Review Article
Heart-lung transplantation: pediatric indications and outcomes Jonathan E. Spahr, Shawn C. West Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA; University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA Correspondence to: Jonathan E. Spahr, MD. Clinical Director, Pediatric Pulmonology, Children’s Hospital of Pittsburgh of UPMC. Associate Professor of Pediatrics, University of Pittsburgh School of Medicine, 4221 Penn Avenue, Pittsburgh, PA 15224, USA. Email: [email protected]; Shawn C. West, MD. Assistant Professor of Pediatrics, University of Pittsburgh School of Medicine. Heart and Heart-Lung Transplantation, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Email: [email protected].
Abstract: As indications for heart-lung transplant (HLT) have changed to some degree in the past 30 years, this treatment is being used less frequently in children due to more advanced care of severe heart and lung disease. This is fortunate as the outcomes for HLT are poor compared to other solid organ transplants and this is mainly due to the poorer outcome of the lung graft. Keywords: Heart-lung transplant (HLT); pediatric; indications; outcomes Submitted Jan 21, 2014. Accepted for publication Jun 23, 2014. doi: 10.3978/j.issn.2072-1439.2014.07.05 View this article at: http://dx.doi.org/10.3978/j.issn.2072-1439.2014.07.05
Indications for pediatric heart lung transplantation (HLT) The first HLT was performed in 1981 for a patient with primary pulmonary hypertension (PPHN) (1). The second HLT was performed for Eisenmenger’s syndrome with unrepaired congenital heart disease. Indications for HLT remain similar today (2). Combined heart double lung transplant is typically offered in cases with end-stage dysfunction of both the heart and the lungs (3). Multi-organ transplantation comes with increased risk to the patient and so heart transplantation (HT) or double lung transplantation (DLT) is considered instead of HLT and preferred when only one organ is affected to the extent of causing end-stage disease. HLT was performed in infants in the 1980s and 1990s for technical reasons instead of isolated heart or lung transplants, but this practice has largely disappeared as technical issues have been overcome with advances in surgery and greater expertise (4). In cases where patients have end-stage lung disease associated with or causing cardiac dysfunction, congenital heart disease with pulmonary hypertension, or congenital heart disease associated with pulmonary artery/ vein abnormalities, HLT may be indicated (5,6). HLT may also be considered for retransplantation following either HT or lung transplantation. In the case of pulmonary
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hypertension, if cardiac function is preserved, DLT alone is indicated. In the case of pulmonary hypertension with severe right heart failure or left heart failure, HLT would then be indicated. It should be stressed that each case needs to be considered carefully and each organ closely scrutinized to determine the need for transplantation. The ability of the right heart to recover function can be difficult to predict and needs to have careful consideration when deciding the best option for the patient (HLT or DLT) (7). Care must be individualized as there are cases in which the stress of transplanting the “end-stage” organ would further compromise the function of the other and so it would be in the patient’s best interest to perform HLT. Evaluation for HLT typically occurs when a patient has an underlying disease compromising cardiac and pulmonary function and has a predicted survival of less than two years due to that underlying disease. A predicted survival of greater than two years would suggest that a patient would not derive a survival benefit from HLT and should not be listed for HLT given current outcomes (3). HLT is most indicated when patients have a survival expectancy of a few months to a year. Survival expectancy of less than a few months risks death while awaiting transplantation due to current wait times on the HLT list. Requiring inotropic support, mechanical ventilation, and/or mechanical circulatory support prior to transplant also lowers survival
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J Thorac Dis 2014;6(8):1129-1137
Spahr and West. Pediatric heart-lung transplant: indications/outcomes
1130
Table 1 Indications for heart lung transplant by year of age from 1988-2013 Age 5 (N = 66) (N=66)
2013 JHLT. 2013 Oct; 32(10): 989-997
Figure 2 From the ISHLT data report (3). Pediatric HLT leading causes of death. Notice that lung allograft failure from Bronchiolitis is quite prevalent after 1 year whereas cardiovascular death is relatively rare.
