Cardiology Commons^™

Proteogenomics Of Hypertrophic Cardiomyopathy Reveals Subtype-Specific Therapy, Ke Ma, Jie Yang, Hongchang Guo, Ping Li, Xiaowei Li, Zhujun Dong, Jing Zhang, Congcong Zhang, Pengli Yang, Chongpei Hua, Shuolin Zhu, Guoqing Li, Jianchao Zhang, Ningyu Ding, Jizheng Wang, Xin-Liang Ma, Zhuofeng Lin, Jianzeng Dong, Yang Li, Yulin Li

Department of Emergency Medicine Faculty Papers

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease with diverse prognosis. The underlying mechanisms remain unknown, resulting in limited risk stratification and therapeutic strategies. This study aimed to elucidate molecular subtypes of HCM through integrated proteogenomic analysis and explore subtype-specific therapeutic strategies.

METHODS: We conducted an integrated proteogenomic analysis of 132 patients with HCM using myocardial samples, incorporating whole-exome sequencing, RNA sequencing, and proteomics. Unsupervised clustering was used to identify HCM subtypes, which were validated in heart tissues and human induced pluripotent stem cell-derived cardiomyocytes from 2 independent HCM subsets. Subtype-specific signatures and pathways were explored, and their causal link …

Cardiomyocyte-Derived Small Extracellular Vesicle: A New Mechanism Driving Diabetic Cardiac Fibrosis And Cardiomyopathy, Yu Li, Yunhui Du, Yang Liu, Xiuhuan Chen, Xinxin Li, Yanru Duan, Yanwen Qin, Huirong Liu, Xinliang Ma, Shaoping Nie, Huina Zhang

Department of Emergency Medicine Faculty Papers

Rationale: Diabetic cardiomyopathy is one of the major diabetic cardiovascular complications in which fibrosis plays a critical pathogenetic role. However, the precise mechanisms by which diabetes triggers cardiac fibrosis in the heart remain elusive. Small extracellular vesicles (sEVs) play an important role in the cellular communication. Nevertheless, whether and how diabetes may adversely alter sEVs-mediated cardiomyocyte-fibroblast communication, promoting diabetic cardiac fibrosis and contributing to diabetic cardiomyopathy, has not been previously investigated. Methods and results: High-fat diet (HFD)-induced and genetic (db/db) type 2 diabetic models were utilized. Cardiomyocyte sEVs (Myo-sEVs) were isolated by ultracentrifugation. Normal cardiomyocyte-derived Myo-sEVs attenuated diabetic cardiac fibrosis …

A Chinese Scoring System For Predicting Successful Retrograde Collateral Traverse In Patients With Chronic Total Coronary Occlusion, Qiu Yu Li, Xiao Long Lin, Fan Qi Li, Zi Chao Cheng, Jia Yu Tian, Dong Hui Zhao, Wayne Bond Lau, Jing Hua Liu, Qian Fan

Department of Emergency Medicine Faculty Papers

BACKGROUND: Retrograde approach technique has been challenging in percutaneous coronary interventional treatment of chronic total occlusion (CTO) coronary disease. The present study endeavors to determine a novel Chinese scoring system for predicting successful collateral channels traverse via retrograde approach.

METHODS: The demographic characteristics and angiographic characteristics of 309 CTO patient were analyzed by univariable and multivariable analysis for selecting potential predictors. And the nomogram was used to establish the scoring system. Then it was evaluated by the internal and external validation.

RESULTS: The predictors of Age, Connections between collateral channels and recipient vessels, and Channel Tortuosity (ACT) were identified with …

Utility Of S100a12 As An Early Biomarker In Patients With St-Segment Elevation Myocardial Infarction, Xiaolin Zhang, Minghui Cheng, Naijing Gao, Yi Li, Chenghui Yan, Xiaoxiang Tian, Dan Liu, Miaohan Qiu, Xiaozeng Wang, Bo Luan, Jie Deng, Shouli Wang, Hongyan Tian, Geng Wang, Xin-Liang Ma, Gregg W Stone, Yaling Han

Department of Emergency Medicine Faculty Papers

Importance: S100A12 is a calcium binding protein which is involved in inflammation and progression of atherosclerosis.

