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Survey of current practice related to grading of rejection in cardiac transplant recipients in North America
Cardiovascular Pathology 20 (2011) 261 – 265
Original Article
Survey of current practice related to grading of rejection in cardiac transplant recipients in North America Joseph J. Maleszewski a , Lauren M. Kucirka b , Dorry L. Segev b,c , Marc K. Halushka d,⁎ a Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA Department of Surgery, Division of Transplant Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA c Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD, USA d Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
b
Received 7 May 2010; received in revised form 7 June 2010; accepted 15 July 2010
Abstract Background: The acceptance and implementation of the International Society for Heart and Lung Transplantation's most recently adopted grading system (ISHLT-2004), which supplanted the ISHLT-1990 system for diagnosing cardiac allograft rejection, are unknown. Methods: We performed an online survey of pathologists at cardiac transplant centers in the United States and Canada to determine how cardiac transplant rejection is reported. The survey consisted of a series of questions related to biopsy volume, the rejection grading system used, and reasons why that grading system was used. Results: Survey responses were obtained from 96 of 122 centers in the United States and Canada. Eighty-seven percent of respondents reported adopting the ISHLT-2004 grading system, either exclusively or in combination with other grading systems. Overall, 45% of respondents use only the ISHLT-2004 grading system, 40% issue reports containing both the ISHLT-2004 and the ISHLT-1990 grading systems, 12% use only the ISHLT-1990 system, and 3% use either the ISHLT-2004 or the ISHLT-1990 system in combination with an older scoring system. The primary reasons for not using the ISHLT-2004 grading system exclusively were (1) the perceived preference of cardiologists and cardiac surgeons at that particular center (77%) and (2) a belief that the ISHLT-2004 grading system is not as informative as the ISHLT-1990 grading system (62%). Conclusions: There is appreciable variability in the system(s) used for reporting rejection among North American cardiac transplant centers. Understanding the reasons behind this variability will be crucial for the optimization of future grading systems for cardiac allograft rejection. © 2011 Elsevier Inc. All rights reserved. Keywords: Humoral rejection; Cardiac transplantation; Pathology; Cardiac rejection; Survey
1. Introduction For nearly 40 years, endomyocardial biopsy has been the gold standard for the surveillance of cardiac transplant rejection. Over that same time period, grading schemes to evaluate the histopathology of cardiac rejection have undergone several transformations. In the early years, regional and institutional grading systems were used, but the lack of international uniformity in grading delayed advancements in treatment and comparisons between institutions [1]. There were no sources of support for this research. The authors have no disclosures to make regarding this project. ⁎ Corresponding author. 720 Rutland Avenue, Ross Building, Rm 632L, Baltimore, MD 21205, USA. Tel.: +1 410 614 8138; fax: +1 410 502 5862. E-mail address: [email protected] (M.K. Halushka). 1054-8807/10/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2010.07.003
In 1990, the International Society for Heart and Lung Transplantation (ISHLT), published the first consensus statement on the grading of rejection in cardiac allografts [2]. This system proved enormously popular and became the standard for all clinical trials [3]. In 2004, changes were made that streamlined the ISHLT-1990 criteria, reducing the scale from seven grades to four. Most controversial was the decision to include former focal moderate (Grade 2) rejection with former mild (1A and 1B) rejection as a single mild rejection grade, designated as 1R. The ISHLT-2004 grading system for cardiac allograft rejection has now been in place for 6 years [4], with little analysis of its use and implementation. Only one study has evaluated ISHLT-2004 and found no improvements in reproducibility of diagnoses by the ISHLT-2004 system vs. the ISHLT-1990 version [5].
