The AJT Report
The AJT Report: News and issues that affect organ and tissue transplantation
Advances in mechanical circulatory devices have challenged heart transplantation as the gold standard therapy for patients with heart failure. This month, we explore just how close we are to tipping the balance between using the devices as bridges to transplantation and as destination therapies. Also this month, we look at possible changes to the OPTN/UNOS heart allocation policy.
Heart Failure Options Broaden
Tipping the balance between artificial and transplanted hearts
We're oh-so-close. Impressive advances in mechanical circulatory support (MCS) devices such as left ventricular assist devices (LVADs) and total artificial hearts (TAHs) for biventricular heart failure have challenged heart transplantation as the gold standard therapy for patients with end-stage heart failure. Whether we're at that point yet continues to be debated as researchers and physicians take a close look at MCS devices, not only as bridges to transplantation, but also as destination therapies.
In an editorial published in the European Journal of Cardio-Thoracic Surgery, a team from the University of California, Los Angeles noted that MCS therapy “is achieving similar outcomes as heart transplantation but is available in potentially unlimited numbers,” unlike donor hearts. Members of the Japanese Association for Thoracic Surgery said in General Thoracic and Cardiovascular Surgery that “with assist devices like HeartMate II on the market, the need for patients to be bridged to heart transplantation may begin to diminish.” Harvard researchers noted in the journal Circulation that, “since the approval of a continuous-flow destination device in January 2010, there has already been a 10-fold increase in the implantation of left ventricular assist devices for lifetime support.”
SynCardia Systems Inc., manufacturer of the world's first and only TAH approved by the U.S. Food and Drug Administration (FDA), Health Canada and the European Commission, say on their website that their device supported a transplant candidate for nearly four years prior to receiving a transplant. Furthermore, the company currently has a Humanitarian Use Device (HUD) designation from the FDA to use TAH as destination therapy.
Despite this research, doubts remain as to whether LVADs or TAHs are at the point where they can replace heart transplantation in advanced heart failure.
Left Ventricular Assist Devices
Until recently, LVADs were too large to fit in many people's chests. Now the devices are smaller and have much better outcomes (about 75% to 80% at one year, when implanted as destination therapy) and more favorable adverse event profiles; they are also much more reliable than the previous generation of devices, says Jeffrey Teuteberg, MD, medical director of the artificial heart program at the University of Pittsburgh and chair of the Mechanical Circulatory Support Council of the International Society for Heart and Lung Transplantation.
“About one-third of approved continuous flow devices are placed in patients listed for transplant, about one-third are in patients not currently candidates but who may become so after support (so-called bridge-to-candi-dacy) and about one-third [are used] as destination therapy,” Dr. Teuteberg says. “Destination therapy is the one indication that is growing the most.” He adds that “there is a lot of back and forth about whether the outcomes, particularly in older patients, with MCS are equivalent to transplantation. For those who received a heart transplant in their 70s, the outcomes [of MCS as destination therapy] in the first year or so are comparable to transplant and, with the shortage of donor hearts, this may become the trend.” However, he says, there hasn't been a large enough number of patients supported for long enough to really compare medium- and long-term outcomes between MCS and transplant.
- Newer mechanical circulatory support (MCS) devices are smaller and more reliable than the prior generation of technological devices.
- Increasing numbers of reports conclude that in some cases of heart failure, the devices can be used not only as bridges to transplantation, but also as destination therapies.
- Disagreement remains about whether the outcomes with the devices are equivalent to transplantation, as long-term data are not yet available.
With LVADs, “We have one- and two-year outcomes, but not a whole lot more, so it's not yet an alternative to transplantation,” says David Vega, MD, director of Emory University's Heart Transplant Program in Atlanta and former chair of the Thoracic Organ Transplantation Committee of the Organ Procurement and Transplantation Network/United Network for Organ Sharing.
The median survival with a transplant is around 12 years, but we don't have experience with LVADs out that far, says Todd F. Dardas, MD, a cardiovascular diseases fellow at the University of Washington, Seattle. Additionally, he says, “LVAD patients remain at a high risk of deterioration from severe complications such as infection.”
Total Artificial Hearts
A TAH is a niche device used in situations where a traditional LVAD cannot be used and, currently, the only approved TAH is the SynCardia temporary total artificial heart. Mandeep Mehra, MD, executive director of the Center for Advanced Heart Disease at Brigham and Women's Hospital in Boston, says the TAH used to be powered by a large driver console that weighed nearly a quarter ton. More recently, he adds, the driver has been replaced with a portable 13-pound device that enables patients to move around more liberally, allowing for discharge out of the hospital.
