The challenges and impact of microvascular injury in ST-elevation myocardial infarction

References

• Falk E, Nakano M, Bentzon JF, et al. Update on acute coronary syndromes: the pathologists’ view. Eur Heart J. 2013;34(10):719–728.
   PubMed Web of Science ®Google Scholar
• McManus DD, Gore J, Yarzebski J, et al. Recent trends in the incidence, treatment, and outcomes of patients with STEMI and NSTEMI. Am J Med. 2011;124(1):40–47.
   PubMed Web of Science ®Google Scholar
• Jernberg T, Johanson P, Held C, et al. Association between adoption of evidence-based treatment and survival for patients with ST-elevation myocardial infarction. JAMA. 2011;305(16):1677–1684.
   PubMed Web of Science ®Google Scholar
• Pedersen F, Butrymovich V, Kelbaek H, et al. Short- and long-term cause of death in patients treated with primary PCI for STEMI. J Am Coll Cardiol. 2014;64(20):2101–2108.
   PubMed Web of Science ®Google Scholar
• Van Kranenburg M, Magro M, Thiele H, et al. Prognostic value of microvascular obstruction and infarct size, as measured by CMR in STEMI patients. JACC Cardiovasc Imaging. 2014;7(9):930–939.
   PubMed Web of Science ®Google Scholar
• de Waha S, Desch S, Eitel I, et al. Relationship and prognostic value of microvascular obstruction and infarct size in ST-elevation myocardial infarction as visualized by magnetic resonance imaging. Clin Res Cardiol. 2012;101(6):487–495.
   PubMed Web of Science ®Google Scholar
• Mayr A, Klug G, Schocke M, et al. Late microvascular obstruction after acute myocardial infarction: relation with cardiac and inflammatory markers. Int J Cardiol. 2012;157(3):391–396.
   PubMed Web of Science ®Google Scholar
• Hamirani YS, Wong A, Kramer CM, et al. Effect of microvascular obstruction and intramyocardial hemorrhage by CMR on LV remodeling and outcomes after myocardial infarction: a systematic review and meta-analysis. JACC Cardiovasc Imaging. 2014;7(9):940–952.
   PubMed Web of Science ®Google Scholar
• Lombardo A, Niccoli G, Natale L, et al. Impact of microvascular obstruction and infarct size on left ventricular remodeling in reperfused myocardial infarction: a contrast-enhanced cardiac magnetic resonance imaging study. Int J Cardiovasc Imaging. 2012;28(4):835–842.
   PubMed Web of Science ®Google Scholar
• de Waha S, Desch S, Eitel I, et al. Impact of early vs. late microvascular obstruction assessed by magnetic resonance imaging on long-term outcome after ST-elevation myocardial infarction: a comparison with traditional prognostic markers. Eur Heart J. 2010;31(21):2660–2668.
   PubMed Web of Science ®Google Scholar
• Klug G, Mayr A, Schenk S, et al. Prognostic value at 5 years of microvascular obstruction after acute myocardial infarction assessed by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2012;14:46.
   PubMed Web of Science ®Google Scholar
• Eitel I, de Waha S, Wohrle J, et al. Comprehensive prognosis assessment by CMR imaging after ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2014;64(12):1217–1226.
   PubMed Web of Science ®Google Scholar
• Bekkers SC, Yazdani SK, Virmani R, et al. Microvascular obstruction: underlying pathophysiology and clinical diagnosis. J Am Coll Cardiol. 2010;55(16):1649–1660.
   PubMed Web of Science ®Google Scholar
• Robbers LF, Eerenberg ES, Teunissen PF, et al. Magnetic resonance imaging-defined areas of microvascular obstruction after acute myocardial infarction represent microvascular destruction and haemorrhage. Eur Heart J. 2013;34(30):2346–2353.
   PubMed Web of Science ®Google Scholar
• Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest. 2013;123(1):92–100.
   PubMed Web of Science ®Google Scholar
• Reimer KA, Lowe JE, Rasmussen MM, et at. The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation. 1977;56(5):786–794.
   PubMed Web of Science ®Google Scholar
• Kloner RA, Rude RE, Carlson N, et al. Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first? Circulation. 1980;62(5):945–952.
   PubMed Web of Science ®Google Scholar
• Kloner RA, Ganote CE, Jennings RB. The “no-reflow” phenomenon after temporary coronary occlusion in the dog. J Clin Invest. 1974;54(6):1496–1508.