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J.J. Maleszewski et al. / Cardiovascular Pathology 20 (2011) 261–265
Moreover, anecdotal evidence suggests that there is considerable variability between institutions in the implementation of ISHLT-2004. It appears that some pathologists, reluctant to stop using the popular ISHLT-1990 system, have developed hybrid reporting incorporating both ISHLT-2004 and ISHLT-1990. With the above considerations in mind, the current study has been performed to determine the prevalence of ISHLT-2004 usage by practicing pathologists at cardiac transplant centers in the United States and Canada. We hypothesized that ISHLT-2004 had not fully replaced ISHLT-1990, although the reasons for this were unknown. 2. Methods 2.1. Scope of survey Between April 16 and May 20, 2009, we performed a survey of heart transplant pathologists' use of and attitudes toward the ISHLT-2004 grading system of cell-mediated rejection and their practice regarding antibody-mediated rejection (reported elsewhere) [6]. The target population included one pathologist who currently signed out endomyocardial specimens from each of the busiest 113 adult and pediatric cardiac transplant centers in the United States (based on UNOS data) and nine in Canada. 2.2. Survey dissemination We collected e-mail addresses of pathologists from a variety of public sources including transplant center websites, professional society websites, and PubMed, as previously described in detail [6]. 2.3. Survey creation and administration Survey questions were written by two experienced heart transplant pathologists with knowledge of practices at multiple institutions (JJM and MKH). The survey was reviewed and piloted by cardiovascular pathology colleagues as described [6]. Surveys were administered electronically using SurveyMonkey (http://www.SurveyMonkey.com). Those who did not wish to complete the survey online were given the option to complete it over the phone with answers submitted to SurveyMonkey by one of the study authors (MKH). 2.4. Survey content
2.4.2. Center volume Approximately how many biopsies are signed out on a weekly basis by all pathologists in your practice? (a) (b) (c) (d) (e)
b1 (b50/year) 1–5 (50–250/year) 6–10 (300–500/year) 11–20 (500–1000/year) N20 (1000+/year)
2.4.3. Scoring system Please indicate which scoring systems you report (select all that apply): (a) (b) (c) (d) (e)
ISHLT 2004 revised grading system (0, 1R, 2R, 3R) ISHLT 1990 grading system (0, 1A, 1B, 2, 3A, 3B, 4) Billingham grading system Texas Heart Institute grading system Other
2.4.4. Respondents who indicated exclusive use of ISHLT-2004 Participants who indicated they exclusively used ISHLT2004 were asked to rate their level of satisfaction with this system on a scale of 1 (very dissatisfied) to 5 (very satisfied). 2.4.5. Respondents who indicated nonexclusive use of ISHLT-2004 Participants were asked to rank each of the following reasons (a–d) for not exclusively using ISHLT-2004 as either (1) a very important reason; (2) a somewhat important reason; (3) a reason, but not particularly important; or (4) not a reason. (a) I was unaware there was a 2004 revision of the ISHLT scoring system (b) I am comfortable with a previous grading system (c) The cardiologists/cardiovascular surgeons prefer an older scoring system to the 2004 revised ISHLT scoring system (d) I believe information is lost in the 2004 revised ISHLT scoring system 2.4.6. Decision making For each scoring system use, respondents were asked to indicate whether the decision to use the system was: (a) Based on a decision by the pathology group (b) Based on a decision by the supported cardiologists (c) Based on a decision by the supported cardiac surgeons
Participants were asked to respond to the following questions.
