Yuka Otaki

Increase in epicardial fat volume is associated with greater coronary artery calcification progression in subjects at intermediate risk by coronary calcium score: A serial study using non-contrast cardiac CT

OBJECTIVE Epicardial fat volume (EFV) is related to calcified coronary plaques. However, it is unknown whether baseline EFV or changes in EFV affect the progression of coronary artery calcification over time. METHODS We identified 375 consecutive asymptomatic subjects with an intermediate risk of developing coronary artery disease, who underwent serial non-contrast CT at least 3-5 years apart. Subjects were divided into tertiles of CCS progression (% increase) between the 2 scans. Subjects from the upper tertile (High Progressors) were matched by age and gender to 81 subjects from the lower tertile (Low Progressors). All subjects underwent serial measurements of CCS and EFV. Relationships between EFV and CCS progression, and change in plaque number were examined. RESULTS At baseline, there was no difference in EFV, and EFV indexed to body surface area (EFVi) between the groups. At follow-up, EFV, EFVi and percent increase in EFVi-change were higher in High Progressors than Low Progressors (EFV, 102 ± 38 cm(3) vs. 90 ± 35 cm(3), p=0.03; EFVi, 50 ± 16cm(3)/m(2) vs. 46 ± 15 cm(3)/m(2), p=0.03; percent increase in EFVi-change, 15 ± 22% vs. 7 ± 20%, p=0.02). On multivariate analysis, after adjusting for conventional risk factors, EFVi increase ≥15% [odds ratio (OR) 2.3, p<0.05], log (baseline CCS) [OR 0.3, p<0.0001] and scan interval time [p=0.003, OR 1.0] were predictive of being a High Progressor. EFVi increase ≥ 15% (β=3.0, p=0.02) and hypertension (β=3.1, p=0.01) were independent predictors of number of new calcified plaques on follow-up. CONCLUSION Increase in EFV is associated with greater progression of coronary artery calcification in intermediate-risk subjects.

Weight change modulates epicardial fat burden: A 4-year serial study with non-contrast computed tomography

INTRODUCTION Epicardial fat volume (EFV) is linked to cardiovascular event risk. We aimed to investigate the relationships between EFV and weight change. METHODS From the EISNER (Early Identification of Subclinical Atherosclerosis using Non-invasive Imaging Research) Registry with baseline and follow-up coronary calcium scans (1248 subjects), we selected a cohort of 374 asymptomatic subjects matched using age decade, gender and coronary calcium score (CCS) as a measure of subclinical cardiovascular risk, who underwent 2 scans at an interval of 4.1±0.4 years. Using semi-automated validated software, pericardial contours were generated on all slices by spline interpolation from 5 to 10 control points. EFV was computed as fat volume within the pericardial contours. Weight gain/loss was defined as >5% change. RESULTS At baseline, EFV was moderately correlated to weight, body mass index (BMI) and waist circumference (r=0.51, 0.41 and 0.50, p<0.0001). EFV change was weakly correlated to change in weight (r=0.37, p<0.0001), BMI (r=0.39, p<0.0001) and waist circumference (r=0.21, p=0.002). On multivariable linear regression analysis, weight change [β=1.2, 95% confidence interval (CI) 0.9-1.5, p<0.001], BMI change (β=1.2, 95% CI 0.9-1.5, p<0.001), gender (β=-6.4, 95% CI -10.9 to -1.8, p=0.006) and hypertension (β=4.7, 95% CI 0.5-9.0, p=0.03) predicted EFV change. EFV decreased in 54 subjects with weight loss and increased in 71 subjects with weight gain (-2.3±21.1% vs. 23.3±24.4%, p<0.001). CONCLUSIONS EFV is related to body weight, BMI and waist circumference. Reduction in weight may stabilize or reduce EFV, while weight gain may promote EFV increase.