   PubMed Web of Science ®Google Scholar
• Ambrosio G, Weisman HF, Mannisi JA, et al. Progressive impairment of regional myocardial perfusion after initial restoration of postischemic blood flow. Circulation. 1989;80(6):1846–1861.
   PubMed Web of Science ®Google Scholar
• Tsao PS, Aoki N, Lefer DJ, et al. Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat. Circulation. 1990;82(4):1402–1412.
   PubMed Web of Science ®Google Scholar
• Maxwell L, Gavin JB. The role of post-ischaemic reperfusion in the development of microvascular incompetence and ultrastructural damage in the myocardium. Basic Res Cardiol. 1991;86(6):544–553.
   PubMed Web of Science ®Google Scholar
• Kloner RA, Giacomelli F, Alker KJ, et al. Influx of neutrophils into the walls of large epicardial coronary arteries in response to ischemia/reperfusion. Circulation. 1991;84(4):1758–1772.
   PubMed Web of Science ®Google Scholar
• O’Farrell FM, Attwell D. A role for pericytes in coronary no-reflow. Nat Rev Cardiol. 2014;11(7):427–432.
   PubMed Web of Science ®Google Scholar
• O’Regan DP, Ariff B, Neuwirth C, et al. Assessment of severe reperfusion injury with T2* cardiac MRI in patients with acute myocardial infarction. Heart. 2010;96(23):1885–1891.
   PubMed Web of Science ®Google Scholar
• Niccoli G, Spaziani C, Cosentino N, et al. Predictors of myocardial microvascular obstruction in patients treated by primary percutaneous coronary intervention and a short ischemic time. Int J Cardiol. 2011;153(1):113–115.
   PubMed Web of Science ®Google Scholar
• Frohlich GM, Meier P, White SK, et al. Myocardial reperfusion injury: looking beyond primary PCI. Eur Heart J. 2013;34(23):1714–1722.
   PubMed Web of Science ®Google Scholar
• Reffelmann T, Kloner RA. Microvascular reperfusion injury: rapid expansion of anatomic no reflow during reperfusion in the rabbit. Am J Physiol Heart Circ Physiol. 2002;283(3):H1099–107.
   PubMed Web of Science ®Google Scholar
• Griffiths EJ, Halestrap AP, Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion. Biochem J. 1995;307 (Pt 1)93–98.
   PubMed Web of Science ®Google Scholar
• Weiss JN, Korge P, Honda HM, et al. Role of the mitochondrial permeability transition in myocardial disease. Circ Res. 2003;93(4):292–301.
   PubMed Web of Science ®Google Scholar
• Borutaite V, Jekabsone A, Morkuniene R, et al. Inhibition of mitochondrial permeability transition prevents mitochondrial dysfunction, cytochrome c release and apoptosis induced by heart ischemia. J Mol Cell Cardiol. 2003;35(4):357–366.
   PubMed Web of Science ®Google Scholar
• Heusch G, Boengler K, Schulz R. Inhibition of mitochondrial permeability transition pore opening: the Holy Grail of cardioprotection. Basic Res Cardiol. 2010;105(2):151–154.
   PubMed Web of Science ®Google Scholar
• Ye YX, Basse-Lusebrink TC, Arias-Loza PA, et al. Monitoring of monocyte recruitment in reperfused myocardial infarction with intramyocardial hemorrhage and microvascular obstruction by combined fluorine 19 and proton cardiac magnetic resonance imaging. Circulation. 2013;128(17):1878–1888.
   PubMed Web of Science ®Google Scholar
• Betgem RP, de Waard GA, Nijveldt R, et al. Intramyocardial haemorrhage after acute myocardial infarction. Nat Rev Cardiol. 2015;12(3):156–167.
   PubMed Web of Science ®Google Scholar
• Bresnahan GF, Roberts R, Shell WE, et al. Deleterious effects due to hemorrhage after myocardial reperfusion. Am J Cardiol. 1974;33(1):82–86.
   PubMed Web of Science ®Google Scholar
• Garcia-Dorado D, Theroux P, Solares J, et al.,Determinants of hemorrhagic infarcts. Histologic observations from experiments involving coronary occlusion, coronary reperfusion, and reocclusion. Am J Pathol. 1990;137(2):301–311.
