Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.

Automated spatially targeted optical micro proteomics identifies fibroblast- and macrophage-specific regulation of myocardial infarction scar maturation in rats.

Myocardial infarction (MI) results from occlusion of blood supply to the heart muscle causing death of cardiac muscle cells. Following myocardial infarction (MI), extracellular matrix deposition and scar formation mechanically stabilize the injured heart as damaged myocytes undergo necrosis and removal. Fibroblasts and macrophages are key drivers of post-MI scar formation, maturation, and ongoing long-term remodelling; however, their individual contributions are difficult to assess from bulk analyses of infarct scar. Here, we employ state-of-the-art automated spatially targeted optical micro proteomics (autoSTOMP) to photochemically tag and isolate proteomes associated with subpopulations of fibroblasts (SMA+) and macrophages (CD68+) in the context of the native, MI tissue environment. Over a time course of 6-weeks post-MI, we captured dynamic changes in the whole-infarct proteome and determined that some of these protein composition signatures were differentially localized near SMA+ fibroblasts or CD68+ macrophages within the scar region. These results link specific cell populations to within-infarct protein remodelling and illustrate the distinct metabolic and structural processes underlying the observed physiology of each cell type.

Common and specific proteins and pathways in heart and cerebral ischemia.

OBJECTIVE: To understand the similarities and differences between acute ischemic stroke and acute myocardial infarction (AMI) to help in the development of specific or common treatment strategies. METHODS: Using an aptamer-based proteomic array, we measured and compared 1310 circulating proteins in the blood of 40 patients with AIS, 9 patients with AMI, and 31 healthy controls. Pathway enrichment analysis was performed using GSEA and g:profiler. RESULTS: Ninety-four proteins were differentially expressed in AIS, and 284 were differentially expressed in AMI. Of these, 8 were specific to cerebral ischemia, and 197 were specific to myocardial infarction. Forty-two proteins were altered in both ischemia processes. Most altered pathways in AIS could be classified as immune response, cell cycle processing, molecular transport, or signaling. Pathways altered in AMI were mostly related to lipid metabolism and transport, highlighting cholesterol metabolic processes and estrogen signaling. In both types of ischemia, we found pathways related to metabolism, specifically purine metabolism, and signaling processes, such as TNF signaling or MAPK1/3. CONCLUSIONS: The present study revealed proteins and pathways that were specifically altered in cerebral ischemia, in cardiac ischemia, or in both diseases, providing information on the similarities and differences of ischemic conditions. The role of common and specific proteins and pathways should be explored in detail to find possible therapeutic targets.

High-resolution mapping of sensory fibers at the healthy and post-myocardial infarct whole transgenic hearts.

The sensory nervous system is critical to maintain cardiac function. As opposed to efferent innervation, less is known about cardiac afferents. For this, we mapped the VGLUT2-expressing cardiac afferent fibers of spinal and vagal origin by using the VGLUT2::tdTomato double transgenic mouse as an approach to visualize the whole hearts both at the dorsal and ventral sides. For comparison, we colabeled mixed-sex transgenic hearts with either TUJ1 protein for global cardiac innervation or tyrosine hydroxylase for the sympathetic network at the healthy state or following ischemic injury. Interestingly, the nerve density for global and VGLUT2-expressing afferents was found significantly higher on the dorsal side compared to the ventral side. From the global nerve innervation detected by TUJ1 immunoreactivity, VGLUT2 afferent innervation was detected to be 15-25% of the total network. The detailed characterization of both the atria and the ventricles revealed a remarkable diversity of spinal afferent nerve ending morphologies of flower sprays, intramuscular endings, and end-net branches that innervate distinct anatomical parts of the heart. Using this integrative approach in a chronic myocardial infarct model, we showed a significant increase in hyperinnervation in the form of axonal sprouts for cardiac afferents at the infarct border zone, as well as denervation at distal sites of the ischemic area. The functional and physiological consequences of the abnormal sensory innervation remodeling post-ischemic injury should be further evaluated in future studies regarding their potential contribution to cardiac dysfunction.

