Showing papers in "Journal of Heart and Lung Transplantation in 2005"

Revision of the 1990 Working Formulation for the Standardization of Nomenclature in the Diagnosis of Heart Rejection

Abstract: In 1990, an international grading scheme for the grading of pulmonary allograft rejection was adopted by the International Society for Heart and Lung Transplantation (ISHLT) and was modified in 1995 by an expanded group of pathologists. The original and revised classifications have served the lung transplant community well, facilitating communication between transplant centers with regard to both patient management and research. In 2006, under the direction of the ISHLT, a multi-disciplinary review of the biopsy grading system was undertaken to update the scheme, address inconsistencies of use, and consider the current knowledge of antibody-mediated rejection in the lung. This article summarizes the revised consensus classification of lung allograft rejection. In brief, acute rejection is based on perivascular and interstitial mononuclear infiltrates, Grade A0 (none), Grade A1 (minimal), Grade A2 (mild), Grade A3 (moderate) and Grade A4 (severe), as previously. The revised (R) categories of small airways inflammation, lymphocytic bronchiolitis, are as follows: Grade B0 (none), Grade B1R (low grade, 1996, B1 and B2), Grade B2R (high grade, 1996, B3 and B4) and BX (ungradeable). Chronic rejection, obliterative bronchiolitis (Grade C), is described as present (C1) or absent (C0), without reference to presence of inflammatory activity. Chronic vascular rejection is unchanged as Grade D. Recommendations are made for the evaluation of antibody-mediated rejection, recognizing that this is a controversial entity in the lung, less well developed and understood than in other solid-organ grafts, and with no consensus reached on diagnostic features. Differential diagnoses of acute rejection, airway inflammation and chronic rejection are described and technical considerations revisited. This consensus revision of the working formulation was approved by the ISHLT board of directors in April 2007.

Three-Year Results of a Randomized, Double-Blind, Controlled Trial of Mycophenolate Mofetil Versus Azathioprine in Cardiac Transplant Recipients

Abstract: Background This study reports the 36-month results of a randomized, double-blind, active-controlled trial of mycophenolate mofetil (MMF) vs azathioprine (AZA) in heart transplant patients. Methods Patients were randomized at the time of transplant to receive MMF (1,500 mg twice a day, N = 327) or AZA (1.5 to 3 mg/kg in 4 daily doses, N = 323) in addition to cyclosporine and corticosteroids; 289 patients in each group received study drug. Data were analyzed in all randomized patients (enrolled) and in patients who received study medications (treated). Clinical and graft assessments continued for 36 months. Results For the co-primary end-point, 53 of 289 (18.3%) AZA-treated patients either died or received another transplant compared with 34 of 289 (11.8%) MMF-treated patients ( p p = 0.029). In patients undergoing intravascular ultrasound, the change in mean maximal intimal thickness was less for the MMF group than for the AZA group (0.06 ± 0.03 mm vs 0.13 ± 0.03 mm, respectively; p = 0.056). No significant differences between treatments were observed in quantitative coronary angiographic measurements of transplant coronary vasculopathy. Congestive heart failure, atrial arrhythmia and leukopenia were more common in the AZA group, whereas diarrhea, esophagitis, Herpes simplex , Herpes zoster and cytomegalovirus (CMV) tissue invasion were more common in MMF-treated patients. Conclusion MMF reduces mortality and graft loss up to 36 months after transplantation.

Gastrointestinal bleeding from arteriovenous malformations in patients supported by the Jarvik 2000 axial-flow left ventricular assist device

Abstract: The long-term effects of axial-flow mechanical circulatory support in humans are unclear. We report 3 cases of chronic gastrointestinal bleeding after implantation of a Jarvik 2000 axial-flow left ventricular assist device. The bleeding was refractory to aggressive management and in 2 cases resolved only after orthotopic cardiac transplantation.

Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part III: donor-related risk factors and markers.

