The Effect of Glucocorticoid Therapy on Left Ventricular Remodelling in Acute Myocardial Infarction (RECONSIDER)

Summary

Introduction: In the setting of acute ST-segment elevation myocardial infarction (STEMI) coronary wedge pressure (CWP) emerges as a new marker for the advanced form of pre-procedural microvascular obstruction (MVO), which is associated with inflammatory interstitial edema. Through its anti-inflammatory effects, glucocorticoid therapy may prove beneficial in patients with high CWP. Aim: To identify the presence of the advanced form of MVO before primary percutaneous coronary intervention (PPCI) by CWP measurement and to test the benefit of cortisol therapy, in terms of infarct size and left ventricular remodeling, in patients with raised CWP. Methods: 50 patients with a first STEMI, candidates for PPCI, with proximal coronary occlusion, will undergo CWP measurement followed by percutaneous revascularization. Cardiac MRI will be performed 3-5 days after the procedure. A cutoff for CWP in predicting MVO, interstitial oedema and intramyocardial haemorrhage will be derived.Based on the above mentioned cutoff, 180 patients with continuous elevation of the pressure line will be randomized, by a 1:1 model, either to cortisol therapy or to placebo. Inflammatory parameters will be determined from peripheral blood samples. Patients will undergo cardiac magnetic resonance (CMR) imaging 3 to 5 days after revascularization. Study endpoints: The primary endpoint will be the extent of MVO, interstitial edema and hemorrhage. Secondary endpoints will include infarct size, myocardial salvage, left ventricular volumes and ejection fraction. The clinical endpoints of all-cause and cardiovascular death, myocardial re-infarction, target vessel revascularization, stent thrombosis and stroke will be recorded at 6 months.

Timeline

Start

2018-03-08

Primary completion

2019-12-31

Completion

2020-12

Publications

• Background Westman PC, Lipinski MJ, Luger D, Waksman R, Bonow RO, Wu E, Epstein SE. Inflammation as a Driver of Adverse Left Ventricular Remodeling After Acute Myocardial Infarction. J Am Coll Cardiol. 2016 May 3;67(17):2050-60. doi: 10.1016/j.jacc.2016.01.073.
• Background Kramer MC, van der Wal AC, Koch KT, Ploegmakers JP, van der Schaaf RJ, Henriques JP, Baan J Jr, Rittersma SZ, Vis MM, Piek JJ, Tijssen JG, de Winter RJ. Presence of older thrombus is an independent predictor of long-term mortality in patients with ST-elevation myocardial infarction treated with thrombus aspiration during primary percutaneous coronary intervention. Circulation. 2008 Oct 28;118(18):1810-6. doi: 10.1161/CIRCULATIONAHA.108.780734. Epub 2008 Oct 13.
• Background Patel N, Petraco R, Dall'Armellina E, Kassimis G, De Maria GL, Dawkins S, Lee R, Prendergast BD, Choudhury RP, Forfar JC, Channon KM, Davies J, Banning AP, Kharbanda RK. Zero-Flow Pressure Measured Immediately After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Provides the Best Invasive Index for Predicting the Extent of Myocardial Infarction at 6 Months: An OxAMI Study (Oxford Acute Myocardial Infarction). JACC Cardiovasc Interv. 2015 Sep;8(11):1410-1421. doi: 10.1016/j.jcin.2015.04.029.
• Background Iancu AC, Rafiroiu D, Marc M. Is Coronary Wedge Pressure a Technique to Identify High-Risk Patients Who May Benefit From Alternative Treatment in Acute Myocardial Infarction?: Is This The Next Step? JACC Cardiovasc Interv. 2016 Jan 11;9(1):104-105. doi: 10.1016/j.jcin.2015.10.018. No abstract available.
• Background Ndrepepa G, Tiroch K, Fusaro M, Keta D, Seyfarth M, Byrne RA, Pache J, Alger P, Mehilli J, Schomig A, Kastrati A. 5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction. J Am Coll Cardiol. 2010 May 25;55(21):2383-9. doi: 10.1016/j.jacc.2009.12.054.
• Background Iancu A, Ober C, Bondor CI, Cadis H. Microvascular effect of intracoronary eptifibatide in acute myocardial infarction. Cardiology. 2012;123(1):46-53. doi: 10.1159/000341197. Epub 2012 Sep 12.
• Background Giugliano GR, Giugliano RP, Gibson CM, Kuntz RE. Meta-analysis of corticosteroid treatment in acute myocardial infarction. Am J Cardiol. 2003 May 1;91(9):1055-9. doi: 10.1016/s0002-9149(03)00148-6.
• Background Barzilai D, Plavnick J, Hazani A, Einath R, Kleinhaus N, Kanter Y. Use of hydrocortisone in the treatment of acute myocardial infarction. Summary of a clinical trial in 446 patients. Chest. 1972 May;61(5):488-91. doi: 10.1378/chest.61.5.488. No abstract available.
• Background Seropian IM, Toldo S, Van Tassell BW, Abbate A. Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction. J Am Coll Cardiol. 2014 Apr 29;63(16):1593-603. doi: 10.1016/j.jacc.2014.01.014. Epub 2014 Feb 13.

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