Marisa M. Lubbers

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.

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).

Relative myocardial blood flow by dynamic computed tomographic perfusion imaging predicts hemodynamic significance of coronary stenosis better than absolute blood flow.

ObjectivesQuantitative myocardial perfusion imaging by computed tomography (CT) was recently introduced to calculate myocardial blood flow (MBF). Because absolute MBF thresholds may be affected by technique, methodology, and the microvasculature, we investigated whether a relative measure of MBF improves accuracy to identify hemodynamically significant coronary stenosis. Materials and MethodsIn this prospective study, 42 patients (mean [SD] age, 62.3[8.7] years; 8 women) with suspected or known coronary disease underwent dynamic CT myocardial perfusion imaging using adenosine vasodilation, before invasive angiography (coronary angiography) with fractional flow reserve (FFR). Within each myocardial territory MBF, the MBF relative to remote myocardium (MBFratio) was calculated and compared with coronary angiography and FFR. ResultsOf the 91 vessels interrogated by FFR (median, 0.81; interquartile range, 0.73–0.94), 45 vessels (49%) had an FFR value lower than 0.8 and were considered hemodynamically significant. Hyperemic MBF was lower in ischemic territories: 75.6 ± 22.5 mL per 100 mL/min versus 98.3 ± 23.1 mL per 100 mL/min (P < 0.0001). The MBFratio correlated better with FFR (P = 0.76) than the absolute MBF did (P = 0.52). Receiver operating curve analysis showed better discrimination by MBFratio: area under the curve of 0.85 versus 0.75 (P = 0.02). The MBF of remote myocardium varied between 60.7 and 167.2 mL per 100 mL/min and was lower in patients without heart rate acceleration (P = 0.0035). ConclusionsThe MBFratio seems to better identify hemodynamically significant coronary artery disease than does the absolute MBF determined by dynamic CT perfusion imaging. This may be caused by microvascular status or related to the methodology.

‘Prognostic implications of non-culprit plaques in acute coronary syndrome: non-invasive assessment with coronary CT angiography’

Aims Non-culprit plaques are responsible for a substantial number of future events in patients with acute coronary syndrome (ACS). In this study, we evaluated the prognostic implications of non-culprit plaques seen on coronary computed tomography angiography (CTA) in patients with ACS. Methods and results Coronary CTA was performed in 169 patients (mean 59 ± 11 years, 129 males) admitted with ACS. Data sets were assessed for the presence of obstructive non-culprit plaques (>50% luminal narrowing), segment involvement score, and quantitative measures of plaque burden, after censoring initial culprit plaques. Follow-up was performed for the occurrence of major adverse cardiovascular events (MACEs) unrelated to the initial culprit plaque; cardiac death, second ACS, or coronary revascularization after 90 days. After a median follow-up of 4.8 (IQR 2.6–6.6) years, MACE occurred in 36 (24%) patients: 6 cardiac deaths, 16 second ACS, and 14 coronary revascularizations. Dyslipidaemia (hazard ratio [HR] 3.1 [95% confidence interval 1.5–6.6]) and diabetes mellitus (HR 4.8 [2.3–10.3]) were univariable clinical predictors of MACE. Patients with remaining obstructive non-culprit plaques (HR 3.66 [1.52–8.80]) and higher plaque burden index (HR 1.22 [1.01–1.48]) had a more risk of MACE. In multivariate analysis, with diabetes, dyslipidaemia, and plaque burden index, obstructive non-culprit plaques (HR 3.76 [1.28–11.09]) remained an independent predictor of MACE. Conclusion Almost a quarter of the study population experienced a new event arising from a non-culprit plaque during a follow-up of almost 5 years. ACS patients with remaining obstructive non-culprit plaques or high plaque burden have an increased risk of future MACE.

Coronary CT angiography derived fractional flow reserve: Methodology and evaluation of a point of care algorithm

