Severe mitral regurgitation unmasked after bilateral lung transplantation

A 33-year-old female patient with advanced idiopathic pulmonary artery hypertension underwent bilateral lung transplantation. The postsurgical course was complicated by prolonged mechanical ventilation and acute hypoxemia with recurrent episodes of pulmonary edema. An echocardiogram revealed improved right-sided pressures along with a dilated left atrium, a structurally normal mitral valve, and a new posterior-oriented severe mitral regurgitation. The patient's condition improved after treatment with arterial vasodilators and diuretics, and she has remained in World Health Organization functional class I after almost 36 months of follow-up. We hypothesize that cardiac ventricle remodeling and a geometric change in mitral valve apparatus after transplantation led to the hemodynamic changes and recurrent pulmonary edema seen in our patient. Our case is, to our knowledge, the second report of severe valvular regurgitation in a structurally normal mitral valve apparatus in the postoperative period and the first of a patient to be treated without valve replacement

Granulocyte/macrophage colony-stimulating factor treatment improves alveolar epithelial barrier function in alcoholic rat lung

Chronic alcohol abuse increases the risk of developing acute lung injury approximately threefold in septic patients, and ethanol ingestion for 6 wk in rats impairs alveolar epithelial barrier function both in vitro and in vivo. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a trophic factor for the alveolar epithelium, and a recent phase II clinical study suggests that GM-CSF therapy decreases sepsis-mediated lung injury. Therefore, we hypothesized that GM-CSF treatment could improve ethanol-mediated defects in the alveolar epithelium during acute stresses such as endotoxemia. In this study, we determined that recombinant rat GM-CSF improved lung liquid clearance (as reflected by lung tissue wet:dry ratios) in ethanol-fed rats anesthetized and then challenged with 2 ml of saline via a tracheostomy tube. Furthermore, GM-CSF treatment improved lung liquid clearance and decreased epithelial protein leak in both control-fed and ethanol-fed rats after 6 h of endotoxemia induced by Salmonella typhimurium lipopolysaccharide given intraperitoneally, but with the greater net effect seen in the ethanol-fed rats. Our previous studies indicate that chronic ethanol ingestion decreases lung liquid clearance by increasing intercellular permeability. Consistent with this, GM-CSF treatment in vitro decreased permeability of alveolar epithelial monolayers derived from both control-fed and ethanol-fed rats. As in the endotoxemia model in vivo, the effect of GM-CSF was most dramatic in the ethanol group. Together, these results indicate that GM-CSF treatment has previously unrecognized effects in promoting alveolar epithelial barrier integrity and that these salutary effects may be particularly relevant in the setting of chronic alcohol abuse

Successful Preoperative Optimization for Lung Transplantation With Transcatheter Mitral Valve Repair

Surgically treatable valvular heart disease is common in patients with end-stage lung disease. Nevertheless, advanced lung disease is often seen as a contraindication to cardiac surgery, and severe valvular disease is seen as a contraindication to lung transplantation. This report describes the case of a patient presenting with very severe chronic obstructive pulmonary disease and severe mitral regurgitation who was managed with transcatheter mitral valve repair and who subsequently underwent successful lung transplantation. Critical valvular heart disease in patients with chronic respiratory failure may be amenable to transcatheter therapy, which may favorably affect lung transplantation candidacy

Unusual indication for extracorporeal membrane oxygenation immediately after successful sequential bilateral lung transplantation: a case report

Ischemia-reperfusion injury-induced primary graft dysfunction after lung transplantation is a major cause of early morbidity and mortality. We report an unusual case of primary graft dysfunction grade III following uneventful off-pump bilateral sequential lung transplantation caused by paradoxical left ventricular failure due to systolic anterior motion of the mitral valve-induced left ventricular outflow tract obstruction. Cardiac failure was precipitated by profound dehydration and administration of high doses of vasopressin and norepinephrine. Immediate connection to extracorporeal membrane oxygenation treated the graft failure-associated respiratory-pulmonary hypoxia and reversed the cardiogenic shock syndrome. Hypovolemia together with a hyperdynamic state resulting from catecholamine administration may result in the development of dynamic left ventricular outflow tract obstruction even if baseline cardiac evaluation is unremarkable. Early detection and intensive efforts to reverse the underlying conditions including cessation of catecholamine therapy and correction of hypovolemia are essential

