Scholars@Duke
Thomas Joseph Povsic

Thomas Joseph Povsic

Adjunct Professor of Medicine
Medicine, Cardiology
povsi001@mc.duke.edu
Duke Box 103208, Durham, NC 27710
DUMC Box 103208, Durham, NC 27710

Selected Publications

Apolipoprotein A-I infusions and cardiovascular outcomes in acute myocardial infarction according to baseline LDL-cholesterol levels: the AEGIS-II trial.

Journal Article European heart journal · December 2024 Background and aimsIn the AEGIS-II trial (NCT03473223), CSL112, a human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity, did not significantly reduce the risk of the primary endpoint through 90 days vs. placebo aft ... Full text Cite

Effect of Reconstituted Human Apolipoprotein A-I on Recurrent Ischemic Events in Survivors of Acute MI.

Journal Article Journal of the American College of Cardiology · June 2024 BackgroundThe AEGIS-II trial hypothesized that CSL112, an intravenous formulation of human apoA-I, would lower the risk of plaque disruption, decreasing the risk of recurrent events such as myocardial infarction (MI) among high-risk patients with ... Full text Cite

Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction.

Journal Article The New England journal of medicine · May 2024 BackgroundCardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein - has been associated with an increased ... Full text Cite

Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial.

Journal Article Circulation. Cardiovascular interventions · May 2024 BackgroundXC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refr ... Full text Cite

Cell Therapy Improves Quality-of-Life in Heart Failure: Outcomes From a Phase III Clinical Trial.

Journal Article Stem Cells Transl Med · February 14, 2024 Patients with heart failure experience limitations in daily activity and poor quality-of-life. Prospective surveillance of health-related quality-of-life supplemented traditional death and hospitalization outcomes in the multinational, randomized, double-b ... Full text Link to item Cite

Highlights From the Circulation Family of Journals

Journal Article Circulation · October 17, 2023 Full text Cite

EXACT Trial: Results of the Phase 1 Dose-Escalation Study.

Journal Article Circ Cardiovasc Interv · August 2023 BACKGROUND: New therapies are needed for patients with refractory angina. Encoberminogene rezmadenovec (XC001), a novel adenoviral-5 vector coding for all 3 major isoforms of VEGF (vascular endothelial growth factor), demonstrated enhanced local angiogenes ... Full text Link to item Cite

Femoral Vascular Closure Devices and Bleeding, Hemostasis, and Ambulation Following Percutaneous Coronary Intervention.

Conference Journal of the American Heart Association · January 2023 Background The effectiveness of vascular closure devices (VCDs) to reduce bleeding after transfemoral percutaneous coronary intervention remains unsettled. Methods and Results Participants in the REGULATE-PCI (Effect of the REG1 anticoagulation system vers ... Full text Cite

Emerging role of positron emission tomography (PET) imaging in cardiac surgery.

Journal Article J Card Surg · December 2022 Historically, structural and anatomical imaging has been the mainstay in the diagnosis and management of cardiovascular diseases. In recent years there has been a shift toward increased use of functional imaging studies, including positron emission tomogra ... Full text Link to item Cite

Correction to: The Evolution of Virtual Physiologic Assessments and Virtual Coronary Intervention to Optimize Revascularization (Current Cardiovascular Imaging Reports, (2021), 14, 4, (4), 10.1007/s12410-021-09554-6)

Journal Article Current Cardiovascular Imaging Reports · August 1, 2022 The original version of the article contains a typo of the 2nd author’s name. It should read as “Konstantinos Dean Boudoulas. ... Full text Cite

Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations.

Journal Article Am Heart J · November 2021 BACKGROUND: Patients with refractory angina (RA) have poor quality of life and new therapies are needed. XC001 is a novel adenoviral vector expressing multiple isoforms of vascular endothelial growth factor (VEGF) promoting an enhanced local angiogenic eff ... Full text Link to item Cite

Acute Hemodynamic Effects and Tolerability of Phosphodiesterase-1 Inhibition With ITI-214 in Human Systolic Heart Failure.

Journal Article Circ Heart Fail · September 2021 BACKGROUND: PDE1 (phosphodiesterase type 1) hydrolyzes cyclic adenosine and guanosine monophosphate. ITI-214 is a highly selective PDE1 inhibitor that induces arterial vasodilation and positive inotropy in larger mammals. Here, we assessed pharmacokinetics ... Full text Link to item Cite

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol.

Journal Article J Am Coll Cardiol · August 3, 2021 BACKGROUND: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is unce ... Full text Link to item Cite

Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial.

Journal Article Open Heart · July 2021 BACKGROUND: Most cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect ... Full text Link to item Cite

Reparative cell therapy for the heart: critical internal appraisal of the field in response to recent controversies.

