Remote Ischemic Preconditioning for Percutaneous Coronary Intervention: Waiting for Godot?

T he year 2016 marked the 30th anniversary of the discovery of the phenomenon of “ischemic conditioning,” dating back to the mid-1980s when Murry, Jennings, and Reimer noted that pretreating the canine left circumflex coronary artery with 4, 5-minute cycles of occlusion and reflow before subsequent occlusion of the vessel for 40 minutes led to a 25% reduction in myocardial infarction (MI) size. Several variations on the original concept have since evolved, and ischemic conditioning types are now known to include preconditioning, postconditioning, pharmacologic cardioprotection, and remote conditioning. Remote ischemic conditioning (RIC) was first studied around 1993 when dogs that had intermittent canine left circumflex coronary artery occlusion before left anterior descending occlusion experienced decreased infarct size. Later, this expanded to encompass cycles of inflation/ deflation of a sphygmomanometer placed around the upper (or lower) extremity before (preconditioning) or after (postconditioning) percutaneous coronary intervention (PCI). RIC is most commonly performed by inflating a blood pressure cuff around the arm, typically for 3 or 5 minutes, and 1 to 4 cycles, with most contemporary studies using 4 5-minute cuff inflations. Given its simplicity, RIC could readily be initiated in an ambulance during transport for primary PCI in acute MI, or could be administered before a planned coronary revascularization with either PCI or coronary artery bypass graft surgery. Ischemic conditioning has been the focus of extensive investigative efforts: a PubMed search on “ischemic preconditioning” on September 8, 2018 provided 10 301 results. While many preclinical studies have shown benefit, clinical studies have provided less consistent results. Remote ischemic preconditioning did not reduce the incidence of major adverse cardiac and cerebral events in 2 large randomized-controlled cardiac surgery trials, the RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) trial and the ERICCA (Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Surgery) trial. Although this might be related to use of propofol for sedation (which may diminish or abolish the effect of ischemia-induced cardioprotection), in ERICCA the incidence of cardiovascular death was numerically higher in the remote ischemic preconditioning group (P=0.08), suggesting possible harm. Unlike cardiac surgery, there are no completed large randomized-controlled trials assessing the effect of RIC during PCI. RIC holds the most promise for treating MI patients, with small studies showing improved salvage index by nuclear imaging, reduced infarct size and edema by magnetic resonance imaging, and improved ST-segment elevation resolution and cardiac biomarker rise. The ongoing 5413 patient CONDI2/ERIC-PPCI (Effect of Remote Ischaemic Conditioning on Clinical Outcomes in STEMI Patients Undergoing PPCI) trial is examining the impact of RIC on the 12month incidence of cardiac death and hospitalization for heart failure, and results are anticipated in 2019. In the setting of elective PCI, several relatively small studies such as the CRISP Stent (Cardiac Remote Ischemic Preconditioning in Coronary Stenting) study have shown that RIC can reduce the incidence of periprocedural MI, chest pain, ischemic ECG changes, and in at least 1 study, reduce the combined end point of all-cause mortality, nonfatal MI, transient ischemic attack or stroke, and heart failure hospitalizations. Other studies, however, were negative, with interpretation of conflicting data somewhat limited by interstudy differences in methodology and study populations. In this issue of the Journal of the American Heart Association (JAHA), Yong et al examined the impact of RIC on the coronary microcirculation, as assessed by the index of microcirculatory resistance, coronary flow reserve, and hyperemic transit time. In a carefully designed study, they randomized 30 patients with stable coronary artery disease, undergoing The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Minneapolis Heart Institute, Minneapolis, MN. Correspondence to: Emmanouil S. Brilakis, MD, PhD, Minneapolis Heart Institute, 920 E 28th St #300, Minneapolis, MN 55407. E-mail: esbrilakis@gmail.com J Am Heart Assoc. 2018;7:e010755. DOI: 10.1161/JAHA.118.010755. a 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.