In a national analysis of more than 900 patients with primary pulmonary arterial hypertension (PAH), bilateral lung transplantation was associated with survival outcomes comparable to heart-lung transplantation, supporting its role as the preferred strategy for most patients without structural cardiac disease, according to a Journal of Heart and Lung Transplantation study.1
Using data from the United Network for Organ Sharing registry, investigators identified 914 adults who underwent transplantation for PAH between 2004 and 2022, including 776 who received bilateral lung transplants and 138 who underwent combined heart-lung transplantation. Heart-lung transplantation is typically reserved for patients with structural or irreversible cardiac disease, though practice patterns vary by center. The primary outcome was all-cause mortality at one year, with five-year mortality as a secondary end point.
One- and five-year survival were similar between groups. These findings remained consistent across subgroups stratified by cardiac index, including patients with more severely reduced cardiac output at listing, suggesting that even patients with advanced hemodynamic compromise did not derive a clear survival advantage from dual-organ transplantation.
“Among patients with advanced PAH referred for transplantation, there is often true clinical equipoise when choosing between bilateral lung transplantation and heart-lung transplantation, particularly when the likelihood of right ventricular recovery is uncertain,” said Baharan Zarrabian, DO, MPH, on behalf of the research team. “Overall, our findings support bilateral lung transplantation as an effective treatment for the majority of patients with PAH.”
Early postoperative courses differed between groups. Bilateral lung recipients were more likely to require extracorporeal membrane oxygenation (ECMO) and prolonged intubation at 72 hours. The investigators noted that higher early ECMO use in the bilateral lung cohort likely reflects the time required for right ventricular recovery following isolated lung transplantation. ECMO use at 72 hours was associated with increased mortality in the overall cohort.
During follow-up, overall mortality was approximately 44%. Although a greater proportion of deaths occurred among heart-lung recipients, overall survival did not differ significantly between groups. All reported retransplantations occurred in patients who initially underwent bilateral lung transplantation, though the authors cautioned that this finding may reflect differences in patient selection rather than true differences in graft durability.
Dr. Zarrabian said the research also highlights broader system-level implications. Preferential use of bilateral lung transplantation in appropriate candidates may help preserve scarce donor hearts for patients with primary cardiac disease while maintaining comparable long-term survival. In a resource-constrained transplant environment, such allocation considerations remain clinically relevant.
For Laura Kathleen Frye, MD, FCCP, Co-Chair of the joint CHEST/American Thoracic Society Clinical Practice Committee and Member-at-Large of the Lung Transplant Section, the results reinforce current practice.
“Clinically, the central takeaway is that bilateral lung transplantation can serve as the default strategy for most patients with primary PAH who do not have structural heart disease,” Dr. Frye said. “Even among patients with lower cardiac index, there was no survival advantage to heart-lung transplantation.”
She added that the findings support the concept that right ventricular dysfunction in PAH is primarily afterload-driven and reversible following normalization of pulmonary vascular resistance.
“Severe hemodynamics alone should not automatically mandate dual organ transplant,” Dr. Frye said. “The study reinforces existing decision-making rather than redefining it, providing outcome-level validation for a widely used strategy.”
Several limitations merit consideration. As an observational registry-based analysis, the study is subject to residual confounding and potential confounding by indication, as organ allocation decisions are center-specific. Detailed echocardiographic measures of ventricular function were not available, limiting comparison of cardiac dysfunction across groups.
Dr. Frye also noted potential era effects. The study spans nearly two decades, during which PAH therapies, organ allocation policies, and perioperative management, including ECMO strategies, have evolved. More recent transplants also lacked complete long-term follow-up.
“As such, the results reflect aggregate experience across eras and should be confirmed in modern cohorts,” she said.
Looking ahead, the investigators noted ongoing uncertainty.
“Significant uncertainties persist, particularly regarding how to identify patients with advanced PAH and occult cardiomyopathy who are unlikely to derive sufficient benefit from bilateral lung transplantation alone,” Dr. Zarrabian said, adding that greater reliance on advanced diagnostic modalities to predict reversibility of right ventricular dysfunction may help refine transplant selection.
For now, the findings suggest that in the absence of structural heart disease, bilateral lung transplantation offers survival comparable to heart-lung transplantation for most patients with primary PAH.
References
1. Zarrabian B, Pennington KM, Cajigas HR, et al. Comparative outcomes of bilateral lung and heart-lung transplantation in primary pulmonary arterial hypertension: a UNOS database study. J Heart Lung Transplant. Published online December 16, 2025. doi:10.1016/j.healun.2025.11.028
