Pediatric Cardiology

, Volume 34, Issue 2, pp 207–212

Combined Heart–Lung Transplantation: A Perspective on the Past and the Future

Authors

    • Cardiopulmonary Failure and Transplant ProgramsNationwide Children’s Hospital
    • The Ohio State University College of Medicine
  • Mark Galantowicz
    • Cardiopulmonary Failure and Transplant ProgramsNationwide Children’s Hospital
    • The Ohio State University College of Medicine
  • Timothy M. Hoffman
    • Cardiopulmonary Failure and Transplant ProgramsNationwide Children’s Hospital
    • The Ohio State University College of Medicine
Review Article

DOI: 10.1007/s00246-012-0397-2

Cite this article as:
Hayes, D., Galantowicz, M. & Hoffman, T.M. Pediatr Cardiol (2013) 34: 207. doi:10.1007/s00246-012-0397-2
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Abstract

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.

Keywords

Combined heart–lung transplantationCongenital heart diseaseEisenmenger’s syndromePulmonary arterial hypertension

Introduction

Combined heart–lung transplantation has been a therapeutic option for cardiopulmonary failure for both adult and pediatric patients since the early 1980s. The index cases of combined heart–lung transplant (HLT) were reported in 1982 [44]. The first patient was a 45-year-old woman with primary pulmonary hypertension; the second was a 30-year-old man with Eisenmenger’s syndrome due to atrial and ventricular septal defects; and the third was a 29-year-old woman with transposition of the great vessels and associated defects [44]. Consequently, there was an increase in the number of HLTs performed with a peak for both adult and pediatric patients in 1989 with a total of 284 and 61 performed that year, respectively (Figs. 1, 2) [4, 17]. During the next few decades, there was been a slow decrease in the number of HLTs reported to the International Society for Heart and Lung Transplantation (ISHLT) registry. The most recent report from the ISHLT registry summarized these downward trends in HLT in both adult [17] and pediatric patients [4, 8, 31].
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Fig. 1

Number of HLTs performed in adult patients each year as reported to the ISHLT. Data for 2009 includes up to June 2009. Modified with permission from Christie et al. [17]

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Fig. 2

Number of HLTs performed in pediatric patients each year as reported to the ISHLT registry. Data for 2009 includes up to June 2009. Modified with permission from ISHLT [31]

Indications and Recent Trends

Since the establishment of the ISHLT registry in 1982, the leading indications for HLT in adult patients are congenital heart disease with Eisenmenger’s syndrome (36 %), idiopathic pulmonary arterial hypertension (28 %), cystic fibrosis (14 %), and acquired heart disease (5 %) [17]. In contrast, the primary indications for HLT in pediatric patients are cystic fibrosis (28 %), pulmonary arterial hypertension (25 %), congenital heart disease (22 %), and Eisenmenger’s syndrome (13 %) [31]. During the past decade, there has been a decrease in the number of HLTs for cystic fibrosis in the United States with HLT still remaining an option in Europe and non-North American countries. These trends of shifting away from HLT to bilateral lung transplant is related to less need for cardiopulmonary bypass if only the lungs are transplanted [12]. Furthermore, fewer patients with pulmonary arterial hypertension are requiring less thoracic transplant in general because of new and improved medical therapies available. The growing trend of fewer HLTs being performed has resulted in no change in survival of these patients as seen in Kaplan–Meier survival curves by era in both adult and pediatric patients (Figs. 3, 4) [31]. The subtle trend for improved survival, albeit not significant, in pediatric patients from 1989 to 1993 is likely to a spike in the number of HLTs being performed. Despite the decreasing number of HLTs, the current cost remains comparable with other multiple-organ transplants as well as transplantation of single thoracic organs (Fig. 5) [9]. This cost includes health care use 30 days before and 180 days after admission for organ transplantation.
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Fig. 3

Kaplan–Meier Survival for adult HLT recipients by era: January 1982–June 2009. Modified with permission from ISHLT [17]

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Fig. 4

Kaplan–Meier Survival for pediatric HLT recipients by era: January 1982–June 2009. Modified with permission from ISHLT [31]

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Fig. 5

Estimated United States average 2011 transplant costs per member per month in dollars for thoracic transplants and multiorgan transplants. Modified from Bentley & Hanson [9]. S single; B bilateral; H–L heart–lung; H–K heart–kidney; K–P kidney–pancreas; KL kidney–liver, – intestine–other organs; OMO other multiorgan

“Domino” Transplant

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 [6]. The domino procedure continues to be performed but much less frequently than in the past [13, 10, 14, 18, 20, 25, 3537, 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 [3].

Organ Allocation

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 [38].

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 [15]. 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.

Allograft Surveillance

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; [33] 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 [24]. In fact, surveillance endomyocardial biopsy specimens in asymptomatic patients are not recommended at most programs after HLT, particularly after 4–6 months [24]. 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 [28], 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.

Conclusion

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.

Copyright information

© Springer Science+Business Media, LLC 2012