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Background The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI). Objectives The goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI. Methods A prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization. Results As of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p, Central Illustration

Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (8% g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy.We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary endpoint is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary endpoints include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary endpoints.The MINT trial will inform RBC transfusion practice in patients with acute MI.

Background In-hospital ST-elevation myocardial infarction (STEMI) is associated with a higher mortality rate than out-of-hospital STEMI. Quality measures and universal protocols for treatment of in-hospital STEMI do not exist, likely contributing to delays in recognition and treatment. Hypothesis To analyze differences in mortality among three subsets of patients who develop in-hospital STEMI. Methods This was a multicenter, retrospective observational study of patients who developed in-hospital STEMI at six United States medical centers between 2008 and 2017. Patients were stratified into three groups: (1) cardiac, (2) periprocedure, or (3) noncardiac/nonpostprocedure. Outcomes examined include time from electrocardiogram (ECG) acquisition to cardiac catheterization lab arrival (ECG-to-CCL) and survival to discharge. Results We identified 184 patients with in-hospital STEMI (mean age 68.7 years, 58.7% male). Group 1 (cardiac) patients had a shorter average ECG-to-CCL time (69 minutes) than group 2 (periprocedure, 215 minutes) and group 3 (noncardiac/nonpostprocedure, 199 minutes). Compared to group 1, survival to discharge was lower for group 2 (OR 0.33, P = .102) and group 3 (OR 0.20, P = .016). After adjusting for prespecified covariates, the relationship between group and survival showed a similar trend but did not reach statistical significance. Conclusions Patients who develop in-hospital STEMI in the context of a preceding procedure or noncardiac illness appear to have longer reperfusion times and higher in-hospital mortality than patients admitted with cardiac diagnoses. Larger studies are warranted to further investigate these observations. Health systems should place an increased emphasis on developing quality metrics and implementing quality improvement initiatives to improve outcomes for in-hospital STEMI.

BACKGROUND Cardiac catheterization is among the most performed medical procedures in the modern era. There were sporadic reports indicating that cardiac arrhythmias are common during cardiac catheterization, and there are risks of developing serious and potentially life-threatening arrhythmias, such as sustained ventricular tachycardia (VT), ventricular fibrillation (VF) and high-grade conduction disturbances such as complete heart block (CHB), requiring immediate interventions. However, there is lack of systematic overview of these conditions. AIM To systematically review existing literature and gain better understanding of the incidence of cardiac arrhythmias during cardiac catheterization, and their impact on outcomes, as well as potential approaches to minimize this risk. METHODS We applied a combination of terms potentially used in reports describing various cardiac arrhythmias during common cardiac catheterization procedures to systematically search PubMed, EMBASE and Cochrane databases, as well as references of full-length articles. RESULTS During right heart catheterization (RHC), the incidence of atrial arrhythmias (premature atrial complexes, atrial fibrillation and flutter) was low (< 1%); these arrhythmias were usually transient and self-limited. RHC associated with the development of a new RBBB at a rate of 0.1%-0.3% in individuals with normal conduction system but up to 6.3% in individuals with pre-existing left bundle branch block. These patients may require temporary pacing due to transient CHB. Isolated premature ventricular complexes or non-sustained VT are common during RHC (up to 20% of cases). Sustained ventricular arrhythmias (VT and/or VF) requiring either withdrawal of catheter or cardioversion occurred infrequently (1%-1.3%). During left heart catheterizations (LHC), the incidence of ventricular arrhythmias has declined significantly over the last few decades, from 1.1% historically to 0.1% currently. The overall reported rate of VT/VF in diagnostic LHC and coronary angiography is 0.8%. The risk of VT/VF was higher during percutaneous coronary interventions for stable coronary artery disease (1.1%) and even higher for patients with acute myocardial infarctions (4.1%-4.3%). Intravenous adenosine and papaverine bolus for fractional flow reserve measurement, as well as intracoronary imaging using optical coherence tomography have been reported to induce VF. Although uncommon, LHC and coronary angiography were also reported to induce conduction disturbances including CHB. CONCLUSION Cardiac arrhythmias are common and potentially serious complications of cardiac catheterization procedures, and it demands constant vigilance and readiness to intervene during procedures.

To study the correlation between intra-procedural left ventricular end-diastolic pressure (LVEDP) and the development of contrast-induced acute kidney injury (CI-AKI) in patients undergoing percutaneous coronary intervention (PCI).A single center retrospective observational study compared clinical and hemodynamic characteristics of patients who developed post-PCI CI-AKI with those did not. CI-AKI was defined as an absolute increase in serum creatinine ≥0.5 mg/dl or an increase ≥25% from baseline 48-72 h after the administration of contrast medium. Among 1301 consecutive patients who underwent PCI, 125 patients (9.6%) developed CI-AKI. The CI-AKI group had a higher average LVEDP (18.4 ± 8.7 vs 14.4 ± 6.6 mm Hg; p .0001) and higher prevalence of elevated LVEDP (≥20 mm Hg) than those without CI-AKI (47.2% vs 23.3%, p .0001). After adjustments, elevated LVEDP remained independently associated with CI-AKI (OR 2.21; 95% CI 1.40-3.50). LVEDP predicted the development of CI-AKI with a receiver operating characteristic area under curve (AUC) of 0.64. The association between elevated LVEDP and the risk of CI-AKI was stronger in patients with reduced ejection fraction (EF ≤ 40%) (OR = 4.08; 95% CI: 1.68-9.91) than those with preserved EF (OR = 1.69; 95% CI: 0.94-3.04) (p value for interaction = .0003). Patients who had LVEDP ≥ 20 mm Hg and LVEF ≤ 40% had a post-PCI incidence rate of developing CI-AKI of 36.5%.Elevated intra-procedural LVEDP (≥20 mm Hg) is independently associated with increased risk of CI-AKI for patients undergoing cardiac catheterization and PCI, especially in the setting of reduced LVEF (≤40%).

