With improvements in the diagnosis and treatment of pulmonary arterial hypertension (PAH) including the use of combination therapy to target multiple pathways of the disease, survival rates have increased over time.1 However, in the significant number of patients with severe PAH who do not adequately respond to medical therapy, lung transplantation is an important option that confers substantial gains in long-term survival and health-related quality of life.
The course of PAH and treatment response are often unpredictable, and patients can appear well even when they have severe disease and right ventricular (RV) dysfunction.2 When the cardiac reserve is depleted, patients can deteriorate quickly and without warning. Thus, clinicians must remain vigilant to “recognize the patient who is deteriorating or not reaching an acceptable therapeutic target, and ensure that they are referred for transplant if potentially eligible,” John Granton, BSc, MD, FRCPC, director of the pulmonary hypertension program and staff physician at Toronto General Hospital in Canada, told Pulmonology Advisor.
Because transplant delays have been implicated in elevated waitlist mortality,3 the program at Toronto General Hospital strongly recommends early referral, which also allows the opportunity for patients and physicians to “deﬁne and mitigate risk factors such as obesity and deconditioning [and] provides time for patients to seek opinions from alternative [lung transplantation] centers if deemed ineligible, given acceptance criteria is often center dependent,” Dr Granton and colleagues stated in a recent paper.4
Evaluation for lung transplantation involves a multidisciplinary assessment of disease severity, expected prognosis, and potential contraindications, as well as hemodynamic, laboratory, and imaging testing. The extent of this process is another reason that early referral is ideal. “Prolonged delays from protracted attempts at medically managing an unstable patient should be avoided,” they noted.
Before the lung allocation score (LAS) was introduced in the United States in 2005, patients were prioritized for lung transplantation based on the length of time they had been on the waiting list. The LAS was intended to reduce the time on the waitlist and associated mortality, ensure the most appropriate allocation of organs, and simplify the overall process. Since its introduction, waitlist placement is based on blood type, size, and LAS, and there have been fewer deaths post-LAS.5
Although the LAS accurately predicts waitlist death, it “lacks capacity to adequately discriminate between high- and low-risk PAH patients, resulting in persistently high waitlist mortality (approximately 20% mortality within 1 year of listing in the United States for idiopathic PAH,” the investigators wrote.6 There are several available bridging therapies that can support unwell patients in the perioperative period. “Bridging of patients on mechanical support can facilitate transition to transplant, potentially allowing for some RV recovery prior to transplantation, and also afford some opportunity for the RV to recover postoperatively,” Dr Granton explained.
Each bridging strategy has strengths and weaknesses and the choice of technique in each patient depends on multiple factors such as disease severity, urgency for organ support, RV function and hemodynamics, comorbidities, and expected length of time until lung transplantation. In addition, the lack of trial data comparing each technique underscores the importance of clinician experience with the chosen technique.
- Extracorporeal life support (ECLS). ECLS is aimed at offloading the RV and avoiding end-organ damage that could preclude lung transplantation. This may be achieved with either extracorporeal membrane oxygenation (ECMO) or the pumpless Novalung. Findings show that ECLS led to reduced death rates for patients with PAH on a lung transplantation waitlist.7 However, its use is generally limited to approximately 2 weeks as complications increase along with the duration of ECLS.
- Advantages of the Novalung vs ECMO “include a low risk [for] cannula dislodgement, which allows mobilization and physiotherapy to proceed in select cases, lower inotrope requirement, and the potential for lengthier support owing to its pumpless setup and the capacity to exchange diffusion membranes at the bedside,” according to the paper. Surgical access via sternotomy or minithoracotomy is the main disadvantage, and temporary ECMO support is needed in some cases to allow establishment of the Novalung configuration.