2.5. Statistical methods
2.4.1. Eligibility Do you sign out endomyocardial biopsy specimens from cardiac transplant recipients? (Yes/No).
Comparisons between exclusive and nonexclusive users of ISHLT-2004 were made using two-sided chi-squared tests (categorical and binary variables) and two-sided t tests
J.J. Maleszewski et al. / Cardiovascular Pathology 20 (2011) 261–265
263
(continuous variables). Univariate logistic regression was used to examine the associations between exclusive usage of ISHLT-2004 and whether the choice of diagnostic scheme was made by the pathology group or by cardiologists or cardiac surgeons. All analyses were performed using STATA 10/MP (College Station, TX, USA). 3. Results 3.1. Characteristics of survey respondents The group of respondents included 94 pathologists, representing 96 (77%) of 122 centers and 82% of the cardiac transplant volume in the United States and Canada. Ninetyone percent of respondents reported weekly volumes of 1–20 transplant biopsy cases per week, while 9% reported N20 transplant biopsies per week. Respondents represented a diverse range of experience, transplant biopsy volume levels, and types of pathology practices [6]. Fifty percent of respondents had been in practice 16 or more years. The majority of respondents (75%) reported regularly attending pathology-related conferences. Most (74%) reported rarely or never publishing articles related to cardiovascular pathology. 3.2. Use of the ISHLT-2004 grading systems Forty-five percent of respondents reported exclusive use of ISHLT-2004 for grading cell-mediated rejection in their cardiac transplant biopsy cases. Forty percent reported using ISHLT-2004 in conjunction with ISHLT-1990. Thirteen percent of centers report not using ISHLT-2004 under any circumstances (Fig. 1). 3.3. ISHLT-2004 satisfaction and reasons for use There was considerable variation in satisfaction among those who exclusively used ISHLT-2004: 66% somewhat or very satisfied, 18% neutral, and 16% somewhat or very dissatisfied (Fig. 2). Among those who did not exclusively use the ISHLT-2004 grading system, the most common
Fig. 1. Percent of respondents who reported using each grading system or combination of grading systems in their practice.
Fig. 2. Reported satisfaction with exclusive use of ISHLT 2004.
reason reported was that their cardiologists and/or cardiac surgeons preferred a different system (Fig. 3). The second most frequently cited reason was a belief that important information is lost in ISHLT-2004. A smaller percentage (32%) of respondents indicated their comfort with a prior system as a reason not to exclusively use ISHLT-2004. Only one respondent was unaware of the existence of the ISHLT2004 system. 3.4. Correlation of ISHLT-2004 use and practice variables There was little difference in years in practice, weekly biopsy volume, publication rates, or frequency of pathology meeting attendance between exclusive and nonexclusive users of ISHLT-2004 (Table 1). When we examined associations between decision making and exclusive use of ISHLT-2004, we found that centers that based their choice of grading system on a decision by the pathologists (as opposed to cardiologists or cardiac surgeons) had a 3.64-fold higher odds of exclusively using ISHLT-2004 (95% CI 1.47–8.99, P=.005; Table 2). 4. Discussion Six years have elapsed since the revised 2004 International Society for Heart and Lung Transplantation Working Formulation of Cardiac Allograft Pathology (ISHLT-2004) was published [4]. Its adoption by practicing pathologists had not been determined. Our findings indicate that 55% of centers have not completely converted to exclusive use of ISHLT-2004. The reasons for this appear to be a combination of cardiologists/surgeon preference and a sentiment that grading systems other than ISHLT-2004 provide additional important information. Our survey suggests, from the perspective of pathologists, that cardiologists and/or cardiac surgeons are the most resistant to full implementation of ISHLT-2004. As we did not survey cardiologists or cardiac surgeons, we cannot determine what their concerns with ISHLT-2004 might be, or if this is just a perception of the pathologists surveyed. Considering the overall similarity of ISHLT-
264
J.J. Maleszewski et al. / Cardiovascular Pathology 20 (2011) 261–265 Table 2 Decision making regarding exclusive or nonexclusive use of the ISHLT 2004 grading system, univariate logistic regression models
Fig. 3. Reasons for not exclusively using the ISHLT-2004 grading system.
