Why the Morning?
The preference of myocardial infarction, sudden death, and stroke for morning hours is an epidemiological fact, but the biological mechanism is not well understood. In this week’s issue of the journal Circulation (Circulation. 2004;109:2507–2510), researchers from the Mayo Clinic Foundation in Rochester, Minn, found that brachial artery flow–mediated endothelium-dependent vasodilation is blunted in the early morning, which may explain why adverse cardiac events occur at that time of day.
In this study led by Maria E. Otto, MD, PhD, of the Mayo Clinic, 19 men and 11 women, all healthy and without sleep disorder, underwent measurement for brachial artery flow–mediated endothelium-dependent vasodilation and endothelium-independent dilation at 3 different times: before they went to sleep at about 9:00 pm, on waking the next day at 6:00 am, and at 11:00 am, 5 hours after waking. All subjects slept well.
Brachial artery flow–mediated endothelium-dependent vasodilation decreased markedly in the early morning after waking compared with the measurement made before the subjects went to sleep. The measurement had recovered by late morning. Endothelium-independent dilation was similar at the 3 periods of observation.
The authors noted, “We have noted a significant reduction in morning levels of endothelium-mediated vasodilation in healthy subjects. This morning decrease in flow-mediated vasodilation needs to be recognized in clinical studies of endothelial function so that comparisons of measurements are performed at approximately the same time of day. The morning-related attenuation of endothelial function may also have implications for our understanding of the morning peak in cardiac and vascular events.”
Road to the LVAD: The End of the Beginning
Houston, Tex—The road to development of a usable left ventricular assist device (LVAD) has been rocky, and 40 years since the journey began, the leaders in its development said during a conference on the device at the Texas Heart Institute that they are no farther than the end of the beginning.
“I view where we are as just at the beginning,” said John Watson, PhD, Professor of Bioengineering at the University of California at San Diego and former director of the artificial heart program at the National Heart, Lung and Blood Institute during its most formative years. “We are not cost-effective at this point. I believe we can become cost-effective and improve the quality of life and survival for these patients substantially.”
Most of those who spoke at the “The Implantable Left Ventricular Assist Device: From Concept to Clinical Reality” conference, hosted at the Texas Heart Institute in Houston, saw the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) results, which were published in 2001, as a pivotal point in the development of mechanical assist devices (N Engl J Med. 2001;345:1435–1443OpenUrlCrossRefPubMed).
“Patients in REMATCH were beyond [New York Heart Association] Class IV,” said Dr Watson. “Not only did we deal with patients sicker than anyone imagined, we saw outcomes that are beyond expectations.”
Victor Poirier, MS, Chief Technology Advisor to Thoratec Corporation in Woburn, Mass, said he began his work with the first LVADs in 1966. “We were engineers,” he said. “After looking at the natural heart, we said, ‘This is just a pump.’ We proposed to develop an artificial heart in three years. The initial concept was a nuclear-powered, totally sealed artificial heart system.”
In the intervening period, it was back to the drawing board many times for Mr Poirier and his colleagues as they fought the dilemma of the heat generated by a nuclear system, other methods of power such as the bulky pneumatic systems, and then electricity.
“We learned the body was a hostile environment,” he said. “Many materials wouldn’t last in the body. They corroded, even though they were coated.” The development of textured surfaces took many days, he said.
Where to implant the heart assist device and how to prevent both thrombosis and the buildup of plaque took many years to solve. Patients died as doctors fought to save them with equipment that was not yet perfected.
“Model 13 was the prototype that became the HeartMate,” he said. The HeartMate and the Novacor, both of which have received US Food and Drug Administration approval after many years of trial, have become the “workhorses” of LVAD procedures.
It was an extraordinarily long and expensive process costing $87 million from concept to commercial device, he said. Using the machine as a bridge to transplantation became accepted, and REMATCH took the field into a whole new area—using the LVAD as a bridge to recovery. Currently, he said, physicians have been able to remove the HeartMate in 85 patients who have recovered from heart failure.
O.H. Frazier, MD, Chief of Cardiopulmonary Transplantation and Co-Director of the Cullen Cardiovascular Research Laboratories at the Texas Heart Institute, noted that the LVAD represents the interface of biomedical engineering and clinical research. “One of the challenges of clinical research is to find areas of compatibility between medicine and science,” he said.
