Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: trials and tribulations.
Ontology highlight
ABSTRACT:
SUBMITTER: Hausenloy DJ
PROVIDER: S-EPMC5381598 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: trials and tribulations.
Hausenloy Derek J DJ Botker Hans Erik HE Engstrom Thomas T Erlinge David D Heusch Gerd G Ibanez Borja B Kloner Robert A RA Ovize Michel M Yellon Derek M DM Garcia-Dorado David D
European heart journal 20170401 13
Similar Datasets
Project description:AimThe aim of the study was to discover the metabolomic changes in plasma that occur during human Ischemia-Reperfusion (I/R) injury and to evaluate the diagnostic utility of plasma metabolomic biomarkers for determination of myocardial injury. Deciphering the details of plasma metabolome in ST-segment elevation myocardial infarction (STEMI) patients before and after primary percutaneous coronary interventions (PPCI) would allow for better understanding of the mechanisms involved during acute myocardial ischemia and reperfusion in humans. We performed a detailed non-targeted metabolomic analysis of plasma from 27 STEMI patients who had undergone PPCI in the first 48 hrs employing a LC-MS approach. Plasma metabolome at ischemic condition was compared to multiple time points after PPCI which allowed us to focus on changes in the reperfusion phase. Classification of the differential metabolites based on chemical taxonomy identified a major role for lipids and lipid-derived molecules. Biochemical pathway analysis identified valine, leucine and isoleucine biosynthesis, vitamin B6 metabolism and glutathione metabolism as the most significant metabolic pathways representing early response to I/R injury. We also identified phenyl alanine, tyrosine, linoleic acid and glycerophospholipid metabolism as the most significant pathways representing late response to I/R injury. A panel of three metabolites pentadecanoic acid, linoleoyl carnitine and 1-linoleoylglycerophosphocholine was discovered to have diagnostic value in determining the extent of I/R injury based on cardiac biomarkers. Using a non-targeted LC-MS approach, we have successfully generated the most comprehensive data to date on significant changes in the plasma metabolome in STEMI patients who had undergone PPCI in the first 48 hrs showing that lipid metabolites represent the largest cohort of molecules undergoing significant change.
| S-EPMC6692400 | biostudies-literature
Project description:BackgroundIn patients with ST-segment elevation myocardial infarction (STEMI), it is unknown how patient delay modulates the beneficial effects of timely reperfusion.AimsTo assess the prognostic significance of a contact-to-balloon time of less than 90 min on in-hospital mortality in different categories of symptom-onset-to-first-medical-contact (S2C) times.MethodsA total of 20 005 consecutive patients from the Feedback Intervention and Treatment Times in ST-segment Elevation Myocardial Infarction (FITT-STEMI) programme treated with primary percutaneous coronary intervention (PCI) were included.ResultsThere were 1554 deaths (7.8%) with a J-shaped relationship between mortality and S2C time. Mortality was 10.0% in patients presenting within 1 hour, and 4.9%, 6.0% and 7.3% in patient groups with longer S2C intervals of 1-2 hours, 2-6 hours and 6-24 hours, respectively. Patients with a short S2C interval of less than 1 hour (S2C<60 min) had the highest survival benefit from timely reperfusion with PCI within 90 min (OR 0.27, 95% CI 0.23 to 0.31, p<0.0001) as compared with the three groups with longer S2C intervals of 1 hour<S2C≤2 hours (OR 0.44, 95% CI 0.33 to 0.59, p<0.0001), 2 hours<S2C≤6 hours (OR 0.49, 95% CI 0.38 to 0.64, p<0.0001) and 6 hours<S2C≤24 hours (OR 0.42, 95% CI 0.30 to 0.58, p<0.0001).ConclusionsTimely reperfusion with a contact-to-balloon time of less than 90 min is most effective in patients presenting with short S2C intervals of less than 1 hour, but has also beneficial effects in patients with S2C intervals of up to 24 hours.Trial registration numberNCT00794001.
