Cardiology Commons^™

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 …

Favorable Outcomes Of Lvad As Bridge To Simultaneous Heart-Kidney Transplantation, Vinay Thohan, Ghulam Murtaza, Carlos O. Encarnacion, Nasir Sulemanjee, Omar Cheema, Thomas Hastings, Chi Cho, Frank Downey, John Crouch

The VAD Journal

Background

Chronic kidney disease (CKD) is an established risk factor for incident cardiovascular disease and progression of heart failure disease state, and is associated with decreased survival after left ventricular assist device (LVAD) therapy or heart transplantation (HT). Combined heart-kidney transplantation (HKT) compared with isolated HT recently has been shown to have survival advantage among patients whose estimated glomerular filtration rate is less than 37 ml/min/m². Data on LVAD to HKT are limited.

Methods

At our center, a total of 803 patients have received HT, 594 patients LVAD therapy, and 23 patients HKT from single donors; of those …

Tolerability Of Intermittent Hemodialysis In A Cohort Of Patients With Left Ventricular Assist Device, Christopher Areephanthu, Amr Elhusseini, Bennet George, Jessica Mcabee, B. Peter Sawaya

The VAD Journal

Background: The use of left ventricular assist device (LVAD) has emerged as a popular treatment for patients with advanced heart failure. It is not uncommon for these patients to suffer from renal failure requiring renal replacement therapy. The purpose of this study is to assess hemodynamic parameters and ability to complete the prescribed hemodialysis session in a series of patients who underwent numerous dialysis treatments.

Methods: Nine patients with Heart Mate II LVAD received 170 intermittent inpatient hemodialysis treatments between January 1, 2010 and December 31, 2012. Assessment included vital signs, ultrafiltrate removed, hemodialysis duration, symptoms, early terminations (ET), and …

The Short-Term And Long-Term Effects Of Biofeedback-Assisted Relaxation Therapy In Patients With Heart Failure: A Randomized Control Study, Tsuey-Yuan Huang, Debra K. Moser, Shiow-Li Hwang

Nursing Faculty Publications

Background: Relaxation techniques can reduce sympathetic nervous system activation and stress, potentially improving heart failure patients’ physical and psychological outcomes.

Purpose: To examine the effects of biofeedback-assisted relaxation (BFAR) therapy in patients with heart failure.

Methods: A prospective randomized control study was conducted. Participants in the treatment group received BFAR therapy, while participants in the control group received standard of care. Short-term outcomes were physical symptoms and psychosocial variables measured at baseline and 3 months; long-term outcomes were cardiac events and mortality assessed at 12 months.

Results: Fifty-two heart failure patients participated in the study: 23 (mean age 60.0 ± …

The Utility Of Perioperative Transesophageal Echocardiography After Left Ventricular Assist Device Implant: A Case Report, Andrew Parks, Bennet George, Alexis Shafii, Mikel Smith, Maya Guglin

The VAD Journal

Immediate post-operative evaluation of patients who have received a left ventricular assist device (LVAD) can be a daunting task. We present a case of a 51-year-old female who developed ventricular tachycardia soon after returning from the operating theatre and describe the role transesophageal echocardiogram played in helping prompt urgent and definitive treatment.

Adverse Events In Continuous-Flow Lvad Recipients: Gastrointestinal Bleeding Is Still Notable?, Marija Petrovic, Sriram Nathan, Rajko Radovancevic, Indranee Rajapreyar, Kevin J. Dasher, Mehmet H. Akay, Bindu Akkanti, Pranav Loyalka, Biswajit Kar, Igor D. Gregoric

The VAD Journal

Background: The etiology and risk factors associated with gastrointestinal bleeding (GIB) in patients with continuous-flow left ventricular assist devices (CF-LVADs) are currently unknown. Therefore, we sought to assess the risk factors for GIB in these patients.