Journal Article ESC Heart Fail · June 2021 The concept that cell-based repair of myocardial injury might be possible was introduced almost two decades ago; however, the field of cardiovascular reparative medicine has been criticized as translation to clinically effective approaches has been slow. T ... Full text Link to item Cite

Gaining Efficiency in Clinical Trials With Cardiac Biomarkers: JACC Review Topic of the Week.

Journal Article J Am Coll Cardiol · April 20, 2021 The momentum of cardiovascular drug development has slowed dramatically. Use of validated cardiac biomarkers in clinical trials could accelerate development of much-needed therapies, but biomarkers have been used less for cardiovascular drug development th ... Full text Link to item Cite

The Evolution of Virtual Physiologic Assessments and Virtual Coronary Intervention to Optimize Revascularization

Journal Article Current Cardiovascular Imaging Reports · April 1, 2021 Purpose of Review: In this review, we summarize the use of virtual physiologic functional assessments of coronary artery disease and their utility to guide virtual coronary intervention (VCI). Recent Findings: Virtual fractional flow reserve (vFFR), corona ... Full text Cite

Stem Cells in Cardiovascular Diseases: 30,000-Foot View.

Journal Article Cells · March 9, 2021 Stem cell and regenerative approaches that might rejuvenate the heart have immense intuitive appeal for the public and scientific communities. Hopes were fueled by initial findings from preclinical models that suggested that easily obtained bone marrow cel ... Full text Link to item Cite

Therapeutic Approaches for the No-Option Refractory Angina Patient.

Journal Article Circ Cardiovasc Interv · February 2021 The combination of an aging population and improved survival rates among patients with coronary artery disease has resulted in an increase in the number of patients with refractory angina or anginal equivalent symptoms despite maximal medical therapy. Pati ... Full text Link to item Cite

Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

Journal Article N Engl J Med · January 14, 2021 BACKGROUND: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS: We randomly assigne ... Full text Link to item Cite

Cardiopoietic stem cell therapy in ischaemic heart failure: long-term clinical outcomes.

Journal Article ESC Heart Fail · December 2020 AIMS: This study aims to explore long-term clinical outcomes of cardiopoiesis-guided stem cell therapy for ischaemic heart failure assessed in the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial. METHODS AND RESULTS: CHART-1 is ... Full text Link to item Cite

CD34+ cell therapy significantly reduces adverse cardiac events, health care expenditures, and mortality in patients with refractory angina.

Conference Stem Cells Transl Med · October 2020 Patients with refractory angina who are suboptimal candidates for further revascularization have improved exercise time, decreased angina frequency, and reduced major adverse cardiac events with intramyocardial delivery of CD34+ cells. However, the effect ... Full text Link to item Cite

Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): a randomized, placebo-controlled, double-blinded trial.

Journal Article Eur Heart J · September 21, 2020 AIMS: Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute myocardial infarction (MI), dilated cardiomyopathy, and Duchenne m ... Full text Link to item Cite

"Protocol for a phase 2, randomized, double-blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-myocardial infarction": study protocol for a randomized controlled trial.

Journal Article Trials · August 26, 2020 BACKGROUND: Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Previous trials using bone marrow cells, selected stem cell populations, or cardiac stem cell progenitors require in ... Full text Link to item Cite

Novel Biomarkers, ST-Elevation Resolution, and Clinical Outcomes Following Primary Percutaneous Coronary Intervention.

Journal Article J Am Heart Assoc · July 7, 2020 Background Despite restoration of epicardial flow following primary percutaneous coronary intervention (PPCI), microvascular reperfusion as reflected by ST-elevation resolution (ST-ER) resolution remains variable and its pathophysiology remains unclear. Me ... Full text Link to item Cite

Major bleeding in patients with peripheral artery disease: Insights from the EUCLID trial.

Journal Article Am Heart J · February 2020 BACKGROUND: Rates and predictors of major bleeding in patients with peripheral artery disease (PAD) treated with antiplatelets have not been well studied. This post hoc analysis of EUCLID aimed to determine the incidence of major/minor bleeding, predictors ... Full text Open Access Link to item Cite

High-throughput targeted proteomics discovery approach and spontaneous reperfusion in ST-segment elevation myocardial infarction.

Journal Article Am Heart J · February 2020 BACKGROUND: Although spontaneous reperfusion (SR) prior to primary percutaneous coronary intervention (pPCI) is associated with improved outcomes, its pathophysiology remains unclear. The objective of the study was to explore associations between SR in ST- ... Full text Link to item Cite

Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome.

Journal Article J Am Coll Cardiol · January 21, 2020 BACKGROUND: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). OBJECTIVES: A pre-specified ana ... Full text Link to item Cite

Risk Categorization Using New American College of Cardiology/American Heart Association Guidelines for Cholesterol Management and Its Relation to Alirocumab Treatment Following Acute Coronary Syndromes.