1990 and ISHLT-2004, the major distinction of the two schemes is the removal of the reporting of old focal, moderate rejection (ISHLT-1990 Grade 2). We can only speculate that Grade 2 rejection may have led to change in treatment at some institutions. Sixty-two percent of respondents suggested that lost information in ISHLT-2004 was a reason in not adopting Table 1 Comparison of those who exclusively use the ISHLT 2004 grading system (right column) and those who do not (left column) Not exclusive ISHLT 2004 (n=49, 54.4%)
Exclusive ISHLT 2004 (n=41, 45.6%)
Years in practice b5 14.3 9.8 6–10 18.3 22.0 11–15 14.3 22.0 16–20 18.4 14.6 N20 34.7 31.7 Weekly biopsy volume b1 2.0 0.0 1–5 26.0 39.0 6–10 28.0 31.7 11–20 32.0 24.4 N20 12.0 4.9 Publish cardiovascular-pathology related papers Never 38.8 24.4 Rarely 32.7 51.2 Frequently 28.6 24.4 Attend national cardiovascular pathology meetings Almost never 4.1 7.3 Occasionally 20.4 19.5 Frequently 75.5 73.2
P value .8
.4
.2
.8
Grading scheme decision making
Odds of exclusive ISHLT-2004 use
P value
Based on a decision by pathologists in your group Based on a decision by supported cardiologists Based on a decision by supported cardiac surgeons
3.64 (1.47–8.99)
.005
1.28 (0.55–2.96)
.6
1.85 (0.54–6.35)
.3
this grading scheme exclusively. Again, we believe the merger of focal moderate (ISHLT-1990 Grade 2) and mild rejection (ISHLT-1990 Grade 1A and 1B) into a single category (Grade 1R) may be at the root of this concern. It has been suggested that Grade 2 lesions do not exist but actually represent Quilty lesions [3,7]. This interpretation is not universally accepted. For example, ISHLT-1990 Grade 2 is rarely reported in our institutions, but when it is, it represents a clinically actionable event, generally precipitating closer follow-up of the patient and an earlier return to biopsy. Other centers increase immunosuppression with a Grade 2 diagnosis [8,9]. Such information could not be conveyed within the ISHLT-2004 guidelines. This may have been a goal of the ISHLT-2004 taskforce as some clinicians felt that focal moderate (ISHLT-1990 Grade 2) diagnoses were being improperly overtreated [10]. Will a lack of complete implementation of ISHLT2004 affect patient care or the ability of centers to coordinate multi-institutional trials? No. Wisely, ISHLT2004 merged, but did not split or replace, the ISHLT1990 criteria. Therefore, the 13% of groups that continue to use ISHLT-1990 exclusively can easily translate those values into the revised ISHLT-2004 grades for continuity of reporting. Whenever a new scoring system is introduced, its rate of adoption may change significantly over time. Clearly, well-crafted, easy-to-use scoring schemes that provide the best patient care will attain the most rapid and highest rate of implementation. We have found that after 6 years, 55% of centers have not fully and exclusively implemented ISHLT-2004. It is unknown how well ISHLT-2004 has been adopted relative to other scoring systems such as the ISHLT-1990 system or the ISHLT lung rejection working formulations of 1996 and 2007 as no survey of this type had been performed on those systems. We believe that 6 years after the publication of ISHLT-2004 institutions that do not use this system exclusively are unlikely to fully convert. Rather, our data indicate that this scoring system will not be fully implemented due to the concerns listed above. We hope our survey will inform the people who generate these scoring systems about their success and may indicate areas to revisit in future iterations of the grading system.
J.J. Maleszewski et al. / Cardiovascular Pathology 20 (2011) 261–265
Acknowledgments The authors thank Dr. John Veinot for his assistance in identifying Canadian transplant centres. The authors thank Drs. Dylan Miller, Carmela Tan, Chi Lai, and Charles Steenbergen for their critical assessment of our survey questions and all 94 survey participants.
