Cardiovascular Diseases Commons^™

An Improved Reporter Identifies Ruxolitinib As A Potent And Cardioprotective Camkii Inhibitor, Oscar E Reyes Gaido, Nikoleta Pavlaki, Jonathan M Granger, Olurotimi O Mesubi, Bian Liu, Brian L Lin, Alan Long, David Walker, Joshua Mayourian, Kate L Schole, Chantelle E Terrillion, Lubika J Nkashama, Mohit M Hulsurkar, Lauren E Dorn, Kimberly M Ferrero, Richard L Huganir, Frank U Müller, Xander H T Wehrens, Jun O Liu, Elizabeth D Luczak, Vassilios J Bezzerides, Mark E Anderson

Faculty, Staff and Students Publications

Ca2+/calmodulin-dependent protein kinase II (CaMKII) hyperactivity causes cardiac arrhythmias, a major source of morbidity and mortality worldwide. Despite proven benefits of CaMKII inhibition in numerous preclinical models of heart disease, translation of CaMKII antagonists into humans has been stymied by low potency, toxicity, and an enduring concern for adverse effects on cognition due to an established role of CaMKII in learning and memory. To address these challenges, we asked whether any clinically approved drugs, developed for other purposes, were potent CaMKII inhibitors. For this, we engineered an improved fluorescent reporter, CaMKAR (CaMKII activity reporter), which features superior sensitivity, kinetics, and …

Troponin In Acute Chest Pain To Risk Stratify And Guide Effective Use Of Computed Tomography Coronary Angiography (Target-Ctca): A Randomised Controlled Trial, Kuan Ken Lee, David Lowe, Rachel O'Brien, Ryan Wereski, Anda Bularga, Caelan Taggart, Matthew T H Lowry, Amy V Ferry, Michelle C Williams, Giles Roditi, John Byrne, Chris Tuck, Denise Cranley, Praveen Thokala, Steve Goodacre, Catriona Keerie, John Norrie, David E Newby, Alasdair J Gray, Nicholas L Mills

Faculty, Staff and Student Publications

BACKGROUND: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death.

METHODS: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. …

Esophageal Lesion Reveals An Aortic Pseudoaneurysm In The Setting Of Actinomyces Odontolyticus Bacteremia, Anneliese Grewing, Harsha Jujjavarapu, Cameron Price, Lindsay F Eilers, Sloane Zimmerman, Nahid Hiermandi, Athar M Qureshi, Richard Kellermayer, Jolie J Britt

Faculty, Staff and Students Publications

A toddler presented with hematemesis a few weeks after ingesting a penny. Workup revealed an esophageal lesion communicating with an aortic pseudoaneurysm in the setting of Actinomyces odontolyticus bacteremia. A. odontolytica is an oropharyngeal bacteria known to cause fistulas when introduced into tissue planes. (Level of Difficulty: Intermediate.)

Pediatric Swine Model Of Methicillin-Resistant Staphylococcus Aureus Sepsis-Induced Coagulopathy, Disseminated Microvascular Thrombosis, And Organ Injuries, Trung C Nguyen, Juan C Marini, Bobby Guillory, Christian Valladolid-Brown, Marina Martinez-Vargas, Deepika Subramanyam, Daniel Cohen, Sonya C Cirlos, Fong Lam, Barbara Stoll, Inka C Didelija, Caitlin Vonderohe, Renan Orellana, Arun Saini, Subhashree Pradhan, Dalia Bashir, Moreshwar S Desai, Saul Flores, Manpreet Virk, Hossein Tcharmtchi, Amir Navaei, Sheldon Kaplan, Linda Lamberth, Kristina G Hulten, Brooks P Scull, Carl E Allen, Ayse Akcan-Arikan, K Vinod Vijayan, Miguel A Cruz

Faculty, Staff and Students Publications

Sepsis-induced coagulopathy leading to disseminated microvascular thrombosis is associated with high mortality and has no existing therapy. Despite the high prevalence of Gram-positive bacterial sepsis, especially methicillin-resistant

HYPOTHESIS: Our objective is to develop a pediatric sepsis-induced coagulopathy swine model that last 70 hours.

