Postlung Transplant Survival is Equivalent Regardless of Cytomegalovirus Match Status

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1 Postlung Transplant Survival is Equivalent Regardless of Cytomegalovirus Match Status Mark J. Russo, MD, MS, David I. Sternberg, MD, Kimberly N. Hong, MHSA, Robert A. Sorabella, BA, Alan J. Moskowitz, MD, Annetine C. Gelijns, PhD, Jessie R. Wilt, MD, Frank D Ovidio, MD, PhD, Steve M. Kawut, MD, MS, Selim M. Arcasoy, MD, and Joshua R. Sonett, MD Lung Transplant Program and International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Surgery; and Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York Background. The purpose of this study was to assess (1) the relationship between donor recipient cytomegalovirus (CMV) serologic status and posttransplant survival in the current era and (2) temporal changes in posttransplant survival by CMV matching status. Methods. De-identified data were obtained from the United Network for Organ Sharing. Based on pretransplant CMV serologic status ( or ) of recipients (R) and donors (D), posttransplant survival was compared among three groups: D R, D R, and D R. Primary analysis focused on transplants performed January 1, 2000 to December 31, 2004, in recipients 18 years of age or older. To assess temporal trends in survival among groups, all lung transplants occurring between January 1, 1990, and December 31, 2004, were considered and divided into three periods based on transplant year: 1990 through 1994, 1995 through 1999, and 2000 through The primary outcome measure was survival, reported as rate of death per 100 patient-years. Kaplan Meier analysis with log-rank test was used for time-toevent analysis. Results. During the current era (2000 through 2004), D R (n 951), D R (n 2,676), and D R (n 772) exhibited no differences in survival (p 0.561), with rates of death per 100 patient-years of 16.6 (95% confidence interval, 14.9 to 18.5), 15.0 (95% confidence interval, 14.0 to 16.0), and 14.7 (95% confidence interval, 13.0 to 16.6), respectively. However, survival was significantly different for groups in the earlier eras of 1990 through 1994 (p < 0.001) and 1995 through 1999 (p < 0.001). During the three periods, survival improved significantly in D R (p < 0.001) and D R (p < 0.001), but survival in D R (p 0.351) did not change significantly with time. Conclusions. In the current era, survival after lung transplantation is statistically equivalent regardless of CMV match status. Although in previous eras survival was worse among the D R and D R groups, in this era of aggressive CMV prophylaxis, CMV mismatch should not be sufficient grounds to decline a lung allograft offer. (Ann Thorac Surg 2007;84: ) 2007 by The Society of Thoracic Surgeons Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality in solid organ transplant recipients, particularly after lung transplantation [1]. After early experience with lung transplantation, many centers adopted a policy of CMV seromatching of recipients and donors to avoid transplantation of lungs from CMVpositive (CMV ) donors to CMV-negative (CMV ) recipients (CMV mismatching). However, because of the scarcity of organs and the conflicting findings of more recent studies exploring this relationship between CMV serologic status and outcomes [2 10], this practice has not been universally applied. The primary objectives of this study were to assess (1) the relationship between donor recipient CMV serologic Accepted for publication May 11, Presented at the Forty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 29 31, Address correspondence to Dr Sonett, Division of Cardiothoracic Surgery, New York-Presbyterian Hospital/Columbia, PH Room 104, 14th Floor, 622 W 168th St, New York, NY 10032; js2106@columbia.edu. status and survival in the current era and (2) temporal changes in survival by CMV serologic status. We hypothesized that, although CMV recipient donor mismatch in previous eras may have been associated with worse posttransplant survival, with the advent of more effective and aggressive CMV prophylaxis strategies, CMV mismatching in the current era is no longer associated with worse posttransplant survival. Although numerous studies have explored the effect of CMV serologic status on outcomes, these