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Precision Cardiology to Benefit from New Atlas of Cells of the Adult Human Heart

Posted in Cardiovascular Research, Frontiers in Cardiology and Cardiovascular Disorders, Origins of Cardiovascular Disease, Resident-cell-based, Single Cell Genomics, Single-cell sequencing, Systemic Inflammatory Diseases as CVD Risk, Variation in human protein-coding regions on September 29, 2020| Leave a Comment »

Precision Cardiology to Benefit from New Atlas of Cells of the Adult Human Heart

Reporters: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

 

The Voice of Dr. Pearlman on potential clinical implications of the New Atlas:

 

Published on 9/24/2020 in Nature

Litviňuková, M., Talavera-López, C., Maatz, H. et al. Cells of the adult human heart. Nature (2020). https://doi.org/10.1038/s41586-020-2797-4

 

Abstract

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require deeper understanding of the healthy heart’s molecular processes. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavor. Here, using state-of-the-art analyses of large-scale single-cell and nuclei transcriptomes, we characterise six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes, and fibroblasts, revealing distinct atrial and ventricular subsets with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment we identify cardiac resident macrophages with inflammatory and protective transcriptional signatures. Further, inference of cell-cell interactions highlight different macrophage-fibroblast-cardiomyocyte networks between atria and ventricles that are distinct from skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a healthy reference for future studies.

Author information

Author notes

  1. These authors contributed equally: Monika Litviňuková, Carlos Talavera-López, Henrike Maatz, Daniel Reichart
  2. These authors jointly supervised this work: J. G. Seidman, Christine E. Seidman, Michela Noseda, Norbert Hubner, Sarah A. Teichmann

Affiliations

  1. Cellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom

    Monika Litviňuková, Carlos Talavera-López, Krzysztof Polanski, Kenny Roberts, Liz Tuck, Eirini S. Fasouli, Hongbo Zhang, Omer Bayraktar & Sarah A. Teichmann

  2. Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany

    Monika Litviňuková, Henrike Maatz, Catherine L. Worth, Eric L. Lindberg, Masatoshi Kanda, Giannino Patone & Norbert Hubner

  3. EMBL – EBI, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom

    Carlos Talavera-López

  4. Department of Genetics, Harvard Medical School, Boston, MA, United States

    Daniel Reichart, Emily R. Nadelmann, Daniel M. DeLaughter, Hiroko Wakimoto, Joshua M. Gorham, J. G. Seidman & Christine E. Seidman

  5. Dept Physics/Cavendish Laboratory, University of Cambridge, JJ Thompson Ave, Cambridge, CB3 0EH, United Kingdom

    Sarah A. Teichmann

  6. Department of Cardiology, University Heart & Vascular Center, University of Hamburg, Hamburg, Germany

    Daniel Reichart

  7. National Heart and Lung Institute, Imperial College London, London, United Kingdom

    Michael Lee, Sara Samari, Joseph J. Boyle & Michela Noseda

  8. British Heart Foundation Centre of Research Excellence and Centre of Regenerative Medicine, Imperial College London, London, United Kingdom

    Michela Noseda

  9. Department of Surgery, University of Cambridge, NIHR Cambridge Biomedical Centre, and Cambridge Biorepository for Translational Medicine, Cambridge, United Kingdom

    Krishnaa T. Mahbubani & Kourosh Saeb-Parsy

  10. Charité-Universitätsmedizin, Berlin, Germany

    Norbert Hubner

  11. Berlin Institute of Health (BIH), Berlin, Germany

    Norbert Hubner

  12. DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany

    Barbara McDonough & Norbert Hubner

  13. Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA, United States

    Barbara McDonough & Christine E. Seidman

  14. Howard Hughes Medical Institute, Chevy Chase, MD, United States

    Christine E. Seidman

  15. Institute of Computational Biology (ICB), HMGU, Neuherberg, Germany

    Matthias Heinig

  16. Department of Informatics, Technische Universitaet Muenchen (TUM), Munich, Germany

    Matthias Heinig

  17. Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

    Hao Zhang, Anissa Viveiros & Gavin Y. Oudit

  18. Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

    Hao Zhang, Anissa Viveiros & Gavin Y. Oudit

  19. Department of Histology and Embryology of Zhongshan School of Medicine, Sun-Yat Sen University, Guangzhou, China

    Hongbo Zhang

  20. Department of Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo, Japan

    Masatoshi Kanda

Corresponding authors

Correspondence to J. G. Seidman or Christine E. Seidman or Michela Noseda or Norbert Hubner or Sarah A. Teichmann.

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Imaging-guided cancer treatment

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, CANCER BIOLOGY & Innovations in Cancer Therapy, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Coagulation Therapy and Internal Bleeding, Components and IRB related issues, Computational Biology/Systems and Bioinformatics, CT, Disease Biology, Drug Delivery Platform Technology, Ecosystems & Industrial Concentration in the Medical Device Sector, FDA, FDA Regulatory Affairs, Gene Regulation and Evolution, Genetics & Pharmaceutical, GLP, Health Economics and Outcomes Research, Healthcare costs and reimbursement, Human Immune System in Health and in Disease, Image Processing/Computing, Imaging-based Cancer Patient Management, Innovation in Immunology Diagnostics, ISO 14155, Medical and Population Genetics, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Medical Imaging Technology, Methods, Molecular Genetics & Pharmaceutical, MRI, Nanotechnology for Drug Delivery, Nuclear Medicine, Personalized and Precision Medicine & Genomic Research, Population Health Management, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Reproductive Biology & Bio Instrumentation, Resident-cell-based, Small Molecules in Development of Therapeutic Drugs, Technology Advance Assessment of, Technology Transfer: Biotech and Pharmaceutical, Translational Research, Translational Science, Ultra Sound, tagged , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , on September 30, 2014| Leave a Comment »

Imaging-guided cancer treatment

Writer & reporter: Dror Nir, PhD

It is estimated that the medical imaging market will exceed $30 billion in 2014 (FierceMedicalImaging). To put this amount in perspective; the global pharmaceutical market size for the same year is expected to be ~$1 trillion (IMS) while the global health care spending as a percentage of Gross Domestic Product (GDP) will average 10.5% globally in 2014 (Deloitte); it will reach ~$3 trillion in the USA.

Recent technology-advances, mainly miniaturization and improvement in electronic-processing components is driving increased introduction of innovative medical-imaging devices into critical nodes of major-diseases’ management pathways. Consequently, in contrast to it’s very small contribution to global health costs, medical imaging bears outstanding potential to reduce the future growth in spending on major segments in this market mainly: Drugs development and regulation (e.g. companion diagnostics and imaging surrogate markers); Disease management (e.g. non-invasive diagnosis, guided treatment and non-invasive follow-ups); and Monitoring aging-population (e.g. Imaging-based domestic sensors).

In; The Role of Medical Imaging in Personalized Medicine I discussed in length the role medical imaging assumes in drugs development.  Integrating imaging into drug development processes, specifically at the early stages of drug discovery, as well as for monitoring drug delivery and the response of targeted processes to the therapy is a growing trend. A nice (and short) review highlighting the processes, opportunities, and challenges of medical imaging in new drug development is: Medical imaging in new drug clinical development.

The following is dedicated to the role of imaging in guiding treatment.

Precise treatment is a major pillar of modern medicine. An important aspect to enable accurate administration of treatment is complementing the accurate identification of the organ location that needs to be treated with a system and methods that ensure application of treatment only, or mainly to, that location. Imaging is off-course, a major component in such composite systems. Amongst the available solution, functional-imaging modalities are gaining traction. Specifically, molecular imaging (e.g. PET, MRS) allows the visual representation, characterization, and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In oncology, it can be used to depict the abnormal molecules as well as the aberrant interactions of altered molecules on which cancers depend. Being able to detect such fundamental finger-prints of cancer is key to improved matching between drugs-based treatment and disease. Moreover, imaging-based quantified monitoring of changes in tumor metabolism and its microenvironment could provide real-time non-invasive tool to predict the evolution and progression of primary tumors, as well as the development of tumor metastases.

A recent review-paper: Image-guided interventional therapy for cancer with radiotherapeutic nanoparticles nicely illustrates the role of imaging in treatment guidance through a comprehensive discussion of; Image-guided radiotherapeutic using intravenous nanoparticles for the delivery of localized radiation to solid cancer tumors.

 Graphical abstract

 Abstract

One of the major limitations of current cancer therapy is the inability to deliver tumoricidal agents throughout the entire tumor mass using traditional intravenous administration. Nanoparticles carrying beta-emitting therapeutic radionuclides [DN: radioactive isotops that emits electrons as part of the decay process a list of β-emitting radionuclides used in radiotherapeutic nanoparticle preparation is given in table1 of this paper.) that are delivered using advanced image-guidance have significant potential to improve solid tumor therapy. The use of image-guidance in combination with nanoparticle carriers can improve the delivery of localized radiation to tumors. Nanoparticles labeled with certain beta-emitting radionuclides are intrinsically theranostic agents that can provide information regarding distribution and regional dosimetry within the tumor and the body. Image-guided thermal therapy results in increased uptake of intravenous nanoparticles within tumors, improving therapy. In addition, nanoparticles are ideal carriers for direct intratumoral infusion of beta-emitting radionuclides by convection enhanced delivery, permitting the delivery of localized therapeutic radiation without the requirement of the radionuclide exiting from the nanoparticle. With this approach, very high doses of radiation can be delivered to solid tumors while sparing normal organs. Recent technological developments in image-guidance, convection enhanced delivery and newly developed nanoparticles carrying beta-emitting radionuclides will be reviewed. Examples will be shown describing how this new approach has promise for the treatment of brain, head and neck, and other types of solid tumors.

The challenges this review discusses

  • intravenously administered drugs are inhibited in their intratumoral penetration by high interstitial pressures which prevent diffusion of drugs from the blood circulation into the tumor tissue [1–5].
  • relatively rapid clearance of intravenously administered drugs from the blood circulation by kidneys and liver.
  • drugs that do reach the solid tumor by diffusion are inhomogeneously distributed at the micro-scale – This cannot be overcome by simply administering larger systemic doses as toxicity to normal organs is generally the dose limiting factor.
  • even nanoparticulate drugs have poor penetration from the vascular compartment into the tumor and the nanoparticles that do penetrate are most often heterogeneously distributed

How imaging could mitigate the above mentioned challenges

  • The inclusion of an imaging probe during drug development can aid in determining the clearance kinetics and tissue distribution of the drug non-invasively. Such probe can also be used to determine the likelihood of the drug reaching the tumor and to what extent.

Note: Drugs that have increased accumulation within the targeted site are likely to be more effective as compared with others. In that respect, Nanoparticle-based drugs have an additional advantage over free drugs with their potential to be multifunctional carriers capable of carrying both therapeutic and diagnostic imaging probes (theranostic) in the same nanocarrier. These multifunctional nanoparticles can serve as theranostic agents and facilitate personalized treatment planning.

  • Imaging can also be used for localization of the tumor to improve the placement of a catheter or external device within tumors to cause cell death through thermal ablation or oxidative stress secondary to reactive oxygen species.

See the example of Vintfolide in The Role of Medical Imaging in Personalized Medicine

vinta

Note: Image guided thermal ablation methods include radiofrequency (RF) ablation, microwave ablation or high intensity focused ultrasound (HIFU). Photodynamic therapy methods using external light devices to activate photosensitizing agents can also be used to treat superficial tumors or deeper tumors when used with endoscopic catheters.

  • Quality control during and post treatment

For example: The use of high intensity focused ultrasound (HIFU) combined with nanoparticle therapeutics: HIFU is applied to improve drug delivery and to trigger drug release from nanoparticles. Gas-bubbles are playing the role of the drug’s nano-carrier. These are used both to increase the drug transport into the cell and as ultrasound-imaging contrast material. The ultrasound is also used for processes of drug-release and ablation.

