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Biomedical subjects

John V Conte

Publications and source records attributed to John V Conte.

At least 37 records · Page 2Linked to original sources

Mild vs severe pulmonary hypertension before heart transplantation: different effects on posttransplantation pulmonary hypertension and mortality.

BACKGROUND: Pulmonary hypertension (PH) is common in severe heart failure, but the effect of mild PH on posttransplantation PH and survival after heart transplantation has not been well described. METHODS: This cohort study examined preoperative and postoperative hemodynamics in 172 heart transplant recipients at Johns Hopkins Hospital followed for up to 15.1 years. PH was defined as pulmonary vascular resistance > or =2.5 Wood units, as measured during routine right heat catheterization; mild to moderate PH was defined as PVR between 2.5 and 4.9 Wood units; and severe PH was defined as PVR > or =5.0 Wood units. RESULTS: Seventy-one patients (41.3%) had PH, mostly of mild/moderate severity (77.5%), at the last routine hemodynamic monitoring before transplantation (median time before transplantation, 2.7 months). During follow-up, 105 patients (62.9%) developed PH at some point after transplantation, and 48 patients died (cumulative incidence, 76.5%). Mild/moderate preoperative PH was associated with increased risk of posttransplantation PH at 1, 3, and 6 months, but not with later episodes of PH. Mild/moderate preoperative PH was not associated with a higher mortality rate, but each 1 Wood unit increase in preoperative PVR demonstrated a trend toward increased mortality. Severe preoperative PH was associated with death within the first year after adjusting for potential confounders, but not with overall mortality or mortality at other time points. CONCLUSIONS: Mild to moderate preoperative PH is associated with increased risk of developing early but not late posttransplantation PH and may suggest different management strategies. Although PH was not consistently associated with mortality, increasing severity of the preoperative PH suggests potentially worse prognosis.

Academic Medical Centers↗

Impact of secondary pulmonary hypertension on lung transplant outcome.

INTRODUCTION: Secondary pulmonary hypertension (SPH), defined as a mean pulmonary artery pressure (PAM) greater than 25 mm Hg, complicates end-stage lung diseases of varying etiology. Although previous studies have suggested that SPH does not adversely affect outcome, no study has assessed the impact of the degree of SPH. METHODS: A retrospective review of the lung transplant database was used to identify patients who underwent either single-lung (SLT) or bilateral lung transplantation (BLT) complicated by SPH. SPH patients were stratified into low SPH (PAM = 30-40 mm Hg) and high SPH (PAM > or = 40 mm Hg). Each group was further sub-categorized into SLT or BLT. Patients with a heart-lung transplant or primary pulmonary hypertension were excluded. Recipients without pulmonary hypertension transplanted over the same time were used as controls. Data are reported as controls vs low SPH vs high SPH. RESULTS: One hundred-four patients received lung transplants between August 1998 and March 2003. There were 45 patients (18 men and 27 women) with SPH. Of these, 28 patients had low SPH, and 17 patients had high SPH. Forty-two patients (18 men and 24 women) without PH were the controls. There were no significant differences between groups except pre-operative oxygen dependence (81% vs 100% vs 94%, respectively) and use of CPB (28.6% vs 57.1% vs 64.7%, respectively). PAO2-PaO2 gradients and PaO2/FIO2 ratios were significantly worse in the high SPH group (116.2 vs 132.9 vs 186.3; p < 0.006) and (277.8 vs 234.3 vs 214.4; p < 0.026) respectively. There was no statistical difference in length of mechanical ventilation or duration of intensive care unit stay between groups. PAMs were significantly different pre-operatively (22.2 +/- 0.8 vs 34.0 +/- 0.6 vs 47.8 +/- 2.0; p < 0.001) and post-operatively (20.9 +/- 1.1 vs 23.7 +/- 1.3 vs 24.8 +/- 2.1; p < 0.001). There were no operative deaths. There were 3 early deaths in the control group, 1 in the low SPH group, and 3 in the high SPH group, none were related to pulmonary hypertension. Actuarial survival at 12, 24, and 48 months was not significantly different among the groups nor between SLT or BLT with SPH. CONCLUSION: Although SPH increases the risk of reperfusion injury; survival is equivalent with mild or moderate pulmonary hypertension. Either SLT or BLT may be used in patients with SPH without compromising outcome. This has the added benefit of expanding the donor pool.

