B. Ko

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).

Computed tomography stress myocardial perfusion imaging in patients considered for revascularization: a comparison with fractional flow reserve

AIMS Adenosine stress computed tomography myocardial perfusion imaging (CTP) is an emerging non-invasive method for detecting myocardial ischaemia. Its value when compared with fractional flow reserve (FFR), a highly accurate index of ischaemia, is unknown. Our aim was to determine the diagnostic accuracy of CTP and its incremental value when used with computed tomography coronary angiography (CTA) for detecting ischaemia compared with FFR. METHODS AND RESULTS Forty-two patients (126 vessel territories), who had at least one ≥50% angiographic stenosis on invasive angiography considered for non-urgent revascularization, were included and underwent FFR and CT assessment, including CTP, delayed contrast enhancement scan and CTA all acquired using 320-detector row CT, and prospective ECG gating. Fractional flow reserve was determined in 86 territories subtended by vessels with ≥50% stenosis upon visual assessment. Fractional flow reserve ≤0.8 was considered to indicate significant ischaemia. Computed tomography myocardial perfusion imaging correctly identified 31/41 (76%) ischaemic territories and 38/45 (84%) non-ischaemic territories. Per-vessel territory sensitivity, specificity, positive, and negative predictive values of CTP were 76, 84, 82, and 79%, respectively. The combination of a ≥50% stenosis on CTA and perfusion defect on CTP was 98% specific for ischaemia, while the presence of <50% stenosis on CTA and normal perfusion on CTP was 100% specific for exclusion of ischaemia. Mean radiation for CTP and combined CT was 5.3 and 11.3 mSv, respectively. CONCLUSION Computed tomography myocardial perfusion imaging is moderately accurate in identifying perfusion defects associated with ischaemia as assessed by FFR in patients considered for revascularization. In territories, where CTA and CTP are concordant, CTA/CTP is highly accurate in the detection and exclusion of ischaemia. This is achievable with acceptable radiation exposure using 320-detector row CT and prospective ECG gating.

Transluminal Attenuation Gradient in Coronary Computed Tomography Angiography Is a Novel Noninvasive Approach to the Identification of Functionally Significant Coronary Artery Stenosis: A Comparison With Fractional Flow Reserve

OBJECTIVE The purpose of this study was to assess the diagnostic accuracy of TAG320 in predicting functional stenosis severity evaluated by fractional flow reserve (FFR). BACKGROUND Coronary computed tomography angiography (CCTA) has limited specificity for predicting functionally significant stenoses. Recent studies suggest that contrast gradient attenuation along an arterial lesion, or transluminal attenuation gradient (TAG), may provide assessment of functional significance of coronary stenosis. The use of 320-detector row computed tomography (CT), enabling near isophasic, single-beat imaging of the entire coronary tree, may be ideal for TAG functional assessment of a coronary arterial stenosis. METHODS We assessed the diagnostic accuracy of TAG320 using 320-row CCTA with FFR for the evaluation of functional stenosis severity in consecutive patients undergoing invasive coronary angiography and FFR for stable chest pain. The luminal radiological contrast attenuation (Hounsfield units [HU]) was measured at 5-mm intervals along the artery from ostium to a distal level where the cross-sectional area decreased to <2.0 mm(2). TAG320 was defined as the linear regression coefficient between luminal attenuation and axial distance. Functionally significant coronary stenosis was defined as ≤0.8 on FFR. RESULTS In our cohort of 54 patients (age 62.7 ± 8.7 years, 35 men, 78 vessels), TAG320 in FFR-significant vessels was significantly lower when compared with FFR nonsignificant vessels (-21 [-27; -16] vs. -11 [-16; -3] HU/10 mm, p < 0.001). On receiver-operating characteristic analysis, a retrospectively determined TAG320 cutoff of -15.1 HU/10 mm predicted FFR ≤0.8 with (a bootstrapped resampled) a sensitivity of 77%, specificity of 74%, positive predictive value of 67%, and negative predictive value of 86%. The combined TAG320 and CCTA assessment had an area under the curve of 0.88. There was incremental value of adding TAG320 to CCTA assessment for detection of significant FFR by Wald test (p = 0.0001) and integrated discrimination improvement index (0.11, p = 0.002). CONCLUSIONS Assessment of TAG320 with a 320-detector row CT provides acceptable prediction of invasive FFR and may provide a noninvasive modality for detecting functionally significant coronary stenoses. Combined TAG320 and CCTA assessment may have incremental predictive value over CCTA alone for detecting functionally significant coronary arterial stenoses; however, larger studies are required to determine the benefit of combined TAG320 and CCTA assessment.