 HIFU

Additional example; Multifunctional nanoparticles for tracking CED (convection enhanced delivery)  distribution within tumors: Nanoparticle that could serve as a carrier not only for the therapeutic radionuclides but simultaneously also for a therapeutic drug and 4 different types of imaging contrast agents including an MRI contrast agent, PET and SPECT nuclear diagnostic imaging agents and optical contrast agents as shown below. The ability to perform multiple types of imaging on the same nanoparticles will allow studies investigating the distribution and retention of nanoparticles initially in vivo using non-invasive imaging and later at the histological level using optical imaging.

 multi

Conclusions

Image-guided radiotherapeutic nanoparticles have significant potential for solid tumor cancer therapy. The current success of this therapy in animals is most likely due to the improved accumulation, retention and dispersion of nanoparticles within solid tumor following image-guided therapies as well as the micro-field of the β-particle which reduces the requirement of perfectly homogeneous tumor coverage. It is also possible that the intratumoral distribution of nanoparticles may benefit from their uptake by intratumoral macrophages although more research is required to determine the importance of this aspect of intratumoral radionuclide nanoparticle therapy. This new approach to cancer therapy is a fertile ground for many new technological developments as well as for new understandings in the basic biology of cancer therapy. The clinical success of this approach will depend on progress in many areas of interdisciplinary research including imaging technology, nanoparticle technology, computer and robot assisted image-guided application of therapies, radiation physics and oncology. Close collaboration of a wide variety of scientists and physicians including chemists, nanotechnologists, drug delivery experts, radiation physicists, robotics and software experts, toxicologists, surgeons, imaging physicians, and oncologists will best facilitate the implementation of this novel approach to the treatment of cancer in the clinical environment. Image-guided nanoparticle therapies including those with β-emission radionuclide nanoparticles have excellent promise to significantly impact clinical cancer therapy and advance the field of drug delivery.

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Protected: Analysis of Cardio-Electrical Synchronization of In vitro Cultured Stem Cells

Posted in Electrophysiology, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Personalized and Precision Medicine & Genomic Research, Resident-cell-based, Stem Cells for Regenerative Medicine, tagged on September 23, 2014|

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Introduction to e-Series A: Cardiovascular Diseases, Volume Four Part 2: Regenerative Medicine

Posted in Acute Myocardial Infarction, Biological Networks, Gene Regulation and Evolution, Ca2+ triggered activation, Calcium Signaling, Calmodulin Kinase and Contraction, Cardiac & Vascular Repair Tools Subsegment, Cardiac muscle regeneration, Cardiomyopathy, Cardiovascular Pharmacogenomics, Cardiovascular Research, Cell Biology, Signaling & Cell Circuits, Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH), Circulating Progenitor Cells, Coagulation Therapy and Internal Bleeding, Competition in regenerative stem cell science, Computational Biology/Systems and Bioinformatics, Curation, De novo synthesis, Diabetes Mellitus, Discovery process, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Drug Delivery Platform Technology, Endothelial cells, Epigenetics and Cardiovascular Risks, Experimental validation, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Genomic Testing: Methodology for Diagnosis, HTN, Medical Devices R&D and Inventions, Molecular Genetics & Pharmaceutical, Na-K transport, Na-K-ATPase, Nitric Oxide in Health and Disease, Nutrition, Origins of Cardiovascular Disease, PCI, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Proteomics, Regenerative Biology and Medicine, Resident-cell-based, Stem Cells for Regenerative Medicine, tagged , , , , , , , , , , , , , , , , , , , , , , , , , on April 27, 2014| Leave a Comment »

Introduction to e-Series A: Cardiovascular Diseases, Volume Four Part 2: Regenerative Medicine

Author and Curator: Larry H Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN

This document is entirely devoted to medical and surgical therapies that have made huge strides in

  • simplification of interventional procedures,
  • reduced complexity, resulting in procedures previously requiring surgery are now done, circumstances permitting, by medical intervention.

This revolution in cardiovascular interventional therapy is regenerative medicine.  It is regenerative because it is largely driven by

  • the introduction into the impaired vasculature of an induced pleuripotent cell, called a stem cell, although
  • the level of differentiation may not be a most primitive cell line.

There is also a very closely aligned development in cell biology that extends beyond and including vascular regeneration that is called synthetic biology.  These developments have occurred at an accelerated rate in the last 15 years. The methods of interventional cardiology were already well developed in the mid 1980s.  This was at the peak of cardiothoracic bypass surgery.

Research on the endothelial cell,

  • endothelial cell proliferation,
  • shear flow in small arteries, especially at branch points, and
  • endothelial-platelet interactions

led to insights about plaque formation and vessel thrombosis.

Much was learned in biomechanics about the shear flow stresses on the luminal surface of the vasculature, and there was also

  • the concomitant discovery of nitric oxide,
  • oxidative stress, and
  • the isoenzymes of nitric oxide synthase (eNOS, iNOS, and nNOS).

It became a fundamental tenet of vascular biology that

  • atherogenesis is a maladjustment to oxidative stress not only through genetic, but also
  • non-genetic nutritional factors that could be related to the balance of omega (ω)-3 and omega (ω)-6 fatty acids,
  • a pro-inflammatory state that elicits inflammatory cytokines, such as, interleukin-6 (IL6) and c-reactive protein(CRP),
  • insulin resistance with excess carbohydrate associated with type 2 diabetes and beta (β) cell stress,
  • excess trans- and saturated fats, and perhaps
  • the now plausible colonic microbial population of the gastrointestinal tract (GIT).

There is also an association of abdominal adiposity,

  • including the visceral peritoneum, with both T2DM and with arteriosclerotic vessel disease,
  • which is presenting at a young age, and has ties to
  • the effects of an adipokine, adiponectin.

Much important work has already been discussed in the domain of cardiac catheterization and research done to

  • prevent atheroembolization.and beyond that,
  • research done to implant an endothelial growth matrix.

Even then, dramatic work had already been done on

  • the platelet structure and metabolism, and
  • this has transformed our knowledge of platelet biology.

The coagulation process has been discussed in detailed in a previous document.  The result was the development of a

  • new class of platelet aggregation inhibitors designed to block the activation of protein on the platelet surface that
  • is critical in the coagulation cascade.

In addition, the term long used to describe atherosclerosis, atheroma notwithstanding, is “hardening of the arteries”.  This is particularly notable with respect to mid-size arteries and arterioles that feed the heart and kidneys. Whether it is preceded by or develops concurrently with chronic renal insufficiency and lowered glomerular filtration rate is perhaps arguable.  However, there is now a body of evidence that points to

  • a change in the vascular muscularis and vessel stiffness, in addition to the endothelial features already mentioned.

This has provided a basis for

  • targeted pharmaceutical intervention, and
  • reduction in salt intake.

So we have a  group of metabolic disorders, which may alone or in combination,

  • lead to and be associated with the long term effects of cardiovascular disease, including
  • congestive heart failure.

This has been classically broken down into forward and backward failure,

  • depending on decrease outflow through the aorta (ejection fraction), or
  • decreased venous return through the vena cava,

which involves increased pulmonary vascular resistance and decreased return into the left atrium.

This also has ties to several causes, which may be cardiac or vascular. This document, as the previous, has four pats.  They are broadly:

  1. Stem Cells in Cardiovascular Diseases
  2. Regenerative Cell and Molecular Biology
  3. Therapeutics Levels In Molecular Cardiology
  4. Research Proposals for Endogenous Augmentation of circulating Endothelial Progenitor Cells (cEPCs)

As in the previous section, we start with the biology of the stem cell and the degeneration in cardiovascular diseases, then proceed to regeneration, then therapeutics, and finally – proposals for augmenting therapy with circulating endogenous endothelial progenitor cells (cEPCs).

 

context

stem cells

 

theme

regeneration

 

 

 

 

theme

Therapeutics

 

theme

augmentation

 

 

 

 

 

 

 

 

 

 

Key pathways involving NO

Key pathways involving NO

 

 

 

 

stem cell lin28

stem cellLlin28

1479-5876-10-175-1-l translational research with feedback loops

Tranlational Research -Lab to Bedside

 

 

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Cardiovascular Diseases and Pharmacological Therapy: Curations by Aviva Lev-Ari, PhD, RN

Posted in Acute Myocardial Infarction, Anemia in CVD Patients, Atherogenic Processes & Pathology, CANCER BIOLOGY & Innovations in Cancer Therapy, Cardiac and Cardiovascular Surgical Procedures, Cardiac muscle regeneration, Cardiomyopathy, Cardiovascular Pharmacogenomics, Cardiovascular Research, Cerebrovascular and Neurodegenerative Diseases, Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH), Circulating Progenitor Cells, Coagulation Therapy and Internal Bleeding, Competition in regenerative stem cell science, Computational Biology/Systems and Bioinformatics, Congenital Heart Disease, Curation, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Drug Delivery Platform Technology, Drug Toxicity, Electrophysiology, Epigenetics and Cardiovascular Risks, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, HTN, HTN in Youth, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Nitric Oxide in Health and Disease, Origins of Cardiovascular Disease, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacogenomics, Pharmacologic toxicities, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Regenerative Biology and Medicine, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Resident-cell-based, Spontaneous Coronary Artery Dissection (SCAD), Stem Cells for Regenerative Medicine, Systemic Inflammatory Response Related Disorders, Technology Transfer: Biotech and Pharmaceutical, Translational Effectiveness, Translational Research, Translational Science on April 17, 2014| Leave a Comment »

Cardiovascular Diseases and Pharmacological Therapy: Curations by Aviva Lev-Ari, PhD, RN, 2006 – 4/2018

 

+120 articles listed below cover the following topics:

  • National Trends: Cardiovascular-related Hospital stay, Cost of Treatment & Societal Burden
  • Introduction to Drug Types: De Novo Brand, Generic, Biologics, Biosimsilars
  • Anti-Inflammatory & Systemic Inflammatory
  • Anti-thrombotic Drug Class & Novel Oral Anticoagulants (NOACs)
  • Pharmaco-Genetics response to Congenital and Spontaneous Mutations: new drugs and new biomarkers for Atherosclerosis, Genetic-related Novel Anti-Cholesterol, Lipids, LDL, HDL, Hypertriglyceridemia Hyperlipidemia
  • Epigenetics, Gender differences and Life Style: DM, Obesity, Hormonal Markers, Diets, Chrono-therapeutics
  • BP Management: Genetics & Human Adaptive Immunity
  • Anti-arrhythmic Drugs – Atrial Fibrillation (AF) & Silent Cerebral Infarctions
  • MI, Acute Coronary Syndrome (ACS) and Heart Failure (HF)
  • Calcium &Cardiovascular Diseases: Contractile Dysfunction, Calcium as Neurotransmitter Sensor
  • Regeneration: Cardiac System (cardiomyogenesis) and Vasculature (angiogenesis)
  • Vascular Biology, Atherosclerosis and Molecular Cardiology

 

A new mechanism of action to attack in the treatment of coronary artery disease (CAD), Novartis developed Ilaris (canakinumab), a human monoclonal antibody targeting the interleukin-1beta innate immunity pathway

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/04/06/a-new-mechanism-of-action-to-attack-in-the-treatment-of-coronary-artery-disease-cad-novartis-developed-ilaris-canakinumab-a-human-monoclonal-antibody-targeting-the-interleukin-1beta-innate-i/

 

Advantages and Disadvantages of Novel Oral Anticoagulants (NOACs)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/03/20/advantages-and-disadvantages-of-novel-oral-anticoagulants-noacs/

 

Acute Coronary Syndrome (ACS): Strategies in Anticoagulant Selection: Diagnostics Approaches – Genetic Testing Aids vs. Biomarkers (Troponin types and BNP)

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/03/13/acute-coronary-syndrome-acs-strategies-in-anticoagulant-selection-diagnostics-approaches-genetic-testing-aids-vs-biomarkers-troponin-types-and-bnp/

 

Cholesterol Lowering Novel PCSK9 drugs: Praluent [Sanofi and Regeneron] vs Repatha [Amgen] – which drug cuts CV risks enough to make it cost-effective?