HLT success, surveillance of the transplanted lungs with lung function, bronchoscopy, biopsy, and radiographs (often CT scanning) is important in the post-transplant period (18-23). Examinations, echocardiograms and evaluation of exercise capacity are also used to evaluate the heart graft health. Allograft rejection of the heart graft in HLT occurs less often than with HT alone (24). Therefore, rejection following HLT is most likely to occur in the lung graft. Surveillance endomyocardial biopsies are not indicated except in cases where heart rejection is suspected from cardiac studies and/or transbronchial lung biopsies are contraindicated. Monitoring for complications from immunosuppressive regimens include screening for systemic hypertension, renal insufficiency, hypercholesterolemia, diabetes, and osteoporosis (25). Finally, monitoring for conditions that are more prevalent in transplanted individuals such as post-transplant lymphoproliferative disease (PTLD) and malignancy are also of great importance (26). The immunosuppressive regimen for any transplant that involves the lung is more intense because of the greater possibility for rejection of the lung graft. Because of this, complications that come from the immunosuppressive regimen and PTLD/malignancy need to be monitored for frequently and carefully. Because the monitoring is extensive and complications are common in the post-
© Pioneer Bioscience Publishing Company. All rights reserved.
transplant period, many transplant experts counsel patients prior to transplant that having the procedure is like “trading one disease for another” (27). Furthermore, these outcomes have significant impact on the timing and decision to transplant as lung transplantation should occur when it is absolutely necessary in order to maximize the benefit of the transplant. Bronchiolitis obliterans (BO) and infection have the greatest impact on long-term survival, and constant exposure of the lung to ambient air as well as aspiration of upper airway and/or refluxed gastroesophageal secretions are likely the major contributors to graft failure and death. BO is the pathologic mechanism by which chronic rejection occurs in the lung. Because of its significant prevalence and tendency to relentlessly progress, BO claims the lives of most individuals who survive the early post-operative period (28). This is the case for DLT and so this is why HLT survival primarily is dependent upon the lung graft. Figure 2 illustrates the impact that BO has in mortality following HLT and the relative non-impact that cardiovascular disease has on mortality. One can also see the impact that infection has on mortality. Again, this is due to the intensity of the immunosuppressive regimen needed to preserve lung graft health and prevent rejection. There are, however, two other factors that may affect survival of the HLT differently from DLT alone. These are
www.jthoracdis.com
J Thorac Dis 2014;6(8):1129-1137
Journal of Thoracic Disease, Vol 6, No 8 August 2014
A
1135
Pediatric heart-lung transplants kaplan-meier survival (Transplants: January 1982 – June 2011) 100
< 11(N = 21) < (N=21) 1-5 (N = 104) 1-5 (N=104) 6-10 (N = 127) 6-10 (N=127) 11-17 (N = 417) 11-17 (N=417)
Survival (%)
75
Median survival survival (years):
Heart-lung transplantation: pediatric indications and outcomes Jonathan E. Spahr, Shawn C. West Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA; University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA Correspondence to: Jonathan E. Spahr, MD. Clinical Director, Pediatric Pulmonology, Children’s Hospital of Pittsburgh of UPMC. Associate Professor of Pediatrics, University of Pittsburgh School of Medicine, 4221 Penn Avenue, Pittsburgh, PA 15224, USA. Email: [email protected]; Shawn C. West, MD. Assistant Professor of Pediatrics, University of Pittsburgh School of Medicine. Heart and Heart-Lung Transplantation, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Email: [email protected].
Abstract: As indications for heart-lung transplant (HLT) have changed to some degree in the past 30 years, this treatment is being used less frequently in children due to more advanced care of severe heart and lung disease. This is fortunate as the outcomes for HLT are poor compared to other solid organ transplants and this is mainly due to the poorer outcome of the lung graft. Keywords: Heart-lung transplant (HLT); pediatric; indications; outcomes Submitted Jan 21, 2014. Accepted for publication Jun 23, 2014. doi: 10.3978/j.issn.2072-1439.2014.07.05 View this article at: http://dx.doi.org/10.3978/j.issn.2072-1439.2014.07.05
Indications for pediatric heart lung transplantation (HLT) The first HLT was performed in 1981 for a patient with primary pulmonary hypertension (PPHN) (1). The second HLT was performed for Eisenmenger’s syndrome with unrepaired congenital heart disease. Indications for HLT remain similar today (2). Combined heart double lung transplant is typically offered in cases with end-stage dysfunction of both the heart and the lungs (3). Multi-organ transplantation comes with increased risk to the patient and so heart transplantation (HT) or double lung transplantation (DLT) is considered instead of HLT and preferred when only one organ is affected to the extent of causing end-stage disease. HLT was performed in infants in the 1980s and 1990s for technical reasons instead of isolated heart or lung transplants, but this practice has largely disappeared as technical issues have been overcome with advances in surgery and greater expertise (4). In cases where patients have end-stage lung disease associated with or causing cardiac dysfunction, congenital heart disease with pulmonary hypertension, or congenital heart disease associated with pulmonary artery/ vein abnormalities, HLT may be indicated (5,6). HLT may also be considered for retransplantation following either HT or lung transplantation. In the case of pulmonary
© Pioneer Bioscience Publishing Company. All rights reserved.
