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Eur J Cardiothorac Surg 2007;32:634-638. doi:10.1016/j.ejcts.2007.07.007
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Coronary atherosclerosis of the donor heart — impact on early graft failure

Onnen Grauhan*, Henryk Siniawski, Michael Dandel, Hans Lehmkuhl, Christoph Knosalla, Miralem Pasic, Yu-Guo Weng, Roland Hetzer

German Heart Institute, Berlin, Germany

Received 26 July 2006; received in revised form 28 June 2007; accepted 2 July 2007.

* Corresponding author. Address: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Tel.: +49 30 4593 2000/01; fax: +49 30 4593 2023. (Email: grauhan{at}dhzb.de).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 Appendix A
 References
 
Objective: Due to the shortage of donor hearts, the criteria for organ acceptability have been considerably extended and donor grafts with coronary atherosclerosis are among those offered. This study evaluated whether and to what degree pre-existing coronary atherosclerosis may be acceptable. Methods: A total of 1253 consecutive HTx recipients were investigated retrospectively for donor-transmitted coronary atherosclerosis (DCAS). Donor-transmitted coronary atherosclerosis was defined as focal atherosclerosis with stenosis of at least 50%. Inclusion criteria were absence of pre-HTx angiogram but performance of angiogram or autopsy within 6 months after heart transplantation. Kaplan–Meier analysis and log-rank test were used. Results: Eighty-five out of 1253 (6.8%) cases were excluded, since coronary evaluation was not performed within 6 months (n = 45) or hearts had undergone pre-transplant angiography (n = 40). In 1086 patients no donor-transmitted coronary atherosclerosis was found (NDCAS group) and in 82 patients (7%) donor-transmitted coronary atherosclerosis was diagnosed by angiography (n = 49) or autopsy (n = 33). Single-vessel donor-transmitted coronary atherosclerosis was found in 53/82 patients (DCAS1 group) and double- or triple-vessel donor-transmitted coronary atherosclerosis in 26/82 patients (DCAS2/3 group). Three of the 82 patients with donor-transmitted coronary atherosclerosis were excluded since the autopsy report was unclear regarding degree of atherosclerosis. Early after heart transplantation the 30-day mortality in the NDCAS and DCAS1 groups was 12.2% versus 13.2% whereas in the DCAS2/3 group it was 61.5%. Beyond the first year the annual decrease with and without donor-transmitted coronary atherosclerosis (single-vessel disease) is comparable. Conclusions: Donor screening without coronary angiogram overlooks significant atherosclerotic lesions in a considerable number of cases (7.0%). Therefore, angiographic donor screening should be performed. Donor grafts with single-vessel coronary atherosclerosis may be accepted as marginal hearts; however, in our opinion, revascularisation (CABG, PTCA) should be considered. Grafts with two- or even three-vessel coronary atherosclerosis seem to have a serious risk for early graft failure. Beyond the first year the outcome of healthy grafts and grafts with donor-transmitted coronary atherosclerosis seems to be comparable.

Key Words: Organ donor • Coronary atherosclerosis • Coronary angiography


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 Appendix A
 References
 
Pathological studies have shown that coronary atherosclerosis occurs in the coronary arteries long before clinical coronary artery disease occurs, i.e., in the young and healthy, who may become heart donors [1–5]. Furthermore, the shortage of donor organs has resulted in an increase in the mean age of heart donors worldwide during the past two decades [6]. In addition, 20 years ago most of the donors were trauma victims, representing the young and healthy, but meanwhile the typical donor has suffered from spontaneous intracerebral bleeding due to cerebrovascular aneurysms or arterial hypertension. Therefore, in addition to the higher donor age, the cardiovascular risk profile of the ‘donor pool’ seems to be more adverse than in the healthy population, and it has to be suspected that there is a significant prevalence of coronary atherosclerosis in an apparently healthy cardiac donor population. Finally, it has been shown that the transmission of pre-existing coronary atherosclerosis represents a high risk of early graft failure after transplantation [7].

