Combined Heart–Lung Transplantation: A Perspective on the Past and the Future
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- Hayes, D., Galantowicz, M. & Hoffman, T.M. Pediatr Cardiol (2013) 34: 207. doi:10.1007/s00246-012-0397-2
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During the last 20 years, there has been a shift away from combined heart–lung transplantation (HLT) in favor of bilateral lung transplantation. This paradigm shift allowed for the donor heart to be transplanted to another patient. However, HLT remains to be the definitive surgical treatment for certain congenital heart disorders and Eisenmenger’s syndrome. With a growing population of adult patients with congenital heart disease, there remains a need for HLT. This article provides a perspective on the past and the future of HLT.
KeywordsCombined heart–lung transplantationCongenital heart diseaseEisenmenger’s syndromePulmonary arterial hypertension
Indications and Recent Trends
Historically, the normal hearts in patients undergoing HLT, such as in cystic fibrosis, would be donated for heart transplantation. This so-called “domino” procedure was performed in which the normal recipient heart was explanted along with diseased lungs and then implanted into a separate patient awaiting a heart transplant. In fact, the first “domino-donor” transplant performed in the United States was in May 1987, when a 28-year-old patient with cystic fibrosis received a combined HLT after donating his heart to a 38-year-old patient with end-stage ischemic cardiomyopathy . The domino procedure continues to be performed but much less frequently than in the past [1–3, 10, 14, 18, 20, 25, 35–37, 40, 41, 43, 48, 51]. Despite decreasing use of domino transplants, the clinical outcomes were comparable with lung transplantation alone. Although there are fewer reported domino procedures, they continue in certain patient populations. For instance, a domino heart from a 3-month-old infant with primary pulmonary hypertension undergoing heart–lung transplantation was donated to a 3-month-old infant with complex congenital heart disease .
The HLT recipient is listed under both the lung and heart allocation systems through the United Network for Organ Sharing (UNOS). In addition, they receive an en bloc harvested heart and lung allograft. In 2005, UNOS implemented a lung-allocation scoring system. This new listing system went away from a system that prioritized the amount of time accumulated on the waiting list by patients to a system that actually incorporated severity of disease and the likelihood of survival after transplantation into what is termed a “lung-allocation score” (LAS). The LAS includes numerous variables that helps determine both severity of illness and potential recovery after transplant. In contrast, the LAS system has no equivalent to the listing status of 1A, in which cardiac candidates obtain the highest priority for allocation of donor hearts.
Clinicians should be aware that the LAS system does not adequately reflect severity of disease in patients with pulmonary arterial hypertension who are actually better served by the cardiac-listing criteria. Thus, patients listed for HLT may be better served as a status 1A heart. However, the criteria for 1A heart listing are not always applicable to patients with pulmonary hypertension or congenital heart disease; therefore, an application for 1A status with exemption would be required. In fairness, appeals to UNOS for modification of the LAS are permitted for patients with pulmonary arterial hypertension. An increase in the LAS is possible if patients have clinical deterioration despite optimal therapy, right atrial pressure >15 mm Hg, or cardiac index <1.8 L/min/m2.
Congenital Heart Disease
There has been considerable progress in pediatric cardiothoracic surgery leading to more patients with congenital heart disease surviving into adulthood. However, progressive cardiopulmonary dysfunction occurs; thus, transplantation becomes the only treatment option. In addition to Eisenmenger’s syndrome, HLT is the preferred procedure for patients with complex congenital heart disease, including patients with single-ventricle anatomy, unsuccessfully repaired lesions, uncorrectable lesions, or severely decreased left-ventricular function. More recently, pulmonary arterial hypertension has been described as an evolving problem in patients with congenital heart disease, which leads to unique needs [21, 45]. Despite high operative mortality due to increased bleeding, infection, and graft failure, patients with congenital heart disease have excellent long-term prognosis if they survive the first posttransplant year .
In cases of simple congenital heart disease, bilateral lung transplantation with repair of the congenital defect is a potential therapeutic option. The cardiac lesions that could be considered for this treatment include atrial or ventricular septal defect, Scimitar syndrome, and pulmonary venous stenosis . In addition, congenital heart disorders, such as multiple peripheral pulmonary arterial stenoses or pulmonary arteriovenous malformations, could be considered for bilateral lung transplantation.
