Regional myocardial function after intracoronary bone marrow cell injection in reperfused anterior wall infarction - a cardiovascular magnetic resonance tagging study

Einar Hopp, Ketil Lunde, Svein Solheim, Svend Aakhus, Harald Arnesen, Kolbjørn Forfang, Thor Edvardsen, Hans-Jørgen Smith, Einar Hopp, Ketil Lunde, Svein Solheim, Svend Aakhus, Harald Arnesen, Kolbjørn Forfang, Thor Edvardsen, Hans-Jørgen Smith

Abstract

Background: Trials have brought diverse results of bone marrow stem cell treatment in necrotic myocardium. This substudy from the Autologous Stem Cell Transplantation in Acute Myocardial Infarction trial (ASTAMI) explored global and regional myocardial function after intracoronary injection of autologous mononuclear bone marrow cells (mBMC) in acute anterior wall myocardial infarction treated with percutaneous coronary intervention.

Methods: Cardiovascular magnetic resonance (CMR) tagging was performed 2-3 weeks and 6 months after revascularization in 15 patients treated with intracoronary stem cell injection (mBMC group) and in 13 controls without sham injection. Global and regional left ventricular (LV) strain and LV twist were correlated to cine CMR and late gadolinium enhancement (LGE).

Results: In the control group myocardial function as measured by strain improved for the global LV (6 months: -13.1 ± 2.4 versus 2-3 weeks: -11.9 ± 3.4%, p = 0.014) and for the infarct zone (-11.8 ± 3.0 versus -9.3 ± 4.1%, p = 0.001), and significantly more than in the mBMC group (inter-group p = 0.027 for global strain, respectively p = 0.009 for infarct zone strain). LV infarct mass decreased (35.7 ± 20.4 versus 45.7 ± 29.5 g, p = 0.024), also significantly more pronounced than the mBMC group (inter-group p = 0.034). LV twist was initially low and remained unchanged irrespective of therapy.

Conclusions: LGE and strain findings quite similarly demonstrate subtle differences between the mBMC and control groups. Intracoronary injection of autologous mBMC did not strengthen regional or global myocardial function in this substudy.

Trial registration: ClinicalTrials.gov: NCT00199823.

Figures

Figure 1
Figure 1
Baseline apical tagging analysis in a 49 year old male patient in the mBMC group. Upper part: The curves represent strain in the apical segments, analyzed with HARP software from a short axis CMR tagging sequence. The vertical box represents the end systolic frame (F6). There is almost normal function in the lateral wall, dysfunction in the inferior wall, while septum and the anterior wall are almost akinetic with possible post-systolic contraction. Note increasing noise during diastolic frames, due to T1 relaxation of the tagged myocardium. Lower part: Left: Short axis apical LGE image with hyperintensity in the anterior wall, septum and part of the inferior wall. Mid and right: Short axis apical end diastolic (mid) and end systolic (right) tagging images with application of the semi-automatically traced lines from HARP software. Circumferential mid-wall end systolic strain was calculated from deformation of the orange mid-wall line.
Figure 2
Figure 2
Bull's eye plots over baseline LGE and strain in the 16 LV segments model. 2 a: Average infarct involvement (percent) in each segment (n = 448). 2 b: Average strain (percent) in each segment (n = 402). Negative strain values indicate myocardial shortening, and a strain value with amplitude higher than -14% is considered normal.

