Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial

doi:10.1016/S0140-6736(13)61450-6

The Lancet

Volume 382, Issue 9892, 17–23 August 2013, Pages 597-604

https://doi.org/10.1016/S0140-6736(13)61450-6 Get rights and content

Summary

Background

Remote ischaemic preconditioning has been associated with reduced risk of myocardial injury after coronary artery bypass graft (CABG) surgery. We investigated the safety and efficacy of this procedure.

Methods

Eligible patients were those scheduled to undergo elective isolated first-time CABG surgery under cold crystalloid cardioplegia and cardiopulmonary bypass at the West-German Heart Centre, Essen, Germany, between April, 2008, and October, 2012. Patients were prospectively randomised to receive remote ischaemic preconditioning (three cycles of 5 min ischaemia and 5 min reperfusion in the left upper arm after induction of anaesthesia) or no ischaemic preconditioning (control). The primary endpoint was myocardial injury, as reflected by the geometric mean area under the curve (AUC) for perioperative concentrations of cardiac troponin I (cTnI) in serum in the first 72 h after CABG. Mortality was the main safety endpoint. Analysis was done in intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT01406678.

Findings

329 patients were enrolled. Baseline characteristics and perioperative data did not differ between groups. cTnI AUC was 266 ng/mL over 72 h (95% CI 237–298) in the remote ischaemic preconditioning group and 321 ng/mL (287–360) in the control group. In the intention-to-treat population, the ratio of remote ischaemic preconditioning to control for cTnI AUC was 0·83 (95% CI 0·70–0·97, p=0·022). cTnI release remained lower in the per-protocol analysis (0·79, 0·66–0·94, p=0·001). All-cause mortality was assessed over 1·54 (SD 1·22) years and was lower with remote ischaemic preconditioning than without (ratio 0·27, 95% CI 0·08–0·98, p=0·046).

Interpretation

Remote ischaemic preconditioning provided perioperative myocardial protection and improved the prognosis of patients undergoing elective CABG surgery.

Funding

German Research Foundation.

Introduction

Remote ischaemic preconditioning by brief episodes of ischaemia and reperfusion in a remote organ or vascular territory provides protection from injury by myocardial ischaemia and reperfusion.1, 2, 3 In cardiac and coronary artery bypass graft (CABG) surgery in particular, adverse outcomes relate mainly to periprocedural myocardial injury.⁴ In the translation of remote ischaemic preconditioning from bench to bedside, first proof-of-principle and small randomised, controlled trials have shown decreased release of myocardial biomarkers after aortic,⁵ congenital cardiac,6, 7 adult valve,8, 9, 10 and CABG surgery.11, 12, 13, 14, 15 Whether or not such reduction in cardiac biomarkers translates into better clinical outcomes is unclear.

We did a randomised, controlled clinical trial to assess whether remote ischaemic preconditioning reduced concentrations of cardiac troponin I (cTnI) in serum and to analyse the safety and clinical outcomes of remote ischaemic preconditioning after elective, isolated, primary, on-pump CABG surgery.

Section snippets

Study design and participants

This was a prospective, single-centre, double-blind, randomised, controlled trial. Eligible patients were adults with triple-vessel coronary artery disease, who were scheduled to undergo primary, isolated, elective CABG surgery under cardiopulmonary bypass at the West-German Heart Centre, Essen, Germany, between April, 2008, and October, 2012. Patients were recruited consecutively during preadmission consultations. Exclusion criteria were preoperative renal insufficiency (serum creatinine

Discussion

This study confirms in a large cohort the findings of previous reports11, 12, 13, 14, 15 that remote ischaemic preconditioning reduces perioperative myocardial injury during elective CABG surgery (panel, appendix pp 2–7).³ The cardioprotective effects were measured as a 17·3% reduction in the cTnI AUC by remote ischaemic preconditioning. We further showed a persistent benefit from remote ischaemic preconditioning, with better survival and lower numbers of major adverse cardiac and

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ArticlesCardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design and participants

Discussion

Lancet

Lancet

J Am Coll Cardiol

J Surg Res

Lancet

Lancet

Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion

Circulation

Association of myocardial enzyme elevation and survival following coronary artery bypass graft surgery

JAMA

Remote ischemic preconditioning reduces myocardial and renal injury after elective abdominal aortic aneurysm repair: a randomized controlled trial

Circulation

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Pediatr Cardiol

Effect of limb ischemic preconditioning on myocardial injury in patients undergoing mitral valve replacement surgery. A randomized controlled trial

Circ J

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Remote ischaemic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood cardioplegia: a randomised controlled trial

Heart

Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest

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Protection by remote ischaemic preconditioning during coronary artery bypass graft surgery with isoflurane but not with propofol—a clinical trial

Acta Anaesthesiol Scand

Articles
Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial