Dynamic Myocardial Perfusion CT for the Detection of Hemodynamically Significant Coronary Artery Disease.

OBJECTIVES: In this international, multicenter study, using third-generation dual-source computed tomography (CT), we investigated the diagnostic performance of dynamic stress CT myocardial perfusion imaging (CT-MPI) in addition to coronary CT angiography (CTA) compared to invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR). BACKGROUND: CT-MPI combined with coronary CTA integrates coronary artery anatomy with inducible myocardial ischemia, showing promising results for the diagnosis of hemodynamically significant coronary artery disease in single-center studies. METHODS: At 9 centers in Europe, Japan, and the United States, 132 patients scheduled for ICA were enrolled; 114 patients successfully completed coronary CTA, adenosine-stress dynamic CT-MPI, and ICA. Invasive FFR was performed in vessels with 25% to 90% stenosis. Data were analyzed by independent core laboratories. For the primary analysis, for each coronary artery the presence of hemodynamically significant obstruction was interpreted by coronary CTA with CT-MPI compared to coronary CTA alone, using an FFR of ≤0.80 and angiographic severity as reference. Territorial absolute myocardial blood flow (MBF) and relative MBF were compared using C-statistics. RESULTS: ICA and FFR identified hemodynamically significant stenoses in 74 of 289 coronary vessels (26%). Coronary CTA with ≥50% stenosis demonstrated a per-vessel sensitivity, specificity, and accuracy for the detection of hemodynamically significant stenosis of 96% (95% CI: 91%-100%), 72% (95% CI: 66%-78%), and 78% (95% CI: 73%-83%), respectively. Coronary CTA with CT-MPI showed a lower sensitivity (84%; 95% CI: 75%-92%) but higher specificity (89%; 95% CI: 85%-93%) and accuracy (88%; 95% CI: 84%-92%). The areas under the receiver-operating characteristic curve of absolute MBF and relative MBF were 0.79 (95% CI: 0.71-0.86) and 0.82 (95% CI: 0.74-0.88), respectively. The median dose-length product of CT-MPI and coronary CTA were 313 mGy·cm and 138 mGy·cm, respectively. CONCLUSIONS: Dynamic CT-MPI offers incremental diagnostic value over coronary CTA alone for the identification of hemodynamically significant coronary artery disease. Generalized results from this multicenter study encourage broader consideration of dynamic CT-MPI in clinical practice. (Dynamic Stress Perfusion CT for Detection of Inducible Myocardial Ischemia [SPECIFIC]; NCT02810795).

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.

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.

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.

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.

Stable angina pectoris: head-to-head comparison of prognostic value of cardiac CT and exercise testing.

PURPOSE: To determine and compare the prognostic value of cardiac computed tomographic (CT) angiography, coronary calcium scoring, and exercise electrocardiography (ECG) in patients with chest pain who are suspected of having coronary artery disease (CAD). MATERIALS AND METHODS: This study complied with the Declaration of Helsinki, and the local ethics committee approved the study. Patients (n = 471) without known CAD underwent exercise ECG and dual-source CT at a rapid assessment outpatient chest pain clinic. Coronary calcification and the presence of 50% or greater coronary stenosis (in one or more vessels) were assessed with CT. Exercise ECG results were classified as normal, ischemic, or nondiagnostic. The primary outcome was a major adverse cardiac event (MACE), defined as cardiac death, nonfatal myocardial infarction, or unstable angina requiring hospitalization and revascularization beyond 6 months. Univariable and multivariable Cox regression analysis was used to determine the prognostic values, while clinical impact was assessed with the net reclassification improvement metric. RESULTS: Follow-up was completed for 424 (90%) patients; the mean duration of follow-up was 2.6 years. A total of 44 MACEs occurred in 30 patients. Four of the MACEs were cardiac deaths and six were nonfatal myocardial infarctions. The presence of coronary calcification (hazard ratio [HR], 8.22 [95% confidence interval {CI}: 1.96, 34.51]), obstructive CAD (HR, 6.22 [95% CI: 2.77, 13.99]), and nondiagnostic stress test results (HR, 3.00 [95% CI: 1.26, 7.14]) were univariable predictors of MACEs. In the multivariable model, CT angiography findings (HR, 5.0 [95% CI: 1.7, 14.5]) and nondiagnostic exercise ECG results (HR, 2.9 [95% CI: 1.2, 7.0]) remained independent predictors of MACEs. CT angiography findings showed incremental value beyond clinical predictors and stress testing (global χ(2), 37.7 vs 13.7; P < .001), whereas coronary calcium scores did not have further incremental value (global χ(2), 38.2 vs 37.7; P = .40). CONCLUSION: CT angiography findings are a strong predictor of future adverse events, showing incremental value over clinical predictors, stress testing, and coronary calcium scores. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110744/-/DC1.