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Introduction: Chronic kidney disease (CKD) is associated with significant morbidity and mortality after lung transplantation (LTX). Calcineurin inhibitor (CNI) nephrotoxicity is the leading cause of CKD. After kidney transplantation, polyomavirus-associated nephropathy (PyVAN) is a well-recognized problem. This study aims to evaluate the role of polyomavirus in patients after LTX., Methods: From January 2017 to January 2020, all lung transplant recipients who performed follow-up visits in our center were included in the study and retrospectively assessed. We measured renal function (creatinine levels before and after transplantation), JCPyV, and BKPyV load by polymerase chain reaction (PCR) in serum and urine samples after transplantation., Results: In total, 104 consecutive patients (59 males, 56.7%) with a mean age of 49.6 ± 11.1 years were identified. JCPyV was found in urine of 36 patients (34.6%) and serum of 3 patients (2.9%). BKPyV was found in urine of 40 patients (38.5%) and serum of 4 patients (3.8%), respectively. Urine evidence for JCPyV (p < 0.001, coefficient: +21.44) and BKPyV (p < 0.001, coefficient: +29.65) correlated highly with further kidney function decline., Conclusion: Kidney function deterioration is associated with JCPyV and BKPyV viruria in patients after LTX. This might indicate a role of PyVAN in lung transplant recipients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Phenotyping chronic lung allograft dysfunction (CLAD) in single lung transplant (SLTX) recipients is challenging. The aim of this study was to assess the diagnostic and prognostic value of longitudinal lung function tests in SLTX recipients with CLAD., Methods: A total of 295 SLTX recipients were analyzed and stratified according to native lung physiology. In addition to spirometry, measurements of static lung volumes and lung capacities were used to phenotype patients and to assess their prognostic value. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n = 71)., Results: Of 224 lung transplant recipients, 105 (46.9%) developed CLAD. Time to CLAD onset (hazard ratio [HR]: 0.82, 95% CI: 0.74-0.90; p < 0.001), severity of CLAD at onset (HR: 0.97, 95% CI: 0.94-0.99; p = 0.009), and progression after onset of CLAD (HR: 1.03, 95% CI: 1.00-1.05; p = 0.023) were associated with outcome. Phenotypes at onset were bronchiolitis obliterans syndrome (BOS) (59.1%), restrictive allograft syndrome (RAS) (12.4%), mixed phenotype (6.7%), and undefined phenotype (21.9%). Survival estimates differed significantly between phenotypes (p = 0.004), with RAS and mixed phenotype being associated with the worst survival, followed by BOS and undefined phenotype. Finally, a higher hazard for mortality was noticed for RAS (HR: 2.34, 95% CI: 0.99-5.52; p = 0.054) and mixed phenotype (HR: 3.30, 95% CI: 1.20-9.11; p = 0.021) while controlling for time to CLAD onset and severity of CLAD at onset., Conclusions: Phenotyping CLAD in SLTX remains challenging with a high number of patients with an undefined phenotype despite comprehensive lung function testing. However, phenotyping is of prognostic value. Furthermore, early, severe, and progressive CLADs are associated with worse survival., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Tobacco use after lung transplantation is associated with adverse outcome. Therefore, active smoking is regarded as a contraindication for lung transplantation and should be excluded prior to placement on the waiting list. The aim of the study was to compare self-reporting with a systematic cotinine based screening approach to identify patients with active nicotine abuse. Nicotine use was systematically assessed by interviews and cotinine test in all lung transplant candidates at every visit in our center. Patients were classified according to the stage prior to transplantation and cotinine test results were compared to self-reports and retrospectively analyzed until June 2019. Of 620 lung transplant candidates, 92 patients (14.8%) had at least one positive cotinine test. COPD as underlying disease (OR 2.102, CI 1.110-3.981; p = 0.023), number of pack years (OR 1.014, CI 1.000-1.028; p = 0.047) and a time of cessation less than one year (OR 2.413, CI 1.410-4.128; p = 0.001) were associated with a positive cotinine test in multivariable regression analysis. The majority of non-COPD patients (n = 13, 72.2%) with a positive test had a cessation time of less than one year. 78 patients (84.7%) falsely declared not consuming any nicotine-based products prior to the test. Finally, all never smokers were test negative. In conclusion, our data demonstrate that active nicotine use is prevalent in transplant candidates with a high prevalence of falsely declaring nicotine abstinence. COPD was the main diagnosis in affected patients. Short cessation time and a high number of pack years are risk factors for continued nicotine abuse., Competing Interests: The authors have declared that no competing interests exist.