Coronary artery disease (CAD) costs healthcare billions of dollars annually and is the leading cause of death despite available noninvasive diagnostic tools.This study aims to examine the usefulness of machine learning in predicting hemodynamically significant CAD using routine demographics, clinical factors, and laboratory data.Consecutive patients undergoing cardiac catheterization between March 17, 2015, and July 15, 2016, at UNC Chapel Hill were screened for comorbidities and CAD risk factors. In this pilot, single-center, prospective cohort study, patients were screened and selected for moderate CAD risk (n = 185). Invasive coronary angiography and CAD prediction with machine learning were independently performed. Results were blinded from operators and patients. Outcomes were followed up for up to 90 days for major adverse cardiovascular and renal events (MACREs). Greater than 70% stenosis or a fractional flow reserve less than or equal to 0.8 represented hemodynamically significant coronary disease. A random forest model using demographic, comorbidities, risk factors, and lab data was trained to predict CAD severity. The Random Forest Model predictive accuracy was assessed by area under the receiver operating characteristic curve with comparison to the final diagnoses made from coronary angiography.Hemodynamically significant CAD was predicted by 18-point clinical data input with a sensitivity of 81% ± 7.8%, and specificity of 61% ± 14.4% by the established model. The best machine learning model predicted a 90-day MACRE with specificity of 44.61% ± 14.39%, and sensitivity of 57.13% ± 18.70%.Machine learning models based on routine demographics, clinical factors, and lab data can be used to predict hemodynamically significant CAD with accuracy that approximates current noninvasive functional modalities.

In-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is higher in those with COVID-19 than in those without COVID-19. The factors that predispose to this mortality rate and their relative contribution are poorly understood. This study developed a risk score inclusive of clinical variables to predict in-hospital mortality in patients with COVID-19 and STEMI.Baseline demographic, clinical, and procedural data from patients in the North American COVID-19 Myocardial Infarction registry were extracted. Univariable logistic regression was performed using candidate predictor variables, and multivariable logistic regression was performed using backward stepwise selection to identify independent predictors of in-hospital mortality. Independent predictors were assigned a weighted integer, with the sum of the integers yielding the total risk score for each patient.In-hospital mortality occurred in 118 of 425 (28%) patients. Eight variables present at the time of STEMI diagnosis (respiratory rate of35 breaths/min, cardiogenic shock, oxygen saturation of93%, age of55 ​years, infiltrates on chest x-ray, kidney disease, diabetes, and dyspnea) were assigned a weighted integer. In-hospital mortality increased exponentially with increasing integer risk score (Cochran-Armitage χThe risk of in-hospital mortality in patients with COVID-19 and STEMI can be accurately predicted and discriminated using readily available clinical information.

Background We investigate whether deep learning (DL) neural networks can reduce erroneous human “judgment calls” on bedside echocardiograms and help distinguish Takotsubo syndrome (TTS) from anterior wall ST segment elevation myocardial infarction (STEMI). Methods We developed a single-channel (DCNN[2D SCI]), a multi-channel (DCNN[2D MCI]), and a 3-dimensional (DCNN[2D+t]) deep convolution neural network, and a recurrent neural network (RNN) based on 17,280 still-frame images and 540 videos from 2-dimensional echocardiograms in 10 years (1 January 2008 to 1 January 2018) retrospective cohort in University of Iowa (UI) and eight other medical centers. Echocardiograms from 450 UI patients were randomly divided into training and testing sets for internal training, testing, and model construction. Echocardiograms of 90 patients from the other medical centers were used for external validation to evaluate the model generalizability. A total of 49 board-certified human readers performed human-side classification on the same echocardiography dataset to compare the diagnostic performance and help data visualization. Findings The DCNN (2D SCI), DCNN (2D MCI), DCNN(2D+t), and RNN models established based on UI dataset for TTS versus STEMI prediction showed mean diagnostic accuracy 73%, 75%, 80%, and 75% respectively, and mean diagnostic accuracy of 74%, 74%, 77%, and 73%, respectively, on the external validation. DCNN(2D+t) (area under the curve [AUC] 0·787 vs. 0·699, P = 0·015) and RNN models (AUC 0·774 vs. 0·699, P = 0·033) outperformed human readers in differentiating TTS and STEMI by reducing human erroneous judgement calls on TTS. Interpretation Spatio-temporal hybrid DL neural networks reduce erroneous human “judgement calls” in distinguishing TTS from anterior wall STEMI based on bedside echocardiographic videos. Funding University of Iowa Obermann Center for Advanced Studies Interdisciplinary Research Grant, and Institute for Clinical and Translational Science Grant. National Institutes of Health Award (1R01EB025018–01).

BACKGROUND: Myocardial bridging (MB) is increasingly recognized to stimulate atherogenesis, which may contribute to an acute coronary syndrome. Stenting the coronary segment with MB has been recognized to have an increased risk of in-stent restenosis, stent fracture and coronary perforation. The safety and efficacy of stenting the culprit lesion with overlaying MB in ST elevation myocardial infarction (STEMI) as primary reperfusion therapy has not been established. CASE SUMMARY: We reported a patient who presented with inferior STEMI with a culprit lesion of an acute thrombotic occlusion in the right coronary artery and thrombolysis and thrombin inhibition in myocardial infarction 0 flow. After the stent placement during primary percutaneous coronary intervention, intravascular ultrasound revealed MB overlying the stented segment where heavy atherosclerotic plaque were present. Likely due to the combination of plaque herniation or prolapse caused by MB, as well as local increased inflammation and thrombogenicity, acute stent thrombosis occurred at this region, which led to acute stent failure. The patient required an emergent repeated cardiac catheterization and placing a second layer of stent to enhance the radial strength and reduce the inter-strut space. CONCLUSION: Plaque herniation or prolapse after stenting a MB segment in STEMI is a potential etiology for acute stent failure.