studies suffered from a number of limitations. First, these studies were largely single-center studies and therefore limited in size. Furthermore, these studies were completed before the implementation of more effective and aggressive CMV prophylaxis strategies or did not consider temporal changes in CMV prophylaxis strategies. This study differed from previous studies because, by analyzing the United Network for Organ Sharing (UNOS) database, it examined the national experience with lung transplantation during a 15-year period. Moreover, by dividing the 2007 by The Society of Thoracic Surgeons /07/$32.00 Published by Elsevier Inc doi: /j.athoracsur

2 1130 RUSSO ET AL Ann Thorac Surg CMV MATCH STATUS IN LUNG TRANSPLANTATION 2007;84: analysis period into discrete time intervals, it considers possible advances in management strategies with time. Finally, this study examined the association between CMV match status and posttransplant morbidity, including bronchiolitis obliterans, infection, and rejection. Material and Methods Data Collection Use of these data are consistent with the regulations of our university s institutional review board and the UNOS Data Use Agreement. The Standard Transplant Analysis and Research Dataset was provided by UNOS (data source number ). It contains information collected from the UNetsm forms, including the Transplant Candidate Registration form, the Transplant Recipient Registration form, and the Transplant Recipient Follow-up form. These data are the basis of the UNOS Thoracic Registry. Study Population All recipients age 18 years and older undergoing lung transplantation between January 1, 1990, and December 31, 2004, were included in the study population. Patients were followed from the date of transplantation to February 27, 2006, which was the last day of follow-up data provided by UNOS. Mean patient follow-up period was years. Primary analysis focused on lung transplants performed January 1, 2000, to December 31, 2004 (current era). This 5-year period was used for primary analysis because 2000 was the first complete year that UNOS collected data regarding use of ganciclovir or valganciclovir for CMV prophylaxis. Patients were categorized into three groups according to donor recipient CMV serologic status: donor CMV Recipient CMV (D R ), donor CMV or CMV Recipient CMV (D R ), and donor CMV Recipient CMV (D R ). If CMV recipient or donor serologic status was omitted, patients (n 1,513; 12.37%) were excluded from the analysis. Outcome Measures The primary outcome measure was survival reported as median posttransplant survival and rate of death (RD) per 100 patient-years with 95% confidence intervals (CI). Kaplan Meier analysis with Cox proportional hazards regression (HR) was used for time-to-event analysis. Outcome of interest was death (n 6,213, 53.7%) or retransplant (n 331, 2.9%), whichever came first. Patients lost to follow-up (n 280, 2.4%) or alive at last known follow-up (4,742, 41.0%) were censored at the date of last known follow-up. Other outcomes of interest included severe rejection free survival (FS), severe infection FS, and bronchiolitis obliterans (BO) FS. Severe rejection was defined as the need for hospitalization as a result of rejection. Severe infection was defined as the need for hospitalization as a result of infection. Bronchiolitis obliterans was defined as bronchiolitis obliterans grade 1 or higher. Ganciclovir or valganciclovir prophylaxis (GVP) indicates posttransplant use of ganciclo- Table 1. Patient Characteristics for All Lung Transplant Recipients Aged 18 and Older ( ) D R D R D R Total Variable Number SD/% Number SD/% Number SD/% Number SD/% Recipients % % % 4399 Mean age (y) Male sex % % % % Body mass index (kg/m 2 ) FEV Race White % % % % AA % % % % Hispanic % % % % Other 4 0.4% % 4 0.5% % Cause of ESLD IPF % % % % CF % % % % COPD % % % % OTH % % % % Type of transplant Single % % % % Double % % % % Ischemic time (h) Donor age (y) AA African American; CF cystic fibrosis; CMV cytomegalovirus; COPD chronic obstructive pulmonary disease; D donor CMV( ); D donor CMV or ; ESLD end-stage lung disease; FEV 1 forced expiratory volume in 1 second; IPF idiopathic pulmonary fibrosis; OTH other; R recipient CMV( ); R recipient CMV( ); SD standard deviation.

