- Email: [email protected]
Unprotected left main coronary artery stenting for cardiac allograft vasculopathy
Unprotected Left Main Coronary Artery Stenting for Cardiac Allograft Vasculopathy Albert W. Chan, MD, MSc, FRCP(C), Ronald G. Carere, MD, FRCP(C), FACC, Shailesh Khatri, MBBS, FRACP, Anthony Della Siega, MD, FRCP(C), Andrew P. Ignaszewski, MD, FRCP(C), FACC, and John G. Webb, MD, FRCP(C), FACC Cardiac allograft vasculopathy is the leading cause of death after the first year of transplantation. Treatment outcomes with medication, balloon angioplasty, bypass surgery, and retransplantation have been disappointing. We present our initial experience with stenting of the left main coronary artery in the setting of allograft vasculopathy. J Heart Lung Transplant 2001;20:776–780.
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ardiac allograft vasculopathy (CAV) develops in 25% to 50% of patients by 5 years post-cardiac transplantation, and is the commonest cause of death after the first year.1– 4. The incidence of coronary artery disease-related events (death or retransplantation) is about 7% at 5 years.1. Risk factors for CAV include age, male gender, and hypertension in the donor, and male gender, early severe rejection, cytomegaloviral infection, immunosuppressive drugs, insulin resistance, hyperlipidemia, and hypertension in the recipient.1,5,6 Detection of CAV has been through routine surveillance cardiac catheterization. Coronary bypass surgery is the standard treatment for native left main coronary artery (LMCA) disease. Unfortunately, in post-transplant patients, surgery is associated with high peri-operative mortality and poor survival rates at 1 year.7 Retransplantation is limited by the shortage of donors and poor late survival.8 Coronary balloon angioplasty is associated with a From the Division of Cardiology, St. Paul’s Hospital, Vancouver, British Columbia, Canada Submitted June 23, 2000; revised September 12, 2000; accepted October 5, 2000. Reprint requests: Dr. John G. Webb, Director of Interventional Cardiology and Cardiac Catheterization, St. Paul’s Hospital, 502-1160 Burrard Street, Vancouver, British Columbia, V6Z 2E8, Canada. Telephone: (604) 681-5836. Fax: (604) 669-3356. Email: [email protected]. Copyright © 2001 by the International Society for Heart and Lung Transplantation. 1053-2498/01/$–see front matter PII S1053-2498(00)00227-8
776
high restenosis rate in the setting of CAV. 7 Coronary stenting is a more attractive alternative, 9,10 since the results of stenting in the native LMCA in high-risk surgical candidates seem to be acceptable.11–16 Unprotected LMCA stenting is defined as such a procedure performed in the setting where none of the left coronary arteries (anterior descending, circumflex, or intermedius) is anastomosed to a patent bypass graft and, hence, is associated with transient global myocardial ischemia. We report our initial experience with palliative coronary stenting of the unprotected LMCA in the heart transplantation population (Table I).
PATIENT 1 Accelerated CAV in the LMCA occurred in a patient at 2 years post-cardiac transplantation for sarcoid heart disease (Figure 1, top panel). Leg amputation due to arterial thrombosis and left hemiparesis precluded retransplantation. The procedure was carried out using a 8-French left Judkins short-tip guide catheter and 2, 0.014inch Choice wires (Scimed, Maple Grove, MN). One traversed the left anterior descending (LAD) and the other the ramus intermedius (RI). The ostial LMCA lesion was pre-dilated using a 3 mm Maxxum balloon (Scimed, Galway, Ireland). A 9-mm, 7-cell NIRoyal stent (Scimed, Maple Grove, MN) was deployed using a 3.5 mm ⫻ 13 mm balloon and dilated to 14 atmospheres. Dissection was treated with 2 additional 9-mm stents in the distal LMCA and the ostial LAD (Figure 1, middle panel).