Journal Article Circulation · November 5, 2019 BACKGROUND: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non-high-density lipoprotein cholesterol ≥100 mg/dL despite m ... Full text Link to item Cite

Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial.

Journal Article Circ Cardiovasc Qual Outcomes · November 2019 BACKGROUND: In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coron ... Full text Link to item Cite

Alirocumab in Patients With Polyvascular Disease and Recent Acute Coronary Syndrome: ODYSSEY OUTCOMES Trial.

Journal Article J Am Coll Cardiol · September 3, 2019 BACKGROUND: Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inh ... Full text Link to item Cite

Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery.

Journal Article J Am Coll Cardiol · September 3, 2019 BACKGROUND: Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. OBJECTIVES: This study sought to determine the clinical benefit of adding alirocum ... Full text Link to item Cite

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial.

Journal Article Eur Heart J · September 1, 2019 AIMS: The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related ... Full text Link to item Cite

Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial.

Journal Article Lancet Diabetes Endocrinol · August 2019 BACKGROUND: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4-1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary ... Full text Link to item Cite

Effect of Alirocumab on Mortality After Acute Coronary Syndromes.

Journal Article Circulation · July 9, 2019 BACKGROUND: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrom ... Full text Link to item Cite

P2Y12 Inhibitor Switching in Response to Routine Notification of CYP2C19 Clopidogrel Metabolizer Status Following Acute Coronary Syndromes.

Conference JAMA Cardiol · July 1, 2019 IMPORTANCE: Physician behavior in response to knowledge of a patient's CYP2C19 clopidogrel metabolizer status is unknown. OBJECTIVE: To investigate the association of mandatory reporting of CYP2C19 pharmacogenomic testing, provided to investigators with no ... Full text Open Access Link to item Cite

Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation.

Journal Article The New England journal of medicine · April 2019 BackgroundAppropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear.MethodsIn an international trial with a two-by- ... Full text Cite

Beyond pharmacological treatment: an insight into therapies that target specific aspects of heart failure pathophysiology.

Journal Article Lancet · March 9, 2019 Heart failure is a common syndrome associated with substantial morbidity and mortality. The management of symptoms and the strategies for improving prognosis have largely been based on pharmacological treatments. The pathophysiology of heart failure is com ... Full text Link to item Cite

Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events: The ODYSSEY OUTCOMES Trial.

Journal Article J Am Coll Cardiol · February 5, 2019 BACKGROUND: The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute co ... Full text Link to item Cite

Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials: A Pooled Analysis of 9259 Deaths in 9 Trials.

Journal Article Circulation · February 2019 BackgroundModern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cau ... Full text Cite

Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome.

Journal Article N Engl J Med · November 29, 2018 BACKGROUND: Patients who have had an acute coronary syndrome are at high risk for recurrent ischemic cardiovascular events. We sought to determine whether alirocumab, a human monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9), wou ... Full text Link to item Cite

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial.

Journal Article Lancet · October 27, 2018 BACKGROUND: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine t ... Full text Link to item Cite

A Path Forward for Regenerative Medicine.

Journal Article Circ Res · August 3, 2018 Although clinical trials of cell-based approaches to cardiovascular disease have yielded some promising results, no cell-based therapy has achieved regulatory approval for a cardiovascular indication. To broadly assess the challenges to regulatory approval ... Full text Link to item Cite

Autologous CD34+ cell therapy improves exercise capacity, angina frequency and reduces mortality in no-option refractory angina: a patient-level pooled analysis of randomized double-blinded trials.

Journal Article European heart journal · June 2018 AimsAutologous CD34+ (auto-CD34+) cells represent an attractive option for the treatment of refractory angina. Three double-blinded randomized trials (n = 304) compared intramyocardial (IM) auto-CD34+ cells with IM placebo injections to affect tot ... Full text Cite

Drug-eluting stents versus bare-metal stents in saphenous vein grafts: a double-blind, randomised trial.

Journal Article Lancet · May 19, 2018 BACKGROUND: Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed t ... Full text Link to item Cite

The (Translational) Road Less Traveled.

Journal Article Circ Res · January 19, 2018 Full text Link to item Cite

Emerging Therapies for Congestive Heart Failure.

Journal Article Clin Pharmacol Ther · January 2018 The treatment of atherosclerotic heart disease has improved remarkably over the last several decades; however, the outlook for patients with symptomatic congestive heart failure with reduced ejection fraction remains bleak. Current drug therapies target th ... Full text Link to item Cite

Understanding operator stent choice in the catheterization laboratory using a pre-procedure survey: Opportunities for quality improvement.