- Atrial septostomy. A right-to-left interatrial shunt “acts as a ‘blow-off valve’ for the pressure-volume loaded RV, decompressing it while enhancing systemic ﬂow via left ventricular (LV) preload augmentation, at the expense of systemic oxygenation,” wrote the researchers. The use of atrial septostomy as a treatment strategy for PAH has increased, despite a scarcity of clinical data and lack of clarity regarding indications, timing, and techniques used. Data indicate an 86% survival rate in patients undergoing atrial septostomy and 90% of patients experience functional class improvement.8 Atrial septostomy can be used for a much longer duration than ECLS and thus can be initiated earlier.
- Potts anastomosis. This procedure “provides a permanent, posttricuspid right-to-left shunt, thereby ofﬂoading the RV without sacriﬁcing upper body oxygenation,” as described in the paper. The limited data on the technique mostly pertain to pediatric patients, and despite improved function, symptoms, and biomarkers, the associated mortality rates are significant.9 It is unclear whether Potts anastomosis may be a suitable option in adult patients. “While it does not preclude [lung transplantation], has theoretical advantages over [atrial septostomy], and has enduring positive results in select cases, the high associated procedural risk infers primarily a palliative role at this stage.”
The post-transplant 30-day mortality rates in patients with PAH have been reported to be 15.3%, compared with 4.5% in patients with chronic obstructive pulmonary disease without antitrypsin deficiency.10 Primary graft dysfunction (PGD) is the main cause of post-transplant early mortality in PAH. Recent findings point to female gender, African-American descent, elevated body mass index, and the use of cardiopulmonary bypass as risk factors for PGD.
To address the risk for perioperative complications in this patient population, some lung transplantation centers extend the use of ECLS into the post-transplant period. “This varies from center to center. Some centers place all patients with PAH on ECMO after lung transplant,” said Dr Granton. “Others, like our program, make that call on a patient by patient basis, sometimes preoperatively at time of listing or intraoperatively.”
Dr Granton believes that future research in this area should explore “refinements on extracorporeal systems to facilitate bridging — could miniaturization mean that extracorporeal support could be destination therapy for some patients akin to left ventricular devices?” In addition, reducing “primary graft dysfunction and chronic lung allograft dysfunction are ongoing areas of active investigation.”
- McGoon MD, Benza RL, Escribano-Subias P, et al. Pulmonary arterial hypertension: epidemiology and registries. J Am Coll Cardiol. 2013;62(25 Suppl):D51-D59.
- Miller DP, Farber HW. “Who’ll be the next in line?” The lung allocation score in patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2013;32(12):1165-1167.
- Galiè N, Corris PA, Frost A, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D60-D72.
- Baillie TJ, Granton JT. Lung transplantation for pulmonary hypertension and strategies to bridge to transplant. Semin Respir Crit Care Med. 2017;38(5):701-710.
- Egan TM, Edwards LB. Effect of the lung allocation score on lung transplantation in the United States. J Heart Lung Transplant. 2016;35(4):433-439.
- Chen H, Shiboski SC, Golden JA, et al. Impact of the lung allocation score on lung transplantation for pulmonary arterial hypertension. Am J Respir Crit Care Med. 2009;180(5):468-474.
- de Perrot M, Granton JT, McRae K, et al. Impact of extracorporeal life support on outcome in patients with idiopathic pulmonary arterial hypertension awaiting lung transplantation. J Heart Lung Transplant. 2011;30(9):997-1002.
- Sandoval JTA. The right ventricle in health and disease: atrial septostomy. In: Voelkel NF, Schranz D, eds. The Right Ventricle in Health and Disease. New York, NY: Springer; 2015:419-437.
- Baruteau AE, Serraf A, Lévy M, et al. Potts shunt in children with idiopathic pulmonary arterial hypertension: long-term results. Ann Thorac Surg. 2012;94(3):817-824.
- Yusen RD, Edwards LB, Dipchand AI, et al; for the International Society for Heart and Lung Transplantation. 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. J Heart Lung Transplant. 2016;35(10):1170-1184.