Series A: e-Books on Cardiovascular Diseases
Series A Content Consultant: Justin D Pearlman, MD, PhD, FACC
VOLUME TWO
Cardiovascular Original Research:
Cases in Methodology Design for Content Co-Curation
The Art of Scientific & Medical Curation
http://www.amazon.com/dp/B018Q5MCN8
Justin D Pearlman, MD, PhD, FACC
Larry H Bernstein, MD, FCAP
and
Aviva Lev-Ari, PhD, RN
Editor-in-Chief BioMed e-Series of e-Books
Leaders in Pharmaceutical Business Intelligence, Boston
avivalev-ari@alum.berkeley.edu
Submission for Category: Book
Nomination of e-Book, Series A: Cardiovascular Diseases, Volume 2, Cases in Development of Scientific Curation Methodology
2016 Communication Awards Nomination Form Result #9143807
The National Academies of Sciences, Engineering, and Medicine
2016 Communication Awards for Excellence in Reporting and Communicating Science, Medicine and Engineering
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Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation |
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The explosion of scientific information has created difficulties tying together disparate discoveries, ideas, and potential applications. Pharmaceutical Business Intelligence is developing an innovative methodology for Global access to Biomedical knowledge rather than traditional search. To attain this complex goal they disseminate ORIGINAL Research via Content Curation by experts using critical thinking process & interpretation over open access networks, offering better organization and visibility of critical information useful for innovations in academic, clinical, and industrial research. Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation at http://www.amazon.com/dp/B018Q5MCN8 is nominated as an example of this methodology. |
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Other e-Books in the BioMedicine e-Series
Series A: e-Books on Cardiovascular Diseases
Content Consultant: Justin D Pearlman, MD, PhD, FACC
Volume One: Perspectives on Nitric Oxide
Sr. Editor: Larry Bernstein, MD, FCAP, Editor: Aviral Vatsa, PhD and Content Consultant: Stephen J Williams, PhD
available on Kindle Store @ Amazon.com
http://www.amazon.com/dp/B00DINFFYC
Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation
Curators: Justin D Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP, Aviva Lev-Ari, PhD, RN
- Causes
- Risks and Biomarkers
- Therapeutic Implications
Volume Three: Etiologies of CVD: Epigenetics, Genetics & Genomics
Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
- Causes
- Risks and Biomarkers
- Therapeutic Implications
Volume Four: Therapeutic Promise: CVD, Regenerative & Translational Medicine
Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
- Causes
- Risks and Biomarkers
- Therapeutic Implications
Volume Five: Pharmaco-Therapies for CVD
Volume Curators: Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
- Causes
- Risks and Biomarkers
- Therapeutic Implications
Volume Six: Interventional Cardiology and Cardiac Surgery for Disease Diagnosis and Guidance of Treatment
Volume Curators: Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
- Causes
- Risks and Biomarkers
- Therapeutic Implications
In addition to the Seven Volumes of SERIES A: Cardiovascular Diseases, Not included in SERIES A is a Three Volume Series by Dr. Pearlman, Editor, on Cardiovascular Diseases, positioned as Academic Textbooks for Training Residents in Cardiology and Texts for CEU Courses in Cardiology [Hardcover, Softcover, e-Books].
- CVD 1: Causes of Cardiovascular Diseases
- CVD 2: Risk Assessment of Cardiovascular Diseases
- CVD 3: Management of Cardiovascular Diseases
- CVD 4: Volume Seven: Cardiac Imaging
Series B: e-Books on Genomics & Medicine
Content Consultant: Larry H Bernstein, MD, FCAP
Volume 1: Genomics and Individualized Medicine
Sr. Editor: Stephen J Williams, PhD
Editors: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Volume 2: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology
Editors: Stephen J Williams, PhD and TBA
Volume 3: Institutional Leadership in Genomics
Editors: Aviva Lev-Ari, PhD, RN and TBA
Series C: e-Books on Cancer & Oncology
Content Consultant: Larry H Bernstein, MD, FCAP
Volume 1: Cancer and Genomics
Sr. Editor: Stephen J Williams, PhD
Editors: Ritu Saxena, PhD, Tilda Barliya, PhD
Volume 2: Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery
Author, Curator and Editor: Larry H Bernstein, MD, FCAP
Guest Authors: Stephen J Williams, PhD, Dror Nir, PhD and Tilda Barliya, PhD, Demet Sag, PhD
Volume 3: Cancer Patients’ Resources on Therapies
Sr. Editor: TBA
Series D: e-Books on BioMedicine
Content Consultant: Larry H Bernstein, MD, FCAP
Volume 1: Metabolic Genomics & Pharmaceutics
Author, Curator and Editor: Larry H Bernstein, MD, FCAP
Volume 2: Infectious Diseases
Editor: TBA
Volume 3: Immunology and Therapeutics
Author, Curator and Editor: Larry H Bernstein, MD, FCAP
Series E: Patient-centered Medicine
Content Consultant: Larry H Bernstein, MD, FCAP
Volume 1: The VOICES of Patients, HealthCare Providers, Care Givers and Families: Personal Experience with Critical Care and Invasive Medical Procedures
Author, Curator and Editor: Larry H Bernstein, MD, FCAP
Volume 2: Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders
Author, Curator and Editor: Larry H Bernstein, MD, FCAP
Volume 3: Milestones in Physiology & Discoveries in Medicine and Genomics
Author, Curator and Editor: Larry H Bernstein, MD, FCAP
Volume 4: Medical 3D BioPrinting – The Revolution in Medicine
Our DOMAINS in Scientific Media
I. Pharmaceutical: Biologics, Small Molecules, Diagnostics
II. Life Sciences: Genomics and Cancer Biology
III. Patient-centered Medicine: Focus on #1: Cardiovascular, #2: Cancer, #3: Physiology Metabolomics, Immunology
IV. Biomedicine, BioTech, and MedTech (Medical Devices)
V. HealthCare: Patient-centered Medicine and Personalized/Precision Medicine
This e-Book is a comprehensive review of recent Original Research on Cardiovascular Diseases: Causes, Risks and Management and related opportunities for Targeted Therapy written by Experts, Authors, Writers. The results of Original Research are gaining value added for the e-Reader by the Methodology of Curation. The e-Book’s articles have been published on the Open Access Online Scientific Journal, since April 2012. All new articles on this subject, will continue to be incorporated, as published with periodical updates.
Open Access Online Journal
http://www.pharmaceuticalIntelligence.com
is a scientific, medical and business, multi-expert authoring environment for information syndication in several domains of Life Sciences, Medicine, Pharmaceutical and Healthcare Industries, BioMedicine, Medical Technologies & Devices. Scientific critical interpretations and original articles are written by PhDs, MDs, MD/PhDs, PharmDs, Technical MBAs as Experts, Authors, Writers (EAWs) on an Equity Sharing basis.
About Series A: e-Books on Cardiovascular Diseases – Content Consultant Justin D. Pearlman MD ME PhD MA FACC
Cover image: Dr. Pearlman produced this image by applying dynamic magnetic resonance imaging to a patient with a patent foramen ovale. The 3D reconstruction shows blood movement in chambers of the heart, which includes a narrow funnel of shunt flow between left and right atrial chambers through an opening in a flap of tissue that normally seals a trap door called the foramen ovale. The foramen ovale provides a bypass of the lungs in utero.
Dr. Pearlman has many different perspectives developed during the years, including:
- Chief of Cardiology,
- non-invasive imaging,
- molecular biology,
- mathematics,
- imaging research
contributed a number of firsts:
- non-endemic Chagas diagnosis,
- intensity projection angiography,
- magnetization tagging,
- myocardial injury mapping by magnetic resonance contrast retention,
- myocardial viability by MRI,
- atheroma lipid liquid crystal characterization,
- outpatient inotropic infusion therapy,
- angiogenesis imaging,
- multimodal in vivo stem cell imaging,
- real-time velocity beam MRI,
- in vivo microscopic MRI,
- dobutamine stress echocardiography for low gradient valve disease,
- alternative stress tests,
- diagnostic electrocardiography in magnetic environments,
- statistical methods to solve error propagation of large array genomics,
- discovery of monocyte role in native coronary collateral development,
- image tracked stem cell treatment of heart attacks,
- singularity editing in differential topology.