Journal Article Cardiovasc Revasc Med · December 2017 OBJECTIVES: We sought to characterize how the perceived risk of early dual antiplatelet therapy (DAPT) discontinuation is incorporated into operator decision-making regarding stent choice, using a simple pre-procedure survey screening for clinical variable ... Full text Open Access Link to item Cite

Benefit of cardiopoietic mesenchymal stem cell therapy on left ventricular remodelling: results from the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) study.

Journal Article Eur J Heart Fail · November 2017 AIMS: Left ventricular (LV) reverse remodelling is an important marker of improved outcomes in patients with advanced heart failure (HF). We examined the impact of the intramyocardial administration of bone-marrow-derived, lineage-directed, autologous card ... Full text Link to item Cite

Navigating the Future of Cardiovascular Drug Development-Leveraging Novel Approaches to Drive Innovation and Drug Discovery: Summary of Findings from the Novel Cardiovascular Therapeutics Conference.

Journal Article Cardiovasc Drugs Ther · August 2017 PURPOSE: The need for novel approaches to cardiovascular drug development served as the impetus to convene an open meeting of experts from the pharmaceutical industry and academia to assess the challenges and develop solutions for drug discovery in cardiov ... Full text Link to item Cite

Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial.

Journal Article Lancet (London, England) · May 2017 BackgroundDual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, ... Full text Open Access Cite

Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.

Journal Article Eur Heart J · March 1, 2017 AIMS: Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based ... Full text Link to item Cite

ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR) Trial: Rationale and Design.

Journal Article Cell Transplant · February 16, 2017 Autologous cardiosphere-derived cells (CDCs) were the first therapeutic modality to demonstrate myocardial regeneration with a decrease in scar size and an increase in viable, functional tissue. Widespread applicability of autologous CDC therapy is limited ... Full text Link to item Cite

The Athena trials: Autologous adipose-derived regenerative cells for refractory chronic myocardial ischemia with left ventricular dysfunction.

Journal Article Catheter Cardiovasc Interv · February 1, 2017 OBJECTIVE: To assess safety and feasibility of autologous adipose-derived regenerative cells (ADRCs), for treatment of chronic ischemic cardiomyopathy patients. BACKGROUND: Preclinical and early clinical trials suggest ADRCs have excellent potential for is ... Full text Link to item Cite

A critical reappraisal of aspirin for secondary prevention in patients with ischemic heart disease.

Journal Article Am Heart J · November 2016 Aspirin was established more than a quarter century ago as an evidence-based therapy to reduce recurrent cardiovascular events in patients with coronary artery disease based on limited data by contemporary standards. Indeed it is unclear how regulatory age ... Full text Link to item Cite

The RENEW Trial: Efficacy and Safety of Intramyocardial Autologous CD34(+) Cell Administration in Patients With Refractory Angina.

Journal Article JACC Cardiovasc Interv · August 8, 2016 OBJECTIVES: This study tested whether intramyocardial (IM) administration of mobilized, purified autologous CD34(+) cells would improve total exercise time (TET) and angina frequency in patients with refractory angina. BACKGROUND: IM administration of auto ... Full text Link to item Cite

Mesenchymal Stem Cells for Treatment of Peripheral Vascular Disease

Chapter · June 13, 2016 Peripheral vascular disease is a highly prevalent disorder, but more importantly is associated with a high degree of morbidity and a high risk or mortality. Treatment options for this disorder are limited and novel approaches are severely needed. Cell ther ... Full text Cite

Translation and Clinical Development of Antithrombotic Aptamers.

Journal Article Nucleic Acid Ther · June 2016 Thrombosis is a necessary physiological process to protect the body from uncontrolled bleeding. Pathological thrombus formation can lead to devastating clinical events including heart attack, stroke, deep vein thrombosis, pulmonary embolism, and disseminat ... Full text Link to item Cite

A randomized trial to compare the safety of rivaroxaban vs aspirin in addition to either clopidogrel or ticagrelor in acute coronary syndrome: The design of the GEMINI-ACS-1 phase II study.

Journal Article Am Heart J · April 2016 Dual antiplatelet therapy (DAPT), the combination of aspirin and a P2Y12 inhibitor, given for 12 months remains the standard of care after presentation with acute coronary syndrome (ACS) because it has been shown to be associated with a significant reducti ... Full text Link to item Cite

Endothelial Progenitor Cell Levels Predict Future Physical Function: An Exploratory Analysis From the VA Enhanced Fitness Study.

Journal Article J Gerontol A Biol Sci Med Sci · March 2016 BACKGROUND: Levels of circulating progenitor cells (CPCs) are depleted with aging and chronic injury and are associated with level of physical functioning; however, little is known about the correlation of CPCs with longer-term measures of physical capabil ... Full text Link to item Cite

Human Vascular Microphysiological System for in vitro Drug Screening.