Pirfenidone demonstrated pleiotropic antiinflammatory effects in various experimental and clinical settings. The aim of this study was to assess the impact of previous treatment with pirfenidone on short-term outcomes after single lung transplantation (SLTx). Therefore, patients with idiopathic pulmonary fibrosis (IPF) who were undergoing SLTx were screened retrospectively for previous use of pirfenidone and compared to respective controls. Baseline parameters and short-term outcomes were recorded and analyzed. In total, 17 patients with pirfenidone were compared with 26 patients without antifibrotic treatment. Baseline characteristics and severity of disease did not differ between groups. Use of pirfenidone did not increase blood loss, wound-healing, or anastomotic complications. Severity of primary graft dysfunction at 72 hours was less (0.3 ± 0.6 vs 1.4 ± 1.3, P = .002), and length of mechanical ventilation (37.5 ± 34.8 vs 118.5 ± 151.0 hours, P = .016) and intensive care unit (ICU) stay (6.6 ± 7.1 vs 15.6 ± 20.3, P = .089) were shorter in patients with pirfenidone treatment. An independent beneficial effect of pirfenidone was confirmed by regression analysis while controlling for confounding variables (P = .016). Finally, incidence of acute cellular rejections within the first 30 days after SLTx was lower in patients with previous pirfenidone treatment (0.0% vs 19.2%; P = .040). Our data suggest a beneficial role of previous use of pirfenidone in patients with IPF who were undergoing SLTx., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Extracorporeal circulation (ECC) is an invaluable tool in lung transplantation (lutx). More than the past years, an increasing number of centers changed their standard for intraoperative ECC from cardiopulmonary bypass (CPB) to extracorporeal membrane oxygenation (ECMO) - with differing results. This meta-analysis reviews the existing evidence. An online literature research on Medline, Embase, and PubMed has been performed. Two persons independently judged the papers using the ACROBAT-NRSI tool of the Cochrane collaboration. Meta-analyses and meta-regressions were used to determine whether veno-arterial ECMO (VA-ECMO) resulted in better outcomes compared with CPB. Six papers - all observational studies without randomization - were included in the analysis. All were considered to have serious bias caused by heparinization as co-intervention. Forest plots showed a beneficial trend of ECMO regarding blood transfusions (packed red blood cells (RBCs) with an average mean difference of -0.46 units [95% CI = -3.72, 2.80], fresh-frozen plasma with an average mean difference of -0.65 units [95% CI = -1.56, 0.25], platelets with an average mean difference of -1.72 units [95% CI = -3.67, 0.23]). Duration of ventilator support with an average mean difference of -2.86 days [95% CI = -11.43, 5.71] and intensive care unit (ICU) length of stay with an average mean difference of -4.79 days [95% CI = -8.17, -1.41] were shorter in ECMO patients. Extracorporeal membrane oxygenation treatment tended to be superior regarding 3 month mortality (odds ratio = 0.46, 95% CI = 0.21-1.02) and 1 year mortality (odds ratio = 0.65, 95% CI = 0.37-1.13). However, only the ICU length of stay reached statistical significance. Meta-regression analyses showed that heterogeneity across studies (sex, year of ECMO implementation, and underlying disease) influenced differences. These data indicate a benefit of the intraoperative use of ECMO as compared with CPB during lung transplant procedures regarding short-term outcome (ICU stay). There was no statistically significant effect regarding blood transfusion needs or long-term outcome. The superiority of ECMO in lutx patients remains to be determined in larger multi-center randomized trials.

Background: This retrospective single-center study aimed to analyze transfusion requirements, coagulation parameters, and outcome parameters in patients undergoing lung transplantation (LuTx) with intraoperative extracorporeal circulatory support, comparing cardiopulmonary bypass (CPB), and extracorporeal membrane oxygenation (ECMO)., Methods: Over a 3-year period, 49 of a total of 188 LuTx recipients were identified being set intraoperatively on either conventional CPB (n = 22) or ECMO (n = 27). Intra- and postoperative transfusion and coagulation factor requirements as well as early outcome parameters were analyzed., Results: LuTx patients on CPB had significantly higher intraoperative transfusion requirements when compared with ECMO patients, that is, packed red cells (9 units [5-18] vs. 6 units [4-8], p = 0.011), platelets (3.5 units [2-4] vs. 2 units [0-3], p = 0.034), fibrinogen (5 g [4-6] vs. 0 g [0-4], p = 0.013), prothrombin complex concentrate (3 iU [2-5] vs. 0 iU [0-2], p = 0.001), and tranexamic acid (2.5 mg [2-5] vs. 2.0 mg [1-3], p = 0.002). Also, ventilator support requirements (21 days [7-31] vs. 5 days [3-21], p = 0.013) and lengths of ICU stays (36 days [14-62] vs. 15 days [6-44], p = 0.030) were markedly longer in CPB patients. There were no differences in 30-day and 1-year mortality rates., Conclusion: These data indicate a perioperative advantage of ECMO usage with low-dose heparinization over conventional CPB for extracorporeal circulatory support during LuTx. Long-term outcome is not affected., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Lung transplantation for end-stage pulmonary disease is an established procedure and the number of transplantations is increasing worldwide even in developing countries. Usually donor lungs are transported in an inflated state and the bronchi are closed with a stapler device., Case Report: We present a technique that avoids costly stapler devices and is even less time consuming than reloading the staplers. After both lungs are inflated the separation of the two main bronchi is facilitated by using sterile umbilical cord clamps for the bronchus closure. We did not experience any air leaks and since the bronchi are resected prior to implantation there is always enough space to place the clamps., Conclusions: The umbilical cord clamp technique reduces the explantation costs for lung retrievals significantly. The technique is less time consuming and offers equal safety compared to stapler devices.