Relation of Diagonal Ear Lobe Crease to the Presence, Extent, and Severity of Coronary Artery Disease Determined by Coronary Computed Tomography Angiography

Controversy exists concerning the relation between diagonal ear lobe crease (DELC) and coronary artery disease (CAD). We examined whether DELC is associated with CAD using coronary computed tomography (CT) angiography. We studied 430 consecutive patients without a history of coronary artery intervention who underwent CT angiography on a dual-source scanner. Presence of DELC was agreed by 2 blinded observers. Two blinded readers evaluated CT angiography images for presence of CAD and for significant CAD (≥50% stenosis). Chi-square and t tests were used to assess demographic differences between subgroups with and without DELC and the relation of DELC to 4 measurements of CAD: any CAD, significant CAD, multivessel disease (cutoff ≥2), and number of segments with plaque (cutoff ≥3). Multivariable logistic regression was performed to adjust for CAD confounders: age, gender, symptoms, and CAD risk factors. Mean age was 61 ± 13 and 61% were men. DELC was found in 71%, any CAD in 71%, and significant CAD in 17% of patients. After adjusting for confounders, DELC remained a significant predictor of all 4 measurements of CAD (odds ratio 1.8 to 3.3, p = 0.002 to 0.017). Sensitivity, specificity, and positive and negative predictive values for DELC in detecting any CAD were 78%, 43%, 77%, and 45%. Test accuracy was calculated at 67%. Area under the receiver operator characteristic curve was 61% (p = 0.001). In conclusion, in this study of patients imaged with CT angiography, finding DELC was independently and significantly associated with increased prevalence, extent, and severity of CAD.

Threshold for the Upper Normal Limit of Indexed Epicardial Fat Volume: Derivation in a Healthy Population and Validation in an Outcome-Based Study

Epicardial fat volume (EFV) quantified on noncontrast cardiac computed tomography relates to cardiovascular prognosis. We sought to define the upper normal limit of body surface area (BSA)-indexed EFV (EFVi) in a healthy population and to validate it as a predictor of major adverse cardiovascular events (MACE). We analyzed noncontrast cardiac computed tomography scans of 226 healthy subjects with a low Framingham Risk Score (FRS; ≤6%) performed for coronary calcium scoring (CCS). EFV was quantified using validated software and indexed to BSA. We defined the 95th percentile as the upper normal limit. Subsequently, we reanalyzed a separate cohort of 232 participants from a previously published case-control study with 4-year follow-up and 58 cases of MACE to test the additive value of an abnormally high EFVi for predicting MACE. Of the 226 healthy participants 51% were men (mean age 52 ± 9 years). EFV correlated to BSA (r = 0.373, p <0.0001). Median, range, and 25th and 75th percentiles of the non-normally distributed EFVi were 33.3, 10.8 to 96.6, and 24.5 and 45.5 cm(3)/m(2). The 95th percentile definition of the upper normal limit of EFVi was 68.1 cm(3)/m(2). For prediction of MACE, EFVi values higher than the newly defined threshold emerged as a significant and independent predictor after controlling for confounders (odds ratio 2.8, 95% confidence interval 1.3 to 6.4, p = 0.012) and trended in its additive value to the combination of CCS ≥400 and FRS (area under the receiver operating characteristic curve 0.714 vs 0.675, p = 0.1277). In conclusion, in a healthy population we determined 68.1 cm(3)/m(2) as the 95th percentile threshold for abnormally high EFVi. EFVi exceeding this value independently predicted MACE and trended to add to CCS and FRS in this prediction.

Impact of Family History of Coronary Artery Disease in Young Individuals (from the CONFIRM Registry)

Although family history (FH) of coronary artery disease (CAD) is considered a risk factor for future cardiovascular events, the prevalence, extent, severity, and prognosis of young patients with FH of CAD have been inadequately studied. From 27,125 consecutive patients who underwent coronary computed tomographic angiography, 6,308 young patients (men aged <55 years and women aged <65 years) without known CAD were identified. Obstructive CAD was defined as >50% stenosis in a coronary artery >2 mm diameter. Risk-adjusted logistic regression, Kaplan-Meier, and Cox proportional-hazards models were used to compare patients with and without FH of CAD. Compared with subjects without FH of CAD, those with FH of CAD (FH+) had higher prevalences of any CAD (40% vs 30%, p <0.001) and obstructive CAD (11% vs 7%, p <0.001), with multivariate odds of FH+ increasing the likelihood of obstructive CAD by 71% (p <0.001). After a mean follow-up period of 2 ± 1 years (42 myocardial infarctions and 39 all-cause deaths), FH+ patients experienced higher annual rates of myocardial infarction (0.5% vs 0.2%, log-rank p = 0.001), with a positive FH the strongest predictor of myocardial infarction (hazard ratio 2.6, 95% confidence interval 1.4 to 4.8, p = 0.002). In conclusion, young FH+ patients have higher presence, extent, and severity of CAD, which are associated with increased risk for myocardial infarction. Compared with other clinical CAD risk factors, positive FH in young patients is the strongest clinical predictor of future unheralded myocardial infarction.

