The Journal of Heart and Lung Transplantation
Volume 29, Issue 8 , Pages 847-852, August 2010

Temporal trends in heart transplantation from high-risk donors: Are there lessons to be learned? A multi-institutional analysis

  • Jose N. Nativi, MD

      Affiliations

    • Department of Cardiology, University of Utah Health Science Center, U.T.A.H. Cardiac Transplant Program, and VA Salt Lake City HCS, Utah
    • ,
  • Robert N. Brown, BS

      Affiliations

    • Department of Cardiovascular Surgery, University of Alabama at Birmingham, Birmingham, Alabama
    • ,
  • David O. Taylor, MD

      Affiliations

    • Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
    • ,
  • Abdallah G. Kfoury, MD

      Affiliations

    • Department of Cardiology, Intermountain Medical Center, U.T.A.H. Cardiac Transplant Program, Salt Lake City, Utah
    • ,
  • James K. Kirklin, MD

      Affiliations

    • Department of Cardiovascular Surgery, University of Alabama at Birmingham, Birmingham, Alabama
    • ,
  • Josef Stehlik, MD, MPH

      Affiliations

    • Department of Cardiology, University of Utah Health Science Center, U.T.A.H. Cardiac Transplant Program, and VA Salt Lake City HCS, Utah
    • Corresponding Author InformationReprint requests: Josef Stehlik, MD, University of Utah Health Sciences Center, 50 N Medical Dr, 4A100 SOM, Salt Lake City, UT 84132. Telephone: 801-582-1565 (x4543). Fax: 801-584-2532
    • ,
  • Cardiac Transplant Research Database Group

published online 21 May 2010.

Article Outline

Background

In 2003 the Department of Health and Human Services sponsored the Organ Donation Breakthrough Collaborative (ODBC) with the aim to increase organ donation. After the ODBC, increases in the number of all solid organs transplanted, except for heart, were seen. The aim of this study was to determine if ODBC resulted in temporal changes in the use of hearts from high-risk donors.

Methods

We analyzed data from the Cardiac Transplant Research Database in three eras: 1990–1995, 1996–2002, and 2003–2007. We explored temporal changes in high-risk donor characteristics: age, gender, hypertension, diabetes mellitus, abnormal echocardiogram, and ischemic time.

Results

Between 1990 and 2007, 7,220 patients underwent transplantation in 26 centers. Donors in the first era were least likely to have high-risk characteristics of higher age (mean, 30 years), female gender (30%), hypertension (8%), diabetes mellitus (1%), structural abnormalities on echocardiogram (7%), and prolonged graft ischemic time (mean, 163 minutes). In the second era, there was a significant increase in the use of donors with the above mentioned high-risk characteristics—32 years, 33%, 10%, 3%, 8% and 181 minutes, respectively. In the third post-ODBC era, no further increase was seen in high-risk donors, but rather a trend for avoidance of risk—32 years, 28%, 10%, 2%, 5% and 186 minutes, respectively.

Conclusion

Significant temporal changes in the characteristics of heart donors have occurred in the past 17 years. Recent temporal changes, however, cannot be directly attributed to the ODBC efforts.

Keywords: heart transplantation, organ donation, high-risk characteristics, donor selection

 

The shortage of donor organs has long remained a major problem in organ transplantation. In 2007, 97,248 individuals in need of organ transplantation were registered on the United Network for Organ Sharing (UNOS) waiting lists, but only 27,578 organs were transplanted that year.1 Different approaches have been used over the years in an attempt to increase the number of organs transplanted. These efforts have focused on increasing the number of donors and donor families consenting to donation, as well as on increasing the number of organs transplanted from consenting donors.

