Mohamed Marwan

Diagnostic Performance of Noninvasive Fractional Flow Reserve Derived From Coronary Computed Tomography Angiography in Suspected Coronary Artery Disease: The NXT Trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps)

OBJECTIVES The goal of this study was to determine the diagnostic performance of noninvasive fractional flow reserve (FFR) derived from standard acquired coronary computed tomography angiography (CTA) datasets (FFR(CT)) for the diagnosis of myocardial ischemia in patients with suspected stable coronary artery disease (CAD). BACKGROUND FFR measured during invasive coronary angiography (ICA) is the gold standard for lesion-specific coronary revascularization decisions in patients with stable CAD. The potential for FFR(CT) to noninvasively identify ischemia in patients with suspected CAD has not been sufficiently investigated. METHODS This prospective multicenter trial included 254 patients scheduled to undergo clinically indicated ICA for suspected CAD. Coronary CTA was performed before ICA. Evaluation of stenosis (>50% lumen reduction) in coronary CTA was performed by local investigators and in ICA by an independent core laboratory. FFR(CT) was calculated and interpreted in a blinded fashion by an independent core laboratory. Results were compared with invasively measured FFR, with ischemia defined as FFR(CT) or FFR ≤0.80. RESULTS The area under the receiver-operating characteristic curve for FFR(CT) was 0.90 (95% confidence interval [CI]: 0.87 to 0.94) versus 0.81 (95% CI: 0.76 to 0.87) for coronary CTA (p = 0.0008). Per-patient sensitivity and specificity (95% CI) to identify myocardial ischemia were 86% (95% CI: 77% to 92%) and 79% (95% CI: 72% to 84%) for FFR(CT) versus 94% (86 to 97) and 34% (95% CI: 27% to 41%) for coronary CTA, and 64% (95% CI: 53% to 74%) and 83% (95% CI: 77% to 88%) for ICA, respectively. In patients (n = 235) with intermediate stenosis (95% CI: 30% to 70%), the diagnostic accuracy of FFR(CT) remained high. CONCLUSIONS FFR(CT) provides high diagnostic accuracy and discrimination for the diagnosis of hemodynamically significant CAD with invasive FFR as the reference standard. When compared with anatomic testing by using coronary CTA, FFR(CT) led to a marked increase in specificity. (HeartFlowNXT-HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography [HFNXT]; NCT01757678).

Clinical ResearchClinical TrialsDiagnostic Performance of Noninvasive Fractional Flow Reserve Derived From Coronary Computed Tomography Angiography in Suspected Coronary Artery Disease: The NXT Trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps)

OBJECTIVES The goal of this study was to determine the diagnostic performance of noninvasive fractional flow reserve (FFR) derived from standard acquired coronary computed tomography angiography (CTA) datasets (FFR(CT)) for the diagnosis of myocardial ischemia in patients with suspected stable coronary artery disease (CAD). BACKGROUND FFR measured during invasive coronary angiography (ICA) is the gold standard for lesion-specific coronary revascularization decisions in patients with stable CAD. The potential for FFR(CT) to noninvasively identify ischemia in patients with suspected CAD has not been sufficiently investigated. METHODS This prospective multicenter trial included 254 patients scheduled to undergo clinically indicated ICA for suspected CAD. Coronary CTA was performed before ICA. Evaluation of stenosis (>50% lumen reduction) in coronary CTA was performed by local investigators and in ICA by an independent core laboratory. FFR(CT) was calculated and interpreted in a blinded fashion by an independent core laboratory. Results were compared with invasively measured FFR, with ischemia defined as FFR(CT) or FFR ≤0.80. RESULTS The area under the receiver-operating characteristic curve for FFR(CT) was 0.90 (95% confidence interval [CI]: 0.87 to 0.94) versus 0.81 (95% CI: 0.76 to 0.87) for coronary CTA (p = 0.0008). Per-patient sensitivity and specificity (95% CI) to identify myocardial ischemia were 86% (95% CI: 77% to 92%) and 79% (95% CI: 72% to 84%) for FFR(CT) versus 94% (86 to 97) and 34% (95% CI: 27% to 41%) for coronary CTA, and 64% (95% CI: 53% to 74%) and 83% (95% CI: 77% to 88%) for ICA, respectively. In patients (n = 235) with intermediate stenosis (95% CI: 30% to 70%), the diagnostic accuracy of FFR(CT) remained high. CONCLUSIONS FFR(CT) provides high diagnostic accuracy and discrimination for the diagnosis of hemodynamically significant CAD with invasive FFR as the reference standard. When compared with anatomic testing by using coronary CTA, FFR(CT) led to a marked increase in specificity. (HeartFlowNXT-HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography [HFNXT]; NCT01757678).