References [1] McAllister HA. Histologic grading of cardiac allograft rejection: a quantitative approach. J Heart Transplant 1990;9(3):277–82. [2] Billingham ME, Cary NR, Hammond ME, Kemnitz J, Marboe C, McCallister, et al. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Heart Rejection Study Group. The International Society for Heart Transplantation. J Heart Transplant 1990;9 (6):587–93. [3] Billingham M, Kobashigawa JA. The revised ISHLT heart biopsy grading scale. J Heart Lung Transplant 2005;24(11):1709. [4] Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, et al. Revision of the 1990 working formulation for the
[5]
[6]
[7]
[8]
[9]
[10]
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standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant 2005;24(11):1710–20. Yang HM, Lai CK, Gjertson DW, Baruch-Oren T, Ra SH, Watts W, et al. Has the 2004 revision of the International Society of Heart and Lung Transplantation grading system improved the reproducibility of the diagnosis and grading of cardiac transplant rejection? Cardiovasc Pathol 2009;18(4):198–204. Kucirka LM, Maleszewski JJ, Segev DL, Halushka MK. Survey of North American pathologist practices regarding antibody-mediated rejection in cardiac transplant biopsies. Cardiovasc Pathol 2010, doi:10.1016/j.carpath.2010.03.008. Fishbein MC, Bell G, Lones MA, Czer LS, Miller JM, Harasty D, Trento A. Grade 2 cellular heart rejection: does it exist? J Heart Lung Transplant 1994;13(6):1051–7. Felkel TO, Smith AL, Reichenspurner HC, LaFleur B, Lutz JF, Kanter KR, et al. Survival and incidence of acute rejection in heart transplant recipients undergoing successful withdrawal from steroid therapy. J Heart Lung Transplant 2002;21(5):530–9. Beniaminovitz A, Itescu S, Lietz K, Donovan M, Burke EM, Groff BD, et al. Prevention of rejection in cardiac transplantation by blockade of the interleukin-2 receptor with a monoclonal antibody. N Engl J Med 2000;342(9):613–9. Doty JR, Walinsky PL, Salazar JD, Alejo DE, Greene PS, Baumgartner WA. Conservative management of late rejection after heart transplantation: a 10-year analysis. Ann Surg 1998;228(3):395–401.
Original Article
Survey of current practice related to grading of rejection in cardiac transplant recipients in North America Joseph J. Maleszewski a , Lauren M. Kucirka b , Dorry L. Segev b,c , Marc K. Halushka d,⁎ a Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA Department of Surgery, Division of Transplant Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA c Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD, USA d Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
b
Received 7 May 2010; received in revised form 7 June 2010; accepted 15 July 2010
Abstract Background: The acceptance and implementation of the International Society for Heart and Lung Transplantation's most recently adopted grading system (ISHLT-2004), which supplanted the ISHLT-1990 system for diagnosing cardiac allograft rejection, are unknown. Methods: We performed an online survey of pathologists at cardiac transplant centers in the United States and Canada to determine how cardiac transplant rejection is reported. The survey consisted of a series of questions related to biopsy volume, the rejection grading system used, and reasons why that grading system was used. Results: Survey responses were obtained from 96 of 122 centers in the United States and Canada. Eighty-seven percent of respondents reported adopting the ISHLT-2004 grading system, either exclusively or in combination with other grading systems. Overall, 45% of respondents use only the ISHLT-2004 grading system, 40% issue reports containing both the ISHLT-2004 and the ISHLT-1990 grading systems, 12% use only the ISHLT-1990 system, and 3% use either the ISHLT-2004 or the ISHLT-1990 system in combination with an older scoring system. The primary reasons for not using the ISHLT-2004 grading system exclusively were (1) the perceived preference of cardiologists and cardiac surgeons at that particular center (77%) and (2) a belief that the ISHLT-2004 grading system is not as informative as the ISHLT-1990 grading system (62%). Conclusions: There is appreciable variability in the system(s) used for reporting rejection among North American cardiac transplant centers. Understanding the reasons behind this variability will be crucial for the optimization of future grading systems for cardiac allograft rejection. © 2011 Elsevier Inc. All rights reserved. Keywords: Humoral rejection; Cardiac transplantation; Pathology; Cardiac rejection; Survey
1. Introduction For nearly 40 years, endomyocardial biopsy has been the gold standard for the surveillance of cardiac transplant rejection. Over that same time period, grading schemes to evaluate the histopathology of cardiac rejection have undergone several transformations. In the early years, regional and institutional grading systems were used, but the lack of international uniformity in grading delayed advancements in treatment and comparisons between institutions [1]. There were no sources of support for this research. The authors have no disclosures to make regarding this project. ⁎ Corresponding author. 720 Rutland Avenue, Ross Building, Rm 632L, Baltimore, MD 21205, USA. Tel.: +1 410 614 8138; fax: +1 410 502 5862. E-mail address: [email protected] (M.K. Halushka). 1054-8807/10/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2010.07.003
In 1990, the International Society for Heart and Lung Transplantation (ISHLT), published the first consensus statement on the grading of rejection in cardiac allografts [2]. This system proved enormously popular and became the standard for all clinical trials [3]. In 2004, changes were made that streamlined the ISHLT-1990 criteria, reducing the scale from seven grades to four. Most controversial was the decision to include former focal moderate (Grade 2) rejection with former mild (1A and 1B) rejection as a single mild rejection grade, designated as 1R. The ISHLT-2004 grading system for cardiac allograft rejection has now been in place for 6 years [4], with little analysis of its use and implementation. Only one study has evaluated ISHLT-2004 and found no improvements in reproducibility of diagnoses by the ISHLT-2004 system vs. the ISHLT-1990 version [5].