Adult↗

Antibody-mediated rejection in human cardiac allografts: evaluation of immunoglobulins and complement activation products C4d and C3d as markers.

Antibody-mediated rejection (AMR) in human heart transplantation is an immunopathologic process in which injury to the graft is in part the result of activation of complement and it is poorly responsive to conventional therapy. We evaluated by immunofluorescence (IF), 665 consecutive endomyocardial biopsies from 165 patients for deposits of immunoglobulins and complement. Diffuse IF deposits in a linear capillary pattern greater than 2+ were considered significant. Clinical evidence of graft dysfunction was correlated with complement deposits. IF 2+ or higher was positive for IgG, 66%; IgM, 12%; IgA, 0.6%; C1q, 1.8%; C4d, 9% and C3d, 10%. In 3% of patients, concomitant C4d and C3d correlated with graft dysfunction or heart failure. In these 5 patients AMR occurred 56-163 months after transplantation, and they responded well to therapy for AMR but not to treatment with steroids. Systematic evaluation of endomyocardial biopsies is not improved by the use of antibodies for immunoglobulins or C1q. Concomitant use of C4d and C3d is very useful to diagnose AMR, when correlated with clinical parameters of graft function. AMR in heart transplant patients can occur many months or years after transplant.

Biomarkers↗

Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy.

BACKGROUND: Gene expression profiling refines diagnostic and prognostic assessment in oncology but has not yet been applied to myocardial diseases. We hypothesized that gene expression differentiates ischemic and nonischemic cardiomyopathy, demonstrating that gene expression profiling by clinical parameters is feasible in cardiology. METHODS AND RESULTS: Affymetrix U133A microarrays of 48 myocardial samples from Johns Hopkins Hospital (JHH) and the University of Minnesota (UM) obtained (1) at transplantation or left ventricular assist device (LVAD) placement (end-stage; n=25), (2) after LVAD support (post-LVAD; n=16), and (3) from newly diagnosed patients (biopsy; n=7) were analyzed with prediction analysis of microarrays. A training set was used to develop the profile and test sets to validate the accuracy of the profile. An etiology prediction profile developed in end-stage JHH samples was tested in independent samples from both JHH and UM with 100% sensitivity and 100% specificity in end-stage samples and 33% sensitivity and 100% specificity in both post-LVAD and biopsy samples. The overall sensitivity was 89% (95% CI 75% to 100%), and specificity was 89% (95% CI 60% to 100%) over 210 random partitions of end-stage samples into training and test sets. Age, gender, and hemodynamic differences did not affect the profile's accuracy in stratified analyses. Select gene expression was confirmed with quantitative polymerase chain reaction. CONCLUSIONS: Gene expression profiling accurately predicts cardiomyopathy etiology, is generalizable to samples from separate institutions, is specific to disease stage, and is unaffected by differences in clinical characteristics. This strongly supports ongoing efforts to incorporate expression profiling-based biomarkers in determining prognosis and response to therapy in heart failure.

Adult↗

Antithymocyte globulin is associated with complement deposition in cardiac transplant biopsies.

Polyclonal antithymocyte globulin preparations contain antibodies with reactivity to endothelial cells. Therefore, we investigated whether treatment with this reagent caused complement deposition in human cardiac transplants. Frozen tissue was available from endomyocardial biopsies of 75 patients, who were transplanted between April 1995 and April 2000. Nine of these patients were converted from cyclosporin A (CsA) to horse antithymocyte globulin (ATGAM) in the first month after transplantation. All of the biopsies were stained by immunofluorescence for C4d as evidence of activation of the classical pathway of complement. In addition, biopsies from patients treated with ATGAM and control patients were stained for deposition of horse immunoglobulin (Ig)G. All nine patients who received ATGAM had deposition of horse IgG and C4d. Two color stains demonstrated that the horse IgG colocalized with the C4d staining. No staining for horse IgG or C4d was evident in biopsies obtained before ATGAM treatment. Likewise, no staining for horse IgG was detected in seven control patients who had C4d staining. Most patients treated with ATGAM had no histologic evidence of rejection, but did have myocyte damage and macrophage infiltration. Thus prophylactic treatment with ATGAM is associated with the deposition of horse IgG and activation of complement in the transplant.

