Reperfusion In Myocardial Infarction Research Articles

In the transition from fibrinolysis to primary PCI, the HERO trials help refine STEMI ECG interpretation and Q wave analysis potentially alters future management.

Electrocardiogram sub-studies from the Hirulog Early Reperfusion/Occlusion 1 and 2 trials, which tested bivalirudin as an adjunctive anticoagulant to fibrinolysis in ST-elevation myocardial infarction, have contributed to the literature. The concept of using the presence of infarct lead Q waves to determine reperfusion benefit has subsequently been explored in multiple primary percutaneous coronary intervention studies. The angiographic findings before percutaneous coronary intervention combine with the baseline electrocardiogram to accurately diagnose ST-elevation myocardial infarction and evaluate its potential territory. This review discusses the relative merits of the presence of infarct lead Q waves versus time duration from symptom onset using observational data from cohorts of patients from multiple clinical trials. The presence of infarct lead Q waves at presentation has been repeatedly shown to be superior to time duration from symptom onset in determining prognosis, despite that continuous variable (time duration) statistically should be more powerful than dichotomous variable (Q wave). If quantitative or semi-quantitative measurement of Q waves correlates well with irreversible myocardial injury in vivo (a research goal of many cardiac magnetic resonance imaging studies), Q waves measurements by mirroring ST-elevation myocardial infarction evolution better than the current metric of time duration of symptoms will impact future ST-elevation myocardial infarction reperfusion management. Newer methodology will more quickly capture and transmit electrocardiogram information including infarct lead Q waves potentially before first medical contact, and help differentiate new evolving Q waves of the ongoing ST-elevation myocardial infarction from old changes. Q waves as the new metric in ST-elevation myocardial infarction reperfusion should be tested in upcoming trials.

Predictors of myocardial functional recovery following successful reperfusion of acute ST elevation myocardial infarction.

Following acute ST elevation myocardial infarction (STEMI), restoration of large-vessel patency does not mean complete perfusion recovery. Little is known regarding the predictors of successful myocardial reperfusion for the STEMI patients undergoing pharmacologic and mechanical reperfusion strategies. The aim of this clinical study was to find out the predictors of myocardial functional recovery following reperfusion of acute STEMI, represented by 3-month global longitudinal strain (GLS) value assessed by speckle tracking echocardiography. The study population included 400 patients presented with first acute STEMI with successful reperfusion by thrombolysis (group I) or primary percutaneous coronary intervention (PPCI) (group II). Electrocardiography (ECG) at baseline and 90minutes after coronary reperfusion was performed with assessment of ST resolution. Basal and 3-month follow-up echocardiography was performed with assessment of ejection fraction (EF), myocardial performance index (MPI), systolic myocardial excursion (S'), and GLS. There was nonsignificant difference between patients of both groups regarding age (P=0.422) and gender (P=0.272). Also, there was a nonsignificant difference between both groups regarding the risk factors of coronary artery disease like hypertension (P=0.511), diabetes mellitus (P=0.332), and smoking (P=0.381). But there was significant statistical difference between both groups regarding dyslipidemia (P=0.012). Ninety-minute ST resolution was significantly higher in PPCI group (P=0.042). Moreover, PPCI group had significant improvement of EF (P=0.013) during follow-up, and highly significant improvement of MPI, S' and GLS (P˂0.001) compared to the basal echocardiographic study. The percentage of change (∆) of each of the echocardiographic parameter was compared between both groups and revealed statistically significant improvement regarding EF, highly significant improvement of MPI, S' and GLS in favor of PPCI arm (group II). Multivariate regression analysis demonstrated that pain to reperfusion time, MI territory, ST resolution, and basal GLS value are the most important predictors for LV functional recovery. The study found pain to reperfusion time, MI territory, ST resolution, basal GLS value are the most important predictors of myocardial functional recovery. Regular follow-up with echocardiography for STEMI patients with different reperfusion strategies has informative impact on long-term clinical outcome. Also the study confirmed that PPCI is better than thrombolysis not only in restoring epicardial coronary flow but also in restoring microvascular and tissue perfusion assuring better myocardial functional recovery and better long-term clinical outcomes.