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/03/12/cholesterol-lowering-novel-pcsk9-drugs-praluent-sanofi-and-regeneron-vs-repatha-amgen-which-drug-cuts-cv-risks-enough-to-make-it-cost-effective/

 

Higher BMI (Obesity Marker): Earlier onset of incident CVD followed by Shorter overall Survival – Men and women of all ages

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/03/05/higher-bmi-obesity-marker-earlier-onset-of-incident-cvd-followed-by-shorter-overall-survival-men-and-women-of-all-ages/

 

ODYSSEY Outcomes trial evaluating the effects of a PCSK9 inhibitor, alirocumab, on major cardiovascular events in patients with an acute coronary syndrome to be presented at the American College of Cardiology meeting on March 10.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/02/28/odyssey-outcomes-trial-evaluating-the-effects-of-a-pcsk9-inhibitor-alirocumab-on-major-cardiovascular-events-in-patients-with-an-acute-coronary-syndrome-to-be-presented-at-the-america/

 

Sex and Gender Connections: Heart and Brain Disease in Women

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/02/28/sex-and-gender-connections-heart-and-brain-disease-in-women/

 

In 2018 Cardiovascular PharmacoTherapy Market: Anti-thrombotic Drug Class Segment will continue to bring in the biggest profit and dominate production

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/02/27/in-2018-cardiovascular-pharmacotherapy-market-anti-thrombotic-drug-class-segment-will-continue-to-bring-in-the-biggest-profit-and-dominate-production/

 

Cost per Inpatient Hospital Stay: Five cardiovascular issues ranked in the top 10 – #1 Heart valve disorders, #2 Acute myocardial infarction (heart attack), #4 Coronary atherosclerosis, #7 Septicemia, #10 Acute cerebrovascular disease

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/02/27/cost-per-inpatient-hospital-stay-five-cardiovascular-issues-ranked-in-the-top-10-1-heart-valve-disorders-2-acute-myocardial-infarction-heart-attack-4-coronary-atherosclerosis/

 

There may be a genetic basis to CAD and that CXCL5 may be of therapeutic interest

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/02/09/there-may-be-a-genetic-basis-to-cad-and-that-cxcl5-may-be-of-therapeutic-interest/

 

FDA Approval marks first presentation of bivalirudin in frozen, premixed, ready-to-use formulation

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/01/24/fda-approval-marks-first-presentation-of-bivalirudin-in-frozen-premixed-ready-to-use-formulation/

 

What Level of Blood Pressure (BP) should be Treated? Comments on the New Guidelines

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/01/24/what-level-of-blood-pressure-bp-should-be-treated-comments-on-the-new-guidelines/

 

FDA approval on 12/1/2017 of Amgen’s evolocumb (Repatha) a PCSK9 inhibitor for the prevention of heart attacks, strokes, and coronary revascularizations in patients with established cardiovascular disease

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/12/01/fda-approval-on-12-1-2017-of-amgens-evolocumb-repatha-a-pcsk9-inhibitor-for-the-prevention-of-heart-attacks-strokes-and-coronary-revascularizations-in-patients-with-established-cardiovascular-di/

 

Long-term Canakinumab Treatment Lowering Inflammation Independent of Lipid Levels for Residual Inflammatory Risk Benefit – Personalized Medicine for Recurrent MI, Strokes and Cardiovascular Death

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/11/21/long-term-canakinumab-treatment-lowering-inflammation-independent-of-lipid-levels-for-residual-inflammatory-risk-benefit-personalized-medicine-for-recurrent-mi-strokes-and-cardiovascular-death/

 

Daily Highlights at 2017 American Heart Association Annual Meeting Scientific Sessions

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/11/14/daily-highlights-at-2017-american-heart-association-annual-meeting-scientific-sessions/

 

2017 Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults – A REPORT OF THE American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/11/14/2017-guideline-for-the-prevention-detection-evaluation-and-management-of-high-blood-pressure-in-adults-a-report-of-the-american-college-of-cardiology-american-heart-association-task-force-on-clin/

 

2017 American Heart Association Annual Meeting: Sunday’s Science at #AHA17 – Presidential Address

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/11/13/2017-american-heart-association-annual-meeting-sundays-science-at-aha17-presidential-address/

 

Systemic Inflammatory Diseases as Crohn’s disease, Rheumatoid Arthritis and Longer Psoriasis Duration May Mean Higher CVD Risk

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/10/09/systemic-inflammatory-diseases-as-crohns-disease-rheumatoid-arthritis-and-longer-psoriasis-duration-may-mean-higher-cvd-risk/

 

Shaun Coughlin from UCSF Cardiovascular Research Center to cardio group for the Novartis Institute for Biomedical Research in Cambridge, MA

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/08/17/shaun-coughlin-from-ucsf-cardiovascular-research-center-to-cardio-group-for-the-novartis-institute-for-biomedical-research-in-cambridge-ma/

 

In Europe, BigData@Heart aim to improve patient outcomes and reduce societal burden of atrial fibrillation (AF), heart failure (HF) and acute coronary syndrome (ACS).

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/07/10/in-europe-bigdataheart-aim-to-improve-patient-outcomes-and-reduce-societal-burden-of-atrial-fibrillation-af-heart-failure-hf-and-acute-coronary-syndrome-acs/

 

SNP-based Study on high BMI exposure confirms CVD and DM Risks – no associations with Stroke

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/07/10/snp-based-study-on-high-bmi-exposure-confirms-cvd-and-dm-risks-no-associations-with-stroke/

 

Tweets by @pharma_BI and @AVIVA1950 at World Medical Innovation Forum – CARDIOVASCULAR • MAY 1-3, 2017, BOSTON, MA

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/05/05/tweets-by-pharma_bi-and-aviva1950-at-world-medical-innovation-forum-cardiovascular-%E2%80%A2-may-1-3-2017-boston-ma/

 

e-Proceedings for Day 1,2,3: World Medical Innovation Forum – CARDIOVASCULAR • MAY 1-3, 2017, BOSTON, MA

Curator and Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/05/05/e-proceedings-for-day-123-world-medical-innovation-forum-cardiovascular-%E2%80%A2-may-1-3-2017-boston-ma/

REAL TIME Highlights and Tweets: Day 1,2,3: World Medical Innovation Forum – CARDIOVASCULAR • MAY 1-3, 2017, BOSTON, MA

Author and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/05/03/deliverables-day-123-world-medical-innovation-forum-cardiovascular-%E2%80%A2-may-1-3-2017-boston-ma-httpsworldmedicalinnovation-orgagenda-highlights-of-live-day-1-world-medical/

 

Expedite Use of Agents in Clinical Trials: New Drug Formulary Created – The NCI Formulary is a public-private partnership between NCI, part of the National Institutes of Health, and pharmaceutical and biotechnology companies

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/01/12/expedite-use-of-agents-in-clinical-trials-new-drug-formulary-created-the-nci-formulary-is-a-public-private-partnership-between-nci-part-of-the-national-institutes-of-health-and-pharmaceutical-and/

 

Reversing Heart Disease: Combination of PCSK9 Inhibitors and Statins – Opinion by Steven Nissen, MD, Chairman of Cardiovascular Medicine at Cleveland Clinic

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/29/reversing-heart-disease-combination-of-pcsk9-inhibitors-and-statins-opinion-by-steven-nissen-md-chairman-of-cardiovascular-medicine-at-cleveland-clinicopinion-on-reversing-heart-disease-combinat/

 

Coronary Heart Disease Research: Sugar Industry influenced national conversation on heart disease – Adoption of Low Fat Diet vs Low Carbohydrates Diet

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/09/17/coronary-heart-disease-research-sugar-industry-influenced-national-conversation-on-heart-disease-adoption-of-low-fat-diet-vs-low-carbohydrates-diet/

 

Pathophysiology in Hypertension: Opposing Roles of Human Adaptive Immunity

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/08/19/pathophysiology-in-hypertension-opposing-roles-of-human-adaptive-immunity/

 

PCSK9 inhibitors: Reducing annual drug prices from more than $14 000 to $4536 would be necessary to meet a $100 000 per QALY threshold per JAMA

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/08/17/pcsk9-inhibitors-reducing-annual-drug-prices-from-more-than-14%E2%80%AF000-to-4536-would-be-necessary-to-meet-a-100%E2%80%AF000-per-qaly-threshold-per-jama/

 

The presence of any Valvular Heart Disease (VHD) did not influence the comparison of Dabigatran [Pradaxa, Boehringer Ingelheim] with Warfarin

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/08/16/the-presence-of-any-valvular-heart-disease-vhd-did-not-influence-the-comparison-of-dabigatran-pradaxa-boehringer-ingelheim-with-warfarin/

 

Resveratrol, an antioxidant found in red wine presented since 2003 presented for its potential to lower risk for cardiovascular disease and neurodegeneration by increasing cell survival and slowing aging: 2014 Study – Diet rich in resveratrol offers no health boost

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/07/25/resveratrol-an-antioxidant-found-in-red-wine-2014-study-resveratrol-offers-no-health-boost/

 

Amgen’s Corlanor® can help Reduce the Risk of Hospitalization for Patients with worsening Heart Failure

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/05/04/amgens-corlanor-can-help-reduce-the-risk-of-hospitalization-for-patients-with-worsening-heart-failure/

 

Effectiveness of Anti-arrhythmic Drugs: Amiodarone and Lidocaine, for treating sudden cardiac arrest, increasing likelihood of Patients Surviving Emergency Transport to Hospital

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/04/04/effectiveness-of-anti-arrhythmic-drugs-amiodarone-and-lidocaine-for-treating-sudden-cardiac-arrest-increasing-likelihood-of-patients-surviving-emergency-transport-to-hospital/

 

Efficacy and Tolerability of PCSK9 Inhibitors by Patients with Muscle-related Statin Intolerance – New Cleveland Clinic study published in JAMA 4/2016

Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/04/03/efficacy-and-tolerability-of-pcsk9-inhibitors-by-patients-with-muscle-related-statin-intolerance-new-cleveland-clinic-study-published-in-jama-42016/

 

Triglycerides: Is it a Risk Factor or a Risk Marker for Atherosclerosis and Cardiovascular Disease ? The Impact of Genetic Mutations on (ANGPTL4) Gene, encoder of (angiopoietin-like 4) Protein, inhibitor of Lipoprotein Lipase

Reporters, Curators and Authors: Aviva Lev-Ari, PhD, RN and Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/03/13/triglycerides-is-it-a-risk-factor-or-a-risk-marker-for-atherosclerosis-and-cardiovascular-disease-the-impact-of-genetic-mutations-on-angptl4-gene-encoder-of-angiopoietin-like-4-protein-that-in/

 

In One-Hour: A Diagnosis of Heart Attack made possible by one Blood Test

Reporter: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/01/14/in-one-hour-a-diagnosis-of-heart-attack-made-possible-by-one-blood-test/

 

Heart-Failure–Related Mortality Rate: CDC Reports comparison of 2000, 2012, 2014  – the decease is steadily reversed

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/05/heart-failure-related-mortality-rate-cdc-reports-comparison-of-2000-2012-2014-the-decease-is-steadily-reversed/

 

PCSK9: A Recent Discovery in Understanding Cholesterol Regulation @ AMGEN Cardiovascular

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/08/04/pcsk9-a-recent-discovery-in-understanding-cholesterol-regulation-amgen-cardiovascular/

 

Praluent – FDA approved as Cholesterol-lowering Medicine for Patient non responsive to Statin due to Genetic origin of Hypercholesterolemia

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/07/27/praluent-fda-approved-as-cholesterol-lowering-medicine-for-patient-non-responsive-to-statin-due-to-genetic-origin-of-hypercholesterolemia/

 

Atherosclerosis: What is New in Biomarker Discovery

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/07/01/atherosclerosis-what-is-new-in-biomarker-discovery/

 

Cangrelor wins Clopidogrel (Plavix): reduction of Risk of a composite of all-cause mortality, myocardial infarction, ischemia driven revascularization, and stent thrombosis

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/04/16/cangrelor-wins-clopidogrel-plavix-reduction-of-risk-of-a-composite-of-all-cause-mortality-myocardial-infarction-ischemia-driven-revascularization-and-stent-thrombosis/

 

Sets of co-expressed Genes influence Blood Pressure Regulation: Genome-wide Association and mRNA expression @US National Heart, Lung, and Blood Institute

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/04/16/sets-of-co-expressed-genes-influence-blood-pressure-regulation-genome-wide-association-and-mrna-expression-us-national-heart-lung-and-blood-institute/

 

HDL-C: Target of Therapy – Steven E. Nissen, MD, MACC, Cleveland Clinic vs Peter Libby, MD, BWH

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/11/07/hdl-c-target-of-therapy-steven-e-nissen-md-macc-cleveland-clinic-vs-peter-libby-md-bwh/

 

Atrial Fibrillation and Silent Cerebral Infarctions: A Meta Analysis Study and Literature Review

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/11/04/atrial-fibrillation-and-silent-cerebral-infarctions-a-meta-analysis-study-and-literature-review/

