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Volume September


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Heart Institute
    Volume 5, No.1
   September 2007
                        Message from the Head of
                          The Heart Institute
                                                           To all our friends

                                                            Best wishes for
                                                      A Happy and Healthy New Year
Dear friends and supporters,
Summer is winding down and we are about to begin a new Jewish year, always an
opportune time to reflect on our accomplishments of the passing year.
At Hadassah Medical Center the work of construction and renewal is underway, and
everyone – patients, visitors and staff – can see and feel the changes. In our Heart
Institute we have not rested on our laurels, and are making great strides in the
community implementing our Heart Failure Center program.

In this issue of our Newsletter, we focus on valvular heart disease and especially the
new epidemic of aortic stenosis. With the general aging of the population, we are seeing
more and more patients in their 8th and 9th decade suffering from this degenerative
disease. Currently the only solution is valve replacement surgery, a major procedure for
patients in this age group.
In our Heart Center we are trying to develop other, less invasive solutions.
In addition, as we reported in our previous issue, our Cardiovascular Research Center is
progressing with the work of Dr. Mony Shuvy, a talented early-career researcher,
utilizing his innovative animal model of aortic valve calcification to assess new treatment
options to slow or reverse the progress of the disease.

On the eve of the new Jewish year, I would like to express to you, all our friends and the
extended Hadassah family, our deepest appreciation of your continuing interest and
support, as well as best wishes for a happy, healthy and peaceful New Year.
As always, we welcome your comments, questions and contributions to our newsletter.
You are also warmly invited to visit us virtually on our website, at
Cardiology .

Shalom and Shana Tova,
Professor Chaim Lotan

      The Heart Institute Newsletter, Vol 5, No.1, September 2007
      Editor: Judith Shidlowsky
                 News from The Heart Failure Center

The Hadassah Health Failure Center has started its activity of providing support and
recommendations for heart failure patients hospitalized in Hadassah and for patients
receiving ambulatory treatment in the various Health Management Services
(“Kupat Holim”) clinics in Jerusalem. To provide this specialized care, the personnel has
been enlarged by recruitment of Ms Orly Ezra, a nurse with vast experience in acute and
chronic heart disease care as well as cardiac rehabilitation. The staff of physicians, led
by Prof. Andre Keren and Dr Dan Admon, now also includes Dr Israel Gotsman and Dr
Marina Potekhin, physicians with strong background in heart muscle diseases
(cardiomyopathies) and heart failure management.

The activity of the Heart Failure Center involves close cooperation with the Internal
Medicine Division led by Prof Yaakov Naparstek. This extends to increasing involvement
of the heart failure staff in the care of heart failure patients hospitalized in the various
departments of the Internal Medicine Division, in establishment of new internal
guidelines for management of heart failure patients in the departments of Internal
Medicine and Cardiology at Hadassah, teaching of students and physicians-in-training
and initiation of joint research projects.

       The Heart Institute Newsletter, Vol 5, No.1, September 2007
       Editor: Judith Shidlowsky
                       ?? Questions and Answers: ??
                               Aortic Stenosis
Q: What is aortic stenosis?
A: Aortic stenosis is narrowing of the aortic valve. This valve opens to allow a one-way
flow of oxygen-rich blood from the left ventricle of the heart into the major artery called
the aorta, through which it flows on to the rest of the body. A narrowing of the valve
demands the heart work harder to pump blood through the smaller opening, pressure
builds up in the left ventricle, and this over time wears out the heart muscle prematurely.

Q: Why is aortic stenosis more common in the elderly?
A: One of the most common causes of aortic stenosis is a buildup of calcium on the
valve. This builds up gradually over the years, and eventually can make the valve thick
and rigid. The left ventricle will work extra hard to continue pumping blood under these
conditions, and it generally takes many years before the damage becomes such that
function is seriously reduced.
Many of the same factors that increase a person’s risk for atherosclerosis (“hardening of
the arteries”) are risk factors for aortic stenosis: smoking, high blood pressure,
hypercholesterolemia and diabetes.

Q: What are the symptoms of aortic stenosis?
A: Symptoms can include:
    - Chest pain (angina); a heavy tight feeling in the chest often brought on by exercise,
      when the heart has to pump harder.
    - Dizziness or faintness, especially after physical exertion.
    - Tiredness or shortness of breath during physical exertion; shortness of breath
      suddenly in the middle of the night. Shortness of breath is a symptom of heart
      failure, the major complication of aortic stenosis.
    - A fast, slow or uneven heartrate.
    - A feeling that the heart is pounding, racing or beating unevenly.
In cases where these symptoms are caused by aortic stenosis, they are an indication
that serious damage has already been done, and treatment is urgently required.

Q: How can aortic stenosis be treated?
A: The common treatment for a valve that has become severely insufficient is surgery to
replace it with a prosthetic or preserved donor valve. Advances have being made in the
field of interim treatment by balloon valvuloplasty in the cathlab.

       The Heart Institute Newsletter, Vol 5, No.1, September 2007
       Editor: Judith Shidlowsky
         News from our Cardiovascular Research Center

Aortic valve calcification is the most common valvular disease in the elderly. This is
caused by valvular bone formation (calcification) which eventually leads to deformation
and dysfunction of the valve.

