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Dr D. Craig Miller (Stanford, Calif). I congratulate Dr Farivar and Dr Cohn for bringing something to our attention that may prove to be very important in the future. Certainly it is scientifically much more appealing than what some of you in the room may be old enough to remember. In the late 1970s and early 1980s, Don Magilligan and others were saying, “We're only going to get so many heartbeats out of these tissue valves. Why don't we use β-blockers and slow down their heart rates? Maybe the valves would last longer.” Those were the old days. This is very promising and exciting, and it stems from the work being done in the native aortic valve in elderly patients with aortic sclerosis, where Emile Moeller at Penn and his vascular biology colleagues think they are going to take another operation away from us. But don't get too paranoid, because the very promising work in elderly patients with aortic sclerosis does not apply to younger patients with calcific aortic sclerosis, in whom the valve was originally a bicuspid valve. In fact, at the American Heart Association meeting in 2002, Dr Moeller said that the Penn Institutional Review Board believed it was unethical to randomize large cohorts of patients with native valve aortic sclerosis. The uncontrolled data had already proved to their satisfaction that statins retard progression of aortic sclerosis. I personally do not think that has been proven conclusively, but that is what Moeller relayed. In any event, there has been no information, until the material you just heard, about what happens when patients with bioprosthetic valves are treated with statins.

This paper was submitted early and actually has already been revised and accepted for publication in the Journal by Andrew Wechsler. Tirone David has written an editorial pertaining to this paper and a similar one from Germany by Nollert and associates concerning the effects of hyperlipidemia on the durability of the Hancock pericardial valve. Both papers will be fast-tracked because the Editor believes this question is important.

Tirone David looked at 635 old Hancock I valves from Stanford implanted in the 1970s and 1980s and observed for 15 years or more. He could show no adverse impact of hyperlipidemia on structural valve deterioration (SVD). He then looked at 913 patients undergoing aortic valve replacement at the Toronto General Hospital in the 1990s (Hancock II, Carpentier-Edwards pericardial, and Toronto SPV) and again could find no apparent adverse influence of hyperlipidemia on SVD.

Some of you may have been wondering why the freedom from SVD curves in Toronto with any kind of tissue valve are so good. Tirone himself has admitted that maybe it is because in Ontario almost everybody is already on a statin; maybe they never will see an effect there in their more recent patients. Another factor pertaining to the mitral position is that only the very sickest and very elderly patients undergo mitral valve replacement with a tissue bioprosthesis; the majority of valves are repaired.

In any event, this is promising work, even though it is just the first step. I do have one statistical question: When you get down to the case match controls, exclude the statin matches, and then you rematch for age, you get to some very small Ns. How does this affect the reliability of your statistics?

My real question is this: What is the next step? How are we going to confirm that this is true or not in larger, multicenter analyses? Tell us where you are headed. In today's world, at least in California, it appears that almost everybody is already on atorvastatin calcium (Lipitor) or some statin, even if they do not have coronary disease; therefore, how can you ever hope to test your hypothesis? What is the next step to obtain conclusive proof that treatment of hypercholesterolemia into the low normal range—and I should emphasize that the values shown here used to be accepted as normal in the North American population B—delays bioprosthetic SVD in large patient cohorts?

Dr Farivar. Dr Miller, thank you. This is the first report in bioprosthetic valves, and to get to the truth, I think we need a prospective randomized controlled trial. I would envision a multicenter trial enrolling subjects who have implanted tissue valves and subcritical coronary stenosis and are not receiving statins. We should randomize them into two groups—one to receive HMG-CoA reductase inhibitors and the other to receive placebo—and to follow the progression of bioprosthetic tissue valve calcium accumulation over 1 to 2 years, using methods that are similar to a study recently published concerning the native aortic valve. Shavelle and associates have recently shown in the Lancet that statins reduce the accumulation of calcium in the native aortic valve, as assessed by electron beam computed tomographic scanning, for calcium in the valve. These studies could be performed concurrently with surveillance scans of the coronary arteries to determine whether statins also prevent the progression of coronary calcification.