Eiji Kunita

Characterization of Noncalcified Coronary Plaques and Identification of Culprit Lesions in Patients With Acute Coronary Syndrome by 64-Slice Computed Tomography

OBJECTIVES We sought to characterize noncalcified coronary atherosclerotic plaques in culprit and remote coronary atherosclerotic lesions in patients with acute coronary syndrome (ACS) with 64-slice computed tomography (CT). BACKGROUND Lower CT density, positive remodeling, and adjacent spotty coronary calcium are characteristic vessel changes in unstable coronary plaques. METHODS Of 147 consecutive patients who underwent contrast-enhanced 64-slice CT examination for coronary artery visualization, 101 (ACS; n = 21, non-ACS; n = 80) having 228 noncalcified coronary atherosclerotic plaques (NCPs) were studied. Each NCP detected within the vessel wall was evaluated by determining minimum CT density, vascular remodeling index (RI), and morphology of adjacent calcium deposits. RESULTS The CT visualized more NCPs in ACS patients (65 lesions, 3.1 +/- 1.2/patient) than in non-ACS patients (163 lesions, 2.0 +/- 1.1/patient). Minimum CT density (24 +/- 22 vs. 42 +/- 29 Hounsfield units [HU], p < 0.01), RI (1.14 +/- 0.18 vs. 1.08 +/- 0.19, p = 0.02), and frequency of adjacent spotty calcium of NCPs (60% vs. 38%, p < 0.01) were significantly different between ACS and non-ACS patients. Frequency of NCPs with minimum CT density <40 HU, RI >1.05, and adjacent spotty calcium was approximately 2-fold higher in the ACS group than in the non-ACS group (43% vs. 22%, p < 0.01). In the ACS group, only RI was significantly different between 21 culprit and 44 nonculprit lesions (1.26 +/- 0.16 vs. 1.09 +/- 0.17, p < 0.01), and a larger RI (> or = 1.23) was independently related to the culprit lesions (odds ratio: 12.3; 95% confidential interval: 2.9 to 68.7, p < 0.01), but there was a substantial overlap of the distribution of RI values in these 2 groups of lesions. CONCLUSIONS Sixty-four-slice CT angiography demonstrates a higher prevalence of NCPs with vulnerable characteristics in patients with ACS as compared with stable clinical presentation.

Association between epicardial adipose tissue volume and characteristics of non-calcified plaques assessed by coronary computed tomographic angiography

BACKGROUND The aim of this study was to investigate whether high epicardial adipose tissue (EAT) volume is related to the presence of vulnerable coronary plaque components as assessed by computed tomography (CT). METHODS We evaluated 357 patients referred for 64-slice CT, and assessed coronary plaque components and EAT volume. Vulnerable coronary plaque components were defined as the presence of non-calcified plaque (NCP), including low-density plaque (LDP: <39 HU) and positive remodeling (PR: remodeling index>1.05). In accordance with a previous report, patients were assigned to two groups: low (<100 ml) or high (≥100 ml) EAT volume. RESULTS Compared to the low EAT volume group, the high EAT volume group had a higher prevalence of NCP (74% vs. 59%, p=0.003). Additionally, the high EAT volume group had a higher prevalence of LDP with PR than the low EAT volume group (46% vs. 25%, p<0.001). Interestingly, a high EAT volume was an independent predictor of LDP with PR (odds ratio 2.56, 95% confidence interval 1.38-4.85, p=0.003) after adjusting for age, gender, traditional cardiovascular risk factors, body mass index (BMI), abdominal visceral adipose tissue (VAT), and coronary artery calcium (CAC) scores. CONCLUSIONS A high EAT volume was associated with the presence of vulnerable plaque components, independent of obesity measurements (BMI and VAT) and CAC scores.

Association between visceral adipose tissue area and coronary plaque morphology assessed by CT angiography.

