Mechanical Circulatory Support – A Historical Review

As the American Society for Artificial Organs (ASAIO) celebrates it 50th anniversary, we reflect on some of the landmark events that took place on the road to developing a mechanical pump to support the human circulation. The first step on this journey took place when Dr. Michael E. DeBakey developed the concept for a blood pump as a medical student. His roller-pump was perfected in the early 1950’s—during the time that ASAIO was being conceived. It was this DeBakey roller pump that became the workhorse for essentially every heart/lung machine in the world. Dr. DeBakey’s interest in cardiac assist devices persisted during the 1960s, as evidenced by the work that was being carried out in his laboratory. These animal studies led to several successful clinical applications. For instance, in 1963 he was the first to use a ventricular assist device clinically using a gas-energized double-lumen Silastic tube reinforced with Dacron to augment flow from the left atrium to the descending aorta. Other concepts included the use of implantable biventricular assist devices and the development of an external gas-energized synchronized hemispheric pump constructed of Dacron-reinforced silastic. Dr. DeBakey tested this in several hundred animals and, on the basis of these results he implanted the pump into two patients who failed to wean from cardiopulmonary bypass. In each case these individuals had complete recovery following a period of device support (4 and 10 days). Thus, the first successful left ventricular assist device (LVAD) was used as a bridge to recovery in 1966.1 In 1963, Dr. DeBakey introduced to Congress the notion that an artificial heart could be constructed to support the circulation in patients with end-stage heart failure. Based on the initial work of his team at Baylor College of Medicine, which he had charged with determining the feasibility of building such a device, DeBakey argued that, “experimentally it is possible to replace the heart with an artificial heart in animals that had been known to survive as long as 36 hours. This idea I’m sure can be taken to full fruition if we had more funds to support more work, particularly in the bioengineering area.”2 One year later, under President Lyndon Johnson’s administration, the National Heart and Lung Institute established the United States Artificial Heart Program. This marked the first success in a series of regulatory and financing hurdles that would challenge researchers over the next 40 years. Even at the inception of the Artificial Heart Program, DeBakey and his colleagues realized that the goal to total cardiac replacement would be compounded by numerous problems that required long-term investigation. The focus was placed on both left ventricular assist devices and total artificial hearts. The FDA began regulating medical devices in 1976, with the Medical Device Amendment to the Food, Drug and Cosmetic Act. The purpose of this was to provide reasonable assurance of safety and effectiveness for all devices. While this provided an element of safety, it also provided a significant delay in the development and testing of devices clinically in the United States, to the degree that over the past two decades most of the initial devices are tested clinically overseas prior to being tested in the United States. Of the several centers involved in artificial heart research during the following decade, the first to achieve clinical success was Dr. Willem Kolff’s lab in Salt Lake City. This success resulted from a combination of skills that were brought into the research effort. Although the technology of the pump itself was not that dissimilar from other pumps in the country, the experience of Dr. Don Olsen as a veterinarian and biomedical engineer who not only had the understanding of the principles behind the development of the artificial heart, but also had a superb talent in surgical skills and management of anesthesia which contributed to the positive results that were realized in the laboratory. It was this expertise that permitted animals to not only survive a total artificial heart implant operation, but to successfully be rehabilitated for months after surgery. Due to these positive results, the FDA approved the Jarvik program for seven clinical permanent implants; in 1982 Dr. Barney Clark became the first patient to receive a permanent implant of the total artificial heart as a destination device. Drs. William DeVries and Lyle Joyce were the co-surgeons on this event on December 2, 1982.3 After Dr. Clark’s death, 112 days following implant, the University of Utah went through an extensive review, with no definite commitment to completing the series of seven. Other centers throughout the country were requesting FDA permission for investigating their devices as well, and in 1984 there was a paradigm shift in that the FDA approved the total artificial heart and other LVADs as a bridge to transplantation, rather than use as destination therapy. There were significant technical limitations to the Jarvik-7 total artificial heart due to its size. Among the programs to receive FDA approval for the Jarvik-7 total artificial heart program was the Minneapolis Heart Institute. The first patient to present a need for biventricular support at this institution was a young lady who was by far too small to receive a Jarvik-7. Approval for compassionate use of a 30% smaller heart, the Jarvik-7–70, was then obtained, and she successfully underwent implantation of this smaller device. It worked as well, if not better, than the larger device, and very shortly thereafter the FDA approved this device for all other centers to use. This led to a subsequent implant into a 13-year-old boy at the Minneapolis Heart Institute, who is the youngest patient ever to have received a total artificial heart. He is still alive following transplantation. Other investigators were simultaneously developing various ventricular assist devices. In 1984, Dr. Don Hill successfully used the Pierce-Donachy pump developed Thoratec Laboratories as a bridge to transplantation. The design of the Thoratec pump was such that it can be used as a univentricular or biventricular support device. At the same time, Dr. Peer Portner oversaw development of the Novacor VAD, which was also implantable. It differed from other pneumatic devices that were being used in that it was an electric device. This device was successfully used as a bridge to transplant in 1984 at Stanford.4 Victor Porier and his group at Thermo Cardiosystems Inc. developed the Heartmate device, a pulsatile pump that was unique for its textured blood contacting surfaces leading to cellular in-growth and the requirement of only minimal antithrombotic therapy. Dr. O.H. Frazier used this device successfully as a bridge to transplantation in 1988.5 The majority of the cardiac surgeons throughout the country, however, did not have access to these high-tech, expensive implantable devices. They chose to provide short-term support for patients who could not be weaned from the heart/lung machine using one of the two centrifugal pumps that had been developed (Sarns and Biomedicus). These pumps gave evidence that non-pulsatile flow was adequate to maintain all secondary organs. The next device that confirmed the body’s acceptance of a continuous-flow device was the development of the Wampler Hemopump. This impeller rotated at greater than 25,000 rpm and under these circumstances the patients had minimal hemolysis. Again, other organs would successfully improve and it appeared that the human body would easily accept continuous flow. These ideas led to pump miniaturization through the development of axial flow pumps. Dr. George Noon and Dr. DeBakey, in conjunction with the National Aeronautics and Space Administration (NASA) developed the first of these to be used clinically for long term support—the DeBakey VAD. Thus, axial flow ventricular assist devices emerged as a promising new mechanism for supporting the circulation as a bridge to transplantation. The success of early LVAD implantations for bridge to transplantation provided the foundation for using these devices as destination therapy. The landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial validated this idea, demonstrating a 48% reduction in mortality with implantation of an LVAD compared to optimal medical treatment.6 This set the stage for perfection of devices with the intent of using them for destination. The future left ventricular assist devices most certainly will be smaller if they are configured as an axial or centrifugal flow pump. Patients needing biventricular support will perhaps have the option of two assist devices or a total artificial heart. One total artificial heart (AbioCor) is likewise showing promise as a totally implantable total artificial heart. As one reflects over the major events that have occurred in the 50-year history of the American Society for Artificial Internal Organs, it is evident that there have been many bumps in the road. However, through the perseverance of those who have dedicated their careers to this goal, significant milestones have been reached to the degree that the future for cardiac assistance appears quite secure.Figure: Lyle Joyce, MD, PhD Minnesota Thoracic AssociatesFigure: Dr. Lyle Joyce and then President Lyndon JohnsonFigure: Dr. Lyle Joyce receives his Medical School Degree from Dr. DeBakey 1973Figure: Dr. George Noon with Dr. DeBakey in the early 80’sFigure: Dr. David Joyce with Dr. DeBakey during his research fellowship in the Division of Transplant and Assist Devices 2004.