The Journal of Heart and Lung Transplantation - Articles in Press

Different prognostic impact of the tissue Doppler-derived E/e′ ratio on mortality in Chagas cardiomyopathy patients with heart failure - Corrected Proof

2012-02-03

Background: Risk assessment of Chagas cardiomyopathy patients is essential for clinical decision making. The ratio of the ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/e′) is a powerful predictor of adverse outcome in patients with heart failure. However, its prognostic value remains to be established in the setting of Chagas cardiomyopathy. This study investigated the effect of E/e′ on mortality according to different degrees of left ventricular (LV) systolic function in patients with Chagas cardiomyopathy. Methods: The study prospectively enrolled 232 patients (143 men) with Chagas cardiomyopathy (mean age, 48 ± 12 years). End points were death or cardiac transplantation. Results: During a mean follow-up of 3.4 years, 107 patients had an adverse cardiac event, with an overall events rate of 13.2/year. Cox proportional hazards model was used with New York Heart Association functional class, LV ejection fraction, right ventricular function, indexed left atrial volume, E/e′ ratio, and the statistical interaction term between E/e′ ratio and LV ejection fraction. The effect of E/e′ ratio on mortality depended on the degree of LV systolic dysfunction. An increasing E/e′ ratio was a strong predictor of outcome in patients with mild to moderate LV dysfunction but was inversely associated with mortality in patients with severe systolic dysfunction. Conclusion: This study demonstrated the role of the interaction between LV ejection fraction and E/e′ ratio in predicting prognosis in Chagas cardiomyopathy patients. The E/e′ ratio had a stronger prognostic value in patients with mild and moderate LV dysfunction and was inversely associated with mortality in patients with advanced systolic heart failure.

The role of the Heart Failure Survival Score and psychosocial stress in predicting event-free survival in patients referred for heart transplantation - Corrected Proof

Gerdi Weidner, Heike Spaderna — 2012-02-02

We read with interest the article “Selecting patients for heart transplantation: Comparison of the Heart Failure Survival Score (HFSS) and the Seattle Heart Failure Model (SHFM)” by Goda et al. Their study showed that the HFSS and the SHFM are similarly predictive of event-free survival in heart transplant (HTx) candidates enrolled at a single center in the USA.

Utility of exercise stress echocardiography in pediatric cardiac transplant recipients: A single-center experience - Corrected Proof

2012-02-02

Background: Annual coronary angiography (ANG) to assess for significant epicardial coronary artery disease (CAD) is an integral part of follow-up care for pediatric cardiac transplant recipients at Children's Hospital Boston. Exercise stress echocardiography (ESE) is an important, non-invasive tool for the detection of ischemia in adults but has been rarely used in children. Therefore, the aim of this study was to assess the feasibility and utility of ESE in excluding ANG-detected epicardial CAD at our center, where ESE has been implemented since 2007. Methods: We conducted a retrospective review of all pediatric cardiac transplant recipients at our institution who had undergone ESE and ANG between January 2007 and December 2010, and with testing performed < 12 months apart. ESE results were compared against ANG. Results: The study cohort comprised 47 cardiac transplant recipients. One patient's ESE images were inadequate for interpretation. Of the remaining 46 patients, ESE had a sensitivity of 88.9% (95% confidence limits [CL], 51.8%, 99.7%), a specificity of 91.9% (95% CL, 71.8%, 98.3%), and a negative predictive value of 97% (95% CL, 85.1%, 99.1%) for the ANG-detected CAD. Conclusions: This large, single-center study showed ESE was feasible and had a high specificity and excellent negative predictive value in excluding epicardial CAD in pediatric cardiac transplant recipients. Future prospective, large-scale studies are needed to confirm these findings and help identify a subset of children for whom a negative ESE could decrease the frequency of routine ANG.

Prognostic factors in severe pulmonary hypertension patients who need parenteral prostanoid therapy: The impact of late referral - Corrected Proof

2012-01-30

Background: Oral drugs have made the treatment of pulmonary hypertension (PH) feasible in non-expert centers, which could delay patient access to prostanoid therapy. Methods: Fifty-seven consecutive patients with precapillary PH received a prostanoid in our center. Data at prostanoid initiation included modality of center referral, medical history, New York Heart Association [NYHA] class, exercise capacity, echocardiographic parameters, and hemodynamics. Results: Overall survival at 1, 2, and 3 years was 85%, 69%, 55%, respectively. Non-survivors had worse NYHA class III/IV (17/12) than survivors (27/1; p < 0.01) and exercise capacity on 6-minute-walk distance (254 ± 114 vs 354 ± 91 meters; p < 0.01). Non-survivors were more frequently referred on oral therapy (83% vs 36%; p < 0.01) and had a higher rate of urgent prostanoid treatment (69% vs 17%; p < 0.0001). Multivariate analysis (hazard ratio [95% confidence interval]) found the independent prognostic factors were urgent prostanoid therapy (2.0 [1.1–3.9]) and NYHA class (3.5 [1.5–8.2]). Survivors had a significant response to prostanoid, improving NYHA class from 2.8 ± 0.4 to 2.3 ± 0.5 (p = 0.002), 6-minute walk distance from 354 ± 91 to 426 ± 82 meters (p = 0.0001), and pulmonary hemodynamics (pulmonary artery pressure from 56 ± 13 to 44 ± 18 mm Hg [p < 0.05]; cardiac index from 2.0 ± 1.2 to 3.1 ± 1.2 liters/min/m2 [p = 0.002], and pulmonary vascular resistance from 17 ± 10 to 8 ± 6 WU [p = 0.001]). Conclusions: Referral of patients on oral treatment to a tertiary PH center is delayed and significantly affects prognosis.