P3685Prolonged Tpeak-Tend interval is associated with ventricular fibrillation during reperfusion in ST-elevation myocardial infarction

P3685Prolonged Tpeak-Tend interval is associated with ventricular fibrillation during reperfusion in ST-elevation myocardial infarction

P3456Impact of ST segment resolution on 30-day outcome in patients with preserved ejection fraction after reperfusion of ST-elevation myocardial infarction

P3456Impact of ST segment resolution on 30-day outcome in patients with preserved ejection fraction after reperfusion of ST-elevation myocardial infarction

P849Early global longitudinal strain predicts 30-day outcome in patients with preserved ejection fraction after reperfusion of ST-elevation myocardial infarction

P849Early global longitudinal strain predicts 30-day outcome in patients with preserved ejection fraction after reperfusion of ST-elevation myocardial infarction

Discovery of Novel 1,3,8-Triazaspiro[4.5]decane Derivatives That Target the c Subunit of F1/FO-Adenosine Triphosphate (ATP) Synthase for the Treatment of Reperfusion Damage in Myocardial Infarction.

Recent cardiology research studies have reported the role, function, and structure of the mitochondrial permeability transition pore (mPTP) and have shown that its opening plays a key role in the progression of myocardial cell death secondary to reperfusion. In this manuscript, we validated a new pharmacological approach as an adjunct to reperfusion in myocardial infarction (MI) treatment and describe the discovery, optimization, and structure-activity relationship (SAR) studies of the first small-molecule mPTP opening inhibitors based on a 1,3,8-triazaspiro[4.5]decane scaffold that targets the c subunit of the F1/FO-ATP synthase complex. We identified three potential compounds with good mPTP inhibitory activity and beneficial effects in a model of MI, including a decreased apoptotic rate in the whole heart and overall improvement of cardiac function upon administration during reperfusion. The selected compounds did not show off-target effects at the cellular and mitochondrial levels. Moreover, the compounds preserved the mitochondrial ATP content despite interacting with the ATP synthase complex.

Radioiodinated Pentixather for SPECT Imaging of Expression of the Chemokine Receptor CXCR4 in Rat Myocardial-Infarction-Reperfusion Models.

The purpose of this study is to develop a specific CXCR4-targeting radioiodinated agent (125I- or 131I-pentixather) for single-photon-emission-computed-tomography (SPECT) imaging of CXCR4 expression in myocardial-infarction-reperfusion (MI/R) rat models. After SPECT-CT imaging with 125I-pentixather at 4, 12, and 36 h and 3 and 7 days after MI/R, the models were validated by ex vivo autoradiography, TTC staining, and immunohistochemistry and in vivo echocardiography and classical 99mTc-MIBI perfusion imaging. The SPECT-CT images showed that the infarcted myocardium (IM) could be visualized with high quality as early as 4 h and reached the maximum at 3 days after MI/R and that CXCR4 upregulation was still visible at 7 days after MI/R. In the biodistribution study, high uptakes in the IM (0.99 ± 0.13, 1.52 ± 0.29, 1.75 ± 0.22, 1.94 ± 0.27, and 0.61 ± 0.14% ID/g at 4, 12, and 36 h and 3 and 7 days after MI/R, respectively) were observed that were much higher than that of normal myocardium. The highest uptake was reached at 3 days after MI/R, which agreed well with the SPECT results. In addition, the radioactivity uptakes of the IM in both the biodistribution and SPECT imaging could be blocked effectively by excess amounts of AMD3465, indicating the high specificity of radioiodinated pentixather to CXCR4. On the basis of its promising properties, 125I-pentixather may serve as a powerful CXCR4-expression diagnostic probe for evaluating lesions and monitoring therapy responses in patients with cardiovascular diseases.

Adjunctive laser-stimulated stem-cells therapy to primary reperfusion in acute myocardial infarction in humans: Safety and feasibility study.