BACKGROUND Recently several publications described the diagnostic value of coronary CT angiography (coronary CTA) derived fractional flow reserve (CTA-FFR). For a recently introduced on-site CTA-FFR application, detailed methodology and factors potentially affecting performance have not yet been described. OBJECTIVE To provide a methodological background for an on-site CTA-FFR application and evaluate the effect of patient and acquisition characteristics. METHODS The on-site CTA-FFR application utilized a reduced-order hybrid model applying pressure drop models within stenotic regions. In 116 patients and 203 vessels the diagnostic performance of CTA-FFR was investigated using invasive FFR measurements as a reference. The effect of several potentially relevant factors on CTA-FFR was investigated. RESULTS 90 vessels (44%) had a hemodynamically relevant stenosis according to invasive FFR (threshold ≤0.80). The overall vessel-based sensitivity, specificity and accuracy of CTA-FFR were 88% (CI 95%:79-94%), 65% (55-73%) and 75% (69-81%). The specificity was significantly lower in the presence of misalignment artifacts (25%, CI: 6-57%). A non-significant reduction in specificity from 74% (60-85%) to 48% (26-70%) was found for higher coronary artery calcium scores. Left ventricular mass, diabetes mellitus and large vessel size increased the discrepancy between invasive FFR and CTA-FFR values. CONCLUSIONS On-site calculation of CTA-FFR can identify hemodynamically significant CAD with an overall per-vessel accuracy of 75% in comparison to invasive FFR. The diagnostic performance of CTA-FFR is negatively affected by misalignment artifacts. CTA-FFR is potentially affected by left ventricular mass, diabetes mellitus and vessel size.

Computed Tomography Angiography with a 192-slice Dual-source Computed Tomography System: Improvements in Image Quality and Radiation Dose

Purpose: This study aims to compare image quality, radiation dose, and the influence of the heart rate on image quality of high-pitch spiral coronary computed tomography angiography (CCTA) using 128-slice (second generation) dual-source CT (DSCT) and a 192-slice DSCT (third generation) scanner. Materials and Methods: Two consecutive cohorts of fifty patients underwent CCTA by high-pitch spiral scan mode using 128 or 192-slice DSCT. The 192-slice DSCT system has a more powerful roentgen tube (2 × 120 kW) that allows CCTA acquisition at lower tube voltages, wider longitudinal coverage for faster table speed (732 m/s), and the use of iterative reconstruction. Objective image quality was measured as the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality was evaluated using a Likert scale. Results: While the effective dose was lower with 192-slice DSCT (1.2 ± 0.5 vs. 0.6 ± 0.3 mSv; P < 0.001), the SNR (18.9 ± 4.3 vs. 11.0 ± 2.9; P < 0.001) and CNR (23.5 ± 4.8 vs. 14.3 ± 4.1; P < 0.001) were superior to 128-slice DSCT. Although patients scanned with 192-slice DSCT had a faster heart rate (59 ± 7 vs. 56 ± 6; P = 0.045), subjective image quality was scored higher (4.2 ± 0.8 vs. 3.0 ± 0.7; P < 0.001) compared to 128-slice DSCT. Conclusions: High-pitch spiral CCTA by 192-slice DSCT provides better image quality, despite a higher average heart rate, at lower radiation doses compared to 128-slice DSCT.

Sex Differences in the Performance of Cardiac Computed Tomography Compared With Functional Testing in Evaluating Stable Chest Pain: Subanalysis of the Multicenter, Randomized CRESCENT Trial (Calcium Imaging and Selective CT Angiography in Comparison to Functional Testing for Suspected Coronary Artery Disease).

Background— Cardiac computed tomography (CT) represents an alternative diagnostic strategy for women with suspected coronary artery disease, with potential benefits in terms of effectiveness and cost-efficiency. Methods and Results— The CRESCENT trial (Calcium Imaging and Selective CT Angiography in Comparison to Functional Testing for Suspected Coronary Artery Disease) prospectively randomized 350 patients with stable angina (55% women; aged 55±10 years), mostly with an intermediate coronary artery disease probability, between cardiac CT and functional testing. 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. Sex differences were studied as a prespecified subanalysis. Enrolled women presented more frequently with atypical chest pain and had a lower pretest probability of coronary artery disease compared with men. Independently of these differences, cardiac CT led in both sexes to a fast final diagnosis when compared with functional testing, although the effect was larger in women (P interaction=0.01). The reduced need for further testing after CT, compared with functional testing, was most evident in women (P interaction=0.009). However, no sex interaction was observed with respect to changes in angina and quality of life, cumulative diagnostic costs, and applied radiation dose (all P interactions≥0.097). Conclusions— Cardiac CT is more efficient in women than in men in terms of time to reach the final diagnosis and downstream testing. However, overall clinical outcome showed no significant difference between women and men after 1 year. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01393028.Background— Cardiac computed tomography (CT) represents an alternative diagnostic strategy for women with suspected coronary artery disease, with potential benefits in terms of effectiveness and cost-efficiency. Methods and Results— The CRESCENT trial (Calcium Imaging and Selective CT Angiography in Comparison to Functional Testing for Suspected Coronary Artery Disease) prospectively randomized 350 patients with stable angina (55% women; aged 55±10 years), mostly with an intermediate coronary artery disease probability, between cardiac CT and functional testing. 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. Sex differences were studied as a prespecified subanalysis. Enrolled women presented more frequently with atypical chest pain and had a lower pretest probability of coronary artery disease compared with men. Independently of these differences, cardiac CT led in both sexes to a fast final diagnosis when compared with functional testing, although the effect was larger in women ( P interaction=0.01). The reduced need for further testing after CT, compared with functional testing, was most evident in women ( P interaction=0.009). However, no sex interaction was observed with respect to changes in angina and quality of life, cumulative diagnostic costs, and applied radiation dose (all P interactions≥0.097). Conclusions— Cardiac CT is more efficient in women than in men in terms of time to reach the final diagnosis and downstream testing. However, overall clinical outcome showed no significant difference between women and men after 1 year. Clinical Trial Registration— URL: . Unique identifier: [NCT01393028][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01393028&atom=%2Fcirccvim%2F10%2F2%2Fe005295.atom

