Influence of preinfarction angina and coronary collateral blood flow on the efficacy of remote ischaemic conditioning in patients with ST segment elevation myocardial infarction: post hoc subgroup analysis of a randomised controlled trial

Abstract

ObjectivesRemote ischaemic conditioning (RIC) confers cardioprotection in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We investigated whether preinfarction angina and coronary collateral blood flow (CCBF) to the infarct-related artery modify the efficacy of RIC.DesignPost hoc subgroup analysis of a randomised controlled trial.ParticipantsA total of 139 patients with STEMI randomised to treatment with pPCI or RIC+pPCI.InterventionsRIC was performed prior to pPCI as four cycles of 5 min upper arm ischaemia and reperfusion with a blood pressure cuff.Primary outcome measureMyocardial salvage index (MSI) assessed by single-photon emission computerised tomography. We evaluated the efficacy of RIC in subgroups of patients with or without preinfarction angina or CCBF.ResultsOf 139 patients included in the study, 109 had available data for preinfarction angina status and 54 had preinfarction angina. Among 83 patients with Thrombolysis In Myocardial Infarction flow 0/1 on arrival, 43 had CCBF. Overall, RIC+pPCI increased median MSI compared with pPCI alone (0.75 vs 0.56, p=0.045). Mean MSI did not differ between patients with and without preinfarction angina in either the pPCI alone (0.58 and 0.57; 95% CI −0.17 to 0.19, p=0.94) or the RIC+pPCI group (0.66 and 0.69; 95% CI −0.18 to 0.10, p=0.58). Mean MSI did not differ between patients with and without CCBF in the pPCI alone group (0.51 and 0.55; 95% CI −0.20 to 0.13, p=0.64), but was increased in patients with CCBF versus without CCBF in the RIC+pPCI group (0.75 vs 0.58; 95% CI 0.03 to 0.31, p=0.02; effect modification from CCBF on the effect of RIC on MSI, p=0.06).ConclusionsPreinfarction angina did not modify the efficacy of RIC in patients with STEMI undergoing pPCI. CCBF to the infarct-related artery seems to be of importance for the cardioprotective efficacy of RIC.Trial registration numberNCT00435266, Post-results.

Clinical translation of myocardial conditioning

“…Hence, the extent of collateralization has also been thought to negatively influence the ability to demonstrate an effect of any novel cardioprotective strategy. However, consistent with previous findings (174,220), Pryds et al (234) have recently validated that the area at risk did not differ between patients with and without coronary collateral blood flow to the infarct-related artery and that coronary collateral blood flow rather increased myocardial salvage index in patients with STEMI undergoing primary PCI. We interpreted this finding as the possibility that the coronary collateral circulation may facilitate the delivery of circulating humoral cardioprotective factors generated during the RIC stimulus and transported to the myocardium threatened by I/R injury.…”

“…Although the development of functional collateral vessels presumably requires time (342), a preconditioning effect is expected to be almost immediate and potentially interfere with RIC. Although the results are not consistent (174), we have not found overall effect of preinfarction angina on myocardial salvage (234). Most importantly, preinfarction angina before STEMI did not compromise the efficacy of RIC.…”

Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

“…Only the studies by White et al and Liu et al confirmed their findings of reduced enzymatic levels with a more robust marker of absolute infarct size, using CMR 41,45 . However, relying on measures of absolute infarct size may be troublesome in studies of limited sample size as several factors may influence infarct size independently of the intervention studied [164][165][166] . While some of those factors may be measured and adjusted for, other factors such as temporal variation of degree of coronary occlusion and extent of collaterals are more difficult to reliably detect.…”

Prognostic Implications of Coronary Collaterals in Transmural Infarct-Related Percutaneous Coronary Interventions

“…4 Remote ischemic preconditioning (RIC) has been evaluated as adjunct therapy in patients with STEMI managed with PCI. 5 A typical protocol for RIC is 20 minutes ischemia by inflation of an arm blood pressure cuff to 200 mm Hg, followed by reperfusion, with a reported decrease in myocardial endothelial dysfunction with cardiac ischemia. 6 The presence of CCBF involving the STEMI-related artery benefited patients undergoing RIC in addition to PCI as measured by myocardial salvage index (MSI).…”