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Clinical Characteristics and Outcomes of Patients with Adult Congenital Heart Disease Listed for Heart and Heart‒Lung Transplantation in the Eurotransplant Region

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Clinical Characteristics and Outcomes of Patients with Adult Congenital Heart Disease Listed for Heart and Heart‒Lung Transplantation in the Eurotransplant Region ARTICLE IN PRESS http://www.jhltonline.org ORIGINAL CLINICAL SCIENCE Clinical characteristics and outcomes of patients with adult congenital heart disease listed for heart and heart‒lung transplantation in the Eurotransplant region Peter Moritz Becher, MD,a,b Benedikt Schrage, MD,a,b Jessica Weimann, MSc,a Jacqueline Smits, MD,c Christina Magnussen, MD,a,b Hermann Reichenspurner, MD, PhD,b,d Alina Goling, MSc,a Inez Rodrigus, MD,e Julia Dumfarth, MD,f Michel de Pauw, MD,g Katrien Francois,¸ MD,h Olivier van Caenegem, MD,i Arnaut Ancion, MD,j Johan Van Cleemput, MD,k Davor Milicic, MD,l Ajay Moza, MD,m Peter Schenker, MD,n Luise Rohrich,€ MD,o Felix Schonrath,€ MD,o Josef Thul, MD,p Michael Steinmetz, MD,q,r Bastian Schmack, MD,s Arjang Ruhparwar, MD,s Gregor Warnecke, MD,t Sebastian V. Rojas, MD,t Tim Sandhaus, MD,u Assad Haneya, MD,v Sandra Eifert, MD,w Henryk Welp, MD,x Laszlo Ablonczy, MD,y Florian Wagner, MD,d Dirk Westermann, MD,a,b Alexander M. Bernhardt, MD,d Dorit Knappe, MD,a Stefan Blankenberg, MD,a,b Paulus Kirchhof, MD,a,b,z,aa Elvin Zengin, MD,a,1 and Christoph Sinning, MDa,b,1 From the aDepartment of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany; bPartner Site Hamburg/Kiel/Lubeck,€ German Center of Cardiovascular Research (DZHK), Berlin, Germany; cEurotransplant, Leiden, The Netherlands; dDepartment of Cardiovascular Surgery, University Heart and Vascular Center Hamburg, Hamburg, Germany; eDepartment of Cardiovascular Surgery, Universitair Ziekenhuis Antwerpen, Antwerpen, Belgium; fDepartment of Cardiovascular Surgery, University of Innsbruck, Innsbruck, Austria; gDepartments of Cardiology; hCardiovascular Surgery, Universitair Ziekenhuis Gent, Gent, Belgium; iDepartment of Cardiac Research, Universite Catholique de Lou- vain Clinique Saint-Luc, Brussels, Belgium; jDepartment of Cardiology, Centre Hospitalier Universitaire de Liege, Liege, Belgium; kDepartment of Cardiology, Universitair Ziekenhuis Leuven, Leuven, Belgium; lDepartment of Cardiology, Medi- cal Faculty University of Zagreb, Zagreb, Croatia; mDepartment of Cardiovascular Surgery, University Hospital Aachen, Aachen, Germany; nDepartment of Surgery, University Hospital Bochum, Bochum, Germany; oDepartment of Cardiotho- racic and Vascular Surgery, German Heart Center Berlin, Berlin, Germany; pDepartment of Pediatric Cardiology, Univer- sity Hospital Giessen/Marburg, Giessen, Germany; qDepartment of Pediatric Cardiology, University Hospital Gottingen,€ Gottingen,€ Germany; rPartner Site Gottingen,€ German Centre of Cardiovascular Research (DZHK), Berlin, Germany; sDepartment of Cardiovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany; tDepartment of Cardio- vascular Surgery, University Hospital Hannover, Hannover, Germany; uDepartment of Cardiovascular Surgery, University Hospital Jena, Jena, Germany; vDepartment of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Kiel, Germany; wDepartment of Cardiovascular Surgery, Heart Center Leipzig, Leipzig, Germany; xDepartment of Cardiovas- cular Surgery, University Hospital Munster,€ Munster,€ Germany; yGottsegen Gyorgy€ Hungarian Institute of Cardiology, Budapest, Hungary; zUniversity Hospital Birmingham, Institute of Cardiovascular Sciences, Birmingham, United King- dom; and the aaSWBH and UHB NHS Trusts, Birmingham, United Kingdom. 1053-2498/$ - see front matter Ó 2020 International Society for Heart and Lung Transplantation. All rights reserved. https://doi.org/10.1016/j.healun.2020.07.012 ARTICLE IN PRESS 2 The Journal of Heart and Lung Transplantation, Vol 00, No 00, Month 2020 KEYWORDS: BACKGROUND: The therapeutic success in patients with congenital heart disease (CHD) leads to a ACHD; growing number of adults with CHD (adult CHD [ACHD]) who develop end-stage heart failure. We heart transplantation; aimed to determine patient characteristics and outcomes of ACHD listed for heart transplantation. waiting list; METHODS: Using data from all the patients with ACHD in 20 transplant centers in the Eurotransplant region mortality; from 1999 to 2015, we analyzed patient characteristics, waiting list, and post-transplantation outcomes. outcomes RESULTS: A total of 204 patients with ACHD were listed during the study period. The median age was 38 years, and 62.3% of the patients were listed in high urgency (HU), and 37.7% of the patients were in transplantable (T)-listing status. A total of 23.5% of the patients died or were delisted owing to clini- cal worsening, and 75% of the patients underwent transplantation. Median waiting time for patients with HU-listing status was 4.18 