0038: Addressing the controversy of estimating right ventricular systolic pressure by echocardiography: insights from 307 patients with advanced lung disease or pulmonary arterial hypertension

BackgroundThere is a controversy on the reliability of echocardiography in estimating right ventricular systolic pressure (RVSP) in advanced lung disease (ALD) and idiopathic pulmonary arterial hypertension (PAH) patients. This study aimed to develop a quality control method for echocardiographic RVSP assessment to provide guidance.MethodsWe selected consecutive patients referred from 2001 to 2012 for ALD or PAH, in whom an echocardiogram and a right heart catheterization (RHC) were performed within five days. In order to assess reader level influence on echo interpretation, three levels of readers (multi-reader echo-lab, level 2 and 3) estimated RVSP (based on the tricuspid regurgitation TR maximal velocity). Invasive and non-invasive RVSPs were compared using Pearson’s coefficient and Bland-Altman analysis. PH classification performance was also assessed. Reasons for under- and overestimation were systematically analysed.ResultsAmong the 307 patients included (mean age 50±13, 41% male), two-thirds had pulmonary hypertension (PH). RVSP was measurable in 56% of patients. There was a strong correlation between echo and RHC (r=0.84 for echo-lab; 0.86 level 2 and 0.96 level 3). For PH classification, areas under the curve of level 2 and 3 RVSPs were excellent (0.94 and 0.97);>45mmHg was associated with 86% sensitivity and 100% specificity. No severe PH (mPAP≥35mmHg) was missed. The main reason for underestimation was the absence of a well-defined TR envelope and for overestimation the inability to identify the complete envelope by decreasing the gain.ConclusionEchocardiography’s reliability for RVSP estimation can be improved when careful attention is paid to simple practical signal quality parameters, clearly identified by the present study

Single-institution Study Evaluating the Utility of Surveillance Bronchoscopy After Lung Transplantation

Background: Many lung transplant physicians advocate surveillance bronchoscopy with transbronchial lung biopsy and bronchoalveolar lavage (TBB/BAL) to monitor lung recipients despite limited evidence this strategy improves outcomes. This report compares rates of infection (INF), acute rejection (AR), bronchiolitis obliterans syndrome (BOS) and survival in lung allograft recipients managed with surveillance TBB/BAL (SB) versus those with clinically indicated TBB/BAL (CIB)

Donor-Derived West Nile Virus Infection in Solid Organ Transplant Recipients

We describe four solid-organ transplant recipients with donor-derived West Nile virus (WNV) infection (encephalitis 3, asymptomatic 1) from a common donor residing in a region of increased WNV activity. All four transplant recipients had molecular evidence of WNV infection in their serum and/or cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction (RT-PCR) testing. Serum from the organ donor was positive for WNV IgM but negative for WNV RNA, whereas his lymph node and spleen tissues tested positive for WNV by RT-PCR. Combination therapy included intravenous immunoglobulin (4 cases), interferon (3 cases), fresh frozen plasma with WNV IgG (2 cases), and ribavirin (1 case). Two of the four transplant recipients survived.Review of the 20 published cases of organ-derived WNV infection found that this infection is associated with a high incidence of neuroinvasive disease (70%) and severe morbidity and mortality (30%). Median time to onset of symptomatic WNV infection was 13 days after transplantation (range 5-37 days). Initial unexplained fever unresponsive to antibiotic therapy followed by rapid onset of neurologic deficits was the most common clinical presentation. Confirmation of infection was made by testing serum and CSF for both WNV RNA by RT-PCR and WNV IgM by serological assays. Treatment usually included supportive care, reduction of immunosuppression, and frequent intravenous immunoglobulin. The often negative results for WNV by current RT-PCR and serological assays and the absence of clinical signs of acute infection in donors contribute to the sporadic occurrence of donor-derived WNV infection. Potential organ donors should be assessed for unexplained fever and neurological symptoms, particularly if they reside in areas of increased WNV activity

Fortification of preservation solution with nitroprusside does not alter lung allograft survival in clinical human lung transplantation

Background: Nitric oxide improves gas exchange following primary lung allograft dysfunction. Nitroprusside, a potent nitric oxide donor, has reduced reperfusion injury and improved oxygenation in experimental lung transplantation. Methods: We sought to study the effect on lung allograft outcomes of fortifying the preservation solution with nitroprusside. We conducted a single-center clinical study of 46 consecutive lung recipients between 1998 and 2000: 24 patients received donor organs preserved in modified Euro-Collins solution with prostaglandin E1 (PGE1) (control group), and 22 patients received organs preserved in modified Euro-Collins with PGE1 and nitroprusside (NP group). The primary endpoint was overall survival. Results: Baseline characteristics were similar between the groups except for a significantly longer graft ischemic time in the NP group vs the control group (253.3 +/- 52 vs 225.3 +/- 41 minutes, respectively, P=0.04). No significant differences were found in partial pressure arterial oxygen to fraction inspired oxygen ratio a

Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation

Invasive pulmonary disease due to the mold Aspergillus fumigatus can be life-threatening in lung transplant recipients, but the risk factors remain poorly understood. To study this process, we used a tracheal allograft mouse model that recapitulates large airway changes observed in patients undergoing lung transplantation. We report that microhemorrhage-related iron content may be a major determinant of A. fumigatus invasion and, consequently, its virulence. Invasive growth was increased during progressive alloimmune-mediated graft rejection associated with high concentrations of ferric iron in the graft. The role of iron in A. fumigatus invasive growth was further confirmed by showing that this invasive phenotype was increased in tracheal transplants from donor mice lacking the hemochromatosis gene (Hfe(-/-)). The invasive phenotype was also increased in mouse syngrafts treated with topical iron solution and in allograft recipients receiving deferoxamine, a chelator that increases iron bioavailability to the mold. The invasive growth of the iron-intolerant A. fumigatus double-knockout mutant (Delta sreA/Delta cccA) was lower than that of the wild-type mold. Alloimmune-mediated microvascular damage and iron overload did not appear to impair the host's immune response. In human lung transplant recipients, positive staining for iron in lung transplant tissue was more commonly seen in endobronchial biopsy sections from transplanted airways than in biopsies from the patients' own airways. Collectively, these data identify iron as a major determinant of A. fumigatus invasive growth and a potential target to treat or prevent A. fumigatus infections in lung transplant patients