Combined CT coronary angiography and stress myocardial perfusion imaging for hemodynamically significant stenoses in patients with suspected coronary artery disease: a comparison with fractional flow reserve

OBJECTIVES We sought to determine the accuracy of combined coronary computed tomography angiography (CTA) and computed tomography stress myocardial perfusion imaging (CTP) in the detection of hemodynamically significant stenoses using fractional flow reserve (FFR) as a reference standard in patients with suspected coronary artery disease. BACKGROUND CTP can be qualitatively assessed by visual interpretation or quantified by the transmural perfusion ratio determined as the ratio of subendocardial to subepicardial contrast attenuation. The incremental value of each technique in addition to coronary CTA to detect hemodynamically significant stenoses is not known. METHODS Forty symptomatic patients underwent FFR and 320-detector computed tomography assessment including coronary CTA and CTP. Myocardial perfusion was assessed using the transmural perfusion ratio and visual perfusion assessment. Computed tomography images were assessed by consensus of 2 observers. Transmural perfusion ratio <0.99 was used as the threshold for abnormal perfusion. FFR ≤0.8 indicated hemodynamically significant stenoses. RESULTS Coronary CTA detected FFR-significant stenoses with 95% sensitivity and 78% specificity. The additional use of visual perfusion assessment and the transmural perfusion ratio both increased the specificity to 95%, with sensitivity of 87% and 71%, respectively. The area under the receiver-operating characteristic curve for coronary CTA + visual perfusion assessment was significantly higher than both coronary CTA (0.93 vs. 0.85, p = 0.0003) and coronary CTA + the transmural perfusion ratio (0.93 vs. 0.79, p = 0.0003). Per-vessel and per-patient accuracy for coronary CTA, coronary CTA + the transmural perfusion ratio, and coronary CTA + visual perfusion assessment was 83% and 83%, 87% and 92%, and 92% and 95%, respectively. CONCLUSIONS In suspected coronary artery disease, combined coronary CTA + CTP identifies patients with hemodynamically significant stenoses with >90% accuracy compared with FFR. When interpreted with coronary CTA, visual perfusion assessment provided superior incremental value in the detection of FFR-significant stenoses compared with the quantitative transmural perfusion ratio assessment.

Coronary plaque quantification and fractional flow reserve by coronary computed tomography angiography identify ischaemia-causing lesions

Abstract Aims Coronary plaque characteristics are associated with ischaemia. Differences in plaque volumes and composition may explain the discordance between coronary stenosis severity and ischaemia. We evaluated the association between coronary stenosis severity, plaque characteristics, coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT), and lesion-specific ischaemia identified by FFR in a substudy of the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). Methods and results Coronary CTA stenosis, plaque volumes, FFRCT, and FFR were assessed in 484 vessels from 254 patients. Stenosis >50% was considered obstructive. Plaque volumes (non-calcified plaque [NCP], low-density NCP [LD-NCP], and calcified plaque [CP]) were quantified using semi-automated software. Optimal thresholds of quantitative plaque variables were defined by area under the receiver-operating characteristics curve (AUC) analysis. Ischaemia was defined by FFR or FFRCT ≤0.80. Plaque volumes were inversely related to FFR irrespective of stenosis severity. Relative risk (95% confidence interval) for prediction of ischaemia for stenosis >50%, NCP ≥185 mm3, LD-NCP ≥30 mm3, CP ≥9 mm3, and FFRCT ≤0.80 were 5.0 (3.0–8.3), 3.7 (2.4–5.6), 4.6 (2.9–7.4), 1.4 (1.0–2.0), and 13.6 (8.4–21.9), respectively. Low-density NCP predicted ischaemia independent of other plaque characteristics. Low-density NCP and FFRCT yielded diagnostic improvement over stenosis assessment with AUCs increasing from 0.71 by stenosis >50% to 0.79 and 0.90 when adding LD-NCP ≥30 mm3 and LD-NCP ≥30 mm3 + FFRCT ≤0.80, respectively. Conclusion Stenosis severity, plaque characteristics, and FFRCT predict lesion-specific ischaemia. Plaque assessment and FFRCT provide improved discrimination of ischaemia compared with stenosis assessment alone.

A stepwise approach to the visual interpretation of CT-based myocardial perfusion

Cardiovascular anatomic and functional testing have been longstanding and key components of cardiac risk assessment. As part of that strategy, CT-based imaging has made steady progress, with coronary computed tomography angiography (CTA) now established as the most sensitive noninvasive strategy for assessment of significant coronary artery disease. Myocardial CT perfusion imaging (CTP), as the functional equivalent of coronary CTA, is being tested in currently ongoing multicenter trials and is proposed to enhance the accuracy of coronary CTA alone. However, unlike coronary CTA that has published guidelines for interpretation and is rapidly gaining applicability in the noninvasive risk assessment paradigms, myocardial CTP is rapidly evolving, and guidance on a standard approach to its interpretation is lacking. In this article we describe a practical stepwise approach for interpretation of myocardial CTP that should add to the clinical applicability of this modality. These steps include (1) coronary CTA interpretation for potentially obstructive atherosclerosis, (2) reconstruction and preprocessing of myocardial CTP images, (3) image quality assessment and the identification of potentially confounding artifacts, (4) rest and stress image interpretation for enhancement patterns and areas of hypoattenuation, and (5) correlation of coronary anatomy and myocardial perfusion deficits. This systematic review uses already published methods from multiple clinical studies and is intended for general usage, independent of the platform used for image acquisition.

