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State of the Heart

The Future of Cardiology
Part 2

By Sean Henahan, Access Excellence
Copyright 2001 Info

This is the second part of an interview on the latest developments in cardiology. Sean Henahan interviewed Dr. Rose Marie Robertson, outgoing president of the American Heart Association and director for the Women's Heart Health Institute at Vanderbilt University Medical Center.
(click here to return to Part 1 of the interview)

Q: What are we learning about individual differences in response to a given treatment? We hear more and more about the concept of 'tailoring' treatment based on a genetic profile.

A: We are talking about a new way to design and prescribe drugs. Traditionally we have used a very primitive approach- we find a plant that is said to have some medicinal property. Reaching blindly into the closet that mother nature prepares, we pull out compounds and test effects. If it seems to have a profile of useful effects in human disease, we pursue that. We might then make versions with fewer side effects or more convenient dosing, variations on a theme.

Now we can do some different things. We can characterize the place on a cell where the drug has an effect. We can now understand the molecular structure and the actual physical chemical structure of that receptor and can predict what will interact with it. In some cases we can actually design a drug to react with a specific receptor. Or we can predict what compound made by the body would interact with it. One aspect of molecular biology and physical chemistry has been to help us design drugs better.

When we give drugs, not everyone responds the same. There are many reasons for that. Sometimes there are differences in how people break a drug down. The drug might stay in the blood stream of one person much longer than another person. One person may simply not respond to a drug at all while the next individual does. There are variations in all of us in a number of important enzyme systems. The cytochrome P450 system would be a good example. There are genetic polymorphisms between individuals , making different forms of the same enzyme. Depending which one you make, your response to a drug can be quite different. The way we know that is to give the drug to someone and see how they respond. This involves a careful process of testing and titrating, keeping in mind that some people will have a stronger response.

If you could predict that a patient might not handle a drug well, you could alter the way you deliver that drug or select a different drug. It also may effect how a drug would interact with other drugs in an individual. The electrical systems of some individuals hearts have a difference in repolarization, that is, how the heart muscle handles ions. That changes the electrical activity of the cell. If someone is susceptible to certain drugs those drugs could cause serious or fatal heart rhythm problems. Other people could take those drugs with impunity. We are finally beginning to sort this out.

Q: Hypertension, or elevated blood pressure, has long been recognized as a risk factor for heart disease. Since the 1960s there has been a campaign to increase public awareness and encourage treatment. How successful has the effort been?

A: I can hardly say it has been a success. Objectively, we have to say, given all the information we have, we have really failed to deliver this information to the public in a way that is effective. Less than 27% of the public with recognized hypertension have the hypertension controlled to goal levels.

We do know that in both young and old, bringing the blood pressure down to goal levels enormously reduces the risk of stroke, heart failure and death. We have a whole panoply of drugs that are highly effective, we can almost always find a combination of lifestyle changes and a drug or combination of drugs that can control blood pressure without undue side effects.

Despite all this information, we are not doing it. It is really hard to explain why. There are many barriers to people getting appropriate care. Some people don't know they have hypertension. Others know they have hypertension but either don't have access to medical system because of socioeconomic status or where they live. Still others don't access the system even though they could, because health is just not high enough on their radar screens.

We also know that a high proportion of prescriptions for anti-hypertension medications that are written are not even filled. Some are filled but not taken for very long. Some of the fault clearly lies with the medical profession. We don't communicate well enough with our patients. We may prescribe a medication, the patient takes pill and notices something and stops taking it. It might or might not be related to the treatment, but we don't get out the message that if they have a problem they should call us right away. They shouldn't wait until the next office visit, missing all that time in between when we could have been making things better.

I think the public is becoming more empowered and becoming more insistent, wanting their blood pressure numbers to be made normal. I see patients saying 'I'm on treatment for my high blood pressure, but I still have high blood pressure, shouldn't it be lower?' The answer is yes. Patient-physician partnership is essential.

