Treatment with epoprostenol of pulmonary arterial hypertension following mitral valve replacement for mitral stenosis.

Pulmonary hypertension frequently complicates mitral stenosis. Increased pulmonary artery pressure results from raised left atrial pressure, pulmonary arteriolar constriction, and obliterative changes in the pulmonary vascular bed, and usually responds to surgical relief of mitral stenosis. However, severe pulmonary hypertension may persist after surgical treatment of mitral stenosis. We describe a patient whose severe pulmonary hypertension following mitral valve replacement was treated successfully with continuous intravenous epoprostenol.

Scintigraphic diagnosis of a right to left shunt in end-stage lung disease.

PURPOSE: The presence of a right to left shunt influences the surgical approach to lung transplantation in patients with end-stage pulmonary disease. The purposes of this study included comparing contemporaneous lung scintigraphy with cardiac catheterization in the detection of intracardiac shunts in patients with end-stage lung disease and the point prevalence of right to left shunting was determined in patients with several different types of end-stage lung disease. METHODS: Hundred and twenty six patients with end-stage lung disease who were candidates for lung transplantation underwent perfusion images of the lungs with Tc-99m-labeled macro-aggregated albumin (MAA). Planar scans of the brain and the kidneys were performed contemporaneously. Statistical analyses included correlation ofthe clinical, laboratory and scintigraphic variables. Group means were compared with the students t-test (two-tailed P-value). RESULTS: There were 21 patients with primary pulmonary hypertension (PPH), 72 with emphysematous lung disease (COPD), 22 with pulmonary fibrotic disease (PF) and 11 with congenital heart disease (CHD) leading to pulmonary hypertension. Only 13 patients (10.3%) were found to have a right to left shunt. Of these, 4 had PPH, 2 had PF, and 7 had CHD. No shunts were found in patients with emphysema. All the positive studies had abnormally increased activity in both the brain and the kidneys. However, there were 25 cases with renal activity and none of these patients had brain activity or clinical evidence of a shunt. Increased pulmonary artery pressure was associated with scintigraphic presence of a shunt. There were no cases of a right to left shunt with a mean pulmonary artery pressure less than 50 mm Hg. In the subset of patients with a pulmonary pressure greater than 50 mm Hg, approximately 40% of the patients had a right to a left shunt. There were no measurable differences in the spirometry results, right ventricular ejection fraction (RVEF) or left ventricular ejection fraction (LVEF) in the subgroup of patients with PPH and right to left shunt in comparison with patients with PPH but without a right to left shunt. CONCLUSIONS: The findings indicate that images of the brain, but not the kidneys, are an effective way to diagnose extrapulmonary right to left shunts in patients with end-stage pulmonary disease. The problem of a right to left shunt is uncommon in patients with emphysematous lung disease and relatively common in patients with primary pulmonary hypertension.

Bronchogenic carcinoma complicating lung transplantation.

BACKGROUND: Malignancy is a well-recognized complication of solid-organ transplantation. Although a variety of malignancies have been reported in lung transplant recipients, a paucity of information exists regarding the incidence and clinical course of bronchogenic carcinoma in this patient population. METHODS: We conducted a retrospective cohort study of our lung transplant experience at the University of Pennsylvania. RESULTS: We identified 6 patients with bronchogenic carcinoma detected at the time of, or developing after, transplantation. The incidence of bronchogenic carcinoma was 2.4%. All patients with lung cancer had a history of smoking, with an average of 79 +/- 39 pack-years. A total of 5 patients had chronic obstructive pulmonary disease, and 1 had idiopathic pulmonary fibrosis. Lung cancers were all of non-small-cell histology and first developed in native lungs. Three patients had bronchogenic carcinoma at the time of surgery. The remaining 3 patients were diagnosed between 280 and 1,982 days post-transplantation. Of the 6 patients, 4 presented with a rapid course suggestive of an infectious process. The 1- and 2-year survival rates after diagnosis were 33% and 17%, respectively. CONCLUSION: Lung transplant recipients are at risk for harboring or developing bronchogenic carcinoma in their native lungs. Rapid progression to locally advanced or metastatic disease commonly occurs, at times mimicking an infection. Bronchogenic carcinoma should be considered in the differential diagnosis of pleuroparenchymal processes involving the native lung.

