Major bleeding complications, including strokes, have been so common in the nation's four permanent artificial-heart recipients that Humana Heart Institute should reconsider its research plan before further implants, according to leading experts in the field.
Food and Drug Administration officials said they do not plan to stop the experiment but will request a "special report" on scientific progress to date from Symbion Inc., which makes the mechanical heart.
"Maybe we need to pause," said Dr. Allan M. Lansing, head of Humana's Louisville heart program. He said changes are needed in the treatment program and the device, and added: "I think it will be unlikely that we'll put another device in exactly the same as the previous one."
Concern was renewed Monday when the third recipient of an artificial heart, Murray P. Haydon, suffered a minor stroke, 107 days after his implant. His progress was reported yesterday as "excellent," and he resumed therapy on an exercise bicycle.
But William J. Schroeder, who received an implant Nov. 25 and has lived longest with one, has been hospitalized and unable to speak since last month when a second debilitating stroke left him with serious brain damage. In early April, Jack C. Burcham died from a jelly-like clot in his chest 10 days after implant. Initial recipient Barney B. Clark suffered neurological and bleeding problems before dying 112 days after implant .
"I am very worried. Unless they have some expectation they have the problem under control, then I think they should probably pause for a while," said Dr. Claude Lenfant, director of the federal National Heart, Lung and Blood Institute.
Lenfant said he recently received a report recommending government development of a fully implanted, battery-powered mechanical heart. The Humana device is tethered to an air-driven power system outside the body.
"I certainly would consider recent problems a good reason to examine the procedure to see if they can find anything that is causing all of these clots," said Yale University professor of medicine Dr. Robert J. Levine, who served on the government's advisory panel.
"At any time when the facts force you to be pessimistic, there should be a presumption for not going forward unless you've found a way to make things better," Levine said.
Arthur Caplan, associate director of New York's Hastings Center, a think-tank on biomedical issues, said: "I would like to see them have a brief moratorium to discuss what they have learned so far." He said the FDA and a local institutional review board, established to oversee experimentation on humans and required by law to protect their rights, should take a closer look at findings to date.
Referring to the Humana project, Dr. Albert R. Jonsen, a professor of medical ethics at University of California at San Francisco, said, "They ought to pause and regroup." He served on the government's artificial-heart advisory panel and is advising Humana.
Jonsen and American Heart Association President Dr. Thomas Ryan of Boston University Medical Center said that each case should be carefully reviewed before another implant, and that Humana should appoint an outside scientific panel to scrutinize data and recommend how to proceed with research.
Because Humana is funding and conducting such research, it is "somewhat in the setting of judge and jury," Ryan said.
He criticized Humana for "inviting such wide media coverage," saying, "It's hard for the public to put in perspective these very tragic complications, and it's folly to try to judge it in the newspaper."
Surgeon William C. DeVries, who has FDA permission to perform three more implants, said Tuesday that strokes have become a "common complication of the procedure." He pledged to learn from one patient and make changes for the next and to warn future recipients about the more apparent risk of blood clots and strokes. "We may not know the answer to this until we have done 100," he said.
Although each implant recipient signed extensive consent forms outlining the device's highly experimental nature and its consequences, second thoughts have been expressed.
For instance, even before Schroeder's second stroke, his wife, Margaret, told Life magazine that her husband originally "thought he'd either die or be better . . . . If he had anticipated the hardship this has been on the family, he might not have done it."
In recommending a pause, Humana's Lansing said the treatment program and the heart device should be revamped. "All of us are concerned about . . . bleeding or clotting with each one," he said. "We're already looking at modifications."
Shortly before Haydon's implant, Lansing had said that, if Haydon suffered a stroke as had Schroeder, "it will certainly give us a cause to pause, but I don't know whether it would stop the group completely."
After Schroeder's first stroke last December, when only he and Clark had undergone the surgery, Lansing painted the experiment as a long medical sports event, noting that a baseball World Series can last seven games and saying:
"There are seven implants planned. We may have had an error in the first game and an error in the second game. We haven't lost the second game yet, but we're still only in the second game. The purpose of this whole thing is to find out answers . . . . "
"Even if you lost the first two games, you wouldn't pack up and go home," Lansing said, adding, "We would like to win the series with the patient going home, enjoying life with his family, fishing and working in the garden."
This week, he acknowledged that the implants have been a "four out of seven series" in which "we have lengthened lives but . . . not improved the quality of lives."
In addition to rethinking drug therapy to keep blood from clotting, Lansing said, "We probably need to make some modifications in the valves and drive system" so that the device will be "less traumatic on the blood." He said such discussions have begun.
The FDA must approve any modification of the device. "We gave permission for seven, and . . . I don't think we have any information to cause us to want to stop . . . . The strokes . . . are extremely unfortunate . . . but they were not unanticipated," said Glenn Rahmoeller, the FDA's director of the cardiovascular devices division.
He said the "institutional review board has the primary responsibility for the ethical aspects of the study and can stop the study at any time." After Clark died, such deliberations resulted in a long delay before DeVries could attempt his second experiment.
Humana has agreed to sponsor as many as 100 implants if progress is made, and
critics have questioned how the independence of the its review board at Humana Hospital-Audubon is and how closely it is monitoring the experiment. Lansing said the 14-person board, composed of hospital physicians, nurses, members of the clergy, a pharmacist and lay members, "gets a report on the situation at two- to four-week intervals."