Successful Coronary Artery Bypass Grafting for High-Risk Left Main Coronary Artery Atherosclerosis After Cardiac Transplantation Jack G. Copeland, MD, Samuel M. Butman, MD, and Gulshan Sethi, MD Division of Cardiothoracic Surgery and Section of Cardiology, University of Arizona Health Sciences Center, Tucson, Arizona
Severe stenosis of the left main coronary artery developed in a 58-year-old woman 9 years after orthotopic heart transplantation. Because of serious reversible myocardial ischemia and the high-risk nature of the coronary disease, coronary artery bypass grafting was performed, with no complications. Possible risk factors for the development of coronary arterial disease and its management in the transplant population are discussed. (Ann Thorac Surg 1990;49:106-10)
A
ccelerated graft atherosclerosis is a major obstacle in long-term management of cardiac transplant recipients. It may be acute, occurring as sudden death, silent myocardial infarction, or acute congestive heart failure, or it may be identified as silent myocardial ischemia, detected by routine stress testing, or detected as asymptomatic coronary arterial narrowing on routine annual coronary angiography [l-31. Attempts to identify patients who are at risk for premature coronary atherosclerosis have not had reliable results, and antiplatelet regimens and changes in the immunosuppressive therapy have not been of proven benefit. Coronary revascularization by coronary artery bypass grafting has not been advocated or attempted because of the diffuse nature of the coronary arterial disease in this population, and because chronic steroid and immunosuppressive therapy increase the risk of perioperative infections and delay in the wound healing process. Recently, successful percutaneous coronary angioplasty for discrete proximal coronary stenoses has been reported in selected patients [4]. Our patient, who underwent cardiac transplantation more than 9 years ago, had new asymptomatic proximal atherosclerotic coronary arterial narrowings 1year before dyspnea on exertion developed; she was diagnosed as having new and severe left main arterial stenosis. Coronary revascularization was believed necessary because of the high-risk location of the coronary stenoses, evidence of serious reversible ischemia on exercise thallium scintigraphy, and the risk associated with the waiting period for retransplanta tion. The patient is a 58-year-old woman who underwent orthotopic cardiac transplantation for idiopathic cardioAccepted for publication June 28, 1989. Address reprint requests to Dr Butman, Cardiology Section, Rm 6402, University Hospital, 1501 N Campbell Ave, Tucson, AZ 85724.
0 1990 by The Society of Thoracic Surgeons
myopathy on December 3, 1979. Her clinical course, events, and yearly laboratory data are summarized in Table 1. She had adult-onset diabetes and required an oral hypoglycemic agent for the 3 years before her current admission to the hospital. Systemic hypertension developed 2 years before this admission and was well controlled with antihypertensive therapy. Accelerated graft atherosclerosis was first documented 6 years after transplantation, with minimal coronary arterial stenosis of the proximal left anterior descending artery and pruning of the distal vessels. One year before her current admission, she was noted to have a 50% stenosis at the takeoff of the circumflex artery and a long 45% narrowing of the proximal left anterior descending artery as measured by digital calipers (Fig 1). The right coronary artery was free of notable disease. The myocardial blush was poor on left coronary angiography, and there was pruning of the distal vessels. Exercise thallium scintigraphy did not show evidence of reversible myocardial ischemia, although perfusion of the anterolateral wall was less than normal (Fig 2). Twentyfour-hour ambulatory monitoring of the ST segment for silent ischemia was also normal. Seven years after transplantation, 2 years before the present admission, for unrelated reasons, her immunosuppressive regimen was changed from one of prednisone and azathioprine to cyclosporine, azothioprine, and a lowered dose of prednisone. In the 3 months before the present admission, the patient noted the onset of exertional chest discomfort and dyspnea. She was able to exercise for 8.4 minutes on a modified Bruce protocol, and thallium scintigraphy showed a large area of reversible ischemia in the anterolateral wall (Fig 3). Significant ST segment depression was evident, which was also