3 Ann Thorac Surg RUSSO ET AL 2007;84: CMV MATCH STATUS IN LUNG TRANSPLANTATION 1131 Survival in the Current Era During the current era (2000 through 2004), D R (n 951), D R (n 2,676), and D R (n 772) exhibited no differences in median survival (p 0.561), with the RD per 100 patient-years of 16.6 (95% CI, 14.9 to 18.5), 15.0 (95% CI, 14.0 to 16.0), and 14.7 (95% CI, 13.0 to 16.6), respectively (Fig 1). In the multivariable Cox proportional Fig 1. Kaplan Meier survival analysis after lung transplantation by cytomegalovirus (CMV) serologic status. (D donor CMV ; Dx donor CMV or ; R recipient CMV ; R recipient CMV.) vir or valganciclovir for CMV prophylaxis. These secondary analyses were limited to the current era. Data Analysis Continuous variables were reported as means standard deviation and compared using the Student s t test. To compare categorical variables, the 2 test was used. The conventional probability value of 0.05 or less was used to determine level of statistical significance. All reported probability values are two-sided. Kaplan Meier analysis with log-rank test was used for time-to-event analysis for actuarial survival, as well as severe rejection FS, severe infection FS, and BO-FS. Cox proportional HR was also performed (backward, remove p 0.15) to assess the simultaneous effect of multiple variables on survival after lung transplant including donor age younger than 50, recipient age younger than 60, cause of end-stage lung disease (ESLD: pulmonary hypertension, idiopathic pulmonary fibrosis, cystic fibrosis, chronic obstructive pulmonary disease), type of transplant (single versus double), and ischemic time less than 4 hours. Median time to event was the day of follow-up when 50% of uncensored patients experienced the event of interest. Patients lost to follow-up were censored at the time of last known follow-up. To assess temporal trends in survival, patients were divided into three eras based on year of transplant: ERA1 (1990 through 1994), ERA2 (1995 through 1999), and ERA3 (2000 through 2004). All data were analyzed using a statistical software package, Stata 9 (Stata Corp, College Station, TX). Results Study Population Primary analysis focused on 5,068 lung transplantations performed 2000 through 2004, including 10,780.4 years at risk with a median survival of 5.01 years; 50.1% of donors (n 1,178) and 65.9% of recipients (n 1,448) were CMV positive (CMV ). Demographic and clinical characteristics of the study patients are summarized in Table 1. Fig 2. Kaplan Meier survival functions for posttransplant survival within each of the three eras stratified by cytomegalovirus (CMV) match status. (A) Group 2 (D R ); (B) group 2 (Dx R ); (C) group 3 (D R ). 4-year incremental time periods for the 1991 to 2004 era. (D donor CMV ; Dx donor CMV or ; R recipient CMV ; R recipient CMV.)

4 1132 RUSSO ET AL Ann Thorac Surg CMV MATCH STATUS IN LUNG TRANSPLANTATION 2007;84: hazards regression, donor age of 50 years or older (HR 1.22, 95% CI, 1.05 to 1.40), recipient age older than 60 years (HR 1.29, 95% CI, 1.14 to 1.46), double-lung transplant (HR 0.84, 95% CI, 0.75 to 0.94), chronic obstructive pulmonary disease cause of ESLD (HR 0.82, 95% CI, 0.73 to 0.92), and pulmonary hypertension cause of ESLD (HR 1.36, 95% CI, 1.03 to 1.8) were associated with survival. Cytomegalovirus status D R (p 0.257) and D R (p 0.283), however, were not associated with decreased survival. 698 days) D R (739 days) D R (869 days; Fig 3). Conversely, severe rejection FS did not differ significantly (p 0.46) across the three groups. Likewise, BO-FS was not significantly different (p 0.57) across the three groups; however, when stratified by GVP, recipients who received prophylaxis in the D R (p 0.001) and D R (p 0.055) groups had significantly better BO-FS, whereas BO-FS in the D R group (p.547) was not different on the basis of GVP status (Fig 4). Temporal Trends Temporal effects on survival are summarized in Figure 2. There was an overall improvement in posttransplant survival with each subsequent period; this is illustrated moving from ERA 1 (n 2,196) to ERA 2 (n 4,098) to ERA3(n 5,082), with the IRD decreasing from 16.0 to 15.9 to 15.6 per 100 patient-years; consistent with this trend, median survival increased from 4.23 years to 4.35 years to 5.00 years. In multivariable Cox proportional hazard regression of ERA1, CMV status D R (HR 1.23, 1.02 to 1.48) and D R (HR 1.36, to 1.63) were associated with worse survival; other factors associated with survival included recipient age of 60 years or older (HR 1.24, 1.04 to 1.48), double-lung transplant (HR 0.78, 0.69 