Kazuhiro Osawa

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).

Additional diagnostic value of first-pass myocardial perfusion imaging without stress when combined with 64-row detector coronary CT angiography in patients with coronary artery disease

Objective Multi-detector coronary CT angiography (CCTA) can detect coronary stenosis, but it has a limited ability to evaluate myocardial perfusion. We evaluated the usefulness of first-pass CT-myocardial perfusion imaging (MPI) in combination with CCTA for diagnosing coronary artery disease (CAD). Methods A total of 145 patients with suspected CAD were enrolled. We used 64-row multi-detector CT (Definition Flash, Siemens). The same coronary CCTA data were used for first-pass CT-MPI without drug loading. Images were reconstructed by examining the signal densities at diastole as colour maps. Diagnostic accuracy was assessed by comparison with invasive coronary angiography. Results First-pass CT-MPI in combination with CCTA significantly improved diagnostic performance compared with CCTA alone. With per-vessel analysis, the sensitivity, specificity, positive predictive value and negative predictive value increased from 81% to 85%, 87% to 94%, 63% to 79% and 95% to 96%, respectively. The area under the receiver operating characteristic curve for detecting CAD also increased from 0.84 to 0.89 (p=0.02). First-pass CT-MPI was particularly useful for assessing segments that could not be directly evaluated due to severe calcification and motion artefacts. Conclusions First-pass CT-MPI has an additional diagnostic value for detecting coronary stenosis, in particular in patients with severe calcification.

Comparison of two-dimensional and real-time three-dimensional transesophageal echocardiography in the assessment of aortic valve area

BACKGROUND The accuracy of two-dimensional transesophageal echocardiography (2D-TEE) for the measurement of aortic valve area (AVA) in patients with aortic stenosis (AS) depends upon the cross-section selected for imaging. Real-time three-dimensional transesophageal echocardiography (3D-TEE) may overcome this limitation of 2D-TEE. The goal of this study was to compare 3D-TEE with 2D-TEE for the measurement of AVA. METHODS AND RESULTS Twenty-five patients with AS underwent TEE. In 2D-TEE, the aortic valve image was obtained at the orifice level in the short-axis view, and AVA was measured by planimetry of the acquired images (2D-AVA). In 3D-TEE, 3D data containing the entire aortic valve were obtained. Then, a short-axis cross-section containing the smallest orifice in mid-systole was cut from the 3D data during image postprocessing, and the AVA was measured by planimetry (3D-AVA). The 3D-AVA was significantly smaller than the 2D-AVA (0.79±0.35cm(2) vs. 0.93±0.40cm(2), p<0.0001), but there was a strong correlation between 3D-AVA and 2D-AVA (R=0.94). Although the frame rate was lower in 3D-TEE than in 2D-TEE (17±6Hz vs. 58±16Hz), the 3D-AVA determined at each frame during systole showed that the difference between 3D-AVA and 2D-AVA was not explained by the lower frame rate. The time required for image acquisition of the aortic valve was shorter with 3D-TEE than with 2D-TEE (p=0.0005). CONCLUSIONS The geometric AVA is smaller with 3D-TEE than with 2D-TEE, and the difference is not due to the lower frame rate of 3D-TEE. The improved accuracy of 3D-TEE along with reduced image acquisition time indicates that 3D-TEE is superior to 2D-TEE for the assessment of AVA.

Nonalcoholic Hepatic Steatosis Is a Strong Predictor of High-Risk Coronary-Artery Plaques as Determined by Multidetector CT