In 2003 the Department of Health and Human Services sponsored the Organ Donation Breakthrough Collaborative (ODBC), a national forum of practitioners in organ transplantation.2 The main goal of this effort was to increase the number of organs transplanted per donor through sharing and implementing best practices from high-performing organ procurement organizations and hospitals. A total of 131 of the 200 large hospitals and 50 of the 60 organ procurement organizations in United States participated in the ODBC. The ODBC encouraged aggressive pursuit of every donation opportunity with strategies that included early deployment of the organ procurement organization staff, family reapproaches for consent, expert donor management, and more aggressive efforts for organ placement.2

The goal of the ODBC was to increase the number of eligible death events resulting in organ transplantation (conversion rate) to 75% and to increase the number of organs transplanted per donor, including those transplanted from higher-risk donors.2 As a result, the conversion rate increased from 50% in 2003 to 69% in 2007, and the organ availability between 2003 and 2007 increased in 47 of 58 donation service areas.3

After the implementation of the 2003 ODBC approaches, an increase in the total number of organs transplanted in the United States was seen for several consecutive years. This was a result of an increase in all donor categories: deceased standard criteria donor, deceased extended criteria donor, and in donation after cardiac death, with the latter two seeing bigger increases than the group of deceased standard criteria donors.3 Although the increase in the number of organs transplanted was true for most organ transplants, heart transplantation was the only solid organ where it was not realized.1 The aim of this study was to examine temporal changes in the use of hearts from high-risk donors, including those that may have resulted from the ODBC.

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Methods 

The collection and analysis of data for this study was approved by Institutional Review Boards at all participation institutions.

The study group consisted of all adult patients who underwent heart transplantation between 1990 and 2007 at 26 centers participating in Cardiac Transplant Research Database (CTRD, see the Appendix). CTRD is a voluntary prospective registry of heart transplantation clinical data. Three eras were selected for comparison: 1990–1995, 1996–2002, and 2003–2007. The events that defined the era selection were (1) the reduction in the stringency of donor selection in heart transplantation in the middle and late 1990s,4, 5, 6, 7, 8, 9 and (2) the 2003 ODBC.

We explored temporal changes in the following donor characteristics: age >55 years, gender, history of hypertension, history of diabetes mellitus, abnormal donor echocardiogram (left ventricular hypertrophy ≥13 mm, left ventricular ejection fraction <50%, more than mild valvular regurgitation or stenosis, more than minimal coronary atherosclerosis) and graft ischemic time. We selected these specific variables because they have been associated with increased risk,10, 11 and at the same time, the feasibility of increased use of donors with these characteristics has been explored, for example, by the Crystal City Conference on maximizing use of organs recovered from the cadaveric donor.4

Comparisons among the three eras were made using the t-test or chi-square tests, as appropriate. Statistical significance was defined as a value of p < 0.05.

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Results 

A total of 7,220 patients received heart transplant between 1990 and 2007 in 26 centers participating in CTRD. Between the first and the second era, there was a significant increase in the mean age of the donors, from 29.6 to 31.9 years (p ≤ .0001). No further increase in donor age was seen in the third era, where the mean age was 31.8 (p = 0.9; Figure 1). Between the first and second eras, utilization of hearts from female donors increased significantly, from 29.6% to 32.9% (p = 0.01). There was a significant decrease in the proportion of female donors in the third era, however, when only 28% of the donors were female (p = 0.0003; Figure 2).

The proportion of donors with hypertension increased from 7.8% in the first era to 10.4% in the second era (p = 0.05), and no further increase was seen in the third era—10.3% (p = 0.9; Figure 3). Donors with diabetes mellitus increased noticeably from 0.8% in the first era to 2.6% in the second era (p ≤ 0.001), with a subsequent decrease, although not statistically significant, to 2.2% in the third era (p = 0.3; Figure 3).

The use of donor hearts with structural abnormalities detected on echocardiograms showed a tendency for increase between the first two eras (7.0 % to 7.7%, p = 0.4), but reversed significantly in the third era, to 5.5% (p = 0.004; Figure 3). Finally, allograft ischemic time was the only characteristic that continued to increase along the different eras, 163 minutes to 181 minutes to 186 minutes (Figure 1).

These results indicate that donors in the first era were least likely to have characteristics associated with increased risk. In the second era, there was a significant increase in the use of high-risk donors as the proportion of multiple high-risk characteristics increased. In the most recent era, no further increase in the use of organs from high-risk donors was seen; in fact, a reverse trend suggesting avoidance of risk was noted.

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Discussion 

Our study demonstrates significant changes in the use of cardiac allografts from high-risk donors in different eras. The analysis confirms that experience from the mid-1990s, which suggested favorable outcomes with the use of high-risk heart allografts, resulted in overall increase in the use of donors with high-risk characteristics. Our data also indicate that in heart transplantation, the approaches proposed by ODBC did not result in further increase in the utilization of high-risk donors; rather, a trend in the opposite direction was present.

