Reperfusion In Myocardial Infarction Research Articles

GW28-e0821 Transplantation of mesenchymal stem cells carrying the human receptor activity-modifying protein 1 gene improves cardiac function and inhibits neointimal proliferation in the carotid angioplasty and myocardial infarction rabbit model

we investigated the effects of MSCs overexpressing the human receptor activity-modifying protein 1 (hRAMP1) on heart function and artery repair in rabbit models of myocardial infarction (MI) reperfusion and carotid artery injury. MSCs transfected with a recombinant adenovirus containing the hRAMP1

In-hospital 'CODE STEMI' improves door-to-balloon time in patients undergoing primary percutaneous coronary intervention.

Reducing time to reperfusion for ST-segment elevation myocardial infarction (STEMI) is essential in improving outcomes. Consequently, numerous strategies have been employed to reduce median door-to-balloon time (DTBT). CODE STEMI is an ED physician-activated STEMI notification system. On activation, an announcement is made over the hospital's public announcement (PA) system. We prospectively analysed all in-hours STEMI patients who had primary percutaneous coronary intervention (PPCI) Pre-CODE STEMI (2014) and after CODE STEMI was implemented (2015). The primary end-points were median DTBT and the proportion of STEMI patients achieving a DTBT ≤90 min. The secondary end-points were in-hospital outcomes, and a composite of major adverse cardiac events (MACE) and hospital readmission rates at 30 days and 12 months. There were 41 and 42 patients in Pre-CODE STEMI and CODE STEMI groups respectively. Baseline characteristics were similar. DTBT was significantly reduced by 22.1 min from 67.1 ± 34.9 min Pre-CODE STEMI to 45.0 ± 22.7 min (P = 0.001) in the CODE STEMI group. Door-to-door time (DTDT) was also reduced from 46.3 ± 30.9 min to 29.4 ± 23.3 min (P = 0.006). A greater proportion of CODE STEMI patients achieved the target DTBT ≤90 min (95.2% vs 73.2%, P = 0.007). CODE STEMI patients had less systolic dysfunction measured by a left ventricle ejection fraction of ≤40% (10.0% vs 27.8%, P = 0.07). There were trends to lower in-hospital mortality rates (4.8% vs 9.8%, P = 0.43), MACE at 30 days and 12 months (4.8% vs 9.8%, P = 0.43; 11.9% vs 22.0%, P = 0.25). The novel in-hospital in-hours CODE STEMI notification system significantly reduced DTBT in patients undergoing PPCI.

Attenuation of ischemia/reperfusion-induced inhibition of the rapid component of delayed rectifier potassium current by Isosteviol through scavenging reactive oxygen species

Isosteviol has been demonstrated to play a protective role during ischemia reperfusion (I/R) myocardial infarction. However, the underlying electrophysiological mechanisms of isosteviol are still unknown. Our previous study showed that the rapid component of the delayed rectifier potassium channel (IKr) plays an important role in the prolongation of I/R-induced QT interval-related arrhythmia. This study aimed to investigate whether isosteviol could attenuate I/R-induced prolongation of the action potential duration (APD) along with inhibition of IKr, and we aimed to clarify the electrophysiological mechanism of isosteviol to determine its cardioprotective effects in guinea pigs. We observed that the APD90 were 298.5±41.6ms in control, 528.6±56.7ms during I/R, and reduced to 327.8±40.5ms after 10μmol/L of isosteviol treatment. The IKr currents were 1.44±0.06 pA·pF−1in the control group, 0.50±0.07pA·pF−1during I/R, and recovered to 1.20±0.12pA·pF−1after 10μmol/L of isoteviol treatment. Moreover, isosteviol reduced the over-production of reactive oxygen species (ROS) during I/R. Importantly, isosteviol does not affect the IKr and human ether-a-go-go-related gene currents of normal cardiomyocytes. It attenuated the I/R-induced inhibition of IKr due to reduced over-production of ROS. Furthermore, isosteviol is safe and has no cardiotoxicity, and it might be beneficial for coronary reperfusion therapy.