to 0.90), and chronic obstructive pulmonary disease cause of ESLD (HR 0.70, 0.52 to 0.95). Likewise in ERA2, CMV status D R (HR 1.18, 1.05 to 1.33) and D R (HR 1.39, 1.21 to 1.59) were associated with worse survival; other factors associated with survival included donor age of 50 years or older (HR 1.22, 1.08 to 1.39), recipient age of 60 years or older (HR 1.39, 1.26 to 1.54), chronic obstructive pulmonary disease cause of ESLD (HR 0.89, 0.81 to 0.97), pulmonary hypertension cause of ESLD (HR 1.23, 1.25 to 1.54), and doublelung transplant (HR 0.77, 0.70 to 0.84). To further assess the effect of era and CMV status on survival, additional Cox regression was performed using observations from all time points and incorporating the variables shown above along with interaction terms for CMV status and era of transplantation. In this model, the interaction terms were statistically significant (all p 0.001) further supporting the differential impact of CMV matching on outcome by (or depending on) the era of transplantation, which was demonstrated in the era-specific regression models. In the D R group, survival improved significantly (p 0.01), with the IRD decreasing from ERA1 (18.0; 95% CI, 15.8 to 20.3) to ERA (95% CI, 14.9 to 18.5). Likewise, in the D R group, survival improved significantly (p 0.01), with the IRD decreasing from ERA (95% CI, 15.6 to 17.5) to ERA (95% CI, 14.0 to 16.0). However, in the D R group, survival was not statistically different (p 0.32) with IRDs in ERA1, ERA2, and ERA3 of 13.3 (95% CI, 11.8 to 14.9), 12.8 (95% CI, 11.5 to 14.1), and 14.7 (95% CI, 13.0 to 16.6), respectively. Posttransplant Morbidity in the Current Era: Bronchiolitis Obliterans, Infection, and Rejection Severe infection FS was significantly different (p 0.032) across groups, with D R (with median time to event Fig 3. Kaplan Meier survival functions for posttransplant bronchiolitis obliterans, infection, and rejection free survival in the current era. (A) Bronchiolitis obliterans; (B) infection; (C) rejection. (D donor cytomegalovirus ; Dx donor cytomegalovirus or ; R recipient cytomegalovirus ; R recipient cytomegalovirus.)

5 Ann Thorac Surg RUSSO ET AL 2007;84: CMV MATCH STATUS IN LUNG TRANSPLANTATION Prophylaxis in the Current Era Between 2000 and 2004, GVP use varied by group D R (n 745, 91.3%), D R (n 1,936, 85.4%), and D R (n 289, 49.6%). In addition, univariate regression demonstrated a significant increase (p 0.001) in GVP use from 2000 (n 597; 79.4%) to 2004 (n 841; 84.5%). Compared with those not receiving GVP, use of GVP was associated with a significant improvement in 30-day (n 2,992, 96.9% versus n 740, 94.8%; p 0.005) and 90-day survival (n 2,739, 92.6% versus n 686, 90.1%; p 0.023), but there was no significant difference at later time points. Comment 1133 Given the critical scarcity of organs available for transplantation, achieving maximal benefit from this therapy is predicated on optimal use of the donor pool. To this end, the risks and benefits associated with matching characteristics of donors and recipients must be better understood. Although early experience suggested poor outcomes in cases of CMV recipient donor mismatch, significant advances in CMV prophylaxis have been widely reported. For example, Zamora and associates [11] reported no CMV infections, CMV-related disease, or CMV-related mortality among 60 lung transplant patients actively taking valganciclovir compared with 15%, 20%, and 1.4% incidence, respectively, in 140 patients taking acyclovir. Findings presented here demonstrate that in the current era of aggressive ganciclovir-based CMV prophylaxis, CMV mismatching is not associated with worse posttransplant survival (Fig 1). This change with time resulted from improvements in survival among the D R and D R groups, although survival in the D R group remained unchanged during the three eras (Fig 2). The lack of long-term data regarding CMV prophylaxis makes it impossible to attribute these findings solely to more effective CMV-prophylactic strategies. In fact, it is possible that other factors, including improved patient selection, advances in operative techniques, and other advances in posttransplant management, explain these observations. In multivariable Cox proportional hazards regression, D R and D R were associated with worse survival before 2000; however, in the current era there was no demonstrable relationship between these characteristics and survival while controlling for other factors. There was also a statistically significant interaction between CMV status and the era of transplantation in these