new. Coronary angiography revealed a new 85% stenosis of the left main coronary artery, as well as progression of the disease in the proximal circumflex and left anterior descending coronary arteries (Fig 4). The hemodynamic data are shown in Table 2. On examination, the patient appeared cushingoid, her blood pressure was 118/78 mm Hg, and cardiac examination revealed a fourth heart sound. Examination of the extremities revealed healed superficial ulcers and brawny discoloration in the lower legs. There were no obvious usable venous conduits in either the greater or lesser saphenous venous systems because of previous bilateral greater saphenous vein strippings. The decision to perform coronary artery bypass grafting 0003-4975/90/$3.50
COPELAND ET AL CABG AFTER CARDIAC TRANSPLANTATION
Ann Thorac Surg 1990;49: 1 0 6 10
107
Table 1. Lipid Levels and Immunosuppressive and Medical Therapy During Follow-up Years After Transplantation Variable Heart rate (bpm) Systolic BP (mm Hg) Diastolic BP (mm Hg) Total cholesterol (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Triglycerides (mgW ASA use Prednisone (mg/day) Cyclosporine (mg/day) Azothioprine (mg/day1 Exercise time (min) MUGA EF (%) No. of acute rejections
Preoperative
1
2
3
4
5
6
7
8
9
85
100
98
100
103
NA
100
112
98
100
100
100
125
122
118
NA
128
128
160
118
70
60
70
95
78
NA
98
98
100
78
NA
NA
NA
252
222
277
277
214
222
184
NA
NA
NA
109
118
188
187
120
NA
200
NA
NA
NA
38
35
35
36
26
NA
NA
NA
215
361
231
345
271
404
340
272
369
No NA
Yes 20
Yes 25
Yes 25
Yes 20
Yes 20
Yes 17.5
No 7.5
No 7.5
No 7.5
NA
NA
NA
NA
NA
NA
NA
300
300
260
NA
75
100
100
100
100
100
100
100
100
NP
NP
NP
NA
46 1
42 0
31 0
42 0
1.0 6 NA
6.5 55 3
6.0 54 0
NP 33 0
6.5 31 0
ASA = acetylsalicylic acid; BP = blood pressure; EF = ejection fraction; LDL = low-density lipoprotein; NP = not performed. NA = not applicable or not available; MUGA = multigated acquisition;
was made because of the patient’s symptoms, evidence of serious exercise-induced ischemia, a marked myocardial perfusion abnormality, her high-risk coronary anatomy, and our belief that she was not a good candidate for retransplantation. The coronary artery bypass procedure
HDL
=
8.4 40
0
high-density lipoprotein;
was performed with standard techniques. A segment of vein was harvested from the right arm, and the left internal mammary artery was dissected off the chest wall. The left ventricle and apical portion of the right ventricle were encased in a markedly thickened and tightly adher-
A
B Fig 1. Left coronary angiogram in a right anterior oblique projection shows 45% narrowing of the proximal left anterior descending artery and a 50% stenosis of the proximal circumflex artery at its origin. The left main artery is free of disease.
Fig 2. Exercise (A) and redistribution ( B ) tomographic thallium images 1 year before operation. An area of poor perfusion is apparent along the anterior wall, but no reversible ischemia was evident during the 4-hour or 24-hour resting studies. No electrocardiographic evidence of ischemia was noted.
108
COPELAND ET AL CABG AFTER CARDIAC TRANSPLANTATION
Ann Thorac Surg 1990;49:1Of+lO
Table 2. Hemodynamic Measurements Before Coronary
Artery Bypass Grafting Chamber
A
B
Fig 3. Exercise (A) and redistribution (B) tomographic thallium images 1 week before operation. A larger area of poor perfusion is now apparent along the anterolateral wall, which redistributes at 4 hours. New significant electrocardiographic evidence of ischemia was also noted during exercise.
ent visceral pericardium. Pericardiectomy appeared to enhance myocardial filling and contractility. Because of the relatively large size of the circumflex vessel (2 mm) and small caliber of the distal left anterior descending artery (1 to 1.5 mm) by probe calibration, we elected to anastomose the left internal mammary artery to the circumflex-marginal artery; we anastomosed the vein harvested from the right forearm to the left anterior descending artery. The patient was weaned from cardiopulmonary bypass without difficulty and was discharged on the eleventh postoperative day. An exercise thallium study performed 3 weeks postoperatively showed no evidence of reversible ischemia (Fig 5). The patient was able to exercise for 7.2 minutes despite the presence of an upper respiratory infection; she stopped because of leg fatigue, but attained a heart rate of 150 beats per minute and a systolic blood pressure of 144 mm Hg for a double product of 21,600. After 6 months of follow-up, she remains asymptomatic.
