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Purpose of Review Since its inception in 1902 by Willem Einthoven, the electrocardiogram (ECG) has fundamentally undergone minimal technological advances. Nevertheless, its clinical utility is critical, and it remains an essential tool to diagnose, risk stratify, and guide reperfusion and invasive strategies in patients with suspected acute coronary syndromes. ECG reading can be demanding, with many healthcare professionals lacking the necessary expertise to accurately interpret them. This is exacerbated by the need to constantly revisit old dogmas pertinent to the interpretation of ECGs. Recent Findings Notably, ECG leads record the global electrical activity of the heart toward and away from each electrode rather than local events. The long-held central paradigm that the various ECG leads record local events underneath specific electrodes should therefore be reassessed. For example, ST segment elevation in leads V1 and V2 usually denote antero-apical rather than septal infarction, often a misnomer utilized by the majority of clinicians. The ECG diagnosis of ST-elevation myocardial infarction (STEMI) is sometimes challenging and discerning it from non-ST-elevation myocardial infarction (NSTEMI) is of paramount importance to implement timely acute reperfusion therapy. In fact, when qualifications for emergency reperfusion therapy are based on STEMI ECG criteria, nearly one-third of cases with acute coronary occlusion are missed. Diagnostic ST elevation in the absence of left ventricular (LV) hypertrophy or left bundle-branch block (LBBB) is defined by a specific set of sex-specific criteria for new ST elevation at the J point in contiguous precordial or limb leads. However, other ECG criteria need to be kept in mind. These include, but are not limited to, new or presumably new left bundle branch block (LBBB), which is often considered as an STEMI-equivalent; ST depression in two or more precordial leads (V1–V4), denoting a true inferolateral transmural myocardial infarction; and the infrequent presentation with hyperacute T-wave changes. Summary As our understanding of the pathology of ischemic reperfusion injury has evolved and following the introduction of new imaging modalities such as cardiac magnetic resonance imaging, we need to re-assess the old dogmas pertinent to the interpretation of ECGs and update the terms and classifications.

Patients with occlusion myocardial infarction (OMI) and no ST-elevation on presenting ECG are increasing in numbers. These patients have a poor prognosis and would benefit from immediate reperfusion therapy, but we currently have no accurate tools to identify them during initial triage. Herein, we report the first observational cohort study to develop machine learning models for the ECG diagnosis of OMI. Using 7,313 consecutive patients from multiple clinical sites, we derived and externally validated an intelligent model that outperformed practicing clinicians and other widely used commercial interpretation systems, significantly boosting both precision and sensitivity. Our derived OMI risk score provided superior rule-in and rule-out accuracy compared to routine care, and when combined with the clinical judgment of trained emergency personnel, this score helped correctly reclassify one in three patients with chest pain. ECG features driving our models were validated by clinical experts, providing plausible mechanistic links to myocardial injury.

Aims This review summarizes the findings of preclinical studies evaluating the pleiotropic effects of ticagrelor. These include attenuation of ischemia–reperfusion injury (IRI), inflammation, adverse cardiac remodeling, and atherosclerosis. In doing so, it aims to provide novel insights into ticagrelor’s mechanisms and benefits over other P2Y12 inhibitors. It also generates viable hypotheses for the results of seminal clinical trials assessing ticagrelor use in acute and chronic coronary syndromes. Methods and Results A comprehensive review of the preclinical literature demonstrates that ticagrelor protects against IRI in the setting of both an acute myocardial infarction (MI), and when MI occurs while on chronic treatment. Maintenance therapy with ticagrelor also likely mitigates adverse inflammation, cardiac remodeling, and atherosclerosis, while improving stem cell recruitment. These effects are probably mediated by ticagrelor’s ability to increase local interstitial adenosine levels which activate downstream cardio-protective molecules. Attenuation and augmentation of these pleiotropic effects by high-dose aspirin and caffeine, and statins respectively may help explain variable outcomes in PLATO and subsequent randomized controlled trials (RCTs). Conclusion Most RCTs and meta-analyses have not evaluated the pleiotropic effects of ticagrelor. We need further studies comparing cardiovascular outcomes in patients treated with ticagrelor versus other P2Y12 inhibitors that are mindful of the unique pleiotropic advantages afforded by ticagrelor, as well as possible interactions with other therapies (e.g., aspirin, statins, caffeine).