| S-EPMC8103948 | biostudies-literature
Project description:It is assumed that platelets in diseased conditions share similar properties to platelets in healthy conditions, although this has never been examined in detail for myocardial infarction (MI). We examined platelets from patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) compared with platelets from healthy volunteers to evaluate for differences in platelet phenotype and function. Platelet activation was examined and postreceptor signal transduction pathways were assessed. Platelet-derived plasma biomarkers were evaluated by receiver operator characteristic curve analysis. Maximum platelet activation through the thromboxane receptor was greater in STEMI than in NSTEMI but less through protease-activated receptor 1. Extracellular-signal related-kinase 5 activation, which can activate platelets, was increased in platelets from subjects with STEMI and especially in platelets from patients with NSTEMI. Matrix metalloproteinase 9 (MMP9) protein content and enzymatic activity were several-fold greater in platelets with MI than in control. Mean plasma MMP9 concentration in patients with MI distinguished between STEMI and NSTEMI (area under curve [AUC] 75% [confidence interval (CI) 60-91], P = 0.006) which was superior to troponin T (AUC 66% [CI 48-85, P = 0.08), predicting STEMI with 80% sensitivity (95% CI 56-94), 90% specificity (CI 68-99), 70% AUC (CI 54-86, P < 0.0001), and NSTEMI with 50% sensitivity (CI 27-70), 90% specificity (CI 68-99), 70% AUC (CI 54-86, P = 0.03). Platelets from patients with STEMI and NSTEMI show differences in platelet surface receptor activation and postreceptor signal transduction, suggesting the healthy platelet phenotype in which antiplatelet agents are often evaluated in preclinical studies is different from platelets in patients with MI.
| S-EPMC5898983 | biostudies-literature
Project description:Background We systematically reviewed trials comparing different reperfusion strategies for ST-segment-elevation myocardial infarction and used multivariate network meta-analysis to compare outcomes across these strategies. Methods and Results We identified 31 contemporary trials in which patients with ST-segment-elevation myocardial infarction were randomized to ≥2 of the following strategies: fibrinolytic therapy (n=4212), primary percutaneous coronary intervention (PCI) (n=6139), or fibrinolysis followed by routine early PCI (n=5006). We categorized the last approach as "facilitated PCI" when the median time interval between fibrinolysis to PCI was <2 hours (n=2259) and as a "pharmacoinvasive approach" when this interval was ≥2 hours (n=2747). We evaluated outcomes of death, nonfatal reinfarction, stroke, and major bleeding using a multivariate network meta-analysis and a Bayesian analysis. Among the strategies evaluated, primary PCI was associated with the lowest risk of mortality, nonfatal reinfarction, and stroke. For mortality, primary PCI had an odds ratio of 0.73 (95% CI, 0.61-0.89) when compared with fibrinolytic therapy. Of the remaining strategies, the pharmacoinvasive approach was the next most favorable with an odds ratio for death of 0.79 (95% CI, 0.59-1.08) compared with fibrinolytic therapy. The Bayesian model indicated that when the 2 strategies examining routine early invasive therapy following fibrinolysis were directly compared, the probability of adverse outcomes was lower for the pharmacoinvasive approach relative to facilitated PCI. Conclusions A pharmacoinvasive approach is safer and more effective than facilitated PCI and fibrinolytic therapy alone. This has significant implications for ST-segment-elevation myocardial infarction care in settings where timely access to primary PCI, the preferred treatment for ST-segment-elevation myocardial infarction, is not available.
| S-EPMC7429064 | biostudies-literature
Project description:ObjectiveTo investigate the relationship between ST-segment resolution (STR) and myocardial scar thickness after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI).MethodsForty-two STEMI patients with single-branch coronary artery stenosis or occlusion were enrolled. ST-segment elevations were measured at emergency admission and at 24 h after PCI. Late gadolinium-enhanced cardiac magnetic resonance imaging (CMR-LGE) was performed 7 days after PCI to evaluate myocardial scars. Statistical analyses were performed to assess the utility of STR to predict the development of transmural (> 75%) or non-transmural (< 75%) myocardial scars, according to previous study.ResultsThe sensitivity and specificity of STR for predicting transmural scars were 96% and 88%, respectively, at an STR cut-off value of 40.15%. The area under the curve was 0.925. Multivariate logistic proportional hazards regression analysis disclosed that patients with STR < 40.15% had a 170.90-fold higher probability of developing transmural scars compared with patients with STR ≥ 40.15%. Pearson correlation and linear regression analyses showed STR percentage was significantly associated with myocardial scar thickness and size.ConclusionSTR < 40.15% at 24 h after PCI may provide meaningful diagnostic information regarding the extent of myocardial scarification in STEMI patients.
