Effects of delayed remote ischemic preconditioning on peri-operative myocardial injury in patients undergoing cardiac surgery - A randomized controlled trial.

Remote ischemic preconditioning (RIPC) has two time windows for organ protection: acute and delayed. Previous studies have mainly focused on the acute time window to evaluate organ protection by RIPC. We evaluated myocardial protection by delayed RIPC in adult patients undergoing cardiac surgery. A total of 160 adult patients undergoing cardiac surgery with cardiopulmonary bypass were randomized to receive either delayed RIPC (four cycles of 5min of ischemia followed by 5min of reperfusion by inflation to 200mmHg and deflation of a blood pressure cuff on the upper arm) or the control treatment 24-48h before surgery. The primary endpoint was post-operative troponin I levels serially measured for 72h. Secondary endpoints included post-operative serum creatinine levels, acute kidney injury, and composite complications. There were no significant differences in post-operative troponin I values. The incidence of acute kidney injury, defined by the Acute Kidney Injury Network staging system, was lower in the delayed RIPC group compared to the control group (30.0% vs. 47.5%; relative risk, 0.768; 95% confidence interval, 0.599-0.985; p=0.023). Moreover, the occurrence of composite complications was lower in the delayed RIPC group compared with the control group (65.0% vs. 81.3%; relative risk, 0.536; 95% confidence interval, 0.311-0.924; p=0.020). While RIPC did not provide cardioprotective effects in patients undergoing cardiac surgery, it appeared to reduce acute kidney injury, as well as the rate of composite complications.

Kim TK ，Min JJ ，Cho YJ ，Hausenloy DJ ，Ahn H ，Kim KH ，Hwang HY ，Hong DM ，Jeon Y ... -  《-》

Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial.

Remote ischaemic preconditioning (RIPC), using brief cycles of limb ischaemia/reperfusion, is a non-invasive, low-cost intervention that may reduce perioperative myocardial injury (PMI) in patients undergoing cardiac surgery. We investigated whether RIPC can also improve short-term clinical outcomes. One hundred and eighty patients undergoing elective coronary artery bypass graft (CABG) surgery and/or valve surgery were randomised to receive either RIPC (2-5 min cycles of simultaneous upper arm and thigh cuff inflation/deflation; N=90) or control (uninflated cuffs placed on the upper arm and thigh; N=90). The study primary end point was PMI, measured by 72 h area under the curve (AUC) serum high-sensitive troponin-T (hsTnT); secondary end point included short-term clinical outcomes. RIPC reduced PMI magnitude by 26% (-9.303 difference (CI -15.618 to -2.987) 72 h hsTnT-AUC; p=0.003) compared with control. There was also evidence that RIPC reduced the incidence of postoperative atrial fibrillation by 54% (11% RIPC vs 24% control; p=0.031) and decreased the incidence of acute kidney injury by 48% (10.0% RIPC vs 21.0% control; p=0.063), and intensive care unit stay by 1 day (2.0 days RIPC (CI 1.0 to 4.0) vs 3.0 days control (CI 2.0 to 4.5); p=0.043). In a post hoc analysis, we found that control patients administered intravenous glyceryl trinitrate (GTN) intraoperatively sustained 39% less PMI compared with those not receiving GTN, and RIPC did not appear to reduce PMI in patients given GTN. RIPC reduced the extent of PMI in patients undergoing CABG and/or valve surgery. RIPC may also have beneficial effects on short-term clinical outcomes, although this will need to be confirmed in future studies. ClinicalTrials.gov ID: NCT00397163.

Candilio L ，Malik A ，Ariti C ，Barnard M ，Di Salvo C ，Lawrence D ，Hayward M ，Yap J ，Roberts N ，Sheikh A ，Kolvekar S ，Hausenloy DJ ，Yellon DM ... -  《-》

A pilot study investigating the effects of remote ischemic preconditioning in high-risk cardiac surgery using a randomised controlled double-blind protocol.

Young PJ ，Dalley P ，Garden A ，Horrocks C ，La Flamme A ，Mahon B ，Miller J ，Pilcher J ，Weatherall M ，Williams J ，Young W ，Beasley R ... -  《-》

Repeated Episodes of Remote Ischemic Preconditioning for the Prevention of Myocardial Injury in Vascular Surgery.