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TABLE I Clinical profile* of the patients. Patients Age (years) Gender Years after transplantation Etiology of heart failure before transplantation Cormorbidities Diabetes mellitus Hypertension Hyperlipidemia Renal dysfunction Homocysteinemia History of significant graft rejection ⬍ 6 months after transplantation Cytomegalovirus-seronegative recipient Left ventricular ejection fraction (%)
1
2
3
50 Female 2 Sarcoidosis
59 Male 8 Ischemic
58 Male 4 1st Idiopathic 2nd Graft vasculopathy
⫹ – ⫹ – ⫹ –
– ⫹ ⫹ ⫹ ⫹ –
– ⫹ ⫹ ⫹ ⫹ ⫹
– 50
⫹ 60
– 30
⫹, present; –, absent. *Diabetes mellitus—fasting serum glucose level ⬎6.9 mmol/liter; hypertension: systemic blood pressure ⬎140 mm Hg systolic or ⬎90 mm Hg diastolic; hyperlipidemia; LDL cholesterol ⬎3.4 mmol/liter, triglycerides ⬎2.3 mmol/liter; homocysteinemia: serum homocysteine level ⬎9.2 mol/liter; left ventricular ejection fraction was estimated using Simpson’s method from the right anterior oblique view during angiography; renal dysfunction: serum creatinine ⬎140 mol/liter or an increase of ⬎30% post-transplantation; significant graft rejection: recurrent ISHLT rejection grade 3A or above.
The anti-coagulation regimen included pre-medication with aspirin, ticlopidine, and abciximab, followed by ticlopidine 500 mg daily for 2 weeks and aspirin indefinitely. The patient remained hemodynamically stable throughout the procedure. One year later, the minimal lumen diameter (MLD) of the LMCA had diffusely reduced to 2.8 mm by quantitative analysis (Figure 1, bottom panel).
PATIENT 2 This patient presented with CAV in his LAD and the circumflex (Cx) at 5 years post-cardiac transplantation. The Cx was totally occluded. The LAD was initially treated with coronary stenting. Restenosis required repeat angioplasty. One year later, a new LMCA stenosis and progression of a mid right coronary artery (RCA) lesion were documented with patency of the LAD stent (Figure 2, top). We initially revascularized the RCA using a 3.5 mm ⫻ 15 mm NIRoyal stent. For the LMCA lesion, a FL4 guide catheter (Scimed, Maple Grove, Minnesota) and a 0.014-inch Choice wire were used. A 15-mm NIRoyal stent was deployed by using a 4.0 mm ⫻ 15 mm balloon without pre-dilation, and no residual stenosis was present (Figure 2, middle panel). The patient received 30 days of clopidogrel 75 mg/day plus aspirin indefinitely. Repeat coronary angiography at 3 months showed diffuse in-stent restenosis (MLD ⫽ 2.6
mm) (Figure 2, bottom panel). The patient was listed for retransplantation.
PATIENT 3 The first cardiac allograft of this patient was complicated by CAV requiring retransplantation. Four years after retransplantation, CAV required stenting of the RCA. Just 8 months later, progression of previously mild disease in the LMCA, the LAD, and the RI was documented (Figure 3, a). Angioplasty was carried out with a 8-French FL4 guiding catheter, a Choice PT wire, which crossed to the LAD, and a Balance Middleweight wire (Guidant, Santa Clara, CA), which advanced to the RI. The LMCA lesion was pre-dilated with an undersized (3.5 mm ⫻ 20 mm) balloon at 6 atmospheres. A 9-mm NIRoyal stent was dilated to 4 mm in diameter in the ostium of the LMCA, resulting in no residual stenosis. The LAD lesion was pre-dilated with a 2.5 mm ⫻ 20 mm balloon, followed by deployment of the 16-mm long NIRoyal stent using the same balloon (Figure 3, b). The proximal RI lesion was treated with balloon angioplasty. Abciximab was given during the procedure. Clopidogrel was given for 30 days, in addition to aspirin. Five months after this procedure, the patient presented with cardiogenic shock and pulmonary edema. The LMCA was occluded, and the LAD
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FIGURE 2 Stenotic lesion was in the trunk of the
LMCA and the Cx was chronically occluded (top panel). Direct stenting of the LMCA resulted in no residual stenosis (middle panel). Follow-up angiography at 3 months shows restenosis (bottom panel).