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J.J. Maleszewski et al. / Cardiovascular Pathology 20 (2011) 261–265
Moreover, anecdotal evidence suggests that there is considerable variability between institutions in the implementation of ISHLT-2004. It appears that some pathologists, reluctant to stop using the popular ISHLT-1990 system, have developed hybrid reporting incorporating both ISHLT-2004 and ISHLT-1990. With the above considerations in mind, the current study has been performed to determine the prevalence of ISHLT-2004 usage by practicing pathologists at cardiac transplant centers in the United States and Canada. We hypothesized that ISHLT-2004 had not fully replaced ISHLT-1990, although the reasons for this were unknown. 2. Methods 2.1. Scope of survey Between April 16 and May 20, 2009, we performed a survey of heart transplant pathologists' use of and attitudes toward the ISHLT-2004 grading system of cell-mediated rejection and their practice regarding antibody-mediated rejection (reported elsewhere) [6]. The target population included one pathologist who currently signed out endomyocardial specimens from each of the busiest 113 adult and pediatric cardiac transplant centers in the United States (based on UNOS data) and nine in Canada. 2.2. Survey dissemination We collected e-mail addresses of pathologists from a variety of public sources including transplant center websites, professional society websites, and PubMed, as previously described in detail [6]. 2.3. Survey creation and administration Survey questions were written by two experienced heart transplant pathologists with knowledge of practices at multiple institutions (JJM and MKH). The survey was reviewed and piloted by cardiovascular pathology colleagues as described [6]. Surveys were administered electronically using SurveyMonkey (http://www.SurveyMonkey.com). Those who did not wish to complete the survey online were given the option to complete it over the phone with answers submitted to SurveyMonkey by one of the study authors (MKH). 2.4. Survey content
2.4.2. Center volume Approximately how many biopsies are signed out on a weekly basis by all pathologists in your practice? (a) (b) (c) (d) (e)
b1 (b50/year) 1–5 (50–250/year) 6–10 (300–500/year) 11–20 (500–1000/year) N20 (1000+/year)
2.4.3. Scoring system Please indicate which scoring systems you report (select all that apply): (a) (b) (c) (d) (e)
ISHLT 2004 revised grading system (0, 1R, 2R, 3R) ISHLT 1990 grading system (0, 1A, 1B, 2, 3A, 3B, 4) Billingham grading system Texas Heart Institute grading system Other
2.4.4. Respondents who indicated exclusive use of ISHLT-2004 Participants who indicated they exclusively used ISHLT2004 were asked to rate their level of satisfaction with this system on a scale of 1 (very dissatisfied) to 5 (very satisfied). 2.4.5. Respondents who indicated nonexclusive use of ISHLT-2004 Participants were asked to rank each of the following reasons (a–d) for not exclusively using ISHLT-2004 as either (1) a very important reason; (2) a somewhat important reason; (3) a reason, but not particularly important; or (4) not a reason. (a) I was unaware there was a 2004 revision of the ISHLT scoring system (b) I am comfortable with a previous grading system (c) The cardiologists/cardiovascular surgeons prefer an older scoring system to the 2004 revised ISHLT scoring system (d) I believe information is lost in the 2004 revised ISHLT scoring system 2.4.6. Decision making For each scoring system use, respondents were asked to indicate whether the decision to use the system was: (a) Based on a decision by the pathology group (b) Based on a decision by the supported cardiologists (c) Based on a decision by the supported cardiac surgeons
Participants were asked to respond to the following questions.
