http://repub.eur.nl/res/aut/30738/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39359/ 2013-04-01T00:00:00Z Objective: To evaluate the influence of LDL receptor (LDLR) -negative mutational status on CT coronary atherosclerosis in asymptomatic statin treated patients with heterozygous familial hypercholesterolemia (FH). Methods: Coronary CT angiography (CCTA) was performed in 145 FH patients (93 men; mean age 52 ± 8) screened for LDLR and apolipoprotein B (APOB) mutations. The extent of coronary plaque was compared between two groups: 1) 59 patients (41%) heterozygous for LDLR-negative mutations (LDLR-negative) and 2) 86 patients (59%) with reduced or normal LDLR function (LDLR-positive) consisting of 32 LDLR-defective mutations, 8 APOB mutations and 46 patients in whom no mutation could be identified.The diseased segments score (DSS) was the primary study endpoint defined as the number of coronary artery segments (0-17) with >20% luminal diameter narrowing. We compared the DSS between LDLR-negative and LDLR-positive patients. Within the LDLR-positive group a secondary analysis was performed between identified (LDLR-defective, APOB) and unidentified mutational status. Results: The median DSS was higher in LDLR-negative than in LDLR-positive patients (4 (1-7) and 2 (0-5); P = 0.017). After adjustment for risk factors, LDLR-negative mutational status remained an independent predictor of the DSS (B = 1.09; P = 0.047). The DSS in the LDLR-positive group was similar for patients with identified and patients with unidentified mutational status. Conclusion: In asymptomatic statin treated patients with a clinical diagnosis of FH, LDLR-negative mutational status is associated with a higher extent of subclinical CT coronary atherosclerosis. http://repub.eur.nl/res/pub/33177/ 2011-12-01T00:00:00Z Purpose: To compare image quality, radiation dose, and their relationship with heart rate of computed tomographic (CT) coronary angiographic scan protocols by using a 128-section dual-source CT scanner. Materials and Methods: Institutional review board approved the study; all patients gave informed consent. Two hundred seventy-two patients (175 men, 97 women; mean ages, 58 and 59 years, respectively) referred for CT coronary angiography were categorized according to heart rate: less than 65 beats per minute (group A) and 65 beats per minute or greater (group B). Patients were randomized to undergo prospective high-pitch spiral scanning and narrow-window prospective sequential scanning in group A (n = 160) or wide-window prospective sequential scanning and retrospective spiral scanning in group B (n = 112). Image quality was graded (1 = nondiagnostic; 2 = artifacts present, diagnostic; 3 = no artifacts) and compared (Mann-Whitney and Student t tests). Results: In group A, mean image quality grade was significantly lower with high-pitch spiral versus sequential scanning (2.67 ± 0.38 [standard deviation ] vs 2.86 ± 0.21; P <.001). In a subpopulation (heart rate, <55 beats per minute), mean image quality grade was similar (2.81 ± 0.30 vs 2.94 ± 0.08; P =.35). In group B, image quality grade was comparable between sequential and retrospective spiral scanning (2.81 ± 0.28 vs 2.80 ± 0.38; P =.54). Mean estimated radiation dose was significantly lower (high-pitch spiral vs sequential scanning) in group A (for 100 kV, 0.81 mSv ± 0.30 vs 2.74 mSv ± 1.14 [ P <.001]; for 120 kV, 1.65 mSv ± 0.69 vs 4.21 mSv ± 1.20 [ P <.001]) and in group B (sequential vs retrospective spiral scanning) (for 100 kV, 4.07 mSv ± 1.07 vs 5.54 mSv ± 1.76 [P =.02]; for 120 kV, 7.50 mSv ± 1.79 vs 9.83 mSv ± 3.49 [P =.1]). Conclusion: A high-pitch spiral CT coronary angiographic protocol should be applied in patients with regular and low (<55 beats per minute) heart rates; a sequential protocol is preferred in all others. http://repub.eur.nl/res/pub/33200/ 2011-12-01T00:00:00Z Objectives: We determined the extent, severity, distribution and type of coronary plaques in cardiac asymptomatic patients with familial hypercholesterolemia (FH) using computed tomography (CT). Background: FH patients have accelerated progression of coronary artery disease (CAD) with earlier major adverse cardiac events. Non-invasive CT coronary angiography (CTCA) allows assessing the coronary plaque burden in asymptomatic patients with FH. Materials and methods: A total of 140 asymptomatic statin treated FH patients (90 men; mean age 52 ± 8 years) underwent CT calcium scoring (Agatston) and CTCA using a Dual Source CT scanner with a clinical follow-up of 29 ± 8 months. The extent, severity (obstructive or non-obstructive plaque based on >50% or <50% lumen diameter reduction), distribution and type (calcified, non-calcified, or mixed) of coronary plaque were evaluated. Results: The calcium score was 0 in 28 (21%) of the patients. In 16% of the patients there was no CT-evidence of any CAD while 24% had obstructive disease. In total 775 plaques were detected with CT coronary angiography, of which 11% were obstructive. Fifty four percent of all plaques were calcified, 25% non-calcified and 21% mixed. The CAD extent was related to gender, treated HDL-cholesterol and treated LDL-cholesterol levels. There was a low incidence of cardiac events and no cardiac death occurred during follow-up. Conclusion: Development of CAD is accelerated in intensively treated male and female FH patients. The extent of CAD is related to gender and cholesterol levels