DISCUSSION FIGURE 1 LMCA before intervention (top panel).
Stents in the proximal and distal segments of the LMCA, and in the ostial LAD, with normal blood flow to Cx through the stent struts (middle panel). Diffuse intimal proliferation in the LMCA with patent lumen in 1 year (bottom panel).
and the Cx were filled via collaterals from the RCA (Figure 3, c). The occlusion was promptly treated with repeat stenting of the LMCA, LAD, RI, and Cx. Intra-aortic balloon pump and eptifibitide infusion were used. TIMI grade 3 flow was achieved (Figure 3, d). The patient was subsequently discharged from the hospital and remained stable at 3-month follow-up.
Routine surveillance coronary angiography is the standard diagnostic test for CAV. A relationship between percutaneous coronary angioplasty and subsequent new left main stenosis has been reported,17–20 possibly as a consequence of catheter manipulation causing endothelial damage and intimal hyperplasia. The development of new left main stenosis in Patient 2 raises speculation that accelerated CAV in the LMCA may similarly develop as a result of catheter manipulation. Coronary bypass surgery has been the standard of treatment for native LMCA disease.21,22 Elective left main angioplasty has been associated with high angiographic success rates (94% to 99%) but a disappointing late outcome (1-year mortality and event-free survival were 15% to 56% and 38% to 44%, respectively).11,12,23 The latter is related to the
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FIGURE 3 (a) Accelerated CAV developed in the LMCA and the LAD. (b) Angiography
immediately after stenting. (c) LMCA occlusion associated with cardiogenic shock occurred at 5 months. (d) LMCA and the three main branches were immediately treated with stents.
unpredictable and catastrophic consequences of abrupt vessel closure and the high restenosis rate. Coronary stenting using high-pressure inflation appears to be a superior therapy. Four recent series (a total of 331 patients)14 –-16,24 of elective LMCA stenting reported procedural success in 98% to 100% with favorable results at 1 year (0% to 8% mortality, 78% to 82% event-free survival) in non-CAV patients. The majority of the restenosis occurred in the distal LMCA bifurcation.14,16,24 Due to the shortage of donors and poor results with bypass surgery, percutaneous coronary intervention may be a last option for the patients who develop CAV. Two heart transplant patients who underwent unprotected LMCA stenting have been previously reported in the medical literature; 1 required elective intubation and ventilation,25 and the other received cardiopulmonary support.26 In our cases, initial technical success was achieved in all patients. Two patients remained well at 3 months and 12 months of follow-up, but the third patient had a reocclusion within 5 months after the procedure. Stent selection must be individualized. We uti-
lized NIRoyal stents in all 3 cases as its radiopaque gold coating provided excellent radiopacity, facilitating precise placement. Other stents with adequate radial support would also be suitable.11,16 Co-existence of significant RCA disease with LMCA stenosis may prompt revascularization of the RCA before palliative left main angioplasty (as in Patient 2). Ischemic times of less than 1 minute were well tolerated in the presence of a patent RCA and preserved LV function.11 Because of this, in the absence of cardiogenic shock, the intra-aortic balloon pump was not used in 2 patients. One of the major concerns of stenting the LMCA is acute or sub-acute stent thrombosis, which would result in massive myocardial infarction, cardiogenic shock, and death. Adjunctive therapy for coronary stenting, such as clopidogrel and glycoprotein IIb/ IIIa inhibitors, should be strongly considered to minimize the risk of complication. Currently, we routinely give clopidogrel 300 mg before procedure, followed by 75 mg daily for 30 days in addition to aspirin 325 mg daily. Coronary angiography should be repeated within a few months after LMCA stenting in CAV.