Journal Article Sci Rep · February 18, 2016 In vitro human tissue engineered human blood vessels (TEBV) that exhibit vasoactivity can be used to test human toxicity of pharmaceutical drug candidates prior to pre-clinical animal studies. TEBVs with 400-800 μM diameters were made by embedding human ne ... Full text Open Access Link to item Cite

Current State of Stem Cell Therapy for Ischemic Heart Disease.

Journal Article Curr Cardiol Rep · February 2016 Improvements in the care of patients with ischemic cardiovascular disease have led to improved survival but also a burgeoning population of patients with advanced ischemic heart disease. Cell therapies offer a novel approach toward cardiac "rejuvenation" v ... Full text Link to item Cite

Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial design.

Journal Article Eur J Heart Fail · February 2016 AIMS: Cardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient-derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinic ... Full text Link to item Cite

Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial.

Journal Article Lancet · January 23, 2016 BACKGROUND: REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of ... Full text Link to item Cite

Autologous CD34+ Cell Therapy for Refractory Angina: 2-Year Outcomes From the ACT34-CMI Study.

Journal Article Cell Transplant · 2016 An increasing number of patients have refractory angina despite optimal medical therapy and are without further revascularization options. Preclinical studies indicate that human CD34+ stem cells can stimulate new blood vessel formation in ischemic myocard ... Full text Link to item Cite

Human Tissue Engineered Blood Vessels for in vitro Drug Testing

Conference TISSUE ENGINEERING PART A · September 1, 2015 Link to item Cite

Evaluation and treatment of patients with lower extremity peripheral artery disease: consensus definitions from Peripheral Academic Research Consortium (PARC).

Journal Article J Am Coll Cardiol · March 10, 2015 The lack of consistent definitions and nomenclature across clinical trials of novel devices, drugs, or biologics poses a significant barrier to accrual of knowledge in and across peripheral artery disease therapies and technologies. Recognizing this proble ... Full text Link to item Cite

Predictors of Long-term Clinical Endpoints in Patients With Refractory Angina

Journal Article JOURNAL OF THE AMERICAN HEART ASSOCIATION · February 2015 Full text Link to item Cite

Predictors of long-term clinical endpoints in patients with refractory angina.

Journal Article J Am Heart Assoc · January 30, 2015 BACKGROUND: Clinical outcomes in patients with refractory angina (RA) are poorly characterized and variably described. Using the Duke Database for Cardiovascular Disease (DDCD), we explored characteristics that drive clinical endpoints in patients with cla ... Full text Link to item Cite

The effect of the REG2 Anticoagulation System on thrombin generation kinetics: a pharmacodynamic and pharmacokinetic first-in-human study.

Journal Article Journal of thrombosis and thrombolysis · October 2014 The REG2 Anticoagulation System consists of pegnivacogin, a subcutaneously administered aptamer factor IXa inhibitor, and its intravenous active control agent, anivamersen. Its effect on thrombin generation is unknown. A prospectively designed thrombin gen ... Full text Cite

Use of the REG1 anticoagulation system in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the phase II RADAR-PCI study.

Journal Article EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology · August 2014 AimsWe sought to determine the feasibility of conducting percutaneous coronary intervention (PCI) in high-risk acute coronary syndrome (ACS) patients utilising the REG1 system consisting of pegnivacogin, an aptameric factor IXa inhibitor, and its ... Full text Cite

Rate- and rhythm-control therapies in patients with atrial fibrillation: a systematic review.

Journal Article Ann Intern Med · June 3, 2014 BACKGROUND: The comparative effectiveness of treatments for atrial fibrillation (AF) is uncertain. PURPOSE: To evaluate the comparative effectiveness of rate- and rhythm-control therapies. DATA SOURCES: English-language studies in PubMed, EMBASE, and the C ... Full text Link to item Cite

Anticoagulation and monitoring of a novel and reversible factor IXa inhibitor

Journal Article Drug Development Research · December 1, 2013 Clinical Development Phases I-III Regulatory, Quality, Manufacturing Thrombosis as a clinical phenotype is ubiquitous in human diseases and conditions, ranging from atherosclerosis and other vascular disorders to trauma, surgery, malignancy, infections, bl ... Full text Cite

Lower levels of circulating progenitor cells are associated with low physical function and performance in elderly men with impaired glucose tolerance: a pilot substudy from the VA Enhanced Fitness trial.

Journal Article J Gerontol A Biol Sci Med Sci · December 2013 BACKGROUND: Aging is marked by a decline in physical function. Although the biological underpinnings for this remain unclear, loss of regenerative capacity has been proposed as one cause of the loss of physical function that occurs over time. The quantity ... Full text Link to item Cite

EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction: the REVEAL EPC substudy.

Journal Article J Thromb Thrombolysis · November 2013 Erythropoietin (EPO) was hypothesized to mitigate reperfusion injury, in part via mobilization of endothelial progenitor cells (EPCs). The REVEAL trial found no reduction in infarct size with a single dose of EPO (60,000 U) in patients with ST-segment elev ... Full text Link to item Cite

Safety of very early sheath removal in patients treated with REG1 for acute coronary syndromes: insights from the RADAR trial.