Interaction of exercise training with taurine attenuates infarct size and cardiac dysfunction via Akt-Foxo3a-Caspase-8 signaling pathway.

This research aimed to investigate the synergistic protective effect of exercise training and taurine on Akt-Foxo3a-Caspase-8 signaling related to infarct size and cardiac dysfunction. Therefore, 25 male Wistar rats with MI were divided into five groups: sham (Sh), control-MI(C-MI), exercise training-MI(Exe-MI), taurine supplementation-MI(Supp-MI), and exercise training + taurine-MI(Exe + Supp-MI). The taurine groups were given a 200 mg/kg/day dose of taurine by drinking water. Exercise training was conducted for 8 weeks (5 days/week), each session alternated 2 min with 25-30% VO2peak and 4 min with 55-60% VO2peak for 10 alternations. Then, the left ventricle tissue samples were taken from all groups. Exercise training and taurine activated Akt and decreased Foxo3a. Expression of the caspase-8 gene was increased in cardiac necrosis after MI, While, after 12 weeks of intervention decreased. Results exhibited that exercise training combined with taurine has a greater effect than either alone on activating the Akt-Foxo3a-caspase signaling pathway (P < 0.001). MI-induced myocardial injury leads to increase collagen deposition (P < 0.001) and infarct size and results in cardiac dysfunction via reduced stroke volume, ejection fraction, and fractional shortening (P < 0.001). Exercise training and taurine improved cardiac functional parameters (SV, EF, FS) and infarct size (P < 0.001) after 8 weeks of intervention in rats with MI. Also, the interaction of exercise training and taurine has a greater effect than alone on these variables. Interaction of exercise training with taurine supplementation induces a general amelioration of the cardiac histopathological profiles and improves cardiac remodeling via activating Akt-Foxo3a-Caspase-8 signaling with protective effects against MI.

Clinical outcomes of hundred large Impella implantations in cardiogenic shock patients based on individual clinical scenarios.

BACKGROUND: Large Impella systems (5.0 or 5.5; i.e., Impella 5+) (Abiomed Inc., Danvers, MA, USA) help achieve better clinical outcomes through relevant left ventricular unloading in acute cardiogenic shock (CS). Here, we report our experience with Impella 5+, while focusing on the clinical outcomes depending on individual case scenarios in patients with acute CS. METHODS: This single-center retrospective observational study included 100 Impella 5+ implantations conducted on patients with acute CS from November 2018 to October 2021. After excluding 10 reimplantation cases, 90 cases were enrolled for further analysis. RESULTS: In-hospital and 30-day mortality rates were 56.7% (n = 51) and 48.9% (n = 44), respectively. In-hospital mortality was lower in patients with acute myocardial infarction (AMI) than in non-AMI patients (p = 0.07). Young age and low lactate levels were the independent predictors of successful transition and survival after permanent mechanical circulatory support/heart transplantation (pMCS/HTX) (age, p = 0.03; lactate level, p = 0.04; survived after pMCS/HTX, n = 11; died on Impella, n = 41). During simultaneous utilization of venoarterial extracorporeal membrane oxygenation therapy and Impella 5+, termed ECMELLA therapy, high dose of noradrenaline was a predictive factor for in-hospital mortality by multivariate analysis (n = 0.02). CONCLUSIONS: Our results suggest that enhanced Impella support might have better clinical outcomes among acute CS patients supported with large Impella, those with AMI than those with no AMI. Young age and low lactate levels were predictors of successful bridging to pMCS/HTX and favorable clinical outcomes thereafter. The clinical outcomes of ECMELLA therapy might depend on noradrenaline dose at the time of Impella 5+ implantation.

