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Multislice computed tomography (MSCT) has shown high negative predictive value in ruling out obstructive coronary artery disease. Preliminary studies in patients with valvular heart disease (VHD) have demonstrated the potential of MSCT angiography (CTA) in such patients, precluding need for invasive angiography (XA). However, larger prospectively designed studies, including patients with atrial fibrillation and incorporating dose reduction algorithms, are needed.To evaluate the clinical utility of 64-slice CT in the preoperative assessment in patients with VHD, we prospectively studied 452 consecutive patients undergoing routine cardiac catheterization for eligibility. Two hundred thirty-seven patients underwent both MSCT and XA. Segment-based, vessel-based, and patient-based agreement between CTA and XA was estimated assuming that “nonevaluable” segments were positive for significant coronary stenosis. In a patient-based analysis, sensitivity, specificity, positive predictive value, and negative predictive values of CTA were 95%, 89%, 66%, and 99%, respectively; in vessel-based analysis, 90%, 92%, 48%, and 99%, respectively; and in segment-based analysis, 89%, 97%, 38%, and 100%, respectively. No significant differences were found between patients with or without atrial fibrillation. A CAC value of 390 was the best cutoff for the identification of patients with positive or inconclusive CTA (which would not be exempted from XA in the clinical setting).In the preoperative assessment of patients with predominant VHD, the diagnostic accuracy of 64-slice CTA for ruling out the presence of significant coronary artery disease is very good even when including patients with irregular heart rhythm. Using this approach, CAC quantification before CTA can be successfully used to identify patients who should be referred directly to XA, sparing unnecessary exposure to radiation.