Adenosine stress perfusion cardiac magnetic resonance imaging in patients undergoing intracoronary bone marrow cell transfer after ST-elevation myocardial infarction: the BOOST-2 perfusion substudy
In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6 months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced LVEF. Regional myocardial perfusion as determined by adenosine stress perfusion cardiac magnetic resonance imaging (S-CMR) may be more sensitive than global LVEF in detecting BMC treatment effects. Here, we sought to evaluate (i) the changes of myocardial perfusion in the infarct area over time (ii) the effects of BMC therapy on infarct perfusion, and (iii) the relation of infarct perfusion to LVEF recovery at 6 months.
Methods and results
In 51 patients from BOOST-2 (placebo, n = 10; BMC, n = 41), S-CMR was performed 5.1 ± 2.9 days after PCI (before placebo/BMC treatment) and after 6 months. Infarct perfusion improved from baseline to 6 months in the overall patient cohort as reflected by the semi-quantitative parameters, perfusion defect–infarct size ratio (change from 0.54 ± 0.20 to 0.43 ± 0.22; P = 0.006) and perfusion defect–upslope ratio (0.54 ± 0.23 to 0.68 ± 0.22; P < 0.001), irrespective of randomised treatment. Perfusion defect–upslope ratio at baseline correlated with LVEF recovery (r = 0.62; P < 0.001) after 6 months, with a threshold of 0.54 providing the best sensitivity (79%) and specificity (74%) (area under the curve, 0.79; 95% confidence interval, 0.67–0.92).
Infarct perfusion improves from baseline to 6 months and predicts LVEF recovery in STEMI patients undergoing early PCI. Intracoronary BMC therapy did not enhance infarct perfusion in the BOOST-2 trial.
KeywordsSt-elevation myocardial infarction Adenosine stress perfusion cardiac magnetic resonance imaging Bone marrow cell therapy
We would like to thank the following physicians, research assistants, and study nurses for their support of the trial: I. Schridde and S. Tammen (Hannover); E. Erdmann, M. Halbach, B. Krausgrill, and T. Schewior (Cologne); B. Blank (Berlin); W. Bethge (Tübingen); R. Bülow, M. Heukäufer, and T. Neumann (Greifswald); A. Dösch (Heidelberg); and U. Sechtem (Stuttgart). We thank F.J. Neumann (Bad Krozingen) and G. Steinhoff (Rostock) who served as members of the Data and Safety Monitoring Board.
This work was supported by the German Research Foundation (DR 148/13-1 Programme Clinical Trials), the Alfried Krupp von Bohlen and Halbach-Foundation, and the Robert Bosch Stiftung.
- 1.Szummer K, Wallentin L, Lindhagen L, Alfredsson J, Erlinge D, Held C et al (2017) Improved outcomes in patients with ST-elevation myocardial infarction during the last 20 years are related to implementation of evidence-based treatments: experiences from the SWEDEHEART registry 1995–2014. Eur Heart J 38(41):3056–3065CrossRefGoogle Scholar
- 2.Zahler D, Lee-Rozenfeld K, Ravid D, Rozenbaum Z, Banai S, Keren G, Shacham Y (2019) Relation of lowering door-to-balloon time and mortality in ST segment elevation myocardial infarction patients undergoing percutaneous coronary intervention. Clin Res Cardiol. https://doi.org/10.1007/s00392-019-01438-6 Google Scholar
- 3.Mamas MA, Anderson SG, O'Kane PD, Keavney B, Nolan J, Oldroyd KG et al (2014) Impact of left ventricular function in relation to procedural outcomes following percutaneous coronary intervention: insights from the British Cardiovascular Intervention Society. Eur Heart J 35(43):3004–3012CrossRefGoogle Scholar
- 4.Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H et al (2018) 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 39(2):119–177CrossRefGoogle Scholar
- 8.Fisher SA, Zhang H, Doree C, Mathur A, Martin-Rendon E (2015) Stem cell treatment for acute myocardial infarction. Cochrane Database Syst Rev 9:CD006536Google Scholar
- 10.Puntmann VO, Valbuena S, Hinojar R, Petersen SE, Greenwood JP, Kramer CM et al (2018) Society for Cardiovascular Magnetic Resonance (SCMR) expert consensus for CMR imaging endpoints in clinical research: part I—analytical validation and clinical qualification. J Cardiovasc Magn Reson 20(1):67CrossRefGoogle Scholar
- 12.Kramer CM, Barkhausen J, Flamm SD, Kim RJ, Nagel E, Society for Cardiovascular Magnetic Resonance Board of Trustees Task Force on Standardized P. Standardized cardiovascular magnetic resonance (CMR) protocols (2013) update. J Cardiovasc Magn Reson 2013(15):91Google Scholar
- 16.Wong DT, Leung MC, Richardson JD, Puri R, Bertaso AG, Williams K et al (2012) Cardiac magnetic resonance derived late microvascular obstruction assessment post ST-segment elevation myocardial infarction is the best predictor of left ventricular function: a comparison of angiographic and cardiac magnetic resonance derived measurements. Int J Cardiovasc Imaging 28(8):1971–1981CrossRefGoogle Scholar