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Eur J Cardiothorac Surg 1999;16:163-168
© 1999 Elsevier Science NL

Coronary artery bypass grafting after orthotopic heart transplantation

^a Department of Thoracic and Cardiovascular Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
^b Department of Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
^c Department of Anaethesiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

Corresponding author. Tel.: +49-30-4593-2001; fax: +49-30-4593-2100
e-mail: musci{at}dhzb.de

	Abstract

Top Abstract 1. Introduction 2. Patients and methods 3. Discussion 4. Conclusions Appendix A References

 
Objective: Graft coronary disease (GCD) remains the major determinant of long-term survival after heart transplantation. Therapeutic strategies for the prevention or retardation of GCD in the cardiac allograft are limited, and palliative surgical coronary revascularization has been attempted. The aim of this report was to retrospectively analyze our results of coronary artery bypass grafting after cardiac transplantation. This paper correlates the outcome of patients with the pathohistological and angiographic type of lesion in order to identify transplant recipients who may profit from surgical myocardial revascularization. Methods: Seven patients with a mean age of 55 years (range 45–61 years) underwent coronary artery bypass grafting as a result of GCD at a mean of 67 months (range 6–128 months) after cardiac transplantation. By the inclusion of the clinical history and the angiographic pattern of GCD lesions, the primary indications for surgical revascularization, operative results, pathohistological studies and follow-ups were examined. Results: Elective surgery was performed in two patients with proximal, severe triple vessel disease (Type A lesion) and in one patient in whom the primary reason for cardiac surgery was severe tricuspid regurgitation. This patient electively received a tricuspid valve replacement and concomitant single vessel bypass surgery for proximal GCD (Type A lesion). Emergency surgery was performed in four patients: preoperatively three patients post-infarction developed worsening congestive heart failure, which resulted in low cardiac output syndrome. One patient with combined Types A and B/C lesions required emergency surgery for dissection of the right coronary artery (RCA) after an angioplasty procedure. Angiographically all these patients showed diffuse, distal arteriopathy (combined Type B/C lesions). The electively operated patients (n=3) and the patient with dissection of the RCA (n=1) had successful operations and survived beyond hospital discharge (overall survival for coronary artery bypass graft (CABG) in GCD patients 4 out of 7; 57%). All three patients with distal arteriopathy, who underwent emergency surgery, died in hospital from left ventricular failure (43%). The four patients discharged from hospital with a mean follow-up of 10 months (range 2–32 months) are all in good clinical condition. Conclusions: Coronary artery bypass grafting can be successfully performed in a subgroup of cardiac transplant patients with Type A lesions. However, the state of diffusely diseased distal arteries (Type B/C lesions), which is prevalent in this group of patients, limits the use of bypass surgery.

Key Words: Coronary bypass surgery • Graft coronary disease • Heart transplantation

	1. Introduction

Top Abstract 1. Introduction 2. Patients and methods 3. Discussion 4. Conclusions Appendix A References

 
More than 30 years after the first clinical implantation, orthotopic heart transplantation (HTX) has become a routine operation world-wide for patients with end-stage heart disease [1,2]. Despite this, graft coronary disease (GCD), an unusually accelerated form of coronary artery disease, remains the major determinant of long-term survival. In patients who survive for more than 1 year after transplantation, it is the primary cause of death. Even though many factors have been implicated (Table 1), the etiology of this aggressive and diffuse disease remains unclear [3]. Angiographically the disease is classified as proximal Type A lesions when compared with distally located Type B and C lesions (Table 2).

The aim of this report was to retrospectively analyze our results of coronary artery bypass grafting after cardiac transplantation. This paper correlates the outcome of patients with the pathohistological and angiographical type of lesion in order to identify transplant recipients who may profit from surgical myocardial revascularization.