For these reasons, the number of screening angiographies to evaluate the donor coronaries prior to transplantation is increasing slowly but surely [8], and donor grafts with proven coronary atherosclerosis are among those offered. However, the experience with these donors is very limited and, therefore, the purpose of the present study was to evaluate whether and to what degree pre-existing coronary atherosclerosis of the donor heart may be acceptable.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusion
 Appendix A
 References
 
Between April 1986 and December 2000, 1253 patients underwent heart transplantation at our institution. These consecutive recipients were investigated retrospectively for donor-transmitted coronary atherosclerosis (DCAS). To prevent a bias concerning the outcome of grafts with pre-existing atherosclerotic lesions, donor hearts were excluded if they had been evaluated by angiography prior to organ harvesting. Further, evaluation of graft coronaries by angiogram or autopsy had to have been performed within 6 months after transplantation to exclude lesions that developed after transplantation (transplant vasculopathy).

Coronary angiograms were reviewed by an experienced angiographer using the Pie Medical Imaging system, Rubo DICOM viewer and QCA system. Analogue angiograms that were filmed prior to 1999 first had to be digitalised. Multiple angiographic views were obtained for optimal visualisation of the coronary arteries. For each identifiable lesion, the angiographer determined vessel diameter at the stenosis and at an adjacent angiographically normal reference site to quantify the percentage of stenosis diameter. Focal and non-circumferential atherosclerosis with ≥50% stenosis in proximal segments of at least one coronary vessel was regarded as native and transmitted coronary artery disease (DCAS).

Autopsies were performed by an experienced cardiac pathologist. Coronary atherosclerosis was graded retrospectively as ‘absent’, ‘subcritical’ or ‘significant’. In accordance with the criteria of cardiac catheterisation given above, ‘significant’ atherosclerosis was defined as focal and non-circumferential atherosclerosis with ≥50% stenosis in proximal segments of at least one coronary vessel.

Statistical analysis was performed using Kaplan–Meier analysis and log-rank test. A p-value of <0.05 was considered to be significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusion
 Appendix A
 References
 
Eighty-five out of 1253 (6.8%) cases were excluded from the study, since coronary evaluation was not performed within 6 months (n = 45) or because hearts had undergone pre-transplant angiography (n = 40) (Fig. 1 ). In 1086 patients no donor-transmitted coronary atherosclerosis was found (NDCAS group) and in 82 patients (7%) donor-transmitted coronary atherosclerosis was diagnosed by angiography (n = 49) or autopsy (n = 33). Three of the 82 patients with donor-transmitted coronary atherosclerosis had to be excluded from further analysis since the autopsy report showed coronary atherosclerosis but was unclear regarding the number of vessels involved. Single-vessel disease was found in 53/82 patients (DCAS1 group) and double- or triple-vessel disease in 26/82 patients (DCAS2/3 group).


Figure 1
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  		Fig. 1. Distribution of 1253 investigated grafts; 82 + 3 = 85 grafts had to be excluded. NDCAS, no coronary atherosclerosis; DCAS1, single-vessel coronary atherosclerosis; DCAS2/3, double- or triple-vessel coronary atherosclerosis; DCAS123, unknown involvement, therefore excluded from analysis.

 
The early risk of death (30-day mortality) with healthy grafts (NDCAS group) and grafts with donor-transmitted single-vessel disease (DCAS1 group) was comparable (Table 1 ; Fig. 2 ). However, patients receiving a graft with double- or triple-vessel disease (group DCAS2/3) had a seriously higher risk of suffering from early death (30-day mortality). An analysis of the causes of death showed that this has to be due to the higher rate of early graft failure of grafts with double- or triple-vessel disease (11/26 (42.3%)) compared to grafts with single-vessel disease (4/53 (7.5%)) or healthy grafts (68/1086 (6.3%)) (Table 1).