 

Intracranial Vascular Stenosis: Comparison of Clinical Trials: Percutaneous Transluminal Angioplasty and Stenting (PTAS) vs. Clot-inhibiting Drugs: Aspirin and Clopidogrel (dual antiplatelet therapy) – more Strokes if Stenting

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/15/intracranial-vascular-stenosis-comparison-of-clinical-trials-percutaneous-transluminal-angioplasty-and-stenting-ptas-vs-clot-inhibiting-drugs-aspirin-and-clopidogrel-dual-antiplatelet-therapy/

 

Hypertension: It is Autoimmunity that Underlies its Development in Humans

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/08/hypertension-it-is-autoimmunity-that-underlies-its-development-in-humans/

 

OPINION LEADERSHIP on Cardiovascular Diseases

Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation

  • Cardiovascular Diseases, Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation. On Amazon.com since 11/30/2015

http://www.amazon.com/dp/B018Q5MCN8

 Epilogue to Volume Two

Author and Curator: Aviva Lev-Ari, PhD, RN, Editor-in-Chief, BioMed e-Series of e-Books

https://pharmaceuticalintelligence.com/2014/07/31/opinion-leadership-on-cardiovascular-diseases/

 

Risk of Major Cardiovascular Events by LDL-Cholesterol Level (mg/dL): Among those treated with high-dose statin therapy, more than 40% of patients failed to achieve an LDL-cholesterol target of less than 70 mg/dL.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/07/29/risk-of-major-cardiovascular-events-by-ldl-cholesterol-level-mgdl-among-those-treated-with-high-dose-statin-therapy-more-than-40-of-patients-failed-to-achieve-an-ldl-cholesterol-target-of-less-th/

 

Commentary on Biomarkers for Genetics and Genomics of Cardiovascular Disease: Views by Larry H Bernstein, MD, FCAP

Commissioned article, Author: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2014/07/16/commentary-on-biomarkers-for-genetics-and-genomics-of-cardiovascular-disease-views-by-larry-h-bernstein-md-fcap/

 

Coagulation Therapy: Leading New Drugs – Efficacy Comparison

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/05/10/coagulation-therapy-leading-new-drugs-efficacy-comparison/

 

Apixaban (Eliquis): Mechanism of Action, Drug Comparison and Additional Indications

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/05/10/apixaban-eliquis-mechanism-of-action-drug-comparison-and-additional-indications/

 

Boston Heart Diagnostics (BHD) offers Statin Induced Myopathy (SLCO1B1) Genotype test and genetic tests targeting ApoE, Factor V Leiden, prothrombin (Factor II), and CYP2C19

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/17/boston-heart-diagnostics-bhd-offers-statin-induced-myopathy-slco1b1-genotype-test-and-genetic-tests-targeting-apoe-factor-v-leiden-prothrombin-factor-ii-and-cyp2c19/

 

@@@ Cardiovascular Diseases and Pharmacological Therapy: Curations by Aviva Lev-Ari, PhD, RN

Curator: Aviva Leve-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/17/cardiovascular-diseases-and-pharmacological-therapy-curations-by-aviva-lev-ari-phd-rn/

 

Richard Lifton, MD, PhD of Yale University & Howard Hughes Medical Institute: Recipient of 2014 Breakthrough Prizes Awarded in Life Sciences for the Discovery of Genes and Biochemical Mechanisms that cause Hypertension

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/03/03/richard-lifton-md-phd-of-yale-university-and-howard-hughes-medical-institute-recipient-of-2014-breakthrough-prizes-awarded-in-life-sciences-for-the-discovery-of-genes-and-biochemical-mechanisms-tha/

 

Differences in Health Services Utilization and Costs between Antihypertensive Medication Users Versus Nonusers in Adults with Diabetes and Concomitant Hypertension from Medical Expenditure Panel Su…

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/28/differences-in-health-services-utilization-and-costs-between-antihypertensive-medication-users-versus-nonusers-in-adults-with-diabetes-and-concomitant-hypertension-from-medical-expenditure-panel-su-2/

 

2014 Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism Conference: San Francisco, Ca. Conference Dates: San Francisco, CA 3/18-21, 2014

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/26/2014-epidemiology-and-prevention-nutrition-physical-activity-and-metabolism-conference-san-francisco-ca-conference-dates-san-francisco-ca-318-21-2014/

 

2014 High Blood Pressure Research Conference, 9/9 – 9/12, 2014 — Hilton SF Union Square, San Francisco, CA

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/24/2014-high-blood-pressure-research-conference-99-912-2014-hilton-sf-union-square-san-francisco-ca/

 

Females and Non-Atherosclerotic Plaque: Spontaneous Coronary Artery Dissection – New Insights from Research and DNA Ongoing Study

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/12/female-and-non-atherosclerotic-plaque-spontaneous-coronary-artery-dissection-new-insights-from-research-and-dna-ongoing-study/

 

Hypertension – JNC 8 Guideline: Henry R. Black, MD, Michael A. Weber, MD and Raymond R. Townsend, MD

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/12/hypertension-jnc-8-guideline-henry-r-black-md-michael-a-weber-md-and-raymond-r-townsend-md/

 

Why Don’t You Trust Generic Drugs as Much as Brand Name …

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/10/why-dont-you-trust-generic-drugs-as-much-as-brand-name/

 

National Trends, 2005 – 2011: Adverse-event Rates Declined among Patients Hospitalized for Acute Myocardial Infarction or Congestive Heart Failure

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/04/national-trends-2005-2011-adverse-event-rates-declined-among-patients-hospitalized-for-acute-myocardial-infarction-or-congestive-heart-failure/

 

Is Pharmacogenetic-based Dosing of Warfarin Superior for Anticoagulation Control?

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/04/is-pharmacogenetic-based-dosing-of-warfarin-superior-for-anticoagulation-control/

 

Prolonged Wakefulness: Lack of Sufficient Duration of Sleep as a Risk Factor for Cardiovascular Diseases – Indications for Cardiovascular Chrono-therapeutics

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/02/prolonged-wakefulness-lack-of-sufficient-duration-of-sleep-as-a-risk-factor-for-cardiovascular-diseases-indications-for-cardiovascular-chrono-therapeutics/

 

Testosterone Therapy for Idiopathic Hypogonadotrophic Hypogonadism has Beneficial and Deleterious Effects on Cardiovascular Risk Factors

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/30/testosterone-therapy-for-idiopathic-hypogonadotrophic-hypogonadism-has-beneficial-and-deleterious-effects-on-cardiovascular-risk-factors/

 

Calcium and Cardiovascular Diseases: A Series of Twelve Articles in Advanced Cardiology

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/28/calcium-and-cardiovascular-diseases-a-series-of-twelve-articles-in-advanced-cardiology/

 

Acute Myocardial Infarction: Curations of Cardiovascular Original Research – A Bibliography

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/22/acute-myocardial-infarction-curations-of-cardiovascular-original-research-a-bibliography/

 

On-Hours vs Off-Hours: Presentation to ER with Acute Myocardial Infarction – Lower Survival Rate if Off-Hours

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/22/on-hours-vs-off-hours-presentation-to-er-with-acute-myocardial-infarction-lower-survival-rate-if-off-hours/

 

2014 Winter in New England: The Effect of Record Cold Temperatures on Cardiovascular Diseases

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/21/2014-winter-in-new-england-the-effect-of-record-cold-temperatures-on-cardiovascular-diseases/

 

Voices from the Cleveland Clinic: On the New Lipid Guidelines and On the ACC/AHA Risk Calculator

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/21/voices-from-the-cleveland-clinic-on-the-new-lipid-guidelines-and-on-the-accaha-risk-calculator/

 

Is it Hypertension or Physical Inactivity: Cardiovascular Risk and Mortality – New results in 3/2013

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/19/is-it-hypertension-or-physical-inactivity-cardiovascular-risk-and-mortality-new-results-in-32013/

 

Regeneration: Cardiac System (cardiomyogenesis) and Vasculature (angiogenesis)

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/15/regeneration-cardiac-system-and-vasculature

 

Conceived: NEW Definition for Co-Curation in Medical Research

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/04/conceived-new-definition-for-co-curation-in-medical-research/

 

The Young Surgeon and The Retired Pathologist: On Science, Medicine and HealthCare Policy – The Best Writers Among the WRITERS

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/12/10/the-young-surgeon-and-the-retired-pathologist-on-science-medicine-and-healthcare-policy-best-writers-among-the-writers/

 

Diabetes-risk Forecasts: Serum Calcium in Upper-Normal Range (>2.5 mmol/L) as a New Biomarker

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/09/25/diabetes-risk-forecasts-serum-calcium-in-upper-normal-range-2-5-mmoll-as-a-new-biomarker/

 

Do Novel Anticoagulants Affect the PT/INR? The Cases of XARELTO (rivaroxaban) or PRADAXA (dabigatran)

Curators: Lal, V., Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/09/23/do-novel-anticoagulants-affect-the-ptinr-the-cases-of-xarelto-rivaroxaban-and-pradaxa-dabigatran/

 

Calcium-Channel Blocker, Calcium Release-related Contractile Dysfunction (Ryanopathy) and Calcium as Neurotransmitter Sensor

Curators: Justin D. Pearlman, MD, PhD, FACC, Larry H. Bernstein, MD FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/09/16/calcium-channel-blocker-calcium-as-neurotransmitter-sensor-and-calcium-release-related-contractile-dysfunction-ryanopathy/

 

Disruption of Calcium Homeostasis: Cardiomyocytes and Vascular Smooth Muscle Cells: The Cardiac and Cardiovascular Calcium Signaling Mechanism

Curators: Larry H. Bernstein, MD FCAP, Justin D. Pearlman, MD, PhD, FACC, and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/09/12/disruption-of-calcium-homeostasis-cardiomyocytes-and-vascular-smooth-muscle-cells-the-cardiac-and-cardiovascular-calcium-signaling-mechanism/

 

Synaptotagmin functions as a Calcium Sensor: How Calcium Ions Regulate the fusion of vesicles with cell membranes during Neurotransmission

Curators:  Larry H. Bernstein, MD FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/09/10/synaptotagmin-functions-as-a-calcium-sensor-how-calcium-ions-regulate-the-fusion-of-vesicles-with-cell-membranes-during-neurotransmission/

 

Cardiac Contractility & Myocardium Performance: Ventricular Arrhythmias and Non-ischemic Heart Failure – Therapeutic Implications for Cardiomyocyte Ryanopathy (Calcium Release-related Contractile Dysfunction) and Catecholamine Responses

Curators: Justin D. Pearlman, MD, PhD, FACC, Larry H. Bernstein, MD FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/28/cardiac-contractility-myocardium-performance-ventricular-arrhythmias-and-non-ischemic-heart-failure-therapeutic-implications-for-cardiomyocyte-ryanopathy-calcium-release-related-contractile/

 

Cardiovascular Original Research: Cases in Methodology Design for Content Curation and Co-Curation

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/29/cardiovascular-original-research-cases-in-methodology-design-for-content-curation-and-co-curation/

 

Heart Transplant (HT) Indication for Heart Failure (HF): Procedure Outcomes and Research on HF, HT @ Two Nation’s Leading HF & HT Centers

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/07/09/research-programs-george-m-linda-h-kaufman-center-for-heart-failure-cleveland-clinic/

 

Congenital Heart Disease (CHD) at Birth and into Adulthood: The Role of Spontaneous Mutations

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/06/09/congenital-heart-disease-at-birth-and-into-adulthood-the-role-of-spontaneous-mutations-the-genes-and-the-pathways/

 

Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/06/03/clinical-indications-for-use-of-inhaled-nitric-oxide-ino-in-the-adult-patient-market-clinical-outcomes-after-use-therapy-demand-and-cost-of-care/

 

Inhaled Nitric Oxide in Adults: Clinical Trials and Meta Analysis Studies – Recent Findings

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/06/02/inhaled-nitric-oxide-in-adults-with-acute-respiratory-distress-syndrome/

 

Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management

Curators: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/05/24/imaging-biomarker-for-arterial-stiffness-pathways-in-pharmacotherapy-for-hypertension-and-hypercholesterolemia-management/

 

Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/05/17/synthetic-biology-on-advanced-genome-interpretation-for-gene-variants-and-pathways-what-is-the-genetic-base-of-atherosclerosis-and-loss-of-arterial-elasticity-with-aging/

 

Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems

Curators: Justin D. Pearlman, MD, PhD, FACC, Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/15/diagnosis-of-cardiovascular-disease-treatment-and-prevention-current-predicted-cost-of-care-and-the-promise-of-individualized-medicine-using-clinical-decision-support-systems-2/

 

Gene, Meis1, Regulates the Heart’s Ability to Regenerate after Injuries.