analyses. Moreover, the observed improvement in survival was limited to D R and D R groups and coincided with the U.S. Food and Drug Administration s approval of valganciclovir in March 2001 as well as increased use of CMV prophylaxis. Therefore, it seems that more effective and aggressive CMV prophylaxis contributed to the observation that, in the current era, survival after lung transplant is equivalent regardless of CMV match status. Fig 4. Kaplan Meier survival functions for posttransplant bronchiolitis obliterans stratified by cytomegalovirus (CMV) match status and CMV prophylaxis. (A) Group I (D R ); (B) group II (Dx R ); (C) group III (D R ). (D donor CMV ; Dx donor CMV or ; R recipient CMV ; R recipient CMV.) Posttransplant Morbidity: Rejection, Infection, and Bronchiolitis Obliterans This study found no demonstrable relationship between CMV mismatch status and severe rejection FS or BO-FS. Likewise, BO-FS did not differ by CMV match status. However, BO-FS was improved in recipients in the D R and D R groups receiving GVP. Given previous studies demonstrating that CMV may be a risk factor

6 1134 RUSSO ET AL Ann Thorac Surg CMV MATCH STATUS IN LUNG TRANSPLANTATION 2007;84: for BO in lung transplantation patients, [4, 12, 13], this finding suggests that GVP may protect against the development of BO in cases with seropositive recipients or donors. However, in this study, D R had a significantly worse severe infection FS. The explanation for this is outside of the scope of this study, but it may result from increased risk of CMV-related infection owing to CMV mismatch status. Unfortunately, detailed information regarding type of infection was not available. Limitations Patient registries often suffer from variability in data entry. However, fields contained within this database were generally well populated with a 95% to 99% data entry rate for the majority of variables; moreover, both the percentage of recipients and donors with CMV by serology [14] and survival [15] was similar to data reported in other studies, supporting the validity of these findings. Although the UNOS reporting system provided definitions for such complications as BO and rejection in data guidelines, definitions may vary by center. Time-to-event analysis for BO-FS, severe rejection FS, and severe infection FS assumes that the event of interest is the only possible outcome. Therefore, if death occurred before this outcome, the patients were censored. As part of future studies we will perform analysis of competing outcomes to assess factors predicting long-term survival; this analysis was omitted here because it was outside the scope of this study. Conclusion and Implications In the current era, there is no demonstrable difference in survival after lung transplantation among CMVmismatched recipients compared with other serologic combinations. These findings suggest that in this era of aggressive CMV prophylaxis, CMV mismatch does not confer greater posttransplant morbidity or mortality. Although in previous eras survival was worse among the D R and D R groups, in the current era, CMV mismatch should not be sufficient grounds to decline a lung allograft offer. However, further studies are needed to further optimize CMV prophylaxis in lung transplant recipients. We thank UNOS for supplying these data and Katarina Anderson, PhD, for her assistance with our analysis. This work was supported in part by Health Resources and Services Administration contract The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. References 1. Limaye AP, Raghu G, Koelle DM, Ferrenberg J, Huang ML, Boeckh M. High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy. J Infect Dis 2002;185: Bonatti H, Tabarelli W, Ruttmann E, et al. Impact of cytomegalovirus match on survival after cardiac and lung transplantation. Am Surg 2004;70: Bando K, Paradis IL, Komatsu K, et al. Analysis of timedependent risks for infection, rejection, and death after pulmonary transplantation. J Thorac Cardiovasc Surg 1995;109: Smith MA, Sundaresan S, Mohanakumar T, et al. Effect of development of antibodies to HLA and cytomegalovirus mismatch on lung transplantation survival and development of bronchiolitis obliterans syndrome. J Thorac Cardiovasc Surg 1998;116: Ganesh JS, Rogers CA, Banner NR, Bonser RS, Steering Group of the UK Cardiothoracic Transplant Audit. Donor cause of death and mid-term survival in lung transplantation. J Heart Lung Transplant 2005;24: Heng D, Sharples LD, McNeil K, Stewart S, Wreghitt T, Wallwork J. Bronchiolitis obliterans syndrome: incidence, natural history, prognosis, and risk factors. J Heart Lung Transplant 1998;17: Tamm M, Aboyoun CL, Chhajed PN, Rainer S, Malouf MA, Glanville AR. Treated cytomegalovirus pneumonia is not associated with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2004;170: (Epub 2004 Aug 5). 