Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention

Sloth, Astrid Drivsholm; Schmidt, Michael; Munk, Kim; Kharbanda, Rajesh K.; Redington, Andrew N.; Schmidt, Morten; Pedersen, Lars; Sørensen, Henrik Toft; Bøtker, Hans Erik; Investigators, Condi

doi:10.1093/eurheartj/eht369

Cited by 253 publications

(213 citation statements)

References 23 publications

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“…The absence in change of hemodynamic recovery in our study is in accordance with previous studies testing Rotigaptide and the new analogue danegaptide [1][2][3][4][5][6][7][8][9][10][11][12][13]20,[42][43][44]. Although we did not observe statistically significant changes in post-ischemic hemodynamic outcome between the different groups the pattern followed the expected responses according to infarct size reduction.…”

Section: Baselinesupporting

confidence: 92%

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Effects of Rotigaptide and RIC on Ischemia Reperfusion Injury in the In Vitro Rabbit Heart

Salman¹,

Johnsen²,

Tr³

et al. 2017

Cardiovasc Pharm Open Access

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Background: Remote Ischemic Preconditioning (rIPC) and the antiarrhythmic peptide analogue, Rotigaptide (ZP123), protects against myocardial ischemia-reperfusion injury through potentially similar mechanisms. We aimed to study whether the cardioprotective effects of Rotigaptide and rIPC interacts. Methods:We used male New Zealand White rabbit hearts mounted in a Langendorff system and exposed to 30 min of global no-flow ischemia and 120 min of reperfusion. A total of 48 rabbits were randomized into 6 groups: control (n=6), Rotigaptide (1 µM) before (n=9) or after (n=9) ischemia, rIPC (n=7), rIPC+Rotigaptide before (n=9) or after (n=8) ischemia. rIPC was induced by four cycles of 5-min ischemia and reperfusion on the left hind limb achieved by intermittent tourniquet occlusion. Primary endpoint was infarct size measured by tetrazolium staining.Results: rIPC reduced infarct size compared to controls. Rotigaptide alone did not affect infarct size irrespective of administration before ischemia or during reperfusion. The combination of rIPC and Rotigaptide before ischemia reduced infarct size, whereas the effect of rIPC was abrogated by Rotigaptide when administered during reperfusion. No significant changes in hemodynamic recovery were observed when compared to control group. Conclusion:In contrast to in vivo rIPC, in vitro Rotigaptide did not yield cardioprotection in our rabbit model, but Rotigaptide attenuated the effect of rIPC. These findings indicate that modification of myocardial gap junction is involved in cardioprotection by rIPC.

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Section: Baselinesupporting

confidence: 92%

“…Combined acute ischemia and reperfusion injury may lead to irreversible tissue injury and cell death and determines final infarct size. Protecting the heart beyond the myocardial salvage achieved by early revascularization is crucial as infarct size is directly linked to patient outcome [1].…”

Section: Introductionmentioning

confidence: 99%

Effects of Rotigaptide and RIC on Ischemia Reperfusion Injury in the In Vitro Rabbit Heart

Salman¹,

Johnsen²,

Tr³

et al. 2017

Cardiovasc Pharm Open Access

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“…Remote ischemic conditioning by repetitive limb ischemia/reperfusion also reduces myocardial damage in patients undergoing elective interventional2 or surgical coronary revascularization3, 4, 5, 6 and in those with reperfused acute myocardial infarction 7, 8, 9, 10, 11, 12, 13. Cardioprotection was confirmed by reduced release of cardiac biomarkers2, 3, 4, 5, 6, 10 or by increased salvage in cardiac imaging7, 8, 9, 11 but also resulted in improved short‐5, 8 and more long‐term2, 4, 13, 14, 15 clinical outcome in retrospective analyses. Recently, the first prospective, randomized trial on patients with reperfused acute myocardial infarction confirmed improved clinical outcome as a primary end point of remote ischemic conditioning during follow‐up for 3.6 years 13.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial and Contractile Function of Human Right Atrial Tissue in Response to Remote Ischemic Conditioning

Kleinbongard

Gedik

Kirca

et al. 2018

JAHA

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BackgroundRemote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion attenuates myocardial ischemia/reperfusion injury. We aimed to identify a functional parameter reflecting the RIPC‐induced protection in human. Therefore, we measured mitochondrial function in right atrial tissue and contractile function of isolated right atrial trabeculae before and during hypoxia/reoxygenation from patients undergoing coronary artery bypass grafting with RIPC or placebo, respectively.Methods and ResultsOne hundred thirty‐seven patients under isoflurane anesthesia underwent RIPC (3×5 minutes blood pressure cuff inflation on the left upper arm/5 minutes deflation, n=67) or placebo (cuff uninflated, n=70), and right atrial appendages were harvested before ischemic cardioplegic arrest. Myocardial protection by RIPC was assessed from serum troponin I/T concentrations over 72 hours after surgery. Atrial tissue was obtained for isolation of mitochondria (RIPC/placebo: n=10/10). Trabeculae were dissected for contractile function measurements at baseline and after hypoxia/reoxygenation (60 min/30 min) and for western blot analysis after hypoxia/reoxygenation (RIPC/placebo, n=57/60). Associated with cardioprotection by RIPC (26% decrease in the area under the curve of troponin I/T), mitochondrial adenosine diphosphate–stimulated complex I respiration (+10%), adenosine triphosphate production (+46%), and calcium retention capacity (+37%) were greater, whereas reactive oxygen species production (−24%) was less with RIPC than placebo. Contractile function was improved by RIPC (baseline, +7%; reoxygenation, +24%). Expression and phosphorylation of proteins, which have previously been associated with cardioprotection, were not different between RIPC and placebo.ConclusionsCardioprotection by RIPC goes along with improved mitochondrial and contractile function of human right atrial tissue.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01406678.

