Cardiology Commons^™

Best3-Mediated Mekk2/3 Activation: A Novel Therapeutic Target In Aortopathies, Tatiana Zyrianova, Benjamin Lopez, Kathlyn Zou, Charles Gu, Dayna Pham, Sriharsha Talapaneni, Christopher M. Waters, Riccardo Olcese, Andreas Schwingshackl

Saha Cardiovascular Research Center Faculty Publications

Influenza-A virus (IAV) infects yearly an estimated one billion people worldwide, resulting in 300,000–650,000 deaths. Preventive vaccination programs and antiviral medications represent the mainstay of therapy, but with unacceptably high morbidity and mortality rates, new targeted therapeutic approaches are urgently needed. Since inflammatory processes are commonly associated with measurable changes in the cell membrane potential (Em), we investigated whether Em hyperpolarization via TREK-1 (K2P 2.1) K þ channel activation can protect against influenza-A virus (IAV)-induced pneumonia. We infected mice with IAV, which after 5 days caused 10–15% weight loss and a decrease in spontaneous activity, representing a clinically relevant infection. …

Exercise And Ischemia-Activated Pathways In Limb Muscle Angiogenesis And Vascular Regeneration, Vihang A Narkar

Faculty, Staff and Student Publications

Exercise has a profound effect on cardiovascular disease, particularly through vascular remodeling and regeneration. Peripheral artery disease (PAD) is one such cardiovascular condition that benefits from regular exercise or rehabilitative physical therapy in terms of slowing the progression of disease and delaying amputations. Various rodent pre-clinical studies using models of PAD and exercise have shed light on molecular pathways of vascular regeneration. Here, I review key exercise-activated signaling pathways (nuclear receptors, kinases, and hypoxia inducible factors) in the skeletal muscle that drive paracrine regenerative angiogenesis. The rationale for highlighting the skeletal muscle is that it is the largest organ recruited …

Induction Of Thrombotic Thrombocytopenic Purpura By Dengue Virus Infection In A Critical Patient: Role Of Therapeutic Plasma Exchange, Rathindra Nath Biswas, Sudipta Sekhar Das, Anupam Chakrapani, Subrata Sen

Faculty, Staff and Student Publications

Thrombotic thrombocytopenic purpura (TTP) secondary to dengue fever is a very unusual occurrence. Both conditions are fatal and can result in significant mortality and morbidity if left untreated. In this case, we present a young lady who suffered dengue fever followed by microangiopathic anemia, thrombocytopenic purpura, and altered sensorium. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. As soon as, we diagnosed the patient as having TTP, we treated her with serial plasma exchange therapy, steroids, and monoclonal antibodies such as rituximab. The patient responded very well to the treatment and completely recovered from neurological symptoms …

Using Rna-Based Therapies To Target The Kidney In Cardiovascular Disease, Trecia C Palmer, Robert W Hunter

Faculty, Staff and Student Publications

RNA-based therapies are currently used for immunisation against infections and to treat metabolic diseases. They can modulate gene expression in immune cells and hepatocytes, but their use in other cell types has been limited by an inability to selectively target specific tissues. Potential solutions to this targeting problem involve packaging therapeutic RNA molecules into delivery vehicles that are preferentially delivered to cells of interest. In this review, we consider why the kidney is a desirable target for RNA-based therapies in cardiovascular disease and discuss how such therapy could be delivered. Because the kidney plays a central role in maintaining cardiovascular …

Flecainide For Conversion And Maintenance Of Sinus Rhythm After Mitral Valve Replacement In Rheumatic Atrial Fibrillation, Umesh Tripathi, Aditya Kapoor, Surendra Kumar Agarwal, Prabhat Tewari, Shantanu Pande, Bipin Chandra, Ankit Sahu, Roopali Khanna, Sudeep Kumar, Naveen Garg, Satyendra Tewari

Faculty, Staff and Student Publications

BACKGROUND: Despite successful mitral valve replacement (MVR), many patients remain in AF. Flecainide can be useful in these patients but has not been used because of underlying structural heart disease.

METHODS: We assessed oral flecainide for conversion and maintenance of SR in 25 patients of chronic rheumatic AF following MVR (age 34.4 yrs, mean AF duration: 3.6 yrs). Non-converters underwent DC cardioversion at 24 h and 4 weeks. Patients received flecainide and bb/diltiazem at discharge.