   PubMed Web of Science ®Google Scholar
• Marra MP, Cacciavillani L, Corbetti F, et al. The contribution of intramyocardial hemorrhage to the “no-reflow phenomenon”: a study performed by cardiac magnetic resonance. Echocardiography. 2010;27(9):1120–1129.
   PubMed Web of Science ®Google Scholar
• Kell DB. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics. 2009;2:2.
   PubMed Web of Science ®Google Scholar
• Williams RE, Zweier JL, Flaherty JT. Treatment with deferoxamine during ischemia improves functional and metabolic recovery and reduces reperfusion-induced oxygen radical generation in rabbit hearts. Circulation. 1991;83(3):1006–1014.
   PubMed Web of Science ®Google Scholar
• Halliwell B, Gutteridge JM. Role of free radicals and catalytic metal ions in human disease: an overview. Method Enzymol. 1990;186:1–85.
   PubMed Web of Science ®Google Scholar
• Limbruno U, De Carlo M, Pistolesi S, et al. Distal embolization during primary angioplasty: histopathologic features and predictability. Am Heart J. 2005;150(1):102–108.
   PubMed Web of Science ®Google Scholar
• Heusch G, Kleinbongard P, Bose D, et al. Coronary microembolization: from bedside to bench and back to bedside. Circulation. 2009;120(18):1822–1836.
   PubMed Web of Science ®Google Scholar
• Napodano M, Peluso D, Marra MP, et al. Time-dependent detrimental effects of distal embolization on myocardium and microvasculature during primary percutaneous coronary intervention. JACC Cardiovasc Interven. 2012;5(11):1170–1177.
   PubMed Web of Science ®Google Scholar
• De Maria GL, Cuculi F, Patel N, et al. How does coronary stent implantation impact on the status of the microcirculation during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction? Eur Heart J. 2015;36(45):3165–3177.
   PubMed Web of Science ®Google Scholar
• Shiono Y, Kubo T, Tanaka A, et al. Impact of attenuated plaque as detected by intravascular ultrasound on the occurrence of microvascular obstruction after percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. JACC Cardiovasc Interven. 2013;6(8):847–853.
   PubMed Web of Science ®Google Scholar
• Higuma T, Soeda T, Abe N, et al. A combined optical coherence tomography and intravascular ultrasound study on plaque rupture, plaque erosion, and calcified nodule in patients with st-segment elevation myocardial infarction: incidence, morphologic characteristics, and outcomes after percutaneous coronary intervention. JACC Cardiovasc Interven. 2015;8(9):1166–1176.
   PubMed Web of Science ®Google Scholar
• Niccoli G, Burzotta F, Galiuto L, et al. Myocardial no-reflow in humans. J Am Coll Cardiol. 2009;54(4):281–292.
   PubMed Web of Science ®Google Scholar
• Collet J-P, Montalescot G. The acute reperfusion management of STEMI in patients with impaired glucose tolerance and type 2 diabetes. Diab Vasc Dis Res. 2005;2(3):136–143.
   PubMedGoogle Scholar
• Eitel I, Hintze S, de Waha S, et al. Prognostic impact of hyperglycemia in nondiabetic and diabetic patients with ST-elevation myocardial infarction: insights from contrast-enhanced magnetic resonance imaging. Circ Imaging. 2012;5(6):708–718.
   PubMed Web of Science ®Google Scholar
• Mather AN, Crean A, Abidin N, et al. Relationship of dysglycemia to acute myocardial infarct size and cardiovascular outcome as determined by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2010;12:61.
   PubMed Web of Science ®Google Scholar
• Ferdinandy P. Myocardial ischaemia/reperfusion injury and preconditioning: effects of hypercholesterolaemia/hyperlipidaemia. Br J Pharmacol. 2003;138(2):283–285.
   PubMed Web of Science ®Google Scholar
• Zhao JL, Yang YJ, You SJ, et al. Different effects of postconditioning on myocardial no-reflow in the normal and hypercholesterolemic mini-swines. Microvasc Res. 2007;73(2):137–142.
   PubMed Web of Science ®Google Scholar
• Golino P, Maroko PR, Carew TE. The effect of acute hypercholesterolemia on myocardial infarct size and the no-reflow phenomenon during coronary occlusion-reperfusion. Circulation. 1987;75(1):292–298.