CT stress myocardial perfusion imaging using Multidetector CT—A review

Computed tomography coronary angiography (CTA) accurately detects and excludes coronary artery disease (CAD); however, the physiological significance of coronary artery lesions may be uncertain. CT myocardial perfusion imaging (CTP) acquired during vasodilator stress provides a novel and emerging method for detection of myocardial ischemia. Multiple studies have established the feasibility of CTP and suggested its incremental value when used in combination with CTA in the identification of hemodynamically significant stenoses as compared with CTA alone. Despite these encouraging clinical data, CT perfusion assessment is in its infancy, as further research is required to validate and optimize this new technique. Combined CTA/CTP imaging has significant potential, as it offers the convenience of assessing both coronary anatomy and myocardial perfusion in one single examination at a radiation dose equivalent to contemporary nuclear medicine imaging. In this review, we provide an overview of the fundamentals of CT perfusion imaging, recent advances in scanner types and imaging techniques and protocols, and current literature on the accuracy of CTP, concluding with its future challenges and directions.

Diagnostic Performance of Transluminal Attenuation Gradient and Noninvasive Fractional Flow Reserve Derived from 320–Detector Row CT Angiography to Diagnose Hemodynamically Significant Coronary Stenosis: An NXT Substudy

PURPOSE To compare the diagnostic performance of 320-detector row computed tomography (CT) coronary angiography-derived computed fractional flow reserve (FFR; FFRCT), transluminal attenuation gradient (TAG; TAG320), and CT coronary angiography alone to diagnose hemodynamically significant stenosis as determined by invasive FFR. MATERIALS AND METHODS This substudy of the prospective NXT study (no. NCT01757678) was approved by each participating institutions review board, and informed consent was obtained from all participants. Fifty-one consecutive patients who underwent 320-detector row CT coronary angiographic examination and invasive coronary angiography with FFR measurement were included. Independent core laboratories determined coronary artery disease severity by using CT coronary angiography, TAG320, FFRCT, and FFR. TAG320 is defined as the linear regression coefficient between luminal attenuation and axial distance from the coronary ostium. FFRCT was computed from CT coronary angiography data by using computational fluid dynamics technology. Diagnostic performance was evaluated and compared on a per-vessel basis by the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS Among 82 vessels, 24 lesions (29%) had ischemia by FFR (FFR ≤ 0.80). FFRCT exhibited a stronger correlation with invasive FFR compared with TAG320 (Spearman ρ, 0.78 vs 0.47, respectively). Overall per-vessel accuracy, sensitivity, specificity, and positive and negative predictive values for TAG320 (<15.37) were 78%, 58%, 86%, 64%, and 83%, respectively; and those of FFRCT were 83%, 92%, 79%, 65%, and 96%, respectively. ROC curve analysis showed a significantly larger AUC for FFRCT (0.93) compared with that for TAG320 (0.72; P = .003) and CT coronary angiography alone (0.68; P = .008). CONCLUSION FFRCT computed from 320-detector row CT coronary angiography provides better diagnostic performance for the diagnosis of hemodynamically significant coronary stenoses compared with CT coronary angiography and TAG320.

Superior CT coronary angiography image quality at lower radiation exposure with second generation 320-detector row CT in patients with elevated heart rate: a comparison with first generation 320-detector row CT

BACKGROUND This study aims to compare the image quality of second generation versus first generation 320-computed tomography coronary angiography (CTCA) in patients with heart rate ≥65 bpm as it has not been specifically reported. METHODS Consecutive patients who underwent CTCA using second-generation-320-detector-row-CT were prospectively enrolled. A total of 50 patients with elevated (≥65 bpm) heart rate and 50 patients with controlled (<65 bpm) heart rate were included. Age and gender matched patients who were scanned with the first-generation-320-detector-row-CT were retrospectively identified. Image quality in each coronary artery segment was assessed by two blinded CT angiographers using the five-point Likert scale. RESULTS In the elevated heart rate cohorts, while there was no significant difference in heart rate during scan-acquisition (66 vs. 69 bpm, P=0.308), or body mass index (28.5 vs. 29.6, P=0.464), the second generation scanner was associated with better image quality (3.94±0.6 vs. 3.45±0.8, P=0.001), and with lower radiation (2.8 vs. 4.3 mSv, P=0.009). There was no difference in scan image quality for the controlled heart rate cohorts. CONCLUSIONS The second generation CT scanner provides better image quality at lower radiation dose in patients with elevated heart rate (≥65 bpm) compared to first generation CT scanner.