Subcutaneous phaeohyphomycotic cysts caused by Exophiala jeanselmei in a lung transplant patient.

BACKGROUND: Phaeohyphomycosis is a skin fungal infection caused by dematiaceous fungi that often affects immunocompromised patients. Local recurrence after medication or surgical treatment is common in these patients. We present a case in which a 42-year-old woman status post-bilateral lung transplant developed phaeohyphomycotic cysts with local recurrence and then was successfully treated by local excision with pre- and postsurgery oral itraconazole treatment. OBJECTIVE: To demonstrate the utility of pre- and postsurgery oral itraconazole in immunocompromised patients with recurrent phaeohyphomycosis. METHODS: Local excision with pre- and postsurgery oral itraconazole treatment. RESULTS: Simple excision or excision with postsurgery oral itraconazole resulted in local recurrence in this patient. Local excision with pre- and postsurgery oral itraconazole was effective in preventing the local recurrence. CONCLUSION: Phaeohyphomycosis can run a prolonged course in immunocompromised patients with multiple recurrences. Local excision with pre- and postsurgery oral itraconazole can be used to treat these patients with recurrent phaeohyphomycosis.

Recreational use of aminorex and pulmonary hypertension.

Pulmonary hypertension has been associated with ingestion of the appetite suppressant aminorex. A similar compound, 4-methyl-aminorex (street names, "U-4-E-uh" [pronounced euphoria] or "ice"), is a "designer" drug with central stimulant activity. This drug was discovered on the property of three individuals with diagnoses of pulmonary hypertension. The association between "recreational" aminorex manufacture and ingestion and the development of pulmonary hypertension is described.

Fatal hyperammonemia after orthotopic lung transplantation.

BACKGROUND: A case of fatal hyperammonemia complicating orthotopic lung transplantation was previously reported. OBJECTIVE: To describe the incidence, clinical features, and treatment of hyperammonemia associated with orthotopic lung transplantation. DESIGN: Retrospective cohort analysis. SETTING: Academic medical center and lung transplantation center in Philadelphia, Pennsylvania. PATIENTS: 145 sequential adult patients who underwent orthotopic lung transplantation. MEASUREMENTS: Plasma ammonium levels. RESULTS: Six of the 145 patients who had had orthotopic lung transplantation developed hyperammonemia, all within the first 26 days after transplantation. The 30-day post-transplantation mortality rate was 67% for patients with hyperammonemia compared with 17% for those without hyperammonemia (P = 0.01). Development of major gastrointestinal complications (P = 0.03), use of total parenteral nutrition (P < 0.001), and lung transplantation for primary pulmonary hypertension (P = 0.045) were associated with hyperammonemia. CONCLUSIONS: Hyperammonemia is a potentially fatal event occurring after orthotopic lung transplantation. It is associated with high nitrogen load, concurrent medical stressors, primary pulmonary hypertension, and hepatic glutamine synthetase deficiency.

Hyperacute rejection of a pulmonary allograft. Immediate clinical and pathologic findings.

The clinical and pathologic findings seen in hyperacute rejection are well documented in renal and cardiac allografts. We describe the second case of hyperacute rejection in a pulmonary allograft and detail the immediate clinicopathologic findings. The patient underwent a single lung transplant for severe COPD with postoperative course complicated by acute rejection and graft failure. Eleven days later, the patient underwent a second transplant with intra-operative course complicated by rapid pulmonary edema and copious production of frothy, pink fluid from the bronchial orifice of the allograft followed by death within four hours of anastomoses. Intraoperative biopsy and autopsy demonstrated platelet/fibrin thrombi, marked interstitial neutrophilia, alveolar edema, and antibody deposition on the endothelial surface and vasculature walls. Prior to the first transplant, the patient's serum had 0% panel reactive antibody and was crossmatch compatible with the first allograft. The patient's serum prior to the second transplant contained cross-reacting antibodies to the donor's B and T lymphocytes. The immediate clinical findings in this case are similar to the findings in a previously reported case. This report is the first documentation of the immediate pathologic features of hyperacute rejection in a lung allograft which are similar to those seen with other organ allografts.

