http://www.jhltonline.org
ANNUAL ISHLT REGISTRY REPORTS
Organ Allocation Around the World: Insights From the ISHLT International Registry for Heart and Lung Transplantation Josef Stehlik, MD, MPH,a,b Lynne W. Stevenson, MD,c Leah B. Edwards, PhD,a Maria G. Crespo-Leiro, MD,d Juan F. Delgado, MD,e Richard Dorent, MD,f Maria Frigerio, MD,g Peter Macdonald, MD,h Guy A. MacGowan, MD,i Alessandro Nanni Costa, MD,j Joseph G. Rogers, MD,k Ashish S. Shah, MD,l Rhiannon Taylor,m Rajaiyer V. Venkateswaran, MD,n and Mandeep R. Mehra, MDc From the aISHLT Transplant Registry, Dallas, Texas; bUniversity of Utah School of Medicine, Salt Lake City, Utah; c Brigham and Women’s Hospital Heart and Vascular Center, Harvard University, Boston, Massachusetts; dHospital Universitario A Coruña, La Coruña, Spain; eHospital 12 de Octubre, Madrid, Spain; fAgence de la biomédecine, Saint-Denis, France; gNiguarda-Ca’ Granda Hospital, Milan, Italy; hSt. Vincent’s Hospital, Sydney, New South Wales, Australia; iFreeman Hospital, Newcastle upon Tyne, United Kingdom; jCentro Nazionale Trapianti, Roma, Italy; kDuke University, Durham, North Carolina; lThe Johns Hopkins Hospital, Baltimore, Maryland; mNational Health Service Blood and Transplant, Bristol, United Kingdom; and the nWythenshawe Hospital, Manchester, United Kingdom.
The 2014 reports of the International Society for Heart and Lung Transplantation (ISHLT) International Registry for Heart and Lung Transplantation (Registry) bring expanded analyses of outcomes in patients who have undergone retransplantation. The experience of more than 170,000 heart, lung, and heart-lung transplant recipients transplanted over 30 years provided an opportunity for a robust exploration of this topic. The appropriateness of retransplantation has recently been undergoing critical review.1–5 We believe the analyses presented in the Registry reports provide important new information and insights that will be valuable as our professional community re-examines timing and candidate selection for retransplantation. The Registry continues to serve as a valuable tool to answer clinical questions, beyond the data presented in the annual reports. The Transplant Registry Early Career Award is a good mechanism that facilitates this work and catalyzes mentorship and collaboration across institutions and countries. Applications for the 2014 Award were submitted by applicants and mentors from 6 countries on 3 continents—
Reprint requests: Josef Stehlik, MD, MPH, Division of Cardiology, University of Utah Health Sciences Center, U.T.A.H. Cardiac Transplant Program, 50 N Medical Dr, 4A100 SOM, Salt Lake City, UT 84132. Telephone: 801-585-2340. Fax: 801-581-7735. E-mail address: [email protected] 1053-2498/$ - see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.healun.2014.08.001
Australia, Belgium, Czech Republic, Germany, Spain, Sweden, and the United States. The high quality of these applications resulted in 4 funded awards this year.6 The applications for next year’s award are due in January 2015 (http://www.ishlt.org/awards/awardTxRegistry.asp). The Registry also continued to work with members around the world to identify institutions and data collectives interested in participation in the Registry. Centers that joined the Registry in the past year include the Federal Research Center of Transplantology and Artificial Organs in Moscow, Russia, the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, and the Apollo Hospital in Chennai, India—all centers in countries that have not previously participated in the Registry. The Masih Daneshvari Hospital in Tehran became the second center in Iran, along with Tehran University of Medical Sciences, to join the Registry, and the Gangham Severance Hospital in Seoul joined the Severance Hospital as the second South Korean center to submit data. In addition, the Registry Committee has partnered with the International & Inter-society Coordination Committee (I2C2) of the ISHLT to work on establishing new collaborations in research, education, and advocacy. Examples include relations with the Turkish Society of Cardiovascular Surgery (activities spearheaded by Dr Ruchan Akar and Dr Murat Sargin), the Ministry of Health of Brazil (Dr Heder Borba), the Latin American and
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Caribbean Transplant Society (Dr Juan Mejia, Dr Alejandro Bertolotti), and the Ministry of Health of Argentina (Dr Carlos Soratti). The perspectives of an increasing number of the Registry participants (Figure 1), which mirror the breadth of the international membership in our Society, also allow for exploration of topics that may not be directly or fully addressed by Registry data collection. One of the ever more pressing topics is how to align the evolving non-transplant options in advanced heart and lung disease, the changing donor and recipient demographics, and organ allocation. To illustrate the utility of the Registry data and of the international expertise of the Society’s members, we provide a brief perspective focused on heart transplant data. During the past 3 decades, new traffic laws and improvements in automobile and workplace safety have resulted in a decrease in the accident-related death rates in young adults.7 In addition, the populations of many nations have continued to age. Consequently, the average age of organ donors has increased, as has the age of donors accepted for heart transplantation. The median age of a heart donor increased from 20 years in 1983 to 32 years in 2011, with the steepest increase being experienced in Europe, where the median donor age in 2011 reached 43 years.8 These demographic changes have a real effect on posttransplant survival. For example, the higher donor age in Europe would be expected to result in a 20% increase of mortality risk compared with the North American donor pool. Donor medical comorbidities, such as diabetes mellitus and hypertension, have also increased.9 The demographics of the heart transplant recipient have changed perhaps even more dramatically. Recipients being
transplanted in their 60s now comprise 30% of all adult heart transplants, with patients in their 70s receiving heart transplants with a higher frequency than ever before.8 Recipient comorbidities have increased steadily; at the time of transplant, 25% of recipients have diabetes mellitus, 45% have hypertension, 46% have had prior sternotomy, 7% have had malignancy, and 33% are allosensitized. The most visible recent change probably relates to the use of mechanical assist devices as a bridge to transplantation. Close to 40% of all adult recipients are bridged to transplant with a durable device. Further, although use of mechanical assist as a bridge to transplant had been infrequent in older patients in the recent past, this trend was fully reversed. As of 2011, transplant candidates older than 60 years are equally or even more likely to be supported by a mechanical assist device at the time of transplant compared with younger recipients. In view of the increasing complexity of donor and recipient profiles, the charge we have is to find ways to maintain (or increase) transplant volumes, preserve good post-transplant outcomes, maintain equity in organ allocation, and keep mortality on the transplant waiting list as low as possible. Renewed efforts to optimize the donation process and donor management have shown promise.10 Interventions to improve donor hemodynamic management have been tested in different countries, and sizeable increases in the number of organs suitable for transplantation resulted from these efforts. These interventions included sharing and implementing best practices from top performing organ procurement teams,11 implementing early protocol-driven donor management,12,13 and introducing didactic training for key hospital-based health care professionals.14,15
Figure 1 Countries participating in the International Society for Heart and Lung Transplantation International Registry for Heart and Lung Transplantation in 2013. A red flag indicates national or collaborative data submission, and a yellow flag indicates direct submission of data by individual centers. The country abbreviations are listed in the Appendix.
Stehlik et al.
Country
Key Heart Transplant Waiting List Parameters in a Sample of 5 Countries in North America, Europe, Australia, and New Zealand
Allocation algorithm
Median Transplanted waiting time in status
(%)
(days)
Patients on the list in Patients transplanted 2012 (at start of the year/newly listed) Transplant rate in 2012 in 2012
(No.)
(No.)
Patients with MCS at transplant
Patients transplanted/ patients on the list
Patients transplanted/ patients newly listed (VAD/ECMO)
(%)
(%)
(%)
Donor consent legislation
Heart Organ transplantsa donorsa
(per million)
(per million)
United Kingdom
Urgent Non-urgent
60 40
14 293
116
352 (141/212)
33
54
19 (16/3)
Opt in
2.1
17
France
High urgency 1 High urgency 2 Regional urgency Non-urgent
39 8 8 45
9 102 219 189
397
830 (300/530)
48
75
27 (13/14)
Opt out
6.1
25
Spain
Urgent status 0 Urgent status 1 Elective status
14 21 65
8 7 80
247
433 (101/332)
57
74
15 (9/6)
Opt out
5.3
35
Italy
1 high urgency 2A, 2B
14 86
3 292
231
1,100 (709/391)
32
59
9 (9/0)
Opt in/opt outb 4.6
20
Australia & Urgent New Zealand Non-urgent
8 92
15 120
85
186 (78/108)
46
79
40 (40/0)
Opt in
3.3
15
USA
64 31 5
78 224 618
2,378
36
76
40% (39/1)
Opt in
7.6
26
1A high urgency 1B intermediate 2 low urgency
6,669 (3,526/3,143)
Organ Allocation Around the World
Table 1
ECMO, extracorporeal membrane oxygenation; MCS, mechanical circulatory support; USA, United States of America; VAD, ventricular assist device (temporary or durable) or total artificial heart. a Based on 2010 data. b All are invited to register their donation intent. In the absence of declared intent, the law establishes presumed consent, but family input is typically sought.