METHODS AND MODELS: Ten 3 weeks old piglets, implanted with telemetry devices for continuous hemodynamic monitoring, were IV injected with MRSA (

RESULTS: Compared with the saline treated piglets (control), the septic piglets within 24 hours had significantly lower neurologic and respiratory scores. Over time, PT, d-dimer, and fibrinogen increased, while platelet counts and activities of factors …

The Correlation Between Neonatal Intensive Care Unit Safety Culture And Quality Of Care, Karan Sud, Navneet Narula, Elena Aikawa, Eloisa Arbustini, Philippe Pibarot, Giampaolo Merlini, Robert S Rosenson, Surya V Seshan, Edgar Argulian, Amir Ahmadi, Fang Zhou, Andre L Moreira, Nancy Côté, Sotirios Tsimikas, Valentin Fuster, Sam Gandy, Robert O Bonow, Olga Gursky, Jagat Narula

Faculty, Staff and Student Publications

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits …

A Multisite Retrospective Review Of Direct Oral Anticoagulants Compared To Warfarin In Adult Fontan Patients, Amir Kazerouninia, Justin Georgekutty, Payton Kendsersky, Ryan D Byrne, Brendan Seto, Patricia Y Chu, Yunfei Wang, Fred H Rodriguez, Clayton Smith, Anita Saraf, Michael S Lloyd, Benjamin P Frischhertz, Dhaval R Parekh, Peter R Ermis, Wayne J Franklin, Wilson W Lam

Faculty, Staff and Students Publications

PURPOSE: Direct oral anticoagulants (DOACs) are not recommended in adult Fontan patients (Level of Evidence C). We hypothesized that DOACs are comparable to warfarin and do not increase thrombotic and embolic complications (TEs) or clinically significant bleeds.

METHODS: We reviewed the medical records of adult Fontan patients on DOACs or warfarin at three major medical centers. We identified 130 patients: 48 on DOACs and 107 on warfarin. In total, they were treated for 810 months on DOACs and 5637 months on warfarin.

RESULTS: The incidence of TEs in patients on DOACs compared to those on warfarin was not increased in …

The Impact Of Covid-19 On A Large Pragmatic Clinical Trial Embedded In Primary Care, Sarah M Leatherman, Cynthia Hau, Alison Klint, Peter A Glassman, Addison A Taylor, Ryan E Ferguson, William C Cushman, Areef Ishani

Faculty, Staff and Students Publications

INTRODUCTION: The COVID-19 pandemic had significant impact on clinical care and clinical trial operations, but the impact on decentralized pragmatic trials is unclear. The Diuretic Comparison Project (DCP) is a Point-of Care (POC) pragmatic trial testing whether chlorthalidone is superior to hydrochlorothiazide in preventing major cardiovascular (CV) events and non-cancer death. DCP utilized telephone consent, data collection from the electronic health record and Medicare, forwent study visits, and limited provider commitment beyond usual care. We assessed the impact of COVID-19 on recruitment, follow-up, data collection, and outcome ascertainment in DCP.

METHODS: We compared data from two 8-month periods: Pre-Pandemic (July …

Cardiac Pericytes Mediate The Remodeling Response To Myocardial Infarction, Pearl Quijada, Shuin Park, Peng Zhao, Kamal Ss Kolluri, David Wong, Kevin D Shih, Kai Fang, Arash Pezhouman, Lingjun Wang, Ali Daraei, Matthew D Tran, Elle M Rathbun, Kimberly N Burgos Villar, Maria L Garcia-Hernandez, Thanh Td Pham, Charles J Lowenstein, M Luisa Iruela-Arispe, S Thomas Carmichael, Eric M Small, Reza Ardehali

Faculty, Staff and Students Publications

Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4-expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac …

Oxidative Stress And Micrornas In Endothelial Cells Under Metabolic Disorders, Morgan Minjares, Wendy Wu, Jie-Mei Wang

Pharmaceutical Sciences Faculty Publications

Reactive oxygen species (ROS) are radical oxygen intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds the buffering capacity of antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC dysfunction shifts the vascular system into a pro-coagulative, proinflammatory state, thereby increasing the risk of developing cardiovascular (CV) diseases and metabolic disorders. Studies have turned to the investigation of microRNA treatment for CV risk factors, as these post-transcription regulators are known to co-regulate ROS. In this review, we will discuss ROS pathways and generation, normal endothelial cell physiology and ROS-induced …

Is There A Role For Plant-Based “Meat” In Cardiovascular Disease Prevention?, Aziza Jadallah, Usmaan Al-Shehab, Adam Friedman