Inhibition of renin angiotensin aldosterone system causes abrogation of obliterative airways disease through inhibition of tumor necrosis factor-α–dependant interleukin-17 - Corrected Proof

2012-01-30

Background: Alloimmune-induced immune responses to self-antigens are involved in the development of chronic lung allograft rejection. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have been shown to modulate autoimmune diseases. This study investigated the effect of modulation of the renin angiotensin aldosterone system (RAAS) a murine model of obliterative airways disease (OAD). Methods: Major histocompatibility complex (MHC) class I antibodies were administered intrabronchially to C57Bl/6 mice on Days 1, 2, 3, and 6, and weekly thereafter. ACEI/ARB (10 mg/kg/day) were administered in water 5 days before antibody administration. Antibodies were analyzed by enzyme-linked immunosorbent assay, cytokines by Luminex, Th-frequency by enzyme-linked immunosorbent spot, and transcription factors by Western blotting and real-time polymerase chain reaction. Results: Significant decreases (50%–70%) in airway lesions and fibrous deposition were noted in lungs at Day 30 in the animals administered ACEI and ARB vs controls. Antibody concentrations to self-antigens also decreased from 14 ± 21 to 62 ± 18 μg/ml for collagen V and from 263 ± 43 to 84 ± 28 μg/ml for K-α1 tubulin. Th-precursor frequency and cytokine analysis showed increased interleukin (IL)-10 (3-fold increase) and decreased levels of IL-6 (3.4-fold) and IL-17 (4-fold decrease; p < 0.05) in ACEI and ARB groups. There was also messenger RNA level downregulation of tumor necrosis factor-α (8.6-fold) and p38/mitogen-activated protein (MAP)kinase (3.1-fold) in the treatment groups. Conclusions: Our results demonstrate that modulation of RAAS leads to downregulation of IL-17 through tumor necrosis factor-α–dependant IL-6 through p38/MAPKinase pathway and thus abrogation of anti-MHC–induced OAD.

Older patients (age 65+) report better quality of life, psychological adjustment, and adherence than younger patients 5 years after heart transplant: A multisite study - Corrected Proof

2012-01-24

Background: Research examining age differences after heart transplant (HT) has focused primarily on morbidity and mortality outcomes, with little emphasis on potential age differences in quality of life and psychosocial outcomes. The objective of the study was to determine whether older patients have more positive adjustment and quality of life several years after HT compared with younger patients. Methods: The study recruited 555 patients who were at least 5 years post-HT from 4 United States medical centers. The sample included 165 older patients (≥ 60 years at HT), 300 middle-aged patients (between 45 and 59 years), and 90 younger patients (< 45 years). Of these, 78% were men, 88% were white, and most were well educated (14.04 mean years of education). Outcome measures examined quality of life, social support, mood, coping strategies, stress, health functioning, and adherence. Hypotheses regarding outcomes were derived from incidental findings from the original study. Results: Statistics included multivariate analyses of covariance, followed by univariate analyses of covariance that controlled for differences in sex, race, years of education, and marital status. Older HT patients were more satisfied with quality of life (p < 0.001) and social support (p = 0.003), had less HT-related stress (p < 0.001), negative affect (p < 0.001), depression (p < 0.001), better overall functioning (p = 0.035), less use of negative coping strategies (p = 0.006), less difficulty with adherence (p < 0.001), and better actual adherence (p < 0.001) than younger and middle-aged HT patients. Conclusions: Older patients in this large sample had better quality of life, psychosocial adjustment, and adherence after HT than middle-aged and younger patients. If replicated, this age advantage should at least be considered when assessing age as a criterion for HT clinical decision making and organ allocation policy.

Radical reduction of smooth muscle cells in explanted lung of a LAM patient treated with sirolimus: First case report - Corrected Proof

M. Angeles Montero, Antonio Roman, Cristina Berastegui — 2012-01-24

Lymphangioleiomyomatosis (LAM) is a rare and progressive disease that usually affects pre-menopausal women. Lung transplantation has been the only treatment for advanced LAM since the activation of mammalian target-of-rapamycin (mTOR) signaling pathways was identified in these patients.

Increase of ABCG2/BCRP+ side population stem cells in myocardium after ventricular unloading - Corrected Proof

2012-01-16

Background: A significant decrease in mean cardiomyocyte DNA content and increased numbers of diploid cardiomyocytes after unloading has been demonstrated, suggesting a numerical increase of cardiomyocytes. Despite a thorough search in that study, no mitoses explaining a potential net increase of cardiomyocytes has been observed. The heart harbors several stem cell populations, including c-kit (CD117)+ stem cells and side population cells (SPC), which may proliferate after unloading and thus contribute to the generation of diploid cardiomyocytes. In this study we sought to determine, whether there is an increase of ABCG2+ SPC and CD117+ stem cells after unloading. Methods: In paired myocardial samples (prior to and after LVAD), the number of cells with immunoexpression of ABCG2, c-kit/CD117 and MEF-2 was assessed by immunohistochemistry. Their number was morphometrically determined and these data were correlated with the mean cardiomyocyte DNA content. Results: A significant increase of SPC and cells with coexpression of c-kit and MEF-2 after unloading was observed from 0.00013% in CHF to 0.0011%, and 0.013% to 0.035%, respectively after unloading (p = 0.001). A significant positive correlation between both SPC and cells with coexpression of c-kit and MEF-2 expression was observed (p = 0.007 and 0.01). No correlation was found between the number of SPC and the mean cardiomyocyte DNA content. Conclusions: SPC are increased significantly in the myocardium after ventricular unloading, suggesting a role for stem cell proliferation during “reverse cardiac remodeling.” These cells might proliferate and commit to different cell lineages, such as cardiomyocytes or endothelium, and thus ameliorate cardiac function.

Survival after biventricular mechanical circulatory support: Does the type of device matter? - Corrected Proof

2012-01-16

Background: Biventricular support can be achieved using paracorporeal biventricular assist devices (BiVADs), the total artificial heart (TAH), and implantable VADs. This study evaluated the influence of the device on patient survival. Methods: Data from 383 patients (321 men [84%]) undergoing primary, planned biventricular support using durable devices between 2000 and 2010 were extracted from the French multicentric Groupe de Réflexion sur l'Assistance Mécanique (GRAM) registry. Mean age was 41.6 ± 14.0 years. Patients were classified as group 1, 255 (67%) with paracorporeal BiVADs; group 2, 90 (24%) with TAH; and group 3, 38 (10%) with implantable BiVADs. Results: Mean patient support duration was 82.8 ± 107.4 days and similar among groups (p = 0.53). Bridging to transplantation was successful in 211 patients (55%) and to recovery in 23 (6%). Mortality on device was similar among groups (p = 0.16). TAH patients had a significantly lower stroke rate (p < 0.0001). Actuarial estimates for survival while on support were 75.2% ± 2.3%, 64.4% ± 2.7%, 61.1% ± 2.8%, and 56.8% ± 3.1% at 30, 60, 90, and 180 days, respectively, and were similar among groups. However, TAH patients undergoing prolonged support (≥90 days) showed a trend toward improved survival (p = 0.08). Actuarial post-transplant survival estimates were, respectively, 81.7 ± 2.7, 75.3 ± 3.0, 73.0 ± 3.0, and 64.7 ± 3.7 at 1 month and 1, 3, and 5 years and were similar among groups (p = 0.84). Conclusion: Survival while on support and after heart transplantation did not differ significantly in patients supported with paracorporeal BiVADs, implantable BiVADs, or the TAH. Patients undergoing prolonged support (>90 days) tended to have improved survival when supported with TAH compared with BiVADs, which may be related to a lower incidence of neurologic events.