Clinical impact and predictors of complete ST segment resolution after primary percutaneous coronary intervention: A subanalysis of the ATLANTIC Trial.

In the ATLANTIC (Administration of Ticagrelor in the catheterization laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery) trial the early use of aspirin, anticoagulation, and ticagrelor coupled with very short medical contact-to-balloon times represent good indicators of optimal treatment of ST-elevation myocardial infarction and an ideal setting to explore which factors may influence coronary reperfusion beyond a well-established pre-hospital system. This study sought to evaluate predictors of complete ST-segment resolution after percutaneous coronary intervention in ST-elevation myocardial infarction patients enrolled in the ATLANTIC trial. ST-segment analysis was performed on electrocardiograms recorded at the time of inclusion (pre-hospital electrocardiogram), and one hour after percutaneous coronary intervention (post-percutaneous coronary intervention electrocardiogram) by an independent core laboratory. Complete ST-segment resolution was defined as ≥70% ST-segment resolution. Complete ST-segment resolution occurred post-percutaneous coronary intervention in 54.9% ( n=800/1456) of patients and predicted lower 30-day composite major adverse cardiovascular and cerebrovascular events (odds ratio 0.35, 95% confidence interval 0.19-0.65; p<0.01), definite stent thrombosis (odds ratio 0.18, 95% confidence interval 0.02-0.88; p=0.03), and total mortality (odds ratio 0.43, 95% confidence interval 0.19-0.97; p=0.04). In multivariate analysis, independent negative predictors of complete ST-segment resolution were the time from symptoms to pre-hospital electrocardiogram (odds ratio 0.91, 95% confidence interval 0.85-0.98; p<0.01) and diabetes mellitus (odds ratio 0.6, 95% confidence interval 0.44-0.83; p<0.01); pre-hospital ticagrelor treatment showed a favorable trend for complete ST-segment resolution (odds ratio 1.22, 95% confidence interval 0.99-1.51; p=0.06). This study confirmed that post-percutaneous coronary intervention complete ST-segment resolution is a valid surrogate marker for cardiovascular clinical outcomes. In the current era of ST-elevation myocardial infarction reperfusion, patients' delay and diabetes mellitus are independent predictors of poor reperfusion and need specific attention in the future.

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

Metformin improves cardiovascular prognosis in patients with diabetes mellitus, compared to alternative glucose-lowering drugs, despite similar glycemic control. Direct cardiovascular protective properties have therefore been proposed, and studied in preclinical models of myocardial infarction. We now aim to critically assess the quality and outcome of these studies. We present a systematic review, quality assessment and meta-analysis of the effect of metformin in animal studies of experimental myocardial infarction. Through a comprehensive search in Pubmed and EMBASE, we identified 27 studies, 11 reporting on ex vivo experiments and 18 reporting on in vivo experiments. The primary endpoint infarct size as percentage of area at risk was significantly reduced by metformin in vivo (MD -18.11[-24.09,-12.14]) and ex vivo (MD -18.70[-25.39, -12.02]). Metformin improved the secondary endpoints left ventricular ejection fraction (LVEF) and left ventricular end systolic diameter. A borderline significant effect on mortality was observed, and there was no overall effect on cardiac hypertrophy. Subgroup analyses could be performed for comorbidity and timing of treatment (infarct size and mortality) and species and duration of ischemia (LVEF), but none of these variables accounted for significant amounts of heterogeneity. Reporting of possible sources of bias was extremely poor, including randomization (reported in 63%), blinding (33%), and sample size calculation (0%). As a result, risk of bias (assessed using SYRCLE’s risk of bias tool) was unclear in the vast majority of studies. We conclude that metformin limits infarct-size and improves cardiac function in animal models of myocardial infarction, but our confidence in the evidence is lowered by the unclear risk of bias and residual unexplained heterogeneity. We recommend an adequately powered, high quality confirmatory animal study to precede a randomized controlled trial of acute administration of metformin in patients undergoing reperfusion for acute myocardial infarction.

