Case Report. A 57-year-old woman underwent orthotopic cardiac transplant in 1997 secondary to nonischemic cardiomyopathy. Her symptoms of heart failure started in 1993 after a week of flu-like illness. A year later, she was diagnosed with congestive heart failure with an ejection fraction of 20–30%, which was less than 20% one year later. In 1995 she experienced two episodes of ventricular tachycardia and was offered an automatic implantable cardioverter defibrillator (AICD), but she refused. She received a heart transplant in 1997. Six years after the orthotopic cardiac transplant, she presented to the hospital with chest pressure associated with nausea and vomiting. Her coronary risk factors were notable for hypertension and diabetes mellitus and family history of coronary artery disease. Her immunosuppressant medications included tacrolimus (4 mg orally twice a day), mycophenolate mofetil (500 mg orally twice a day) and prednisone (5 mg orally per day) since her transplant. Her baseline cardiac catheterization in 2001 revealed minimal coronary artery disease (Figure 1), hyperdynamic left ventricular systolic function and mild pulmonary hypertension.
Coronary angiography in 2003 revealed an 80% diffuse stenosis in the mid-portion of left anterior descending artery (LAD), 50–60% stenosis in obtuse marginal and minimal luminal irregularities in the left circumflex coronary artery. Percutaneous coronary intervention (PCI) with deployment of a 2.5 x 18 mm Cypher™ sirolimus-eluting stent (Cordis Corp., Miami, Florida) was performed in the mid-LAD at 12 atm. Another 3.0 x 23 mm sirolimus drug-eluting stent was deployed proximal to this segment. The final angiographic results showed that the patient had 0% residual stenosis in the stented segment with TIMI 3 flow. The patient was discharged on clopidogrel for 3 months in addition to her usual medications.
After one year, the patient came for the surveillance of her coronary artery disease with coronary angiography. Both right and left heart catheterization and intravascular ultrasound was performed. Coronary angiography at this time showed that the LAD had a hazy lesion at the take-off of diagonal #1 (D1). The two Cypher stents in the LAD were widely patent (Figure 2). There was a complete occlusion in the mid-portion of left circumflex coronary artery (Figure 3) and the left main artery was normal.
Mechanized intravascular ultrasound pullback of the entire LAD and the left main, using a 40 MHz Atlantis™ (Boston Scientific Corp., Natick, Massachusetts) imaging catheter was performed. This demonstrated moderate intimal proliferation throughout the vessel. In most of the area, the thickness was 0.5 mm and thickness in the left main artery was 0.25 mm. No proliferation was observed in the Cypher stents. The LAD at D1, proximal to the stent, had a minimum lumen area (MLA) of 4 mm², with a reference area of 7.5 mm² and hence a significant lesion (Figure 4). This lesion in the LAD was treated with a 3.0 x 18 mm Cypher stent with no significant snow plowing into the diagonal. The second lesion in the circumflex artery was stented with 3.0 x 13 mm Cypher stent deployed at 15 atm with excellent results. The patient was discharged on aspirin and clopidogrel.

Discussion. Cardiac allograft vasculopathy (CAV) is the main cause of illness and death the first year after transplant. CAV is an unusually accelerated and diffuse form of coronary artery disease in the transplanted heart. CAV, a disease of the donor’s heart in the recipient,² involves both intramyocardial and epimyocardial branches of the transplanted coronary artery and vein. Based on histological examination, CAV ranges from concentric fibrous intimal thickening to diffuse, complex atherosclerotic plaques that bear a close resemblance to native atherosclerosis.³ The etiology of CAV is multifactorial. The exact pathogenesis remains to be established, but there is growing evidence that both immunologic and nonimmunologic factors contribute to the vascular injury, which leads to disease process.
The early diagnosis of CAV is difficult, as it requires invasive testing. Noninvasive tests, including electrocardiography, exercise radionuclide ventriculography and thallium scintigraphy are not well established as screening tools.⁴ Because of the unreliable information of the noninvasive test, annual angiography is performed for diagnostic and surveillance purposes in many centers. The incidence of CAV visible on angiography is 11–14% after 1 year of transplantation, and 42% patients had CAV after 5 years of transplantation on coronary angiography.⁵ Intravascular ultrasound (IVUS) has emerged as the most sensitive invasive method for early detection and monitoring of CAV and has been shown to bereproducible.⁶ IVUS reveals significant intimal thickening in up to 75% of patients after one year post-transplantation⁷ compared to 11–14% of angiography results. IVUS provides the additional information about the plaque composition, including calcification, microcalcification, fibrous cellular tissue and fatty cellular tissue.
The development of immunosuppressive agents to prevent acute allograft rejection and the proliferation of smooth muscle cells may reduce the frequency and severity of vasculopathy. Today the effective immunosuppressive agents include sirolimus, everolimus, azathioprine and cyclosporine. Sirolimus and everolimus are immunosuppressants that inhibit the cellular proliferation stimulated by the growth factors-driven signal transduction in response to alloantigen. In a randomized, open-label study, sirolimus was compared with azathioprine in combination with cyclosporine and steroids. This showed that the proportion of patients with grade 3a or greater, acute rejection was 32% for sirolimus and 56.8% for azathioprine.⁸
Coronary revascularization procedures, such as atherectomy, percutanous transluminal angioplasty and stent placement have been used to decrease mortality and morbidity in CAV. A study of 332 heart transplant recipients with PTCA revealed a high level of primary success with a low periprocedural complication rate. But in this study, overall mortality in this population was increased as a consequence of a high level of coronary events.⁹ In contrast to low procedure morbidity rates with native coronary artery disease, restenosis and mortality rates are higher in the CAV patient.¹⁰ PCI with stent implantation has been done with some good results. Benz et al. showed a significant reduction in restenosis both early and late after PTCA, with a nearly 50% reduction in restenosis at 8 months.¹¹ Little data exist regarding drug-eluting stent outcomes in the treatment of CAV. To our knowledge, this is the first reported case of drug-eluting stenting in a heart transplant patient. This case report with one-year follow-up of a heart transplant patient who received a drug-eluting stent with good results. The findings are very impressive in the sense that the coronary arteries that were free of significant stenosis on previous angiography showed advanced disease, but the site of the drug-eluting stents were free of any drug neointimal proliferation.