What have we learned from CONFIRM? Prognostic implications from a prospective multicenter international observational cohort study of consecutive patients undergoing coronary computed tomographic angiography

Coronary computed tomographic angiography (CCTA) employing CT scanners of 64-detector rows or greater represents a novel non-invasive method for detection of coronary artery disease (CAD), providing excellent diagnostic information when compared to invasive angiography. In addition to its high diagnostic performance, prior studies have shown that CCTA can provide important prognostic information, although these prior studies have been generally limited to small cohorts at single centers. The Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter registry, or CONFIRM, is a large, prospective, multinational, dynamic observational cohort study of patients undergoing CCTA. This registry currently represents more than 32,000 consecutive adults suspected of having CAD who underwent ≥64-detector row CCTA at 12 centers in 6 countries between 2005 and 2009. Based on its large sample size and adequate statistical power, the data derived from CONFIRM registry have and will continue to provide key answers to many important topics regarding CCTA. Based on its multisite international national design, the results derived from CONFIRM should be considered as more generalizable than prior smaller single-center studies. This article summarizes the current status of several studies from CONFIRM registry.

The relationship between epicardial fat volume and incident coronary artery calcium.

BACKGROUND Epicardial fat volume (EFV) has been associated with prevalent but not incident coronary artery calcium. However, the relationship between EFV and development of incident coronary calcium (incCC) has not been reported. OBJECTIVE We evaluated the relationship between epicardial fat volume and the development of coronary artery calcium over 3-5 years. METHODS From 1248 subjects who underwent 2 serial noncontrast cardiac CT scans 3-5 years (median, 4 years) apart to measure coronary calcium score of 0 who subsequently developed incident coronary calcium (incCC(+)) were matched to 106 controls in whom coronary calcium score remained 0 (incCC(-)). EFV was calculated by determination of the pericardial contour, followed by identification of fat voxels with the use of validated software (QFAT). Baseline EFV and EFV indexed to body surface area (EFVi) and subsequent EFV and EFVi changes were compared between incCC(-) and incCC(+) populations. A significant EFV increase was defined as a ≥10% and ≥25% increase from the baseline value. RESULTS Baseline EFVi was similar between the 2 groups [EFVi, 40.9 ± 17.9 cm³ (median, 38.3 cm³) in incCC(-) vs 40.3 ± 16.3 cm³ (median, 37.0 cm³) in incCC(+); P = 0.96]. On the follow-up CT, EFVi increased in 74.5% of incCC(-) and in 76.4% of incCC(+) (P = 0.75). EFVi changes between the 2 groups were similar [4.9 ± 8.9 cm³ (median, 4.9 cm³) in incCC(-) vs 4.2 ± 8.0 cm³) (median, 3.5 cm³) in incCC(+); P = 0.67]. On multivariate analysis, after adjusting for cardiovascular risk factors, incCC was not related to an increase in EFVi at a 10% or 25% level. CONCLUSIONS In very low-risk subjects with a coronary calcium score of 0, baseline EFVi and change in EFVi after 3-5 years were not related to the development of incidental coronary artery calcium.

Quantitation of left ventricular ejection fraction reserve from early gated regadenoson stress Tc-99m high-efficiency SPECT.