Abstract: T w I t p umerous studies have attempted to identify recipientelated characteristics that portend poor clinical outomes after lung transplantation. As already covered in he previous parts of this series, a major cause of orbidity and mortality during the early post-operative eriod is primary graft dysfunction (PGD). Unfortuately, most studies have included small numbers of atients or have used variable or unclear definitions for GD. PGD increases early morbidity and mortality and ccounts for roughly 50% of early (30-day) deaths. herefore, risk factors for PGD are likely also risk actors for short-term morbidity or mortality, which are ften better defined. In this investigation, we characterize he association of various recipient-related risk factors and arkers with PGD. There are multiple potential risk actors that affect early clinical outcomes after lung ransplantation, only one of which is PGD. We thereore also briefly cover other causes of early graft ysfunction and/or mortality that are part of the differntial diagnosis when considering PGD. Although many f the earlier studies used a PaO2:FIO2 ratio of 150 at 24 ours and/or radiographic patterns as part of their definiion of PGD, other studies used alternate definitions, often aking comparisons and definitive conclusions difficult.

Ten-year follow-up of a randomized trial of pravastatin in heart transplant patients.

Abstract: Background Outcomes from this trial's first year data demonstrated significant benefit in heart transplant patients treated with pravastatin in cholesterol levels, survival, rejection with hemodynamic compromise, the development of cardiac allograft vasculopathy, and decreased natural killer cell cytotoxicity. Other heart transplant studies have shown similar benefit. We now report the 10-year follow-up of this study. Methods Ninety-seven heart transplant recipients were randomized to pravastatin ( n = 47) or no pravastatin ( n = 50) within 2 weeks after surgery both in combination with cyclosporine and corticosteroids. Ten-year outcomes include survival, cholesterol levels, and development of cardiac allograft vasculopathy documented by coronary angiography. Results Forty-two percent of the control patients crossed over to pravastatin treatment during the second year of the study, and 81% of the control patients were eventually placed on statin therapy by the 10-year follow-up. The control group had subsequent low and comparable cholesterol levels in Years 2 to10 of the study compared with the patients originally randomized to pravastatin. Intent-to-treat analysis demonstrated that the pravastatin group compared with control had increased 10-year survival (68% vs 48%, p = 0.026). The 10-year freedom from angiographic cardiac allograft vasculopathy and/or death in the pravastatin group was significantly greater compared with the control group (43% vs 20%, p = 0.009). Conclusion The 10-year follow-up of this study suggests that the use of pravastatin in heart transplant patients maintains survival benefit and appears to reduce the development of cardiac allograft vasculopathy.

The Impact and Outcome of Transplant Coronary Artery Disease in a Pediatric Population: A 9-Year Multi-institutional Study

Abstract: Background Transplant coronary artery disease (TCAD) limits survival in heart transplant recipients; however, its incidence in children is unknown. The purpose of this study was to determine the angiographic incidence of TCAD, potential risk factors, and outcomes in a large pediatric cohort. Methods From January 1993 to December 1, a total of 1,222 children, aged newborn to 17 years, underwent primary cardiac transplantation at 20 institutions. A total of 2,049 coronary angiograms were performed in 751 patients. All angiograms were graded for coronary disease and results were submitted to the Pediatric Heart Transplant Study database. We analyzed time-related freedom from graded severity and events from coronary disease, and we examined risk factors. Results The incidence of angiographic abnormalities at 1, 3, and 5 years was 2%, 9%, and 17%, respectively; however, moderate-to-severe disease occurred in only 6% at 5 years, compared with 15% in the adult transplant database ( p p = 0.05). Overall freedom from graft loss caused by primary TCAD was 99%, 96%, and 91% at 1, 5, and 9 years after heart transplantation, respectively. Death or graft loss occurred within 2 years of diagnosis in patients with severe disease; 24% of patients with any coronary disease died within 2 years. Conclusions The incidence of TCAD in children is smaller than the incidence in adults, but increases with age. Graft loss is infrequent in children; however, severe coronary disease correlates with poor prognosis.

Intravenous Ribavirin Is a Safe and Cost-effective Treatment for Respiratory Syncytial Virus Infection After Lung Transplantation