Background Nonalcoholic fatty liver disease is associated with a risk of coronary artery disease (e.g., diabetes mellitus, dyslipidemia, metabolic syndrome). We evaluated whether nonalcoholic hepatic steatosis is associated with high-risk plaques as assessed by multidetector computed tomography (CT). Methods This retrospective study involved 414 participants suspected of having coronary artery disease. Nonalcoholic hepatic steatosis was defined as a liver-to-spleen fat ratio of <1.0 and the presence and appropriate characteristics of coronary-artery plaques as assessed by coronary CT angiography. High-risk plaques were identified, as were low-density plaques, positive remodeling, and spotty calcification. Results Compared with patients who did not have nonalcoholic hepatic steatosis, patients with nonalcoholic hepatic steatosis had more low-density plaques (21% vs. 44%, p<0.01), positive remodeling (41% vs. 58%, p = 0.01), and spotty calcification (12% vs. 36%, p<0.01). The number of high-risk plaques in patients with nonalcoholic hepatic steatosis was greater than in those without nonalcoholic hepatic steatosis (p<0.01). Patients with nonalcoholic hepatic steatosis were more likely to have high-risk plaques than were those with only an elevated level of visceral adipose tissue (≥86 cm2; 35% vs. 16%, p<0.01). Multivariate analyses that included nonalcoholic hepatic steatosis, amount of visceral adipose tissue, and the presence/absence of traditional risk factors demonstrated that nonalcoholic hepatic steatosis was an independent predictor of high-risk plaques (odds ratio: 4.60; 95% confidence interval: 1.94–9.07, p<0.01). Conclusions Diagnosis of nonalcoholic hepatic steatosis may be of value when assessing the risk of coronary artery disease.

Non-invasive computed fractional flow reserve from computed tomography (CT) for diagnosing coronary artery disease – Japanese results from NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps).

BACKGROUND Recently, a non-invasive method using computational fluid dynamics to calculate vessel-specific fractional flow reserve (FFRCT) from routinely acquired coronary computed tomography angiography (CTA) was described. The Analysis of Coronary Blood Flow Using CT Angiography: Next Steps (NXT) trial, which was a prospective, multicenter trial including 254 patients with suspected coronary artery disease, noted high diagnostic performance of FFRCT compared with invasive FFR. The aim of this post-hoc analysis was to assess the diagnostic performance of non-invasive FFRCT vs. standard stenosis quantification on coronary CTA in the Japanese subset of the NXT trial. METHODS AND RESULTS A total of 57 Japanese participants were included from Okayama University (n=36), Kyoto University (n=17), and Keio University (n=4) Hospitals. Per-patient diagnostic accuracy of FFRCT(74%; 95% confidence interval [CI]: 60-85%) was higher than for coronary CTA (47%; 95% CI: 34-61%, P<0.001) arising from improved specificity (63% vs. 27%, P<0.001). FFRCT correctly reclassified 53% of patients and 63% of vessels with coronary CTA false positives as true negatives. When patients with Agatston score >1,000 were excluded, per-patient accuracy of FFRCT was 83% with a high specificity of 76%, similar to the overall NXT trial findings. CONCLUSIONS FFRCT has high diagnostic performance compared with invasive FFR in the Japanese subset of patients in the NXT trial.

Diagnostic Performance of First-Pass Myocardial Perfusion Imaging without Stress with Computed Tomography (CT) Compared with Coronary CT Angiography Alone, with Fractional Flow Reserve as the Reference Standard

Coronary computed tomography angiography (CCTA) in combination with first-pass CT myocardial perfusion imaging (MPI) has a better diagnostic performance than CCTA alone, compared with invasive coronary angiography as the reference standard. The aim of this study was to investigate the additional diagnostic value of first-pass CT-MPI without stress for detecting hemodynamic significance of coronary stenosis, compared with invasive fractional flow reserve (FFR). We recruited 53 patients with suspected coronary artery disease undergoing both CCTA and first-pass CT-MPI without stress and invasive FFR, and 75 vessels were analyzed. We used the same raw data for CCTA and CT-MPI. First-pass CT-MPI was reconstructed by examining the diastolic signal densities as a bull’s eye map. Invasive FFR <0.8 was considered as positive. On per-vessel analysis, the area under the receiver operating characteristic curve for CCTA plus first-pass CT-MPI and CCTA alone was 0.81 (0.73–0.90) and 0.70 (0.61–0.81), respectively (P = 0.036). CCTA plus first-pass CT-MPI without stress showed 0.73 sensitivity, 0.74 specificity, 0.53 positive predictive value, and 0.87 negative predictive value for detecting hemodynamically significant coronary stenosis. First-pass CT-MPI without stress correctly reclassified 38% of CCTA false-positive vessels as true negative. First-pass CT-MPI without stress combined with CCTA demonstrated excellent diagnostic accuracy, compared with invasive FFR as the reference standard. This technique could complement CCTA for diagnosis of coronary artery disease.