Although our study cannot identify the exact reasons for this trend, we believe it is important to try to identify the probable reasons why the ODBC, in contrast to other solid organs, did not result in an increase of heart transplantation in the United States. It is possible that liberalization of the donor selection criteria in heart transplantation in the 1990s had already resulted in practice changes that were similar to those proposed by ODBC, and as a result, an increase in donor heart utilization from high-risk donors was not realized.

The trends that led to this liberalization of organ donation before the establishment of the ODBC could be related to the publication of favorable outcomes with high-risk donors and also to the introduction of “alternate waiting lists” by some programs. These alternate lists are used as a means by which patients not considered good candidates for heart transplantation can received high-risk organs.12 This practice has been associated with greater morbidity and mortality compared with standard transplantation but better outcomes compared with the natural history of end-stage heart disease.13, 14

Although short-term survival with heart allografts from high-risk donors has been shown to be favorable, the long-term risk of death associated with the high-risk characteristics we explored has remained fairly unchanged over the years.15, 16, 17, 18, 19, 20, 21 A recent analysis of the CTRD registry showed that overall survival after transplantation gradually improved during the timeframe examined in our study; however, the relative risk of death associated with the high-risk characteristics examined did not change.10

Some of the excess long-term risk may be attributed to faster development and progression of cardiac allograft vasculopathy (CAV) in donors of older age and those with history of hypertension and diabetes mellitus. For example, Lietz et al19 demonstrated that CAV developed within 12 months after transplant in 34% of recipients of allografts from donors older than 40 years compared with 17% of recipients of allografts from donors younger than 20 years.19 Because CAV is a major cause of death beyond 5 years after heart transplantation, the effect of donor-associated risk on long-term survival would be expected to be considerable.11

An additional explanation for the trend toward a lower-risk cardiac donor could be related to the advances in mechanical circulatory support therapy, specifically ventricular assist device (VAD) use as bridge to transplantation. Expanding experience with VADs, as well as smaller size and improved durability of newer VADs in recent years, have allowed for predictable stabilization of advanced heart failure patients. In addition, most such patients can be discharged from the hospital and await transplantation as outpatients. Therefore, VAD therapy has decreased the frequency of a scenario where a higher-risk donor is more likely to be accepted for an ill patient on the transplant waiting list due to lack of viable alternatives. On the other hand, some patients with VAD complications and malfunction will require urgent heart transplantation and may necessitate acceptance of organs from high-risk donors.

Another factor contributing to the decrease of high-risk donors in the last era could be related to the effects of the 2006 Thoracic Organ Allocation Change that expanded regional sharing of organs for patients in status 1A and 1B. As a result, higher percentages of organs are allocated to the sickest heart transplant candidates, and it is possible that transplant clinicians can therefore be more selective in acceptance of organs for these patients.22

Our data support the notion that the lack of increase in utilization of high-risk donors is an important reason for the absence of an increase in heart transplantation after ODBC. The renewed debate regarding the long-term outcomes with use of expanded criteria donors in solid organ transplantation23, 24, 25, 26 points to the importance of balancing donor-associated risk with the desire to increase the number of transplants. Continued examination of the effect of utilization of organs from high-risk donors on the waiting time for transplantation, on the risk of death while on UNOS waiting list, and on the long-term outcome after transplantation is of great importance.

This study has some limitations. In our analysis we used a premise that temporal changes in donor characteristics resulted fully from a deliberate change in donor selection by transplant clinicians. This notion would be, at least in part, supported by the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients statistics. The number of consented donors increased by 30% between 2003 and 2007, mostly as a result of an increase in the number of older donors and donors with comorbidities.27 During the same time, the non-recovery rate of hearts has increased by 30%, and thus, there was no significant growth in the number of hearts transplanted. The logical explanation is that the changes in the non-recovery rate were driven by the clinicians who decided on organ acceptance. Additional less intuitive factors cannot be excluded, however, and may have been unaccounted for in our analysis.