Background: In this prospective study we investigated the impact of the proton pump inhibitor (PPI) pantoprazole on the bioavailability of mycophenolic acid (MPA) after oral administration of enteric-coated mycophenolate sodium (EC-MPS; Myfortic) in heart or lung transplant recipients. Previously we demonstrated that pantoprazole reduces the MPA exposure of mycophenolate mofetil (MMF; CellCept) by 34% in area under the concentration-time curve (AUC). Because gastrointestinal side-effects are common after organ transplantation, we investigated the effect of PPI on MPA levels in patients receiving EC-MPS., Methods: MPA plasma concentrations and inosine monophosphate dehydrogenase (IMPDH) activity at baseline, 30 minutes and 1, 2, 3 and 4 hours were obtained from 21 patients. These patients were treated with pantoprazole 40 mg once daily and EC-MPS twice daily at a mean dose of 960 mg. Measurements were repeated after pantoprazole withdrawal., Results: MPA concentrations and IMPDH activities did not reveal any significant difference during PPI treatment and after withdrawal. MPA AUC, MPA C(max) (maximal MPA concentration), the time until C(max) was reached (T(max)) and IMPDH activity AUC all showed no significant difference., Conclusion: We did not find an influence of pantoprazole on EC-MPS pharmacokinetics such as we did for MMF in our previous investigation. A further prospective, large, cross-over study is planned to support these preliminary results. Given that MPA exposure by AUC correlates with the incidence of acute rejection episodes and transplant vasculopathy, the present findings may have clinical implications., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to design and validate a lung donor score that reflects experts' perceived risk of allograft failure. All lung donors reported to Eurotransplant from 1999 to 2007 [N=6080] were used to create a lung donor score. Based on observed discard rates and using multivariate regression, points were assigned for six preprocurement donor variables. Donors reported in 2008 were used to validate the score [N=751]. All the six factors significantly predicted discard; as an example, the following donor with points: age 55-59years: 2; compromised history: 4; smoking: 2; shadow on chest X-ray: 2; purulent secretion during bronchoscopy: 2; and Pao(2) /Fio(2) ratio below 300mmHg: 3. Discard rates for donors with a lung donor score of 6 points (class 1) was 18%, while 36% and 54% of the donors with a score of 7-8 (class 2) and 9+(class 3) were discarded (P<0.001), respectively. In addition, the donor lung score was significantly associated with 1-year survival: class 1: 91%; class 2: 80%; and class 3: 72% (P=0.017). The lung donor score accurately reflects the likelihood of organ acceptance and predicts patient mortality, and its application at time of donor reporting may facilitate donor risk assessment and patient selection., (© 2010 The Authors. Transplant International © 2010 European Society for Organ Transplantation.)