Abstract: Background Community-acquired viral infections, such as respiratory syncytial virus (RSV), represent a risk factor for bronchiolitis obliterans syndrome (BOS), the major limiting factor for long-term survival after lung transplantation (LTx). RSV often presents with acute bronchiolitis and may be fatal in 10% to 20% of patients. Standard therapies for RSV include nebulized ribavirin with or without steroids, but are costly and inconvenient. We investigated the utility of intravenous (IV) ribavirin with steroids for the treatment of RSV infection after LTx. Methods RSV was identified in nasopharyngeal and throat swabs (NPS) using indirect fluorescent antibody (IFA) testing in 18 symptomatic patients, which was confirmed by viral culture in 14. Data were collected for the period between April 2002 and October 2004. The study included 10 men and 8 women, mean age 42 ± 15 (range 18 to 63) years. Transplant procedures were 5 single LTx and 13 bilateral LTx. RSV diagnosis was made on Day 1,374 ± 1,270 (range 61 to 4,598, median 935) post-operatively. Underlying diagnoses included cystic fibrosis (n = 9), emphysema (n = 7) and pulmonary fibrosis (n = 2). All 18 patients received intravenous (IV) ribavirin (33 mg/kg on Day 1 and 20 mg/kg/day thereafter in 3 divided doses) with oral prednisolone (1 mg/kg) until repeat NPS were negative for RSV on IFA. Median therapy was 8 days (6 to 15). Results The mortality rate was 0%. Mean FEV1 fell from 2.1 ± 1.0 liter (0.7 to 3.7 liters) to 1.8 ± 0.9 liter (0.5 to 3.6 liters) (p Conclusions This is the largest reported series of treated RSV cases after LTx and the first to show that therapy with IV ribavirin and oral corticosteroids is well tolerated and effective. Cost utility vs nebulized therapy has been established. Early diagnosis and management are essential to prevent airway epithelial injury and subsequent BOS.

Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation.

Abstract: Background Pre-transplant fixed pulmonary hypertension is associated with higher post-transplant mortality. In this study, we assessed the significance of pre-transplant reversible pulmonary hypertension in patients undergoing cardiac transplantation. Methods Overall, we studied 182 patients with baseline normal pulmonary pressures or reversible pulmonary hypertension, defined as a decrease in pulmonary vascular resistance (PVR) to ≤2.5 Wood units (WU), who underwent cardiac transplantation. Multiple recipient and donor characteristics were assessed to identify independent predictors of mortality. Results The average duration of follow-up was 42 ± 28 months. Forty patients (22%) died during the follow-up period. Baseline hemodynamics for alive vs dead patients were as follows: pulmonary artery systolic (PAS) 42 ± 15 vs 52 ± 15 mm Hg; PA diastolic 21 ± 9 vs 25 ± 9 mm Hg; PA mean 28 ± 11 vs 35 ± 10 mm Hg; transpulmonary gradient (TPG) 9 ± 4 vs 11 ± 7 mm Hg (all p p = 0.08); and PVR 2.3 ± 1.5 vs 2.9 ± 1.6 WU ( p = 0.06). In an unadjusted analysis, patients with PAS >50 mm Hg had a higher risk of death (odds ratio [OR] 5.96, 95% confidence interval [CI] 1.46 to 19.84 as compared with PAS ≤30 mm Hg). There was no significant difference in survival among patients with baseline PVR 4.0 WU, but patients with TPG ≥16 had a higher risk of mortality (OR 4.93, 95% CI 1.84 to 13.17). PAS pressure was an independent predictor of mortality (OR 1.04, 95% CI 1.02 to 1.06). Recipient body mass index, history of sternotomy; and donor ischemic time were the other independent predictors of mortality. Conclusion Pre-transplant pulmonary hypertension, even when reversible to a PVR of ≤2.5 WU, is associated with a higher mortality post-transplant.

Nodular endocardial infiltrates (Quilty lesions) cause significant variability in diagnosis of ISHLT Grade 2 and 3A rejection in cardiac allograft recipients.

Abstract: Background Endomyocardial biopsy is used to guide therapy after heart transplantation. An accurate and reliable diagnosis of rejection is critical for proper patient management. Methods A sub-set of 827 biopsies from 273 patients were identified from 8 centers participating in the Cardiac Allograft Gene Expression Observational Study. These included all biopsies graded by local center pathologists as International Society for Heart and Lung Transplantation (ISHLT) Grade 1B or higher and also randomly chosen Grade 0 and 1A biopsies. Each of these cases was reviewed in a blinded manner by 3 study pathologists in the absence of clinical data. The study pathologists were assigned an ISHLT grade and noted nodular endocardial infiltrates (Quilty lesions). Results The study pathologists were significantly more likely than local pathologists to diagnose ISHLT Grade 0, 1A and 3B rejection and significantly less likely to diagnose ISHLT Grade 1B, 2 and 3A rejection. Concordance between local and study pathologists was lowest for Grade 2 (17% agreement). Quilty lesions were noted in 3.3% of local Grade 0 cases and in 31% and 37% of local Grade 2 and 3A cases, respectively. Quilty lesions were recognized by study pathologists in 35% of local Grade 2 cases "downgraded" to Grade 0 or 1, but in only 10% of local Grade 2 cases confirmed by study pathologists. Conclusions The greatest variability between pathologists in application of the ISHLT grading system is in Grade 2 biopsies, and Quilty lesions are a major contributing factor to the lack of concordance. Accurate application of the ISHLT grading system requires improved recognition and understanding of Quilty lesions.

