The effect of coronary bifurcation and haemodynamics in prediction of atherosclerotic plaque development: a serial computed tomographic coronary angiographic study.

AIMS: The aim of this study was to examine the effect of the daughter branches on the haemodynamics and the potential prediction of atherosclerotic plaque development as well as the best flow division model for accurate blood flow modelling. METHODS AND RESULTS: We analysed computed tomography coronary angiography retrospective data portraying 17 coronary artery bifurcations in 15 patients recruited into the PROSPECT MSCT study. Baseline and three-year follow-up imaging data were used to reconstruct coronary artery anatomy. In the baseline models blood flow simulations were performed using three flow division approaches: stress-free, Murray's law and Doriot's fit. Blood flow simulation was also performed omitting the daughter branch. The association between ESS estimated in models that incorporated the daughter branches and lumen reduction was higher than the cases where the side branch was omitted. Murray's law provides the most accurate results when comparing the different flow division models. More specifically, low ESS is a predictor of significant lumen reduction (p=0.007), plaque burden increase (p=0.0006) and necrotic core change (p=0.025). CONCLUSIONS: The ESS distribution in coronary models including the daughter branches and based on the calculations implementing Murray's law allows more accurate prediction of atherosclerotic evolution than ESS estimated in models including only the main vessel.

Prediction of atherosclerotic disease progression using LDL transport modelling: a serial computed tomographic coronary angiographic study.

AIM: To investigate the efficacy of low-density lipoprotein (LDL) transport simulation in reconstructed arteries derived from computed tomography coronary angiography (CTCA) to predict coronary segments that are prone to progress. METHODS AND RESULTS: Thirty-two patients admitted with an acute coronary event who underwent 64-slice CTCA after percutaneous coronary intervention and at 3-year follow-up were included in the analysis. The CTCA data were used to reconstruct the coronary anatomy of the untreated vessels at baseline and follow-up, and LDL transport simulation was performed in the baseline models. The computed endothelial shear stress (ESS), LDL concentration, and CTCA-derived plaque characteristics were used to identify predictors of substantial disease progression (defined as an increase in the plaque burden at follow-up higher than two standard deviations of the intra-observer variability of the expert who performed the analysis). Fifty-eight vessels were analysed. High LDL concentration [odds ratio (OR): 2.16; 95% confidence interval (CI): 1.64-2.84; P = 0.0054], plaque burden (OR: 1.40; 95% CI: 1.13-1.72; P = 0.0017), and plaque area (OR: 3.46; 95% CI: 2.20-5.44; P≤ 0.0001) were independent predictors of a substantial disease progression at follow-up. The ESS appears as a predictor of disease progression in univariate analysis but was not an independent predictor when the LDL concentration was entered into the multivariate model. The accuracy of the model that included the LDL concentration was higher than the accuracy of the model that included the ESS (65.1 vs. 62.5%). CONCLUSIONS: LDL transport modelling appears a better predictor of atherosclerotic disease progression than the ESS, and combined with the atheroma characteristics provided by CTCA is able to detect with a moderate accuracy segments that will exhibit a significant plaque burden increase at mid-term follow-up.

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.

Computed tomography segmental calcium score (SCS) to predict stenosis severity of calcified coronary lesions.