BackgroundEjection fraction (EF) reserve has been found to be a useful adjunct for identifying high risk coronary artery disease in cardiac positron emission tomography (PET). We aimed to evaluate EF reserve obtained from technetium-99m sestamibi (Tc-99m) high-efficiency (HE) SPECT.MethodsFifty patients (mean age 69 years) undergoing regadenoson same-day rest (8-11 mCi)/stress (32-42 mCi) Tc-99m gated HE SPECT were enrolled. Stress imaging was started 1 minute after sequential intravenous regadenoson .4 mg and Tc-99m injections, and was composed of five 2 minutes supine gated acquisitions followed by two 4 minutes supine and upright images. Ischemic total perfusion deficit (ITPD) ≥5 % was considered as significant ischemia.ResultsSignificantly lower mean EF reserve was obtained in the 5th and 9th minute after regadenoson bolus in patients with significant ischemia vs patients without (5th minute: −4.2 ± 4.6% vs 1.3 ± 6.6%, P = .006; 9th minute: −2.7 ± 4.8% vs 2.0 ± 6.6%, P = .03).ConclusionsNegative EF reserve obtained between 5th and 9th minutes of regadenoson stress demonstrated best concordance with significant ischemia and may be a promising tool for detection of transient ischemic functional changes with Tc-99m HE-SPECT.Spanish AbstractAntecedentesSe ha encontrado que la reserva de la Fracción de Eyección (FE) en la tomografía de emisión de positrones cardiaca (PET, positron emission tomography por sus siglas en ingles) es una herramienta útil adicional en la identificación de pacientes con enfermedad arterial coronaria de alto riesgo. Nuestro objetivo fue evaluar la reserva de la FE obtenida por SPECT de alta eficiencia (AE) con Tecnecio-99m (Tc-99m) sestamibi.MétodosCincuenta pacientes (edad promedio 69 años) a quienes se les realizo un SPECT de AE con Tc‐99m sincronizado con el electrocardiograma en un solo día reposo (8-11mCi)/estrés 32-42mCi) con regadenoson fueron incluidos La adquisición de las imágenes de estrés se inicio un minuto después de la administración secuencial intravenosa de regadenoson .4mg y Tc-99m, compuesta de 5 adquisiciones sincronizadas con el electrocardiograma de 2 minutos cada una en supino seguidas de dos adquisiciones de 4 minutos cada una en supino y sentado. Un defecto total de perfusión isquémico (DTPI) ≥5% fue considerado como isquemia significativa.ResultadosEl promedio obtenido de la Reserva de la FE fue significativamente menor en los minutos 5to y 9no posterior al bolo de regadenoson en pacientes con isquemia significativa comparados con pacientes sin isquemia (5to minuto: −4.2 ± 4.6% vs 1.3 ± 6.6%, p= 0.006; 9no minuto: −2.7 ± 4.8% vs 2.0 ± 6.6%, p = 0.03).ConclusionesUna Reserva de la FE negativa obtenida en los minutos 5to y 9no del estrés con regadenoson demostró una mejor concordancia con la presencia de isquemia significativa y podría ser un herramienta promisoria para la detección de cambios funcionales isquémicos transitorios con un estudio SPECT de AE con Tc-99m.Chinese Abstract背景对于心脏PET显像, 射血分数 (EF) 储备 已成为评判高风险冠心病的有效辅助手段。本文旨在评价采用Tc-99m甲氧基异丁基异睛显影剂和高能SPECT测定EF储备的可行性。方法入选55行类伽腺苷一日法静息 (8-11mCi) /负荷 (32-42mCi) 门控高能SPECT显像的患者, 平均年龄为69岁。在连续静脉注射类伽腺苷 (0.4mg) 和Tc-99m一分钟后开始负荷图像的采集。负荷图像包括5个2分钟的仰卧位门控采集和后续2个分别为仰卧位和直立位的4分钟门控采集。总灌注缺损≧5%为显著缺血。结果注射类伽腺苷后, 显著缺血患者的平均EF储备在第5和第9分钟时较无缺血患者显著降低 (第5分钟: −4.2 ± 4.6% vs. 1.3 ± 6.6%, p = 0.006; 第9分钟: −2.7 ± 4.8% vs. 2.0 ± 6.6%, p=0.03)。结论在类伽腺苷负荷时, 第5至9分钟测得的EF储备负值与显著缺血的一致性最佳, 这很可能成为Tc-99m高能SPECT检测一过性心肌缺血伴随的心功能改变的有效手段。

Gender differences in the prevalence, severity, and composition of coronary artery disease in the young: a study of 1635 individuals undergoing coronary CT angiography from the prospective, multinational confirm registry

