Pediatr Transplantation 2014: 18: 204–210
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pediatric Transplantation DOI: 10.1111/petr.12208
Impact of congenital heart disease on outcomes of pediatric heart-lung transplantation Keeshan BC, Goldfarb SB, Lin KY, Kreindler JL, Kaufman BD, Gaynor JW, Shaddy RE, Rossano JW. Impact of congenital heart disease on outcomes of pediatric heart-lung transplantation. Abstract: HLT is reserved for children with cardiopulmonary disease not amendable to alternative therapies. Children with CHD with or without ES may be considered for HLT. Outcomes of HLT in this population are not well described. To test the hypothesis that CHD without ES is associated with worse graft survival and identify factors associated with poor outcome, a retrospective analysis of the UNOS database was performed. One hundred and seventy-eight pediatric HLTs were performed between 1987 and 2011. CHD was the diagnosis in 65 patients, of which 34 had CHD without ES. Patients with CHD without ES had decreased patient survival (median 1.31 yr) compared with CHD with ES (4.80 yr, p = 0.05). On multivariable analysis, the following were associated with graft failure: CHD without ES (adjusted HR 1.69, 95% CI 1.09–2.62), younger age (1.04, 1.01–1.08), pretransplant mechanical ventilation (1.75, 1.01–3.06), pretransplant ECMO (3.07, 1.32–7.12), pretransplant PRAs (1.53, 1.06–2.20), and transplant era (1.85, 1.16–2.94). In children with CHD who require HLT, underlying physiology influences outcomes. Those without ES have a worse prognosis. The diagnosis of CHD without ES and preoperative factors may inform decisions in a complex patient population.
Advancements in the medical and surgical treatment for CHD over recent decades have improved long-term survival of most forms of CHD (1, 2). However, despite major advances in therapeutic management, for a subset population, progressive decline in cardiopulmonary dysfunction may lead to pulmonary hypertension or irreversible parenchymal disease (3, 4). HLT may be considered in patients with end-stage cardiopulmonary disease from CHD with or without ES, as characterized by elevated pulmonary vascular resistance and right-to-left shunting
Abbreviations: ANOVA, analysis of variance; ASD, atrial septal defect; CHD, congenital heart disease; ECMO, extracorporeal membrane oxygenation; ES, Eisenmenger syndrome; HLT, heart-lung transplant; HR, hazard ratios; IPAH, idiopathic pulmonary arterial hypertension; IQR, interquartile range; ISHLT, International Society for Heart and Lung Transplantation; OPTN, Organ Procurement and Transplant Network; PRA, panel-reactive antibodies; UNOS, United Network of Organ Sharing.
204
Britton C. Keeshan1, Samuel B. Goldfarb2, Kimberly Y. Lin3, James L. Kreindler2, Beth D. Kaufman3, James W. Gaynor4, Robert E. Shaddy3 and Joseph W. Rossano3 1
The Children’s Hospital of Philadelphia, Philadelphia, PA, USA, 2Division of Pulmonary Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA, 3Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA, 4Division of Cardiothoracic Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA Key words: congenital heart disease – transplantation – heart-lung – outcomes – pediatric Britton Keeshan, The Children’s Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA 19104, USA Tel.: 215 796 4238 Fax: 215 590 2768 E-mail: [email protected] Accepted for publication 15 November 2013
through a systemic to pulmonary circulatory connection (5), as well as irreversible pulmonary vascular/parenchymal disease not amenable to other therapies (6, 7). However, advances in lung transplantation (8), understanding of generally poor outcomes, and organ shortage (4) have led to decreased numbers of HLTs since its inception in the 1980s. Children undergoing HLT are a heterogeneous population with varying pathologies, ages, co-morbid conditions, and outcomes that create unique issues (7). Demand for thoracic organ transplantation is increasing, while the number of donors remains roughly the same, resulting in longer lists of patients waiting for organs, particularly children (9). Such a setting highlights the need for better understanding of outcomes data. In addition, predictive modeling is needed, both to improve the matching procedure between recipients and grafts (10) and also to provide accurate data for more informed clinical decision making.
