Angiographic Estimates of Myocardium at Risk During Acute Myocardial Infarction: a Validation Study Using Cardiac MRI José T. Ortiz, Sheridan N. Meyers, Daniel C. Lee, Preeti Kansal, Thomas A. Holly, Francis J. Klocke, Charles J. Davidson, Robert O. Bonow, Edwin Wu Feinberg Cardiovascular Research Institute Chicago, Illinois

Background Determinants of infarct size  Duration of coronary occlusion  Residual flow in the territory at risk Collaterals Antegrade flow in the IRA  Hemodynamic factors: Blood pressure, HR.  Area at risk

Background The “Wavefront Phenomenon” of Myocardial Ischemic Cell Death Reimer K, Jennings R et al. Lab Inv 1979;40: Myocardium at risk Final infarct Duration of coronary occlusion 40 minutes 3 hours96 hours

Background SPECT-Tc 99m Area at risk = Perfusion defect before reperfusion Infarct size = Perfusion defect 2 weeks later Myocardial salvage = area at risk - infarct size Christian T et al. Circulation 1992;86:81-90 Gibbons RJ et al. NEJM 1993;328: Kastrati A et al. Lancet 2002;359:920-25

Background Limitations of SPECT for assessment of area at risk Requires imaging within 6 hours post- PCI. Not available during off-hours. Low spatial resolution. Redistribution. Requires to separate studies to compute myocardial salvage.

Aims of the study  To assess the clinical usefulness of coronary angiography to retrospectively quantify the area at risk of infarction.  To study the relationship between the anatomic area at risk by angiography and the infarct endocardial surface area on DE-CMR images.

Methods APPROACH-modified score Culprit lesion Location Infarct related artery Side branches Size Diagonal Posterolateral (LAD) (All others) SmallMediumLarge LAD (Right dominance or Left dominance) Distal Mid Proximal Proximal LCx (Right dominance) Obtuse marginal Small Medium Large Proximal LCx (Left dominance) Posterior descending artery (PDA) Small Medium Large RCA (Right dominance) Mid LCx (Left dominance) Posterior descending artery (PDA) Small Medium Large Mid LCx (Right dominance)

Methods Area at risk calculation Area at risk: 11 points Total LV: 26 points BARI (%LV) = 42.3% BARI-score Occluded LAD Patent LAD

Methods Infarct Endocardial Surface Area (i-ESA) calculation Infarct = cm 2 Non-infarct = cm 2 Total = 85.3 cm 2 i-ESA = 40 % LV

Methods First STEMI No prior history of MI CMR done within the first week 121 subjects 23 subjects with TIMI flow >0 98 subjects 12 subjects.Time not available 86 subjects 1 IRA not identified 2 previous CABG 83 subjects

Results Patient characteristics Clinical characteristics Multivessel disease55 (66%) LAD IRA42 (51%) TIMI 3/274/7 TIMI 1/01/1 CMR Ejection fraction (%)40±10 Infarct size (%LV mass)22±11 (9%-60%)

Results Area at risk by angiography vs infarct size by CMR Among subjects with transmural infarct, the anatomic area at risk matched the infarct size on ce-CMR. Bland- Altman analysis showed a bias of 2.42 % LV myocardial wall (95%CI: ) and 1.14% (95%CI: ) for BARI and APPROACH scores when compared to infarct size. In patients with non-transmural infarcts, infarct size by ce-CMR (17.3 ±8% LV) was significantly smaller than the anatomic area at risk by BARI (30.5±10% LV) and APPROACH score (29.6±10% LV)

Results Area at risk by angiography vs i-ESA In the whole group, the infarct-ESA highly correlated with the anatomical area at risk by both BARI and APPROACH scores. Bland-Altman analysis showed a bias of -1.66% LV (95% CI: ) and -2.81% of the left ventricle (95% CI: ) between infarct-ESA and anatomical area at risk by BARI and APPROACH-scores, respectively. Ortiz-Pérez JT et al. EHJ 2007:28;

Results BARIAPPROACH Area at risk by angiography (P = 0.8 for the trend) Infarct size (P < for the trend) Ortiz-Pérez JT et al. EHJ 2007:28;

Results Effect of collaterals and time to reperfusion Myocardial salvage by BARI Myocardial salvage by APPROACH Infarct transmurality score

Conclusions  The myocardium at risk can be estimated by coronary angiography and by measuring the endocardial extent of the infarct on DE-CMR images, independently of the presence of collaterals and the time to reperfusion.  This combined angiographic and CMR method permits prediction of potential infarct size and therefore allows quantification of myocardial salvage provided by reperfusion therapies.

Conclusions  The benefits of collateral flow and early reperfusion occurs by means of reduction in infarct transmural extent.  These findings confirm in humans the wavefrront phenomenon of evolving myocardial infarction described by Reimer and Jennings 30 years ago.