LIST of VIDEOS
Insert HERE list
List of Contributors & Contributors’ Biographies
Justin D. Pearlman MD ME PhD MA FACC
Editorial Functions: All articles
Sectional Authorship and Curations: Introduction to Volume Two, Introduction to Part 2, Introduction to Part 5, 2.1.1, 3.2.4, 3.2.6, 3.3.1, 3.3.2, 3.3.3, 3.3.4, 4.2.3, 4.4.1, 4.5.1, 4.5.2, 4.5.3, 4.5.4, 4.5.5, 5.1.2, 5.1.3, 5.1.8, 5.2.2, 5.2.3, 5.3.1
Author and Curator: Introduction to Volume Two, Introduction to Part 2, Introduction to Part 3, Introduction to Part 4, Introduction to Part 5, 2.0, 2.1.1, 2.2.1, 2.2.2, 2.2.3, 2.2.4, 3.1.1.1, 3.2.1, 3.2.2, 3.2.3, 3.2.4, 3.2.5, 3.2.6, 3.2.7, 3.2.8, 4.1.1, 4.2.4, 4.2.5, 4.2.6, 4.2.7, 4.2.8, 4.3.1, 4.3.2, 4.4.2, 4.4.3, 5.1.1, 5.1.3, 5.1.8, 5.1.9, 5.1.10, 5.2.2, 5.2.3, Summary to Volume Two
Article Curator: 1.1, 1.2, 1.3, 1.4, 1.5, 2.1.1, 2.1.2, 2.1.3, 2.2.1, 2.2.2, 2.2.4, 2.3, 3.1.1.1, 3.1.2.1, 3.1.2.2., 3.1.3.1, 3.2.2, 3.2.3, 3.2.4, 3.2.5, 3.2.6, 3.2.7, 3.2.8, 3.3.1, 3.3.2, 3.3.3, 3.3.4, 4.1.1, 4.2.1, 4.2.2, 4.2.3, 4.2.4, 4.2.5, 4.2.7, 4.2.8, 4.2.9, 4.3.1, 4.3.2, 4.3.3, 4.3.4, 4.3.5, 4.3.6, 4.4.1, 4.4.2, 4.4.3, 4.4.4, 4.5.1, 4.5.2, 4.5.3, 4.5.4, 4.4.5, 5.1.1, 5.1.2, 5.1.3, 5.1.4, 5.1.5, 5.1.6, 5.1.7, 5.1.9, 5.1.10, 5.1.11, 5.1.12, 5.1.13, 5.2.1, 5.2.2, 5.2.3, 5.3.1, 5.4.1, Epilogue to Volume Two
Article Contributor: 5.1.2
Curator: 3.2.2, 4.1.1
Electronic Table of Contents (eTOCs) of Volume Two
Introduction to Volume Two
Part 1: The Methodology of Curation for Scientific Research Findings
1.1 The Methodology Explained
1.1.1 Curation by a Single Curator
1.1.2 Co-Curation by Several Experts, Authors, Writers
1.1.3 Editor’s Curation of an electronic Table of Contents (eTOCs) of an e-Book or a Hardcover Volume
1.2 The Creation Process of a Curation as an Alternative Model for Scientific Publishing
1.3 FIVE steps in the Creation Process of a Curation
1.3.1 CURATION and Co-CURATION of Scientific articles in conjunction with Experts, Authors, Writers critique and synthesis
1.3.2 Assembly of articles into e-Books using ONE of a Kind electronic Table of Contents (eTOCs) architecture
1.3.3 Assembly of e-Books into e-Series
1.3.4 Publishing of e-Series on Amazon.com
1.3.5 Distribution of e-Series to Professional Associations via their Internet website
1.4 Other Alternative Types to the Academic Publishing Model
1.5 Methodology of Curation Applied to Medical Research Findings
1.5.1 The Voice of Content Consultant on The Methodology of Curation
1.5.2 Curation is Uniquely Distinguished by the Historical Exploratory Ties that Bind
Part 2: Cardiovascular Disease – Predicted Cost of Care and the
Affordable Care Act
Introduction
2.1 Cost of Care for Cardiovascular Medical Diagnoses
2.1.1 Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & AHA Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems
2.1.2 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
2.1.3 Heart Disease: Economic and Personal Effects
2.2 Impact of 2013 HealthCare Reform in the US
2.2.1 The Affordable Care Act: A Considered Evaluation. Part I. The legislative act (ACA) and the model for implementation (Insurance Gateways).
2.2.2 The Affordable Care Act: A Considered Evaluation. Part II: The Implementation of the ACA, Impact on Physicians and Patients, and the Dis-Ease of the Accountable Care Organizations.
2.2.3 The Affordable Care Act: A Considered Evaluation. Part III. Final Implementation of the Affordable Care Act and a Patient and Community Outcomes Focus
2.2.4 Post Acute Care – Driver of Variation in Healthcare Costs
2.3 Patient Protection and Affordable Care Act Featured at RAND
Part 3: Causes of Cardiovascular Diseases
3.1 Human Genome: Congenital Etiological Sources of Cardiovascular Disease
3.1.1 Genomics & Genetics of Cardiovascular Disease Diagnoses
3.1.1.1 Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA’s Circulation Cardiovascular Genetics, 3/2010 – 3/2013
3.1.2 Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging
3.1.2.1 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
3.1.2.2 Transposon-mediated Gene Therapy improves Pulmonary Hemodynamics and attenuates Right Ventricular Hypertrophy: eNOS gene therapy reduces Pulmonary vascular remodeling and Arterial wall hyperplasia
3.1.3 Genetics of Conduction Disease
3.1.3.1 Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis
3.2 The Role of Calcium in Health and Disease
3.2.1 Identification of Biomarkers that are Related to the Actin Cytoskeleton – Part I
3.2.2 Role of Calcium, the Actin Skeleton, and Lipid Structures in Signaling and Cell Motility – Part II
3.2.3 Ca2+-Stimulated Exocytosis: The Role of Calmodulin and Protein Kinase C in Ca2+ Regulation of Hormone and Neurotransmitter
3.2.4 Disruption of Calcium Homeostasis: Cardiomyocytes and Vascular Smooth Muscle Cells: The Cardiac and Cardiovascular Calcium Signaling Mechanism – Part VIII
3.2.5 Synaptotagmin functions as a Calcium Sensor: How Calcium Ions Regulate the fusion of vesicles with cell membranes during Neurotransmission – Part X
3.2.6 The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and Ryanodine Receptors in Cardiac Failure, Arterial Smooth Muscle, Post-ischemic Arrhythmia, Similarities and Differences, and Pharmaceutical Targets
3.2.7 Atherosclerosis Independence: Genetic Polymorphisms of Ion Channels Role in the Pathogenesis of Coronary Microvascular Dysfunction and Myocardial Ischemia (Coronary Artery Disease (CAD))
3.2.8 Calcium Signaling, Cardiac Mitochondria and Metabolic Syndrome
3.3 Vasculature and Myocardium: Diagnosing the Conditions of Disease
3.3.1 State of Cardiology on Wall Stress, Ventricular Workload and Myocardial Contractile Reserve: Aspects of Translational Medicine (TM)
3.3.2 Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus
3.3.3 Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions
3.3.4 Mitral Valve Repair: Who is a Patient Candidate for a Non-Ablative Fully Non-Invasive Procedure?
Part 4: Risks and Biomarkers for Cardiovascular Diseases
4.1 The Role of Calcium in Health and Disease
4.1.1 Renal Distal Tubular Ca2+ Exchange Mechanism in Health and Disease – Part III
4.2 Vasculature and Myocardium: Diagnosing the Conditions of Disease – Biomarkers of Acute Cardiovascular Events
4.2.1 No Early Symptoms – An Aortic Aneurysm Before It Ruptures – Is There A
Way To Know If I Have it?
4.2.2 Females and Non-Atherosclerotic Plaque: Spontaneous Coronary Artery Dissection: New Insights from Research and DNA Ongoing Study
4.2.3 Cardiovascular Diseases: Decision Support Systems for Disease
Management Decision Making
4.2.4 Dealing with the Use of the High Sensitivity Troponin (hs cTn) Assays
4.2.5 Prognostic Marker Importance of Troponin I in Acute Decompensated
Heart Failure (ADHF): Troponin I in acute decompensated heart failure:
insights from the ASCEND-HF study
4.2.6 More on the Performance of High Sensitivity Troponin T and with Amino
Terminal Pro BNP in Diabetes
4.2.7 The Cardio-Renal Syndrome (CRS) in Heart Failure (HF)
4.2.8 Vasoplegia in Orthotopic Heart Transplant Patients
4.2.9 Myocardial Infarction: The New Definition
After Revascularization
4.3 Biomarkers of Long Term Risk of Cardiovascular Disease
4.3.1 Special Considerations in Blood Lipoproteins, Viscosity, Assessment
and Treatment
4.3.2 What is the Role of Plasma Viscosity in Hemostasis and Vascular
Disease risk?
4.3.3 High-Density Lipoprotein (HDL): An Independent Predictor of
Endothelial Function & Atherosclerosis, A Modulator, An Agonist, A Biomarker
for Cardiovascular Risk
4.3.4 Artherogenesis: Predictor of CVD – the Smaller and Denser LDL
Particles
4.3.5 Hypertriglyceridemia concurrent Hyperlipidemia: Vertical Density
Gradient Ultracentrifugation a Better Test to Prevent Undertreatment of
High-Risk Cardiac Patients
4.3.6 Cholesteryl Ester Transfer Protein (CETP) Inhibitor: Potential of
Anacetrapib to treat Atherosclerosis and CAD
4.4 Conduction Dysfunction and ElectroPhysiology of the Heart
4.4.1 On Devices and On Algorithms: Arrhythmia after Cardiac Surgery Prediction and ECG Prediction of Paroxysmal Atrial Fibrillation Onset
4.4.2 Genetic Analysis of Atrial Fibrillation
4.4.3 Oxidized Calcium Calmodulin Kinase and Atrial Fibrillation
4.4.4 Renal Function Biomarker, β-trace protein (BTP) as a Novel Biomarker for Cardiac Risk Diagnosis in Patients with Atrial Fibrilation
4.5 Cardiovascular Imaging: Diagnosing the Condition of the Disease and Determining Course of Treatment
4.5.1 Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management
4.5.2 Coronary Circulation Combined Assessment: Optical Coherence Tomography (OCT), Near-Infrared Spectroscopy (NIRS) and Intravascular Ultrasound (IVUS) – Detection of Lipid-Rich Plaque and Prevention of Acute Coronary Syndrome (ACS)
4.5.3 Emerging Clinical Applications for Cardiac CT: Plaque Characterization, SPECT Functionality, Angiogram’s and Non-Invasive FFR
4.5.4 Fractional Flow Reserve (FFR) & Instantaneous wave-free ratio (iFR): An Evaluation of Catheterization Lab Tools (Software Validation) for Ischemic Assessment (Diagnostics) – Change in Paradigm: The RIGHT vessel not ALL vessel
4.5.5 Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone
Part 5: Advances in Treatment of Cardiovascular Diseases
5.1 Vasculature and Myocardium: Diagnosing the Conditions of Disease
5.1.1 Erythropoietin (EPO) and Intravenous Iron (Fe) as Therapeutics for Anemia in Severe and Resistant CHF: The Elevated N-terminal proBNP Biomarker
5.1.2 Do Novel Anticoagulants Affect the PT/INR? The Cases of XARELTO (rivaroxaban) or PRADAXA (dabigatran)
5.1.3 Alternative Designs for the Human Artificial Heart: The Patients in Heart Failure – Outcomes of Transplant (donor)/Implantation (artificial) and Monitoring Technologies for the Transplant/Implant Patient in the Community
5.1.4 Vascular Surgery: International, Multispecialty Position Statement on Carotid Stenting, 2013 and Contributions of a Vascular Surgeon at Peak Career – Richard Paul Cambria, MD
5.1.5 Heart Transplant (HT) Indication for Heart Failure (HF): Procedure Outcomes and Research on HF, HT @ Two Nation’s Leading HF & HT Centers
5.1.6 Endovascular Lower-extremity Revascularization Effectiveness: Vascular Surgeons (VSs), Interventional Cardiologists (ICs) and Interventional Radiologists (IRs)
5.1.7 Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care
5.1.8 AHA, ACC Change in Requirement for Surgical Support for PCI Performance: Class IIb -> Class III, Level of Evidence A: Support Nonemergent PCI without Surgical Backup (Change of class IIb, Level of evidence B)
5.1.9 Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization
5.1.10 Vascular Repair: Stents and Biologically Active Implants
5.1.11 Regeneration: Cardiac System (cardiomyogenesis) and Vasculature (angiogenesis)
5.1.12 Fight against Atherosclerotic Cardiovascular Disease: A Biologics not a Small Molecule – Recombinant Human lecithin-cholesterol acyltransferase (rhLCAT) attracted AstraZeneca to acquire AlphaCore
5.1.13 Harnessing New Players in Atherosclerosis to Treat Heart Disease
5.2 The Role of Calcium in Health and Disease
5.2.1 Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD – Part VI
5.2.2 Cardiac Contractility & Myocardium Performance: Ventricular Arrhythmiasand Non-ischemic Heart Failure – Therapeutic Implications for Cardiomyocyte Ryanopathy (Calcium Release-related Contractile Dysfunction) and Catecholamine Responses – Part VII
5.2.3 Calcium-Channel Blockers, Calcium Release-related Contractile Dysfunction (Ryanopathy) and Calcium as Neurotransmitter Sensor – Part IX
5.3 Conduction Dysfunction and ElectroPhysiology of the Heart
5.3.1 Cardiac Resynchronization Therapy (CRT) to Arrhythmias: Pacemaker/Implantable Cardioverter Defibrillator (ICD) Insertion
5.4 Cardiovascular Imaging: Diagnosing the Condition of the Disease and Determining Course of Treatment
5.4.1 3D Cardiovascular Theater – Hybrid Cath Lab/OR Suite, Hybrid Surgery, Complications Post PCI and Repeat Sternotomy
Summary to Volume Two
Epilogue to Volume Two
Introduction to Volume Two
The Voice of our Content Consultant to Seven-Volume e-SERIES A: Cardiovascular Diseases:
Justin Pearlman, MD, PhD, FACC
The leading causes of death and disability involve the heart and blood vessels. The basic causes of disease are nature and nurture, i.e., genetic or epigenic predisposition (nature) versus behavior mediated exposures (nurture).