P5557Long term follow-up of the trial of routine angioplasty and stenting after fibrinolysis to enhance reperfusion in acute myocardial infarction (transfer AMI)

P5557Long term follow-up of the trial of routine angioplasty and stenting after fibrinolysis to enhance reperfusion in acute myocardial infarction (transfer AMI)

Comparative efficacy and safety of reperfusion therapy with fibrinolytic agents in patients with ST-segment elevation myocardial infarction: a systematic review and network meta-analysis

Fibrinolytic therapy offers an alternative to mechanical reperfusion for ST-segment elevation myocardial infarction (STEMI) in settings where health-care resources are scarce. Comprehensive evidence comparing different agents is still unavailable. In this study, we examined the effects of various fibrinolytic drugs on clinical outcomes. We did a network meta-analysis based on a systematic review of randomised controlled trials comparing fibrinolytic drugs in patients with STEMI. Several databases were searched from inception up to Feb 28, 2017. We included only randomised controlled trials that compared fibrinolytic agents as a reperfusion therapy in adult patients with STEMI, whether given alone or in combination with adjunctive antithrombotic therapy, against other fibrinolytic agents, a placebo, or no treatment. Only trials investigating agents with an approved indication of reperfusion therapy in STEMI (streptokinase, tenecteplase, alteplase, and reteplase) were included. The primary efficacy outcome was all-cause mortality within 30-35 days and the primary safety outcome was major bleeding. This study is registered with PROSPERO (CRD42016042131). A total of 40 eligible studies involving 128 071 patients treated with 12 different fibrinolytic regimens were assessed. Compared with accelerated infusion of alteplase with parenteral anticoagulants as background therapy, streptokinase and non-accelerated infusion of alteplase were significantly associated with an increased risk of all-cause mortality (risk ratio [RR] 1·14 [95% CI 1·05-1·24] for streptokinase plus parenteral anticoagulants; RR 1·26 [1·10-1·45] for non-accelerated alteplase plus parenteral anticoagulants). No significant difference in mortality risk was recorded between accelerated infusion of alteplase, tenecteplase, and reteplase with parenteral anticoagulants as background therapy. For major bleeding, a tenecteplase-based regimen tended to be associated with lower risk of bleeding compared with other regimens (RR 0·79 [95% CI 0·63-1·00]). The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy increased the risk of major bleeding by 1·27-8·82-times compared with accelerated infusion alteplase plus parenteral anticoagulants (RR 1·47 [95% CI 1·10-1·98] for tenecteplase plus parenteral anticoagulants plus glycoprotein inhibitors; RR 1·88 [1·24-2·86] for reteplase plus parenteral anticoagulants plus glycoprotein inhibitors). Significant differences exist among various fibrinolytic regimens as reperfusion therapy in STEMI and alteplase (accelerated infusion), tenecteplase, and reteplase should be considered over streptokinase and non-accelerated infusion of alteplase. The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy should be discouraged. None.

Is cardiac magnetic resonance necessary for prediction of left ventricular remodeling in patients with reperfused ST-segment elevation myocardial infarction?

As cardiac magnetic resonance imaging (CMR) has become widely used for evaluation of myocardial viability after acute myocardial infarction, the additional value of CMR parameters for prediction of left ventricle (LV) remodeling has been receiving interest. The aim of the study was to investigate the additional predictive value of CMR parameters for LV remodeling after successful reperfusion of ST-segment elevation myocardial infarction (STEMI) using multiple predictive models. LV remodeling was defined as ≥20% increase in end-diastolic volume at 6 month follow-up echocardiography. Using multiple stepwise regression analysis, conventional risk model was classified as following; model 1 (clinical factors), model 2 (model 1 + angiographic factors), model 3 (model 2 + echocardiographic factors) and CMR-added model; model 4 (model 3 + CMR factors). Among 262 enrolled patients, 25.1% showed LV remodeling. There were significant increments of c-statistics from the predictive model 1 to model 3 (AUC; 0.675 [0.60-0.75], 0.708 [0.64-0.78], 0.756 [0.69-0.82], respectively. all p < 0.05). However, model 4, which added the CMR variables, did not show any increase in predictive value compared with model 3 (AUC; 0.763 [0.70-0.83] versus 0.756 [0.69-0.82], p = 0.11). During the 28.2months of median follow up, the incidence of hospitalization for heart failure was significantly higher in the patients with LV remodeling (6.1% vs. 0.5%, p = 0.02). CMR parameters did not provide incremental predictive value above the assessment by conventional echocardiography-based risk model in patients with STEMI.