To estimate the probability of ≥ 50% coronary stenoses based on computed tomography (CT) segmental calcium score (SCS) and clinical factors. The Institutional Review Board approved the study. A training sample of 201 patients underwent CT calcium scoring and conventional coronary angiography (CCA). All patients consented to undergo CT before CCA after being informed of the additional radiation dose. SCS and calcification morphology were assessed in individual coronary segments. We explored the predictive value of patient's symptoms, clinical history, SCS and calcification morphology. We developed a prediction model in the training sample based on these variables then tested it in an independent test sample. The odds ratio (OR) for ≥ 50% coronary stenosis was 1.8-fold greater (p = 0.006) in patients with typical chest pain, twofold (p = 0.014) greater in patients with acute coronary syndromes, twofold greater (p < 0.001) in patients with prior myocardial infarction. Spotty calcifications had an OR for ≥ 50% stenosis 2.3-fold (p < 0.001) greater than the absence of calcifications, wide calcifications 2.7-fold (p < 0.001) greater, diffuse calcifications 4.6-fold (p < 0.001) greater. In middle segments, each unit of SCS had an OR 1.2-fold (p < 0.001) greater than in distal segments; in proximal segments the OR was 1.1-fold greater (p = 0.021). The ROC curve area of the prediction model was 0.795 (0.95 confidence interval 0.602-0.843). Validation in a test sample of 201 independent patients showed consistent diagnostic performance. In conjunction with calcification morphology, anatomical location, patient's symptoms and clinical history, SCS can be helpful to estimate the probability of ≥ 50% coronary stenosis.

Quantification of the myocardial area at risk using coronary CT angiography and Voronoi algorithm-based myocardial segmentation.

OBJECTIVES: The purpose of this study was to estimate the myocardial area at risk (MAAR) using coronary computed tomography angiography (CTA) and Voronoi algorithm-based myocardial segmentation in comparison with single-photon emission computed tomography (SPECT). METHODS: Thirty-four patients with coronary artery disease underwent 128-slice coronary CTA, stress/rest thallium-201 SPECT, and coronary angiography (CAG). CTA-based MAAR was defined as the sum of all CAG stenosis (>50%) related territories (the ratio of the left ventricular volume). Using automated quantification software (17-segment model, 5-point scale), SPECT-based MAAR was defined as the number of segments with a score above zero as compared to the total 17 segments by summed stress score (SSS), difference (SDS) score map, and comprehensive SPECT interpretation with either SSS or SDS best correlating CAG findings (SSS/SDS). Results were compared using Pearson's correlation coefficient. RESULTS: Forty-nine stenoses were observed in 102 major coronary territories. Mean value of CTA-based MAAR was 28.3 ± 14.0%. SSS-based, SDS-based, and SSS/SDS-based MAAR was 30.1 ± 6.1%, 20.1 ± 15.8%, and 26.8 ± 15.7%, respectively. CTA-based MAAR was significantly related to SPECT-based MAAR (r = 0.531 for SSS; r = 0.494 for SDS; r = 0.814 for SSS/SDS; P < 0.05 in each). CONCLUSIONS: CTA-based Voronoi algorithm myocardial segmentation reliably quantifies SPECT-based MAAR. KEY POINTS: • Voronoi algorithm allows for three-dimensional myocardial segmentation of coronary CT angiography • Stenosis-related CT myocardial territories correlate to SPECT based area at risk • CT angiography myocardial segmentation may assist in clinical decision-making.

Positive remodeling at 3 year follow up is associated with plaque-free coronary wall segment at baseline: a serial IVUS study.

AIMS: At present it is unknown what limits the arterial remodeling process during atherosclerotic plaque formation. In healthy arteries remodeling is regulated by the shear stress induced response by the endothelium. As endothelium at the plaque site is assumed to be dysfunctional, we tested the hypothesis that plaque free wall (PFW) determines vascular remodeling during atherosclerotic plaque build-up. METHODS & RESULTS: 66 human coronary ROIs (38 patients) were studied at baseline and at 3 years follow up applying intravascular ultrasound (IVUS). From the IVUS images the lumen and external elastic membrane contours were delineated to assess wall thickness (WT), vessel area (VA), Plaque Area (PA) and plaque burden (PA/VA*100%). WT < 0.5 mm was defined as normal and determined the arc of the PFW (0-360°). Positive remodeling was defined as relative difference of VA over time >5%. At baseline, IVUS-PFW was inversely related to plaque burden (p < 0.05). Positive remodeling was most frequently observed in ROIs with IVUS-PFW > 180° (i.e. larger than half of the circumference) compared to PFW < 180° (55% vs. 12%, p < 0.05). Accordingly, plaques with IVUS-PFW > 180° at baseline had the largest change in VA (1.1 ± 2.1 vs. -0.4 ± 0.6 mm(2), p < 0.05) with an odds ratio of 9.2 to develop positive remodeling. CONCLUSIONS: Our serial IVUS data show that IVUS-PFW is a determinant of vascular remodeling. ROIs with PFW > 180 at baseline had the highest probability to undergo positive remodeling.

