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CLINICAL RESEARCH: HEART FAILURE

In-Stent Restenosis and Remote Coronary Lesion Progression Are Coupled in Cardiac Transplant Vasculopathy But Not in Native Coronary Artery Disease

Michael Jonas, MD^_*,,,_*, James C. Fang, MD^_*, John C. Wang, MD^_*, Satyendra Giri, MD^_*, Dan Elian, MD, Yedael Har-Zahav, MD, Hung Ly, MD^_*, Philip A. Seifert, MS, Jeffrey J. Popma, MD^_* and Campbell Rogers, MD^_*,

^_* Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
Heart Institute, Sheba Medical Center, Tel Hashomer, Israel
Harvard–MIT Division of Health Sciences and Technology, Cambridge, Massachusetts

Manuscript received July 13, 2005; revised manuscript received January 6, 2006, accepted January 9, 2006.

^_* Reprint requests and correspondence: Dr. Michael Jonas, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115. (Email: tmjonas{at}yahoo.com).

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 post-mortem 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 mm 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 (R² = 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.

Abbreviations and Acronyms   CAV = cardiac allograft vasculopathy   DES = drug-eluting stent   DS = diameter stenosis   ISR = in-stent restenosis   IVUS = intravascular ultrasound   LL = late lumen loss   MI = myocardial infarction   MLD = minimal lumen diameter   PCI = percutaneous coronary intervention   QCA = quantitative coronary angiography

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