Animals↗

Mycotic aortocoronary saphenous vein graft aneurysm presenting with unstable angina pectoris.

We report the case of a 60-year-old man with a history of coronary bypass surgery 20 years prior who had a fever, chest pain, and a mediastinal mass develop after a complicated postoperative course of abdominal aortic aneurysm resection. A mycotic aneurysm of the saphenous vein graft to his left anterior descending coronary artery was diagnosed based on blood culture results and visualization of the aneurysm before resection. A summary of the saphenous vein graft aneurysm and pseudoaneurysm cause, diagnosis, and management is detailed.

Abdominal Abscess↗

The course of neurofibromatosis type 1 on immunosuppression after lung transplantation: report of 2 cases.

We describe 2 patients with neurofibromatosis type 1 (NF1) who underwent lung transplantation. Case 1 reports a patient with NF1 with no complications 5 years after bilateral lung transplantation. Case 2 details a patient with NF1 diagnosed with both post-transplant lymphoproliferative disorder (PTLD) and massive intra-abdominal sarcoma consistent with a malignant nerve sheath tumor 9 months after lung transplantation. There was no clinical evidence of sarcoma preceding or immediately following lung transplant as demonstrated by a normal abdominal sonogram 3 months post-transplantation. Although an increased risk for cancer has been documented in NF1, the rapid malignant degeneration of a neurofibroma following transplantation raises concern about immunosuppression and transplantation candidacy among individuals with NF1.

Abdominal Neoplasms↗

Impact of 24 h continuous hypothermic perfusion on heart preservation by assessment of oxidative stress.

INTRODUCTION: Despite investigating numerous solutions, additives, and techniques over the last two decades, extending donor heart preservation beyond 4-6 h has not been achieved. Hypothermic heart preservation (HP) induces oxidative stress (OS) with reactive oxygen species (ROS) production, causing DNA cleavage and impairing repair. Quantification of cardiomyocyte concentrations of DNA damage by-products (8-oxoG) and mismatch repair enzymes (MYH, OGG-1, MSH2) reflects the severity of OS. If increased repair enzyme production is insufficient to repair injury, cell death occurs and functional outcomes are impacted. We investigated continuous hypothermic perfusion (CHP), a new form of HP, and the mechanism of injury associated with hypothermic storage, by assessing functional outcome and OS after allotransplantation of canine hearts. METHODS: Fourteen canine hearts were harvested using standard techniques after baseline echocardiograms and haemodynamic parameters were obtained. The hearts were implanted after 24 h CHP (n = 10) or 4 h static preservation (SP; n = 4). After weaning from cardiopulmonary bypass (CPB), recipients were kept alive for 6 h. Repeat echocardiograms and haemodynamic parameters were obtained. Quantification of MYH, OGG-1, and MSH2 concentrations were performed on biopsies using immunohistochemistry and Western blot analysis. RESULTS: Twelve out of 14 hearts (8/10 CHP; 4/4 SP) were successfully weaned on moderate inotropic support. Post-implant echocardiogram, completed in 6/10 CHP and 2/4 SP hearts, demonstrated hyperdynamic function and normal wall motion. The expression and activity of DNA repair enzymes was identical between normal baseline and CHP hearts. CONCLUSION: CHP reduces OS associated with prolonged hypothermic preservation and may allow longer preservation periods without compromising function. CHP offers several potential advantages: (1) resuscitation of non-beating heart donor organs, (2) time for HLA tissue typing, (3) facilitate interventions improving graft function, and (4) increased organ sharing.