   PubMed Web of Science ®Google Scholar
• Osipov RM, Bianchi C, Feng J, et al. Effect of hypercholesterolemia on myocardial necrosis and apoptosis in the setting of ischemia-reperfusion. Circulation. 2009;120(11 Suppl):S22–30.
   PubMed Web of Science ®Google Scholar
• Iwakura K, Ito H, Kawano S, et al. Chronic pre-treatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction. Eur Heart Journal. 2006;27(5):534–539.
   PubMed Web of Science ®Google Scholar
• Niccoli G, Scalone G, Cosentino N, et al. Protective effect of pre-infarction angina on microvascular obstruction after primary percutaneous coronary intervention is blunted in humans by cardiovascular risk factors. Circ J. 2014;78(8):1935–1941.
   PubMed Web of Science ®Google Scholar
• Gibson CM, Schomig A. Coronary and myocardial angiography: angiographic assessment of both epicardial and myocardial perfusion. Circulation. 2004;109(25):3096–3105.
   PubMed Web of Science ®Google Scholar
• Niccoli G, Cosentino N, Spaziani C, et al No-reflow: incidence and detection in the cath-lab. Curr Pharm Des. 2013;19(25):4564–4575.
   PubMed Web of Science ®Google Scholar
• Fearon WF, Balsam LB, Farouque HM, et al. Novel index for invasively assessing the coronary microcirculation. Circulation. 2003;107(25):3129–3132.
   PubMed Web of Science ®Google Scholar
• Hoole SP, Jaworski C, Brown AJ, et al. Serial assessment of the index of microcirculatory resistance during primary percutaneous coronary intervention comparing manual aspiration catheter thrombectomy with balloon angioplasty (IMPACT study): a randomised controlled pilot study. Open Heart. 2015;2(1):e000238.
   Google Scholar
• Fearon WF, Shah M, Ng M, et al. Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2008;51(5):560–565.
   PubMed Web of Science ®Google Scholar
• Feldman LJ, Coste P, Furber A, et al. Incomplete resolution of ST-segment elevation is a marker of transient microcirculatory dysfunction after stenting for acute myocardial infarction. Circulation. 2003;107(21):2684–2689.
   PubMed Web of Science ®Google Scholar
• Amaya N, Nakano A, Uzui H, et al. Relationship between microcirculatory dysfunction and resolution of ST-segment elevation in the early phase after primary angioplasty in patients with ST-segment elevation myocardial infarction. Int J Cardiol. 2012;159(2):144–149.
   PubMed Web of Science ®Google Scholar
• Rommel KP, Baum A, Mende M, et al. Prognostic significance and relationship of worst lead residual ST segment elevation with myocardial damage assessed by cardiovascular MRI in myocardial infarction. Heart. 2014;100(16):1257–1263.
   PubMed Web of Science ®Google Scholar
• Reinstadler SJ, Baum A, Rommel KP, et al. ST-segment depression resolution predicts infarct size and reperfusion injury in ST-elevation myocardial infarction. Heart. 2015;101(22):1819–1825.
   PubMed Web of Science ®Google Scholar
• Rommel KP, Badarnih H, Desch S, et al. QRS complex distortion (Grade 3 ischaemia) as a predictor of myocardial damage assessed by cardiac magnetic resonance imaging and clinical prognosis in patients with ST-elevation myocardial infarction. Eur Heart J Cardiovasc Imaging. 2015; jev135. doi:10.1093/ehjci/jev135. [Epub ahead of print].
   Google Scholar
• Ito H, Maruyama A, Iwakura K, et al. Clinical implications of the ‘no reflow’ phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation. 1996;93(2):223–228.
   PubMed Web of Science ®Google Scholar
• Hayat SA, Senior R. Myocardial contrast echocardiography in ST elevation myocardial infarction: ready for prime time?. Eur Heart J. 2008;29(3):299–314.
   PubMed Web of Science ®Google Scholar
• Amanieu C, Sanchez I, Arion S, et al. Acute myocardial infarction: early CT aspects of myocardial microcirculation obstruction after percutaneous coronary intervention. Eur Radiol. 2013;23(9):2405–2412.
   PubMed Web of Science ®Google Scholar
• Ogasawara S, Mukawa H, Sone T, et al. Presence of myocardial hypoenhancement on multidetector computed tomography after primary percutaneous coronary intervention in acute myocardial infarction predicts poor prognosis. Int J Cardiol. 2015;184:101–107.