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Predictors of long-term patency after coronary stenting have not been reported in the cardiac transplant population. Whether any of the risk factors for CAV apply to stent restenosis is unknown. Although the use of intravascular ultrasonography (IVUS) to improve stent apposition was advocated by some investigators,24,27 whether IVUS guidance beyond angiography provides additional benefit for LMCA stenting (reducing restenosis) has been recently debated. With the use of high-pressure balloon inflation and preventive clopidogrel therapy for sub-acute thrombosis, recent large series supported the feasibility of LMCA stenting performed under angiographic guidance alone.16 IVUS was not used in our cases. Once a patient develops recurrent CAV, retransplantation should be considered. Our cases suggest that unprotected LMCA stenting in cardiac transplant patients is feasible, but its long-term clinical benefit remains uncertain. Since no optimal treatment has been established for CAV, stenting of the LMCA may be considered as a therapeutic option in this group of patients. However, the appropriate indications for such procedure remain to be determined. Newer technology, such as brachytherapy and pharmacologically coated stents, may offer hope for these patients but the safety and efficacy of these need to be established. An internationally coordinated registry may provide insight for the optimal treatment strategy of CAV. REFERENCES 1. Costanzo MR, Naftel DC, Pritzker MR et al. Heart transplant coronary artery disease detected by coronary angiography: a multi-institutional study of pre-operative donor and recipient risk factors. J Heart Lung Transplant 1998;17:744 –53. 2. Johnson DE, Alderman EL, Schroeder JS et al. Transplant coronary artery disease: Histopathologic correlations with angiographic morphology. J Am Coll Cardiol 1991;17:449 –57. 3. Uretsky BF, Muralli S, Reedy S et al. Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation 1987;76:827–34. 4. Grattan MT, Moreno-Cabral CE, Starnes VA et al. Eightyear results of cyclosporine-treated patients with cardiac transplants. J Thorac Cardiovasc Surg 1990;99:500 –9. 5. Weis M, Von Scheidt W. Cardiac allograft vasculopathy: a review. Circulation 1997;96:2069 –77. 6. Melnick JL, Adam E, DeBakey ME. Possible role of cytomegalovirus in atherogenesis. JAMA 1990;263:2204 –7. 7. Halle AA, DiSciascio G, Massin EK et al. Coronary angioplasty, atherectomy and bypass surgery in cardiac transplant recipients. J Am Coll Cardiol 1995;26:120 – 8. 8. Karawande SV, Ensley RD, Renlund DG et al. Cardiac retransplantation: a viable option? The Registry of the International Society for Heart and Lung Transplantation. Ann Thorac Surg 1992;54:840 – 4.
The Journal of Heart and Lung Transplantation July 2000 9. Jain SP, Ramee SR, White CJ et al. Coronary stenting in cardiac allograft vasculopathy. J Am Coll Cardiol 1998;32: 1636 – 40. 10. Wong PM, Piamsomboon C, Mathur A et al. Efficacy of coronary stenting in the management of cardiac allograft vasculopathy. Am J Cardiol 1998;82:239 – 41. 11. Ellis SG, Tamai H, Nobuyoshi M et al. Contemporary percutaneous treatment of unprotected left main coronary stenoses: initial results from a multicenter registry analysis 1994-1996. Circulation 1997;96:3867–72. 12. Kosuga K, Tamai H, Kawashima A et al. Initial and longterm results of elective angioplasty in unprotected left main coronary artery. Am J Cardiol 1999;1:32–7. 13. Karam C, Fajadet J, Cassagneau B et al. Results of stenting of unprotected left main coronary artery stenosis in patients at high surgical risk. Am J Cardiol 1998;82:975– 8. 14. Wong P, Wong V, Tse KK et al. A prospective study of elective stenting in unprotected left main coronary disease. Cathet Cardiovasc Intervent 1999;46:153–9. 15. Kornowski R, Klutstein M, Satler LF et al. Impact of stents on clinical outcomes in percutaneous left main coronary artery revascularization. Am J Cardiol 1998;82:32–7. 16. Silvestri M, Barragan P, Sainsons J et al. Unprotected left main coronary artery stenting: immediate and medium-term outcome of 140 elective procedures. J Am Coll Cardiol 2000;35:1543–50. 