Animals↗

Surrogate markers and risk factors for chronic lung allograft dysfunction.

Obliterative bronchiolitis (OB) is the histologic correlate of chronic allograft dysfunction in pulmonary transplantation. The histologic diagnosis of OB is challenging, therefore a physiologic definition, bronchiolitis obliterans syndrome (BOS) based on pulmonary function tests has been used as a surrogate marker for OB for the last decade. BOS has proven to be the best available surrogate marker for OB and is predictive of the ultimate endpoints of graft and patient survival. Multiple other clinical markers have been reported and proposed as alternates for or complements to BOS grade, but all need further evaluation and validation in large, prospective clinical trials. Lastly, given the early occurrence and high incidence of chronic allograft dysfunction, the easily measurable endpoint of BOS grade, and our lack of understanding of ways to prevent or alter the course of BOS, lung transplant recipients represent an ideal population for clinical trials targeting prevention and treatment of chronic allograft dysfunction.

Adult↗

Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study.

Bronchiolitis obliterans syndrome remains the leading cause of morbidity and mortality in the pulmonary transplant population. Previous studies show that macrolide antibiotics may be efficacious in the treatment of panbronchiolitis and cystic fibrosis. In the latter, azithromycin decreases the number of respiratory exacerbations, improves FEV1, and improves quality of life. We hypothesized that oral azithromycin therapy may improve lung function in patients with bronchiolitis obliterans syndrome. To test this hypothesis, we conducted an open-label pilot trial using maintenance azithromycin therapy in six lung transplant recipients (250 mg orally three times per week for a mean of 13.7 weeks). In this study, five of these six individuals demonstrated significant improvement in pulmonary function, as assessed by FEV1, as compared with their baseline values at the start of azithromycin therapy. The mean increase in the percentage of predicted FEV1 values in these individuals was 17.1% (p </= 0.05). In addition, the absolute FEV1 increased by 0.50 L (range -0.18 to 1.36 L). These data suggest a potential role for maintenance macrolide therapy in the treatment of bronchiolitis obliterans syndrome in lung transplant recipients.

Administration, Oral↗

Pulmonary resection following lung transplantation.

BACKGROUND: The morbidity of lung transplantation is higher than other solid organ transplants. Little is known about the outcomes of patients who require pulmonary resection following lung transplantation. We reviewed our experience to evaluate and discern any variables affecting outcome of pulmonary resections performed following lung transplantation. METHODS: A retrospective review of the lung transplant database was performed. Data are presented as mean +/- standard error (median). RESULTS: A total of 136 lung transplants (80 single lung transplants [SLT], 55 bilateral lung transplants [BLT], and 3 heart-lung transplants [HLT]) were performed from August 1995 to February 2002. Twelve pulmonary resections, 7 lobectomies, and 5 wedge resections were performed on 11 patients. The indication for lobectomy was infection in 5 of 7 lobectomies (3 fungal, 2 bacterial), mass in 1 of 7, and infarction in 1 of 7. The indication for wedge resection was native lung hyperinflation in 4 of 5 wedge resections and mass in 1 of 5. The native lung was resected in 3 of 7 lobectomies and 4 of 5 wedge resections. An allograft lobectomy was performed following 1 SLT and 3 BLT and a wedge resection was performed after 1 SLT. The mean time to pulmonary resection was 12.4 +/- 3.9 (9.1) months. Survival postresection was 17.2 +/- 5.8 (8.3) months and 5 of 11 patients are still alive. There were no bronchial stump leaks following lobectomy. CONCLUSIONS: Major pulmonary resections can safely be performed following lung transplant. We recommend early intervention to optimize outcomes.

Adult↗

The predictive value and inter-observer variability of donor chest radiograph interpretation in lung transplantation.