Rowan-Virtua Research Day

Diet is an established risk factor for cardiovascular disease. The American Heart Association recommends following a whole-food, minimally processed diet emphasizing fruit and vegetables to reduce cardiovascular mortality. Recently, processed plant-based meat substitutes, such as Beyond Meat® and Impossible™ foods have become easily accessible to consumers and are advertised as a healthful addition to a plant-based diet. However, these products are highly processed and contain high amounts of saturated fat and sodium. The purpose of this research is to investigate the effect of processed plant-based meat diets on adverse cardiovascular events compared to animal-based meat diets and minimally processed healthful …

Aneurysmal Subarachnoid Hemorrhage In Pregnancy: National Trends Of Treatment, Predictors, And Outcomes, Kasra Khatibi, Hamidreza Saber, Smit Patel, Lucido Luciano Ponce Mejia, Naoki Kaneko, Viktor Szeder, May Nour, Reza Jahan, Satoshi Tateshima, Geoffrey Colby, Gary Duckwiler, Yalda Afshar

School of Medicine Faculty Publications

Introduction Aneurysmal subarachnoid hemorrhage (aSAH) is a rare event associated with significant pregnancy-associated maternal and neonatal morbidity and mortality. The optimal treatment strategy and clinical outcome of aSAH in pregnancy remains unclear. We aimed to investigate the treatment utilizations and outcomes of aSAH in pregnant people. Methods Using the 2010-2018 National Inpatient Sample, we identified all birth hospitalizations of women between ages of 18 to 45 associated with subarachnoid hemorrhage and aneurysm treatment were included. Multivariate analyses were used to evaluate the effect of pregnancy state, mode of treatment of aneurysms, severity of subarachnoid hemorrhage on mortality and discharge destination …

Cytochrome P450 1b1 And 12/15 Lipoxygenase Interaction In Paraventricular Nucleus In Angiotensin Ii-Induced Hypertension In Females, Shubha Ranjan Dutta

Theses and Dissertations (ETD)

Background: Angiotensin (Ang) II releases arachidonic acid (AA) from tissue phospholipids that is metabolized by 12/15-lipoxygenase (ALOX15) generating 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (HETE) which have been implicated in cardiovascular and renal diseases. This study was conducted to investigate a) the contribution of ALOX15 to Ang II-induced hypertension and associated pathogenesis in female mice, and b) the interaction between the cytochrome P450 (CYP)1B1-generated metabolite of 17β-estradiol (E2) (2-methoxyestradiol, 2-ME) and ALOX15 in the paraventricular nucleus (PVN) as a mechanism that protects against Ang II-induced hypertension and its associated pathogenesis in female mice. Methods: Experiments were conducted in intact and ovariectomized (OVX) …

A Novel Approach To Diagnostic Left And Right Heart Catheterization In A Patient With A Mechanical Prosthetic Tricuspid Valve, Seulgi E Kim, Dhaval Parekh, Wilson Lam

Faculty, Staff and Students Publications

A 47-year-old patient was experiencing dyspnea and fatigue concerning for right ventricular hypertension and new heart failure. Because of the risks associated with catheter entrapment, prosthetic valve leaflet damage, and valve thrombosis associated with crossing a mechanical valve, a novel technique was used for diagnostic left and right heart catheterization in a patient with mechanical tricuspid valve replacement and tortuous pulmonary arteries. Using a percutaneous subxiphoid approach to avoid traversing the mechanical valve without discontinuing anticoagulation, a Volcano fractional flow reserve pressure wire (Philips Volcano) was advanced for distal measurements of pressures and saturations.

Dietary Effects On Monocyte Phenotypes In Subjects With Hypertriglyceridemia And Metabolic Syndrome, Zeqin Lian, Xiao-Yuan Dai Perrard, Antu Kalathookunnel Antony, Xueying Peng, Lu Xu, Jing Ni, Bingqian Zhang, Veronica O'Brien, Anum Saeed, Xiaoming Jia, Aliza Hussain, Bing Yu, Scott I Simon, Frank M Sacks, Ron C Hoogeveen, Christie M Ballantyne, Huaizhu Wu

Faculty, Staff and Students Publications

In patients with hypertriglyceridemia, a short-term low–saturated fat vs high–saturated fat diet induced lower plasma lipids and improved monocyte phenotypes. These findings highlight the role of diet fat content and composition for monocyte phenotypes and possibly cardiovascular disease risk in these patients. (Effects of Dietary Interventions on Monocytes in Metabolic Syndrome; NCT03591588)

Prevention Of Obesity-Related Morbidity & Mortality In Adults, Rachelle Virgin

Masters Theses/Capstone Projects

Poster presentation on the prevention of obesity related morbidity and mortality in adults.