Comprehensive assessment of morphology and severity of atrial septal defects in adults by CT

BACKGROUND Cardiac CT is an excellent tool for evaluating the anatomy of a secundum atrial septal defect (ASD). However, a comprehensive assessment of its usefulness, including measurement of the pulmonary to systemic blood flow ratio in secundum ASD patients, has not been performed. OBJECTIVE Therefore, this study was designed to evaluate the usefulness of CT for assessing the hemodynamics of secundum ASD in adults compared with transesophageal echocardiography (TEE), transthoracic echocardiography, and invasive catheterization. METHODS Fifty adult patients with secundum ASD were enrolled. Cardiac CT scans (128-slice multidetector CT instrument) were acquired. These were followed by 2-dimensional reconstruction of the secundum ASDs to determine the defect size, the rim length between the outer edge of the defect, and the pulmonary to systemic blood flow (Qp/Qs) ratio. RESULTS The maximum sizes of the secundum ASDs derived from CT and TEE studies were comparable (21.2 ± 8.0 vs. 20.0 ± 7.3 mm; P = .41; r = 0.960; P < .001). The rim lengths for the aortic, mitral, and tricuspid valves; the inferior vena cava; and posterior atrium were also comparable between CT and TEE measurements. The mean Qp/Qs ratio that was derived from CT measurements was comparable with that found by invasive catheterization (2.3 ± 0.7 vs. 2.3 ± 0.8; P = .73; r = 0.786; P < .001). CONCLUSION Cardiac CT is feasible for assessing pathology and the severity of secundum ASD in adults.

Coronary Artery Calcification.

Coronary artery calcification (CAC) is an established marker of subclinical atherosclerosis and an independent predictor of future coronary heart disease in the asymptomatic primary prevention population, particularly in the intermediate risk cohort. CAC also helps in reclassifying those patients and their risk of cardiovascular events into higher or lower risk categories. MESA (Multi-Ethnic Study of Atherosclerosis) is a National Heart, Lung, and Blood Institute-sponsored population-based medical research study involving 6,814 men and women from 6 U.S. communities without a medical history of clinical cardiovascular disease. The evidence from this population cohort revealed that CAC scoring was independently predictive and highly effective at risk stratification of major adverse cardiac events. This review provides available data based on MESA. We focus on the utility of CAC for cardiovascular disease risk stratification of individuals, and we describe its diagnostic value in identifying patients at risk.

Rationale and design of a randomized trial of apixaban vs warfarin to evaluate atherosclerotic calcification and vulnerable plaque progression

Vitamin K antagonists (VKAs) are known to increase vascular calcification, suggesting increased cardiovascular disease events. Apixaban is an oral direct factor Xa inhibitor superior to warfarin at preventing stroke or systemic embolism and may stabilize coronary atherosclerosis. The potential benefits of avoiding VKA therapy and the favorable effects of factor Xa inhibitors could contribute to cardiovascular disease event reduction. We hypothesized that apixaban inhibits vascular calcification and coronary atherosclerosis progression compared with warfarin in patients with atrial fibrillation (AF). This study is a single‐center, prospective, randomized, open‐label study. From May 2014 to December 2015, 66 patients with nonvalvular AF who experienced VKA therapy were enrolled. Patients were randomized into either warfarin or apixaban cohorts and followed for 52 weeks. The primary objective is to compare the rate of change in coronary artery calcification (CAC) from baseline to follow‐up in apixaban vs warfarin cohorts. The key secondary objective is to compare the rate of incident plaques and quantitative changes in plaque types between patients randomized to either warfarin or apixaban cohorts using serial coronary computed tomography angiography. Expert readers will blindly assess CAC and coronary artery plaques. It is thought that this trial will result in significant differences in CAC and coronary artery plaque progression between the VKA and apixaban. The results are anticipated to provide a novel insight into treatment selection for AF patients. The study is registered at http://www.clinicaltrials.gov (NCT 02090075).