Low-level laser therapy (LLLT) has photobiostimulatory effects on stem cells and may offer cardioprotection. This cell-based therapy may compliment primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI). In this randomized control trial, our primary objective was to determine the safety and feasibility of LLLT application to the bone marrow in patients with STEMI undergoing PPCI. We randomly assigned patients undergoing PPCI to LLLT or non-laser therapy (NLT). In the LLLT group, 100 s of laser therapy was applied to the tibia bone prior to PPCI, as well as 24 and 72 h post-PPCI. In the control group, the power source was turned off. The primary outcome was the difference in door-to-balloon (D2B) time, and additional outcomes included differences in circulating cell counts, cardiac enzymes, and left-ventricular ejection fraction (LVEF) at pre-specified intervals post-PPCI. Twenty-four patients were randomized to LLLT (N = 12) or NLT (N = 12). No adverse effects of the treatment were detected. The D2B time was not significantly different between the groups (41 ± 8 vs 48 ± 1 min; P = 0.73). Creatinine Phosphokinase area under the curve, was lower after LLLT (22 ± 10) compared to NLT (49 ± 12), but this was not statistically significant (P = 0.08). Troponin-T was significantly lower after LLLT (2.7 ± 1.4 ng/mL) in comparison to NLT (5.2 ± 1.8 ng/mL. P < 0.05). At 9 months, LVEF improved in both groups without a significant difference between LLLT (55 ± 9%) and NLT (52 ± 9%; P = 0.90). LLLT is a safe and feasible adjunctive cell-based therapy to PPCI that may benefit ischemic myocardium.

Imaging of chemokine receptor CXCR4 expression in culprit and nonculprit coronary atherosclerotic plaque using motion-corrected [68Ga]pentixafor PET/CT

PurposeThe chemokine receptor CXCR4 is a promising target for molecular imaging of CXCR4+ cell types, e.g. inflammatory cells, in cardiovascular diseases. We speculated that a specific CXCR4 ligand, [68Ga]pentixafor, along with novel techniques for motion correction, would facilitate the in vivo characterization of CXCR4 expression in small culprit and nonculprit coronary atherosclerotic lesions after acute myocardial infarction by motion-corrected targeted PET/CT.MethodsCXCR4 expression was analysed ex vivo in separately obtained arterial wall specimens. [68Ga]Pentixafor PET/CT was performed in 37 patients after stent-based reperfusion for a first acute ST-segment elevation myocardial infarction. List-mode PET data were reconstructed to five different datasets using cardiac and/or respiratory gating. Guided by CT for localization, the PET signals of culprit and various groups of nonculprit coronary lesions were analysed and compared.ResultsEx vivo, CXCR4 was upregulated in atherosclerotic lesions, and mainly colocalized with CD68+ inflammatory cells. In vivo, elevated CXCR4 expression was detected in culprit and nonculprit lesions, and the strongest CXCR4 PET signal (median SUVmax 1.96; interquartile range, IQR, 1.55–2.31) was observed in culprit coronary artery lesions. Stented nonculprit lesions (median SUVmax 1.45, IQR 1.23–1.88; P = 0.048) and hot spots in naive remote coronary segments (median SUVmax 1.34, IQR 1.23–1.74; P = 0.0005) showed significantly lower levels of CXCR4 expression. Dual cardiac/respiratory gating provided the strongest CXCR4 PET signal and the highest lesion detectability.ConclusionWe demonstrated the basic feasibility of motion-corrected targeted PET/CT imaging of CXCR4 expression in coronary artery lesions, which was triggered by vessel wall inflammation but also by stent-induced injury. This novel methodology may serve as a platform for future diagnostic and therapeutic clinical studies targeting the biology of coronary atherosclerotic plaque.