| S-EPMC8454141 | biostudies-literature
Project description:ImportanceChallenges to improving ST-segment elevation myocardial infarction (STEMI) care are formidable in low- to middle-income countries because of several system-level factors.ObjectiveTo examine access to reperfusion and percutaneous coronary intervention (PCI) during STEMI using a hub-and-spoke model.Design, setting, and participantsThis multicenter, prospective, observational study of a quality improvement program studied 2420 patients 20 years or older with symptoms or signs consistent with STEMI at primary care clinics, small hospitals, and PCI hospitals in the southern state of Tamil Nadu in India. Data were collected from the 4 clusters before implementation of the program (preimplementation data). We required a minimum of 12 weeks for the preimplementation data with the period extending from August 7, 2012, through January 5, 2013. The program was then implemented in a sequential manner across the 4 clusters, and data were collected in the same manner (postimplementation data) from June 12, 2013, through June 24, 2014, for a mean 32-week period.ExposuresCreation of an integrated, regional quality improvement program that linked the 35 spoke health care centers to the 4 large PCI hub hospitals and leveraged recent developments in public health insurance schemes, emergency medical services, and health information technology.Main outcomes and measuresPrimary outcomes focused on the proportion of patients undergoing reperfusion, timely reperfusion, and postfibrinolysis angiography and PCI. Secondary outcomes were in-hospital and 1-year mortality.ResultsA total of 2420 patients with STEMI (2034 men [84.0%] and 386 women [16.0%]; mean [SD] age, 54.7 [12.2] years) (898 in the preimplementation phase and 1522 in the postimplementation phase) were enrolled, with 1053 patients (43.5%) from the spoke health care centers. Missing data were common for systolic blood pressure (213 [8.8%]), heart rate (223 [9.2%]), and anterior MI location (279 [11.5%]). Overall reperfusion use and times to reperfusion were similar (795 [88.5%] vs 1372 [90.1%]; P = .21). Coronary angiography (314 [35.0%] vs 925 [60.8%]; P < .001) and PCI (265 [29.5%] vs 707 [46.5%]; P < .001) were more commonly performed during the postimplementation phase. In-hospital mortality was not different (52 [5.8%] vs 85 [5.6%]; P = .83), but 1-year mortality was lower in the postimplementation phase (134 [17.6%] vs 179 [14.2%]; P = .04), and this difference remained consistent after multivariable adjustment (adjusted odds ratio, 0.76; 95% CI, 0.58-0.98; P = .04).Conclusions and relevanceA hub-and-spoke model in South India improved STEMI care through greater use of PCI and may improve 1-year mortality. This model may serve as an example for developing STEMI systems of care in other low- to middle-income countries.
| S-EPMC5814984 | biostudies-literature
Project description:ObjectivesLittle is known about the clinical prognosis of gasdermin D (GSDMD) in patients with ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate the association of GSDMD with microvascular injury, infarction size (IS), left ventricular ejection fraction (LVEF), and major adverse cardiac events (MACEs), in STEMI patients with primary percutaneous coronary intervention (pPCI).MethodsWe retrospectively analyzed 120 prospectively enrolled STEMI patients (median age 53 years, 80% men) treated with pPCI between 2020 and 2021 who underwent serum GSDMD assessment and cardiac magnetic resonance (CMR) within 48 h post-reperfusion; CMR was also performed at one year follow-up.ResultsMicrovascular obstruction was observed in 37 patients (31%). GSDMD concentrations ≧ median (13 ng/L) in patients were associated with a higher risk of microvascular obstruction and IMH (46% vs. 19%, P = 0.003; 31% vs. 13%, P = 0.02, respectively), as well as with a lower LVEF both in the acute phase after infarction (35% vs. 54%, P < 0.001) and in the chronic phase (42% vs. 56%, P < 0.001), larger IS in the acute (32% vs. 15%, P < 0.001) and in the chronic phases (26% vs. 11%, P < 0.001), and larger left ventricular volumes (119 ± 20 vs. 98 ± 14, P = 0.003) by CMR. Univariable and multivariable Cox regression analysis results showed that patients with GSDMD concentrations ≧ median (13 ng/L) had a higher incidence of MACE (P < 0.05).ConclusionsHigh GSDMD concentrations in STEMI patients are associated with microvascular injury (including MVO and IMH), which is a powerful MACE predictor. Nevertheless, the therapeutic implications of this relation need further research.