Detection of Coronary Artery Stenoses by Low-Dose, Prospectively ECG-Triggered, High-Pitch Spiral Coronary CT Angiography

OBJECTIVES We sought to evaluate the diagnostic accuracy of a new prospectively electrocardiogram (ECG)-triggered high-pitch scan mode for coronary computed tomography angiography (CTA), which allows an effective dose of less than 1 mSv. BACKGROUND Coronary CTA provides increasingly reliable image quality, but the associated radiation exposure can be high. METHODS Seventy-five patients with suspected coronary artery disease and in sinus rhythm were screened for participation. After exclusion of 25 patients for body weight >100 kg or failure to lower heart rate to ≤ 60 beats/min, 50 patients were studied by prospectively ECG-triggered high-pitch spiral computed tomography (CT). Coronary CTA was performed using a dual-source CT system with 2 × 128 × 0.6-mm collimation, 0.28-s rotation time, a pitch of 3.4, 100-kVp tube voltage, and current of 320 mA. Data acquisition was prospectively triggered at 60% of the R-R interval and completed within 1 cardiac cycle. Diagnostic accuracy for detection of coronary artery stenoses ≥ 50% diameter stenosis was determined by comparison to invasive coronary angiography. Per-patient diagnostic performance was the primary form of analysis. RESULTS In all 50 patients (34 males, 59 ± 12 years of age), imaging was successful. For the detection of 16 patients with at least 1 coronary artery stenosis, CT demonstrated a sensitivity of 100% (95% confidence interval [CI]: 79% to 100%) and specificity of 82% (95% CI: 65% to 93%). The positive predictive value was 72% (95% CI: 49% to 89%) and the negative predictive value was 100% (95% CI: 87% to 100%). Sensitivity was 100% (95% CI: 88% to 100%) and specificity was 94% (95% CI: 89% to 97%) on a per-vessel basis. Per-segment sensitivity was 92% (95% CI: 80% to 97%), and specificity was 98% (95% CI: 96% to 98%). Mean dose-length product for coronary CTA was 54 ± 6 mGy · cm, the effective dose was 0.76 ± 0.08 mSv (0.64 to 0.95 mSv). CONCLUSIONS In nonobese patients with a low and stable heart rate, prospectively ECG-triggered high-pitch spiral coronary CTA provides high diagnostic accuracy for the detection of coronary artery stenoses.

Image Quality in a Low Radiation Exposure Protocol for Retrospectively ECG-Gated Coronary CT Angiography

OBJECTIVE The purpose of our study was to systematically compare the image quality of dual-source CT coronary angiography using 100 kV instead of 120 kV. SUBJECTS AND METHODS One hundred patients with a body weight </= 85 kg were included. A dual-source CT scanner was used (330-milliseconds rotation, 0.6-mm collimation, 56 +/- 7 mL of IV contrast agent at 5 mL/s). Each patient was randomized either to scanning protocol group 1 (120 kV and 330 mAs) or protocol group 2 (100 kV and 330 mAs). ECG pulsing was used for all patients. Data sets were assessed by two independent observers for image quality, signal-to-noise ratio, and contrast-to-noise-ratio. Effective dose was determined based on dose-length product. RESULTS There were no significant differences in body weight or heart rate between the two groups (70 +/- 10 kg and 57 +/- 8 bpm [beats per minute] vs 70 +/- 9 kg and 59 +/- 8 bpm). Use of 100 kV led to significant reduction of radiation exposure (group 1: 12.7 +/- 1.7 mSv; volume CT dose index [CTDI(vol)], 47.8 +/- 6.1 mGy and group 2: 7.8 +/- 2.0 mSv; CTDI(vol), 28.6 +/- 6.3 mGy; p < 0.001). Interobserver agreement in assessing image quality (kappa = 0.71) was close. Mean patient-based image quality scores were not significantly different (group 1, 2.7 +/- 0.5 and group 2, 2.6 +/- 0.4; p = 0.75). Also, vessel-based scores showed no significant differences. Beyond the level of significance, group 1 and group 2 showed one and two nonassessable patients and two and three nonassessable vessels, respectively. Mean intraluminal attenuation, contrast enhancement, and image noise were significantly higher for 100 kV, whereas signal-to-noise and contrast-to-noise-ratios were not different between the two scanning protocols. CONCLUSION The use of lower tube voltage leads to significant reduction in radiation exposure in noninvasive coronary CT angiography. Image quality in nonobese patients is not negatively influenced.