Journal Article The Journal of invasive cardiology · November 2013 BackgroundRADAR compared REG1 (25%, 50%, 75%, 100% reversal) with unfractionated heparin (UFH) in 640 acute coronary syndrome (ACS) patients (479 REG1 patients, 161 UFH patients) undergoing an invasive management strategy. We sought to determine w ... Cite

Modulation of circulating angiogenic factors and tumor biology by aerobic training in breast cancer patients receiving neoadjuvant chemotherapy.

Journal Article Cancer Prev Res (Phila) · September 2013 Aerobic exercise training (AET) is an effective adjunct therapy to attenuate the adverse side-effects of adjuvant chemotherapy in women with early breast cancer. Whether AET interacts with the antitumor efficacy of chemotherapy has received scant attention ... Full text Link to item Cite

A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: results of the RADAR trial.

Journal Article European heart journal · August 2013 AimsWe sought to determine the degree of anticoagulation reversal required to mitigate bleeding, and assess the feasibility of using pegnivacogin to prevent ischaemic events in acute coronary syndrome (ACS) patients managed with an early invasive ... Full text Cite

A phase 3, randomized, double-blinded, active-controlled, unblinded standard of care study assessing the efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina: design of the RENEW study.

Journal Article Am Heart J · June 2013 Preclinical trials indicate that CD34+ cells represent an effective angiogenic stem cell component. Early-phase clinical trials suggest that intramyocardial administration of autologous CD34+ cells may improve functional capacity and symptoms of angina. RE ... Full text Link to item Cite

Comparative analysis of circulating endothelial progenitor cells in age-related macular degeneration patients using automated rare cell analysis (ARCA) and fluorescence activated cell sorting (FACS).

Journal Article PLoS One · 2013 BACKGROUND: Patients with age-related macular degeneration (ARMD) begin with non-neovascular (NNV) phenotypes usually associated with good vision. Approximately 20% of NNV-ARMD patients will convert to vision debilitating neovascular (NV) ARMD, but precise ... Full text Link to item Cite

Depletion of circulating progenitor cells precedes overt diabetes: a substudy from the VA enhanced fitness trial.

Journal Article J Diabetes Complications · 2013 BACKGROUND: One theory of aging and disease development is that chronic injury (pathology) results in activation of regenerative processes and initial repair, with overt disease arising only after exhaustion of reparative capability leads to inadequate rep ... Full text Link to item Cite

Incidence and clinical significance of cardiac biomarker elevation during stem cell mobilization, apheresis, and intramyocardial delivery: an analysis from ACT34-CMI.

Journal Article Am Heart J · November 2012 BACKGROUND: Cell therapy is a promising therapeutic for a variety of cardiovascular conditions including refractory angina. Elevation of cardiac biomarkers during cell delivery has been frequently described, but the clinical implications have never been st ... Full text Link to item Cite

Probing the mechanisms of intradialytic hypertension: a pilot study targeting endothelial cell dysfunction.

Journal Article Clin J Am Soc Nephrol · August 2012 BACKGROUND AND OBJECTIVES: Intradialytic hypertension may be caused by an impaired endothelial cell response to hemodialysis. Carvedilol has been shown to improve endothelial cell function in vivo and to block endothelin-1 release in vitro. This study hypo ... Full text Link to item Cite

A double-blind, randomized, controlled, multicenter study to assess the safety and cardiovascular effects of skeletal myoblast implantation by catheter delivery in patients with chronic heart failure after myocardial infarction.

Journal Article Am Heart J · October 2011 BACKGROUND: We sought to determine the safety and preliminary efficacy of transcatheter intramyocardial administration of myoblasts in patients with heart failure (HF). METHODS: MARVEL is a randomized placebo-controlled trial of image-guided, catheter-base ... Full text Link to item Cite

Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR pharmacokinetic and pharmacodynamic substudy.

Journal Article European heart journal · October 2011 AimsEstablishing factor IX inhibition in patients with acute coronary syndrome/non-ST-elevation myocardial infarction (ACS/NSTEMI), a setting characterized by increased factor IX activity, is critical to investigate the REG1 system in this target ... Full text Cite

Intramyocardial, autologous CD34+ cell therapy for refractory angina.

Journal Article Circ Res · August 5, 2011 RATIONALE: A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function. OBJECTIVE: Evalu ... Full text Link to item Cite

Intradialytic hypertension and its association with endothelial cell dysfunction.