Right atrium a wave v wave Mean Right ventricle Pulmonary artery Systolic/diastolic Mean Pulmonary capillary wedge a wave v wave Mean Left ventricular
Pressure (mm Hg) 20 20 15 40/17 40125 28 27 25 22 170125
Comment Cardiac transplantation in our current series of tripletherapy patients has resulted in a survival rate of 94% for 1 year and 92% for 2 years. This patient originally started in a noncyclosporine protocol group (5-year actuarial survival, 34%) and was switched to cyclosporine because of severe osteoporosis and striking cushingoid features. She was diabetic and moderately obese and had had four rejection episodes and five episodes of serious infection. Because of her less than ideal condition at age 58 years, she was believed not to be a good candidate for retransplantation when her left main coronary artery stenosis was diagnosed. Furthermore, the 6-to-12-month waiting period for a donor for a blood type 0 potential cardiac recipient was believed to be prohibitive in view of her dyspnea, positive thallium stress test, and 85% left main stenosis [5]. Coronary revascularization, whether by percutaneous
A
B
Fig 4. Left coronary angiogram in a right anterior oblique projection. The left main artery now has an 85% stenosis in its midportion.
Fig 5. Exercise (A) and redistribution (B)tomographic thallium images 6 weeks after operation. An area of mild decreased perfusion is apparent along the anterior wall, but there is no evidence of reversible ischemia. No new electrocardiographic evidence of ischemia was noted during exercise.
Ann Thorac Surg 1990:49:106-10
coronary angioplasty or by coronary artery bypass grafting, is generally not applicable to most patients with graft atherosclerosis because the disease process is diffuse, involving the distal vessels, and because it is frequently rapidly progressive [2, 6, 71. Retransplantation has been the only option available for most heart transplant recipients with severe accelerated coronary artery disease, although several cases of successful coronary angioplasty have been reported [4,8]. Longer follow-up information is needed for better assessment of the impact of this latter approach, as is also true for this patient who underwent successful coronary artery bypass grafting. Because of evidence of left main coronary artery disease and severe stenosis of the proximal left anterior descending and circumflex arteries, we considered percutaneous coronary angioplasty with percutaneous cardiopulmonary bypass, but with the long-term results of this technique unknown and the high risk in this patient with a previous open heart operation, this method of myocardial revascularization and protection was not pursued [ 9 ] . The pathophysiology of accelerated graft atherosclerosis is unknown, but it may involve injury during preservation or an immunological response at the endothelium of the coronary vessels, or it may be multifactorial, involving one or more known risk factors for coronary artery disease [2, 7, 10, 111. Attempts to relate development of accelerated graft atherosclerosis with the usual risk factors associated with coronary artery disease have not been useful in the management of these patients, although lowering of serum lipids and discontinuing smoking are recommended by most researchers [l, 2, 7, 12-14]. The use of platelet inhibiting agents has also not been of proven benefit, although experimental animal work has suggested a role for platelet inhibiting agents [15, 161. Our patient had adult-onset diabetes and systemic hypertension and was a nonsmoker. Her cholesterol and triglyceride levels were elevated, with a low level of high-density lipoprotein cholesterol at her last screening 1 year before angiographic documentation of the left main stenosis. Reports conflict, however, with regard to the value of these determinants in predicting development of accelerated graft atherosclerosis [2, 12-14]. Coronary angiography in the previous year may have precipitated development of the left main stenosis, if the left coronary catheter had irritated and denuded the endothelium, resulting in a localized hyperplastic reaction similar to that which occurs in restenosis after successful coronary angioplasty [17]. This is unlikely because the coronary stenoses of the left anterior descending and circumflex arteries had also progressed substantially. This patient also had anatomical evidence of major constrictive pericarditis at the time of operation, with visibly significant improvement in ventricular filling after pericardiectomy. The preoperative hemodynamic measurements were obtained at an outside institution, and specific waveform data are unavailable, although the pressures may have suggested a restrictive process (Table 2). This is an important finding in view of the frequency of restrictive abnormalities observed after transplantation. This report of successful coronary bypass grafting in a cardiac transplant recipient has shown that even high-risk
COPELAND ET AL CABG AFTER CARDIAC TRANSPLANTATION
109
patients may benefit from coronary revascularization if high-risk coronary anatomy is present or if the patient is severely symptomatic. Based on our experience and that of other investigators, we believe that coronary revascularization by either coronary bypass grafting or coronary angioplasty should be considered in patients who are at risk of sudden death or serious cardiac dysfunction while being considered for or awaiting retransplantation. Efforts at earlier identification of accelerated graft atherosclerosis are of prognostic importance and may provide time for considering current therapeutic alternatives [181. Reducing the risk of development of coronary artery occlusive disease in heart transplant recipients and its progression during long-term follow-up is one of the most important unsolved challenges to continued improvement in longevity after successful cardiac transplantation.
