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Medical Insider Blog

Adult Stem Cell Therapy Offers Options

  • Posted Jun 25, 2009
  • Alan Niederman, MD, FACC, FACP

In my blog on June 04, 2009, I discussed angina. In spite of all physicians have to offer patients who suffer from coronary atherosclerotic heart disease, some individuals end up with no further treatment options. They often have had coronary artery bypass surgery and multiple angioplasties. They are on maximal medical therapy and still they have disabling angina. Coronary bypass requires an adequate vessel to bypass into. Often the heart arteries are 1 mm or less at these sites and cannot accept the bypass grafts. Similarly, angioplasty requires adequate vessel size to be possible.

Humans are the only species on earth who develop collaterals. Collaterals are natural connections from one heart artery to another that develop because of restricted blood flow. Sometimes these collaterals are quite robust. Sometimes they are not. When they are present, heart damage can be very limited in a heart attack situation because the heart still gets blood in spite of the upstream artery blockage. When they are not present, the damage can be profound and often death or severe disability occurs. The mechanisms for the creation of collaterals are not known. It is not well understood how to improve them.

Over the past years it has become possible to promote the collateral blood flow by various treatments. One such treatment is stem cell therapy in the form of CD34+ cells. We participated in the Baxter Phase II ACT34-CMI study to document the safety of stem cell injections. This study involved 26 study sites. We were the 7th highest enrollers. There were a total of 167 patients, and we enrolled 10.

The study enrolled patients with no options. There were three treatment groups, placebo, low dose and high dose. This was a safety study and not powered to show effect. In spite of this, the study proved that it was safe to perform and did provide a significant benefit to the patients. In fact, it is the first time that this patient population showed a significant improvement in treadmill walking times. A third phase is scheduled to begin early next year.

Next: How it's done.


Adult Stem Cell Research

  • Posted Jun 22, 2009
  • Alan Niederman, MD, FACC, FACP
NOGA mapping image

NOGA mapping image

One of the primary purposes for the creation of the JMHVRI was to have Holy Cross Hospital involved with cutting-edge research. This has allowed us to participate in the most exciting research development in years.

In my 20 years of research at the clinical level, my team and I have had the privilege of being involved with important breakthroughs in the clinical and drug treatment of cardiac disease. We have participated in the development and approval process of most of the drugs I now use for the treatment of heart disease. Much of our work continues in this mode. Our work with adult stem cells portends an improved future for cardiac patients.

To date, we have been involved with two stem cell projects and one project utilizing a stem cell protein. We are the only site in south Florida and one of three sites in Florida.

Adult stem cells are undifferentiated cells that multiply by cell division to replenish dying cells and regenerate damaged tissue. They are derived from adult tissue samples. Although the process is unique, it is not strong enough to repair all the cells that die naturally or by accident. If you have a heart attack, the few adult cardiac stem cells in your heart are not numerous enough to repair the damage. The reasons are unknown and an active area of research. We have no way of obtaining adult cardiac stem cells because we cannot biopsy the heart adequately to obtain them.

Therefore, the studies utilize other stem cells to obtain the results we are clinically trying to obtain. These cells or protein material are then injected directly into the heart from the leg in a manner similar to angiography and angioplasty using an additional special machine known as NOGA. NOGA technology is similar to the technology used in electrophysiology studies to isolate and identify areas of the heart of interest; in our case, those areas of the heart which are scarred or lacking adequate blood supply. After identification, special catheters are used for the injections.

Next... The Baxter CD34+ stem cell study for the treatment of angina.


Study to Lower Cholesterol Now Enrolling

  • Posted Jun 19, 2009
  • Alan Niederman, MD, FACC, FACP

I have been involved with the study of compounds regulating cholesterol synthesis in many different forms, and have been principal investigator of many clinical trials studying this topic. Our newest study here at the JMHVRI will be headed by Dr. Molly Zachariah. This study sponsored by Schering-Plough is to test the safety of SCH 900271 in patients with high cholesterol for a period of 8 weeks. The entire study can last for up to 22 weeks.The compound being tested is a nicotinic acid (nothing to do with nicotine from cigarettes) receptor agonist. This drug is to mimic the use of niacin, which is useful in raising HDL, but is very difficult to take because of side effects, primarily itching and flushing. Raising HDL 1% lowers cardiovascular mortality by up to 3%.

Niacin was first identified in 1873 by Hugo Weidel and is the vitamin which prevents the disease pellagra, one of the five diseases caused by vitamin deficiency. The name comes from the contraction NIcotinic ACid + vitamIN. It is Vitamin B3. In cardiology it is used to reduce total cholesterol, triglycerides, very-low-density lipoprotein, LDL and increase HDL. Niacin blocks the breakdown of fats to VLDL. Doses used are generally 1000-2000mg. two to three times a day.