Perceived quality of life of children after successful bridging to heart transplantation - Corrected Proof

2012-01-12

Background: Mechanical circulatory support is increasingly used to bridge children with end-stage heart failure to transplant. Quality of life (QoL) has not been systematically evaluated in children bridged to heart transplant. Methods: All children transplanted for cardiomyopathy during 2001 to 2008 and currently being followed at our center (n = 84) had QoL assessed during 2006 to 2009, at a median of 3 years post-transplant, using a validated generic measure (PedsQL4.0). Results: Twenty-six children, aged 2.7 to 18 (median 7.4) years who were bridged to transplant, were compared with 58 children, aged 2.0 to 18.0 (median 13.0) years, who were transplanted in the same era without bridging. There were no significant differences between the 2 groups on any domains of QoL assessed by children or parents, although the small number of bridged patients increases the likelihood of a Type II error. Bridged children who were younger (r = 0.48, p = 0.02) or more recently transplanted (r = 0.42, p = 0.04) were scored by their parents as having poorer emotional QoL. Regression analysis indicated that age at transplant was the only medical or demographic variable associated with parent-reported total QoL scores (β = 0.27, p = 0.01). With few links between QoL scores and medical or demographic factors, other subjective psychologic factors may be of greater salience in determining QoL. Conclusions: Despite greater severity of illness, children who required mechanical bridging to transplantation report a QoL comparable to that of other children undergoing heart transplantation. Younger children may require greater psychologic support to reach their full potential in terms of QoL.

A new preservation solution for lung transplantation: Evaluation in a porcine transplantation model - Corrected Proof

2012-01-09

Background: Lung preservation injury is still a major problem in lung transplantation. The aim of the current study was to evaluate the effects of a new preservation solution (Custodiol-N) for lung preservation. Methods: Using an in vivo pig model, 7 lungs each were preserved for 24 hours after perfusion with: low-potassium dextran (LPD) solution as control (Group I); base solution of Custodiol-N without iron chelators (Group II); Custodiol-N (Group III); or Custodiol-N supplemented with dextran 40 (Group IV). Four animals received a sham operation. After left lung transplantation and contralateral lung exclusion, hemodynamics and blood gases were monitored for 6 hours; tissue samples were taken at the end of the experiments. Results: All animals survived the transplantation procedure. Base solution– and Custodiol-N–preserved lungs (Groups II and III) showed graft function similar to that of LPD-preserved lungs (Group I), showing a trend toward improved values. Custodiol-N with dextran (Group IV) led to a significant reduction of mean pulmonary arterial pressure (20 ± 2 vs 28 ± 3 mm Hg, p < 0.01) and pulmonary vascular resistance (410 ± 51 vs 588 ± 83 dyne/s/cm5, p < 0.01), and oxygenation ratio was significantly higher (536 ± 52 vs 313 ± 107 mm Hg at 6 hours, p < 0.01) and PCO2 values were significantly lower (51 ± 9 vs 77 ± 5 mm Hg at 6 hours, p < 0.01) at 6 hours compared with LPD (Group I). Custodiol-N (Groups II to IV) showed a trend toward a lower wet/dry ratio and reduced oxidative stress; in the presence of dextran (Group IV), the difference was again statistically significant, when compared with LPD (Group I). Conclusions: Custodiol-N solution is a new alternative preservation solution for lung transplantation that offers significantly superior protection compared with LPD when dextran 40 is added.

Prevalence, predictors, and survival in pulmonary hypertension related to end-stage chronic obstructive pulmonary disease - Corrected Proof

2012-01-09

Background: The prevalence, prognostic importance, and factors that predict the presence and degree of pulmonary hypertension (PH) diagnosed with right heart catheterization (RHC) in patients with end-stage chronic obstructive pulmonary disease (COPD) remain unclear. Methods: This retrospective study included 409 patients (61% women) with COPD/emphysema or α-1-antitrypsin deficiency who underwent lung transplant evaluation during 1991 to 2010. We analyzed the occurrence and degree of PH and compared demographics, oxygenation, lung function, hemodynamics, functional capacity, and survival in patients with and without PH. Prediction of PH was assessed using univariate and multivariate regression analysis. Results: The mean age at evaluation was 54 ± 7 years. All patients were in New York Heart Association functional class III-IV, with forced expiratory volume in 1 second of 23% ± 7% and total lung capacity of 126% ± 21% of predicted. PH was present in 146 (36%). The analysis excluded 53 (13%) with pulmonary venous hypertension (PVH). The distribution of the mean pulmonary artery pressure (mPAP) in patients with or without PH showed a unimodal normally distributed population, with a mean of 23.8 ± 6.0 mm Hg. Predictors of PH were partial pressures of oxygen and carbon dioxide. The 5-year survival rate was 37% in COPD patients with PH vs 63% in patients without PH (p = 0.016). Survival after lung transplantation did not differ (p = 0.37). Conclusions: RHC verified PH in 36% of COPD patients. Hypoxemia and hypercapnia were associated with mPAP. PH is associated with worse survival in COPD, but PH does not influence the prognosis after lung transplantation.

Risk Assessment in Pulmonary Hypertension Associated with Heart Failure and Preserved Ejection Fraction - Corrected Proof

2012-01-06

Background: Pulmonary hypertension (PH) is common in patients with left heart failure (HF), especially those with HF and preserved ejection fraction (HFpEF). However, there is limited data on risk stratification in these patients. Methods: Baseline clinical and hemodynamic variables of 339 patients with World Health Organization (WHO) Group 2 PH, 90% of whom had HFpEF, were studied to derive a multivariate Cox proportional hazards model. A simplified prognostic risk score was created based on the outcome of all-cause mortality. Nine predictors, significant after stepwise multivariable regression (p < 0.05), were used to create the risk score. Components of the risk score were functional class, diastolic blood pressure, pulmonary artery saturation, interstitial lung disease, hypotension on initial presentation, right ventricular hypertrophy, diffusion capacity of the lung for carbon monoxide, and 2 serum creatinine variables (≤ 0.9 mg/dl and ≥ 1.4 mg/dl). Results: Overall 2-year survival was 73.8% ± 2.4% in the derivation cohort, and 87.5% ± 2.3%, 66.4% ± 4.9%, and 24.4% ± 6.7% for risk scores of 0 to 2, 3 to 4, and 5+, respectively (p < 0.0001 for the trend), with a C-index of 0.76 (95% confidence interval [CI], 0.71–0.81). The risk score was validated in 2 independent PH-HFpEF cohorts: 179 patients with a C-index of 0.68 (95% CI, 0.55–0.80) and 117 patients with a C-index of 0.68 (95% CI, 0.53–0.83). For the 3 cohorts combined (N = 635), the overall C-index was 0.72 (95% CI 0.68–0.76). In all 3 cohorts individually and in the 3 cohorts combined, the risk score predicted death (hazard ratio, 1.4–1.6; p < 0.01). Conclusions: Several clinical factors independently predict death in PH-HFpEF confirmed by validation. A novel risk score composed of these factors can be used to determine prognosis and may be useful in making therapeutic decisions.