CHD and pediatric heart-lung transplantation
While general long-term survival of HLT in the pediatric population mirrors that of the adult and pediatric patients undergoing lung transplantation, condition-specific outcomes in the pediatric population have not been well described. The ISHLT data have suggested comparable outcome data for patients with ES and IPAH, with both groups doing better than the more heterogeneous groups with CHD (11, 12). Although the etiology of poor outcomes in these patients has not been identified, those with CHD in the absence of ES may be at particular risk owing to their complex anatomy, previous surgical palliation, and earlier onset of dysfunction necessitating transplant. To better understand the impact of CHD on pediatric HLT, we sought to describe outcomes of pediatric HLT in patients with CHD, test the hypothesis that CHD without ES has a detrimental effect on long-term graft survival independent of donor and recipient characteristics, and identify predictive parameters associated with poor outcome that may help inform clinical decision making.
for significant contributory variables, were then determined and reported.
Results
There were 178 pediatric HLTs performed between 1987 and 2011. Primary diagnosis leading to listing for HLT is documented in Table 1. Cardiac etiologies accounted for the primary diagnosis in 41.0% (n = 73) of those listed compared with 38.8% (n = 69) with primarily pulmonary diagnosis. IPAH accounted for the majority of the pulmonary indication for HLT and 29% (n = 52) of pediatric HLTs overall. There was no specified diagnosis in 20.2% (n = 36) of pediatric HLTs. Of the primarily cardiac etiologies, CHD was the most common diagnosis (n = 65). CHD was further classified as those with ES versus those without (n = 31 and n = 34, respectively). Overall CHD without ES accounted for 19.1% of all pediatric HLTs between 1987 and 2011.
Table 1. Pediatric heart-lung transplant by diagnosis
Materials and methods The UNOS Database contains data regarding every organ donation and transplant occurring in the United States since the OPTN inception in 1986. We performed a retrospective analysis of the UNOS Database for all pediatric (age 10% ECMO Mechanical ventilation Total bilirubin Creatinine Diagnosis IPAH ES CHD w/o ES Donor CMV+ Donor inotrope (Yes vs. No) Ischemic time 2001 to present vs. 2000 and earlier
0.95 0.99 1.07 1.00 1.23 1.24 3.35 2.64 0.95 0.69
0.92–0.97 0.97–1.01 0.76–1.50 1.00–1.00 0.85–1.79 0.87–1.75 1.69–6.65 1.67–4.17 0.85–1.07 0.39–1.28
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pediatric Transplantation DOI: 10.1111/petr.12208
Impact of congenital heart disease on outcomes of pediatric heart-lung transplantation Keeshan BC, Goldfarb SB, Lin KY, Kreindler JL, Kaufman BD, Gaynor JW, Shaddy RE, Rossano JW. Impact of congenital heart disease on outcomes of pediatric heart-lung transplantation. Abstract: HLT is reserved for children with cardiopulmonary disease not amendable to alternative therapies. Children with CHD with or without ES may be considered for HLT. Outcomes of HLT in this population are not well described. To test the hypothesis that CHD without ES is associated with worse graft survival and identify factors associated with poor outcome, a retrospective analysis of the UNOS database was performed. One hundred and seventy-eight pediatric HLTs were performed between 1987 and 2011. CHD was the diagnosis in 65 patients, of which 34 had CHD without ES. Patients with CHD without ES had decreased patient survival (median 1.31 yr) compared with CHD with ES (4.80 yr, p = 0.05). On multivariable analysis, the following were associated with graft failure: CHD without ES (adjusted HR 1.69, 95% CI 1.09–2.62), younger age (1.04, 1.01–1.08), pretransplant mechanical ventilation (1.75, 1.01–3.06), pretransplant ECMO (3.07, 1.32–7.12), pretransplant PRAs (1.53, 1.06–2.20), and transplant era (1.85, 1.16–2.94). In children with CHD who require HLT, underlying physiology influences outcomes. Those without ES have a worse prognosis. The diagnosis of CHD without ES and preoperative factors may inform decisions in a complex patient population.
Advancements in the medical and surgical treatment for CHD over recent decades have improved long-term survival of most forms of CHD (1, 2). However, despite major advances in therapeutic management, for a subset population, progressive decline in cardiopulmonary dysfunction may lead to pulmonary hypertension or irreversible parenchymal disease (3, 4). HLT may be considered in patients with end-stage cardiopulmonary disease from CHD with or without ES, as characterized by elevated pulmonary vascular resistance and right-to-left shunting
Abbreviations: ANOVA, analysis of variance; ASD, atrial septal defect; CHD, congenital heart disease; ECMO, extracorporeal membrane oxygenation; ES, Eisenmenger syndrome; HLT, heart-lung transplant; HR, hazard ratios; IPAH, idiopathic pulmonary arterial hypertension; IQR, interquartile range; ISHLT, International Society for Heart and Lung Transplantation; OPTN, Organ Procurement and Transplant Network; PRA, panel-reactive antibodies; UNOS, United Network of Organ Sharing.