Clinical benefit of drugs targeting mitochondrial function as an adjunct to reperfusion in ST-segment elevation myocardial infarction: A meta-analysis of randomized clinical trials

AimsTo perform a systematic review and meta-analysis of randomized clinical trials (RCT) comparing the effectiveness of drugs targeting mitochondrial function vs. placebo in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical coronary reperfusion. MethodsInclusion criteria: RCTs enrolling STEMI patients treated with primary percutaneous coronary intervention (PCI) and comparing drugs targeting mitochondrial function vs. placebo. Odds ratios (OR) were computed from individual studies and pooled with random-effect meta-analysis. ResultsFifteen studies were identified involving 5680 patients. When compared with placebo, drugs targeting mitochondrial component/pathway were not associated with significant reduction of cardiovascular and all-cause mortality (OR 0.9, 95% CI 0.7–1.17 and OR 0.92, 95% CI 0.69–1.23, respectively). However, these agents significantly reduced hospital admission for heart failure (HF) (OR 0.64; 95% CI 0.45–0.92) and increased left ventricular ejection fraction (LVEF) (OR 1.44; 95% CI 1.15–1.82). After analysis for subgroups according to the mechanism of action, drugs with direct/selective action did not reduce any outcome. Conversely, those with indirect/unspecific action showed a significant effect on cardiovascular mortality (0.65, 95% CI 0.46–0.92), all-cause mortality (OR 0.69, 95% CI 0.52–0.92), hospital readmission for HF (OR 0.41, 95% CI 0.28–0.6) and LVEF (OR 1.49, 95% CI 1.09–2.05). ConclusionsAdministration of drugs targeting mitochondrial function in STEMI patients undergoing primary PCI appear to have no effect on mortality, but may reduce hospital readmission for HF. The drugs with a broad-spectrum mechanism of action seem to be more effective in reducing adverse events.

Evaluation of Radioiodinated 1,4-Naphthoquinones as Necrosis Avid Agents for Rapid Myocardium Necrosis Imaging

Identifying necrotic myocardium in ischemic regions is of great importance for risk stratification and clinical decision-making. However, rapid noninvasive imaging of necrotic myocardium is still challenging. This study sought to evaluate the potential of 1,4-naphthoquinones to rapidly visualize necrotic myocardium and the possible mechanisms of necrosis avidity. Six 1,4-naphthoquinones were radiolabeled with iodine-131 and the necrosis avidity was estimated in mouse models with muscular necrosis by gamma counting and autoradiography. The necrotic myocardium imaging property and biodistribution of [131I]naphthazarin (6) were determined in rat models with re-perfused myocardial infarction. A possible mechanism of necrosis avidity was explored by in vitro DNA-binding and in vivo blocking experiments. The radiochemical purities of the six radiotracers were greater than 95%. The uptakes in necrotic muscles of all six radiotracers were higher than those in viable muscles, and [131I]naphthazarin (6) showed the highest necrotic-to-viable ratio and necrosis-to-blood ratio at all tested time points. The necrotic myocardium could be clearly visualized by single-photon emission computed tomography/x-ray computed tomography (SPECT/CT) using [131I]naphthazarin (6) as early as 3h post-injection. Post-mortem biodistribution showed the uptake of [131I]naphthazarin (6) in necrotic myocardium was 11.67-fold higher than that in viable myocardium. Absorption spectra and emission spectra suggested naphthazarin (6) could bind to DNA through intercalation. The uptake of [131I]naphthazarin (6) in necrotic muscle could be significantly blocked by excessive ethidium bromide (a typical DNA intercalator) and cold naphthazarin (6) with 63.49 and 71.96% decline at 3h post-injection in vivo, respectively. 1,4-Naphthoquinones retained necrosis avidity and [131I]naphthazarin (6) rapidly visualized necrotic myocardium. The necrosis avidity mechanism of [131I]naphthazarin (6) may be attributed to its binding with exposed DNA in necrotic tissues.