RESULTS: Single oral dose of Flecainide achieved SR in 6/25 (24%) while 19/25 achieved SR after DCC; at24 h 21/25 (84%) were in SR. With …

Cardiovascular Disease Risk Factors Among Middle-Aged And Older Adult Vietnamese American Members Of A Northern California Health Plan, Donna B Haysbert, Joan C Lo, Nirmala D Ramalingam, Nancy P Gordon

Faculty, Staff and Student Publications

OBJECTIVE: There is increasing recognition that cardiovascular disease (CVD) risk factors vary by Asian subgroups. We examined CVD risk factor prevalence among Vietnamese adults in a northern California health plan.

METHODS: We used electronic health record data to examine smoking, overweight/obesity (body mass index ≥23.0 kg/m

RESULTS: Current smoking prevalence was 20.3% for middle-aged men, 7.0% for older men, and

CONCLUSIONS: Study results suggest that more research on health conditions, lifestyle, and social factors among Vietnamese American adults is needed to develop culturally competent interventions to reduce CVD risk in this growing ethnic group.

Cytosolic Dna Sensing Protein Pathway Is Activated In Human Hearts With Dilated Cardiomyopathy, Leila Rouhi, Sirisha M Cheedipudi, Benjamin Cathcart, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: The genome is constantly exposed to numerous stressors, which induce DNA lesions, including double-stranded DNA breaks (DSBs). DSBs are the most dangerous, as they induce genomic instability. In response to DNA damage, the cell activates nuclear DNA damage response (DDR) and the cytosolic DNA sensing protein (CDSP) pathways, the latter upon release of the DSBs to the cytosol. The CDSP pathway activates NFκB and IRF3, which induce the expression of the pro-inflammatory genes. There is scant data on the activation of the CDSP pathway in human hearts with dilated cardiomyopathy (DCM).

AIM: We aimed to determine expression levels of …

Association Of The Bb Genotype Of The Abo Gene With The Risk Of Acute Myocardial Infarction In Hospital-Based Study, Farzana Abubakar Yousuf, Iqbal Azam Syed, Asal Khan Tareen, Khawar A. Kazmi, Jibran Sualeh Muhammad, Mohammad Perwaiz Iqbal

Department of Biological & Biomedical Sciences

Objectives: The ABO gene locus has been identified to be associated with myocardial infarction in patients with coronary heart disease. The primary focus of this hospital-based study was to explore the relationship of ABO blood groups and ABO genotypes with acute myocardial infarction (AMI) in Karachi, Pakistan.
Methods: In a comparative cross-sectional study, an equal number of adult AMI patients and healthy controls (n=275 in each group; age range 30-70 years, both males and females) were recruited from the Aga Khan University and NICVD, Karachi, with informed consent. The blood samples were analyzed for ABO blood groups and other biomarkers. …

Machine Learning-Based Prediction Of Acute Mortality In Emergency Department Patients Using Twelve-Lead Electrocardiogram, Po-Cheng Chang, Zhi-Yong Liu, Yu-Chang Huang, Yu-Chun Hsu, Jung-Sheng Chen, Ching-Heng Lin, Richard Tsai, Chung-Chuan Chou, Ming-Shien Wen, Hung-Ta Wo, Wen-Chen Lee, Hao-Tien Liu, Chun-Chieh Wang, Chang-Fu Kuo

Faculty, Staff and Student Publications

BACKGROUND: The risk of mortality is relatively high among patients who visit the emergency department (ED), and stratifying patients at high risk can help improve medical care. This study aimed to create a machine-learning model that utilizes the standard 12-lead ECG to forecast acute mortality risk in ED patients.