17. Harper JM, Shah Y, Kern MJ, Vandormal MG. Progression of left main coronary artery stenosis following left anterior descending coronary artery angioplasty. Cathet Cardiovasc Diagn 1987;13:398 – 400. 18. Haraphongse M, Rossall RE. Subacute left main coronary stenosis following percutaneous transluminal coronary angioplasty. Cathet Cardiovasc Diagn 1987;13:401– 4. 19. Graf RH, Verani MS. Left main coronary artery stenosis: a possible complication of transluminal coronary angioplasty. Cathet Cardiovasc Diagn 1984;10:163– 6. 20. Waller BF, Pinkerton CA, Foster LN. Morphologic evidence of accelerated left main coronary artery stenosis: a late complication of percutaneous transluminal balloon angioplasty of the proximal left anterior descending coronary artery. J Am Coll Cardiol 1987;9:1019 –23. 21. The Veterans Administration Coronary Artery Bypass Surgery Cooperative Study Group. Eleven-year survival in the Veterans Administration randomized trial of coronary bypass surgery for stable angina. N Engl J Med 1984;311:1333–9. 22. Varnauskas E. Twelve-year follow-up of survival in the randomized European Coronary Surgery Study. N Engl J Med 1988;319:332–7. 23. O’Keefe JH, Hartzler GO, Rutherford BD et al. Left main coronary angioplasty: early and late results of 127 acute and elective procedures. Am J Cardiol 1989;64:144 –7. 24. Park SJ, Park SW, Hong MK et al. Stenting of unprotected left main coronary artery stenoses: immediate and late outcomes. J Am Coll Cardiol 1998;31:37– 42. 25. Weston MW, Spoto E, Aranda J, Sears N. Endovascular stenting of an unprotected left main coronary artery stenosis in a heart transplant patient. Clin Cardiol 1998;21:919 –22. 26. Kong W, Le May MR, Labinaz M, Daview RA. Stenting of an unprotected left main coronary artery stenosis in a cardiac transplant patient. Can J Cardiol 1999;15:1131–5. 27. Hong MK, Park SW, Lee CW et al. Intravascular ultrasound findings in stenting of unprotected left main coronary artery stenosis. Am J Cardiol 1998;82:670 –3.
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ardiac allograft vasculopathy (CAV) develops in 25% to 50% of patients by 5 years post-cardiac transplantation, and is the commonest cause of death after the first year.1– 4. The incidence of coronary artery disease-related events (death or retransplantation) is about 7% at 5 years.1. Risk factors for CAV include age, male gender, and hypertension in the donor, and male gender, early severe rejection, cytomegaloviral infection, immunosuppressive drugs, insulin resistance, hyperlipidemia, and hypertension in the recipient.1,5,6 Detection of CAV has been through routine surveillance cardiac catheterization. Coronary bypass surgery is the standard treatment for native left main coronary artery (LMCA) disease. Unfortunately, in post-transplant patients, surgery is associated with high peri-operative mortality and poor survival rates at 1 year.7 Retransplantation is limited by the shortage of donors and poor late survival.8 Coronary balloon angioplasty is associated with a From the Division of Cardiology, St. Paul’s Hospital, Vancouver, British Columbia, Canada Submitted June 23, 2000; revised September 12, 2000; accepted October 5, 2000. Reprint requests: Dr. John G. Webb, Director of Interventional Cardiology and Cardiac Catheterization, St. Paul’s Hospital, 502-1160 Burrard Street, Vancouver, British Columbia, V6Z 2E8, Canada. Telephone: (604) 681-5836. Fax: (604) 669-3356. Email: [email protected]. Copyright © 2001 by the International Society for Heart and Lung Transplantation. 1053-2498/01/$–see front matter PII S1053-2498(00)00227-8
776
high restenosis rate in the setting of CAV. 7 Coronary stenting is a more attractive alternative, 9,10 since the results of stenting in the native LMCA in high-risk surgical candidates seem to be acceptable.11–16 Unprotected LMCA stenting is defined as such a procedure performed in the setting where none of the left coronary arteries (anterior descending, circumflex, or intermedius) is anastomosed to a patent bypass graft and, hence, is associated with transient global myocardial ischemia. We report our initial experience with palliative coronary stenting of the unprotected LMCA in the heart transplantation population (Table I).