Effect of preoperative pulmonary artery pressure on early survival after lung transplantation for idiopathic pulmonary fibrosis.

Abstract: Background Idiopathic pulmonary fibrosis (IPF) is the second largest indication for lung transplantation worldwide. Average 90-day mortality rates for this procedure are 22%. It is unclear what factors predispose patients with IPF to this increased early posttransplant mortality. Pulmonary hypertension may increase the risk of development of early posttransplant complications through several mechanisms. We examined the effect of secondary pulmonary hypertension on 90-day mortality after lung transplantation for IPF. Methods An International Society for Heart and Lung Transplant Registry cohort study of 830 patients with IPF transplanted from January 1995 to June 2002 was undertaken. Risk factors were assessed individually and adjusted for confounding by a multivariable logistic regression model. Results In the univariate analysis, pulmonary hypertension and bilateral-lung transplantation were significant risk factors for increased 90-day mortality. Multivariate analysis confirmed that mean pulmonary artery pressure and bilateral procedure remain independent risk factors after adjustment for potential confounders. Recipient age, ischemia time, cytomegalovirus status mismatch, and donor age were not independent risk factors for early mortality. Conclusions Bilateral-lung transplantation carries a greater risk of early mortality than single-lung transplantation for IPF. Increasing pulmonary artery pressure is a risk factor for death after single-lung transplantation in IPF. Mean pulmonary artery pressure should be included in the overall risk assessment of patients with IPF evaluated for lung transplantation.

Experience and Result of Extracorporeal Membrane Oxygenation in Treating Fulminant Myocarditis with Shock: What Mechanical Support Should Be Considered First?

Abstract: Background Extracorporeal membrane oxygenation (ECMO), instead of ventricular assist device (VAD), could work as the first-line treatment of choice for fulminant myocarditis (FM) with profound shock if intraaortic balloon pumping was inadequate. We reviewed our experience in treating FM with ECMO and compared it with the literature that described the use of VAD. Methods Fifteen consecutive patients (age 27.1 ± 19.3 years) who had FM with profound shock were rescued with ECMO emergently. Hypotension, depressed left ventricular ejection fraction (19.1% ± 6.1%), and oliguria occurred in all patients with high-dose catecholamine (inotropic equivalents: 69.0 ± 37.7 μg/kg/min) and ventilator support. Before ECMO support, 6 patients received intraaortic balloon pumping support, 5 received external cardiac massage, 5 needed a temporary pacemaker, and 4 needed continuous hemofiltration. The pre-ECMO cardiac enzyme and liver enzyme levels were abnormally high. Results Fourteen patients (93.3%) could be weaned off mechanical support. Three of 14 successfully weaned patients died later as a result of complications. Survival to discharge was 73.3%, and none of survivors needed heart transplantation. The ECMO duration was 137.7 ± 74.5 hours. The ECMO-related neurological complication (6.7%) and the reexploration rate for hemostasis (8.9%) were lower than the myocarditis group supported by VAD from the literature review. The 11 survivors exhibited no cardiac dysfunction during the follow-up period. Conclusions Owning to advantages of fewer complications, easier application, and biventricular support, ECMO can be considered as the first-line treatment of mechanical support for FM with profound shock when intraaortic balloon pumping is inadequate or infeasible.

Cellular and hemodynamics responses of failing myocardium to continuous flow mechanical circulatory support using the DeBakey-Noon left ventricular assist device: a comparative analysis with pulsatile-type devices.