The full list of cardiovascular diseases stems quite simply from looking at all cardiovascular structures and functions, for each can have deviant design and/or function. Murphy’s law “what can go wrong will” does not entirely apply because many deviations are incompatible with life in the first place. Furthermore, the body has a limited number of ways that it responds.
Nonetheless, there is a wide variety of cardiovascular disease. The blood pressure can be too high (hypertension) or too low (hypotension). The heart can be too big (cardiomegaly) or too small (hypoplastic heart), too stiff (diastolic failure, restrictive cardiomyopathy, constrictive cardiomyopathy) or too soft (aneurysm). The heart can pump too much (high output failure) or too little (low output failure). The heartbeat rhythm may be too slow (bradycardia) or too fast (tachycardia). In addition to too much or too little, there are numerous other ways to invoke Murphy’s law. For example there are hundreds arrhythmias (abnormal rhythm mechanisms). Mechanisms for abnormal structure or function include: congenital, developmental, neoplastic, metabolic, inflammatory, infectious, extrinsic (injury), and degenerative.
Teleologically many of the genetic issues may be labeled “maladaptive” in the sense that in certain circumstances the genetically programmed organic functions cause more harm than benefit. For example, when a patient develops heart failure and reduces blood delivery to the kidneys, the kidneys fight back by retaining sodium desperately, and by sending signals to stimulate thirst. Whether or not it is “well-intended” the kidneys make the problem worse, as the retained salt water volume overloads the beleaguered failing heart, so the heart dilates and develops worsening mitral valve leakage, thus delivering even less forward to the kidneys, while in addition the lungs get wetter and struggle to take up sufficient oxygen. On the nurture side, the patients intake of salt has major impact on this harmful chain of events, which can be counteracted by disciplined behavior (salt restriction, optimal use of diuretics).
As we learn more about the details of the body’s signals and receptors, we can manufacture medications to counteract the “maladaptive genetics” as well as learn about additional behavior changes that may mitigate or even reverse each disease state. The reason for the quotation marks about “maladaptive genetics” is that the genetic and homeostatic systems may in fact be truly adaptive to the overriding population reproductive success that drives gene pool prevalence, as that drive may include promoting death of the elderly to make room for the young and not compete for their resources. Some of the most fascinating enigmas relate to the teleology of disease. For example why do we have complex systems that disassemble circulating cholesterol lipoproteins only to reassemble them within the wall of blood vessels, where they lead to endothelial (vessel lining) disruption, thrombosis, and vessel occlusion. Such arterial wall damage is the leading mechanism of strokes and heart attacks.
As part of my PhD research I documented that the lipids that cause hardening of arteries are liquid crystals which transition between solid and liquid at body temperature (37C) under the influence of the concentration of triglycerides. One could posit a protective effect against vessel dilation, at a large cost. Thus stroke and heart attack may be consequences of a defense mechanism gone awry (maladaptive defenses). Similarly, is inflammation a defense mechanism gone awry? Inflammation is a component of the damage to blood vessels, but patients who take an anti-inflammatory medication for more than 18 months have a 50% risk of developing a new arterial blockage. These are complex systems, and we simply do not know enough about them. As you read through the discoveries and ideas in the following sections, consider their value in clarifying many aspects of health and disease, including causation, assessment, management, and also edification of the complex systems, their purposes, as well as their “maladaptive” impact and the checks and balances.
On the Domain Universe of Volume Two
Curation, HealthCare System in the US, and Calcium Signaling Effects on Cardiac Contraction, Heart Failure, and Atrial Fibrillation, and the Relationship of Calcium Release at the Myoneural Junction to Beta Adrenergic Release
by Larry H. Bernstein, MD, FCAP
The Curation approach to the scientific document has advantages over the multiple authored textbooks that are and have been pervasive as a result of the traditional publication technology. It has been stated by the founder of ScoopIt, that amount of time involved is considerably less than required for the original publications used, but the organization and construction is a separate creative process.
In these curations we amassed on average five articles in one curation, to which, two or three curators contributed their views. There were surprises, and there were unfulfilled answers along the way. The greatest problem that is being envisioned is the building a vision that bridges and unmasks the hidden “dark matter” between the now declared “OMICS”, to get a more real perspective on what is conjecture and what is actionable. This is in some respects unavoidable because the genome is an alphabet that is matched to the mino acid sequences of proteins, which themselves are three dimensional drivers of sequences of metabolic reactions that can be altered by the accumulation of substrates in critical placements, and in addition, the proteome has functional proteins whose activity is a regulatory function and not easily identified. In the end, we have to have a practical conception, recognizing the breadth of evolutionary change, and make sense of what we have, while searching for more.
We introduced the content as follows:
1. The concept of Curation in the digital context, and it’s application to medicine and related scientific discovery.
Topics were chosen were used to illustrate this process in the form of a pattern, which is mostly curation, but is significantly creative, as it emerges in the context of this e-book.
- Alternative solutions in Treatment of Heart Failure (HF), medical devices, biomarkers and agent efficacy is handled all in one chapter.
- PCI for valves vs Open heart Valve replacement
- PDA and Complications of Surgery — only curation could create the picture of this unique combination of debate, as exemplified of Endarterectomy (CEA) vs Stenting the Carotid Artery (CAS), ischemic leg, renal artery stenosis.
2. The Etiology, or causes, of cardiovascular diseases consist of mechanistic explanations for dysfunction relating to the heart or vascular system. Every one of a long list of abnormalities has a path that explains the deviation from normal. With the completion of the analysis of the human genome, in principle all of the genetic basis for function and dysfunction are delineated. While all genes are identified, and the genes code for all the gene products that constitute body functions, there remains more unknown than known.
3. Human genome, and in combination with improved imaging methods, genomics offers great promise in changing the course of disease and aging.
4. If we tie together Part 2 and Part 3, 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.
Curation
Curation is an active filtering of the web’s and peer reviewed literature found by such means – immense amount of relevant and irrelevant content. As a result content may be disruptive. However, in doing good curation, one does more than simply assign value by presentation of creative work in any category. Great curators comment and share experience across content, authors and themes.
Great curators may see patterns others don’t, or may challenge or debate complex and apparently conflicting points of view. Answers to specifically focused questions comes from the hard work of many in laboratory settings creatively establishing answers to definitive questions, each a part of the larger knowledge-base of reference. There are those rare “Einstein’s” who imagine a whole universe, unlike the three blindmen of the Sufi tale. One held the tail, the other the trunk, the other the ear, and they all said this is an elephant!
In my reading, I learn that the optimal ratio of curation to creation may be as high as 90% curation to 10% creation. Creating content is expensive. Curation, by comparison, is much less expensive. The same source says “Scoop.it is my content marketing testing “sandbox”. In sharing, he says that comments provide the framework for what and how content is shared.
Healthcare and Affordable Care Act
We enter year 2014 with the Affordable Care Act off to a slow start because of the implementation of the internet signup requiring a major repair, which is, unfortunately, as expected for such as complex job across the US, and with many states unwilling to participate. But several states – California, Connecticut, and Kentucky – had very effective state designed signups, separate from the federal system. There has been a very large rush and an extension to sign up. There are many features that we can take note of:
1. The healthcare system needed changes because we have the most costly system, are endowed with advanced technology, and we have inexcusable outcomes in several domains of care, including, infant mortality, and prenatal care – but not in cardiology.