	2. Patients and methods

Top Abstract 1. Introduction 2. Patients and methods 3. Discussion 4. Conclusions Appendix A References

 
Seven patients underwent coronary artery bypass grafting as a result of GCD, which was diagnosed by annual angiography. By including the clinical history and the angiographic pattern of the GCD lesions, the primary indications for surgical revascularization, the operative results, the pathohistological studies and the follow-ups were examined.

2.1. Clinical profile
Seven patients (six males, one female), with a mean age of 55 years (range 45–61 years), underwent bypass surgery at a mean of 67 months (range 6–128 months) after cardiac transplantation. Demographic and clinical characteristics are given in Table 3 which show that one patient needed bypass surgery very early (6 months) after HTX and that two patients needed bypass surgery after an excess of 10 years (120 and 128 months) after HTX. Four patients had previously undergone unsuccessful angioplasty. The mean time from transplantation to angioplasty was 50 months (range 24–80 months). The mean time to bypass surgery following angioplasty was 9.3 months (range 3–17 months).

The other three patients (group 2; numbers 5–7) were operated on electively and preoperatively they were in a stable clinical condition. In one of these patients the primary reason for cardiac surgery was severe tricuspid regurgitation due to rupture of anterior and posterior leaflet chordae resulting in biventricular heart failure. This patient received a tricuspid valve replacement and concomitant single vessel bypass surgery. Angiographically these three patients showed a predominantly proximal type of GCD (Type A lesion) with one patient having high-risk left main coronary artery atherosclerosis.

Bypass surgery was performed using hypothermic right atrial-aortic cardiopulmonary bypass. The heart was arrested using cold cardioplegic solution (Kirsch solution buffered with sodium bicarbonate and Haes), which was supplemented by a continuous cold pericardial irrigation system. Grafts were performed using lengths of reversed great saphenous vein (n=8). In the elective cases left (n=2) or right internal thoracic artery (n=1) was used and anastomosed to the left anterior descending coronary artery. Mean aortic clamp time and perfusion time was 38.2 min (32–47 min) and 288.3 (184–465 min) for group 1 and 52.6 min (37–63 min) and 91 min (68–113 min), respectively for group 2.

2.3. Pathohistological studies
Prior to surgery all patients underwent a right heart endomyocardial biopsy, and in all cases no episode of acute rejection was present. In contrast to the angiography, pathohistological studies of all patients showed diffuse arteriopathy with peripheral obliteration of arterioles and capillaries. Histological slices of the paraffin-embedded right ventricular rejection control samples were stained with immunomarkers for smooth muscles cells (SMCs; -actin) and endothelial cells (CD 31). They showed intensive wall thickening by proliferation of SMCs of arterioles (Fig. 1) and severe endothelial cell swelling in arterioles and capillaries. Histomorphometric analysis, carried out by counting vessels and SMCs in a test field of 100 compartments, showed no statistical difference between the two groups.

View larger version (140K): [in this window] [in a new window]   Fig. 1. Histological slice from right ventricular biopsy of a GCD patient stained with an immunomarker for smooth muscle cells (SMC, -actin). Intensive wall thickening of arterioles is due to proliferation of SMCs.

The effect of distal GCD, detected on the arteriogram before bypass surgery, was examined (Table 2). Three (75%) out of four patients with distal arteriopathy (Type B/C lesions) died as opposed to none of the patients without distal arteriopathy (n=3).

The four patients discharged from hospital with a mean follow-up of 17.7 months (range 9–34 months) are all in good clinical condition. The complications encountered in this group included acute renal failure in one and infection in another patient.

	3. Discussion

Top Abstract 1. Introduction 2. Patients and methods 3. Discussion 4. Conclusions Appendix A References

 
This paper underlines specifically the problems of bypass surgery in a very special collective of patients. Because of the denervation of the afferent cardiac nervous system, most cardiac transplant recipients do not suffer from the classic symptoms of ischemia. Although there is evidence of partial reinnervation of the cardiac allograft [17], angina pectoris may infrequently occur in heart transplant recipients. Therefore, the first clinical manifestations of allograft ischemia predominantly includes congestive heart failure, ventricular arrhythmias, silent myocardial infarction or sudden cardiac death.