In an article published last year in the American Journal of Transplantation, Jon Kobashigawa, MD, associate director of clinical affairs at Cedars-Sinai Heart Institute in Los Angeles, said that “looking into the future, sizing, energy drive and portability issues will still be significant key factors of clinic usage of the TAH. Currently, patients with the TAH can be discharged home with the much lighter weighing freedom driver system,” from SynCardia.
SynCardia spokesperson Don Isaacs says that the FDA has approved HUD designation for both its 70cc and 50cc TAHs to be used for destination therapy. “Once Humanitarian Device Exemption applications have been approved by the FDA, up to 8,000 U.S. patients annually (4,000 each for the 50cc and 70cc) who are not transplant eligible will be able to receive the TAH on a permanent basis,” he says.
In the General Thoracic and Cardiovascular Surgery article, the authors cited results from the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial that took place from 1998 to 2001 and the HeartMate II destination therapy pivotal clinical trial by Thor-atec that occurred from 2005 to 2007. 2 The authors believe that the “prospects of LVADs as a viable alternative to heart transplantation are becoming more realistic.”
The annual report of the Interagency Registry for Mechanically Assisted Circulatory Support, published in February of this year, noted that more than 40% of implants in 2012 were designated as destination therapy. The authors said that destination therapy continues to carry a slightly higher risk than bridge-to-transplant therapy. However, when adjusted for risk factor prevalence in each group, the difference in predicted one-year survival is only about 5%. Current survival for all MCS patients followed for six years is 80% at one year and 70% at two years.
“The holy grail for mechanical heart devices is to use them to ultimately facilitate recovery of the failing heart so that they may be removed (explanted) without needing to perform a heart transplant,” says Dr. Mehra. “This notion is still a dream for us all, but we continue to exercise our efforts to use these devices in a complementary manner to induce recovery.”
OPTN/UNOS Committee Discusses Changes to Heart Allocation Policy
According to Steven A.Webber, MD, chair of the Thoracic Organ Transplantation Committee of the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS),the organization is in the early stages of discussion regarding changes to the heart allocation policy. Joseph G. Rogers, vice chair of the committee, adds, “The Thoracic Committee recognized that there were persistent challenges with the current allocation scheme. Regional disparities in access persist and there are cohorts of ill patients that are not adequately accounted for by the current system.” Therefore, the committee is collecting data and preparing for an analysis.
One of the topics that the committee may address is the designation of patients who have been implanted with a left ventricular assist device (LVAD). They are currently given 1A priority for 30 days.
In a paper in the Journal of the American College of Cardiology, Todd F. Dardas, MD, with the University of Washington, Seattle, says this 1A status policy “creates disparities in risk among status 1A registrants” and “organs should not be allocated to stable registrants such as those with implanted LVADs if higher risk patients could receive the organ.”1 He tells “The AJT Report” that he believes LVADs are a good treatment, but that the problem is that LVADs are taking up room on the list. “Urgency on the transplant list is determined by therapeutic intensity and not by risk,” he says.
Josef Stehlik, MD, MPH, associate professor of medicine at the University of Utah School of Medicine in Salt Lake City, agrees that patients on LVADs are at low risk of mortality, but says LVADs also cause reduction of waitlist mortality. “Maybe we should not jump quickly into taking away higher urgency status for LVAD supported patients,” he says.
David Vega, MD, former chair of the Thoracic Organ Transplantation Committee, recently presented an abstract at the annual meeting of the International Society for Heart and Lung Transplantation.2 His team found a significant difference in two-year outcomes after heart transplantation when examined by the urgency criteria at the time of transplant, especially when comparing LVAD patients with and without LVAD complications. Dr. Vega told “The AJT Report” that the results after transplant were much worse if the patient was transplanted for device-related complications, when compared with transplantation under the 30-day 1A status.
“Most of the patients who get LVAD as a bridge-to-transplant are already quite sick. There just isn't a donor available for them,” he says. “Now, they are told they have to get really sick again before we'll transplant them. That doesn't make sense.” AJT
1. Dardas T, Mokadam NA, Pagani F, Aaronson K, Levy WC. Transplant registrants with implanted left ventricular assist devices have insufficient risk to justify elective organ procurement and transplantation network status 1A time. J Am Coll Cardiol 2012; 60:36-43.
2. Vega D, Edwards LB. Outcomes after heart transplantation in adult recipients based on medical urgency status/criteria: Implications for heart allocation in the USA [abstract]. J Heart Lung Transplant 2012; 31(suppl): S12.