Pediatric Intervention

PCI in Patients with Cardiac Allograft Vasculopathy

Michael S. Lee, MD, FACC, FSCAI, University of California, Los Angeles Medical Center, Los Angeles, California
Michael S. Lee, MD, FACC, FSCAI, University of California, Los Angeles Medical Center, Los Angeles, California

Patients with end-stage congestive heart failure refractory to medical therapy may benefit from orthotopic heart transplantation (OHT).1 Cardiac allograft vasculopathy is a major cause of allograft failure and mortality after the first year following OHT.2 The incidence of cardiac allograft vasculopathy is approximately 40% to 50% at five-year follow-up and is associated with a 50% rate of death or repeat OHT at five years.3 In pediatric patients, the development of cardiac allograft vasculopathy also portends a poor prognosis, with a 50% allograft survival rate at 2.8 years, and freedom from death or graft loss of less than 30% within four years.4

Interestingly, less than half of the pediatric patients underwent routine follow-up coronary angiography after OHT, which may be explained by the younger, smaller patients, as well as the need for general anesthesia. 

What is cardiac allograft vasculopathy?

Cardiac allograft vasculopathy is associated with focal lesions in the proximal and mid-coronary segments and severe diffuse disease, or “pruning,” of the distal vessels. Although the exact mechanism is unknown, both immune and non-immune systems may play a role in the development of cardiac allograft vasculopathy. It occurs less frequently in pediatric patients compared with their adult counterparts and appears to be related to the plasticity of the immature immune system, as well as less cardiovascular risk factors for atherosclerosis in younger donors and recipients.4 Freedom from cardiac allograft vasculopathy in pediatric patients is 66% at 10 years.5 


Treatment is limited. Although pravastatin decreases the incidence of cardiac allograft vasculopathy, medical therapy has largely been disappointing in preventing or treating it.6 Coronary artery bypass surgery is rarely performed, especially in pediatric patients, in part due to poor distal targets because of the pruning of the distal vessels. Data are very limited, with small numbers of patients, and the results are mixed, with survival ranging from 20% to 80% at five-year follow-up.7-11 Repeat OHT in pediatric patients may be an option, but is associated with higher mortality.12 In addition to the paucity of organs and the ethical dilemmas, repeat sternotomy can be more technically challenging and increase the risk of infection. 

A palliative treatment option for severe cardiac allograft vasculopathy is percutaneous coronary intervention (PCI).  The majority of the data with PCI in patients with cardiac allograft vasculopathy is in the adult population. PCI in patients with cardiac allograft vasculopathy is associated with higher major adverse cardiac events, including higher rates of in-stent restenosis. The UCLA Medical Center experience demonstrated that drug-eluting stents reduced in-stent restenosis compared with bare metal stents.13 PCI with sirolimus- and paclitaxel-eluting stents provided similar outcomes in patients with cardiac allograft vasculopathy.14 However, PCI with drug-eluting stents provided no clinical benefit compared with bare metal stents at long-term follow-up.15 Once in-stent restenosis developed, long-term outcomes in patients who underwent PCI for cardiac allograft vasculopathy was poor, with a lower survival rate compared to patients without in-stent restenosis (38.5% vs. 84.2%, p<0.001).16 In a multi-center, international registry, PCI was safe and effective for the treatment of patients with cardiac allograft vasculopathy and unprotected left main coronary artery disease.17 

The long-term safety and efficacy of PCI in pediatric patients with cardiac allograft vasculopathy is unknown. Several small series have been published. In the largest and longest experience of pediatric patients who underwent PCI for cardiac allograft vasculopathy, UCLA Medical Center and University of Arkansas for Medical Sciences, Arkansas Children’s Hospital in Little Rock, Arkansas, reported the combined outcomes of 12 patients who had a mean age of 15 years.18 At a mean follow-up of seven years, 50% experienced a major adverse cardiac event as defined by all-cause death, myocardial infarction and target vessel revascularization. In addition, 41% of patients underwent repeat OHT. 

PCI in pediatric patients may be more technically difficult due to smaller femoral and radial arteries that make access more challenging, a smaller aortic root that requires smaller guiding catheters, and smaller coronary arteries that require smaller stents. Given that these pediatric cardiac allograft vasculopathy patients undergo cardiac catheterization with general anesthesia and are almost always hypotensive with systolic blood pressures less than 100 mmHg, the administration of intracoronary nitroglycerin is often not feasible in arteries that are highly prone to vasospasm.  

