In-stent restenosis and remote coronary lesion progression are coupled in cardiac transplant vasculopathy but not in native coronary artery disease

OBJECTIVES The purpose of this study was to describe the clinical, angiographic, and histological features of concomitant in-stent restenosis (ISR) and cardiac allograft vasculopathy (CAV) progression. BACKGROUND Cardiac allograft vasculopathy is a major challenge to long-term success of heart transplantation. Coronary stenting for CAV is hampered by ISR. METHODS Quantitative coronary angiography compared late lumen loss (LL) at stented and reference, non-stented segments during 1-year follow-up in post-heart transplant and control atherosclerosis patients. Stented and non-stented arteries with CAV were also obtained postmortem for immunohistochemical analysis. RESULTS In 37 stented lesions (25 patients), 1-year binary restenosis occurred in 37.8%. Patients with ISR had higher long-term cardiac death/myocardial infarction rates than patients without ISR (53.8% vs. 9.1%, p = 0.03). In the same 25 patients, 34 CAV lesions with non-significant obstructions were identified as reference controls. After 1 year, patients who developed ISR also had more control lesion LL (0.78 +/- 0.38 min vs. 0.39 +/- 0.27 mm, p < 0.006) compared to patients without ISR. In the post-transplant patients, in-stent LL was closely coupled to control segment LL (W = 0.63, p < 0.05). Conversely, in native atherosclerosis patients, ISR and remote disease progression were not correlated. Histological staining of stented and control arteries from CAV patients revealed similar pathologies common to ISR and non-intervened CAV segments. CONCLUSIONS Progression of CAV at non-intervened segments and ISR correlate strongly and share common histopathology. Optimized treatment for patients with aggressive CAV needs to address the widespread nature of this disease, even when it presents as an initially focal lesion.