ST-Elevation Acute Myocardial Infarction in Australia—Temporal Trends in Patient Management and Outcomes 1999–2016

Increased access to reperfusion for ST elevation myocardial infarction (STEMI) has contributed to reduced mortality internationally. We describe temporal trends in pre-hospital care, in-hospital management and outcomes of the STEMI population in Australia. Temporal trends with multiple regression analysis on the management and outcomes of STEMI patients enrolled across 46 Australian hospitals in the Australian cohort of the Global Registry of Acute Coronary Events (GRACE) and the Cooperative National Registry of Acute Coronary Care Guideline Adherence and Clinical Events (CONCORDANCE) between February 1999 and August 2016. 4,110 patients were treated for STEMI, mean age 62.5±13.7years (SD). The median door-to-balloon time of primary percutaneous coronary intervention (PPCI) decreased by 11minutes (p<0.01) although there was no increase in rates of PPCI (p=0.35). Access to non-primary PCI increased by 39% (p<0.01), provisioning of fibrinolysis decreased by 13% (p<0.01) and the median door-to-needle time of 35minutes remained unchanged (p=0.09). Prescription of medical therapies in-hospital remained high, and at discharge there was an increase in prescription of statins (p<0.01); aspirin including antiplatelets (p<0.01), beta blockers (p=0.023) and ACE/ARB (p=0.02). The occurrence of any in-hospital adverse clinical events declined by 78% (p<0.01) albeit, there was no reduction in mortality in-hospital (p=0.84) or within 6 months (p=0.81). Over time, there has been increased access to non-primary PCI; shorter door-to-balloon times for PPCI; less adverse events in-hospital and fewer readmissions for unplanned revascularisation without the realisation of reduced mortality in-hospital or at 6 months. CONCORDANCE Registry ACTRN: 12614000887673.

Identifying predictors of patient delay for reperfusion in myocardial infarction: Does it matter?

Identifying predictors of patient delay for reperfusion in myocardial infarction: Does it matter?

Correction: A systematic review and meta-analysis of the protective effects of metformin in experimental myocardial infarction

[This corrects the article DOI: 10.1371/journal.pone.0183664.].

Effect Of Membrane Sealing Copolymer Poloxamer188 On Cardiac Mitochondrial Subpopulations In A Porcine Model Of Acute Myocardial Infarction

Acute myocardial infarction (AMI) is characterized by the sudden loss of blood supply to the coronary arteries, leading to permanent cell death if left untreated. Every year, around 800,000 Americans are affected by AMI. Currently, the only successful treatment for AMI is the restoration of blood flow using angioplasty and fibrinolytic drugs. In spite of a higher success rate post treatment, AMI greatly increases the risk of future arrhythmia, stroke and cardiac arrest. Additionally, the abrupt reintroduction of oxygen to the ischemic tissue causes reperfusion injury (RI). In the mitochondria, RI leads to calcium overload, increased ROS production, opening of mitochondrial permeability transition pore (MPTP) and release of caspases, all contributing to cell death. Hence, mitochondria offer a promising target in reducing reperfusion injury post AMI. Previously, we showed that the administration of the membrane sealing copolymer Poloxamer188 (P188) post ST‐elevation myocardial infarction (STEMI) reperfusion reduced infarct size and improved cardiac myocardial and mixed mitochondrial function in pigs. In this current study, our aim was to identify the specific effects of P188 in improving the mitochondrial function post STEMI of the two cardiac mitochondrial subpopulations‐subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria. Female pigs that underwent 45 minutes of partial left anterior descending artery (LAD) occlusion were randomized to be reperfused with P188 (250 mg/kg, n=5) or saline(n=5). Each of these animals received an initial intracoronary bolus of either drug for 30 minutes, followed by an intravenous drip of the same dose for 3 hours. At 4 hours post reperfusion, the hearts were harvested and cardiac SSM and IFM were isolated from both the ischemic (LAD) and healthy circumflex (Circ) area through differential centrifugation. Their functions were assessed by measuring mitochondrial oxygen consumption and calcium buffering capacity. Initial results show that P188 likely improved complex 1 mediated mitochondrial oxygen consumption in the SSM (not significant) while there was no effect on IFM. P188 also improved the calcium buffering capacity of cardiac SSM and IFM (p=0.009 for SSM and p=0.03 for IFM) in the ischemic area. Together these results show a potential treatment benefit of P188 on cardiac SSM. Future studies include measurement of the levels of reactive oxygen species and total calcium content in the mitochondria, assessment of mitochondrial damage through electron microscopy as well as investigation of the mechanism of benefit conferred by P188 in the mitochondria. To our knowledge, this is the first study to investigate the effect of P188 in cardiac mitochondrial subpopulations. Results from this study will help in the development of better targeted compounds with greater accuracy for the treatment of heart disease.Support or Funding InformationSource of funding: National Institutes of Heath, RO1 HL122323‐01A1This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Long-term Follow-up of the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)