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Recent studies have also examined the next step of the donation-transplantation process—the decisions surrounding acceptance of a particular donor allograft. It appears that current heart allograft utilization could be increased without elevating the risk of post-transplant mortality. Empiric quantification of the risk associated with a particular donor is difficult, and it has been proposed that a number of donor allografts with acceptable risk are currently being discarded. Ongoing studies are examining whether better assessment of risk associated with a particular donor allograft may result in an increase in the number of available donor hearts accepted for transplantation.16,17 Finally, there is the task of adapting our organ allocation processes to the changing epidemiology of donors and recipients and the evolving therapeutic options for advanced heart disease. Although the logistical challenges associated with the process of organ donation and organ management are reasonably similar among countries with established organ transplantation programs, organ donation rates and heart transplantation rates vary significantly among these countries. The differences among organ allocation rules are even more pronounced. Key heart transplant indicators from a sample of countries are listed in Table 1. All sampled countries have established different tiers of transplant urgency status; however, the definition of urgency is variable. Large differences also exist among the individual countries in the proportion of patients who are transplanted in the highest urgency status and in the median time from listing to transplantation in the high urgency status. This illustrates that the specifics of an allocation system have great effect on these key parameters. Some countries have a fairly restrictive definition of highest urgency such that only o15% of listed patients are transplanted in this status (Spain, Italy, Australia/New Zealand); this, in turn, results in short median times to transplantation of 8, 3, and 15 days, respectively. Then there are countries where a significant proportion of patients are transplanted in the highest urgency status—United Kingdom (60%) and France (39%)— yet, the median waiting time to transplant is still short, at 14 and 9 days, respectively. This would suggest that the waiting list is managed very carefully in these countries, such that the number of patients placed in the highest urgency status does not overwhelm the limited supply of donor organs. Finally, data for the United States show that most patients in this country are transplanted in a high urgency status (64% in status 1A, 31% in status 1B, and only 5% in lower urgency status 2) but also that under the current allocation rule, the ability to expeditiously transplant a heart patient has been lost, for the median waiting time for a transplant in the highest urgency status 1A is now 78 days.18 Regardless of the specifics of a particular allocation system, 2 aspects of the allocation rules continue to present a particular challenge. The first is that allocation algorithms often incorporate provisions for allocation to an individual center or an arbitrarily defined geographic area, rather than exclusively allocation to an individual patient. On the positive side, these geographic arrangements provide a strong incentive for local teams to create efficient processes that maximize the use of organs by increasing donation awareness, early identification of potential donors, and
implementation of optimal donor management. However, allocation of organs based on a wider regional, national, and even multinational prioritization of candidates at the highest risk of death has been shown to result in a decrease of waiting list mortality and an increase of transplant benefit.19 In our assessment, most allocation algorithm revisions are therefore moving away from center-specific rules (including “pay-back” rules) and in favor of broader sharing of organs. Continuation of active efforts to improve the number and quality of donors across the board will eventually benefit every region, even with the wider regional sharing of organs. The second highly charged aspect of heart allocation relates to the now prevalent use of mechanical assist therapies in transplant candidates. Allocation arrangements in the countries reviewed in Table 1 range from a significant advantage to even stable patients supported with ventricular assist devices (VADs) to no advantage unless a serious VAD complication occurs. Supporters for higher priority for transplant candidates receiving VAD would argue that lack of allocation priority for VAD patients results in very long waiting times in many. And, when a serious VAD-associated complication occurs, this may negate the expected benefit of the bridge-to-transplant therapy, because a sub-set of these patients will become transplant ineligible or have a higher risk of post-transplant morbidity and mortality. On the other hand, the concern with providing a significant advantage to patients with VADs brings up questions of equity, because these patients often have a lower risk of waiting list mortality compared with patients with other indications for urgent listing.20 The specifics of the algorithms may also influence the likelihood with which the transplant candidates will require mechanical assist therapies. This is being taken into consideration by health care funding agencies in the individual countries, which further complicates possible decisions on allocation rule changes. In summary, changes in donor and recipient profiles, coupled with new therapeutic options in advanced heart and lung disease, present new perspectives on organ allocation and candidate selection. As we embrace these new realities, and as changes in thoracic allocation policies are being considered by many, the rich international experience offers an opportunity to identify and implement regulatory and clinical practice changes that will ensure transplantation continues to provide our patients an opportunity to regain longevity and an active lifestyle. We would like to thank the members and staff at the many participating centers and data exchange organizations around the world for making these global observations possible (Appendix 1).
Disclosure statement The authors thank staff at the national transplant organizations for contributing data for this report. All relevant disclosures for the authors are on file with the ISHLT and can be made available for review by contacting the Executive Director of the ISHLT. All relevant disclosures for the Registry Director, Executive Committee Members and authors are on file with the ISHLT and can be made available for review by contacting the Executive Director of the ISHLT
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Appendix List of Thoracic Transplant Centers Reporting Data to the International Society for Heart and Lung Transplantation Transplant Registry for Transplants Performed Between January 1, 2012, and June 30, 2013 Country (ISO code)
Center
Argentina (ARG)
Fundacion Favaloro Hospital Italiano St. Vincent Royal Children The Prince Charles Hospital The Alfred Hospital Royal Perth Hospital Allgemeines Krankenhaus Wien Universitätsklinik Innsbruck Landeskrankenhaus Graz Hôpital Erasme Bruxelles Universitair Ziekenhuis Antwerpen Onze Lieve Vrouw Ziekenhuis Aalst Universitair Ziekenhuis Gent Centre Hospitalier Universitaire Liège Cliniques Universitaires, Université Catholique de Louvain UZ Gasthuisberg Leuven Heart Institute–Universidade São Paulo Hospital das Clinicas Hospital de Messejana Real Hospital Portugues de Beneficiencia Em Pernambuco Instituto de Medicina Integral Instituto de Cardiologia do Distrito Federal Hospital de Clinicas de Porto Alegre Royal Victoria Hospital The Toronto General Hospital Hospital Notre-Dame Quebec Heart Institute–Laval Hospital University of Alberta Hospitals/Walter C. Mackenzie Health Sciences St. Paul’s Hospital Vancouver General Hospital The Hospital For Sick Children Hospital Gustavo Fricke Instituto Nacional del Torax Clinica Cardiovascular Fundacion Valle Del Lili Fundacion Cardioinfantil–Instituto de Cardiologia Fundacion Cardiovascular de Colombia Fundacion Clinica Shaio University Clinical Hospital Zagreb University Hospital Dubrava University Hospital Motol Skejby University Hospital Rigshospitalet, National University Hospital Tartu University Hospital Helsinki University Central Hospital Children’s Hospital, University of Helsinki Marseille Sainte Marguerite (APM) (A)–Chirurgie Thoracique Marseille Timone adultes (APM) (A)–Chirurgie Cardiaque Marseille Timone enfants (APM) (AþP)–Chirurgie Cardio-Vasculaire Caen (A)–Chirurgie Cardiaque Dijon (A)–Chirurgie Cardiaque Toulouse (A)–Chirurgie Thoracique Toulouse (A)–Chirurgie Cardio-Vasculaire Bordeaux (AþP)–Unite de Transplantation Cardiaque Bordeaux (AþP)–Chirurgie Thoracique Montpellier (A)–Unite de Transplantation Cardio-Thoracique Rennes (A)–Centre Cardio-Pneumologique
