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

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

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

Reporter: Aviva Lev-Ari, PhD, RN

Medscape Medical News from the

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

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

April 04, 2014

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

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

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

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

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

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

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

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

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

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

*By MRI or CT, primary end point

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

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

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

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

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

 

SOURCE

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

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Cardiac Perfusion Exam, Rapid Heart Scanner, CT, MRI and PET imaging – Innovations in Radiology @ Beth Israel Deaconess Medical Center

Posted in Atherogenic Processes & Pathology, Cardiovascular Research, Frontiers in Cardiology and Cardiovascular Disorders, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism on February 12, 2014| Leave a Comment »

Cardiac Perfusion Exam, Rapid Heart Scanner, CT, MRI and PET imaging – Innovations in Radiology @ Beth Israel Deaconess Medical Center

Reporter: Aviva Lev-Ari, PhD, RN

 

UPDATED on 7/31/2018

VIEW VIDEO

https://www.dicardiology.com/videos/video-state-ct-myocardial-perfusion-imaging?eid=333021707&bid=2191253

A discussion with Gianluca Pontone, M.D., Ph.D., FSCCT, director of cardiovascular MRI, Centro Cardiologico Manzino, Milan, Italy, at the Society of Cardiovascular Computed Tomography (SCCT) 2018 meeting. He said CT can be comparable to the gold-standards of nuclear and MRI perfusion depending on the scanner used to acquire the images.

Read the article “CT Perfusion Imaging Ready for Mainstream.” 

Five New Imaging Tests Can Help Diagnose A Variety Of Illnesses Better

December 15, 2010 5:20 PM

(credit: Beth Israel Deaconess Medical Center)

(credit: Beth Israel Deaconess Medical Center)

By Michael Lasalandra, Beth Israel Deaconess Medical Center Correspondent

The evolution of imaging technology has resulted in doctors’ being able to more quickly and accurately diagnose many potentially life-threatening disorders, including serious abdominal issues, and coronary artery disease, as well as brain tumors and other cancers, to name a few.

“Current technologic advances in CT, MRI and PET imaging reflect advancements that have evolved over the past 20 years,” said Dr. Max Rosen, Executive Vice Chairman Radiology, Beth Israel Deaconess Medical Center. “They are a leap forward towards more personalized medicine focused on an individual patient’s specific problem. The improvements are leading to more rapid and accurate diagnoses, which potentially can lead to more effective, lifesaving treatments.”

Five examples:

Breast MRI

 

five new imaging tests1 Five New Imaging Tests Can Help Diagnose A Variety Of Illnesses Better

Breast MRI

MRI (magnetic resonance imaging) machines do not expose patients to radiation. Instead, they use a magnetic field, radio frequency pulses and a computer to obtain images. While mammograms, which use x-ray technology, are the primary method for screening for breast cancer, MRI can be used to work up more subtle cases, or for breast cancers which cannot be seen on a mammogram says Dr. Rosen. Typically, breast MRI is reserved to screen women who are at high risk for developing breast cancer, to determine extent of cancer involvement in newly diagnosed patients,  to problem-solve a suspicious finding on other imaging, or to aid in surgical planning.

Abdominal CT scan

 

five new imaging tests 1 Five New Imaging Tests Can Help Diagnose A Variety Of Illnesses Better

Abdominal CT Scan

Also known as computed tomography, CT scans combine a series of X-rays taken from a variety of different angles to produce cross-sectional images of the bones and soft tissues inside the body. These are often used in the Emergency Room setting to rapidly and accurately diagnose abdominal pain. “CT can accurately identify the cause of the pain,” says Dr. Rosen. “Common causes would be appendicitis, diverticulitis, kidney stones or inter-abdominal bleeding.” Such scans are also extremely useful for patients who have been in traumatic accidents. Multi-row detector CT scans can rapidly image the entire chest, abdomen and pelvis in less than a minute and can identify life-threatening fractures or other complications, he notes.

Coronary CT Angiogram to evaluate heart arteries

 

five new imaging tests 21 Five New Imaging Tests Can Help Diagnose A Variety Of Illnesses Better

Coronary CT Angiogram

This test is useful in identifying narrowing in the coronary arteries. “By injecting an IV contrast dye into the vein and using a fast scanner, you can get beautiful images of the coronary arteries,” says Dr. Rosen. “You can see if there is plaque and if it is causing any narrowing.” The test is used for patients who have been having chest pain or for those at high risk for coronary disease with atypical chest pain and can identify those patients who are not having a heart attack, he says. The advantage is that cardiac catheterization – where a balloon-tipped catheter is snaked through the coronary artery – may be avoided. However, if the CTA is abnormal, the catheterization may still need to be performed prior to bypass surgery or to dilate the blocked artery using a balloon catheter or metallic stent.

PET-CT scan for cancer assessment

 

five new imaging tests 31 Five New Imaging Tests Can Help Diagnose A Variety Of Illnesses Better

PET-CT scan

Positron emission tomography, also called a PET scan, is a type of nuclear medicine imaging. It uses tiny amounts of radioactive material as tracers to diagnose a variety of diseases, including many types of cancer. The scan can visualize metabolic activity in an area of suspected abnormality such as a tumor. Doctors can use PET and CT data and images together for greater diagnostic accuracy than either technique offers alone. PET-CT allows them to see not only the size of the tumors, but also their biological behavior and whether or not they are responding to therapy. This hybrid technology “is the beginning of a new wave of molecular imaging where you can target a specific tumor to help characterize it as well as see if it is growing or metabolizing,” Dr. Rosen says.

fMRI (functional MRI) for evaluation and treatment planning of brain tumors

 

five new imaging tests 61 Five New Imaging Tests Can Help Diagnose A Variety Of Illnesses Better

fMRI (functional MRI) for evaluation and treatment planning of brain tumors

Functional Magnetic Resonance Imaging (fMRI) is a type of specialized MRI scan. It assesses the change in blood flow related to neural activity in the brain or spinal cord. It is widely used for brain mapping due to its high accuracy and absence of radiation. fMRI is often combined with Diffusion Tensor Imaging (DTI), which measures water diffusion in the brain, for imaging brain tumors. These methods can assist in planning surgery to avoid complications that might occur with less detailed preoperative evaluation. fMRI and DTI are routinely used when the tumor location is such that there is a concern for neurological deficits occurring during surgery. This type of imaging is usually performed shortly before surgery and can be critical in decisions of whether and how to approach the tumor, Dr. Rosen says.

meningioma of olfactory groove 550x415 Five New Imaging Tests Can Help Diagnose A Variety Of Illnesses Better
fmri550x415 Five New Imaging Tests Can Help Diagnose A Variety Of Illnesses Better

Above content provided by Beth Israel Deaconess Medical Center. For advice about your medical care, consult your doctor.

More Articles From Beth Israel Deaconess Medical Center:Five New Imaging Tests Can Help Diagnose A Variety Of Illnesses Better | Airport Security Scanners: Are They Safe? | What Is The Best Breast Cancer Screening Tool? | Cardiac CT Scan An Alternative To Catheterization |Ultrasound Option For Shoulders, Knees | Radiation Reduction | ERCP For Stomach Pain | Five New Imaging Tests Can Help Diagnose A Variety Of Illnesses Better | Airport Security Scanners: Are They Safe? | Women And Sport Injuries – Why It’s A Different Game | Common Sports Injuries – How To Protect Yourself | Repetitive Injuries: Physical Therapy Keeps ‘Wounded Warrior’ On Top Of Game | Skiers, Take Note: ACL Injuries Are Serious, But Not Career Ending |Weekend Warriors: Prevent Injuries | Coming Back From ACL Tear | Athletes & Shoulder Arthritis

SOURCE

http://boston.cbslocal.com/2010/12/15/five-new-imaging-tests-can-help-diagnose-a-variety-of-illnesses-better/

How PET imaging works

 

MIPSMany cancers use more glucose (sugar) than most normal tissues. The Nuclear Medicine physician can take advantage of this by injecting glucose with a small amount of radioactivity attached to the glucose molecule. The PET scanner is then used to obtain images of the distribution of glucose metabolism throughout the body. The amount of glucose used by tissues in the body provides information to help guide further diagnostic and therapeutic options.

What is the purpose of the CT scanner? The CT scanner is needed because the major disadvantage of PET imaging is that the anatomic detail seen in a PET scan is inferior to that of a conventional CT scan. This means that although PET can see the general location of an area of abnormal glucose uptake, the exact localization of the abnormality can be difficult using PET images alone.

Anatomic Information Obtained with CT Scanning

fusion imageCT (Computed Tomography) scanning provides high-resolution images that show anatomy beautifully. But CT does not do a very good job of demonstrating physiology. Therefore, if an abnormality is seen on CT scanning, it is not always obvious if that abnormality is benign or malignant (cancer).

By obtaining both CT and PET images together, and fusing the images, the Nuclear Medicine physician can simultaneously see both anatomic and physiologic changes in the body that provide the most accurate information available today for the imaging diagnosis and localization of cancer.

SOURCE 

http://www.bidmc.org/CentersandDepartments/Departments/Radiology/Exams/NuclearMedicine/Exams/PETCT.aspx#sthash.faab9AeR.dpuf 

Cardiac Perfusion Exam

Overview

An Cardiac Perfusion scan is a test that helps your doctor see if you have coronary artery disease. Coronary artery disease is a narrowing of the blood vessels that supply oxygen to the heart muscle. If the heart muscle doesn’t get enough oxygen, it can cause chest pain or angina. Because angina typically occurs during exercise, we often do this test with you walking on a treadmill.

During this test, a radioactive material is used to take pictures of the heart. The substance is injected into your blood and travels to the heart muscle through the coronary arteries. We then take pictures of your heart, which will help your doctor decide if you have coronary artery disease.

How do I prepare for this test?

Common Foods, Beverages, and Medications Containing Caffeine

Do not take any of these for 12 hours before your nuclear medicine cardiac perfusion test. Please note: Many “decaffeinated” drinks are also not allowed!

Coffee:

Regular or decaffeinated, any variety

Tea

Regular or decaffeinated, any variety

Soft Drinks:

Regular or decaffeinated, any variety
Cola, Dr. Pepper, Mello Yellow, Mountain Dew, Mr. Pibb, Tab

Foods:

Cocoa, Chocolate

Over-the-Counter Medicines:

Anacin, Excedrin, NoDoz

Prescribed Medications:

Cafegot (all forms), Darvon Compound, Fiorinal, Synalog DC, Wigraine (all forms)

  • Do not eat or drink anything containing caffeine for 12 hours before this test. This includes coffee, tea, colas, and chocolate. Other things containing caffeine are listed here.
  • Do not smoke for two hours before this test.
  • Do not eat or drink anything except water for two hours before this test.

May I take my medication?

  • You may be asked to decrease or stop certain medicines for this test. Follow your doctor’s instructions regarding medication. Do not stop your medication unless your doctor tells you to. You should start all your medicines again after the test is over. Please bring a complete listing of all your medicines with you.
  • If you are a diabetic and take insulin or another diabetes medication, please check with your doctor for advice regarding doses before and after this test. Please bring your insulin or oral diabetes medicine to the hospital so you can take the dose recommended by your doctor.

What should I wear?

Please wear comfortable clothes that break at the waist (a shirt or blouse) and flat walking shoes or sneakers. Sneakers are strongly recommended. Electrodes will be placed on your chest so that your heart can be monitored during exercise. Women must remove their bras for the procedure. If you wear an unusually large or small size of clothing, please bring your own T-shirt and pants. You will be working hard during this test. Comfortable clothing will make things easier for you.

What happens during this test?

There are three parts to the test: Taking pictures, exercising, and taking more pictures.

  1. For the first part of the test, we will put an intravenous (IV) line in your arm. This will feel like a pin prick like when you have blood drawn. The radioactive material is then injected through the IV. You will not feel anything from this injection. We will wait 30-45 minutes while the radioactive material circulates in your body. Then, while you are lying down, we will take pictures of your heart with a special camera for about 30 minutes.
  2. For the second part of the test, you will exercise by walking on a treadmill. Your heart will be monitored with an EKG, and we will take your blood pressure many times during this part of the test. A radioactive material will be injected into the IV about 1 minute before you stop exercising. You will not feel anything when the radioactive material is injected. We will again wait a short time while the radioactive material circulates in your bloodstream.
  3. The third part of the test is taking more pictures. You will lie down as before and the camera will take pictures for about 30 minutes.

How long will the test take?

The test takes a total of 3-4 hours.

After The Exam

A doctor from nuclear medicine will provide the results of this test to your doctor. Your doctor will put together the results of this test and your other tests and then will explain the meaning of these results to you.

All the pictures that result from the Cardiac Perfusion exam are catalogued and stored as digital images. These are then displayed on specialized high resolution video monitors and interpreted by the nuclear medicine physician.

In the example images to the left, the physician will note a defect during the exercise phase of the examination which becomes improved during the resting phase.

How safe is this test?

Nuclear medicine procedures are very safe. Your body is able to eliminate the radioactive materials that are used very quickly.

The radiation dose from this test is about 13 mSv.

SOURCE

Rapid Heart Scanner

Introducing… a more advanced way to view the Heart

Beth Israel Deaconess Medical Center is the first in New England to offer patients the Cardius X-ACT Rapid Cardiac Imager. This advanced nuclear imaging system scans for coronary artery disease in half the time of traditional nuclear medicine scans. It’s more comfortable, too. Instead of lying on the stomach with arms stretched above the head, the new upright design allows patients, many with difficult symptoms such as chest pain and pressure, to remain in a seated position during the test.

Cardius X-ACT Rapid Cardiac Imager

  • More Comfort: scan performed in seated position with a shorter imaging time
  • Higher Clarity: state-of-the-art 3D image with motion stabilizer
  • Quicker Results: reports sent directly to ordering physician– same day, in most cases
  • Open Design: accommodates bariatric, claustrophobic and COPD patients

What to Expect:

When the patient arrives, an intravenous (IV) line will be placed in his arm and a small amount of radioactive material will be injected. There are no effects from the injection. After waiting 30-45 min while the material circulates, images will be taken of the heart at rest. The imaging session takes about 10 minutes.

Patient will then undergo a treadmill stress test and a second injection through the IV. After waiting 30-45 minutes a second set of images will be taken to show cardiac blood flow during exercise.

By using the computer to slice and spin the high-resolution 3-D scans taken by the Cardius imager, radiologists can see any part of the heart and the blood flow surrounding it, making diagnosis better and faster than ever before. A radiologist will read the images and provide results to your doctor within 24-hours.

The exam is covered by most medical insurance.

The rapid heart scanner is located in the nuclear medicine department on the first floor of the Rabb building, main entrance, East Campus, 330 Brookline Avenue, Boston. For more information call 617-667-2071.

SOURCE

Other related article published in this Open Access Online Scientific Journal:

Acute Chest Pain/ER Admission: Three Emerging Alternatives to Angiography and PCI – Corus CAD, hs cTn, CCTA

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/03/10/acute-chest-painer-admission-three-emerging-alternatives-to-angiography-and-pci/

Read Full Post »

“Sudden Cardiac Death,” SudD is in Ferrer inCode’s Suite of Cardiovascular Genetic Tests to be Commercialized in the US

Posted in Acute Myocardial Infarction, Atherogenic Processes & Pathology, Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, CANCER BIOLOGY & Innovations in Cancer Therapy, Cardiomyopathy, Cardiovascular Research, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Computational Biology/Systems and Bioinformatics, Congenital Heart Disease, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Genomic Testing: Methodology for Diagnosis, Healthcare costs and reimbursement, Human Immune System in Health and in Disease, Imaging-based Cancer Patient Management, Immunodiagnostics, Innovation in Immunology Diagnostics, Interviews with Scientific Leaders, Medical and Population Genetics, Metabolomics, Molecular Genetics & Pharmaceutical, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Nanotechnology for Drug Delivery, Nutrigenomics, Origins of Cardiovascular Disease, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Pharmacologic toxicities, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Proteomics, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Scientist: Career considerations, Technology Capital Expenses, Translational Research, Translational Science on February 10, 2014| Leave a Comment »

“Sudden Cardiac Death,” SudD is in Ferrer inCode’s Suite of Cardiovascular Genetic Tests to be Commercialized in the US

Curator: Aviva Lev-Ari, PhD, RN

Article ID #111: “Sudden Cardiac Death,” SudD is in Ferrer inCode’s Suite of Cardiovascular Genetic Tests to be Commercialized in the US. Published on 2/10/2014

WordCloud Image Produced by Adam Tubman

Uncertainty around reimbursement for targeted NGS tests is faced by Molecular Diagnostic and Genomics Services companies

VIEW VIDEO

Democratization of Genomic Medicine: Michael Bolick @ TEDxTalks

Ferrer inCode’s Suite of Cardiovascular Genetic Tests included the following tests: 

  • SudD inCode (Sudden Cardiac Death)
  • Cardio inCode,
  • Thrombo inCode, and
  • Nutri inCode

Selah Genomics, Ferrer inCode to Offer NGS-based Cardiovascular Test in US

2014/02/06

Selah Genomics, a Greenville, S.C.-based molecular diagnostic and genomics services company, has partnered with Spanish pharmaceutical company Ferrer inCode to commercialize Ferrer inCode’s suite of cardiovascular genetic tests in the US.