Myocardial infarction, patient decision delay and help-seeking behaviour: a thematic analysis.

To explore patient decision delay, the symptom experience and factors that motivated the patient experiencing myocardial infarction to go to the emergency department. Reperfusion for myocardial infarction is more effective if performed as soon as possible after the onset of symptoms. Multiple studies show that prehospital delay is long and can average several hours. A qualitative descriptive design using semi-structured interviews. All consecutive myocardial infarction patients who between July 2013-January 2014 at a single-centre metropolitan tertiary hospital in Western Australia were included. Patient responses to an open-ended question were recorded and transcribed verbatim. Data were analysed using Braun & Clarke (Qual Res Psychol, 3, 2006, 77-101) thematic analysis method. Of the 367 eligible, 255 provided consent. Three themes emerged from the qualitative analyses: (1) onset and response to symptoms, and this included three subthemes: context of the event, diversity of symptom interpretation and response to symptoms; (2) help-seeking behaviour, and this included the patient seeking help from various lay and professional sources; and (3) help-seeking outcomes, which include calling the emergency ambulance, going to emergency department, seeing a general practitioner, seeing a general practitioner who advised them to go home. The context of the event, their symptomatology and the layperson who was the first point of contact influenced the decision for the patient to go to the emergency department. Many patients used private transport or contacted their general practitioner. New knowledge from this study emphasises the importance of the layperson understanding the appropriate response is to seek prompt care through immediate emergency transport by ambulance to emergency department. This study highlights the need to educate both the patient and the wider public, not only to seek prompt care but to also to call the emergency ambulance to arrange transport to the emergency department.

Timely Reperfusion in Stroke and Myocardial Infarction Is Not Correlated: An Opportunity for Better Coordination of Acute Care.

Timely reperfusion is critical in acute ischemic stroke (AIS) and ST-segment-elevation myocardial infarction (STEMI). The degree to which hospital performance is correlated on emergent STEMI and AIS care is unknown. Primary objective of this study was to determine whether there was a positive correlation between hospital performance on door-to-balloon (D2B) time for STEMI and door-to-needle (DTN) time for AIS, with and without controlling for patient and hospital differences. Prospective study of all hospitals in both Get With The Guidelines-Stroke and Get With The Guidelines-Coronary Artery Disease from 2006 to 2009 and treating ≥10 patients. We compared hospital-level DTN time and D2B time using Spearman rank correlation coefficients and hierarchical linear regression modeling. There were 43 hospitals with 1976 AIS and 59 823 STEMI patients. Hospitals' DTN times for AIS did not correlate with D2B times for STEMI (ρ=-0.09; P=0.55). There was no correlation between hospitals' proportion of eligible patients treated within target time windows for AIS and STEMI (median DTN time <60 minutes: 21% [interquartile range, 11-30]; median D2B time <90 minutes: 68% [interquartile range, 62-79]; ρ=-0.14; P=0.36). The lack of correlation between hospitals' DTN and D2B times persisted after risk adjustment. We also correlated hospitals' DTN time and D2B time data from 2013 to 2014 using Get With The Guidelines (DTN time) and Hospital Compare (D2B time). From 2013 to 2014, hospitals' DTN time performance in Get With The Guidelines was not correlated with D2B time performance in Hospital Compare (n=546 hospitals). We found no correlation between hospitals' observed or risk-adjusted DTN and D2B times. Opportunities exist to improve hospitals' performance of time-critical care processes for AIS and STEMI in a coordinated approach.