Australiaa (AUS)
Austriab (AUT)
Belgiumb (BEL)
Brazil (BRA)
Canada (CAN)
Chile (CHL) Colombia (COL)
Croatiab (HRV) The Czech Republic (CZE) Denmarkc (DNK) Estonia (EST) Finlandc (FIN) Franced (FRA)
Continued on page 980
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Appendix (Continued ) Country (ISO code)
Germanyb (DEU)
India (IND) Iran (IRN) Irelande (IRL) Israel (ISR) Italy (ITA) Japan (JPN)
Center Tours (AþP)–Chirurgie Cardiaque Grenoble (A)–Chirurgie Cardiaque Grenoble (A)–Pneumologie Nantes (AþP)–Chirurgie Cardio-Vasculaire Nancy (AþP)–Chirurgie Cardio-Pulmonaire Lille (AþP)–Chirurgie Cardio-Vasculaire Clermont-Ferrand (A)–Chirurgie Cardiaque Strasbourg (A)–Chirurgie Thoracique Strasbourg (A)–Chirurgie Cardio-Pulmonaire Lyon (AþP)–Pole de Transplantation Pulmonaire Lyon I (HCL) (AþP)–Pole de Transplantation Cardiaque Lyon II (HCL) (A)–Pole de Transplantation Cardiaque Paris Pitié-Salpêtrière (AP-HP) (AþP)–Chirurgie Cardio-Vasculaire Paris Necker Enfants Malades (AP-HP) (AþP)–Cardiologie Pediatrique Clichy Beaujon (AP-HP) (A)–Pneumologie B et Transplantation Pulmonaire Paris Bichat (AP-HP) (A)–Chirurgie Cardio-Vasculaire Paris Georges Pompidou (AP-HP) (A)–Transplantation Cardiaque Paris Georges Pompidou (AP-HP) (AþP)–Transplantation. Pneumologie et Cardio-Pulmonaire Rouen (AþP)–Chirurgie Thoracique et Cardio-Vasculaire Limoges (A)–Chirurgie Cardiaque Suresnes Foch (A)–Chirurgie Thoracique Le Plessis-Robinson Marie-Lannelongue (AþP)–Chirurgie Cardiaque Le Plessis-Robinson Marie-Lannelongue (AþP)–Chirurgie Thoracique Cardio-Vasculaire Créteil Henri Mondor (AP-HP) (A)–Chirurgie Cardio-Vasculaire Universität des Saarlandes Homburg/Saar Herzzentrum Dresden GmbH Deutsches Herzzentrum Berlin Universitätsklinik Köln Universität Leipzig–Herzzentrum Kerckhoff Klinik, Bad Nauheim Klinikum der Universität Regensburg Herzzentrum Nordrhein-Westfalen Bad Oeynhausen Universitätsklinikum Essen Johannes Gutenberg Universität Mainz Heinrich-Heine-Universität Düsseldorf Universitätsklinikum Münster Ruprecht-Karls-Universität Heidelberg Medizinische Hochschule Hannover Universitätsklinikum Göttingen Universitätsklinikum Aachen Klinikum der Justus-Liebig-Universität Giessen Universitätsklinikum Schleswig-Holstein Kiel Johann Wolfgang Goethe Universität Frankfurt/Main Friedrich Schiller Universität Jena Friedrich Alexander Universität Erlangen Universitätsklinikum Würzburg Ludwig Maximilians Universität München Universitätsklinikum Hamburg Klinikum der Albert-Ludwigs-Universität Freiburg im Breisgau Apollo Hospital Cardiac Surgery and Transplantation Research Center Masih Daneshvari Hospital Mater Hospital Rabin Medical Center (Belinson Campus) Sheba Medical Center Policlinico S. Orsola–Universita degli Studi Tohoku University Hospital Osaka University Hospital
Continued on page 981
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Appendix (Continued ) Country (ISO code) b
Netherlands (NLD)
New Zealand (NZL) Norwayc (NOR) Poland (POL) The Republic of Korea (KOR) Russia (RUS) Saudi Arabia (SAU) Sloveniab (SVN) South Africa (ZAF) Spain (ESP)
Swedenc (SWE) Switzerland (CHE) Turkey (TUR)
United Kingdome (UK)
United Statesi (USA)
Center Universitair Medisch Centrum Utrecht Erasmus Medisch Centrum Rotterdam Universitair Medisch Centrum Groningen Green Lane Hospital Auckland City Hospital Rikshospitalet–National Hospital of Norway Regional Pulmonary Hospital Gangnam Severance Hospital Severance Hospital Federal V. Shumakov Research Centre of Transplantology & Artificial Organs King Faisal Specialist Hospital and Research Center University Medical Center Ljubljana Milpark Hospital Complejo Hospitalario Universitario Juan Canalejof,g Hospital Universitario Marques de Valdecillaf,h Hospital de Bellvitge, Barcelonah Hospital Virgen Del Rocio, Sevillah Hospital Santa Creu I Sant Pau, Barcelonah Hospital Universitario 12 de Octubref,h Hospital Universitario Reina Sofiaf,h Hospital Gregorio Marañón, Madridh Hospital Universitario Puerta de Hierrof Hospital Universitari I Politècnic La Fe, Valenciaf,h Hospital Clinic I Provincial, Barcelonah Hospital Universitario Vall D’Hebronf,h Hospital Central de Asturiasg Hospital La Paz Infantilf,h Hospital Virgen de La Arrixaca, Murciah Hospital Miguel Servet, Zaragozah Hospital Clínico, Valladolidh Sahlgrenska University Hospital University Hospital of Lund University Hospital Zurich Istanbul Florence Nightingale Hospital Heart Center, Ankara University Hospital of Akdeniz University Great Ormand Street Hospital for Children University of Glasgow/Glasgow Royal Infirmary The Freeman Hospital Harefield Hospital Wythenshawe Hospital Queen Elizabeth Hospital Papworth Hospital University of Alabama Hospital, Birmingham, AL Baptist Medical Center, Little Rock, AR Arkansas Children’s Hospital, Little Rock, AR Phoenix Children’s Hospital, Phoenix, AZ Mayo Clinic Hospital, Phoenix, AZ St. Joseph’s Hospital and Medical Center, Phoenix, AZ University Medical Center, University of Arizona, Tucson, AZ Children’s Hospital Los Angeles, Los Angeles, CA Cedars-Sinai Medical Center, Los Angeles, CA Loma Linda University Medical Center, Loma Linda, CA Lucile Salter Packard Children’s Hospital, Palo Alto, CA California Pacific Medical Center, San Francisco, CA UCSD Medical Center, San Diego, CA UCSF Medical Center, San Francisco, CA Sutter Memorial Hospital, Sacramento, CA Sharp Memorial Hospital, San Diego, CA Stanford University Medical Center, Stanford, CA
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Appendix (Continued ) Country (ISO code)
Center UCLA Medical Center, Los Angeles, CA Keck Hospital of USC, Los Angeles, CA Children’s Hospital Colorado, Aurora, CO University of Colorado Hospital/HSC, Aurora, CO Hartford Hospital, Hartford, CT Yale New Haven Hospital, New Haven, CT Children’s National Medical Center, Washington, DC Washington Hospital Center, Washington, DC Alfred I duPont Hospital for Children, Wilmington, DE All Children’s Hospital, St. Petersburg, FL Florida Hospital Medical Center, Orlando, FL Memorial Regional/Joe DiMaggio Children’s Hospital, Hollywood, FL Jackson Memorial Hospital, Miami, FL Mayo Clinic Florida, Jacksonville, FL Tampa General Hospital, Tampa, FL Shands Hospital at University of FL, Gainesville, FL Children’s Healthcare of Atlanta, Atlanta, GA Emory University Hospital, Atlanta, GA Piedmont Hospital, Atlanta, GA St. Joseph’s Hospital of Atlanta, Atlanta, GA University of Iowa Hospital and Clinics, Iowa City, IA Advocate Christ Medical Center, Oak Lawn, IL Ann and Robert H. Lurie Children’s Hospital, Chicago, IL Loyola University Medical Center, Maywood, IL Northwestern Memorial Hospital, Chicago, IL Rush University Medical Center, Chicago, IL University of Chicago Medical Center, Chicago, IL Indiana University Health, Indianapolis, IN Lutheran Hospital of Ft Wayne, Ft Wayne, IN St. Vincent Hospital and Health Care Center, Indianapolis, IN Jewish Hospital, Louisville, KY University of Kentucky Medical Center, Lexington, KY Ochsner Foundation Hospital, New Orleans, LA Boston Children’s Hospital, Boston, MA Massachusetts General Hospital, Boston, MA Tufts Medical Center, Boston, MA Brigham and Women’s Hospital, Boston, MA Johns Hopkins Hospital, Baltimore, MD University of Maryland Medical System, Baltimore, MD Children’s Hospital of Michigan, Detroit, MI Henry Ford Hospital, Detroit, MI SpeCenterum Health, Grand Rapids, MI University of Michigan Medical Center, Ann Arbor, MI Abbott Northwestern Hospital, Minneapolis, MN St. Mary’s Hospital (Mayo Clinic), Rochester, MN University of Minnesota Medical Center, Minneapolis, MN Barnes-Jewish Hospital, St. Louis, MO Cardinal Glennon Children’s Hospital, St. Louis, MO St. Louis Children’s Hospital, St. Louis, MO St. Luke’s Hospital of Kansas City, Kansas City, MO University of MS Medical Center, Jackson, MS Wake Forest Baptist Medical Center, Winston-Salem, NC Carolinas Medical Center, Charlotte, NC Duke University Hospital, Durham, NC UNC Hospitals, Chapel Hill, NC Children’s Hospital and Medical Center, Omaha, NE The Nebraska Medical Center, Omaha, NE Newark Beth Israel Medical Center, Newark, NJ Robert Wood Johnson University Hospital, New Brunswick, NJ New York-Presbyterian/Columbia, New York, NY
