NHLBI Working Group
Next Generation Ventricular Assist Devices for Destination Therapy
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
- 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
- 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
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
- 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
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