Impaired thrombolytic status predicts adverse cardiac events in patients undergoing primary percutaneous coronary intervention.

Antithrombotic medications reduce thrombosis but increase bleeding. Identification of ST-elevation myocardial infarction (STEMI) patients at risk of recurrent thrombosis could allow targeted treatment with potent antithrombotic medications, with less potent agents in others, to reduce bleeding. Conventional platelet function tests assess platelet reactivity only, yet there is increasing evidence that endogenous thrombolytic potential determines outcome following thrombus initiation. We investigated whether assessing both platelet reactivity and endogenous thrombolysis, could identify STEMI patients at high-risk of recurrent thrombotic events. Thrombotic status was assessed in STEMI patients, before and after primary percutaneous coronary intervention (PPCI), at discharge and at 30 days; with 12 months' follow-up. The time to form an occlusive thrombus under high shear (occlusion time, OT), and time to restore flow by endogenous thrombolysis (lysis time, LT) was measured using the point-of-care Global Thrombosis Test (GTT) in the cardiac catheterisation laboratory. Impaired endogenous thrombolysis (prolonged LT ≥ 3000 s), seen in 13 % patients pre-PPCI, was related to major adverse cardiac events, MACE (HR: 3.31, 95 %CI: 1.02-10.78, p = 0.045), driven by cardiovascular death (HR: 4.17, 95 %CI: 0.99-17.51, p = 0.05). Enhanced (rapid) endogenous thrombolysis (LT < 1000 s) was associated with spontaneous reperfusion, ST-segment resolution and Thrombolysis In Myocardial Infarction 3 flow pre-PPCI. Baseline OT was shorter in those with MACE (especially recurrent myocardial infarction and stroke) than those without (253 ± 150 s vs 354 ± 134 s, p=0.017). Endogenous thrombolysis, when impaired, is associated with increased cardiovascular risk, and when enhanced, with spontaneous reperfusion. Endogenous thrombolysis may be a novel target for pharmacological intervention, and allow targeting of potent antithrombotic medications to high-risk patients.

Quantified coronary frequency domain optical coherence tomography signal analysis for the evaluation of erythrocyte-rich thrombus: ex-vivo validation study.

Previous study has demonstrated that erythrocyte-rich thrombi contain more inflammatory cells and reflect high thrombus burden, leading to impaired myocardial reperfusion in myocardial infarction. The aim of this study is to investigate the utility of quantified frequency domain optical coherence tomography (FD-OCT) signal analysis in evaluating the erythrocyte-rich thrombus with ex-vivo materials. We evaluated 54 specimens of coronary artery thrombus obtained by thrombectomy catheter from 8 patients who underwent primary percutaneous coronary intervention. The thrombi were immersed in saline immediately after thrombectomy and FD-OCT image acquisition was performed ex-vivo. Quantitative analysis for all contiguous frames was performed by the dedicated automated software (OCT system software, Light Lab Inc.). For the maximum thrombus area, mean signal intensity (MSI) and normalized standard deviation of signal (NSD) was evaluated. All thrombi were stained using double staining of phosphotungstic acid-hematoxylin and eosin to enable automatic extraction of erythrocyte from fibrin. Computer-assisted analysis was performed using dedicated image processing software (WinROOF, Mitani Corp., Tokyo, Japan) for color identification of the erythrocyte area. Erythrocyte-rich thrombus, defined as % erythrocyte [(erythrocyte area/total thrombus area) × 100] ≥ 10%, showed significantly lower MSI [4.39 ± 0.24 vs. 4.74 ± 0.35, p = 0.002] than that of <10%. The cut-off point for prediction of erythrocyte-rich thrombus was defined as MSI ≤ 4.56, sensitivity: 87.5%, specificity: 82.9%, area under the curve: 0.836, respectively). The present ex-vivo study suggested the utility of quantified FD-OCT signal analysis on the detection of erythrocyte-rich thrombus.