2.5. Statistical methods
2.4.1. Eligibility Do you sign out endomyocardial biopsy specimens from cardiac transplant recipients? (Yes/No).
Comparisons between exclusive and nonexclusive users of ISHLT-2004 were made using two-sided chi-squared tests (categorical and binary variables) and two-sided t tests
J.J. Maleszewski et al. / Cardiovascular Pathology 20 (2011) 261–265
263
(continuous variables). Univariate logistic regression was used to examine the associations between exclusive usage of ISHLT-2004 and whether the choice of diagnostic scheme was made by the pathology group or by cardiologists or cardiac surgeons. All analyses were performed using STATA 10/MP (College Station, TX, USA). 3. Results 3.1. Characteristics of survey respondents The group of respondents included 94 pathologists, representing 96 (77%) of 122 centers and 82% of the cardiac transplant volume in the United States and Canada. Ninetyone percent of respondents reported weekly volumes of 1–20 transplant biopsy cases per week, while 9% reported N20 transplant biopsies per week. Respondents represented a diverse range of experience, transplant biopsy volume levels, and types of pathology practices [6]. Fifty percent of respondents had been in practice 16 or more years. The majority of respondents (75%) reported regularly attending pathology-related conferences. Most (74%) reported rarely or never publishing articles related to cardiovascular pathology. 3.2. Use of the ISHLT-2004 grading systems Forty-five percent of respondents reported exclusive use of ISHLT-2004 for grading cell-mediated rejection in their cardiac transplant biopsy cases. Forty percent reported using ISHLT-2004 in conjunction with ISHLT-1990. Thirteen percent of centers report not using ISHLT-2004 under any circumstances (Fig. 1). 3.3. ISHLT-2004 satisfaction and reasons for use There was considerable variation in satisfaction among those who exclusively used ISHLT-2004: 66% somewhat or very satisfied, 18% neutral, and 16% somewhat or very dissatisfied (Fig. 2). Among those who did not exclusively use the ISHLT-2004 grading system, the most common
Fig. 1. Percent of respondents who reported using each grading system or combination of grading systems in their practice.
Fig. 2. Reported satisfaction with exclusive use of ISHLT 2004.
reason reported was that their cardiologists and/or cardiac surgeons preferred a different system (Fig. 3). The second most frequently cited reason was a belief that important information is lost in ISHLT-2004. A smaller percentage (32%) of respondents indicated their comfort with a prior system as a reason not to exclusively use ISHLT-2004. Only one respondent was unaware of the existence of the ISHLT2004 system. 3.4. Correlation of ISHLT-2004 use and practice variables There was little difference in years in practice, weekly biopsy volume, publication rates, or frequency of pathology meeting attendance between exclusive and nonexclusive users of ISHLT-2004 (Table 1). When we examined associations between decision making and exclusive use of ISHLT-2004, we found that centers that based their choice of grading system on a decision by the pathologists (as opposed to cardiologists or cardiac surgeons) had a 3.64-fold higher odds of exclusively using ISHLT-2004 (95% CI 1.47–8.99, P=.005; Table 2). 4. Discussion Six years have elapsed since the revised 2004 International Society for Heart and Lung Transplantation Working Formulation of Cardiac Allograft Pathology (ISHLT-2004) was published [4]. Its adoption by practicing pathologists had not been determined. Our findings indicate that 55% of centers have not completely converted to exclusive use of ISHLT-2004. The reasons for this appear to be a combination of cardiologists/surgeon preference and a sentiment that grading systems other than ISHLT-2004 provide additional important information. Our survey suggests, from the perspective of pathologists, that cardiologists and/or cardiac surgeons are the most resistant to full implementation of ISHLT-2004. As we did not survey cardiologists or cardiac surgeons, we cannot determine what their concerns with ISHLT-2004 might be, or if this is just a perception of the pathologists surveyed. Considering the overall similarity of ISHLT-
264
J.J. Maleszewski et al. / Cardiovascular Pathology 20 (2011) 261–265 Table 2 Decision making regarding exclusive or nonexclusive use of the ISHLT 2004 grading system, univariate logistic regression models
Fig. 3. Reasons for not exclusively using the ISHLT-2004 grading system.