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/05/03/gene-meis1-regulates-the-hearts-ability-to-regenerate-after-injuries/

 

Prostacyclin and Nitric Oxide: Adventures in Vascular Biology – A Tale of Two Mediators

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/04/30/prostacyclin-and-nitric-oxide-adventures-in-vascular-biology-a-tale-of-two-mediators/

 

Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/04/28/genetics-of-conduction-disease-atrioventricular-av-conduction-disease-block-gene-mutations-transcription-excitability-and-energy-homeostasis/

 

Economic Toll of Heart Failure in the US: Forecasting the Impact of Heart Failure in the United States – A Policy Statement From the American Heart Association

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/04/25/economic-toll-of-heart-failure-in-the-us-forecasting-the-impact-of-heart-failure-in-the-united-states-a-policy-statement-from-the-american-heart-association/

 

Harnessing New Players in Atherosclerosis to Treat Heart Disease

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/04/25/harnessing-new-players-in-atherosclerosis-to-treat-heart-disease/

 

Cholesteryl Ester Transfer Protein (CETP) Inhibitor: Potential of Anacetrapib to treat Atherosclerosis and CAD

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/04/07/cholesteryl-ester-transfer-protein-cetp-inhibitor-potential-of-anacetrapib-to-treat-atherosclerosis-and-cad/

 

Hypertriglyceridemia concurrent Hyperlipidemia: Vertical Density Gradient Ultracentrifugation a Better Test to Prevent Undertreatment of High-Risk Cardiac Patients

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/04/04/hypertriglyceridemia-concurrent-hyperlipidemia-vertical-density-gradient-ultracentrifugation-a-better-test-to-prevent-undertreatment-of-high-risk-cardiac-patients/

 

Fight against Atherosclerotic Cardiovascular Disease: A Biologics not a Small Molecule – Recombinant Human lecithin-cholesterol acyltransferase (rhLCAT) attracted AstraZeneca to acquire AlphaCore

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/04/03/fight-against-atherosclerotic-cardiovascular-disease-a-biologics-not-a-small-molecule-recombinant-human-lecithin-cholesterol-acyltransferase-rhlcat-attracted-astrazeneca-to-acquire-alphacore/

 

High-Density Lipoprotein (HDL): An Independent Predictor of Endothelial Function & Atherosclerosis, A Modulator, An Agonist, A Biomarker for Cardiovascular Risk

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/03/31/high-density-lipoprotein-hdl-an-independent-predictor-of-endothelial-function-artherosclerosis-a-modulator-an-agonist-a-biomarker-for-cardiovascular-risk/ 

 

Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA’s Circulation Cardiovascular Genetics, 3/2010 – 3/2013

Curators: Aviva Lev-Ari, PhD, RN and Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2013/03/07/genomics-genetics-of-cardiovascular-disease-diagnoses-a-literature-survey-of-ahas-circulation-cardiovascular-genetics-32010-32013/

 

The Heart: Vasculature Protection – A Concept-based Pharmacological Therapy including THYMOSIN

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/02/28/the-heart-vasculature-protection-a-concept-based-pharmacological-therapy-including-thymosin/

 

Thymosin References

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/02/27/thymosin-references/

 

Arteriogenesis and Cardiac Repair: Two Biomaterials – Injectable Thymosin beta4 and Myocardial Matrix Hydrogel

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2013/02/27/arteriogenesis-and-cardiac-repair-two-biomaterials-injectable-thymosin-beta4-and-myocardial-matrix-hydrogel/

 

PCI Outcomes, Increased Ischemic Risk associated with Elevated Plasma Fibrinogen not Platelet Reactivity

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/01/10/pci-outcomes-increased-ischemic-risk-associated-with-elevated-plasma-fibrinogen-not-platelet-reactivity/

 

Heart Renewal by pre-existing Cardiomyocytes: Source of New Heart Cell Growth Discovered

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/12/23/heart-renewal-by-pre-existing-cardiomyocytes-source-of-new-heart-cell-growth-discovered/

 

Special Considerations in Blood Lipoproteins, Viscosity, Assessment and Treatment

Curators: Larry H. Bernstein and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/11/28/special-considerations-in-blood-lipoproteins-viscosity-assessment-and-treatment/

 

Peroxisome proliferator-activated receptor (PPAR-gamma) Receptors Activation: PPARγ transrepression for Angiogenesis in Cardiovascular Disease and PPARγ transactivation for Treatment of Diabetes

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/11/13/peroxisome-proliferator-activated-receptor-ppar-gamma-receptors-activation-pparγ-transrepression-for-angiogenesis-in-cardiovascular-disease-and-pparγ-transactivation-for-treatment-of-dia/

 

Cardiovascular Risk Inflammatory Marker: Risk Assessment for Coronary Heart Disease and Ischemic Stroke – Atherosclerosis.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/10/30/cardiovascular-risk-inflammatory-marker-risk-assessment-for-coronary-heart-disease-and-ischemic-stroke-atherosclerosis/

 

Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination?

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/10/19/clinical-trials-results-for-endothelin-system-pathophysiological-role-in-chronic-heart-failure-acute-coronary-syndromes-and-mi-marker-of-disease-severity-or-genetic-determination/

 

Sustained Cardiac Atrial Fibrillation: Management Strategies by Director of the Arrhythmia Service and Electrophysiology Lab at The Johns Hopkins Hospital

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/10/16/sustained-cardiac-atrial-fibrillation-management-strategies-by-director-of-the-arrhythmia-service-and-electrophysiology-lab-at-the-johns-hopkins-hospital/

 

Endothelin Receptors in Cardiovascular Diseases: The Role of eNOS Stimulation

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/10/04/endothelin-receptors-in-cardiovascular-diseases-the-role-of-enos-stimulation/

 

Inhibition of ET-1, ETA and ETA-ETB, Induction of NO production, stimulation of eNOS and Treatment Regime with PPAR-gamma agonists (TZD): cEPCs Endogenous Augmentation for Cardiovascular Risk Reduction – A Bibliography

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/10/04/inhibition-of-et-1-eta-and-eta-etb-induction-of-no-production-and-stimulation-of-enos-and-treatment-regime-with-ppar-gamma-agonists-tzd-cepcs-endogenous-augmentation-for-cardiovascular-risk-reduc/

Positioning a Therapeutic Concept for Endogenous Augmentation of cEPCs — Therapeutic Indications for Macrovascular Disease: Coronary, Cerebrovascular and Peripheral

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/08/29/positioning-a-therapeutic-concept-for-endogenous-augmentation-of-cepcs-therapeutic-indications-for-macrovascular-disease-coronary-cerebrovascular-and-peripheral/ 

 

Cardiovascular Outcomes: Function of circulating Endothelial Progenitor Cells (cEPCs): Exploring Pharmaco-therapy targeted at Endogenous Augmentation of cEPCs

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/08/28/cardiovascular-outcomes-function-of-circulating-endothelial-progenitor-cells-cepcs-exploring-pharmaco-therapy-targeted-at-endogenous-augmentation-of-cepcs/

 

Endothelial Dysfunction, Diminished Availability of cEPCs, Increasing CVD Risk for Macrovascular Disease – Therapeutic Potential of cEPCs

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/08/27/endothelial-dysfunction-diminished-availability-of-cepcs-increasing-cvd-risk-for-macrovascular-disease-therapeutic-potential-of-cepcs/

 

Vascular Medicine and Biology: Classification of Fast Acting Therapy for Patients at High Risk for Macrovascular Events – Macrovascular Disease – Therapeutic Potential of cEPCs

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/08/24/vascular-medicine-and-biology-classification-of-fast-acting-therapy-for-patients-at-high-risk-for-macrovascular-events-macrovascular-disease-therapeutic-potential-of-cepcs/

 

 

Ethical Considerations in Studying Drug Safety — The Institute of Medicine Report

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/08/23/ethical-considerations-in-studying-drug-safety-the-institute-of-medicine-report/

 

Cardiac Arrhythmias: A Risk for Extreme Performance Athletes

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/08/08/cardiac-arrhythmias-a-risk-for-extreme-performance-athletes/

 

Biosimilars: Intellectual Property Creation and Protection by Pioneer and by Biosimilar Manufacturers

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/07/30/biosimilars-intellectual-property-creation-and-protection-by-pioneer-and-by-biosimilar-manufacturers/

 

Biosimilars: Financials 2012 vs. 2008

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/07/30/biosimilars-financials-2012-vs-2008/

 

Biosimilars: CMC Issues and Regulatory Requirements

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/07/29/biosimilars-cmc-issues-and-regulatory-requirements/

 

Cardiovascular Disease (CVD) and the Role of agent alternatives in endothelial Nitric Oxide Synthase (eNOS) Activation and Nitric Oxide Production

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/07/19/cardiovascular-disease-cvd-and-the-role-of-agent-alternatives-in-endothelial-nitric-oxide-synthase-enos-activation-and-nitric-oxide-production/

 

Resident-cell-based Therapy in Human Ischaemic Heart Disease: Evolution in the PROMISE of Thymosin beta4 for Cardiac Repair

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/04/30/93/

 

Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/05/29/445/

 

Macrovascular Disease – Therapeutic Potential of cEPCs: Reduction Methods for CV Risk

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/07/02/macrovascular-disease-therapeutic-potential-of-cepcs-reduction-methods-for-cv-risk/

 

Mitochondria Dysfunction and Cardiovascular Disease – Mitochondria: More than just the “powerhouse of the cell”

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/07/09/mitochondria-more-than-just-the-powerhouse-of-the-cell/

 

Bystolic’s generic Nebivolol – positive effect on circulating Endothelial Progenitor Cells endogenous augmentation

Curator: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2012/07/16/bystolics-generic-nebivolol-positive-effect-on-circulating-endothilial-progrnetor-cells-endogenous-augmentation/

Lev-Ari, A. Heart Vasculature (2007) Regeneration and Protection of Coronary Artery Endothelium and Smooth Muscle: A Concept-based Pharmacological Therapy of a Combined Three Drug Regimen.

Bouve College of Health Sciences, Northeastern University, Boston, MA 02115

 

Lev-Ari, A. & Abourjaily, P. (2006a) “An Investigation of the Potential of circulating Endothelial Progenitor Cells (cEPC) as a Therapeutic Target for Pharmacologic Therapy Design for Cardiovascular Risk Reduction.”

  • Part I: Macrovascular Disease – Therapeutic Potential of cEPCs – Reduction methods for CV risk.
  • Part II:(2006b) Therapeutic Strategy for cEPCs Endogenous Augmentation: A Concept-based Treatment Protocol for a Combined Three Drug Regimen.
  • Part III: (2006c)Biomarker for Therapeutic Targets of Cardiovascular Risk Reduction by cEPCs Endogenous Augmentation using New Combination Drug Therapy of Three Drug Classes and Several Drug Indications.

Northeastern University, Boston, MA 02115

 

Curator: Medical Research – 557 articles in Books

Editorial & Publication of Articles in e-Books by Leaders in Pharmaceutical Business Intelligence: Contributions of Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/16/editorial-publication-of-articles-in-e-books-by-leaders-in-pharmaceutical-business-intelligence-contributions-of-aviva-lev-ari-phd-rn/

 

 

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Stem-Cell Therapy for Ischemic Heart Failure: Clinical Trial MSC Demonstrates Efficacy

Posted in Cardiac and Cardiovascular Surgical Procedures, Cell Biology, Signaling & Cell Circuits, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Origins of Cardiovascular Disease, Regenerative Biology and Medicine, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Resident-cell-based, Stem Cells for Regenerative Medicine on April 8, 2014| Leave a Comment »

Stem-Cell Therapy for Ischemic Heart Failure: Clinical Trial MSC Demonstrates Efficacy

Reporter: Aviva Lev-Ari, PhD, RN

Medscape Medical News from the

This coverage is not sanctioned by, nor a part of, the American College of Cardiology.