Objective: We sought to investigate the utility of S100A12 as a biomarker for the early diagnosis and prognostication of patients presenting with ST-segment elevation myocardial infarction (STEMI).

Design, Setting, and Participants: S100A12 was measured in 1023 patients presenting to the emergency department with acute chest pain between June 2012 and November 2015. An independent cohort of 398 patients enrolled at 3 different hospitals served as a validation cohort.

Main Outcomes and Measures: The primary clinical endpoint of interest was major adverse cardiac and cerebral …

Implications Of C1q/Tnf-Related Protein Superfamily In Patients With Coronary Artery Disease., Yanwei Zhang, Caihong Liu, Jing Liu, Rui Guo, Zheyi Yan, Wenxia Liu, Wayne Bond Lau, Xiangying Jiao, Jimin Cao, Kun Xu, Yongping Jia, Xin-Liang Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

The C1q complement/TNF-related protein superfamily (CTRPs) displays differential effects on the regulation of metabolic homeostasis, governing cardiovascular function. However, whether and how they may serve as predictor/pro-diagnosis factors for assessing the risks of coronary artery disease (CAD) remains controversial. Therefore, we performed a clinical study to elaborate on the implication of CTRPs (CTRP1, CTRP5, CTRP7, and CTRP15) in CAD. CTRP1 were significantly increased, whereas CTRP7 and CTRP15 levels were decreased in CAD patients compared to the non-CAD group. Significant differences in CTRP1 levels were discovered between the single- and triple-vascular-vessel lesion groups. ROC analysis revealed that CTRP7 and CTRP15 may …

Sevoflurane Pre-Conditioning Ameliorates Diabetic Myocardial Ischemia/Reperfusion Injury Via Differential Regulation Of P38 And Erk., Dina Xie, Jianli Zhao, Rui Guo, Liyuan Jiao, Yanqing Zhang, Wayne Bond Lau, Bernard Lopez, Theodore Christopher, Erhe Gao, Jimin Cao, Xin-Liang Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

Diabetes mellitus (DM) significantly increases myocardial ischemia/reperfusion (MI/R) injury. During DM, cardioprotection induced by conventional pre-conditioning (PreCon) is decreased due to impaired AMP-activated protein kinase (AMPK) signaling. The current study investigated whether PreCon with inhaled anesthetic sevoflurane (SF-PreCon) remains cardioprotective during DM, and identified the involved mechanisms. Normal diet (ND) and high-fat diet (HFD)-induced DM mice were randomized into control and SF-PreCon (3 cycles of 15-minute period exposures to 2% sevoflurane) groups before MI/R. SF-PreCon markedly reduced MI/R injury in DM mice, as evidenced by improved cardiac function (increased LVEF and ±Dp/dt), decreased infarct size, and decreased apoptosis. To determine …

Heat Shock Factor 1-Mediated Transcription Activation Of Omi/Htra2 Induces Myocardial Mitochondrial Apoptosis In The Aging Heart., Dan Liu, Linguo Wu, Ye Wu, Xin Wei, Wen Wang, Suli Zhang, Ming Yi, Jing Li, Huirong Liu, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

BACKGROUND: Increased cardiac apoptosis is a hallmark of the elderly, which in turn increases the risk for developing cardiac disease. The overexpression of Omi/HtrA2 mRNA and protein contributes to apoptosis in the aged heart. Heat shock factor 1 (HSF1) is a transcription factor that binds to the promoter of Omi/HtrA2 in the aging myocardium. However, whether HSF1 participates in cardiomyocyte apoptosis via transcriptional regulation of Omi/HtrA2 remains unclear. The present study was designed to investigate whether HSF1 plays a role in Omi/HtrA2 transcriptional regulation and myocardial apoptosis.