PATIENT 1 Accelerated CAV in the LMCA occurred in a patient at 2 years post-cardiac transplantation for sarcoid heart disease (Figure 1, top panel). Leg amputation due to arterial thrombosis and left hemiparesis precluded retransplantation. The procedure was carried out using a 8-French left Judkins short-tip guide catheter and 2, 0.014inch Choice wires (Scimed, Maple Grove, MN). One traversed the left anterior descending (LAD) and the other the ramus intermedius (RI). The ostial LMCA lesion was pre-dilated using a 3 mm Maxxum balloon (Scimed, Galway, Ireland). A 9-mm, 7-cell NIRoyal stent (Scimed, Maple Grove, MN) was deployed using a 3.5 mm ⫻ 13 mm balloon and dilated to 14 atmospheres. Dissection was treated with 2 additional 9-mm stents in the distal LMCA and the ostial LAD (Figure 1, middle panel).
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TABLE I Clinical profile* of the patients. Patients Age (years) Gender Years after transplantation Etiology of heart failure before transplantation Cormorbidities Diabetes mellitus Hypertension Hyperlipidemia Renal dysfunction Homocysteinemia History of significant graft rejection ⬍ 6 months after transplantation Cytomegalovirus-seronegative recipient Left ventricular ejection fraction (%)
1
2
3
50 Female 2 Sarcoidosis
59 Male 8 Ischemic
58 Male 4 1st Idiopathic 2nd Graft vasculopathy
⫹ – ⫹ – ⫹ –
– ⫹ ⫹ ⫹ ⫹ –
– ⫹ ⫹ ⫹ ⫹ ⫹
– 50
⫹ 60
– 30
⫹, present; –, absent. *Diabetes mellitus—fasting serum glucose level ⬎6.9 mmol/liter; hypertension: systemic blood pressure ⬎140 mm Hg systolic or ⬎90 mm Hg diastolic; hyperlipidemia; LDL cholesterol ⬎3.4 mmol/liter, triglycerides ⬎2.3 mmol/liter; homocysteinemia: serum homocysteine level ⬎9.2 mol/liter; left ventricular ejection fraction was estimated using Simpson’s method from the right anterior oblique view during angiography; renal dysfunction: serum creatinine ⬎140 mol/liter or an increase of ⬎30% post-transplantation; significant graft rejection: recurrent ISHLT rejection grade 3A or above.
The anti-coagulation regimen included pre-medication with aspirin, ticlopidine, and abciximab, followed by ticlopidine 500 mg daily for 2 weeks and aspirin indefinitely. The patient remained hemodynamically stable throughout the procedure. One year later, the minimal lumen diameter (MLD) of the LMCA had diffusely reduced to 2.8 mm by quantitative analysis (Figure 1, bottom panel).
PATIENT 2 This patient presented with CAV in his LAD and the circumflex (Cx) at 5 years post-cardiac transplantation. The Cx was totally occluded. The LAD was initially treated with coronary stenting. Restenosis required repeat angioplasty. One year later, a new LMCA stenosis and progression of a mid right coronary artery (RCA) lesion were documented with patency of the LAD stent (Figure 2, top). We initially revascularized the RCA using a 3.5 mm ⫻ 15 mm NIRoyal stent. For the LMCA lesion, a FL4 guide catheter (Scimed, Maple Grove, Minnesota) and a 0.014-inch Choice wire were used. A 15-mm NIRoyal stent was deployed by using a 4.0 mm ⫻ 15 mm balloon without pre-dilation, and no residual stenosis was present (Figure 2, middle panel). The patient received 30 days of clopidogrel 75 mg/day plus aspirin indefinitely. Repeat coronary angiography at 3 months showed diffuse in-stent restenosis (MLD ⫽ 2.6
mm) (Figure 2, bottom panel). The patient was listed for retransplantation.
