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J Am Coll Cardiol, 2005; 45:1538-1542, doi:10.1016/j.jacc.2004.12.076
© 2005 by the American College of Cardiology Foundation
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EXPEDITED REVIEWS

Intravascular Ultrasound Evidence of Angiographically Silent Progression in Coronary Atherosclerosis Predicts Long-Term Morbidity and Mortality After Cardiac Transplantation

E. Murat Tuzcu, MD, FACC*,*, Samir R. Kapadia, MD, FACC*, Ravish Sachar, MD*, Khaled M. Ziada, MD{dagger}, Timothy D. Crowe, BS*, Jingyuan Feng, MS{ddagger}, William A. Magyar, BS*, Robert E. Hobbs, MD, FACC*, Randall C. Starling, MD, FACC*, James B. Young, MD, FACC*, Patrick McCarthy, MD, FACC§ and Steven E. Nissen, MD, FACC*

* Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
{dagger} Gill Heart Institute, University of Kentucky, Lexington, Kentucky
{ddagger} Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio
§ Division of Cardiothoracic Surgery, Northwestern University, School of Medicine, Chicago, Illinois.

Manuscript received September 2, 2004; revised manuscript received November 21, 2004, accepted December 10, 2004.

* Reprint requests and correspondence: Dr. E. Murat Tuzcu, Department of Cardiovascular Medicine, Desk F-25, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. (Email: tuzcue{at}ccf.org).

OBJECTIVES: The aim of this study was to determine whether angiographically silent early coronary intimal thickening could predict long-term morbidity and mortality.

BACKGROUND: Although intravascular ultrasound (IVUS) is widely used to detect early transplant coronary disease, its prognostic significance has not been well defined.

METHODS: The study cohort consisted of 143 patients who underwent early multivessel (2.1 ± 0.7 arteries/patient) IVUS examination 1.0 ± 0.5 month and 12.0 ± 1.0 month after transplantation. The change in intimal thickness was evaluated using paired analysis of 1,069 matched sites. Rapidly progressive vasculopathy was defined as the change in intimal thickness ≥0.5 mm. Patients were followed for a primary end point of all-cause mortality and a secondary composite end point of mortality and nonfatal myocardial infarction (MI). Angiographic disease, defined as any ≥50% diameter stenosis, was assessed in 126 patients.

RESULTS: Intravascular ultrasound at one year demonstrated rapid progression in 54 (37%) of 143 patients and new lesions in 67 (47%) of 143 of patients. At a mean clinical follow-up of 5.9 years, more patients with rapidly progressive vasculopathy died, as compared with those without (26% vs. 11%, p = 0.03). Death and MI also occurred more frequently among those with rapid progression than in those without it (51% vs. 16%, p < 0.0001). There was no significant difference in outcome in patients with and without donor-transmitted lesions. Angiographic disease was found in 11 (22%) of 50 patients with and in 2 (2.1%) of 76 patients without (p = 0.003) rapidly progressive vasculopathy. The IVUS-defined rapid progression correlated highly with future development of angiographic disease (p = 0.0005).

CONCLUSIONS: Rapidly progressive vasculopathy by IVUS, defined as an increase of ≥0.5 mm in intimal thickness within the first year after transplantation, is a powerful predictor of all-cause mortality, MI, and angiographic abnormalities. Accordingly, such patients may be candidates for more aggressive anti-atherosclerotic and/or immunosuppressive therapy.

Abbreviations and Acronyms
  CAD = coronary artery disease
  CMV = cytomegalovirus
  IVUS = intravascular ultrasound
  MI = myocardial infarction




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