After the results of the first multicenter, prospective randomized clinical trial (RCT) evaluating long-term efficacy of oral beta-blockers in patients with preserved left ventricular ejection fraction (LVEF) after ST elevation myocardial infarction (STEMI), we decided to conduct an updated systematic review and meta-analysis to evaluate the long-term efficacy of oral beta-blocker use in patients with preserved LVEF who underwent percutaneous coronary intervention (PCI) for STEMI. A time-limited search from January 1, 1999, to April 16, 2020, on PubMed and EMBASE was conducted on April 16, 2020, for observational studies and clinical trials evaluating the efficacy of long-term oral beta-blockers in patients with preserved LVEF after STEMI treated with PCI. The comparative outcomes between beta-blockers and non-beta-blockers were assessed by pooling weighted odds ratio (OR) with 95% confidence interval (CI) using random-effects model. The outcomes of interest were all-cause mortality and major adverse cardiac event (MACE). Twelve studies (11 observational and 1 RCT) comprising 32,108 patients (19,740 on beta-blocker therapy and 12,368 without beta-blocker therapy) were included. Of which, 75% percent were male (mean age of 64 years: 63.87 ± 3.01 years on beta-blocker therapy and 64.76 ± 3.02 years on non-beta-blocker therapy; P = 0.129) with a follow-up of up to 4.7 years. Unadjusted all-cause mortality [OR = 0.58 (95% CI: 0.42-0.79)] and adjusted all-cause mortality [OR = 0.64 (95% CI: 0.48-0.87)] were significantly lower in patients on the long-term beta-blocker therapy group. However, unadjusted MACE [OR = 0.87 (95% CI: 0.70-1.08)] was not reduced with beta-blocker therapy in these patients. Patients with preserved LVEF after STEMI treated with PCI on long-term oral beta-blocker therapy have a significant reduction in risk of all-cause mortality, without an effect on MACE rates. The only RCT included showed neutral effect, so results of ongoing RCTs are anticipated. Considering that the only high-quality data (RCT) suggest a neutral effect, one should be cautious in interpreting the conclusion.

The pivotal studies that led to the recommendations for emergent reperfusion therapy for ST-elevation myocardial infarction (STEMI) were conducted for the most part over 25 years ago. At that time, contemporary standard treatments including aspirin, statin, and even anticoagulation were not commonly used. The 2013 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines and the 2017 European Society of Cardiology guidelines give a class I recommendation (with the level of evidence A) for primary percutaneous coronary intervention (pPCI) in patients with STEMI and ischemic symptoms of less than 12 h. However, if the patient presents to a hospital without pPCI capacity, and it is anticipated that pPCI cannot be performed within 120 min of first medical contact, fibrinolytic therapy is indicated (if there are no contraindications) (class I indication, level of evidence A). Our review of the pertinent literature shows that the current recommendation for inferior STEMI is based on the level of evidence lower than A. We can consider level B even C, supporting the recommendation for fibrinolytic therapy if pPCI is not available for inferior STEMI.