Adverse events from nitrate administration during right ventricular myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: The current guidelines of the American Heart Association (AHA) and European Society of Cardiology (ESC) recommend that when right ventricular myocardial infarction (RVMI) is present patients are not administered nitrates, due to the risk that decreasing preload in the setting of already compromised right ventricular ejection fraction may reduce cardiac output and precipitate hypotension. The cohort study (n=40) underlying this recommendation was recently challenged by new studies suitable for meta-analysis (cumulatively, n=1050), suggesting that this topic merits systematic review. METHODS: The protocol was registered on PROSPERO and published in Evidence Synthesis. Six databases were systematically searched in May 2022: PubMed, Embase, MEDLINE Complete, Cochrane CENTRAL Register, CINAHL and Google Scholar. Two investigators independently assessed for quality and bias and extracted data using Joanna Briggs Institute tools and methods. Risk ratios and 95% CIs were calculated, and meta-analysis performed using the random effects inverse variance method. RESULTS: Five studies (n=1113) were suitable. Outcomes included haemodynamics, GCS, syncope, arrest and death. Arrest and death did not occur in the RVMI group. Meta-analysis was possible for sublingual nitroglycerin 400 µg (2 studies, n=1050) and found no statistically significant difference in relative risk to combined inferior and RVMI at 1.31 (95% CI 0.81 to 2.12, p=0.27), with an absolute effect of 3 additional adverse events per 100 treatments. Results remained robust under sensitivity analysis. CONCLUSIONS: This review suggests that the AHA and ESC contraindications are not supported by evidence. Key limitations include all studies having concomitant inferior and RVMI, not evaluating beneficial effects and very low certainty of evidence. As adverse events are transient and easily managed, nitrates are a reasonable treatment modality to consider during RVMI on current evidence. PROSPERO REGISTRATION NUMBER: CRD42020172839.

Impact of prehospital opioid dose on angiographic and clinical outcomes in acute coronary syndromes.

BACKGROUND: An adverse interaction whereby opioids impair and delay the gastrointestinal absorption of oral P2Y12 inhibitors has been established, however the clinical significance of this in acute coronary syndrome (ACS) is uncertain. We sought to characterise the relationship between prehospital opioid dose and clinical outcomes in patients with ACS. METHODS: Patients given opioid treatment by emergency medical services (EMS) with ACS who underwent percutaneous coronary intervention (PCI) between 1 January 2014 and 31 December 2018 were included in this retrospective cohort analysis using data linkage between the Ambulance Victoria, Victorian Cardiac Outcomes Registry and Melbourne Interventional Group databases. Patients with cardiogenic shock, out-of-hospital cardiac arrest and fibrinolysis were excluded. The primary end point was the risk-adjusted odds of 30-day major adverse cardiac events (MACE) between patients who received opioids and those that did not. RESULTS: 10 531 patients were included in the primary analysis. There was no significant difference in 30-day MACE between patients receiving opioids and those who did not after adjusting for key patient and clinical factors. Among patients with ST-elevation myocardial infarction (STEMI), there were significantly more patients with thrombolysis in myocardial infarction (TIMI) 0 or 1 flow pre-PCI in a subset of patients with high opioid dose versus no opioids (56% vs 25%, p<0.001). This remained significant after adjusting for known confounders with a higher predicted probability of TIMI 0/1 flow in the high versus no opioid groups (33% vs 11%, p<0.001). CONCLUSIONS: Opioid use was not associated with 30-day MACE. There were higher rates of TIMI 0/1 flow pre-PCI in patients with STEMI prescribed opioids. Future prospective research is required to verify these findings and investigate alternative analgesia for ischaemic chest pain.

External validation of the Manchester Acute Coronary Syndromes ECG risk model within a pre-hospital setting.