PATIENT 3 The first cardiac allograft of this patient was complicated by CAV requiring retransplantation. Four years after retransplantation, CAV required stenting of the RCA. Just 8 months later, progression of previously mild disease in the LMCA, the LAD, and the RI was documented (Figure 3, a). Angioplasty was carried out with a 8-French FL4 guiding catheter, a Choice PT wire, which crossed to the LAD, and a Balance Middleweight wire (Guidant, Santa Clara, CA), which advanced to the RI. The LMCA lesion was pre-dilated with an undersized (3.5 mm ⫻ 20 mm) balloon at 6 atmospheres. A 9-mm NIRoyal stent was dilated to 4 mm in diameter in the ostium of the LMCA, resulting in no residual stenosis. The LAD lesion was pre-dilated with a 2.5 mm ⫻ 20 mm balloon, followed by deployment of the 16-mm long NIRoyal stent using the same balloon (Figure 3, b). The proximal RI lesion was treated with balloon angioplasty. Abciximab was given during the procedure. Clopidogrel was given for 30 days, in addition to aspirin. Five months after this procedure, the patient presented with cardiogenic shock and pulmonary edema. The LMCA was occluded, and the LAD
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The Journal of Heart and Lung Transplantation July 2000
FIGURE 2 Stenotic lesion was in the trunk of the
LMCA and the Cx was chronically occluded (top panel). Direct stenting of the LMCA resulted in no residual stenosis (middle panel). Follow-up angiography at 3 months shows restenosis (bottom panel).
DISCUSSION FIGURE 1 LMCA before intervention (top panel).
Stents in the proximal and distal segments of the LMCA, and in the ostial LAD, with normal blood flow to Cx through the stent struts (middle panel). Diffuse intimal proliferation in the LMCA with patent lumen in 1 year (bottom panel).
and the Cx were filled via collaterals from the RCA (Figure 3, c). The occlusion was promptly treated with repeat stenting of the LMCA, LAD, RI, and Cx. Intra-aortic balloon pump and eptifibitide infusion were used. TIMI grade 3 flow was achieved (Figure 3, d). The patient was subsequently discharged from the hospital and remained stable at 3-month follow-up.
Routine surveillance coronary angiography is the standard diagnostic test for CAV. A relationship between percutaneous coronary angioplasty and subsequent new left main stenosis has been reported,17–20 possibly as a consequence of catheter manipulation causing endothelial damage and intimal hyperplasia. The development of new left main stenosis in Patient 2 raises speculation that accelerated CAV in the LMCA may similarly develop as a result of catheter manipulation. Coronary bypass surgery has been the standard of treatment for native LMCA disease.21,22 Elective left main angioplasty has been associated with high angiographic success rates (94% to 99%) but a disappointing late outcome (1-year mortality and event-free survival were 15% to 56% and 38% to 44%, respectively).11,12,23 The latter is related to the
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FIGURE 3 (a) Accelerated CAV developed in the LMCA and the LAD. (b) Angiography
immediately after stenting. (c) LMCA occlusion associated with cardiogenic shock occurred at 5 months. (d) LMCA and the three main branches were immediately treated with stents.