2. These changes that are notable are:
- The disparities in outcome are magnified by a large disparity in highest to lowest income bracket.
- This is also reflected in educational status, and which plays out in childhood school lunches, and is also affected by larger class size and cutbacks in school programs.
- This is not helped by a large paralysis in the two party political system and the three legs of government unable to deal with work and distraction.
- Unemployment is high, and the banking and home construction, home buying, and rental are in realignment, but interest rates are problematic.
3. The medical care system is affected by the issues above, but the complexity is not to be discounted.
- The medical schools are unable at this time to provide the influx of new physicians needed, so we depend on a major influx of physicians from other countries
- The technology for laboratories, proteomic and genomic as well as applied medical research is rejuvenating the practice in cardiology more rapidly than any other field.
- In fields that are imaging related the life cycle of instruments is shorter than the actual lifetime use of the instruments, which introduces a shortening of ROI.
- Hospitals are consolidating into large consortia in order to maintain a more viable system for referral of specialty cases, and also is centralizing all terms of business related to billing.
- There is reduction in independent physician practices that are being incorporated into the hospital enterprise with Part B billing under the Physician Organization – as in Partners in Greater Boston, with the exception of “concierge” medical practices.
- There is consolidation of specialty laboratory services within state, with only the most specialized testing going out of state (Quest, LabCorp, etc.)
- Medicaid is expanded substantially under the new ACA.
- The federal government as provider of services is reducing the number of contractors for – medical devices, diabetes self-testing, etc.
- The current rearrangements seeks to provide a balance between capital expenses and fixed labor costs that it can control, reduce variable costs (reagents, pharmaceutical), and to take in more patients with less delay and better performance – defined by outside agencies.
Cardiology, Genomics, and calcium ion signaling and ion-channels in cardiomyocyte function in health and disease – including heart failure, rhythm abnormalities, and the myoneural release of neurotransmitter at the vesicle junction
This portion is outlined as follows:
2.1 Human Genome: Congenital Etiological Sources of Cardiovascular Disease |
2.2 The Role of Calcium in Health and Disease |
2.3 Vasculature and Myocardium: Diagnosing the Conditions of Disease |
Genomics & Genetics of Cardiovascular Disease Diagnoses |
Actin cytoskeleton |
Wall stress, ventricular workload, contractile reserve |
Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging |
Calcium and actin skeleton, signaling, cell motility |
Hypertension & vascular compliance |
Genetics of Conduction Disease |
Ca+ stimulated exostosis: calmodulin & PKC (neurotransmitter) |
Complications & MVR |
Disruption of Ca2+ homeostasis cardiac & vascular smooth muscle |
||
Synaptotagmin as Ca2+ sensor & vesicles |
||
Atherosclerosis & ion channels |
It is increasingly clear that there are mutations that underlie many human diseases, and this is true of the cardiovascular system. The mutations are mistakes in the insertion of a purine nucleotide, which may or may not have any consequence. This is why the associations that are being discovered in research require careful validation, and even require demonstration in “models” before pursuing the design of pharmacological “target therapy”. The genomics in cardiovascular disease involves very serious congenital disorders that are asserted early in life, but the effects of and development of atherosclerosis involving large and medium size arteries has a slow progression and is not dominated by genomic expression. This is characterized by loss of arterial elasticity. In addition there is the development of heart failure, which involves the cardiomyocyte specifically. The emergence of regenerative medical interventions, based on pleuripotent inducible stem cell therapy is developing rapidly as an intervention in this sector.
Part 1: The Methodology of Curation for
Scientific Research Findings
1.1, 1.2, 1.3, 1.4, 1.5 The Methodology of Curation for Scientific Research Findings
Aviva Lev-Ari, PhD, RN, Editor-in-Chief, BioMed e-Series of e-Books
1.1 The Methodology Explained
1.1.1 Curation by a Single Curator
1.1.2 Co-Curation by Several Experts, Authors, Writers
1.1.3 Editor’s Curation of an electronic Table of Contents (eTOCs) of an e-Book or a Hardcover Volume
1.2 The Creation Process of a Curation as an Alternative Model for Scientific Publishing
1.3 FIVE steps in the Creation Process of a Curation
1.3.1 CURATION and Co-CURATION of Scientific articles in conjunction with Experts, Authors, Writers critique and synthesis
1.3.2 Assembly of articles into e-Books using ONE of a Kind electronic Table of Contents (eTOCs) architecture
1.3.3 Assembly of e-Books into e-Series
1.3.4 Publishing of e-Series on Amazon.com
1.3.5 Distribution of e-Series to Professional Associations via their Internet websites
1.4 Other Alternative Types to the Academic Publishing Model
1.5 Methodology of Curation Applied to Medical Research Findings
1.5.1 The Voice of Content Consultant on The Methodology of Curation
1.5.2 Curation is Uniquely Distinguished by the Historical Exploratory Ties that Bind
SOURCES on Curation and Science
Part 2: Cardiovascular Disease:
Predicted Cost of Care and the
Affordable Care Act
The voice of Series A Content Consultant, Justin D Pearlman, MD, PhD, FACC
This Section addresses the burgeoning cost of cardiovascular health care and the role of the Affordable Care Act.
There is no denying the rising costs of healthcare, with key cardiovascular examples documented herein. Nor can anyone effectively deny potential gains from changes in American Healthcare, many of which the Affordable Care Act had intended to improve. Key aspects include promotion of prevention, improved widespread timely access to care and improved compliance with prevention. This section aims to sidestep the partisan politics to highlight reasons for healthcare change and reasons for contentions about the current and planned changes.
The main reasons for change are that our healthcare system has been on a non-sustainable course of increase in its portion of the gross national product as well as its portion of family budgets, and despite its escalating expense numerous measures of net public as well as personal benefit rank low. Furthermore, there is general agreement on a level of publicly supported safety net, at least for the elderly and for children, and that support is on a course towards bankruptcy. Also, it is widely recognized that the safety net should not rely as heavily as it has on expensive emergency department care. Also, there were unfair practices such as an insurance company dropping coverage after a patient became seriously ill. There are also ideologic arguments, that government is better or worse than a competitive private sector at administering efficient fair protection. Private enterprise is expected to place profits first, but satisfaction of each additional customer is generally favored, whereas politicians arguably are influenced by their ability to win over 51% of the population just before elections and their ability to garner major campaign contributions which may favor special interests. Businesses that are regulated to be transparent generally cannot cater to special interest funding the way politicians can. Hence one of the major arguments is why insurance cannot be an open competition across the entire country, or possibly world-wide, to drive down prices. As an alternative to requiring nation-wide insurance coverage, consider regulation to get rid of the group bundling advantage altogether (require that all service providers must price match the lowest they offer without regard to “insurance”). As another alternative to insurance, convert healthcare cost coverage to a long term loan and cap the “insurance agency premium” to a shrinking percentage so that “insurance” becomes an unnecessary value-added service analogous to concierge parking).
Major areas of contention include who and how to measure and control healthcare costs, the role of individual responsibility and individual freedom versus overriding public interests, the merits and demerits of government control of choices, the role of insurance, and the full impact of changes (however well-intended) on health care delivery, choices, employment and the cost of doing business.
There are many aspects of these issues that are prone to confusion and manipulation. For example, the cost of healthcare includes the cost of development of new and improved methods of prevention, diagnosis, and disease management. The United States has long shoulder a large share of that development cost for the entire world, then lets other countries get bulk purchase discounts on the product, while Americans pay top dollar.
The total costs of healthcare can rise as the scope of opportunities to intervene expands with new discoveries, but that can be offset by improvements in efficiency and prevention. When estimating costs, include the role of investment in the future, return on that investment, and the impact of healthcare changes on revenue, employment, and prevention.
It is vital to our future to consider fully not only the wishful thinking upsides but also the downsides of every proposal. Halting the rise in the cost of healthcare can mean shackling innovation and progress. The new tax on medical devices has that impact. The innovations that are curtailed could have been contributors to our gross national product, stimulating revenues, employment, and exports. If cost of development goes up in the United States, developments may ship overseas or stagnate (or both), and we may end up paying more to other countries for the technology that would have been a home grown revenue path.
The issue of individual freedom versus overriding public interest is manifest in the legality of tobacco use, its increased taxation, and the legality and illegality of many other means of self harm. To the extent that the government pays for the costs of the harm, it can invoke a public interest in preventing the choices that promote harm. Those issues have lead to the arguments supporting limitation on the size of your drinks, limiting your access to salt and sugar, and suggested penalties for obesity and so on, which subjugate choice in pursuit of attempts to reduce public support burdens. Curtailment of individual choice risks imposing “typically beneficial” choices on individuals who may not fit the mold and may actually be harmed. For example, in addition to people who develop or worsen hypertension or heart failure due to excess sodium intake, there are people who need elevated sodium intake to prevent postural hypotension and syncope. We are all genetically different. Policies aim for the typical often to the detriment of variants.
The ideas of a “universal insurance” or a “mandated insurance” have implicitly redefined what insurance really means. Insurance originated as a means of distributing actual risk, such that 100 fishermen, for example, might contribute to a joint fund to replace a fishing boat in case one sinks. Someone with no interest in fishing had very little interest in buying a share of such a fund. Individual choice enabled risk sharing over virtually anything, such that Jordan’s Furniture of Boston could make a giveaway deal with customers dependent on future Red Sox game play, and buy insurance to cover the risk of a fluke season that might create exorbitant expenses of honoring the deal with fans. Similarly, oil companies could get support for risky ventures with insurance to defray the low likelihood high costs of failures or reparations. Insurance enables a small entity to participate at an affordable cost when the deep pockets needed for contingencies would otherwise be prohibitive. The Affordable Care Act removed risk as a factor in healthcare “insurance” and spread the cost of healthcare expenses to include many people at minimal or no risk (for example, men paying for gynecologic costs and elderly paying for birth control coverage). The implicit change technically does not qualify any more as insurance but rather as a new tax to cover the cost of a distributed health benefits system, so declared by the Supreme Court. Why should such a system have any linkage at all to employment? Should change of employer result in change of coverage and thereby potential requirements to change physicians? Should such a system block people from the original benefits of insurance, i.e., choosing a level of risk reduction and benefits suited to the individual choices and concerns? Should all citizens be forced to focus on health as the same level of priority? In that case, it may become reasonable to block someone from working “too hard,” require no more than part time work for all, and block people from employments that pose elevated risks.