OBJECTIVES: The Manchester Acute Coronary Syndromes ECG (MACS-ECG) prediction model calculates a score based on objective ECG measurements to give the probability of a non-ST elevation myocardial infarction (NSTEMI). The model showed good performance in the emergency department (ED), but its accuracy in the pre-hospital setting is unknown. We aimed to externally validate MACS-ECG in the pre-hospital environment. METHODS: We undertook a secondary analysis from the Pre-hospital Evaluation of Sensitive Troponin (PRESTO) study, a multi-centre prospective study to validate decision aids in the pre-hospital setting (26 February 2019 to 23 March 2020). Patients with chest pain where the treating paramedic suspected acute coronary syndrome were included. Paramedics collected demographic and historical data and interpreted ECGs contemporaneously (as 'normal' or 'abnormal'). After completing recruitment, we analysed ECGs to calculate the MACS-ECG score, using both a pre-defined threshold and a novel threshold that optimises sensitivity to differentiate AMI from non-AMI. This was compared with subjective ECG interpretation by paramedics. The diagnosis of AMI was adjudicated by two investigators based on serial troponin testing in hospital. RESULTS: Of 691 participants, 87 had type 1 AMI and 687 had complete data for paramedic ECG interpretation. The MACS-ECG model had a C-index of 0.68 (95% CI: 0.61 to 0.75). At the pre-determined cut-off, MACS-ECG had 2.3% (95% CI: 0.3% to 8.1%) sensitivity, 99.5% (95% CI: 98.6% to 99.9%) specificity, 40.0% (95% CI: 10.2% to 79.3%) positive predictive value (PPV) and 87.6% (87.3% to 88.0%) negative predictive value (NPV). At the optimal threshold for sensitivity, MACS-ECG had 50.6% sensitivity (39.6% to 61.5%), 83.1% specificity (79.9% to 86.0%), 30.1% PPV (24.7% to 36.2%) and 92.1% NPV (90.4% to 93.5%). In comparison, paramedics had a sensitivity of 71.3% (95% CI: 60.8% to 80.5%) with 53.8% (95% CI: 53.8% to 61.8%) specificity, 19.7% (17.2% to 22.45%) PPV and 93.3% (90.8% to 95.1%) NPV. CONCLUSION: Neither MACS-ECG nor paramedic ECG interpretation had a sufficiently high PPV or NPV to 'rule in' or 'rule out' NSTEMI alone.

Performance of a prehospital HEART score in patients with possible myocardial infarction: a prospective evaluation.

INTRODUCTION: The History, Electrocardiogram (ECG), Age, Risk Factors and Troponin (HEART) score is commonly used to risk stratify patients with possible myocardial infarction as low risk or high risk in the Emergency Department (ED). Whether the HEART score can be used by paramedics to guide care were high-sensitivity cardiac troponin testing available in a prehospital setting is uncertain. METHODS: In a prespecified secondary analysis of a prospective cohort study where paramedics enrolled patients with suspected myocardial infarction, a paramedic Heart, ECG, Age, Risk Factors (HEAR) score was recorded contemporaneously, and a prehospital blood sample was obtained for subsequent cardiac troponin testing. HEART and modified HEART scores were derived using laboratory contemporary and high-sensitivity cardiac troponin I assays. HEART and modified HEART scores of ≤3 and ≥7 were applied to define low-risk and high-risk patients, and performance was evaluated for an outcome of major adverse cardiac events (MACEs) at 30 days. RESULTS: Between November 2014 and April 2018, 1054 patients were recruited, of whom 960 (mean 64 (SD 15) years, 42% women) were eligible for analysis and 255 (26%) experienced a MACE at 30 days. A HEART score of ≤3 identified 279 (29%) as low risk with a negative predictive value of 93.5% (95% CI 90.0% to 95.9%) for the contemporary assay and 91.4% (95% CI 87.5% to 94.2%) for the high-sensitivity assay. A modified HEART score of ≤3 using the limit of detection of the high-sensitivity assay identified 194 (20%) patients as low risk with a negative predictive value of 95.9% (95% CI 92.1% to 97.9%). A HEART score of ≥7 using either assay gave a lower positive predictive value than using the upper reference limit of either cardiac troponin assay alone. CONCLUSIONS: A HEART score derived by paramedics in the prehospital setting, even when modified to harness the precision of a high-sensitivity assay, does not allow safe rule-out of myocardial infarction or enhanced rule-in compared with cardiac troponin testing alone.

Serum uric acid in patients with ST-segment elevation myocardial infarction: An innocent bystander or leading actor?

Elevated serum uric acid (SUA) levels have been associated with several cardiovascular risk factors and the progression of coronary artery disease. In the setting of acute myocardial infarction, increasing evidence suggests that high SUA levels could be related to adverse outcomes. Interestingly elevated SUA levels have been linked to endothelial dysfunction, inflammation and oxidative stress. The aim of this review is to discuss the potential negative effects of SUA in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, analyzing the possible underlying pathophysiological mechanisms.