ST elevation myocardial infarction (STEMI) occurring in patients hospitalized for a noncardiac condition is associated with a high mortality rate and thus we sought to determine the mechanisms underlying STEMI in this patient population. This is a single center retrospective study of 70 patients who had STEMI while hospitalized on a noncardiac service and underwent coronary angiography. Thrombotic in-hospital STEMI was defined by angiographic or intravascular imaging evidence of intracoronary thrombus, plaque rupture, or stent thrombosis. Thirty-six (51%) inpatient STEMIs developed in the operating room or various postoperative stages and 6 (9%) after endoscopy or a percutaneous procedure. Thrombotic etiologies were found in 39 (56%) patients. Nonthrombotic etiologies included vasospasm, supply-demand mismatch, and takotsubo cardiomyopathy. Patients in the thrombotic group were more likely to have antiplatelet medications discontinued on admission, had higher peak troponin levels and were more likely to undergo percutaneous coronary intervention than patients in the nonthrombotic group. Exposure to vasopressors, time from ECG to angiography, post-STEMI ejection fraction, length of stay, and in-hospital mortality were similar in both groups. There was no difference in the use of percutaneous coronary intervention in patients but longer ECG to coronary angiography times and fivefold higher in-hospital mortality in thrombotic inpatient STEMI compared with 643 patients who presented with an out-of-hospital STEMI during the same time period. In conclusion, thrombotic and nonthrombotic mechanisms cause STEMI in hospitalized patients and are associated with a high mortality.

During the coronavirus disease 2019 (COVID-19) pandemic, more patients are presenting with complications late after acute myocardial infarction. We report the case of a 71-year-old man who delayed seeking medical care for 2 weeks, despite progressive shortness of breath, cough, and tactile fever, for fear of contracting COVID-19 in the hospital. Clinical and echocardiographic evaluation revealed a ventricular septal rupture secondary to acute myocardial infarction. The patient underwent urgent cardiac catheterization, followed by successful saphenous vein grafting to the left anterior descending coronary artery and open surgical repair of the ventricular septal rupture with a bovine pericardial patch. This case highlights a potential long-lasting negative effect that the COVID-19 pandemic will have on the care-seeking behavior and health of patients with acute cardiovascular disease.

We sought to test the hypothesis that patients undergoing ultrasound-assisted catheter-directed thrombolysis (USAT) with standard alteplase and heparin dosing would not develop significant depletion of systemic fibrinogen, which may account for the lower risk of bleeding seen in contemporary trials. We also sought to compare the relative outcomes of individuals with submassive pulmonary embolism (PE) undergoing USAT and anticoagulation alone.Utilizing a single-center prospective registry, we identified 102 consecutive adult patients with submassive PE who were considered for USAT based on a standardized treatment algorithm between November 2016 and May 2019. Patients not receiving USAT therapy were treated with anticoagulation alone.Baseline characteristics were generally similar between groups (n = 51 in each group). Major bleeding rates were not significantly different between groups (2.0% vs 5.9% in USAT vs control, respectively; P=.62). Notably, no USAT patient experienced clinically significant hypofibrinogenemia (mean trough fibrinogen, 369.8 ± 127.1 mg/dL; minimum, 187 mg/dL). The mean trough fibrinogen of patients experiencing any bleeding event (major or minor) was 306.6 mg/dL (SE, 23.9 mg/dL) vs 380.3 mg/dL (SE, 20.4 mg/dL) in those without a bleeding event (P=.02).In this cohort analysis of patients undergoing USAT, there was no evidence for clinically significant depletion of fibrinogen or intracranial hemorrhage. Although our data suggest an association between lower fibrinogen levels and bleeding events, our results are not clear enough to suggest a clinically useful fibrinogen cut-off value. Further study is needed to determine the utility of routine fibrinogen monitoring in this population.

Aims Shock index (SI), defined as the ratio of heart rate (HR) to systolic blood pressure (SBP), is easily obtained and predictive of mortality in patients with ST-segment elevation myocardial infarction. However, large-scale evaluations of SI in patients with non-ST-segment elevation myocardial infarction (NSTEMI) are lacking. Methods and results Hospitalizations for acute myocardial infarction were sampled from four US areas by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. Shock index was derived from the HR and SBP at first presentation and considered high when ≥0.7. From 2000 to 2014, 18 301 weighted hospitalizations for NSTEMI were sampled and had vitals successfully obtained. Of these, 5753 (31%) had high SI (≥0.7). Patients with high SI were more often female (46% vs. 39%) and had more prevalent chronic kidney disease (40% vs. 32%). TIMI (Thrombolysis in Myocardial Infarction) risk scores were similar between the groups (4.3 vs. 4.2), but GRACE (Global Registry of Acute Coronary Syndrome) score was higher with high SI (140 vs. 118). Angiography, revascularization, and guideline-directed medications were less often administered to patients with high SI, and the 28-day mortality was higher (13% vs. 5%). Prediction of 28-day mortality by SI as a continuous measurement [area under the curve (AUC): 0.68] was intermediate to that of the GRACE score (AUC: 0.87) and the TIMI score (AUC: 0.54). After adjustments, patients with high SI had twice the odds of 28-day mortality (odds ratio = 2.02; 95% confidence interval: 1.46–2.80). Conclusion The SI is easily obtainable, performs moderately well as a predictor of short-term mortality in patients hospitalized with NSTEMI, and may be useful for risk stratification in emergency settings.