A CT-based Medina classification in coronary bifurcations: does the lumen assessment provide sufficient information?

AIMS: To evaluate the distribution of atherosclerosis at bifurcations with computed tomography coronary angiography (CTCA) and propose a novel CT-Medina classification for bifurcation lesions. METHODS: In 26 patients (age 55 ± 10 years, 81% male) imaged with CTCA, 39 bifurcations were studied. The bifurcations analysis included the proximal main vessel, the distal main vessel and the side branch (SB). Plaque contours were manually traced on CTCA; the lumen, vessel and plaque area were measured, as well as plaque burden (%). The carina cross-sections were divided into four equal parts according to the expected wall shear stress (WSS) to assess circumferential plaque distribution. All the bifurcation lesions were classified using the Medina classification and a novel CT-Medina classification combining lumen narrowing and plaque burden ≥70%. RESULTS: Presence of severe plaque (plaque burden ≥70%) by CTCA was demonstrated in 12.8% (5/39) of the proximal segments, 15.4% (6/39) of the distal segments and 7.7% (3/39) of the SB segments. The thickest plaque was located more often in low WSS parts of the carina cross-sections, whereas the flow divider was rarely affected. Although in the majority of bifurcations plaque was present, based on the Medina classification 92% of the assessed bifurcations were identified as 0,0,0. Characterization of bifurcation lesions using the new CT-Medina classification provided additional information in seven cases (18%) compared to the Medina classification CONCLUSION: Atherosclerotic plaque is widely present in all bifurcation segments, even in the absence of coronary lumen stenosis. A CT-Medina classification combining lumen and plaque parameters is more informative than angiographic classification of bifurcation lesions and could potentially facilitate the decision-making on the treatment of these lesions.

Quantitative computed tomographic coronary angiography: does it predict functionally significant coronary stenoses?

BACKGROUND: Coronary lesions with a diameter narrowing ≥50% on visual computed tomographic coronary angiography (CTCA) are generally considered for referral to invasive coronary angiography. However, similar to invasive coronary angiography, visual CTCA is often inaccurate in detecting functionally significant coronary lesions. We sought to compare the diagnostic performance of quantitative CTCA with visual CTCA for the detection of functionally significant coronary lesions using fractional flow reserve (FFR) as the reference standard. METHODS AND RESULTS: CTCA and FFR measurements were obtained in 99 symptomatic patients. In total, 144 coronary lesions detected on CTCA were visually graded for stenosis severity. Quantitative CTCA measurements included lesion length, minimal area diameter, % area stenosis, minimal lumen diameter, % diameter stenosis, and plaque burden [(vessel area-lumen area)/vessel area×100]. Optimal cutoff values of CTCA-derived parameters were determined, and their diagnostic accuracy for the detection of flow-limiting coronary lesions (FFR≤0.80) was compared with visual CTCA. FFR was ≤0.80 in 54 of 144 (38%) coronary lesions. Optimal cutoff values to predict flow-limiting coronary lesion were 10 mm for lesion length, 1.8 mm2 for minimal area diameter, 73% for % area stenosis, 1.5 mm for minimal lumen diameter, 48% for % diameter stenosis, and 76% for plaque burden. No significant difference in sensitivity was found between visual CTCA and quantitative CTCA parameters (P>0.05). The specificity of visual CTCA (42%; 95% confidence interval [CI], 31%-54%) was lower than that of minimal area diameter (68%; 95% CI, 57%-77%; P=0.001), % area stenosis (76%; 95% CI, 65%-84%; P<0.001), minimal lumen diameter (67%; 95% CI, 55%-76%; P=0.001), % diameter stenosis (72%; 95% CI, 62%-80%; P<0.001), and plaque burden (63%; 95% CI, 52%-73%; P=0.004). The specificity of lesion length was comparable with that of visual CTCA. CONCLUSIONS: Quantitative CTCA improves the prediction of functionally significant coronary lesions compared with visual CTCA assessment but remains insufficient. Functional assessment is still required in lesions of moderate stenosis to accurately detect impaired FFR.