References

    1. Nogueira FB, Silva SA, Haddad AF, Peixoto CM, Carvalho RM, Tuche FA, Soares VE, Sousa AL, Rabischoffsky A, Mesquita CT, Borojevic R, Dohmann HF. Systolic function of patients with myocardial infarction undergoing autologous bone marrow transplantation. Arq Bras Cardiol. 2009;93:374–72. doi: 10.1590/S0066-782X2009001000010.
    1. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grogaard HK, Bjornerheim R, Brekke M, Muller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006;355:1199–1209. doi: 10.1056/NEJMoa055706.
    1. Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hertenstein B, Ganser A, Drexler H. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet. 2004;364:141–148. doi: 10.1016/S0140-6736(04)16626-9.
    1. van der Laan A, Hirsch A, Nijveldt R, van d V, van der Giessen WJ, Doevendans PA, Waltenberger J, Ten Berg JM, Aengevaeren WR, Zwaginga JJ, Biemond BJ, van Rossum AC, Tijssen JG, Zijlstra F, Piek JJ. Bone marrow cell therapy after acute myocardial infarction: the HEBE trial in perspective, first results. Neth Heart J. 2008;16:436–439. doi: 10.1007/BF03086194.
    1. Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W, Kalantzi M, Herbots L, Sinnaeve P, Dens J, Maertens J, Rademakers F, Dymarkowski S, Gheysens O, Van Cleemput J, Bormans G, Nuyts J, Belmans A, Mortelmans L, Boogaerts M, Van de Werf F. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet. 2006;367:113–121. doi: 10.1016/S0140-6736(05)67861-0.
    1. Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med. 2006;355:1210–1221. doi: 10.1056/NEJMoa060186.
    1. Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, Hecker H, Schaefer A, Arseniev L, Hertenstein B, Ganser A, Drexler H. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation. 2006;113:1287–1294. doi: 10.1161/CIRCULATIONAHA.105.575118.
    1. Herbots L, D'hooge J, Eroglu E, Thijs D, Ganame J, Claus P, Dubois C, Theunissen K, Bogaert J, Dens J, Kalantzi M, Dymarkowski S, Bijnens B, Belmans A, Boogaerts M, Sutherland G, Van deWerf F, Rademakers F, Janssens S. Improved regional function after autologous bone marrow-derived stem cell transfer in patients with acute myocardial infarction: a randomized, double-blind strain rate imaging study. Eur Heart J. 2009;30:662–670. doi: 10.1093/eurheartj/ehn532.
    1. Dill T, Schachinger V, Rolf A, Mollmann S, Thiele H, Tillmanns H, Assmus B, Dimmeler S, Zeiher AM, Hamm C. Intracoronary administration of bone marrow-derived progenitor cells improves left ventricular function in patients at risk for adverse remodeling after acute ST-segment elevation myocardial infarction: results of the Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction study (REPAIR-AMI) cardiac magnetic resonance imaging substudy. Am Heart J. 2009;157:541–547. doi: 10.1016/j.ahj.2008.11.011.
    1. Beitnes JO, Gjesdal O, Lunde K, Solheim S, Edvardsen T, Arnesen H, Forfang K, Aakhus S. Left ventricular systolic and diastolic function improve after acute myocardial infarction treated with acute percutaneous coronary intervention, but are not influenced by intracoronary injection of autologous mononuclear bone marrow cells: a 3 year serial echocardiographic sub-study of the randomized-controlled ASTAMI study. Eur J Echocardiogr. 2011;12:98–106. doi: 10.1093/ejechocard/jeq116.
    1. Schaefer A, Zwadlo C, Fuchs M, Meyer GP, Lippolt P, Wollert KC, Drexler H. Long-term effects of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: 5-year results from the randomized-controlled BOOST trial--an echocardiographic study. Eur J Echocardiogr. 2010;11:165–171. doi: 10.1093/ejechocard/jep191.
    1. Edvardsen T, Rosen BD. Why do we need magnetic resonance imaging in cardiology? Scand Cardiovasc J. 2005;39:260–263. doi: 10.1080/14017430500405015.
    1. Shehata ML, Cheng S, Osman NF, Bluemke DA, Lima JA. Myocardial tissue tagging with cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2009;11:55. doi: 10.1186/1532-429X-11-55.
    1. Sievers B, Brandts B, Franken U, Trappe HJ. Single and biplane TrueFISP cardiovascular magnetic resonance for rapid evaluation of left ventricular volumes and ejection fraction. J Cardiovasc Magn Reson. 2004;6:593–600. doi: 10.1081/JCMR-120038081.
    1. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation. 2002;105:539–542. doi: 10.1161/hc0402.102975.
    1. Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy J, Finn JP, Klocke FJ, Judd RM. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation. 1999;100:1992–2002.
    1. Schuijf JD, Kaandorp TA, Lamb HJ, van der Geest RJ, Viergever EP, van der Wall EE, de RA, Bax JJ. Quantification of myocardial infarct size and transmurality by contrast-enhanced magnetic resonance imaging in men. Am J Cardiol. 2004;94:284–288. doi: 10.1016/j.amjcard.2004.04.020.
    1. Bondarenko O, Beek AM, Hofman MB, Kuhl HP, Twisk JW, van Dockum WG, Visser CA, van Rossum AC. Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR. J Cardiovasc Magn Reson. 2005;7:481–485. doi: 10.1081/JCMR-200053623.
