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CLINICAL RESEARCH: HEART FAILURE

Inflammatory Burden of Cardiac Allograft Coronary Atherosclerotic Plaque Is Associated With Early Recurrent Cellular Rejection and Predicts a Higher Risk of Vasculopathy Progression

Eugenia Raichlin, MD^_*,, Jang-Ho Bae, MD, Sudhir S. Kushwaha, MD^_*, Ryan J. Lennon, MS, Abhiram Prasad, MD^_*, Charanjit S. Rihal, MD^_* and Amir Lerman, MD^_*,,_*

^_* Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
Center for Coronary Physiology and Imaging, Mayo Clinic, Rochester, Minnesota
Division of Biostatistics, Mayo Clinic, Rochester, Minnesota

Manuscript received July 22, 2008; revised manuscript received December 2, 2008, accepted December 8, 2008.

^_* Reprint requests and correspondence: Dr. Amir Lerman, Division of Cardiovascular Disease, Mayo Clinic, Mary Bright 4-523, First Street SW, Rochester, Minnesota 55905 (Email: Lerman.Amir{at}mayo.edu).

Objectives: This study was designed to investigate tissue characterization of the coronary allograft atherosclerotic plaque with virtual histology intravascular ultrasound (VH-IVUS) imaging to assess the presence and predictors of vessel wall inflammation and its significance in cardiac allograft vasculopathy (CAV) progression.

Background: A unique form of accelerated atherosclerosis, CAV remains the leading cause of late morbidity and mortality in heart transplant patients. The pathogenesis of CAV is not fully elucidated.

Methods: A total of 86 patients with coronary allograft vasculopathy underwent VH-IVUS examination of the left anterior descending coronary artery 3.61 ± 3.04 years following cardiac transplantation. Based on the VH-IVUS plaque characteristics, coronary allograft plaque was divided on virtual histology intravascular ultrasound-derived "inflammatory" (VHD-IP) (necrotic core and dense calcium 30%) and "noninflammatory" plaque (VHD-NIP) (necrotic core and dense calcium <30%). Total rejection scores were calculated based on the 2004 International Society of Heart and Lung Transplantation rejection grading system.

Results: In the whole study population, the mean percentage of fibrous, fibrofatty, dense calcified, and necrotic core plaques in a mean length of 62.3 ± 17.4 mm of the left anterior descending coronary artery were 50 ± 17%, 16 ± 11%, 15 ± 11%, and 18 ± 9%, respectively. Patients with a 6-month total rejection score >0.3 had significantly higher incidence of VHD-IP than those with a 6-month total rejection score 0.3 (69% vs. 33%, p = 0.011). The presence of VHD-IP at baseline was associated with a significant increase in plaque volume (2.42 ± 1.78 mm³/mm vs. –0.11 ± 1.65 mm³/mm, p = 0.010), plaque index (7 ± 9% vs. 0 ± 8%, p = 0.04), and remodeling index (1.24 ± 0.44 vs. 1.09 ± 0.36, p = 0.030) during 12 months of follow-up when compared with the presence of VHD-NIP at baseline and during follow-up.

Conclusions: The presence of VHD-IP as assessed by VH-IVUS is associated with early recurrent rejection and with higher subsequent progression of CAV. A VH-IVUS assessment may add important information in the evaluation of transplant recipients.

Key Words: cardiac transplantation • rejection • coronary allograft • vasculopathy • intravascular ultrasound

Abbreviations and Acronyms   CAV = coronary allograft vasculopathy   hsCRP = high-sensitivity C-reactive protein   R = rejection grade   TRS = total rejection score   VHD-IP = virtual histology intravascular ultrasound-derived inflammatory plaque   VHD-NIP = virtual histology intravascular ultrasound-derived noninflammatory plaque   VH-IVUS = virtual histology intravascular ultrasound

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