Design and Methods: This was a retrospective, non-randomized, non-controlled study at a single center. Between 2012 and 2014, 65 men and 6 women (mean age = 55 ± 12 years) underwent CF-LVAD implantation at our institution. Overall, 23.9% of patients (17/71) had at least one GIB episode. Endoscopy confirmed GIB in 13/17. Arteriovenous malformation was the major GIB source in 8/13 (61%). …

Fever Of Unknown Origin In Patient After Left Ventricular Assist Device Implantation, Eugenia Raichlin, Sara Varnado, John Y. Um, Michael J. Moulton, Ronald Zolty Dr

The VAD Journal

Mechanical circulatory support (MCS) is a lifesaving procedure in patients with refractory cardiogenic shock. Despite improvement in surgical techniques, ICU care and restored hemodynamics, some patients on MCS remain severely debilitated due to multiple medical problems, including infections, respiratory failure, de-conditioning and nutritional deficits.

Here we present a case of a patient with persistent high degree fever, devastating muscle weakness, and elevated lactate dehydrogenase (LDH) level, who dramatically responded to treatment with vitamin B 12.

Epigenetics Of Lipid Phenotypes, Sergi Sayols-Baixeras, Marguerite R. Irvin, Donna K. Arnett, Roberto Elosua, Stella W. Aslibekyan

Epidemiology and Environmental Health Faculty Publications

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (eg, CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay …

Cardiomems™ In Lvad Patients: A Case Series, Maya Guglin, Bennet George, Sarah Branam, Amanda Hart

The VAD Journal

Patients with a left ventricular assist device (LVAD) commonly encounter issues with volume status post-implant. Volume overload can result from incomplete compensation of left ventricular failure or from right ventricular failure. The CardioMEMS™ intracardiac hemodynamic monitoring device is an area of growing interest regarding the management of chronic congestive heart failure, however, its utility has not been serially investigated in patients with an LVAD. We present a case series of patients with ventricular assist devices care for at our institution in which the CardioMEMS™ device aided in the management of volume status and pump performance.

Ligation Of The Outflow Graft Of The Left Ventricular Assist Device For Management Of Hemolysis Due To Pump Thrombosis, Jean Touchan, Alexis Shafii, Maya Guglin

The VAD Journal

Pump thrombosis is a serious complication of continuous-flow left ventricular assist devices (LVAD). Treatment options include medical thrombolysis, surgical pump exchange or urgent heart transplantation. We are reporting a case of pump thrombosis with active hemolysis and acute renal failure managed surgically by isolating the LVAD while awaiting renal recovery and donor heart availability.

An Interactive Videogame Designed To Improve Respiratory Navigator Efficiency In Children Undergoing Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Jonathan D. Grabau, Kristin N. Andres, Moriel H. Vandsburger, David K. Powell, Vincent L. Sorrell, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Background: Advanced cardiovascular magnetic resonance (CMR) acquisitions often require long scan durations that necessitate respiratory navigator gating. The tradeoff of navigator gating is reduced scan efficiency, particularly when the patient’s breathing patterns are inconsistent, as is commonly seen in children. We hypothesized that engaging pediatric participants with a navigator-controlled videogame to help control breathing patterns would improve navigator efficiency and maintain image quality.

Methods: We developed custom software that processed the Siemens respiratory navigator image in real-time during CMR and represented diaphragm position using a cartoon avatar, which was projected to the participant in the scanner as visual feedback. The …

Caregiver Burden Is Low Nine To Twelve Months After Ventricular Assist Device Implantation, Roxana Ghashghaei, Hao Tran, Jorge Silva, Barry H. Greenberg, Denise Barnard, Eric Adler

The VAD Journal

Background:

Prior studies have found that caregivers of chronically ill patients, including those with heart failure, have significant stress and burden. Ventricular Assist Devices (VADs) are a promising therapeutic modality for end stage heart failure. However, caregiver burden has not previously been studied in the caregivers of VAD patients.

Methods:

We studied 31 caregivers of VAD patients receiving care at University of California, San Diego. Validated instruments tools, such as the Bakas Caregiving Outcomes scale and Oberst Caregiving Demand and Difficulty sub-scales, were used to measure the caregivers’ psychological burden.