Abstract: Background An increasing number of continuous flow pumps are currently under clinical studies, however very little data exist on the hemodynamic and cellular responses of the failing heart to continuous flow support. The purpose of this investigation was to characterize the response of the failing myocardium to continuous flow support. Methods We compared echocardiographic and cellular markers of failing myocardium at the time of left ventricular assist device (LVAD) implantation and explantation in 20 consecutive patients (12 pulsatile flow [Novacor] and 8 continuous flow [DeBakey-Noon]). Results The use of mechanical support with both continuous- or pulsatile-type LVADs resulted in a reduction of left ventricular end-diastolic dimension (LVEDD), end-diastolic volume (EDV), end-systolic volume (ESV) and left atrial volume (LAV), as well as a decrease in mitral E/A ratio, tricuspid regurgitation velocity (TRV) and pulmonary valve acceleration time (PVAT). Comparative analyses for patients treated with a continuous- vs pulsatile-type LVAD support showed a greater degree of unloading with the latter type, as shown by the effect on LVEDD (−13.7% vs −33.7%, p = 0.0.004), EDV (−23.5% vs −41.2%, p = 0.015), ESV (−25.6% vs −57.6%, p = 0.001) and LAV (−25.2% vs −40.4%, p = 0.071). The hemodynamic effects of continuous vs pulsatile LVAD support were similar, as shown by their effect on mitral E/A ratio (−23.9% vs −39.9%, p = NS), TRV (−26.4% vs −23.8%, p = NS) and PVAT (28.5% vs 38.5%, p = NS). Only pulsatile support demonstrated a statistically significant percent change in mass (−6.3% vs −20.6%, p = 0.038). Continuous and pulsatile forms of mechanical support demonstrated equivalent reductions in myocardial tumor necrosis factor-α (TNF-α), total collagen and mycocyte size. Conclusions Our findings show that, although there are differences between these 2 devices in magnitude of unloading, both forms of support effectively normalize cellular markers of the failing phenotype.

Gastroesophageal reflux (symptomatic and silent): a potentially significant problem in patients with cystic fibrosis before and after lung transplantation.

Abstract: Background The significance of gastroesophageal reflux (GER) and aspiration are unclear in cystic fibrosis (CF) and may contribute to declining lung function before and after lung transplantation (LTx). Methods We sought to establish whether GER occurs in patients with CF on the LTx waiting list and after LTx. We then investigated whether GER correlates with patients’ symptoms. Adults with CF on the waiting list and after LTx were prospectively recruited. Completion of a valid, structured symptom questionnaire was followed by ambulatory, dual-probe, 24-hour esophageal pH monitoring. Results Twenty-four patients were studied, including 11 (6 males) in the pre-LTx group and 13 (9 males) in the post-LTx group. The pre-LTx group was 29.3 ± 8.2 years of age, and the post-LTx group was 32.7 ± 8.2 years of age. DeMeester score (normal value Conclusions GER, symptomatic and silent, is a significant problem in CF. This condition should be aggressively treated and surgery should be considered if GER persists on re-testing.

Human metapneumovirus infection in lung transplant recipients: Clinical presentation and epidemiology

Abstract: Background In immunocompromised patients, respiratory viruses are likely to lead to lower respiratory tract infections that cause severe morbidity and mortality. We conducted a prospective study from September 2003 to March 2004 to investigate the epidemiology and impact of human metapneumovirus (hMPV) on lung transplant recipients. Methods We collected 265 nasopharyngeal aspirates and bronchoalveolar lavages: 51 samples originated from immunocompromised adults, 49 from lung transplant recipients, and 2 from a bone marrow recipient. Additionally, 209 samples from hospitalized non-immunocompromised children and 5 samples from immunocompromised children were analyzed for replicating hMPV by a combined cell culture and reverse transcriptase polymerase chain reaction method that includes DNA sequencing of selected isolates. Results Twelve samples from lung transplant recipients (25%), 29 from non-immunocompromised children (14%), and 2 from a child with a renal transplant were positive for hMPV. Most of the cases clustered within 2 outbreaks in October/November and March. In immunocompromised patients, hMPV was isolated throughout the entire observation period. The same viral strains circulated in hospitalized children and in lung transplant recipients. A different strain was isolated during the interepidemic period, suggesting that hMPV infections may be transmitted among lung transplant recipients independently from the community outbreak situation. Clinical signs and symptoms varied from no symptoms to severe pneumonia or acute graft rejection. Significantly, the only deaths occurred in the hMPV-positive group. Of interest, identification of replicating hMPV significantly correlated with rejection symptoms present at the time point of sample collection. Conclusions Results of the study suggest that hMPV may be added to the list of pathogens that are possibly associated with episodes of allograft rejection.

Health-related quality of life in two hundred-eighty lung transplant recipients.

