Myocardial salvage in acute myocardial infarction assessed by magnetic resonance imaging – influences by the antioxidative agent N-acetylcystein
Journal of Cardiovascular Magnetic Resonance volume 11, Article number: O27 (2009)
Myocardial salvage can be assessed retrospectively by T2-weighted and delayed enhancement images as shown in animal studies . Currently there are only limited data in humans with acquisition of T2-weighted images not covering the full ventricle . Animal trials showed that the antioxidant effects of N-Acetylcystein (N-ACC) reduce reperfusion injury and N-ACC might prevent the occurrence of contrast-induced nephropathy (CIN) in patients undergoing primary PCI.
Aim of this trial was to establish myocardial salvage imaging by MR as a surrogate endpoint in a randomized single-blinded trial and to show that high-dose N-ACC reduces reperfusion injury by its antioxidative properties. Furthermore, N-ACC might reduce the incidence of contrast-induced nephropathy (CIN).
Two hundred-fifty-one patients undergoing primary PCI were randomized to either high-dose N-ACC (2 × 1200 mg/d for 48 hours) or placebo plus optimal hydratation. The two primary endpoints were: 1) occurrence of CIN defined as an increase in the serum creatinine concentration of >25% from the baseline value within 72 h; 2) Myocardial salvage measured by T2-weighted STIR-images (covering the left ventricle from base to apex) and delayed enhancement MRI at day 2–4 after primary PCI. Myocardial salvage index was calculated as area at risk-infarct size/area at risk.
Secondary endpoints were infarct size and microvascular obstruction, ST-resolution at 90 minutes and occurrence of MACE at 30 day follow-up.
Due to contraindications MRI could not be performed in 31 patients. All images were assessable for the calculation of the myocardial salvage index. The area at risk was 47.3% of the left ventricular mass (IQR 33.9; 58.8) in the N-ACC group versus 42.7% (IQR 33.7; 53.0; p = 0.39) in the placebo group. The primary endpoint reperfusion injury measured by myocardial salvage index was not different between both treatment groups (57.7; IQR 39.2; 78.0 versus 61.1; IQR 40.6; 77.7; p = 0.32). In addition, no differences in infarct size (18.3%; IQR 9.3; 26.4 versus 14.9%; IQR 8.0; 26.4; p = 0.48) and microvascular obstruction (0.7%; IQR 0.2; 1.5 versus 0.6%; IQR 0.0; 1.2; p = 0.25) as well as in ST-segment resolution were observed. The median volume of an iso-osmolar contrast agent during PCI was 190 ml (IQR 130, 250 ml) in the N-ACC and 180 (IQR 143; 228 ml) in the placebo group (p = 0.67). The primary endpoint CIN occurred in 14% in the N-ACC group and in 22% in the placebo group (p = 0.12).
MRI can reliably measure the area at risk and infarct size retrospectively and served as a surrogate endpoint in this randomized clinical trial which showed that high-dose N-ACC does not provide an additional clinical benefit to placebo with respect to prevention of myocardial reperfusion injury and CIN and in patients undergoing primary PCI.
Aletras AH, Tilak GS, Natanzon A, et al: Retrospective determination of the area at risk for reperfused acute myocardial infarction with T2-weighted cardiac magnetic resonance imaging: Histopathological and displacement encoding with stimulated echoes (DENSE) functional validations. Circulation. 2006, 113: 1865-1870. 10.1161/CIRCULATIONAHA.105.576025.
Friedrich MG, Abdel-Aty H, Taylor A, Schulz-Menger J, Messroghli D, Dietz R: The salvaged area at risk in reperfused acute myocardial infarction as visualized by cardiovascular magnetic resonance. J Am Coll Cardiol. 2008, 51: 1581-1587. 10.1016/j.jacc.2008.01.019.
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Thiele, H., Eitel, I., Hildebrand, L. et al. Myocardial salvage in acute myocardial infarction assessed by magnetic resonance imaging – influences by the antioxidative agent N-acetylcystein. J Cardiovasc Magn Reson 11 (Suppl 1), O27 (2009). https://doi.org/10.1186/1532-429X-11-S1-O27