Aspirin loading (chewable or intravenous) as soon as possible after presentation is a class I recommendation by current ST elevation myocardial infarction (STEMI) guidelines. Earlier achievement of therapeutic antiplatelet effects by aspirin loading has long been considered the standard of care. However, the effects of the loading dose of aspirin (alone or in addition to a chronic maintenance oral dose) have not been studied. A large proportion of myocardial cell death occurs upon and after reperfusion (reperfusion injury). Numerous agents and interventions have been shown to limit infarct size in animal models when administered before or immediately after reperfusion. However, these interventions have predominantly failed to show significant protection in clinical studies. In the current review, we raise the hypothesis that aspirin loading may be the culprit. Data obtained from animal models consistently show that statins, ticagrelor, opiates, and ischemic postconditioning limit myocardial infarct size. In most of these studies, aspirin was not administered. However, when aspirin was administered before reperfusion (as is the case in the majority of studies enrolling STEMI patients), the protective effects of statin, ticagrelor, morphine, and ischemic postconditioning were attenuated, which can be plausibly attributable to aspirin loading. We therefore suggest studying the effects of aspirin loading before reperfusion on the infarct size limiting effects of statins, ticagrelor, morphine, and/ or postconditioning in large animal models using long reperfusion periods (at least 24 h). If indeed aspirin attenuates the protective effects, clinical trials should be conducted comparing aspirin loading to alternative antiplatelet regimens without aspirin loading in patients with STEMI undergoing primary percutaneous coronary intervention.

Acute ST-elevation myocardial infarction (STEMI) is associated with a high incidence of complications as well as a considerable hospitalization rate and economic burden. Preliminary evidence suggests that remote ischemic conditioning (RIC) is a promising non-invasive intervention that may effectively and safely reduce myocardial infarct size, subsequent cardiac events and complications, and mortality. However, RIC's cardio-protective effect remains under debate, especially for single timepoint RIC programs. Adequately powered large-scale randomized controlled trials investigating clinical outcomes are thus needed to clarify the role of full disease cycle RIC programs.The intelligent "Internet Plus"-based full disease cycle remote ischemic conditioning (i-RIC) trial is a pragmatic, multicenter, randomized controlled, parallel group, clinical trial. The term, intelligent "Internet Plus"-based full disease cycle, refers to smart devices aided automatic and real-time monitoring of remote ischemic pre-, per- or post-conditioning intervention for patients with STEMI undergoing percutaneous coronary intervention (PCI). Based on this perspective, 4700 STEMI patients from five hospitals in China will be randomized to a control and an intervention group. The control group will receive PCI and usual care, including pharmacotherapy, before and after PCI. The intervention group will receive pre-, per-, and post-operative RIC combined with long-term i-RIC over a one-month period in addition. A smartphone application, an automated cuff inflation/deflation device and "Internet Plus"-based administration will be used in the long-term phase. The primary outcome is the combined cardiac death or hospitalization for heart failure rate. Secondary outcomes include clinical and functional outcomes: major adverse cardiac and cerebrovascular events rate, all-cause mortality, myocardial reinfarction rate, readmission rate for heart failure and ischemic stroke rate, unplanned revascularization rate, plasma concentration of myocardial infarction-related key biomarkers, infarct size, cardiac function, cardiopulmonary endurance, health-related quality of life, total hospital length of stay, total medical cost, and compliance with treatment regime.The i-RIC trial is designed to test the hypothesis that clinical and functional outcomes can be improved with the i-RIC program in STEMI patients undergoing PCI. The concept of RIC is expected to be enhanced with this intelligent "Internet Plus"-based program focusing on the full disease cycle. If the i-RIC program results in superior improvement in primary and secondary outcomes, it will offer an innovative treatment option for STEMI patients and form the basis of future recommendations.Chinese Clinical Trial Registry ( http://www.chictr.org.cn ): ChiCTR2000031550, 04 April 2020.