| S-EPMC10325858 | biostudies-literature
Project description:BackgroundWhilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial.Methods and outcomesThe aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6-8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6-8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6-8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6-8 days and six months. FUNDING, ETHICS AND REGULATORY APPROVALS: This study is funded by a grant from the UK Medical Research Council. This protocol is approved by the Scotland A Research Ethics Committee and has also received clinical trial authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number: 2010-023571-26).Trial registrationClinicalTrials.gov: NCT01388504 and Current Controlled Trials: ISRCTN57596739.
| S-EPMC3659075 | biostudies-literature
Project description:BackgroundIschemia-reperfusion injury following ST-segment-elevation myocardial infarction (STEMI) is a leading determinant of clinical outcome. In experimental models of myocardial ischemia, succinate accumulation leading to mitochondrial dysfunction is a major cause of ischemia-reperfusion injury; however, the potential importance and specificity of myocardial succinate accumulation in human STEMI is unknown. We sought to identify the metabolites released from the heart in patients undergoing primary percutaneous coronary intervention for emergency treatment of STEMI.Methods and resultsBlood samples were obtained from the coronary artery, coronary sinus, and peripheral vein in patients undergoing primary percutaneous coronary intervention for acute STEMI and in control patients undergoing nonemergency coronary angiography or percutaneous coronary intervention for stable angina or non-STEMI. Plasma metabolites were analyzed by targeted liquid chromatography and mass spectrometry. Metabolite levels for coronary artery, coronary sinus, and peripheral vein were compared to derive cardiac and systemic release ratios. In STEMI patients, cardiac magnetic resonance imaging was performed 2 days and 6 months after primary percutaneous coronary intervention to quantify acute myocardial edema and final infarct size, respectively. In total, 115 patients undergoing acute STEMI and 26 control patients were included. Succinate was the only metabolite significantly increased in coronary sinus blood compared with venous blood in STEMI patients, indicating cardiac release of succinate. STEMI patients had higher succinate concentrations in arterial, coronary sinus, and peripheral venous blood than patients with non-STEMI or stable angina. Furthermore, cardiac succinate release in STEMI correlated with the extent of acute myocardial injury, quantified by cardiac magnetic resonance imaging.ConclusionSuccinate release by the myocardium correlates with the extent of ischemia.
| S-EPMC6015393 | biostudies-literature
Project description:Remote ischemic conditioning (RIC) is a noninvasive therapeutic strategy that uses brief cycles of blood pressure cuff inflation and deflation to protect the myocardium against ischemia-reperfusion injury. The objective of this systematic review was to determine the impact of RIC on myocardial salvage index, infarct size, and major adverse cardiovascular events when initiated before catheterization. Electronic searches of Medline, Embase, and Cochrane Central Register of Controlled Trials were conducted and reference lists were hand searched. Randomized controlled trials comparing percutaneous coronary intervention (PCI) with and without RIC for patients with ST-segment-elevation myocardial infarction were included. Two reviewers independently screened abstracts, assessed quality of the studies, and extracted data. Data were pooled using random-effects models and reported as mean differences and relative risk with 95% confidence intervals. Eleven articles (9 randomized controlled trials) were included with a total of 1220 patients (RIC+PCI=643, PCI=577). Studies with no events were excluded from meta-analysis. The myocardial salvage index was higher in the RIC+PCI group compared with the PCI group (mean difference: 0.08; 95% confidence interval, 0.02-0.14). Infarct size was reduced in the RIC+PCI group compared with the PCI group (mean difference: -2.46; 95% confidence interval, -4.66 to -0.26). Major adverse cardiovascular events were lower in the RIC+PCI group (9.5%) compared with the PCI group (17.0%; relative risk: 0.57; 95% confidence interval, 0.40-0.82). RIC appears to be a promising adjunctive treatment to PCI for the prevention of reperfusion injury in patients with ST-segment-elevation myocardial infarction; however, additional high-quality research is required before a change in practice can be considered.
| S-EPMC5524098 | biostudies-literature