Abstract: Background Health-related quality of life (HRQoL) has increasingly been accepted as a supplementary outcome measure for patients after lung transplantation (LTx). Methods Using a retrospective cross-sectional study design, 280 LTx recipients (3 months to 14 years after LTx) were asked to assess their HRQoL using a generic (Quality of Life Profile for Chronic Diseases) questionnaire, which was previously validated for this specific population. In addition, the questionnaire was also performed by 155 healthy participants. Results All sub-scale findings ranged from 2.40 to 3.08 (0 to 4) for all patients after LTx. A significantly reduced HRQoL was reported by the sub-cohort of patients living 5 to 6 years with the allograft for all sub-scales (p < 0.006), except for Social Functioning, and was associated with the incidence of bronchiolitis obliterans syndrome (BOS; p < 0.05). Cystic fibrosis patients (p < 0.05), single-lung transplant recipients (p < 0.05) and patients of older age (p < 0.05) showed significantly decreased physical ability ratings. Patients who remained free of infection and late acute rejection episodes scored themselves significantly higher with regard to their Relaxation Capabilities (p < 0.05 for rejection; p < 0.05 for infection) and Social Functioning (p < 0.01 for rejection; p < 0.05 for infection) vs patients who experienced infection or rejection episodes. Comparisons with a normative cohort showed similar HRQoL scales for LTx patients and the healthy population, except with regard to Social Functioning (p < 0.01). Conclusions Self-ratings for HRQoL were high for all dimensions for the entire sample, and remained relatively similar even for medium- and long-term survivors. HRQoL was dependent on incidence of infections, rejections and the onset of BOS. Despite differences in life expectancy of LTx patients compared with the healthy population, HRQoL self-ratings were within similar ranges.

The Copenhagen National Lung Transplant Group: survival after single lung, double lung, and heart-lung transplantation.

Abstract: Objective To review the 13-year clinical experience of a single center's adult lung transplantation program. Methods From January 1992 to December 2003, 369 lung transplantations were performed on 362 patients. Single lung transplantation was performed in 234 cases, double lung transplantation in 113 cases (comprising en-bloc double lung transplantation in 44 cases and bilateral sequential lung transplantation in 69 cases), heart-lung transplantation in 21 cases, and lobe of lung transplantation in 1 case. Recipient diagnoses included chronic obstructive pulmonary disease (COPD) ( n = 175), α 1 antitrypsin (α 1 AT) deficiency ( n = 86), cystic fibrosis ( n = 36), pulmonary fibrosis ( n = 20), Eisenmenger syndrome and secondary pulmonary hypertension ( n = 24), primary pulmonary hypertension ( n = 8), sarcoidosis ( n = 7), silicosis ( n = 4), bronchiectasis ( n = 1), and graft-vs-host disease ( n = 1). Results For patients surviving to discharge, the median duration of the intensive care unit stay was 3 days (1–67), and the median duration of the post-operative hospital stay was 37 days (16–144). Mortality for the entire series was 6% at 30 days and 10% at 90 days. The main causes of post-operative inpatient death were primary graft failure (41%), sepsis (29%), cardiac (15%), and hemorrhage (9%). The 1-, 3-, 5-, and 10-year actuarial survival rates for the entire series was 81%, 68%, 63%, and 36%, respectively. There were no significant differences in survival between types of transplant. No significant differences in survival were seen between α 1 AT deficiency and COPD patients after stratifying for age. Cox regression analysis demonstrated that age 60 years or older, donor age 50 years or older, and a recipient pre-operative body mass index of 25 or higher were independent predictors of poor survival. Conclusions This center has 1-, 3-, and 5-year survival rates comparable to other high volume centers. Recipient age, pre-operative body mass index, and donor age significantly influence outcome after lung transplantation.

Early institution of mechanical support improves outcomes in primary cardiac allograft failure.

Abstract: Background Primary graft failure (PGF) is the leading cause of early mortality after cardiac transplantation, accounting for 27.1% of deaths within 30 days. PGF is defined as severe dysfunction of the cardiac allograft without any obvious anatomic or immunological cause. The purpose of this study was to analyze our last 9 years of experience with cardiac transplantation to determine predictors of PGF and the influence on survival of our policy of early institution of mechanical circulatory support (MCS) in these patients. Methods Data on 214 consecutive cardiac transplants performed at The Alfred Hospital between January 1996 and August 2004 were reviewed. PGF was defined as right or left or biventricular failure manifesting as hypotension (systolic blood pressure 2 ) and pulmonary capillary wedge pressure >20 mm Hg after coming off cardiopulmonary bypass despite inotropic support of up to 5 μg/min adrenaline and without any other obvious cause for the graft dysfunction. Results PGF developed in 51 patients (24%). Significant factors in the development of PGF were long ischemic time, which became significant over 4 hours (odds ratio, 1.43; p = 0.01) and increased donor age (odds ratio, 1.027; p = 0.045). Fifteen patients required mechanical support, and of these, 10 survived to leave hospital. Conclusions PGF is the major cause of early mortality after cardiac transplantation. Significant risks for PGF are long allograft ischemic time and increased donor age. Once the patient has survived 30 days, however, the longer-term survival is not influenced by PGF. Our management strategy of early mechanical support has yielded good outcomes in this population with a high risk of early death.