OBJECTIVE Prior studies examining coronary atherosclerosis in the young have been limited by retrospective analyses in small cohorts. We examined the relationship between cardiovascular risk factors (RFs) and prevalence and severity of coronary atherosclerosis in a large, prospective, multinational registry of consecutive young individuals undergoing coronary computerized tomographic angiography (CCTA). METHOD AND RESULTS Of 27 125 patients undergoing CCTA, 1635 young (<45 years) individuals without known coronary artery disease (CAD) or coronary anomalies were identified. Coronary plaque was assessed for any CAD, obstructive CAD (≥50% stenosis), and presence of calcified plaque (CP) and non-calcified plaque (NCP). Among 1635 subjects (70% men, age 38 ± 6 years), any CAD, obstructive CAD, CP, and NCP were observed in 19, 4, 5, and 8%, respectively. Compared with women, men demonstrated higher rates of any CAD (21 vs. 12%, P < 0.001), CP (6 vs. 3%, P = 0.01), and NCP (9 vs. 5%, P = 0.008), although no difference was observed for rates of obstructive CAD (5 vs. 4%, P = 0.46). Any CAD, obstructive CAD, and NCP were higher for young individuals with diabetes, hypertension, dyslipidaemia, current smoking, or family history of CAD; while only diabetes and dyslipidaemia were associated with CP. Increasing cardiovascular RFs was associated with a greater prevalence and extent and severity of CAD, with individuals with 0, 1, 2, ≥3 RFs manifesting a dose-response increase in any CAD (P < 0.001, for trend), obstructive CAD (P < 0.001, for trend), NCP (P < 0.001, for trend), and CP (P < 0.001, for trend). In multivariable analysis adjusting for sex and cardiovascular RFs, male sex was the strongest predictor for any CAD (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.43-2.66, P < 0.001), CP (OR = 1.46, 95% CI = 1.08-1.98, P = 0.01), and NCP (OR = 1.33, 95% CI = 1.06-1.67, P = 0.01); family history of CAD was the strongest predictor for obstructive CAD (OR = 2.71, 95% CI = 1.65-4.45, P < 0.001). CONCLUSION Any and obstructive CAD is present in 1 in 5 and 1 in 20 young individuals, respectively, with family history associated with the greatest risk of obstructive CAD.

Relationship Between Quantitative Adverse Plaque Features From Coronary Computed Tomography Angiography and Downstream Impaired Myocardial Flow Reserve by 13N-Ammonia Positron Emission Tomography A Pilot Study

Background—We investigated the relationship of quantitative plaque features from coronary computed tomography (CT) angiography and coronary vascular dysfunction by impaired myocardial flow reserve (MFR) by 13N-Ammonia positron emission tomography (PET). Methods and Results—Fifty-one patients (32 men, 62.4±9.5 years) underwent combined rest–stress 13N-ammonia PET and CT angiography scans by hybrid PET/CT. Regional MFR was measured from PET. From CT angiography, 153 arteries were evaluated by semiautomated software, computing arterial noncalcified plaque (NCP), low-density NCP (NCP<30 HU), calcified and total plaque volumes, and corresponding plaque burden (plaque volumex100%/vessel volume), stenosis, remodeling index, contrast density difference (maximum difference in luminal attenuation per unit area in the lesion), and plaque length. Quantitative stenosis, plaque burden, and myocardial mass were combined by boosted ensemble machine-learning algorithm into a composite risk score to predict impaired MFR (MFR⩽2.0) by PET in each artery. Nineteen patients had impaired regional MFR in at least 1 territory (41/153 vessels). Patients with impaired regional MFR had higher arterial NCP (32.4% versus 17.2%), low-density NCP (7% versus 4%), and total plaque burden (37% versus 19.3%, P<0.02). In multivariable analysis with 10-fold cross-validation, NCP burden was the most significant predictor of impaired MFR (odds ratio, 1.35; P=0.021 for all). For prediction of impaired MFR with 10-fold cross-validation, receiver operating characteristics area under the curve for the composite score was 0.83 (95% confidence interval, 0.79–0.91) greater than for quantitative stenosis (0.66, 95% confidence interval, 0.57–0.76, P=0.005). Conclusions—Compared with stenosis, arterial NCP burden and a composite score combining quantitative stenosis and plaque burden from CT angiography significantly improves identification of downstream regional vascular dysfunction.