METHODS: The database included patients who visited the EDs and underwent standard 12-lead ECG between October 2007 and December 2017. A convolutional neural network (CNN) ECG model was developed to classify survival and mortality using 12-lead ECG tracings acquired from 345,593 ED patients. For machine learning model development, the patients were …

Artificial Intelligence-Enabled Electrocardiographic Screening For Left Ventricular Systolic Dysfunction And Mortality Risk Prediction, Yu-Chang Huang, Yu-Chun Hsu, Zhi-Yong Liu, Ching-Heng Lin, Richard Tsai, Jung-Sheng Chen, Po-Cheng Chang, Hao-Tien Liu, Wen-Chen Lee, Hung-Ta Wo, Chung-Chuan Chou, Chun-Chieh Wang, Ming-Shien Wen, Chang-Fu Kuo

Faculty, Staff and Student Publications

BACKGROUND: Left ventricular systolic dysfunction (LVSD) characterized by a reduced left ventricular ejection fraction (LVEF) is associated with adverse patient outcomes. We aimed to build a deep neural network (DNN)-based model using standard 12-lead electrocardiogram (ECG) to screen for LVSD and stratify patient prognosis.

METHODS: This retrospective chart review study was conducted using data from consecutive adults who underwent ECG examinations at Chang Gung Memorial Hospital in Taiwan between October 2007 and December 2019. DNN models were developed to recognize LVSD, defined as LVEF

RESULTS: The mean age of patients in the testing dataset was 63.7 ± 16.3 years (46.3% …

Endothelial Activation And Fibrotic Changes Are Impeded By Laminar Flow-Induced Chk1-Senp2 Activity Through Mechanisms Distinct From Endothelial-To-Mesenchymal Cell Transition, Minh T H Nguyen, Masaki Imanishi, Shengyu Li, Khanh Chau, Priyanka Banerjee, Loka Reddy Velatooru, Kyung Ae Ko, Venkata S K Samanthapudi, Young J Gi, Ling-Ling Lee, Rei J Abe, Elena Mcbeath, Anita Deswal, Steven H Lin, Nicolas L Palaskas, Robert Dantzer, Keigi Fujiwara, Mae K Borchrdt, Estefani Berrios Turcios, Elizabeth A Olmsted-Davis, Sivareddy Kotla, John P Cooke, Guangyu Wang, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

BACKGROUND: The deSUMOylase sentrin-specific isopeptidase 2 (SENP2) plays a crucial role in atheroprotection. However, the phosphorylation of SENP2 at T368 under disturbed flow (D-flow) conditions hinders its nuclear function and promotes endothelial cell (EC) activation. SUMOylation has been implicated in D-flow-induced endothelial-to-mesenchymal transition (endoMT), but the precise role of SENP2 in counteracting this process remains unclear.

METHOD: We developed a phospho-specific SENP2 S344 antibody and generated knock-in (KI) mice with a phospho-site mutation of SENP2 S344A using CRISPR/Cas9 technology. We then investigated the effects of SENP2 S344 phosphorylation under two distinct flow patterns and during hypercholesteremia (HC)-mediated EC activation.

RESULT: …

A Unified Model Of Age-Related Cardiovascular Disease, Michael Fossel, Joe Bean, Nina Khera, Mikhail G Kolonin

Faculty, Staff and Student Publications

Despite progress in biomedical technologies, cardiovascular disease remains the main cause of mortality. This is at least in part because current clinical interventions do not adequately take into account aging as a driver and are hence aimed at suboptimal targets. To achieve progress, consideration needs to be given to the role of cell aging in disease pathogenesis. We propose a model unifying the fundamental processes underlying most age-associated cardiovascular pathologies. According to this model, cell aging, leading to cell senescence, is responsible for tissue changes leading to age-related cardiovascular disease. This process, occurring due to telomerase inactivation and telomere attrition, …

Coronary Artery Calcium Score On Standard Of Care Oncologic Ct Scans For The Prediction Of Adverse Cardiovascular Events In Patients With Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy, Efstratios Koutroumpakis, Ting Xu, Juan Lopez-Mattei, Tinsu Pan, Yang Lu, Jorge A Irizarry-Caro, Radhe Mohan, Xiaodong Zhang, Qing H Meng, Ruitao Lin, Tianlin Xu, Anita Deswal, Zhongxing Liao

Faculty, Staff and Student Publications

INTRODUCTION: Chemoradiotherapy (CRT) has been associated with increased incidence of cardiovascular (CV) adverse events (CVAE). Coronary artery calcium scoring (CAC) has shown to predict coronary events beyond the traditional CV risk factors. This study examines whether CAC, measured on standard of care, non-contrast chest CT (NCCT) imaging, predicts the development of CVAE in patients with non-small cell lung cancer (NSCLC) treated with CRT.