Background There are limited data on the characteristics of 30‐day readmission after hospitalization with coronavirus disease 2019 (COVID‐19). Objectives To examine the rate, timing, causes, predictors and outcomes of 30‐day readmission after COVID‐19 hospitalization. Methods From 13 March to 9 April 2020, all patients hospitalized with COVID‐19 and discharged alive were included in this retrospective observational study. Multivariable logistic regression was used to identify the predictors of 30‐day readmission, and a restricted cubic spline function was utilized to assess the linearity of the association between continuous predictors and 30‐day readmission. Results A total of 1062 patients were included in the analysis, with a median follow‐up time of 62 days. The mean age of patients was 56.5 years, and 40.5% were women. At the end of the study, a total of 48 (4.5%) patients were readmitted within 30 days of discharge, and a median time to readmission was 5 days. The most common primary diagnosis of 30‐day readmission was a hypoxic respiratory failure (68.8%) followed by thromboembolism (12.5%) and sepsis (6.3%). The patients with a peak serum creatinine level of ≥1.29 mg/dL during the index hospitalization, compared to those with a creatinine of

Background Acute myocardial infarction (AMI) with in‐hospital onset (AMI‐IHO) has poor prognosis but is clinically underappreciated. Whether its occurrence has changed over time is uncertain. Methods and Results Since 1987, the ARIC (Atherosclerosis Risk in Communities) study has conducted adjudicated surveillance of AMI hospitalizations in 4 US communities. Our analysis was limited to patients aged 35 to 74 years with symptomatic AMI. Patients with symptoms initiating after hospital arrival were considered AMI‐IHO. A total of 26 678 weighted hospitalizations (14 276 unweighted hospitalizations) for symptomatic AMI were identified from 1995 to 2014, with 1137 (4%) classified as in‐hospital onset. The population incidence rate of AMI‐IHO increased in the 4 ARIC communities from 1995 through 2004 to 2005 through 2014 (12.7—16.9 events per 100 000 people; P for 20‐year trend P for 20‐year trend =0.03). The 10‐year proportions were stable for patients aged 35 to 64 years (3.0%–3.4%; P for 20‐year trend =0.3) but increased for patients aged ≥65 years (4.6%–7.8%; P for 20‐year trend =0.008; P for interaction by age group =0.04). AMI‐IHO had a more severe clinical course with lower use of AMI therapies or invasive strategies and higher in‐hospital (7% versus 3%), 28‐day (19% versus 5%), and 1‐year (29% versus 12%) mortality ( P< 0.0001 for all). Conclusions In this population‐based community surveillance, AMI‐IHO increased from 2005 to 2014, particularly among older patients. Quality initiatives to improve recognition and management of AMI‐IHO should be especially focused on hospitalized patients aged >65.

Background: Distinguishing Takotsubo syndrome (TTS) from acute anterior wall myocardial infarction is often difficult based on clinic characteristics, biomarkers, electrocardiograms and noninvasive images, leading to dilemmas regarding treatment decisions. The aim of this study was to determine whether deep learning (DL) neural networks can reduce erroneous human “judgment calls” on bedside echocardiograms and improve differential diagnostic accuracy. Methods: We developed deep convolution neural networks (DCNNs), including a single-channel (DCNN[2D SCI]), a multi-channel (DCNN[2D MCI]) and a 3-dimensional (DCNN[2D+t]) network, and a recurrent neural network (RNN) based on the same database consisting of 17,280 still-frame images and 540 videos from 2-dimensional (2D) echocardiograms in a 12-year retrospective cohort of 540 patients in the University of Iowa (UI) and eight other medical centers in the United States. The diagnosis of anterior wall ST segment elevation myocardial infarction (STEMI) and TTS were all confirmed by the coronary angiography. Echocardiograms from 450 UI patients were randomly divided into training and testing sets for internal training, testing, and model construction. Echocardiograms of 90 patients from the other medical centers were used for external validation to evaluate the model generalizability. A total of 49 board-certified human readers (22 cardiologists, 11 senior echocardiographers, and 8 point-of-care ultrasound-trained clinicians) performed human-side classification on the same echocardiography dataset to compare the diagnostic performance and help data visualization. Findings: The DCNN (2D SCI), DCNN (2D MCI), DCNN(2D+t), and RNN models established based on UI dataset for the control versus disease prediction showed mean diagnostic accuracy of 78%, 83%, 92%, and 81% respectively. The DCNN (2D SCI), DCNN (2D MCI), DCNN(2D+t), and RNN models established based on UI dataset for TTS versus STEMI prediction showed mean diagnostic accuracy 73%, 75%, 80%, and 75% respectively, and the mean diagnostic accuracy of 74%, 74%, 77%, and 73%, respectively, on the external validation. The area under the receiver operating characteristic curve (AUC) analysis showed that DCNN(2D+t) (0·787 vs. 0·699, P = 0·015) and RNN models (0·774 vs. 0·699, P = 0·033) consistently outperformed human readers in differentiating TTS and STEMI by reducing the erroneous judgement calls on TTS from human readers. Interpretation: Spatio-temporal hybrid DL neural networks reduce erroneous human “judgement calls” in distinguishing TTS from anterior wall STEMI based on bedside echocardiographic videos, demonstrating the potential of DL neural networks to support frontline triage and management of cardiovascular emergencies. Funding: University of Iowa Obermann Center for Advanced Studies Interdisciplinary Research Grant, and Institute for Clinical and Translational Science Grant. Declaration of Interest: We declare no competing interests. Ethical Approval: The research protocols and waiver of informed consent were approved by the human subjects committee of the UI institutional review board.

Introduction: Shock index (SI), defined as the ratio of heart rate (HR) to systolic blood pressure (SBP), is easily obtained and has been reported to predict all-cause mortality in acute myocardial infarction (AMI) hospitalizations, primarily among patients with STEMI. Large-scale investigations examining the prognostic value of SI in patients with NSTEMI are lacking. Methods: Hospitalizations for acute myocardial infarction were sampled from 4 US areas by the ARIC Study and classified by physician review. HR and SBP at first presentation were abstracted from the medical record. Pulseless patients, those with unobtainable SBP, and transfer patients were excluded. An SI value ≥0.7 was considered high. The TIMI risk score for NSTE-ACS was calculated using the established algorithm. Predictions of all-cause 28-day mortality were analyzed using receiver operating characteristics (ROC). Results: From 2000-2014, 18,301 weighted hospitalizations for NSTEMI patients were sampled and had vitals successfully obtained. Of these, 5753 (31%) had high SI (≥0.7). Patients with high SI were more often female (46% vs 39%) and older (65 vs 63 years), with more prevalent chronic kidney disease (40% vs. 32%), pneumonia (16% vs 8%), and complication by acute heart failure (42% vs 30%). However, the TIMI risk score was comparable for the 2 groups (4.3 vs. 4.2). Angiography (36% vs 58%), revascularization (19% vs 41%), and guideline-directed medications were less often administered to patients with high SI, and the 28-day mortality was nearly 3 times higher (13% vs 5%). Continuous values of SI were more predictive of 28-day mortality than the TIMI risk score, both overall (ROC-AUC: 0.68 vs 0.54; P P Conclusion: The SI outperformed the TIMI risk score for prediction of short-term mortality in patients hospitalized with NSTEMI, and may be useful for risk stratification in emergency settings.