Automated three-dimensional quantification of noncalcified coronary plaque from coronary CT angiography: comparison with intravascular US.

PURPOSE To determine the accuracy of a previously developed automated algorithm (AUTOPLAQ [APQ]) for rapid volumetric quantification of noncalcified and calcified plaque from coronary computed tomographic (CT) angiography in comparison with intravascular ultrasonography (US). MATERIALS AND METHODS This study was approved by the institutional review board and was HIPAA compliant; all patients provided written informed consent. APQ combines derived scan-specific attenuation threshold levels for lumen, plaque, and knowledge-based segmentation of coronary arteries for quantification of plaque components. APQ was validated with retrospective analysis of 22 coronary atherosclerotic plaques in 20 patients imaged with coronary CT angiography and intravascular US within 2 days of each other. Coronary CT angiographic data were acquired by using dual-source CT. For each patient, well-defined plaques without calcifications were selected, and plaque volume was measured with APQ and manual tracing at CT and with intravascular US. Measurements were compared with paired t test, correlation, and Bland-Altman analysis. RESULTS There was excellent correlation between noncalcified plaque volumes quantified with APQ and intravascular US (r = 0.94, P < .001), with no significant differences (P = .08). Mean plaque volume with intravascular US was 105.9 mm³ ± 83.5 (standard deviation) and with APQ was 116.6 mm³ ± 80.1. Mean plaque volume with manual tracing from CT was 100.8 mm³ ± 81.7 and with APQ was 116.6 mm³ ± 80.1, with excellent correlation (r = 0.92, P < .001) and no significant differences (P = .23). CONCLUSION Automated scan-specific threshold level-based quantification of plaque components from coronary CT angiography allows rapid, accurate measurement of noncalcified plaque volumes, compared with intravascular US, and requires a fraction of the time needed for manual analysis.

Clinical Characteristics of Patients with Obstructive Coronary Lesions in the Absence of Coronary Calcification: An Evaluation by Coronary CT Angiography

Background: Multidetector CT allows detection of coronary artery calcium and, after contrast injection, visualisation of the coronary artery lumen. It is commonly assumed that the absence of coronary calcification makes the presence of obstructive coronary lesions highly unlikely. This study evaluates the clinical characteristics of patients with at least one symptomatic, high-grade coronary artery stenosis in both computed tomography and invasive angiography but absence of any coronary calcification and compares the results with patients with stenoses in the setting of detectable coronary calcium Patients and methods: The study retrospectively identified 21 consecutive patients with symptoms in whom a high-grade coronary artery stenosis had been identified in 64-slice or dual-source CT coronary angiography (Siemens Sensation 64 or Siemens Definition, 120 kV, 50 to 85 ml of intravenous contrast at 5 ml/s) in the absence of coronary calcium and in whom that finding had been confirmed by invasive coronary angiography. Clinical presentation (“unstable”: all forms of acute coronary syndrome versus “stable”: stable chest pain or dyspnoea on exertion) and standard cardiovascular risk factors were assessed, and the results were compared with 42 consecutive patients with symptoms in whom both coronary calcium and coronary stenoses had been identified in computed tomography and invasive coronary angiography. Results: The majority of patients with coronary stenoses in the absence of coronary calcium presented with “unstable” symptoms (non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina), significantly more frequently than patients with detectable calcification (71% vs 26%, p = 0.001). The age range of patients without calcium was 33 to 76 years, their mean age was younger (53 (SD 13) vs 63 (8) years, p<0.001), but none of the risk factors showed any significant difference compared with patients with calcification. Conclusion: The presence of significant coronary artery stenosis in the absence of coronary calcium is possible. It is more likely in the setting of unstable angina or NSTEMI than in stable chest pain and occurs more frequently in younger patients.