METHODS: Patients with NSCLC treated with CRT at MD Anderson Cancer Center from 7/2009 until 4/2014 and who had at least one NCCT scan within 6 months from their first CRT were identified. CAC scoring was performed …

Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum

Electronic Theses and Dissertations

Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …

Discovery And Systematic Characterization Of Risk Variants And Genes For Coronary Artery Disease In Over A Million Participants, Krishna G Aragam, Tao Jiang, Anuj Goel, Stavroula Kanoni, Brooke N Wolford, Deepak S Atri, Elle M Weeks, Minxian Wang, George Hindy, Wei Zhou, Christopher Grace, Carolina Roselli, Nicholas A Marston, Frederick K Kamanu, Ida Surakka, Loreto Muñoz Venegas, Paul Sherliker, Satoshi Koyama, Kazuyoshi Ishigaki, Bjørn O Åsvold, Michael R Brown, Ben Brumpton, Paul S De Vries, Olga Giannakopoulou, Panagiota Giardoglou, Daniel F Gudbjartsson, Ulrich Güldener, Syed M Ijlal Haider, Anna Helgadottir, Maysson Ibrahim, Adnan Kastrati, Thorsten Kessler, Theodosios Kyriakou, Tomasz Konopka, Ling Li, Lijiang Ma, Thomas Meitinger, Sören Mucha, Matthias Munz, Federico Murgia, Jonas B Nielsen, Markus M Nöthen, Shichao Pang, Tobias Reinberger, Gavin Schnitzler, Damian Smedley, Gudmar Thorleifsson, Moritz Von Scheidt, Jacob C Ulirsch, Biobank Japan, Epic-Cvd, David O Arnar, Noël P Burtt, Maria C Costanzo, Jason Flannick, Kaoru Ito, Dong-Keun Jang, Yoichiro Kamatani, Amit V Khera, Issei Komuro, Iftikhar J Kullo, Luca A Lotta, Christopher P Nelson, Robert Roberts, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Thomas R Webb, Aris Baras, Johan L M Björkegren, Eric Boerwinkle, George Dedoussis, Hilma Holm, Kristian Hveem, Olle Melander, Alanna C Morrison, Marju Orho-Melander, Loukianos S Rallidis, Arno Ruusalepp, Marc S Sabatine, Kari Stefansson, Pierre Zalloua, Patrick T Ellinor, Martin Farrall, John Danesh, Christian T Ruff, Hilary K Finucane, Jemma C Hopewell, Robert Clarke, Rajat M Gupta, Jeanette Erdmann, Nilesh J Samani, Heribert Schunkert, Hugh Watkins, Cristen J Willer, Panos Deloukas, Sekar Kathiresan, Adam S Butterworth, Cardiogramplusc4d Consortium

Faculty, Staff and Student Publications

The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in …

Study Protocol Cover-All: Clinical Impact Of A Volumetric Image Method For Confirming Tumour Coverage With Ablation On Patients With Malignant Liver Lesions, Yuan-Mao Lin, Iwan Paolucci, Brian M Anderson, Caleb S O'Connor, Bastien Rigaud, Maria Briones-Dimayuga, Kyle A Jones, Kristy K Brock, Bryan M Fellman, Bruno C Odisio

Faculty, Staff and Student Publications

Purpose: This study aims to evaluate the intra-procedural use of a novel ablation confirmation (AC) method, consisting of biomechanical deformable image registration incorporating AI-based auto-segmentation, and its impact on tumor coverage by quantitative three-dimensional minimal ablative margin (MAM) CT-generated assessment.