To keep a perspective, consider as an alternative means of health safety net a requirement that every hospital would provide space and support, and every pharmacist, nurse, physician, medical administrator and technologist as well as pharmacies and medical equipment companies would contribute a portion of time and resources to a free care safety net system with no overhead of paperwork for qualifications, a lawsuit free zone, that would address the basics of prevention and management of prevalent conditions such as obesity, diabetes, hypertension and heart failure, at near zero cost to taxpayers, with pairing of providers for quality control instead of government oversight or threat of lawsuit. This safety net could be independent of health savings accounts or insurance policies for additional care coverage suitable to the individuals interests and choices. Contrast that with a system that requires layers of investment in non-medical support of a new system that includes expansion of the internal revenue service as administrators of taxes guised as penalties to the healthy who legally evade paying for a service they don’t feel they need (the Affordable Care act does not in fact require insurance, rather it modifies tax according to coverage).
Regarding specific controversies, consider the delay of requirement for specific companies but not for small businesses or the public, exemptions for the White House, Supreme Court and Congress, and consider the presumably unintended consequence of driving companies to limit the number of employees and curtail full time employment in favor of more people with partial employment and fewer benefits (promoting a “part time society”). Also consider the leveling impact of government which some feel punishes extraordinary care and promotes game-players delivering cheap mediocre care focused on the government measures instead of the patient. The government has suggested linking payments to outcomes, but that is subject to patient selection bias and gamesmanship. Also consider the medium and long term impact of curtailing physician incomes such that those with highest skill will benefit from switching professions or countries. The Affordable Care Act includes making it ILLEGAL to provide free care that might be a competition to Medicare, and it provides specific punishment to physicians who are outliers for any reason (there are cases claiming they were punished for seeing high numbers of Medicare patients, for NOT charging, or were subject to fines for being more efficient than their peers). As a specific issue from the new laws that some deem contra-productive, cardiology intervention centers recently have been levied hefty new fines for catheterization of more patients than the median number for the size of their community.
What are the best methods of maintaining checks and balances to avoid abuses, promote low cost health and provide a reasonable safety net for all Americans? Is “insurance” really the best way to reign in costs? Do we require government takeover of healthcare? Should the safety net pay for all illegals? Should it not include personal responsibility regarding self-inflicted injuries? Should it require means testing, at the expense of a burgeoning administration layer? Should everyone pay to maximize the health of those who abuse their health? Can we have a distinction between safety net care and our entire healthcare system? Is it really reasonable to have no caps on the cost of care for an individual at the expense of curtailing benefits to the majority (for example, unlimited expenditure for a non-curable permanently unconscious child thereby reducing funds to help hardworking adults)? This is by no means an exhaustive list of the controversies. It is a strong argument for continued analysis of actual as opposed to desired impact of legislation, greater participation at the helm of people trained in health care, greater transparency and openness to alternative solutions.
Are there viable alternatives? How about generating a safety net completely independent of insurance, by requiring every hospital to provide 5% of space to free care, and 5% time from each nurse, doctor, technician, 5% of production from each medical equipment manufacturer and each pharmaceutical company, in a liability-free zone policed by independent double coverage instead of burdensome documentation, with virtually no overhead costs and no government funding or tax payer costs. How about the government contribution simplified to (a) enforcement of transparency, (b) provision of a secure world-wide database controlled by the patient to receive every report and enable access to a caretaker on a permission and as needed basis (to substantially alleviate duplicate testing, data access difficulties, and current need to regenerate patient information frequently from scratch), and (c) patient rights and patient education to improve appropriate basis for selection and reward of efficient quality services.
Introduction to Part 2
Larry H Bernstein, MD, FCAP
The Cost to Value Conundrum in Cardiovascular Healthcare Provision
Author: Larry H. Bernstein, MD, FCAP
Volume 2 of the e-series on Cardiovascular Diseases 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 synthesis
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 2 is a highly important treatment that is not technological, but about the system now outdated to support our healthcare system, the most technologically 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.
SOURCE
http://macro-economic-design.blogspot.com/p/book.html
2.0 The Cost to Value Conundrum in Cardiovascular Healthcare Provision
Larry H. Bernstein, MD, FCAP
2.1 Cost of Care for Cardiovascular Medical Diagnoses
2.1.1 Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & AHA Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems
Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FACP, and Aviva Lev-Ari, PhD, RN
2.1.2 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
Aviva Lev-Ari, PhD, RN
2.1.3 Heart Disease: Economic and Personal Effects
Reporter: Aviva Lev-Ari, PhD, RN
2.2 Impact of 2013 HealthCare Reform in the US
2.2.1 The Affordable Care Act: A Considered Evaluation. Part I. The legislative act (ACA) and the model for implementation (Insurance Gateways).
Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
2.2.2 The Affordable Care Act: A Considered Evaluation. Part II: The Implementation of the ACA, Impact on Physicians and Patients, and the Dis-Ease of the Accountable Care Organizations.
Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
2.2.3 The Affordable Care Act: A Considered Evaluation. Part III. Final Implementation of the Affordable Care Act and a Patient and Community Outcomes Focus
Larry H Bernstein, MD, FCAP
2.2.4 Post Acute Care – Driver of Variation in Healthcare Costs
Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
2.3 Patient Protection and Affordable Care Act Featured at RAND
Aviva Lev-Ari, PhD, RN
Part 3: Causes of Cardiovascular Diseases
Introduction to Part 3
Larry H Bernstein, MD, FCAP
The etiology, or causes, of cardiovascular diseases consist of mechanistic explanations for dysfunction relating to the heart or vascular system. Every one of a long list of abnormalities has a path that explains the deviation from normal. With the completion of the analysis of the human genome, in principle all of the genetic basis for function and dysfunction are delineated. While all genes are identified, and the genes code for all the gene products that constitute body functions, there remains more unknown than known. In part, the discrepancy is due to additional factors such as regulation of gene expression, post transcriptional modifications of gene products, and complex interactions. In addition, we do not have complete characterization of deviations from normal function, nor do we have a very well developed ability to modify the genes, gene products, complex interactions. We also have limitations in evaluating the impact of interventions intended either to correct a flaw, or compensate for it. Never-the-less, the story starts with the human genome, and in combination with improved imaging methods, genomics offers great promise in changing the course of disease and aging.
Part 3 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 2 and Part 3, 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.
2013 as A Year of Revolutionizing Medicine and Top 11 Cardiology Stories – Eric Topol
The e-Reader is advised to View the following VIDEOS on the Heart.org website as an Introduction to Cardiovascular Diseases
http://watchlearnlive.heart.org/CVML_Player.php
3.1 Human Genome: Congenital Etiological Sources of Cardiovascular Disease
3.1.1 Genomics & Genetics of Cardiovascular Disease Diagnoses
Aviva Lev-Ari, PhD, RN and Larry H Bernstein, MD, FCAP
3.1.2 Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging
Aviva Lev-Ari, PhD, RN
Aviva Lev-Ari, PhD, RN
3.1.3 Genetics of Conduction Disease
Aviva Lev-Ari, PhD, RN
3.2 The Role of Calcium in Health and Disease
Introduction by Larry H. Bernstein, MD, FCAP
It is incumbent on me to call attention to the huge contribution that research on calcium (Ca2+) signaling has made toward the understanding of cardiac contraction and to the maintenance of the heart rhythm. The heart is a syncytium, different than skeletal and smooth muscle, and the innervation is by the vagus nerve, which has terminal endings at vesicles which discharge at the myocyte junction. The heart specifically has calmodulin kinase CaMK II, and it has been established that calmodulin is involved in the calcium spark that triggers contraction. That is only part of the story. Ion transport occurs into or out of the cell, the latter termed exostosis. Exostosis involves CaMK II and pyruvate kinase (PKC), and they have independent roles. This also involves K+-Na+-ATPase. The cytoskeleton is also discussed, but the role of aquaporin in water transport appears elsewhere, as the transport of water between cells. When we consider the Gibbs-Donnan equilibrium, which precedes the current work by a century, we recall that there is an essential balance between extracellular Na+ + Ca2+ and the intracellular K+ + Mg2+, and this has been superseded by an incompletely defined relationship between ions that are cytoplasmic and those that are mitochondrial. The glass is half full!
3.2.1 Identification of Biomarkers that are Related to the Actin Cytoskeleton – Part I
Larry H Bernstein, MD, FCAP
3.2.2 Role of Calcium, the Actin Skeleton, and Lipid Structures in Signaling and Cell Motility – Part II
Larry H. Bernstein, MD, FCAP, Stephen Williams, PhD and Aviva Lev-Ari, PhD, RN
3.2.3 Ca2+-Stimulated Exocytosis: The Role of Calmodulin and Protein Kinase C in Ca2+ Regulation of Hormone and Neurotransmitter
Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
3.2.4 Disruption of Calcium Homeostasis: Cardiomyocytes and Vascular Smooth Muscle Cells: The Cardiac and Cardiovascular Calcium Signaling Mechanism – Part VIII
Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
3.2.5 Synaptotagmin functions as a Calcium Sensor: How Calcium Ions Regulate the fusion of vesicles with cell membranes during Neurotransmission – Part X
Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
3.2.6 The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and Ryanodine Receptors in Cardiac Failure, Arterial Smooth Muscle, Post-ischemic Arrhythmia, Similarities and Differences, and Pharmaceutical Targets
Larry H Bernstein, MD, FCAP, Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
3.2.7 Atherosclerosis Independence: Genetic Polymorphisms of Ion Channels Role in the Pathogenesis of Coronary Microvascular Dysfunction and Myocardial Ischemia (Coronary Artery Disease (CAD))
Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
3.2.8 Calcium Signaling, Cardiac Mitochondria and Metabolic Syndrome
Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
3.3 Vasculature and Myocardium: Diagnosing the Condition of Disease
3.3.1 State of Cardiology on Wall Stress, Ventricular Workload and Myocardial Contractile Reserve: Aspects of Translational Medicine (TM)
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
3.3.2 Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
3.3.3 Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
3.3.4 Mitral Valve Repair: Who is a Patient Candidate for a Non-Ablative Fully Non-Invasive Procedure?
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
Part 4: Risks and Biomarkers for Cardiovascular Diseases
Introduction
Larry H Bernstein, MD, FCAP
Biomarkers are biologic indicators of the status, severity, mechanism or genetic predisposition to disease, typically consisting of a test for the concentration of a protein or chemical. Many of the biomarker tests use antibodies (biologic molecules designed to match the biomarker like a glove), linked to production of a color signal so that color intensity reports concentration (prevalence of the marker). The completion of the human genome map means that all candidate precursors are known in principle. The genetic map is not the whole story, because the rate of production (translation) from the genetic map and the post-translational modifications as well as the distribution and clearance rates (destruction, transport) all play important roles.