He noted that when Michael E. DeBakey, MD, Chancellor Emeritus of Baylor College of Medicine became interested in LVADs in the mid-1960s, he saw them as a way to allow patients to recover. In 1966, Dr DeBakey used an LVAD successfully for the first time in a woman who could not be weaned from the heart-lung bypass machine,
“We realized we would have difficulty in getting her off the pump,” said Dr DeBakey, who keynoted the symposium. “We had the pump ready. We were unable to wean her off the pump, even though we used the bypass for 21/2 hours. As soon as we attached the pump, we were able to wean her off. It was truly an experimental procedure. I was anxious to get her off the pump as soon as possible because I didn’t know what would happen. She was on the pump 10 days.” Later, he said, the woman enjoyed a complete recovery and went back to work in Mexico as a hairdresser, only to be killed in an automobile accident 6 years later.
In the 1970s, Dr DeBakey became disappointed in the development of the artificial hearts because of the problems of the blood interface. “There has been some progress in controlling thrombus formation in these pumps,” he said. “We haven’t solved these problems.”
More recently, he has been involved in the development of a small axial-flow pump called the Micromed DeBakey VAD [ventricular assist device], which was developed in cooperation with George Noon, MD, Professor of Surgery at Baylor College of Medicine and NASA. Dr DeBakey’s involvement began when he was involved in the heart transplantation of a NASA engineer, David Saucier, in 1984. Mr Saucier brought NASA engineers in on the project.
When he and Dr Noon showed the engineers the bulky pulsatile pumps then under development, one of the engineers asked, “Does it have to be pulsatile?” Dr DeBakey said he still does not know the answer, but “I said no.” That was when the engineers suggested the axial-flow pumps.
The axial pumps lent themselves to miniaturization, and the heart that resulted weighs less than 4 oz and is one tenth the size of pulsatile pumps. It has been tested extensively in Europe and is currently involved in studies in the United States. Recently, a miniaturized version of the pump was implanted in a child at Texas Children’s Hospital. The child who received it did not survive until a donor could be found.
In an era when the pumps are being considered as “destination” therapy rather than a bridge, Dr DeBakey was asked when the benefits of such treatment outweigh the risks. “When the patient is dying, and you have no procedure that will save that patient unless you use the method—in this case, the ventricular assist device.”
Although improvement in the blood interface problem has been made, “we haven’t eliminated the problem,” he said. “At this time, we have to be cautious in our recommendation for destination therapy, particularly in terms of estimating the survival time for heart failure patients.” However, he said, the risk of the surgery and adverse events is now small enough to justify the use of LVADS in a fairly significant number of patients.
The field of pump development has grown extensively, said Eric Rose, MD, Surgeon-in-Chief of Columbia Presbyterian Medical Center and Professor of Surgery at Columbia University College of Physicians and Surgeons in New York, NY. “Worldwide, there are more than 30 pumps being developed that are small rotary pumps. Eighteen are centrifugal, 10 are axial flow, and 2 are hybrids of the two. The greatest clinical experience is with the DeBakey VAD, but the Jarvik 2000 device and HeartMate II have made it into clinical use, as well as a device from Australia. An array of new devices is coming forward. Whether they are an improvement over the pulsatile devices is an open question. While we are looking at new pump, the old device has had 40 improvements since REMATCH. The new pumps will require head-to-head comparison with the old devices.”
Currently, he said, 67 centers are approved for destination therapy, and more than 40 destination therapy implants have been done nationwide since the beginning of 2004. “Multiple new devices will enter trials for destination therapy in the next 5 years.”
Matching the patient to the treatment is crucial, said Dr Frazier. For example, he said, liver failure is a big obstacle to the success of LVAD treatment because patients are too sick at that point. “In 1986, I did five cases. They all died. In 1987, I did none. Early in 1998, I did the first patient on the day I saw his hepatic function deteriorate. I did 11 successful ones, and eight are still living. We bridged the first patient successfully.”
“We all live with ghosts in this field. It has made me more productive because you have to recognize the courage of our patients.”