Materials and methods: This single-center, randomized, phase II, intent-to-treat trial is enrolling 100 subjects with primary and secondary liver tumors (≤ 3 tumors, 1-5 cm in diameter) undergoing microwave or radiofrequency ablation with a goal of achieving ≥ 5 mm MAM. For the experimental arm, the proposed novel AC method is utilized for ablation applicator(s) placement verification and MAM assessment. …

Polygenic Risk Score Improves The Accuracy Of A Clinical Risk Score For Coronary Artery Disease, Austin King, Lang Wu, Hong-Wen Deng, Hui Shen, Chong Wu

Faculty, Staff and Student Publications

BACKGROUND: The value of polygenic risk scores (PRSs) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves the prediction of CAD beyond pooled cohort equations. METHODS: An observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case-control sample of 9499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine …

Radiation Therapy Induces Immunosenescence Mediated By P90rsk, Masaki Imanishi, Haizi Cheng, Sivareddy Kotla, Anita Deswal, Nhat-Tu Le, Eduardo Chini, Kyung Ae Ko, Venkata S K Samanthapudi, Ling-Ling Lee, Joerg Herrmann, Xiaolei Xu, Cielito Reyes-Gibby, Sai-Ching J Yeung, Keri L Schadler, Syed Wamique Yusuf, Zhongxing Liao, Roza Nurieva, El-Ad David Amir, Jared K Burks, Nicolas L Palaskas, John P Cooke, Steven H Lin, Michihiro Kobayashi, Momoko Yoshimoto, Jun-Ichi Abe

Faculty, Staff and Student Publications

Radiation therapy (RT) to the chest increases the patients’ risk of cardiovascular disease (CVD). A complete understanding of the mechanisms by which RT induces CVD could lead to specific preventive, therapeutic approaches. It is becoming evident that both genotoxic chemotherapy agents and radiation induce mitochondrial dysfunction and cellular senescence. Notably, one of the common phenotypes observed in cancer survivors is accelerated senescence, and immunosenescence is closely related to both cancer risk and CVD development. Therefore, suppression of immunosenescence can be an ideal target to prevent cancer treatment-induced CVD. However, the mechanism(s) by which cancer treatments induce immunosenescence are incompletely characterized. …

Cardiovascular Outcomes In Patients With Chronic Kidney Disease And Covid-19: A Multi-Regional Data-Linkage Study, Emilie J Lambourg, Peter J Gallacher, Robert W Hunter, Moneeza Siddiqui, Eve Miller-Hodges, James D Chalmers, Dan Pugh, Neeraj Dhaun, Samira Bell

Faculty, Staff and Student Publications

BACKGROUND: Data describing cardiovascular outcomes in patients with coronavirus disease 2019 (COVID-19) and chronic kidney disease (CKD) are lacking. We compared cardiovascular outcomes of patients with and without COVID-19, stratified by CKD status.

METHODS: This retrospective, multi-regional data-linkage study utilised individual patient-level data from two Scottish cohorts. All patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Cohort 1 between 1 February 2020 and 31 March 2021 and in Cohort 2 between 28 February 2020 and 8 February 2021 were included.

RESULTS: Overall, 86 964 patients were tested for SARS-CoV-2. There were 36 904 patients (mean±sd age 61±21 …

Rad Regulation Of Cav12 Channels Controls Cardiac Fight-Or-Flight Response, Arianne Papa, Sergey I Zakharov, Alexander N Katchman, Jared S Kushner, Bi-Xing Chen, Lin Yang, Guoxia Liu, Alejandro Sanchez Jimenez, Robyn J Eisert, Gary A Bradshaw, Wen Dun, Shah R Ali, Aaron Rodriques, Karen Zhou, Veli Topkara, Mu Yang, John P Morrow, Emily J Tsai, Arthur Karlin, Elaine Wan, Marian Kalocsay, Geoffrey S Pitt, Henry M Colecraft, Manu Ben-Johny, Steven O Marx

Faculty, Staff and Student Publications

Fight-or-flight responses involve β-adrenergic-induced increases in heart rate and contractile force. In the present study, we uncover the primary mechanism underlying the heart's innate contractile reserve. We show that four protein kinase A (PKA)-phosphorylated residues in Rad, a calcium channel inhibitor, are crucial for controlling basal calcium current and essential for β-adrenergic augmentation of calcium influx in cardiomyocytes. Even with intact PKA signaling to other proteins modulating calcium handling, preventing adrenergic activation of calcium channels in Rad-phosphosite-mutant mice (4SA-Rad) has profound physiological effects: reduced heart rate with increased pauses, reduced basal contractility, near-complete attenuation of β-adrenergic contractile response and diminished …

Impact Of Social Determinants Of Health On Anticoagulant Use Among Patients With Atrial Fibrillation: Systemic Review And Meta-Analysis, Rasha Khatib, Nicole Glowacki, John Byrne, Peter Brady

Faculty, Staff and Student Publications

BACKGROUND: A growing body of literature now exists examining associations between social determinants of health (SDOH) and adverse outcomes in patients with atrial fibrillation; however, little is available on anticoagulant prescriptions and the impact of SDOH.