EACVI/EHRA Expert Consensus Document on the role of multi-modality imaging for the evaluation of patients with atrial fibrillation

Atrial fibrillation (AF) is the commonest cardiac rhythm disorder. Evaluation of patients with AF requires an electrocardiogram, but imaging techniques should be considered for defining management and driving treatment. The present document is an expert consensus from the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association. The clinical value of echocardiography, cardiac magnetic resonance (CMR), computed tomography (CT), and nuclear imaging in AF patients are challenged. Left atrial (LA) volume and strain in echocardiography as well as assessment of LA fibrosis in CMR are discussed. The value of CT, especially in planning interventions, is highlighted. Fourteen consensus statements have been reached. These may serve as a guide for both imagers and electrophysiologists for best selecting the imaging technique and for best interpreting its results in AF patients.

Quantification of non-calcified coronary atherosclerotic plaques with dual-source computed tomography: comparison with intravascular ultrasound

Background The quantification of non-calcified coronary plaques using multidetector computed tomography has not been extensively investigated. Objective To evaluate the ability of dual-source computed tomography (DSCT) to quantify non-calcified plaque volumes using intravascular ultrasound (IVUS) as the standard of reference. Methods The datasets of 70 patients with suspected or known coronary artery disease who underwent DSCT (330 ms gantry rotation, 2×64×0.6 mm collimation, 60–90 ml contrast agent) were analysed before invasive coronary angiography, with IVUS performed as part of the diagnostic procedure. 100 individual non-calcified coronary atherosclerotic plaques (one to three plaques per patient) with suitable fiducial markers were matched and selected for plaque volume measurements using manual segmentation. Only DSCT datasets with good or excellent image quality were considered for analysis. Results Intra and interobserver variability for plaque volume measurements by DSCT were 6±5% and 11±7%, respectively. Mean total plaque volume by DSCT was 89±66 mm3 (range 14–400 mm3). Mean total plaque volume by IVUS was 90±73 mm3 (range 16–409 mm3). The mean difference between DSCT and IVUS was 1±34 mm3 (range −131–85 mm3). Despite the good correlation for plaque volume measurements (r=0.89, p<0.001), agreement between the two methods was only modest (Bland–Altman limits of agreement −67 to +65 mm3). Conclusions Non-calcified plaque volumes as determined by DSCT yielded good correlation but only modest agreement in comparison with IVUS.

Influence of slice thickness and reconstruction kernel on the computed tomographic attenuation of coronary atherosclerotic plaque

BACKGROUND The computed tomographic (CT) attenuation of coronary atherosclerotic plaque has been proposed as a marker for tissue characterization and may thus potentially contribute to the assessment of plaque instability. OBJECTIVE We analyzed the influence of reconstruction parameters on CT attenuation measured within noncalcified coronary atherosclerotic lesions. METHODS Seventy-two patients were studied by contrast-enhanced dual-source CT coronary angiography (330 millisecond rotation time, 2 x 64 x 0.6 mm collimation, 120 kV, 400 mAs, 80 mL contrast agent intravenously at 6 mL/s), and a total of 100 distinct noncalcified coronary atherosclerotic plaques were identified. Image data sets were reconstructed with a soft (B20f), medium soft (B26f), and sharp (B46f) reconstruction kernel. With the medium soft kernel, image data sets were reconstructed with a slice thickness/increment of 0.6/0.3 mm, 0.75/0.4 mm, and 1.0/0.5mm. Within each plaque, CT attenuation was measured. RESULTS Mean CT attenuation using the medium soft kernel was 109 +/- 58 HU (range, -16 to 168 HU). Using the soft kernel, mean density was 113 +/- 57 HU (range, -13 to 169 HU), and using a sharp kernel, mean density was 97 +/- 49 HU (range, -23 to 131 HU). Similarly, reconstructed slice thickness had a significant influence on the measured CT attenuation (mean values for medium soft kernel: 102 +/- 52 HU versus 109 +/- 58 HU versus 113 +/- 57 HU for 0.6-mm, 0.75-mm, and 1.0-mm slice thickness). The differences between 0.75-mm and 0.6-mm slice thickness (P = 0.05) and between medium sharp and sharp kernels (P = 0.02) were statistically significant. CONCLUSIONS Image reconstruction significantly influences CT attenuation of noncalcified coronary atherosclerotic plaque. With decreasing spatial resolution (softer kernel or thicker slices), CT attenuation increases significantly. Using absolute CT attenuation values for plaque characterization may therefore be problematic.

