Surveillance for post-transplant coronary artery vasculopathy: Shifting gears from diagnosis to prognosis

Coronary artery vasculopathy (CAV) developing in the allograft significantly limits event-free survival after heart transplantation. Some evidence of CAV can be detected by coronary angiography in 10% and 50% of patients 1 and 5 years after transplantation, respectively. However, the disease is characterized by concentric and diffuse arterial hyperplasia in both proximal and distal coronary segments, and thus may be underestimated by coronary angiography. Furthermore, the diagnostic challenge is heightened by the absence of typical angina due to denervation of the transplanted heart. More sensitive detection techniques using intravascular ultrasound suggest that early evidence of CAV such as intimal thickening is prevalent in an even larger number of patients than detected by coronary angiography. The pathogenesis of this intriguing and challenging condition is still somewhat speculative. The fact that patients without traditional risk factors, such as young patients transplanted for dilated cardiomyopathy, are at risk of CAV suggests a mechanism distinct from atherosclerosis. The involvement of allograft vessels with sparing of the host’s native arterial system indicates that the disease is not solely caused by immunosuppressive therapy or systemic factors in the host. The current knowledgebase suggests that CAV is the result of immunological differences between the graft and host, leading to immunologically mediated arterial hyperplasia. Once the condition develops, no intervention has been shown to definitively reverse the process. The clinical course is usually one of progressive myocardial ischemia leading to left ventricular dysfunction and heart failure. The diffuse nature of the arteriosclerotic process renders conventional coronary revascularization less useful, and re-transplantation remains the only definitive therapy. One-year survival is an abysmal 20% after a clinical ischemic event. Thus, current clinical practice guidelines recommend annual surveillance coronary angiography in heart transplant recipients, the intent being early diagnosis of CAV. However, this approach is not optimal because of the associated patient risk and discomfort, and the performance characteristics of coronary ‘‘luminography,’’ which are more suited for the detection of discrete rather than diffuse coronary involvement. In this issue of the Journal, Alain Manrique and colleagues report on a study of 110 patients who had gated stress-rest SPECT myocardial perfusion imaging (MPI) using Tl-201 or Tc-99m sestamibi and surveillance coronary angiography within one month of each other, at least 18 months after heart transplantation. While prior studies have explored the utility of MPI in post-transplant patients, Manrique and colleagues used contemporary imaging methodology, i.e., gated SPECT imaging with mostly Tc-99m tracer, and thus had information on both perfusion and function. Abnormal coronary angiograms were classified into grade 1 (minor, diffuse irregularities or focal stenosis\50%) or grade 2 (obstructive disease) CAV. Outcomes measured consisted of cardiac events related to CAV: cardiac death, nonfatal MI, or re-transplantation, the primary endpoint, and late ([2 months after SPECT) revascularization, the secondary endpoint. From a clinical perspective, the most relevant results pertain to the prognostic utility of SPECT in this population. It is noteworthy that 53% of SPECT performed an average of 66 ± 37 months (range 20-168 months) showed normal myocardial perfusion. While we are not told how many of these patients also had normal left ventricular function (stress ejection fraction C50%, and end-systolic volume B35 mL), we could perhaps infer that this number was high based on the good correlation between the summed stress score and left ventricular function. What is striking is the fact that in patients who had normal left ventricular perfusion and function on SPECT, the event free survival was 100% to at least From the Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA. Reprint requests: Prem Soman, MD, PhD, Cardiovascular Institute, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213; somanp@upmc.edu. J Nucl Cardiol 2010;17:172–4. 1071-3581/$34.00 Copyright 2010 by the American Society of Nuclear Cardiology. doi:10.1007/s12350-010-9198-2