Continued on page 983
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Appendix (Continued ) Country (ISO code)
Center Strong Memorial Hospital, Rochester, NY Montefiore Medical Center, Bronx, NY Mount Sinai Medical Center, New York, NY Westchester Medical Center, Valhalla, NY Cleveland Clinic Foundation, Cleveland, OH Nationwide Children’s Hospital, Columbus, OH Children’s Hospital Medical Center, Cincinnati, OH Ohio State University Medical Center, Columbus, OH University Hospital of Cleveland, Cleveland, OH Integris Baptist Medical Center, Oklahoma City, OK Oregon Health and Science University, Portland, OR Allegheny General Hospital, Pittsburgh, PA Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA Children’s Hospital of Philadelphia, Philadelphia, PA Penn State Milton S Hershey Medical Center, Hershey, PA Hahnemann University Hospital, Philadelphia, PA University of Pittsburgh Medical Center, Pittsburgh, PA Thomas Jefferson University Hospital, Philadelphia, PA Temple University Hospital, Philadelphia, PA The Hospital of the University of PA, Philadelphia, PA Cardiovascular Center of Puerto Rico, San Juan, PR Medical University of South Carolina, Charleston, SC Baptist Memorial Hospital, Memphis, TN Vanderbilt University Medical Center, Nashville, TN University Hospital, San Antonio, TX Children’s Medical Center of Dallas, Dallas, TX Seton Medical Center, Austin, TX Medical City Dallas Hospital, Dallas, TX Memorial Hermann Hospital, Houston, TX St Luke’s Episcopal Hospital, Houston, TX Methodist Specialty and Transplant Hospital, San Antonio, TX University of Texas Medical Branch, Galveston, TX The Methodist Hospital, Houston, TX University Hospital–St. Paul, Dallas, TX Scott and White Memorial Hospital, Temple, TX Texas Children’s Hospital, Houston, TX Baylor University Medical Center, Dallas, TX Intermountain Medical Center, Murray, UT University of Utah Medical Center, Salt Lake City, UT Primary Children’s Medical Center, Salt Lake City, UT Inova Fairfax Hospital, Falls Church, VA MCV Hospitals, Richmond, VA McGuire VA Medical Center, Richmond, VA Sentara Norfolk General Hospital, Norfolk, VA University of Virginia HSC, Charlottesville, VA Seattle Children’s Hospital, Seattle, WA Sacred Heart Medical Center, Spokane, WA University of Washington Medical Center, Seattle, WA Children’s Hospital of Wisconsin, Milwaukee, WI Froedtert Memorial Lutheran Hospital, Milwaukee, WI Aurora St. Luke’s Medical Center, Milwaukee, WI University of Wisconsin Hospital and Clinics, Madison, WI
ISO, International Organization for Standardization. a Data provided via Australia and New Zealand Cardiothoracic Transplant Registry (ANZCOTR). b Data provided via Eurotransplant (ET). c Data provided via Scandiatransplant. d Data provided via L’Agence de la Biomédicine. e Data provided via United Kingdom Transplant Support Service Authority (UKTSSA). f Lung data provided via OrganizaciónNacional de Trasplantes (ONT). g Heart data provided directly to ISHLT Registry. h Heart data provided via RegistroEspañol de TrasplanteCardíaco. i Data provided via United Network for Organ Sharing (UNOS).
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References 1. Vanderlaan RD, Manlhiot C, Conway J, et al. Perioperative factors associated with in-hospital mortality or retransplantation in pediatric heart transplant recipients. J Thorac Cardviovasc Surg 2014;148:282-9. 2. Kobashigawa J, Zuckermann A, Macdonald P, et al. Report from a consensus conference on primary graft dysfunction after cardiac transplantation. J Heart Lung Transplant 2014;33:327-40. 3. Conway J, Manlhiot C, Kirk R, et al. Mortality and morbidity after retransplantation after primary heart transplant in childhood: an analysis from the registry of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2014;33:241-51. 4. Khan MS, Mery CM, Zafar F, et al. Is mechanically bridging patients with a failing cardiac graft to retransplantation an effective therapy? Analysis of the United Network of Organ Sharing database. J Heart Lung Transplant 2012;31:1192-8. 5. Goldraich L, Stehlik J, Kucheryavaya AY, Edwards LB, Ross HJ. Retransplantation versus medical therapy for cardiac allograft vasculopathy (CAV): analysis of the International Society for Heart and Lung Transplantation (ISHLT) Registry. J Heart Lung Transplant 2014;33:S90. 6. International Society for Heart and Lung Transplantation. ISHLT grants and awards program. Available at: http://ishlt.org/awards/currentRecipients.asp. 7. Silver D, Macinko J, Bae JY, Jimenez G, Paul M. Variation in U.S. traffic safety policy environments and motor vehicle fatalities 1980– 2010. Public Health 2013;127:1117-25. 8. Lund LH, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: thirtieth official adult heart transplant report—2013; focus theme: age. J Heart Lung Transplant 2013;32:951-64. 9. Nativi JN, Brown RN, Taylor DO, Kfoury AG, Kirklin JK, et al. Temporal trends in heart transplantation from high-risk donors: are there lessons to be learned? A multi-institutional analysis. J Heart Lung Transplant 2010;29:847-52. 10. Kransdorf EP, Stehlik J. Donor evaluation in heart transplantation: the end of the beginning. J Heart Lung Transplant 2014, http://dx.doi.org/ 10.1016/j.healun.2014.05.002: [E-pub ahead of print].
11. U.S. Department of Health and Human Services, Health Resources and Services Administration. Office of Special Programs, Division of Transplantation. The organ donation breakthrough collaborative: best practices final report. Contract 240-94-0037. Task Order No. 12. Washington, DC: U.S. Department of Health and Human Services; 2003. 12. Venkateswaran RV, Patchell VB, Wilson IC, et al. Early donor management increases the retrieval rate of lungs for transplantation. Ann Thorac Surg 2008;85:278-86: discussion 286. 13. Venkateswaran RV, Steeds RP, Quinn DW, et al. The haemodynamic effects of adjunctive hormone therapy in potential heart donors: a prospective randomized double-blind factorially designed controlled trial. Eur Heart J 2009;30:1771-80. 14. de la Rosa G, Dominguez-Gil B, Matesanz R, et al. Continuously evaluating performance in deceased donation: the Spanish quality assurance program. Am J Transplant 2012;12:2507-13. 15. Matesanz R, Dominguez-Gil B, Coll E, de la Rosa G, Marazuela R. Spanish experience as a leading country: what kind of measures were taken? Transplant Int 2011;24:333-43. 16. Weiss ES, Allen JG, Kilic A, et al. Development of a quantitative donor risk index to predict short-term mortality in orthotopic heart transplantation. J Heart Lung Transplant 2012;31:266-73. 17. Smits JM, De Pauw M, de Vries E, et al. Donor scoring system for heart transplantation and the impact on patient survival. J Heart Lung Transplant 2012;31:387-97. 18. Stevenson LW. The urgent priority for transplantation is to trim the waiting list. J Heart Lung Transplant 2013;32:861-7. 19. Singh TP, Almond CS, Taylor DO, Graham DA. Decline in heart transplant wait list mortality in the United States following broader regional sharing of donor hearts. Circ Heart Fail 2012;5: 249-58. 20. Wever-Pinzon O, Drakos SG, Kfoury AG, et al. Morbidity and mortality in heart transplant candidates supported with mechanical circulatory support: is reappraisal of the current United network for organ sharing thoracic organ allocation policy justified? Circulation 2013;127:452-62.