Based on our experiences, patients with congenital heart disease are living longer, further into their adult years, and are developing more severe pulmonary arterial hypertension. Furthermore, their pulmonary arterial hypertension seems to be less responsive to currently available medical therapies. We predict that this trend will continue, which will result in a patient population that will be more likely to require HLT. A key factor is the timing of referral for HLT consideration, so one might recommend referral to an HLT transplant program earlier in the disease course, when New York Heart Association functional class III or IV is present regardless of the ongoing medical therapy or when there is rapidly progressing disease.
The close monitoring of HLT recipients includes pulmonary-function testing, chest radiographs, echocardiography, and laboratory testing by specialists in both pulmonology and cardiology. A major component of posttransplant care of these patients is the acquisition and histopathologic evaluation of allograft tissue for signs of acute rejection. Pulmonologists often assume the lead in the care of HLT recipients because surveillance bronchoscopy with transbronchial biopsies are being performed much more frequently in the early posttransplant period [7, 11, 13, 19, 22, 23, 27, 29, 30, 33, 34, 39, 46, 47, 49, 52, 53]. Currently, there is no consensus regarding surveillance transbronchial biopsy frequency, but most are often performed in the first year after transplant due to the greater rate of both acute rejection and infection. Surveillance transbronchial biopsy specimens have shown acute rejection in a lung allograft in asymptomatic patients;  however, isolated acute allograft rejection involving the heart is infrequent and less common [5, 32, 42] with the majority of episodes occurring early [26, 32, 42], whereas asymptomatic episodes being rarely detected by surveillance endomyocardial biopsies >4 to 6 months after transplantation . In fact, surveillance endomyocardial biopsy specimens in asymptomatic patients are not recommended at most programs after HLT, particularly after 4–6 months . Regarding chronic allograft rejection, the ISHLT registry reported a 30 % incidence of cardiac allograft vasculopathy within 5 years after heart transplant compared with 8 % after HLT [16, 50]. Speculations exist that there could be immunoprotective mechanisms involved when transplanting both the heart and lungs. However, our group reported aggressive vasculopathy in two HLT recipients that occurred in the presence of stable chronic lung allograft rejection , which would contradict a protective mechanism. Therefore, we believe that clinicians should be aware of varying forms of allograft rejection in HLT recipients and not necessarily dictate clinical care based entirely on histopathologic findings of one organ suggesting the function of the other.
Perspective on the Future
Similar to heart or lung transplantation alone, the donor pool for HLT is likely to stay fixed in number; thus, experience in caring for these patients, particularly in pediatrics, may not expand rapidly. To that end, improvements in outcomes, especially in infants, may take decades to be achieved. Therefore, advancements in HLT will likely lag behind compared with advancements in heart and lung failure care. Furthermore, clinical outcomes after HLT would be more optimal if care was concentrated at a smaller number of programs, which would also increase the opportunity for research.
Although domino transplants are not frequently performed, this procedure offers some advantages compared to routine cadaveric donor transplantation. Management of the donor is easier, including donor-recipient HLA matching, and procurement can be performed more efficiently under tighter control of ischemia times by the transplant surgeons. Furthermore, domino transplants may allow for the removal of more diseased and infected tissue from patients with suppurative lung diseases (cystic fibrosis, bronchiectasis, etc.), thus decreasing the difficulty of airway and vascular anastomoses in younger children. In contrast, there are disadvantages to HLT compared with lung transplantation: increased wait time for transplant, need for donor heart–lung block, need for cardiopulmonary bypass and anticoagulation, and potential heart allograft complications, including cardiac denervation as well as acute and chronic cardiac rejection.
Although the number of HLT procedures being performed is decreasing, adult congenital heart disease represents a growing population that may alter this trend. This particular patient population presents unique surgical and medical challenges to transplantation owing to their complex anatomy, multiple previous palliative and/or corrective procedures, increased pulmonary vascular resistance, and debilitated condition. In our opinion, HLT will likely experience an increase in the number of procedures in the near future as a result of adults surviving longer after congenital heart disease palliation. Subsequently, and more ideally, a small number of thoracic transplant programs will need to continue maintaining their ability to provide HLT and posttransplant care for these complicated but rewarding patients. Aggressive management of these patients requires a team of specialists with specialized expertise to assess both allografts and to improve long-term outcomes.