Remote ischemic preconditioning (RIPC) involves the phenomenon whereby transient episodes of limb ischemia induced by cuff inflation provide cardioprotection. The effectiveness of RIPC in vascular surgery is uncertain. This randomized, controlled trial was designed to investigate the potential of two episodes of RIPC to provide myocardial protection in patients undergoing vascular surgery. Patients undergoing an elective major vascular procedure (open abdominal aortic aneurysm (AAA) repair, endovascular aneurysm repair, and lower-limb bypass grafting) were randomized into RIPC group (n = 42) or control group (n = 43). Remote ischemic preconditioning consisted of three 5-minute cycles of upper limb cuff occlusion with 5-minutes of reperfusion between cycles, both 24 hours and immediately before surgery. Control patients received a similarly timed sham treatment. Cardiac high-sensitivity troponin T (hsTnT) concentration was measured in plasma at 6, 12, 24, and 48 hours post-surgery, and at 72, 96, and 120 hours in patients still in hospital. Perioperative clinical adverse events and readmissions within ∼12 months were recorded. Myocardial injury was demonstrated perioperatively in 43% of RIPC patients and 49% of controls, as defined by a significant hsTnT elevation. These incidences were statistically equivalent (odds ratio 0.79, 95% confidence interval 0.33-1.85, P = .58). The 48-hour area under the curve for hsTnT change from baseline also revealed no difference (RIPC vs control median: 5.3 vs 7.5 ng/L.h, P = .22). Each group had one type I and one type II myocardial infarction and no difference in complications or readmissions. This trial could not confirm that two episodes of RIPC reduce myocardial injury following vascular surgery. Along with other equivocal studies, it appears that RIPC does not induce a clear benefit in vascular surgery.

Thomas KN ，Cotter JD ，Williams MJ ，van Rij AM ... -  《-》

No protection of heart, kidneys and brain by remote ischemic preconditioning before transfemoral transcatheter aortic valve implantation: Interim-analysis of a randomized single-blinded, placebo-controlled, single-center trial.

Remote ischemic preconditioning (RIPC) reduces myocardial injury and improves clinical outcome in patients undergoing coronary revascularization, but only in the absence of propofol-anesthesia. We investigated whether RIPC provides protection of heart, kidneys and brain and improves outcome in patients undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI). Patients undergoing TF-TAVI were randomized to receive RIPC (3cycles of 5min left upper arm ischemia and 5min reperfusion) or placebo. The primary endpoint was myocardial injury, reflected by the area under the curve for serum troponin I concentrations (AUC-TnI) over the first 72h. Secondary endpoints included the incidences of periprocedural myocardial infarction, delayed gadolinium enhancement on postprocedural cardiac MRI, acute kidney injury, periprocedural stroke, and the incidence and volume of new lesions on postprocedural cerebral MRI. All-cause and cardiovascular mortality and major adverse cardiac and cerebrovascular events (MACCE) were assessed over 1-year follow-up. A prespecified interim-analysis was performed after the last patient had completed 1-year follow-up (NCT02080299). 100 consecutive patients were enrolled between September 2013 and June 2015. There were no significant between-group differences in the primary endpoint of peri-interventional myocardial injury (ratio RIPC/placebo AUC-TnI: 0.87, 95% CI: 0.57-1.34, p=0.53) or the secondary endpoints of cardiac, renal and cerebral impairment. There was no significant treatment effect in subgroup-analyses of patients undergoing cardiac or cerebral MRI. Mortality and MACCE did not differ. No RIPC-related adverse events were observed. RIPC did neither protect heart, kidneys and brain nor improve clinical outcome in patients undergoing TF-TAVI.

Kahlert P ，Hildebrandt HA ，Patsalis PC ，Al-Rashid F ，Jánosi RA ，Nensa F ，Schlosser TW ，Schlamann M ，Wendt D ，Thielmann M ，Kottenberg E ，Frey U ，Neuhäuser M ，Forsting M ，Jakob HG ，Rassaf T ，Peters J ，Heusch G ，Kleinbongard P ... -  《-》