ANNUAL ISHLT REGISTRY REPORTS
Organ Allocation Around the World: Insights From the ISHLT International Registry for Heart and Lung Transplantation Josef Stehlik, MD, MPH,a,b Lynne W. Stevenson, MD,c Leah B. Edwards, PhD,a Maria G. Crespo-Leiro, MD,d Juan F. Delgado, MD,e Richard Dorent, MD,f Maria Frigerio, MD,g Peter Macdonald, MD,h Guy A. MacGowan, MD,i Alessandro Nanni Costa, MD,j Joseph G. Rogers, MD,k Ashish S. Shah, MD,l Rhiannon Taylor,m Rajaiyer V. Venkateswaran, MD,n and Mandeep R. Mehra, MDc From the aISHLT Transplant Registry, Dallas, Texas; bUniversity of Utah School of Medicine, Salt Lake City, Utah; c Brigham and Women’s Hospital Heart and Vascular Center, Harvard University, Boston, Massachusetts; dHospital Universitario A Coruña, La Coruña, Spain; eHospital 12 de Octubre, Madrid, Spain; fAgence de la biomédecine, Saint-Denis, France; gNiguarda-Ca’ Granda Hospital, Milan, Italy; hSt. Vincent’s Hospital, Sydney, New South Wales, Australia; iFreeman Hospital, Newcastle upon Tyne, United Kingdom; jCentro Nazionale Trapianti, Roma, Italy; kDuke University, Durham, North Carolina; lThe Johns Hopkins Hospital, Baltimore, Maryland; mNational Health Service Blood and Transplant, Bristol, United Kingdom; and the nWythenshawe Hospital, Manchester, United Kingdom.
The 2014 reports of the International Society for Heart and Lung Transplantation (ISHLT) International Registry for Heart and Lung Transplantation (Registry) bring expanded analyses of outcomes in patients who have undergone retransplantation. The experience of more than 170,000 heart, lung, and heart-lung transplant recipients transplanted over 30 years provided an opportunity for a robust exploration of this topic. The appropriateness of retransplantation has recently been undergoing critical review.1–5 We believe the analyses presented in the Registry reports provide important new information and insights that will be valuable as our professional community re-examines timing and candidate selection for retransplantation. The Registry continues to serve as a valuable tool to answer clinical questions, beyond the data presented in the annual reports. The Transplant Registry Early Career Award is a good mechanism that facilitates this work and catalyzes mentorship and collaboration across institutions and countries. Applications for the 2014 Award were submitted by applicants and mentors from 6 countries on 3 continents—
Reprint requests: Josef Stehlik, MD, MPH, Division of Cardiology, University of Utah Health Sciences Center, U.T.A.H. Cardiac Transplant Program, 50 N Medical Dr, 4A100 SOM, Salt Lake City, UT 84132. Telephone: 801-585-2340. Fax: 801-581-7735. E-mail address: [email protected] 1053-2498/$ - see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.healun.2014.08.001
Australia, Belgium, Czech Republic, Germany, Spain, Sweden, and the United States. The high quality of these applications resulted in 4 funded awards this year.6 The applications for next year’s award are due in January 2015 (http://www.ishlt.org/awards/awardTxRegistry.asp). The Registry also continued to work with members around the world to identify institutions and data collectives interested in participation in the Registry. Centers that joined the Registry in the past year include the Federal Research Center of Transplantology and Artificial Organs in Moscow, Russia, the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, and the Apollo Hospital in Chennai, India—all centers in countries that have not previously participated in the Registry. The Masih Daneshvari Hospital in Tehran became the second center in Iran, along with Tehran University of Medical Sciences, to join the Registry, and the Gangham Severance Hospital in Seoul joined the Severance Hospital as the second South Korean center to submit data. In addition, the Registry Committee has partnered with the International & Inter-society Coordination Committee (I2C2) of the ISHLT to work on establishing new collaborations in research, education, and advocacy. Examples include relations with the Turkish Society of Cardiovascular Surgery (activities spearheaded by Dr Ruchan Akar and Dr Murat Sargin), the Ministry of Health of Brazil (Dr Heder Borba), the Latin American and
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Caribbean Transplant Society (Dr Juan Mejia, Dr Alejandro Bertolotti), and the Ministry of Health of Argentina (Dr Carlos Soratti). The perspectives of an increasing number of the Registry participants (Figure 1), which mirror the breadth of the international membership in our Society, also allow for exploration of topics that may not be directly or fully addressed by Registry data collection. One of the ever more pressing topics is how to align the evolving non-transplant options in advanced heart and lung disease, the changing donor and recipient demographics, and organ allocation. To illustrate the utility of the Registry data and of the international expertise of the Society’s members, we provide a brief perspective focused on heart transplant data. During the past 3 decades, new traffic laws and improvements in automobile and workplace safety have resulted in a decrease in the accident-related death rates in young adults.7 In addition, the populations of many nations have continued to age. Consequently, the average age of organ donors has increased, as has the age of donors accepted for heart transplantation. The median age of a heart donor increased from 20 years in 1983 to 32 years in 2011, with the steepest increase being experienced in Europe, where the median donor age in 2011 reached 43 years.8 These demographic changes have a real effect on posttransplant survival. For example, the higher donor age in Europe would be expected to result in a 20% increase of mortality risk compared with the North American donor pool. Donor medical comorbidities, such as diabetes mellitus and hypertension, have also increased.9 The demographics of the heart transplant recipient have changed perhaps even more dramatically. Recipients being
transplanted in their 60s now comprise 30% of all adult heart transplants, with patients in their 70s receiving heart transplants with a higher frequency than ever before.8 Recipient comorbidities have increased steadily; at the time of transplant, 25% of recipients have diabetes mellitus, 45% have hypertension, 46% have had prior sternotomy, 7% have had malignancy, and 33% are allosensitized. The most visible recent change probably relates to the use of mechanical assist devices as a bridge to transplantation. Close to 40% of all adult recipients are bridged to transplant with a durable device. Further, although use of mechanical assist as a bridge to transplant had been infrequent in older patients in the recent past, this trend was fully reversed. As of 2011, transplant candidates older than 60 years are equally or even more likely to be supported by a mechanical assist device at the time of transplant compared with younger recipients. In view of the increasing complexity of donor and recipient profiles, the charge we have is to find ways to maintain (or increase) transplant volumes, preserve good post-transplant outcomes, maintain equity in organ allocation, and keep mortality on the transplant waiting list as low as possible. Renewed efforts to optimize the donation process and donor management have shown promise.10 Interventions to improve donor hemodynamic management have been tested in different countries, and sizeable increases in the number of organs suitable for transplantation resulted from these efforts. These interventions included sharing and implementing best practices from top performing organ procurement teams,11 implementing early protocol-driven donor management,12,13 and introducing didactic training for key hospital-based health care professionals.14,15
Figure 1 Countries participating in the International Society for Heart and Lung Transplantation International Registry for Heart and Lung Transplantation in 2013. A red flag indicates national or collaborative data submission, and a yellow flag indicates direct submission of data by individual centers. The country abbreviations are listed in the Appendix.
Stehlik et al.
Country
Key Heart Transplant Waiting List Parameters in a Sample of 5 Countries in North America, Europe, Australia, and New Zealand
Allocation algorithm
Median Transplanted waiting time in status
(%)
(days)
Patients on the list in Patients transplanted 2012 (at start of the year/newly listed) Transplant rate in 2012 in 2012
(No.)
(No.)
Patients with MCS at transplant
Patients transplanted/ patients on the list
Patients transplanted/ patients newly listed (VAD/ECMO)
(%)
(%)
(%)
Donor consent legislation
Heart Organ transplantsa donorsa
(per million)
(per million)
United Kingdom
Urgent Non-urgent
60 40
14 293
116
352 (141/212)
33
54
19 (16/3)
Opt in
2.1
17
France
High urgency 1 High urgency 2 Regional urgency Non-urgent
39 8 8 45
9 102 219 189
397
830 (300/530)
48
75
27 (13/14)
Opt out
6.1
25
Spain
Urgent status 0 Urgent status 1 Elective status
14 21 65
8 7 80
247
433 (101/332)
57
74
15 (9/6)
Opt out
5.3
35
Italy
1 high urgency 2A, 2B
14 86
3 292
231
1,100 (709/391)
32
59
9 (9/0)
Opt in/opt outb 4.6
20
Australia & Urgent New Zealand Non-urgent
8 92
15 120
85
186 (78/108)
46
79
40 (40/0)
Opt in
3.3
15
USA
64 31 5
78 224 618
2,378
36
76
40% (39/1)
Opt in
7.6
26
1A high urgency 1B intermediate 2 low urgency
6,669 (3,526/3,143)
Organ Allocation Around the World
Table 1
ECMO, extracorporeal membrane oxygenation; MCS, mechanical circulatory support; USA, United States of America; VAD, ventricular assist device (temporary or durable) or total artificial heart. a Based on 2010 data. b All are invited to register their donation intent. In the absence of declared intent, the law establishes presumed consent, but family input is typically sought.