OBJECTIVE There is mounting evidence regarding the cardiovascular benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) among patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes mellitus (T2DM). There is paucity of data assessing real-world practice patterns for these drug classes. We aimed to assess utilization rates of these drug classes and facility-level variation in their use. RESEARCH DESIGN AND METHODS We used the nationwide Veterans Affairs (VA) health care system data set from 1 January 2020 to 31 December 2020 and included patients with established ASCVD and T2DM. Among these patients, we assessed the use of SGLT2i and GLP-1 RA and the facility-level variation in their use. Facility-level variation was computed using median rate ratios (MRR), a measure of likelihood that two random facilities differ in use of SGLT2i and GLP-1 RA in patients with ASCVD and T2DM. RESULTS Among 537,980 patients with ASCVD and T2DM across 130 VA facilities, 11.2% of patients received an SGLT2i while 8.0% of patients received a GLP-1 RA. Patients receiving these cardioprotective glucose-lowering drug classes were on average younger and had a higher proportion of non-Hispanic Whites. Overall, median (10th–90th percentile) facility-level rates were 14.92% (9.31–22.50) for SGLT2i and 10.88% (4.44–17.07) for GLP-1 RA. There was significant facility-level variation among SGLT2i use—MRRunadjusted: 1.41 (95% CI 1.35–1.47) and MRRadjusted: 1.55 (95% CI 1.46 –1.63). Similar facility-level variation was observed for use of GLP-1 RA—MRRunadjusted: 1.34 (95% CI 1.29–1.38) and MRRadjusted: 1.78 (95% CI 1.65–1.90). CONCLUSIONS Overall utilization rates of SGLT2i and GLP-1 RA among eligible patients are low, with significantly higher residual facility-level variation in the use of these drug classes. Our results suggest opportunities to optimize their use to prevent future adverse cardiovascular events among these patients.

Background In the standard ECG display, limb leads are presented in a non-anatomical sequence: I, II, III, aVR, aVL, aVF. The Cabrera system is a display format which instead presents the limb leads in a cranial/left-to-caudal/right sequence, i.e. in an anatomically sequential order. Lead aVR is replaced in the Cabrera display by its inverted version, −aVR, which is presented in its logical place between lead I and lead II. Main text In this debate article possible implications of using the Cabrera display, instead of the standard, non-contiguous lead display, are presented, focusing on its use in patients with possible acute coronary syndrome. The importance of appreciating reciprocal limb-lead ECG changes and the diagnostic and prognostic value of including aVR or lead −aVR in ECG interpretation in acute coronary syndrome is covered. Illustrative cases and ECGs are presented with both the standard and contiguous limb lead display for each ECG. A contiguous lead display is useful when diagnosing acute coronary syndrome in at least 3 ways: 1) when contiguous leads are present adjacent to each other, identification of ST elevation in two contiguous leads is simple; 2) a contiguous lead display facilitates understanding of lead relationships as well as reciprocal changes; 3) it makes the common neglect of lead aVR unlikely. Conlusions It is logical to display the limb leads in their sequential anatomical order and it may have advantages both in diagnostics and ECG learning.

Acute myocardial infarction (MI) is still a large source of morbidity and mortality worldwide. Although early reperfusion therapy has been prioritized in the modern era of percutaneous coronary intervention and thrombolysis, attempts at incremental improvements in clinical outcomes by reducing MI size have not been successful so far. Herein, we review the studies that have evaluated immediate-onset antiplatelet therapy as attempts to improve meaningful clinical outcomes in ST-segment elevation MI (STEMI). Unfortunately, many of the adjunctive pharmacotherapies have proven to be disappointing. Recent studies performed in the background of routine oral administration of P2Y12 adenosine receptor inhibitors, which may take several hours to take full effect, and aspirin have largely shown no improvement in outcomes, despite an earlier onset of antiplatelet activity of the investigative agents. Further progress in improving outcomes during STEMI may depend on exploring therapeutics that modulate the pathophysiology of microvascular damage during ischemia–reperfusion injury, a phenomenon whose effects evolve over hours to days. We speculate that the dynamic nature of the no-reflow phenomenon may be an explanation for these disappointing results with the intravenous antiplatelet agents. We hope that appreciation for what has not worked in this domain may direct future research efforts to focus on novel pathways. Myocardial ischemia and reperfusion injury are very much still a lingering issue. Despite significant improvements in door-to-balloon times, rates of in-hospital mortality for STEMI remain unchanged. Outcomes following successfully reperfused STEMI are likely determined by the initial size of myocardial necrosis (ie, cardiomyocyte death during the period of ongoing ischemia), patency of the infarct-related epicardial coronary artery, possible reperfusion injury, the microvascular no-reflow phenomenon, and adverse remodeling after infarction.