There are many roles for biomarkers:
- risk assessment
- disease status
- mechanism of injury
- severity of disease
- response to interventionsThe following addresses a small set of examples from an exhausting list of biomarkers.
4.1 The Role of Calcium in Health and Disease
4.1.1 Renal Distal Tubular Ca2+ Exchange Mechanism in Health and Disease – Part III
Larry H. Bernstein, MD, FCAP, Stephen J. Williams, PhD and Aviva Lev-Ari, PhD, RN
4.2 Vasculature and Myocardium: Diagnosing the Condition of Disease – Biomarkers of Acute Cardiovascular Events
4.2.1 No Early Symptoms – An Aortic Aneurysm Before It Ruptures – Is There A Way To Know If I Have it?
Aviva Lev-Ari, PhD, RN
4.2.2 Females and Non-Atherosclerotic Plaque: Spontaneous Coronary Artery Dissection: New Insights from Research and DNA Ongoing Study
Aviva Lev-Ari, PhD, RN
4.2.3 Cardiovascular Diseases: Decision Support Systems for Disease Management Decision Making
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
4.2.4 Dealing with the Use of the High Sensitivity Troponin (hs cTn) Assays
Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
4.2.5 Prognostic Marker Importance of Troponin I in Acute Decompensated Heart Failure (ADHF): Troponin I in acute decompensated heart failure: insights from the ASCEND-HF study
Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
4.2.6 More on the Performance of High Sensitivity Troponin T and with Amino Terminal Pro BNP in Diabetes
Larry H. Bernstein, MD, FCAP
4.2.7 The Cardio-Renal Syndrome (CRS) in Heart Failure (HF)
Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
4.2.8 Vasoplegia in Orthotopic Heart Transplant Patients
Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
4.2.9 Myocardial Infarction: The New Definition After Revascularization
Aviva Lev-Ari, PhD, RN
4.3 Biomarkers of Long Term Risk of Cardiovascular Disease
4.3.1 Special Considerations in Blood Lipoproteins, Viscosity, Assessment and Treatment
Larry H Bernstein, MD FCAP and Aviva Lev-Ari, PhD, RN
4.3.2 What is the Role of Plasma Viscosity in Hemostasis and Vascular Disease risk?
Larry H Bernstein, MD and Aviva Lev-Ari, PhD, RN
4.3.3 High-Density Lipoprotein (HDL): An Independent Predictor of Endothelial Function & Atherosclerosis, A Modulator, An Agonist, A Biomarker for Cardiovascular Risk
Aviva Lev-Ari, PhD, RN
4.3.4 Artherogenesis: Predictor of CVD – the Smaller and Denser LDL Particles
Aviva Lev-Ari, PhD, RN
4.3.5 Hypertriglyceridemia concurrent Hyperlipidemia: Vertical Density Gradient Ultracentrifugation a Better Test to Prevent Undertreatment of High-Risk Cardiac Patients
Aviva Lev-Ari, PhD, RN
4.3.6 Cholesteryl Ester Transfer Protein (CETP) Inhibitor: Potential of Anacetrapib to treat Atherosclerosis and CAD
Aviva Lev-Ari, PhD, RN
4.4 Conduction Dysfunction and ElectroPhysiology of the Heart
4.4.1 On Devices and On Algorithms: Arrhythmia after Cardiac Surgery Prediction and ECG Prediction of Paroxysmal Atrial Fibrillation Onset
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
4.4.2 Genetic Analysis of Atrial Fibrillation
Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
4.4.3 Oxidized Calcium Calmodulin Kinase and Atrial Fibrillation
4.4.4 Renal Function Biomarker, β-trace protein (BTP) as a Novel Biomarker for Cardiac Risk Diagnosis in Patients with Atrial Fibrilation
Aviva Lev-Ari, PhD, RN
4.4 Cardiovascular Imaging: Diagnosing the Condition of the Disease and Determining Course of Treatment
4.5.1 Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
4.5.2 Coronary Circulation Combined Assessment: Optical Coherence Tomography (OCT), Near-Infrared Spectroscopy (NIRS) and Intravascular Ultrasound (IVUS) – Detection of Lipid-Rich Plaque and Prevention of Acute Coronary Syndrome (ACS)
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
4.5.3 Emerging Clinical Applications for Cardiac CT: Plaque Characterization, SPECT Functionality, Angiogram’s and Non-Invasive FFR
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
4.5.4 Fractional Flow Reserve (FFR) & Instantaneous wave-free ratio (iFR): An Evaluation of Catheterization Lab Tools (Software Validation) for Ischemic Assessment (Diagnostics) – Change in Paradigm: The RIGHT vessel not ALL vessels
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
4.5.5 Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
Part 5: Advances in Treatment of Cardiovascular Diseases
Introduction
Larry H Bernstein, MD, FCAP – PENDING
and
Justin D Pearlman, MD, PhD, FACC
When a patient presents to an emergency room with reduced exertion tolerance and other symptoms suggestive of heart attack, the urgent issue is to identify whether or not there is an imminent risk of permanent and progressively on-going muscle damage. If the electrocardiogram shows diagnostic elevations (STEMI) then emergency intervention is generally vital, embodied by the expression “time is muscle.”
The term “chest pain” is widely used, but we teach patients that it is a convenience phrase but it does not have to be in the chest and it does not have to be pain. There is a wide range of symptoms that qualify as “chest pain” including pressure in the chest, neck, left arm or jaw, a sense of oppression or doom, squeezing, or other symptoms above the waist that may correspond to personalized symptoms of inadequate blood supply to the heart.
When a threat to the heart is identified, the next step is to activate an “acute coronary syndrome” (ACS) protocol which aims to abort thrombosis and promote improved blood delivery to the impaired region of the heart.
In some cases the propensity to form a thrombus (blood clot) contributing to impairment of blood delivery to a part of the heart is chronic. After stent placement, medications to impede the contribution of platelets to thrombosis is a standard treatment (aspirin, and typically for the first two years after stent placement other anti-platelet agents), but there is a growing interest in anticoagulants (the fibrinous spider-web like component of thrombosis). This matter is addressed in our article: Do Novel Anticoagulants Affect the PT/INR?
5.1 Vasculature and Myocardium: Diagnosing the Conditions of Disease
5.1.1 Erythropoietin (EPO) and Intravenous Iron (Fe) as Therapeutics for Anemia in Severe and Resistant CHF: The Elevated N-terminal proBNP Biomarker
Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
5.1.2 Do Novel Anticoagulants Affect the PT/INR? The Cases of XARELTO (rivaroxaban) or PRADAXA (dabigatran)
Vivek Lal, MBBS, MD, F.Cl.R, Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
5.1.3 Alternative Designs for the Human Artificial Heart: The Patients in Heart Failure – Outcomes of Transplant (donor)/Implantation (artificial) and Monitoring Technologies for the Transplant/Implant Patient in the Community
Larry H. Bernstein, MD, FCAP, Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
5.1.4 Vascular Surgery: International, Multispecialty Position Statement on Carotid Stenting, 2013 and Contributions of a Vascular Surgeon at Peak Career – Richard Paul Cambria, MD
Aviva Lev-Ari, PhD, RN
5.1.5 Heart Transplant (HT) Indication for Heart Failure (HF): Procedure Outcomes and Research on HF, HT @ Two Nation’s Leading HF & HT Centers
Aviva Lev-Ari, PhD, RN
5.1.6 Endovascular Lower-extremity Revascularization Effectiveness: Vascular Surgeons (VSs), Interventional Cardiologists (ICs) and Interventional Radiologists (IRs)
Aviva Lev-Ari, PhD, RN
5.1.7 Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care
Aviva Lev-Ari, PhD, RN
5.1.8 AHA, ACC Change in Requirement for Surgical Support for PCI Performance: Class IIb -> Class III, Level of Evidence A: Support Nonemergent PCI without Surgical Backup (Change of class IIb, Level of evidence B)
Justin Pearlman, MD, PhD, FACC and Larry H Bernstein, MD, FCAP
5.1.9 Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization
Larry H Bernstein, MD, FACP and Aviva Lev-Ari, PhD, RN
5.1.10 Vascular Repair: Stents and Biologically Active Implants
Larry H Bernstein, MD, FACP and Aviva Lev-Ari, PhD, RN
5.1.11 Regeneration: Cardiac System (cardiomyogenesis) and Vasculature (angiogenesis)
Aviva Lev-Ari, PhD, RN
5.1.12 Fight against Atherosclerotic Cardiovascular Disease: A Biologics not a Small Molecule – Recombinant Human lecithin-cholesterol acyltransferase (rhLCAT) attracted AstraZeneca to acquire AlphaCore
Aviva Lev-Ari, PhD, RN
5.1.13 Harnessing New Players in Atherosclerosis to Treat Heart Disease
Aviva Lev-Ari, PhD, RN
5.2 The Role of Calcium in Health and Disease
5.2.1 Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD – Part VI
Aviva Lev-Ari, PhD, RN
5.2.2 Cardiac Contractility & Myocardium Performance: Ventricular Arrhythmiasand Non-ischemic Heart Failure – Therapeutic Implications for Cardiomyocyte Ryanopathy (Calcium Release-related Contractile Dysfunction) and Catecholamine Responses – Part VII
Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
5.2.3 Calcium-Channel Blockers, Calcium Release-related Contractile Dysfunction (Ryanopathy) and Calcium as Neurotransmitter Sensor – Part IX
Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
5.3 Conduction Dysfunction and ElectroPhysiology of the Heart
The voice of our Series A Content Consultant: Justin D Pearlman, MD, PhD, FACC
Therapeutic intervention in cardiovascular disease comprises numerous avenues including genetic manipulation, pharmaceuticals, electric and mechanical devices, and physiologic manipulations as well as emotional and logistic support.