Endomyocardial biopsy and selective coronary angiography are low-risk procedures in pediatric heart transplant recipients: Results of a multicenter experience - Corrected Proof

2012-01-03

Background: No prior reports documenting the safety and diagnostic yield of cardiac catheterization and endomyocardial biopsy (EMB) in heart transplant recipients include multicenter data. Methods: Data on the safety and diagnostic yield of EMB procedures performed in heart transplant recipients were recorded in the Congenital Cardiac Catheterization Outcomes Project database at 8 pediatric centers during a 3-year period. Adverse events (AEs) were classified according to a 5-level severity scale. Generalized estimating equation models identified risk factors for high-severity AEs (HSAEs; Levels 3–5) and non-diagnostic biopsy samples. Results: A total of 2,665 EMB cases were performed in 744 pediatric heart transplant recipients (median age, 12 years [interquartile range, 4.8, 16.7]; 54% male). AEs occurred in 88 cases (3.3%), of which 28 (1.1%) were HSAEs. AEs attributable to EMB included tricuspid valve injury, transient complete heart block, and right bundle branch block. Amongst 822 cases involving coronary angiography, 10 (1.2%) resulted in a coronary-related AE. There were no myocardial perforations or deaths. Multivariable risk factors for HSAEs included fewer prior catheterizations (p = 0.006) and longer case length (p < 0.001). EMB yielded sufficient tissue for diagnosis in 99% of cases. Longer time since heart transplant was the most significant predictor of a non-diagnostic biopsy sample (p < 0.001). Conclusions: In the current era, cardiac catheterizations involving EMB can be performed in pediatric heart transplant recipients with a low AE rate and high diagnostic yield. Risk of HSAEs is increased in early post-transplant biopsies and with longer case length. Longer time since heart transplant is associated with non-diagnostic EMB samples.

A novel method of measuring cardiac preservation injury demonstrates University of Wisconsin solution is associated with less ischemic necrosis than Celsior in early cardiac allograft biopsy specimens - Corrected Proof

2012-01-03

Background: No consensus exists on the optimal heart preservative solution (HPS) for cardiac allograft preservation. The significance of varying degrees of acute ischemic necrosis (AIN) in early transplant biopsy specimens is unknown. We investigated the effects of HPS on early cardiac histopathology by developing a novel grading system of AIN. Methods: A retrospective review of our institutional database of orthotopic heart transplants (OHT) identified hearts preserved with University of Wisconsin (UW) or Celsior solutions. AIN severity was graded on early post-transplant biopsy specimens. Primary stratification was by HPS. Multivariable models examined mortality, AIN grade, primary graft dysfunction (PGD), and right heart failure (RHF). Results: From 1996 to 2010, 42 of 174 adult OHTs were preserved with UW and 132 with Celsior, from which 431 biopsy specimens were reviewed. UW and Celsior had similar 30-day (p = 0.79) and 1-year mortality (p = 0.92). Celsior was associated with significantly more AIN on the first (p = 0.02) and second (p = 0.04) specimens and persisted on multivariable analysis for the first (odds ratio, 2.93; 95% confidence interval, 1.26–6.83; p = 0.01) and second biopsy specimen (2.08; 0.99–4.34; p = 0.05). When stratified by AIN score, 30-day and 1-year mortality were similar (p > 0.05). Adjusted analysis showed increasing AIN score on the first biopsy was strongly associated with an increased incidence of PGD (1.59; 1.02–2.47; p = 0.04) and RHF (2.45; 1.14–5.27; p = 0.02). Conclusions: Our grading system provides a simple, reproducible method for determining AIN. UW is associated with less AIN than Celsior solution. Early biopsy ischemia is associated with PGD and RHF. AIN may have prognostic significance and its routine evaluation should be considered.

Donor scoring system for heart transplantation and the impact on patient survival - Corrected Proof

2011-12-19

Background: The aim of this study was to design and validate a heart donor score that reflects experts' perceived risk of allograft failure. Methods: All heart donors reported to Eurotransplant between January 1, 2005 and December 31, 2008 (N = 4,110) were used to create a donor score. Based on observed discard rates and using multivariate regression, points were assigned for the following donor factors: age; cause of death; body mass index (BMI); diabetes mellitus (DM); duration of ICU stay; compromised history (drug, abuse, sepsis, meningitis, malignancy, HBsAg+ or anti-HCV+); hypertension; cardiac arrest; echocardiography; coronary angiogram; serum sodium; and noradrenaline and dopamine/dobutamine doses. The donor score was obtained by adding all points. All heart donors reported to Eurotransplant in 2009 were included to validate the score (N = 885). Results: All donor factors, except BMI, DM and duration of ICU stay, significantly predicted discard. Based on the median value of the score, donors were classified into low-risk donors (LRDs: ≤16 points) and high-risk donors (HRDs: ≥17 points). In the validation set, discard rates were significantly different when comparing HRDs (35%) and LRDs (7%) (p < 0.0001). In addition, the heart donor score was significantly associated with 3-year survival: LRD 81.5% vs HRD 70.0% (p = 0.004). Conclusions: The heart donor score accurately reflects the likelihood of organ acceptance and predicts long-term patient mortality. Application of this score at time of donor reporting may facilitate donor risk assessment and allow for more appropriate matching of extended criteria donor hearts.