Further, data for donors offered for patients in our study whose hearts were not used were not available. It is conceivable that the donor pool for patients included in our study differed from the national average. Our study focused only on the most prevalent high-risk characteristics; it is possible that changes in additional variables could have also contributed to the changes we described. We also implied that changes in utilization of organs from high-risk donors resulted in changes in overall transplant volume. It is possible, however, that additional factors contributed to changes in transplant volumes.

Finally, the CRTD is a voluntary registry, and the transplants performed at the 26 institutions that contributed data for our study represented only 17% of heart transplants performed in the U.S. during that timeframe. As such, the results may not be fully representative of donor selection trends at a national level.

In conclusion, significant temporal changes in the characteristics of heart donors have occurred in the past 17 years. Recent temporal changes, however, cannot be directly attributed to the ODBC efforts.

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Disclosure statement 

The authors are grateful to the Cardiac Transplant Research Database staff for biostatistical and logistical support.

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

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Appendix 

Study Centers in the Cardiac Transplant Research Database

1.Abbott Northwestern Hospital/Minneapolis Heart Institute, Minneapolis, Minnesota

2.Brigham and Women's Hospital, Boston, Massachusetts

3.The Cleveland Clinic Foundation, Cleveland, Ohio

4.Downstate Heart Transplant Center, Peoria, Illinois

5.Henry Ford Hospital, Detroit, Michigan

6.Hershey Medical Center, Penn State University, Hershey, Pennsylvania

7.Johns Hopkins Hospital, Baltimore, Maryland

8.Loyola University Medical Center, Maywood, Illinois

9.Mid-America Heart Institute of St. Luke's Hospital, Kansas City, Missouri

10.Medical College of Virginia, Richmond, Virginia

11.Massachusetts General Hospital, Boston, Massachusetts

12.Mayo Clinic—St. Mary's Hospital, Rochester, Minnesota

13.Ohio State University, Columbus, Ohio

14.Rush-Presbyterian—St. Luke's Med Center, Chicago, Illinois

15.Medical University of South Carolina, Charleston, South Carolina

16.Sharp Memorial Hospital, San Diego, California

17.St. Luke's Episcopal Hospital, Houston, Texas

18.Sentara Norfolk General Hospital, Norfolk, Virginia

19.Baylor College of Medicine/The Methodist Hospital, Houston, Texas

20.Temple University Hospital, Philadelphia, Pennsylvania

21.University of Alabama at Birmingham, Birmingham, Alabama

22.University of Cincinnati Medical Center, Cincinnati, Ohio

23.University of Iowa Hospitals & Clinics, Iowa City, Iowa

24.University of Michigan Medical Center, Ann Arbor, Michigan

25.University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

26.Utah Transplant Affiliated Hospitals, Salt Lake City, Utah

27.University of Texas Southwestern/St. Paul Medical Center/Baylor, Dallas, Texas

28.VA Medical Center, Richmond (Medical College of Virginia affiliated), Richmond, Virginia