References 1. Copeland JC. Cardiac transplantation. Curr Prob Cardiol 1988;13:188-214. 2. Gao SZ, Schroeder JS, Alderman EL, et al. Clinical and laboratory correlates of accelerated coronary artery disease in the cardiac transplant patient. Circulation 1987;76(Suppl 5): 56-61. 3. Gao SZ, Schroeder J, Hunt S, Billingham M, Stinson E. Myocardial infarction in cardiac transplant patients [Abstract]. Circulation 1988;78(Suppl2):438. 4. Vetrovec GW, Cowley MJ, Newton CM, et al. Applications of percutaneous transluminal coronary angioplasty in cardiac transplantation. Circulation 1988;78(Suppl 3):83-6. 5. European Coronary Surgery Study Group. Prospective randomized study of coronary artery bypass surgery in stable angina pectoris. Lancet 1980;2:491-5. 6. Pascoe EA, Barnhart GR, Carter WH, et al. The prevalence of cardiac allograft atherosclerosis. Transplantation 1987;44: 838-9. 7. Gao SZ, Alderman EL, Schroeder JS, Silverman JF, Hunt SA. Accelerated coronary vascular disease in the heart transplant patient: coronary arteriographic findings. J Am Coll Cardiol 1988;12:334-40. 8. Gao SZ, Schroeder JS, Hunt S, Stinson EB. Retransplantation for severe accelerated coronary artery disease in heart transplant recipients. Am J Cardiol 1988;62:876-81. 9. Vogel RA. The Maryland experience: angioplasty and valvuloplasty using percutaneous cardiopulmonary support. Am J Cardiol 1988;62:11K4K. 10. Palmer DC, Tsai CC, Roodman ST, et al. Heart graft atherosclerosis. An ominous finding. Transplantation 1985;39:38.5 8. 11. Billingham ME. Diseases of the transplanted heart. In: Symons C, ed. Specific heart muscle disease. Bristol, Great Britain: John Wright-Bon, 1983:130-9. 12. Uretsky BF, Murali S, Reddy PS, et al. Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation 1987;76:827-34. 13. Wahlers T, Herrmann G, Jurmann M, Fieguth HG, Haverich A. Risk factors for the development of graft atherosclerosis in patients following orthotopic cardiac transplantation [Abstract]. J Heart Transplant 1988;760. 14. Zusman DR, Stinson EB, Oyer PE, et al. Determinants of accelerated graft atherosclerosis in conventional and cyclosporine treated heart transplant recipients [Abstract]. Heart Transplant 1985;4:587.
110
COPELAND ET AL CABG AFTER CARDIAC TRANSPLANTATION
15. Lurie KG, Billingham ME, Jamieson SW, Harrison DC, Reitz BA. Pathogenesis and prevention of graft atherosclerosis in an experimental heart transplant model. Transplantation 1981;31:41-7. 16. Griepp RB, Stinson EB, Bieber CP, et al. Control of graft atherosclerosis in human heart transplant recipients. Surgery 1977;81:262-9.
Ann Thorac Surg 1990;49:10&10
17. Blackshear JL, OCallaghan WG, Califf RM. Medical approaches to prevention of restenosis after coronary angioplasty. J Am Coll Cardiol 1987;9:83448. 18. Dyne P, Butman S, Hurst P, Wild J, Copeland J. Accelerated graft atherosclerosis after cardiac transplantation: Can serial angiograms identify recipients at risk [Abstract]? Clin Res 1989;3792A.
Notice From the American Board of Thoracic Surgery The part 1 (written) examination will be held at the HyattRegency, Dallas Fort Worth Airport, Dallas TX, on February 3, 1991. The closing date for registration is August 1, 1990. To be admissible for the part I1 (oral) examination, a candidate must have successfully completed the part I (written) examination.