Histologic and functional evaluation of lungs reconditioned by ex vivo lung perfusion - Corrected Proof

2011-12-02

BACKGROUND: Only about 15% of donor lungs are considered suitable for transplantation (LTx). Ex vivo lung perfusion (EVLP) has been developed as a method to reassess and repair damaged lungs. We report our experience with EVLP in non-acceptable donor lungs and evaluate its ability to recondition these lungs.METHODS: We studied lungs from 16 brain-dead donors rejected for LTx. After harvesting, the lungs were stored at 4°C for 10 hours and subjected to normothermic EVLP with Steen Solution (Vitrolife, Göteborg, Sweden) for 60 minutes. For functional evaluation, the following variables were assessed: partial pressure of arterial oxygen (Pao2), pulmonary vascular resistance (PVR), and lung compliance (LC). For histologic assessment, lung biopsy was done before harvest and after EVLP. Tissue samples were examined under light microscopy. To detect and quantify apoptosis, terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling assay was used.RESULTS: Thirteen lung donors were refused for having impaired lung function. The mean Pao2 obtained in the organ donor at the referring hospital was 193.7 mm Hg and rose to 489 mm Hg after EVLP. During EVLP, the mean PVR was 652.5 dynes/sec/cm5 and the mean LC was 48 ml/cm H2O. There was no significant difference between the mean Lung Injury Score before harvest and after EVLP. There was a trend toward a reduction in the median number of apoptotic cells after EVLP.CONCLUSIONS: EVLP improved lung function (oxygenation capacity) of organs considered unsuitable for transplantation. Lung tissue structure did not deteriorate even after 1 hour of normothermic perfusion.

Withdrawal of proliferation signal inhibitors due to adverse events in the maintenance phase of heart transplantation - Corrected Proof

2011-12-02

Background: The increasing use of proliferation signal inhibitors (PSIs) has raised the issue of their risk profile. We sought to determine the causes, incidence, risk factors, and consequences of withdrawal due to adverse events of PSIs in maintenance heart transplantation.Methods: This was a retrospective study from 9 centers of the Spanish Registry for Heart Transplantation. Demographic, clinical, analytic, and evolution data were obtained for patients in whom a PSI (sirolimus or everolimus) was used between October 2001 and March 2009.Results: In the first year, 16% of 548 patients could not tolerate PSIs. This incidence rate stabilized to 3% to 4% per year thereafter. The most frequent causes for discontinuation were edema (4.7%), gastrointestinal toxicity (3.8%), pneumonitis (3.3%), and hematologic toxicity (2.0%). In multivariate analysis, withdrawal of PSI was related to the absence of statin therapy (p = 0.006), concomitant treatment with anti-metabolites (p = 0.006), a poor baseline renal function (p = 0.026), and multiple indications for PSI use (p = 0.04). Drug discontinuation was associated with a decline in renal function (p = 0.045) but not with an excess in mortality (p = 0.42).Conclusions: In this large cohort of maintenance heart transplant recipients taking a PSI, 16% withdrew treatment in the first year, and 25% had stopped PSI due to severe adverse events by the fourth year. This high rate of toxicity-related PSI withdrawal could limit the clinical utility of this otherwise novel class of immunosuppressive agents.

Pneumonectomy acutely after pediatric bilateral lung transplantation: Management of communicating thoracic spaces - Corrected Proof

Andres X. Samayoa, George B. Mallory, David L.S. Morales — 2011-12-02

Imbalance or free communication of the thoracic and mediastinal spaces can cause critical compression, herniation, or shifting of vital structures. We report a patient with a pneumonectomy after bilateral lung transplantation (LTx) in which all pleural and mediastinal spaces were freely communicating.

Pre-operative risk factors and clinical outcomes associated with vasoplegia in recipients of orthotopic heart transplantation in the contemporary era - Corrected Proof

2011-11-24

Background: Patients who underwent orthotopic heart transplant (OHT) can develop vasoplegia, which is associated with high mortality and morbidity. Herein we examine the pre-operative risk in OHT recipients at our institution.Methods: We reviewed peri-operative data from 311 consecutive adult patients who underwent OHT between January 2003 and June 2008. Vasoplegia was defined as persistent low systemic vascular resistance, despite multiple intravenous pressor drugs at high dose, between 6 and 48 hours after surgery.Results: In our cohort of 311 patients, 35 (11%) patients developed vasoplegia syndrome; these patients were more likely to be UNOS Status 1A, with a higher body surface area (1.8 ± 0.25 vs 1.63 ± 0.36, p = 0.0007), greater history of thyroid disease (38.2% vs 18.5%, p = 0.0075) and a higher rate of previous cardiothoracic surgery (79% vs 48%, p = 0.0006). Pre-operatively, they were more frequently treated with aspirin (73% vs 48%, p = 0.005) and mechanical assist devices (ventricular assist devices [VADs]: 45% vs 17%, p < 0.0001; total artificial hearts: 8.6% vs 0%, p < 0.0001), and less treated with milrinone (14.7% vs 45.8%, p = 0.0005). Bypass time (118 ± 37 vs 142 ± 39 minutes, p = 0.0002) and donor heart ischemic time (191 ± 46 vs 219 ± 51 minutes, p = 0.002) were longer, with higher mortality (3.2% vs 17.1%, p = 0.0003) and morbidity in the first 30 days after transplant. In the multivariate analysis, history of thyroid disease (odds ratio [OR] = 2.7, 95% CI 1.0 to 7.0, p = 0.04) and VAD prior to transplant (OR = 2.8, 95% CI 1.07 to 7.4, p = 0.03) were independent risk factors for development of vasoplegia syndrome.Conclusions: High body mass index, long cardiopulmonary bypass time, prior cardiothoracic surgery, mechanical support, use of aspirin, and thyroid disease are risk factors associated with development of vasoplegia syndrome.

Post-transplant lymphoproliferative disorder after lung transplantation: A review of 35 cases - Corrected Proof

2011-11-24

Background: Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation. The risk of developing PTLD varies depending on a number of factors, including the organ transplanted and the degree of immunosuppression used.Methods: We report a retrospective analysis of 35 patients with PTLD treated at our center after lung transplantation. Of 705 patients who received allografts, 34 (4.8%) developed PTLD. One patient underwent transplantation elsewhere and was treated at our center.Results: PTLD involved the allograft in 49% of our patients and the gastrointestinal (GI) tract lumen in 23%. Histologically, 39% of tumors were monomorphic and 48% polymorphic. The time to presentation defined the location and histology of disease. Of 17 patients diagnosed within 11 months of transplantation, PTLD involved the allograft in 12 (71%) and the GI tract in 1 (p = 0.01). This “early” PTLD was 85% polymorphic (p = 0.006). Conversely, of the 18 patients diagnosed more than 11 months after transplant, the lung was involved in 5 (28%) and the GI tract in 7 (39%; p = 0.01). “Late” PTLD was 71% monomorphic (p = 0.006). Median overall survival after diagnosis was 18.57 months. Overall survival did not differ between all lung transplant recipients and those who developed PTLD.Conclusions: PTLD is an uncommon complication after lung transplantation, and its incidence declined remarkably in the era of modern immunosuppression. We report several factors that are important for predisposition toward, progression of, and treatment of PTLD after lung transplantation.

