Lung Transplantation for Pulmonary Hypertension and Strategies to Bridge to Transplant

Abstract

Despite an expanded armamentarium of medical therapies, pulmonary arterial hypertension (PAH) remains a progressive disease associated with significant morbidity and premature mortality. Lung transplantation (LT) is the last safety net for patients failing medical therapy, providing excellent overall long-term survival and health-related quality-of-life outcomes in line with more common parenchymal lung disease indications. Waitlist mortality remains disproportionally elevated, however, reflecting an inability of the lung allocation score to completely capture PAH disease severity, and a propensity for PAH to deteriorate rapidly without warning, even in patients who appear externally “well.” Early referral to a LT center can mitigate these risks and facilitate rapid listing if necessary. Several bridging therapies are available to support severely unwell patients to LT, such as extracorporeal life support (ECLS) and atrial septostomy. Unique perioperative considerations include higher rates of primary graft dysfunction and dynamic right ventricular outflow obstruction which may, at least in part, reflect rapid afterload reduction in the face of a conditioned right ventricle. Extending ECLS into the perioperative period may ameliorate these risks by allowing more gradual adaptation of both ventricles to their new loading conditions. Chronic lung allograft dysfunction, particularly bronchiolitis obliterans syndrome, remains a major cause of long-term morbidity and mortality, and complications from corticosteroid and immunosuppressive therapy are common. Nevertheless, the morbidity, mortality, and burden of disease management after LT continue to improve and compare favorably to that of refractory PAH in carefully selected patients.

Advances in the management of pulmonary arterial hypertension

“…Patients with an estimated 1-year mortality >10% based on a comprehensive assessment should also be considered for lung transplant. [85][86][87] Certain procedures can act as a bridge to transplant or as destination palliative therapy in severe symptomatic PAH. 87 Atrial septostomy is one such intervention, allowing for right heart decompression through creating an iatrogenic shunt.…”

“…[85][86][87] Certain procedures can act as a bridge to transplant or as destination palliative therapy in severe symptomatic PAH. 87 Atrial septostomy is one such intervention, allowing for right heart decompression through creating an iatrogenic shunt. This procedure has been shown to improve functional class, exercise tolerance, symptoms, and even survival.…”

“…Transplant is recommended for patients with PAH who fall into WHO functional class III or IV on maximal medical therapy and patients with rapidly progressive disease, as evidenced by worsening 6 min walk distance, rising NT-proBNP, and worsening RV function and hemodynamics. Patients with an estimated 1-year mortality >10% based on a comprehensive assessment should also be considered for lung transplant 85-87. Certain procedures can act as a bridge to transplant or as destination palliative therapy in severe symptomatic PAH 87.…”

Venoarterial Versus Venovenous Extracorporeal Membrane Oxygenation As Bridge to Lung Transplantation

“…1 Secondary pulmonary arterial hypertension and/or right ventricular dysfunction, which are manifestations of advancedstage disease that require bridge with extracorporeal membrane oxygenation (ECMO), develop in many patients with fibrotic lung diseases awaiting lung transplantation. 2 A large body of data supports the use of ECMO in lung transplant candidates who develop respiratory compromise while waiting for lung trnsplantation. [3][4][5][6][7][8] Most of these studies have used venovenous (VV) ECMO as a bridge to lung transplantation, with favorable outcomes in bridge efficiency and short-and medium-term outcomes.…”