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  		Table 1 Cause of early death (30-day mortality) in NDCAS, DCAS1 and DCAS2/3 groups
 

Figure 2
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  		Fig. 2. Survival (Kaplan–Meier) after transplantation in the groups: NDCAS, no coronary atherosclerosis; DCAS1, single-vessel coronary atherosclerosis; DCAS2/3, double- or triple-vessel coronary atherosclerosis. Survival (%), ±SEM and patients at risk are plotted in Table 2 and log-rank test in Table 3.

 
On the other hand, beyond the first year the annual decrease in all groups was comparable, with 5.4% per year for patients with a healthy graft and 4.0% per year for patients with a graft with donor-transmitted single-vessel disease. However, so far, there were only five patients with double- or triple-vessel disease who survived beyond the first year.

There were no significant differences between the NDCAS, DCAS1 and DCAS2/3 groups with regard to donor age, recipient age, ischaemic time, inotropic support or recipient pulmonary vascular resistance (PVR) (Tables 2 and 3 ).


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  		Table 2 Statistical data of Fig. 2
 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusion
 Appendix A
 References
 
Donor screening without coronary angiogram overlooks significant atherosclerotic lesions in a considerable number of cases [9] and donor-transmitted coronary atherosclerosis has been described as a risk factor for early graft failure after transplantation [8]. Therefore, in our opinion, angiographic donor screening is essential and as shown previously it should be performed in all donors over 40 years of age or if risk factors for coronary atherosclerosis (diabetes, arterial hypertension, etc.) were present [7,9]. Economic as well as logistic arguments against the screening have been disproved [8] and suspicion that donor angiography could impair donor kidney function has been shown to be unfounded [10].

Since in the past, donor screening by coronary angiography has rarely been performed, there is only limited experience with pre-existing coronary lesions. Our results show that donor grafts with single-vessel involvement – even without revascularisation – seem to have similar outcome after transplantation to healthy grafts. It seems to be more than plausible that the ‘amount of myocardium at risk’ would be a more valuable parameter than solely the number of coronary arteries involved, but this question is beyond the scope of this study (Fig. 3 ). In our opinion, each haemodynamically relevant lesion (>50%) of a large- or medium-size coronary vessel should be treated interventionally during the donor screening angiography (PTCA, stent) or by coronary surgery (IMA, CABG) during the transplantation procedure. Since coronary stenting requires more aggressive anti-thrombotic medication PTCA may be the better choice in this setting; however, the most reliable revascularisation can be achieved by coronary surgery. In the past a few cases of successful heart transplantation with concomitant CABG have been reported by different centres [11–18], showing that this approach could be a valuable option (Fig. 4 ).


Figure 3
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  		Fig. 3. Donor screening angiogram of a 55-year-old graft revealed a 75% proximal LAD stenosis. The organ was accepted for transplantation with concomitant revascularisation by LIMA graft but suffered spontaneous fibrillation just before the harvesting, indicating that even single-vessel CAS may not be worry-free! (Due to pre-transplant angiography this graft was not included in the study).

 

Figure 4
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  		Fig. 4. Coronary angiogram 22 months after transplantation with occluded LAD stent and patent venous graft to LAD: a 64-year-old donor heart with good left ventricular function but atrial fibrillation; screening angiography showed a significant proximal stenosis in the left anterior descending coronary artery and a significant lesion in a small circumflex artery with a dominant right coronary artery. Stenosis of the proximal LAD was treated by stenting during donor screening angiography. Because of suboptimal flow after stenting, an additional coronary bypass was performed during transplantation. (Due to pre-transplant angiography this graft was not included in the study).

 
According to our results, donor grafts with two- or even three-vessel involvement – and without revascularisation – have a worse outcome after transplantation than healthy grafts. This raises the question of whether the outcome can be improved, assuming that myocardial performance in the echocardiographic investigation was normal, if these grafts undergo complete revascularisation during transplantation.


