Current Cardiovascular Imaging Reports

, Volume 4, Issue 2, pp 98–107

Measuring Treatment Effects in Clinical Trials Using Cardiac MRI

  • Suzanne de Waha
  • Georg Fuernau
  • Ingo Eitel
  • Philipp Lurz
  • Steffen Desch
  • Gerhard Schuler
  • Holger Thiele


Cardiac MRI (CMR) offers the potential to assess valid and reliable parameters associated with cardiac diseases and the corresponding clinical prognosis. It has therefore emerged as a tool for outcome measures, resulting in lower study sample sizes, shorter duration of clinical studies, and subsequently less trial costs. This review focuses on the theoretical and practical background of CMR in measuring treatment effects in clinical trials.


Cardiac magnetic resonance imaging Clinical trials Outcome measures 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    •• Ward MM: Primer: measuring the effects of treatment in clinical trials. Nat Clin Pract Rheumatol 2007, 3:291-7. This paper focuses on the basic features of clinical trials and their impact on the interpretation of the results. PubMedCrossRefGoogle Scholar
  2. 2.
    • Pennell DJ: Cardiovascular magnetic resonance. Circulation 2010, 121:692-705. This review reports on current clinical indications of CMR throughout a broad range of clinical applications. PubMedCrossRefGoogle Scholar
  3. 3.
    • Coelho-Filho OR, Nallamshetty L, Kwong RY: Risk stratification for therapeutic management and prognosis. Heart Fail Clin 2009, 5:437-55, vii. This article reviews the current evidence on the prognostic impact of CMR in a wide range of cardiac conditions. PubMedCrossRefGoogle Scholar
  4. 4.
    Biomarkers and surrogate end points: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001, 69:89-95Google Scholar
  5. 5.
    Committee for Proprietary Medicinal Products (CPMP). Statistical Priniciples for Clinical Trials (ICH Topic E9). CPMP/ICH/363/96. In London, UK 1998.Google Scholar
  6. 6.
    Browner W: Getting ready to estimate sample size: hypotheses and underlying principles. In Designing clinical research: an epidemiologic approach, edn 2, 51-64 (Eds Hulley SB et al) 2001Google Scholar
  7. 7.
    Chow SC LJ: Design and analysis of clinical trials. New York: John Wiley and Sons 1998Google Scholar
  8. 8.
    Lockie T, Nagel E, Redwood S, Plein S: Use of cardiovascular magnetic resonance imaging in acute coronary syndromes. Circulation 2009, 119:1671-81.PubMedCrossRefGoogle Scholar
  9. 9.
    Bellenger NG, Burgess MI, Ray SG, et al.: Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance; are they interchangeable? Eur Heart J 2000, 21:1387-96.PubMedCrossRefGoogle Scholar
  10. 10.
    Stewart S, MacIntyre K, Hole DJ, et al.: More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 2001, 3:315-22.PubMedCrossRefGoogle Scholar
  11. 11.
    Dill T, Schachinger V, Rolf A, et al.: 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, 157:541-7.PubMedCrossRefGoogle Scholar
  12. 12.
    Thiele H, Schuster A, Erbs S, et al.: Cardiac magnetic resonance imaging at 3 and 15 months after application of circulating progenitor cells in recanalised chronic total occlusions. Int J Cardiol 2009, 135:287-95.PubMedCrossRefGoogle Scholar
  13. 13.
    Yusuf S, Diener HC, Sacco RL, et al.: Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med 2008, 359:1225-37.PubMedCrossRefGoogle Scholar
  14. 14.
    Cowan BR, Young AA, Anderson C, et al.: Left ventricular mass and volume with telmisartan, ramipril, or combination in patients with previous atherosclerotic events or with diabetes mellitus (from the ONgoing Telmisartan Alone and in Combination With Ramipril Global End point Trial [ONTARGET]). Am J Cardiol 2009, 104:1484-9.PubMedCrossRefGoogle Scholar
  15. 15.
