Pulmonary arterial hypertension (PAH) causes pulmonary vascular remodeling and increases pulmonary vascular resistance. The rise in right ventricular afterload can cause right heart failure, which is a leading cause of death in these patients. PAH may be idiopathic, heritable, or associated with connective tissue diseases or congenital heart diseases and driven by drug or toxin exposure. The goal of the medical therapy for PAH is to achieve a low-risk status (either through the REVEAL Risk Score or European Society of Cardiology/European Respiratory Society model) for one-year mortality.1–2 For patients with PAH who fail medical therapy and remain in the New York Heart Association III/IV functional class, lung transplantation remains the only definitive treatment.3–4
In patients with PAH, early referrals for lung transplantation is encouraged. This provides an opportunity to target modifiable risk factors, complete the evaluation, and optimize candidacy (comorbid conditions, health maintenance). This gives patients time to establish a therapeutic relationship and grasp the complexities of the process and the outcomes.
1. What are the main indications for extracorporeal life support (ECLS) in patients with PAH awaiting lung transplantation?
ECLS is primarily indicated in patients with PAH with refractory right ventricular (RV) failure who are listed for lung transplantation and experience hemodynamic instability or hypoxemia despite maximal medical therapy.5 The need for ECLS arises when there is evidence of end-organ dysfunction, persistent low cardiac output, or severe hypoxemia that cannot be managed with pharmacologic interventions alone.6
Early identification of patients at risk for acute decompensation is critical, as timely initiation of ECLS can stabilize patients and serve as a bridge to transplantation. Extracorporeal membrane oxygenation (ECMO) should be considered in transplant candidates with rapidly deteriorating clinical status or those with acute RV failure unresponsive to medical therapy. ECLS is not recommended for patients without an anticipated recovery or planned use as bridge to transplant, as it does not provide long-term benefit in this context.7–8
2. Which types of mechanical circulatory support (MCS) are most commonly used in patients with PAH undergoing lung transplantation, and what are their relative advantages?
The trend in expert centers is toward routine use of ECMO as the first-line MCS for patients with PAH undergoing lung transplantation. ECMO bridge to lung transplant is associated with 90% posttransplant survival rates with careful patient selection and timely provision of MCS.5
Various MSC strategies include
- ECMO: both venoarterial (VA) ECMO and venovenous (VV) ECMO
- Right ventricular assist devices (RVADs)
- Atrial septostomy (mostly as a palliative strategy)
The most commonly used MCS modalities in this setting is VA-ECMO. It is preferred owing to its ability to provide both respiratory and hemodynamic support, reduce RV afterload, and facilitate intraoperative and postoperative management. Postoperative ECMO may mitigate the risk of primary graft dysfunction (PGD) and support graft function during the critical early posttransplant period.5,9
3. How does preoperative right heart function influence the need for MCS during lung transplantation in PAH?
Preoperative right heart function is a key determinant of intraoperative and postoperative MCS requirements. Echocardiographic parameters such as elevated RV systolic pressure, increased tricuspid regurgitation pressure gradient, reduced tricuspid annular plane systolic excursion, and enlarged pulmonary artery diameter are included as predictive parameters of the need for MCS.
Patients with more severe RV dysfunction and higher pulmonary pressures are more likely to require intraoperative ECMO to maintain hemodynamic stability during transplantation. These parameters can also help identify patients at higher risk of perioperative mortality as well as guide transplant candidacy decisions.10
4. What are the intraoperative considerations for MCS in patients with PAH during lung transplantation?
Intraoperative management focuses on maintaining hemodynamic stability, minimizing RV strain, and ensuring adequate oxygenation. VA-ECMO is typically initiated prior to explantation of the native lungs to offload the RV and maintain systemic perfusion. Careful monitoring of coagulation parameters, including thromboelastography, volume status, and oxygen delivery, is essential. The transition off ECMO support to graft function must be gradual to prevent acute graft dysfunction. The choice of cannulation strategy (central vs peripheral) is individualized based on patient anatomy and surgical approach.5–6
5. What are the postoperative benefits and risks of ECMO support following lung transplantation in PAH?
Postoperative ECMO can reduce the incidence and severity of primary graft dysfunction by providing ongoing support during the period of maximal reperfusion injury risk and allow lung protective ventilation as well as reduce airway complications.5–6,11 It allows for gradual adaptation of the transplanted lungs to the recipient’s circulation and supports RV recovery.
However, ECMO carries risks including bleeding, infection, thromboembolism, and limb ischemia. The decision to continue ECMO postoperatively is based on intraoperative hemodynamics, graft function, and RV performance. In experienced centers, ECMO has been shown to improve early outcomes and may enhance long-term survival in this high-risk population.5,12
6. How does the use of MCS impact survival and long-term outcomes following lung transplantation for PAH?
The use of ECMO as intraoperative and postoperative support has been associated with improved early survival and reduced incidence of severe PGD. One-year survival rates in experienced centers now exceed 80% to 90% for patients with PAH undergoing lung transplantation with ECMO support.12 However, long-term outcomes remain less favorable than for other transplant indications, with persistent risks of chronic rejection and late graft failure. The high perioperative risk profile of patients with PAH highlights the importance of specialized multidisciplinary care and individualized perioperative management strategies.
7. What are the key challenges and complications associated with MCS in patients with PAH undergoing lung transplantation?
Key challenges include managing coagulopathy, bleeding, infection, and thromboembolic events related to ECMO. Patients with PAH are particularly susceptible to RV failure, PGD, and hemodynamic instability during the perioperative period. PGD, especially grade 3, has been reported, contributing to early morbidity and mortality.13 Meticulous anticoagulation management, infection prophylaxis, and vigilant monitoring for device-related complications are essential. The complexity of these cases necessitates care in high-volume centers with expertise in both lung transplantation and MCS.
8. What do current guidelines recommend regarding the timing of referral and listing for lung transplantation in patients with PAH, and how does this relate to MCS utilization?
Early referrals for lung transplantation are recommended in patients with PAH who remain at intermediate or high risk despite optimized medical therapy. Predictors of poor prognosis, such as advanced functional class and adverse hemodynamics, should prompt timely listing.3
Early identification and listing allow for planned use of MCS as a bridge to transplant rather than as an emergency intervention, which is associated with better outcomes.14–15 Delayed referral increases the risk of acute decompensation and emergent MCS, which carries higher morbidity and mortality.16
References
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10. Expert Consensus Panel, Hartwig M, van Berkel V, et al. The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: The use of mechanical circulatory support in lung transplantation. J Thorac Cardiovasc Surg. 2023;165(1):301-326. doi:10.1016/j.jtcvs.2022.06.024
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12. Kolaitis NA. Lung transplantation for pulmonary arterial hypertension. Chest. 2023;164(4):992-1006. doi:10.1016/j.chest.2023.04.021
13. Takahashi T, Terada Y, Pasque MK, et al. Outcomes of extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation. Ann Thorac Surg. 2023;115(5):1273-1280. doi:10.1016/j.athoracsur.2022.09.048
14. Vicaire H, Pavec JL, Mercier O, et al. Risk stratification in patients with pulmonary arterial hypertension at the time of listing for lung transplantation. J Heart Lung Transplant. 2022;41(9):1285-1293. doi:10.1016/j.healun.2022.05.013
15. Savale L, Benazzo A, Corris P, et al. Transplantation, bridging, and support technologies in pulmonary hypertension. Eur Respir J. 2024;64(4):2401193. doi:10.1183/13993003.01193-2024
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