Assessment of coronary artery remodelling by dual-source CT: a head-to-head comparison with intravascular ultrasound

Background While it is widely assumed that coronary CT angiography permits detection and quantification of ‘positive remodelling’ of coronary atherosclerotic lesions, there is a paucity of data comparing CT with established reference methods. Objective To assess the accuracy of dual-source CT for detecting positive versus absent or negative coronary artery remodelling of coronary atherosclerotic lesions as compared with intravascular ultrasound (IVUS). Methods The datasets were evaluated of 38 patients referred for invasive coronary angiography and in whom an IVUS study of one coronary vessel was performed. Coronary CT angiography was performed within 24 h before invasive coronary angiography. Using dual-source CT (Siemens Healthcare, Forchheim, Germany), a contrast-enhanced volume dataset was acquired (120 kV, 400 mA/rot, collimation 2×64×0.6 mm, 60–80 ml contrast agent, intravenous). IVUS was performed using a 40 MHz IVUS catheter (Atlantis, Boston Scientific Corporation, Natick, Massachusetts, USA) and motorised pullback at 0.5 mm/s. 48 corresponding non-calcified and partially calcified plaques within the coronary artery system were identified in both CT and IVUS using bifurcation points as fiducial markers. In CT datasets, multiplanar reconstructions orthogonal to the centre line of the coronary artery were rendered and cross-sectional vessel area was measured at the site of maximal narrowing as well as at a reference segment proximal to the lesion for each of the 48 plaques. The remodelling index (RI) was calculated by dividing the vessel area at the site of maximal narrowing by the area of the reference segment. Corresponding vessel areas and RIs were also determined in IVUS. Results CT classified 41 plaques as positively remodelled (RI≥1.05) and seven as having either absent or negative remodelling (RI<1.05). In IVUS 29 plaques demonstrated positive remodelling, while 19 did not. Mean cross-sectional vessel areas measured by CT at the lesion and at the reference segment were 19±5 mm2 and 17± 5 mm2, respectively, versus 18±5 mm2 and 17±5 mm2 for IVUS (mean difference 1±2 mm2 and −0.2±1 mm2, p<0.0001 and 0.8, respectively). The mean RI in CT was significantly larger than in IVUS (1.2±0.2 vs 1.1±0.2, p<0.0001). Correlation between CT and IVUS was higher for vessel area measurements (r>0.9, p<0.0001) than for remodelling indices (r=0.7, p<0.0001) with Bland–Altman analysis showing a systematic overestimation of vessel areas and RI in CT. Interobserver agreement was moderate for CT and IVUS measurements. Receiver operating characteristic curve analysis showed that a RI of 1.1 in CT identified positively remodelled plaques in IVUS with a sensitivity of 83% and a specificity of 78% (area under the curve=0.8, 95% CI 0.7 to 1.0). Using the standard cut-off point of 1.05 to identify positively remodelled plaques in CT resulted in a sensitivity of 100%, and a specificity of 45%. Conclusion Coronary CT angiography allows analysis of coronary artery remodelling. The degree of positive remodelling is typically overestimated by CT. A threshold of 1.1 for the RI may be optimal to classify plaques as ‘positively remodelled’ in coronary CT angiography.