Feasibility of Simple Evaluation of Coronary Artery Calcium Using a Number of Chest Computed Tomography Slices: A Multicenter Study.

Objective: We aimed to evaluate the visual measurements of coronary artery calcium (CAC) on nonelectrocardiogram (ECG)-gated chest computed tomography (CT) using a simple scoring method that involves counting the number of CT slices containing CAC. Materials and Methods: We analyzed 163 participants who underwent both coronary and chest CT examinations at six centers within 3 months. Agatston scores were calculated on standard ECG-gated scans and classified as none (0), mild (1-99), moderate (100-400), or severe (>400). Next, chest CT images were reconstructed to standard 5.0 mm axial slices. Then, CAC on chest CT scans was measured using two methods: the Weston score (sum of the assigned score of each vessel, range: 0-12) and number of slices showing CAC (Ca-slice#). Results: When the Weston score and Ca-slice# were divided into four levels according to the optimal divisional levels corresponding to the Agatston score classes, good agreements with the 4-grade Agatston score were observed (kappa value=0.610 and 0.794, respectively). The sensitivity and specificity of Ca-slice# ≥9 to identify severe Agatston scores of >400 were 86% and 96%, respectively. Conclusion: The Ca-slice#, a simple scoring method using chest CT scans, was in good agreement with the ECG-gated Agatston score.

A mid-ventricular variant of Takotsubo syndrome: was it triggered by insular cortex damage?

Takotsubo syndrome (TTS) is a transient cardiomyopathy that is often associated with cerebrovascular diseases. Earlier studies have supported the concept that the cardiovascular system is regulated by a central autonomic network (CAN) consisting of the insular cortex (IC), anterior cingulate gyrus and amygdala. We report the case of a 79-year-old female diagnosed with a mid-ventricular variant of TTS concomitant with right IC ischaemic stroke. After 12 h of hospitalization, she experienced a sudden collapse. Rapid cardiopulmonary resuscitation resulted in a return of spontaneous circulation. Subsequent left ventriculography revealed akinesis in the mid-portion of the left ventricle with vigorous contraction of the basal and apex segment. Two weeks after admission, cardiac ultrasound showed improved left ventricular contraction. Right IC ischaemia in this patient might have been associated with a dysregulation of the CAN and subsequent increased sympathetic nervous system activity that triggered TTS.

Early drop in systolic blood pressure, heart rate at admission, and their effects on worsening renal function in elderly patients with acute heart failure.

BACKGROUND: Regardless of patients' baseline renal function, worsening renal function (WRF) during hospitalization is associated with poor outcomes. In individuals with acute heart failure (AHF), one predictor of WRF is an early drop in systolic blood pressure (SBP). Few studies have investigated WRF in elderly AHF patients or the influence of these patients' heart rate (HR) at admission on the relationship between an early SBP drop SBP and the AHF. METHODS: We measured the SBP and HR of 245 elderly AHF inpatients (83 ± 6.0 years old, females 51%) at admission and another six times over the next 48 h. We defined 'WRF' as a serum creatinine increase ≥0.3 mg/dL by Day 5 post-admission. We calculated the 'early SBP drop' as the difference between the admission SBP value and the lowest value during the first 48 h of hospitalization. RESULTS: There were significant differences between the 36 patients with WRF and the 209 patients without WRF: early SBP drop (51 vs. 33 mmHg, p < 0.01) and HR at admission (79 vs. 90 bpm, p < 0.05), respectively. In the multiple logistic regression analysis adjusted for the confounders, higher early SBP drop (p < 0.04) and lower HR at admission (p < 0.01) were significantly associated with WRF. No significant association was shown for the interaction term of early SBP drop × HR at admission with WRF. CONCLUSIONS: In these elderly AHF patients, exaggerated early SBP drop and lower HR at admission were significant independent predictors of WRF, and these factors were additively associated with WRF.

Visit-to-visit Blood Pressure Variability and Arterial Stiffness: Which Came First: The Chicken or the Egg?

Earlier studies have shown that visit-to-visit blood pressure (BP) variability (VVV) served as a significant independent risk factor of stroke, specifically, in the high-risk elderly of cardiovascular disease (CVD). Although the mechanism is not clearly understood, arterial remodeling such as carotid artery, coronary artery and large aortic artery would be a strong moderator in the relationship between VVV and CVD incidence. Recent studies have provided evidence that VVV predicted the progression of arterial stiffness. While the class of antihypertensive agents is suggested to be an important determinant of VVV, long-acting calcium channel blockers use (CCBs) is associated with the reduction of VVV, and thus, is suggested to decrease the arterial stiffness. Specifically, the relationship between VVV and coronary arterial remodeling has never been reviewed until now. This article summarizes the recent literature on these topics. In the elderly hypertensives, strict BP control using CCBs could play a pivotal role in suppressing arterial stiffening via VVV reduction.

