Admir Dedic

Fractional Flow Reserve Computed from Noninvasive CT Angiography Data: Diagnostic Performance of an On-Site Clinician-operated Computational Fluid Dynamics Algorithm

PURPOSE To validate an on-site algorithm for computation of fractional flow reserve (FFR) from coronary computed tomographic (CT) angiography data against invasively measured FFR and to test its diagnostic performance as compared with that of coronary CT angiography. MATERIALS AND METHODS The institutional review board provided a waiver for this retrospective study. From coronary CT angiography data in 106 patients, FFR was computed at a local workstation by using a computational fluid dynamics algorithm. Invasive FFR measurement was performed in 189 vessels (80 of which had an FFR ≤ 0.80); these measurements were regarded as the reference standard. The diagnostic characteristics of coronary CT angiography-derived computational FFR, coronary CT angiography, and quantitative coronary angiography were evaluated against those of invasively measured FFR by using C statistics. Sensitivity and specificity were compared by using a two-sided McNemar test. RESULTS For computational FFR, sensitivity was 87.5% (95% confidence interval [CI]: 78.2%, 93.8%), specificity was 65.1% (95% CI: 55.4%, 74.0%), and accuracy was 74.6% (95% CI: 68.4%, 80.8%), as compared with the finding of lumen stenosis of 50% or greater at coronary CT angiography, for which sensitivity was 81.3% (95% CI: 71.0%, 89.1%), specificity was 37.6% (95% CI: 28.5%, 47.4%), and accuracy was 56.1% (95% CI: 49.0%, 63.2%). C statistics revealed a larger area under the receiver operating characteristic curve (AUC) for computational FFR (AUC, 0.83) than for coronary CT angiography (AUC, 0.64). For vessels with intermediate (25%-69%) stenosis, the sensitivity of computational FFR was 87.3% (95% CI: 76.5%, 94.3%) and the specificity was 59.3% (95% CI: 47.8%, 70.1%). CONCLUSION With use of a reduced-order algorithm, computation of the FFR from coronary CT angiography data can be performed locally, at a regular workstation. The diagnostic accuracy of coronary CT angiography-derived computational FFR for the detection of functionally important coronary artery disease (CAD) was good and was incremental to that of coronary CT angiography within a population with a high prevalence of CAD.

Standardized evaluation framework for evaluating coronary artery stenosis detection, stenosis quantification and lumen segmentation algorithms in computed tomography angiography

Though conventional coronary angiography (CCA) has been the standard of reference for diagnosing coronary artery disease in the past decades, computed tomography angiography (CTA) has rapidly emerged, and is nowadays widely used in clinical practice. Here, we introduce a standardized evaluation framework to reliably evaluate and compare the performance of the algorithms devised to detect and quantify the coronary artery stenoses, and to segment the coronary artery lumen in CTA data. The objective of this evaluation framework is to demonstrate the feasibility of dedicated algorithms to: (1) (semi-)automatically detect and quantify stenosis on CTA, in comparison with quantitative coronary angiography (QCA) and CTA consensus reading, and (2) (semi-)automatically segment the coronary lumen on CTA, in comparison with experts manual annotation. A database consisting of 48 multicenter multivendor cardiac CTA datasets with corresponding reference standards are described and made available. The algorithms from 11 research groups were quantitatively evaluated and compared. The results show that (1) some of the current stenosis detection/quantification algorithms may be used for triage or as a second-reader in clinical practice, and that (2) automatic lumen segmentation is possible with a precision similar to that obtained by experts. The framework is open for new submissions through the website, at http://coronary.bigr.nl/stenoses/.

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.

Calcium imaging and selective computed tomography angiography in comparison to functional testing for suspected coronary artery disease: the multicentre, randomized CRESCENT trial

AIMS To compare the effectiveness and safety of a cardiac computed tomography (CT) algorithm with functional testing in patients with symptoms suggestive of coronary artery disease (CAD). METHODS AND RESULTS Between April 2011 and July 2013, 350 patients with stable angina, referred to the outpatient clinic of four Dutch hospitals, were prospectively randomized between cardiac CT and functional testing (2 : 1 ratio). The tiered cardiac CT protocol included a calcium scan followed by CT angiography if the Agatston calcium score was between 1 and 400. Patients with test-specific contraindications were not excluded from study participation. By 1 year, fewer patients randomized to cardiac CT reported anginal complaints (P = 0.012). The cumulative radiation dose was slightly higher in the CT group (6.6 ± 8.7 vs. 6.1 ± 9.3 mSv; P < 0.0001). After 1.2 years, event-free survival was 96.7% for patients randomized to CT and 89.8% for patients randomized to functional testing (P = 0.011). After CT, the final diagnosis was established sooner (P < 0.0001), and additional downstream testing was required less frequently (25 vs. 53%, P < 0.0001), resulting in lower cumulative diagnostic costs (€369 vs. €440; P < 0.0001). CONCLUSION For patients with suspected stable CAD, a tiered cardiac CT protocol offers an effective and safe alternative to functional testing. Incorporating the calcium scan into the diagnostic workup was safe and lowered diagnostic expenses and radiation exposure.

Coronary CT Angiography for Suspected ACS in the Era of High-Sensitivity Troponins: Randomized Multicenter Study.

BACKGROUND It is uncertain whether a diagnostic strategy supplemented by early coronary computed tomography angiography (CCTA) is superior to contemporary standard optimal care (SOC) encompassing high-sensitivity troponin assays (hs-troponins) for patients suspected of acute coronary syndrome (ACS) in the emergency department (ED). OBJECTIVES This study assessed whether a diagnostic strategy supplemented by early CCTA improves clinical effectiveness compared with contemporary SOC. METHODS In a prospective, open-label, multicenter, randomized trial, we enrolled patients presenting with symptoms suggestive of an ACS at the ED of 5 community and 2 university hospitals in the Netherlands. Exclusion criteria included the need for urgent cardiac catheterization and history of ACS or coronary revascularization. The primary endpoint was the number of patients identified with significant coronary artery disease requiring revascularization within 30 days. RESULTS The study population consisted of 500 patients, of whom 236 (47%) were women (mean age 54 ± 10 years). There was no difference in the primary endpoint (22 [9%] patients underwent coronary revascularization within 30 days in the CCTA group and 17 [7%] in the SOC group [p = 0.40]). Discharge from the ED was not more frequent after CCTA (65% vs. 59%, p = 0.16), and length of stay was similar (6.3 h in both groups; p = 0.80). The CCTA group had lower direct medical costs (€337 vs. €511, p < 0.01) and less outpatient testing after the index ED visit (10 [4%] vs. 26 [10%], p < 0.01). There was no difference in incidence of undetected ACS. CONCLUSIONS CCTA, applied early in the work-up of suspected ACS, is safe and associated with less outpatient testing and lower costs. However, in the era of hs-troponins, CCTA does not identify more patients with significant CAD requiring coronary revascularization, shorten hospital stay, or allow for more direct discharge from the ED. (Better Evaluation of Acute Chest Pain with Computed Tomography Angiography [BEACON]; NCT01413282).

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.

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.

Quantitative CT 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.

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%.

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.