Dipyridamole is an old anti-platelet and coronary vasodilator agent that inhibits platelet phosphodiesterase and increases interstitial adenosine levels. Its use in coronary artery disease (CAD) has fallen out of practice in the modern era with the advent of new anti-platelet agents, and most modern guidelines on the management of CAD either neglect to comment on its utility or outright recommend against it. The majority of the studies used in these guidelines are outdated and took place in an era when high doses of aspirin were used and statins were not widely utilized. There is growing evidence in rat models of dipyridamole’s synergy with statins through adenosine modulation resulting in significant myocardial protection against ischemia–reperfusion injury and limitation of infract size. The data in human studies are limited but show a similar potential synergy between dipyridamole and statins. It would thus be prudent to reconsider the recommendations against the use of dipyridamole in CAD and to re-evaluate its possible role and potential benefits through well-designed randomized trials combining it with statins, low-dose aspirin, and/or other anti-platelet agents.

Aim:To compare the safety and efficacy of direct oral anticoagulants (DOAC) relative to vitamin K antagonists (VKA) for the treatment of left ventricular thrombus (LVT).Methods:This retrospective study enrolled patients diagnosed with LVT from 2014-2017. Patient characteristics and outcomes within 12 months of LVT diagnosis were recorded and analyzed. A meta-analysis was also performed by pooling our results with existing data in literature.Results:14 DOAC and 59 VKA patients were included. Baseline demographic and clinical characteristics were similar except for age. Although more strokes within 12 months occurred in VKA (15%) than in DOAC (0%) patients, this was not statistically significant ( P = 0.189). There were no significant differences in outcomes between patients on DOAC and VKA for acute coronary syndrome (ACS) (7%, vs 3.4%, P = .477), LVT resolution (86% vs 76%, P = .499) or bleeding (14% vs 14%, P = 1) within 12 months. The meta-analysis included 6 studies (n = 408 for DOACs; n = 1207 for VKA). There were no significant differences between DOACs versus VKAs with respect to odds for unresolved thrombus (OR 0.61, 95% CI 0.26,1.41), embolic events (OR 1.24, 95% CI 0.90,1.69), embolic events and death (OR 1.10, 95% CI 0.84,1.45) or bleeding events (OR 1.13, 95% CI 0.74,1.72).Conclusions:Our study and meta-analysis suggest similar efficacy and safety of DOACs in the treatment of LVT compared to VKA. These findings underscore the need for a randomized controlled trial.

The Fourth Universal Definition of Myocardial Infarction (FUDMI) focuses on the distinction between nonischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI, and the ECG is the main available tool for (a) detecting acute ischemia, (b) triage, and (c) risk stratification upon presentation. This review focuses on multiple aspects of ECG interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI.

Background The reported positive predictive value (PPV) for the “de Winter ECG pattern” to predict an acute left anterior descending artery (LAD) lesion is inconsistent. Besides, the morphology of upsloping or nonupsloping ST depression (STD) may have different significance of severity and prognostication. Methods We searched the MEDLINE database using “de Winter” or “junctional ST‐depression with tall symmetrical T‐waves” or “tall T wave” or “STEMI equivalent” as the item up to March 2020. We compared the ECG differences between the different culprit arteries and various morphological STD. Results A total of 70 patients with analyzable ECGs were included. In 60 patients (LAD group), the LAD was the culprit artery, while in 10 patients (non‐LAD group), there were other etiologies. Maximal STD in V2 or V3 had a PPV of 89% of all patients and 98% of patients without ST elevation in V2 to detect an acute LAD lesion. The presence of q/Q‐wave or poor R‐wave progression in the precordial leads was significantly more often found in patients with upsloping STD than in patients with nonupsloping STD in the LAD group (84% vs. 27%, p