   PubMed Web of Science ®Google Scholar
• Klug G, Metzler B. Assessing myocardial recovery following ST-segment elevation myocardial infarction: short- and long-term perspectives using cardiovascular magnetic resonance. Expert Rev Cardiovasc Ther. 2013;11(2):203–219.
   PubMedGoogle Scholar
• Wu KC. CMR of microvascular obstruction and hemorrhage in myocardial infarction. J Cardiovasc Magn Reson. 2012;14:68.
   PubMed Web of Science ®Google Scholar
• Reinstadler SJ, Thiele H, Eitel I. Risk stratification by cardiac magnetic resonance imaging after ST-elevation myocardial infarction. Curr Opin Cardiol. 2015;30(6):681–689.
   PubMed Web of Science ®Google Scholar
• Fuernau G, Eitel I, Franke V, et al. Myocardium at risk in ST-segment elevation myocardial infarction comparison of T2-weighted edema imaging with the MR-assessed endocardial surface area and validation against angiographic scoring. JACC Cardiovasc Imaging. 2011;4(9):967–976.
   PubMed Web of Science ®Google Scholar
• Klug G, Trieb T, Schocke M, et al. Quantification of regional functional improvement of infarcted myocardium after primary PTCA by contrast-enhanced magnetic resonance imaging. J Magn Reson Imaging. 2009;29(2):298–304.
   PubMed Web of Science ®Google Scholar
• Ganame J, Messalli G, Dymarkowski S, et al. Impact of myocardial haemorrhage on left ventricular function and remodelling in patients with reperfused acute myocardial infarction. Eur Heart J. 2009;30(12):1440–1449.
   PubMed Web of Science ®Google Scholar
• Kumar A, Green JD, Sykes JM, et al. Detection and quantification of myocardial reperfusion hemorrhage using T2*-weighted CMR. JACC Cardiovasc Imaging. 2011;4(12):1274–1283.
   PubMed Web of Science ®Google Scholar
• Pedersen SF, Thrysoe SA, Robich MP, et al. Assessment of intramyocardial hemorrhage by T1-weighted cardiovascular magnetic resonance in reperfused acute myocardial infarction. J Cardiovasc Magn Reson. 2012;14:59.
   PubMed Web of Science ®Google Scholar
• Basso C, Corbetti F, Silva C, et al. Morphologic validation of reperfused hemorrhagic myocardial infarction by cardiovascular magnetic resonance. Am J Cardiol. 2007;100(8):1322–1327.
   PubMed Web of Science ®Google Scholar
• Kali A, Tang RL, Kumar A, et al. Detection of acute reperfusion myocardial hemorrhage with cardiac MR imaging: T2 versus T2. Radiology. 2013;269(2):387–395.
   PubMed Web of Science ®Google Scholar
• Kandler D, Lucke C, Grothoff M, et al. The relation between hypointense core, microvascular obstruction and intramyocardial haemorrhage in acute reperfused myocardial infarction assessed by cardiac magnetic resonance imaging. Eur Radiol. 2014;24(12):3277–3288.
   PubMed Web of Science ®Google Scholar
• Karagounis L, Sorensen SG, Menlove RL, et al. Does thrombolysis in myocardial infarction (TIMI) perfusion grade 2 represent a mostly patent artery or a mostly occluded artery? Enzymatic and electrocardiographic evidence from the TEAM-2 study. Second multicenter thrombolysis trial of eminase in acute myocardial infarction. J Am Coll Cardiol. 1992;19(1):1–10.
   PubMed Web of Science ®Google Scholar
• Vogt A, Von Essen R, Tebbe U, et al. Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: retrospective analysis of four German multicenter studies. J Am Coll Cardiol. 1993;21(6):1391–1395.
   PubMed Web of Science ®Google Scholar
• Fearon WF, Low AF, Yong AS, et al. Prognostic value of the index of microcirculatory resistance measured after primary percutaneous coronary intervention. Circulation. 2013;127(24):2436–2441.
   PubMed Web of Science ®Google Scholar
• De Lemos JA, Braunwald E. ST segment resolution as a tool for assessing the efficacy of reperfusion therapy. J Am Coll Cardiol. 2001;38(5):1283–1294.
   PubMed Web of Science ®Google Scholar
• Wu KC, Zerhouni EA, Judd RM, et al. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation. 1998;97(8):765–772.
