The purpose of this study is to compare the effects of a certain contrast agent (iodixanol) to two other commonly used contrast agents called Iopamidol (Isovue) and iohexol (Omnipaque), on heart and kidney safety in patients undergoing a cardiac CT angiogram. The investigators will evaluate whether iodixanol 320 (Visipaque®), an iso-osmolar agent, is better tolerated (flushing, injection site pain/warmth, headache, nausea) and provides equal image quality compared with iohexol 350 (Omnipaque®) and Isovue 370 during 64-slice multidetector computed tomography angiography (MDCTA). A fourth group (Visipaque 270) will be included, using low radiation dose technology during acquisition, to evaluate image quality, tolerability, and contrast enhancement compared to both Visipaque 320 and Omnipaque and Isovue. In addition to image quality, tolerability, and contrast enhancement, the investigators will evaluate heart rate, adverse events, reimaging, costs, and patient satisfaction among all four cohorts.

The study will recruit 400 participants already undergoing CT angiography and consent and randomize them to one of four groups. Each of the possible contrast agents used are commonly used for CT angiography, so the primary risk is loss of confidentiality and being asked questions about tolerability. All other facets of the study (3 lead ECG, beta blockade, nitroglycerine use, CT angiography and contrast administration) are standard of care and being done for clinical uses.

CTA infusion is administered using a 5 ml/sec IV iodinated contrast infusion. 50-70 ml of iodinated contrast is used for the scan depending on the patient's body habitus. The total contrast dose must not exceed 70 ml. An automated bolus tracking feature (SmartPrep, GE Healthcare, Milwaukee, USA) is used to judge contrast bolus arrival and optimize image quality. Patients will be asked to hold their breaths during scanning for up to 10 seconds. A Field of View (FOV) of 25 cm is adjusted to include the heart from below the carina to just below diaphragm. The aorta will be included in the FOV to exclude aortic pathology (ie. dissection, aneurysm, etc.). For patients in sinus rhythm, prospective ECG gating centered at 75% of the R-R interval is used while those in Atrial fibrillation or HR >65 despite oral and IV medications, a retrospective gating is used. The following parameters are used Tube voltage = 100-120kV (based on body habitus), tube current = 400 mA, gantry rotation speed = 0.35 seconds, slice thickness = 0.625 mm, rows = 64, coverage = 128-160 mm.

Estimated radiation dose is = 2-5 mSv dependent on BMI, cardiac height and heart rate. A post acquisition software (Adaptive Statistical Iterative Reconstruction, GE healthcare, Milwaukee, USA) is used to reduce pixel noise standard deviation (noise) by 30 percent and allows for reduced mA in the acquisition while still yielding diagnostic images, thereby reducing total dose required. At the conclusion of each acquisition, technologists collect a survey of patient satisfaction quantifying side effects of different contrasts: flushing, headache, nausea, and pain at injection site as mild, moderate or severe.

Advantage Workstation 4.6 software (GE healthcare, Milwaukee, USA) is used for post acquisition processing. Readers, who are blinded to the type of contrast media used, assess image quality by measuring contrast enhancement in aorta, LV myocardium, left main, proximal Left Anterior Descending artery, proximal and distal Right Coronary arteries. Subjects with coronary artery bypass graft and stents are excluded. Heart rate (HR) variability during the scan is also evaluated. A comparison of the degree of contrast enhancement of the coronary lumen as well as the differences for each of the four contrast agents will be measured and reported, stratified by 100 kVp and 120 kVp acquisition. The image quality of 17 coronary artery segments will be graded by two cardiologists in consensus with the use of a four-point scale (1= excellent, 2=good, 3=fair , 4= poor enhancement) blinded to contrast agent administration.

Statistical Analysis:

All analysis is conducted using SPSS 18.0 for window (SPSS Inc., Chicago, IL, USA). Comparisons between groups are performed using a Student t-test for continuous variables with normal distributions and the Mann-Whitney U test for continuous variables with non-normal distributions. Categorical variables were analyzed by means of χ2 analysis. Correlation between minimum HR and maximum HR was calculated with the Pearson correlation coefficient. The Cochran-Mantel-Haenszel test was used for analyzing the difference in visual quality between two groups.

Inclusion Criteria:

Subjects may be included in the study if they meet all of the following criteria:

1. The subject is over 18 years old.
2. Subject scheduled to undergo a contrast-enhanced CCTA examination
3. The subject has no contra-indication to receiving iodinated contrast administration (allergy, renal insufficiency).
4. The subject has provided signed and dated informed consent

Exclusion criteria:

Subjects must be excluded from participating in this study if they meet the following criteria:

1. Subjects have known contra-indication to contrast administration:

   • Renal insufficiency as defined by GFR < 50
   • Known contrast allergy

2. Pregnant or possibly pregnant subjects will be excluded -Women of childbearing potential will undergo urine pregnancy test prior to CT scanning.

study was performed as outlined, sample sizes are appropriate, there were no technical problems.