The opportunities to halt progression, mitigate and even reverse harm take many forms: replace missing signals, suppress excessive signals, provide genes and/or cells to replace or repair damage, compensate for over or under activity with complementary functions, or intervene electrically and/or mechanically. While it is often quite effective to intervene at the source of a problem, effective treatments have often been devised that act downstream from the cause, interrupting or countermanding some aspect of the cascade of consequences. For example, ion channels may cause sinus arrest, leading to failure to activate heart contractions in a timely fashion. Pacemakers do not correct the malfunctioning sinus node, but rather act downstream to provide an alternative means to activate timely heart contractions. Currently pacemakers do not aim to bridge into the specialized conduction system of the heart, rather they directly activate distal muscle. Consequently the activation sequence is distinct and is not as well synchronized, resulting in a wobbling motion of the heart called dysynchrony. In extreme, the distinct activation pattern of dysynchrony can lower the effectiveness of each heart beat (reduced stroke volume and reduced ejection fraction). More advanced pacemakers initiate contraction from two different locations (left and right ventricle) at staggered times aimed to produce a more synchronized net contraction timing. If a patient has an intact specialized conduction system, pacing to activate that system produces a more normal synchronized contraction of heart muscle. Atrial pacemakers have that effect, but often disease requiring pacemakers includes not only sinus node dysfunction but also abnormal conduction. Theory has to be tested to evaluate reliability and extent of benefit. Solutions that cover a wide range of abnormalities are generally easiest to apply, whereas solutions that are very specific often have better results.
As the mysteries of the human genome products are unraveled, we learn more and more about key components. As we learn more details about the controlling biologic functions we can expand our ability to manipulate them, predict the consequences, and identify new and possibly more effective or more efficient means to promote an improved outcome.
5.3.1 Cardiac Resynchronization Therapy (CRT) to Arrhythmias: Pacemaker/Implantable Cardioverter Defibrillator (ICD) Insertion
Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
5.4 Cardiovascular Imaging: Diagnosing the Condition of the Disease and Determining Course of Treatment
5.4.1 3D Cardiovascular Theater – Hybrid Cath Lab/OR Suite, Hybrid Surgery, Complications Post PCI and Repeat Sternotomy
Aviva Lev-Ari, PhD, RN
Summary to Volume Two
Voice of Justin D Pearlman, MD, PhD, FACC
This volume introduces a fresh look at keeping abreast of cardiovascular disease. In particular it explains and exemplifies the how and why of curation as a methodology for discourse. Curation is designed to edify and facilitate awareness and cohesive access to biomedical knowledge otherwise buried in subspecialty scientific journals in the Life Sciences and Medicine. Particular themes of focus include discovery, innovation and translation to clinical care, including linkages and underpinnings that might otherwise be mislabeled as esoteric. Key components of curation include expert identification of data, ideas and innovations of interest, expert interpretation of the original research results, integration with context, digesting, highlighting, correlating and presenting in novel light.
Three aspects of curation are notable:
(1) self-driven analytic reviews by a content expert,
(2) exciting topics assigned to an expert curator for analytic coherent fusion,
(3) teamwork of multiple experts on a focused theme, complementing each others’ contributions by weaving distinct threads.
Examples presented included review of electro-mechanical coupling and action potential, the roles of calcium redistribution in biology, the roles of biomarkers, healthcare and the Affordable Care Act, the human genome as basis for cardiovascular diseases, and the evolution of treatment options to manage cardiovascular diseases. These examples of Curation demonstrate added value of curation over traditional stand alone single author or multi-author research reports and review articles.
The superstructure of curations includes multiple additional creative elements:
1. eTOCs = electronic table of contents: fresh thought-provoking organizing themes link a path to a diverse trail of publications (analogous to creating a path in the forest)
2. Extracts highlighting notable elements of publications that mark a path
3. Voice of Expert commentary providing context and direction
The Electronic Table of Contents (eTOCs) serves several functions:
1. eTOCs collates information from multiple sources into coherent themes
2. eTOCs enables multiple pathways to information, including both Longitudinal and cross-sectional organizational themes.
3. eTOCs presents nested pathways through the forest, including nesting of topics by overreaching theme, chapters, Curations, reports and references.
4. eTOCs assemblies of thought provide fresh vistas that promote innovation and rethinking
In ekistics (urban design) Francis Bacon emphasized the importance of pathways linked to purpose, recommending a landmark magnet as an attractor for pursuits along a created path. Analogously, if the continually expanding collective knowledge embodied in subspecialty publications represents a forest of data and ideas, then Curation creates pathways in that forest that serve not only to keep the reader from getting lost, but also, as recommended by Francis Bacon, creates pathways that serve attractive purposes, with special vistas, highlights, themes, coherence, motivations and purposes.
CONTEXT (for each, Causes, Risks, Biomarkers and Therapeutics):
- Volume One: Perspectives on Nitric Oxide in Disease Mechanisms
- Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation
- Volume Three: Etiologies of Cardiovascular Diseases – Epigenetics, Genetics & Genomics
- Volume Four: Therapeutic Promise: Cardiovascular Diseases, Regenerative & Translational Medicine
- Volume Five: Pharmaco-Therapies for Cardiovascular Diseases
- Volume Six: Interventional Cardiology, Cardiac Surgery and Cardiovascular Imaging for Disease Diagnosis and Guidance of Treatment
Epilogue to Volume Two
Aviva Lev-Ari, PhD, RN, Editor-in-Chief, BioMed e-Series of e-Books
Part 1: Curation is another Methodology for Creation of Scientific Knowledge.
OPINION LEADERSHIP: We are developers of new methodologies for Research Finding exposition and dissemination
The Curation process involves development of numerous avenues for exposition of the scientific product and its dissemination, among them:
- scientific articles on Scientific Journals,
- Books, e-Books
- Addresses by Leader Scientists,
- multimedia presentations (Audio and Video),
- Expert Panel Discussions,
- Correspondence among Scientists,
- archive of experiment results, thematic Literature surveys,
- Libraries of Open Source Code,
- Comprehensive Thematic Bibliographies,
- Shareable Libraries of Annotated Genomics Research
In our curations we have used several from the above list. We take great pride in our presentations of critiques and synthesis of research results. We represent one alternative to Academic Publishing. Instead of divergence into millions of publications per year, we focus on the Frontier, we select several seminal articles and aggregate the outcomes, their significance in context and creatively we identify interrelations not included in each of the components of the assembly.
Part 2: Cardiovascular Diseases – Predicted Cost of Care and the Affordable Care Act
- Cost of Care for Cardiovascular Medical Diagnoses
- Impact of 2013 HealthCare Reform in the US
- Patient Protection and Affordable Care Act Featured at RAND
OPINION LEADERSHIP: We identify the potential of Cardiac Regeneration to be the frontier for Cardiovascular Disease near-cure
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.
https://www.sciencemag.org/content/338/6114/1549.summary
OPINION LEADERSHIP: We identify ACCESS to HealthCare Services to be the cardinal factor of success for the Affordable Care Act (ACA).
On January 10, 2014 Jonathan Cohn wrote in the New Republic: The Kids Are Alright: Another Obamacare Lesson from Massachusetts
Youth is not be the same thing as health. A 33-year-old with diabetes will run up bigger physician and drug bills than a 61-year-old with no serious medical problems. But, as a general rule, younger means healthier. And the early numbers haven’t seemed that encouraging.
Overall, according to a study by the Kaiser Family Foundation, about 40 percent of the people who could eventually buy coverage through Obamacare marketplaces are between the ages of 18 and 34. But, as of December, just 22 percent of the people signing up for coverage in California were in that demographic. Other states reported similar data. The federal government hasn’t yet provided an age breakdown for people getting insurance through healthcare.gov, the website it operates on behalf of 36 other states. But it will probably provide that information soon. When it does, the numbers may not look any better.
Is this a big deal? One way to answer that question is by looking at the best test case available: Massachusetts, which introduced a similar reform scheme in 2007. Thanks to analysis from Jonathan Gruber, the MIT economist who was an architect of both the Massachusetts and federal reforms, we know that enrollment was slow to get rolling in Massachusetts—and that, relatively speaking, healthy people came into the system late. Now Gruber has done a new analysis, breaking down enrollment specifically by age, and provided it to the New Republic.
The graph above tells the story. Over the course of the first year, the proportion of young people (in this case, ages 19 to 34) who had obtained health coverage through the Massachusetts insurance exchange grew. In other words, they were more likely to sign up late.
The precise figures don’t mean a lot, in part because the Massachusetts analogy is hardly perfect. John Sexton of Breitbart (yes, that Breitbart) has written about some of the key distinctions. But the trend is pretty clear—and, according to Gruber, it provides some important lessons. “These data aren’t 100 percent predictive for every state, most importantly because of differences across states in the share of the potential market that is young,” Gruber says. “But these facts highlight two things. First, you don’t need a huge/majority share of enrollees to be young for markets to function well. Second, the young tend to wait to sign up until closer to the deadline.
