Cardiovascular Diseases Commons^™

Protection From Aortic Aneurysm By Bmal1 Deletion From Smooth Muscle Cells, Jenny Lutshumba

Theses and Dissertations--Physiology

Abdominal aortic aneurysm (AAA) is a devastating condition that occurs primarily among older people with high mortality when a rupture occurs. Currently there is no proven pharmacological therapy for AAA due to poor understanding of the underlying pathogenesis. The brain and muscle transcription factor ARNT-like (Bmal1), which is known to regulate circadian rhythm, has been implicated in vascular pathologies including atherosclerosis and vascular remodeling, but its role in AAA has not been explored.

Vascular smooth muscle is a central player in aneurysm formation and development because it is critical in all three aortic aneurysm hallmark processes including (a) degradation of …

Assessing Provider Adherence To The 2013 Acc/Aha Hyperlipidemia Guideline, Adrienne Johnston

DNP Projects

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the United States and accounts for more than 17.3 million deaths per year with hyperlipidemia as one of the leading risk factors. The 2013 American Heart Association/American College of Cardiology (AHA/ACC) hyperlipidemia guideline recommends healthy lifestyle habits, risk estimation of the development of cardiovascular disease using a risk calculator, and intensity dosed statin therapy. There has been controversy among providers resulting in confusion and inconsistent application of the guideline. Purpose: The purpose of this project was to examine provider adherence to the AHA/ACC hyperlipidemia guideline in a primary …

Use Of Sex-Specific Clinical And Exercise Risk Scores To Identify Patients At Increased Risk For All-Cause Mortality, Paul C. Cremer, Yuping Wu, Haitham M. Ahmed, Lee M. Pierson, Danielle M. Brennan, Mouaz H. Al-Mallah, Clinton A. Brawner, Jonathan K. Ehrman, Steven J. Keteyian, Roger S. Blumenthal, Michael J. Blaha, Leslie Cho

Mathematics and Statistics Faculty Publications

Importance Risk assessment tools for exercise treadmill testing may have limited external validity. Cardiovascular mortality has decreased in recent decades, and women have been underrepresented in prior cohorts.

Objectives To determine whether exercise and clinical variables are associated with differential mortality outcomes in men and women and to assess whether sex-specific risk scores better estimate all-cause mortality.

Design, Setting, and Participants This retrospective cohort study included 59 877 patients seen at the Cleveland Clinic Foundation (CCF cohort) from January 1, 2000, through December 31, 2010, and 49 278 patients seen at the Henry Ford Hospital (FIT cohort) from January 1, …

Orthogonal Decomposition Of Left Ventricular Remodeling In Myocardial Infarction, Xingyu Zhang, Pau Medrano-Gracia, Bharath Ambale-Venkatesh, David A. Bluemke, Brett R. Cowan, J. Paul Finn, Alan H. Kadish

Office of the President Publications and Research

BACKGROUND: Left ventricular size and shape are important for quantifying cardiac remodeling in response to cardiovascular disease. Geometric remodeling indices have been shown to have prognostic value in predicting adverse events in the clinical literature, but these often describe interrelated shape changes. We developed a novel method for deriving orthogonal remodeling components directly from any (moderately independent) set of clinical remodeling indices.

RESULTS: Six clinical remodeling indices (end-diastolic volume index, sphericity, relative wall thickness, ejection fraction, apical conicity, and longitudinal shortening) were evaluated using cardiac magnetic resonance images of 300 patients with myocardial infarction, and 1991 asymptomatic subjects, obtained from …

Comparison Of Inappropriate Shocks And Other Health Outcomes Between Single- And Dual-Chamber Implantable Cardioverter-Defibrillators For Primary Prevention Of Sudden Cardiac Death: Results From The Cardiovascular Research Network Longitudinal Study Of Implantable Cardioverter-Defibrillators, Pamela N. Peterson, Robert T. Greenlee, Alan S. Go, David J. Magid, Andrea Cassidy-Bushrow, Romel Garcia-Montilla, Alan H. Kadish

Office of the President Publications and Research

Background In US clinical practice, many patients who undergo placement of an implantable cardioverter‐defibrillator (ICD) for primary prevention of sudden cardiac death receive dual‐chamber devices. The superiority of dual‐chamber over single‐chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single‐ and dual‐chamber ICDs for primary prevention.