Even when given in special preparations the agent causes troubling itching and flushing. Although harmless, the reactions are difficult to tolerate even in highly committed patients. This study will evaluate the compound for safety and effects on patients with documented levels of cholesterol. If successful, the compound will then go on to the next stage of study for efficacy.

To be considered for this study, patients may not take lipid lowering agents, such as Lipitor or other common drugs. These individuals are excluded from participation in the study. The individuals we are most interested in are those whose cholesterol problems are being treated by diet modification.

If you are interested please call the JMHVRI at 954-229-8400.

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Targeting Cardiovascular Risk

  • Posted Jun 15, 2009
  • Alan Niederman, MD, FACC, FACP

bulls-eyeIt was not until the early 1980s that the medical community changed its view that myocardial infarction and strokes could be prevented. Randomized clinical studies provided data that smoking cessation, Beta blockers, antiplatelet agents and angiotensin - converting enzyme inhibition - each reduced the risk of vascular events. Add to this the profound reduction in events shown in the data from the Heart Protection Study.

This study from England randomized over 20,000 patients and followed the study participants for over 5 years. These patients had no recognized indication to take a statin drugs. Their cholesterol levels were felt to be normal or they were women, elderly or diabetic.

Data showed the risk of major vascular events (MI or stroke) was reduced by over 30%. Statins significantly reduced the risk of developing angina. Angioplasty, surgery and amputations were also significantly reduced. The same study also looked at vitamin C and E, finding neither contributed to the lowering of the risk of vascular events.

This work has been furthered more recently. The HPS used simvastatin (Zocor) in a 40 mg dose vs. placebo. TNT, or Treating To New Targets, used atorvastatin (Lipitor) in doses of 80mg vs. 10mg. (It is no longer ethical to withhold treatment in these patients). The findings were provocative. Not only were statins useful, but the larger the dose the more benefit was attained -- a 22% relative risk reduction.

One further patient population has been found to benefit. The Jupiter study presented at the American Heart Association 2008 meeting was a study that randomized 17,802 men and women who had normal LDL levels ( mean 108 ) and a CRP > 2 to placebo or 20mg of rosuvastatin (Crestor). This was a four year study stopped after 1.9 years because of a 44% reduction in the combined end point of nonfatal MI, nonfatal stroke, unstable angina, revascularization and confirmed cardiovascular death.

Across the board, statins lower patients' cardiovascular risk in significant ways. I urge my readers to discuss these drugs with your doctors to see if they are right for you.

Next: research available from the JMHVRI for the lowering of LDL cholesterol.


Atherosclerosis: A Lifelong Enemy

  • Posted Jun 15, 2009
  • Alan Niederman, MD, FACC, FACP

In my last blog I reviewed some basic information about statin use for the treatment of atherosclerotic disease.  Atherosclerosis manifests itself in many forms.  In the heart it manifests itself as angina and myocardial infarction; in the brain, as strokes -- either minor or major; in the legs, it manifests as painful calves or buttocks when you walk.  We call this claudication.  In the abdomen, as abdominal aneurysms, which rupture and can cause a quick death.  In fact, most deaths in the United States are due to this process; in all, over one million deaths a year.

At least once a week I hear the phrase "but my cholesterol has always been good." Unfortunately, as physicians, we do not have a practical way to determine the differences between two people who have the same cholesterol and different outcomes.  Cholesterol is a combination of the components triglycerides, LDL cholesterol and HDL cholesterol.  These three components are in constant motion with triglyceride being added to LDL to form HDL.  Our livers manufacture cholesterol because it is a basic building block of our body.  We, in general, only eat 10% of our total cholesterol level -- so diet alone is never enough to treat documented atherosclerosis.

Since the Vietnam War, we have known that atherosclerosis starts at a very early age.  Most of the autopsies done at that time showed some atherosclerosis and in some individuals it was quite advanced.  Once you have atherosclerosis you can not get rid of the damage.  Early treatment is warranted and now, in some instances, we have started treating children.

Next: The HPS and the dawn of a new paradigm.


Statins 101

  • Posted Jun 10, 2009
  • Alan Niederman, MD, FACC, FACP

shopping-for-medsThe statin drugs, such as Zocor and Lipitor to name a few, have revolutionized the practice of cardiology.  These drugs discovered by Akira Endo and Masao Kuroda in Japan in 1971 when investigating inhibitors known as HMG-CoA reductase.  The first agent isolated was mevastatin followed by the isolation of lovastatin from the mold Aspergillus terrus.