BackgroundThe Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) demonstrated superiority of routine early coronary angiography (and percutaneous coronary intervention [PCI]) compared with standard therapy in fibrinolytic-treated patients with ST-segment elevation myocardial infarction (STEMI) at 30 days. The aim of the current study was to evaluate the long-term (>7 year) effects of an early invasive strategy. MethodsWe linked the study cohort and administrative datasets to assess long-term follow-up status including repeat procedures, hospitalizations, and major adverse cardiovascular events (MACE). Kaplan-Meier and Cox regression analysis were used to evaluate the relationship between randomized treatment and long-term adverse outcomes. ResultsA total of 881 patients had long-term follow-up and were included in our study. After a mean follow-up of 7.8 years, there were no significant differences in death, myocardial infarction (MI), unstable angina, stroke, transient ischemic attack (TIA), or heart failure admissions (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.73–1.13]; P = 0.41) between those randomized to an early invasive vs standard treatment strategy. Following the index hospitalization, there were no significant difference in the rates of coronary revascularization between the early invasive and the standard therapy groups (81 [19.3%] vs 76 [17.9%]; P = 0.61). ConclusionsDespite the short-term benefit and safety of an early invasive strategy in patients with STEMI receiving fibrinolysis, no statistically significant differences in MACE were observed over 7.8 years.

Danshen (Salvia miltiorrhiza Bunge): A Prospective Healing Sage for Cardiovascular Diseases

Danshen (Salvia miltiorrhiza Bunge) is a valued herbal plant in the Traditional Chinese Medicine. The dried root of this plant (Radix Salvia miltiorrhiza), either alone or in combination with other herbal ingredients, has been used for hundreds of years to treat numerous ailments, especially cardiovascular diseases. For the past several decades, many studies have tried to delineate the putative cardioprotective effects of this folk medicine through the lens of modern scientific research. In this review, we have summarized the current knowledge about the pharmacological potentials of danshen. The main focus is laid on the predominant bioactive compounds in danshen, which include phenolic acids and tanshinones. We discussed the absorption and metabolism of these compounds, and examine in detail the cardioprotective mechanisms during atherosclerosis, thrombosis, and myocardial infarction reperfusion.

Implication of serum microRNA-7a/B with myocardial cell injury induced by ischemia reperfusion

Objective: To investigate the association between serum microRNA-7a/b and Myocardial Cell Injury (MCI) induced by ischemia reperfusion in Acute Myocardial Infarction (AMI) patients. Methods: Sixty (60) senile AMI patients were selected and placed in the observation group (A group), while 60 healthy people served as the healthy control group (group B). Depending on their conditions after emergency thrombolytic therapy, the AMI patients were sub-divided into no-reflow group (A1 group, 23 cases) and reperfusion group (A2 group, 37 cases). Blood levels of high-sensitive C-reactive protein (hs-CRP) and N-terminal pro-natriuretic peptide (NT-proBNP) were determined in all patients. MicroRNA-7a/b expressions were measured in venous blood 24 h and 120 h before and after thrombolytic therapy. Results: There were significant, time-dependent increases in microRNA-7a/b expression after thrombolytic therapy, when compared with the control group (p<0.05). Results of correlation analysis showed that microRNA-7a/b was positively correlated with hs-CRP (r1=0.666, p<0.05; but negatively correlated with D-D (r2=-0.642, p<0.05). Conclusion: In myocardial cell injury induced by ischemia reperfusion, microRNA-7a/b expression is linked to oxidative stress and apoptosis of cardiomyocytes. Thus I/RI might be mitigated by regulating the expression of this microRNA.