Journal Article Clin J Am Soc Nephrol · August 2011 BACKGROUND AND OBJECTIVES: Intradialytic hypertension is associated with adverse outcomes, yet the mechanism is uncertain. Patients with intradialytic hypertension exhibit imbalances in endothelial-derived vasoregulators nitric oxide and endothelin-1, indi ... Full text Link to item Cite

Dose selection for a direct and selective factor IXa inhibitor and its complementary reversal agent: translating pharmacokinetic and pharmacodynamic properties of the REG1 system to clinical trial design.

Journal Article Journal of thrombosis and thrombolysis · July 2011 We performed detailed pharmacokinetic and pharmacodynamic modeling of REG1, an anticoagulation system composed of the direct factor IXa (FIXa) inhibitor pegnivacogin (RB006) and its matched active control agent anivamersen (RB007), with a focus on level of ... Full text Cite

Intravenous erythropoietin in patients with ST-segment elevation myocardial infarction: REVEAL: a randomized controlled trial.

Journal Article JAMA · May 11, 2011 CONTEXT: Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. OBJECTIVE: To evaluate the safet ... Full text Link to item Cite

A randomized, partially blinded, multicenter, active-controlled, dose-ranging study assessing the safety, efficacy, and pharmacodynamics of the REG1 anticoagulation system in patients with acute coronary syndromes: design and rationale of the RADAR Phase IIb trial.

Journal Article American heart journal · February 2011 Anticoagulants are the cornerstone of current acute coronary syndrome (ACS) therapy; however, anticoagulation regimens that aggressively reduce ischemic events are almost uniformly associated with more bleeding. REG1, an anticoagulation system, consists of ... Full text Cite

Translating nucleic acid aptamers to antithrombotic drugs in cardiovascular medicine.

Journal Article J Cardiovasc Transl Res · December 2010 Nucleic acid aptamers offer several distinct advantages for the selective inhibition of protein targets within the coagulation cascade. A highly attractive feature of aptamers as antithrombotics is their ability to encode for complementary "controlling age ... Full text Link to item Cite

Design and rationale of the Reduction of Infarct Expansion and Ventricular Remodeling with Erythropoietin after Large Myocardial Infarction (REVEAL) trial.

Journal Article Am Heart J · November 2010 BACKGROUND: Acute myocardial infarction (MI) remains a leading cause of death despite advances in pharmacologic and percutaneous therapies. Animal models of ischemia/reperfusion have demonstrated that single-dose erythropoietin may reduce infarct size, dec ... Full text Link to item Cite

Aging is not associated with bone marrow-resident progenitor cell depletion.

Journal Article J Gerontol A Biol Sci Med Sci · October 2010 Changes in progenitor cell biology remain at the forefront of many theories of biologic aging, but there are limited studies evaluating this in humans. Aging has been associated with a progressive depletion of circulating progenitor cells, but age-related ... Full text Link to item Cite

The effect of aspirin on endothelial progenitor cell biology: preliminary investigation of novel properties.

Journal Article Thromb Res · September 2010 UNLABELLED: Atherosclerosis develops in an environment of endothelial injury and inflammation. Circulating endothelial progenitor cells (EPCs) are required for vascular repair and restoration of normal endothelial function. We tested the hypothesis that th ... Full text Link to item Cite

Cell therapy for heart failure: the need for a new therapeutic strategy.

Journal Article Expert Rev Cardiovasc Ther · August 2010 Improvements in the treatment of ischemic heart disease have led to a significant growth in the numbers of patients with systolic heart failure secondary to myocardial injury. Current therapies fail to address the loss of contractile tissue due to myocardi ... Full text Link to item Cite

Nucleic acid aptamers as antithrombotic agents: Opportunities in extracellular therapeutics.

Journal Article Thromb Haemost · March 2010 Antithrombotic therapy for the acute management of thrombotic disorders has been stimulated and guided actively by our current understanding of platelet biology, coagulation proteases, and vascular science. A translatable platform for coagulation, based so ... Full text Link to item Cite

Translating Nucleic Acid Aptamers to Antithrombotic Drugs in Cardiovascular Medicine

Journal Article Journal of Cardiovascular Translational Research · 2010 Cite

Comparison of endothelial cell phenotypic markers of late-outgrowth endothelial progenitor cells isolated from patients with coronary artery disease and healthy volunteers.

Journal Article Tissue Eng Part A · November 2009 The lack of easily isolated autologous endothelial cell (EC) sources is one of the major challenges with vascular tissue engineering interventions. This article examines the isolation and expansion of late-outgrowth endothelial progenitor cells (EPCs) from ... Full text Link to item Cite

Aldehyde dehydrogenase activity allows reliable EPC enumeration in stored peripheral blood samples.

Journal Article J Thromb Thrombolysis · October 2009 BACKGROUND: Interest in the biology of endogenous progenitor cells (EPCs) continues to grow as evidence of their role in vascular repair mounts. EPC enumeration requires specialized laboratory techniques and is performed immediately after sample acquisitio ... Full text Link to item Cite

Common endothelial progenitor cell assays identify discrete endothelial progenitor cell populations.