Results:

Nearly half of the caregivers were the patient’s spouse …

Left And Right Ventricular Dyssynchrony And Strains From Cardiovascular Magnetic Resonance Feature Tracking Do Not Predict Deterioration Of Ventricular Function In Patients With Repaired Tetralogy Of Fallot, Linyuan Jing, Gregory J. Wehner, Jonathan D. Suever, Richard Charnigo, Sudad Alhadad, Evan Stearns, Dimitri Mojsejenko, Christopher M. Haggerty, Kelsey Hickey, Anne Marie Valente, Tal Geva, Andrew J. Powell, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Background: Patients with repaired tetralogy of Fallot (rTOF) suffer from progressive ventricular dysfunction decades after their surgical repair. We hypothesized that measures of ventricular strain and dyssynchrony would predict deterioration of ventricular function in patients with rTOF.

Methods: A database search identified all patients at a single institution with rTOF who underwent cardiovascular magnetic resonance (CMR) at least twice, > 6 months apart, without intervening surgical or catheter procedures. Seven primary predictors were derived from the first CMR using a custom feature tracking algorithm: left (LV), right (RV) and inter-ventricular dyssynchrony, LV and RV peak global circumferential strains, and LV and …

Acute Appendicitis: A Potential Complication Of Continuous-Flow Left Ventricular Assist Device Support, Joshua S. Roark, Akinniran A. Abisogun, Jason N. Katz

The VAD Journal

Acute appendicitis, while common in younger patients, is an unusual cause for hospitalization among older adults. We report a case series of 3 individuals who had been previously implanted with a continuous-flow left ventricular assist device (CF-LVAD) for end-stage heart failure, and who subsequently developed acute appendicitis. Both axial-flow technology and nonpulsatile systemic blood flow have been implicated as potential causes for bleeding and thrombosis in contemporary LVAD populations(1-3). This case series represents the first report of acute appendicitis as an adverse event following LVAD implantation and represents a patient demographic that would historically be at very low-risk for this …

Total Artificial Heart Imaging And Complications: A Pictorial Review, Carrie K. Gomez, Susan K. Hobbs

The VAD Journal

Heart failure is a serious cause of morbidity and mortality with many patients ultimately requiring heart transplantation. As the rate of heart failure continues to increase and surpass the number of available donor hearts, the need for cardiac assist devices is rapidly rising. The total artificial heart has emerged as an effective therapeutic option in patients with end-stage biventricular heart failure who are awaiting orthotopic heart transplantation. The TAH replaces the patient’s native ventricle and valves and has one of the highest bridge to transplant rates. Many complications have been associated with the TAH including infections, bleeding, thrombosis, device malfunction, …

Incidence Of Pump Thrombosis In Heartmate Ii During Destination Therapy, Rohan Samson, Abhishek Jaiswal, Frank Smart, Thierry H. Lejemtel

The VAD Journal

Pump thrombosis (PT) occurs during destination therapy (DT) with HeartMate II, a continuous blood flow left ventricular assist device (St Jude, Pleasanton, CA, USA). With adherence to stringent post-operative and long-term anticoagulation a low incidence of PT was initially reported during DT. The increased PT incidence during DT that was reported in early 2013 was attributed to lenient anticoagulation. A wide range of PT incidence during DT is being reported since the return to stringent post-operative and long-term anticoagulation. We searched PubMed from January 2008 to February 2016 for reports of PT during mechanical circulatory support with HeartMate II and …

Structure And Functions Of Angiotensinogen, Hong Lu, Lisa A. Cassis, Craig W. Vander Kooi, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides. Although AGT is generally considered as a passive substrate of the renin–angiotensin system, there is accumulating evidence that the regulation and functions of AGT are intricate. Understanding the diversity of AGT properties has been enhanced by protein structural analysis and animal studies. In addition to whole-body genetic deletion, AGT can be regulated in vivo by cell-specific procedures, adeno-associated viral approaches and antisense oligonucleotides. Indeed, the availability of these multiple manipulations of AGT in vivo has provided new insights into the multifaceted roles of AGT. In this review, the combination of …

Normal Lactate Dehydrogenase Does Not Exclude Pump Thrombosis In Left Ventricular Assist Devices, Julie Shelton Do, Bennet George Md, Amanda Hart Bsn, Rn, Maya Guglin Md

The VAD Journal

Left ventricular assist device (LVAD) pump thrombosis is a well-known complication of LVAD placement. Elevated lactate dehydrogenase (LDH) has classically been the first objective marker of pump thrombosis. In this case, we present a patient found to have normal serum LDH values but was ultimately found to have significant pump thrombosis.