A candidate applying for admission to the certifying examination must fulfill all the requirements of the board in force at the time the application is received. Please address all communications to the American Board of Thoracic Surgery, One Rotary Center, Suite 803, Evanston, IL 60201.
Severe stenosis of the left main coronary artery developed in a 58-year-old woman 9 years after orthotopic heart transplantation. Because of serious reversible myocardial ischemia and the high-risk nature of the coronary disease, coronary artery bypass grafting was performed, with no complications. Possible risk factors for the development of coronary arterial disease and its management in the transplant population are discussed. (Ann Thorac Surg 1990;49:106-10)
A
ccelerated graft atherosclerosis is a major obstacle in long-term management of cardiac transplant recipients. It may be acute, occurring as sudden death, silent myocardial infarction, or acute congestive heart failure, or it may be identified as silent myocardial ischemia, detected by routine stress testing, or detected as asymptomatic coronary arterial narrowing on routine annual coronary angiography [l-31. Attempts to identify patients who are at risk for premature coronary atherosclerosis have not had reliable results, and antiplatelet regimens and changes in the immunosuppressive therapy have not been of proven benefit. Coronary revascularization by coronary artery bypass grafting has not been advocated or attempted because of the diffuse nature of the coronary arterial disease in this population, and because chronic steroid and immunosuppressive therapy increase the risk of perioperative infections and delay in the wound healing process. Recently, successful percutaneous coronary angioplasty for discrete proximal coronary stenoses has been reported in selected patients [4]. Our patient, who underwent cardiac transplantation more than 9 years ago, had new asymptomatic proximal atherosclerotic coronary arterial narrowings 1year before dyspnea on exertion developed; she was diagnosed as having new and severe left main arterial stenosis. Coronary revascularization was believed necessary because of the high-risk location of the coronary stenoses, evidence of serious reversible ischemia on exercise thallium scintigraphy, and the risk associated with the waiting period for retransplanta tion. The patient is a 58-year-old woman who underwent orthotopic cardiac transplantation for idiopathic cardioAccepted for publication June 28, 1989. Address reprint requests to Dr Butman, Cardiology Section, Rm 6402, University Hospital, 1501 N Campbell Ave, Tucson, AZ 85724.
0 1990 by The Society of Thoracic Surgeons
myopathy on December 3, 1979. Her clinical course, events, and yearly laboratory data are summarized in Table 1. She had adult-onset diabetes and required an oral hypoglycemic agent for the 3 years before her current admission to the hospital. Systemic hypertension developed 2 years before this admission and was well controlled with antihypertensive therapy. Accelerated graft atherosclerosis was first documented 6 years after transplantation, with minimal coronary arterial stenosis of the proximal left anterior descending artery and pruning of the distal vessels. One year before her current admission, she was noted to have a 50% stenosis at the takeoff of the circumflex artery and a long 45% narrowing of the proximal left anterior descending artery as measured by digital calipers (Fig 1). The right coronary artery was free of notable disease. The myocardial blush was poor on left coronary angiography, and there was pruning of the distal vessels. Exercise thallium scintigraphy did not show evidence of reversible myocardial ischemia, although perfusion of the anterolateral wall was less than normal (Fig 2). Twentyfour-hour ambulatory monitoring of the ST segment for silent ischemia was also normal. Seven years after transplantation, 2 years before the present admission, for unrelated reasons, her immunosuppressive regimen was changed from one of prednisone and azathioprine to cyclosporine, azothioprine, and a lowered dose of prednisone. In the 3 months before the present admission, the patient noted the onset of exertional chest discomfort and dyspnea. She was able to exercise for 8.4 minutes on a modified Bruce protocol, and thallium scintigraphy showed a large area of reversible ischemia in the anterolateral wall (Fig 3). Significant ST segment depression was evident, which was also new. Coronary angiography