Outcomes of Delayed Chest Closure After Bilateral Lung Transplantation

Delayed chest closure (DCC) may be used after bilateral lung transplantation when significant bleeding/coagulopathy or severe pulmonary edema exists. Primary chest closure (PCC) in these patients can lead to heart and lung compression causing cardiopulmonary instability. The purpose of this study is to describe factors associated with DCC and evaluate outcomes after DCC. We performed a retrospective review of all patients undergoing bilateral lung transplantation between September 2003 and March 2005. Statistical significance was determined by two-tailed t test or Fisher’s exact test. Twenty-eight bilateral lung transplantations were performed. Indication for transplant was chronic obstructive pulmonary disease (13), pulmonary fibrosis (5), cystic fibrosis (5), sarcoidosis (3), and pulmonary hypertension (1). Seven patients (25%) required DCC. Mean time to DCC was 5.3 days. Six patients (86%) with DCC required tracheostomy versus 4 patients (20%) with PCC ( p = 0.003). Mean days to discharge was 44 in the DCC group and 21 in the PCC group ( p = 0.03). Thirty-day survival was 100% in the DCC group and 95% in the PCC group ( p = 1.0). There were no wound infections in either group, and 1 patient in the PCC group had sternal nonunion. Delayed chest closure was associated with cardiopulmonary bypass use ( p = 0.006), cardiopulmonary bypass time longer than mean cardiopulmonary bypass time (mean, 224 minutes; p = 0.04), PaO 2/FiO 2 less than mean + 1 SD (value = 4.63, p = 0.0002), evidence of moderate/severe reperfusion injury on chest radiograph ( p = 0.0002), and PaO 2/FiO 2 less than mean plus moderate/severe reperfusion injury on chest radiograph ( p = 0.002). Cardiopulmonary bypass use, prolonged cardiopulmonary bypass time, and significant reperfusion injury, as determined by chest radiograph and a low PaO 2/FiO 2 ratio were all associated with an increased incidence of DCC in our bilateral lung transplantation patients. These patients had no wound infections or sternal complications, and although they had longer hospital stays than PCC patients, DCC did not affect operative survival. Delayed chest closure can be employed safely, when necessary, after bilateral lung transplantation with outcomes similar to patients with PCC

Bilateral Lung Transplant With Pulmonary Thromboendarterectomy for Eisenmenger’s Syndrome

Patients with secondary pulmonary hypertension frequently present for evaluation for lung transplantation. In some of these patients, Eisenmenger’s syndrome has developed from chronic left to right intracardiac shunts. A smaller group of these patients will also have associated pulmonary artery aneurysms. There is a paucity of literature discussing this topic, however, and currents reports have suggested the need to replace the abnormal pulmonary artery. This paper discusses a patient in whom Eisenmenger’s syndrome developed from an atrial septal defect, and resultant pulmonary artery aneurysms and mural thrombi, who underwent successful bilateral lung transplantation with thromboendarterectomy and atrial septal defect closure

Angiotensin II mediates glutathione depletion, transforming growth factor-β1 expression, and epithelial barrier dysfunction in the alcoholic rat lung