Impact of the Coronary Artery Calcium Score on Mid- to Long-Term Cardiovascular Mortality and Morbidity Measured With Coronary Computed Tomography Angiography.

BACKGROUND: Although the coronary artery calcium score (CACS) is a prognostic measurement in asymptomatic individuals, it is measured in symptomatic patients using coronary computed tomography angiography (CCTA). We aimed to examine the predictive value of the CACS for mid- to long-term cardiovascular mortality and morbidity in patients who underwent CCTA. Methods and Results: We studied 736 patients with suspected coronary artery disease (CAD) who underwent CCTA. During a median follow-up period of 6.5 years, there were 39 primary outcomes (composite of cardiovascular disease death, non-fatal myocardial infarction, and non-fatal stroke). The estimated 10-year cumulative rates of the primary outcome were significantly increased across CACS classes (3.9%, 9.2%, 11.8%, and 18.2% in CACS of 0, 1-99, 100-399, and ≥400, respectively, P<0.001). These rates of cardiovascular disease death and stroke were also significantly increased across CACS classes. Multivariate Cox proportional hazard analysis showed that a CACS ≥100 was independently predictive for the primary outcome (hazard ratio [HR] 2.82, 95% confidence interval [CI] 1.40-6.00, P=0.003), as well as the presence of ≥50% stenosis on CCTA (HR 2.27, 95% CI 1.13-4.46, P=0.022). CONCLUSIONS: An elevated CACS with the use of CCTA is an independent predictor of mid- to long-term cardiovascular mortality and morbidity in patients suspected of having CAD.

Coronary plaque characteristics in computed tomography and 2-year outcomes: The PREDICT study.

BACKGROUND: Coronary computed tomography angiography (CCTA) not only provides information regarding luminal stenoses but also allows for visualization of mural atheromatous changes (coronary plaques). OBJECTIVE: We sought to elucidate whether plaques seen on CCTA enable prediction of 2-year outcomes in patients with suspected and known coronary artery disease (CAD). METHODS: Of 3015 patients who underwent CCTA, the images and 2-year clinical courses of 2802 patients were independently analyzed. The primary endpoint was the composite of all-cause death and acute coronary syndrome. RESULTS: During the 2-year observation period, 49 (1.7%) patients developed the primary outcome. The 2-year rates of the primary outcome in the normal (n = 515, no mural lesions), calcium (n = 654, calcified lesion alone), and plaque groups (n = 1633, presence of noncalcified or partially calcified plaques) were 0.2%, 2.0%, and 2.1%, respectively (P = 0.0028). Adverse plaque features such as low attenuation, positive remodeling, spotty calcification, and the napkin-ring sign (low-attenuation core with a higher-attenuation rim) were assessed by an independent core laboratory. Stepwise multivariate Cox proportional hazard analysis showed that a plaque with two or more characteristics (adjusted hazard ratio, 1.98; 95% confidence interval, 1.09-3.60; P = 0.0254), age of ≥67 years (mean), statin treatment after CCTA, and obstructive stenosis remained independent predictors of the primary outcome. CONCLUSIONS: Plaque imaging in CCTA has predictive value for the 2-year outcome and is a useful identifier for high-risk patients among those with known and suspected CAD.

Insulin resistance and subclinical abnormalities of global and regional left ventricular function in patients with aortic valve sclerosis.

BACKGROUND: Insulin resistance, as a key mediator of metabolic syndrome, is thought to be associated with pathogenesis of calcific aortic valve disease and altered left ventricular (LV) function and structure. However, in patients with aortic valve sclerosis (AVS), the association between insulin resistance and subclinical impairment of LV function is not fully elucidated. METHODS: We studied 57 patients (mean age 70 ± 8 years, 22 women) with asymptomatic AVS but normal LV ejection fraction in echocardiography. LV longitudinal and circumferential strain and strain rate was analyzed using two-dimensional speckle tracking echocardiography. Patients with uncontrolled hypertension and diabetes mellitus, chronic kidney disease, and concomitant coronary artery disease were excluded. They were divided into the insulin-resistant group (AVS+IR; N = 28) and no insulin-resistant group (AVS-IR; N = 29) according to the median value of homeostatic model assessment index. Computed tomography scans were also performed to measure the aortic valve calcium score and the visceral adipose tissue (VAT) area. In addition, age- and sex- adjusted 28 control subjects were recruited for the comparison. RESULTS: There were no significant differences in LV ejection fraction or mass index among the groups. The AVS+IR group had a higher aortic valve calcium score (median 94 versus 21, P = 0.022) and a larger VAT area (113 ± 42 cm2 versus 77 ± 38 cm2, P = 0.001) than the AVS-IR group. Notably, LV global longitudinal strain, strain rate (SR), and early diastolic SR were significantly lower in the AVS+IR group than in the AVS-IR group and in control subjects (strain: -16.2 ± 1.6% versus -17.2 ± 1.2% and -18.9 ± 0.8%; SR: -1.18 ± 0.26 s(-1) versus -1.32 ± 0.21 s(-1) and -1.52 ± 0.08 s(-1); early diastolic SR: -1.09 ± 0.23 s(-1) versus -1.23 ± 0.18 s(-1) and -1.35 ± 0.12 s(-1); P < 0.05 for all comparison), whereas circumferential function were not significantly different. Multiple linear regression analyses revealed insulin resistance as an independent determinant of LV longitudinal strain (P = 0.017), SR (P = 0.047), and early diastolic SR (P = 0.049) regardless of LV mass index or VAT area. CONCLUSIONS: Insulin resistance is a powerful independent predictor of subclinical LV dysfunction regardless of concomitant visceral obesity and LV hypertrophy. Thus, it may be a novel therapeutic target to prevent subsequent heart failure in patients with AVS.