PURPOSE: Evaluate the impact of SDOH on anticoagulant prescriptions in patients with atrial fibrillation.

DATA SOURCES: Medline and Embase databases up to January 2021.

STUDY SELECTION: Noninterventional studies were included if they reported associations between at least 1 of 14 SDOH domains and anticoagulant prescription in patients with atrial fibrillation. Two investigators independently screened and collected data.

DATA EXTRACTION: Two investigators independently screened and …

Heterogeneity In The Prevalence Of Premature Hypertension Among Asian American Populations Compared With White Individuals: A National Health Interview Survey Study, Sina Kianoush, Mahmoud Al Rifai, Anwar T. Merchant, Xiaoming Jia, Zainab Samad, Aneil Bhalla, Ayesha Khan, Dongshan Zhu, Salim S. Virani

Section of Cardiology

Background: Differences in prevalence of risk factors such as hypertension may explain heterogeneity in cardiovascular risk across Asian American populations.
Methods: We used National Health Interview Survey (NHIS) data from 2006 to 2018 among White, Chinese, Asian Indian, Filipino, and 'other Asians' (Japanese, Korean, and Vietnamese). Unadjusted and adjusted odds ratios (aOR) with 95% confidence intervals were reported using logistic regression models for the association between race and self-reported premature hypertension (age old). Models were adjusted for sex, education, body mass index, smoking status, diabetes, and coronary heart disease.
Results: We studied 99,864 participants with history of hypertension (mean age, …

Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Ellen S Regalado, Shaine A Morris, Alan C Braverman, Ellen M Hostetler, Julie De Backer, Ruosha Li, Reed E Pyeritz, Anji T Yetman, Elena Cervi, Sherene Shalhub, Richmond Jeremy, Scott Lemaire, Maral Ouzounian, Arturo Evangelista, Catherine Boileau, Guillaume Jondeau, Dianna M Milewicz

Faculty, Staff and Student Publications

BACKGROUND: Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.

OBJECTIVES: This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.

METHODS: A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, …

Associations Between Adherence To The Dietary Approaches To Stop Hypertension (Dash) Diet And Six Glucose Homeostasis Traits In The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Gautam Ramesh, Alexis C Wood, Matthew A Allison, Stephen S Rich, Elizabeth T Jensen, Yii-Der I Chen, Jerome I Rotter, Alain G Bertoni, Mark O Goodarzi

Children’s Nutrition Research Center Staff Publications

Background and aims: The DASH diet conveys protection against type 2 diabetes mellitus (T2D) Via plant-based and non-plant-based recommendations. Research has not identified which glucose homeostasis pathways are improved. We examined associations between adherence to a DASH diet and six glucose homeostasis traits, probing whether associations could be attributed to the plant-based (DASH-P) and/or non-plant based (DASH-NP) components.

Methods and results: We included data from 295 adults without T2D (age 59.3 ± 9.00 years; 63.46% non-Hispanic White and 36.54% African American, self-reported race ancestry) participating in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). An oral glucose tolerance test (OGTT) …

Effect Of Calcium Chloride And Isoflurane On Force Frequency Relationship In Canines, Harrison Patrizio, Lawrence Mulligan

Rowan-Virtua Research Day

Proper calcium cycling is critical for a optimally functioning heart.

Improper calcium cycling in humans can contribute to heart failure.

Human calcium cycling is difficult to study due to the risks of damaging the patient’s cardiac tissue.

Risk of further damaging cardiac tissue is substantially increased in a heart failure patient.

Past studies focus on studying the effects of changing calcium cycling in lab rats.

Current research shows limited alternative methods in studying relationships between calcium cycling and FFR in larger mammals.