There have been several anectodal case reports of successful coronary artery bypass surgery in heart transplant recipients [18,19]. A single-center experience has been reported by Heroux et al. [20], which describes five hospital survivors who underwent bypass surgery very early in the post-transplantation period, i.e. on average 14±10 months. In contrast, two recently published studies that examined the effect of the presence of distal coronary disease on the angiogram before bypass surgery, showed an operative mortality rate of between 33% and 40% [21,22]. In the largest series collected by Halle et al. (1995) in a multicenter review, 12 patients underwent surgery on average at 5 years post-transplantation. The most significant risk factor for mortality in this group was the presence of distal obliterative disease as shown by conventional contrast angiography. Four of the five patients (80%) with distal arteriopathy died as opposed to one of seven patients (14%) without distal arteriopathy.

This report confirms the results of our study, i.e. presence of angiographic distal arteriopathy should be considered a significant factor in patient selection for surgical coronary revascularization. Those patients who could be operated on electively (group 2; n=3) together with the patient with dissection of RCA (n=1), angiographically showed predominantly proximal Type A lesions. They had successful operations and an excellent postoperative course. All patients survived beyond hospital discharge and at a mean follow-up of 17.7 months (range 9–34 months) they are all in good clinical condition (Table 3). Interestingly, the mean time from HTX to bypass surgery for these patients (111 months; range 85–128 months) was significantly longer than for the patients in group 1 (31 months; range 6–55 months).

The significant detrimental influence of distal arteriopathy on patients’ survival in our series is underlined by the fact that all three patients of group 1 angiographically showed predominately combined Type B/C lesions (Table 2). Preoperatively these patients developed worsening congestive heart failure, and the reason for perioperative or postoperative myocardial failure may have been the presence of diffuse disease of the microcirculation which may fail to provide adequate myocardial perfusion during and after cardiopulmonary bypass. Our experience has also confirmed what has been known for a long time, that angiography underestimates the presence and severity of GCD [23,24] and does not give a good impression of the state of the distal arteries. In contrast to the angiography, our pathohistological study showed diffuse arteriopathy with severe peripheral obliteration of arterioles and capillaries in all patients, which shows that perhaps GCD could be diagnosed from endomyocardial biopsies [25,26]. In future, ICUS and use of coronary flow reserve measurements may enable a better judgement of the presence or absence or severity of distal obliterative disease [27], which could improve the results of bypass surgery in GCD patients.

The limitations of our study include the fact that it was a retrospective analysis of only a small number of patients. None of the patients had any functional assessment of the distal vascular bed. The follow-up time was short. Despite these limitations, the present series represents the largest single-center study of bypass surgery in cardiac transplant recipients.

	4. Conclusions

Top Abstract 1. Introduction 2. Patients and methods 3. Discussion 4. Conclusions Appendix A References

 
From the experience described above, and together with other recent reports, our current policy, based on annual clinical and angiographic reviews, is that coronary angioplasty is to be considered as a method of treatment for severe, local stenoses. This method may be applied in this selected group of cardiac transplant recipients since comparable primary success and complication rates to routine angioplasty have been found [6].

Coronary artery bypass grafting can successfully be performed in a subgroup of cardiac transplant patients predominantly with Type A lesions. However, the state of diffusely diseased distal arteries (Type B/C lesions), which were prevalent in this group of patients, limits the use of bypass surgery. In this group of patients bypass surgery should only be used cautiously.

Long-term follow-up is obviously necessary in order to truly assess the impact of coronary artery bypass surgery on allograft coronary disease.

	Acknowledgments

 
We thank Ms T. Derwent for her help in reviewing the manuscript.

	Footnotes

 
Presented at the 12th Annual Meeting of the European Association for Cardio-thoracic Surgery, Brussels, Belgium, September 20–23, 1998.

