[Show abstract][Hide abstract] ABSTRACT: Background:
Unstable plaque characteristics on coronary CT angiography (CTA), serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) concentrations are associated with cardiovascular events.
To investigate the association between coronary CTA defined quantifiable plaque characteristics, hs-cTnT and NT-proBNP.
81 consecutive stable chest pain patients with an intermediate-to-high risk were analyzed. Coronary CTA was performed using a 64-slice multidetector-row CT-scanner. Total coronary plaque volume, calcified volume, non-calcified volume, plaque burden, remodeling index (RI) and number of plaques were measured using dedicated software. A total plaque score ("Sum plaque score") incorporating total plaque volume, RI, plaque burden and number of plaques was defined. Hs-cTnT and NT-proBNP concentrations were measured in serum samples before coronary CTA.
Univariate regression analysis demonstrated significant associations of hs-cTnT and NT-proBNP with total plaque volume (r hs-cTnT = .256; r NT-proBNP = .270), calcified volume (r hs-cTnT = .344; r NT-proBNP = .344), RI (r hs-cTnT = .335; r NT-proBNP = .342) and number of plaques (r hs-cTnT = .355; r NT-proBNP = .301) (all P values ≤ .021). Non-calcified plaque volume showed no association with hs-cTnT and NT-proBNP (r hs-cTnT = .050; r NT-proBNP = .087; P value = .660 and P value = .442). The "Sum plaque score" showed the highest correlation compared to other plaque parameters (r hs-cTnT = .362; r NT-proBNP = .409; P value = .001 and P value ≤ .001).
Our data suggest that coronary plaque morphology parameters, derived by dedicated software, are associated with serum hs-cTnT and NT-proBNP concentrations.
Full-text · Article · Oct 2015 · Journal of cardiovascular computed tomography
[Show abstract][Hide abstract] ABSTRACT: Purpose
Epicardial adipose tissue (EAT) is emerging as a risk factor for coronary artery disease (CAD). The aim of this study was to determine the applicability and efficiency of automated EAT quantification.
Methods and Materials
EAT volume was assessed both manually and automatically in 157 coronary CTA patients. Manual assessment consisted of a short axis-based manual measurement while automated assessment on both contrast and non-contrast enhanced datasets was achieved through novel prototype software (syngo.via, Siemens Healthcare). Duration of both quantification methods was recorded and EAT volumes were compared using paired samples t-test. Correlation of volumes was determined using intraclass correlation coefficient; agreement was tested using Bland-Altman analysis. The association between EAT and CAD was estimated using logistic regression.
Automated quantification was significantly less time consuming than automated quantification (17±2 vs. 280±78 seconds, p<0.0001). Although manual EAT volume differed significantly from automated EAT volume (75±33 cm³ vs. 95±45 cm³, p<0.001), a good correlation between both assessments was found (r=0.76, p<0.001). For all methods, EAT volume was positively associated with the presence of CAD. Stronger predictive value for the severity of CAD was achieved through automated quantification on both contrast enhanced and non-contrast enhanced datasets.
Automated EAT quantification is a quick method to estimate EAT and may serve as a predictor for CAD presence and severity.
No preview · Article · May 2014 · Journal of Cardiovascular Computed Tomography
[Show abstract][Hide abstract] ABSTRACT: Objective:
Aberrant neutrophil activation occurs during the advanced stages of atherosclerosis. Once primed, neutrophils can undergo apoptosis or release neutrophil extracellular traps. This extracellular DNA exerts potent proinflammatory, prothrombotic, and cytotoxic properties. The goal of this study was to examine the relationships among extracellular DNA formation, coronary atherosclerosis, and the presence of a prothrombotic state.
Approach and results:
In a prospective, observational, cross-sectional cohort of 282 individuals with suspected coronary artery disease, we examined the severity, extent, and phenotype of coronary atherosclerosis using coronary computed tomographic angiography. Double-stranded DNA, nucleosomes, citrullinated histone H4, and myeloperoxidase-DNA complexes, considered in vivo markers of cell death and NETosis, respectively, were established. We further measured various plasma markers of coagulation activation and inflammation. Plasma double-stranded DNA, nucleosomes, and myeloperoxidase-DNA complexes were positively associated with thrombin generation and significantly elevated in patients with severe coronary atherosclerosis or extremely calcified coronary arteries. Multinomial regression analysis, adjusted for confounding factors, identified high plasma nucleosome levels as an independent risk factor of severe coronary stenosis (odds ratio, 2.14; 95% confidence interval, 1.26-3.63; P=0.005). Markers of neutrophil extracellular traps, such as myeloperoxidase-DNA complexes, predicted the number of atherosclerotic coronary vessels and the occurrence of major adverse cardiac events.