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Recent studies have also examined the next step of the donation-transplantation process—the decisions surrounding acceptance of a particular donor allograft. It appears that current heart allograft utilization could be increased without elevating the risk of post-transplant mortality. Empiric quantification of the risk associated with a particular donor is difficult, and it has been proposed that a number of donor allografts with acceptable risk are currently being discarded. Ongoing studies are examining whether better assessment of risk associated with a particular donor allograft may result in an increase in the number of available donor hearts accepted for transplantation.16,17 Finally, there is the task of adapting our organ allocation processes to the changing epidemiology of donors and recipients and the evolving therapeutic options for advanced heart disease. Although the logistical challenges associated with the process of organ donation and organ management are reasonably similar among countries with established organ transplantation programs, organ donation rates and heart transplantation rates vary significantly among these countries. The differences among organ allocation rules are even more pronounced. Key heart transplant indicators from a sample of countries are listed in Table 1. All sampled countries have established different tiers of transplant urgency status; however, the definition of urgency is variable. Large differences also exist among the individual countries in the proportion of patients who are transplanted in the highest urgency status and in the median time from listing to transplantation in the high urgency status. This illustrates that the specifics of an allocation system have great effect on these key parameters. Some countries have a fairly restrictive definition of highest urgency such that only o15% of listed patients are transplanted in this status (Spain, Italy, Australia/New Zealand); this, in turn, results in short median times to transplantation of 8, 3, and 15 days, respectively. Then there are countries where a significant proportion of patients are transplanted in the highest urgency status—United Kingdom (60%) and France (39%)— yet, the median waiting time to transplant is still short, at 14 and 9 days, respectively. This would suggest that the waiting list is managed very carefully in these countries, such that the number of patients placed in the highest urgency status does not overwhelm the limited supply of donor organs. Finally, data for the United States show that most patients in this country are transplanted in a high urgency status (64% in status 1A, 31% in status 1B, and only 5% in lower urgency status 2) but also that under the current allocation rule, the ability to expeditiously transplant a heart patient has been lost, for the median waiting time for a transplant in the highest urgency status 1A is now 78 days.18 Regardless of the specifics of a particular allocation system, 2 aspects of the allocation rules continue to present a particular challenge. The first is that allocation algorithms often incorporate provisions for allocation to an individual center or an arbitrarily defined geographic area, rather than exclusively allocation to an individual patient. On the positive side, these geographic arrangements provide a strong incentive for local teams to create efficient processes that maximize the use of organs by increasing donation awareness, early identification of potential donors, and
implementation of optimal donor management. However, allocation of organs based on a wider regional, national, and even multinational prioritization of candidates at the highest risk of death has been shown to result in a decrease of waiting list mortality and an increase of transplant benefit.19 In our assessment, most allocation algorithm revisions are therefore moving away from center-specific rules (including “pay-back” rules) and in favor of broader sharing of organs. Continuation of active efforts to improve the number and quality of donors across the board will eventually benefit every region, even with the wider regional sharing of organs. The second highly charged aspect of heart allocation relates to the now prevalent use of mechanical assist therapies in transplant candidates. Allocation arrangements in the countries reviewed in Table 1 range from a significant advantage to even stable patients supported with ventricular assist devices (VADs) to no advantage unless a serious VAD complication occurs. Supporters for higher priority for transplant candidates receiving VAD would argue that lack of allocation priority for VAD patients results in very long waiting times in many. And, when a serious VAD-associated complication occurs, this may negate the expected benefit of the bridge-to-transplant therapy, because a sub-set of these patients will become transplant ineligible or have a higher risk of post-transplant morbidity and mortality. On the other hand, the concern with providing a significant advantage to patients with VADs brings up questions of equity, because these patients often have a lower risk of waiting list mortality compared with patients with other indications for urgent listing.20 The specifics of the algorithms may also influence the likelihood with which the transplant candidates will require mechanical assist therapies. This is being taken into consideration by health care funding agencies in the individual countries, which further complicates possible decisions on allocation rule changes. In summary, changes in donor and recipient profiles, coupled with new therapeutic options in advanced heart and lung disease, present new perspectives on organ allocation and candidate selection. As we embrace these new realities, and as changes in thoracic allocation policies are being considered by many, the rich international experience offers an opportunity to identify and implement regulatory and clinical practice changes that will ensure transplantation continues to provide our patients an opportunity to regain longevity and an active lifestyle. We would like to thank the members and staff at the many participating centers and data exchange organizations around the world for making these global observations possible (Appendix 1).
Disclosure statement The authors thank staff at the national transplant organizations for contributing data for this report. All relevant disclosures for the authors are on file with the ISHLT and can be made available for review by contacting the Executive Director of the ISHLT. All relevant disclosures for the Registry Director, Executive Committee Members and authors are on file with the ISHLT and can be made available for review by contacting the Executive Director of the ISHLT
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Appendix List of Thoracic Transplant Centers Reporting Data to the International Society for Heart and Lung Transplantation Transplant Registry for Transplants Performed Between January 1, 2012, and June 30, 2013 Country (ISO code)
Center
Argentina (ARG)
Fundacion Favaloro Hospital Italiano St. Vincent Royal Children The Prince Charles Hospital The Alfred Hospital Royal Perth Hospital Allgemeines Krankenhaus Wien Universitätsklinik Innsbruck Landeskrankenhaus Graz Hôpital Erasme Bruxelles Universitair Ziekenhuis Antwerpen Onze Lieve Vrouw Ziekenhuis Aalst Universitair Ziekenhuis Gent Centre Hospitalier Universitaire Liège Cliniques Universitaires, Université Catholique de Louvain UZ Gasthuisberg Leuven Heart Institute–Universidade São Paulo Hospital das Clinicas Hospital de Messejana Real Hospital Portugues de Beneficiencia Em Pernambuco Instituto de Medicina Integral Instituto de Cardiologia do Distrito Federal Hospital de Clinicas de Porto Alegre Royal Victoria Hospital The Toronto General Hospital Hospital Notre-Dame Quebec Heart Institute–Laval Hospital University of Alberta Hospitals/Walter C. Mackenzie Health Sciences St. Paul’s Hospital Vancouver General Hospital The Hospital For Sick Children Hospital Gustavo Fricke Instituto Nacional del Torax Clinica Cardiovascular Fundacion Valle Del Lili Fundacion Cardioinfantil–Instituto de Cardiologia Fundacion Cardiovascular de Colombia Fundacion Clinica Shaio University Clinical Hospital Zagreb University Hospital Dubrava University Hospital Motol Skejby University Hospital Rigshospitalet, National University Hospital Tartu University Hospital Helsinki University Central Hospital Children’s Hospital, University of Helsinki Marseille Sainte Marguerite (APM) (A)–Chirurgie Thoracique Marseille Timone adultes (APM) (A)–Chirurgie Cardiaque Marseille Timone enfants (APM) (AþP)–Chirurgie Cardio-Vasculaire Caen (A)–Chirurgie Cardiaque Dijon (A)–Chirurgie Cardiaque Toulouse (A)–Chirurgie Thoracique Toulouse (A)–Chirurgie Cardio-Vasculaire Bordeaux (AþP)–Unite de Transplantation Cardiaque Bordeaux (AþP)–Chirurgie Thoracique Montpellier (A)–Unite de Transplantation Cardio-Thoracique Rennes (A)–Centre Cardio-Pneumologique
