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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, Timothy D. Crowe, BS^_*, Jingyuan Feng, MS, 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
Gill Heart Institute, University of Kentucky, Lexington, Kentucky
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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