   PubMed Web of Science ®Google Scholar
• Gerber BL, Rochitte CE, Melin JA, et al. Microvascular obstruction and left ventricular remodeling early after acute myocardial infarction. Circulation. 2000;101(23):2734–2741.
   PubMed Web of Science ®Google Scholar
• Hombach V, Grebe O, Merkle N, et al. Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging. Eur Heart J. 2005;26(6):549–557.
   PubMed Web of Science ®Google Scholar
• Bodi V, Sanchis J, Nunez J, et al. Prognostic value of a comprehensive cardiac magnetic resonance assessment soon after a first ST-segment elevation myocardial infarction. JACC Cardiovasc Imaging. 2009;2(7):835–842.
   PubMed Web of Science ®Google Scholar
• de Waha S, Eitel I, Desch S, et al. Prognosis after ST-elevation myocardial infarction: a study on cardiac magnetic resonance imaging versus clinical routine. Trials. 2014;15:249.
   PubMed Web of Science ®Google Scholar
• Hadamitzky M, Langhans B, Hausleiter J, et al. Prognostic value of late gadolinium enhancement in cardiovascular magnetic resonance imaging after acute ST-elevation myocardial infarction in comparison with single-photon emission tomography using Tc99m-Sestamibi. Eur Heart J Cardiovasc Imaging. 2014;15(2):216–225.
   PubMed Web of Science ®Google Scholar
• Reinstadler SJ, Klug G, Feistritzer HJ, et al. Prognostic value of left ventricular global function index in patients after ST-segment elevation myocardial infarction. Eur Heart J Cardiovasc Imaging. 2015; jev129. doi:10.1093/ehjci/jev129. [Epub ahead of print].
   Google Scholar
• Regenfus M, Schlundt C, Krahner R, et al. Six-year prognostic value of microvascular obstruction after reperfused ST-elevation myocardial infarction as assessed by contrast-enhanced cardiovascular magnetic resonance. Am J Cardiol. 2015;116(7):1022–1027.
   PubMed Web of Science ®Google Scholar
• Husser O, Monmeneu JV, Sanchis J, et al. Cardiovascular magnetic resonance-derived intramyocardial hemorrhage after STEMI: Influence on long-term prognosis, adverse left ventricular remodeling and relationship with microvascular obstruction. Int J Cardiol. 2013;167(5):2047–2054.
   PubMed Web of Science ®Google Scholar
• Mather AN, Fairbairn TA, Ball SG, et al. Reperfusion haemorrhage as determined by cardiovascular MRI is a predictor of adverse left ventricular remodelling and markers of late arrhythmic risk. Heart. 2011;97(6):453–459.
   PubMed Web of Science ®Google Scholar
• Beek AM, Nijveldt R, Van Rossum AC. Intramyocardial hemorrhage and microvascular obstruction after primary percutaneous coronary intervention. Int J Cardiovasc Imaging. 2010;26(1):49–55.
   PubMed Web of Science ®Google Scholar
• Eitel I, Desch S, Fuernau G, et al. Prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance in acute reperfused myocardial infarction. J Am Coll Cardiol. 2010;55(22):2470–2479.
   PubMed Web of Science ®Google Scholar
• Eitel I, Desch S, de Waha S. Long-term prognostic value of myocardial salvage assessed by cardiovascular magnetic resonance in acute reperfused myocardial infarction. Heart. 2011;97(24):2038–2045.
   PubMed Web of Science ®Google Scholar
• Li XD, Yang YJ, Hao YC, et al. Effect of pre-procedural statin therapy on myocardial no-reflow following percutaneous coronary intervention: a meta analysis. Chin Med J. 2013;126(9):1755–1760.
   PubMed Web of Science ®Google Scholar
• Kim JS, Kim J, Choi D, et al. Efficacy of high-dose atorvastatin loading before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the STATIN STEMI trial. JACC Cardiovasc Interven. 2010;3(3):332–339.
   PubMed Web of Science ®Google Scholar
• Fuernau G, Eitel I, Wohrle J, et al. Impact of long-term statin pretreatment on myocardial damage in ST elevation myocardial infarction (from the AIDA STEMI CMR Substudy). Am J Cardiol. 2014;114(4):503–509.