   5. Conclusion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
Appendix A
 References
 
Donor grafts with single-vessel CAS may be accepted as marginal hearts; however, in our opinion, revascularisation (CABG, PTCA) should be considered. Grafts with two- or even three-vessel CAS carry a serious risk for early graft failure. Beyond the first year the outcome of healthy grafts and grafts with donor-transmitted single-vessel coronary atherosclerosis is comparable. This seems to apply even for two- and three-vessel coronary atherosclerosis, but up to now the number of patients surviving beyond the first year is small (n = 5).


   Appendix A
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 Appendix A
References
 
Conference discussion

Dr F.U. Sack (Heidelberg, Germany): Your conclusion, I really can follow it. But we’re all aware of the shortage of donor organs. What do you do when an organ donor is offered from a small country hospital where definitely no angiography would be available? And it is most of our donors we get from there. And it's hard to convince them, all the hassle, to do that for you. It's our experience. It's nice to say we would like to have it, but in reality we would fail in most of the cases to get one.

Dr Grauhan: No, I don’t think that you have to refuse the heart only because there is no angiography. Of course, you have to go to the hospital and to check the heart by palpation and you have to know that there is danger of transmission of this disease. That's the first point.

And the second point is that it's not impossible to have coronary angiography. We try to get angiographies in all donors, and we found that 90% of the donors in our donor region – and it's the former German Democratic Republic, so there are not so many possibilities to do that – 90% of the hospitals are able to do that.

I think the main point is that you have to ask for angiography very early. You don’t have to ask if the donor is on the table, that's too late.

Dr Sack: But another question regarding the palpation of the coronary arteries. You’re quite aware of the fact that in your routine cardiac surgery you have many patients with aortic stenosis, you have the angiogram performed and you see no stenosis of the coronary vessels. But during the operation you find many times really hard coronary vessels. Palpation, that is not a guide for the evaluation of a donor heart.

Dr Grauhan: This is a further argument for angiography. If you don’t have a coronary angiography and you see sclerosis in the donor heart, you don’t know what to do. You have to reject it. If you have angiography, you may see there is no really stenotic vessel or there might be one vessel with relevant or significant stenosis, then you can perform CABG. So it's very important to have angiography to manage these donors.

Dr E. Wolner (Vienna, Austria): You have now accepted a donor with an LAD disease. What you are doing during the transplantation, you perform bypass surgery during transplantation or PTCA? In our experience, in 60% of the patients, I think it's impossible to have a coronary angiography before.

Dr Grauhan: If we have an LAD stenosis and we have good ventricular function, we will accept this graft and perform a bypass during the transplantation.

Dr Wolner: How many cases, approximately, you have in your series which have at the time of transplantation bypass surgery?

Dr Grauhan: Three of them. The 1200 patients that we have analysed in the presented study don’t have had screening angiography. If there was a pre-transplant angiography, we have excluded it from the study because the question was the outcome of inadvertently transmitted CAD and we don’t want to have a bias. But in the other rare cases where we had angiography, we had three cases with revascularisation during transplant with good results.

Dr C. McGregor (Rochester, Minnesota, USA): Do you discuss this with the potential recipient? Do you say to the recipient: This donor heart has coronary artery disease and therefore there may be less of a long-term outcome? Do you discuss this with the recipient?

Dr Grauhan: The problem of donor-transmitted CAD is the short-term outcome, not the long-term outcome. However, we discuss it with the recipient in case we have to do the bypass. If there are only some sclerotic lesions, or changes, we don’t do that.