Selah will first validate Ferrer’s next-generation sequencing-based test for sudden cardiac death, SudD inCode, on Illumina’s MiSeq system to run out of its CLIA-certified laboratory.

Meantime, Selah plans to validate three other Ferrer inCode PCR-based cardiovascular tests — Cardio inCode, Thrombo inCode, and Nutri inCode — in its own lab using PCR, but may eventually combine the tests into one comprehensive panel to run on an NGS system, Selah CEO Michael Bolick told Clinical Sequencing News.

Selah already offers its PrecisionPath targeted Cancer Test in collaboration with the Greenville Health System’s Institute for Translational Oncology Research. All consenting cancer patients at ITOR receive the PrecisionPath test, which runs on Life Technologies’ Ion Torrent PGM and uses the Ion AmpliSeq technology.

Currently, Selah receives between 10 and 20 samples per week for PrecisionPath, and it plans to roll the test out nationwide later this year.

Bolick said that the company is also developing Hepatitis C and HIV assays for the MiSeq, and that the firm will likely purchase Illumina’s MiSeqDx, which recently received clearance from the US Food and Drug Administration.

Selah also collaborates with pharmaceutical companies to develop companion diagnostic tests. Bolick anticipates that the firm will use the MiSeqDx for those tests since they will “ultimately need [pre-market approval].” Having an FDA-cleared platform on which to develop the tests will be helpful in gaining a PMA designation, he said.

Selah also offers Exome Sequencing Services on the Ion Proton for research use only. In addition, it has a

  • Pacific Biosciences RS II and
  • Roche’s 454 GS FLX in house.

Bolick said that the company is currently using the PacBio machine for discovery work in infectious disease.

Ferrer inCode’s SudD inCode Test

currently assesses 55 genes related to structural heart problems that cause sudden cardiac arrest, Robert Jenkins, who manages Ferrer inCode’s UK and Americas groups, told CSN. However, the company is planning to

  • expand the test to 104 genes and also to include
  • genes related to conductive myopathy,
  • sudden infant death, and
  • aneurysms.

While the test sequences the entire genes, only well-known causative variants are reported, Jenkins said. However, the firm has been collecting all the sequenced variants, so it could potentially add content to the test if enough evidence is gathered to validate any of those variants as clinically significant.

Ferrer inCode currently runs SudD inCode on the MiSeq as an LDT, which is how Selah will validate and market the test in the US.

Jenkins said that for now, Ferrer plans to keep the Cardio, Nutri, and Thrombo inCode tests PCR-based.

  • Cardio inCode looks at around 125 variants involved in genetic risk for cardiac disease.

When it is used with traditional markers such as

  • lipid profiling, an individual’s
  • smoking and drinking habits, and
  • body mass index,

Jenkins said the genetic test helps to reclassify around 20 percent to 25 percent of individuals deemed in the intermediate risk category as either high or low risk.

Thrombo inCode Test

is an approximately 20-variant thrombosis test for individuals that have had a thrombotic event or who have had a history of unsuccessful pregnancies. Often, the cause of thrombosis can go unexplained via testing from serological workups, Jenkins said.

Nutri inCode Test

is a nutrigenomics test that looks at around 90 SNPs. In combination with lifestyle factors, it helps individuals develop a tailored genetics-based plan to reduce obesity, Jenkins said.

Bolick said that while Selah will validate and develop each of these tests individually out of its laboratory, it is also deciding whether to combine the tests into one next-gen sequencing-based test.

Jeremy Stuart, Selah’s VP of genomic services, told CSN that one option would be to incorporate the individual SNPs assessed in the Thrombo, Cardio, and Nutri tests into the SudD test.

Bolick said that the company is now in discussions with third party payors about reimbursement for the tests and is readying a regional pilot program to offer the sequencing-based cardiovascular test as part of a corporate wellness program. The pilot will help Selah figure out a pricing structure and will also demonstrate a “return on investment to the corporation, by allowing for better determination of risk of heart disease,” Bolick said.

Currently, Selah’s other NGS test, PrecisionPath, is being paid for by ITOR. However, Bolick said that initial conversations with third party payors about launching the assay outside of the Greenville Health System have been positive.

Reimbursement success will play a role in determining how the company expands beyond its current tests. For instance, while Selah is interested in moving into

  • clinical exome sequencing,

Stuart said that right now there is a “lot of uncertainty around reimbursement for targeted NGS tests, let alone exome sequencing.” Selah will first “establish reimbursement for those and then may expand into what’s possible for exome sequencing,” Stuart said. But currently, the exome market is research use only.

SOURCE

http://www.ferrerincode.com/en/node/98

Selah Genomics

SELAH GENOMICS: HARNESS THE POWER OF PRECISION FOR MORE PERSONALIZED TREATMENT

Selah Genomics is a clinical diagnostic specialist supporting healthcare providers and the pharmaceutical industry with advanced molecular and genomic diagnostic services. Selah’s services add value to early stage drug development, clinical trials and regulatory processes in the pharmaceutical industry and helps clinicians and healthcare providers treat and monitor patients, thereby improving patient outcomes.

With the Power of Precision, Selah Genomics provides the best in molecular diagnostic testing, assay validation and genomic profiling that all leads to one common goal: to provide better outcomes for patients.

Michael Bolick, CEO

Michael is a serial entrepreneur with 25 years of experience in the life science and healthcare industries. Most recently, he led a management buyout of Lab21 Ltd’s US-based operations to form Selah Genomics Inc. Prior to co-founding Selah Genomics, Michael served as President of Lab21 Inc which was formed following Lab21 Ltd’s acquisition of his prior company, Selah Technologies LLC. He founded Selah Technologies LLC to commercialize nanotechnologies licensed from Clemson University. Selah focused these nanotechnologies to enable doctors to see cancer during surgery. Prior to founding Selah Technologies, Michael’s career included roles of increasing responsibility in the pharmaceutical sector.

Michael is a Fellow in the Liberty Fellowship Class of 2011. Liberty Fellowship is a program designed specifically for emerging state leaders to reinforce values necessary to lead an exemplary life both personally and professionally. Michael serves as Immediate Past Chair of SCBIO, South Carolina’s Life Sciences Industry Association. Michael earned his bachelor’s degree in Chemical Engineering from North Carolina State University.

  • Selah Genomics specializes in supporting healthcare providers and the pharmaceutical industry with advanced molecular and genomic diagnostic services.

    read more »

    Latest News

    Find out what the buzz is about

    • Greenville Health System, Roswell Park Adopt Targeted Sequencing in Cancer Treatment

      8 May 2013

    • Selah, GHS expand personalized medicine

      2 May 2013

    • The Democratization of Genomic Medicine: Michael Bolick at TEDxGreenville

      21 Apr 2013

    • Greenville Magazine features Selah Genomics

      1 Apr 2013

    • Upstate Biotech Firm Expands to Columbia

      14 Mar 2013

    • Genetic Engineering and Biotechnology News; “Selah Genomics Establishes Second Clinical Genomics Center”

      20 Feb 2013

    • Selah Genomics Forms Second Clinical Genomic Center

      19 Feb 2013

  • Clinical Laboratory

    Helping physicians by applying our scientific expertise and skills in advanced molecular diagnostic assay development in a CLIA-certified laboratory.

    read more »

  • PrecisionPath™

    Genomic profiling of solid tumors, identifying actionable targets today and enabling the discovery of clinically relevant genes for tomorrow.

    read more »

  • Genomic Services


    Selah Genomics provides a suite of services focused on support of molecular biomarker discovery, assay validation and prospective/retrospective clinical trial testing in support of companion diagnostic development and commercialization.

    read more »

 SOURCE

THE FAST-TRACK TO DISCOVERY AND CLINICAL UTILIZATION

Selah Genomics provides a suite of services focused on support of molecular biomarker discovery, assay validation and prospective/retrospective clinical trial testing in support of companion diagnostic development and commercialization. Selah operates NGS platforms from Life Technologies, Illumina, Roche and PacBio as well as an array of real time PCR and other supporting instrumentation systems. We help you select the best platform for each Project in support of your particular goals. Our prime focus – to help fast-track the clinical utilization and commercialization of your biomarker.

Selah enjoys a key corporate relationship with the Greenville Health System’s (GHS) Institute of Translational Oncology Research (ITOR) conducting multiple clinical trials and identification of new oncology biomarkers.

GHS is the 13th largest public hospital in the United States and ITOR has the largest Phase 1 clinical trial program in South Carolina, including a track record of 16 first-in-human trials. The close relationship with ITOR is an enormous asset for Selah. Not only does it allow Selah to provide state-of-the-art molecular diagnostics support for ITOR clinical studies but it leads to first-hand daily interaction with cancer physicians. This interaction stimulates early identification and development of new biomarker panels.

Selah’s Clinical Genomics Center at ITOR is physically located within GHS & ITOR. In addition, Selah operates a Clinical Genomics Center at Innovista on the campus of the University of South Carolina.

SOURCE

http://selahgenomics.com/genomic-services/

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Preserved vs Reduced Ejection Fraction: Available and Needed Therapies

Posted in Cardiomyopathy, Cardiovascular Research, Congenital Heart Disease, Electrophysiology, Frontiers in Cardiology and Cardiovascular Disorders, HTN, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Origins of Cardiovascular Disease, Pharmacotherapy of Cardiovascular Disease on February 3, 2014| Leave a Comment »

Preserved vs Reduced Ejection Fraction: Available and Needed Therapies

Reporter: Aviva Lev-Ari, PhD, RN

 

Ejection Fraction Heart Failure Measurement

Updated:Jul 9,2013

The ejection fraction (EF) is an important measurement in determining how well your heart is pumping out blood and in diagnosing and tracking heart failure.

A significant proportion of patients with heart failure happen to have a normal ventricular ejection fraction at echocardiography during examination. Previously called diastolic heart failure, it is nowadays referred to as heart failure with normal ejection fraction (HFNEF) or HF with preserved ejection fraction.

  1. Perserved ejection fraction (HFpEF) – also referred to as diastolic heart failure.  The heart muscle contracts normally but the ventricles do not relax as they should during ventricular filling (or when the ventricles relax).
  2. Reduced ejection fraction (HFREF) – also referred to as systolic heart failure.  The heart muscle does not contract effectively and less oxygen-rich blood is pumped out to the body.

What it is?
A measurement of how much blood the left ventricle pumps out with each contraction.

What it means.
An ejection fraction of 60 percent means that 60 percent of the total amount of blood in the left ventricle is pushed out with each heartbeat.

What’s normal?

  • A normal heart’s ejection fraction may be between 55 and 70.
  • You can have a normal ejection fraction reading and still have heart failure. If the heart muscle has become so thick and stiff that the ventricle holds a smaller-than-usual volume of blood, it might still seem to pump out a normal percentage of the blood that enters it. In reality, though, the total amount of blood pumped isn’t enough to meet your body’s needs.

What’s too low?

  • A measurement under 40 may be evidence of heart failure or cardiomyopathy.
  • An EF between 40 and 55 indicates damage, perhaps from a previous heart attack, but it may not indicate heart failure.
  • In severe cases, EF can be very low.

What’s too high?
EF higher than 75 percent may indicate a heart condition like hypertrophic cardiomyopathy.

Tests for measuring EF:

SOURCE
http://www.heart.org/HEARTORG/Conditions/HeartFailure/SymptomsDiagnosisofHeartFailure/Ejection-Fraction-Heart-Failure-Measurement_UCM_306339_Article.jsp

 

February 03, 2014

Both drug and device therapies have been shown to improve the outlook for patients with heart failure and reduced ejection fraction, but three leading cardiologists point to the lack of proven treatments for the other half of heart failure patients — those with preserved ejection fraction.

VIEW VIDEO

http://www.medpagetoday.com/HOTTOPICSWhatworksWhatDoesnt/special-reports/SpecialReports-Videos/394

SOURCE

From: MedPage Today <daily.headlines@medpagetoday.com>
To: <avivalev-ari@alum.berkeley.edu>

Heart Failure With Preserved Ejection Fraction

Circulation.2011; 124: e540-e543doi: 10.1161/​CIRCULATIONAHA.111.071696

 

  1. James E. Udelson, MD

+Author Affiliations


  1. From the Division of Cardiology and the CardioVascular Center, Tufts Medical Center, Boston, MA.
  1. Correspondence to James E. Udelson, MD, Tufts Medical Center, 800 Washington St, Box 70, Boston, MA 02111. E-mail judelson@tuftsmedicalcenter.org

 

Key Words:

It is now well established that among patients with the clinical syndrome of heart failure (HF), approximately half have preserved systolic function, known most commonly as heart failure with preserved ejection fraction (HFpEF). Although originally considered to be predominantly a syndrome that pathophysiologically involves abnormalities in diastolic function (relaxation and/or stiffness), ongoing investigation suggests that, although diastolic abnormalities may be present in many patients, other aspects of pathophysiology likely also contribute to symptoms.

Many recent articles have continued to explore aspects of this fascinating clinical syndrome. This review will summarize advances in understanding of the HFpEF syndrome, focusing on epidemiology, pathophysiology, and therapeutics.

Pathophysiology

Controversy continues regarding the prevalence of true abnormities of myocardial diastolic function in the syndrome of HFpEF. In a comprehensive invasive and noninvasive hemodynamic study in a group of highly selected patients with hemodynamically confirmed HFpEF, Prasad et al7 reported that compared with age-matched referent controls, increased static ventricular stiffness was not a universal finding in patients with HFpEF, although LV relaxation as assessed by tissue Doppler was consistently abnormal.

Substantial and growing attention has been given to the role of the cardiac interstitium in the pathophysiology of HFpEF. Zile and colleagues8 examined a panel of biomarkers for ability to discriminate symptomatic HFpEF from those with asymptomatic LV hypertrophy. This study showed that a panel of plasma biomarkers reflecting changes in extracellular matrix fibrillar collagen synthesis and degradation predicted the presence of HFpEF with an area under the curve of 0.79 and was more powerful than using N-terminal pro–B-type natriuretic peptide or clinical variables. Consistent with these findings, investigators from the Cardiovascular Health Study reported that biomarkers reflecting myocardial fibrosis, including carboxyl-terminal peptide of procollagen type I, carboxyl-terminal telopeptide of collagen type I, and amino-terminal peptide of procollagen type III, are significantly elevated in elderly patients with HFpEF and indeed are also elevated in those with systolic HF.9 Krum et al10 reported on a substudy from I-PRESERVE showing that increased baseline plasma levels of all collagen markers were associated with the I-PRESERVE primary outcome end point, although the relationship was not significant in a multivariable model. In a comprehensive human study, Westermann and colleagues11 interrogated the influence of cardiac inflammation on extracellular matrix remodeling in patients with HFpEF. Using endomyocardial biopsy samples to isolate primary human cardiac fibroblasts, the authors interrogated the gene expression of extracellular matrix proteins after stimulation with transforming growth factor-β. They reported an increase of cardiac collagen accompanied by a decrease in the collagenase system of the heart, as well as a correlation between cardiac collagen, inflammatory cells, and diastolic dysfunction. They concluded that inflammation contributes to diastolic abnormalities in HFpEF by stimulating extracellular matrix accumulation. All of these data suggest that the interstitium may be a promising therapeutic target if specific therapies can be deployed.

Although abnormalities in myocardial diastolic properties have been the focus of pathophysiological studies in patients with HFpEF in the past, many recent investigations have examined other structural and functional contributors. Kurt and colleagues12reported that HFpEF patients have similar LV mass and left atrial volume in comparison with patients with LV hypertrophy who are not in HF, although a measure of left atrial strain was reduced, and left atrial stiffness was useful in discriminating patients with HFpEF from those with LV hypertrophy without HF symptoms.

Several studies examined pathophysiology in HFpEF patients during exercise stress, which is when most patients have symptoms. Phan and colleagues13 reported that chronotropic incompetence, as measured by the percentage of the heart rate reserve used during maximal exercise, was more commonly present in patients with HFpEF compared with referent controls, as was abnormal heart rate recovery. Using dobutamine stress echocardiography with color tissue Doppler imaging, Chattopadhyay et al14 reported evidence of impaired diastolic reserve during stress, as well as stress-induced increase in the LV end-diastolic pressure, likely resulting in exercise intolerance because 6-minute walk distance was inversely correlated with the measures of diastolic function at rest and stress. Borlaug and colleagues15 examined hemodynamic responses to stress as a potential diagnostic approach in patients with exertional dyspnea, in whom making a specific diagnosis may be challenging. The investigators studied patients with exertional dyspnea, preserved EF, normal brain natriuretic peptide levels, and normal resting hemodynamics. Exercise-induced elevation in pulmonary capillary wedge pressure was used to define HFpEF and was associated with blunted increases in heart rate and cardiac output and blunted systemic vasodilation. An exercise pulmonary artery systolic pressure ≥45 mm Hg identified HFpEF with 96% sensitivity and 95% specificity. These data suggest that patients who present a challenge for specific diagnosis should undergo an exercise hemodynamic study.

Two studies examined clinical or echocardiographic variables that might be useful in estimating LV filling pressures in patients with HFpEF. Drazner et al16 reported that right atrial pressures often reflected left-sided filling pressures in HFpEF, suggesting that estimation of jugular venous pressure could be used to assess volume status. However, the echocardiographic indexes E/e′ and E/Vp did not appear to reliably track changes in left-sided filling pressures in patients with HFpEF.17

Studies using translational models explored the underlying mechanism of the transition from compensated LV hypertrophy to a state of HF. In a transverse aortic constriction model adding mineralocorticoid (deoxycorticosterone acetate) excess, Mohammed et al18reported that mice treated with deoxycorticosterone acetate showed progressive activation of markers of oxidative stress but no evidence of mineralocorticoid receptor–dependent gene transcription. They concluded that pressure-overload hypertrophy sensitizes the heart to mineralocorticoid excess and that the transition to HF with preserved EF is associated with mechanisms independent of mineralocorticoid receptor–dependent gene transcription. In a study of cardiac energy metabolism in which Dahl salt-sensitive rats fed a high-salt diet were used to drive a transition from compensated LV hypertrophy to HF, Kato and colleagues19 reported that glucose uptake increased with LV hypertrophy and further increased at the HF stage, with decreased fatty acid uptake and corresponding changes in gene expression related to the metabolic pathways as well as mitochondrial function with the onset of HF. Dichloroacetate, which enhances glucose oxidation, attenuated the transition to HF, associated with increased energy reserves and reduced oxidative stress. The data from these models suggest potential therapeutic directions for the future, although mineralocorticoid receptor antagonism is already under comprehensive study.

Therapeutics

As noted, large randomized trials in broad populations of patients with HFpEF in which agents such as angiotensin receptor blockers were used have generally shown neutral results. Smaller trials continue to explore potential therapeutic directions for this challenging-to-manage syndrome. Kitzman and colleagues20 randomized 71 elderly HFpEF patients with compensated symptoms and controlled blood pressure into a 12-month follow-up double-blind trial of enalapril 20 mg/d versus placebo.

There was no effect of the angiotensin-converting enzyme inhibitor on

  • the primary end point of peak exercise oxygen consumption and
  • no effect on multiple secondary end points including 6-minute walk distance,
  • aortic distensibility,
  • LV mass, or
  • neurohormones.

The findings are consistent with the longer-term natural history outcomes of angiotensin receptor blocker trials.

Many of the same authors examined a nonpharmacological approach in a 16-week randomized study of supervised exercise training in 53 elderly patients with HFpEF.21The primary outcome was peak exercise oxygen uptake, which increased significantly in the exercise group compared with the control group (2.3±2.2 versus −0.3±2.1 mL/kg per meter; P=0.0002). Many secondary end points were also improved, including exercise time, 6-minute walk distance, and ventilatory anaerobic threshold. In contrast to some trials of exercise training, a key to the favorable results of this study may have been the good compliance with the exercise training regimen among the enrolled patients. These important data suggest an important therapeutic direction.

Favorable results were also seen in a small study involving an important subgroup of HFpEF patients, those with pulmonary hypertension. Guazzi and coworkers22 randomized 44 such patients to sildenafil at a dose of 50 mg 3 times per day or to placebo for 6 months. At the end of the trial, sildenafil was associated with decreased mean pulmonary artery and reduced right atrial pressure and improved right ventricular function. They also reported reduced lung water content and improved alveolar-capillary gas conductance, as well as improved measure of left-sided systolic and diastolic cardiac function. Results were maintained at 12 months.

Hence, although large trials using neurohormonal antagonists that have been favorable in HF with reduced EF have not shown favorable results in HFpEF, these early studies suggest promising therapeutic directions to explore. Such studies also enhance our understanding of pathophysiology and point the way to larger and more definitive investigations.

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

Posted in Atherogenic Processes & Pathology, Electrophysiology, Frontiers in Cardiology and Cardiovascular Disorders, HTN, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism on February 2, 2014| Leave a Comment »

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

Curator: Aviva Lev-Ari, PhD, RN

This article has the following structure:

  • Sleep Drives Metabolite Clearance from the Adult Brain
  • Sleep and Cardiovascular Disease
  • Sleep Duration as a Risk Factor for Cardiovascular Disease – a Review of the Recent Literature
  • The Society for Cardiovascular Angiography and Interventions: Poor sleep has been linked to CVD Biomarkers
  • Hemostatic Alterations in Patients With Obstructive Sleep Apnea and the Implications for Cardiovascular Disease*
  • Elevated C-Reactive Protein in Patients With Obstructive Sleep Apnea
  • SOURCES on Sleep in Science 
  • REFERENCES on Sleep Deprivation, Physiological Processes and Cardiovascular Diseases
Science 18 October 2013:
Vol. 342 no. 6156 pp. 373-377
DOI: 10.1126/science.1241224

Sleep Drives Metabolite Clearance from the Adult Brain

  1. Lulu Xie1,*,
  2. Hongyi Kang1,*,
  3. Qiwu Xu1,
  4. Michael J. Chen1,
  5. Yonghong Liao1,
  6. Meenakshisundaram Thiyagarajan1,
  7. John O’Donnell1,
  8. Daniel J. Christensen1,
  9. Charles Nicholson2,
  10. Jeffrey J. Iliff1,
  11. Takahiro Takano1,
  12. Rashid Deane1,
  13. Maiken Nedergaard1,†

+Author Affiliations


  1. 1Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

  2. 2Department of Neuroscience and Physiology, Langone Medical Center, New York University, New York, NY 10016, USA.
  1. ↵†Corresponding author. E-mail: nedergaard@urmc.rochester.edu

  1. ↵* These authors contributed equally to this work.

The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.

 

Figure Source: Goodnight. Sleep Clean.

By MARIA KONNIKOVA JAN. 11, 2014

http://www.nytimes.com/2014/01/12/opinion/sunday/goodnight-sleep-clean.html?emc=eta1&_r=0

Concepts presented in this article about Sleep

  • Maiken Nedergaard, a Danish biologist who has been leading research into sleep function at the University of Rochester’s medical school, told me. “It has to have a basic evolutional function. Otherwise it would have been eliminated.”
  • sleep is essential for forming and consolidating memories and that it plays a central role in the formation of new neuronal connections and the pruning of old ones.
  • Sleep, may play a crucial role in our brain’s physiological maintenance
  • Dr. Nedergaard proposed a brain equivalent of the lymphatic system, a network of channels that cleared out toxins with watery cerebrospinal fluid. She called it the glymphatic system, a nod to its dependence on glial cells (the supportive cells in the brain that work largely to maintain homeostasis and protect neurons) and its function as a sort of parallel lymphatic system.
  • the brain’s interstitial space — the fluid-filled area between tissue cells that takes up about 20 percent of the brain’s total volume — was mainly dedicated to physically removing the cells’ daily waste.
  • When the mouse brain is sleeping or under anesthesia, it’s busy cleaning out the waste that accumulated while it was awake.
  • “We saw almost no inflow of cerebrospinal fluid into the brain when the mice were awake, but then when we anesthetized them, it started flowing. It’s such a big difference I kept being afraid something was wrong,” says Dr. Nedergaard.
  • Not in Humans yet, So far the glymphatic system has been identified as the neural housekeeper in baboons, dogs and goats. “If anything,” Dr. Nedergaard says, “it’s more needed in a bigger brain.”
  • According to the National Sleep Foundation, adults should sleep seven to nine hours. On average, we’re getting one to two hours less sleep a night than we did 50 to 100 years ago and 38 minutes less on weeknights than we did as little as 10 years ago. Between 50 and 70 million people in the United States suffer from some form of chronic sleep disorder.
  • At the University of Pennsylvania’s Center for Sleep and Circadian Neurobiology, Sigrid Veasey has been focusing on precisely how restless nights disturb the brain’s normal metabolism. What happens to our cognitive function when the trash piles up?
  • The faster the fluids clear the decks, the more effectively the brain’s metabolism is functioning.

Consequences of Lack of Sufficient Duration of Sleep

  • the acceleration of neurodegenerative diseases like Alzheimer’s and Parkinson’s. While we don’t know whether sleep loss causes the disease, or the disease itself leads to sleep loss. there is a buildup of the types of proteins that the glymphatic system normally clears out during regular sleep, like beta-amyloids and tau, both associated with Alzheimer’s and other types of dementia.
  • sleep deprivation, as everyone who has experienced it knows, impedes our ability to concentrate, to pay attention to our environment and to analyze information creatively.
  • brains can recover quite readily from short-term sleep loss, chronic prolonged wakefulness and sleep disruption stresses the brain’s metabolism.
  • degeneration of key neurons involved in alertness and proper cortical function and a buildup of proteins associated with aging and neural degeneration.
  • Recovery from sleep loss is slower than we’d thought,” Dr. Veasey notes.
  • mpaired clearance in the awake brain: skipping sleep does irreparable damage to the brain, prematurely aging it or setting it up for heightened vulnerability to other insults.
  • work longer hours, become more stressed, sleep less, impair our brain’s ability to clean up after all that hard work, and become even less able to sleep soundly
  • there’s no evidence that aided sleep is as effective as natural sleep.

New directions for Drug Development

Future drug interventions could focus directly on the glymphatic system, to promote the enhanced cleaning power of the sleeping brain in a brain that is fully awake. One day, scientists might be able to successfully mimic the expansion of the interstitial space that does the mental janitorial work so that we can achieve maximally efficient round-the-clock brain trash pickup.

Curr Probl Cardiol. 2005 Dec;30(12):625-62.

Sleep and cardiovascular disease

Wolk R, Gami AS, Garcia-Touchard A, Somers VK.

Abstract

Sleep is an important modulator of cardiovascular function, both in physiological conditions and in disease states.

In individuals without a primary sleep disorder Sleep may exert significant effects on the

  • autonomic nervous system,
  • systemic hemodynamics,
  • cardiac function,
  • endothelial function, and
  • coagulation.

Some of these influences can be directly linked to specific modulatory effects of sleep stages per se; others result from the natural circadian rhythm of various physiological processes.

There is a temporal association between physiological sleep and

  • occurrence of vascular events,
  • cardiac arrhythmias, and
  • sudden death.

Epidemiological and pathophysiological studies also indicate that there may be a causal link between

  • primary sleep abnormalities (sleep curtailment, shift work, and sleep-disordered breathing) and
  • cardiovascular and metabolic disease, such as hypertension, atherosclerosis, stroke, heart failure, cardiac arrhythmias, sudden death, obesity, and the metabolic syndrome.

Finally, sleep disturbances may occur as a result of several medical conditions (including obesity, chronic heart failure, and menopause) and may therefore contribute to cardiovascular morbidity associated with these conditions. Further understanding of specific pathophysiological pathways linking sleep disorders to cardiovascular disease is important for developing therapeutic strategies and may have important implications for cardiovascular chronotherapeutics.

Sleep Duration as a Risk Factor for Cardiovascular Disease- a Review of the Recent Literature

Curr Cardiol Rev. 2010 February; 6(1): 54–61.
PMCID: PMC2845795
This article has been cited by other articles in PMC.

Abstract

Sleep loss is a common condition in developed countries, with evidence showing that people in Western countries are sleeping on average only 6.8 hour (hr) per night, 1.5 hr less than a century ago. Although the effects of sleep deprivation on our organs have been obscure, recent epidemiological studies have revealed relationships between sleep deprivation and hypertension (HT), coronary heart disease (CHD), and diabetes mellitus (DM). This review article summarizes the literature on these relationships. Because sleep deprivation increases sympathetic nervous system activity, this increased activity serves as a common pathophysiology for HT and DM. Adequate sleep duration may be important for preventing cardiovascular diseases in modern society.

Keywords: Sleep duration, hypertension, coronary heart disease, diabetes mellitus.

The Society for Cardiovascular Angiography and Interventions: Poor sleep has been linked to

  • high blood pressure,
  • atherosclerosis (clogging or hardening of the arteries),
  • heart failure,
  • heart attack,
  • stroke,
  • diabetes, and
  • obesity.

Poor sleep appears to increase substances in your body, such as c-reactive protein, that indicate inflammation is a problem. So, inflammation, which is how the body responds to injury, infection or disease, may be part of the reason poor sleep affects your cardiovascular system. Poor sleep also causes the body to produce more stress hormones, which may contribute to cardiovascular disease.

On the other hand, sometimes symptoms related to cardiovascular disease can be a cause of poor sleep. Angina (chest pain), arrhythmias (abnormal heart rhythms), sleep apnea (a series of breathing pauses during sleep that stress your cardiovascular system), and fluid build-up in the lungs due to heart failure may all disrupt sleep.

The good news is there are steps you can take to improve your sleep. Always talk to your doctor about your sleep problems, however minor you think they might be. There may be lifestyle changes or treatments that can help you sleep better. And read on, so SecondsCount.org can help you improve the quality of sleep you get.

http://www.scai.org/SecondsCount/Treatment/HealthyLiving/SleepandCardiovascularDisease.aspx

Hemostatic Alterations in Patients With Obstructive Sleep Apnea and the Implications for Cardiovascular Disease*

Roland von Känel; Joel E. Dimsdale
Chest. 2003;124(5):1956-1967. doi:10.1378/chest.124.5.1956
Abstract

Study objectives: Patients with obstructive sleep apnea (OSA) are at increased risk for coronary artery and cerebrovascular diseases. Numerous studies suggest that a hypercoagulable state is prospectively related to atherothrombotic events. This review explores whether changes in hemostasis may constitute one biological link between OSA and vascular disease.

Design: Ten studies on hemostatic variables in OSA were located by electronic library search and descriptively reviewed. Work on hemostatic function with physiologic conditions similar to those found in OSA (hypoxemia and hyperactivity of the sympathetic nervous system) was considered to discuss potential molecular mechanisms of procoagulant disturbances in OSA.

Measurements and results: The reviewed data suggest that, as compared to non-OSA control subjects, patients with OSA have elevated plasma fibrinogen levels, exaggerated platelet activity, and reduced fibrinolytic capacity. Although not consistently shown, severity of OSA (ie, apnea-hypopnea index) and plasma epinephrine were independent predictors of platelet activity, and average minimal oxygen saturation was an independent predictor of fibrinogen. In some studies, treatment with continuous positive airway pressure decreased platelet activity, plasma fibrinogen levels, and activity of clotting factor VII.

Conclusions: There is some evidence for a hypercoagulable state in OSA, which might help explain the increased prevalence of vascular diseases in this population. To further confirm such a notion, future studies need to be performed on sufficiently large samples to be able to control for confounders of hemostatic activity. Prospective studies are needed to examine the association between hemostasis molecules and strong vascular end points.

SOURCE

 

Elevated C-Reactive Protein in Patients With Obstructive Sleep Apnea

Circulation.2002; 105: 2462-2464

  1. Abu S.M. Shamsuzzaman, MBBS, PhD;
  2. Mikolaj Winnicki, MD, PhD;
  3. Paola Lanfranchi, MD;
  4. Robert Wolk, MD, PhD;
  5. Tomas Kara, MD;
  6. Valentina Accurso, MD;
  7. Virend K. Somers, MD, PhD

+Author Affiliations


  1. From the Mayo Clinic Rochester, Rochester, Minn.
  1. Correspondence to Virend K Somers, MD, DPhil, Divisions of Hypertension and Cardiovascular Diseases, Mayo Clinic Rochester, 200 First St, SW, Rochester, MN 55905. E-mail somers.virend@mayo.edu

Abstract

Background— Obstructive sleep apnea (OSA) has been increasingly linked to cardiovascular and cerebrovascular disease. Inflammatory processes associated with OSA may contribute to cardiovascular morbidity in these patients. We tested the hypothesis that OSA patients have increased plasma C-reactive protein (CRP).

Methods and Results— We studied 22 patients (18 males and 4 females) with newly diagnosed OSA, who were free of other diseases, had never been treated for OSA, and were taking no medications. We compared CRP measurements in these patients to measurements obtained in 20 control subjects (15 males and 5 females) who were matched for age and body mass index, and in whom occult OSA was excluded. Plasma CRP levels were significantly higher in patients with OSA than in controls (median [range] 0.33 [0.09 to 2.73] versus 0.09 [0.02 to 0.9] mg/dL, P<0.0003). In multivariate analysis, CRP levels were independently associated with OSA severity (F=6.8, P=0.032).

Conclusions— OSA is associated with elevated levels of CRP, a marker of inflammation and of cardiovascular risk. The severity of OSA is proportional to the CRP level.