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“…Recently, Sloth et al [89] published 4-year follow-up data on our original study, showing that the improved myocardial salvage translates into clinical prognostic benefit, as MACCE occurred for 17 (13.5%) patients in the RIC treated group compared with 32 (25.6%) patients in the control group, yielding a HR of 0.49 (95%CI: 0.27-0.89, P = 0.018). Furthermore, only 5 deaths (4%) occurred in the intervention group compared with 15 (12%) in the control group, yielding a HR of 0.32 (95%CI: 0.12-0.88, P = 0.027) (Figure 2) [89] . Specific evaluation of death causes suggested a reduction in both cardiac and noncardiac mortality, although only the latter was statistically significantly reduced (and most likely arose by chance).…”

Section: Remote Ischemic Conditioning In Unpredictable Ischemiamentioning

confidence: 96%

“…The authors observed 11 deaths in the control group and only 3 deaths in the RIC group (P = 0.046). The combined endpoint [89] . Eur Heart J (2014) 35: 168-175. pPCI: Primary percutaneous intervention; RIC: Remote ischemic conditioning.…”

Section: Remote Ischemic Conditioning In Predictable Ischemiamentioning

confidence: 99%

Novel adjunctive treatments of myocardial infarction

Schmidt

Pryds

Bøtker

2014

WJC

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Myocardial infarction is a major cause of death and disability worldwide and myocardial infarct size is a major determinant of prognosis. Early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome, but reperfusion may induce further myocardial damage itself. Development of adjunctive therapies to limit myocardial reperfusion injury beyond opening of the coronary artery gains increasing attention. A vast number of experimental studies have shown cardioprotective effects of ischemic and pharmacological conditioning, but despite decades of research, the translation into clinical effects has been challenging. Recently published clinical studies, however, prompt optimism as novel techniques allow for improved clinical applicability. Cyclosporine A, the GLP-1 analogue exenatide and rapid cooling by endovascular infusion of cold saline all reduce infarct size and may confer clinical benefit for patients admitted with acute myocardial infarcts. Equally promising, three follow-up studies of the effect of remote ischemic conditioning (RIC) show clinical prognostic benefit in patients undergoing coronary surgery and percutaneous coronary intervention. The discovery that RIC can be performed noninvasively using a blood pressure cuff on the upper arm to induce brief episodes of limb ischemia and reperfusion has facilitated the translation of RIC into the clinical arena. This review focus on novel advances in adjunctive therapies in relation to acute and elective coronary procedures.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Myocardial infarction; Primary percutaneous intervention; Coronary artery by-pass graft; Ischemiareperfusion injury; Ischemic preconditioning; Remote ischemic conditioning; Cyclosporine; Cooling; Exenatide Core tip: Patients with ischemic heart disease have a high risk of developing myocardial infarction, which is associated with considerable morbidity and mortality. Limiting the detrimental consequences of myocardial infarction is a major focus of cardiovascular research. Recent clinical studies suggest that novel adjunctive therapy with pharmacological and ischemic conditioning reduce ischemia-reperfusion injury in patients during coronary procedures. In three independent randomized trials, remote ischemic conditioning (RIC) improves clinical outcome in patients undergoing acute or elective percutaneous intervention or coronary artery bypass surgery. RIC can be performed safely and noninvasively by intermittent inflation of a blood-pressure cuff on the upper arm and is easily applicable in most clinical settings. worldwide [1,2] . Since 1990, more people have died from coronary artery disease than any other death cause [3,4] . In China, a staggering 230 million are estimated to suffer from cardiovascular disease, and three million Chinese die of cardiovascular disease annually, accounting for 41% of all deaths [5,6] . In the United States alone, cardiov...

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Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention

Abstract: Remote ischaemic conditioning before primary percutaneous coronary intervention seemed to improve long-term clinical outcomes in patients with ST-elevation myocardial infarction.

Cited by 253 publications

References 23 publications

Effects of Rotigaptide and RIC on Ischemia Reperfusion Injury in the In Vitro Rabbit Heart

Effects of Rotigaptide and RIC on Ischemia Reperfusion Injury in the In Vitro Rabbit Heart

Mitochondrial and Contractile Function of Human Right Atrial Tissue in Response to Remote Ischemic Conditioning

Novel adjunctive treatments of myocardial infarction

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