The source of this calcification was not previous clear. In our research lab, we were able
to isolate normal valve cells and study the effects various substances and treatments
had on them. For the first time, we were able to demonstrate that calcification is indeed
the transformation of healthy valve cells to bone producing cells.

In our last issue, we reported on the project of Dr. Moni Shuvy which developed an
innovative animal model of aortic stenosis, induced in laboratory rats by feeding a
special diet. Utilizing these animals, Dr. Shuvy’s team investigated the question of
whether this calcification process can be reversed. Follow-up of the animals after the
special diet was stopped showed regression of the valve calcification. This experiment
was the first in the world which demonstrated the reversibility of the process.

This novel observation should enable us, through continuing to investigate the nature of
the pathogenesis of the reversible calcification, to investigate and develop modes of
treatment to slow or reverse the process of aortic valve stenosis.

                Cardiac CT of laboratory rats, with the aortic valve encircled in green.
 Pink coloration reveals location of calcification. The image on the left is of a healthy control animal,
       with no calcification of the aortic valve. The image on the right is of one of the animals
         in the experimental diet group, clearly showing the calcification of the aortic valve.

       The Heart Institute Newsletter, Vol 5, No.1, September 2007
       Editor: Judith Shidlowsky
                          News from Our Cathlab:
         Aortic valvuloplasty for non-operable aortic stenosis
Aortic stenosis is severe narrowing of the valve that connects the heart with the aorta –
the main blood vessel that supplies the body with blood. The process involves elderly
patients and thus it is growing in incidence as the population is getting older.
These patients suffer from angina pectoris (chest pain), arrhythmias and heart failure
that are associated with shortened longevity. The current therapy for severe aortic
stenosis is open heart surgery with replacement of the calcified valve by an artificial one.
The surgery is not benign, and mortality is increased in very elderly patients or in those
with severe co-morbidities. Up to one third of the patients with severe aortic stenosis are
thus defined “inoperable”, due to the high rate of expected peri-operative mortality.
In the interventional cardiology unit we perform a percutaneous valve dilatation, which
relieves the tight narrowing of the degenerated valve and allows these inoperable
patients a significantly better quality of life. In many patients this can be a bridging
procedure, buying time for the patient’s condition to temporarily stabilize enough for
him/her to undergo the surgery.
Additionally, we are hard at work in development of percutaneous aortic valve
replacement procedure, performed during catheterization. We have hopes that this
procedure will become available to patients in the next year, as an alternative to surgery.
During this past summer we have treated three very elderly inoperable patients, all
ladies above the age of ninety (!) who were bedridden due to severe heart failure and
hospitalized for weeks or months. Dr. Haim Danenberg, our director of interventional
cardiology, and his team performed the valvuloplasty procedure which requires only
minor local anesthesia and a very short recovery procedure. Using highly sophisticated
equipment and techniques all three valves were dilated without adverse events. The
pressure was relieved and the heart could function with a much lower resistance to its
Symptomatic relief was observed immediately. The three ladies were quickly allowed out
of bed and discharged from the hospital, and will celebrate the coming Rosh HaShana
with their families at home – Shana Tova!

           Normal aortic valve                    Stenosed, degenerated aortic valve

       The Heart Institute Newsletter, Vol 5, No.1, September 2007
       Editor: Judith Shidlowsky
     From the laboratory bench to the scientific literature:
                    Other valvular news
Insufficiency (leaking) of the mitral valve (which separates the left atrium and the left
ventricle) is a frequent complication of heart attack. This can happen even with relatively
small infarctions, and may lead to heart failure.
A joint team of researchers, with Dr Ronen Beeri from our lab and Dr Robert Levine from
the Massachusetts General Hospital in Boston, are studying this complication, which
can cause significant suffering to patients. An animal model, which allows separation of
the effects of the heart attack from those caused by the leaking valve, has enabled us to
demonstrate that this conditions adds significantly to the damage to the heart muscle
already caused by the infarction. The damage was apparent in the molecular
mechanisms of compensation which exist inside every heart cell, and this correlated
with the large-scale changes which were demonstrated with novel techniques such as
3-dimensional echocardiography.
We also demonstrated that repairing this condition at an early stage may reverse the
damage caused by it almost completely. In cooperation with Dr Roger Hajjar from Mt
Sinai Medical Center in New York, we used a revolutionary approach in which we
repaired one of the damaged molecular mechanisms using gene therapy, correcting
the failing ventricle’s function.
This work will be published next month in two leading US cardiology journals.

       A 3-dimensional echo picture of a left ventricle with a leaking mitral valve (“MR”) and
              without a leaking valve (“No MR”). It can easily be seen that the heart
                   with a leaking valve is enlarged and hence more damaged.

       The Heart Institute Newsletter, Vol 5, No.1, September 2007
       Editor: Judith Shidlowsky
     To All Our Friends and Supporters

     The entire Heart Institute staff
   Wishes you a very Happy and Healthy
                New Year

The Heart Institute Newsletter, Vol 5, No.1, September 2007
Editor: Judith Shidlowsky

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