A case of sudden-onset painless unilateral vision loss postintravenous streptokinase in a patient of acute inferior-wall myocardial infarction

Coronary thrombolysis with intravenous (IV) streptokinase is widely used as a strategy for coronary reperfusion for acute myocardial infarction (MI). Systemic administration of fibrinolytic agents is associated with hemorrhagic risks such as cerebral hemorrhage, gastrointestinal bleeding, cardiogenic shock, and unusual complications such as splenic rupture, aortic dissection, and cholesterol embolization. Herein, we report a case of intraocular hemorrhage 1 day after the IV administration of streptokinase for acute inferior-wall MI.

Pre-conditioning and post-conditioning in myocardial infarction.

Despite the special attention in the context of myocardial reperfusion in acute myocardial infarction (thrombolysis or primary angioplasty), the mortality of these patients continues to remain high. New ways of therapeutic intervention are therefore needed to improve the quality of life of these patients and also to reduce the size of myocardial necrosis. This is one of the new targets in the management of patients with acute myocardial infarction.

Impacto da adoção de processos de trabalho hospitalares na redução do tempo porta-balão

RESUMO Introdução: O tempo entre a instalação dos sintomas e a reperfusão do vaso responsável pelo infarto agudo do miocárdio com supradesnivelamento do segmento ST está diretamente relacionado à morbimortalidade do paciente. As diretrizes preconizam que o tempo dispendido entre a chegada ao hospital e a realização da intervenção coronária percutânea (ICP) seja de, no máximo, 90 minutos, denominado tempo porta-balão. Poucos hospitais atingem esta meta. Este estudo teve como objetivo avaliar a eficácia da implementação de processos de trabalho [...]

Higher admission glycaemia independently of diagnosed or unrecognised diabetes mellitus is a risk factor for failed myocardial tissue reperfusion and higher mortality after primary angioplasty.

Admission hyperglycaemia worsens reperfusion in ST-segment elevation myocardial infarction (STEMI). ST-segment elevation resolution parallels myocardial tissue reperfusion and predicts the outcome of primary percutaneous coronary intervention (pPCI). We investigated whether higher glycaemia on admission impairs tissue-level reperfusion after pPCI for STEMI, as-sessed with the single-lead Schröder method of ST-segment resolution analysis (maxSTE). Among 323 patients (60.4 ± 11.5 years, 27.8% female), 13.4% of nondiabetic subjects and 58.2% of those with known diabetic history (17%) were admitted with glycaemia > 11.1 mmol/L. Failed tissue reperfusion, recognised if high-risk maxSTE criteria were fulfilled, was present among 25% of patients. The overall 180-day mortality rate was 6.8% (n = 22). Admission glycaemia ≥ 8.75 mmol/L appeared as the single risk factor for failed tissue reperfusion (ROC area = 0.638, standard error = 0.038, p < 0.001). Even after adjustment for diabetes history, patients with admission glycaemia ≥ 8.75 mmol/L (44.5%) had 2.36-fold higher risk (95% confidence interval [CI] 1.25-4.46, p = 0.008) of failed tissue reperfusion. After exclusion of patients with known diabetes and those with acute blood glucose level > 11.1 mmol/L (28%), admission glycaemia remained an independent predictor of failed tissue reperfusion (odds ratio [OR] 1.32, 95% CI 1.03-1.69, p = 0.028). Admission glycae-mia and failed tissue reperfusion (high- vs. low-risk maxSTE category) were the independent predictors of 180-day mortality (OR 1.18, 95% CI 1.05-1.32, p = 0.004 and OR 3.84, 95% CI 1.12-13.21, p = 0.033, respectively). Higher admission glycaemia in patients treated with pPCI for STEMI predicts failed myocardial tissue reperfusion and 180-day mortality, independently of prior or acute diabetic status.