ST-segment elevation (STE) in the lead aVR indicates global ischemia of the myocardium and is often associated with obstructive coronary artery disease (CAD). We report a serial of cases presenting with STE in aVR and diffuse ST depressions in more than six other leads as a common feature, but of different etiologies, i.e., severe anemia due to gastrointestinal bleeding; drug over-dose-induced vasospasm and tachycardia, and severe CAD involving distal left main and ostial right coronary arteries, which required specific management approaches. We categorize the possible causes of STE in aVR with or without diffuse ST depression ECG according to whether anticoagulation/antithrombotic agents are indicated, contra-indicated, and propose a systematic approach in evaluating and managing these patients.

Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder that essentially can affect any organ in the human body. The hallmark of the pathogenesis in TTP is the large von Willebrand factor multimers on platelet-mediated micro-thrombi formation, leading to microvascular thrombosis. Autopsy studies showed that cardiac arrest and myocardial infarction are the most common immediate causes of death in these patients. Clinical manifestations of cardiac involvement in TTP vary dramatically, from asymptomatic elevation of cardiac biomarkers, to heart failure, MI and sudden cardiac death. There is limited knowledge about optimal cardiac evaluation and management in patients with TTP. The absence of typical cardiac symptoms, combined with complicated multi-organ involvement in TTP, may contribute to the under-utilization of cardiac evaluation and treatment. Prompt diagnosis and timely initiation of effective therapy could be critically important in selected cases. Based on our experience and this review of the literature, we developed several recommendations for focused cardiac evaluation for patients with acute TTP: (1) patients with suspected or confirmed TTP should be screened for the potential presence of cardiac involvement with detailed history and physical, electrocardiogram and cardiac enzymes; (2) clinical deterioration of TTP patients warrants immediate cardiac reevaluation; (3) TTP patients with clinical evidence of cardiac involvement should be monitored for telemetry, cardiac biomarkers and evaluated with transthoracic echocardiography. These patients require urgent targeted TTP treatment as well as cardiac-specific treatment. Aspirin therapy is indicated for all TTP patients. Since epicardial coronary artery involvement is rare, cardiac catheterization is usually not required, given the high risk for hemorrhage and kidney injury; (4) we recommend evidence-based medical therapy for ischemic symptoms and heart failure. TTP patients with evidence of cardiac involvement would also benefit from routine cardiology follow up during remission.

Patients hospitalized for noncardiac conditions often experience increased levels of stress and hemodynamic challenges, making them susceptible to acute coronary events. The clinical features, management strategy, and outcomes of inpatient non-ST segment elevation myocardial infarction (NSTEMI) have not been described. This single-center retrospective study identified patients with inpatient NSTEMI from the University of North Carolina Hospitals discharge database in February 2008 to April 2014 using International Classification of Diseases, Ninth Revision (ICD-9) codes. This process generated an initial list of 485 cases that were subsequently manually reviewed. The associations of cardiac catheterization with in-hospital mortality and length of stay were analyzed using multivariable logistic regression and multiple linear regression. A total of 302 patients were confirmed to have inpatient NSTEMI, with 154 patients admitted to surgical and 148 admitted to nonsurgical services. The in-hospital mortality rate of patients with inpatient NSTEMI was high (19%). Patients with inpatient NSTEMI who underwent cardiac catheterization had lower in-hospital mortality rates than those who did not undergo cardiac catheterization (6% vs 25%; adjusted odds ratio 0.19, 95% confidence interval 0.07 to 0.50) and were discharged 6.8 days earlier (95% confidence interval 2.3 to 11.2 days). Inpatient NSTEMIs on surgical services compared with nonsurgical services were more likely to generate cardiology consultation (96% vs 62%, p 0.0001) and left heart catheterization (41% vs 24%, p = 0.002), with similar rates of revascularization (56% vs 56%, p = 1.0). In conclusion, both nonsurgical and surgical patients with inpatient NSTEMI who underwent invasive management had lower in-hospital mortality rates and shorter lengths of stay.

Effective removal or dissolution of large blood clots remains a challenge in clinical treatment of acute thrombo-occlusive diseases. Here we report the development of an intravascular microbubble-mediated sonothrombolysis device for improving thrombolytic rate and thus minimizing the required dose of thrombolytic drugs. We hypothesize that a sub-megahertz, forward-looking ultrasound transducer with an integrated microbubble injection tube is more advantageous for efficient thrombolysis by enhancing cavitation-induced microstreaming than the conventional high-frequency, side-looking, catheter-mounted transducers. We developed custom miniaturized transducers and demonstrated that these transducers are able to generate sufficient pressure to induce cavitation of lipid-shelled microbubble contrast agents. Our technology demonstrates a thrombolysis rate of 0.7 ± 0.15 percent mass loss/min in vitro without any use of thrombolytic drugs.