OBJECTIVES We sought to investigate the association between visceral adipose tissue (VAT) with the presence, extent, and characteristics of noncalcified coronary plaques (NCPs) using 64-slice computed tomography angiography (CTA). BACKGROUND Although visceral adiposity is associated with cardiovascular events, its association with NCP burden and vulnerability is not well known. METHODS The study population consisted of 427 patients (age 67 ± 11 years; 63% men) with proven or suspected coronary artery disease who underwent 64-slice CTA. We assessed the presence and number of NCPs for each patient. The extent of NCP was tested for the difference between high (≥ 2) and low (≤ 1) counts. We further evaluated the vulnerable characteristics of NCPs with positive remodeling (remodeling index >1.05), low CT density (≤ 38 HU), and the presence of adjacent spotty calcium. Plain abdominal scans were also performed to measure the VAT and subcutaneous adipose tissue area. RESULTS A total of 260 (61%) patients had identifiable NCPs. Multivariate analyses revealed that increased VAT area (per 1 standard deviation, 58 cm(2)) was significantly associated with both the presence (odds ratio [OR]: 1.68; 95% confidence interval [CI]: 1.28 to 2.22) and extent (OR: 1.31; 95% CI: 1.03 to 1.68) of NCP. Other body composition measures, including subcutaneous adipose tissue area, body mass index, and waist circumference were not significantly associated with either presence or extent of NCP. Increased VAT area was also independently associated with the presence of NCP with positive remodeling (OR: 1.71; 95% CI: 1.18 to 2.53), low CT density (OR: 1.69; 95% CI: 1.17 to 2.47), and adjacent spotty calcium (OR: 1.52; 95% CI: 1.03 to 2.27). CONCLUSIONS Increased VAT area was significantly associated with NCP burden and vulnerable characteristics identified by CTA. Our findings may explain the excessive cardiovascular risk in patients with visceral adiposity, and support the potential role of CTA to improve risk stratification in such patients.

Noncalcified atherosclerotic lesions with vulnerable characteristics detected by coronary CT angiography and future coronary events

BACKGROUND The ability of coronary CT angiography (CTA) findings such as plaque characteristics to predict future coronary events remains controversial. OBJECTIVE We investigated whether noncalcified atherosclerotic lesions (NCALs) detected by coronary CTA were predictive of future coronary events. METHODS A total of 511 patients who underwent coronary CTA were followed for cardiovascular events over a period of 3.3 ± 1.2 years. The primary end point was defined as hard events, including cardiac death, nonfatal myocardial infarction, or unstable angina that required urgent hospitalization. Early elective coronary revascularizations (n = 58) were excluded. The relationship between features of NCALs and outcomes is described. RESULTS A total of 15 hard events (2 cardiac deaths, 7 myocardial infarctions, 6 cases of unstable angina that required urgent hospitalization) were documented in the remaining 453 patients with modest risks during a follow-up period of 3.3 ± 1.2 years. For these hard events, a univariate Cox proportional hazard model showed that the hazard ratio for the presence of >50% stenosis was 7.27 (95% CI, 2.62-21.7; P = .0002). Although the presence of NCAL by itself was not statistically significant, NCALs with low attenuation and positive remodeling (low-attenuation plaque [LAP] and positive remodeling [PR]; plaque CT number ≤ 34 HU and remodeling index ≥ 1.20) showed an adjusted hazard ratio of 11.2 (95% CI, 3.71-36.7; P < .0001). With C-statistics analysis, when both LAP and PR and >50% stenosis were added, the C-statistic was significantly improved compared with the basal model adjusted for age, sex, and log2 (Agatston score +1) (0.900 vs 0.704; P = .0018). CONCLUSIONS Identification of NCALs with LAP and PR characteristics by coronary CTA provides additional prognostic information to coronary stenosis for the prediction of future coronary events.

Underestimation of aortic valve area in calcified aortic valve disease: effects of left ventricular outflow tract ellipticity.

BACKGROUND The aortic valve area (AVA) is usually calculated using the continuity equation (CE) in which the left ventricular outflow tract (LVOT) area is estimated assuming circular geometry. We sought to evaluate the LVOT ellipticity with 64-multidetector computed tomography (MDCT) and to assess the impact of LVOT ellipticity on the evaluation of CE-based AVA in patients with calcified aortic valves. METHODS We prospectively studied 110 patients with calcified aortic valves including 54 aortic stenosis (AS) with both 64-MDCT and transthoracic echocardiography. Double oblique transversal images for planimetry of the aortic valve and LVOT were obtained during the midsystolic phase. The short and long-axis diameters of the planimetered LVOT were measured. RESULTS The MDCT planimetered LVOT area was underestimated by the diameter-derived (π × r(2)) LVOT area using echocardiography (444 ± 70 mm(2) versus 369 ± 63 mm(2); p<0.001). The mean difference in AVA values calculated using the CE and planimetry was 0.43 ± 0.23 cm(2) and mean measurement error of CE-based AVA was 18%. When the CE-based AVA was corrected using the MDCT planimetered LVOT area, the measurement error decreased from 28 ± 5 to 5 ± 2% in patients with severe aortic stenosis (AVA<1.0 cm(2)), whereas from 16 ± 5 to 3 ± 6% in others. CONCLUSION Ellipticity of LVOT is associated with underestimation of AVA measurements using the CE. CE-based AVA corrected with MDCT planimetered LVOT area is useful especially in severe AS.