Long-term outcome of bosentan treatment in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with the scleroderma spectrum of diseases

Abstract: Background Bosentan improves clinical outcomes in pulmonary arterial hypertension (PAH), particularly in the idiopathic (IPAH) subset. Scant data are available regarding PAH associated with the scleroderma spectrum of diseases (APAH-SSD). Here we review our experience with bosentan in these 2 groups. Methods Included were all patients at our center with either IPAH or APAH-SSD in whom bosentan was the first-line, single-agent therapy with at least 6 months of follow-up. Changes in the World Health Organization (WHO) functional class from baseline to the most recent follow-up on monotherapy were compared between the 2 groups, as well as overall survival and time to a composite end point of hepatotoxicity requiring discontinuation, use of additional therapy, or death. Results Nineteen IPAH and 17 APAH-SSD subjects with similar baseline clinical characteristics and a median follow-up 9 months (range, 6–44) were analyzed. In IPAH subjects, WHO class improved from 3.1 ± 0.5 at baseline to 2.4 ± 0.8 ( p = 0.005). No change occurred in the APAH-SSD group: 2.9 ± 0.3 vs. 2.8 ± 0.8; p = 0.5. Hepatotoxicity requiring discontinuation developed in 6 patients (17%). Seven (37%) IPAH and 8 SSD patients (47%) reached the composite end point ( p = NS). Overall survival at 1 and 2 years was 100% and 100% vs 87% and 79% for IPAH and APAH-SSD patients, respectively ( p = 0.075). Conclusions First-line bosentan monotherapy is associated with long-term improvement in functional class and good overall survival in patients with WHO class III IPAH. Most APAH-SSD patients experienced stability or decline in functional class and tended to have a higher mortality.

Fate of infants with hypoplastic left heart syndrome listed for cardiac transplantation: a multicenter study.

Abstract: Background Infants with hypoplastic left heart syndrome (HLHS) commonly undergo cardiac transplantation as primary management. Methods We examined outcomes of primary transplantation for unpalliated HLHS. We analyzed data from the 20 institutions of the Pediatric Heart Transplant Study Group, from January 1, 1993, through December 31, 1998, using actuarial and parametric survival analysis and competing outcomes analysis. Results During the 6 years studied, 1,234 patients were listed for cardiac transplantation; 262 patients (21.2%) had unpalliated HLHS. The number (and percentage) of patients with HLHS decreased from 58 (27% of patients listed) in 1993 to 30 (14%) in 1998. Overall, 25% of infants with HLHS died while waiting; primary cause of death was cardiac failure (50%). Of the remaining patients awaiting transplantation, 23 (9%) underwent Norwood/Fontan-type surgeries as interim palliation: 52% died. Ultimately, 175 patients underwent cardiac transplantation (67%); 50% received organs by 2 months after listing. Post-transplant actuarial survival was 72% at 5 years, with 76% of deaths (35/46) occurring within 3 months; early mortality was caused primarily by graft failure within the first 30 days after transplantation (in 54%). Among 1-month survivors, survival at 1 and at 5 years was 92% and 85%, respectively. Of the 262 patients listed with unpalliated HLHS, overall survival, taking into account mortality after listing and after transplantation, was 68% at 3 months and 54% at 5 years. Conclusions Cardiac transplantation offers good intermediate survival for infants with unpalliated HLHS.

Induction therapy with basiliximab allows delayed initiation of cyclosporine and preserves renal function after cardiac transplantation.

