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  • richardmitnick 8:39 am on August 30, 2017 Permalink | Reply
    Tags: , “BASILICA valve-in-valve” procedure, Cardiac team is first in world to employ new aortic technique, , Replace a patient's failed artificial aortic valve, U Washington Health Beat   

    From U Washington: “Cardiac team is first in world to employ new aortic technique” 

    U Washington

    University of Washington

    08.17.2017
    Brian Donohue
    bdonohue@uw.edu
    206.543.7856

    Patients No. 1 and 2 recovering well after UW Medicine specialists perform novel heart-valve procedure.

    1
    UW Medicine cardiologist Danny Dvir, center of frame, leads a team of UW Medicine heart specialists in performing a never-before-tried technique to replace a patient’s failed artificial aortic valve. Courtesy of Dr. Danny Dvir

    A UW Medicine cardiologist has taken another step into the realm of heart surgeons in performing a first-in-the-world intentional cut via catheter to replace a patient’s failed artificial aortic valve.

    The patient, Myra Gaines, of Kennewick, Washington, underwent the “BASILICA valve-in-valve” procedure July 17 at the University of Washington Medical Center. Her daughter, Kim Lee, said Gaines celebrated her 87th birthday on Aug. 4 and was “doing real well” as she reached the milestone of 30 postoperative days. “We walk around the block four times a day,” Lee proudly reported last week.

    Dr. Danny Dvir led Gaines’ 2½-hour procedure, assisted by Drs. Mark Reisman, Gabriel Aldea, and Burkhard Mackensen. They received guidance from visiting physician scientists from the National Institutes of Health (NIH) in Maryland and Henry Ford Hospital in Detroit.

    “It feels like the start of a new era. We’re going beyond implanting equipment through tubes. We are doing minimally invasive surgery, cutting inside the body, via catheter,” Dvir said excitedly.

    The team also performed the second such procedure that day on Caroline Chapman of Soldotna, Alaska, who also is recovering well, a family member said.

    The two cases represent a subset of people whose original surgical valve has failed and needs replacing, but whose anatomies put them at high risk of dying during a traditional valve-in-valve procedure. Both cases involved compassionate use of a never-before-used technique because no alternatives existed and the patients’ conditions were grave.

    Dvir’s intentional laceration to the old valve device before implanting the new valve greatly reduces the likelihood of a catastrophic complication. And it suggests that more life-extending care is possible via catheters, thin tubes threaded into blood vessels by heart specialists – and especially so when patients are too weak for open surgery.

    Background: Replacing diseased aortic valves

    Four valves open and shut to during each heart beat and provide blood to the body. The aortic valve, between the left ventricle and the aorta, has three scalloped leaflets that open and close in sync. When disease makes the leaflets too weak or too rigid to close tightly, blood pressure can drop and the rest of the heart must work harder. People can experience breathing difficulty, chest pain, and fatigue. Heart failure can develop.

    Since the early 1960’s, surgeons have replaced faulty human aortic valves with metal alloy frames and leaflets composed of metal or cow or pig tissue. These replacement valves are sutured in place during open-heart surgery, which, 50-plus years later, is still the gold-standard repair.

    In the past 10 years, though, artificial tissue valves that can be tightly folded and then expanded like origami have enabled cardiologists to do this job, too, transporting and placing the devices with a catheter threaded through a blood vessel into the heart.

    This minimally invasive “transcatheter aortic valve replacement” – TAVR, for short – allows patients who are too old or weak for open heart surgery to receive the same life-extending device.

    TAVR also has enabled valve-in-valve procedures when original implants fail – as with Gaines’ device, which had been surgically implanted in 2011.

    Every year, more than 5 million Americans are diagnosed with heart-valve disease, giving rise to 80,000 to 90,000 U.S. aortic valve replacements annually. Artificial-tissue valves work well, but often start to fail after five to 15 years.

    Problem-solving the risk of specific anatomies

    Dvir, regarded internationally as a valve-in-valve expert, was recruited by UW Medicine last year. He recognized that a small subset of patients who undergo the aortic procedure have an anatomy whereby placing the second valve significantly heightens risk of obstructing blood flow to the coronary arteries because they’re so close to the valve junction.

    The reason: Placing the new valve inside the old valve, like one sleeve within another, permanently forces the leaflets of the old implant into the “open” or upright position. For patients whose coronary arteries are farther from the valve, this is no problem. But if those vessel branches are too near the valve, a permanently open leaflet could easily block blood flow and spur a heart attack.

    A previous workaround tried to address this, with limited success. Dvir said many valve-in-valve recipients whose coronary branches are near the valve do not survive a procedure using that previous approach.

    Dvir was aware of work done at the National Heart Lung and Blood Institute by Drs. Jaffar Khan and Robert Lederman. Lederman’s lab, part of the NIH, develops new medical approaches and translates them into medical practice.