and ranges from absence of plaque in one out of 6 patients to extensive CAD with plaque causing >50% lumen obstruction in almost a quarter of patients with FH. http://repub.eur.nl/res/pub/34304/ 2011-07-01T00:00:00Z Objective: To determine the calcium score and coronary plaque burden in asymptomatic statin-treated patients with heterozygous familial hypercholesterolaemia (FH) compared with a control group of patients with low probability of coronary artery disease, having non-anginal chest pain, using CT. Design, setting and patients: 101 asymptomatic patients with FH (mean age 53±7 years; 62 men) and 126 patients with non-anginal chest pain (mean age 56±7 years; 80 men) underwent CT calcium scoring and CT coronary angiography. All patients with FH were treated with statins during a period of 10±8 years before CT. The coronary calcium score and plaque burden were determined and compared between the two patient groups. Results: The median total calcium score was significantly higher in patients with FH (Agatston score=87, IQR 5-367) than in patients with non-anginal chest pain (Agatston score=7, IQR 0-125; p<0.001). The overall coronary plaque burden was significantly higher in patients with FH (p<0.01). Male patients with FH, whose low-density lipoprotein cholesterol levels were reduced by statins below 3.0 mmol/l, had significantly less coronary calcium (p<0.01) and plaque burden (p=0.02). Conclusion: The coronary plaque burden is high in asymptomatic middle-aged patients with FH despite intense statin treatment. http://repub.eur.nl/res/pub/33668/ 2011-06-20T00:00:00Z Background: Although conventional (CAG) and computed tomography angiography (CTA) are reliable diagnostic modalities for exclusion of obstructive coronary artery disease (CAD), they are costly and with considerable exposure to radiation and contrast media. We compared the accuracy of coronary calcium scanning (CCS) and exercise electrocardiography (X-ECG) as less expensive and non-invasive means to rule out obstructive CAD. Methods: In a rapid-access chest pain clinic, 791 consecutive patients with stable chest pain were planned to undergo X-ECG and dual-source CTA with CCS. According to the Duke pre-test probability of CAD patients were classified as low (< 30%), intermediate (30-70%) or high risk (> 70%). Angiographic obstructive CAD (> 50% stenosis by CAG or CTA) was found in 210/791 (27%) patients, CAG overruling any CTA results. Results: Obstructive CAD was found in 12/281 (4%) patients with no coronary calcium and in 73/319 (23%) with a normal X-ECG (p < 0.001). No coronary calcium was associated with a substantially lower likelihood ratio compared to X-ECG; 0.11, 0.13 and 0.13 vs. 0.93, 0.55 and 0.46 in the low, intermediate and high risk group. In low risk patients a negative calcium score reduced the likelihood of obstructive CAD to less than 5%, removing the need for further diagnostic work-up. CCS could be performed in 754/756 (100%) patients, while X-ECG was diagnostic in 448/756 (59%) patients (p < 0.001). Conclusions: In real-world patients with stable chest pain CCS is a reliable initial test to rule out obstructive CAD and can be performed in virtually all patients. http://repub.eur.nl/res/pub/24419/ 2009-07-01T00:00:00Z Objectives: We sought to evaluate the contribution of noninvasive dual-source computed tomography angiography (CTA) in the comprehensive assessment of symptomatic patients after coronary artery bypass grafting (CABG). Background: Assessment of bypass grafts and distal runoffs by invasive coronary angiography is cumbersome and often requires extra procedure time, contrast load, and radiation exposure. Methods: Dual-source CTA was performed in 52 (41 men, mean age 66.6 ± 13.2 years) symptomatic post-CABG patients scheduled for invasive coronary angiography. No oral or intravenous beta blockers or sedation were administered before the scan. Mean interval between CABG surgery and CTA was 9.6 ± 7.2 (range 0 to 20) years. Mean heart rate during scanning was 64.5 ± 13.2 (range 48 to 92) beats/min. Seventy-five percent of patients had both arterial and venous grafts. A total of 152 graft segments and 142 distal runoffs vessels were analyzed. Native coronary segments were divided into nongrafted (n = 118) and grafted segments (n = 289). A significant stenosis was defined as ≥50% lumen diameter reduction, and quantitative coronary angiography served as reference standard. Results: The diagnostic accuracy of CTA for the detection or exclusion of significant stenosis in arterial and venous grafts on a segment-by-segment analysis was 100%. Sensitivity, specificity, positive predictive value, and negative predictive value to detect significant stenosis were 95% (95% confidence interval [CI]: 73% to 100%), 100% (95% CI: 96% to 100%), 100% (95% CI: 79% to 100%), 99% (95% CI: 95% to 100%) in distal runoffs respectively; 100% (95% CI: 97% to 100%), 96% (95% CI: 90% to 98%), 97% (95% CI: 93% to 99%), 100% (95% CI: 95% to 100%) in grafted native coronary arteries respectively; and 97% (95% CI: 83% to 100%), 92% (95% CI: 83% to 96%), 83% (95% CI: 67% to 92%), 99% (95% CI: 92% to 100%) in nongrafted native coronary arteries, respectively. Conclusions: Noninvasive CTA is successful for evaluating bypass grafts in symptomatic post-CABG patients, whereas invasive coronary angiography is still required for the assessment of significant stenosis in distal runoffs and native coronary arteries.