The National Heart, Lung, and Blood Institute convened a Working Group of investigators on October 18, 2004, in Bethesda, Maryland via conference call, to assess challenges and opportunities for developing next-generation ventricular assist devices (VADs) specifically for permanent use, otherwise known as "destination therapy." This group was composed of cardiothoracic surgeons, heart failure cardiologists, and bioengineers, all with significant scientific and/or clinical experience with ventricular assist devices. Their objectives were to: advise the NHLBI on the current state of ventricular assist devices for destination therapy, assess the limitations of currently available VADs, identify all populations that might benefit from destination therapy and the required performance characteristics of mechanical circulatory support devices for each of these populations, suggest strategies to minimize adverse events and prolong safe and effective VAD support, and make prioritized and implementable recommendations for research activities.
Heart transplantation remains severely limited due to a lack of available organs. After reviewing the 2-year results of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial, the Food and Drug Administration granted a Premarket Approval for the Thoratec HeartMate VAD to be used for destination therapy and the Centers for Medicare and Medicaid Services expanded Medicare coverage to include such therapy. The substantial number of second- and third-generation devices that are being (or will soon be) tested for safety and efficacy in clinical trials demonstrates continuing interest in VAD development by the biomedical device industry. However, each device currently in clinical use, or under development, has limitations already recognized to retard or jeopardize clinical use. Other treatment alternatives lack the potential for displacing destination therapy as the best option for the growing number of patients with end-stage heart failure. The Working Group concluded that addressing the current shortcomings of LVADs may be the best strategy for improving clinical outcomes for such patients. Furthermore, any improvements that could be made would also result in VADs becoming an attractive therapy to treat patients with less advanced, but progressive, heart failure.
Limitations of currently available VADs
- Risk of thromboembolic events
- Risk of infection, especially due to percutaneous control or drive lines
- Limited durability
- Large device size
- Limited physiological control strategies during prolonged use
- Uncertainty about the long-term consequences of non-pulsatile flow
- Adverse effects on gastrointestinal system with abdominal wall device placement
- Substantial invasive surgery
- High costs
Some limitations are common to most of the VADs currently available (e.g., risks of thromboembolism and infection, invasive surgery, and costs). The issues of durability, size, and gastrointestinal system problems are generally more closely associated with pulsatile flow VADs, while the issues of control strategies and non-pulsatility are commonly associated with continuous flow VADs.
Populations for current- and next-generation VADs
The Working Group agreed that the current patient population for destination therapy is limited to those patients who have advanced NYHA class IV heart failure and are not transplant candidates or are transplant candidates but will likely not receive a transplant. Most such candidates are inotrope-dependent or supported by intra-aortic balloon pumps and have severely limited VO2 max levels in the range of 9-11 ml/min/m2. The Working Group noted that the survival of destination therapy patients in REMATCH was 52 percent at one year, but only 23 percent at two years, and that survival would likely have been better if the destination therapy patients were less severely ill at the time of implantation. However, to justify earlier use of VAD, clinical staging and risk profiles need to be developed to better identify appropriate candidates for destination therapy and to identify exclusion criteria. The Working Group agreed that any benefits from destination therapy would be limited if the decision to implant an LVAD were delayed so much that a patient's health was substantially deteriorated before implantation. Improved clinical staging and risk profiling, based on current medical treatment and life expectancy projections, should help to address this problem.
Some discussants suggested that the REMATCH trial results do not provide compelling indications for broader use of VAD destination therapy, due to the cost and morbidity associated with it. In comparison with other less-daunting therapies under development, many heart failure cardiologists do not believe that the risk/benefit ratio for destination therapy is favorable enough for most of their patients. Cardiologists participating in the Working Group indicated that a 50 percent survival at two years, with minimal time in the hospital after implantation, would be considered a more acceptable outcome when considering destination therapy.
Another reason identified for the current low number of destination therapy patients (estimated to reach ~250 in 2004) is the lack of generally accepted guidelines for use of these devices in end-stage heart failure patients. Heart failure treatment guidelines are currently being developed by at least two separate organizations and are expected to include indications for destination therapy. Because the complications associated with the use of currently available VADs are so substantial, the Working Group indicated that major advances in VAD device technology to reduce the confounding co-morbidities are needed.
Strategies to minimize adverse events and to prolong safe and effective VAD support
The Working Group identified the following strategies to minimize adverse events and prolong safe and effective VAD support:
- Analyze data from heart failure patients to develop guidelines for selecting patients for destination therapy.
- Develop improved anti-thrombotic therapies and device technologies to reduce thromboembolic events. Computational and experimental fluid dynamic studies within prosthetic heart valves have been successfully used to identify areas of thrombus deposition. These and similar technologies and strategies should be further developed to apply to ventricular assist devices. Further research and development of biocompatible materials was also suggested.
- Improve device designs so that they require less-invasive surgery and are easier to use.
- Develop improved device-tissue interfaces and implantation techniques to inhibit pocket infections.
- Develop improved control strategies for continuous flow VADs to provide better clinical performance.
- Develop better battery and energy transmission technologies.
The Working Group recognized that such work will necessarily involve multidisciplinary teams composed of bioengineers, cardiologists, cardiothoracic surgeons, materials' scientists, biologists, and other scientists.
- Support multidisciplinary research to improve or develop technologies to address the problems of limited biocompatibility, device-related thrombosis, infection, reliability, and control of currently available VADs.
- Develop a heart failure risk profile to identify patients who would most benefit from destination therapy. This tool should provide a way to accurately assess prognosis in patients with either dilated cardiomyopathy or heart failure.
Note: In May, 2004, the NHLBI issued a Request for Proposals (NHLBI-HV-05-08) to establish a data and clinical coordinating center to manage a registry of patients receiving a mechanical circulatory support device to treat end stage heart failure. The registry data are expected to facilitate clinical evaluation and patient management, aid better device development, and enhance future research. As such, the registry is expected to have a significant role in addressing the problems of currently available VADs and developing a heart failure risk profile to identify patients most likely to benefit from destination therapy, as recommended by the Working Group
J. Timothy Baldwin, Ph.D., NHLBI, NIH
Working Group Members
Chair: Robert Robbins, MD., Falk Cardiovascular Research Center, Stanford University Medical Center
Cardiothoracic Surgery Members:
- Walter Dembitsky, M.D., Sharp Memorial Hospital
- James Kirklin, M.D., University of Alabama at Birmingham
- Robert Kormos, M.D., University of Pittsburgh Medical Center
- James Long, Ph.D., M.D, Utah Artificial Heart Program, LDS Hospital
- William S. Pierce, M.D, Milton S. Hershey Medical Center
- Mariell L. Jessup, M.D., University of Pennsylvania Medical Center
- Lynne Warner Stevenson, M.D., Brigham & Womens Hospital
- James B. Young, M.D., Cleveland Clinic Foundation
- Chris O'Connor, M.D., Duke University Medical Center
- Peer Portner, M.D., Stanford University School of Medicine
- Gus Rosenberg, Ph.D., Hershey Medical Center
NHLBI Staff Members:
- Tim Gardner, M.D.
- Patrice Desvigne-Nickens, M.D.
- Suzanne Goldberg, R.N.
- Alice Mascette, M.D.
- Sunil Pandit, Ph.D.
Last updated: April 30, 2005