METHODS AND RESULTS: Assessment of the hearts of mice of different ages was …

Antibody-Based Ticagrelor Reversal Agent In Healthy Volunteers., Deepak L. Bhatt, Charles V. Pollack, Jeffrey I. Weitz, Lisa K. Jennings, Sherry Xu, Susan E. Arnold, Bret R. Umstead, Michael C. Mays, John S. Lee

Department of Emergency Medicine Faculty Papers

BACKGROUND: Ticagrelor is an oral P2Y₁₂ inhibitor that is used with aspirin to reduce the risk of ischemic events among patients with acute coronary syndromes or previous myocardial infarction. Spontaneous major bleeding and bleeding associated with urgent invasive procedures are concerns with ticagrelor, as with other antiplatelet drugs. The antiplatelet effects of ticagrelor cannot be reversed with platelet transfusion. A rapid-acting reversal agent would be useful.

METHODS: In this randomized, double-blind, placebo-controlled, phase 1 trial, we evaluated intravenous PB2452, a monoclonal antibody fragment that binds ticagrelor with high affinity, as a ticagrelor reversal agent. We assessed platelet function in …

Patients With Refractory Out-Of-Cardiac Arrest And Sustained Ventricular Fibrillation As Candidates For Extracorporeal Cardiopulmonary Resuscitation - Prospective Multi-Center Observational Study., Takahiro Nakashima, Teruo Noguchi, Yoshio Tahara, Kunihiro Nishimura, Soshiro Ogata, Satoshi Yasuda, Daisuke Onozuka, Naoto Morimura, Ken Nagao, David F. Gaieski, Yasufumi Asai, Hiroyuki Yokota, Satoshi Nara, Mamoru Hase, Takahiro Atsumi, Tetsuya Sakamoto

Department of Emergency Medicine Faculty Papers

BACKGROUND: We investigated whether patients with out-of-hospital cardiac arrest (OHCA) and sustained ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) or conversion to pulseless electrical activity/asystole (PEA/asystole) benefit more from extracorporeal cardiopulmonary resuscitation (ECPR). Methods and Results: We analyzed data from the Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan, which was a prospective, multicenter, observational study with 22 institutions in the ECPR group and 17 institutions in the conventional CPR (CCPR) group. Patients were divided into 4 groups by cardiac rhythm and CPR group. The primary endpoint was favorable neurological outcome, defined as Cerebral Performance Category 1 …

Coronary Angiography After Cardiac Arrest - The Right Timing Or The Right Patients?, Benjamin S. Abella, David F. Gaieski

Department of Emergency Medicine Faculty Papers

No abstract provided.

Myocardial Dysfunction After Out-Of-Hospital Cardiac Arrest: Predictors And Prognostic Implications., Yuan Yao, Nicholas James Johnson, Sarah Muirhead Perman, Vimal Ramjee, Anne Victoria Grossestreuer, David Foster Gaieski

Department of Emergency Medicine Faculty Papers

We aim to determine the incidence of early myocardial dysfunction after out-of-hospital cardiac arrest, risk factors associated with its development, and association with outcome. A retrospective chart review was performed among consecutive out-of-hospital cardiac arrest (OHCA) patients who underwent echocardiography within 24 h of return of spontaneous circulation at three urban teaching hospitals. Our primary outcome is early myocardial dysfunction, defined as a left ventricular ejection fraction < 40% on initial echocardiogram. We also determine risk factors associated with myocardial dysfunction using multivariate analysis, and examine its association with survival and neurologic outcome. A total of 190 patients achieved ROSC and underwent echocardiography within 24 h. Of these, 83 (44%) patients had myocardial dysfunction. A total of 37 (45%) patients with myocardial dysfunction survived to discharge, 39% with intact neurologic status. History of congestive heart failure (OR 6.21; 95% CI 2.54-15.19), male gender (OR 2.27; 95% CI 1.08-4.78), witnessed arrest (OR 4.20; 95% CI 1.78-9.93), more than three doses of epinephrine (OR 6.10; 95% CI 1.12-33.14), more than four defibrillations (OR 4.7; 95% CI 1.35-16.43), longer duration of resuscitation (OR 1.06; 95% CI 1.01-1.10), and therapeutic hypothermia (OR 3.93; 95% CI 1.32-11.75) were associated with myocardial dysfunction. Cardiopulmonary resuscitation immediately initiated by healthcare personnel was associated with lower odds of myocardial dysfunction (OR 0.40; 95% CI 0.17-0.97). There was no association between early myocardial dysfunction and mortality or neurological outcome. Nearly half of OHCA patients have myocardial dysfunction. A number of clinical factors are associated with myocardial dysfunction, and may aid providers in anticipating which patients need early diagnostic evaluation and specific treatments. Early myocardial dysfunction is not associated with neurologically intact survival.

