Background
Despite recent advances in medical management, pulmonary arterial hypertension (PAH) remains a severe and progressive disease with per-year mortality approaching 15%. Progression of the disease is marked by right ventricular failure as the predominant cause of death. Histological findings in PAH include evidence of vascular remodeling, including intimal hyperplasia, medial hypertrophy and fibrosis, endothelial cell dysfunction, and inflammation. Recent studies have hypothesized a role for abnormal fatty acid metabolism and lipid deposition in both heart and lung tissue as a marker for progression of disease, although the precise relationship is unknown.
Lung transplantation remains the only curative treatment for patients with end-stage chronic respiratory failure. With demand for organs greatly outnumbering supply, patients qualifying for lung transplantation face long wait times, and high peri-operative morbidity and morality. Here, we describe the case of a 34 year old female with a history of idiopathic PAH (iPAH) who under-went bilateral lung transplantation at our institution (UCLA), following a 34-day course of VA–ECMO, with a discussion of histological features of her explanted lung tissue.
Case Description:
A 34 y/o female with a history of iPAH and hyperparathyroidism underwent bilateral lung transplantation at UCLA. The patient was admitted with severe decompensated heart failure, and despite escalation of medical management, underwent three PEA arrests resulting in the initiation of urgent VA ECMO.
While awaiting a suitable donor organ, the patient developed C. difficile colitis, GI bleed, spontaneous subdural hematoma, and thromboembolic complications. Following 34 days of VA ECMO, the patient underwent bilateral lung transplantation and tricuspid annuloplasty, with intra-operative course notable for evidence of an aortic thrombus on TEE and severe coagulopathy post cardiopulmonary bypass requiring massive transfusion, including receiving PCC and recombinant Factor VII. Post-operatively the patient developed severe lactic acidosis on POD#1 and was started on CRRT. She was extubated on POD #3, but had aphonia and weak cough, and was re-intubated on POD #4, and underwent percutanous tracheostomy the same day. Post-operative ultrasound imaging showed evidence of splenic and hepatic lobe infarcts. Post-operative transthoracic echocardiography revealed significantly improved RV and RA size, mildly reduced RV systolic function, and normal LV function. The patient was de-cannulated to room air on post-operative day 29, and discharged on post-operative day 36.
Discussion:
We reviewed the histology from explanted lungs and PA of this patient (Fig. 1), which demonstrated fibrosis (1a, 1c), smooth muscle proliferation (1a, 1b), and lipid deposition in the PA (1d). This patient was an example of the ability to use ECMO as a bridge to lung transplantation, which has become more common in high-volume transplant centers, due to the benefits of avoiding intubation and sedation. An awareness of consequences of prolonged ECMO, including thromboembolic complications and profound intraoperative coagulopathy is critical to patient management. This case highlights the importance of interdisciplinary coordination between cardiac surgeons, intensivists, and cardiac anesthesiologists in the management of complicated patients. We also take a precision medicine approach to investigate the pathophysiologic signature of the disease by doing histologic analysis of the lungs and PA.