    “This is an example of a very rapid collaboration in which Dvir learned of one technology we had and asked if it was applicable to a problem he has with his patients. We’re applying it first to patients in desperate need who have no other options,” said Lederman, who was present at the Seattle procedures.

    2
    Dr. Dvir demonstrates how the failed replacement valve is cut before the second valve is implanted. Randy Carnell

    Dvir described the technique: “We created a mechanism to surgically cut that leaflet in the original valve, so that when it’s pushed up, it creates a V shape and blood can get past it to the artery. We do it just before we place the second valve.”

    Through the catheter, he and the team introduced a wire snare designed to catch the target leaflet and pull it taut, then introduced a second wire and electrified it to cut the leaflet from root to tip.

    The procedure’s complexity is appreciable: Unlike open-heart surgery, TAVR procedures afford no clear visual. Cardiologists navigate procedures on monitors, using landmarks derived from three tools: CT scan, x-ray angiography and transesophageal echocardiography, the latter two of which are live video images that help guide the catheter to its destination and then orient valves.

    The new technique was named BASILICA: Bioprosthetic Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction.

    Dr. Adam Greenbaum of the Henry Ford Hospital also was in Seattle to help guide the first two BASILICA repairs, after which he performed the third such case.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    u-washington-campus
    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.
    So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

     
  • richardmitnick 9:28 am on July 24, 2017 Permalink | Reply
    Tags: , , , , Native mass spectrometry, Signaling islands in cells: targets for precision drug design, U Washington Health Beat   

    From U Washington: “Signaling islands in cells: targets for precision drug design” 

    U Washington

    University of Washington

    07.13.2017
    Leila Gray

    1
    A critical component of the cell signaling system, anchored protein kinase A, has some flexible molecular parts, allowing it to both contract and stretch, with floppy arms that can reach out to find appropriate targets. John Scott Lab.

    Research results reported in the journal Science overturn long-held views on a basic messaging system within living cells.

    The findings suggest new approaches to designing precisely targeted drugs for cancer and other serious diseases.

    Dr. John D. Scott, professor and chair of pharmacology at the University of Washington School of Medicine and a Howard Hughes Medical Institute Investigator, along with Dr. F. Donelson Smith of the UW and HHMI, led this study, which also involved Drs. Claire and Patrick Eyers and their group at the University of Liverpool. Visit the Scott lab web site, Cell Signaling in Space and Time.

    The researchers explained that key cellular communication machinery is more regionally constrained inside the cell than was previously thought. Communication via this vital system is akin to social networking on your Snapchat account.

    Within a cell, the precise positioning of such messaging components allows hormones, the body’s chief chemical communicators, to transmit information to exact places inside the cell. Accurate and very local activation of the enzyme that Scott and his group study helps assure a correct response occurs in the right place and at the right time.

    “The inside of a cell is like a crowded city,” said Scott, “It is a place of construction and tearing down, goods being transported and trash being recycled, countless messages, (such as the ones we have discovered), assembly lines flowing, and packages moving. Strategically switching on signaling enzyme islands allows these biochemical activities to keep the cell alive and is important to protect against the onset of chronic diseases such as diabetes, heart disease and certain cancers.”

    Advances in electron microscopy and native mass spectrometry enabled the researchers to determine that a critical component of the signaling system, anchored protein kinase A, remains intact during activation. Parts of the molecule are flexible, allowing it to both contract and stretch, with floppy arms that can reach out to find appropriate targets.

    Still, where the molecule performs its act, space is tight. The distance is, in fact, about the width of two proteins inside the cell.

    2
    Green, circled area show where the enzyme in the signalling study is active in mitochondria, the powerhouses of living cells. John D. Scott.

    “We realize that in designing drugs to reach such targets that they will have to work within very narrow confines, ” Scott said.

    One of his group’s collective goals is figuring out how to deliver precision drugs to the right address within this teeming cytoplasmic metropolis.

    “Insulating the signal so that the drug effect can’t happen elsewhere in the cell is an equally important aspect of drug development because it could greatly reduce side effects,” Scott said.

    An effort to take this idea of precision medicine a step further is part of the Institute for Targeted Therapeutics at UW Medicine in Seattle. The institute is being set up by Scott and his colleagues in the UW Department of Pharmacology.

    The scientists are collaborating with cancer researchers to better understand the molecular causes — and possible future treatments — for a certain liver malignancy. This particular liver cancer arises from a mutation that produces an abnormal form of the enzyme that is the topic of this current work, protein kinase A, and alters the enzyme’s role in cell signaling.

    Other advances that gave the researchers a clearer view of the signaling mechanisms reported in Science include CRISPR gene editing, live-cell imaging techniques, and more powerful ways to look at all components of a protein complex.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    u-washington-campus
    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.
    So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

     
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