Combined presence of aortic valve calcification and mitral annular calcification as a marker of the extent and vulnerable characteristics of coronary artery plaque assessed by 64-multidetector computed tomography

OBJECTIVE We examined the association of aortic valve calcification (AVC) and mitral annular calcification (MAC) to coronary atherosclerosis using 64-multidetector computed tomography (MDCT). BACKGROUND Valvular calcification is considered a manifestation of atherosclerosis. The impact of multiple heart valve calcium deposits on the distribution and characteristics of coronary plaque is unknown. METHODS We evaluated 322 patients referred for 64-MDCT, and assessed valvular calcification and the extent of calcified (CAP), mixed (MCAP), and noncalcified coronary atherosclerotic plaque (NCAP) in accordance with the 17-coronary segments model. We assessed the vulnerable characteristics of coronary plaque with positive remodeling, low-density plaque (CT density ≤38 Hounsfield units), and the presence of adjacent spotty calcification. RESULTS In 49 patients with both AVC and MAC, the segment numbers of CAP and MCAP were larger than in those with a lack of valvular calcification and an isolated AVC (p<0.001 for both). Multivariate analyses revealed that a combined presence of AVC and MAC was independently associated with the presence (odds ratio [OR] 9.36, 95% confidence interval [95%CI] 1.55-56.53, p=0.015) and extent (β-estimate 1.86, p<0.001) of overall coronary plaque. When stratified by plaque composition, it was associated with the extent of CAP (β-estimate 1.77, p<0.001) and MCAP (β-estimate 1.04, p<0.001), but not with NCAP. Moreover, it was also related to the presence of coronary plaque with all three vulnerable characteristics (OR 4.87, 95%CI 1.85-12.83, p=0.001). CONCLUSION The combined presence of AVC and MAC is highly associated with the presence, extent, and vulnerable characteristics of coronary plaque identified by 64-MDCT.

Prognostic value of coronary artery calcium and epicardial adipose tissue assessed by non-contrast cardiac computed tomography

OBJECTIVE Epicardial adipose tissue (EAT) accumulation is believed to be associated with development of coronary atherosclerosis. We investigated whether EAT volume as assessed by computed tomography (CT) has value in prediction of future cardiac events. METHODS We studied 722 patients without proven coronary artery disease (CAD) who underwent non-contrast cardiac CT. EAT volume and coronary artery calcium (CAC) score were measured simultaneously. Patients were followed as to the occurrence of coronary events (cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and late coronary revascularization≥3 months after CT examination). RESULTS During a 3.7±1.7 years follow-up period, 37 coronary events were documented. Annual event rates increased across CAC score categories (0.3%, 1.0%, 2.4%, and 4.3%, in 0, 1-99, 100-399, and ≥400, respectively, p<0.001); these were significantly higher in the higher EAT volume group (>median; 107.2 mL, 0.7% vs., 2.1%, adjusted hazard ratio; 2.65, p=0.0090). Cox-proportional hazard analysis demonstrated that a combination of CAC score≥100 and high EAT volume had a significantly higher event rate than CAC score<100 and low EAT volume group (adjusted hazard ratio 11.6, p<0.0001). Using Cox regression models, incremental prognostic values were identified by adding high EAT volume to clinical risks plus CAC score≥100 (global χ2, 6.7; p=0.059). CONCLUSION We suggest that high EAT volume may be an independent predictor of future coronary events and increases predictive values of CAC score in patients without proven CAD.

Effects of statin therapy on non-calcified coronary plaque assessed by 64-slice computed tomography