204
Britton C. Keeshan1, Samuel B. Goldfarb2, Kimberly Y. Lin3, James L. Kreindler2, Beth D. Kaufman3, James W. Gaynor4, Robert E. Shaddy3 and Joseph W. Rossano3 1
The Children’s Hospital of Philadelphia, Philadelphia, PA, USA, 2Division of Pulmonary Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA, 3Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA, 4Division of Cardiothoracic Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA Key words: congenital heart disease – transplantation – heart-lung – outcomes – pediatric Britton Keeshan, The Children’s Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA 19104, USA Tel.: 215 796 4238 Fax: 215 590 2768 E-mail: [email protected] Accepted for publication 15 November 2013
through a systemic to pulmonary circulatory connection (5), as well as irreversible pulmonary vascular/parenchymal disease not amenable to other therapies (6, 7). However, advances in lung transplantation (8), understanding of generally poor outcomes, and organ shortage (4) have led to decreased numbers of HLTs since its inception in the 1980s. Children undergoing HLT are a heterogeneous population with varying pathologies, ages, co-morbid conditions, and outcomes that create unique issues (7). Demand for thoracic organ transplantation is increasing, while the number of donors remains roughly the same, resulting in longer lists of patients waiting for organs, particularly children (9). Such a setting highlights the need for better understanding of outcomes data. In addition, predictive modeling is needed, both to improve the matching procedure between recipients and grafts (10) and also to provide accurate data for more informed clinical decision making.
CHD and pediatric heart-lung transplantation
While general long-term survival of HLT in the pediatric population mirrors that of the adult and pediatric patients undergoing lung transplantation, condition-specific outcomes in the pediatric population have not been well described. The ISHLT data have suggested comparable outcome data for patients with ES and IPAH, with both groups doing better than the more heterogeneous groups with CHD (11, 12). Although the etiology of poor outcomes in these patients has not been identified, those with CHD in the absence of ES may be at particular risk owing to their complex anatomy, previous surgical palliation, and earlier onset of dysfunction necessitating transplant. To better understand the impact of CHD on pediatric HLT, we sought to describe outcomes of pediatric HLT in patients with CHD, test the hypothesis that CHD without ES has a detrimental effect on long-term graft survival independent of donor and recipient characteristics, and identify predictive parameters associated with poor outcome that may help inform clinical decision making.
for significant contributory variables, were then determined and reported.
Results
There were 178 pediatric HLTs performed between 1987 and 2011. Primary diagnosis leading to listing for HLT is documented in Table 1. Cardiac etiologies accounted for the primary diagnosis in 41.0% (n = 73) of those listed compared with 38.8% (n = 69) with primarily pulmonary diagnosis. IPAH accounted for the majority of the pulmonary indication for HLT and 29% (n = 52) of pediatric HLTs overall. There was no specified diagnosis in 20.2% (n = 36) of pediatric HLTs. Of the primarily cardiac etiologies, CHD was the most common diagnosis (n = 65). CHD was further classified as those with ES versus those without (n = 31 and n = 34, respectively). Overall CHD without ES accounted for 19.1% of all pediatric HLTs between 1987 and 2011.
Table 1. Pediatric heart-lung transplant by diagnosis
Materials and methods The UNOS Database contains data regarding every organ donation and transplant occurring in the United States since the OPTN inception in 1986. We performed a retrospective analysis of the UNOS Database for all pediatric (age 10% ECMO Mechanical ventilation Total bilirubin Creatinine Diagnosis IPAH ES CHD w/o ES Donor CMV+ Donor inotrope (Yes vs. No) Ischemic time 2001 to present vs. 2000 and earlier
0.95 0.99 1.07 1.00 1.23 1.24 3.35 2.64 0.95 0.69
0.92–0.97 0.97–1.01 0.76–1.50 1.00–1.00 0.85–1.79 0.87–1.75 1.69–6.65 1.67–4.17 0.85–1.07 0.39–1.28