Chewed Versus Swallowed Ticagrelor In P2y12 Inhibitor-Naïve Patients Undergoing Percutaneous Coronary Intervention, Thomas F. Wilson, Muddasir Ashraf, M. Fuad Jan, Tonga Nfor, Louie Kostopoulos, Joaquin Solis, Jayant Khitha, Ahmad Khraisat, Anthony C. Defranco, Tanvir Bajwa, Suhail Q. Allaqaband

Journal of Patient-Centered Research and Reviews

Purpose: Dual antiplatelet therapy is standard for patients undergoing percutaneous coronary intervention (PCI) with stents. Traditionally, patients swallow the loading dose of a P2Y12 inhibitor before or during PCI. Time to achieve adequate platelet inhibition after swallowing the loading dose varies significantly. Chewed tablets may allow more rapid inhibition of platelet aggregation. However, data for this strategy in patients with stable ischemic heart disease or non-ST-elevation acute coronary syndrome (NSTE-ACS) are less robust.

Methods: In this single-center prospective trial, 112 P2Y12-naïve patients with stable ischemic heart disease or NSTE-ACS on aspirin therapy and who received ticagrelor after coronary angiography but …

Assessment Of Predictors Of Early Postoperative Complications After Primary Robotically Assisted Roux-En-Y Gastric Bypass: A Multicenter, Retrospective Cohort Study, Pouya Iranmanesh, Shinil K Shah, Mickael Chevallay, Christian Toso, Stefan P Mönig, Monika E Hagen, Erik B Wilson, Minoa K Jung

Faculty, Staff and Student Publications

BACKGROUND: Robotic Roux-en-Y gastric bypass (RRYGB) is performed in an increasing number of bariatric centers worldwide. Previous studies have identified a number of demographic and clinical variables as predictors of postoperative complications after laparoscopic Roux-en-Y gastric bypass (LRYGB). Some authors have suggested better early postoperative outcomes after RRYGB compared to LRYGB. The objective of the present study was to assess potential predictors of early postoperative complications after RRYGB.

METHODS: A retrospective analysis of two prospective databases containing patients who underwent RRYGB between 2006 and 2019 at two high volumes, accredited bariatric centers was performed. Primary outcome was rate of 30 …

Reclassification Of Pre-Heart Failure Stages Using Cardiac Biomarkers: The Aric Study, Xiaoming Jia, Mahmoud Al Rifai, Chiadi E Ndumele, Salim S Virani, James A De Lemos, Emmanuel Lee, Amil M Shah, Justin B Echouffo-Tcheugui, Biykem Bozkurt, Ron Hoogeveen, Elizabeth Selvin, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

BACKGROUND: The recent heart failure (HF) guideline recommends the inclusion of cardiac biomarkers in defining Stage B HF.

OBJECTIVES: The authors evaluated the impact of incorporating cardiac biomarkers to reclassify HF in 5,324 participants (mean age: 75.8 years) without prevalent HF enrolled in the ARIC (Atherosclerosis Risk In Communities) study and assessed prognosis of Stage B using cardiac biomarkers.

METHODS: Using N-terminal pro-B-type natriuretic peptide (/mL or ≥125 pg/mL), high-sensitivity troponin T (/L or ≥14 ng/L), and abnormal cardiac structure/function by echocardiography, individuals were classified as Stage A

RESULTS: Overall, 4,326 (81.3%) individuals were classified as Stage B

CONCLUSIONS: Incorporating …

Heart Failure-Type Symptom Score Trajectories In Ckd: Findings From The Chronic Renal Insufficiency Cohort (Cric) Study, Carl P Walther, Julia S Benoit, Nisha Bansal, Vijay Nambi, Sankar D Navaneethan, Cric Study Investigators

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individuals with CKD to understand the patterns and trajectories of HF-type symptoms in this setting.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF.

PREDICTORS: Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and electrocardiographic parameters.