Outcomes Of External Repair Of Heartmate Ii™ Lvad Percutaneous Leads, Jay D. Pal, Claudius Mahr, Jason W. Smith, Todd F. Dardas, Jay Pinette, David J. Farrar, Nahush A. Mokadam

The VAD Journal

Background: The HeartMate II Left Ventricular Assist Device (LVAD) receives power via a percutaneous lead connected to an external controller and batteries. At times, this lead can be damaged during normal wear, as well as by traumatic fracture, which may jeopardize the functionality of the LVAD. If there is significant internal damage, surgical replacement of the LVAD is required. However it is possible to repair externally damaged leads by replacing the distal portion of the lead to avoid pump replacement. We report the overall experience and outcomes in patients with external lead repairs.

Methods: A procedure for full …

Exploring Body Mass Index Changes In Left Ventricular Assist Device Patients, Raquel E. Thomas, Corrine Hanson, Glenda Woscyna, Brian D. Lowes

The VAD Journal

Background: Current treatment options for end-stage heart failure, such as transplantation, can be limited by obesity guidelines. Mechanical devices such as Left Ventricular Assistive Devices (LVAD) can bridge heart failure patients to transplantation, however, after implantation; some patients may experience weight gain that precludes them from transplantation. Therefore, the objective of this study was to evaluate weight changes after the implantation of an LVAD.

Methods: A retrospective review of 130 patients receiving an LVAD were divided into two groups based on BMI at the time of implantation: obese (>30 kg/m²) and non-obese (/m²). Patients were …

A Protocol For Collecting Human Cardiac Tissue For Research, Cheavar A. Blair, Premi Haynes, Stuart G. Campbell, Charles Chung, Mihail I. Mitov, Donna Dennis, Mark R. Bonnell, Charles W. Hoopes, Maya Guglin, Kenneth S. Campbell

The VAD Journal

This manuscript describes a protocol at the University of Kentucky that allows a translational research team to collect human myocardium that can be used for biological research. We have gained a great deal of practical experience since we started this protocol in 2008, and we hope that other groups might be able to learn from our endeavors. To date, we have procured ~4000 samples from ~230 patients. The tissue that we collect comes from organ donors and from patients who are receiving a heart transplant or a ventricular assist device because they have heart failure. We begin our manuscript by …

The Utility Of Remote Hemodynamic Monitoring Devices In Patients With A Ventricular Assist Device, Bennet George, Amanda Hart, Sarah Branam, Maya Guglin

The VAD Journal

Remote intracardiac hemodynamic monitoring is a growing area of interest to help aid in the management of patients with chronic congestive heart failure. The utility of remote hemodynamic monitoring has not previously been investigated with a ventricular assist device population. We present two cases of patients with ventricular assist devices in which we employed remote hemodynamic monitoring data to aid in patient management.

Cardiac Remodeling And Dysfunction In Childhood Obesity: A Cardiovascular Magnetic Resonance Study, Linyuan Jing, Cassi M. Binkley, Jonathan D. Suever, Nivedita Umasankar, Christopher M. Haggerty, Jennifer Rich, Christopher D. Nevius, Gregory J. Wehner, Sean M. Hamlet, David K. Powell, Aurelia Radulescu, H. Lester Kirchner, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Faculty Publications

Background: Obesity affects nearly one in five children and is associated with increased risk of premature death. Obesity-related heart disease contributes to premature death. We aimed to use cardiovascular magnetic resonance (CMR) to comprehensively characterize the changes in cardiac geometry and function in obese children.