    Shimada YJ, Shiota M, Siegel RJ, Shiota T: Accuracy of right ventricular volumes and function determined by three-dimensional echocardiography in comparison with magnetic resonance imaging: a meta-analysis study. J Am Soc Echocardiogr 2010, 23:943-53.PubMedCrossRefGoogle Scholar
  16. 16.
    Kim HK, Kim YJ, Park EA, et al.: Assessment of haemodynamic effects of surgical correction for severe functional tricuspid regurgitation: cardiac magnetic resonance imaging study. Eur Heart J 2010, 31:1520-8.PubMedCrossRefGoogle Scholar
  17. 17.
    Jahnke C, Fischer J, Gerds-Li JH, et al.: Serial monitoring of reverse left-atrial remodeling after pulmonary vein isolation in patients with atrial fibrillation: A magnetic resonance imaging study. Int J Cardiol 2010.Google Scholar
  18. 18.
    Nagel E, Lehmkuhl HB, Bocksch W, et al.: Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography. Circulation 1999, 99:763-70.PubMedGoogle Scholar
  19. 19.
    Schwitter J, Wacker CM, van Rossum AC, et al.: MR-IMPACT: comparison of perfusion-cardiac magnetic resonance with single-photon emission computed tomography for the detection of coronary artery disease in a multicentre, multivendor, randomized trial. Eur Heart J 2008, 29:480-9.PubMedCrossRefGoogle Scholar
  20. 20.
    Watkins S, McGeoch R, Lyne J, et al.: Validation of magnetic resonance myocardial perfusion imaging with fractional flow reserve for the detection of significant coronary heart disease. Circulation 2009, 120:2207-13.PubMedCrossRefGoogle Scholar
  21. 21.
    Ingkanisorn WP, Kwong RY, Bohme NS, et al.: Prognosis of negative adenosine stress magnetic resonance in patients presenting to an emergency department with chest pain. J Am Coll Cardiol 2006, 47:1427-32.PubMedCrossRefGoogle Scholar
  22. 22.
    Jahnke C, Nagel E, Gebker R, et al.: Prognostic value of cardiac magnetic resonance stress tests: adenosine stress perfusion and dobutamine stress wall motion imaging. Circulation 2007, 115:1769-76.PubMedCrossRefGoogle Scholar
  23. 23.
    Chan CW, Kwong YL, Kwong RY, et al.: Improvement of myocardial perfusion reserve detected by cardiovascular magnetic resonance after direct endomyocardial implantation of autologous bone marrow cells in patients with severe coronary artery disease. J Cardiovasc Magn Reson 2010, 12:6.PubMedCrossRefGoogle Scholar
  24. 24.
    Kwong RY, Chan AK, Brown KA, et al.: Impact of unrecognized myocardial scar detected by cardiac magnetic resonance imaging on event-free survival in patients presenting with signs or symptoms of coronary artery disease. Circulation 2006, 113:2733-43.PubMedCrossRefGoogle Scholar
  25. 25.
    Plein S, Younger JF, Sparrow P, et al.: Cardiovascular magnetic resonance of scar and ischemia burden early after acute ST elevation and non-ST elevation myocardial infarction. J Cardiovasc Magn Reson 2008, 10:47.PubMedCrossRefGoogle Scholar
  26. 26.
    Kim RJ, Albert TS, Wible JH, et al.: Performance of delayed-enhancement magnetic resonance imaging with gadoversetamide contrast for the detection and assessment of myocardial infarction: an international, multicenter, double-blinded, randomized trial. Circulation 2008, 117:629-37.PubMedCrossRefGoogle Scholar
  27. 27.
    Wagner A, Mahrholdt H, Holly TA, et al.: Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study. Lancet 2003, 361:374-9.PubMedCrossRefGoogle Scholar
  28. 28.
    Kelle S, Roes SD, Klein C, et al.: Prognostic value of myocardial infarct size and contractile reserve using magnetic resonance imaging. J Am Coll Cardiol 2009, 54:1770-7.PubMedCrossRefGoogle Scholar
  29. 29.
    Thiele H, Schindler K, Friedenberger J, et al.: Intracoronary compared with intravenous bolus abciximab application in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: the randomized Leipzig immediate percutaneous coronary intervention abciximab IV versus IC in ST-elevation myocardial infarction trial. Circulation 2008, 118:49-57.PubMedCrossRefGoogle Scholar
  30. 30.
    Atar D, Petzelbauer P, Schwitter J, et al.: Effect of intravenous FX06 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction results of the F.I.R.E. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury) trial. J Am Coll Cardiol 2009, 53:720-9.PubMedCrossRefGoogle Scholar
  31. 31.
    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.Google Scholar
  32. 32.
    Sardella G, Mancone M, Bucciarelli-Ducci C, et al.: Thrombus aspiration during primary percutaneous coronary intervention improves myocardial reperfusion and reduces infarct size: the EXPIRA (thrombectomy with export catheter in infarct-related artery during primary percutaneous coronary intervention) prospective, randomized trial. J Am Coll Cardiol 2009, 53:309-15.PubMedCrossRefGoogle Scholar
  33. 33.
    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, 113:1865-70.PubMedCrossRefGoogle Scholar
  34. 34.
    Friedrich MG, Abdel-Aty H, Taylor A, et al.: The salvaged area at risk in reperfused acute myocardial infarction as visualized by cardiovascular magnetic resonance. J Am Coll Cardiol 2008, 51:1581-7.PubMedCrossRefGoogle Scholar
  35. 35.
    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, 55:2470-9.PubMedCrossRefGoogle Scholar
  36. 36.
    Lonborg J, Kelbaek H, Vejlstrup N, et al.: Cardioprotective effects of ischemic postconditioning in patients treated with primary percutaneous coronary intervention, evaluated by magnetic resonance. Circ Cardiovasc Interv 2010, 3:34-41.PubMedCrossRefGoogle Scholar
  37. 37.
    Thiele H, Hildebrand L, Schirdewahn C, et al.: Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouS Coronary Intervention Acute Myocardial Infarction N-ACC) Trial. J Am Coll Cardiol 2010, 55:2201-9.PubMedCrossRefGoogle Scholar
  38. 38.
    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, 30:1440-9.PubMedCrossRefGoogle Scholar
  39. 39.
    Lamb HJ, Beyerbacht HP, de Roos A, et al.: Left ventricular remodeling early after aortic valve replacement: differential effects on diastolic function in aortic valve stenosis and aortic regurgitation. J Am Coll Cardiol 2002, 40:2182-8.PubMedCrossRefGoogle Scholar
  40. 40.
    Oosterhof T, van Straten A, Vliegen HW, et al.: Preoperative thresholds for pulmonary valve replacement in patients with corrected tetralogy of Fallot using cardiovascular magnetic resonance. Circulation 2007, 116:545-51.PubMedCrossRefGoogle Scholar
  41. 41.
    Lurz P, Nordmeyer J, Muthurangu V, et al.: Comparison of bare metal stenting and percutaneous pulmonary valve implantation for treatment of right ventricular outflow tract obstruction: use of an x-ray/magnetic resonance hybrid laboratory for acute physiological assessment. Circulation 2009, 119:2995-3001.PubMedCrossRefGoogle Scholar
  42. 42.
    Kirk P, Roughton M, Porter JB, et al.: Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation 2009, 120:1961-8.PubMedCrossRefGoogle Scholar
  43. 43.
    Modell B, Khan M, Darlison M, et al.: Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2008, 10:42.PubMedCrossRefGoogle Scholar
  44. 44.
    Assomull RG, Prasad SK, Lyne J, et al.: Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy. J Am Coll Cardiol 2006, 48:1977-85.PubMedCrossRefGoogle Scholar
  45. 45.
    Bruder O, Wagner A, Jensen CJ, et al.: Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2010, 56:875-87.PubMedCrossRefGoogle Scholar
  46. 46.
    Hughes DA, Elliott PM, Shah J, et al.: Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa. Heart 2008, 94:153-8.PubMedCrossRefGoogle Scholar
  47. 47.
    Vignaux O, Dhote R, Duboc D, et al.: Clinical significance of myocardial magnetic resonance abnormalities in patients with sarcoidosis: a 1-year follow-up study. Chest 2002, 122:1895-901.PubMedCrossRefGoogle Scholar
  48. 48.
    Friedrich MG, Sechtem U, Schulz-Menger J, et al.: Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol 2009, 53:1475-87.PubMedCrossRefGoogle Scholar
  49. 49.
    Butler CR, Thompson R, Haykowsky M, et al.: Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review. J Cardiovasc Magn Reson 2009, 11:7.PubMedCrossRefGoogle Scholar
  50. 50.
    Gaddam K, Corros C, Pimenta E, et al.: Rapid reversal of left ventricular hypertrophy and intracardiac volume overload in patients with resistant hypertension and hyperaldosteronism: a prospective clinical study. Hypertension 2010, 55:1137-42.PubMedCrossRefGoogle Scholar
  51. 51.
    Kirschbaum SW, Springeling T, Boersma E, et al.: Complete percutaneous revascularization for multivessel disease in patients with impaired left ventricular function: pre- and post-procedural evaluation by cardiac magnetic resonance imaging. JACC Cardiovasc Interv 2010, 3:392-400.PubMedCrossRefGoogle Scholar
  52. 52.
    Pegg TJ, Selvanayagam JB, Francis JM, et al.: A randomized trial of on-pump beating heart and conventional cardioplegic arrest in coronary artery bypass surgery patients with impaired left ventricular function using cardiac magnetic resonance imaging and biochemical markers. Circulation 2008, 118:2130-8.PubMedCrossRefGoogle Scholar
  53. 53.
    Yao K, Huang R, Qian J, et al.: Administration of intracoronary bone marrow mononuclear cells on chronic myocardial infarction improves diastolic function. Heart 2008, 94:1147-53.PubMedCrossRefGoogle Scholar
  54. 54.
    Pegg TJ, Selvanayagam JB, Karamitsos TD, et al.: Effects of off-pump versus on-pump coronary artery bypass grafting on early and late right ventricular function. Circulation 2008, 117:2202-10.PubMedCrossRefGoogle Scholar
  55. 55.
    Webb CM, Elkington AG, Kraidly MM, et al.: Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease. Am J Cardiol 2008, 101:618-24.PubMedCrossRefGoogle Scholar
  56. 56.
    Cheng AS, Selvanayagam JB, Jerosch-Herold M, et al.: Percutaneous treatment of chronic total coronary occlusions improves regional hyperemic myocardial blood flow and contractility: insights from quantitative cardiovascular magnetic resonance imaging. JACC Cardiovasc Interv 2008, 1:44-53.PubMedCrossRefGoogle Scholar
  57. 57.
    Abbate A, Kontos MC, Grizzard JD, et al.: Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study). Am J Cardiol 2010, 105:1371-7 e1PubMedCrossRefGoogle Scholar
  58. 58.
    Wohrle J, Merkle N, Mailander V, et al.: Results of intracoronary stem cell therapy after acute myocardial infarction. Am J Cardiol 2010, 105:804-12.PubMedCrossRefGoogle Scholar
  59. 59.
    Haeck JD, Kuijt WJ, Koch KT, et al.: Infarct size and left ventricular function in the PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-segment Elevation (PREPARE) trial: ancillary cardiovascular magnetic resonance study. Heart 2010, 96:190-5.PubMedCrossRefGoogle Scholar
  60. 60.
    Patel MR, Worthley SG, Stebbins A, et al.: Pexelizumab and infarct size in patients with acute myocardial infarction undergoing primary percutaneous coronary Intervention: a delayed enhancement cardiac magnetic resonance substudy from the APEX-AMI trial. JACC Cardiovasc Imaging 2010, 3:52-60.PubMedCrossRefGoogle Scholar
  61. 61.