For over 75 years an effect known as the Shoenheim effect was observed but not understood.  If you fed mice low cholesterol diets their livers manufactured more cholesterol and they had levels higher than when they started.  This same effect occurs in humans.  This concept of receptor mediation was discovered and explained by Michael Brown and Joseph Goldstein.  Their work was rewarded with the 1985 Nobel Prize for Medicine and stands as some of the most important work of the 20th century.

 The statins are divided into those which are synthetic and have had their molecular structure altered and those which are natural and fermentation derived.  Red rice yeast has the substance mevastatin in it and that is it's mechanism of action.  Pravastatin known as Pravachol is also naturally derived.  Simvastatin is an altered molecule from a fermentation derived source.  The most potent statins are Lipitor and Crestor.  Crestor and all statin drugs provide a dose dependant response.  The large number of trials of the drugs have provided us with average dose reductions per dose.  If your LDL or bad  cholesterol is 150 you can lower it on average 45% by taking 5 mg of Crestor.  This rises to 63% for the 40mg dose.

 Goals have been set by the various groups associated with atherosclerotic disease whether it is in your heart vessels, head vessels or your peripheral vessels.  If you are at risk the goal is less than 100mg/dl.  If you have disease your goal is 70 mg/dl.  Adjusting the dose becomes easy at that point.

 Next up: why we use the statins.

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Treating Cardiac Disease

  • Posted Jun 04, 2009
  • Alan Niederman, MD, FACC, FACP

Angina is what we call the symptom of chest discomfort that is caused by lack of blood flow to the heart muscle.  It has multiple causes but the one that is most common is atheroscelerotic blockages in the heart arteries causing limitation of blood flow.  It can be at rest or exercise because the symptom is a result of  a combination of a person's heart rate and blood pressure.  These same blockages can lead to heart attack in other circumstances. The most common treatment for angina is medication.  These drugs fall into various classes of medication. The oldest is nitroglycerine, which has been in use since 1870 when it was first used by Thomas Bruton in England for the treatment of angina and reported in The Lancet in 1879.  It is only recently that the mechanism of action of nitroglycerine has been understood as an example of how long it takes for science to catch up with the practice of medicine.  Beta-Blockers are a mainstay of treatment.  They were invented by a brilliant Scottish doctor and pharmacologist Dr. James Whyte Black in the late 1950s.  Interestingly, he also invented Cimetidine, which was a new class of drugs to treat stomach ulcers known to most people as Tagamet.  For these and other advances, he was awarded the Nobel Prize for Medicine in 1988.  Beta blockers are used to control both the heart rate and the blood pressure in patients with angina.  This allows the heart to receive sufficient oxygen carrying blood for energy utilization. Calcium channel blockers are medications that have predominantly heart rate slowing or vasodilatation mechanisms of action.  These are commonly used as drugs such as Norvasc, Cardizem, Procardia or Calan.  They lower the heart rate and overall blood pressure much as the Beta Blockers. Next week I will discuss what is probably the most important advance, in atherosclerotic heart disease, the statin drugs.


Blog Dedicated to Research Launched

  • Posted Jun 01, 2009
  • Alan Niederman, MD, FACC, FACP

bright-ideaWelcome to the JMHVRI blog. My purpose in hosting this blog is to be personal and educational. I will strive to bring the practice of cardiology and the groundbreaking research that my colleagues and I do to your attention. We are here for our community as Holy Cross and the Sisters of Mercy have been for over 50 years.

Heart disease is the leading cause of death in the United States for both men and women. Much has been learned over the past years but significant issues still remain. Information is now widely available on the Internet but much of it requires interpretation and some is just incorrect. This site will be a place to discuss these issues and concerns.

The JMHVRI is involved in groundbreaking research. We are the only site in South Florida for some of this work. I will highlight these studies so that you can participate or pass the information on to others who might be in need.

Our research institute is currently working on Adult Stem Cell therapy for the treatment of angina which can not be remedied with medication, surgery or angioplasty and as a treatment for heart failure which is still problematic in spite of all known therapies.

We are working on new therapy to replace Coumadin, as well as a new class of drugs known as Thrombin inhibitors for the treatment of clots. On new ways to treat high cholesterol, on new treatments for heart attacks, on novel drugs for the treatment of congestive heart failure to name just a few of our projects. I will inform you in depth about all these projects and more.

It is an exciting journey and I welcome you to join me.


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About Holy Cross Hospital

Holy Cross Hospital is a nonprofit, Catholic hospital in Fort Lauderdale, Florida, dedicated to innovative, high quality and compassionate care. For nearly six decades, Holy Cross has continuously expanded its services to provide leading-edge care for their patients in Florida and for those from elsewhere in the United States. Holy Cross also offers an International Services program to ensure that patients from outside the U.S. receive the care they need.

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