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  		Table 3 Log-rank-test of Fig. 2
 


   Footnotes
 
\#9734; Presented at the joint 20th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 14th Annual Meeting of the European Society of Thoracic Surgeons, Stockholm, Sweden, September 10–13, 2006.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 Appendix A
 References
 

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  2. Enos WF, Beyer J, Holmes RH. Pathogenesis of coronary disease in American soldiers killed in Korea. JAMA 1955;158:912-914.[Abstract/Free Full Text]
  3. McNamara JJ, Molot MA, Stremple JF, Cutting RT. Coronary artery disease in combat casualties in Vietnam. JAMA 1971;216:1185-1187.[Abstract/Free Full Text]
  4. Virmani R, Robinowitz M, Geer JC, Breslin PP, Beyer JC, McAllister HA. Coronary atherosclerosis revisited in Korean war combat casualties. Arch Pathol Lab Med 1987;111:972-976.[Medline]
  5. Joseph A, Ackerman D, Talley JD, Johnstone J, Kupersmith J. Manifestations of coronary atherosclerosis in young trauma victims – an autopsy study. JACC 1993;22:459-467.[Abstract]
  6. Hosenpud JD, Bennett LE, Keck BM, Boucek MM, Novick RJ. The registry of the International Society of Heart and Lung Transplantation: eighteenth official report. J Heart Lung Transplant 2001;20:805-815.[CrossRef][Medline]
  7. Grauhan O, Chang H, Meyer R, Hiemann N, Albert W, Lehmkuhl H, Dandel M, Hummel M, Knosalla C, Pasic M, Weng Y, Hetzer R. Impact of donor-transmitted coronary atherosclerosis on outcome after heart transplantation. Thorac Cardiovasc Surg 2005;53(Suppl. I):S48-S49.
  8. Grauhan O, Wesslau C, Hetzer R. Routine screening of donor hearts by coronary angiography is feasible. Transplant Proc 2006;38:666-667.[CrossRef][Medline]
  9. Grauhan O, Pazurek J, Hummel M, Lehmkuhl HB, Dandel M, Pasic M, Weng Y, Hetzer R. Donor-transmitted coronary atherosclerosis. J Heart Lung Transplant 2003;22:568-573.[CrossRef][Medline]
  10. Grosse K, Brauer B, Kukuk O, Krueger R, Polster F, Grauhan O, Wesslau C. Does contrast medium administration in organ donors affect early kidney graft function?. Transplant Proc 2006;38:668-669.[CrossRef][Medline]
  11. Musci M, Loebe M, Wellnhofer E, Meyer R, Pasic M, Hummel M, Boksch W, Grauhan O, Weng Y, Hetzer R. Coronary angioplasty, bypass surgery, and retransplantation in cardiac transplant patients with graft coronary disease. Thorac Cardiovasc Surg 1998;46:268-274.[Medline]
  12. Drinkwater DC, Laks H, Blitz A, Kobashigawa J, Sabad A, Moriguchi J, Hamilton M. Outcomes of patients undergoing transplantation with older donor hearts. J Heart Lung Transplant 1996;15:684-691.[Medline]
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  14. Laks H, Gates RN, Ardehali A, Capouya ER, Moriguchi JD, Kobashigawa JA, Stevenson LW. Orthotopic heart transplantation and concurrent coronary bypass. J Heart Lung Transplant 1993;12:810-815.[Medline]
  15. Abid Q, Parry G, Forty J, Dark JH. Concurrent coronary grafting of the donor heart with left internal mammary artery: 10-year experience. J Heart Lung Transplant 2002;21:812-814.[CrossRef][Medline]
  16. Rao JN, Prendergast B, Dark JH. Orthotopic heart transplantation with con-current aortic valve replacement and coronary artery bypass grafting. J Heart Lung Transplant 2000;19:897-899.[CrossRef][Medline]
  17. Kollar A, Donaldson T, Greer E, Howser R, Davis SF, Drinkwater Jr. DC. Left internal mammary artery graft retransplantation from the recipient to the donor heart: a case report. Prog Transplant 2000;10:18-20.[Medline]
  18. Marelli D, Laks H, Bresson S, Ardehali A, Bresson J, Esmailian F, Plunkett M, Moriguchi J, Kobashigawa J. Results after transplantation using donor hearts with preexisting coronary artery disease. J Thorac Cardiovasc Surg 2003;126:821-825.[Abstract/Free Full Text]



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