We have learned a lot about the underlying biology of blood pressure. In particular we have learned how important the renin-angiotensin system is, even in patients who are not hypertensive. X One of the most interesting studies over the last several years was the HOPE (link?) study, in which patients who did not have high BP but had other risk factors for coronary disease were treated with an ACE inhibitor, a drug that inhibits the enzyme that converts angiotensin 1 into angiotensin 2. Preventing high levels of this enzyme has several interesting effects. For example, there is clearly a benefit in terms of reduced risk of heart attack, stroke and death, even in patients who do not have hypertension. Another positive effect with this treatment is a reduction in the incidence of diabetes. That trial opened up a whole new set of indications for a drug that has been around for a while. This shows the importance of continuing to study drugs even after they are on the market for a while.

Q: One of the ironies of better treatment of cardiovascular disease is that the incidence of heart failure is increasing as patients live longer. What have we learned about heart failure that might lead to better treatment of this problem?

A: This is a fascinating area. A number of years ago, people with heart failure were all considered to have the same problem. These patients, with shortness of breath, swollen ankles and physical limitations were all lumped together. Over the years we have recognized that there are many different kinds of heart failure. Some will have heart failure because the heart muscle becomes weak and can't pump as well. That form is often seen in association with coronary heart disease or survival after a heart attack. In other cases, infection of the heart or inflammation of the heart can also cause heart muscle damage.

In another group with heart failure, the heart looks quite different. Instead of being enlarged and not pumping very well, these people will have hearts that are thick and muscular and look like they are pumping very vigorously. But they are so thick and stiff that in fact it is hard for the heart to pump, those people have heart failure for entirely different reasons. The problem is with diastolic function (filling the heart) rather than systolic dysfunction where the heart can't squeeze well enough.

In recent years we have identified the genes that can cause many cases of this form of heart failure, know as hypertrophic cardiomyopathy, where there is more heart muscle than there ought to be. Because we've studied families with this problem we can say that we know specifically which gene causes a problem, and we can identify those whose condition is associated with normal life span, and those with different genetic problem, people may be at risk of dying suddenly at an early age. We would obviously approach those people quite differently. Genetics have a big difference in this area.

Q: The treatment of heart attack has changed drastically over the years. Tell us about that.

A: We now have several ways to intervene when a person shows up with a heart attack that can save lives and reduce or nearly eliminate damage to heart tissue. Our ability to open occluded coronary arteries with angioplasty (opening a blocked artery with an intravenously inserted balloon or stent device) or thrombolytic (clot buster) medicines has saved many lives.

Timing is the key. The impact of these interventions is felt fully only when get there early. The sooner people come to the hospital with a heart attack the better we can do. People often don't have the right concept of what is happening when they have a heart attack. Recent studies reveal that when people have chest discomfort they don't realize that while they are sitting there having that discomfort, wondering what is going on, should I got to the hospital, every minute that they are sitting there they are losing heart muscle cells and they are not going to get them back. There is damage occurring minute by minute The sooner we can restore blood flow, the sooner we can stop this damage from happening. In contrast, when patient does recognize that something is wrong and gets to the hospital, and we get the artery open right away, sometimes you can hardly tell where the heart attack would have been. That is how we wish it were all the time.

This field continues to evolve. Our ability to open arteries with angioplasty, that is putting in a catheter with little balloon, seems quite effective initially. In most patients we can really improve blood flow. But we have seen problems. One problem is called elastic recoil, when the artery recloses once you remove the balloon. Another is that the catheter itself can rough up the lining of the artery, which may lead to formation of blood clots. Now, with the development of new drugs like clopidogrel and ticlopidine, and 2b3a antagonists, were able to inhibit clotting, making these procedures much safer.

Other times we see an an actual dissection of the artery, in which part of the vessel would peel off and close the vessel, causing damage to the heart. The solution has been to insert a small device to mechanically hold that vessel open. This device, which looks something like the spring on a ball-point pen, is called a stent. This is the stent era. They have really improved outcomes. So where we once would have had to go from angioplasty with a closed artery to bypass surgery, now with stents, that hardly ever happens any more. The stent supports against elastic recoil and keep vessel wall open mechanically. The combination of stents and the new anti-clotting medicines and has really been very effective .