MSC Trial: Stem-Cell Therapy for Ischemic HF Inches Forward

April 04, 2014

Receive an email from Medscape whenever new articles on this topic are available.

 WASHINGTON, DC — It was with heavier hearts that ischemic heart-failure patients concluded therapy in a recent randomized trial. More precisely, it was with greater end-systolic myocardial mass and perhaps less myocardial scar.

They had been assigned to receive intramyocardial injections of autologous mesenchymal stromal cells (MSC), a kind of stem cell, for their ischemic heart disease. After six months, their proportion of functional heart muscle had gone up along with LV end-systolic volumes, stroke volume, and LVEF, compared with control patients who had received similar intramyocardial injections of saline.

Those gains, however, failed to translate into clinical benefit as measured by NYHA class and six-minute-walk distance. Interestingly, those measures did improve significantly for patients who received the cell therapy, but also for patients in the control group.

The MSC-HF trial, which entered 59 patients with chronic ischemic heart failure despite maximal medications for whom coronary revascularization wasn’t an option, was reported here this week by Dr Anders Bruun Mathiasen (Rigshospitalet University Hospital Copenhagen, Denmark) at the American College of Cardiology 2014 Scientific Sessions . Those with LVEF <45% and in NYHA functional class 2 to 3 were eligible; the group’s average LVEF was 28%.

At a briefing for media, Dr James B Hermiller (St Vincent Hospital, Indianapolis, IN) said that the trial showed “very dramatic improvements in metrics of heart performance,” but that what might have been functional improvements seemed to be lost in a marked placebo effect among controls. Hermiller wasn’t part of the MSC trial.

The 59 patients had been randomized 2:1 to cell therapy or placebo; MSCs were obtained from all patients, their numbers amplified in the laboratory, and then injected into ischemic viable myocardial regions guided by the NOGA XP (Cordis) catheter-based navigation system.

Of the randomized patients, 37 of the 39 getting cell therapy and 18 of the 20 controls were available for a six-month follow-up. At that time, mean LV end-systolic volume, LVEF, stroke volume, and end-systolic myocardial mass had improved significantly in the MSC-therapy group, both with respect to baseline levels and vs the control group.

Changes in Cardiac Measures Six Months after Mesenchymal Stromal Cell (MSC) Therapy or Placebo in MSC-FH

End points at 6 mo MSC group (p vs baseline) Placebo p (MSC vs placebo)
LV end-systolic volume* (mL) -8.2 (0.001) +6.0 0.001
LVEF (percentage points) +5 (<0.0001) -1.4 <0.0001
Stroke volume (mL) +17.4 (<0.002) -3.1 <0.0001
End-systolic myocardial mass (g) +10.1 (<0.0001) -2.1 <0.0001
Scar-tissue mass (g) -4.4 (<0.017) -0.5 NS

*By MRI or CT, primary end point

There were no such differences in LV end-diastolic volume or LV end-diastolic myocardial mass. The MSC group showed significant improvements vs baseline in NYHA class (p<0.0001), six-minute-walk distance (p=0.001), and overall score on the Kansas City Cardiomyopathy Questionnaire (p=0.0001). But then so did the control group (p=0.001, 0.0004, and 0.003, respectively).

There were no significant differences in severe adverse events, including MI, stroke, HF worsening, syncope, need for revascularization, arrhythmias, or need for implantable defibrillators or biventricular pacemakers.

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Dr William O’Neill (Henry Ford Hospital, Detroit, MI), speaking from the panel following Mathiasen’s presentation of the study, noted that it continues a longtime trend in trials of cell therapyfor cardiomyopathy in having a small sample size. “We still aren’t even close to having this as an accepted mainstay therapy. And I think the challenge for you is to prove that there’s actually clinical benefit by a five-percentage-point increase in ejection fraction when the patients feel equally well in both groups. I wonder how is it that this field is going to progress if we do see some modest benefit in LV function but no other clinical correlates.”

Mathiasen replied, “We are going to follow this study up with a phase 3 trial that will run across six centers in Europe and will treat 140 patients also randomized in a 2:1 pattern. These patients will receive injections of either placebo or allogeneic MSAs from adipose tissue.” And “it will be powered for the same end points as this trial.”

Mathiasen had no disclosures. Hermiller discloses receiving consulting fees or honoraria from St Jude Medical, Abbott Vascular, Boston Scientific, and Medtronic. O’Neill discloses receiving consulting fees or honoraria from Medtronic and Edwards Lifesciences, being an officer or director for Neovasc, and having an ownership stake in or being a partner or other principal with Accumed Systems and Syntheon Cardiology.

 

SOURCE

http://www.medscape.com/viewarticle/823123?nlid=53983_2562&src=wnl_edit_medp_card&uac=93761AJ&spon=2

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ATVB (Arteriosclerosis, Thrombosis and Vascular Biology) 2014 Conference 5/1 – 5/3/2014, Sheraton Centre Toronto – Toronto, Ontario

Posted in Atherogenic Processes & Pathology, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Origins of Cardiovascular Disease, Peripheral Arterial Disease & Peripheral Vascular Surgery, Resident-cell-based, Stem Cells for Regenerative Medicine, Translational Science on March 5, 2014| Leave a Comment »

ATVB (Arteriosclerosis, Thrombosis and Vascular Biology) 2014 Conference  5/1 – 5/3/2014, Sheraton Centre Toronto – Toronto, Ontario

Reporter: Aviva Lev-Ari, PhD, RN

ATVB 2014 Early Registration closes TODAY!
Register NOW and get the BEST rates! 

ATVB 2014

Conference Dates/Location
Thursday, May 1 through Saturday,
May 3, 2014
Sheraton Centre Toronto – Toronto, Ontario

 

ATVB 2014 Scientific Sessions

Register Now

ATVB Council

PVD Council

FGTB Council

  Organized by the Arteriosclerosis, Thrombosis and Vascular Biology Council with participation by the Councils on Peripheral Vascular Disease and Functional Genomics and Translational Biology

 

Register Now to join your colleagues at the Sheraton Centre Toronto on May 1-3 for the ATVB 2014 Scientific Sessions. Meet and network with colleagues from around the world with wide-ranging common interests and expertise in arteriosclerosis, thrombosis, vascular biology, functional genomics, peripheral vascular disease, and vascular surgery research.

 

http://view.heartemail.org/?j=fe52107676610c79731d&m=fe6715707463057a7513&ls=fdbf1571746c01757614787262&l=fe8c1372706d057576&s=fded1576716c007d71137972&jb=ffcf14&ju=fe2917797565027b7d1170&r=0

ATVB 2014 Scientific Sessions

http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/@scon/documents/downloadable/ucm_451535.pdf

Join or renew your AHA/ASA Professional Membership by February 19 and save up to $300 on conference registration. Affiliate with one of these Councils:
Council for Arteriosclerosis, Thrombosis and Vascular Biology
Council on Peripheral Vascular Disease
Council on Functional Genomics and Translational Biology
(Please use Promo code WEJ003ZZ)  

For detailed conference information and For detailed conference information and updates, including program, travel awards, venue and lodging information, visit the conference website.

Sponsored by the American Heart Association’s Council on Arteriosclerosis, Thrombosis and Vascular Biology, Council on Functional Genomics and Translational Biology and Council on Peripheral Vascular Disease.

Contact Us:

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phone: (214) 570-5935or (888) 242-2453

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Regeneration: Cardiac System (cardiomyogenesis) and Vasculature (angiogenesis)

Posted in Cardiovascular Research, Frontiers in Cardiology and Cardiovascular Disorders, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Origins of Cardiovascular Disease, Pre-Clinical Animal Model Development, Regenerative Biology and Medicine, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Resident-cell-based, Stem Cells for Regenerative Medicine, tagged , , , , on January 15, 2014| Leave a Comment »

Regeneration: Cardiac System (cardiomyogenesis) and Vasculature (angiogenesis)

Author and Curator: Aviva Lev-Ari, PhD, RN

 

UPDATED on 4/8/2014

Stem-Cell Therapy for Ischemic Heart Failure: Clinical Trial MSC Demonstrates Efficacy

http://pharmaceuticalintelligence.com/2014/04/08/stem-cell-therapy-for-ischemic-heart-failure-clinical-trial-msc-demonstrates-efficacy/ 

This article represents the FRONTIER on Cardiac Regeneration as developed by Anthony Rosenzweig in Science 338, 1549 (2012).

Point #1: Current Pharmacotherapy for Cardiovascular Diseases and Heart Failure

Point #2: Dynamic model for the Adult heart capacity for cardiomyogenesis to compensate for losses occurring in heart failure: recognition of even limited regenerative capacity in the heart 

Point #3: Results of Multiple Cell Therapy Clinical Trials

Point #4:  The Endogenous Regeneration Potential

Point #5: On pathways regulating cardiomyocyte regeneration in animal models

Point #6: Prof. A. Rosenzweig’s Summary and His Future Outlook of Cardiac Regeneration

This article represents a continuation of the following articles on this topic that were published in this Open Access Online Scientific Journal:

Bernstein HL and A. Lev-Ari 1/14/2014 Circulating Endothelial Progenitors Cells (cEPCs) as Biomarkers

http://pharmaceuticalintelligence.com/2014/01/14/circulating-endothelial-progenitors-cells-as-biomarkers/

Lev-Ari, A. 2/28/2013 The Heart: Vasculature Protection – A Concept-based Pharmacological Therapy including THYMOSIN

http://pharmaceuticalintelligence.com/2013/02/28/the-heart-vasculature-protection-a-concept-based-pharmacological-therapy-including-thymosin/

Lev-Ari, A. 2/27/2013 Arteriogenesis and Cardiac Repair: Two Biomaterials – Injectable Thymosin beta4 and Myocardial Matrix Hydrogel

http://pharmaceuticalintelligence.com/2013/02/27/arteriogenesis-and-cardiac-repair-two-biomaterials-injectable-thymosin-beta4-and-myocardial-matrix-hydrogel/

Lev-Ari, A. 11/13/2012 Peroxisome proliferator-activated receptor (PPAR-gamma) Receptors Activation: PPARγ transrepression for Angiogenesis in Cardiovascular Disease and PPARγ transactivation for Treatment of Diabetes

http://pharmaceuticalintelligence.com/2012/11/13/peroxisome-proliferator-activated-receptor-ppar-gamma-receptors-activation-pparγ-transrepression-for-angiogenesis-in-cardiovascular-disease-and-pparγ-transactivation-for-treatment-of-dia/

Lev-Ari, A. 8/29/2012 Positioning a Therapeutic Concept for Endogenous Augmentation of cEPCs — Therapeutic Indications for Macrovascular Disease: Coronary, Cerebrovascular and Peripheral

http://pharmaceuticalintelligence.com/2012/08/29/positioning-a-therapeutic-concept-for-endogenous-augmentation-of-cepcs-therapeutic-indications-for-macrovascular-disease-coronary-cerebrovascular-and-peripheral/

Lev-Ari, A. 8/28/2012 Cardiovascular Outcomes: Function of circulating Endothelial Progenitor Cells (cEPCs): Exploring Pharmaco-therapy targeted at Endogenous Augmentation of cEPCs

http://pharmaceuticalintelligence.com/2012/08/28/cardiovascular-outcomes-function-of-circulating-endothelial-progenitor-cells-cepcs-exploring-pharmaco-therapy-targeted-at-endogenous-augmentation-of-cepcs/

Lev-Ari, A. 8/27/2012 Endothelial Dysfunction, Diminished Availability of cEPCs, Increasing CVD Risk for Macrovascular Disease – Therapeutic Potential of cEPCs

http://pharmaceuticalintelligence.com/2012/08/27/endothelial-dysfunction-diminished-availability-of-cepcs-increasing-cvd-risk-for-macrovascular-disease-therapeutic-potential-of-cepcs/

Lev-Ari, A. 8/24/2012 Vascular Medicine and Biology: CLASSIFICATION OF FAST ACTING THERAPY FOR PATIENTS AT HIGH RISK FOR MACROVASCULAR EVENTS Macrovascular Disease – Therapeutic Potential of cEPCs

http://pharmaceuticalintelligence.com/2012/08/24/vascular-medicine-and-biology-classification-of-fast-acting-therapy-for-patients-at-high-risk-for-macrovascular-events-macrovascular-disease-therapeutic-potential-of-cepcs/

Lev-Ari, A. 7/19/2012 Cardiovascular Disease (CVD) and the Role of agent alternatives in endothelial Nitric Oxide Synthase (eNOS) Activation and Nitric Oxide Production

http://pharmaceuticalintelligence.com/2012/07/19/cardiovascular-disease-cvd-and-the-role-of-agent-alternatives-in-endothelial-nitric-oxide-synthase-enos-activation-and-nitric-oxide-production/

Lev-Ari, A. 4/30/2012 Resident-cell-based Therapy in Human Ischaemic Heart Disease: Evolution in the PROMISE of Thymosin beta4 for Cardiac Repair

http://pharmaceuticalintelligence.com/2012/04/30/93/

Lev-Ari, A. 7/2/2012 Macrovascular Disease – Therapeutic Potential of cEPCs: Reduction Methods for CV Risk

http://pharmaceuticalintelligence.com/2012/07/02/macrovascular-disease-therapeutic-potential-of-cepcs-reduction-methods-for-cv-risk/

This article represent the FRONTIER on Cardiac Regeneration as developed by Anthony Rosenzweig in Science 338, 1549 (2012).