Abstract: Background Cyclosporine (CsA) is frequently initiated as induction therapy in patients undergoing orthotopic heart transplantation, but our experience has identified a significant rate of post-operative renal dysfunction. We therefore devised a renal-sparing cyclosporine-free induction regimen consisting of the early administration basiliximab, an interleukin-2 receptor monoclonal antibody, followed by the late initiation of cyclosporine on post-operative Day 4. Methods Between September 1998 and December 1999, we treated 25 patients at risk for post-operative renal dysfunction (high-risk basiliximab group) with the new induction regimen and another 33 patients not at risk (low-risk CsA group) for renal dysfunction with our standard cyclosporine protocol. We identified a historical control group (1996 through 1998) of 32 patients at risk for renal dysfunction (high-risk CsA group) who had received our standard cyclosporine protocol. Results The increase in serum creatinine levels after transplantation was less in the high-risk basiliximab group (−0.1 ± 0.7) than in the high-risk CsA group (0.5 ± 1.0, p p = .13). Conclusion Basiliximab induction therapy allows delayed initiation of cyclosporine after cardiac transplantation without an increase in rejection and reduces the risk of post-operative renal dysfunction.

Pediatric Bridge to Heart Transplantation: Application of the Berlin Heart, Medos and Thoratec Ventricular Assist Devices

Abstract: Background Bridge to transplantation (BTT) is an accepted option when a donor heart is not available. Extensive clinical study has been done with BTT in the adult population, but comparatively fewer data are available in the pediatric population with regard to pulsatile devices. Methods Ten pediatric patients are presented, all of whom underwent BTT or recovery with pneumatic paracorporeal systems. The Berlin Heart bi-ventricular assist device (BVAD) was utilized in 1 patient, the Medos VAD in 4 patients (1 left ventricular assist device [LVAD], 3 BVADs) and the Thoratec VAD in 5 patients (3 BVADs, 2 LVADs). The pediatric population consisted of 3 females and 7 males. Mean age of the population was 7.4 years, weight 25 kg and body surface area (BSA) 0.88 m2. Etiology for heart failure consisted of 4 viral, 3 congenital and 3 idiopathic cardiomyopathies. Before implant, all patients had evidence of progressive cardiac failure despite inotropic support, and 2 patients had been on extracorporeal membrane oxygenation (ECMO). Mean duration on the device was 34.3 days (8 to 107 days). Results Two patients suffered stroke and recovered without sequelae. Two patients died of ischemic stroke and 1 of sepsis. Seven patients survived (6 transplanted and 1 weaned) for a survival rate of 70% compared with survival for ECMO as BTT, which was 40% to 50%. All survivors had complications related to bleeding, thromboembolic events and infections. Conclusions The Thoratec VAD can be placed in small patients with large hearts that can accommodate the available cannulas. The Berlin Heart and the Medos VAD have a selection of ventricles with small stroke volumes. All 3 systems can be used successfully in the pediatric population as BTT with better survival than with ECMO.

Pre-Transplant Panel Reactive Antibody in Lung Transplant Recipients is Associated with Significantly Worse Post-Transplant Survival in a Multicenter Study

Abstract: Background The presence of antibodies to human leukocyte antigens (HLA) prior to transplantation has been linked to worse post-transplant outcomes in many solid organ transplants. The effect of these antibodies is less clear in lung transplant recipients, although previous studies have suggested an increased incidence of allograft dysfunction. Methods A retrospective study of all first lung transplant recipients from the University of Toronto (November 1983–July 2001, n = 380) and Duke University (April 1992–June 2000, n = 276) was performed. Demographic data, survival information, and level of last pre-transplant panel reactive antibody (PRA) were collected. PRA level was measured by the complement-dependent cell cytotoxicity assay at both centers. Survival analysis was performed using the Kaplan-Meier method, and groups were compared with the Wilcoxon rank sum test. Results Of 656 lung transplant recipients, 101 (15.4%) had a PRA greater than 0, 37 (5.6%) had a PRA greater than 10%, and 20 (3.0%) had a PRA greater than 25%. Patients with a PRA greater than 25% had decreased median survival than did the rest of the patients (1.5 vs 5.2 years) and at 1 month (70% vs 90%), 1 year (65% vs 76%), and 5 years (31% vs 50%), respectively (p = 0.006, Wilcoxon’s rank sum test) test). Conclusion Significant elevation of PRA prior to lung transplantation is associated with worse survival, especially in the early post-transplant period. This may be due to a direct effect of anti-HLA antibodies on the allograft. The effectiveness of treatments such as plasmapheresis and intravenous immunoglobulin prior to transplantation needs to be evaluated.