friera L, Mateos A, Nuno-Ayala M, Aguero J, Sanchez-Gonzalez J, Garcia-Prieto J, Lopez-Melgar B, Martinez-Tenorio P, Lopez-Martin GJ, Macias A, Perez-Asenjo B, Cabrera JA, Fernandez-Ortiz A, Fuster V, Ibanez B. Impact of the Timing of Metoprolol Administration During STEMI on Infarct Size and Ventricular Function. J Am Coll Cardiol. 2016 May 10;67(18):2093-2104. doi: 10.1016/j.jacc.2016.02.050. Epub 2016 Apr 3.
• Background Er F, Dahlem KM, Nia AM, Erdmann E, Waltenberger J, Hellmich M, Kuhr K, Le MT, Herrfurth T, Taghiyev Z, Biesenbach E, Yuksel D, Eran-Ergoknil A, Vanezi M, Caglayan E, Gassanov N. Randomized Control of Sympathetic Drive With Continuous Intravenous Esmolol in Patients With Acute ST-Segment Elevation Myocardial Infarction: The BEtA-Blocker Therapy in Acute Myocardial Infarction (BEAT-AMI) Trial. JACC Cardiovasc Interv. 2016 Feb 8;9(3):231-240. doi: 10.1016/j.jcin.2015.10.035.
• Background Clemente-Moragon A, Gomez M, Villena-Gutierrez R, Lalama DV, Garcia-Prieto J, Martinez F, Sanchez-Cabo F, Fuster V, Oliver E, Ibanez B. Metoprolol exerts a non-class effect against ischaemia-reperfusion injury by abrogating exacerbated inflammation. Eur Heart J. 2020 Dec 7;41(46):4425-4440. doi: 10.1093/eurheartj/ehaa733.
• Background Van Herck PL, Paelinck BP, Haine SE, Claeys MJ, Miljoen H, Bosmans JM, Parizel PM, Vrints CJ. Impaired coronary flow reserve after a recent myocardial infarction: correlation with infarct size and extent of microvascular obstruction. Int J Cardiol. 2013 Jul 31;167(2):351-6. doi: 10.1016/j.ijcard.2011.12.099. Epub 2012 Jan 13.
• Background Anderson HVS. Acute Coronary Physiology. JACC Cardiovasc Interv. 2020 May 25;13(10):1168-1170. doi: 10.1016/j.jcin.2020.03.037. No abstract available.
• Background Kelshiker MA, Seligman H, Howard JP, Rahman H, Foley M, Nowbar AN, Rajkumar CA, Shun-Shin MJ, Ahmad Y, Sen S, Al-Lamee R, Petraco R; Coronary Flow Outcomes Reviewing Committee. Coronary flow reserve and cardiovascular outcomes: a systematic review and meta-analysis. Eur Heart J. 2022 Apr 19;43(16):1582-1593. doi: 10.1093/eurheartj/ehab775.
• Background Lee JM, Lee SH, Shin D, Choi KH, van de Hoef TP, Kim HK, Samady H, Kakuta T, Matsuo H, Koo BK, Fearon WF, Escaned J. Physiology-Based Revascularization: A New Approach to Plan and Optimize Percutaneous Coronary Intervention. JACC Asia. 2021 May 21;1(1):14-36. doi: 10.1016/j.jacasi.2021.03.002. eCollection 2021 Jun.
• Background Hausenloy DJ, Chilian W, Crea F, Davidson SM, Ferdinandy P, Garcia-Dorado D, van Royen N, Schulz R, Heusch G. The coronary circulation in acute myocardial ischaemia/reperfusion injury: a target for cardioprotection. Cardiovasc Res. 2019 Jun 1;115(7):1143-1155. doi: 10.1093/cvr/cvy286.
• Background Csippa B, Uveges A, Gyurki D, Jenei C, Tar B, Bugarin-Horvath B, Szabo GT, Komocsi A, Paal G, Koszegi Z. Simplified coronary flow reserve calculations based on three-dimensional coronary reconstruction and intracoronary pressure data. Cardiol J. 2023;30(4):516-525. doi: 10.5603/CJ.a2021.0117. Epub 2021 Oct 8.
• Background Terenicheva MA, Shakhnovich RM, Stukalova OV, Pevzner DV, Arutyunyan GK, Demchenkova AY, Merkulova IN, Ternovoy SK. Correlations between clinical and laboratory findings and prognostically unfavorable CMR-based characteristics of acute ST-elevation myocardial infarction. Kardiologiia. 2021 Feb 10;61(1):44-51. doi: 10.18087/cardio.2021.1.n1373. English, Russian.
• Background Terenicheva MA, Stukalova OV, Shakhnovich RM, Ternovoy SK. [The role of cardiac magnetic resonance imaging (cardiovascular magnetic resonance) in defining the prognosis of patients with acute ST-segment elevation myocardial infarction. Part 1. Indications and contraindications to cardiovascular magnetic resonance]. Ter Arkh. 2021 Apr 15;93(4):497-501. doi: 10.26442/00403660.2021.04.200687. Russian.
• Background Terenicheva MA, Stukalova OV, Shakhnovich RM, Ternovoy SK. [The role of cardiac magnetic resonance imaging in defining the prognosis of patients with acute ST-segment elevation myocardial infarction. Part 2. Assessment of the disease prognosis]. Ter Arkh. 2022 May 26;94(4):552-557. doi: 10.26442/00403660.2022.04.201458. Russian.

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Indications