revealed a new 85% stenosis of the left main coronary artery, as well as progression of the disease in the proximal circumflex and left anterior descending coronary arteries (Fig 4). The hemodynamic data are shown in Table 2. On examination, the patient appeared cushingoid, her blood pressure was 118/78 mm Hg, and cardiac examination revealed a fourth heart sound. Examination of the extremities revealed healed superficial ulcers and brawny discoloration in the lower legs. There were no obvious usable venous conduits in either the greater or lesser saphenous venous systems because of previous bilateral greater saphenous vein strippings. The decision to perform coronary artery bypass grafting 0003-4975/90/$3.50
COPELAND ET AL CABG AFTER CARDIAC TRANSPLANTATION
Ann Thorac Surg 1990;49: 1 0 6 10
107
Table 1. Lipid Levels and Immunosuppressive and Medical Therapy During Follow-up Years After Transplantation Variable Heart rate (bpm) Systolic BP (mm Hg) Diastolic BP (mm Hg) Total cholesterol (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Triglycerides (mgW ASA use Prednisone (mg/day) Cyclosporine (mg/day) Azothioprine (mg/day1 Exercise time (min) MUGA EF (%) No. of acute rejections
Preoperative
1
2
3
4
5
6
7
8
9
85
100
98
100
103
NA
100
112
98
100
100
100
125
122
118
NA
128
128
160
118
70
60
70
95
78
NA
98
98
100
78
NA
NA
NA
252
222
277
277
214
222
184
NA
NA
NA
109
118
188
187
120
NA
200
NA
NA
NA
38
35
35
36
26
NA
NA
NA
215
361
231
345
271
404
340
272
369
No NA
Yes 20
Yes 25
Yes 25
Yes 20
Yes 20
Yes 17.5
No 7.5
No 7.5
No 7.5
NA
NA
NA
NA
NA
NA
NA
300
300
260
NA
75
100
100
100
100
100
100
100
100
NP
NP
NP
NA
46 1
42 0
31 0
42 0
1.0 6 NA
6.5 55 3
6.0 54 0
NP 33 0
6.5 31 0
ASA = acetylsalicylic acid; BP = blood pressure; EF = ejection fraction; LDL = low-density lipoprotein; NP = not performed. NA = not applicable or not available; MUGA = multigated acquisition;
was made because of the patient’s symptoms, evidence of serious exercise-induced ischemia, a marked myocardial perfusion abnormality, her high-risk coronary anatomy, and our belief that she was not a good candidate for retransplantation. The coronary artery bypass procedure
HDL
=
8.4 40
0
high-density lipoprotein;
was performed with standard techniques. A segment of vein was harvested from the right arm, and the left internal mammary artery was dissected off the chest wall. The left ventricle and apical portion of the right ventricle were encased in a markedly thickened and tightly adher-
A
B Fig 1. Left coronary angiogram in a right anterior oblique projection shows 45% narrowing of the proximal left anterior descending artery and a 50% stenosis of the proximal circumflex artery at its origin. The left main artery is free of disease.
Fig 2. Exercise (A) and redistribution ( B ) tomographic thallium images 1 year before operation. An area of poor perfusion is apparent along the anterior wall, but no reversible ischemia was evident during the 4-hour or 24-hour resting studies. No electrocardiographic evidence of ischemia was noted.
108
COPELAND ET AL CABG AFTER CARDIAC TRANSPLANTATION
Ann Thorac Surg 1990;49:1Of+lO
Table 2. Hemodynamic Measurements Before Coronary
Artery Bypass Grafting Chamber
A
B
Fig 3. Exercise (A) and redistribution (B) tomographic thallium images 1 week before operation. A larger area of poor perfusion is now apparent along the anterolateral wall, which redistributes at 4 hours. New significant electrocardiographic evidence of ischemia was also noted during exercise.
ent visceral pericardium. Pericardiectomy appeared to enhance myocardial filling and contractility. Because of the relatively large size of the circumflex vessel (2 mm) and small caliber of the distal left anterior descending artery (1 to 1.5 mm) by probe calibration, we elected to anastomose the left internal mammary artery to the circumflex-marginal artery; we anastomosed the vein harvested from the right forearm to the left anterior descending artery. The patient was weaned from cardiopulmonary bypass without difficulty and was discharged on the eleventh postoperative day. An exercise thallium study performed 3 weeks postoperatively showed no evidence of reversible ischemia (Fig 5). The patient was able to exercise for 7.2 minutes despite the presence of an upper respiratory infection; she stopped because of leg fatigue, but attained a heart rate of 150 beats per minute and a systolic blood pressure of 144 mm Hg for a double product of 21,600. After 6 months of follow-up, she remains asymptomatic.