Pulmonary hypertension in collagen vascular disease.

Pulmonary hypertension associated with collagen vascular disease often eludes diagnosis, sometimes causing considerable morbidity or even death before being identified. This review details its characteristic clinical features, appropriate diagnostic and treatment approaches, and expected outcomes.

Extrinsic compression of the left main coronary artery by the pulmonary artery in patients with long-standing pulmonary hypertension.

Left main coronary artery compression by the pulmonary artery may be seen in patients with pulmonary hypertension who are undergoing cardiac catheterization. Cardiac magnetic resonance imaging is useful in these patients to document extrinsic compression, which might otherwise be mistaken for intrinsic atherosclerotic disease.

Giant gastric ulcers and risk factors for gastroduodenal mucosal disease in orthotopic lung transplant patients.

Giant gastric ulcers are defined as ulcers with a diameter greater than 3 cm. Previously they have not been described in lung transplant recipients. We report a high incidence of symptomatic giant gastric ulcers and identify the risk factors for ulcer development in these patients. We examined the records of all 95 patients who had undergone lung transplantation at our institution from November 1991 to July 1995. Fourteen of the patients who underwent lung transplantation developed symptoms that required esophagogastroduodenoscopy. Three of these patients (21%) were found to have giant gastric ulcers. The relative risk of giant gastric ulcer in symptomatic patients undergoing endoscopy after lung transplantation is over 40 times that of population controls. The patients who developed giant gastric ulcers, despite H2 antagonist use, had all received bilateral lung transplantation and had received nonsteroidal antiinflammatory drugs, cyclosporine, and high-dose intravenous corticosteroids. The risk of developing giant gastric ulcers is significantly increased in patients who have undergone bilateral orthotopic lung transplantation. Clinicians should be made aware of this complication in order to avoid use of ulcerogenic medications in this population. Avoidance of these medications could potentially minimize the risk of this complication.

Reperfusion edema after thromboendarterectomy: radiographic patterns of disease.

In patients with chronic pulmonary embolism, pulmonary thromboendarterectomy may result in a unique form of noncardiogenic pulmonary edema termed reperfusion edema. This report reviews the authors' experience after pulmonary thromboendarterectomy with particular emphasis on the radiographic manifestations of reperfusion edema. The clinical and radiographic record of 25 patients who underwent pulmonary thromboendarterectomy at the University of Pennsylvania from 1985 through 1995 were reviewed. The zonal distribution of radiographic opacity, time to maximal opacity, and the time to clearance of reperfusion edema were determined. The relationship of these radiographic manifestations to clinical severity of disease and clinical outcome was examined. Reperfusion edema, characterized by patchy bilateral perihilar alveolar opacities, occurred in all but one patient. There is a lower lung zone predominance of opacities, but in individual cases, striking unilateral or haphazard arrangements of opacities may be seen. In this small sample of patients, no association between preoperative pulmonary arterial pressures and radiographic appearance or clinical outcome was found. However, severity of radiographic opacities, as measured by the extent of involved lung, correlated with disease severity, as measured by time to extubation and time to discharge. Pneumonia, defined as a radiographic opacity that evolves discordantly with the reperfusion edema opacities, occurred in 20% of cases. Reperfusion edema is a common consequence of pulmonary thromboendarterectomy. The severity of radiographic manifestations and clinical severity of disease are related. This characteristically appears as perihilar alveolar opacities.

