Myocardial Infarct Size by CMR in Clinical Cardioprotection Studies: Insights From Randomized Controlled Trials

Abstract

Objectives: The aim of this study was to review randomized controlled trials (RCTs) using cardiac magnetic resonance (CMR) to assess myocardial infarct (MI) size in reperfused patients with ST-segment elevation myocardial infarction (STEMI).

Background: There is limited guidance on the use of CMR in clinical cardioprotection RCTs in patients with STEMI treated by primary percutaneous coronary intervention.

Methods: All RCTs in which CMR was used to quantify MI size in patients with STEMI treated with primary percutaneous coronary intervention were identified and reviewed.

Results: Sixty-two RCTs (10,570 patients, January 2006 to November 2016) were included. One-third did not report CMR vendor or scanner strength, the contrast agent and dose used, and the MI size quantification technique. Gadopentetate dimeglumine was most commonly used, followed by gadoterate meglumine and gadobutrol at 0.20 mmol/kg each, with late gadolinium enhancement acquired at 10 min; in most RCTs, MI size was quantified manually, followed by the 5 standard deviation threshold; dropout rates were 9% for acute CMR only and 16% for paired acute and follow-up scans. Weighted mean acute and chronic MI sizes (≤12 h, initial TIMI [Thrombolysis in Myocardial Infarction] flow grade 0 to 3) from the control arms were 21 ± 14% and 15 ± 11% of the left ventricle, respectively, and could be used for future sample-size calculations. Pre-selecting patients most likely to benefit from the cardioprotective therapy (≤6 h, initial TIMI flow grade 0 or 1) reduced sample size by one-third. Other suggested recommendations for standardizing CMR in future RCTs included gadobutrol at 0.15 mmol/kg with late gadolinium enhancement at 15 min, manual or 6-SD threshold for MI quantification, performing acute CMR at 3 to 5 days and follow-up CMR at 6 months, and adequate reporting of the acquisition and analysis of CMR.

Conclusions: There is significant heterogeneity in RCT design using CMR in patients with STEMI. The authors provide recommendations for standardizing the assessment of MI size using CMR in future clinical cardioprotection RCTs.

Keywords: ST-segment elevation myocardial infarction; cardiovascular magnetic resonance; myocardial infarct size; primary percutaneous coronary intervention; randomized controlled trial; sample size.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses Flow Diagram This figure shows the process of identifying, screening, and selecting the randomized controlled trials (RCTs) included in this study. Of 399 studies screened, 62 RCTs eventually met the inclusion criteria. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 2

Number of Randomized Controlled Trials Published Each Year Since 2006 This bar chart shows the gradual increase in the number of randomized controlled trials (RCTs) published each year over the past 11 years.

Figure 3

Distribution of RCTs by Inclusion of Patients on the Basis of Duration of Symptoms, Infarct-Related Artery Included, and TIMI Flow Grade Pre–Primary Percutaneous Coronary Intervention These 3 pie charts show the percentage of randomized controlled trials (RCTs) including (A) patients on the basis of duration of symptoms, (B) infarct-related artery, and (C) TIMI (Thrombolysis in Myocardial Infarction) flow grade pre–primary percutaneous coronary intervention (PPCI). The majority of the RCTs included patients presenting within 12 h of symptom onset, with ST-segment elevation myocardial infarction in all coronary territories, and with all pre-PPCI TIMI flow grades. LAD = left anterior descending coronary artery; RCA = right coronary artery.

Figure 4

Timing of Acute and Follow-Up CMR These 2 bar charts show the distribution of the timings of the (A) acute and (B) follow-up cardiac magnetic resonance (CMR) in the randomized controlled trials (RCTs) included. There was a wide range of timings for both scans, and the most common timings were 3 to 5 days for the acute scan and 6 months for the follow-up scan.

Figure 5

Quantification Techniques for MI Size The most common myocardial infarct (MI) size quantification method was manual delineation, followed by 5-SD and full width half maximum (FWHM). However, 27% of randomized controlled trials did not specify the method used.

Figure 6

Evolution of Edema-Based Area at Risk, MI Size, Microvascular Obstruction, and Intramyocardial Hemorrhage in Patients With ST-Segment Elevation Myocardial Infarction Within the First 10 Days Post-Reperfusion This is a schematic representation of the evolution edema-based area at risk (AAR) (based on findings from Carrick et al. and Desch et al. [8]), myocardial infarct (MI) size (Carrick et al. and Desch et al. [8]), microvascular obstruction (MVO) (Carrick et al. 20, 30), and intramyocardial hemorrhage (IMH) (Carrick et al. 20, 30) within the first 10 days post-reperfusion, expressed as percentage left ventricular volume or mass (%LV). *The scale on the y-axis is an approximation. LGE = late gadolinium enhancement; PPCI = primary percutaneous coronary intervention.