Remote ischaemic conditioning and healthcare system delay in patients with ST-segment elevation myocardial infarction

Pryds, Kasper; Terkelsen, Christian Juhl; Sloth, Astrid Drivsholm; Munk, Kim; Nielsén, Sören; Schmidt, Michael; Bøtker, Hans Erik; Investigators, Condi

doi:10.1136/heartjnl-2015-308980

Cited by 35 publications

(32 citation statements)

References 28 publications

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“…Simple linear regression analysis was used for crude effect modification analysis, that is, test for interaction. We performed additional multiple linear regression analyses with adjustment for potential confounding variables that could influence on MSI, that is, preprocedural vessel patency (TIMI flow 0/1 vs 2/3),7 healthcare system delay (minutes),12 treatment allocation (pPCI alone vs RIC+pPCI)9 and any baseline variable with a p value of <0.05 in between the studied groups. We justified the use of linear regression models by checking variance of error, the distribution of variance and a normal distribution of residuals prior to their application.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2016

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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.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2016

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“…New treatments demonstrating significant promise in preclinical experiments frequently produce no benefits in clinical trials, 1,39 and the present results hint that timing of intervention might be a key determinant of this mismatch. [40][41][42][43] We believe the discovery of the bimodal nature of post-MI edema will help in the design and new therapies for reducing infarct size and post-MI LV dysfunction. In summary, we present the first demonstration that myocardial edema after MI is not stable in patients but instead follows a bimodal pattern, confirming recent experimental findings in pigs.…”

Section: Chronotherapeutic Approachesmentioning

confidence: 99%

Response by Fernández-Jiménez et al to Letters Regarding Article, “Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage”

et al. 2018

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BACKGROUND: Clinical protocols aimed to characterize the post-myocardial infarction (MI) heart by cardiac magnetic resonance (CMR) need to be standardized to take account of dynamic biological phenomena evolving early after the index ischemic event. Here, we evaluated the time course of edema reaction in patients with ST-segment-elevation MI by CMR and assessed its implications for myocardium-at-risk (MaR) quantification both in patients and in a large-animal model. METHODS: A total of 16 patients with anterior ST-segment-elevation MI successfully treated by primary angioplasty and 16 matched controls were prospectively recruited. In total, 94 clinical CMR examinations were performed: patients with ST-segment-elevation MI were serially scanned (within the first 3 hours after reperfusion and at 1, 4, 7, and 40 days), and controls were scanned only once. T2 relaxation time in the myocardium (T2 mapping) and the extent of edema on T2-weighted short-tau triple inversion-recovery (ie, CMR-MaR) were evaluated at all time points. In the experimental study, 20 pigs underwent 40-minute ischemia/reperfusion followed by serial CMR examinations at 120 minutes and 1, 4, and 7 days after reperfusion. Reference MaR was assessed by contrast-multidetector computed tomography during the index coronary occlusion. Generalized linear mixed models were used to take account of repeated measurements. RESULTS: In humans, T2 relaxation time in the ischemic myocardium declines significantly from early after reperfusion to 24 hours, and then increases up to day 4, reaching a plateau from which it decreases from day 7. Consequently, edema extent measured by T2-weighted short-tau triple inversion-recovery (CMR-MaR) varied with the timing of the CMR examination. These findings were confirmed in the experimental model by showing that only CMR-MaR values for day 4 and day 7 postreperfusion, coinciding with the deferred edema wave, were similar to values measured by reference contrast-multidetector computed tomography. CONCLUSIONS: Post-MI edema in patients follows a bimodal pattern that affects CMR estimates of MaR. Dynamic changes in post-ST-segment-elevation MI edema highlight the need for standardization of CMR timing to retrospectively delineate MaR and quantify myocardial salvage. According to the present clinical and experimental data, a time window between days 4 and 7 post-MI seems a good compromise solution for standardization. Further studies are needed to study the effect of other factors on these variables.

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“…Unlike administering the intervention at the time of PPCI (in the cath lab), it seems more beneficial to do so at an earlier time-point, in the ambulance whilst in transit to the PPCI centre, as has been demonstrated in several proof-of-concept clinical studies on RIC [33], glucose-insulin-potassium therapy [34] and metoprolol [31,35]. In fact, two recent sub-analyses on metoprolol and remote ischemic conditioning suggest a larger IS reduction when therapy is applied early [36,37].…”

Section: Timing Of Treatmentmentioning

confidence: 90%

A critical review on the translational journey of cardioprotective therapies!

Rosselló

Yellon

2016

International Journal of Cardiology

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The failure to translate novel cardioprotective therapies tested in pre-clinical studies into the clinical setting for patient benefit can be attributed to a number of factors at different stages of the research process. This review focuses on the evidences and the gaps with regard to the translational journey of cardioprotective interventions. Gaps are classified into 3 main groups: 1) those related to pre-clinical studies, 2) those associated with the validation of infarct size as a good surrogate and 3) those based on design and interpretation of randomized clinical trials on cardioprotection. Addressing these gaps might increase the chances to successfully translate cardioprotective therapies into improving both post-STEMI heart failure and cardiovascular death rates.

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Remote ischaemic conditioning and healthcare system delay in patients with ST-segment elevation myocardial infarction

Abstract: NCT00435266; post-results.

Cited by 35 publications

References 28 publications

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

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

Response by Fernández-Jiménez et al to Letters Regarding Article, “Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage”

A critical review on the translational journey of cardioprotective therapies!

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