Cost-effectiveness of the implantable HeartMate II left ventricular assist device for patients awaiting heart transplantation - Corrected Proof

Santiago G. Moreno, Nicola Novielli, Nicola J. Cooper — 2011-11-24

Background: Left ventricular assist devices (LVADs) are being proposed as a life-saving therapeutic alternative to conventional medical management for people with end-stage heart failure awaiting transplantation. However, cost-effectiveness assessments of first-generation LVADs have not been encouraging. The cost-effectiveness of the enhanced second-generation LVAD HeartMate II (Thoratec, Pleasanton, CA) is estimated here.Methods: A probabilistic Markov model was developed to extrapolate survival, utility, and resource use over the total lifetime of a hypothetic cohort of patients with end-stage heart failure under the 2 competing therapeutic strategies, using the most robust and recently published evidence about their performance. Cost data are based on UK activity to consider reimbursement in the UK National Health Service setting.Results: HeartMate II had a mean cost per quality-adjusted life-year (QALY) of £258,922 ($414,275). The sensitivity analysis showed that 2 factors mainly explain why HeartMate II is not a cost-effectiveness strategy as a bridge-to-transplant: (1) the survival of heart transplant candidates treated conventionally while on the waiting list has significantly improved in recent years, and (2) the high acquisition cost of the device, £94,200 ($150,720).Conclusions: Although HeartMate II LVAD implantation significantly increases survival compared with conventional medical management, it does not provide good value for the money spent according to established thresholds of cost-effectiveness in the UK. HeartMate II is unlikely to become cost-effective unless the additional survival gained by its use raises and/or the device is given free of charge. Therefore, its implantation to transplant candidates lacks justification in terms of cost-effectiveness.

Development of a quantitative donor risk index to predict short-term mortality in orthotopic heart transplantation - Corrected Proof

2011-11-18

BACKGROUND: No standard index based on donor factors exists for predicting mortality after orthotopic heart transplantation (OHT). We utilized United Network for Organ Sharing (UNOS) data to develop a quantitative donor risk score for OHT.METHODS: We examined a prospectively collected open cohort of 22,252 patients who underwent primary OHT (1996 to 2007). Of the 284 donor-specific variables, those associated with 1-year (year) mortality (exploratory p-value < 0.2) were incorporated into a multivariate (MV) logistic regression model. The final model contained donor factors that improved the explanatory power (by pseudo-R2, area under the curve and likelihood ratio test). A quantitative donor risk score was created using odds ratios (ORs) from the final model. For external validity, a cross-validation strategy was employed whereby the score was generated using a randomly generated subset of cases (n = 17,788) and then independently validated on the remaining patients (n = 4,464).RESULTS: A 15-point scoring system incorporated 4 variables: ischemic time; donor age; race mismatching; and blood urea nitrogen (BUN)/creatinine ratio. Derivation and validation cohort scores ranged from 0 to 5 and 0 to 2, respectively (mean 4.0 ± 2.1 for each). Each increase of 1 point increased the risk of 1-year death by 9% (OR = 0.09 [1.07 to 0.12]) in the derivation cohort and 13% (OR = 0.13 [1.08 to 0.18]) in the validation cohort (each p < 0.001). The odds of 1-year mortality by increments of 3 points were: 0 to 2 points (reference); 3 to 5 points (OR = 0.25 [1.12 to 0.40], p < 0.001); 6 to 8 pts (OR = 0.77 [1.56 to 2.02], p < 0.001); and 9 to 15 points (OR = 1.92 [1.54 to 2.39], p < 0.001). Donor risk score was predictive for 30-day mortality (OR = 0.11 [1.08 to 0.14], p < 0.001) and 5-year cumulative mortality (OR = 0.11 [1.09 to 0.13], p < 0.001).CONCLUSIONS: We present a novel donor risk index for OHT predicting short- and long-term mortality. This donor risk score may prove valuable for donor heart allocation and prognosis after OHT.

Early outcomes of bilateral sequential single lung transplantation after ex-vivo lung evaluation and reconditioning - Corrected Proof

2011-11-17

Background: Ex vivo lung perfusion (EVLP) is a novel approach for extended evaluation and/or reconditioning of donor lungs not meeting standard International Society for Heart and Lung Transplantation criteria for transplantation.Methods: We retrospectively evaluated 13 consecutive EVLP runs between January 2009 and December 2010. Lungs rejected for routine transplantation were implanted to the EVLP circuit and reperfused using acellular supplemented Steen Solution (Vitrolife, Göteborg, Sweden) up to a target flow rate of 40% of the donor's calculated flow at a cardiac index of 3.0 liters/min/m2; target left atrial pressure < 5 mm Hg; and pulmonary artery pressure < 15 mm Hg. Mechanical ventilation was introduced after rewarming to 32°C: tidal volume, 6 to 8 ml/kg; respiratory rate, 7 to 8 breaths/min; duration of inspiration/expiration (I/E) ratio, 1:2; and positive end-expiratory pressure, 5 to 10 cm H2O. Hemodynamic and respiratory data monitoring with hourly clinical assessment were performed. Donor data, conversion rate to transplantation, and recipient outcome were analyzed.Results: Donor data (n = 13) were: age, 44.23 ± 8.33 years; female/male, 8:5; cause of death: intracranial hemorrhage, 11 (85%), stroke, 1 (7.5%), hypoxic brain injury, 1 (7.5%); smoking history, 9 (69%), 17.44 ± 8.92 pack-years; mechanical ventilation, 102.6 ± 91.92 hours; chest x-ray imaging: abnormal, 12 (92.5%); normal, 1 (7.5%). EVLP: mean 141 ± 28.83 minutes. Arterial partial pressure of oxygen/fraction of inspired oxygen 100% before termination of the circuit vs pre-retrieval value: 57.32 ± 9.1 vs 42.36 ± 14.13 kPa (p < 0.05). Six (46%) pairs of donor lungs were transplanted. Median follow-up was 297.5 days (range, 100–390 days), with 100% survival at 3 months.Conclusions: EVLP may facilitate assessment and/or reconditioning of borderline lungs, with a conversion rate of 46 % and good short-term survival.