Alcohol abuse markedly increases the risk of sepsis-mediated acute lung injury. In a rat model, ethanol ingestion alone (in the absence of any other stress) causes pulmonary glutathione depletion, increased expression of transforming growth factor-β1 (TGF-β1), and alveolar epithelial barrier dysfunction, even though the lung appears grossly normal. However, during endotoxemia, ethanol-fed rats release more activated TGF-β1 into the alveolar space where it can exacerbate epithelial barrier dysfunction and lung edema. Ethanol ingestion activates the renin-angiotensin system, and angiotensin II is capable of inducing oxidative stress and TGF-β1 expression. We determined that lisinopril, an angiotensin-converting enzyme inhibitor that decreases angiotensin II formation, limited lung glutathione depletion, and treatment with either lisinopril or losartan, a selective angiotensin II type 1 receptor blocker, normalized TGF-β1 expression. The glutathione precursor procysteine also prevented TGF-β1 expression, suggesting that TGF-β1 may be induced indirectly by angiotensin II-mediated oxidative stress and glutathione depletion. Importantly, lisinopril treatment normalized barrier function in alveolar epithelial cell monolayers from ethanol-fed rats, and treatment with either lisinopril or losartan normalized alveolar epithelial barrier function in ethanol-fed rats in vivo, as reflected by lung liquid clearance of an intratracheal saline challenge, even during endotoxemia. In parallel, lisinopril treatment limited TGF-β1 protein release into the alveolar space during endotoxemia. Together, these results suggest that angiotensin II mediates oxidative stress and the consequent TGF-β1 expression and alveolar epithelial barrier dysfunction that characterize the alcoholic lung

The Role of Donor Chronic Alcohol Abuse in the Development of Primary Graft Dysfunction in Lung Transplant Recipients

Primary graft dysfunction (PGD) following lung transplantation is clinically similar to the acute respiratory distress syndrome. Because alcohol abuse independently increases the incidence of acute respiratory distress syndrome in at-risk individuals, we hypothesized that donor alcohol use is correlated with an increased risk of PGD. As a pilot study, we collected alcohol use histories using a validated instrument, the Alcohol Use Disorder Identification Test questionnaire, from 74 donors and correlated these with the development of PGD in corresponding recipients. Nineteen percent (14/74) of donors were classified as heavy alcohol users, as defined by the Alcohol Use Disorder Identification Test scores ≥8. In the 1st 4 days posttransplantation, similar percentages of recipients developed grade 3 PGD on at least 1 day (heavy alcohol user = 29% [4/14] versus lighter alcohol user = 27% [16/60]); however, recipients receiving a lung from a heavy alcohol user were more likely to have multiple and consecutive days of grade 3 PGD, especially in the 1st 48 hours post-transplant. Both median length of stay in the intensive care unit and hospital were somewhat longer in the heavy alcohol user group (9 versus 7 days and 19.5 versus 17.5 days, respectively). If these preliminary findings are validated in a multi-center study, they would have important implications not only for our understanding of the pathophysiology of PGD but also for the development of novel treatments based on the evolving evidence from experimental and clinical studies on how alcohol abuse renders the lung susceptible to acute edematous injury

Bilateral Lung Transplantation Offers Better Long-Term Survival, Compared With Single-Lung Transplantation, for Younger Patients With Idiopathic Pulmonary Fibrosis

Single-lung transplantation (SLT) and bilateral lung transplantation (BLT) are both good options for patients with end-stage lung disease secondary to idiopathic pulmonary fibrosis. It is, however, unclear whether BLT offers any survival advantage over SLT. The purpose of our study was to evaluate a large group of patients to determine if either SLT or BLT officered a long-term survival advantage for patients with IPF. This was an Institutional Review Board-approved retrospective analysis of the United Network of Organ Sharing database from 1987 to 2008. Survival was determined using Kaplan-Meir estimates and the effect of laterality was determined by Cox proportional hazards and propensity analyses. Lung transplantation for idiopathic pulmonary fibrosis was performed in 3,860 patients (2,431 SLTs and 1429 BLTs). Multivariate and propensity analysis failed to show any survival advantage for BLT (hazard ratio = 0.90, 95% confidence interval = 0.78 to 1.0, p = 0.11). One-year conditional survival favored BLT (hazard ratio 0.73, 95% confidence interval 0.60 to 0.87, p = 0.00064). Risk factors for early death included recipient age over 57 and donor age over 36 years. Bilateral lung transplantation should be considered for younger patients with idiopathic pulmonary fibrosis and results may be optimized when younger donors are used