Cardiac-Derived Ctrp9 Protects Against Myocardial Ischemia/Reperfusion Injury Via Calreticulin-Dependent Inhibition Of Apoptosis., Dajun Zhao, Pan Feng, Yang Sun, Zhigang Qin, Zhengbin Zhang, Yanzhen Tan, Erhe Gao, Wayne Bond Lau, Xin-Liang Ma, Jian Yang, Shiqiang Yu, Xuezeng Xu, Dinghua Yi, Wei Yi

Department of Emergency Medicine Faculty Papers

Cardiokines play an essential role in maintaining normal cardiac functions and responding to acute myocardial injury. Studies have demonstrated the heart itself is a significant source of C1q/TNF-related protein 9 (CTRP9). However, the biological role of cardiac-derived CTRP9 remains unclear. We hypothesize cardiac-derived CTRP9 responds to acute myocardial ischemia/reperfusion (MI/R) injury as a cardiokine. We explored the role of cardiac-derived CTRP9 in MI/R injury via genetic manipulation and a CTRP9-knockout (CTRP9-KO) animal model. Inhibition of cardiac CTRP9 exacerbated, whereas its overexpression ameliorated, left ventricular dysfunction and myocardial apoptosis. Endothelial CTRP9 expression was unchanged while cardiomyocyte CTRP9 levels decreased after simulated …

Variability Of Extracorporeal Cardiopulmonary Resuscitation Utilization For Refractory Adult Out-Of-Hospital Cardiac Arrest: An International Survey Study., Patrick J. Coppler, Benjamin S. Abella, Clifton W. Callaway, Minjung Kathy Chae, Seung Pill Choi, Jonathan Elmer, Won Young Kim, Young-Min Kim, Michael Kurz, Joo Suk Oh, Joshua C. Reynolds, Jon C. Rittenberger, Kelly N. Sawyer, Chun Song Youn, Byung Kook Lee, David F. Gaieski

Department of Emergency Medicine Faculty Papers

Objective: A growing interest in extracorporeal cardiopulmonary resuscitation (ECPR) as a rescue strategy for refractory adult out-of-hospital cardiac arrest (OHCA) currently exists. This study aims to determine current standards of care and practice variation for ECPR patients in the USA and Korea.

Methods: In December 2015, we surveyed centers from the Korean Hypothermia Network (KORHN) Investigators and the US National Post-Arrest Research Consortium (NPARC) on current targeted temperature management and ECPR practices. This project analyzes the subsection of questions addressing ECPR practices. We summarized survey.

Results: Overall, 9 KORHN and 4 NPARC centers reported having ECPR programs and had complete …

Validation Of An Icd Code For Accurately Identifying Emergency Department Patients Who Suffer An Out-Of-Hospital Cardiac Arrest., Shelby K. Shelton, Steve B. Chukwulebe, David F. Gaieski, Benjamin S. Abella, Brendan G. Carr, Sarah M. Perman

Department of Emergency Medicine Faculty Papers

AIM: International classification of disease (ICD-9) code 427.5 (cardiac arrest) is utilized to identify cohorts of patients who suffer out-of-hospital cardiac arrest (OHCA), though the use of ICD codes for this purpose has never been formally validated. We sought to validate the utility of ICD-9 code 427.5 by identifying patients admitted from the emergency department (ED) after OHCA.