Clinically irrelevant circulating human leukocyte antigen antibodies in the presence of ventricular assist devices - Corrected Proof

2011-11-14

Introduction: Identification of anti-human leukocyte antigen (HLA) antibodies by single-antigen beads (SAB) allows for prediction of donor-specific crossmatches (virtual crossmatches), thus facilitating the allocation of organs from deceased donors. However, the clinical relevance of HLA antibodies identified by SAB has been less than clear. This study demonstrates that sera from cardiac transplant candidates with a ventricular assist device (VAD) or infection may contain clinically irrelevant antibodies that bind to the beads but not to lymphocytes.Methods: Investigated were 5 cardiac transplant candidates (3 with VAD, all with infections, and 1 retransplant) with positive HLA antibodies detected by SAB, but negative by cytotoxicity. To determine clinical relevance of the antibodies, flow cytometric crossmatches (FCXM) were performed. Untreated beads and elution buffer–treated beads to dissociate the β-2 microglobulin and the peptide from the heavy chain were used.Results: The virtual crossmatch data were compared with data from actual FCXMs. Of 40 T-cell and B-cell FCXM, SAB-identified HLA antibodies were predictive for only 1 T-cell and 9 B-cell FCXM outcomes. Patients' sera contained a mixture of antibodies directed against cryptic epitopes on the heavy chain and exposed epitopes. The mean fluorescence intensity of antibodies varied from 1,040 to 11,000.Conclusions: Sera from cardiac transplant candidates with or without VAD may contain natural antibodies that do not bind to intact antigens on the cell surface. Therefore, great care must be exercised before denying a life-saving transplant to these patients simply on the basis of SAB results.

Endobronchial valve therapy for pneumothorax as a bridge to lung transplantation - Corrected Proof

2011-11-04

Pneumothoraces and bronchopleural fistulas (BPF) represent a common life-threatening complication in patients with cystic fibrosis (CF). The current treatment paradigm for BPFs, including prolonged thoracostomy tube drainage, surgical repair, and pleurodesis, carries significant risks for patients with CF and can potentially exclude patients from lung transplantation (LT) due to an increased incidence of hemorrhagic complications. This case reports describes the use of an endobronchial valve to successfully seal a prolonged air leak in a patient with CF awaiting LT.

Heart transplantation and cardiac amyloidosis: Approach to screening and novel management strategies - Corrected Proof

2011-11-04

Limited data exist regarding screening methods and outcomes for orthotopic heart transplantation (OHT) in cardiac amyloidosis. As a result, uncertainty exists over the best approach to OHT for cardiac amyloidosis and for the timing of critical post-transplant therapies. This article reviews 6 patients who underwent OHT for cardiac amyloidosis at the Stanford University Amyloid Center from 2008 to present. All patients with light-chain amyloidosis received chemotherapy in the interval between OHT and autologous hematopoietic stem cell transplant. Five patients remain alive up to 25 months after OHT, without evidence of recurrent cardiac amyloid deposition. A novel strategy of OHT, followed by light-chain suppressive chemotherapy before autologous hematopoietic stem cell transplant, is feasible for patients with light-chain amyloidosis.

Parameters of donor–recipient size mismatch and survival after bilateral lung transplantation - Corrected Proof

2011-10-31

Background: The purpose of this study was to investigate the relationship between donor–recipient height, gender and predicted estimates of total lung capacity (pTLC) mismatches and post-transplant survival.Methods: The lung transplant databases at three programs were reviewed. The pTLC ratios (donor pTLC/recipient pTLC) and height ratios (donor height/recipient height) were calculated retrospectively. Patients were grouped according to pTLC ratio ≤1.0 or >1.0 and height ratio ≤1.0 or >1.0, and according to gender (mis-)matching. A time-to-event analysis was performed for risk of death after transplantation conditional on 30-day survival using Kaplan–Meier survival and Cox proportional hazard models.Results: There were 211 adult bilateral lung transplant recipients who qualified for the analysis. Mean follow-up was comparable for all cohorts (range 2.21 to 3.85 years). In the univariate Cox proportional hazard models, a pTLC ratio >1.0 (HR 0.43, p = 0.002) and a height ratio >1.0 (HR 0.61, p = 0.03) were associated with better survival, and a female-donor-to-male-recipient gender mismatch (F-to-M) was associated with worse survival (HR 2.35, p = 0.01). In the multivariate Cox proportional hazard model accounting for F-to-M gender mismatch and height ratio >1.0, a pTLC ratio >1.0 remained associated with survival (HR 0.38, p = 0.015). However, accounting for a pTLC ratio >1.0, a height ratio of >1.0 and F-to-M mismatch were not associated with survival.Conclusions: A pTLC ratio >1.0 is associated with improved survival after bilateral lung transplantation. The pTLC ratio might better reflect allograft–thorax mismatch than the height ratio, as it also accounts for effects of gender on lung and thoracic volumes.

Pediatric heart failure and worsening renal function: Association with outcomes after heart transplantation - Corrected Proof

2011-10-24

Background: Renal function deteriorates in some children awaiting heart transplantation. This study was initiated to assess the effects of worsening renal function (WRF) on post-heart transplantation outcomes and to determine the effect of waiting-list associated WRF on survival after heart transplantation.Methods: All children aged <18 years who underwent their first heart transplantation between 1999 and 2009, had reported plasma creatinine concentrations at listing and at transplantation, and were free of renal replacement therapy at listing were identified using the Organ Procurement and Transplant Network database. The independent effects of WRF on in-hospital mortality and post-discharge survival were assessed using logistic regression and log-rank analyses, respectively.Results: Of the 2,216 children included in the analysis, WRF occurred in 334 (15%) awaiting heart transplantation: WRF was mild (stage 1) in 210 (63%), moderate (stage 2) in 40 (12%), and severe (stage 3) in 84 (25%). All WRF stages were independently associated with in-hospital, post-transplant mortality: mild WRF with adjusted odds ratio (AOR) of 2.1 (95% confidence interval [CI], 1.2–3.5); moderate WRF, 2.7 (95% CI, 1.1–6.7); and severe WRF, 3.6 (95% CI, 2.0–6.5). WRF was not associated with death after discharge (hazard ratio, 1.2; 95% CI, 0.9–1.7) at a median follow-up of 2.7 years.Conclusions: WRF occurs in 15% of children awaiting heart transplantation and is associated with early but not late post-transplant mortality.