29.Washington University Medical Center, St. Louis, Missouri

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References 

  1. Wolfe RA, Merion RM, Roys EC, et al. Trends in organ donation and transplantation in the United States, 1998–2007. Am J Transplant. 2009;9:869–878
  2. Shafer TJ, Wagner D, Chessare J, et al. Organ donation breakthrough collaborative: increasing organ donation through system redesign. Crit Care Nurse. 2006;26:33–42
  3. Tuttle-Newhall JE, Krishnan SM, Levy MF, et al. Organ donation and utilization in the United States: 1998–2007. Am J Transplant. 2009;9:879–893
  4. Zaroff JG, Rosengard BR, Armstrong WF, et al. Consensus conference report: maximizing use of organs recovered from the cadaver donor: cardiac recommendations, March 28–29, 2001, Crystal City, Va. Circulation. 2002;106:836–841
  5. Kron IL, Tribble CG, Kern JA, et al. Successful transplantation of marginally acceptable thoracic organs. Ann Surg. 1993;217:518–522
  6. Ott GY, Herschberger RE, Ratkovec RR, et al. Cardiac allografts from high-risk donors: excellent clinical results. Ann Thorac Surg. 1994;57:76–81
  7. Brock MV, Salazar JD, Cameron DE, et al. The changing profile of the cardiac donor. J Heart Lung Transplant. 2001;20:1005–1009
  8. Chen JM, Sinha P, Rajasinghe HA, et al. Do donor characteristics really matter? (Short- and long-term impact of donor characteristics on recipient survival, 1995–1999). J Heart Lung Transplant. 2002;21:608–610
  9. Khasati NH, Machaal A, Barnard J, et al. Donor heart selection: the outcome of “unacceptable” donors. J Cardiothorac Surg. 2007;2:13
  10. Stehlik J, Feldman DS, Brown RN, et al. Interactions among donor characteristics influence post-transplant survival: a multi-institutional analysis. J Heart Lung Transplant. 2010;29:291–298
  11. Taylor DO, Stehlik J, Edwards LB, et al. Registry of the international society for heart and lung transplantation: twenty-sixth official adult heart transplant report-2009. J Heart Lung Transplant. 2009;28:1007–1022
  12. Laks H, Scholl FG, Drinkwater DC, et al. The alternate recipient list for heart transplantation: does it work?. J Heart Lung Transplant. 1997;16:735–742
  13. Chen JM, Russo MJ, Hammond KM, et al. Alternate waiting list strategies for heart transplantation maximize donor organ utilization. Ann Thorac Surg. 2005;80:224–228
  14. Felker GM, Milano CA, Yager JE, et al. Outcomes with an alternate list strategy for heart transplantation. J Heart Lung Transplant. 2005;24:1781–1786
  15. Bourge RC, Naftel DC, Costanzo-Nordin MR, et al. Pretransplantation risk factors for death after heart transplantation: a multiinstitutional study (The Transplant Cardiologists Research Database Group). J Heart Lung Transplant. 1993;12:549–562
  16. Young JB, Naftel DC, Bourge RC, et al. Matching the heart donor and heart transplant recipient (Clues for successful expansion of the donor pool: a multivariable, multiinstitutional report). J Heart Lung Transplant. 1994;13:353–365
  17. Hunt SA, Baldwin J, Baumgartner W, et al. Cardiovascular management of a potential heart donor: A statement from the Transplantation Committee of the American College of Cardiology. Crit Care Med. 1996;24:1599–1601
  18. Del Rizzo DF, Menkis AH, Pflugfelder PW, et al. The role of donor age and ischemic time on survival following orthotopic heart transplantation. J Heart Lung Transplant. 1999;18:310–319
  19. Lietz K, John R, Mancini DM, et al. Outcomes in cardiac transplant recipients using allografts from older donors versus mortality on the transplant waiting list; Implications for donor selection criteria. J Am Coll Cardiol. 2004;43:1553–1561
  20. McCarthy JF, McCarthy PM, Massad MG, et al. Risk factors for death after heart transplantation: does a single-center experience correlate with multicenter registries?. Ann Thorac Surg. 1998;65:1574–1578
  21. Kuppahally SS, Valantine HA, Weisshaar D, et al. Outcome in cardiac recipients of donor hearts with increased left ventricular wall thickness. Am J Transplant. 2007;7:2388–2395
  22. Vega JD, Moore J, Murray S, et al. Heart transplantation in the United States, 1998–2007. Am J Transplant. 2009;9:932–941
  23. Reese PP, Feldman HI, McBride MA, et al. Substantial variation in the acceptance of medically complex live kidney donors across US renal transplant centers. Am J Transplant. 2008;8:2062–2070
  24. Iordanous Y, Seymour N, Young A, et al. Recipient outcomes for expanded criteria living kidney donors: the disconnect between current evidence and practice. Am J Transplant. 2009;9:1558–1573
  25. Maluf DG, Edwards EB, Kauffman HM. Utilization of extended donor criteria liver allograft: Is the elevated risk of failure independent of the model for end-stage liver disease score of the recipient?. Transplantation. 2006;82:1653–1657
  26. Gastaca M. Extended criteria donors in liver transplantation: adapting donor quality and recipient. Transplant Proc. 2009;41:975–979
  27. The U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients Reports. http://www.ustransplant.org/annual_reports/current/default.htmAccessed: Oct 12, 2009

PII: S1053-2498(10)00237-8

doi:10.1016/j.healun.2010.04.005

The Journal of Heart and Lung Transplantation
Volume 29, Issue 8 , Pages 847-852, August 2010

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