Methods and Results We identified patients receiving a single‐ or dual‐chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health …

Why Is Cardiac Morbidity And Mortality Greater Around Christmas, New Year’S, Monday Mornings And In The Morning Hours: Potential Roles Of Unrecognized Ionized Hypomagnesemia And Release Of Ceramides?, Burton M. Altura, Joshua Burack, R. F. Tranbaugh, Z. Zisbrod, J. N. Cunningham, Nilank C. Shah, Bella T. Altura

Touro College of Osteopathic Medicine (Middletown) Publications and Research

The following is the introduction to this article: There is a growing incidence of lethal cardiac events around Christmas, New Year’s and in the morning hours from 4:00 to 10:00 a.m. which is well-established in the USA and in The Southern Hemisphere [1-7]. In addition, many cardiac deaths often occur on Mondays with no satisfactory explanation [2,3]. Many of these deaths are, for the most part, unexplained and listed as “death from “natural causes”. Although in the USA, the deaths which occur around Christmas and New Years happen in the cold –winter months, this does not account for many cardiac …

Contribution Of A Class Ii Ribonucleotide Reductase To The Manganese Dependence Of Streptococcus Sanguinis, John L. Smith

Theses and Dissertations

Manganese-deficient Streptococcus sanguinis mutants exhibit a dramatic decrease in virulence for infective endocarditis and in aerobic growth in manganese-limited media. Loss of activity of a manganese-dependent, oxygen-dependent ribonucleotide reductase (RNR) could explain the decrease in virulence. When the genes encoding this RNR are deleted, there is no growth of the mutant in aerobic broth culture or in an animal model. Testing the contribution of the aerobic RNR to the phenotype of a manganese transporter mutant, a heterologous class II RNR from Lactobacillus leichmannii called NrdJ that requires B₁₂ rather than manganese as a cofactor was previously introduced into an …

Deletion Of Cardiac Mir-17-92 Cluster Increases Ischemia/ Reperfusion Injury Via Pten Upregulation, Meeta B. Prakash

Theses and Dissertations

The miR-17- 92 cluster is necessary for cell proliferation and development of the cardiovascular system. Deletion of this cluster leads to death in neonatal mice. The role of this cluster still needs to be defined following ischemia and reperfusion. Methods and Results: Adult male mice were injected with Tamoxifen- was to induce inducible cardiac-specific miR-17- 92-deficient (miR-17- 92-def: MCM:TG:miR-17- 92 flox/flox ) and wild type (WT: MCM:NTG:miR-17-92 flox/flox ) mice were subjected to 30 minutes of myocardial ischemia via left anterior descending coronary artery ligation followed by reperfusion for 24 hours. Post I/R survival (48%) and ejection fraction were reduced, …

Contribution Of Asc-Inflammasome To Vascular Endothelial Dysfunction: Role Of Rna Receptor Rig-I, Ashley Pitzer

Theses and Dissertations

Retinoic acid-inducible gene-I (RIG-I) is a putative RNA helicase and recently identified as a cytosolic RNA receptor in mammalian cells. The role of RIG-I in the regulation of vascular function under physiological and pathological conditions is unknown. Recent studies have shown that the inflammasome serves as a crucial initiator of cytokine-mediated inflammation mediating the pathogenesis of cardiovascular disease. The present study tested whether RIG-I activation triggers inflammasome formation and subsequent cytokine-mediated inflammation in the endothelium of mice coronary arteries. Using both genetic and pharmacological interventions of the RIG-I inflammasome, we first characterized whether specific activation of RIG-I via 3pRNA transfection …

Dihydropyridines As Calcium Channel Blockers: An Overview, Thelma Salazar, Andres Gonzalez, Debasish Bandyopadhyay

