CMR detects a reduction in infarct size and myocardial edema when primary PCI is augmented by Remote Ischemic Conditioning. A randomized trial

Abstract

Background: CMR is the imaging modality of choice to quantify myocardial injury in studies of cardioprotection. Remote ischemic conditioning (RIC), using transient limb ischemia and reperfusion, is a novel therapeutic intervention, which can protect the heart against acute ischemia-reperfusion injury (IRI). Whether RIC can reduce myocardial infarct (MI) size, and improve myocardial salvage in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI), is unknown, and was investigated in this randomized control clinical trial using CMR. Methods: 323 consecutive patients with suspected STEMI were screened and randomized to receive either RIC (four-5 minute cycles of upper-arm cuff inflation/deflation) or control (un-inflated cuff) prior to PPCI. 197 met study inclusion criteria of confirmed STEMI with TIMI 0 flow. The primary study endpoint was MI size, measured by late gadolinium enhancement (LGE) on day 3-6. Myocardial edema was quantified for the first time in a clinical trial by T2 mapping, the extent of edema representing the area-at-risk (AAR). T2 values were assessed in remote myocardium and the area-at-risk, providing an additional surrogate marker for the amount of edema present. The Otsu thresholding technique was prevalidated as the most reproducible technique for quantification of both MI and T2 edema compared to 8 other techniques (manual, fwhm, huang, 2-6 sd). Results: RIC reduced MI size by 27% (18.0 ± 10% versus 24.5 ± 12.0%; P = 0.009). However, RIC also reduced the extent of myocardial edema measured by T2-mapping CMR (28.5 ± 9.0% versus 35.1 ± 10.0%; P = 0.003), and lowered mean T2 values (68.7 ± 5.8 ms versus 73.1 ± 6.1 ms; P = 0.001), precluding the use of CMR edema imaging to correctly estimate the area-at-risk (AAR). Using CMR-independent coronary angiography jeopardy scores to estimate the AAR, RIC was found to significantly improve the myocardial salvage index (MSI) when compared with control (0.42 ± 0.29 versus 0.28 ± 0.29; P = 0.03). Conclusions: In STEMI patients treated by PPCI, remote ischemic conditioning, initiated prior to PPCI, reduced myocardial infarct size and increased myocardial salvage. Unexpectedly, RIC also reduced the extent of myocardial edema and lowered T2 values. This supports the cardioprotective efficacy of RIC, but importantly, adds to current controversy questioning the use of T2-CMR to estimate the AAR. (Figure Presented).