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When One Plus One Does Not Equal Two

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Jorge Silva Enciso, MD
University of California San Diego
San Diego, CA, USA

Combined heart and lung transplantation has been sought as the therapeutic option for patients with advanced pulmonary vascular disease including congenital heart disease, fixed pulmonary hypertension with elevated pulmonary vascular resistance (PVR) or idiopathic pulmonary arterial hypertension. The recent ISHTL registry data contains more than 3800 combined heart-lung transplants (HLT) worldwide but the number of HLT performed has decreased in recent years probably due to advances in technology and pharmacological treatments for such patients. Many patients with fixed or irreversible pulmonary hypertension from left heart disease for example are candidates to receive a ventricular assist device as a bridge to transplant with the goal of reducing PVR. Patients with IPAH are improving quality of life, functional class and survival with targeted medical therapy. For CHD patients, however therapeutic options are limited once advanced heart failure occurs. The ISHLT registry notes that CHD is increasingly one of the most common reasons for HLT (35% for CHD, 27% for IPAH and 11% for cardiomyopathy) although survival for HLT has been lower compared to heart or lung transplant alone (HLT survival: 71% at 3 months and 63% at 1 year; lung transplant: 89% at 3 months and 80% at 1 year; heart transplant: 89% at 3 months and 85% at 1 year based on registry 2009-2014 data) [1]. Why is it then that despite adding 2 organs survival is still poor? To date there is paucity of data related to the risk factors associated with mortality in HLT. Some registry studies have found preoperative factors that may impact postoperative outcomes. Kadakia et al. analyzed the long and short term survival of 571 HLT recipients from the United Network for Organ Sharing database over the 1993-2009 era. Forty-six percent survived more than 5 years while 54% survive less than 5 years. The results of the analysis showed that male recipient increase the 1 year mortality risk by almost 2-fold. However, the more significant factors associated with 1 year mortally were those patients that underwent preoperative extracorporeal membrane oxygenation (ECMO) with a 7.55 hazard ratio and mechanical ventilation with 3.5 hazard ratio [2]. These findings are not surprising as patients awaiting HLT are a severely complex and sick population that need additional support-mechanical, ventilator, dialysis prior to transplant compared to heart transplant or lung transplant alone recipients. Unfortunately, these measures can increase risk for adverse postoperative outcomes including death. Several causes of death in the early post-transplant period have been found in HLT recipients. Among them, primary graft failure (PGF) is one of the most common ones with 29% of all HLT recipients developing PGF. Other significant causes include technical complications, cardiovascular and multi-organ failure. Related to graft failure possible causes may be due to acute rejection, primary graft dysfunction or other factors early post-transplant. Among factors linked to acute rejection, male gender, CMV positivity, donor infection and class I PRA greater than 10% have been found to be prognostic [2]. In CHD patients undergoing heart transplant, comparable risk factors have been found associated with early post-transplant mortality including donor-recipient CMV mismatch and elevated PRA. The latter is a common finding in CHD patients as many of them have pre-formed HLA antibodies likely from prior corrective or palliative cardiac surgeries which in turn lengthens operative and allograft ischemic time during transplant surgery. Moreover, the perioperative use of ECMO in this high-risk group is not an uncommon practice that increases overall operative time [3]. Perhaps then, the elevated rate of PGF in the HLT cohort could be related to the elevated number of post-op complications seen early after transplant. The rates of reoperation, need for blood products and dialysis are higher in CHD patients than non-CHD adding further to the risk of future antibody formation in this group [4, 5]. Moreover, ISHLT registry data denote PGF, technical complications and multi-organ failure as the highest causes of death for CHD patients undergoing HLT. Such worrisome outcomes are of concern for future organ allocation of this high-risk population. As the adult CHD population continues to increase and becomes the predominant reason for HLT, we need to be attentive to when appropriately or timely refer patients for HLT and identify the risk factors that increase morbidity and mortality post-HLT. More studies are needed to identify and develop risk stratifying tools based not only on donor or recipient characteristics but also on type of CHD anatomy. Once we recognize the prognostic factors, we will be able to adequately select patients, plan operative needs to reduce postop complications, reduce prolonged ischemic times and tailor immunosuppression for both organs whilst improving survival. ■

Disclosure Statement: The author has no conflicts of interest to disclose.


  1. Yusen RD, Edwards LB, Dipchand AI et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart-Lung Transplant Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2016;35:1170-1184.
  2. Kadakia S, Taghavi S, Jayarajan S et al. Examining Mortality and Rejection in Combined Heart-Lung Transplantations. Thorac Cardiovasc Surg 2017.
  3. Patel ND, Weiss ES, Allen JG et al. Heart transplantation for adults with congenital heart disease: analysis of the United network for organ sharing database. Ann Thorac Surg 2009;88:814-21; discussion 821-2.
  4. Goldberg SW, Fisher SA, Wehman B, Mehra MR. Adults with congenital heart disease and heart transplantation: optimizing outcomes. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2014;33:873-7.
  5. Bhama JK, Shulman J, Bermudez CA et al. Heart transplantation for adults with congenital heart disease: results in the modern era. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2013;32:499-504.

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