OBJECTIVE: Currently the relationship between the evaluation of the donor chest radiograph and the final disposition of potential donor lungs is unknown, yet potential lung donors receive frequent x-rays. We sought to clarify the role donor chest radiographs and donor lung acceptability. METHODS: We conducted a retrospective review of 84 potential organ donors. Radiographs were reviewed separately by three thoracic surgeons and three pulmonologists and either accepted or rejected with no other information. Data was analyzed by Kappa statistic to judge inter-observer variance and it was compared to actual outcome to determine predictive value. RESULTS: The Kappa statistics for observer agreement was 0.149 among the surgeons, 0.510 among the pulmonologists, and 0.336 overall, representing slight, moderate and fair agreement respectively. The reviewers' decisions to accept or reject a lung concurred with the actual clinical outcome 64.2% of the time. The positive predictive value of an accept decision was found to be 78.3% and the negative predictive value of a reject decision was 36.3%. CONCLUSIONS: This study suggests that evaluation of the donor chest x-ray is a highly subjective process and demonstrated the limited role the radiograph presently holds in the determination of organ suitability.

Case-Control Studies↗

Tracheostomy following lung transplantation predictors and outcomes.

The effect of tracheostomy on patients receiving lung transplantation is unknown. We reviewed our experience by performing a retrospective analysis on all lung transplant recipients at our institution. Patients were assigned to each study group based on whether or not they received a tracheostomy in the acute postoperative period. One hundred and fourteen lung transplants were performed, and 16 of those patients received a tracheostomy. In the tracheostomy group, more patients had undergone bilateral-lung transplantation (81% vs. 34%, p = 0.001), more required cardiopulmonary bypass (75% vs. 38%, p = 0.005), more acquired postoperative pneumonia (88% vs. 30%, p < 0.001), had greater reperfusion injury at 48 h (PaO2/FiO2 of 233 vs. 345, p = 0.047), had longer initial periods on the ventilator (21 +/- 7 vs. 2 +/- 0.5 days, p < 0.001), more required re-intubation (56% vs. 18%, p = 0.001), spent longer times in the intensive care unit (30 +/- 7 vs. 5.5 +/- 0.9 days, p < 0.001), and had longer lengths of stay (67 +/- 10 vs. 22 +/- 2 days, p < 0.001). Despite these differences between the two groups, a significant difference in survival at 180 days (75 vs. 81%) did not exist (p = 0.89). Although tracheostomy is more likely in sicker patients, it is not associated with poor long-term outcomes.

Adult↗

Pulmonary eosinophilia following lung transplantation for sarcoidosis in two patients.

Pulmonary eosinophilia is an uncommon problem in lung transplant recipients. We report the unique occurrence of two cases of pulmonary eosinophilia in pulmonary allografts for sarcoidosis. Both patients rapidly acquired bronchiolitis obliterans syndrome (BOS) after resolution of pulmonary eosinophilia. It is known that peripheral eosinophilia is a marker for pulmonary allograft rejection, but its potential in the pathogenesis of BOS is unclear.

Biopsy↗

Combined heart-single-lung transplantation: a unique operation for unique indications.

Combined heart-lung transplantation has been a proven therapeutic option for patients with end-stage cardiopulmonary disease since 1981. Occasional patients are not candidates to receive both lungs en bloc. We describe such a case and propose indications and a surgical technique and present the limited published experience of combined heart-single-lung transplantation.

Heart Diseases↗

Heterotopic abdominal heart transplantation: a pilot study.

The increasingly severe shortage of donor hearts has prompted a liberalization of what is considered an acceptable donor heart. The use of marginally acceptable organs has increased in recent years. Although these marginal donors have proved effective, there still remains a tremendous shortage of donors to treat the large number of patients who are candidates for cardiac transplantation. Further use of marginal donors is limited by the requirement to assume immediate and full support of the circulation. New strategies are required to increase donor organ use even further. The authors developed a model of heterotopic abdominal heart transplant (HAHT) to investigate the possibility of using marginal donor hearts to expand the donor pool for cardiac transplantation. The authors' goal was to show that HAHT was technically feasible and could potentially function as auxiliary circulatory support in the setting of low cardiac output. The hemodynamic and metabolic consequences of a HAHT were investigated in a pilot study that provides proof of concept and lays the groundwork for future investigations.

Abdomen↗