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Cardiovascular disease remains one of the leading causes of death in the United States. It is estimated that 1 in every 3 American adults suffer from high blood pressure. Hypertension, a precursor to most cardiovascular diseases, continues to grow at an alarming rate and is seldom managed carefully. Attempts have been made to manage hypertension and reduce the morbidity and mortality of the cardiovascular organ through methods including diets, increased amount of exercise, and medications. Many commercial drugs have been derived from dihydropyridine due to its antihypertensive property. Dihydropyridine derivatives work by acting as calcium channel blockers blocking the intake …

Fructose And Its Contribution To Cardiovascular Disease And Metabolic Syndrome, Jessica Anderson

Physician Assistant Scholarly Project Posters

The incidence of obesity, cardiovascular disease, and combination of symptoms classified as “metabolic syndrome” that eventually leads to type 2 diabetes have risen dramatically over the past few decades. The current dietary guidelines that advised patients to avoid dietary fats were originally developed in the 1960’s. This led the way for food manufacturers to remove fats in processed foods and replace them with sugars, particularly fructose. At the time there was no clinical trial data that definitively supported these guidelines.

The increased use of fructose as a food additive has dramatically increased the per-capita consumption of this sugar. More recent …

The Effect Of Statins In Primary Prevention On All-Cause Mortality, Brian Adams

Physician Assistant Scholarly Project Posters

During routine yearly physicals, primary care providers often evaluate serum laboratory lipid levels. Many of these patients have no past medical history of cardiovascular events related to atherosclerotic disease. Some patients do not have secondary risk factors, such as diabetes mellitus or smoking history.

Previous cardiovascular events provide stronger indications for the use of HMG-CoA reductase inhibitors (statins). In the absence of these, the provider may turn to current guidelines, in this case the 2013 the American College of Cardiology and the American Heart Association published the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular …

Brugada Syndrome; Preventive Screening Measures To Decrease Associated Cardiac Deaths, Matthew Ryba

Physician Assistant Scholarly Project Posters

• Brugada syndrome is a sodium channel deficiency in the myocardium that can cause arrhythmias and sudden cardiac death. The myocardium deficient sodium channels can be inherited or affected by environment factors such as fever or medications.

• Screening for this syndrome can be challenging because many times the first symptom of Brugada syndrome is cardiac arrest. Though incidents of sudden cardiac deaths are low, sudden cardiac death can impact families and communities.

• In Italy, screening ECG’s is claimed to have reduced sudden cardiac events by 85% (Maron, 2014). Preventing sudden cardiac death in these patients through sensible, reasonable …

Anticoagulation Therapy For The Elderly With Atrial Fibrillation, Rebecca Hoistad

Physician Assistant Scholarly Project Posters

• Atrial fibrillation increases in occurrence as we age with about 9% of patients developing it by age 90. When a patient is diagnosed with atrial fibrillation, one of the drugs that they are prescribed is an anticoagulant. The purpose of this drug is to prevent thrombus formation in addition to preventing an ischemic stroke. Today, there are many options available for anticoagulation therapy. The options include aspirin, vitamin K antagonists like warfarin, factor Xa inhibitors like rivaroxaban and apixaban, direct thrombin inhibitors like dabigatran, and antiplatelet agents such as clopidogrel.

• A review of the literature was done of …

Assessment Of Achieved Systolic Blood Pressure In Newly Treated Hypertensive Patients Aged 60-79 Years Before And After Eighth Joint National Committee Recommendations, Michael S. Kelly, Joseph J. Saseen, Joel C. Marrs

Pharmacy Faculty Articles and Research

Objective:

To determine whether patients who were newly prescribed antihypertensive therapy after the Eighth Joint National Committee (JNC 8) update were treated to a relaxed systolic blood pressure (SBP) goal compared with patients treated before the update.

