2010-09-24 Reza Movehed MD Heart Failure and L-Carnitine
An Interview with Mohammad Reza Movahed, M.D.
September 24, 2010 by Kirkham R. Hamilton, PA-C
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KIRK HAMILTON: Hi, my name is Kirk Hamilton your host of Staying Healthy Today and our message is simple: To provide you credible usable health information from our interviews and our educational resources to help you Stay and Be Well in the busy modern world. Please take a few moments before or after listening to this interview to browse through the Prescription2000.com website, the home of Staying Healthy Today Radio, for our free educational services.
Today's show topic is "Heart Failure and The Role Of L-Carnitine." Our guest today is Dr. Reza Movahed from the Southern Arizona VA Healthcare System at the University of Arizona Sarver Heart Center in Tucson, Arizona. Dr. Movahed has co-authored an article entitled "L-Carnitine Treatment in Patients With Mild Diastolic Failure is Associated With Improvement in Diastolic Function and Symptoms" in the journal Cardiology in 2010.
So welcome Dr. Movahed. Thanks so much for being on the show today.
DR. REZA MOVAHED: Thank you.
KIRK HAMILTON: You know I was going through the CDC website on Heart Failure Facts and I was going through another website called the Heart Failure Society of America website and there was a line or two I'd like you comment on. And it was heart failure is the only major cardiovascular disorder on the rise. Deaths in the United States from heart failure have more than doubled since 1979. And I guess my question is why do you think heart failure is on the rise or do you think that's an accurate statement?
DR. REZA MOVAHED: I think there are many reasons for the rising rate of heart failure. One of the major one is advancing age. The population is aging. The baby boomer is now at the age that they have more heart disease including coronary disease, and that's probably one of the main reasons why heart failure is rising. The other thing, the other reason could be that as we treat patients in earlier stages, we treat aggressively patients who are sicker, like having severe coronary disease, who survive the initial insult like heart attack more often. And then in a chronic phase of the heart attack more patients will develop heart failure and survive into older age. In comparison to previous years when we did not have much successful treatments for patient with acute MIs. I think as our treatment for the cause of heart failure increases and the patient survives longer, this probably translates to higher incidents of heart failure. One other reason is we have better treatment for heart failure and therefore the risk of dying earlier is now not there as much as in the past. So people live longer and therefore the prevalence of heart failure will be also on the rise over the years.
KIRK HAMILTON: So it could be that because we are treating other vascular diseases, stroke, blood pressure and coronary artery disease more effectively that you keep the person around longer so we end up having eventually a sicker heart in a way?
DR. REZA MOVAHED: Yes, that's definitely, particularly patients who would die without those treatments who survive now longer and then as a consequence of that if some of those diseases can - some of those patients will develop heart failure. Like again major MI. And those patients now will enter the, you know, the cycle of the older patient with the more sicker heart, absolutely.
KIRK HAMILTON: So from the CDC website on heart failure, their little fact sheet, it says almost 5.8 million people in the United States have heart failure, another 670,000 are diagnosed each year, and an interesting line was one in five people with heart failure die within a year after the diagnosis.
DR. REZA MOVAHED: Yes, that's very true. And the most common reason for hospitalization for people over 65 is heart failure. And heart failure is actually the leading cause for ambulatory visits in the medical population. Heart failure visits to clinic and emergency rooms is about 3 million to 390,000 annually. The cost of this heart failure is about 37 billion (dollars). This is actually the most expensive diagnosis for medical patients with over 50% of the cost associated with hospitalization.
KIRK HAMILTON: Yeah, the quote that they had on the website was 39 billion (dollars) and that's about 11% of all the cardiovascular disease costs and about 7% of all deaths.
So what are some of the risk factors? Let's start with lifestyle risk factors that you think, just aside from aging. Are there any lifestyle things that people can do to improve their heart?