This project analyzes data to determine the response of the canine force frequency relationship to calcium chloride and …

Free Cholesterol Bioavailability And Atherosclerosis, Rei J Abe, Jun-Ichi Abe, Minh T H Nguyen, Elizabeth A Olmsted-Davis, Abrar Mamun, Priyanka Banerjee, John P Cooke, Longhou Fang, Henry Pownall, Nhat-Tu Le

Faculty, Staff and Student Publications

Purpose of review: As both a cholesterol acceptor and carrier in the reverse cholesterol transport (RCT) pathway, high-density lipoprotein (HDL) is putatively atheroprotective. However, current pharmacological therapies to increase plasma HDL cholesterol (HDL-c) concentration have paradoxically failed to prevent or reduce atherosclerosis and cardiovascular disease (CVD). Given that free cholesterol (FC) transfer between surfaces of lipoproteins and cells is reversible, excess plasma FC can be transferred to the cells of peripheral tissue sites resulting in atherosclerosis. Here, we summarize potential mechanisms contributing to this paradox and highlight the role of excess free cholesterol (FC) bioavailability in atherosclerosis vs. atheroprotection.

Recent …

Src Stimulates Abl-Dependent Phosphorylation Of The Guanine Exchange Factor Net1a To Promote Its Cytosolic Localization And Cell Motility, Andrea M Murad, Hannah L Hill, Yu Wang, Michael Ghannam, Min-Lee Yang, Norma L Pugh, Federico M Asch, Whitney Hornsby, Anisa Driscoll, Jennifer Mcnamara, Cristen J Willer, Ellen S Regalado, Dianna M Milewicz, Kim A Eagle, Santhi K Ganesh

Faculty, Staff and Student Publications

Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD. We queried registries enrolling patients with TAD to define the incidence of SCAD. Of 7568 individuals enrolled, 11 (0.15%) were found to have SCAD. Of the sequenced cases (9/11), pathogenic variants were identified (N = 9), including COL3A1 (N = 3), FBN1 (N = 2), …

Patient Knowledge Of Family History Of Cardiac Events And Risk Factors: Potential For Increase In Preventative Care Of Cardiovascular Diseases, Joseph Marentette

Honors Theses

The following literature review regards the preventative care of cardiovascular disease (CVD) patients with the knowledge of familial cardiac events and personal cardiac risk factors, particularly in younger populations ranging from ages 18 to 39, and develop potential preventative care measures. CVD is preventable with early reduction of risk factors. People can lower the impact of cardiac risk factors through the modification of their current lifestyle and behavioral habits. However, this is limited to the education and motivation of the person. Primary emphasis must be placed on community education and physician-patient interactions regarding CVD and cardiac risk factors. Physicians need …

Identification Of Genetic Loci Simultaneously Associated With Multiple Cardiometabolic Traits, Alexis C Wood, Amit Arora, Michelle Newell, Victoria L Bland, Jin Zhou, Nicola Pirastu, Jose M Ordovas, Yann C Klimentidis

Children’s Nutrition Research Center Staff Publications

Background and aims: Cardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits.

Methods and results: We conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574-456,823). Multiple …

Epidemiology, Clinical Ramifications, And Cellular Pathogenesis Of Covid-19 Mrna-Vaccination-Induced Adverse Cardiovascular Outcomes: A State-Of-The-Heart Review, Talal Almas, Sarah Rehman, Eyad Mansour, Tarek Khedro, Ali Alansari, Jahanzeb Malik, Norah Alshareef, Vikneswaran Raj Nagarajan, Abdulla Hussain Al-Awaid, Reema Alsufyani

Medical College Documents

The coronavirus disease 2019 (COVID-19) has overwhelming healthcare systems globally. To date, a myriad of therapeutic regimens has been employed in an attempt to curb the ramifications of a severe COVID-19 infection. Amidst the ongoing pandemic, the advent and efficacious uptake of COVID-19 vaccination has significantly reduced disease-related hospitalizations and mortality. Nevertheless, many side-effects are being reported after COVID-19 vaccinations and myocarditis is the most commonly reported sequelae post vaccination. Majority of these diseases are associated with COVID-19 mRNA vaccines. Various studies have established a temporal relationship between these complications, yet the causality and the underlying pathogenesis remain hypothetical. In …