Australiaa (AUS)
Austriab (AUT)
Belgiumb (BEL)
Brazil (BRA)
Canada (CAN)
Chile (CHL) Colombia (COL)
Croatiab (HRV) The Czech Republic (CZE) Denmarkc (DNK) Estonia (EST) Finlandc (FIN) Franced (FRA)
Continued on page 980
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Appendix (Continued ) Country (ISO code)
Germanyb (DEU)
India (IND) Iran (IRN) Irelande (IRL) Israel (ISR) Italy (ITA) Japan (JPN)
Center Tours (AþP)–Chirurgie Cardiaque Grenoble (A)–Chirurgie Cardiaque Grenoble (A)–Pneumologie Nantes (AþP)–Chirurgie Cardio-Vasculaire Nancy (AþP)–Chirurgie Cardio-Pulmonaire Lille (AþP)–Chirurgie Cardio-Vasculaire Clermont-Ferrand (A)–Chirurgie Cardiaque Strasbourg (A)–Chirurgie Thoracique Strasbourg (A)–Chirurgie Cardio-Pulmonaire Lyon (AþP)–Pole de Transplantation Pulmonaire Lyon I (HCL) (AþP)–Pole de Transplantation Cardiaque Lyon II (HCL) (A)–Pole de Transplantation Cardiaque Paris Pitié-Salpêtrière (AP-HP) (AþP)–Chirurgie Cardio-Vasculaire Paris Necker Enfants Malades (AP-HP) (AþP)–Cardiologie Pediatrique Clichy Beaujon (AP-HP) (A)–Pneumologie B et Transplantation Pulmonaire Paris Bichat (AP-HP) (A)–Chirurgie Cardio-Vasculaire Paris Georges Pompidou (AP-HP) (A)–Transplantation Cardiaque Paris Georges Pompidou (AP-HP) (AþP)–Transplantation. Pneumologie et Cardio-Pulmonaire Rouen (AþP)–Chirurgie Thoracique et Cardio-Vasculaire Limoges (A)–Chirurgie Cardiaque Suresnes Foch (A)–Chirurgie Thoracique Le Plessis-Robinson Marie-Lannelongue (AþP)–Chirurgie Cardiaque Le Plessis-Robinson Marie-Lannelongue (AþP)–Chirurgie Thoracique Cardio-Vasculaire Créteil Henri Mondor (AP-HP) (A)–Chirurgie Cardio-Vasculaire Universität des Saarlandes Homburg/Saar Herzzentrum Dresden GmbH Deutsches Herzzentrum Berlin Universitätsklinik Köln Universität Leipzig–Herzzentrum Kerckhoff Klinik, Bad Nauheim Klinikum der Universität Regensburg Herzzentrum Nordrhein-Westfalen Bad Oeynhausen Universitätsklinikum Essen Johannes Gutenberg Universität Mainz Heinrich-Heine-Universität Düsseldorf Universitätsklinikum Münster Ruprecht-Karls-Universität Heidelberg Medizinische Hochschule Hannover Universitätsklinikum Göttingen Universitätsklinikum Aachen Klinikum der Justus-Liebig-Universität Giessen Universitätsklinikum Schleswig-Holstein Kiel Johann Wolfgang Goethe Universität Frankfurt/Main Friedrich Schiller Universität Jena Friedrich Alexander Universität Erlangen Universitätsklinikum Würzburg Ludwig Maximilians Universität München Universitätsklinikum Hamburg Klinikum der Albert-Ludwigs-Universität Freiburg im Breisgau Apollo Hospital Cardiac Surgery and Transplantation Research Center Masih Daneshvari Hospital Mater Hospital Rabin Medical Center (Belinson Campus) Sheba Medical Center Policlinico S. Orsola–Universita degli Studi Tohoku University Hospital Osaka University Hospital
Continued on page 981
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Appendix (Continued ) Country (ISO code) b
Netherlands (NLD)
New Zealand (NZL) Norwayc (NOR) Poland (POL) The Republic of Korea (KOR) Russia (RUS) Saudi Arabia (SAU) Sloveniab (SVN) South Africa (ZAF) Spain (ESP)
Swedenc (SWE) Switzerland (CHE) Turkey (TUR)
United Kingdome (UK)
United Statesi (USA)
Center Universitair Medisch Centrum Utrecht Erasmus Medisch Centrum Rotterdam Universitair Medisch Centrum Groningen Green Lane Hospital Auckland City Hospital Rikshospitalet–National Hospital of Norway Regional Pulmonary Hospital Gangnam Severance Hospital Severance Hospital Federal V. Shumakov Research Centre of Transplantology & Artificial Organs King Faisal Specialist Hospital and Research Center University Medical Center Ljubljana Milpark Hospital Complejo Hospitalario Universitario Juan Canalejof,g Hospital Universitario Marques de Valdecillaf,h Hospital de Bellvitge, Barcelonah Hospital Virgen Del Rocio, Sevillah Hospital Santa Creu I Sant Pau, Barcelonah Hospital Universitario 12 de Octubref,h Hospital Universitario Reina Sofiaf,h Hospital Gregorio Marañón, Madridh Hospital Universitario Puerta de Hierrof Hospital Universitari I Politècnic La Fe, Valenciaf,h Hospital Clinic I Provincial, Barcelonah Hospital Universitario Vall D’Hebronf,h Hospital Central de Asturiasg Hospital La Paz Infantilf,h Hospital Virgen de La Arrixaca, Murciah Hospital Miguel Servet, Zaragozah Hospital Clínico, Valladolidh Sahlgrenska University Hospital University Hospital of Lund University Hospital Zurich Istanbul Florence Nightingale Hospital Heart Center, Ankara University Hospital of Akdeniz University Great Ormand Street Hospital for Children University of Glasgow/Glasgow Royal Infirmary The Freeman Hospital Harefield Hospital Wythenshawe Hospital Queen Elizabeth Hospital Papworth Hospital University of Alabama Hospital, Birmingham, AL Baptist Medical Center, Little Rock, AR Arkansas Children’s Hospital, Little Rock, AR Phoenix Children’s Hospital, Phoenix, AZ Mayo Clinic Hospital, Phoenix, AZ St. Joseph’s Hospital and Medical Center, Phoenix, AZ University Medical Center, University of Arizona, Tucson, AZ Children’s Hospital Los Angeles, Los Angeles, CA Cedars-Sinai Medical Center, Los Angeles, CA Loma Linda University Medical Center, Loma Linda, CA Lucile Salter Packard Children’s Hospital, Palo Alto, CA California Pacific Medical Center, San Francisco, CA UCSD Medical Center, San Diego, CA UCSF Medical Center, San Francisco, CA Sutter Memorial Hospital, Sacramento, CA Sharp Memorial Hospital, San Diego, CA Stanford University Medical Center, Stanford, CA
Continued on page 982
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Appendix (Continued ) Country (ISO code)
Center UCLA Medical Center, Los Angeles, CA Keck Hospital of USC, Los Angeles, CA Children’s Hospital Colorado, Aurora, CO University of Colorado Hospital/HSC, Aurora, CO Hartford Hospital, Hartford, CT Yale New Haven Hospital, New Haven, CT Children’s National Medical Center, Washington, DC Washington Hospital Center, Washington, DC Alfred I duPont Hospital for Children, Wilmington, DE All Children’s Hospital, St. Petersburg, FL Florida Hospital Medical Center, Orlando, FL Memorial Regional/Joe DiMaggio Children’s Hospital, Hollywood, FL Jackson Memorial Hospital, Miami, FL Mayo Clinic Florida, Jacksonville, FL Tampa General Hospital, Tampa, FL Shands Hospital at University of FL, Gainesville, FL Children’s Healthcare of Atlanta, Atlanta, GA Emory University Hospital, Atlanta, GA Piedmont Hospital, Atlanta, GA St. Joseph’s Hospital of Atlanta, Atlanta, GA University of Iowa Hospital and Clinics, Iowa City, IA Advocate Christ Medical Center, Oak Lawn, IL Ann and Robert H. Lurie Children’s Hospital, Chicago, IL Loyola University Medical Center, Maywood, IL Northwestern Memorial Hospital, Chicago, IL Rush University Medical Center, Chicago, IL University of Chicago Medical Center, Chicago, IL Indiana University Health, Indianapolis, IN Lutheran Hospital of Ft Wayne, Ft Wayne, IN St. Vincent Hospital and Health Care Center, Indianapolis, IN Jewish Hospital, Louisville, KY University of Kentucky Medical Center, Lexington, KY Ochsner Foundation Hospital, New Orleans, LA Boston Children’s Hospital, Boston, MA Massachusetts General Hospital, Boston, MA Tufts Medical Center, Boston, MA Brigham and Women’s Hospital, Boston, MA Johns Hopkins Hospital, Baltimore, MD University of Maryland Medical System, Baltimore, MD Children’s Hospital of Michigan, Detroit, MI Henry Ford Hospital, Detroit, MI SpeCenterum Health, Grand Rapids, MI University of Michigan Medical Center, Ann Arbor, MI Abbott Northwestern Hospital, Minneapolis, MN St. Mary’s Hospital (Mayo Clinic), Rochester, MN University of Minnesota Medical Center, Minneapolis, MN Barnes-Jewish Hospital, St. Louis, MO Cardinal Glennon Children’s Hospital, St. Louis, MO St. Louis Children’s Hospital, St. Louis, MO St. Luke’s Hospital of Kansas City, Kansas City, MO University of MS Medical Center, Jackson, MS Wake Forest Baptist Medical Center, Winston-Salem, NC Carolinas Medical Center, Charlotte, NC Duke University Hospital, Durham, NC UNC Hospitals, Chapel Hill, NC Children’s Hospital and Medical Center, Omaha, NE The Nebraska Medical Center, Omaha, NE Newark Beth Israel Medical Center, Newark, NJ Robert Wood Johnson University Hospital, New Brunswick, NJ New York-Presbyterian/Columbia, New York, NY