hypertension, if cardiac function is preserved, DLT alone is indicated. In the case of pulmonary hypertension with severe right heart failure or left heart failure, HLT would then be indicated. It should be stressed that each case needs to be considered carefully and each organ closely scrutinized to determine the need for transplantation. The ability of the right heart to recover function can be difficult to predict and needs to have careful consideration when deciding the best option for the patient (HLT or DLT) (7). Care must be individualized as there are cases in which the stress of transplanting the “end-stage” organ would further compromise the function of the other and so it would be in the patient’s best interest to perform HLT. Evaluation for HLT typically occurs when a patient has an underlying disease compromising cardiac and pulmonary function and has a predicted survival of less than two years due to that underlying disease. A predicted survival of greater than two years would suggest that a patient would not derive a survival benefit from HLT and should not be listed for HLT given current outcomes (3). HLT is most indicated when patients have a survival expectancy of a few months to a year. Survival expectancy of less than a few months risks death while awaiting transplantation due to current wait times on the HLT list. Requiring inotropic support, mechanical ventilation, and/or mechanical circulatory support prior to transplant also lowers survival
www.jthoracdis.com
J Thorac Dis 2014;6(8):1129-1137
Spahr and West. Pediatric heart-lung transplant: indications/outcomes
1130
Table 1 Indications for heart lung transplant by year of age from 1988-2013 Age 5 (N = 66) (N=66)
2013 JHLT. 2013 Oct; 32(10): 989-997
Figure 2 From the ISHLT data report (3). Pediatric HLT leading causes of death. Notice that lung allograft failure from Bronchiolitis is quite prevalent after 1 year whereas cardiovascular death is relatively rare.
HLT success, surveillance of the transplanted lungs with lung function, bronchoscopy, biopsy, and radiographs (often CT scanning) is important in the post-transplant period (18-23). Examinations, echocardiograms and evaluation of exercise capacity are also used to evaluate the heart graft health. Allograft rejection of the heart graft in HLT occurs less often than with HT alone (24). Therefore, rejection following HLT is most likely to occur in the lung graft. Surveillance endomyocardial biopsies are not indicated except in cases where heart rejection is suspected from cardiac studies and/or transbronchial lung biopsies are contraindicated. Monitoring for complications from immunosuppressive regimens include screening for systemic hypertension, renal insufficiency, hypercholesterolemia, diabetes, and osteoporosis (25). Finally, monitoring for conditions that are more prevalent in transplanted individuals such as post-transplant lymphoproliferative disease (PTLD) and malignancy are also of great importance (26). The immunosuppressive regimen for any transplant that involves the lung is more intense because of the greater possibility for rejection of the lung graft. Because of this, complications that come from the immunosuppressive regimen and PTLD/malignancy need to be monitored for frequently and carefully. Because the monitoring is extensive and complications are common in the post-
© Pioneer Bioscience Publishing Company. All rights reserved.
transplant period, many transplant experts counsel patients prior to transplant that having the procedure is like “trading one disease for another” (27). Furthermore, these outcomes have significant impact on the timing and decision to transplant as lung transplantation should occur when it is absolutely necessary in order to maximize the benefit of the transplant. Bronchiolitis obliterans (BO) and infection have the greatest impact on long-term survival, and constant exposure of the lung to ambient air as well as aspiration of upper airway and/or refluxed gastroesophageal secretions are likely the major contributors to graft failure and death. BO is the pathologic mechanism by which chronic rejection occurs in the lung. Because of its significant prevalence and tendency to relentlessly progress, BO claims the lives of most individuals who survive the early post-operative period (28). This is the case for DLT and so this is why HLT survival primarily is dependent upon the lung graft. Figure 2 illustrates the impact that BO has in mortality following HLT and the relative non-impact that cardiovascular disease has on mortality. One can also see the impact that infection has on mortality. Again, this is due to the intensity of the immunosuppressive regimen needed to preserve lung graft health and prevent rejection. There are, however, two other factors that may affect survival of the HLT differently from DLT alone. These are
www.jthoracdis.com
J Thorac Dis 2014;6(8):1129-1137
Journal of Thoracic Disease, Vol 6, No 8 August 2014
A
1135
Pediatric heart-lung transplants kaplan-meier survival (Transplants: January 1982 – June 2011) 100
< 11(N = 21) < (N=21) 1-5 (N = 104) 1-5 (N=104) 6-10 (N = 127) 6-10 (N=127) 11-17 (N = 417) 11-17 (N=417)
Survival (%)
75
Median survival survival (years):