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.

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.

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.

Association between heart calcification assessed by echocardiography and future cardiovascular disease mortality and morbidity.

BACKGROUND: Echocardiography can detect calcium deposits in heart valves and aortic root, but the relationship of echocardiographic heart calcification such as aortic valve calcification (AVC), mitral annular calcification (MAC), and aortic root calcification (ARC) with future cardiovascular disease (CVD) mortality and morbidity is not fully elucidated. METHODS: We analyzed data from 943 patients with suspected coronary heart disease (mean age, 65.7 years; 36% female). Echocardiographic total heart calcification (THC) score was determined by summing up the AVC, MAC, and ARC variables; THC-0 (N = 397), THC-1 (N = 236), THC-2 (N = 224), and THC-3 (N = 86). Subjects were followed for mean 2.9 years to assess the risk of death from CVD causes. Cardiovascular morbidity was defined as new episodes of non-fatal myocardial infarction, congestive heart failure, stroke, and surgical treatment of vascular disease. RESULTS: There were 43 CVD deaths and a total of 160 CVD events. Kaplan-Meier curves showed a graded CVD mortality and morbidity across increasing THC score values. With full adjustment, Cox regression hazard ratios (95% confidence intervals) for CVD mortality and morbidity, using no calcification as reference, for THC-1, THC-2, and THC-3 were 2.21 (1.31-3.74), 2.59 (1.53-4.39) and 4.14 (2.30-7.47), respectively. When THC score was added to models with CVD risk factors, C-statistics were significantly larger for CVD mortality (p = 0.048) and for CVD mortality and morbidity (p = 0.004). CONCLUSIONS: THC score, the sum of the amounts of AVC, MAC, and ARC present as estimated by echocardiography, has an independent and incremental prognostic value in a high-risk population.

Association between aortic valve calcification and myocardial ischemia, especially in asymptomatic patients.

UNLABELLED: 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 (201)Tl 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.

Association between plasma high-molecular-weight adiponectin and coronary plaque characteristics assessed by computed tomography angiography in conditions of visceral adipose accumulation.

BACKGROUND: Our group has previously reported that visceral adipose tissue (VAT) accumulation was associated with the extent and vulnerable characteristics of coronary plaques using coronary computed tomography angiography (CTA). An investigation of the associations between these coronary lesions with plasma adiponectin and leptin was performed. METHODS AND RESULTS: A total of 394 patients (220 men and 174 women) in the study were referred for CTA. Plain abdominal scanning was simultaneously performed to evaluate VAT areas. The median level of plasma high-molecular-weight (HMW) adiponectin in patients with CTA-based obstructive coronary artery disease was significantly lower than that in patients without (men: 1.45 vs. 1.88 µg/ml, P=0.002; women: 2.49 vs. 3.44 µg/ml, P<0.001). Multivariate analyses revealed that a lower HMW adiponectin concentration was significantly associated with the presence (men: P=0.019; women: P=0.018) and involved segment numbers (men: P=0.001; women: P=0.003) of coronary plaques. Furthermore, it was significantly related to coronary plaque with all 3 vulnerable characteristics of positive remodeling, low CT density (≤38 Hounsfield units), and adjacent spotty calcium (men: P=0.019; women: P=0.016). These associations were also observed with VAT areas, but not with plasma leptin concentrations, in both genders. CONCLUSIONS: Lower plasma HMW adiponectin is associated with the presence, extent, and vulnerable characteristics of coronary plaques assessed by CTA in both genders.

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.

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.