UNLABELLED Computed tomography angiography (CTA) enables characterization of non-calcified coronary atherosclerotic lesions (NCALs) and assessment of plaque vulnerability. We investigated whether the characteristics of NCALs detected by 64-slice CTA were influenced by preceding statin therapy and serum lipid profiles. METHODS Among 493 consecutive patients who underwent coronary CTA, we enrolled 114 patients with NCALs. We divided the patients into three groups according to preceding statin therapy: intensive statins (IS, n=24), moderate statins (MS, n = 26), and no statin (NS, n = 64). The vulnerability of each NCAL was evaluated by density (low-density plaque defined as CT density ≤ 38 HU), positive remodeling (remodeling index > 1.05), and the presence of adjacent spotty calcification. RESULTS Percentages of patients in the IS, MS, and NS groups with low-density NCALs were 46%, 58%, and 80%, respectively (p = 0.009) and positive remodeling NCALs were 54%, 58%, and 75%, respectively (p = 0.10). We also found an inverse correlation between serum LDL-C level and the minimum plaque CT density. According to the regression equation, a CT density of 38 HU corresponded with LDL-C of 100 mg/dl. The number of low-density plaques was positively correlated with low-density to high-density lipoprotein cholesterol ratio (LDL-C/HDL-C). An LDL-C/HDL-C > 2.5 independently predicted multiple low-density plaques (OR 2.39 [95%CI: 1.28-4.86], p < 0.001). CONCLUSIONS Our CTA findings demonstrate that low-density NCALs occur less frequently in patients with intensive statin pre-treatment. A high LDL-C/HDL-C ratio is also associated with larger numbers of low-density NCALs.

Incremental prognostic value of cardiac computed tomography angiography in asymptomatic aortic stenosis: significance of aortic valve calcium score.

BACKGROUND Cardiac computed tomography angiography (CCTA) provides the simultaneous evaluation of the aortic valve, myocardium, and coronary arteries. In particular, aortic valve calcium score (AVCS) can be accurately measured on the same scanning sequence used to measure coronary artery calcification, with no additional cost or radiation exposure. We sought to evaluate the prognostic value of CCTA measures, including AVCS, in asymptomatic aortic stenosis (AS). METHODS AND RESULTS Sixty-four initially asymptomatic patients with AS with a normal ejection fraction were prospectively enrolled and followed for median 29 (IQR=18-50) months. During follow-up, 27 (42%) patients experienced cardiac events, including five cardiac deaths, eleven aortic valve replacements. Multivariate Cox proportional hazards analysis identified three CCTA measures as significant predictors of cardiac events: aortic valve area (per 0.1cm(2) decrease; hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05-1.34); multi-vessel obstructive coronary artery disease (HR: 2.84, 95% CI: 1.10-7.32); and AVCS (per 100; HR: 1.09, 95% CI: 1.04-1.15). Kaplan-Meier analysis showed that patients with AVCS greater than or equal to the median value of 723 had significantly worse outcomes than those with AVCS less than 723 (p<0.0001). The C-statistic value for cardiac events substantially increased when these CCTA measures were added to clinical characteristics plus echocardiographic peak transaortic velocity (0.913 vs. 0.702, p<0.001). CONCLUSIONS In patients with asymptomatic AS, CCTA measures of valve area, coronary stenosis, and calcification severity provide independent and incremental prognostic value after accounting for the echocardiographic severity of stenosis.

Association Between Aortic Valve Calcification and Myocardial Ischemia, Especially in Asymptomatic Patients

Aortic valve calcification (AVC) is recognized as a manifestation of systemic arteriosclerosis. However, it is unclear whether AVC is associated with myocardial ischemia. Stress myocardial perfusion SPECT (MPS) is widely used for the diagnosis of myocardial ischemia. However, routine MPS is not recommended, particularly in asymptomatic patients. Accordingly, we investigated the hypothesis that the presence of AVC is strongly associated with inducible myocardial ischemia, even among asymptomatic patients. Methods: We investigated 669 consecutive patients who underwent both adenosine stress 201Tl MPS and echocardiography. We evaluated the extent and severity of myocardial ischemia by the summed difference score (SDS). We defined the presence of myocardial ischemia as SDS ≥ 3 and moderate to severe ischemia as SDS ≥ 8. We classified the severity of AVC according to the number of affected aortic leaflets. We also compared the mean SDS and the prevalence of SDS ≥ 3 and SDS ≥ 8 among patients stratified by the severity of AVC. Results: The presence of AVC was significantly associated with myocardial ischemia (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.10–2.23; P = 0.013) and moderate to severe ischemia (OR, 2.16; 95% CI, 1.26–3.80; P = 0.0061). In 311 asymptomatic patients, AVC was strongly associated with moderate to severe ischemia (OR, 4.31; 95% CI, 1.67–12.8; P = 0.0043). However, the SDS value and the prevalence of SDS ≥ 3 and SDS ≥ 8 did not increase with increasing number of affected aortic leaflets. Conclusion: The presence of AVC may be associated with the presence of myocardial ischemia, particularly in asymptomatic patients. However, we found no association between the extent of AVC and inducible myocardial ischemia. The presence of AVC may be a useful anatomic marker to help identify patients at high risk of myocardial ischemia, particularly asymptomatic patients.