As a well-known medical imaging methodology, intravascular ultrasound (IVUS) imaging plays a critical role in diagnosis, treatment guidance and post-treatment assessment of coronary artery diseases. By cannulating a miniature ultrasound transducer mounted catheter into an artery, the vessel lumen opening, vessel wall morphology and other associated blood and vessel properties can be precisely assessed in IVUS imaging. Ultrasound transducer, as the key component of an IVUS system, is critical in determining the IVUS imaging performance. In recent years, a wide range of achievements in ultrasound transducers have been reported for IVUS imaging applications. Herein, a comprehensive review is given on recent advances in ultrasound transducers for IVUS imaging. Firstly, a fundamental understanding of IVUS imaging principle, evaluation parameters and IVUS catheter are summarized. Secondly, three different types of ultrasound transducers (piezoelectric ultrasound transducer, piezoelectric micromachined ultrasound transducer and capacitive micromachined ultrasound transducer) for IVUS imaging are presented. Particularly, the recent advances in piezoelectric ultrasound transducer for IVUS imaging are extensively examined according to their different working mechanisms, configurations and materials adopted. Thirdly, IVUS-based multimodality intravascular imaging of atherosclerotic plaque is discussed. Finally, summary and perspectives on the future studies are highlighted for IVUS imaging applications.

Objective To determine the ability of simple hemodynamic parameters obtained at the time of cardiac catheterization to predict in-hospital mortality following ST-elevation myocardial infarction (STEMI). Background Hemodynamic parameters measured at the time of primary percutaneous coronary intervention (PPCI) could potentially identify high-risk patients who would benefit from aggressive hemodynamic support in the Cardiac Catheterization laboratory. Methods This is a retrospective single-center study of 219 consecutive patients with STEMI. Left ventricular end-diastolic pressure (LVEDP), systolic blood pressure (SBP), and aortic diastolic blood pressure were obtained after successful revascularization. The prognostic ability of LVEDP, pulse pressure, and SBP/LVEDP ratio were compared to major mortality risk scores. Results Patients had a mean age of 60 ±14 years, were predominantly white (73%), male (64%), with anterior wall infarcts in 39%. Comorbidities included diabetes mellitus (27%), heart failure (9%), and chronic kidney disease (7%). In-hospital mortality was 9%. Patients with SBP/LVEDP ≤ 4 had increased risk of in-hospital death (32% vs. 5.3%, P 4. The area under curve (AUC) for SBP/LVEDP ratio for in-hospital mortality (0.69) was more predictive than LVEDP (0.61, P = 0.04) or pulse pressure (0.55, P = 0.02) but similar to Shock Index (ratio of heart rate to SBP) and Modified Shock Index (ratio of HR to mean arterial pressure). Conclusion An SBP/LVEDP ratio ≤ 4 identified a group of STEMI patients at high risk of in-hospital death. © 2017 Wiley Periodicals, Inc.

Timely reperfusion therapy reduces complications and improves survival in ST elevation myocardial infarction (STEMI). An effective chain of survival has been established for STEMIs occur in the community (outpatient STEMI). Recent studies have identified a subgroup of patients who develop STEMI while hospitalized for primary conditions, often not directly related to coronary artery disease (in-hospital STEMI or inpatient STEMI). This article summarizes current understanding of patient demographics, clinical characteristics, care delivery system and outcomes of in-hospital STEMI, comparing with outpatient STEMI. We also identified opportunities for quality improvement and proposed strategies and future directions to improve care for these patients.

Objectives Without early revascularization, both inpatient and outpatient STEMIs have poor outcomes. Reasons for denying PCI for STEMI, however, remain uncertain. This single-center retrospective cohort study compares factors and outcomes associated with ineligibility for PCI between inpatients and outpatients following ST-elevation myocardial infarction (STEMI). Methods A total of 1,759 STEMI patients between June 2009 and January 2015 were assessed. Individual medical records were reviewed to obtain reasons for PCI ineligibility for STEMI patients who did not receive reperfusion therapy. Results Compared to outpatients with STEMI (n = 1,688), inpatients (n = 71) were less likely to receive coronary angiography (60.6% vs 95.9%; P

Hyperphosphatemia, the elevated level of inorganic phosphate (Pi) in serum, is associated with increased cardiovascular morbidities and mortality. The effects of high Pi on endothelial cells are not well studied. This study investigated high Pi-induced endothelial cell apoptosis and the role of microRNA-21. Mouse myocardial endothelial cells (MEC) were cultured in normal (1 mM) and high (5 mM) Pi conditions. Apoptosis was detected by TUNEL staining and flow cytometry. MicroRNA profiles of MEC response to changes in Pi concentration were obtained using gene expression arrays. Expression levels of the microRNA-21 target genes, programmed cell death gene 4 ( PDCD4), poly(ADP-ribose) polymerase ( PARP), and phosphatase and tensin homolog ( PTEN), as well as NF-κB were measured by Western blotting and RT-PCR. MicroRNA-21-specific inhibitors and mimics were used to study effects of microRNA-21 on MEC apoptosis and gene expression regulations. High Pi induced MEC apoptosis and upregulated microRNA-21 expression. MicroRNA-21-specific mimics reproduced high Pi-induced apoptosis in normal Pi medium, and microRNA-21 inhibitors ameliorated the high Pi induction of apoptosis, suggesting that microRNA-21 mediated high Pi-induced MEC apoptosis. The microRNA-21 targets PDCD4, PTEN, PARP, and NF-κB were significantly downregulated in high Pi conditions. High Pi-induced downregulation of PDCD4 was abolished by microRNA-21 inhibitors and selective ERK inhibitor (selumetinib) and was reproduced by microRNA-21 mimics. Inhibitors and mimics of microRNA-21 did not have effects on high Pi-induced NF-κB downregulation. Selumetinib blocked high Pi-induced NF-κB downregulation. MicroRNA-21 mediates high Pi-induced endothelial cell apoptosis, which involves an ERK1/2/microRNA-21/PDCD4 pathway. High Pi-induced downregulation of NF-κB expression is mediated by an ERK1/2 signaling-dependent but microRNA-21-independent mechanism.

