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INTERMACS Registry and the changing landscape of ventricular assist devices
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Just over 50 years has passed since the first total artificial heart was “successfully” implanted into a dog by the recently deceased Willem Kolff, MD, at the Cleveland Clinic. The animal lived 90 minutes with the device in place.
When this experiment was carried out, sophisticated surgical repair of the heart was difficult, particularly if the only option was to arrest the beating heart and do open procedures. More so, heart transplantation was a far-off dream. This dilemma pushed innovation of circulatory support devices for short, intermediate and longer-term applications.
History of VADs
Jack Kennedy said during an address at Rice University in Houston in September 1962, “We choose to go to the moon [and do the other things] in this decade … not because they are easy, [but] because they are hard, because that goal will serve to organize and measure the best of our energies and skills …” From that proclamation emerged an extraordinary support of biomedical technology development, including the National Institutes of Health total artificial heart and mechanical circulatory support device program. This effort, which began in 1964, resulted in the first successful use by Michael DeBakey, MD, of a temporary left ventricular assist device to bridge a patient who had undergone valve replacement for rheumatic heart disease, to recovery when post-repair cardiopulmonary bypass wean became problematic. Then, in December 1967, the first arguably successful human heart transplant was done by Christiaan Barnard, MD. On April 4, 1969, the first total artificial heart insertion was done by Denton Cooley, MD, as a bridge to heart transplant.
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Progress subsequently slowed and should be put into the context of man’s first steps on the moon July 21, 1969. Kennedy’s stated mission had been achieved, but what about the goal of building an acceptable total artificial heart or completely implantable VAD?
Though dramatic progress had been documented, Norman Shumway, MD, commented that xenographic transplant “…would be just around the corner and … always be just around the corner.” Indeed, despite substantive limitations observed during the Dec. 2, 1982, implantation of the Jarvik-7, a device developed with significant assistance of Kolff, one total artificial heart is now clinically available to bridge patients – in dire HF straits – to cardiac transplantation. Additionally, a handful of mechanical circulatory assist devices are now commercially available to either “bridge” to heart transplant or for use as an alternative to heart transplant for so called destination (being home or discharged from the hospital) long-term therapy.
Era of INTERMACS
Summary and analysis of recent applications of mechanical circulatory assist, including the total artificial heart, LVADs, right VADs, and bi-VADs has been provided by the burgeoning, four-year-old INTERMACS registry. INTERMACS is a national registry for patients who are receiving mechanical circulatory support device therapy to treat advanced HF for the reasons summarized previously. This registry was devised as a joint effort of the National Heart, Lung, and Blood Institute, the Centers for Medicare and Medicaid Services, the FDA, clinicians, scientists and industry representatives in conjunction with the University of Alabama at Birmingham and United Network for Organ Sharing. Currently, only FDA-approved durable VADs (defined as having the potential to allow for discharge of patients from the hospital to long-term follow up situations) are entered into the registry.
The goals of INTERMACS include the refinement of patient selection to maximize outcomes with current and new device options; to identify predictors of good outcomes as well as risk factors for adverse events after device implantation; to develop consensus best practice guidelines to improve clinical management by reducing short- and long-term complications of mechanical circulatory support device therapy; to utilize registry information to guide improvements in technology, particularly as next generation devices evolve; and to guide clinical testing and approval of new devices. Furthermore, INTERMACS satisfies CMS mandates for registry participation if medical centers desire designation as a destination therapy device implantation site.
The FDA has worked with the registry to facilitate adverse event definition and reporting. Indeed, a unified definition of patient profiles has been developed as well as precise, and now accepted, definitions of adverse events that clinicians, academicians, regulators and device developers agreed upon. Another unique and advantageous aspect of the registry is a program to obtain tissue and blood samples in patients at the time of device implantation and removal to facilitate future sophisticated scientific investigation of advanced HF.
Particularly important is the fact that the registry is constructed to mimic desirable clinical practices commonly seen in clinical trials but not generally noted in registries, with very precise patient inclusion/exclusion criteria, specific adverse event definitions, complete patient ascertainment, complete data collection and follow up, site and data audits, data analysis freeze, local principal investigator and site certification, adjudication of important outcome events, preplanned and sophisticated analysis of data and an external observational study monitoring board to criticize and suggest procedure.
Presently, INTERMACS has about 95 currently participating hospitals and 1,500 accrued devices. There has been a substantive and important change in patient accrual rate that has been driven, arguably, by the fact that newer continuous flow VADs can be inserted easier and with many fewer major adverse events. Indeed, survival of patients is quite reasonable overall.
Interestingly, this rather dramatic change in registry entry numbers was noted shortly after the FDA approved the HeartMate II device (Thoratec). This observation demonstrates the power of the INTERMACS registry to document paradigm shifts and provide a platform for critical review of patient selection for these devices, and define risk/benefit ratios as well as more precisely and accurately describe adverse events and progress of this field. Touring the INTERMACS website at INTERMACS.org will allow the public to see this information in ongoing, up-to-date, and transparent fashion.
Everyone is awaiting more definitive data analysis and presentation which now will go forward unabated, and rapidly, as this field matures further. Clearly this technology is no longer “….just around the corner.” It is real and it is here.
James B. Young, MD, is Professor of Medicine and Executive Dean, Cleveland Clinic Lerner College of Medicine; the George & Linda Kaufman Chair and Chairman, Endocrinology & Metabolism Institute, Cleveland Clinic. He is HF and Transplantation Section Editor on Cardiology Today’s Editorial Board.
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FIGURE 1: Patient entry into INTERMACS since launch of the registry in June, 2006. |
 FIGURE 2: Survival after device insertion depended on patient profile at the time of insertion, indicating that patients who are “stable but inotrope dependent” have significantly better survival that those patients requiring these procedures when “critical cardiogenic shock” is apparent. |