Prof. A. Rosenzweig is with the Cardiovascular Division at Beth Israel Deaconess Medical Center, Harvard Medical School, and the Harvard Stem Cell Institute, Boston, MA 02215, USA. E-mail: arosenzw@bidmc.harvard.edu

In the United States, heart failure afflicts about 6 million people (1), costs $34.4 billion each year (2), and is now the single most common discharge diagnosis in those over 65 (3). Although enormous progress has been made in managing acute cardiovascular illnesses such as heart attacks, many patients go on to develop late sequelae of their disease, including heart failure and arrhythmia. Thus, the growing number of these patients in some ways represents a burden of our success. It also reflects the incomplete success of most current therapies, which mitigate and manage but do not cure the disease.

Point #1: Current Pharmacotherapy for Cardiovascular Diseases and Heart Failure include:

  • Beta-blockers
  • Angiotensin-converting enzyme inhibitors, and
  • Mineralocorticoid antagonists – in congestive heart failure, they are used in addition to other drugs for additive diuretic effect, which reduces edema and the cardiac workload, and Potassium-sparing diuretics are diuretic drugs that do not promote the secretion of potassium into the urine

These medicines block pathways that are likely compensatory initially but become progressively more maladaptive, thus, prognosis and quality of life remain poor for many heart failure patients.

Point #2: Dynamic model for the Adult heart capacity for cardiomyogenesis to compensate for losses occurring in heart failure: recognition of even limited regenerative capacity in the heart

  • The heart has some endogenous regenerative potential
  • New cardiomyocytes may arise from existing cardiomyocytes  and from
  • Progenitor or stem cells

Point #3: Results of Multiple Cell Therapy Clinical Trials

  • the largest randomized trial thus far— the REPAIR-AMI trial which delivered unfractionated bone marrow cells (BMCs) to patients after a heart attack—as well as
  • a recent meta-analysis of 50 similar trials enrolling 2625 patients (16) suggest that adverse clinical events may actually be less common in BMC-treated patients
  • Autologous BMCs are by far the most common cells used to date but have yielded mixed results. Two recent trials report results with heart-derived donor cells are summariezed, below.  Although both of these studies break new conceptual ground, it is still too early to know how these approaches will hold up in larger studies or impact clinical outcomes, and whether heart-derived cells will have demonstrable advantages over other cell types.

1. The SCIPIO trial targeted patients with cardiac dysfunction undergoing bypass surgery for subsequent delivery of c-kit–positive cells derived from heart tissue harvested at surgery. In interim analyses, cardiac function was substantially better at 4 months in the 14 cell-treated patients available for comparison to seven control patients.

2. In CADUCEUS, autologous cells derived from cardiospheres grown from cardiac biopsies (CDCs) were delivered to patients randomized after myocardial infarction to receive CDCs or usual care. In this trial, although overall heart function was not significantly improved by cell treatment, scar (determined by magnetic resonance imaging) was reduced at 6 and 12 months in the 17 CDC-treated patients but unchanged in the eight control patients.

Point #4:  The Endogenous Regeneration Potential

  • Donor cells have often been selected for their apparent ability to form new cardiomyocytes, the limited clinical data available suggest that relatively few of the donor cells may remain in the heart (20).
  • Other benefits of the cells or molecules delivered with them could include enhanced angiogenesis, cardiomyocyte survival, or endogenous regeneration.
  • The success or failure of cardiovascular cell therapy will ultimately depend on its ability to improve clinical outcomes whatever the mechanisms, and advocates argue that
  • the donor cells may provide a particularly potent mixture of salutary effects. However,
  • the complex and sometimes heterogeneous cell preparations being infused make standardization and reconciling discrepant results particularly challenging. It seems likely that
  • identification and purification of the essential cellular and molecular components mediating any observed benefits will ultimately provide the most effective, safe, and consistent approach.

Point #5: On pathways regulating cardiomyocyte regeneration in animal models

  • Recent work has begun to elucidate the settings and pathways regulating cardiomyocyte regeneration in animal models. Porrello et al. demonstrated a remarkable though transient regenerative capacity of the neonatal murine heart (14), and
  • related studies have begun to define the signaling mechanisms leading to withdrawal of cardiomyocytes from the cell cycle (21).
  • The Hippo pathway is a potent negative regulator of Wnt signaling and cardiomyocyte proliferation (22), which also intersects via Yap with insulin growth factor I (IGF-I) signaling (23).
  • How effectively these pathways can be coopted to promote regeneration after injury is of great interest.
  • Individual pathways may also have multiple effects.
  • Huang et al. ( 24) demonstrate that C/EBP inhibition, previously implicated in exercise-induced cardiac growth and possible cardiomyogenesis (25), also reduces ischemic injury by mitigating inflammation. In addition to
  • Endogenous pathways, reprogramming resident nonprogenitor cells such as fibroblasts through gene delivery has generated contractile cardiomyocyte-like cells (26, 27) that mitigate scar formation and improve function after heart attacks in mice (28).
  • These promising developments have yet to be translated clinically but could provide a path to cardiac repair that obviates the need for exogenous cells.

Point #6: Prof. A. Rosenzweig’s Summary and His Future Outlook of Cardiac Regeneration

  • We are still relatively early in the development of new approaches to cardiovascular disease. It will be some time before we know the conclusion of what will likely be a long and challenging road ahead.
  • Almost as challenging is conveying to patients and policymakers an appropriate perspective that balances unmitigated enthusiasm for the scientific discoveries, cautious optimism for the broader implications, and humble acknowledgment that though even the most appealing ideas may fail, there is only one way to find out.

REFERENCES and NOTES in  Science 338, 1549 (2012).

1. V. L. Roger et al., Circulation 125, e2 (2012).

2. CDC (2012), http://www.cdc.gov/dhdsp/data_statistics/fact_

sheets/docs/fs_heart_failure.pdf

3. C. J. DeFrances, M. N. Podgornik, Adv. Data 371, 1

(2006).

4. T. E. Owan et al., N. Engl. J. Med. 355, 251 (2006).

5. R. S. Bhatia et al., N. Engl. J. Med. 355, 260 (2006).

6. J. Narula et al., N. Engl. J. Med. 335, 1182 (1996).

7. G. Olivetti et al., N. Engl. J. Med. 336, 1131 (1997).

8. A. P. Beltrami et al., Cell 114, 763 (2003).

9. K. Bersell, S. Arab, B. Haring, B. Kühn, Cell 138, 257

(2009).

10. P. C. H. Hsieh et al., Nat. Med. 13, 970 (2007).

11. O. Bergmann et al., Science 324, 98 (2009).

12. J. Kajstura et al., Circ. Res. 107, 305 (2010).

13. K. Kikuchi et al., Nature 464, 601 (2010).

14. E. R. Porrello et al., Science 331, 1078 (2011).

15. V. Schächinger et al., N. Engl. J. Med. 355, 1210 (2006).

16. V. Jeevanantham et al., Circulation 126, 551 (2012).

17. A. Rosenzweig, N. Engl. J. Med. 355, 1274 (2006).

18. R. Bolli et al., Lancet 378, 1847 (2011).

19. R. R. Makkar et al., Lancet 379, 895 (2012).

20. M. Hofmann et al., Circulation 111, 2198 (2005).

21. E. R. Porrello et al., Circ. Res. 109, 670 (2011).

22. T. Heallen et al., Science 332, 458 (2011).

23. M. Xin et al., Sci. Signal. 4, ra70 (2011).

24. G. N. Huang et al., Science 338, 1599 (2012);

10.1126/science.1229765.

25. P. Boström et al., Cell 143, 1072 (2010).

26. M. Ieda et al., Cell 142, 375 (2010).

27. L. Qian et al., Nature 485, 593 (2012).

28. K. Song et al., Nature 485, 599 (2012).

 

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The Cost to Value Conundrum in Cardiovascular Healthcare Provision

Posted in Accountable Care Organizations, Affordable Care Act, Anemia, Atherogenic Processes & Pathology, Best evidence, Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Ca2+ triggered activation, Ca2+ triggered activation, Calcium Signaling, Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Cardiac muscle regeneration, Cardiomyopathy, Cardiovascular Pharmacogenomics, Coagulation Therapy and Internal Bleeding, Computational Biology/Systems and Bioinformatics, Curation, Curation methodology, Cytoskeleton, Diabetes Mellitus, Electrophysiology, Evidence-based decision-making, Experimental validation, Federal Budget Appropriations, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, Health Law & Patient Safety, Healthcare costs and reimbursement, Healthcare Reform, Historical relevance, HTN, HTN in Youth, Indigent Nutrition, Interviews with Scientific Leaders, Ionic Transporters Na+, K, Medical Devices R&D and Inventions, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Medicare and Medicaid, Na-K transport, Na-K-ATPase, Nephrology, Nitric Oxide in Health and Disease, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Pharmaceutical Analytics, Pharmacogenomics, Pharmacologic toxicities, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Prescription Drugs Costs, Regenerative Biology and Medicine, Resident-cell-based, Skilled Nursing Facilities, Stem Cells for Regenerative Medicine, Stents & Tools, Synaptic vesicle, Systematic Error (Bias), Systemic Inflammatory Response Related Disorders, Technology Advance Assessment of, Technology Capital Expenses, Technology Transfer: Biotech and Pharmaceutical, Translational Effectiveness, Translational Science, Uninsured and Underinsured, Valves & Tools, tagged , , , , , , , , , , , , , , , , , , , , , , , , , on January 1, 2014| Leave a Comment »

The Cost to Value Conundrum in Cardiovascular Healthcare Provision

Author: Larry H. Bernstein, MD, FCAP

I write this introduction to Volume 2 of the e-series on Cardiovascular Diseases, which curates the basic structure and physiology of the heart, the vasculature, and related structures, e.g., the kidney, with respect to:

1. Pathogenesis
2. Diagnosis
3. Treatment

Curation is an introductory portion to Volume Two, which is necessary to introduce the methodological design used to create the following articles. More needs not to be discussed about the methodology, which will become clear, if only that the content curated is changing based on success or failure of both diagnostic and treatment technology availability, as well as the systems needed to support the ongoing advances.  Curation requires:

  • meaningful selection,
  • enrichment, and
  • sharing combining sources and
  • creation of new synnthesis

Curators have to create a new perspective or idea on top of the existing media which supports the content in the original. The curator has to select from the myriad upon myriad options available, to re-share and critically view the work. A search can be overwhelming in size of the output, but the curator has to successfully pluck the best material straight out of that noise.

Part 1 is a highly important treatment that is not technological, but about the system now outdated to support our healthcare system, the most technolog-ically advanced in the world, with major problems in the availability of care related to economic disparities.  It is not about technology, per se, but about how we allocate healthcare resources, about individuals’ roles in a not full list of lifestyle maintenance options for self-care, and about the important advances emerging out of the Affordable Care Act (ACA), impacting enormously on Medicaid, which depends on state-level acceptance, on community hospital, ambulatory, and home-care or hospice restructuring, which includes the reduction of management overhead by the formation of regional healthcare alliances, the incorporation of physicians into hospital-based practices (with the hospital collecting and distributing the Part B reimbursement to the physician, with “performance-based” targets for privileges and payment – essential to the success of an Accountable Care Organization (AC)).  One problem that ACA has definitively address is the elimination of the exclusion of patients based on preconditions.  One problem that has been left unresolved is the continuing existence of private policies that meet financial capabilities of the contract to provide, but which provide little value to the “purchaser” of care.  This is a holdout that persists in for-profit managed care as an option.  A physician response to the new system of care, largely fostered by a refusal to accept Medicaid, is the formation of direct physician-patient contracted care without an intermediary.