Diagnostic performance of hyperaemic myocardial blood flow index obtained by dynamic computed tomography: does it predict functionally significant coronary lesions?

AIMS: The severity of coronary artery narrowing is a poor predictor of functional significance, in particular in intermediate coronary lesions (30-70% diameter narrowing). The aim of this work was to compare the performance of a quantitative hyperaemic myocardial blood flow (MBF) index derived from adenosine dynamic computed tomography perfusion (CTP) imaging with that of visual CT coronary angiography (CTCA) and semi-automatic quantitative CT (QCT) in the detection of functionally significant coronary lesions in patients with stable chest pain. METHODS AND RESULTS: CTCA and CTP were performed in 80 patients (210 analysable coronary vessels) referred to invasive coronary angiography (ICA). The MBF index (mL/100 mL/min) was computed using a model-based parametric deconvolution method. The diagnostic performance of the MBF index in detecting functionally significant coronary lesions was compared with visual CTCA and QCT. Coronary lesions with invasive fractional flow reserve of ≤0.75 were defined as functionally significant. The optimal cut-off value of the MBF index to detect functionally significant coronary lesions was 78 mL/100 mL/min. On a vessel-territory level, the MBF index had a larger area under the curve (0.95; 95% confidence interval [95% CI]: 0.92-0.98) compared with visual CTCA (0.85; 95% CI: 0.79-0.91) and QCT (0.89; 95% CI: 0.84-0.93) (both P-values <0.001). In the analysis restricted to intermediate coronary lesions, the specificity of visual CTCA (69%) and QCT (77%) could be improved by the subsequent use of the MBF index (89%). CONCLUSION: In this proof-of-principle study, the MBF index performed better than visual CTCA and QCT in the identification of functionally significant coronary lesions. The MBF index had additional value beyond CTCA anatomy in intermediate coronary lesions. This may have a potential to support patient management.

Stress myocardial perfusion: imaging with multidetector CT.

Computed tomographic (CT) coronary angiography is a well-established, noninvasive imaging modality for detection of coronary stenosis, but it has limited accuracy in demonstrating whether a coronary stenosis is hemodynamically significant. An additional functional test is often required because both anatomic and functional information is needed for guiding patient care. Recent developments in CT technology allow CT evaluation of myocardial perfusion during vasodilator stress, thereby providing information about myocardial ischemia. Investigators in several single-center studies have established the feasibility of performing stress myocardial perfusion CT imaging in small groups of patients and have shown that stress myocardial perfusion CT in combination with CT coronary angiography improved the diagnostic accuracy in comparison with CT coronary angiography alone. However, CT perfusion acquisition protocols must be optimized in terms of acquisition and reconstruction parameters, contrast material protocol injections, and radiation dose. Further research is needed to establish the clinical usefulness of this novel technique. The purpose of this review is to (a) provide an overview of the physiology of coronary circulation and myocardial perfusion; (b) describe the technical prerequisites, challenges, and mathematic modeling related to CT perfusion imaging; (c) note recent advances in CT scanners and CT perfusion protocols; and (d) discuss the interpretation of CT perfusion images. Finally, a review and summary of the current literature are provided, and future directions for research are discussed.

Evolution of reperfusion post-infarction ventricular remodeling: new MRI insights.

BACKGROUND: Our current understanding is that left ventricular (LV) remodeling after acute myocardial infarction (AMI) is caused by expansion of the infarcted myocardium with thinning of the wall and eccentric hypertrophy of the remote myocardium. To study the geometric changes in the remodeling process after reperfused AMI we used cardiac magnetic resonance imaging (CMR). METHODS: Nine juvenile swine underwent a 120-min occlusion of the left circumflex coronary artery followed by reperfusion. CMR was performed at 3 and 36 days post-infarction. Global and regional LV remodeling was assessed including geometric changes of infarcted and remote myocardium; infarct longitudinal length (mm), mean circumferential length (mm), total infarct surface (mm(2)), end-diastolic wall thickness (EDWT) (mm) and transmural extent of infarction (TEI). RESULTS: From 3 days to 36 days post-infarction end-diastolic volume increased by 43% (p<0.01). Infarct mass decreased by 36% (p<0.01), mainly by reduction of EDWT with 26%, while mean infarct circumferential length and longitudinal infarct length did not change. Remote myocardial mass increased by 23%, which was the result of an increase in its circumferential length from 95 ± 10 mm to 113 ± 11 mm (p<0.01), with no change in its EDWT. In contrast, EDWT in the infarct, peri-infarct and border zone decreased. CONCLUSIONS: Contrary to the widely held view the present, using CMR measurements, shows that post-infarction remodeling was not associated with expansion of the infarcted myocardium. These findings suggest that eccentric hypertrophy of the remote myocardium, but not expansion of the infarct region, is responsible for left ventricular dilatation after AMI.

Impact of iterative reconstruction on CT coronary calcium quantification.

OBJECTIVES: We evaluated the influence of sinogram-affirmed iterative reconstruction (SAFIRE) on the coronary artery calcium (CAC) score by computed tomography (CT). MATERIALS AND METHODS: Seventy patients underwent CAC imaging by 128-slice dual-source CT. CAC volume, mass and Agatston score were calculated from images reconstructed by filtered back projection (FBP) without and with incremental degrees of the SAFIRE algorithm (10-50 %). We used the repeated measuring test and the Steel-Dwass test for multiple comparisons of values and the difference ratio among different SAFIRE groups using the FBP as reference. RESULTS: The median Agatston score (range) decreased with incremental SAFIRE degrees: 163 (0.1 - 3,393.3), 158.4 (0.3 - 3,079.3), 137.7 (0.1 - 2,978.0), 120.6 (0 - 2,783.6), 102.6 (0 - 2,468.4) and 84.1 (0 - 2,186.9) for 0 % (FBP), 10 %, 20 %, 30 %, 40 % and 50 % SAFIRE, respectively (P < 0.05). In comparison with FBP, CAC volume (from 8.1 % to 47.7 %), CAC mass (from 5.3 % to 44.7 %) and CAC Agatston score (from 7.3 % to 48.4 %) all decreased with increasing SAFIRE from 10 % to 50 %, respectively (P < 0.05). High-grade SAFIRE resulted in the disappearance of detectable calcium in three cases with low calcium burden. CONCLUSION: SAFIRE noise reduction techniques significantly affected the CAC, which potentially alters perceived cardiovascular risk.

Restriction of the referral of patients with stable angina for CT coronary angiography by clinical evaluation and calcium score: impact on clinical decision making.

OBJECTIVE: To investigate the value of the calcium score (CaSc) plus clinical evaluation to restrict referral for CT coronary angiography (CTCA) by reducing the number of patients with an intermediate probability of coronary artery disease (CAD). METHODS: We retrospectively included 1,975 symptomatic stable patients who underwent clinical evaluation and CaSc calculation and CTCA or invasive coronary coronary angiography (ICA). The outcome was obstructive CAD (≥50 % diameter narrowing) assessed by ICA or CTCA in the absence of ICA. We investigated two models: (1) clinical evaluation consisting of chest pain typicality, gender, age, risk factors and ECG and (2) clinical evaluation with CaSc. Discrimination of the two models was compared. The stepwise reclassification of patients with an intermediate probability of CAD (10-90 %) after clinical evaluation followed by clinical evaluation with CaSc was assessed by clinical net reclassification improvement (NRI). RESULTS: Discrimination of CAD was significantly improved by adding CaSc to the clinical evaluation (AUC: 0.80 vs. 0.89, P < 0.001). CaSc and CTCA could be avoided in 9 % using model 1 and an additional 29 % of CTCAs could be avoided using model 2. Clinical NRI was 57 %. CONCLUSION: CaSc plus clinical evaluation may be useful in restricting further referral for CTCA by 38 % in symptomatic stable patients with suspected CAD. KEY POINTS: • CT calcium scores (CaSc) could proiritise referrals for CT coronary angiography (CTCA) • CaSc provides an incremental discriminatory value of CAD compared with clinical evaluation • Risk stratification is better when clinical evaluation is combined with CaSc • Appropriate use of clinical evaluation and CaSc helps avoid unnecessary CTCA referrals.

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

AIMS: 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). METHODS AND RESULTS: We prospectively included 93 symptomatic patients with newly diagnosed HF of unknown aetiology (59 men; mean age 53 ± 13) and EF <45%, and/or fractional shortening <25%, and/or end-diastolic LV diameter >60 mm (men) or >55 mm (women). In all patients, the CT calcium score (CTCS) was determined. CTCS = 0 excluded CAD HF. Additional CT coronary angiography (CTCA) was performed if CTCS >0. ICA was used as the gold standard for distinguishing between CAD and non-CAD HF in patients with >20% luminal diameter narrowing on CTCA. CAD HF was defined as >50% luminal diameter narrowing in either (i) the left main coronary artery or proximal left anterior descending coronary artery or (ii) in multiple coronary arteries. Diagnostic accuracy and follow-up data (20 ± 16 months) were collected for all patients. CTCS = 0 ruled out CAD HF in 43 patients (46%). The CT algorithm had 100% sensitivity, 95% specificity, 67% positive predictive value, and 100% negative predictive value for detecting CAD HF. Patients with CTCS = 0 or non-CAD HF on CTCA had no coronary events during follow-up, and ICA could have been safely avoided in 76 out of 93 patients (82%). CONCLUSION: In patients with HF of unknown aetiology, cardiac CT combining CTCS and CTCA has high accuracy for detecting CAD HF and can be used effectively as a gatekeeper for ICA.

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.

Carotid plaque burden as a measure of subclinical coronary artery disease in patients with heterozygous familial hypercholesterolemia.

Patients with familial hypercholesterolemia (FH) are at markedly increased risk of developing premature coronary artery disease. The objective of the present study was to evaluate the role of carotid ultrasonography as a measure of subclinical coronary artery disease in patients with FH. The present prospective study compared the presence of subclinical carotid and coronary artery disease in 67 patients with FH (mean age 55 ± 8 years, 52% men) to that in 30 controls with nonanginal chest pain (mean age 56 ± 9 years, 57% men). The carotid intima-media thickness and carotid plaque burden were assessed using B-mode ultrasonography, according to the Mannheim consensus. Coronary artery disease was assessed using computed tomographic coronary angiography. A lumen reduction >50% was considered indicative of obstructive coronary artery disease. The patients with FH and the controls had a comparable carotid intima-media thickness (0.64 vs 0.66 mm, p = 0.490), prevalence of carotid plaque (93% vs 83%, p = 0.361), and median carotid plaque score (3 vs 2, p = 0.216). Patients with FH had a significantly greater median coronary calcium score than did the controls (62 vs 5, p = 0.015). However, the prevalence of obstructive coronary artery disease was comparable (27% vs 31%, p = 0.677). No association was found between the carotid intima-media thickness and coronary artery disease. An association was found between the presence of carotid plaque and coronary artery disease in the patients with FH and the controls. The absence of carotid plaque, observed in 5 patients (7%) with FH, excluded the presence of obstructive coronary artery disease. In conclusion, the patients with FH had a high prevalence of carotid plaque and a significantly greater median coronary calcium score than did the controls. A correlation was found between carotid plaque and coronary artery disease in patients with FH; however, the presence of carotid plaque and carotid plaque burden are not reliable indicators of obstructive coronary artery disease.

Vessel specific coronary artery calcium scoring: an automatic system.

RATIONALE AND OBJECTIVES: The aim of this study was to automatically detect and quantify calcium lesions for the whole heart as well as per coronary artery on non-contrast-enhanced cardiac computed tomographic images. MATERIALS AND METHODS: Imaging data from 366 patients were randomly selected from patients who underwent computed tomographic calcium scoring assessments between July 2004 and May 2009 at Erasmum MC, Rotterdam. These data included data sets with 1.5-mm and 3.0-mm slice spacing reconstructions and were acquired using four different scanners. The scores of manual observers, who annotated the data using commercially available software, served as ground truth. An automatic method for detecting and quantifying calcifications for each of the four main coronary arteries and the whole heart was trained on 209 data sets and tested on 157 data sets. Statistical testing included determining Pearson's correlation coefficients and Bland-Altman analysis to compare performance between the system and ground truth. Wilcoxon's signed-rank test was used to compare the interobserver variability to the system's performance. RESULTS: Automatic detection of calcified objects was achieved with sensitivity of 81.2% per calcified object in the 1.5-mm data set and sensitivity of 86.6% per calcified object in the 3.0-mm data set. The system made an average of 2.5 errors per patient in the 1.5-mm data set and 2.2 errors in the 3.0-mm data set. Pearson's correlation coefficients of 0.97 (P < .001) for both 1.5-mm and 3.0-mm scans with respect to the calcium volume score of the whole heart were found. The average R values over Agatston, mass, and volume scores for each of the arteries (left circumflex coronary artery, right coronary artery, and left main and left anterior descending coronary arteries) were 0.93, 0.96, and 0.99, respectively, for the 1.5-mm scans. Similarly, for 3.0-mm scans, R values were 0.94, 0.94, and 0.99, respectively. Risk category assignment was correct in 95% and 89% of the data sets in the 1.5-mm and 3-mm scans. CONCLUSIONS: An automatic vessel-specific coronary artery calcium scoring system was developed, and its feasibility for calcium scoring in individual vessels and risk category classification has been demonstrated.

Coronary computed tomography versus exercise testing in patients with stable chest pain: comparative effectiveness and costs.

BACKGROUND: To determine the comparative effectiveness and costs of a CT-strategy and a stress-electrocardiography-based strategy (standard-of-care; SOC-strategy) for diagnosing coronary artery disease (CAD). METHODS: A decision analysis was performed based on a well-documented prospective cohort of 471 outpatients with stable chest pain with follow-up combined with best-available evidence from the literature. Outcomes were correct classification of patients as CAD- (no obstructive CAD), CAD+ (obstructive CAD without revascularization) and indication for Revascularization (using a combination reference standard), diagnostic costs, lifetime health care costs, and quality-adjusted life years (QALY). Parameter uncertainty was analyzed using probabilistic sensitivity analysis. RESULTS: For men (and women), diagnostic cost savings were €245 (€252) for the CT-strategy as compared to the SOC-strategy. The CT-strategy classified 82% (88%) of simulated men (women) in the appropriate disease category, whereas 83% (85%) were correctly classified by the SOC-strategy. The long-term cost-effectiveness analysis showed that the SOC-strategy was dominated by the CT-strategy, which was less expensive (-€229 in men, -€444 in women) and more effective (+0.002 QALY in men, +0.005 in women). The CT-strategy was cost-saving (-€231) but also less effective compared to SOC (-0.003 QALY) in men with a pre-test probability of ≥ 70%. The CT-strategy was cost-effective in 100% of simulations, except for men with a pre-test probability ≥ 70% in which case it was 59%. CONCLUSIONS: The results suggest that a CT-based strategy is less expensive and equally effective compared to SOC in all women and in men with a pre-test probability <70%.