Right atrium a wave v wave Mean Right ventricle Pulmonary artery Systolic/diastolic Mean Pulmonary capillary wedge a wave v wave Mean Left ventricular
Pressure (mm Hg) 20 20 15 40/17 40125 28 27 25 22 170125
Comment Cardiac transplantation in our current series of tripletherapy patients has resulted in a survival rate of 94% for 1 year and 92% for 2 years. This patient originally started in a noncyclosporine protocol group (5-year actuarial survival, 34%) and was switched to cyclosporine because of severe osteoporosis and striking cushingoid features. She was diabetic and moderately obese and had had four rejection episodes and five episodes of serious infection. Because of her less than ideal condition at age 58 years, she was believed not to be a good candidate for retransplantation when her left main coronary artery stenosis was diagnosed. Furthermore, the 6-to-12-month waiting period for a donor for a blood type 0 potential cardiac recipient was believed to be prohibitive in view of her dyspnea, positive thallium stress test, and 85% left main stenosis [5]. Coronary revascularization, whether by percutaneous
A
B
Fig 4. Left coronary angiogram in a right anterior oblique projection. The left main artery now has an 85% stenosis in its midportion.
Fig 5. Exercise (A) and redistribution (B)tomographic thallium images 6 weeks after operation. An area of mild decreased perfusion is apparent along the anterior wall, but there is no evidence of reversible ischemia. No new electrocardiographic evidence of ischemia was noted during exercise.
Ann Thorac Surg 1990:49:106-10
coronary angioplasty or by coronary artery bypass grafting, is generally not applicable to most patients with graft atherosclerosis because the disease process is diffuse, involving the distal vessels, and because it is frequently rapidly progressive [2, 6, 71. Retransplantation has been the only option available for most heart transplant recipients with severe accelerated coronary artery disease, although several cases of successful coronary angioplasty have been reported [4,8]. Longer follow-up information is needed for better assessment of the impact of this latter approach, as is also true for this patient who underwent successful coronary artery bypass grafting. Because of evidence of left main coronary artery disease and severe stenosis of the proximal left anterior descending and circumflex arteries, we considered percutaneous coronary angioplasty with percutaneous cardiopulmonary bypass, but with the long-term results of this technique unknown and the high risk in this patient with a previous open heart operation, this method of myocardial revascularization and protection was not pursued [ 9 ] . The pathophysiology of accelerated graft atherosclerosis is unknown, but it may involve injury during preservation or an immunological response at the endothelium of the coronary vessels, or it may be multifactorial, involving one or more known risk factors for coronary artery disease [2, 7, 10, 111. Attempts to relate development of accelerated graft atherosclerosis with the usual risk factors associated with coronary artery disease have not been useful in the management of these patients, although lowering of serum lipids and discontinuing smoking are recommended by most researchers [l, 2, 7, 12-14]. The use of platelet inhibiting agents has also not been of proven benefit, although experimental animal work has suggested a role for platelet inhibiting agents [15, 161. Our patient had adult-onset diabetes and systemic hypertension and was a nonsmoker. Her cholesterol and triglyceride levels were elevated, with a low level of high-density lipoprotein cholesterol at her last screening 1 year before angiographic documentation of the left main stenosis. Reports conflict, however, with regard to the value of these determinants in predicting development of accelerated graft atherosclerosis [2, 12-14]. Coronary angiography in the previous year may have precipitated development of the left main stenosis, if the left coronary catheter had irritated and denuded the endothelium, resulting in a localized hyperplastic reaction similar to that which occurs in restenosis after successful coronary angioplasty [17]. This is unlikely because the coronary stenoses of the left anterior descending and circumflex arteries had also progressed substantially. This patient also had anatomical evidence of major constrictive pericarditis at the time of operation, with visibly significant improvement in ventricular filling after pericardiectomy. The preoperative hemodynamic measurements were obtained at an outside institution, and specific waveform data are unavailable, although the pressures may have suggested a restrictive process (Table 2). This is an important finding in view of the frequency of restrictive abnormalities observed after transplantation. This report of successful coronary bypass grafting in a cardiac transplant recipient has shown that even high-risk
COPELAND ET AL CABG AFTER CARDIAC TRANSPLANTATION
109
patients may benefit from coronary revascularization if high-risk coronary anatomy is present or if the patient is severely symptomatic. Based on our experience and that of other investigators, we believe that coronary revascularization by either coronary bypass grafting or coronary angioplasty should be considered in patients who are at risk of sudden death or serious cardiac dysfunction while being considered for or awaiting retransplantation. Efforts at earlier identification of accelerated graft atherosclerosis are of prognostic importance and may provide time for considering current therapeutic alternatives [181. Reducing the risk of development of coronary artery occlusive disease in heart transplant recipients and its progression during long-term follow-up is one of the most important unsolved challenges to continued improvement in longevity after successful cardiac transplantation.