Methods:

A retrospective cohort study approved by the Colorado Multiple Institutional Review Board. Patients aged 60–79 years, without diabetes or chronic kidney disease (CKD), newly treated for hypertension at a University of Colorado primary care clinics were included. The mean first-achieved and last-stable SBPs of patients newly prescribed antihypertensive medications from 1 January 2012 to 31 December 31 2013 (before cohort) were compared …

Myofilament Calcium Sensitivity: Consequences Of The Effective Concentration Of Troponin I, Jalal K. Siddiqui, Svetlana B. Tikunova, Shane D. Walton, Bin Liu, Meredith Meyer, Pieter P. De Tombe, Nathan Neilson, Peter M. Kekenes-Huskey, Hussam E. Salhi, Paul M.L. Janssen, Brandon J. Biesiadecki, Jonathan P. Davis

Chemistry Faculty Publications

Control of calcium binding to and dissociation from cardiac troponin C (TnC) is essential to healthy cardiac muscle contraction/relaxation. There are numerous aberrant post-translational modifications and mutations within a plethora of contractile, and even non-contractile, proteins that appear to imbalance this delicate relationship. The direction and extent of the resulting change in calcium sensitivity is thought to drive the heart toward one type of disease or another. There are a number of molecular mechanisms that may be responsible for the altered calcium binding properties of TnC, potentially the most significant being the ability of the regulatory domain of TnC to …

Dna Methylation Signatures Of Chronic Low-Grade Inflammation Are Associated With Complex Diseases, Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M. Mendelson, Karen N. Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L. Waite, Roby Joehanes, Weihua Guan, Jennifer A. Brody, Cathy Elks, Riccardo Marioni, Min A. Jhun, Golareh Agha, Jan Bressler, Cavin K. Ward-Caviness, Brian H. Chen, Tianxiao Huan, Kelly Bakulski, Elias L. Salfati, Whi-Empc Investigators, Giovanni Fiorito, Charge Epigenetics Of Coronary Heart Disease, Simone Wahl, Katharina Schramm, Jin Sha, Dena G. Hernandez, Allan C. Just, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10^–7) in the discovery panel …

Seeing The Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach, Narine Muselimyan, Luther Swift, Huda Asfour, Tigran Chahbazian, Ramesh Mazhari, Marco Mercader, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background

Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures.

Objective

To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions.

Methods

Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts. Tissue was illuminated with 365nm light and a series of images were acquired from individual spectral bands within 420-720nm range. By extracting spectral profiles of individual pixels and spectral unmixing, the relative contribution of ablated …

Aspirin Resistance Predicts Adverse Cardiovascular Events In Patients With Symptomatic Peripheral Artery Disease, Tilak Pasala, Jennifer Soo Hoo, Mary Kate Lockhart, Rehan Waheed, Prasanna Sengodan, Jeffrey Alexander, Sanjay Gandhi

The Texas Heart Institute Journal

Antiplatelet therapy reduces the risk of myocardial infarction, stroke, and vascular death in patients who have symptomatic peripheral artery disease. However, a subset of patients who take aspirin continues to have recurrent cardiovascular events. There are few data on cardiovascular outcomes in patients with peripheral artery disease who manifest aspirin resistance.

Patients with peripheral artery disease on long-term aspirin therapy (≥4 wk) were tested for aspirin responsiveness by means of the VerifyNow Aspirin Assay. The mean follow-up duration was 22.6 ± 8.3 months. The primary endpoint was a composite of death, myocardial infarction, or ischemic stroke. Secondary endpoints were the …

Comparative Efficacy Of Nebivolol And Metoprolol To Prevent Tachycardia-Induced Cardiomyopathy In A Porcine Model, Alireza Nazeri, Macarthur A Elayda, Ana Maria Segura, Raymond F Stainback, Joanna Nathan, Vei-Vei Lee, Christina Bove, Luiz Sampaio, Brian Grace, Ali Massumi, Mehdi Razavi

The Texas Heart Institute Journal

Chronic tachycardia is a well-known cause of nonischemic cardiomyopathy. We hypothesized that nebivolol, a β-blocker with nitric oxide activity, would be superior to a pure β-blocker in preventing tachycardia-induced cardiomyopathy in a porcine model.

Fifteen healthy Yucatan pigs were randomly assigned to receive nebivolol, metoprolol, or placebo once a day. All pigs underwent dual-chamber pacemaker implantation. The medication was started the day after the pacemaker implantation. On day 7 after implantation, each pacemaker was set at atrioventricular pace (rate, 170 beats/min), and the pigs were observed for another 7 weeks. Transthoracic echocardiograms, serum catecholamine levels, and blood chemistry data were …