Methods and results: Forty-one obese/overweight (age 12 ± 3 years, 56 % female) and 29 healthy weight children (age 14 ± 3 years, 41 % female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, LV mass index …

Speech At The Reception For Dr. Frazier At The Ishlt 2016. Remarks For O.H. Frazier, M.D., Edwin C. Mcgee Jr

The VAD Journal

No abstract provided.

Orthotopic Heart Transplant Following Implantation Of A Systemic Ventricular Assist Device In A Patient With Congenitally Corrected Transposition Of The Great Arteries And Dextrocardia Situs Inversus Totalis, Bree Ann C. Young, Zachariah B. Nealy, Michael F. Mcgrath, John M. Herre

The VAD Journal

Congenitally corrected transposition of the great arteries (CCTGA) is a rare congenital heart disease that commonly results in congestive heart failure due to exposure of the anatomic right ventricle to systemic pressures. Additional anatomic abnormalities, such as situs inversus, in which the viscera are mirror images of normal anatomy, or dextrocardia in which the heart apex is located on the patient’s right, once were contraindications to transplant in the treatment of advanced heart failure. However, recent advancements now allow for the management of heart failure through mechanical circulatory support and subsequent transplant. This case presents a 52 year-old man with …

Va-Ecmo In Cardiogenic Shock In Adults: Indications And Outcomes, Maya Guglin, Andrew Burchett

The VAD Journal

Background

Use of veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) has become increasingly common as a means of providing hemodynamic support for patients in cardiogenic shock. Data regarding the efficacy of VA-ECMO are provided almost exclusively by single-center, retrospective analyses. These retrospective analyses vary significantly with regards to documentation of the underlying pathophysiologic process resulting in cardiogenic shock.

Methods

Relevant published studies were identified by using a comprehensive search of English-language MEDLINE from 1966 to November 2015. Relevant references found cited in these studies were also analyzed. These studies were analyzed with regard to the indications the authors used for initiation of …

Bleeding And Thromboembolic Events In Patients With Heartmate Ii Mechanical Circulatory Support, Salman Allana, Carrie Chapman, Nancy Sweitzer, Maryl Johnson, Takushi Kohmoto, Margaret Murray, David Murray, Zhanhai Li, Peter S. Rahko

The VAD Journal

Background: Bleeding and thromboembolic events (TE) are common complications following HeartMate II (HMII) implantation. The aim of the study was to review our experience related to bleeding and TE events in patients with a HMII and identify factors associated with increased risk of these events.

Methods: We retrospectively reviewed 70 consecutive patients who received a HMII between May 2006 and December 2011. The patients were followed for 12 months or until cardiac transplantation, device explantation or death. Major bleeding was defined by INTERMACS criteria with intracranial bleeding events added.

Results: There were 48 bleeding events in 28 (40%) patients with …

Tgf-Β Neutralization Enhances Angii-Induced Aortic Rupture And Aneurysm In Both Thoracic And Abdominal Regions, Xiaofeng Chen, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

AngII and TGF-β interact in development of thoracic and abdominal aortic diseases, although there are many facets of this interaction that have not been clearly defined. The aim of the present study was to determine the effects of TGF-β neutralization on AngII induced-aortic pathologies. Male C57BL/6J mice were administered with either a rabbit or mouse TGF-β neutralizing antibody and then infused with AngII. The rabbit TGF-β antibody modestly reduced serum TGF-β concentrations, with no significant enhancements to AngII-induced aneurysm or rupture. Administration of this rabbit TGF-β antibody in mice led to high serum titers against rabbit IgG that may have …

Steroid Binding To Autotaxin Links Bile Salts And Lysophosphatidic Acid Signalling, Willem-Jan Keune, Jens Hausmann, Ruth Bolier, Dagmar Tolenaars, Andreas Kremer, Tatjana Heidebrecht, Robbie P. Joosten, Manjula Sunkara, Andrew J. Morris, Elisa Matas-Rico, Wouter H. Moolenaar, Ronald P. Oude Elferink, Anastassis Perrakis

Gill Heart & Vascular Institute Faculty Publications

Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7α-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors …