Gert-Jan R. ten Kate

Diagnostic Accuracy of Computed Tomography Angiography in Patients After Bypass Grafting: Comparison With Invasive Coronary Angiography

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 >or=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.

Image Quality and Radiation Exposure Using Different Low-Dose Scan Protocols in Dual-Source CT Coronary Angiography: Randomized Study

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.

Accelerated subclinical coronary atherosclerosis in patients with familial hypercholesterolemia

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.

CT coronary plaque burden in asymptomatic patients with familial hypercholesterolaemia

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.

The effect of LDLR-negative genotype on CT coronary atherosclerosis in asymptomatic statin treated patients with heterozygous familial hypercholesterolemia.

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.

Increased Aortic Valve Calcification in Familial Hypercholesterolemia Prevalence, Extent, and Associated Risk Factors

BACKGROUND Familial hypercholesterolemia is typically caused by LDL receptor (LDLR) mutations that result in elevated levels of LDL cholesterol (LDL-C). In homozygous FH, the prevalence of aortic valve calcification (AoVC) reaches 100% and is often symptomatic. OBJECTIVES The objective of this study was to investigate the prevalence, extent, and risk-modifiers of AoVC in heterozygous FH (he-FH) that are presently unknown. METHODS Asymptomatic patients with he-FH and 131 non-familial hypercholesterolemia controls underwent CT computed tomography calcium scoring. AoVC was defined as the presence of calcium at the aortic valve leaflets. The extent of AoVC was expressed in Agatston units, as the AoVC-score. We compared the prevalence and extent of AoVC between cases and controls. In addition, we investigated risk modifiers of AoVC, including the presence of LDLR mutations without residual function (LDLR-negative mutations), maximum untreated LDL-cholesterol (maxLDL), LDL-C, blood pressure, and coronary artery calcification (CAC). RESULTS We included 145 asymptomatic patients with he-FH (93 men; mean age 52 ± 8 years) and 131 non-familial hypercholesterolemia controls. The prevalence (%) and AoVC-score (median, IQR) were higher in he-FH patients than in controls: 41%, 51 (9-117); and 21%, 21 (3-49) (p < 0.001 and p = 0.007). Age, untreated maxLDL, CAC, and diastolic blood pressure were independently associated with AoVC. LDLR-negative mutational he-FH was the strongest predictor of the AoVC-score (OR: 4.81; 95% CI: 2.22 to 10.40; p = <0.001). CONCLUSIONS Compared to controls, he-FH is associated with a high prevalence and a large extent of subclinical AoVC, especially in patients with LDLR-negative mutations, highlighting the critical role of LDL-C metabolism in AoVC etiology.

Coronary CT angiography outperforms calcium imaging in the triage of acute coronary syndrome

BACKGROUND In this prospective study we determine the diagnostic value of coronary CT angiography (CTA) and calcium imaging in low to intermediate risk acute chest pain patients. METHODS One hundred and eleven consecutive patients (57 ± 11 years, 71 males) presenting to the emergency department with chest pain suggestive of acute coronary syndrome (ACS), but without indication for immediate catheter angiography, underwent both coronary CTA and calcium imaging without disclosure of the findings to the treating physicians. RESULTS ACS was diagnosed in 19 patients (17%). Coronary calcium was present in 71 patients (64%). Coronary CTA identified 74 (67%) patients with coronary plaque and 36 (32%) patients with obstructive (≥ 50%) plaque. The sensitivity and specificity of the calcium scan were: 89% and 41%. The sensitivity and specificity of coronary CTA were: 100% and 40% based on the presence of any plaque and 89% and 79% based on the presence of >50% stenosis. C-statistics of the GRACE risk score (0.77 [95% CI 0.66-0.89]) improved after addition of coronary CTA (0.93 [0.88-0.98], p<0.01), though not after addition of calcium scores (0.81 [0.71-0.91], p=0.52). Follow-up at 3 months revealed four late revascularizations (no deaths or myocardial infarctions), all of whom had obstructive CAD with calcium on CT at presentation. CONCLUSIONS Coronary CTA outperforms calcium imaging in the triage of patients suspected of developing ACS. Absence of plaque on coronary CTA allows safe discharge. Coronary CTA has incremental value to clinical risk scores and has the potential to reduce unnecessary hospital admissions.

Computed tomography coronary imaging as a gatekeeper for invasive coronary angiography in patients with newly diagnosed heart failure of unknown aetiology.

To evaluate the accuracy of cardiac computed tomography (CT) in distinguishing CAD and non‐CAD heart failure (HF) and its effectiveness as a gatekeeper for invasive coronary angiography (ICA).

Copeptin in acute chest pain: Identification of acute coronary syndrome and obstructive coronary artery disease on coronary CT angiography

Objective To determine the diagnostic accuracy of copeptin in patients with suspected acute coronary syndrome (ACS) and its correlation with obstructive coronary artery disease (CAD) on coronary CT angiography (CTA). Methods Copeptin was measured at arrival in 65 consecutive patients (56±10 years, 45 men) suspected of ACS and no indication for immediate invasive angiography. All patients underwent coronary CTA without disclosure of the results to the treating physician, and outcomes were classified as obstructive CAD (>50% stenosis) or no obstructive CAD (≤50%) in one or more vessel. Results The final diagnosis of ACS was established in 10 (15%) patients, 6 myocardial infarctions and 4 unstable angina pectoris. Coronary CTA detected obstructive CAD in all patients with ACS and in 10 (15%) patients with no ACS. Copeptin concentrations were higher in patients with ACS (median 7.42 pmol/l (IQR 3.71–18.72)) vs patients with no ACS (3.40 pmol/l (1.13–6.27), p=0.02). Copeptin was not higher in patients with obstructive CAD on coronary CTA (4.87 pmol/l (2.90–8.51) vs 3.60 pmol/l (1.21–6.23), p=0.20) compared with patients with no obstructive CAD. Conclusions Copeptin seems to be elevated in patients with ACS while there is no strong correlation with obstructive coronary disease on CTA.