Primary graft failure following lung transplantation.

STUDY OBJECTIVES: To determine the incidence of primary graft failure (PGF) following lung transplantation, assess possible risk factors, and characterize its effect on outcomes. METHODS: Retrospective review of 100 consecutive patients undergoing lung transplantation at the University of Pennsylvania Medical Center. Fifteen patients meeting diagnostic criteria for PGF (PGF+ group) were compared with 85 patients without this complication (PGF- group). RESULTS: The incidence of PGF was 15%. There was no significant difference in age, sex, underlying pulmonary disease, preoperative pulmonary artery systolic pressure, type of transplant, allograft ischemic times, use of cardiopulmonary bypass, or use of postoperative prostaglandin E1 infusion between the PGF+ and PGF- groups. Induction therapy with antilymphocyte globulin was used less frequently in the PGF+ group (p<0.005). Duration of mechanical ventilatory support was 36+/-43 days vs 4+/-6 days for the PGF+ and PGF- groups, respectively (p<0.0001). Hospital stay was significantly longer in the PGF+ group, averaging 75+/-105 days, compared with 27+/-38 days in the PGF group (p<0.005). One-year actuarial survival for the PGF+ group was only 40% compared with 69% for the PGF- group (p<0.005). Five of the six PGF+ survivors were ambulatory by 1 year; three were completely independent while two continued to require assistance with activities of daily living. Six-minute walk test distance among the ambulatory patients averaged 883+/-463 feet (range, 200 to 1,223 feet) compared with 1513+/-424 feet for the PGF- group (p<0.005). Among the subset of survivors who underwent single lung transplantation for COPD, the mean percent predicted FEV1 at 1 year was 43% for the PGF+ group and 55% for the PGF- groups, but this difference was not statistically significant. CONCLUSIONS: PGF is a devastating postoperative complication, occurring in 15% of patients in the current series, and it is associated with a high mortality rate, lengthy hospitalization, and protracted and often compromised recovery among survivors.

Comparison of short-term functional outcomes following unilateral and bilateral lung volume reduction surgery.

STUDY OBJECTIVES: To compare short-term functional outcomes following unilateral and bilateral lung volume reduction surgery (LVRS) performed in patients with advanced emphysema. METHODS: LVRS was performed unilaterally in 32 patients and bilaterally in 119 patients. Pulmonary function testing and 6-min walk test (6MWT) were performed preoperatively and repeated at 3 to 6 months postoperatively. RESULTS: Bilateral LVRS was associated with increased in-hospital mortality (10% vs 0%, p<0.05) and a higher incidence of postoperative respiratory failure (12.6% vs 0%; p<0.05) compared with unilateral LVRS. There was no significant difference in duration of air leaks between unilateral and bilateral groups, but the mean hospital stay was significantly longer following bilateral LVRS (21.1+/-32.0 days vs 14.2+/-14.0 days; p<0.05). Preoperatively, there was no significant difference between the unilateral and bilateral groups with respect to FEV1, FVC, residual volume, or 6MWT distance. However, for all of these parameters, the magnitude of improvement was significantly greater following bilateral LVRS. Notably, the magnitude of improvement in each parameter following unilateral LVRS exceeded half that following bilateral LVRS, suggesting that functional outcomes after the unilateral procedure were disproportionate to the amount of tissue resected. Serial functional assessment of seven patients undergoing staged unilateral procedures (two unilateral procedures separated in time by at least 3 months) demonstrated somewhat unpredictable responses; failure to achieve a favorable response to the initial procedure did not necessarily portend a similar outcome with the contralateral side, and vise versa. CONCLUSIONS: Bilateral LVRS produces a greater magnitude of short-term functional improvement than does the unilateral procedure and should be considered the procedure of choice for most patients. Unilateral LVRS should be reserved for patients in whom factors contraindicating entrance into one hemithorax exist.

Effect of volume reduction on lung transplant timing and selection for chronic obstructive pulmonary disease.