Hemorrhage promotes inflammation and myocardial damage following acute myocardial infarction: insights from a novel preclinical model and cardiovascular magnetic resonance

BackgroundMyocardial hemorrhage is a frequent complication following reperfusion in acute myocardial infarction and is predictive of adverse outcomes. However, it remains unsettled whether hemorrhage is simply a marker of a severe initial ischemic insult or directly contributes to downstream myocardial damage. Our objective was to evaluate the contribution of hemorrhage towards inflammation, microvascular obstruction and infarct size in a novel porcine model of hemorrhagic myocardial infarction using cardiovascular magnetic resonance (CMR).MethodsMyocardial hemorrhage was induced via direct intracoronary injection of collagenase in a novel porcine model of ischemic injury. Animals (N = 27) were subjected to coronary balloon occlusion followed by reperfusion and divided into three groups (N = 9/group): 8 min ischemia with collagenase (+HEM); 45 min infarction with saline (I-HEM); and 45 min infarction with collagenase (I+HEM). Comprehensive CMR was performed on a 3 T scanner at baseline and 24 h post-intervention. Cardiac function was quantified by cine imaging, edema/inflammation by T2 mapping, hemorrhage by T2* mapping and infarct/microvascular obstruction size by gadolinium enhancement. Animals were subsequently sacrificed and explanted hearts underwent histopathological assessment for ischemic damage and inflammation.ResultsAt 24 h, the +HEM group induced only hemorrhage, the I-HEM group resulted in a non-hemorrhagic infarction, and the I+HEM group resulted in infarction and hemorrhage. Notably, the I+HEM group demonstrated greater hemorrhage and edema, larger infarct size and higher incidence of microvascular obstruction. Interestingly, hemorrhage alone (+HEM) also resulted in an observable inflammatory response, similar to that arising from a mild ischemic insult (I-HEM). CMR findings were in good agreement with histological staining patterns.ConclusionsHemorrhage is not simply a bystander, but an active modulator of tissue response, including inflammation and microvascular and myocardial damage beyond the initial ischemic insult. A mechanistic understanding of the pathophysiology of reperfusion hemorrhage will potentially aid better management of high-risk patients who are prone to adverse long-term outcomes.

A tool for predicting the outcome of reperfusion in ST-elevation myocardial infarction using age, thrombotic burden and index of microcirculatory resistance (ATI score)

Restoration of effective myocardial reperfusion by primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction is difficult to predict. A method to assess the likelihood of a suboptimal response to conventional pharmacomechanical therapies could be beneficial. We aimed to derive and validate a scoring system that can be used acutely at the time of coronary reopening to predict the likelihood of downstream microvascular impairment in patients with STEMI. A score estimating the risk of post-procedural microvascular injury defined by an index of microcirculatory resistance (IMR) >40 was initially derived in a cohort of 85 STEMI patients (derivation cohort). This score was then tested and validated in three further cohorts of patients (retrospective [30 patients], prospective [42 patients] and external [29 patients]). The ATI score (age [>50=1]; pre-stenting IMR [>40 and <100=1; ≥100=2]; thrombus score [4=1; 5=3]) was highly predictive of a post-stenting IMR >40 in all four cohorts (AUC: 0.87; p<0.001-derivation cohort, 0.84; p=0.002-retrospective cohort, 0.92; p<0.001-prospective cohort and 0.81; p=0.006-external cohort). In the whole population, an ATI score ≥4 presented a 95.1% risk of final IMR >40, while no cases of final IMR >40 occurred in the presence of an ATI score <2. The ATI score appears to be a promising tool capable of identifying patients during PPCI who are at the highest risk of coronary microvascular impairment following revascularisation. This procedural risk stratification has a number of potential research and clinical applications and warrants further investigation.

China PEACE risk estimation tool for in-hospital death from acute myocardial infarction: an early risk classification tree for decisions about fibrinolytic therapy

ObjectivesAs the predominant approach to acute reperfusion for ST segment elevation myocardial infarction (STEMI) in many countries, fibrinolytic therapy provides a relative risk reduction for death of ∼16% across the...