DR. REZA MOVAHED: Definitely the first thing is salt intake. It's clear-cut that higher salt intake increases the risk of hypertension and hypertension is one of the causes of heart failure. In the past when hypertension was not well controlled, actually hypertensive - hypertension-related heart failure was extremely high. Other causes - the lifestyle will of course improve and decrease the risk of heart failure including hypertension. The other thing is obesity is very important. And obese people develop more hypertension. The heart has to work harder and there is some evidence that obese people have higher risk for heart failure. Definitely lifestyle like exercise and those positive lifestyle changes will improve the other risk factors that can lead to heart failure. For example, diabetes will be less. People who exercise and are not obese, the risk of coronary disease will go down and therefore the risk of MI and coronary disease-related heart failure. Actually the majority of people who present with systolic heart failure over the age of 40, the reason is coronary disease nowadays. And by having lifestyle changes with less atherosclerosis it will decrease your chance of having heart failure.
KIRK HAMILTON: So getting on to your work. You wrote an interesting article about carnitine and heart failure. And first of all, if you could share simply what's the difference between diastolic heart failure and other forms of heart failure.
DR. REZA MOVAHED: About 20%, approximately one-fourth of the patients of the patients presenting with heart failure have diastolic dysfunction. What this means is that their left ventricular function or heart function is normal during systole, meaning when they squeeze the blood, it is a normal heart. However, in the diastole when the heart relaxes, the fluid has to come and fill up the heart. And this phase, if it is not working very well it, can lead to heart failure. Because when the patient exercises and is going to need a higher cardiac output, this high cardiac output occurring with higher flow back to the heart. So even if the forward flow of the heart is normal, if the filling of the heart is impaired people cannot raise the cardiac output and will go into congestive heart failure secondarily called diastolic dysfunction. Diastole occurs during relaxation of the heart. And that's what the term of diastolic dysfunction is now made for people who have a normal forward flow of the heart, normal systolic function, but impaired relaxation or impaired diastolic function.
KIRK HAMILTON: So it even takes energy for the heart to be in a relaxation or filling phase, I guess, is that correct?
DR. REZA MOVAHED: Absolutely. Actually in all muscles, including the heart, the most energetic phase of the heart is during diastole. Systole, or meaning during contraction, actually is just a passive phase because once diastole occurs in the heart, or even any muscle, you already have ATP, the oxygen carrying energy for the heart, is already attached to the muscle. And in systole the contraction then occurs passively without much energy use. That energy ATP that is in the muscle is already getting done, will be used for the conduction. And then during diastole the heart needs oxygen again in order to relax and then fill out the ATP that are depleted. So actually, you are right, diastole actually is in need of more oxygen for the heart for muscle to get ready for systole.
KIRK HAMILTON: So the whole - one of the points of using carnitine, is it to enhance energy production in the heart muscle? And if you could explain a little bit about the biochemistry of carnitine and why you chose that entity.
DR. REZA MOVAHED: Okay. The energy carrying of any muscle or any cells - the energy, of course, oxygen and energy ATP production, occurs in the mitochondria. So in order for the mitochondria to produce this energy the energy substances such as fatty acids or glucose have to cross the mitochondrial, the membrane. And the fatty acids in order to cross the mitochondrial membrane need carnitine. So in theory, if you can increase the L-carnitine level, you may improve the fatty acid transport into the mitochondria and therefore enhance the energy production, and therefore during the phase that you need energy during diastole you may improve diastolic function. That was the rationale in trying to use L-carnitine and see if the L-carnitine supplementation will improve diastolic function. Now there are people who are L-carnitine deficient due to malnutrition or other diseases and those people have been found to have abnormal diastolic function. And the rationale to using this dose, 1500 mg, is based on the studies that have shown that this dose has been effective in some preliminary data. And that's why we used this dose. And again the reason was to try to see if by improving fatty acid transfer into the mitochondria we may improve the diastolic function. That was the rationale of the study. Again, this study was a small number of patients. This study was a pilot study and to see the effect, and despite using a small number of patients we saw this positive effect on diastolic function so we hope in a larger randomized trial we may be able to prove the concept that we tested in a small number of patients.