A different set of problems are seen with stents. Sometimes the vessel still wants to re-occlude, and closes up. One approach to treat this has been to put a radioactive wire in vessel briefly after to prevent restenosis after angioplasty. We are also now putting in stents that are coated with drugs that help artery stay open.

Q: Haven't there been some efforts to replace dead heart tissue with functioning muscle by transferring cells directly?

A: Yes, there are some remarkable clinical studies underway at the moment. These involve the transfer of stem cells or myocytes directly into the affected heart tissue in patients who have had a heart attack.

The problem with people who have had heart attacks is that, they have a thick fibrous scar on the heart. That scar tissue is not beating, not functioning, not helping the heart pump blood. Until this experimental approach we have not had any way to increase the number of heart muscle cells after they are lost. Now we are moving to the point where we can produce new heart muscle cells, or find cells that might de-differentiate and become new heart muscle cells.

We have thought that in adults there are no myoblasts, that is, cells that can become heart muscle cells. We have found recently that there are actually cells that can differentiate into muscle cells in adult patients. There are not many, but they can be teased to do that.

French researchers took a piece of ordinary muscle tissue from the leg, and found cells in that muscle that could be persuaded to transform into cells that work like heart muscle. Remember, the muscles in are leg are different than the ones in our heart. You can't have muscle in leg or arm working every day, every night, continuously without wearing out, whereas heart muscle continues to work throughout your life.

The French researchers were able to sort out cells that could transform and act like heart muscle cells and to grow them in tissue culture. Then, during a bypass surgery, they injected those cells into a scar area. Remarkably, after the procedure was complete, the researchers could demonstrate that these cells stayed alive, and were able to beat. They weren't perfect, but they were beating in an area where before there was no activity. That was the first patient in the first study of this kind, so we do have a long way to go. Nonetheless, there is tremendous promise there.

In addition, we are also finding stem cells in our blood and bone marrow that we used to think could only become blood cells. It looks like we will be able to tease those stem cells into becoming new blood vessels. This is tremendously encouraging because there are more than 4.5 million in this country with heart failure.

Q: Another approach has been to try and encourage the growth of new vessels to improve impaired blood supply in the heart. What is the outlook on that front?

A: I think this is an exciting field. This could be a beneficial approach in patients with coronary artery disease who have lost blood supply to parts of the heart who may be having chest pain or in those who have lost part of heart function who may not be candidates for bypass surgery. If we could find ways to grow new blood vessels we could supply the heart muscle with oxygen, making it able to work better. The body has its own system for providing new blood vessels when we need them, but doesn't always do so. We are looking at ways to develop either genes or proteins cause new vessels to sprout and produce functional blood flow. We are already beginning to see evidence that providing these compounds like vascular endothelial growth factor et al., either by putting gene in the heart, getting it into cells and having it produce the protein, or just getting the protein there, it appears that we can cause new blood vessels to sprout, in areas of insufficient blood flow.

Q: What are the major challenges in the battle against heart disease?

A: We need more people! We will need a lot of people to come into the field to carry on the clinical work and follow up on findings of human genome project. As more genetic information becomes available we need more people who can look carefully at patients or do basic work in molecular biology. Education is expensive. Many medical students get to a point where they would consider a research career, but have accumulated so much debt, maybe $100,000. A Bill passed recently by the US Congress could help. It would encourage those people to consider research careers by paying back a significant portion of their educational debt..

It is incredibly exciting when you find an answer to even a small part of the questions, it is a terrific feeling. You get tremendous satisfaction when developing ways to treat or prevent diseases, help people lead healthier lives. There is also great intellectual excitement of being able to solve these complex problems. There are no careers that are more satisfying or more fun than medicine and science.


Click here to return to part 1



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1. Tobacco smoking
3. Physical Inactivity
4. High cholesterol
5. Diabetes Mellitus
6.High Blood Pressure

Source: AHA



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Source- Mayo Clinic



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Your heart pumps blood through a network of 60,000 miles of vessels.

Source- Mayo Clinic





For men who donate blood the risk of heart disease is 30% less than that of those who do not.

David Meyers MD (University of Kansas)







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