The Fourth Universal Definition of Myocardial Infarction (FUDMI) [published simultaneously in 2018 in numerous journals including Circulation, Journal of the American College of Cardiology and European Heart Journal] focuses mainly on the distinction between non-ischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI and the ECG is the main available tool for i) detecting acute ischemia, ii) triage and iii) risk stratification upon presentation. This review focuses on multiple aspects of ECG interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI. Our counterpoint view is that: a) the use of the ECG following coronary artery bypass surgery should be better explored and defined; b) the emphasis in the FUDMI on convex versus concave ST-elevation, which is questionable, should be balanced by the fact that many patients with true ST-elevation MI (STEMI) present with a concave form of ST elevation; c) reciprocal ST-depression in STEMI caused by right coronary artery or left circumflex artery occlusion, should be set against the fact that not all anterior STEMIs present with reciprocal ST-depression which can also be seen in cardiomyopathy and left ventricular hypertrophy; d) the "posterior" leads V7-V9 should be placed on a horizontal line from V4, rather than follow the 5th intercostal space; e) ST-depression in V1-V3 is not a manifestation of ischemia of the basal inferior segment, placed horizontally; f) Interpreting ST-T changes in patients with conduction abnormalities and pacemakers should be further defined.

PR‐segment depression with multilead ST‐segment elevation and ST‐segment depression in lead aVR are classic ECG manifestation of acute pericarditis. We present a patient, where the etiology of these ECG features was acute ST‐elevation myocardial infarction due to left circumflex artery occlusion. To avoid misdiagnosis, unnecessary examinations, and inappropriate therapeutic decisions, the possibility of ST‐segment elevation myocardial infarction should be kept in mind even when ECG changes typical for pericarditis are encountered in chest pain patients. Findings of QRS widening and QT interval shortening in leads with ST‐segment elevation could help to differentiate acute ST‐segment elevation myocardial infarction from acute pericarditis.

ST-elevation myocardial (STEMI) is frequently associated with conduction disorders. Regional myocardial ischemia or injury may affect the cardiac conduction system at various locations, and neural reflexes or changes in the balance of the autonomous nervous system may be involved. Sinoatrial and atrioventricular blocks are more frequent in inferior than anterior STEMI, while new left anterior fascicular block and right bundle branch block indicate proximal occlusion of the left anterior descending coronary artery. New left bundle branch block is associated with multi-vessel disease. : Most conduction disorders associated with STEMI are reversible with reperfusion therapy, but they may still impair prognosis because they indicate a large area at risk, extensive myocardial infarction or severe coronary artery disease. : Acute STEMI recognition is possible in patients with a fascicular or right bundle branch block, but future studies need to define the cut-off values for ST depression in the leads V1-V3 in inferolateral MI and for ST elevation in the same leads in anterior STEMI. In the left bundle branch block, concordant ST elevation is a specific sign of acute coronary artery occlusion, but the ECG feature has low sensitivity.

Background Anteroseptal ST elevation myocardial infarction (STEMI) is traditionally defined on the electrocardiogram (ECG) by ST elevation (STE) in leads V1-V3, with or without involvement of lead V4. It is commonly taught that such infarcts affect the basal anteroseptal myocardial segment. While there are suggestions in the literature that Q waves limited to V1-V4 represent predominantly apical infarction, none have evaluated anteroseptal ST elevation territories. We compared the distribution of the myocardium at risk (MaR) in STEMI patients presenting with STE limited to V1-V4 and those with more extensive STE (V1-V6). Methods We identified patients in the MITOCARE study presenting with a first acute STEMI and new STE in at least two contiguous anterior leads from V1 to V6. Patients underwent cardiac magnetic resonance (CMR) imaging three to five days after acute infarction. Results Thirty-two patients met inclusion criteria. In patients with STE in V1-V4 (n = 20), myocardium at risk (MaR) > 50% was seen in 0%, 85%, 75%, 100%, and 90% in the basal anteroseptal, mid anteroseptal, apical anterior, apical septal segments, and apex, respectively. The group with STE in V1-V6 (n = 12), MaR > 50% was seen in 8%, 83%, 83%, 92%, and 83% of the same segments. Conclusions Patients with acute STEMI and STE in leads V1-V4, exhibit MaR in predominantly apical territories and rarely in the basal anteroseptum. We found no evidence to support existence of isolated basal anteroseptal or septal STEMI. “Anteroapical” infarction is a more precise description than “anteroseptal” infarction for acute STEMI patients exhibiting STE in V1-V4.