   PubMed Web of Science ®Google Scholar
• Montalescot G, Antoniucci D, Kastrati A, et al. Abciximab in primary coronary stenting of ST-elevation myocardial infarction: a European meta-analysis on individual patients’ data with long-term follow-up. Eur Heart J. 2007;28(4):443–449.
   PubMed Web of Science ®Google Scholar
• Neumann FJ, Blasini R, Schmitt C, et al. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation. 1998;98(24):2695–2701.
   PubMed Web of Science ®Google Scholar
• Montalescot G, Barragan P, Wittenberg O, et al. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med. 2001;344(25):1895–1903.
   PubMed Web of Science ®Google Scholar
• Thiele H, Wohrle J, Hambrecht R, et al. Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial. Lancet. 2012;379(9819):923–931.
   PubMed Web of Science ®Google Scholar
• Desch S, Wohrle J, Hambrecht R, et al. Intracoronary versus intravenous abciximab bolus in patients with ST-segment elevation myocardial infarction: 1-year results of the randomized AIDA STEMI trial. J Am Coll Cardiol. 2013;62(13):1214–1215.
   PubMed Web of Science ®Google Scholar
• Eitel I, Wohrle J, Suenkel H, et al. Intracoronary compared with intravenous bolus abciximab application during primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: cardiac magnetic resonance substudy of the AIDA STEMI trial. J Am Coll Cardiol. 2013;61(13):1447–1454.
   PubMed Web of Science ®Google Scholar
• Kassimis G, Davlouros P, Patel N, et al. Adenosine as an adjunct therapy in ST elevation myocardial infarction patients: myth or truth? Cardiovasc Drugs Ther. 2015;29(5):481–493. [Epub ahead of print]
   PubMed Web of Science ®Google Scholar
• Marzilli M, Orsini E, Marraccini P, et al. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation. 2000;101(18):2154–2159.
   PubMed Web of Science ®Google Scholar
• Stoel MG, Marques KM, De Cock CC, et al. High dose adenosine for suboptimal myocardial reperfusion after primary PCI: A randomized placebo-controlled pilot study. Catheter Cardiovasc Interv. 2008;71(3):283–289.
   PubMed Web of Science ®Google Scholar
• Niccoli G, Rigattieri S, De Vita MR, et al. Open-label, randomized, placebo-controlled evaluation of intracoronary adenosine or nitroprusside after thrombus aspiration during primary percutaneous coronary intervention for the prevention of microvascular obstruction in acute myocardial infarction: the REOPEN-AMI study (Intracoronary Nitroprusside Versus Adenosine in Acute Myocardial Infarction). JACC Cardiovasc Interven. 2013;6(6):580–589.
   PubMed Web of Science ®Google Scholar
• Niccoli G, Spaziani C, Crea F, et al. Left ventricular remodeling and 1-year clinical follow-up of the REOPEN-AMI trial. J Am Coll Cardiol. 2014;63(14):1454–1455.
   PubMed Web of Science ®Google Scholar
• Garcia-Dorado D, Garcia-del-Blanco B, Otaegui I, et al. Intracoronary injection of adenosine before reperfusion in patients with ST-segment elevation myocardial infarction: a randomized controlled clinical trial. Int J Cardiol. 2014;177(3):935–941.
   PubMed Web of Science ®Google Scholar
• Desmet W, Bogaert J, Dubois C, et al. High-dose intracoronary adenosine for myocardial salvage in patients with acute ST-segment elevation myocardial infarction. Eur Heart J. 2011;32(7):867–877.
   PubMed Web of Science ®Google Scholar
• Ross AM, Gibbons RJ, Stone GW, et al. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol. 2005;45(11):1775–1780.
   PubMed Web of Science ®Google Scholar
• Kloner RA, Forman MB, Gibbons RJ, et al. Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: the AMISTAD-2 trial. Eur Heart J. 2006;27(20):2400–2405.
   PubMed Web of Science ®Google Scholar
• Hillegass WB, Dean NA, Liao L, et al. Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous coronary interventions: initial human clinical experience. J Am Coll Cardiol. 2001;37(5):1335–1343.
   PubMed Web of Science ®Google Scholar
• Amit G, Cafri C, Yaroslavtsev S, et al. Intracoronary nitroprusside for the prevention of the no-reflow phenomenon after primary percutaneous coronary intervention in acute myocardial infarction. A randomized, double-blind, placebo-controlled clinical trial. Am Heart J. 2006;152(5):887.e9–14.