Background: The purpose of the study was to investigate the impact of the lung allocation score (LAS) on mortality among highly urgent (HU) and urgent (U) lung transplant (LTx) candidates in Eurotransplant (ET) and to identify useful additional parameters (LASplus)., Methods: All adult LTx candidates for whom a first request for HU or U status was made in 2008 in ET were included (N = 317). Patients were followed until LTx, death on the waiting list (WL), delisting, or closure date (i.e., January 10, 2010). The relationship between the LAS/LASplus and waiting list, post-transplant, and overall mortality was assessed with a multivariate regression model. The LAS and LASplus were decomposed into their basic waitlist and post-transplant components., Results: Waiting list mortality rate was 22% and 1-year post-transplant mortality rate was 34%. The waitlist component of the LASplus was significantly associated with waiting list mortality (hazard ratio [HR] 1.91, p = 0.021), whereas the LAS was not (p = 0.063). The post-transplant components of both scores were significantly associated with 1-year post-transplant mortality (LAS: HR 2.69, p = 0.005; LASplus: HR 2.55, p = 0.004). Both scores strongly predicted overall mortality (LAS: HR 1.65, p = 0.008; LASplus: HR 1.72, p = 0.005)., Conclusion: LAS accurately predicts overall mortality in critically ill transplant candidates and should therefore be considered as the basis for a new lung allocation policy in ET. An adjustment of the original LAS may be indicated to accurately predict waiting list mortality., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Lung donor recognition and treatment should be further improved. In 2007 only 22% of all donors in Eurotransplant were actual lung donors. During the past decade, Eurotransplant has increased the utilization of lung donors from 43% in 1999 to 54% in 2007. Increasing the number of lung transplants should be done by maximizing this utilization rate. Eurotransplant has 4 mechanisms in place in order to ensure that the highest degree of effectiveness is achieved with every reported lung donor. The Eurotransplant rescue allocation policy--which is one of these mechanisms--accounted for an additional 16.6% of the total transplant volume.

Introduction: Although amphotericin was the gold standard in the treatment of invasive aspergillosis in transplant recipients, nephrotoxicity and lack of efficacy often limits its use. Itraconazole is better tolerated but less efficacious and influences immunosuppressant trough levels significantly. We report our first clinical experience with the use of caspofungin as first-line therapy in heart and lung transplant recipients with invasive aspergillosis., Methods: Caspofungin was administered at 50 to 70 mg/day in heart and lung transplant recipients with renal impairment while invasive aspergillosis was diagnosed and classified. Aspergillus serology, serologic inflammatory markers, and X-rays were taken to monitor infectious activity. Creatinine and immunosuppressant trough levels were monitored closely., Results: Invasive aspergillosis was diagnosed by chest X-ray, serology, and positive sputum in 1 heart-lung, 7 heart, and 4 single-lung transplant recipients, and caspofungin was administered for a mean time of 21 +/- 9 days. Basic immunosuppressants were tacrolimus in 9 patients or cyclosporine in 3. Complete remission was achieved in 10 patients (83%). Adverse effects of caspofungin were fever in 6, diarrhea in 3, and neutropenia in 1. Renal function remained stable (3.2 +/- 1 mg/dl before vs 2.3 +/- 0.9 mg/dl after, p = 0.07). Trough levels of all immunosuppressants did not change significantly during caspofungin treatment (10.9 +/- 4.1 ng/ml before vs 9.9 +/- 4.0 ng/ml after [p = 0.31] for tacrolimus; 214 +/- 98 ng/ml before vs 229 +/- 88 ng/ml after [p = 0.41] for cyclosporin A), while the administered dosage remained stable., Conclusion: In heart and lung transplant recipients with invasive aspergillosis, caspofungin seemed to be an effective anti-fungal agent with a promising safety profile. Further prospective randomized trials are needed to investigate an advantageous role of caspofungin in the treatment of invasive aspergillosis.

Background: Bronchiolitis obliterans syndrome (BOS) is the major problem after lung and heart-lung transplantation (LTx/HLTx). Sirolimus (Sir) and Mycophenolate (MMF) showed a promising efficacy in the treatment of BOS in animal models. The first clinical experience in converting LTx/HLTx-recipients with BOS from calcineurin inhibitor-(CNI)-based immunosuppression to a Sir-MMF based immunosuppression is reported herein., Methods: Six LTx- and five HLTx-recipients (eight men; 0.9 to 8 years after transplantation) with CNI-based immunosuppression (plus MMF) in whom BOS was diagnosed were included in the study. Mean patient age was 37+/-13 years (range 17-62 years). Sir was started with 6 mg and continued adjusted to according target trough levels (8-14 ng/ml). Subsequently, the CNIs were tapered down and finally stopped. Follow up included self determined pulmonary function tests, microbiological screening, chest radiographs, and laboratory studies, Results: Two acute rejection episodes occurred during the study period. The incidence of infection was 2.2+/-1.3 infections/patient-year after conversion. Mean FEV1 decreased after a mean follow up of 14.8+/-1.4 months: from 2.1+/-0.7 l prior conversion to 1.3+/-0.6l after conversion (P=0.03). However, graft function remained stable in three patients and progression of BOS slowed down in three patients. Overall, 2 of 10 patients died due to ongoing BOS while awaiting retransplantation, Conclusions: After BOS was diagnosed, conversion to MMF and Sir stabilized graft function only in some of the converted patients. Therefore, earlier administration of Sir-based immunosuppression might be a more promising approach. Whether conversion to CNI-free immunosuppression can actually ameliorate the extent or progression of BOS has to be investigated in randomized trials.