Therapeutic non-compliance in pediatric patients

Non-compliance with immunosuppressive therapy is associated with rejection and can limit allograft survival. Ringewald et al demonstrated that of the 49 episodes of late rejection in 15 patients, 37 episodes (76%) were associated with non-compliance with immunosuppressive therapy.19 Pediatric patients may not fully grasp the importance of strict adherence to immunosuppressive therapy to minimize the risk of allograft rejection. Non-compliance may be a characteristic of immaturity, ‘acting out,’ and rebelling during the adolescent years. A 17-year-old patient at our institution who was non-compliant with dual anti-platelet therapy died suddenly due to possible stent thrombosis at five months after PCI with a drug-eluting stent.18


PCI is feasible and offers a palliative treatment option in patients with cardiac allograft vasculopathy. PCI is more technically challenging in pediatric patients with cardiac allograft vasculopathy. The potential for non-compliance with immunosuppressive and anti-platelet therapy, which may contribute to adverse clinical outcomes, should be taken into consideration prior to performing PCI in this high-risk group.

Michael S. Lee, MD, may be contacted at


  1. Shah P, Tang D, Shah K, Mehra MR. JHLT highlights 2011: cardiothoracic transplantation, pulmonary hypertension, and mechanical circulatory support. J Heart Lung Transplant. 2012; 31: 1257-1261.
  2. Zimmer R, Lee MS. Transplant coronary artery disease. J Am Coll Cardiol Intv. 2010; 2: 367-377.
  3. Costanzo M, Naftel D, Pritzker M, et al. Heart transplant coronary artery disease detected by coronary angiography: A multi-institutional study of preoperative donor and recipient risk factors. J Heart Lung Transplant. 1998; 17: 744-753.
  4. Pahl E, Naftel DC, Kuhn MA, et al. Pediatric Heart Transplant Study. The impact and outcome of transplant coronary artery disease in a pediatric population: a 9-year multi-institutional study. J Heart Lung Transplant. 2005; 24: 645-651.
  5. Kirk R, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: thirteenth official pediatric heart transplantation report — 2010. J Heart Lung Transplant. 2010; 29: 1119-1128.
  6. Kobashigawa JA, Katznelson S, Laks H, et al. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med. 1995; 333: 621-627.
  7. Goerler H, Simon A, Warnecke G, et al. Cardiac surgery late after heart transplantation: a safe and effective treatment option. J Thorac Cardiovasc Surg. 2010; 140: 433-439.
  8. Rothenburger M, Hülsken G, Stypmann J, et al. Cardiothoracic surgery after heart and heartlung transplantation. Thorac Cardiovasc Surg. 2005; 53: 85-92.
  9. Musci M, Pasic M, Meyer R, et al. Coronary artery bypass grafting after orthotopic heart transplantation. Eur J Cardiothorac Surg.1999; 16: 163-168.
  10. Patel VS, Radovancevic B, Springer W, et al. Revascularization procedures in patients with transplant coronary artery disease. Eur J CardiothoracSurg. 1997; 11: 895-901.
  11. Bhama JK, Nguyen DQ, Scolieri S, et al. Surgical revascularization for cardiac allograft vasculopathy: Is it still an option? J Thorac Cardiovasc Surg. 2009; 137: 1488-1492.
  12. Mahle WT, Vincent RN, Kanter KR. Cardiac retransplantation in childhood: analysis of data from the United Network for Organ Sharing. J Thorac Cardiovasc Surg. 2005; 130: 542-546. 
  13. Lee MS, Kobashigawa JA, Tobis JM. Comparison of percutaneous coronary intervention with bare-metal and drug-eluting stents for cardiac allograft vasculopathy. J Am Coll Cardiol Intv. 2008; 1; 710-715.
  14. Lee MS, Tarantini G, Xhaxho J, et al. Sirolimus- versus paclitaxel-eluting stents for the treatment of cardiac allograft vasculopathy. J Am Coll Cardiol Intv. 2010; 3: 378-382.
  15. Lee MS, Yang T, Kandzari D, Mahmud E, Liao H, Kirtane AJ. Long-term clinical outcomes in patients treated with drug-eluting compared to bare-metal stents for the treatment of transplant coronary artery disease. Catheter Cardiovasc Interv. 2012; 80: 533-538.
  16. Lee MS, Cheng RK, Kandzari DE, Kirtane AJ. Long-term outcomes of heart transplantation recipients with transplant coronary artery disease who develop in-stent restenosis after percutaneous coronary intervention. Am J Cardiol. 2012; 109: 1729-1732.
  17. Lee MS, Yang T, Fearon WF, et al. Long-term outcomes after percutaneous coronary intervention of left main coronary artery for treatment of cardiac allograft vasculopathy after orthotopic heart transplantation. Am J Cardiol. 2010; 106: 1086-1089.
  18. Lee, MD, Sachdeva R, Kim MH, Sachdeva R. Long-term outcomes of percutaneous coronary intervention in transplant coronary artery disease in pediatric heart transplant recipients. J Invasive Cardiol. 2012; 24: 278-281. 
  19. Ringewald JM, Gidding SS, Crawford SE, Backer CL, Mavroudis C, Pahl E. Nonadherence is associated with late rejection in pediatric heart transplant recipients. J Pediatr. 2001; 139: 75-78.