In this respect, the problem is not simple, but is resolvable.  A proposal for improved economic stability has been prepared by Edward Ingram. A concern for American families and businesses is substantially addressed in a macroeconomic design concept, so that financial services like housing, government, and business finance, savings and pensions, boosting confidence at every level giving everyone a better chance of success in planning their personal savings and lifetime and business finances.

http://macro-economic-design.blogspot.com/p/book.html

Part 2 is a collection of scientific articles on the current advances in cardiac care by the best trained physicians the world has known, with mastery of the most advanced vascular instrumentation for medical or surgical interventions, the latest diagnostic ultrasound and imaging tools that are becoming outdated before the useful lifetime of the capital investment has been completed.  If we tie together Part 1 and Part 2, there is ample room for considering  clinical outcomes based on individual and organizational factors for best performance. This can really only be realized with considerable improvement in information infrastructure, which has miles to go.  Why should this be?  Because for generations of IT support systems, they are historically focused on billing and have made insignificant inroads into the front-end needs of the clinical staff.

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Investigational Bioengineered Blood Vessel: Humacyte Presents Interim First-in-Human Data at the American Heart Association (AHA) Scientific Sessions 2013

Posted in Cardiac and Cardiovascular Surgical Procedures, Cardiovascular Research, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Interviews with Scientific Leaders, Nephrology & Regenerative medicine, Origins of Cardiovascular Disease, Peripheral Arterial Disease & Peripheral Vascular Surgery, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Resident-cell-based, Technology Transfer: Biotech and Pharmaceutical, Translational Research, tagged , , , , on November 20, 2013| Leave a Comment »

Investigational Bioengineered Blood Vessel: Humacyte Presents Interim First-in-Human Data at the American Heart Association (AHA) Scientific Sessions 2013

Reporter: Aviva Lev-Ari, PhD, RN

The investigational bioengineered blood vessels represent a research and development milestone in vascular tissue engineering, as this technology could have the potential to help reduce or avoid surgical interventions and hospitalizations for patients with end-stage renal disease.

The Humacyte investigational bioengineered blood vessels are manufactured in a novel bioreactor system. The investigational bioengineered vessels go through a process of decellularization, which is designed to render them potentially non-immunogenic and implantable into any patient. These investigational bioengineered vessels are designed to be stored off-the-shelf for up to 12 months under standard refrigerated conditions, including, if successfully developedand approved,  on-site in hospitals.

 

Gail Thornton
Media Relations, Humacyte
1 908 392 3420 MOBILE
gail@westmillconsulting.com

Jim Modica

West Mill Consulting

908-872-4919

Jim@westmillconsulting.com

Humacyte Presents Interim First-in-Human Data

For Investigational Bioengineered Blood Vessel at the American Heart Association (AHA) Scientific Sessions 2013

  • The Humacyte investigational bioengineered blood vessel technology represents a research and development milestone in vascular tissue engineering.
  • Interim data from 28 patients in a three-center, first-in-human study in Poland indicate that all of the investigational blood vessels to date remain open to blood flow (patent), with no indication of an immune response in recipients, no aneurysms, and flow rates and durability suitable for dialysis.
  • The interim data suggest that the Humacyte investigational technology may have the potential to have high patency rates.
  • Longer follow-up and additional clinical studies will be required to confirm these preliminary observations.

 

RESEARCH TRIANGLE PARK, N.C., November 20, 2013 –Humacyte, Inc., a pioneer in regenerative medicine, today announced the presentation of interim, first-in-human data from an ongoing, multi-center study in Poland, evaluating the company’s investigational bioengineered blood vessel in hemodialysis patients with End-Stage Renal Disease (ESRD). The data were presented by Dr. Jeffrey H. Lawson, M.D., Ph.D., at the American Heart Association Scientific Sessions 2013 in Dallas, Texas (abstract). Dr. Lawson is Professor of Surgery and Pathology with tenure at Duke University Medical Center (Durham, North Carolina, USA), and Director of the Vascular Research Laboratory and Director of Clinical Trials for the Department of Surgery. He is also Clinical Consultant to Humacyte.

This is the first time surgical data from patients have been reported for the Humacyte investigational bioengineered vessel; the interim data come from a cohort of 28 study participants out of a total of 30 that will ultimately be enrolled in the three-site study in Poland (http://clinicaltrials.gov/show/NCT01744418%20CLN-PRO-V001%20NCT01744418). The first patients were implanted with the investigational vessels in December, 2012, and the vessels were first used for hemodialysis in February, 2013. The primary endpoints of the study in Poland are safety, tolerability, and patency to be examined at each visit within the first six months after graft implantation. Patients will be followed for an additional six months.

The interim patient data suggest that the Humacyte investigational bioengineered vessel may potentially be associated with low rates of vessel clotting, low infection rates, and low rates of surgical interventions. Low rates of clotting and intervention are consistent with preclinical data from animal testing that indicated little intimal hyperplasia. Preclinical data also indicated that, in animals, investigational vessels were remodeled to become living and more similar to native tissue. To date in the Polish study, the investigational vessel has remained open to blood flow (patent), with no indication of an immune response in recipients, no aneurysms (abnormal widening or ballooning of part of an artery due to weakness in the blood vessel wall), and flow rates and durability suitable for dialysis. Longer follow-up and additional clinical studies will be required to confirm these preliminary observations.

Co-authors on the presentation were: Drs. Marek Iłżecki, Tomasz Jakimowicz, Alison Pilgrim, Stanisław Przywara, Jacek Szmidt, Jakub Turek, Wojciech Witkiewicz, Norbert Zapotoczny, Tomasz Zubilewicz, and Laura Niklason.

Described by Investigator as “Breakthrough Investigational Technology”

“Based on our experience to date, this is breakthrough investigational technology,” said Principal Investigator Prof. Tomasz Zubilewicz, M.D., Ph.D., head, Department of Vascular Surgery and Angiology, Medical University of Lublin, Poland. “The investigational bioengineered vessel seems like it could have the potential to be shown to be superior to synthetic grafts in vascular access for hemodialysis in all aspects. This technology also has potential for other areas of vascular surgery, including replacement of infected synthetic grafts.”

“We are very encouraged by the Humacyte investigational bioengineered vessel’s performance in end-stage renal disease patients,” said Dr. Lawson. “Tremendous medical need exists for vascular access grafts in patients with ESRD who require dialysis. Based on this interim data and other ongoing research, we believe that the investigational bioengineered vessel has potential to meet this significant need.”

Need to Overcome Limitations of PTFE Grafts

Currently available synthetic vessels made from polytetrafluoroethylene (PTFE) are subject to many complications and about half fail within a year, requiring replacement surgery. PTFE vessels tend to become blocked (have low patency rates), have high rates of stenosis (an abnormal narrowing in a blood vessel that can be associated with hemodialysis), and high intervention rates.

“We continue to make significant progress in our research and development program with the Humacyte investigational bioengineered blood vessel,” said Laura E. Niklason, M.D., Ph.D., professor and vice chair of Anesthesia, professor of Biomedical Engineering, Yale University, and founder, Humacyte. “With our current interim study data, all of the Humacyte vessels have remained open to blood flow, with 20 out of the 28 implants requiring no intervention to date. We are grateful to patients, investigators, regulators and the broader vascular community for their ongoing collaboration and support in advancing this science.”

Unmet Medical Need in Chronic Kidney Disease

The Humacyte investigational technology is being developed with the goal of pursuing approval for use in patients with chronic kidney disease, a major global health problem affecting 26 million Americans[i] and around 40 million people in the European Union (EU).[ii] Individuals who progress to end-stage renal disease (ESRD) require renal replacement therapy (hemodialysis or kidney transplant); more than 380,000 patients currently require hemodialysis in the U.S.[iii] and some 250,000 patients require hemodialysis or have had kidney transplants in the EU.[iv] The investigational bioengineered vessels, if successfully developed and approved for use in ESRD by regulatory authorities, could offer the potential for significant cost savings to the healthcare system. These investigational bioengineered vessels represent a research and development milestone in vascular tissue engineering, as this technology could have the potential to help reduce or avoid surgical interventions and hospitalizations for patients with ESRD.

Investigators Highlight Preliminary Experiences In Patients

The investigators involved with the study in Poland cited their clinical observations in connection with the release of the preliminary patient data obtained for the Humacyte investigational technology.

“It was an exciting experience to be involved with this study, and to participate in this potential breakthrough in vascular surgery. This investigational bioengineered vein is a promising development for vascular surgeons,” said Principal Investigator Prof. Jacek Szmidt, head of the Department of General, Vascular and Transplant Surgery, Medical University of Warsaw, Poland.

“The Humacyte investigational bioengineered vessel was very easy to handle during implantation in this study. The graft maintained excellent mechanical properties, and based on our team’s experience, the complication rate to date has been very low compared with synthetic grafts,” said Investigator Stanisław Przywara, M.D., Ph.D., senior assistant, Department of Vascular Surgery and Angiology, Medical University of Lublin, Poland.

“During implantation in this study, the Humacyte investigational vessel behaved very much like a native vein.  Anastomotic hemostasis was achieved almost immediately. Insertion of needles to perform hemodialysis was easy and as reported by our nephrologists, provides very good adequacy of hemodialysis,” said Investigator Marek Iłżecki, M.D., Ph.D., senior resident, Department of Vascular Surgery and Angiology, Medical University of Lublin, Poland.

U.S. Clinical Trial Started in May, 2013

A multi-center U.S. clinical trial began in May, 2013 under a U.S. Investigational New Drug (IND) application. The U.S. trial will involve up to 20 patients across three sites to assess safety and performance of the innovative, investigational bioengineered blood vessels to provide vascular access for hemodialysis in ESRD patients.

About the Investigational Bioengineered Blood Vessels

The Humacyte investigational bioengineered blood vessels are manufactured in a novel bioreactor system. The investigational bioengineered vessels go through a process of decellularization, which is designed to render them potentially non-immunogenic and implantable into any patient. These investigational bioengineered vessels are designed to be stored off-the-shelf for up to 12 months under standard refrigerated conditions, including, if successfully developed and approved,  on-site in hospitals. Subject to receipt of regulatory approval, these properties could make the investigational bioengineered vessels readily available to surgeons and patients, and could eliminate the wait for vessel production or shipping. Data from studies of the investigational bioengineered vessels in large animal models reflect resistance to thickening for up to one year, and the early human studies that are now underway will provide safety and performance data in patients to support a future application for regulatory approval.

About Humacyte

Humacyte, Inc., a privately held company founded in 2005, is a medical research, discovery and development company with clinical and pre-clinical stage investigational products. Humacyte is primarily focused on developing and commercializing a proprietary novel technology based on human tissue-based products for key applications in regenerative medicine and vascular surgery. The company uses its innovative, proprietary platform technology to engineer human, extracellular matrix-based tissues that are designed be shaped into tubes, sheets, or particulate conformations, with properties similar to native tissues. These are being developed for potential use in many specific applications, with the goal to significantly improve treatment outcomes for a variety of patients, including those with vascular disease and those requiring hemodialysis. The company’s proprietary technologies are designed to result in off-the-shelf products that, once approved, can be utilized in any patient. The company web site is www.humacyte.com.

Forward-Looking Statement

Information in this news release contains “forward-looking statements” about Humacyte. These statements, including statements regarding management’s projections relating to future results and operations, are based on, among other things, management’s views, assumptions and estimates, developed in good faith, all of which are subject to known and unknown factors that may cause actual results, performance or achievements, or industry results, to differ materially from those expressed or implied by such forward-looking statements.

 

References

[iv]http://www.ekha.eu/usr_img/info/factsheet.pdf

SOURCE

From: Gail Thornton <gail@westmillconsulting.com>
Reply-To: Gail Thornton <gail@westmillconsulting.com>
Date: Wed, 20 Nov 2013 09:24:32 -0800 (PST)
To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>
Subject: Re: American Heart Association: Humacyte Investigational Bioengineered Blood Vessels

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