SOURCE

http://circ.ahajournals.org/content/105/21/2462.short

SOURCES on Sleep in Science

Science 18 October 2013:
Vol. 342 no. 6156 pp. 373-377
DOI: 10.1126/science.1241224
  • REPORT

Sleep Drives Metabolite Clearance from the Adult Brain

 

  1. Lulu Xie1,*,
  2. Hongyi Kang1,*,
  3. Qiwu Xu1,
  4. Michael J. Chen1,
  5. Yonghong Liao1,
  6. Meenakshisundaram Thiyagarajan1,
  7. John O’Donnell1,
  8. Daniel J. Christensen1,
  9. Charles Nicholson2,
  10. Jeffrey J. Iliff1,
  11. Takahiro Takano1,
  12. Rashid Deane1,
  13. Maiken Nedergaard1,†

+Author Affiliations


  1. 1Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

  2. 2Department of Neuroscience and Physiology, Langone Medical Center, New York University, New York, NY 10016, USA.
  1. ↵†Corresponding author. E-mail: nedergaard@urmc.rochester.edu

  1. ↵* These authors contributed equally to this work.

 

The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.

  • Received for publication 30 May 2013.
  • Accepted for publication 28 August 2013.

The editors suggest the following Related Resources on Science sites In Science Magazine

In Science Translational Medicine

  • RESEARCH ARTICLE OBESITY AND DIABETES Adverse Metabolic Consequences in Humans of Prolonged Sleep Restriction Combined with Circadian Disruption

    • Orfeu M. Buxton,
    • Sean W. Cain,
    • Shawn P. O’Connor,
    • James H. Porter,
    • Jeanne F. Duffy,
    • Wei Wang,
    • Charles A. Czeisler,
    • and Steven A. Shea

    Sci Transl Med 11 April 2012: 129ra43.

  • RESEARCH ARTICLE SLEEP Uncovering Residual Effects of Chronic Sleep Loss on Human Performance

    • Daniel A. Cohen,
    • Wei Wang,
    • James K. Wyatt,
    • Richard E. Kronauer,
    • Derk-Jan Dijk,
    • Charles A. Czeisler,
    • and Elizabeth B. Klerman

    Sci Transl Med 13 January 2010: 14ra3.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:

  • Taking Out the Garbage During Sleep, and Alzheimer PathologyJournal Watch 2 December 2013: NA32813.
  • Sleep and General Anesthesia Clear the Mouse Brain of Toxic MetabolitesJournal Watch 26 November 2013: NA32960.
  • Cerebral Arterial Pulsation Drives Paravascular CSF-Interstitial Fluid Exchange in the Murine BrainJ. Neurosci. 13 November 2013: 18190-18199.
  • Sleep It Out Science 18 October 2013: 316-317.

SOURCE

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

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

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

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

 

UPDATED on 4/8/2014

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

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

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

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

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

Point #3: Results of Multiple Cell Therapy Clinical Trials

Point #4:  The Endogenous Regeneration Potential

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Point #3: Results of Multiple Cell Therapy Clinical Trials

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

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

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

Point #4:  The Endogenous Regeneration Potential

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

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

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

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

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

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

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

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

sheets/docs/fs_heart_failure.pdf

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

(2006).

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

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

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

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

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

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

(2009).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

10.1126/science.1229765.

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

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

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

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

 

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Publications on Heart Failure by Prof. William Gregory Stevenson, M.D., BWH

Posted in Atherogenic Processes & Pathology, Cardiomyopathy, Cardiovascular Research, Congenital Heart Disease, Electrophysiology, Frontiers in Cardiology and Cardiovascular Disorders, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Origins of Cardiovascular Disease on January 13, 2014| Leave a Comment »

Publications on Heart Failure by Prof. William Gregory Stevenson, M.D., BWH

Reporter: Aviva Lev-Ari, PhD, RN

 

Prof. William Gregory Stevenson, M.D.