Cardio-cerebral infarction in left MCA strokes: a case series and literature review.

The objective of this manuscript is to describe the challenges of Cardio-Cerebral Infarction (CCI) treatment and to highlight the variable approaches in management. CCI is a rare clinical presentation of simultaneous acute ischemic stroke (AIS) and acute myocardial infarction (AMI) and poses a therapeutic challenge for practitioners. Each disease requires timely intervention to prevent irreversible damage; however, optimal management remains unclear. We describe three cases of CCI. All three patients presented with symptomatic left MCA (M1) occlusion, with ST elevation myocardial infarction (STEMI) and left ventricular apical thrombus. Fibrinolysis and mechanical thrombectomy (MT) were discussed in all cases, but only one patient received alteplase (0.9 mg/kg) and none underwent MT. Percutaneous intervention (PCI) was done in only one case. The two patients that did not receive thrombolysis were treated with modified therapeutic heparin (no bolus), and all received antiplatelet therapy. Ultimately, all three patients passed away. CCI poses a clinical challenge for physicians including (1) optimal strategies to enable swift mechanical reperfusion to both the brain and myocardium; (2) difference in dosage of thrombolytics for AIS versus AMI; (3) risk of symptomatic intracerebral hemorrhage following administration of anticoagulation and/or antiplatelet therapy; and (4) caution with use of thrombolytics in the setting of acute STEMI due to the risk of myocardial rupture. In the absence of high quality evidence and clinical guidelines, treatment of CCI is highly individualized.

Manchester ACS Electrocardiograph Model for the Identification of Non-STEMI in the ED.

OBJECTIVE: Acute coronary syndromes (ACS) are a diagnostic challenge for Emergency Medicine (EM) clinicians. To help clinicians assess patients with non-ST-elevation ACS (NSTEACS), clinical decision aids have been developed, combining clinical history, cardiac troponin and the electrocardiograph (ECG). These models ask the clinician to subjectively assess the ECG variable, introducing reliability issues. We set out to derive an ECG model that would provide an objective measure for ischaemia using non-ST-elevation myocardial infarction (NSTEMI) as the primary outcome. METHODS: We derived an ECG model in a retrospective Emergency Department cohort using logistic regression with a primary outcome of NSTEMI. All patients presented with signs or symptoms suggestive of an ACS. The model was validated in a multi-centre prospective Emergency Department cohort. RESULTS: Derivation included 1246 patients, 156 (12.5%) had the primary outcome; validation included 1139 patients, 170 (14.9%) had the primary outcome. Derivation demonstrated Sn 25.6% (95% CI 19.0-33.2), Sp 96.3% (95% CI 95.0-97.4), PPV 50.0% (95% CI 40.0-60.0) and NPV 90.1% (95% CI 89.2-90.9). Validation demonstrated Sn 23.5% (95% CI 17.4% to 30.6%), Sp 95.2% (95% CI 93.6% to 96.4%), PPV 46.0% (95% CI 36.6% to 55.7%) and NPV 87.6% (95% CI 86.7% to 88.5%). CONCLUSION: We have derived and validated an ECG model that is highly specific for NSTEMI and may be suitable for integration into existing clinical decision aids.

Feasibility of prehospital identification of non-ST-elevation myocardial infarction by ECG, troponin and echocardiography.