Our report provides evidence demonstrating that markers of cell death and neutrophil extracellular trap formation are independently associated with coronary artery disease, prothrombotic state, and occurrence of adverse cardiac events. These biomarkers could potentially aid in the prediction of cardiovascular risk in patients with chest discomfort.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: To investigate whether the use of a semi-automated plaque quantification algorithm (reporting volumetric and geometric plaque properties) provides additional prognostic value for the development of acute coronary syndrome (ACS) as compared with conventional reading from cardiac computed tomographic angiography (CCTA). BACKGROUND: CCTA enables the visualization of coronary plaque characteristics, of which some have been shown to predict ACS. METHODS: A total of 1,650 patients underwent 64-slice CCTA and were followed-up for ACS for a mean 26±10 months. In 25 patients who developed ACS and 101 random controls (selected from 993 patients with CAD, but without coronary event), coronary artery disease was evaluated using conventional reading (calcium score, luminal stenosis, morphology), and then independently quantified using semi-automated software (plaque volume, burden [plaque area/vessel area * 100%], area, non-calcified percentage, attenuation, remodeling). Clinical risk profile was calculated with Framingham risk score (FRS). RESULTS: There were no significant differences in conventional reading parameters between controls and patients who developed ACS. Semi-automated plaque quantification showed that compared to controls, ACS patients had higher total plaque volume (median 94 vs. 29 mm(3)) and total non-calcified volume (28 vs. 4 mm(3), p≤0.001 for both). In addition, per plaque maximal volume (median 56 vs. 24 mm(3)), non-calcified percentage (62 vs. 26%) and plaque burden (57 vs. 36%) in ACS patients were significantly higher (p<0.01 for all An receiver operating characteristic (ROC)-model predicting for ACS incorporating FRS and conventional CCTA-reading had an area under the curve (AUC) of 0.64, a second model also incorporating semi-automated plaque quantification had an AUC of 0.79, p<0.05. CONCLUSION: The semi-automated plaque quantification algorithm identified several parameters predictive for ACS and provided incremental prognostic value over clinical risk profile and conventional CT-reading. The application of this tool may improve risk stratification in patients undergoing CCTA.
Full-text · Article · Apr 2013 · Journal of the American College of Cardiology
[Show abstract][Hide abstract] ABSTRACT: This study sought to investigate the association between thrombin generation in plasma and the presence and severity of computed tomography angiographically defined coronary atherosclerosis in patients with suspected coronary artery disease (CAD).
Besides its pivotal role in thrombus formation, experimental data indicate that thrombin can induce an array of pro-atherogenic and plaque-destabilizing effects. Although thrombin plays a role in the pathophysiology of atherosclerosis progression and vascular calcification, the clinical evidence remains limited.
Using 64-slice coronary computed tomographic angiography, we assessed the presence and characteristics of CAD in patients (n = 295; median age 58 years) with stable chest pain. Coronary artery calcification was graded as absent (Agatston score 0), mild (Agatston score 1 to 100), moderate (Agatston score 101 to 400), and severe (Agatston score >400). Calibrated automated thrombography was used to assess endogenous thrombin potential in plasma in vitro. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation in vivo.
TATc plasma levels were substantially higher in patients with CAD versus patients without CAD (p = 0.004). Significant positive correlations were observed between steadily increasing TATc levels and the severity of CAD (r = 0.225, p < 0.001). In multinomial logistic regression models, after adjusting for established risk factors, TATc levels predicted the degree of coronary artery calcification: mild (odds ratio: 1.56, p = 0.006), moderate (odds ratio: 1.56, p = 0.007), and severe (odds ratio: 1.67, p = 0.002). Trends were comparable between the groups when stratified according to the degree of coronary luminal stenosis.
This study provides novel clinical evidence indicating a positive independent association between enhanced in vivo thrombin generation and the presence and severity of coronary atherosclerosis, which may suggest that thrombin plays a role in the pathophysiology of vascular calcification and atherosclerosis progression.