Background/Aims: Circulating miRNAs could serve as biomarkers for diagnosis or prognosis of heart diseases and cerebrovascular diseases. Dexmedetomidine has protective effects in various organs. The effects of dexmedetomidine on circulating miRNAs remain unknown. Here, we investigated differentially expressed miRNA and to predict the target genes of the miRNA in patients receiving dexmedetomidine. Methods: The expression levels of circulating miRNAs of 3 patients were determined through high through-put miRNA sequencing technology. Target genes of the identified differentially expressed miRNAs were predicted using TargetScan 7.1 and miRDB v.5. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to conduct functional annotation and pathway enrichment analysis of target genes respectively. Results: Twelve differentially expressed miRNAs were identified. Five miRNAs were upregulated (hsa-miR-4508, hsa-miR-novel-chr8_87373, hsa-miR-30a-3p, hsa-miR-novel-chr16_26099, hsa-miR-4306) and seven miRNAs (hsa-miR-744-5p, hsa-miR-320a, hsa-miR-novel-chr9_90035, hsa-miR-101-3p, hsa-miR-150-5p, hsa-miR-342-3p, and hsa-miR-140-3p) were downregulated after administration of dexmedetomidine in the subjects. The target genes and pathways related to the differentially expressed miRNAs were predicted and analyzed. Conclusion: The differentially expressed miRNAs may be involved in the mechanisms of action of dexmedetomidine. Specific miRNAs, such as hsa-miR-101-3p, hsa-miR-150-5p and hsa-miR-140-3p, are new potential targets for further functional studies of dexmedetomidine.

Successful reperfusion of an infarct-related coronary artery by primary percutaneous intervention or fibrinolysis during acute ST-elevation myocardial infarction (STEMI) does not always restore myocardial tissue perfusion, a phenomenon termed “no-reflow.” Herein we discuss the pathophysiology of this highly prevalent phenomenon and highlight the most salient aspects of its clinical diagnosis and management as well as the limitations of presently used methods. There is a great need for understanding the dynamic nature of no-reflow, as its occurrence is associated with poor cardiovascular outcomes. The no-reflow phenomenon may lend an explanation to the lack of further improvements in in-hospital mortality in STEMI patients despite decreases in door-to-balloon time. Hence, no-reflow potentially presents an important target for investigators interested in improving outcomes in STEMI. In the era of reperfusion, much effort has been made to decrease myocardial infarct (MI) size by implementing early reperfusion with primary percutaneous coronary intervention (P-PCI) or thrombolytic agents. Door-to-balloon times have improved substantially while concomitant in-hospital mortality improvements lag behind [1]. It is plausible that outcomes after successfully reperfused MI are determined by the initial size of myocardial ischemia, time from onset of ischemia to reperfusion, potential reperfusion injury, patency of the epicardial infarct-related artery, distal thromboembolization, adverse remodeling after infarction, and the microvascular no-reflow phenomenon (NRP). Herein we describe the dynamic pathophysiology of the NRP. Additionally, we present a comparison of clinical diagnostic and therapeutic strategies.