OUTCOME: Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire …

A Design, Development, And Evaluation Of Bio-Patch For Myocardial Tissue Repair, Yaya Zhang

Theses and Dissertations (ETD)

Introduction. Ischemic heart disease (IHD) is a major concern of human health issue. The structural repair and functional recovery of injured hearts is a major challenge in the clinical setting. Preclinical studies over last 10 years have demonstrated the potential of using stem cells to treat IHD, but the efficacy of this therapy is jeopardized by uncontrollable migration and low survival of the injected stem cells. An approach based on tissue engineering enabling target-specific stem cell delivery such as cardiac patches has emerged as an alternative solution for stem cell therapy for IHD. It employs scaffold materials to engulf various …

Genetic Architecture Of Spatial Electrical Biomarkers For Cardiac Arrhythmia And Relationship With Cardiovascular Disease, William J Young, Jeffrey Haessler, Jan-Walter Benjamins, Linda Repetto, Jie Yao, Aaron Isaacs, Andrew R Harper, Julia Ramirez, Sophie Garnier, Stefan Van Duijvenboden, Antoine R Baldassari, Maria Pina Concas, Thuyvy Duong, Luisa Foco, Jonas L Isaksen, Hao Mei, Raymond Noordam, Casia Nursyifa, Anne Richmond, Meddly L Santolalla, Colleen M Sitlani, Negin Soroush, Sébastien Thériault, Stella Trompet, Stefanie Aeschbacher, Fariba Ahmadizar, Alvaro Alonso, Jennifer A Brody, Archie Campbell, Adolfo Correa, Dawood Darbar, Antonio De Luca, Jean-François Deleuze, Christina Ellervik, Christian Fuchsberger, Anuj Goel, Christopher Grace, Xiuqing Guo, Torben Hansen, Susan R Heckbert, Rebecca D Jackson, Jan A Kors, Maria Fernanda Lima-Costa, Allan Linneberg, Peter W Macfarlane, Alanna C Morrison, Pau Navarro, David J Porteous, Peter P Pramstaller, Alexander P Reiner, Lorenz Risch, Ulrich Schotten, Xia Shen, Gianfranco Sinagra, Elsayed Z Soliman, Monika Stoll, Eduardo Tarazona-Santos, Andrew Tinker, Katerina Trajanoska, Eric Villard, Helen R Warren, Eric A Whitsel, Kerri L Wiggins, Dan E Arking, Christy L Avery, David Conen, Giorgia Girotto, Niels Grarup, Caroline Hayward, J Wouter Jukema, Dennis O Mook-Kanamori, Morten Salling Olesen, Sandosh Padmanabhan, Bruce M Psaty, Cristian Pattaro, Antonio Luiz P Ribeiro, Jerome I Rotter, Bruno H Stricker, Pim Van Der Harst, Cornelia M Van Duijn, Niek Verweij, James G Wilson, Michele Orini, Philippe Charron, Hugh Watkins, Charles Kooperberg, Henry J Lin, James F Wilson, Jørgen K Kanters, Nona Sotoodehnia, Borbala Mifsud, Pier D Lambiase, Larisa G Tereshchenko, Patricia B Munroe

Faculty, Staff and Student Publications

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic …

Downregulated Klf2 In Polycythemia Vera And Essential Thrombocythemia Induces Prothrombotic Gene Expression, Jihyun Song, Soo Jin Kim, Jahnavi Gollamudi, Perumal Thiagarajan, Josef T Prchal

Faculty, Staff and Students Publications

Thromboses are major causes of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET) diseases associated with JAK2V617F mutation. However, the molecular mechanism(s) of increased thrombosis in PV and ET remain unknown. Kruppel-like factor 2 (KLF2) is a transcription factor that regulates expression of genes associated with inflammation and thrombosis; the absence of KLF2 in neutrophils causes thrombosis by inducing tissue factor. We studied the role of KLF2 in regulating prothrombotic gene expression in PV and ET. Neutrophils and platelets KLF2 expression in PV and ET was lower than the controls. Furthermore, in patients with thromboses, KLF2 transcripts …

Impact Of Time To Treatment On Endovascular Thrombectomy Outcomes In The Early Versus Late Treatment Time Windows, Negar Asdaghi, Kefeng Wang, Hannah Gardener, Angus Jameson, David Z Rose, Ayham Alkhachroum, Carolina M Gutierrez, Hao Ying, Nils Mueller-Kronast, Nicole B Sur, Chuanhui Dong, Gillian Gordon Perue, Marissa Lepain, Sebastian Koch, Nastajjia Krementz, Erika Marulanda-Londoño, Ricardo Hanel, Brijesh Mehta, Dileep R Yavagal, Tatjana Rundek, Ralph L Sacco, Jose G Romano

Faculty, Staff and Student Publications

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows.

METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and …

Transcatheter Aortic Valve-In-Valve-In-Valve Replacement In A Young Woman With Transcatheter Structural Valve Deterioration Within A Degenerated Aortic Root Homograft, Jonathan C Hong, Vicente Orozco-Sevilla, Jose G Diez, Joseph S Coselli

Faculty, Staff and Students Publications

Transcatheter aortic valve replacement is a well-established procedure for older patients with symptomatic, severe aortic stenosis. However, data are lacking on its durability and long-term complications, particularly in young patients and patients treated for aortic valve regurgitation. This article describes the case of a 27-year-old woman with complex congenital cardiovascular disease who, after 4 previous aortic valve replacement procedures, presented with structural deterioration of her most recent replacement valve, which had been placed by transcatheter aortic valve replacement inside a failed aortic root homograft 6 years earlier. After the patient had undergone this transcatheter aortic valve replacement procedure to treat …

Asthma And Cardiovascular Disease: A Bidirectional Association?, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

No abstract provided.

Association Of Long-Term Change In N-Terminal Pro-B-Type Natriuretic Peptide With Incident Heart Failure And Death, Xiaoming Jia, Mahmoud Al Rifai, Ron Hoogeveen, Justin B Echouffo-Tcheugui, Amil M Shah, Chiadi E Ndumele, Salim S Virani, Biykem Bozkurt, Elizabeth Selvin, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

IMPORTANCE: Most studies, especially in primary prevention patients, have evaluated N-terminal B-type natriuretic peptide (NT-proBNP) at one time point. Evaluation of change in NT-proBNP may improve risk stratification for incident cardiovascular events.

OBJECTIVE: To assess the association between change in NT-proBNP and risk for incident heart failure (HF) and death.

DESIGN, SETTING, AND PARTICIPANTS: Participants were recruited from 4 US communities enrolled in the Atherosclerosis Risk in Community (ARIC) study. Individuals who attended ARIC visits 2 and 4 (approximately 6 years apart) with measurements of NT-proBNP and without prevalent HF were included. Assays of NT-proBNP were conducted between 2011 and …

Mecp2 Regulates Gdf11, A Dosage-Sensitive Gene Critical For Neurological Function, Sameer S Bajikar, Ashley G Anderson, Jian Zhou, Mark A Durham, Alexander J Trostle, Ying-Wooi Wan, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Loss- and gain-of-function of MeCP2 causes Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), respectively. MeCP2 binds methyl-cytosines to finely tune gene expression in the brain, but identifying genes robustly regulated by MeCP2 has been difficult. By integrating multiple transcriptomics datasets, we revealed that MeCP2 finely regulates growth differentiation factor 11 (Gdf11). Gdf11 is down-regulated in RTT mouse models and, conversely, up-regulated in MDS mouse models. Strikingly, genetically normalizing Gdf11 dosage levels improved several behavioral deficits in a mouse model of MDS. Next, we discovered that losing one copy of Gdf11 alone was sufficient to cause multiple neurobehavioral …

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …

Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer

School of Medicine Faculty Publications

BACKGROUND: Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a “2-hit” murine model. METHODS AND RESULTS: Nine-week-old male C57BL/6 N mice (n=15 per group) were treated concurrently with high-fat …

Association Of Circulating Mtdna With Cvd In Hemodialysis Patients And In Vitro Effect Of Exogenous Mtdna On Cardiac Microvascular Inflammation, Zhen Fan, Ya Feng, Li Zang, Yi Guo, Xiao-Yi Zhong

Faculty, Staff and Student Publications

BACKGROUND: Chronic kidney disease (CKD) patients sustain a fairly high prevalence of cardiovascular disease (CVD). Microvascular inflammation is an early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been proposed to be a crucial integrator of inflammatory signals. Herein, the aim of this study was to determine the relationship between CVD, microvessel, and circulating MtDNA in the settings of uremia.

METHODS: Forty-two maintenance hemodialysis (MHD) patients and 36 health controls were enrolled in this study. Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), fibrinogen, and …