months and with T-listing status 9.07 months. There was no difference in crude mortality or delisting between patients who were HU status listed and T status listed (p = 0.65). In multivariable regression analysis, markers for respiratory failure (mechanical ventilation, hazard ratio [HR]: 1.41, 95% CI: 1.11−1.81, p = 0.006) and arrhythmias (anti-arrhythmic medication, HR: 1.42, 95% CI: 1.01−2.01, p = 0.044) were associated with a higher risk of death or delisting. In the overall cohort, post-transplantation mortality was 26.8% after 1 year and 33.4% after 5 years. CONCLUSIONS: Listed patients are at high risk of death without differences in the urgency of listing. Respiratory failure requiring invasive ventilation and possibly arrhythmias requiring anti-arrhythmic medication indicate worse outcomes on waiting list. J Heart Lung Transplant 000;000:1−12 Ó 2020 International Society for Heart and Lung Transplantation. All rights reserved. Advances in surgical and medical care have led to robust information on the number and characteristics of improved outcomes in patients with congenital heart dis- ACHD listed for transplantation. ease (CHD).1,2 As a consequence, the majority of patients The primary aim of this study was to provide compre- nowadays survives to adulthood (adults with CHD, that is, hensive data on patients with ACHD listed for heart trans- adult CHD [ACHD]) with good quality of life.3 Despite the plantation using data from the Eurotransplant Registry. A surgical success, the morbidity and mortality of ACHD is representative data set of patients with ACHD listed for higher than in the general population4 and is linked to the transplantation was created and analyzed for (1) underlying development of heart failure (HF) in adulthood.5 heart condition and repair, (2) clinical characteristics, and HF occurs in approximately 25% of patients with (3) factors associated with adverse outcomes in patients ACHD, even in those patients in whom the congenital mal- with ACHD listed for heart transplantation. formation has been corrected successfully in childhood.6 The time course and presentation are heterogeneous owing Methods to variable congenital malformation and limitation of treat- 7,8 ment options. ACHD with an anatomic right ventricle as Study population the systemic ventricle (e.g., atrial switch operation in patients with transposition of the great arteries [TGAs]) and The data of all consecutive patients with ACHD listed for solid those with a functional single ventricle (e.g., Fontan circu- organ transplantation between January 1, 1999, and December 31, lation) appear to be at higher risk of developing HF.9 Young 2015, from 20 of 52 Eurotransplant centers treating patients with age at initial corrective surgery—often in the first 2 years of ACHD were obtained. The Eurotransplant Registry gathers infor- life—and lack of specific medical therapies8 can contribute mation on all patients listed for solid organ transplantation in the to a high and early demand for heart transplantation in Eurotransplant region through reports from each transplant center ≥ patients with ACHD.10 The use of assist devices has been (Figure 1a). Patients aged 18 years listed for the first orthotopic limited in patients with ACHD owing to anatomic or func- heart transplantation and heart transplantation combined with another organ transplantation were included in the dataset for this tional complexity.11 Shortage of donor organs and compet- study (Figure 1b). Detailed information about the Eurotransplant ing demands from patients without ACHD could be Thoracic Allocation System is provided in the Supplementary aggravated by current criteria to determine high-urgency Material available online at www.jhltonline.org. (HU) heart transplantation‒listing status, which are derived Patients undergoing repeated transplantation as well as patients 12 from the overall HF population. Allocation of resources with arrhythmogenic right ventricular cardiomyopathy, non-com- to those in greatest need is currently hindered by lack of paction cardiomyopathy, or incomplete information regarding the underlying congenital heart defect were excluded from this analy- sis (Figure 1b). 1 These authors have contributed equally to this work. End-points and definitions Reprint requests: Peter Moritz Becher, MD, Department of Cardiology, University Heart and Vascular Center Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. Telephone: +49 (0) 40-7410-18779. Fax: +49 (0) 40- The primary end-point of this study was a composite of 5-year 7410-58862. waiting list mortality or delisting owing to worsening of clinical E-mail address: [email protected] status on the waiting list (e.g., events that occurred after 5 years ARTICLE IN PRESS Becher et al. Adults With CHD and Outcomes in Eurotransplant 3 Figure 1 Study design and patient population. (a) Eurotransplant member states and (b) patients analyzed in the study (flow diagram).
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