Background: Some evidence suggests an association of SGLT2 inhibitors (SGLT2i) with an increased risk of euglycemic DKA (euDKA). The incidence and possible procedure-related triggers of metabolic abnormalities in patients taking SGLT2i after coronary angiography has not been well established. Methods: All patients with diabetes mellitus on a SGLT2i undergoing coronary angiography at a single center from November 2017 to November 2018 were reviewed for periprocedural characteristics and post-procedural metabolic abnormalities. Metabolic abnormalities were defined as: euDKA, DKA with hyperglycemia, or elevated urine ketones without confirmed acidosis. Results: A total of 44 patients with diabetes mellitus on a SGLT2i undergoing coronary angiogram were identified. There was one case of euDKA after angiography and one of hyperglycemic DKA. There was an additional two cases of patients with elevated urine ketones for whom DKA labs were not available. Baseline characteristics including age (p=0.71), type of SGLT2i (p=.20) and hemoglobin A1c (p=.49) were similar between the cases with metabolic abnormalities and those without. Similarly, procedural variables including indication for angiography (p=0.26), amount of contrast used (p=0.47), angiography outcome (p=0.87) and complications (p=0.40) were not statistically different between the groups. Conclusions: With a rare incidence and subtle clinical presentation, cases of euDKA may be missed after angiography, especially if acidosis is attributed to the preceding procedure without further workup. Continued case identification may help determine if specific procedural variables contribute to the development of euDKA. As the fasting state and stress of angiography can be triggers for ketosis, protocols should be developed for post-procedural screening and management in this population. Disclosure M. Shahid: None. S. Pickett: None. X. Jia: None. M. Alam: None. Y. Birnbaum: Other Relationship; Self; AstraZeneca. Other Relationship; Spouse/Partner; AstraZeneca, Boehringer Ingelheim International GmbH.

The classic electrocardiographic (ECG) manifestation of stage I of acute pericarditis is diffuse ST elevation and PR depression with ST depression in lead aVR. One of the most common conditions, that is often confused with acute pericarditis, is the benign diffuse ST elevation, termed "early repolarization with ST elevation" (ERSTE). ERSTE often presents with diffuse ST elevation in the inferior and anterolateral leads, with or without terminal QRS notching or slurring. As ERSTE often presents with ST elevation in leads I and II, frequently there is concomitant ST depression in lead aVR, similar to the acute pericarditis ECG pattern. Moreover, PR depression in the inferior leads and/or PR elevation in lead aVR is often seen. Here we describe four patients with ERSTE, all had ST elevation in II with either ST elevation or isoelectric ST in lead I and concomitant ST depression in aVR. Two also had PR depression in the inferior leads. None of the patients had clinical symptoms or signs of acute pericarditis. In conclusion, diffuse ST elevation in the inferolateral leads associated with ST depression in aVR and even with PR segment depression is commonly found in ERSTE and should not be considered as pathognomonic of only acute pericarditis.

During an ST-elevation myocardial infarction (STEMI), the myocardium undergoes a prolonged period of ischaemia. Reperfusion therapy is essential to minimize cardiac injury but can paradoxically cause further damage. Experimental procedures to limit ischaemia and reperfusion (IR) injury have tended to focus on the cardiomyocytes since they are crucial for cardiac function. However, there is increasing evidence that non-cardiomyocyte resident cells in the heart (as discussed in a separate review in this Spotlight series) as well as circulating cells and factors play important roles in this pathology. For example, erythrocytes, in addition to their main oxygen-ferrying role, can protect the heart from IR injury via the export of nitric oxide bioactivity. Platelets are well-known to be involved in haemostasis and thrombosis, but beyond these roles, they secrete numerous factors including sphingosine-1 phosphate (S1P), platelet activating factor, and cytokines that can all strongly influence the development of IR injury. This is particularly relevant given that most STEMI patients receive at least one type of platelet inhibitor. Moreover, there are large numbers of circulating vesicles in the blood, including microvesicles and exosomes, which can exert both beneficial and detrimental effects on IR injury. Some of these effects are mediated by the transfer of microRNA (miRNA) to the heart. Synthetic miRNA molecules may offer an alternative approach to limiting the response to IR injury. We discuss these and other circulating factors, focussing on potential therapeutic targets relevant to IR injury. Given the prevalence of comorbidities such as diabetes in the target patient population, their influence will also be discussed. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.

The progression of chronic kidney disease to end-stage renal disease (ESRD) is associated with increased incidence and severity of coronary artery disease (CAD). Patients typically undergo cardiac risk assessment prior to renal transplant. Dobutamine stress echocardiography (DSE) is a common non