METHODS: Adult visits to a single ED between January 2007 and July 2012 were retrospectively examined and a keyword search of the electronic medical record (EMR) was used to identify patients. Cardiac arrest was confirmed; and ICD-9 information and location of return …

Cardiac Arrest Risk Standardization Using Administrative Data Compared To Registry Data., Anne V. Grossestreuer, David F. Gaieski, Michael W. Donnino, Joshua I.M. Nelson, Eric L. Mutter, Brendan G. Carr, Benjamin S. Abella, Douglas J. Wiebe

Department of Emergency Medicine Faculty Papers

BACKGROUND: Methods for comparing hospitals regarding cardiac arrest (CA) outcomes, vital for improving resuscitation performance, rely on data collected by cardiac arrest registries. However, most CA patients are treated at hospitals that do not participate in such registries. This study aimed to determine whether CA risk standardization modeling based on administrative data could perform as well as that based on registry data.

METHODS AND RESULTS: Two risk standardization logistic regression models were developed using 2453 patients treated from 2000-2015 at three hospitals in an academic health system. Registry and administrative data were accessed for all patients. The outcome was death …

Shared Decision Making In Patients With Low Risk Chest Pain: Prospective Randomized Pragmatic Trial., Erik P. Hess, Judd E. Hollander, Jason T. Schaffer, Jeffrey A. Kline, Carlos A. Torres, Deborah B. Diercks, Russell Jones, Kelly P. Owen, Zachary F. Meisel, Michel Demers, Annie Leblanc, Nilay D. Shah, Jonathan Inselman, Jeph Herrin, Ana Castaneda-Guarderas, Victor M. Montori

Department of Emergency Medicine Faculty Papers

OBJECTIVE: To compare the effectiveness of shared decision making with usual care in choice of admission for observation and further cardiac testing or for referral for outpatient evaluation in patients with possible acute coronary syndrome.

DESIGN: Multicenter pragmatic parallel randomized controlled trial.

SETTING: Six emergency departments in the United States.

PARTICIPANTS: 898 adults (aged >17 years) with a primary complaint of chest pain who were being considered for admission to an observation unit for cardiac testing (451 were allocated to the decision aid and 447 to usual care), and 361 emergency clinicians (emergency physicians, nurse practitioners, and physician assistants) caring …

The Association Between Hemoglobin Concentration And Neurologic Outcome After Cardiac Arrest., Nicholas J. Johnson, Babette Rosselot, Sarah M. Perman, Kalani Dodampahala, Munish Goyal, David F. Gaieski, Anne V. Grossestreuer

Department of Emergency Medicine Faculty Papers

PURPOSE: The purpose of the study is to determine the association between hemoglobin concentration (Hgb) and neurologic outcome in postarrest patients.

METHODS: We conducted a retrospective cohort study using the Penn Alliance for Therapeutic Hypothermia (PATH) cardiac arrest registry. Inclusion criteria were resuscitated cardiac arrest (inhospital or out of hospital) and an Hgb value recorded within 24 hours of return of spontaneous circulation. The primary outcome was favorable neurologic status at hospital discharge. Survival to hospital discharge was a secondary outcome.

RESULTS: There were 598 eligible patients from 21 hospitals. Patients with favorable neurologic outcome had significantly higher median Hgb …

Branched Chain Amino Acids Cause Liver Injury In Obese/Diabetic Mice By Promoting Adipocyte Lipolysis And Inhibiting Hepatic Autophagy., Fuyang Zhang, Shihao Zhao, Wenjun Yan, Yunlong Xia, Xiyao Chen, Wei Wang, Jinglong Zhang, Chao Gao, Cheng Peng, Feng Yan, Huishou Zhao, Kun Lian, Yan Lee, Ling Zhang, Wayne Bond Lau, Xin-Liang Ma, Ling Tao

Department of Emergency Medicine Faculty Papers

The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD) upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake) reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury. The mechanisms responsible for this quandary remain unknown; the role of BCAA in HF-induced liver injury is unclear. Utilizing HFD or …

Can A Point-Of-Care Troponin I Assay Be As Good As A Central Laboratory Assay? A Midas Investigation., W. Frank Peacock, Deborah Diercks, Robert Birkhahn, Adam J. Singer, Judd Hollander, Richard Nowak, Basmah Safdar, Chadwick D. Miller, Mary Peberdy, Francis Counselman, Abhinav Chandra, Joshua Kosowsky, James Neuenschwander, Jon Schrock, Elizabeth Lee-Lewandrowski, William Arnold, John Nagurney

Department of Emergency Medicine Faculty Papers

BACKGROUND: We aimed to compare the diagnostic accuracy of the Alere Triage Cardio3 Tropinin I (TnI) assay (Alere, Inc., USA) and the PathFast cTnI-II (Mitsubishi Chemical Medience Corporation, Japan) against the central laboratory assay Singulex Erenna TnI assay (Singulex, USA).