	Appendix A

Top Abstract 1. Introduction 2. Patients and methods 3. Discussion 4. Conclusions Appendix A References

 
Conference discussion
Dr A. Ritchie (Cambridge, UK): You've got some of the patients in your group who are coming to revascularization at 2–4 months. Are these not patients in whom the original donor organ is one with coronary artery disease which has been missed? And what are you actually saying about the long-term ACAD patients? I mean these patients have essentially an immunological burn which makes all of the coronary arteries smoothly small. You're never going to achieve revascularization in that group.

Dr Musci: Yes, you're right. I thought long about taking these patients in this group. I wanted to fulfill them. This patient, after 4 months, certainly can be one of those who received coronary artery disease from a donor. But what I wanted to focus on is that bypass surgery is to be done on these patients with proximal stenosis and you should be attentive.

Dr Wheatley (Glasgow, UK): But you would allow that Dr Ritchie's got a point?

Dr Musci: Totally, yes.

Dr E. Wolner (Vienna, Austria): In your PTCA group, are there also included patients in which the cardiologists have used the stents? And do you have, with the stents, the same high restenosis rate, or is there a difference between simple PTCA and stent use?

Dr Musci: In the PTCA group we have eight patients with stents, but the follow-up time is too short yet to make any worthwhile discussion.

	References

Top Abstract 1. Introduction 2. Patients and methods 3. Discussion 4. Conclusions Appendix A References

 