Title Professor of Medicine
Institution Brigham and Women’s Hospital
Department Medicine
Address Brigham and Women’s Hospital Cardiovascular 75 Francis St Boston MA 02115
Phone 617/732-7535
Fax 617/732-7134
  1. Givertz MM, Teerlink JR, Albert NM, Westlake Canary CA, Collins SP, Colvin-Adams M, Ezekowitz JA, Fang JC, Hernandez AF, Katz SD, Krishnamani R, Stough WG, Walsh MN, Butler J, Carson PE, Dimarco JP, Hershberger RE, Rogers JG, Spertus JA, Stevenson WG, Sweitzer NK, Tang WH, Starling RC. Acute decompensated heart failure: update on new and emerging evidence and directions for future research. J Card Fail. 2013 Jun; 19(6):371-89.
    View in: PubMed
  2. Tokuda M, Kojodjojo P, Tung S, Tedrow UB, Nof E, Inada K, Koplan BA, Michaud GF, John RM, Epstein LM, Stevenson WG. Acute failure of catheter ablation for ventricular tachycardia due to structural heart disease: causes and significance. J Am Heart Assoc. 2013; 2(3):e000072.
    View in: PubMed
  3. Ng J, Barbhaiya C, Chopra N, Reichlin T, Nof E, Tadros T, Stevenson WG, John RM. Automatic external defibrillators-friend or foe? Am J Emerg Med. 2013 Aug; 31(8):1292.e1-2.
    View in: PubMed
  4. Steven D, Sultan A, Reddy V, Luker J, Altenburg M, Hoffmann B, Rostock T, Servatius H, Stevenson WG, Willems S, Michaud GF. Benefit of pulmonary vein isolation guided by loss of pace capture on the ablation line: results from a prospective 2-center randomized trial. J Am Coll Cardiol. 2013 Jul 2; 62(1):44-50.
    View in: PubMed
  5. Kojodjojo P, Tokuda M, Bohnen M, Michaud GF, Koplan BA, Epstein LM, Albert CM, John RM, Stevenson WG, Tedrow UB. Electrocardiographic left ventricular scar burden predicts clinical outcomes following infarct-related ventricular tachycardia ablation. Heart Rhythm. 2013 Aug; 10(8):1119-24.
    View in: PubMed
  6. Nof E, Stevenson WG, Epstein LM, Tedrow UB, Koplan BA. Catheter Ablation of Atrial Arrhythmias After Cardiac Transplantation: Findings at EP Study Utility of 3-D Mapping and Outcomes. J Cardiovasc Electrophysiol. 2013 May; 24(5):498-502.
    View in: PubMed
  7. Michaud GF, Stevenson WG. Feeling a little loopy? J Cardiovasc Electrophysiol. 2013 May; 24(5):553-5.
    View in: PubMed
  8. Epstein AE, Dimarco JP, Ellenbogen KA, Estes NA, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Tracy CM, Epstein AE, Darbar D, Dimarco JP, Dunbar SB, Estes NA, Ferguson TB, Hammill SC, Karasik PE, Link MS, Marine JE, Schoenfeld MH, Shanker AJ, Silka MJ, Stevenson LW, Stevenson WG, Varosy PD, Anderson JL, Jacobs AK, Halperin JL, Albert NM, Creager MA, Demets D, Ettinger SM, Guyton RA, Hochman JS, Kushner FG, Ohman EM, Stevenson W, Yancy CW. 2012 ACCF/AHA/HRS Focused Update Incorporated Into the ACCF/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2013 Jan 22; 127(3):e283-352.
    View in: PubMed
  9. Tracy CM, Epstein AE, Darbar D, Dimarco JP, Dunbar SB, Mark Estes NA, Ferguson TB, Hammill SC, Karasik PE, Link MS, Marine JE, Schoenfeld MH, Shanker AJ, Silka MJ, Stevenson LW, Stevenson WG, Varosy PD, Epstein AE, Dimarco JP, Ellenbogen KA, Mark Estes NA, Freedman RA, Gettes LS, Marc Gillinov A, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Kristin Newby L, Page RL, Schoenfeld MH, Silka MJ, Warner Stevenson L, Sweeney MO, Anderson JL, Jacobs AK, Halperin JL, Albert NM, Creager MA, Demets D, Ettinger SM, Guyton RA, Hochman JS, Kushner FG, Ohman EM, Stevenson W, Yancy CW. 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Thorac Cardiovasc Surg. 2012 Dec; 144(6):e127-45.
    View in: PubMed
  10. John RM, Tedrow UB, Koplan BA, Albert CM, Epstein LM, Sweeney MO, Miller AL, Michaud GF, Stevenson WG. Ventricular arrhythmias and sudden cardiac death. Lancet. 2012 Oct 27; 380(9852):1520-9.
    View in: PubMed
  11. Tracy CM, Epstein AE, Darbar D, DiMarco JP, Dunbar SB, Estes NA, Ferguson TB, Hammill SC, Karasik PE, Link MS, Marine JE, Schoenfeld MH, Shanker AJ, Silka MJ, Stevenson LW, Stevenson WG, Varosy PD, Ellenbogen KA, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hayes DL, Page RL, Stevenson LW, Sweeney MO. 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2012 Oct 2; 126(14):1784-800.
    View in: PubMed
  12. Tracy CM, Epstein AE, Darbar D, Dimarco JP, Dunbar SB, Estes NA, Ferguson TB, Hammill SC, Karasik PE, Link MS, Marine JE, Schoenfeld MH, Shanker AJ, Silka MJ, Stevenson LW, Stevenson WG, Varosy PD. 2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Heart Rhythm. 2012 Oct; 9(10):1737-53.
    View in: PubMed
  13. Tokuda M, Tedrow UB, Kojodjojo P, Inada K, Koplan BA, Michaud GF, John RM, Epstein LM, Stevenson WG. Catheter ablation of ventricular tachycardia in nonischemic heart disease. Circ Arrhythm Electrophysiol. 2012 Oct 1; 5(5):992-1000.
    View in: PubMed
  14. John RM, Stevenson WG. Ventricular arrhythmias in patients with implanted cardioverter defibrillators. Trends Cardiovasc Med. 2012 Oct; 22(7):169-73.
    View in: PubMed
  15. Waldo AL, Wilber DJ, Marchlinski FE, Stevenson WG, Aker B, Boo LM, Jackman WM. Safety of the open-irrigated ablation catheter for radiofrequency ablation: safety analysis from six clinical studies. Pacing Clin Electrophysiol. 2012 Sep; 35(9):1081-9.
    View in: PubMed
  16. Tedrow UB, Sobieszczyk P, Stevenson WG. Transvenous ethanol ablation of ventricular tachycardia. Heart Rhythm. 2012 Oct; 9(10):1640-1.
    View in: PubMed
  17. Stevenson WG, Tedrow UB. Ablation for ventricular tachycardia during stable sinus rhythm. Circulation. 2012 May 8; 125(18):2175-7.
    View in: PubMed
  18. Wissner E, Stevenson WG, Kuck KH. Catheter ablation of ventricular tachycardia in ischaemic and non-ischaemic cardiomyopathy: where are we today? A clinical review. Eur Heart J. 2012 Jun; 33(12):1440-50.
    View in: PubMed
  19. Vollmann D, Stevenson WG, Lüthje L, Sohns C, John RM, Zabel M, Michaud GF. Misleading long post-pacing interval after entrainment of typical atrial flutter from the cavotricuspid isthmus. J Am Coll Cardiol. 2012 Feb 28; 59(9):819-24.
    View in: PubMed
  20. Stevenson WG, Hernandez AF, Carson PE, Fang JC, Katz SD, Spertus JA, Sweitzer NK, Tang WH, Albert NM, Butler J, Westlake Canary CA, Collins SP, Colvin-Adams M, Ezekowitz JA, Givertz MM, Hershberger RE, Rogers JG, Teerlink JR, Walsh MN, Stough WG, Starling RC. Indications for cardiac resynchronization therapy: 2011 update from the Heart Failure Society of America Guideline Committee. J Card Fail. 2012 Feb; 18(2):94-106.
    View in: PubMed
  21. Inada K, Tokuda M, Roberts-Thomson KC, Steven D, Seiler J, Tedrow UB, Stevenson WG. Relation of high-pass filtered unipolar electrograms to bipolar electrograms during ventricular mapping. Pacing Clin Electrophysiol. 2012 Feb; 35(2):157-63.
    View in: PubMed
  22. Albert CM, Chen PS, Anderson ME, Cain ME, Fishman GI, Narayan SM, Olgin JE, Spooner PM, Stevenson WG, Van Wagoner DR, Packer DL. Full report from the first annual Heart Rhythm Society Research Forum: a vision for our research future, “dream, discover, develop, deliver”. Heart Rhythm. 2011 Dec; 8(12):e1-12.
    View in: PubMed
  23. Stevenson WG, John RM. Ventricular arrhythmias in patients with implanted defibrillators. Circulation. 2011 Oct 18; 124(16):e411-4.
    View in: PubMed
  24. Tokuda M, Sobieszczyk P, Eisenhauer AC, Kojodjojo P, Inada K, Koplan BA, Michaud GF, John RM, Epstein LM, Sacher F, Stevenson WG, Tedrow UB. Transcoronary ethanol ablation for recurrent ventricular tachycardia after failed catheter ablation: an update. Circ Arrhythm Electrophysiol. 2011 Dec; 4(6):889-96.
    View in: PubMed
  25. John RM, Stevenson WG. Catheter-based ablation for ventricular arrhythmias. Curr Cardiol Rep. 2011 Oct; 13(5):399-406.
    View in: PubMed
  26. Martinek M, Stevenson WG, Inada K, Tokuda M, Tedrow UB. QRS characteristics fail to reliably identify ventricular tachycardias that require epicardial ablation in ischemic heart disease. J Cardiovasc Electrophysiol. 2012 Feb; 23(2):188-93.
    View in: PubMed
  27. Asimaki A, Tandri H, Duffy ER, Winterfield JR, Mackey-Bojack S, Picken MM, Cooper LT, Wilber DJ, Marcus FI, Basso C, Thiene G, Tsatsopoulou A, Protonotarios N, Stevenson WG, McKenna WJ, Gautam S, Remick DG, Calkins H, Saffitz JE. Altered desmosomal proteins in granulomatous myocarditis and potential pathogenic links to arrhythmogenic right ventricular cardiomyopathy. Circ Arrhythm Electrophysiol. 2011 Oct; 4(5):743-52.
    View in: PubMed
  28. Wijnmaalen AP, Roberts-Thomson KC, Steven D, Klautz RJ, Willems S, Schalij MJ, Stevenson WG, Zeppenfeld K. Catheter ablation of ventricular tachycardia after left ventricular reconstructive surgery for ischemic cardiomyopathy. Heart Rhythm. 2012 Jan; 9(1):10-7.
    View in: PubMed
  29. Stevenson WG, Couper GS. A surgical option for ventricular tachycardia caused by nonischemic cardiomyopathy. Circ Arrhythm Electrophysiol. 2011 Aug; 4(4):429-31.
    View in: PubMed
  30. Tokuda M, Kojodjojo P, Epstein LM, Koplan BA, Michaud GF, Tedrow UB, Stevenson WG, John RM. Outcomes of cardiac perforation complicating catheter ablation of ventricular arrhythmias. Circ Arrhythm Electrophysiol. 2011 Oct; 4(5):660-6.
    View in: PubMed
  31. Kosmidou I, Inada K, Seiler J, Koplan B, Stevenson WG, Tedrow UB. Role of repeat procedures for catheter ablation of postinfarction ventricular tachycardia. Heart Rhythm. 2011 Oct; 8(10):1516-22.
    View in: PubMed
  32. Bohnen M, Stevenson WG, Tedrow UB, Michaud GF, John RM, Epstein LM, Albert CM, Koplan BA. Incidence and predictors of major complications from contemporary catheter ablation to treat cardiac arrhythmias. Heart Rhythm. 2011 Nov; 8(11):1661-6.
    View in: PubMed
  33. Wijnmaalen AP, Stevenson WG, Schalij MJ, Field ME, Stephenson K, Tedrow UB, Koplan BA, Putter H, Epstein LM, Zeppenfeld K. ECG identification of scar-related ventricular tachycardia with a left bundle-branch block configuration. Circ Arrhythm Electrophysiol. 2011 Aug; 4(4):486-93.
    View in: PubMed
  34. Steven D, Roberts-Thomson KC, Inada K, Seiler J, Koplan BA, Tedrow UB, Sweeney MO, Epstein LE, Stevenson WG. Long-term follow-up in patients with presumptive Brugada syndrome treated with implanted defibrillators. J Cardiovasc Electrophysiol. 2011 Oct; 22(10):1115-9.
    View in: PubMed
  35. Bohnen M, Shea JB, Michaud GF, John R, Stevenson WG, Epstein LM, Tedrow UB, Albert C, Koplan BA. Quality of life with atrial fibrillation: do the spouses suffer as much as the patients? Pacing Clin Electrophysiol. 2011 Jul; 34(7):804-9.
    View in: PubMed
  36. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Kay GN, Le Huezey JY, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann LS, Smith SC, Priori SG, Estes NA, Ezekowitz MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM, Jacobs AK, Anderson JL, Albert N, Buller CE, Creager MA, Ettinger SM, Guyton RA, Halperin JL, Hochman JS, Kushner FG, Ohman EM, Stevenson WG, Tarkington LG, Yancy CW. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011 Mar 15; 123(10):e269-367.
    View in: PubMed
  37. Wann LS, Curtis AB, Ellenbogen KA, Estes NA, Ezekowitz MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM, Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Kay GN, Le Heuzey JY, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann LS, Jacobs AK, Anderson JL, Albert N, Creager MA, Ettinger SM, Guyton RA, Halperin JL, Hochman JS, Kushner FG, Ohman EM, Stevenson WG, Yancy CW. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on Dabigatran): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011 Mar 15; 123(10):1144-50.
    View in: PubMed
  38. Wann LS, Curtis AB, Ellenbogen KA, Estes NA, Ezekowitz MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on dabigatran): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2011 Mar 15; 57(11):1330-7.
    View in: PubMed
  39. Wann LS, Curtis AB, Ellenbogen KA, Estes NA, Ezekowitz MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM, Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Kay GN, Le Heuzey JY, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann LS, Jacobs AK, Anderson JL, Albert N, Creager MA, Ettinger SM, Guyton RA, Halperin JL, Hochman JS, Kushner FG, Ohman EM, Stevenson WG, Yancy CW. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on dabigatran). A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Heart Rhythm. 2011 Mar; 8(3):e1-8.
    View in: PubMed
  40. Dukkipati SR, d’Avila A, Soejima K, Bala R, Inada K, Singh S, Stevenson WG, Marchlinski FE, Reddy VY. Long-term outcomes of combined epicardial and endocardial ablation of monomorphic ventricular tachycardia related to hypertrophic cardiomyopathy. Circ Arrhythm Electrophysiol. 2011 Apr; 4(2):185-94.
    View in: PubMed
  41. Tedrow UB, Stevenson WG. Recording and interpreting unipolar electrograms to guide catheter ablation. Heart Rhythm. 2011 May; 8(5):791-6.
    View in: PubMed
  42. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NA, Page RL, Ezekowitz MD, Slotwiner DJ, Jackman WM, Stevenson WG, Tracy CM, Fuster V, Rydén LE, Cannom DS, Le Heuzey JY, Crijns HJ, Lowe JE, Curtis AB, Olsson SB, Ellenbogen KA, Prystowsky EN, Halperin JL, Tamargo JL, Kay GN, Wann LS, Jacobs AK, Anderson JL, Albert N, Hochman JS, Buller CE, Kushner FG, Creager MA, Ohman EM, Ettinger SM, Stevenson WG, Guyton RA, Tarkington LG, Halperin JL, Yancy CW. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011 Jan 11; 57(2):223-42.
    View in: PubMed
  43. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NA, Page RL, Ezekowitz MD, Slotwiner DJ, Jackman WM, Stevenson WG, Tracy CM, Fuster V, Rydén LE, Cannom DS, Le Heuzey JY, Crijns HJ, Lowe JE, Curtis AB, Olsson S, Ellenbogen KA, Prystowsky EN, Halperin JL, Tamargo JL, Kay GN, Wann LS, Jacobs AK, Anderson JL, Albert N, Hochman JS, Buller CE, Kushner FG, Creager MA, Ohman EM, Ettinger SM, Stevenson WG, Guyton RA, Tarkington LG, Halperin JL, Yancy CW. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Heart Rhythm. 2011 Jan; 8(1):157-76.
    View in: PubMed
  44. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NA, Page RL, Ezekowitz MD, Slotwiner DJ, Jackman WM, Stevenson WG, Tracy CM, Fuster V, Rydén LE, Cannom DS, Le Heuzey JY, Crijns HJ, Lowe JE, Curtis AB, Olsson S, Ellenbogen KA, Prystowsky EN, Halperin JL, Tamargo JL, Kay GN, Wann L, Jacobs AK, Anderson JL, Albert N, Hochman JS, Buller CE, Kushner FG, Creager MA, Ohman EM, Ettinger SM, Stevenson WG, Guyton RA, Tarkington LG, Halperin JL, Yancy CW. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011 Jan 4; 123(1):104-23.
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  45. Stevenson WG, Asirvatham SJ. Teaching rounds in cardiac electrophysiology. Circ Arrhythm Electrophysiol. 2010 Dec; 3(6):563.
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  46. Rosman JZ, John RM, Stevenson WG, Epstein LM, Tedrow UB, Koplan BA, Albert CM, Michaud GF. Resetting criteria during ventricular overdrive pacing successfully differentiate orthodromic reentrant tachycardia from atrioventricular nodal reentrant tachycardia despite interobserver disagreement concerning QRS fusion. Heart Rhythm. 2011 Jan; 8(1):2-7.
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  47. Gautam S, John RM, Stevenson WG, Jain R, Epstein LM, Tedrow U, Koplan BA, McClennen S, Michaud GF. Effect of therapeutic INR on activated clotting times, heparin dosage, and bleeding risk during ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2011 Mar; 22(3):248-54.
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  48. Inada K, Seiler J, Roberts-Thomson KC, Steven D, Rosman J, John RM, Sobieszczyk P, Stevenson WG, Tedrow UB. Substrate characterization and catheter ablation for monomorphic ventricular tachycardia in patients with apical hypertrophic cardiomyopathy. J Cardiovasc Electrophysiol. 2011 Jan; 22(1):41-8.
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  49. Sacher F, Roberts-Thomson K, Maury P, Tedrow U, Nault I, Steven D, Hocini M, Koplan B, Leroux L, Derval N, Seiler J, Wright MJ, Epstein L, Haissaguerre M, Jais P, Stevenson WG. Epicardial ventricular tachycardia ablation a multicenter safety study. J Am Coll Cardiol. 2010 May 25; 55(21):2366-72.
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  50. Britton KA, Stevenson WG, Levy BD, Katz JT, Loscalzo J. Clinical problem-solving. The beat goes on. N Engl J Med. 2010 May 6; 362(18):1721-6.
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  51. Ross JJ, Britton KA, Desai AS, Stevenson WG. Interactive medical case. The beat goes on. N Engl J Med. 2010 Apr 15; 362(15):e53.
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  52. Tedrow UB, Stevenson WG. Arrhythmias: Catheter ablation for prevention of ventricular tachycardia. Nat Rev Cardiol. 2010 Apr; 7(4):181-2.
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  53. Sacher F, Wright M, Tedrow UB, O’Neill MD, Jais P, Hocini M, Macdonald R, Davies DW, Kanagaratnam P, Derval N, Epstein L, Peters NS, Stevenson WG, Haissaguerre M. Wolff-Parkinson-White ablation after a prior failure: a 7-year multicentre experience. Europace. 2010 Jun; 12(6):835-41.
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  54. Inada K, Roberts-Thomson KC, Seiler J, Steven D, Tedrow UB, Koplan BA, Stevenson WG. Mortality and safety of catheter ablation for antiarrhythmic drug-refractory ventricular tachycardia in elderly patients with coronary artery disease. Heart Rhythm. 2010 Jun; 7(6):740-4.
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  55. Steven D, Seiler J, Roberts-Thomson KC, Inada K, Stevenson WG. Mapping of atrial tachycardias after catheter ablation for atrial fibrillation: use of bi-atrial activation patterns to facilitate recognition of origin. Heart Rhythm. 2010 May; 7(5):664-72.
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  56. Stevenson WG, Tedrow U. Preventing ventricular tachycardia with catheter ablation. Lancet. 2010 Jan 2; 375(9708):4-6.
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  57. Al-Khatib SM, Calkins H, Eloff BC, Packer DL, Ellenbogen KA, Hammill SC, Natale A, Page RL, Prystowsky E, Jackman WM, Stevenson WG, Waldo AL, Wilber D, Kowey P, Yaross MS, Mark DB, Reiffel J, Finkle JK, Marinac-Dabic D, Pinnow E, Sager P, Sedrakyan A, Canos D, Gross T, Berliner E, Krucoff MW. Planning the Safety of Atrial Fibrillation Ablation Registry Initiative (SAFARI) as a Collaborative Pan-Stakeholder Critical Path Registry Model: a Cardiac Safety Research Consortium “Incubator” Think Tank. Am Heart J. 2010 Jan; 159(1):17-24.
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  58. Seiler J, Stevenson WG. Atrial fibrillation in congestive heart failure. Cardiol Rev. 2010 Jan-Feb; 18(1):38-50.
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  59. Steven D, Roberts-Thomson KC, Seiler J, Inada K, Tedrow UB, Mitchell RN, Sobieszczyk PS, Eisenhauer AC, Couper GS, Stevenson WG. Ventricular tachycardia arising from the aortomitral continuity in structural heart disease: characteristics and therapeutic considerations for an anatomically challenging area of origin. Circ Arrhythm Electrophysiol. 2009 Dec; 2(6):660-6.
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  60. Roberts-Thomson KC, Seiler J, Steven D, Inada K, Michaud GF, John RM, Koplan BA, Epstein LM, Stevenson WG, Tedrow UB. Percutaneous access of the epicardial space for mapping ventricular and supraventricular arrhythmias in patients with and without prior cardiac surgery. J Cardiovasc Electrophysiol. 2010 Apr; 21(4):406-11.
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  61. Steven D, Reddy VY, Inada K, Roberts-Thomson KC, Seiler J, Stevenson WG, Michaud GF. Loss of pace capture on the ablation line: a new marker for complete radiofrequency lesions to achieve pulmonary vein isolation. Heart Rhythm. 2010 Mar; 7(3):323-30.
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  62. Roberts-Thomson KC, Steven D, Seiler J, Inada K, Koplan BA, Tedrow UB, Epstein LM, Stevenson WG. Coronary artery injury due to catheter ablation in adults: presentations and outcomes. Circulation. 2009 Oct 13; 120(15):1465-73.
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  63. See VY, Roberts-Thomson KC, Stevenson WG, Camp PC, Koplan BA. Atrial arrhythmias after lung transplantation: epidemiology, mechanisms at electrophysiology study, and outcomes. Circ Arrhythm Electrophysiol. 2009 Oct; 2(5):504-10.