ST-segment elevation myocardial infarction (STEMI) is most commonly caused by an acute thrombotic occlusion of a coronary artery. For patients in whom the onset of STEMI occurs outside of hospital (outpatient STEMI), early reperfusion therapy with either fibrinolysis or primary percutaneous coronary intervention reduces complications and improves survival, compared with delayed reperfusion. STEMI systems of care are defined as integrated groups of separate entities focused on reperfusion therapy for STEMI, generally including emergency medical services, emergency medicine, cardiology, nursing, and hospital administration. These systems of care have been successful at reducing total ischaemia time and outpatient STEMI mortality. By contrast, much less is known about STEMI that occurs in hospitalized patients (inpatient STEMI), which has unique clinical features and much worse outcomes than outpatient STEMI. Inpatient STEMI is associated with older age, a higher female:male ratio, and more comorbidities than outpatient STEMI. Delays in diagnosis and infrequent use of reperfusion therapy probably also contribute to unfavourable outcomes for inpatient STEMI.

Research during cardiology fellowship is important for fellows-in-training, advancing knowledge on cardiovascular diseases and improving quality of patient care. However, the challenges are real and have been well outlined [(1,2)][1]. Individualized and systematic strategies to overcome these

Importance In-hospital ST-segment elevation myocardial infarction (STEMI) is a unique clinical entity with epidemiology, incidence, and outcomes distinct from that of out-of-hospital STEMI and has only within the past 10 years begun to receive increased attention and research. Patients with in-hospital STEMI are older, have more comorbidities, and more frequently have coagulopathies and contraindications for anticoagulation and fibrinolytic therapy. A standardized clinical definition of in-hospital STEMI is lacking. The objectives of this special communication are to (1) summarize the knowledge base regarding in-hospital STEMI; (2) review the challenges of diagnosis and treatment of patients with in-hospital STEMI; (3) present a standardized clinical definition for in-hospital STEMI; and (4) provide a quality improvement protocol to improve diagnosis, triage, and treatment of patients with in-hospital STEMI. Observations Patients with in-hospital STEMI less frequently present with typical angina symptoms, and an electrocardiogram is often obtained owing to changes in clinical status, changes on telemetry, or a finding of elevated cardiac biomarker. The frequent nontypical presentations often lead to substantial delays in the diagnosis of STEMI. Only 34% to 71% of patients with in-hospital STEMI undergo diagnostic catheterization, and only 22% to 56% undergo percutaneous coronary intervention. Even in contemporary reports, some studies report in-hospital mortality in the range of 31% to 42%. Three areas of delay in the treatment of patients with in-hospital STEMI that merit particular attention are (1) delays in electrocardiogram acquisition, (2) delays in electrocardiogram interpretation, and (3) delays in activation of existing STEMI systems of care. Conclusions and Relevance Treatment of patients with in-hospital STEMI is more complex and challenging than treatment of patients who develop out-of-hospital STEMI, leading to delays in diagnosis and triage and less frequent use of reperfusion therapy. Quality improvement programs targeted at decreasing delays and streamlining treatment of such patients may improve treatment and outcome.

Our goal was to measure the association of CXCL5 and molecular phenotypes associated with coronary atherosclerosis severity in patients at least 65 years old. CXCL5 is classically defined as a proinflammatory chemokine, but its role in chronic inflammatory diseases, such as coronary atherosclerosis, is not well defined. We enrolled individuals who were at least 65 years old and undergoing diagnostic cardiac catheterization. Coronary artery disease (CAD) severity was quantified in each subject via coronary angiography by calculating a CAD score. Circulating CXCL5 levels were measured from plasma, and both DNA genotyping and mRNA expression levels in peripheral blood mononuclear cells were quantified via microarray gene chips. We observed a negative association of CXCL5 levels with CAD at an odds ratio (OR) of 0.46 (95% CI, 0.27–0.75). Controlling for covariates, including sex, statin use, hypertension, hyperlipidemia, obesity, self-reported race, smoking, and diabetes, the OR was not significantly affected [OR, 0.54 (95% CI, 0.31–0.96)], consistent with a protective role for CXCL5 in coronary atherosclerosis. We also identified 18 genomic regions with expression quantitative trait loci of genes correlated with both CAD severity and circulating CXCL5 levels. Our clinical findings are consistent with the emerging link between chemokines and atherosclerosis and suggest new therapeutic targets for CAD.

Thrombotic thrombocytopenic purpura (TTP) affects essentially all organ systems. Myocardial injury in TTP is often attributed to microthrombi formation. We present the first case report in the literature of an acute TTP patient with concomitant obstructive coronary artery disease (CAD) and acute myocardial infarction who underwent successful percutaneous coronary intervention (PCI). A 70-year-old female patient who was diagnosed with acute TTP required plasma exchange. The patient also experienced episodes of angina pectoris, elevated cardiac enzymes and global ST segment depressions on ECG. A subsequent non-invasive ischaemia workup revealed significant ischaemia. Coronary angiography revealed obstructive CAD in her right coronary artery, requiring PCI with a bare metal stent placement and dual antiplatelet therapy. The patient tolerated antiplatelet therapy well. At 6 months of follow-up, she had no recurrent angina. This case highlights the potential co-existence of obstructive CAD and acute TTP requiring careful differential diagnosis and treatment.

Timely reperfusion therapy reduces complications and improves survival in ST elevation myocardial infarction (STEMI). An effective chain of survival has been established for STEMIs occur in the community (outpatient STEMI). Recent studies have identified a subgroup of patients who develop STEMI while hospitalized for primary conditions, often not directly related to coronary artery disease (in-hospital STEMI or inpatient STEMI). This article summarizes current understanding of patient demographics, clinical characteristics, care delivery system and outcomes of in-hospital STEMI, comparing with outpatient STEMI. We also identified opportunities for quality improvement and proposed strategies and future directions to improve care for these patients.