PROPHYLACTIC WARFARIN FOLLOWING EXTENSIVE ANTERIOR ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: INSIGHTS FROM THE VITAL HEART RESPONSE REGISTRY

Anticoagulation to prevent left ventricular (LV) thrombus is recommended following anterior infarcts with extensive wall motion abnormalities (Class IIb, LOE C). Rapid reperfusion in contemporary ST-elevation myocardial infarction (STEMI) networks has reduced the incidence of LV thrombus. Additionally, current utilization of potent antithrombotic agents coupled with enhanced understanding of the risk of major bleeding with ‘triple therapy’ requires a reassessment of ‘prophylactic anticoagulation’. Utilizing a regional STEMI reperfusion inclusive registry, we sought to evaluate the outcomes of ‘prophylactic warfarin’ in patients discharged alive following an anterior STEMI with LV dysfunction (LVEF ≤40%).

Antithrombotic therapy before, during and after emergency angioplasty for ST elevation myocardial infarction.

The first three hours after symptom onset hold the maximum potential for myocardial reperfusion and salvage in ST-elevation myocardial infarction (STEMI) patients. During this period timely primary percutaneous coronary intervention (PPCI) or, when PPCI is not promptly feasible, pre-hospital administration of fibrinolyis or a glycoprotein IIb/IIIa-inhibitor (GPI) have been shown to restore coronary patency and reperfusion and even result in myocardial infarction (MI) abortion. On the other hand, oral antiplatelet therapy may not yet guarantee sufficient platelet inhibition. Patients presenting after this golden time have less, if any, benefit from an aggressive antithrombotic treatment prior to PPCI. Antithrombotic treatment during primary angioplasty should be tailored on the basis of the coronary thrombotic burden, vascular approach and the patient's risk of bleeding complications. A GPI-based approach may be favourable in patients presenting early with large MI and high thrombus burden, whereas a bivalirudin-based approach without GPI may be preferred in patients with higher bleeding risk. There are no data to support the use of GPI in bailout conditions. The powerful oral P2Y12 inhibitors, prasugrel and ticagrelor, have been clearly shown to prevent stent thrombosis and recurrent ischaemic events after emergency percutaneous coronary intervention in STEMI patients. Open issues remaining are the treatment of patients with high bleeding risk, such as the elderly and those requiring anticoagulation, as well as the duration of dual antiplatelet therapy after STEMI.

Heart failure in patients with diabetes undergoing primary percutaneous coronary intervention.

Diabetes mellitus is associated with increased risk after acute coronary syndromes. Primary percutaneous coronary intervention is the most effective method of reperfusion for acute ST-elevation myocardial infarction and can limit the ischaemic damage to the left ventricle. However, there are few data on the impact of diabetes mellitus on the risk of heart failure following primary percutaneous coronary intervention. We studied 958 ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention, of whom 263 (27.5%) had diabetes mellitus, with 67 (7.0%) treated with insulin. The primary end points of the study were re-admission for heart failure. Secondary end points were all-cause mortality and recurrent infarctions. The follow-up period was 5 years after hospital discharge. The cumulative incidence of re-admission for heart failure was 8.4%, 15.2% and 26.7% in patients without diabetes mellitus, non-insulin-treated and insulin-treated diabetes mellitus, respectively. Compared with patients without diabetes mellitus, the adjusted hazard ratio for heart failure was 1.95 (95% confidence intervals 1.30-2.93) and 3.09 (95% confidence intervals 1.71-5.60) in non-insulin-treated and insulin-treated diabetes mellitus, respectively. The corresponding hazard ratios for mortality were 1.03 (95% confidence intervals 0.68-1.55) and 2.04 (95% confidence intervals 1.22-3.42), respectively. There was a J-shaped association between fasting glucose levels in the acute phase and risk of mortality (P=0.0001) and a direct association with heart failure (P=0.03). Despite modern treatment of ST-elevation myocardial infarction and high levels of guideline-based medical care, diabetes mellitus had an independent adverse effect on the risk of re-admissions for heart failure, which was particularly high among insulin-treated patients.