1. Barnard C.N. The operation. A human cardiac transplant: an interim report of a successful operation performed at Groote Schuur Hospital. S Afr Med J 1967;41:1271-1274.[Medline]
2. Hosenpud J.D., Bennett L.E., Keck B.M., Fiol B., Boucek M.M., Novick R.J. The registry of the International Society for Heart and Lung Transplantation: 15th Official Report–1998. J Heart Lung Transplant 1998;17:656-668.[Medline]
3. Dong C., Redenbach D., Wood S., Battistini B., Wilson J.E., McManus B.M. The pathogenesis of cardiac allograft vasculopathy. Curr Opin Cardiol 1996;11:183-190.[Medline]
4. Weis M., von Scheidt W. Cardiac allograft vasculopathy. A review. Circulation 1997;96:2069-2077.
5. Smith J.A., Ribakove G.H., Hunt S.A., Miller J., Stinson E.B., Oyer P.E., Robbins R.C., Shumway N.E., Reitz B.A. Heart retransplantation: the 25-year experience at a single institution. J Heart Lung Transplant 1995;14:832-839.[Medline]
6. Halle M., III, Wilson R.F., Massin E.K., et al. Coronary angioplasty in cardiac transplant recipients: results of a multicenter study. Circulation 1992;86:458-462.[Abstract/Free Full Text]
7. Jam S.P., Ventura H.O., Ramee S.R., Collins T.J., Isner J.M., White C.J. Directional coronary atherectomy in heart transplant recipients. J Heart Lung Transplant 1993;12:819-823.[Medline]
8. Bell C., Kern M.J., Aguirre F. Coronary atherectomy complicated by coronary embolus in a cardiac transplant recipient. Am Heart J 1993;125:1172-1175.[Medline]
9. Copeland J.G., Butman S.M., Sethi G. Successful coronary artery bypass grafting for high risk left main coronary artery atherosclerosis after cardiac transplantation. Ann Thorac Surg 1990;49:106-110.[Abstract]
10. Dunning J.J., Kendall S.W., Mullins P.A., et al. Coronary artery bypass grafting nine years after cardiac transplantation. Ann Thorac Surg 1992;54:571-572.[Abstract]
11. Frazier O.H., Vega J.D., Duncan J.M., et al. Coronary artery bypass two years after orthotopic heart transplantation; a case report. J Heart Lung Transplant 1991;10:1036-1040.[Medline]
12. Frazier O.H., Kadipasaoglu K.A., Radovancevic B., Cihan H.B., March R.J., Mirhoseini M., Cooley D.A. Transmyocardial laser revascularization in allograft coronary artery disease. Ann Thorac Surg 1998;65:1138-1141.[Abstract/Free Full Text]
13. March R.J., Grynn T. Cardiac al log raft vasculopathy: the potential role for transmyocardial laser revascularization. J Heart Lung Transplant 1995;14:S242-S246.[Medline]
14. McFadden P.M., Robbins R.J., Ochsner J.L., Van Meter C.H., Majorie S. Transmyocardial revascularization for cardiac transplantation allograft vasculopathy. J Thorac Cardiovasc Surg 1998:1385-1388.
15. Wong P.M., Piamsomboon C., Mathur A., Chastain H.D., II, Singh D.J., Liu M.W., Parks J.M., Iyer S., Dean W.A., Baxley R.C., Bourge G.S.R, Roubins L.S. Efficacy of coronary stenting in the management of cardiac allograft vasculopathy. Am J Cardiol 1998;82:239-241.[Medline]
16. Rabago G., Martin-Trenor A., Lopez Coronado J.L., Calabuig J. Coronary angioplasty and stenting following heart transplantation with older donors. Is this a rational approach?. Eur J Cardiothorac Surg 1998;13:209-211.[Abstract/Free Full Text]
17. Stark R.P., McGinn A.L., Wilson R.F. Chest pain in cardiac transplant recipients: evidence of sensory reinnervation after cardiac transplantation. New Engl J Med 1991;324:1174-1791.[Abstract]
18. Hoffmeier A., Schmid C., Deng M.C., Weyand M., Kerber S., Schmidt C., Scheld H.H. Multiple cardiac procedures after heart transplantation: a case report. Thorac Cardiovasc Surg 1996;44:216-218.[Medline]
19. Miller L.W., Donohue T.J., Wolford T.A. The surgical managment of allograft coronary disease: a paradigm shift. Sem Thorac Cardiovasc Surg 1996;8:133-138.[Medline]
20. Heroux A., Winkel E., Johnson S. Cardiac allograft vasculopathy: Angiograpic features and implications for revascularization (abstract). Circulation 1994;90:1-362.[Free Full Text]
21. Parry A., Roberts M., Parameshwar J., Wallwork J., Schofield P., Large S. The management of post-cardiac transplantation coronary artery disease. Eur J Cardiothorac Surg 1996;10:528-533.[Abstract]
22. Halle M., III, DiSciascio G., Massin E.K., et al. Coronary angioplasty, atherectomy and bypass surgery in cardiac transplant recipients. J Am Coll Cardiol 1995;26:120-128.[Abstract]
23. Dressler F.A., Miller L.W. Necroscopy versus angiography: how accurate is angiography?. J Heart Lung Transplant 1992;11:S56-S59.[Medline]
24. Mason J.W., Strefling A. Small vessel disease of the heart resulting in myocardial necrosis and death despite angiographically normal coronary arteries. Am J Cardiol 1979;44:171-176.[Medline]
25. Musci M., Meyer R., Hummel M., Hetzer R. Light microscopic and immunhistologic investigations in endomyocardial biopsies of right ventricles for early recognition of transplant coronary artery disease. Pathol Res Practice 1997;193/2(88):76.
26. Neish A.S., Loh E., Schoen F.J. Myocardial changes in cardiac transplant-associated coronary arteriosclerosis: potential for timely diagnosis. J Am Coll Cardiol 1992;19:586-592.[Abstract]
27. Wellnhofer E., Bocksch W., Musci M., Hennersdorf F., Lehnkuhi H.B., Dreysse S., Hug J., Hetzer R., Fleck E. Chronic decrease of average peak flow velocity in coronary arteries of transplant recipients. Transplant Proc 1998;30:909-912.[Medline]

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