References 1. Copeland JC. Cardiac transplantation. Curr Prob Cardiol 1988;13:188-214. 2. Gao SZ, Schroeder JS, Alderman EL, et al. Clinical and laboratory correlates of accelerated coronary artery disease in the cardiac transplant patient. Circulation 1987;76(Suppl 5): 56-61. 3. Gao SZ, Schroeder J, Hunt S, Billingham M, Stinson E. Myocardial infarction in cardiac transplant patients [Abstract]. Circulation 1988;78(Suppl2):438. 4. Vetrovec GW, Cowley MJ, Newton CM, et al. Applications of percutaneous transluminal coronary angioplasty in cardiac transplantation. Circulation 1988;78(Suppl 3):83-6. 5. European Coronary Surgery Study Group. Prospective randomized study of coronary artery bypass surgery in stable angina pectoris. Lancet 1980;2:491-5. 6. Pascoe EA, Barnhart GR, Carter WH, et al. The prevalence of cardiac allograft atherosclerosis. Transplantation 1987;44: 838-9. 7. Gao SZ, Alderman EL, Schroeder JS, Silverman JF, Hunt SA. Accelerated coronary vascular disease in the heart transplant patient: coronary arteriographic findings. J Am Coll Cardiol 1988;12:334-40. 8. Gao SZ, Schroeder JS, Hunt S, Stinson EB. Retransplantation for severe accelerated coronary artery disease in heart transplant recipients. Am J Cardiol 1988;62:876-81. 9. Vogel RA. The Maryland experience: angioplasty and valvuloplasty using percutaneous cardiopulmonary support. Am J Cardiol 1988;62:11K4K. 10. Palmer DC, Tsai CC, Roodman ST, et al. Heart graft atherosclerosis. An ominous finding. Transplantation 1985;39:38.5 8. 11. Billingham ME. Diseases of the transplanted heart. In: Symons C, ed. Specific heart muscle disease. Bristol, Great Britain: John Wright-Bon, 1983:130-9. 12. Uretsky BF, Murali S, Reddy PS, et al. Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation 1987;76:827-34. 13. Wahlers T, Herrmann G, Jurmann M, Fieguth HG, Haverich A. Risk factors for the development of graft atherosclerosis in patients following orthotopic cardiac transplantation [Abstract]. J Heart Transplant 1988;760. 14. Zusman DR, Stinson EB, Oyer PE, et al. Determinants of accelerated graft atherosclerosis in conventional and cyclosporine treated heart transplant recipients [Abstract]. Heart Transplant 1985;4:587.
110
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15. Lurie KG, Billingham ME, Jamieson SW, Harrison DC, Reitz BA. Pathogenesis and prevention of graft atherosclerosis in an experimental heart transplant model. Transplantation 1981;31:41-7. 16. Griepp RB, Stinson EB, Bieber CP, et al. Control of graft atherosclerosis in human heart transplant recipients. Surgery 1977;81:262-9.
Ann Thorac Surg 1990;49:10&10
17. Blackshear JL, OCallaghan WG, Califf RM. Medical approaches to prevention of restenosis after coronary angioplasty. J Am Coll Cardiol 1987;9:83448. 18. Dyne P, Butman S, Hurst P, Wild J, Copeland J. Accelerated graft atherosclerosis after cardiac transplantation: Can serial angiograms identify recipients at risk [Abstract]? Clin Res 1989;3792A.
Notice From the American Board of Thoracic Surgery The part 1 (written) examination will be held at the HyattRegency, Dallas Fort Worth Airport, Dallas TX, on February 3, 1991. The closing date for registration is August 1, 1990. To be admissible for the part I1 (oral) examination, a candidate must have successfully completed the part I (written) examination.
A candidate applying for admission to the certifying examination must fulfill all the requirements of the board in force at the time the application is received. Please address all communications to the American Board of Thoracic Surgery, One Rotary Center, Suite 803, Evanston, IL 60201.
