The high frequency of medical complications, particularly strokes, in the first six recipients of the experimental Jarvik-7 artificial heart raises new questions about its use, not only as a permanent device but as a temporary support system for patients awaiting heart transplants.
A series of minor strokes Thursday in 25-year-old Tucson, Ariz., patient Michael Drummond, one week after he received an artificial heart on a temporary basis, forced doctors to speed up their search for a human heart for fear that he would suffer a more massive stroke. The search ended with a transplant operation Saturday.
Drummond yesterday remained in critical but stable condition. He was aware that his artificial heart had been replaced by a human heart, which his parents reported had "relieved some of his anxiety." Hospital spokesman said his speech had improved since his stroke but that he still had some trouble speaking.
Sweden's Karolinska Hospital announced last week that Leif Stenberg, who received a Jarvik-7 permanent artificial heart April 7, had suffered a stroke and was in intensive care there.
Strokes followed earlier brain and bleeding complications in all four patients treated by Dr. William DeVries, the pioneering surgeon who has done four permanent artificial heart implants at the University of Utah and the Humana Heart Institute in Louisville.
The source of the problems remains unknown, but the number of institutions that have received government permission to implant the mechanical heart pump is growing; approval was recently granted to researchers in Pittsburgh and Minneapolis to do temporary implants of the heart.
Officials at Symbion Inc., the Salt Lake City manufacturer of the Jarvik-7 heart, as well as doctors involved, express concern about the frequency of complications, but they argue that more research on human patients is needed to understand what may be going wrong.
But outside physicians and ethical experts question whether the research should proceed at its current pace. They called for a public accounting of the research progress to date and criticized government and local panels for not reviewing the studies more aggressively.
"I think that the research is now straining the limits of moral acceptability," said Arthur Caplan of the Hastings Center, a medical-ethics think tank in Hastings on Hudson, N.Y. "Given the adverse outcomes with all the recipients, there still has not been an independent review and assessment of whether the knowledge attained is worth the experiment . . . . It's time for a moratorium and more public review.
"There has been an unfortunate passing of the buck by federal agencies that has resulted in a great deal of unanswered questions about the ethics of the experiment," he added.
"The researchers have a problem, and I don't see any solution to it at this time," said Dr. Claude Lenfant, director of the National Heart, Lung and Blood Institute. "It is difficult for anyone to judge what's really happening . . . . Unless they have a strategy and a plan to overcome the problem, they should pause and ask themselves questions about whether to proceed."
"At this point, the burden of proof lies with the surgeons and with Symbion to explain why there is justification to go ahead. They should be called upon to explain what they are doing to make it less likely there will be strokes in the future," said Dr. Robert Levine, a Yale University physician who served on a recent government artificial-heart advisory panel.
Levine said he felt permanent implants should be discontinued for the time being but that temporary implants could proceed cautiously, with recipients being updated on potential benefits and risks.
Food and Drug Administration officials said they had no plans to stop the experiments. In June, the agency asked Symbion for a report documenting the scientific progress to date with DeVries' patients.
Don Grabarz, Symbion vice president for regulatory affairs, said Friday the report would be sent this week. But he said it draws "no conclusions" as to the cause of the strokes and bleeding complications. "It basically says that the program should continue and it should be expanded for permanent use to other institutions who desire to do it."
At present, DeVries is the only person in this country with permission to use the Jarvik-7 heart for permanent implant. There are at least two other domestic institutions considering permanent use. Grabarz declined to name them.
Grabarz said, however, that using the heart temporarily to keep dying patients alive while they await a scarce human heart transplant is becoming a "more immediate, viable procedure." Grabarz said the company received a letter Friday from the FDA giving permission for temporary use to Dr. Lyle Joyce of the Minneapolis Heart Institute and that Dr. Bartley Griffith of the University of Pittsburgh has also just received such permission.
Four other groups -- the Texas Heart Institute in Houston, St. Luke's Medical Center in Phoenix, the University of Utah and a Hospital Corp. of America hospital in Florida -- are also preparing to use the Jarvik-7 on a temporary basis, Grabarz said.
Caplan of the Hastings Center said, "The 'temporary bridge' goal is more reasonable than the permanent implant . . . . At the same time, I'm not assured yet that the argument that death justifies every intervention has been balanced against the need to make sure that the subjects are being informed."
"FDA is concerned about the adverse reactions," said Dr. Abhi Acharya, of the agency's division of cardiovascular devices. But, barring something "very startling" in the report, he said the FDA plans to let Symbion and DeVries complete the seven permanent implants already approved and to "carefully monitor" the expanding temporary use.
Caplan urged the FDA to take "a stronger stance." The Heart Institute's Lenfant agreed that the FDA was in the best position to judge the merits of the work.
In March, surgeon Jack G. Copeland and another doctor implanted an artificial heart that had not been approved by the FDA for use in humans. Their patient died after an effort to replace that heart with a second human transplant.
And although FDA guidelines say any recipient of a Jarvik-7 heart must be healthy enough for a human-heart transplant, Copeland said Saturday that he questioned at the time he implanted Drummond's artificial heart whether Drummond could have been considered a "reasonable candidate" for a human heart.
Grabarz said the company did not plan to make its report for the FDA public and he did not know how soon DeVries would publish research on his three Humana patients. The doctor has done a scientific review of the first patient, dentist Barney B. Clark, who suffered neurological and bleeding problems before dying 112 days after his December 1982 implant.
William J. Schroeder, who received an implant last Nov. 25, suffered debilitating strokes in December and May -- and perhaps small, transient ones in between. Now living in an apartment across the street from Humana's Audubon Hospital, he speaks in short sentences, but has a permanent speech impairment and memory loss, Humana spokesmen say.
More than six months after Murray P. Haydon received his artificial heart, he remains in intensive care at Audubon, on a respirator much of the time. He suffered a minor stroke in early June.
Then in early April, Jack C. Burcham died from a jelly-like clot in his chest, 10 days after his artifical heart was implanted.
The only other recipient of a permanent mechanical heart, Swedish patient Stenberg, had appeared to be making the best recovery. Last week, his doctors said he had suffered a stroke, but they made few details public. Earlier, he was said to have suffered temporary visual problems that may have been caused by an earlier blood clot.
In each case, doctors have had to balance the use of blood-thinning drugs to try to prevent the blood clots that can lead to strokes against the risk that such drugs might increase internal bleeding.
Doctors at Tucson's University Medical Center, a University of Arizona teaching hospital, were aware of the potential problems when they implanted the plastic heart in Drummond Aug. 29. Copeland said that day that "the longer the patient is on the heart, the more likely he is to sustain complications, including stroke."
Although Drummond's stroke on Thursday, apparently caused by a shower of small clots, appeared to do slight damage, doctors were concerned that a more serious stroke might rule out the prospect for transplant, making him a permanent artificial-heart recipient.