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  64. Stevenson WG, Saltzman JR. Gastroesophageal reflux and atrial-esophageal fistula. Heart Rhythm. 2009 Oct; 6(10):1463-4.
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  65. Aliot EM, Stevenson WG, Almendral-Garrote JM, Bogun F, Calkins CH, Delacretaz E, Della Bella P, Hindricks G, Jaïs P, Josephson ME, Kautzner J, Kay GN, Kuck KH, Lerman BB, Marchlinski F, Reddy V, Schalij MJ, Schilling R, Soejima K, Wilber D. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Heart Rhythm. 2009 Jun; 6(6):886-933.
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  66. Aliot EM, Stevenson WG, Almendral-Garrote JM, Bogun F, Calkins CH, Delacretaz E, Bella PD, Hindricks G, Jaïs P, Josephson ME, Kautzner J, Kay GN, Kuck KH, Lerman BB, Marchlinski F, Reddy V, Schalij MJ, Schilling R, Soejima K, Wilber D. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Europace. 2009 Jun; 11(6):771-817.
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  67. Raymond JM, Sacher F, Winslow R, Tedrow U, Stevenson WG. Catheter ablation for scar-related ventricular tachycardias. Curr Probl Cardiol. 2009 May; 34(5):225-70.
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  68. Lee JC, Steven D, Roberts-Thomson KC, Raymond JM, Stevenson WG, Tedrow UB. Atrial tachycardias adjacent to the phrenic nerve: recognition, potential problems, and solutions. Heart Rhythm. 2009 Aug; 6(8):1186-91.
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  69. Steven D, Roberts-Thomson KC, Seiler J, Michaud GF, John RM, Stevenson WG. Fibrillation in the superior vena cava mimicking atrial tachycardia. Circ Arrhythm Electrophysiol. 2009 Apr; 2(2):e4-7.
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  70. Roberts-Thomson KC, Seiler J, Steven D, Inada K, John R, Michaud G, Stevenson WG. Short AV response to atrial extrastimuli during narrow complex tachycardia: what is the mechanism? J Cardiovasc Electrophysiol. 2009 Aug; 20(8):946-8.
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  71. Koplan BA, Stevenson WG. Ventricular tachycardia and sudden cardiac death. Mayo Clin Proc. 2009 Mar; 84(3):289-97.
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  72. Khairy P, Stevenson WG. Catheter ablation in tetralogy of Fallot. Heart Rhythm. 2009 Jul; 6(7):1069-74.
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  73. Stevenson WG, Tedrow UB, Koplan BA. Management of ventricular tachycardia complicating cardiac surgery. Heart Rhythm. 2009 Aug; 6(8 Suppl):S66-9.
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  74. Lee JC, Epstein LM, Huffer LL, Stevenson WG, Koplan BA, Tedrow UB. ICD lead proarrhythmia cured by lead extraction. Heart Rhythm. 2009 May; 6(5):613-8.
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  75. Tedrow U, Stevenson WG. Strategies for epicardial mapping and ablation of ventricular tachycardia. J Cardiovasc Electrophysiol. 2009 Jun; 20(6):710-3.
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  76. Stevenson WG. Ventricular scars and ventricular tachycardia. Trans Am Clin Climatol Assoc. 2009; 120:403-12.
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  77. Stevenson WG, Wilber DJ, Natale A, Jackman WM, Marchlinski FE, Talbert T, Gonzalez MD, Worley SJ, Daoud EG, Hwang C, Schuger C, Bump TE, Jazayeri M, Tomassoni GF, Kopelman HA, Soejima K, Nakagawa H. Irrigated radiofrequency catheter ablation guided by electroanatomic mapping for recurrent ventricular tachycardia after myocardial infarction: the multicenter thermocool ventricular tachycardia ablation trial. Circulation. 2008 Dec 16; 118(25):2773-82.
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  78. Seiler J, Lee JC, Roberts-Thomson KC, Stevenson WG. Intracardiac echocardiography guided catheter ablation of incessant ventricular tachycardia from the posterior papillary muscle causing tachycardia–mediated cardiomyopathy. Heart Rhythm. 2009 Mar; 6(3):389-92.
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  79. Eckart RE, Field ME, Hruczkowski TW, Forman DE, Dorbala S, Di Carli MF, Albert CE, Maisel WH, Epstein LM, Stevenson WG. Association of electrocardiographic morphology of exercise-induced ventricular arrhythmia with mortality. Ann Intern Med. 2008 Oct 7; 149(7):451-60, W82.
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  80. Goldberger JJ, Cain ME, Hohnloser SH, Kadish AH, Knight BP, Lauer MS, Maron BJ, Page RL, Passman RS, Siscovick D, Stevenson WG, Zipes DP. American Heart Association/american College of Cardiology Foundation/heart Rhythm Society scientific statement on noninvasive risk stratification techniques for identifying patients at risk for sudden cardiac death: a scientific statement from the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention. Heart Rhythm. 2008 Oct; 5(10):e1-21.
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  81. Goldberger JJ, Cain ME, Hohnloser SH, Kadish AH, Knight BP, Lauer MS, Maron BJ, Page RL, Passman RS, Siscovick D, Siscovick D, Stevenson WG, Zipes DP. American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society scientific statement on noninvasive risk stratification techniques for identifying patients at risk for sudden cardiac death: a scientific statement from the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention. Circulation. 2008 Sep 30; 118(14):1497-1518.
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  82. Goldberger JJ, Cain ME, Hohnloser SH, Kadish AH, Knight BP, Lauer MS, Maron BJ, Page RL, Passman RS, Siscovick D, Stevenson WG, Zipes DP. American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society Scientific Statement on Noninvasive Risk Stratification Techniques for Identifying Patients at Risk for Sudden Cardiac Death. A scientific statement from the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention. J Am Coll Cardiol. 2008 Sep 30; 52(14):1179-99.
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  83. Seiler J, Roberts-Thomson KC, Raymond JM, Vest J, Delacretaz E, Stevenson WG. Steam pops during irrigated radiofrequency ablation: feasibility of impedance monitoring for prevention. Heart Rhythm. 2008 Oct; 5(10):1411-6.
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  84. Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, Bourassa MG, Arnold JM, Buxton AE, Camm AJ, Connolly SJ, Dubuc M, Ducharme A, Guerra PG, Hohnloser SH, Lambert J, Le Heuzey JY, O’Hara G, Pedersen OD, Rouleau JL, Singh BN, Stevenson LW, Stevenson WG, Thibault B, Waldo AL. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008 Jun 19; 358(25):2667-77.
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  85. Sacher F, Tedrow UB, Field ME, Raymond JM, Koplan BA, Epstein LM, Stevenson WG. Ventricular tachycardia ablation: evolution of patients and procedures over 8 years. Circ Arrhythm Electrophysiol. 2008 Aug; 1(3):153-61.
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  86. Vest JA, Seiler J, Stevenson WG. Clinical use of cooled radiofrequency ablation. J Cardiovasc Electrophysiol. 2008 Jul; 19(7):769-73.
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  87. Stevenson WG, Berul CI. Arrhythmia and Electrophysiology: the eagle can land. Circ Arrhythm Electrophysiol. 2008 Apr; 1(1):1.
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  88. Roberts-Thomson KC, Seiler J, Raymond JM, Stevenson WG. Exercise induced tachycardia with atrioventricular dissociation: what is the mechanism? Heart Rhythm. 2009 Mar; 6(3):426-8.
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  89. Zeppenfeld K, Stevenson WG. Ablation of ventricular tachycardia in patients with structural heart disease. Pacing Clin Electrophysiol. 2008 Mar; 31(3):358-74.
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  90. Cooper JM, Sapp JL, Robinson D, Epstein LM, Stevenson WG. A rewarming maneuver demonstrates the contribution of blood flow to electrode cooling during internally irrigated RF ablation. J Cardiovasc Electrophysiol. 2008 Apr; 19(4):409-14.
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  91. Zeppenfeld K, Schalij MJ, Bartelings MM, Tedrow UB, Koplan BA, Soejima K, Stevenson WG. Catheter ablation of ventricular tachycardia after repair of congenital heart disease: electroanatomic identification of the critical right ventricular isthmus. Circulation. 2007 Nov 13; 116(20):2241-52.
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  92. Eckart RE, Hruczkowski TW, Tedrow UB, Koplan BA, Epstein LM, Stevenson WG. Sustained ventricular tachycardia associated with corrective valve surgery. Circulation. 2007 Oct 30; 116(18):2005-11.
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  93. Sacher F, Sobieszczyk P, Tedrow U, Eisenhauer AC, Field ME, Selwyn A, Raymond JM, Koplan B, Epstein LM, Stevenson WG. Transcoronary ethanol ventricular tachycardia ablation in the modern electrophysiology era. Heart Rhythm. 2008 Jan; 5(1):62-8.
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  94. Sacher F, Vest J, Raymond JM, Stevenson WG. Incessant donor-to-recipient atrial tachycardia after bilateral lung transplantation. Heart Rhythm. 2008 Jan; 5(1):149-51.
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  95. Sacher F, Vest J, Raymond JM, Stevenson WG. Atrial pacing inducing narrow QRS tachycardia followed by wide complex tachycardia. J Cardiovasc Electrophysiol. 2007 Nov; 18(11):1213-5.
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  96. Stevenson WG, Soejima K. Catheter ablation for ventricular tachycardia. Circulation. 2007 May 29; 115(21):2750-60.
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  97. Koplan BA, Stevenson WG. Sudden arrhythmic death syndrome. Heart. 2007 May; 93(5):547-8.
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  98. Parkash R, Stevenson WG. Atrial fibrillation and clinical events in chronic heart failure. J Am Coll Cardiol. 2007 Jan 23; 49(3):376; author reply 376-7.
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  99. Sacher F, Jais P, Stephenson K, O’Neill MD, Hocini M, Clementy J, Stevenson WG, Haissaguerre M. Phrenic nerve injury after catheter ablation of atrial fibrillation. Indian Pacing Electrophysiol J. 2007; 7(1):1-6.
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  100. Tedrow UB, Stevenson WG, Wood MA, Shepard RK, Hall K, Pellegrini CP, Ellenbogen KA. Activation sequence modification during cardiac resynchronization by manipulation of left ventricular epicardial pacing stimulus strength. Pacing Clin Electrophysiol. 2007 Jan; 30(1):65-9.
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  101. Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J, Popma JJ, Stevenson W. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: Pathophysiology and clinical trial evidence (risk factors through stable coronary artery disease). Circulation. 2006 Dec 19; 114(25):2850-70.
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  102. Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J, Popma JJ, Stevenson W. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part II: Clinical trial evidence (acute coronary syndromes through renal disease) and future directions. Circulation. 2006 Dec 19; 114(25):2871-91.
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  103. Stevenson WG, Tedrow U. Management of atrial fibrillation in patients with heart failure. Heart Rhythm. 2007 Mar; 4(3 Suppl):S28-30.
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  104. Tedrow U, Stevenson WG. Substrate mapping and the aging atrium. Heart Rhythm. 2007 Feb; 4(2):145-6.
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  105. Eckart RE, Hruczkowski TW, Stevenson WG, Epstein LM. Myopotentials leading to ventricular fibrillation detection after advisory defibrillator generator replacement. Pacing Clin Electrophysiol. 2006 Nov; 29(11):1273-6.
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  106. Perloff JK, Middlekauf HR, Child JS, Stevenson WG, Miner PD, Goldberg GD. Usefulness of post-ventriculotomy signal averaged electrocardiograms in congenital heart disease. Am J Cardiol. 2006 Dec 15; 98(12):1646-51.
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  107. Koplan BA, Epstein LM, Albert CM, Stevenson WG. Survival in octogenarians receiving implantable defibrillators. Am Heart J. 2006 Oct; 152(4):714-9.
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  108. Veenhuyzen GD, Hruczkowski T, Dhir SK, Stevenson WG. Another way to prove the presence and participation of an accessory pathway in supraventricular tachycardia? J Cardiovasc Electrophysiol. 2006 Oct; 17(10):1147-9.
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  109. Yan AT, Shayne AJ, Brown KA, Gupta SN, Chan CW, Luu TM, Di Carli MF, Reynolds HG, Stevenson WG, Kwong RY. Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality. Circulation. 2006 Jul 4; 114(1):32-9.
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  110. Sapp JL, Cooper JM, Zei P, Stevenson WG. Large radiofrequency ablation lesions can be created with a retractable infusion-needle catheter. J Cardiovasc Electrophysiol. 2006 Jun; 17(6):657-61.
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  111. Field ME, Miyazaki H, Epstein LM, Stevenson WG. Narrow complex tachycardia after slow pathway ablation: continue ablating? J Cardiovasc Electrophysiol. 2006 May; 17(5):557-9.
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  112. Tedrow UB, Kramer DB, Stevenson LW, Stevenson WG, Baughman KL, Epstein LM, Lewis EF. Relation of right ventricular peak systolic pressure to major adverse events in patients undergoing cardiac resynchronization therapy. Am J Cardiol. 2006 Jun 15; 97(12):1737-40.
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  113. Ames A, Stevenson WG. Cardiology patient page. Catheter ablation of atrial fibrillation. Circulation. 2006 Apr 4; 113(13):e666-8.
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  114. Koplan BA, Soejima K, Baughman K, Epstein LM, Stevenson WG. Refractory ventricular tachycardia secondary to cardiac sarcoid: electrophysiologic characteristics, mapping, and ablation. Heart Rhythm. 2006 Aug; 3(8):924-9.
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  115. Zei PC, Stevenson WG. Epicardial catheter mapping and ablation of ventricular tachycardia. Heart Rhythm. 2006 Mar; 3(3):360-3.
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  116. Miyazaki H, Stevenson WG, Stephenson K, Soejima K, Epstein LM. Entrainment mapping for rapid distinction of left and right atrial tachycardias. Heart Rhythm. 2006 May; 3(5):516-23.
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  117. Parkash R, Stevenson WG, Epstein LM, Maisel WH. Predicting early mortality after implantable defibrillator implantation: a clinical risk score for optimal patient selection. Am Heart J. 2006 Feb; 151(2):397-403.
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  118. Stevenson WG, Epstein LM. Endpoints for ablation of atrial fibrillation. Heart Rhythm. 2006 Feb; 3(2):146-7.
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  119. Stevenson LW, Stevenson WG. Cost-effectiveness of ICDs. N Engl J Med. 2006 Jan 12; 354(2):205-7; author reply 205-7.
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  120. Nazarian S, Maisel WH, Miles JS, Tsang S, Stevenson LW, Stevenson WG. Impact of implantable cardioverter defibrillators on survival and recurrent hospitalization in advanced heart failure. Am Heart J. 2005 Nov; 150(5):955-60.
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  121. Intini A, Goldstein RN, Jia P, Ramanathan C, Ryu K, Giannattasio B, Gilkeson R, Stambler BS, Brugada P, Stevenson WG, Rudy Y, Waldo AL. Electrocardiographic imaging (ECGI), a novel diagnostic modality used for mapping of focal left ventricular tachycardia in a young athlete. Heart Rhythm. 2005 Nov; 2(11):1250-2.
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  122. Parkash R, Maisel WH, Toca FM, Stevenson WG. Atrial fibrillation in heart failure: high mortality risk even if ventricular function is preserved. Am Heart J. 2005 Oct; 150(4):701-6.
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  123. Reynolds DW, Chen PS, Deal BJ, Donahue JK, Ellenbogen KA, Epstein AE, Friedman PA, Hammill SC, Hohnloser SH, Kanter RJ, Lindsay BD, Natale A, Saffitz J, Stevenson WG. Highlights of Heart Rhythm 2005, the Annual Scientific Sessions of the Heart Rhythm Society, May 4-7, 2005, New Orleans, Louisiana. Heart Rhythm. 2005 Sep; 2(9):1025-33.
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  124. Stevenson WG, Soejima K. Recording techniques for clinical electrophysiology. J Cardiovasc Electrophysiol. 2005 Sep; 16(9):1017-22.
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  125. Tedrow U, Stevenson WG, Benzaquen LR. Apical left ventricular aneurysm presenting with malignant ventricular tachycardia responsive to aneurysmectomy. Heart. 2005 May; 91(5):623.
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  126. Brunckhorst CB, Delacretaz E, Soejima K, Maisel WH, Friedman PL, Stevenson WG. Impact of changing activation sequence on bipolar electrogram amplitude for voltage mapping of left ventricular infarcts causing ventricular tachycardia. J Interv Card Electrophysiol. 2005 Mar; 12(2):137-41.
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  127. Stevenson WG. Catheter ablation of monomorphic ventricular tachycardia. Curr Opin Cardiol. 2005 Jan; 20(1):42-7.
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  128. Stevenson WG. To freeze or burn the epicardium? Heart Rhythm. 2005 Jan; 2(1):91-2.
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  129. Stevenson WG, Chaitman BR, Ellenbogen KA, Epstein AE, Gross WL, Hayes DL, Strickberger SA, Sweeney MO. Clinical assessment and management of patients with implanted cardioverter-defibrillators presenting to nonelectrophysiologists. Circulation. 2004 Dec 21; 110(25):3866-9.
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  130. Tedrow U, Maisel WH, Epstein LM, Soejima K, Stevenson WG. Feasibility of adjusting paced left ventricular activation by manipulating stimulus strength. J Am Coll Cardiol. 2004 Dec 7; 44(11):2249-52.
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  131. Stevenson WG, Stevenson LW. Atrial fibrillation and heart failure–five more years. N Engl J Med. 2004 Dec 2; 351(23):2437-40.
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  132. Brunckhorst CB, Delacretaz E, Soejima K, Jackman WM, Nakagawa H, Kuck KH, Ben-Haim SA, Seifert B, Stevenson WG. Ventricular mapping during atrial and right ventricular pacing: relation of electrogram parameters to ventricular tachycardia reentry circuits after myocardial infarction. J Interv Card Electrophysiol. 2004 Dec; 11(3):183-91.
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  133. Curtis AB, Abraham WT, Chen PS, Ellenbogen KA, Epstein AE, Friedman PA, Hohnloser SH, Kanter RJ, Stevenson WG. Highlights of Heart Rhythm 2004, the Annual Scientific Sessions of the Heart Rhythm Society: May 19 to 22, 2004, in San Francisco, California. J Am Coll Cardiol. 2004 Oct 19; 44(8):1550-6.
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  134. Stevenson WG, Cooper J, Sapp J. Optimizing RF output for cooled RF ablation. J Cardiovasc Electrophysiol. 2004 Oct; 15(10 Suppl):S24-7.
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  135. Soejima K, Stevenson WG. Athens, athletes, and arrhythmias: the cardiologist’s dilemma. J Am Coll Cardiol. 2004 Sep 1; 44(5):1059-61.
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  136. Cooper JM, Sapp JL, Tedrow U, Pellegrini CP, Robinson D, Epstein LM, Stevenson WG. Ablation with an internally irrigated radiofrequency catheter: learning how to avoid steam pops. Heart Rhythm. 2004 Sep; 1(3):329-33.
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  137. Soejima K, Couper G, Cooper JM, Sapp JL, Epstein LM, Stevenson WG. Subxiphoid surgical approach for epicardial catheter-based mapping and ablation in patients with prior cardiac surgery or difficult pericardial access. Circulation. 2004 Sep 7; 110(10):1197-201.
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  138. Brunckhorst CB, Delacretaz E, Soejima K, Maisel WH, Friedman PL, Stevenson WG. Identification of the ventricular tachycardia isthmus after infarction by pace mapping. Circulation. 2004 Aug 10; 110(6):652-9.