BACKGROUND: Prehospital identification and selection of treatment strategy in patients with suspected non-ST-elevation myocardial infarction (NSTEMI) is challenging. The aim of this study was to evaluate the feasibility and diagnostic accuracy of prehospital ECG, troponin T (TnT) and transthoracic echocardiography (TTE) acquired by paramedics in early identification of NSTEMI. METHODS: Consecutive patients requesting an ambulance from Sorlandet Hospital, Norway due to chest pain between November 2017 and January 2020 were screened for inclusion in the study. One ambulance was equipped with ECG recorder, point-of-care TnT test and TTE scanner, and six paramedics were given necessary training. ECG, TnT result and TTE images were acquired prehospitally and transferred to an in-hospital cardiologist. NSTEMI was suspected in patients with ischaemic ECG changes, elevated TnT or myocardial regional wall motion abnormalities (RWMA) at TTE. RESULTS: A total of 253 patients were included in the study. ECG was interpretable by cardiologists in 243 (96%), TnT in 238 (94%) and TTE images in 240 (95%) patients. NSTEMI was the discharge diagnosis in 22 (9%) of these patients. Four (18%) patients with NSTEMI had ischaemic ECG changes, elevated TnT and RWMA at TTE. Eight (36%) patients with NSTEMI had positive findings at two of the diagnostic methods, six (27%) patients had positive findings at one, and four (18%) patients had no positive findings in any of the diagnostic methods. In three patients (14%) with NSTEMI, RWMA was the only positive test. The negative and positive predictive values for RWMA were 42% and 96%, respectively. CONCLUSIONS: Prehospital acquisition of ECG, TnT and interpretable TTE images by paramedics were feasible in most patients with chest pain. Based on these examinations, it was possible to identify the majority of cases with NSTEMI prehospitally and admit the patients directly to a hospital with facilities for percutaneous coronary intervention (PCI) for further treatment. TRIAL REGISTRATION NUMBER: NCT04223986.

Identifying low-risk chest pain in the emergency department without troponin testing: a validation study of the HE-MACS and HEAR risk scores.

INTRODUCTION: Patients presenting to EDs with chest pain of possible cardiac origin represent a substantial and challenging cohort to risk stratify. Scores such as HE-MACS (History and Electrocardiogram-only Manchester Acute Coronary Syndromes decision aid) and HEAR (History, ECG, Age, Risk factors) have been developed to stratify risk without the need for troponin testing. Validation of these scores remains limited. METHODS: We performed a post hoc analysis of the Limit of Detection and ECG discharge strategy randomised-controlled trial dataset (n=629; June 2018 to March 2019; 8 UK hospitals) to calculate HEAR and HE-MACS scores. A <4% risk of major adverse cardiac events (MACE) at 30 days using HE-MACS and a score of <2 calculated using HEAR defined 'very low risk' patients suitable for discharge. The primary outcome of MACE at 30 days was used to assess diagnostic accuracy. RESULTS: MACE within 30 days occurred in 42/629 (7%) of the cohort. HE-MACS and HEAR scores identified 85/629 and 181/629 patients as 'very low risk', with MACE occurring in 0/85 and 1/181 patients, respectively. The sensitivities of each score for ruling out MACE were 100% (95% CI: 91.6% to 100%) for HE-MACS and 97.6% (95% CI: 87.7% to 99.9%) for HEAR. Presenting symptoms within these scores were poorly predictive, with only diaphoresis reaching statistical significance (OR: 4.99 (2.33 to 10.67)). Conventional cardiovascular risk factors and clinician suspicion were related to the presence of MACE at 30 days. CONCLUSION: HEAR and HE-MACS show potential as rule out tools for acute myocardial infarction without the need for troponin testing. However, prospective studies are required to further validate these scores.

Predictors of hospital prenotification for STEMI and association of prenotification with outcomes.

BACKGROUND: Delay to reperfusion in ST-elevation myocardial infarction (STEMI) is detrimental, but can be minimised with prehospital notification by ambulance to the treating hospital. We aimed to assess whether prenotification was associated with improved first medical contact to balloon times (FMC-BT) and whether this resulted in better clinical outcomes. We also aimed to identify factors associated with use of prenotification. METHODS: This was a retrospective study of prospective Victorian Cardiac Outcomes Registry data for patients undergoing primary percutaneous coronary intervention for STEMI from 2013-2018. Postcardiac arrest were excluded. Patients were grouped by whether they arrived by ambulance with prenotification (group 1), arrived by ambulance without prenotification (group 2) or self-presented (group 3). We compared groups by FMC-BT, incidence of major adverse cardiac and cerebrovascular events (MACCE), mortality and factors associated with the use of prenotification. RESULTS: 2891 patients were in group 1 (79.3% male), 1620 in group 2 (75.7% male) and 1220 in group 3 (82.9% male). Patients who had prenotification were more likely to present in-hours (p=0.004) and self-presenters had lowest rates of cardiogenic shock (p<0.001). Prenotification had shorter FMC-BT than without prenotification (104 min vs 132 min, p<0.001) Self-presenters had superior clinical outcomes, with no difference between ambulance groups. Groups 1 and 2 had similar 30-day MACCE outcomes (7.4% group 1 vs 9.1% group 2, p=0.05) and similar mortality (4.6% group 1 vs 5.9% group 2, p=0.07). In multivariable analysis, male gender, right coronary artery culprit and in-hours presentation independently predicted use of prenotification (all p<0.05). CONCLUSION: Differences in clinical characteristics, particularly gender, time of presentation and culprit vessel may influence ambulance prenotification. Ambulance cohorts have high-risk features and worse outcomes compared with self-presenters. Improving system inequality in prehospital STEMI diagnosis is recommended for fastest STEMI treatment.