Obamacare could obviously unfold differently, with plenty of variation from state to state. In some places, participation among the young might not rise the way it did in Massachusetts—or, at least, it might not reach the same levels. But that doesn’t mean those states are destined for an insurance “death spiral,” in which carriers jack up rates so high that only the very sick stay in the system.
Part 3: Causes of Cardiovascular Diseases
- Human Genome: Congenital Etiological Sources of Cardiovascular Disease
- The Role of Calcium in Health and Disease
- Vasculature and Myocardium: Diagnosing the Conditions of Disease
OPINION LEADERSHIP: We identify two pivotal research directions in the effort to understand the Etiology of Cardiovascular Diseases
1. The Research Frontier on Cardiac Regeneration by Anthony Rosenzweig, M.D.
Professor of Medicine, Beth Israel Deaconess Medical Center on Cardiac Regeneration and How does Exercise help the Heart
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
- 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.
Anthony Rosenzweig, M.D. Professor of Medicine, Beth Israel Deaconess Medical Center
We are interested in why the heart fails. Heart failure is an enormous and growing cause of death and disability throughout the world. In addition, the heart provides a model system for studying fundamental cellular processes from cell growth and programmed death, to cell-lineage determination and regeneration. Recently we’ve been interested in understanding how exercise protects the heart against heart failure. A variety of high throughput profiling techniques are being used to identify pathways differentially regulated in heart growth associated with exercise in comparison to the heart growth that precedes heart failure. A recently identified transcriptional pathway involved C/EBPβ and CITED4 not only reproduces many of the effects of exercise and protects the heart from heart failure, but appears to enhance the heart’s regenerative capacity (Bostrom et al Cell, 2010). In vivo gain- and loss-of-function models are being used to explore the functional effects and molecular mechanisms of this pathway in more detail. Other ongoing studies are investigating cardiac micro-RNAs regulated by exercise and their potential protective effects in the heart.
http://connects.catalyst.harvard.edu/Profiles/display/Person/10161
2. Biology of the Nucleus and Gene Expression @ Spiegelman Lab, Harvard Medical School
- Transcriptional Basis of Energy Metabolism
- Regulation of Fat Cell Differentiation
- Metabolic Control through the PGC-1 Coactivators
- Chemical Biology of the PGC-1 Coactivators
β-Aminoisobutyric Acid Induces Browning of White Fat and Hepatic β-Oxidation and Is Inversely Correlated with Cardiometabolic Risk Factors. Cell Metab. 2014 Jan 7;19(1):96-108. doi: 10.1016/j.cmet.2013.12.003.
Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab. 2013 Nov 5;18(5):649-59. doi: 10.1016/j.cmet.2013.09.008. Epub 2013 Oct 10.
http://research4.dfci.harvard.edu/spiegelmanlab/research.htm
Part 4: Risks and Biomarkers for Cardiovascular Diseases
OPINION LEADERSHIP: We identify as fruitful area of further study –
1. Genetic Determinants of Potassium Sensitivity and Hypertension. Integrated Computational and Experimental Analysis of the Neuroendocrine Transcriptome in Genetic Hypertension Identifies Novel Control Points for the Cardiometabolic Syndrome
2. Essential hypertension, a common complex disease, displays substantial genetic influence. Contemporary methods to dissect the genetic basis of complex diseases such as the genome-wide association study are powerful, yet a large gap exists between the fraction of population trait variance explained by such associations and total disease heritability.
3. There are many roles for biomarkers to be subject for further research:
- risk assessment
- disease status
- mechanism of injury
- severity of disease
- response to interventions
The following topics address a small set of examples from an exhausting list of biomarkers:
- The Role of Calcium in Health and Disease
- Vasculature and Myocardium: Diagnosing the Conditions of Disease
- Conduction Dysfunction and ElectroPhysiology of the Heart
- Cardiovascular Imaging: Diagnosing the Condition of the Disease and Determining Course of Treatment
Part 5: Advances in Treatment of Cardiovascular Diseases
- Vasculature and Myocardium: Diagnosing the Conditions of Disease
- The Role of Calcium in Health and Disease
- Conduction Dysfunction and ElectroPhysiology of the Heart
- Cardiovascular Imaging: Diagnosing the Condition of the Disease and Determining Course of Treatment
OPINION LEADERSHIP: We identify the frontier of Treatment for Cardiovascular diseases to embrace potentially the following trends:
Sources of Evidence in Identifying Risk Factors for Cardiovascular Disease will continue to be derived from a combination of research methodologies:
- Basic research
- Epidemiological research
- Descriptive
- Analytical
- Observational
- Case-control studies
- Cohort studies
- Randomized trials
Physical Activity:
- Cumulative long-term PA has a protective effect on incidence of all-cause and CVD-attributable mortality compared with long-term physical inactivity.
- In men, but not women, long-term PA also appears to have a protective effect on incidence of CVD.
Is it Hypertension or Physical Inactivity: Cardiovascular Risk and Mortality – New results in 3/2013
Heart doi:10.1136/heartjnl-2012-303461
Cardiovascular Imaging:
Comparison of the longitudinal, radial, circumferential, rotational and torsional mechanics of the left ventricle (LV) in patients with constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM), and detect the new quantitative parameters to differentiate CP and RCM using two-dimensional speckle tracking imaging (2-D STI) method. Torsion, longitudinal and radial strain measured by 2-D STI method can provide useful information to differentiate CP and RCM.
http://heart.bmj.com/content/97/Suppl_3/A210.2.abstract
Pharmacotherapy:
Increase in use of Biological Based Therapy (BBT) among cardiovascular patients to avoid side effects of prescription drugs.
In recent years, the interest of using Biological Based Therapy (BBT) in disease management has increased dramatically in the medical and layman communities. The amount of valid scientific research in this area of therapy continues to increase. Yet, there are still many unknowns concerning BBT, especially in the area of adverse effects and drug interactions. The finding of a high prevalence of BBT (47.5%) use among cardiovascular patients and the lack of communication between patients and their physicians/pharmacists should be addressed by the health care community. Higher education level, as shown in the present study and other previous investigations [1,3,6,22], is associated with an increased use of BBT, but it does not necessarily mean that these patients are aware of the potential detrimental effects of BBT, as demonstrated in the current study. In cardiovascular patients, the perceived effectiveness and safety of BBT, and assumed lack of side effects of these products as opposed to traditional medications, highlights an area for further education. A high incidence of potential drug-BBT interactions was also identified in this study (42 interactions in 94 users). Given that the use of BBT can have a direct effect on patient care, and users of these therapies do not always voluntarily report their use of these products to their providers, health care professionals need to inquire about BBT use routinely. Collecting complete patient histories and educating patients about potential dangers and possibilities of adverse effects and interactions between prescription medications and BBT (or other CAM) will lead to better overall patient care.
http://www.biomedcentral.com/1472-6882/5/4
Genomics is been harnessed for Familial and non-familial Cardomyopathies Diagnosis and Treatment
Genetic and phenotypic heterogeneity that characterizes all cardiomyopathies pose major clinical challenges. In this article, we focus on the task of diagnosis, exploring how a systematic clinical approach can be used to identify specific disorders and guide the selection of further diagnostic tests, including molecular genetic analysis.
Cardiomyopathies are defined as disorders of heart muscle unexplained by coronary artery disease, hypertension, valvular disease or congenital heart disease.1 They are classified by morphological and functional phenotype into
- hypertrophic cardiomyopathy (HCM),
- dilated cardiomyopathy (DCM),
- restrictive cardiomyopathy (RCM), and
- arrhythmogenic right ventricular cardiomyopathy (ARVC) subtypes
http://heart.highwire.org/content/99/19/1451.extract
Iron Metabolism and Mitochondrial Mechanisms
Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosol
The field of mitochondrial iron metabolism and trafficking that has recently been stimulated by the discovery of proteins involved in mitochondrial iron storage (mitochondrial ferritin) and transport (mitoferrin-1 and -2). In addition, recent work examining mitochondrial diseases (e.g., Friedreich’s ataxia) has established that communication exists between iron metabolism in the mitochondrion and the cytosol. This finding has revealed the ability of the mitochondrion to modulate whole-cell iron-processing to satisfy its own requirements for the crucial processes of heme and ISC synthesis. Knowledge of mitochondrial iron-processing pathways and the interaction between organelles and the cytosol could revolutionize the investigation of iron metabolism.
http://www.pnas.org/content/early/2010/05/20/0912925107
Role of Calcium and Gene therapy in treatment of Pulmonary Arterial Hypertension and Heart Failure
Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure
Sinus Node Dysfunction (SND): Patient Education
Educate patients to recognize symptoms of SND. Family members should learn cardiopulmonary resuscitation (CPR).
Because most pediatric patients with SND have already received surgery for CHD (eg, Mustard procedure, Fontan procedure), their education is focused on recognizing symptoms of CHF and tachya-rrhythmias, such as atrial flutter/fibrillation, which are usually poorly tolerated.
Patients who are on anti-arrhythmic medication for atrial flutter or fibrillation should be instructed to take their medication regularly and to visit the cardiologist as scheduled. They should also be cognizant of the adverse effects and toxicity of the medication.
In patents who have already received a Mustard or Fontan procedure, undergoing yearly echocardiography to monitor cardiac function is advisable. If cardiac function is decreased, anti-CHF management should be started and close follow-ups with the cardiologist are advisable.
Patients who have a pacemaker should be instructed on the means of obtaining regular checks. Such checks are usually achieved from home with a trans-telephonic monitor that transmits to a central monitoring station, which, in turn, contacts the cardiologist in case a problem is detected (eg, device malfunction, arrhythmia).
Patients who have an intra-cardiac defibrillator (ICD) device should receive the same instructions that patients who have pacemakers receive. Because patients with ICDs often are placed on anti-arrhythmic medication, they also should receive instruction regarding medication schedules and information about adverse effects and toxicity.
In addition, in patients with frequent atrial flutter or fibrillation episodes, which are followed by a shock from the ICD, patients are instructed to avoid activities that may pose a risk to themselves and/or other people (eg, driving). They also receive instruction on when to go to the cardiologist or the emergency department.
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