The treatment of pulmonary embolism (PE) is evolving and catheter-based therapies for intermediate risk PE have been shown to improve right ventricular function without increasing bleeding complications. We investigated the hemodynamic effects of conventional thrombolysis infusion catheter (IC-CDT)

Guidelines recommend that STEMI receiving facilities should have “a plan for triage and treatment of simultaneous presentation of STEMI patients”. However, there has not been discussions in the literature about the plan and its efficacy. We identified 6 pairs of simultaneous presentations(STEMI

Atrial fibrillation (AF) is the most common arrhythmia in patients with acute myocardial infarction (AMI) and is associated with additional morbidity and mortality. While AMI outcomes have significantly improved in recent decades, AF remains a significant comorbidity. We analyzed the impact of

Objective— Transplant-associated arteriosclerosis manifests as progressive vascular neointimal expansion throughout the arterial system of allografted solid organs, and eventually compromises graft perfusion and function. Allografts placed in colony stimulating factor (CSF)-1-deficient osteopetrotic ( Csf1 op /Csf1 op ) mice develop very little neointima, a finding attributed to impaired recipient macrophage function. We examined how CSF-1 affects neointima-derived vascular smooth muscle cells, tested the significance of CSF-1 expressed in donor tissue, and evaluated the contribution of secreted versus cell surface CSF-1 isoforms in transplant-associated arteriosclerosis. Methods and Results— CSF-1 activated specific signaling pathways to promote migration, survival, and proliferation of cultured vascular smooth muscle cells. Tumor necrosis factor-α addition increased CSF-1 and CSF-1 receptor expression, and tumor necrosis factor-α-driven proliferation was blocked by anti-CSF-1 antibody. In a mouse vascular allograft model, lack of recipient or donor CSF-1 impaired neointima formation; the latter suggests local CSF-1 function within the allograft. Moreover, reconstitution of donor or recipient cell surface CSF-1, without secreted CSF-1, restored neointimal formation. Conclusion— Vascular smooth muscle cells activation, including that mediated by tumor necrosis factor-α, can be driven in an autocrine/juxtacrine manner by CSF-1. These studies provide evidence for local function of CSF-1 in neointimal expansion, and identify CSF-1 signaling in vascular smooth muscle cells, particularly cell surface CSF-1 signaling, as a target for therapeutic strategies in transplant-associated arteriosclerosis.

To determine the ability of simple hemodynamic parameters obtained at the time of cardiac catheterization to predict in-hospital mortality following ST-elevation myocardial infarction (STEMI).Hemodynamic parameters measured at the time of primary percutaneous coronary intervention (PPCI) could potentially identify high-risk patients who would benefit from aggressive hemodynamic support in the Cardiac Catheterization laboratory.This is a retrospective single-center study of 219 consecutive patients with STEMI. Left ventricular end-diastolic pressure (LVEDP), systolic blood pressure (SBP), and aortic diastolic blood pressure were obtained after successful revascularization. The prognostic ability of LVEDP, pulse pressure, and SBP/LVEDP ratio were compared to major mortality risk scores.Patients had a mean age of 60 ±14 years, were predominantly white (73%), male (64%), with anterior wall infarcts in 39%. Comorbidities included diabetes mellitus (27%), heart failure (9%), and chronic kidney disease (7%). In-hospital mortality was 9%. Patients with SBP/LVEDP ≤ 4 had increased risk of in-hospital death (32% vs. 5.3%, P 0.0001), intra-aortic balloon pump (IABP) usage (51.6% vs. 9.6%, P 0.0001) and combined endpoint of death or IABP usage (58.1% vs. 13.3%, P 0.0001) compared to patients with SBP/LVEDP 4. The area under curve (AUC) for SBP/LVEDP ratio for in-hospital mortality (0.69) was more predictive than LVEDP (0.61, P = 0.04) or pulse pressure (0.55, P = 0.02) but similar to Shock Index (ratio of heart rate to SBP) and Modified Shock Index (ratio of HR to mean arterial pressure).An SBP/LVEDP ratio ≤ 4 identified a group of STEMI patients at high risk of in-hospital death. © 2017 Wiley Periodicals, Inc.

A laser-generated-focused ultrasound (LGFU) transducer generates high-pressure (up to 20 MPa), high-frequency (>10 MHz) shock waves with a tight focal spot. In this work, we aim to demonstrate the feasibility of using LGFU transducers for sonothrombolysis in vitro. A carbon black LGFU transducer was designed, fabricated and characterized. The prototyped LGFU was applied with in-vitro thrombolysis tests involving microbubble contrast agent (MCA). A conventional piezo ultrasound transducer was used as a secondary excitation source to enhance the cavitation effect by dual-frequency excitation. The in vitro test results showed that microbubble-mediated LGFU treatment can yield the lytic rate of approximately 2 mg/min, suggesting that LGFU transducers may be useful in precision high lytic rate sonothrombolysis.

Without early revascularization, both inpatient and outpatient STEMIs have poor outcomes. Reasons for denying PCI for STEMI, however, remain uncertain. This single-center retrospective cohort study compares factors and outcomes associated with ineligibility for PCI between inpatients and outpatients following ST-elevation myocardial infarction (STEMI).A total of 1,759 STEMI patients between June 2009 and January 2015 were assessed. Individual medical records were reviewed to obtain reasons for PCI ineligibility for STEMI patients who did not receive reperfusion therapy.Compared to outpatients with STEMI (n = 1,688), inpatients (n = 71) were less likely to receive coronary angiography (60.6% vs 95.9%; P 0.001) or PCI (50.7% vs 80.9%; P 0.001), with longer ECG/door to first device activation times (97 [78, 131] vs 63 [49, 78] minutes; P 0.001). When coronary angiography was performed, however, similar rates of PCI and procedural success were seen in both groups. Principal contraindication for PCI was risk of bleeding within the inpatient population and complex coronary artery disease within the outpatient population. Total in-hospital mortality was higher in inpatient STEMIs compared to outpatients (42.2% vs 10.0%; P 0.001), but lower for patients eligible for PCI in both groups.Reasons for PCI ineligibility differ between inpatient and outpatient STEMIs. Inpatients have increased risks of bleeding, lower coronary angiography and PCI use, and higher in-hospital mortality. Especially for inpatients, specific PCI STEMI protocols that anticipate and overcome types of ineligibility and delay for cardiac catheterization may improve outcomes.