Monocyte chemoattractant protein-1 is not predictive of cardiac events in patients with non-low-risk chest pain.

BACKGROUND: Prior studies suggest monocyte chemoattractant protein-1 (MCP-1) may be useful for risk stratifying ED patients with chest pain. We hypothesise that MCP-1 will be predictive of 90-day major adverse cardiovascular events (MACEs) in non-low-risk patients. METHODS: A case-control study was nested within a prospective multicentre cohort (STOP-CP), which enrolled adult patients being evaluated for acute coronary syndrome at eight US EDs from 25 January 2017 to 06 September 2018. Patients with a History, ECG, Age, and Risk factor score (HEAR score) ≥4 or coronary artery disease (CAD), a non-ischaemic ECG, and non-elevated contemporary troponins at 0 and 3 hours were included. Cases were patients with 90-day MACE (all-cause death, myocardial infarction or revascularisation). Controls were patients without MACE selected with frequency matching using age, sex, race, and HEAR score or the presence of CAD. Serum MCP-1 was measured. Sensitivity and specificity were determined for cut-off points of 194 pg/mL, 200 pg/mL, 238 pg/mL and 281 pg/mL. Logistic regression adjusting for age, sex, race, and HEAR score/presence of CAD was used to determine the association between MCP-1 and 90-day MACE. A separate logistic model also included high-sensitivity troponin (hs-cTnT). RESULTS: Among 40 cases and 179 controls, there was no difference in age (p=0.90), sex (p=1.00), race (p=0.85), or HEAR score/presence of CAD (p=0.89). MCP-1 was similar in cases (median 191.9 pg/mL, IQR: 161.8-260.1) and controls (median 196.6 pg/mL, IQR: 163.0-261.1) (p=0.48). At a cut-off point of 194 pg/mL, MCP-1 was 50.0% (95% CI 33.8% to 66.2%) sensitive and 46.9% (95% CI 39.4% to 54.5%) specific for 90-day MACE. After adjusting for covariates, MCP-1 was not associated with 90-day MACE at any cut-off point (at 194 pg/mL, OR 0.88 (95% CI 0.43 to 1.79)). When including hs-cTnT in the model, MCP-1 was not associated with 90-day MACE at any cut-off point (at 194 pg/mL, OR 0.85 (95% CI 0.42 to 1.73)). CONCLUSION: MCP-1 is not predictive of 90-day MACE in patients with non-low-risk chest pain.

Potential impact of a novel pathway for suspected myocardial infarction utilising a new high-sensitivity cardiac troponin I assay.

BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) assays promise high diagnostic accuracy for myocardial infarction (MI). In an ED where conventional cTnI was in use, we evaluated an assessment pathway using the new Access hsTnI assay. METHODS: This retrospective analysis recruited ED patients with suspected MI between June and September 2019. All patients received routine care with a conventional cTnI assay (AccuTnI +3: limit of detection (LoD) 10 ng/L, 99th centile upper reference limit (URL) 40 ng/L, abnormal elevation cut-point 80 ng/L). Arrival, then 90-minute or 360-minute cTnI levels for low and non-low risk patients, respectively (ED Assessment of Chest pain score) guided diagnosis and disposition which was at treating physician discretion. The same patients had arrival and 90-minute or 180-minute samples drawn for hs-cTnI levels (Access hsTnI: LoD 2 ng/L, 99th centile URL 10 ng/L (females) and 20 ng/L (males); abnormal elevation above the URL and delta >30%). Treating physicians were blinded to the hs-cTnI results. Using the hs-cTnI values, investigators retrospectively assigned likely diagnosis, disposition and likelihood of a 30-day major adverse cardiac event (MACE). Admission was recommended for significantly rising hs-cTnI elevations. The primary objective was to demonstrate an acceptable unexpected 30-day post-discharge MACE rate of <1%. cTnI elevation rates, diagnostic outcomes and ED disposition were also compared between pathways. RESULTS: For the 935 patients, unexpected 30-day post-discharge MACE rates were 0/935 (0%, 95% CI 0% to 0.4%) with the conventional or novel pathway. For the high-sensitivity and conventional assays, respectively, abnormal elevation rates were 29% (95% CI 26% to 32%) and 19% (95% CI 17% to 22%), for MI were 9% (95% CI 8% to 11%) and 8% (95% CI 6% to 10%), and for hospital admission were 42% (95% CI 39% to 45%) and 43% (95% CI 40% to 47%). CONCLUSION: The novel pathway using the Access hsTnI assay has an acceptably low 30-day MACE rate.

MSC Pretreatment for Improved Transplantation Viability Results in Improved Ventricular Function in Infarcted Hearts.

Many clinical studies utilizing MSCs (mesenchymal stem cells, mesenchymal stromal cells, or multipotential stromal cells) are underway in multiple clinical settings; however, the ideal approach to prepare these cells in vitro and to deliver them to injury sites in vivo with maximal effectiveness remains a challenge. Here, pretreating MSCs with agents that block the apoptotic pathways were compared with untreated MSCs. The treatment effects were evaluated in the myocardial infarct setting following direct injection, and physiological parameters were examined at 4 weeks post-infarct in a rat permanent ligation model. The prosurvival treated MSCs were detected in the hearts in greater abundance at 1 week and 4 weeks than the untreated MSCs. The untreated MSCs improved ejection fraction in infarcted hearts from 61% to 77% and the prosurvival treated MSCs further improved ejection fraction to 83% of normal. The untreated MSCs improved fractional shortening in the infarcted heart from 52% to 68%, and the prosurvival treated MSCs further improved fractional shortening to 77% of normal. Further improvements in survival of the MSC dose seems possible. Thus, pretreating MSCs for improved in vivo survival has implications for MSC-based cardiac therapies and in other indications where improved cell survival may improve effectiveness.

EFFECTS OF ALPHA-LIPOIC ACID ON GLYCEMIC STATUS IN 2 TYPE DIABETES PATIENTS WITH СHRONIC CORONARY SYNDROME.

OBJECTIVE: The aim: To study the possibilities of alpha-lipoic acid (ALA) to control the parameters of carbohydrate metabolism. PATIENTS AND METHODS: Materials and methods: We examined 80 people with type 2 DM and coronary heart disease who suffered non-Q-myocardial infarction (non-Q-MI). All patients at the time of inclusion in the study received oral hypoglycemic agents, ACE inhibitor, ß-blocker, statin and antiplatelet agent. 600 mg of ALA per day for 4 months was added to this treatment. After checking the patients for compliance with the criteria, they were divided into the main and experimental groups. The dosage of alpha-lipoic acid was determined for each of the groups. The results of the treatment were analyzed by determining the mean and standard deviations. RESULTS: Results: At the end of the observation period, a significant decrease in the level of fasting glucose (FG) by 11.6% was found, which corresponded to the average size of the clinical effect. The values of glycosylated hemoglobin (HbA1c) and the insulin resistance index HOMA (HOMA-IR) showed only a tendency to decrease on the background of treatment. The effect of ALA on postprandial glycemia (PPG) and insulin levels was not detected in this study. CONCLUSION: Conclusions: An additional 4-month dose of ALA in addition to baseline therapy showed a moderate effect on the decrease in FG concentration in the absence of significant dynamics in other parameters of glycemic control in the examined patients.