    1. Shapiro EP, Rogers WJ, Beyar R, Soulen RL, Zerhouni EA, Lima JA, Weiss JL. Determination of left ventricular mass by magnetic resonance imaging in hearts deformed by acute infarction. Circulation. 1989;79:706–711.
    1. Wu KC, Zerhouni EA, Judd RM, Lugo-Olivieri CH, Barouch LA, Schulman SP, Blumenthal RS, Lima JA. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation. 1998;97:765–772.
    1. Beitnes JO, Hopp E, Lunde K, Solheim S, Arnesen H, Brinchmann JE, Forfang K, Aakhus S. Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: the ASTAMI randomised, controlled study. Heart. 2009;95:1983–1989. doi: 10.1136/hrt.2009.178913.
    1. Gjesdal O, Hopp E, Vartdal T, Lunde K, Helle-Valle T, Aakhus S, Smith HJ, Ihlen H, Edvardsen T. Global longitudinal strain measured by two-dimensional speckle tracking echocardiography is closely related to myocardial infarct size in chronic ischaemic heart disease. Clin Sci (Lond) 2007;113:287–296. doi: 10.1042/CS20070066.
    1. Cupps BP, Bree DR, Wollmuth JR, Howells AC, Voeller RK, Rogers JG, Pasque MK. Myocardial viability mapping by magnetic resonance-based multiparametric systolic strain analysis. Ann Thorac Surg. 2008;86:1546–1553. doi: 10.1016/j.athoracsur.2008.06.072.
    1. Vartdal T, Brunvand H, Pettersen E, Smith HJ, Lyseggen E, Helle-Valle T, Skulstad H, Ihlen H, Edvardsen T. Early prediction of infarct size by strain Doppler echocardiography after coronary reperfusion. J Am Coll Cardiol. 2007;49:1715–1721. doi: 10.1016/j.jacc.2006.12.047.
    1. Rademakers F, Van de WF, Mortelmans L, Marchal G, Bogaert J. Evolution of regional performance after an acute anterior myocardial infarction in humans using magnetic resonance tagging. J Physiol. 2003;546:777–787. doi: 10.1113/jphysiol.2002.026328.
    1. Meyer GP, Wollert KC, Lotz J, Pirr J, Rager U, Lippolt P, Hahn A, Fichtner S, Schaefer A, Arseniev L, Ganser A, Drexler H. Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial. Eur Heart J. 2009;30:2978–2984. doi: 10.1093/eurheartj/ehp374.
    1. Coghlan C, Hoffman J. Leonardo da Vinci's flights of the mind must continue: cardiac architecture and the fundamental relation of form and function revisited. Eur J Cardiothorac Surg. 2006;29(Suppl 1):S4–17. doi: 10.1016/j.ejcts.2006.03.010.
    1. McDonald IG. The shape and movements of the human left ventricle during systole. A study by cineangiography and by cineradiography of epicardial markers. Am J Cardiol. 1970;26:221–230. doi: 10.1016/0002-9149(70)90787-3.
    1. Helle-Valle T, Remme EW, Lyseggen E, Pettersen E, Vartdal T, Opdahl A, Smith HJ, Osman NF, Ihlen H, Edvardsen T, Smiseth OA. Clinical assessment of left ventricular rotation and strain: a novel approach for quantification of function in infarcted myocardium and its border zones. Am J Physiol Heart Circ Physiol. 2009;297:H257–H267. doi: 10.1152/ajpheart.01116.2008.
    1. Bertini M, Nucifora G, Marsan NA, Delgado V, van Bommel RJ, Boriani G, Biffi M, Holman ER, van der Wall EE, Schalij MJ, Bax JJ. Left ventricular rotational mechanics in acute myocardial infarction and in chronic (ischemic and nonischemic) heart failure patients. Am J Cardiol. 2009;103:1506–1512. doi: 10.1016/j.amjcard.2009.02.010.
    1. Opdahl A, Helle-Valle T, Remme EW, Vartdal T, Pettersen E, Lunde K, Edvardsen T, Smiseth OA. Apical rotation by speckle tracking echocardiography: a simplified bedside index of left ventricular twist. J Am Soc Echocardiogr. 2008;21:1121–1128. doi: 10.1016/j.echo.2008.06.012.
    1. Garot J, Pascal O, Diebold B, Derumeaux G, Gerber BL, Dubois-Rande JL, Lima JA, Gueret P. Alterations of systolic left ventricular twist after acute myocardial infarction. Am J Physiol Heart Circ Physiol. 2002;282:H357–H362.
    1. Han W, Xie MX, Wang XF, Lu Q, Wang J, Zhang L, Zhang J. Assessment of left ventricular torsion in patients with anterior wall myocardial infarction before and after revascularization using speckle tracking imaging. Chin Med J (Engl) 2008;121:1543–1548.
    1. Ortiz-Perez JT, Rodriguez J, Meyers SN, Lee DC, Davidson C, Wu E. Correspondence between the 17-segment model and coronary arterial anatomy using contrast-enhanced cardiac magnetic resonance imaging. JACC Cardiovasc Imaging. 2008;1:282–293. doi: 10.1016/j.jcmg.2008.01.014.
    1. Ibrahim T, Hackl T, Nekolla SG, Breuer M, Feldmair M, Schomig A, Schwaiger M. Acute myocardial infarction: serial cardiac MR imaging shows a decrease in delayed enhancement of the myocardium during the 1st week after reperfusion. Radiology. 2010;254:88–97. doi: 10.1148/radiol.09090660.
    1. Engblom H, Hedstrom E, Heiberg E, Wagner GS, Pahlm O, Arheden H. Rapid initial reduction of hyperenhanced myocardium after reperfused first myocardial infarction suggests recovery of the peri-infarction zone: one-year follow-up by MRI. Circ Cardiovasc Imaging. 2009;2:47–55. doi: 10.1161/CIRCIMAGING.108.802199.
    1. Orn S, Manhenke C, Anand IS, Squire I, Nagel E, Edvardsen T, Dickstein K. Effect of left ventricular scar size, location, and transmurality on left ventricular remodeling with healed myocardial infarction. Am J Cardiol. 2007;99:1109–1114. doi: 10.1016/j.amjcard.2006.11.059.

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