Continued on page 983
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Appendix (Continued ) Country (ISO code)
Center Strong Memorial Hospital, Rochester, NY Montefiore Medical Center, Bronx, NY Mount Sinai Medical Center, New York, NY Westchester Medical Center, Valhalla, NY Cleveland Clinic Foundation, Cleveland, OH Nationwide Children’s Hospital, Columbus, OH Children’s Hospital Medical Center, Cincinnati, OH Ohio State University Medical Center, Columbus, OH University Hospital of Cleveland, Cleveland, OH Integris Baptist Medical Center, Oklahoma City, OK Oregon Health and Science University, Portland, OR Allegheny General Hospital, Pittsburgh, PA Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA Children’s Hospital of Philadelphia, Philadelphia, PA Penn State Milton S Hershey Medical Center, Hershey, PA Hahnemann University Hospital, Philadelphia, PA University of Pittsburgh Medical Center, Pittsburgh, PA Thomas Jefferson University Hospital, Philadelphia, PA Temple University Hospital, Philadelphia, PA The Hospital of the University of PA, Philadelphia, PA Cardiovascular Center of Puerto Rico, San Juan, PR Medical University of South Carolina, Charleston, SC Baptist Memorial Hospital, Memphis, TN Vanderbilt University Medical Center, Nashville, TN University Hospital, San Antonio, TX Children’s Medical Center of Dallas, Dallas, TX Seton Medical Center, Austin, TX Medical City Dallas Hospital, Dallas, TX Memorial Hermann Hospital, Houston, TX St Luke’s Episcopal Hospital, Houston, TX Methodist Specialty and Transplant Hospital, San Antonio, TX University of Texas Medical Branch, Galveston, TX The Methodist Hospital, Houston, TX University Hospital–St. Paul, Dallas, TX Scott and White Memorial Hospital, Temple, TX Texas Children’s Hospital, Houston, TX Baylor University Medical Center, Dallas, TX Intermountain Medical Center, Murray, UT University of Utah Medical Center, Salt Lake City, UT Primary Children’s Medical Center, Salt Lake City, UT Inova Fairfax Hospital, Falls Church, VA MCV Hospitals, Richmond, VA McGuire VA Medical Center, Richmond, VA Sentara Norfolk General Hospital, Norfolk, VA University of Virginia HSC, Charlottesville, VA Seattle Children’s Hospital, Seattle, WA Sacred Heart Medical Center, Spokane, WA University of Washington Medical Center, Seattle, WA Children’s Hospital of Wisconsin, Milwaukee, WI Froedtert Memorial Lutheran Hospital, Milwaukee, WI Aurora St. Luke’s Medical Center, Milwaukee, WI University of Wisconsin Hospital and Clinics, Madison, WI
ISO, International Organization for Standardization. a Data provided via Australia and New Zealand Cardiothoracic Transplant Registry (ANZCOTR). b Data provided via Eurotransplant (ET). c Data provided via Scandiatransplant. d Data provided via L’Agence de la Biomédicine. e Data provided via United Kingdom Transplant Support Service Authority (UKTSSA). f Lung data provided via OrganizaciónNacional de Trasplantes (ONT). g Heart data provided directly to ISHLT Registry. h Heart data provided via RegistroEspañol de TrasplanteCardíaco. i Data provided via United Network for Organ Sharing (UNOS).
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References 1. Vanderlaan RD, Manlhiot C, Conway J, et al. Perioperative factors associated with in-hospital mortality or retransplantation in pediatric heart transplant recipients. J Thorac Cardviovasc Surg 2014;148:282-9. 2. Kobashigawa J, Zuckermann A, Macdonald P, et al. Report from a consensus conference on primary graft dysfunction after cardiac transplantation. J Heart Lung Transplant 2014;33:327-40. 3. Conway J, Manlhiot C, Kirk R, et al. Mortality and morbidity after retransplantation after primary heart transplant in childhood: an analysis from the registry of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2014;33:241-51. 4. Khan MS, Mery CM, Zafar F, et al. Is mechanically bridging patients with a failing cardiac graft to retransplantation an effective therapy? Analysis of the United Network of Organ Sharing database. J Heart Lung Transplant 2012;31:1192-8. 5. Goldraich L, Stehlik J, Kucheryavaya AY, Edwards LB, Ross HJ. Retransplantation versus medical therapy for cardiac allograft vasculopathy (CAV): analysis of the International Society for Heart and Lung Transplantation (ISHLT) Registry. J Heart Lung Transplant 2014;33:S90. 6. International Society for Heart and Lung Transplantation. ISHLT grants and awards program. Available at: http://ishlt.org/awards/currentRecipients.asp. 7. Silver D, Macinko J, Bae JY, Jimenez G, Paul M. Variation in U.S. traffic safety policy environments and motor vehicle fatalities 1980– 2010. Public Health 2013;127:1117-25. 8. Lund LH, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: thirtieth official adult heart transplant report—2013; focus theme: age. J Heart Lung Transplant 2013;32:951-64. 9. Nativi JN, Brown RN, Taylor DO, Kfoury AG, Kirklin JK, et al. Temporal trends in heart transplantation from high-risk donors: are there lessons to be learned? A multi-institutional analysis. J Heart Lung Transplant 2010;29:847-52. 10. Kransdorf EP, Stehlik J. Donor evaluation in heart transplantation: the end of the beginning. J Heart Lung Transplant 2014, http://dx.doi.org/ 10.1016/j.healun.2014.05.002: [E-pub ahead of print].
11. U.S. Department of Health and Human Services, Health Resources and Services Administration. Office of Special Programs, Division of Transplantation. The organ donation breakthrough collaborative: best practices final report. Contract 240-94-0037. Task Order No. 12. Washington, DC: U.S. Department of Health and Human Services; 2003. 12. Venkateswaran RV, Patchell VB, Wilson IC, et al. Early donor management increases the retrieval rate of lungs for transplantation. Ann Thorac Surg 2008;85:278-86: discussion 286. 13. Venkateswaran RV, Steeds RP, Quinn DW, et al. The haemodynamic effects of adjunctive hormone therapy in potential heart donors: a prospective randomized double-blind factorially designed controlled trial. Eur Heart J 2009;30:1771-80. 14. de la Rosa G, Dominguez-Gil B, Matesanz R, et al. Continuously evaluating performance in deceased donation: the Spanish quality assurance program. Am J Transplant 2012;12:2507-13. 15. Matesanz R, Dominguez-Gil B, Coll E, de la Rosa G, Marazuela R. Spanish experience as a leading country: what kind of measures were taken? Transplant Int 2011;24:333-43. 16. Weiss ES, Allen JG, Kilic A, et al. Development of a quantitative donor risk index to predict short-term mortality in orthotopic heart transplantation. J Heart Lung Transplant 2012;31:266-73. 17. Smits JM, De Pauw M, de Vries E, et al. Donor scoring system for heart transplantation and the impact on patient survival. J Heart Lung Transplant 2012;31:387-97. 18. Stevenson LW. The urgent priority for transplantation is to trim the waiting list. J Heart Lung Transplant 2013;32:861-7. 19. Singh TP, Almond CS, Taylor DO, Graham DA. Decline in heart transplant wait list mortality in the United States following broader regional sharing of donor hearts. Circ Heart Fail 2012;5: 249-58. 20. Wever-Pinzon O, Drakos SG, Kfoury AG, et al. Morbidity and mortality in heart transplant candidates supported with mechanical circulatory support: is reappraisal of the current United network for organ sharing thoracic organ allocation policy justified? Circulation 2013;127:452-62.