unpredictable and catastrophic consequences of abrupt vessel closure and the high restenosis rate. Coronary stenting using high-pressure inflation appears to be a superior therapy. Four recent series (a total of 331 patients)14 –-16,24 of elective LMCA stenting reported procedural success in 98% to 100% with favorable results at 1 year (0% to 8% mortality, 78% to 82% event-free survival) in non-CAV patients. The majority of the restenosis occurred in the distal LMCA bifurcation.14,16,24 Due to the shortage of donors and poor results with bypass surgery, percutaneous coronary intervention may be a last option for the patients who develop CAV. Two heart transplant patients who underwent unprotected LMCA stenting have been previously reported in the medical literature; 1 required elective intubation and ventilation,25 and the other received cardiopulmonary support.26 In our cases, initial technical success was achieved in all patients. Two patients remained well at 3 months and 12 months of follow-up, but the third patient had a reocclusion within 5 months after the procedure. Stent selection must be individualized. We uti-
lized NIRoyal stents in all 3 cases as its radiopaque gold coating provided excellent radiopacity, facilitating precise placement. Other stents with adequate radial support would also be suitable.11,16 Co-existence of significant RCA disease with LMCA stenosis may prompt revascularization of the RCA before palliative left main angioplasty (as in Patient 2). Ischemic times of less than 1 minute were well tolerated in the presence of a patent RCA and preserved LV function.11 Because of this, in the absence of cardiogenic shock, the intra-aortic balloon pump was not used in 2 patients. One of the major concerns of stenting the LMCA is acute or sub-acute stent thrombosis, which would result in massive myocardial infarction, cardiogenic shock, and death. Adjunctive therapy for coronary stenting, such as clopidogrel and glycoprotein IIb/ IIIa inhibitors, should be strongly considered to minimize the risk of complication. Currently, we routinely give clopidogrel 300 mg before procedure, followed by 75 mg daily for 30 days in addition to aspirin 325 mg daily. Coronary angiography should be repeated within a few months after LMCA stenting in CAV.
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Chan et al.
Predictors of long-term patency after coronary stenting have not been reported in the cardiac transplant population. Whether any of the risk factors for CAV apply to stent restenosis is unknown. Although the use of intravascular ultrasonography (IVUS) to improve stent apposition was advocated by some investigators,24,27 whether IVUS guidance beyond angiography provides additional benefit for LMCA stenting (reducing restenosis) has been recently debated. With the use of high-pressure balloon inflation and preventive clopidogrel therapy for sub-acute thrombosis, recent large series supported the feasibility of LMCA stenting performed under angiographic guidance alone.16 IVUS was not used in our cases. Once a patient develops recurrent CAV, retransplantation should be considered. Our cases suggest that unprotected LMCA stenting in cardiac transplant patients is feasible, but its long-term clinical benefit remains uncertain. Since no optimal treatment has been established for CAV, stenting of the LMCA may be considered as a therapeutic option in this group of patients. However, the appropriate indications for such procedure remain to be determined. Newer technology, such as brachytherapy and pharmacologically coated stents, may offer hope for these patients but the safety and efficacy of these need to be established. An internationally coordinated registry may provide insight for the optimal treatment strategy of CAV. REFERENCES 1. Costanzo MR, Naftel DC, Pritzker MR et al. Heart transplant coronary artery disease detected by coronary angiography: a multi-institutional study of pre-operative donor and recipient risk factors. J Heart Lung Transplant 1998;17:744 –53. 2. Johnson DE, Alderman EL, Schroeder JS et al. Transplant coronary artery disease: Histopathologic correlations with angiographic morphology. J Am Coll Cardiol 1991;17:449 –57. 3. Uretsky BF, Muralli S, Reedy S et al. Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation 1987;76:827–34. 4. Grattan MT, Moreno-Cabral CE, Starnes VA et al. Eightyear results of cyclosporine-treated patients with cardiac transplants. J Thorac Cardiovasc Surg 1990;99:500 –9. 5. Weis M, Von Scheidt W. Cardiac allograft vasculopathy: a review. Circulation 1997;96:2069 –77. 6. Melnick JL, Adam E, DeBakey ME. Possible role of cytomegalovirus in atherogenesis. JAMA 1990;263:2204 –7. 7. Halle AA, DiSciascio G, Massin EK et al. Coronary angioplasty, atherectomy and bypass surgery in cardiac transplant recipients. J Am Coll Cardiol 1995;26:120 – 8. 8. Karawande SV, Ensley RD, Renlund DG et al. Cardiac retransplantation: a viable option? The Registry of the International Society for Heart and Lung Transplantation. Ann Thorac Surg 1992;54:840 – 4.
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