Iodixanol versus iopromide at coronary CT angiography: Lumen opacification and effect on heart rhythm-the randomized IsoCOR trial

Purpose To show that equal coronary lumen opacification can be achieved with iso- and low-osmolar contrast media when it is injected at the same iodine delivery rate with contemporary cardiac computed tomographic (CT) protocols and to investigate the cardiovascular effect of iso-osmolar contrast media and the image quality achieved. Materials and Methods Institutional review board approval and written informed consent were obtained for the Effect of Iso-osmolar Contrast Medium on Coronary Opacification and Heart Rhythm in Coronary CT Angiography, or IsoCOR, trial. Between November 2015 and August 2016, 306 patients (167 [55%] women) at least 18 years old (weight range, 50-125 kg), were prospectively randomized to receive iso-osmolar iodixanol 270 or low-osmolar iopromide 300 contrast media. All coronary segments were assessed for intraluminal opacification and image quality and were compared by using the Student t test. Heart rate, arrhythmia, patient discomfort, and adverse events also were monitored. Results Mean measured coronary attenuation values ± standard deviation were comparable between the iodixanol 270 and iopromide 300 contrast media groups (469 HU ± 167 vs 447 HU ± 166, respectively [P = .241]; 95% confidence interval: -15.1, 60.0), including those from subanalyses. Adjusted for the lower iodine concentration, the mean iodixanol 270 bolus was larger compared with that of iopromide 300 (76.8 mL ± 11.6 vs 69.7 mL ± 10.8, respectively; P < .001). The higher injection rate was associated with higher pressure (777 kPa ± 308 vs 630 kPa ± 252, respectively; P < .001). Although in the iodixanol 270 group patients experienced less heat discomfort (72% vs 86%, respectively; P < .001), no differences in heart rate or rhythm were observed. Conclusion If injected at comparable iodine delivery rates, the iso-osmolar contrast medium iodixanol 270 is not inferior to low-osmolar contrast medium iopromide 300 for assessment of coronary opacification. Iodixanol 270 was associated with less heat discomfort, but did not affect heart rate differently compared with iopromide 300.

Round-the-clock performance of coronary CT angiography for suspected acute coronary syndrome: Results from the BEACON trial

AbstractObjectiveTo assess the image quality of coronary CT angiography (CCTA) for suspected acute coronary syndrome (ACS) outside office hours.MethodsPatients with symptoms suggestive of an ACS underwent CCTA at the emergency department 24 hours, 7 days a week. A total of 118 patients, of whom 89 (75 %) presented during office hours (weekdays between 07:00 and 17:00) and 29 (25 %) outside office hours (weekdays between 17:00 and 07:00, weekends and holidays) underwent CCTA. Image quality was evaluated per coronary segment by two experienced readers and graded on an ordinal scale ranging from 1 to 3.ResultsThere were no significant differences in acquisition parameters, beta-blocker administration or heart rate between patients presenting during office hours and outside office hours. The median quality score per patient was 30.5 [interquartile range 26.0–33.5] for patients presenting during office hours in comparison to 27.5 [19.75–32.0] for patients presenting outside office hours (p=0.043). The number of non-evaluable segments was lower for patients presenting during office hours (0 [0–1.0] vs. 1.0 [0–4.0], p=0.009).ConclusionImage quality of CCTA outside office hours in the diagnosis of suspected ACS is diminished.Key Points• Quality scores were higher for coronary-CTA during office hours. • There were no differences in acquisition parameters. • There was a non-significant trend towards higher heart rates outside office hours. • Coronary-CTA on the ED requires state-of-the-art scanner technology and sufficiently trained staff. • Coronary-CTA on the ED needs preparation time and optimisation of the procedure.