A prospective, pilot trial was started to evaluate the effect of a sirolimus-based immunosuppressive regimen on acute and chronic rejection in de novo lung transplant patients. Primary lung transplant (LTx) recipients received a sirolimus- and tacrolimus-based immunosuppressive therapy immediately after transplantation. Both immunosuppressants were administered with trough level adjusted, while steroid administration was minimized. Four patients were enrolled (2 single-lung transplants, 1 double-lung transplant, 1 heart-lung transplant) in the study. Mean ischemia time was 387 +/- 92 minutes. Acute rejection (at least Grade A1 ISHLT) was detected in 1 patient. Incidence of infection was 0.6 infection per 100 patient-days (3 Aspergillus infections). Until hospital discharge mean sirolimus trough level was 6.2 +/- 1.2 ng/ml. Depending upon mean sirolimus trough levels of each patient, severe wound-healing complications were seen in 3 patients, resulting in bronchial airway dehiscence in 2 patients with lethal outcome in 1 patient. As a result of these complications, we revised the study design after inclusion of only 4 patients: Sirolimus administration is now started after completion of bronchial wound-healing. Sirolimus-based immunosuppressive therapy administered immediately after lung transplantation seems to be associated with severe wound-healing complications of the bronchial anastomosis.

Immunosuppressants and antifibrotics are currently used to treat patients with various interstitial lung diseases, which may undergo lung transplantation (LTx). The retrospective study aimed to evaluate the potential effects of therapeutic regimen on the perioperative course in patients with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) undergoing LTx. All patients with IPF and PPF undergoing LTx between January 2014 and December 2021 were included. We retrospectively screened for previous use of immunosuppressants and antifibrotic therapy. We analyzed perioperative courses, short-term outcomes, and safety retrospectively. In total, 286 patients with diagnosis of IPF or PPF were analyzed. According to the treatment regimen before LTx, the study cohort was divided into four groups and compared. No differences between antifibrotic monotherapy, combined antifibrotic and immunosuppressive therapy with regard to postoperative complications were observed. Length of mechanical ventilation was shorter in patients with antifibrotics prior to LTx. Pretreatment with antifibrotic monotherapy and a combination of antifibrotic drugs with immunosuppressive therapy, lower body mass index (BMI) and lower blood loss, were independently associated with primary graft dysfunction grades 0–3 72 hours after LTx (p < 0.001). Finally, patients with antifibrotic monotherapy developed significantly less de novo donor-specific antibodies (DSA) (p = 0.009). Higher intraoperative blood loss, etiology of interstitial lung disease (ILD) and older age were independently associated with shorter survival after LTx. Use of antifibrotic monotherapy and a combination of antifibrotic drugs with immunosuppressive therapy in IPF/PPF patients undergoing LTx, proved to be safe and might lead to beneficial effects after LTx. [ABSTRACT FROM AUTHOR]

Background: Protecting against CMV infection and maintaining CMV in latent state are largely provided by CMV‐specific T‐cells in lung transplant recipients. The aim of the study was to assess whether a specific T‐cell response is associated with the risk for CMV infection in seronegative patients who are at high risk for delayed CMV infection. Methods: All CMV‐seronegative recipients (R−) from CMV‐seropositive donors (D+) between January 2018 and April 2019 were included and retrospectively screened for CMV infection before and after assessment of CMV‐specific cell‐mediated immunity. Results: Thirty‐one of the 50 patients (62%) developed early‐onset CMV infection. Lower absolute neutrophil counts were significantly associated with early‐onset CMV infection. Antiviral prophylaxis was ceased after 137.2 ± 42.8 days. CMV‐CMI were measured at a median of 5.5 months after LTx. 19 patients experienced early and late‐onset CMV infection after prophylaxis withdrawal within 15 months post transplantation. Positive CMV‐CMI was significantly associated with lower risk of late‐onset CMV infection after transplantation in logistic and cox‐regression analysis (OR=0.05, p =.01; OR=2,369, p =.026). Conclusion: D+/R− lung transplant recipients are at high risk of developing early and late‐onset CMV infection. Measurement of CMV‐CMI soon after transplantation might further define the CMV infection prediction risk in LTx recipients being at high risk for CMV viremia. [ABSTRACT FROM AUTHOR]

Institutional Affiliations: Chair: Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1: Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Task Force 2: Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Task Force 3: Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children''s Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruña, La Coruña, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Towbin J: Cincinnati Children''s Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Independent Reviewers: Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O''Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium. [Copyright &y& Elsevier]