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  139. Friedman PL, Dubuc M, Green MS, Jackman WM, Keane DT, Marinchak RA, Nazari J, Packer DL, Skanes A, Steinberg JS, Stevenson WG, Tchou PJ, Wilber DJ, Worley SJ. Catheter cryoablation of supraventricular tachycardia: results of the multicenter prospective “frosty” trial. Heart Rhythm. 2004 Jul; 1(2):129-38.
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  140. Sapp JL, Soejima K, Cooper JM, Epstein LM, Stevenson WG. Ablation lesion size correlates with pacing threshold: a physiological basis for use of pacing to assess ablation lesions. Pacing Clin Electrophysiol. 2004 Jul; 27(7):933-7.
    View in: PubMed
  141. Soejima K, Stevenson WG, Sapp JL, Selwyn AP, Couper G, Epstein LM. Endocardial and epicardial radiofrequency ablation of ventricular tachycardia associated with dilated cardiomyopathy: the importance of low-voltage scars. J Am Coll Cardiol. 2004 May 19; 43(10):1834-42.
    View in: PubMed
  142. Tedrow U, Sweeney MO, Stevenson WG. Physiology of cardiac resynchronization. Curr Cardiol Rep. 2004 May; 6(3):189-93.
    View in: PubMed
  143. Sapp JL, Cooper JM, Soejima K, Sorrell T, Lopera G, Satti SD, Koplan BA, Epstein LM, Edelman E, Rogers C, Stevenson WG. Deep myocardial ablation lesions can be created with a retractable needle-tipped catheter. Pacing Clin Electrophysiol. 2004 May; 27(5):594-9.
    View in: PubMed
  144. Stevenson WG, Sweeney MO. Single site left ventricular pacing for cardiac resynchronization. Circulation. 2004 Apr 13; 109(14):1694-6.
    View in: PubMed
  145. Koplan BA, Parkash R, Couper G, Stevenson WG. Combined epicardial-endocardial approach to ablation of inappropriate sinus tachycardia. J Cardiovasc Electrophysiol. 2004 Feb; 15(2):237-40.
    View in: PubMed
  146. Lopera G, Stevenson WG, Soejima K, Maisel WH, Koplan B, Sapp JL, Satti SD, Epstein LM. Identification and ablation of three types of ventricular tachycardia involving the his-purkinje system in patients with heart disease. J Cardiovasc Electrophysiol. 2004 Jan; 15(1):52-8.
    View in: PubMed
  147. Blomström-Lundqvist C, Scheinman MM, Aliot EM, Alpert JS, Calkins H, Camm AJ, Campbell WB, Haines DE, Kuck KH, Lerman BB, Miller DD, Shaeffer CW, Stevenson WG, Tomaselli GF, Antman EM, Smith SC, Alpert JS, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Hiratzka LF, Hunt SA, Jacobs AK, Russell RO, Priori SG, Blanc JJ, Budaj A, Burgos EF, Cowie M, Deckers JW, Garcia MA, Klein WW, Lekakis J, Lindahl B, Mazzotta G, Morais JC, Oto A, Smiseth O, Trappe HJ. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias–executive summary. a report of the American college of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to develop guidelines for the management of patients with supraventricular arrhythmias) developed in collaboration with NASPE-Heart Rhythm Society. J Am Coll Cardiol. 2003 Oct 15; 42(8):1493-531.
    View in: PubMed
  148. Blomström-Lundqvist C, Scheinman MM, Aliot EM, Alpert JS, Calkins H, Camm AJ, Campbell WB, Haines DE, Kuck KH, Lerman BB, Miller DD, Shaeffer CW, Stevenson WG, Tomaselli GF, Antman EM, Smith SC, Alpert JS, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Hiratzka LF, Hunt SA, Jacobs AK, Russell RO, Priori SG, Blanc JJ, Budaj A, Burgos EF, Cowie M, Deckers JW, Garcia MA, Klein WW, Lekakis J, Lindahl B, Mazzotta G, Morais JC, Oto A, Smiseth O, Trappe HJ. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias–executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias). Circulation. 2003 Oct 14; 108(15):1871-909.
    View in: PubMed
  149. Delacretaz E, Soejima K, Brunckhorst CB, Maisel WH, Friedman PL, Stevenson WG. Assessment of radiofrequency ablation effect from unipolar pacing threshold. Pacing Clin Electrophysiol. 2003 Oct; 26(10):1993-6.
    View in: PubMed
  150. Soejima K, Stevenson WG. Catheter ablation of ventricular tachycardia in patients with ischemic heart disease. Curr Cardiol Rep. 2003 Sep; 5(5):364-8.
    View in: PubMed
  151. Tung S, Soejima K, Maisel WH, Suzuki M, Epstein L, Stevenson WG. Recognition of far-field electrograms during entrainment mapping of ventricular tachycardia. J Am Coll Cardiol. 2003 Jul 2; 42(1):110-5.
    View in: PubMed
  152. Stevenson WG, Soejima K. Inside or out? Another option for incessant ventricular tachycardia. J Am Coll Cardiol. 2003 Jun 4; 41(11):2044-5.
    View in: PubMed
  153. Brunckhorst CB, Stevenson WG, Soejima K, Maisel WH, Delacretaz E, Friedman PL, Ben-Haim SA. Relationship of slow conduction detected by pace-mapping to ventricular tachycardia re-entry circuit sites after infarction. J Am Coll Cardiol. 2003 Mar 5; 41(5):802-9.
    View in: PubMed
  154. Koplan BA, Stevenson WG, Epstein LM, Aranki SF, Maisel WH. Development and validation of a simple risk score to predict the need for permanent pacing after cardiac valve surgery. J Am Coll Cardiol. 2003 Mar 5; 41(5):795-801.
    View in: PubMed
  155. Ellison KE, Stevenson WG, Sweeney MO, Epstein LM, Maisel WH. Management of arrhythmias in heart failure. Congest Heart Fail. 2003 Mar-Apr; 9(2):91-9.
    View in: PubMed
  156. Stevenson WG, Epstein LM. Predicting sudden death risk for heart failure patients in the implantable cardioverter-defibrillator age. Circulation. 2003 Feb 4; 107(4):514-6.
    View in: PubMed
  157. Maisel WH, Stevenson WG, Epstein LM. Changing trends in pacemaker and implantable cardioverter defibrillator generator advisories. Pacing Clin Electrophysiol. 2002 Dec; 25(12):1670-8.
    View in: PubMed
  158. Khan HH, Maisel WH, Ho C, Suzuki M, Soejima K, Solomon S, Stevenson WG. Effect of radiofrequency catheter ablation of ventricular tachycardia on left ventricular function in patients with prior myocardial infarction. J Interv Card Electrophysiol. 2002 Dec; 7(3):243-7.
    View in: PubMed
  159. Fenelon G, Stambler BS, Huvelle E, Brugada P, Stevenson WG. Left ventricular dysfunction is associated with prolonged average ventricular fibrillation cycle length in patients with implantable cardioverter defibrillators. J Interv Card Electrophysiol. 2002 Dec; 7(3):249-54.
    View in: PubMed
  160. Soejima K, Stevenson WG, Maisel WH, Sapp JL, Epstein LM. Electrically unexcitable scar mapping based on pacing threshold for identification of the reentry circuit isthmus: feasibility for guiding ventricular tachycardia ablation. Circulation. 2002 Sep 24; 106(13):1678-83.
    View in: PubMed
  161. Maisel WH, Stevenson WG. Syncope–getting to the heart of the matter. N Engl J Med. 2002 Sep 19; 347(12):931-3.
    View in: PubMed
  162. Maisel WH, Stevenson WG, Epstein LM. Reduced atrial blood flow in patients with coronary artery disease. Coron Artery Dis. 2002 Aug; 13(5):283-90.
    View in: PubMed
  163. Soejima K, Stevenson WG. Ventricular tachycardia associated with myocardial infarct scar: a spectrum of therapies for a single patient. Circulation. 2002 Jul 9; 106(2):176-9.
    View in: PubMed
  164. Brunckhorst CB, Stevenson WG, Jackman WM, Kuck KH, Soejima K, Nakagawa H, Cappato R, Ben-Haim SA. Ventricular mapping during atrial and ventricular pacing. Relationship of multipotential electrograms to ventricular tachycardia reentry circuits after myocardial infarction. Eur Heart J. 2002 Jul; 23(14):1131-8.
    View in: PubMed
  165. Friedman RA, Walsh EP, Silka MJ, Calkins H, Stevenson WG, Rhodes LA, Deal BJ, Wolff GS, Demaso DR, Hanisch D, Van Hare GF. NASPE Expert Consensus Conference: Radiofrequency catheter ablation in children with and without congenital heart disease. Report of the writing committee. North American Society of Pacing and Electrophysiology. Pacing Clin Electrophysiol. 2002 Jun; 25(6):1000-17.
    View in: PubMed
  166. Stevenson WG, Ellison KE, Sweeney MO, Epstein LM, Maisel WH. Management of arrhythmias in heart failure. Cardiol Rev. 2002 Jan-Feb; 10(1):8-14.
    View in: PubMed
  167. Maisel WH, Rawn JD, Stevenson WG. Atrial fibrillation after cardiac surgery. Ann Intern Med. 2001 Dec 18; 135(12):1061-73.
    View in: PubMed
  168. Sapp J, Soejima K, Couper GS, Stevenson WG. Electrophysiology and anatomic characterization of an epicardial accessory pathway. J Cardiovasc Electrophysiol. 2001 Dec; 12(12):1411-4.
    View in: PubMed
  169. Sweeney MO, Ellison KE, Stevenson WG. Implantable cardioverter defibrillators in heart failure. Cardiol Clin. 2001 Nov; 19(4):653-67.
    View in: PubMed
  170. Maisel WH, Stevenson WG, Tung S, Blier LE, Brunckhorst CB. Less is more: 4:2:1 block. Circulation. 2001 Sep 4; 104(10):E50.
    View in: PubMed
  171. Delacrétaz E, Stevenson WG. Catheter ablation of ventricular tachycardia in patients with coronary heart disease. Part II: Clinical aspects, limitations, and recent developments. Pacing Clin Electrophysiol. 2001 Sep; 24(9 Pt 1):1403-11.
    View in: PubMed
  172. Maisel WH, Sweeney MO, Stevenson WG, Ellison KE, Epstein LM. Recalls and safety alerts involving pacemakers and implantable cardioverter-defibrillator generators. JAMA. 2001 Aug 15; 286(7):793-9.
    View in: PubMed
  173. Soejima K, Suzuki M, Maisel WH, Brunckhorst CB, Delacretaz E, Blier L, Tung S, Khan H, Stevenson WG. Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping. Circulation. 2001 Aug 7; 104(6):664-9.
    View in: PubMed
  174. Delacretaz E, Stevenson WG. Catheter ablation of ventricular tachycardia in patients with coronary heart disease: part I: Mapping. Pacing Clin Electrophysiol. 2001 Aug; 24(8 Pt 1):1261-77.
    View in: PubMed
  175. Delacretaz E, Ganz LI, Soejima K, Friedman PL, Walsh EP, Triedman JK, Sloss LJ, Landzberg MJ, Stevenson WG. Multi atrial maco-re-entry circuits in adults with repaired congenital heart disease: entrainment mapping combined with three-dimensional electroanatomic mapping. J Am Coll Cardiol. 2001 May; 37(6):1665-76.
    View in: PubMed
  176. Soejima K, Delacretaz E, Suzuki M, Brunckhorst CB, Maisel WH, Friedman PL, Stevenson WG. Saline-cooled versus standard radiofrequency catheter ablation for infarct-related ventricular tachycardias. Circulation. 2001 Apr 10; 103(14):1858-62.
    View in: PubMed
  177. Soejima K, Stevenson WG, Maisel WH, Delacretaz E, Brunckhorst CB, Ellison KE, Friedman PL. The N + 1 difference: a new measure for entrainment mapping. J Am Coll Cardiol. 2001 Apr; 37(5):1386-94.
    View in: PubMed
  178. Delacretaz E, Soejima K, Gottipaty VK, Brunckhorst CB, Friedman PL, Stevenson WG. Single catheter determination of local electrogram prematurity using simultaneous unipolar and bipolar recordings to replace the surface ECG as a timing reference. Pacing Clin Electrophysiol. 2001 Apr; 24(4 Pt 1):441-9.
    View in: PubMed
  179. Stevenson WG, Maisel WH. Electrocardiography artifact: what you do not know, you do not recognize. Am J Med. 2001 Apr 1; 110(5):402-3.
    View in: PubMed
  180. Stevenson WG, Soejima K. Knowing where to look. J Cardiovasc Electrophysiol. 2001 Mar; 12(3):367-8.
    View in: PubMed
  181. Stevenson WG, Stevenson LW. Prevention of sudden death in heart failure. J Cardiovasc Electrophysiol. 2001 Jan; 12(1):112-4.
    View in: PubMed
  182. Stevenson WG, Delacretaz E. Radiofrequency catheter ablation of ventricular tachycardia. Heart. 2000 Nov; 84(5):553-9.
    View in: PubMed
  183. Stevenson WG, Delacretaz E. Strategies for catheter ablation of scar-related ventricular tachycardia. Curr Cardiol Rep. 2000 Nov; 2(6):537-44.
    View in: PubMed
  184. Soejima K, Stevenson WG, Delacretaz E, Brunckhorst CB, Maisel WH, Friedman PL. Identification of left atrial origin of ectopic tachycardia during right atrial mapping: analysis of double potentials at the posteromedial right atrium. J Cardiovasc Electrophysiol. 2000 Sep; 11(9):975-80.
    View in: PubMed
  185. Weinfeld MS, Drazner MH, Stevenson WG, Stevenson LW. Early outcome of initiating amiodarone for atrial fibrillation in advanced heart failure. J Heart Lung Transplant. 2000 Jul; 19(7):638-43.
    View in: PubMed
  186. Maisel WH, Stevenson WG. Sudden death and the electrophysiological effects of angiotensin-converting enzyme inhibitors. J Card Fail. 2000 Jun; 6(2):80-2.
    View in: PubMed
  187. Ellison KE, Stevenson WG, Sweeney MO, Lefroy DC, Delacretaz E, Friedman PL. Catheter ablation for hemodynamically unstable monomorphic ventricular tachycardia. J Cardiovasc Electrophysiol. 2000 Jan; 11(1):41-4.
    View in: PubMed
  188. Delacretaz E, Stevenson WG, Ellison KE, Maisel WH, Friedman PL. Mapping and radiofrequency catheter ablation of the three types of sustained monomorphic ventricular tachycardia in nonischemic heart disease. J Cardiovasc Electrophysiol. 2000 Jan; 11(1):11-7.
    View in: PubMed
  189. Delacretaz E, Soejima K, Stevenson WG, Friedman PL. Short ventriculoatrial intervals during orthodromic atrioventricular reciprocating tachycardia: what is the mechanism? J Cardiovasc Electrophysiol. 2000 Jan; 11(1):121-4.
    View in: PubMed
  190. Soejima K, Delacretaz E, Stevenson WG, Friedman PL. DDD-pacing-induced cardiomyopathy following AV node ablation for persistent atrial tachycardia. J Interv Card Electrophysiol. 1999 Dec; 3(4):321-3.
    View in: PubMed
  191. Stevenson WG, Stevenson LW. Atrial fibrillation in heart failure. N Engl J Med. 1999 Sep 16; 341(12):910-1.
    View in: PubMed
  192. Kocovic DZ, Harada T, Friedman PL, Stevenson WG. Characteristics of electrograms recorded at reentry circuit sites and bystanders during ventricular tachycardia after myocardial infarction. J Am Coll Cardiol. 1999 Aug; 34(2):381-8.
    View in: PubMed
  193. Delacretaz E, Stevenson WG, Winters GL, Mitchell RN, Stewart S, Lynch K, Friedman PL. Ablation of ventricular tachycardia with a saline-cooled radiofrequency catheter: anatomic and histologic characteristics of the lesions in humans. J Cardiovasc Electrophysiol. 1999 Jun; 10(6):860-5.
    View in: PubMed
  194. Delacretaz E, Stevenson WG, Winters GL, Friedman PL. Radiofrequency ablation of atrial flutter. Circulation. 1999 Apr 13; 99(14):E1-2.
    View in: PubMed
  195. Friedman PL, Stevenson WG. Proarrhythmia. Am J Cardiol. 1998 Oct 16; 82(8A):50N-58N.
    View in: PubMed
  196. Ellison KE, Friedman PL, Ganz LI, Stevenson WG. Entrainment mapping and radiofrequency catheter ablation of ventricular tachycardia in right ventricular dysplasia. J Am Coll Cardiol. 1998 Sep; 32(3):724-8.
    View in: PubMed
  197. Lefroy DC, Fang JC, Stevenson LW, Hartley LH, Friedman PL, Stevenson WG. Recipient-to-donor atrioatrial conduction after orthotopic heart transplantation: surface electrocardiographic features and estimated prevalence. Am J Cardiol. 1998 Aug 15; 82(4):444-50.
    View in: PubMed
  198. Stevenson WG, Friedman PL, Kocovic D, Sager PT, Saxon LA, Pavri B. Radiofrequency catheter ablation of ventricular tachycardia after myocardial infarction. Circulation. 1998 Jul 28; 98(4):308-14.
    View in: PubMed
  199. Stevenson WG, Delacretaz E, Friedman PL, Ellison KE. Identification and ablation of macroreentrant ventricular tachycardia with the CARTO electroanatomical mapping system. Pacing Clin Electrophysiol. 1998 Jul; 21(7):1448-56.
    View in: PubMed
  200. Lefroy DC, Ellison KE, Friedman PL, Stevenson WG. Arrhythmia of the month: shortening of ventriculoatrial conduction time during radiofrequency catheter ablation of a concealed accessory pathway. J Cardiovasc Electrophysiol. 1998 Apr; 9(4):445-7.
    View in: PubMed
  201. Ganz LI, Couper GS, Friedman PL, Stevenson WG, Ellison K. Use of telemetered permanent pacemaker intracardiac electrograms to diagnose ventricular tachycardia. Am J Cardiol. 1997 Dec 1; 80(11):1511-3.
    View in: PubMed
  202. stevenson WG, Friedman PL, Ganz LI. Radiofrequency catheter ablation of ventricular tachycardia late after myocardial infarction. J Cardiovasc Electrophysiol. 1997 Nov; 8(11):1309-19.
    View in: PubMed
  203. Stevenson WG, Ellison KE, Lefroy DC, Friedman PL. Ablation therapy for cardiac arrhythmias. Am J Cardiol. 1997 Oct 23; 80(8A):56G-66G.
    View in: PubMed
  204. Ellison KE, Stevenson WG, Couper GS, Friedman PL. Ablation of ventricular tachycardia due to a postinfarct ventricular septal defect: identification and transection of a broad reentry loop. J Cardiovasc Electrophysiol. 1997 Oct; 8(10):1163-6.
    View in: PubMed
  205. Harada T, Stevenson WG, Kocovic DZ, Friedman PL. Catheter ablation of ventricular tachycardia after myocardial infarction: relation of endocardial sinus rhythm late potentials to the reentry circuit. J Am Coll Cardiol. 1997 Oct; 30(4):1015-23.
    View in: PubMed
  206. Stevenson WG, Sweeney MO. Arrhythmias and sudden death in heart failure. Jpn Circ J. 1997 Sep; 61(9):727-40.
    View in: PubMed
  207. Maisel WH, Kuntz KM, Reimold SC, Lee TH, Antman EM, Friedman PL, Stevenson WG. Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in patients admitted to a university hospital. Ann Intern Med. 1997 Aug 15; 127(4):281-4.
    View in: PubMed
  208. Stevenson WG, Sweeney MO. Pharmacologic and nonpharmacologic treatment of ventricular arrhythmias in heart failure. Curr Opin Cardiol. 1997 May; 12(3):242-50.
    View in: PubMed
  209. Stevenson WG, Friedman PL, Sager PT, Saxon LA, Kocovic D, Harada T, Wiener I, Khan H. Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping. J Am Coll Cardiol. 1997 May; 29(6):1180-9.
    View in: PubMed
  210. Hadjis TA, Stevenson WG, Harada T, Friedman PL, Sager P, Saxon LA. Preferential locations for critical reentry circuit sites causing ventricular tachycardia after inferior wall myocardial infarction. J Cardiovasc Electrophysiol. 1997 Apr; 8(4):363-70.
    View in: PubMed
  211. Hadjis TA, Harada T, Stevenson WG, Friedman PL. Effect of recording site on postpacing interval measurement during catheter mapping and entrainment of postinfarction ventricular tachycardia. J Cardiovasc Electrophysiol. 1997 Apr; 8(4):398-404.
    View in: PubMed
  212. Merliss AD, Seifert MJ, Collins RF, Higgins JP, Reimold SC, Lee RT, Friedman PL, Stevenson WG. Catheter ablation of idiopathic left ventricular tachycardia associated with a false tendon. Pacing Clin Electrophysiol. 1996 Dec; 19(12 Pt 1):2144-6.
    View in: PubMed
  213. Stevenson WG, Stevenson LW, Middlekauff HR, Fonarow GC, Hamilton MA, Woo MA, Saxon LA, Natterson PD, Steimle A, Walden JA, Tillisch JH. Improving survival for patients with atrial fibrillation and advanced heart failure. J Am Coll Cardiol. 1996 Nov 15; 28(6):1458-63.
    View in: PubMed
  214. Stevenson WG, Ridker PM. Should survivors of myocardial infarction with low ejection fraction be routinely referred to arrhythmia specialists? JAMA. 1996 Aug 14; 276(6):481-5.
    View in: PubMed
  215. Friedman PL, Stevenson WG, Kocovic DZ. Autonomic dysfunction after catheter ablation. J Cardiovasc Electrophysiol. 1996 May; 7(5):450-9.
    View in: PubMed
  216. Ganz LI, Stevenson WG. Catheter mapping and ablation of ventricular tachycardia. Coron Artery Dis. 1996 Jan; 7(1):29-35.
    View in: PubMed
  217. Stevenson WG, Stevenson LW, Middlekauff HR, Fonarow GC, Hamilton MA, Woo MA, Saxon LA, Natterson PD, Steimle A, Walden JA, et al. Improving survival for patients with advanced heart failure: a study of 737 consecutive patients. J Am Coll Cardiol. 1995 Nov 15; 26(6):1417-23.
    View in: PubMed
  218. Stevenson WG. Ventricular tachycardia after myocardial infarction: from arrhythmia surgery to catheter ablation. J Cardiovasc Electrophysiol. 1995 Oct; 6(10 Pt 2):942-50.
    View in: PubMed
  219. Bartlett TG, Mitchell R, Friedman PL, Stevenson WG. Histologic evolution of radiofrequency lesions in an old human myocardial infarct causing ventricular tachycardia. J Cardiovasc Electrophysiol. 1995 Aug; 6(8):625-9.
    View in: PubMed
  220. Stevenson WG, Sager PT, Natterson PD, Saxon LA, Middlekauff HR, Wiener I. Relation of pace mapping QRS configuration and conduction delay to ventricular tachycardia reentry circuits in human infarct scars. J Am Coll Cardiol. 1995 Aug; 26(2):481-8.
    View in: PubMed
  221. Stevenson WG. Mechanisms and management of arrhythmias in heart failure. Curr Opin Cardiol. 1995 May; 10(3):274-81.
    View in: PubMed
  222. Stevenson WG, Sager PT, Friedman PL. Entrainment techniques for mapping atrial and ventricular tachycardias. J Cardiovasc Electrophysiol. 1995 Mar; 6(3):201-16.
    View in: PubMed
  223. Stevenson WG. Functional approach to site-by-site catheter mapping of ventricular reentry circuits in chronic infarctions. J Electrocardiol. 1994; 27 Suppl:130-8.
    View in: PubMed