Journal Article Am Heart J · February 2009 BACKGROUND: Multiple measures of endothelial progenitor cells (EPCs) have been described, but there has been limited study of the comparability of these assays. We sought to determine the reproducibility of and correlation between alternative EPC assay met ... Full text Link to item Cite

Preliminary observations using optical coherence tomography to assess neointimal coverage of a metal stent in a porcine model.

Journal Article Cardiovasc Revasc Med · 2009 BACKGROUND: Concerns surrounding late stent thrombosis have prompted the development of novel imaging techniques to assess neointimal coverage. Recent clinical studies have evaluated optical coherence tomography (OCT) to evaluate neointimal coverage, but p ... Full text Link to item Cite

Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells.

Journal Article Circulation · November 18, 2008 BACKGROUND: Endothelial progenitor cells (EPCs) contribute to vascular regeneration/repair and thus may protect against scleroderma vasculopathy. We aimed to determine whether circulating EPCs were reduced in scleroderma, whether scleroderma sera could ind ... Full text Link to item Cite

Endothelial progenitor cells: markers of vascular reparative capacity.

Journal Article Ther Adv Cardiovasc Dis · June 2008 Assessment of the propensity for vascular events has been based on measurement of risk factors predisposing one to vascular injury. These assessments are based on the strong associations between risk factors such as hypertension, cholesterol levels, smokin ... Full text Link to item Cite

Circulating progenitor cells can be reliably identified on the basis of aldehyde dehydrogenase activity.

Journal Article J Am Coll Cardiol · December 4, 2007 OBJECTIVES: Our objective was to develop and assess a novel endogenous progenitor cell (EPC) assay based on aldehyde dehydrogenase (ALDH) activity, and to define the relationship of ALDH-bright (ALDH(br)) cells with previously defined EPCs, patient age, an ... Full text Link to item Cite

Stem cells for the ischaemic heart.

Journal Article Expert Opin Biol Ther · May 2006 The discovery of adult progenitor cells capable of generating new vascular and myocardial tissue offers the promise of salvage of ischaemically threatened or irreversibly damaged cardiac tissue. Not surprisingly, great interest has focused on the use of a ... Full text Link to item Cite

A novel method for enumerating circulating endothelial progenitor cells based on ALDH activity

Conference JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY · February 21, 2006 Link to item Cite

Progenitor cell therapy of ischemic heart disease: the new frontier.

Journal Article Future Cardiol · January 2005 The discovery of circulating cells capable of differentiating into vascular structures (endothelial progenitor cells) has both altered our understanding of the pathophysiology of atherosclerosis and offered the possibility of using nature's reparative mech ... Full text Link to item Cite

Beta-arrestin1 mediates insulin-like growth factor 1 (IGF-1) activation of phosphatidylinositol 3-kinase (PI3K) and anti-apoptosis.

Journal Article J Biol Chem · December 19, 2003 beta-arrestins (1 and 2) are widely expressed cytosolic proteins that play central roles in G protein-coupled receptor signaling. beta-arrestin1 is also recruited to the insulin-like growth factor 1 (IGF-1) receptor, a receptor tyrosine kinase, upon agonis ... Full text Link to item Cite

Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds.

Journal Article Proc Natl Acad Sci U S A · November 8, 1994 Cell surface heparan sulfate proteoglycans, such as the syndecans, are required for cellular responses to heparin-binding growth factors and extracellular matrix components. Expression of syndecan-1 and -4 is induced in mesenchymal cells during wound repai ... Full text Link to item Cite

Sequence-Specific Double-Strand Alkylation and Cleavage of DNA Mediated by Triple-Helix Formation

Journal Article Journal of the American Chemical Society · July 1, 1992 Attachment of the nondiffusible electrophile N-bromoacetyl to the 5-position of a thymine at the 5′-end of a pyrimidine oligodeoxyribonucleotide affords sequence specific alkylation of a guanine two base pairs to the 5′-side of a local triple-helix complex ... Full text Cite

Sequence-Specific Alkylation of Double-Helical DNA by Oligonucleotide-Directed Triple-Helix Formation

Journal Article Journal of the American Chemical Society · January 1, 1990 Full text Cite

Triple helix formation by oligonucleotides on DNA extended to the physiological pH range

Journal Article Journal of the American Chemical Society · January 1, 1989 Full text Cite

A STUDY OF CELLULOSE MEMBRANE COVERED ELECTRODES AS ELECTROCHEMICAL SENSORS

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · January 1, 1984 Link to item Cite

IMMOBILIZED ENZYMES IN ANALYTICAL AMPEROMETRIC SENSORS

Journal Article AMERICAN LABORATORY · January 1, 1983 Link to item Cite