KIRK HAMILTON: So this 1500 mg of L-carnitine, this was done in outpatients by oral medicine? Was it 500 mg three times a day or was it all at once or how did you administer it?
DR. REZA MOVAHED: Basically as I remember I think it was all one - administered once a day as an outpatient.
KIRK HAMILTON: Okay. And the Italians use a lot of different kind of carnitines. They use acetyl carnitine more for neurologic problems and they use proprionyl carnitine, I've heard, and is there any reason why you chose L-carnitine?
DR. REZA MOVAHED: I think the main reason was the preliminary studies, all the studies showed that L-carnitine has been effective and we used that dose. And L-carnitine, based on previous studies that showed this, carnitine has been shown to be effective in some patients and that was the rationale to use L-carnitine in cardiac patients - based on the review of previous studies.
KIRK HAMILTON: So you could have patients with normal carnitine levels, but you're using it as almost a pharmaceutical agent to enhance the diastolic function, correct? Is that correct?
DR. REZA MOVAHED: Yes, that's our theory. See, L-carnitine deficiency is a very rare disorder and diastolic dysfunction is much more common. That's why we did not check for L-carnitine levels. If a patient has normal nutrition there is no reason they should have L-carnitine deficiency. This is one of the limitations of our study that we did not have the L-carnitine levels, but we assumed that these patients had normal nutrition, they were not malnourished and as L-carnitine deficiency is so rare that we assumed that these people had a normal L-carnitine and normal nutrition. Therefore we used, in addition to normal diet with normal carnitine levels which we assumed in our patient population, we gave them a higher dose as you said, like a pharmacological dose to see if that will be affecting diastolic function.
KIRK HAMILTON: Was there any side effects with the carnitine? How safe is it?
DR. REZA MOVAHED: No, actually there were no side effects. The patients did not report any side effect during the trial.
KIRK HAMILTON: Is there any interactions with carnitine and other medicines because obviously there's a lot of heart failure patients on a lot of different medicines.
DR. REZA MOVAHED: That's a good question. I don't think we know the answer because in order to do that you need to do pharmacological studies, pharmacodynamic...You have to give L-carnitine and then check the level of the different drugs, and I don't think there's anybody who has done it. It would be expensive to do. And L-carnitine is a supplement and therefore no company is interested in doing this study because it's a supplement and they don't need even need to go to vigorous testing on that. So far as I know nobody has done this test. Maybe it's there and I'm not aware of it. But it may be, there is something again, there are many cardiovascular drugs as you said that may interfere with L-carnitine. This has to be studied in detail, but I am not aware that anybody has done a detailed study about L-carnitine.
KIRK HAMILTON: So would it make sense then, and I know that this wasn't part of your study. But would it be reasonable to give other agents, whatever you want to call L-carnitine, some people call them neutraceuticals, some call them medical nutrition. But things like coenzyme-Q10 which enhances electron transport, ribose which is part of the ATP sugar, to enhance energetics in the heart muscle. Would that be a rational thing to do?
DR. REZA MOVAHED: I think that we have in theory, there's some data that support these nutritional supplements may help the heart. But in order to really recommend them we really need larger randomized double-blinded placebo control studies. However, I can say that our study was a preliminary study in a small number of patients. But again in order to really prove the concept this has to be tested in a large number of patients. And then when it's proven to be effective with no additional side effects then I think it would be alright to rationally use it. Until we have a larger randomized trial, I think these supplementations are more hypothesis generating for the future development of these medications. And the problem is again with all small trials including mine, that you know little mere mistakes in a statistical, or one patient, you know changes in one outcome, it can change the statistic. Therefore really a larger number of patients would be more robust to prove the concept. That's why I call our study a pilot study, a small patient population. And once you see benefit this should be set for larger studies to see if this concept will really work when you enroll a larger number of population, a larger number of patients.
KIRK HAMILTON: So thank you Dr. Movahed for taking the time and your excellent work on L-carnitine and heart failure. And I want to thank you, the audience, for listening to this edition of Staying Health Today Radio. And until next time, Stay and Be Well.
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