    Weir RA, Mark PB, Petrie CJ, et al.: Left ventricular remodeling after acute myocardial infarction: does eplerenone have an effect? Am Heart J 2009, 157:1088-96.PubMedCrossRefGoogle Scholar
  62. 62.
    Tendera M, Wojakowski W, Ruzyllo W, et al.: Intracoronary infusion of bone marrow-derived selected CD34 + CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial. Eur Heart J 2009, 30:1313-21.PubMedCrossRefGoogle Scholar
  63. 63.
    Song YB, Hahn JY, Gwon HC, et al.: Upstream high-dose tirofiban does not reduce myocardial infarct size in patients undergoing primary percutaneous coronary intervention: a magnetic resonance imaging pilot study. Clin Cardiol 2009, 32:321-6.PubMedCrossRefGoogle Scholar
  64. 64.
    Hahn JY, Gwon HC, Choe YH, et al.: Effects of balloon-based distal protection during primary percutaneous coronary intervention on early and late infarct size and left ventricular remodeling: a pilot study using serial contrast-enhanced magnetic resonance imaging. Am Heart J 2007, 153:665 e1-8.Google Scholar
  65. 65.
    Engelmann MG, Theiss HD, Hennig-Theiss C, et al.: Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: final results from the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) trial. J Am Coll Cardiol 2006, 48:1712-21.PubMedCrossRefGoogle Scholar
  66. 66.
    Kang HJ, Lee HY, Na SH, et al.: Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: the MAGIC Cell-3-DES randomized, controlled trial. Circulation 2006, 114:I145-51.PubMedGoogle Scholar
  67. 67.
    Ripa RS, Jorgensen E, Wang Y, et al.: Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial. Circulation 2006, 113:1983-92.PubMedCrossRefGoogle Scholar
  68. 68.
    Janssens S, Dubois C, Bogaert J, et al.: Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 2006, 367:113-21.PubMedCrossRefGoogle Scholar
  69. 69.
    Thiele H, Engelmann L, Elsner K, et al.: Comparison of pre-hospital combination-fibrinolysis plus conventional care with pre-hospital combination-fibrinolysis plus facilitated percutaneous coronary intervention in acute myocardial infarction. Eur Heart J 2005, 26:1956-63.PubMedCrossRefGoogle Scholar
  70. 70.
    Gick M, Jander N, Bestehorn HP, et al.: Randomized evaluation of the effects of filter-based distal protection on myocardial perfusion and infarct size after primary percutaneous catheter intervention in myocardial infarction with and without ST-segment elevation. Circulation 2005, 112:1462-9.PubMedCrossRefGoogle Scholar
  71. 71.
    Wollert KC, Meyer GP, Lotz J, et al.: Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004, 364:141-8.PubMedCrossRefGoogle Scholar
  72. 72.
    Gelfand EV, Haffajee JA, Hauser TH, et al.: Predictors of preserved left ventricular systolic function after surgery for chronic organic mitral regurgitation: a prospective study. J Heart Valve Dis 2010, 19:43-50.PubMedGoogle Scholar
  73. 73.
    Tanner MA, Galanello R, Dessi C, et al.: Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction. J Cardiovasc Magn Reson 2008, 10:12.PubMedCrossRefGoogle Scholar
  74. 74.
    Shimada T, Shimada K, Sakane T, et al.: Diagnosis of cardiac sarcoidosis and evaluation of the effects of steroid therapy by gadolinium-DTPA-enhanced magnetic resonance imaging. Am J Med 2001, 110:520-7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Suzanne de Waha
    • 1
  • Georg Fuernau
    • 1
  • Ingo Eitel
    • 1
  • Philipp Lurz
    • 1
  • Steffen Desch
    • 1
  • Gerhard Schuler
    • 1
  • Holger Thiele
    • 1
  1. 1.Department of Internal Medicine/CardiologyUniversity of Leipzig – Heart CenterLeipzigGermany

Personalised recommendations