Over 2-year disease-free survival after multimodality therapy of a primary cardiac lymphoma - Corrected Proof

Michael Ried, Stephan Hirt, Christof Schmid — 2011-10-24

This comment deals with our study regarding the innovative, sequential therapy of a primary cardiac lymphoma. Primary cardiac T-cell lymphoma is defined as a non-Hodgkin lymphoma (NHL) involving only the heart and/or the pericardium, or as an NHL with the main bulk of the tumor located on the heart. It is an extremely rare disease with a typical heterogeneous clinical manifestation and 100% mortality if left untreated. Herein we describe a clinical follow-up of >26 months in a young female patient with eventful heart failure due to the uncommon diagnosis of a primary cardiac T-cell lymphoma.

Short-term and long-term outcomes of acute kidney injury after lung transplantation - Corrected Proof

2011-10-14

Background: The effect of acute kidney injury (AKI) after lung transplantation has been described infrequently and with inconsistent results. Using a newly adopted and validated definition of AKI proposed by the Acute Kidney Injury Network (AKIN), we examined the incidence of AKI and associated renal morbidity and short-term and long-term mortality.Methods: We retrospectively evaluated data of 657 patients who underwent lung transplantation from 1997 to 2009. Outcomes analyzed were the incidence of AKI, as defined and categorized into 3 stages according to creatinine criteria from the AKIN classification (AKIN 1, AKIN 2, and AKIN 3), cumulative incidence of chronic kidney disease (CKD), as defined by an estimated glomerular filtration rate ≤ 29 ml/min/1.73 m2, and/or the onset of end-stage renal disease, as defined by the need for renal replacement therapy for 8 weeks with no recovery on follow-up or need for kidney transplant, and long-term mortality.Results: We identified 424 patients (65%) who had at least 1 AKI (309 [47%] AKIN 1 and 115 [17%] AKIN 2–3) event in the first 2 weeks after transplantation. At 1 year, the cumulative incidence of CKD was 5.8%, 12.8%, 24.5 % in the no-AKI, AKIN 1, and AKIN 2–3 patients, respectively. After a median follow-up of 2.2 years, 277 (42%) died. One-year patient survival was 91%, 82%, 66% in the no-AKI, AKIN 1, and AKIN 2–3 patients, respectively. Adjusting for age, sex, race, type and cause of lung transplant, diabetes, and hypertension, the hazard ratio for death was 1.7 (95% confidence interval, 1.2–2.2; p = 0.0002) for AKIN 1 and 2.9 (95% confidence interval, 1.7–3.7; p < 0.001) for AKIN 2–3.Conclusions: AKI is a common complication after lung transplantation and is associated with increased risk of CKD and all cause-mortality on long-term follow-up.

Incidence of impaired renal function after lung transplantation - Corrected Proof

2011-10-05

Background: Impaired renal function is a frequent complication after lung transplantation (LTx). Since the early days of LTx, recipient eligibility criteria slowly became less strict, while treatment regimens evolved. These developments may have had opposing effects on the risk for impaired renal function. We aimed to study changes in recipient characteristics in conjunction with incidence of impaired renal function in consecutive series of lung transplant recipients (LTRs).Methods: Three hundred forty adult LTRs (mean age 45 ± 12 years, 50.3% male, median follow-up 3.4 [1.0 to 7.1] years) were divided into four consecutive patient time-series: 1990 to 1996 (n = 93); 1997 to 2001 (n = 79); 2002 to 2005 (n = 89); and 2006 to 2008 (n = 79). The primary end-point was cumulative incidence of doubling of serum creatinine (DSC), taking into account the competing risk of death. Measured glomerular filtration rate (mGFR; 125I-Iothalamate) was assessed as a secondary end-point.Results: Mean age at transplantation (p = 0.001), prevalence of hypertension (p = 0.005), pack-years of former smoking (p = 0.001) and body mass index (p = 0.05) increased across the consecutive series. The cumulative incidence of DSC at 24 months after LTx was 43%, 37%, 35% and 29%, respectively, in the consecutive series (p = 0.01). Despite higher prevalence of renal risk factors, there was lower adjusted risk of DSC in the consecutive series, with hazard ratios [95% CI] of 0.62 [0.34 to 1.15], 0.50 [0.25 to 0.98] and 0.31 [0.154 to 0.67], respectively, compared with the 1990 to 1996 series. Accordingly, mGFRs at 24 months after LTx were 51 ± 17, 53 ± 17, 57 ± 21 and 63 ± 21 ml/min/1.73 m2 in the consecutive series (p = 0.002).Conclusions: Despite the higher prevalence of renal risk factors in more recently transplanted patients, renal outcome after LTx has improved over time. Nevertheless, impaired renal function remains a frequent complication after LTx.

Histopathology of renal failure after heart transplantation: A diverse spectrum - Corrected Proof

2011-09-26

Background: Chronic kidney disease occurs frequently after heart transplantation and is associated with significant morbidity and mortality. Herein we describe the histopathology associated with renal failure in a cohort of heart transplant recipients.Methods: Over a 4-year period all patients with an estimated GFR <30 ml/min/1.73 m2 or significant proteinuria were referred to the kidney transplant clinic for clinical evaluation. A percutaneous renal biopsy was performed as part of a standardized evaluation.Results: Eighteen patients underwent renal biopsy 5.8 ± 4.1 years after transplantation. Hypertension (88.9%), Type 2 diabetes (55.6%) and allograft vasculopathy (38.9%) were prevalent. All patients were receiving calcineurin inhibitors. Mean creatinine was 2.9 ± 1.2 mg/dl with an estimated GFR 27.9 ± 9.1 ml/min/1.73 m2. Eight patients (44%) had proteinuria >1 g per 24 hours. The major histologic findings were nephrosclerosis plus diabetic glomerulopathy (50%), nephrosclerosis and focal segmental glomerulosclerosis (22.2%) and nephrosclerosis alone (22.2%). One patient had direct CNI toxicity consisting of nodular sub-adventitial hyalinosis. Eleven patients (61.1%) had glomerular disease and 11 patients (61.1%) had moderate or severe tubular atrophy. During follow-up, 5 patients (27.8%) started hemodialysis, 4 (22.2%) died, and 2 (11.1%) received a renal transplant.Conclusions: We observed diverse histologic patterns in this series of renal biopsies suggesting that chronic kidney disease after heart transplantation has a complex and varied pathologic basis. Further defining the renal injuries that precede heart transplantation and predispose to the progression of kidney disease after transplant may assist in treating this population.

WITHDRAWN: Predictors of long-term survival in pulmonary hypertension treated with bosentan - Corrected Proof

2011-03-18

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found at (http://www.elsevier.com/locate/withdrawalpolicy.