   PubMed Web of Science ®Google Scholar
• Ito H, Taniyama Y, Iwakura K, et al. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol. 1999;33(3):654–660.
   PubMed Web of Science ®Google Scholar
• Van’t Hof AW, Ten Berg J, Heestermans T, et al. Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial. Lancet. 2008;372(9638):537–546.
   PubMed Web of Science ®Google Scholar
• Werner GS, Lang K, Kuehnert H, et al. Intracoronary verapamil for reversal of no-reflow during coronary angioplasty for acute myocardial infarction. Catheter Cardiovasc Interv. 2002;57(4):444–451.
   PubMed Web of Science ®Google Scholar
• Lonborg J, Vejlstrup N, Kelbaek H, et al Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012;33(12):1491–1499.
   PubMed Web of Science ®Google Scholar
• Burzotta F, Trani C, Romagnoli E, et al. Manual thrombus-aspiration improves myocardial reperfusion: the randomized evaluation of the effect of mechanical reduction of distal embolization by thrombus-aspiration in primary and rescue angioplasty (REMEDIA) trial. J Am Coll Cardiol. 2005;46(2):371–376.
   PubMed Web of Science ®Google Scholar
• Svilaas T, Vlaar PJ, Van Der Horst IC, et al. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med. 2008;358(6):557–567.
   PubMed Web of Science ®Google Scholar
• Vlaar PJ, Svilaas T, Van Der Horst IC, et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet. 2008;371(9628):1915–1920.
   PubMed Web of Science ®Google Scholar
• Frobert O, Lagerqvist B, Olivecrona GK, et al. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med. 2013;369(17):1587–1597.
   PubMed Web of Science ®Google Scholar
• Jolly SS, Cairns JA, Yusuf S, et al. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med. 2015;372(15):1389–1398.
   PubMed Web of Science ®Google Scholar
• Carrick D, Oldroyd KG, McEntegart M, et al. A randomized trial of deferred stenting versus immediate stenting to prevent no- or slow-reflow in acute ST-segment elevation myocardial infarction (DEFER-STEMI). J Am Coll Cardiol. 2014;63(20):2088–2098.
   PubMed Web of Science ®Google Scholar
• Arslan U, Yaman M, Kocaoglu I, et al. Risk of no-reflow in culprit lesion versus culprit vessel PCI in acute STEMI. Coron Artery Dis. 2015;26(6):510–515.
   PubMed Web of Science ®Google Scholar
• Stone GW, Abizaid A, Silber S, et al. Prospective, randomized, multicenter evaluation of a polyethylene terephthalate micronet mesh-covered stent (MGuard) in ST-segment elevation myocardial infarction: The MASTER trial. J Am Coll Cardiol. 2012;60(19):1975–1984.
   PubMed Web of Science ®Google Scholar
• Yoon CH, Chung WY, Suh JW, et al. Distal protection device aggravated microvascular obstruction evaluated by cardiac MR after primary percutaneous intervention for ST-elevation myocardial infarction. Int J Cardiol. 2013;167(5):2002–2007.
   PubMed Web of Science ®Google Scholar
• Zhou SS, Tian F, Chen YD, et al. Combination therapy reduces the incidence of no-reflow after primary per-cutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction. J Geriatr Cardiol. 2015;12(2):135–142.
   PubMedGoogle Scholar
• Stone GW, Maehara A, Witzenbichler B, et al. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial. JAMA. 2012;307(17):1817–1826.
   PubMed Web of Science ®Google Scholar
• Bodi V, Ruiz-Nodar JM, Feliu E, et al. Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine. Int J Cardiol. 2014;175(1):138–146.
   PubMed Web of Science ®Google Scholar
• Mewton N, Thibault H, Roubille F, et al. Postconditioning attenuates no-reflow in STEMI patients. Basic Res Cardiol. 2013;108(6):383.
   PubMed Web of Science ®Google Scholar
• Araszkiewicz A, Grygier M, Pyda M, et al. Postconditioning reduces enzymatic infarct size and improves microvascular reperfusion in patients with ST-segment elevation myocardial infarction. Cardiology. 2014;129(4):250–257.
   PubMed Web of Science ®Google Scholar
• Eitel I, Stiermaier T, Rommel KP, et al. Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial. Eur Heart J. 2015;36(44):3049–3057.
   PubMed Web of Science ®Google Scholar