METHODS: Using the Markers in the Diagnosis of Acute Coronary Syndromes (MIDAS) study population, we evaluated the ability of three different assays to identify patients with acute myocardial infarction (AMI). The MIDAS dataset, described elsewhere, is a prospective multicenter dataset of emergency department (ED) patients with suspected acute coronary syndrome (ACS) and a planned objective myocardial perfusion evaluation. Myocardial infarction …

Right Ventricular Dysfunction After Resuscitation Predicts Poor Outcomes In Cardiac Arrest Patients Independent Of Left Ventricular Function., Vimal Ramjee, Anne V. Grossestreuer, Yuan Yao, Sarah M. Perman, Marion Leary, James N. Kirkpatrick, Paul R. Forfia, Daniel M. Kolansky, Benjamin S. Abella, David F. Gaieski

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Determination of clinical outcomes following resuscitation from cardiac arrest remains elusive in the immediate post-arrest period. Echocardiographic assessment shortly after resuscitation has largely focused on left ventricular (LV) function. We aimed to determine whether post-arrest right ventricular (RV) dysfunction predicts worse survival and poor neurologic outcome in cardiac arrest patients, independent of LV dysfunction.

METHODS: A single-center, retrospective cohort study at a tertiary care university hospital participating in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000 and 2012.

PATIENTS: 291 in- and out-of-hospital adult cardiac arrest patients at the University of Pennsylvania who had return of spontaneous …

Racial Disparities In Intravenous Recombinant Tissue Plasminogen Activator Use Persist At Primary Stroke Centers., Hugo J. Aparicio, Brendan G. Carr, Scott E. Kasner, Michael J. Kallan, Karen C. Albright, Dawn O. Kleindorfer, Michael T. Mullen

Department of Emergency Medicine Faculty Papers

BACKGROUND: Primary stroke centers (PSCs) utilize more recombinant tissue plasminogen activator (rt-PA) than non-PSCs. The impact of PSCs on racial disparities in rt-PA use is unknown.

METHODS AND RESULTS: We used data from the Nationwide Inpatient Sample from 2004 to 2010, limited to states that publicly reported hospital identity and race. Hospitals certified as PSCs by The Joint Commission were identified. Adults with a diagnosis of ischemic stroke were analyzed. Rt-PA use was defined by the International Classification of Diseases, 9th Revision procedure code 99.10. Discharges (304 152 patients) from 26 states met eligibility criteria, and of these 71.5% were …

Advanced Glycation End Products Accelerate Ischemia/Reperfusion Injury Through Receptor Of Advanced End Product/Nitrative Thioredoxin Inactivation In Cardiac Microvascular Endothelial Cells., Yi Liu, Yanzhuo Ma, Rutao Wang, Chenhai Xia, Rongqing Zhang, Kun Lian, Ronghua Luan, Lu Sun, Lu Yang, Wayne B Lau, Haichang Wang, Ling Tao

Department of Emergency Medicine Faculty Papers

The advanced glycation end products (AGEs) are associated with increased cardiac endothelial injury. However, no causative link has been established between increased AGEs and enhanced endothelial injury after ischemia/reperfusion. More importantly, the molecular mechanisms by which AGEs may increase endothelial injury remain unknown. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and incubated with AGE-modified bovine serum albumin (BSA) or BSA. After AGE-BSA or BSA preculture, CMECs were subjected to simulated ischemia (SI)/reperfusion (R). AGE-BSA increased SI/R injury as evidenced by enhanced lactate dehydrogenase release and caspase-3 activity. Moreover, AGE-BSA significantly increased SI/R-induced oxidative/nitrative stress in CMECs (as measured …