1990 and ISHLT-2004, the major distinction of the two schemes is the removal of the reporting of old focal, moderate rejection (ISHLT-1990 Grade 2). We can only speculate that Grade 2 rejection may have led to change in treatment at some institutions. Sixty-two percent of respondents suggested that lost information in ISHLT-2004 was a reason in not adopting Table 1 Comparison of those who exclusively use the ISHLT 2004 grading system (right column) and those who do not (left column) Not exclusive ISHLT 2004 (n=49, 54.4%)
Exclusive ISHLT 2004 (n=41, 45.6%)
Years in practice b5 14.3 9.8 6–10 18.3 22.0 11–15 14.3 22.0 16–20 18.4 14.6 N20 34.7 31.7 Weekly biopsy volume b1 2.0 0.0 1–5 26.0 39.0 6–10 28.0 31.7 11–20 32.0 24.4 N20 12.0 4.9 Publish cardiovascular-pathology related papers Never 38.8 24.4 Rarely 32.7 51.2 Frequently 28.6 24.4 Attend national cardiovascular pathology meetings Almost never 4.1 7.3 Occasionally 20.4 19.5 Frequently 75.5 73.2
P value .8
.4
.2
.8
Grading scheme decision making
Odds of exclusive ISHLT-2004 use
P value
Based on a decision by pathologists in your group Based on a decision by supported cardiologists Based on a decision by supported cardiac surgeons
3.64 (1.47–8.99)
.005
1.28 (0.55–2.96)
.6
1.85 (0.54–6.35)
.3
this grading scheme exclusively. Again, we believe the merger of focal moderate (ISHLT-1990 Grade 2) and mild rejection (ISHLT-1990 Grade 1A and 1B) into a single category (Grade 1R) may be at the root of this concern. It has been suggested that Grade 2 lesions do not exist but actually represent Quilty lesions [3,7]. This interpretation is not universally accepted. For example, ISHLT-1990 Grade 2 is rarely reported in our institutions, but when it is, it represents a clinically actionable event, generally precipitating closer follow-up of the patient and an earlier return to biopsy. Other centers increase immunosuppression with a Grade 2 diagnosis [8,9]. Such information could not be conveyed within the ISHLT-2004 guidelines. This may have been a goal of the ISHLT-2004 taskforce as some clinicians felt that focal moderate (ISHLT-1990 Grade 2) diagnoses were being improperly overtreated [10]. Will a lack of complete implementation of ISHLT2004 affect patient care or the ability of centers to coordinate multi-institutional trials? No. Wisely, ISHLT2004 merged, but did not split or replace, the ISHLT1990 criteria. Therefore, the 13% of groups that continue to use ISHLT-1990 exclusively can easily translate those values into the revised ISHLT-2004 grades for continuity of reporting. Whenever a new scoring system is introduced, its rate of adoption may change significantly over time. Clearly, well-crafted, easy-to-use scoring schemes that provide the best patient care will attain the most rapid and highest rate of implementation. We have found that after 6 years, 55% of centers have not fully and exclusively implemented ISHLT-2004. It is unknown how well ISHLT-2004 has been adopted relative to other scoring systems such as the ISHLT-1990 system or the ISHLT lung rejection working formulations of 1996 and 2007 as no survey of this type had been performed on those systems. We believe that 6 years after the publication of ISHLT-2004 institutions that do not use this system exclusively are unlikely to fully convert. Rather, our data indicate that this scoring system will not be fully implemented due to the concerns listed above. We hope our survey will inform the people who generate these scoring systems about their success and may indicate areas to revisit in future iterations of the grading system.
J.J. Maleszewski et al. / Cardiovascular Pathology 20 (2011) 261–265
Acknowledgments The authors thank Dr. John Veinot for his assistance in identifying Canadian transplant centres. The authors thank Drs. Dylan Miller, Carmela Tan, Chi Lai, and Charles Steenbergen for their critical assessment of our survey questions and all 94 survey participants.
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