8. Luckraz H, Sharples L, McNeil K, Wreghitt T, Wallwork J. Cytomegalovirus antibody status of donor/recipient does not influence the incidence of bronchiolitis obliterans syndrome in lung transplantation. J Heart Lung Transplant 2003;22: Gutierrez CA, Chaparro C, Krajden M, Winton T, Kesten S. Cytomegalovirus viremia in lung transplant recipients receiving ganciclovir and immune globulin. Chest 1998;113: Glanville AR, Valentine VG, Aboyoun CL. CMV mismatch is not a risk factor for survival or severe bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant 2004;23(2 Suppl):S43 (abstract). 11. Zamora MR, Nicolls MR, Hodges TN, et al. Following universal prophylaxis with intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and effective for prevention of CMV infection following lung transplantation. Am J Transplant 2004;4: Kroshus TJ, Kshettry VR, Savik K, John R, Hertz MI, Bolman RM 3rd. Risk factors for the development of bronchiolitis obliterans syndrome after lung transplantation. J Thorac Cardiovasc Surg 1997;114: Keenan RJ, Lega ME, Dummer JS, et al. Cytomegalovirus serologic status and postoperative infection correlated with risk of developing chronic rejection after pulmonary transplantation. Transplantation 1991;51: Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med 1998;338: Trulock EP, Edwards LB, Taylor DO, Boucek MM, Keck BM, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: Twenty-second Official Adult Lung and Heart-Lung Transplant Report J Heart Lung Transplant 2005;24: DISCUSSION DR SCOTT J. SWANSON (New York, New York): Excellent paper. One question that comes to mind is that the slope of those graphs doesn t really change. You have sort of improved the outcome early. So do you think treating CMV differently affects OB and long-term rejection or not? DR STERNBERG: Interesting question. To rephrase your question, does treating CMV affect BOS, there are more than a few reports that it probably does, and there is a putative molecular mechanism given as well, because infection may upregulate TNF-alpha and TNF-alpha may also be pivotal in BOS. So there

7 Ann Thorac Surg RUSSO ET AL 2007;84: CMV MATCH STATUS IN LUNG TRANSPLANTATION may be a molecular mechanism that may be involved as well. I think it probably does. DR SWANSON: I realize all that, but you would expect the slope of the graph to change, then, and it didn t comment on your strategy about CMV prophylaxis? When do you start it? Do you use a preemptive strategy or a purely prophylactic strategy? How often do you check the CMV viral loads, and do you manage the negative negative patients with any CMV prophylaxis in your medical center? DR STERNBERG: Later or earlier? DR SWANSON: At any point. DR STERNBERG: Possibly. DR MALCOLM M. DECAMP (Boston, Massachusetts): I enjoyed that very much. I hope you have closed the door on the controversy of CMV matching of donor and recipient. Can you DR STERNBERG: Thank you for the question. We use a prophylactic strategy. For Group 3, negative negative patients, they are treated with Valcyte for up to a year. For Groups 1 and 2 patients, they get IV ganciclovir bid for 2 weeks, and then they get IV ganciclovir q-daily up until 3 months, and then they get switched to the valganciclovir up until a year, if they tolerate it. If there is a higher risk transplant, we also give CMV immunoglobulin pretransplant. They do get screened for a quantitative PCR, and I believe it s every week or two. Notice From the American Board of Thoracic Surgery The 2007 Part I (written) examination will be held on Monday, December 3, It is planned that the examination will be given at multiple sites throughout the United States using an electronic format. The closing date for registration was August 1, Those wishing to be considered for examination must apply online at To be admissible to the Part II (oral) examination, a candidate must have successfully completed the Part I (written) examination. A candidate applying for admission to the certifying examination must fulfill all the requirements of the Board in force at the time the application is received. Please address all communications to the American Board of Thoracic Surgery, 6333 N St. Clair St, Suite 2320, Chicago, IL 60611; telephone: (312) ; fax: (312) ; info@abts.org by The Society of Thoracic Surgeons Ann Thorac Surg 2007;84: /07/$32.00 Published by Elsevier Inc