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Summary of Genomics and Medicine: Role in Cardiovascular Diseases

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Summary of Genomics and Medicine: Role in Cardiovascular Diseases

Author: Larry H. Bernstein, MD, FCAP

The articles within Chapters and Subchapters you have just read have been organized into four interconnected parts.
  1. Genomics and Medicine
  2. Epigenetics – Modifyable Factors Causing CVD
  3. Determinants of CVD – Genetics, Heredity and Genomics Discoveries
  4. Individualized Medicine Guided by Genetics and Genomics Discoveries
The first part established the
  • rapidly evolving science of genomics
  • aided by analytical and computational tools for the identification of nucleotide substitutions, or combinations of them
that have a significant association with the development of
  • cardiovascular diseases,
  • hypercoagulable state,
  • atherosclerosis,
  • microvascular disease,
  • endothelial disruption, and
  • type-2DM, to name a few.
These may well be associated with increased risk for stroke and/or peripheral vascular disease in some cases,
  • essentially because the involvement of the circulation is systemic in nature.

Part 1

establishes an important connection between RNA and disease expression.  This development has led to
  • the necessity of a patient-centric approach to patient-care.
When I entered medical school, it was eight years after Watson and Crick proposed the double helix.  It was also
  • the height of a series of discoveries elucidating key metabolic pathways.
In the period since then there have been treatments for some of the important well established metabolic diseases of
  • carbohydrate,
  • protein, and
  • lipid metabolism,
such as –  glycogen storage disease, and some are immense challenges, such as
  • Tay Sachs, or
  • Transthyretin-Associated amyloidosis.
But we have crossed a line delineating classical Mendelian genetics to
  • multifactorial non-linear traits of great complexity and
involving combinatorial program analyses to resolve.
The Human Genome Project was completed in 2001, and it has opened the floodgates of genomic discovery.  This resulted in the identification of
genomic alterations in
  • cardiovascular disease,
  • cancer,
  • microbial,
  • plant,
  • prion, and
  • metabolic diseases.
This has also led to
  • the identification of genomic targets
  • that are either involved in transcription or
  • are involved with cellular control mechanisms for targeted pharmaceutical development.
In addition, there is great pressure on the science of laboratory analytics to
  • codevelop with new drugs,
  • biomarkers that are indicators of toxicity or
  • of drug effectiveness.
I have not mentioned the dark matter of the genome. It has been substantially reduced, and has been termed dark because
  • this portion of the genome is not identified in transcription of proteins.
However, it has become a lightning rod to ongoing genomic investigation because of
  • an essential role in the regulation of nuclear and cytoplasmic activities.
Changes in the three dimensional structure of these genes due to
  • changes in Van der Waal forces and internucleotide distances lead to
  • conformational changes that could have an effect on cell activity.

Part 2

is an exploration of epigenetics in cardiovascular diseases.  Epigenetics is
  • the post-genomic modification of genetic expression
  • by the substitution of nucleotides or by the attachment of carbohydrate residues, or
  • by alterations in the hydrophobic forces between sequences that weaken or strengthen their expression.
This could operate in a manner similar to the conformational changes just described.  These changes
  • may be modifiable, and they
  • may be highly influenced by environmental factors, such as
    1. smoking and environmental toxins,
    2. diet,
    3. physical activity, and
    4. neutraceuticals.
While neutraceuticals is a black box industry that evolved from
  • the extraction of ancient herbal remedies of agricultural derivation
    (which could be extended to digitalis and Foxglove; or to coumadin; and to penecillin, and to other drugs that are not neutraceuticals).

The best examples are the importance of

  • n-3 fatty acids, and
  • fiber
  • dietary sulfur (in the source of methionine), folic acid, vitamin B12
  • arginine combined with citrulline to drive eNOS
  • and of iodine, which can’t be understated.
In addition, meat consumption involves the intake of fat that contains

  • the proinflammatory n-6 fatty acid.

The importance of the ratio of n-3/n-6 fatty acids in diet is not seriously discussed when

  • we look at the association of fat intake and disease etiology.
Part 2 then leads into signaling pathways and proteomics. The signaling pathways are
  • critical to understanding the inflammatory process, just as
  • dietary factors tie in with a balance that is maintained by dietary intake,
    • possibly gut bacteria utilization of delivered substrate, and
    • proinflammatory factors in disaease.
These are being explored by microfluidic proteomic and metabolomic technologies that were inconceivable a half century ago.
This portion extended into the diagnosis of cardiovascular disease, and
  • elucidated the relationship between platelet-endothelial interaction in the formation of vascular plaque.
It explored protein, proteomic, and genomic markers
  1. for identifying and classifying types of disease pathobiology, and
  2. for following treatment measures.

Part 3

connected with genetics and genomic discoveries in cardiovascular diseases.

Part 4

is the tie between life style habits and disease etiology, going forward with
  • the pursuit of cardiovascular disease prevention.
The presentation of walking and running, and of bariatric surgery (type 2DM) are fine examples.
It further discussed gene therapy and congenital heart disease.  But the most interesting presentations are
  • in the pharmacogenomics for cardiovascular diseases, with
    1. volyage-gated calcium-channels, and
    2. ApoE in the statin response.

This volume is a splendid example representative of the entire collection on cardiovascular diseases.

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Introduction to Genomics and Epigenomics Roles in Cardiovascular Diseases

Posted in Atherogenic Processes & Pathology, Best evidence, Cardiomyopathy, Cardiovascular Pharmacogenomics, Cardiovascular Research, Coagulation Therapy and Internal Bleeding, Congenital Heart Disease, Cytoskeleton, Diabetes Mellitus, Diagnostic Immunology, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Evidence-based decision-making, Experimental validation, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, HTN, Human Immune System in Health and in Disease, Immunodiagnostics, Innovation in Immunology Diagnostics, International Global Work in Pharmaceutical, Medical and Population Genetics, Metabolomics, Molecular Genetics & Pharmaceutical, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Nitric Oxide in Health and Disease, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmacogenomics, Pharmacologic toxicities, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Pre-Clinical Animal Model Development, Proteomics, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Statistical Methods for Research Evaluation, Systemic Inflammatory Response Related Disorders, Technology Advance Assessment of, Technology Transfer: Biotech and Pharmaceutical, Theoretic convergence, Translational Effectiveness, Translational Research, Translational Science, tagged , , , , , , , , , , , , , , , , , , , , , , , , , on January 5, 2014| Leave a Comment »

Introduction to Genomics and Epigenomics Roles in Cardiovascular Diseases

Author and Curator: Larry H Bernstein, MD, FCAP

This introduction is to a thorough evaluation of a rich source of research literature on the genomic influences, which may have variable strength in the biological causation of atherosclerosis, microvascular disease, plaque formation, not necessarily having expressing, except in a multivariable context that includes the environment, dietary factors, level of emotional stress, sleep habits, and the daily activities of living for affected individuals.  The potential of genomics is carried in the DNA, copied to RNA, and this is most well studied in the micro RNAs (miRNA).  The miRNA has been explored for the appearance in the circulation of specific miRNAs that might be associated with myocyte or endothelial cell injury, and they are also being used as targets for therapeutics by the creation of silencing RNAs (siRNA).  The extent to which there is evidence of success in these studies is limited, but is being translated from animal studies to human disease.  There is also a long history of the measurement of  circulating enzymes and isoenzymes (alanine amino transferase, creatine kinase, and lactate dehydrogenase, not to leave out the adenylate kinase species specific to myocardium), and more recently the release of troponins I and T, and the so far still not fully explored ischemia modified albumin, or of miRNAs for the diagnosis of myocardial infarction.

There is also a significant disagreement about the value of measuring high sensitivity C reactive protein (hs-CRP), which has always been a marker for systemic inflammatory disease, in both chronic rheumatic and infectious diseases having a broad range, so that procalcitonin has appeared to be better for that situation, and for early diagnosis of sepsis. The hs-CRP has been too easily ignored because of

1. the ubiquitous elevations in the population
2. the expressed concerns that one might not be inclined to treat a mild elevation without other risk factors, such as, LDL cholesterolemia, low HDL, absent diabetes or obesity.  Nevertheless, hs-CRP raises an reasonable argument for preventive measures, and perhaps the use of a statin.

There has been a substantial amount of work on the relationship of obesity to both type 2 diabetes mellitus (T2DM) and to coronary vascular disease and stroke.  Here we bring in the relationship of the vascular endothelium, adipose tissue secretion of adiponectin, and platelet activation.  A whole generation of antiplatelet drugs addresses the mechanism of platelet activation, adhession, and interaction with endothelium.   Very interesting work has appeared on RESISTIN, that could bear some fruit in the treatment of both obesity and T2DM.

It is important to keep in mind that epigenomic gene rearrangements or substitutions occur throughout life, and they may have an expression late in life.  Some of the known epigenetic events occur with some frequency, but the associations are extremely difficult to pin down, as well as the strength of the association.  In a population that is not diverse, epigenetic changes are passed on in the population in the period of childbearing age.  The establishment of an epigenetic change is diluted in a diverse population.  There have been a number of studies with different findings of association between cardiovascular disease and genetic mutations in the Han and also in the Uyger Chinese populations, which are distinctly different populations that is not part of this discussion.

This should be sufficient to elicit broad appeal in reading this volume on cardiovascular diseases, and perhaps the entire series.  Below is a diagram of this volume in the series.

PART 1 – Genomics and Medicine
Introduction to Genomics and Medicine (Vol 3)
Genomics and Medicine: The Physician’s View
Ribozymes and RNA Machines
Genomics and Medicine: Genomics to CVD Diagnoses
Establishing a Patient-Centric View of Genomic Data
VIDEO:  Implementing Biomarker Programs ­ P Ridker PART 2 – Epigenetics – Modifiable
Factors Causing CVD
Diseases Etiology
   Environmental Contributors
Implicated as Causing CVD
   Diet: Solids and Fluid Intake
and Nutraceuticals
   Physical Activity and
Prevention of CVD
   Psychological Stress and
Mental Health: Risk for CVD
   Correlation between
Cancer and CVD
PART 3  Determinants of CVD – Genetics, Heredity and Genomics Discoveries
Introduction
    Why cancer cells contain abnormal numbers of chromosomes (Aneuploidy)
     Functional Characterization of CV Genomics: Disease Case Studies @ 2013 ASHG
     Leading DIAGNOSES of CVD covered in Circulation: CV Genetics, 3/2010 – 3/2013
     Commentary on Biomarkers for Genetics and Genomics of CVD
PART 4 Individualized Medicine Guided by Genetics and Genomics Discoveries
    Preventive Medicine: Cardiovascular Diseases
    Walking and Running: Similar Risk Reductions for Hypertension, Hypercholesterolemia,
DM, and possibly CAD
http://pharmaceuticalintelligence.com/2013/04/04/walking-and-running-similar-risk-reductions-for-hypertension-hypercholesterolemia-dm-and-possibly-cad/
    Prevention of Type 2 Diabetes: Is Bariatric Surgery the Solution?
http://pharmaceuticalintelligence.com/2012/08/23/prevention-of-type-2-diabetes-is-bariatric-surgery-the-solution/
Gene-Therapy for CVD
Congenital Heart Disease/Defects
   Medical Etiologies: EBM – LEADING DIAGNOSES, Risks Pharmacogenomics for Cardio-
vascular Diseases
   Signaling Pathways     Response to Rosuvastatin in
Patients With Acute Myocardial Infarction:
Hepatic Metabolism and Transporter Gene
Variants Effect
http://pharmaceuticalintelligence.com/2014/
01/02/response-to-rosuvastatin-in-patients-
with-acute-myocardial-infarction-hepatic-
metabolism-and-transporter-gene-variants-effect/
   Proteomics and Metabolomics      Voltage-Gated Calcium Channel and Pharmaco-
genetic Association with Adverse Cardiovascular
Outcomes: Hypertension Treatment with Verapamil
SR (CCB) vs Atenolol (BB) or Trandolapril (ACE)
http://pharmaceuticalintelligence.com/2014/01/02/
voltage-gated-calcium-channel-and-pharmacogenetic-
association-with-adverse-cardiovascular-outcomes-
hypertension-treatment-with-verapamil-sr-ccb-vs-
atenolol-bb-or-trandolapril-ace/
      SNPs in apoE are found to influence statin response
significantly. Less frequent variants in
PCSK9 and smaller effect sizes in SNPs in HMGCR
http://pharmaceuticalintelligence.com/2014/01/02/snps-in-apoe-are-found-to-influence-statin-response-significantly-less-frequent-variants-in-pcsk9-and-smaller-effect-sizes-in-snps-in-hmgcr/

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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

Posted in Accountable Care Organizations, Affordable Care Act, Atherogenic Processes & Pathology, Best evidence, Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, Ca2+ triggered activation, Ca2+ triggered activation, Calcium Signaling, Calmodulin, Calmodulin Kinase and Contraction, Cardiac muscle regeneration, Cardiomyopathy, Cardiovascular Pharmacogenomics, Cardiovascular Research, Cell Biology, Signaling & Cell Circuits, Congenital Heart Disease, Curation, Curation methodology, Cytoskeleton, De novo synthesis, Dialectic, Discovery process, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Evolutionary cognition, Experimental validation, Explanatory, Federal Budget Appropriations, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Health Economics and Outcomes Research, Healthcare costs and reimbursement, HealthCare IT, Healthcare Reform, Historical relevance, HTN, Indigent Nutrition, Ionic Transporters Na+, K, Medical Devices R&D Investment, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Medicare and Medicaid, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Na-K transport, Na-K-ATPase, Neurohumoral Transmission, Nitric Oxide in Health and Disease, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Pharmacotherapy of Cardiovascular Disease, PKC, Population Health Management, Genetics & Pharmaceutical, Pre-Clinical Animal Model Development, Regenerative Biology and Medicine, Skilled Nursing Facilities, Stem Cells for Regenerative Medicine, Synaptic vesicle, Technology Advance Assessment of, Technology Capital Expenses, Technology Transfer: Biotech and Pharmaceutical, Theoretic convergence, Translational Effectiveness, Translational Research, Translational Science, Uninsured and Underinsured, tagged , , , , , , , , , , , , , , , , , , , , , , , , , , , , , on January 2, 2014| Leave a Comment »

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

Curator and e-book Contributor: Larry H. Bernstein, MD, FCAP
Curator and BioMedicine e-Series Editor-in-Chief: Aviva Lev Ari, PhD, RN

and 

Content Consultant to Six-Volume e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC

This portion summarises what we have covered and is now familiar to the reader.  There are three related topics, and an extension of this embraces other volumes and chapters before and after this reading.  This approach to the 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. We introduce 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 1 and Part 2, there is ample room for considering clinical outcomes based on individual and organizational factors for best performance. This can really only be realized with considerable improvement in information infrastructure, which has miles to go.

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.

Finally, 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 superceded by an incompletely defined relationship between ions that are cytoplasmic and those that are mitochondrial.  The glass is half full!

 

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