BACKGROUND: End-stage chronic obstructive pulmonary disease has traditionally been treated with lung transplantation. For 2 years, our lung transplantation program has placed patients with appropriate criteria for lung transplantation and volume reduction into a prospective management algorithm. These patients are offered the lung volume reduction option as a "bridge" to "extend" the eventual time to transplantation. We examine the results of this pilot program. METHODS: From October 11, 1993, to April 17, 1997, 31 patients were evaluated for lung transplantation who also had physiologic criteria for volume reduction (forced expiratory volume in 1 second < or = 25%; residual volume > 200%; significant ventilation/perfusion heterogeneity). All patients completed 6 weeks of pulmonary rehabilitation and then had baseline pulmonary function and 6-minute walk tests. These patients were then offered volume reduction as a "bridge" and were simultaneously listed for transplantation. Postoperatively, these 31 patients were then divided into two groups: Those with satisfactory results at 4 to 6 months after volume reduction and those with unsatisfactory results. Volume reduction was performed through a video thoracic approach in 87% of the patients and bilateral median sternotomy in the remaining 13%. The condition of the patients was monitored after the operation with repeated pulmonary function tests and 6-minute walk tests at 3-month intervals. RESULTS: Twenty-four of 31 patients (77.4%) had primary success (at 4 to 6 months) results after lung volume reduction and 7 patients (22.6%) had primary failure, including 1 patient who died in the perioperative period (3.2%). Four patients (16.7%) from the primary success cohort had significant deterioration in their pulmonary function during intermediate-term follow-up and were then reconsidered for lung transplantation. Two of them have subsequently undergone transplantation with good postoperative pulmonary function results. Interestingly, three patients had alpha 1-antitrypsin deficiency; two had a poor outcome of lung volume reduction and primary failure. CONCLUSIONS: Lung volume reduction in these patients is safe. Seventy-seven percent of otherwise suitable candidates for lung transplantation achieved initial good results from volume reduction and were deactivated from the list (placed on status 7). Most patients entering our prospective management algorithm have either significantly delayed or completely avoided lung transplantation after volume reduction. Lung volume reduction has substantially affected the practice, timing, and selection of patients for lung transplantation. Our waiting list now has a reduced percentage of patients with a diagnosis of chronic obstructive pulmonary disease compared with 3 years ago. Our experience suggests that lung volume reduction may be limited as a "bridge" in alpha 1-antitrypsin deficiency.

Right ventricular regional function using MR tagging: normals versus chronic pulmonary hypertension.

Right ventricular (RV) regional function, in both normal and diseased states, is not well characterized. Using 1D MR myocardial tagging, RV and septal intramyocardial segmental shortening was noninvasively measured in ten healthy subjects and in seven patients with chronic pulmonary hypertension. The normal RV free wall regional shortening was not uniform. A pattern of increasing RV free wall short-axis shortening was found from the RV outflow tract to the RV apex, and a more complex pattern of RV free wall long-axis shortening was observed. Both regional short- and long-axis shortening were globally reduced in pulmonary hypertension patients, with the greatest decreases in the RV outflow tract and in the basal septal wall region. Regional RV function can be quantitatively evaluated using MR tagging to determine the impact of chronic pulmonary hypertension on RV performance.

Therapeutic options for severe pulmonary hypertension.

Pulmonary hypertension occurs as a consequence of numerous and varied conditions, all of which result in an elevation of pulmonary vascular resistance. Over the past decade, significant progress has been made in understanding the factors which contribute to the progressive nature of pulmonary vascular disease, and in identifying new treatments for pulmonary hypertension. The majority of these therapeutic options are pharmacologic, but for specific circumstances, surgical therapy may be a consideration. This article discusses nonspecific therapies for all patients with pulmonary hypertension, vasodilator therapy (including screening for vasodilator responsiveness, standard oral agents, and newer intravenous or inhalational therapies) and surgical options applicable to specific situations.