Full-text · Article · Dec 2012 · JACC. Cardiovascular imaging
[Show abstract][Hide abstract] ABSTRACT: Both end-stage and milder stages of chronic kidney disease (CKD) are associated with an increased risk of adverse cardiovascular events. Several studies found an association between decreasing renal function and increasing coronary artery calcification, but it remains unclear if this association is independent from traditional cardiovascular risk factors. Therefore, the aim of this study was to investigate whether mild to moderate CKD is independently associated with coronary plaque burden beyond traditional cardiovascular risk factors.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Idiopathic atrial fibrillation (AF) refers to a clinically lacking cardiovascular or pulmonary disease generating the pathophysiologic substrate for the arrhythmia. However, because idiopathic AF is associated with an increased event rate, it could be a harbinger of as-yet undetected underlying heart disease. OBJECTIVE: The purpose of this study was to determine the prevalence of coronary artery disease (CAD) in patients diagnosed with idiopathic paroxysmal AF. METHODS: Of the 3243 patients who underwent cardiac computed tomographic angiography (CTA) in our center between January 2008 and March 2011, we identified a total of 115 consecutive idiopathic paroxysmal AF patients who underwent CTA before electrophysiologic ablation. Patients were compared with 275 age-, sex-, and PROCAM risk score-matched healthy controls in permanent sinus rhythm. All patients were free of hypertension, diabetes, congestive heart failure, previous known coronary artery and peripheral vascular disease, previous stroke, thyroid, pulmonary, and renal disease, and structural abnormalities on echocardiography. RESULTS: Controls more often showed a family history of CAD (38% vs 15%, P <.001), had a higher prevalence of smoking (25% vs 14%, P = .021), higher fasting blood glucose levels (5.5 ± 0.7 mmol/L vs 5.4 ± 0.6 mmol/L, P = .025), and smaller atrial diameters (37 ± 4 mm vs 40 ± 5 mm, P <.001) compared to AF patients. Notwithstanding the above, idiopathic AF patients significantly more often suffered from subclinical CAD compared to controls (49% vs 34%, P = .008). Multivariable regression analysis revealed that beside (as expected) age and gender, a history of AF and left atrial diameter were significant predictors of underlying CAD. CONCLUSION: Half of patients originally diagnosed with idiopathic paroxysmal AF show concealed underlying CAD. The detection and treatment of CAD at an early stage could improve the prognosis of these patients.
Full-text · Article · Aug 2012 · Heart rhythm: the official journal of the Heart Rhythm Society
[Show abstract][Hide abstract] ABSTRACT: Recent studies have demonstrated the association between increased concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and the incidence of myocardial infarction, heart failure, and mortality. However, most prognostic studies to date focus on the value of hs-cTnT in the elderly or general population. The value of hs-cTnT in symptomatic patients visiting the outpatient department remains unclear. The aim of this study was to investigate the prognostic value of hs-cTnT as a biomarker in patients with symptoms of chest discomfort suspected for coronary artery disease and to assess its additional value in combination with other risk stratification tools in predicting cardiac events.
[Show abstract][Hide abstract] ABSTRACT: Epicardial adipose tissue (EAT) volume has been associated with coronary artery disease (CAD). As diabetes mellitus type 2 (DM2) patients have higher EAT volumes, it has been suggested that EAT may play a role in promoting CAD in these patients. The aim of this study was to examine the association between EAT and CAD in DM2, impaired fasting glucose (IFG) and control patients presenting with stable chest pain.
A total of 410 stable chest pain patients underwent multidetector cardiac computed tomography angiography (CCTA) to assess the presence of CAD. The extent of CAD was expressed as the number of affected segments. The EAT volume was measured using three-dimensional volumetric quantification. The EAT was compared using ANOVA, logistic and linear regression models were used to assess its predictive value. Multivariable regression analysis corrected for traditional risk factors was performed. Eighty-three patients had DM2, 118 IFG and there were 209 controls. DM2 as well as IFG patients had higher EAT volumes compared with controls (98 ± 41, 92 ± 39, and 75 ± 34 cm(3), respectively; P < 0.001). EAT predicted the presence (OR: 1.01; P < 0.001) and the extent of CAD (B: 0.01; P < 0.001). The associations were equal in all subgroups. However, in a multivariable regression model corrected for traditional cardiovascular risk factors, EAT was not an independent predictor for the presence or extent of CAD (OR: 1.00; P = 0.88 and B: -0.11; P = 0.68, respectively).
The EAT volume is associated with CAD in DM2, IFG, and control patients. However, EAT is not an independent predictor for CAD in patients presenting with stable chest pain.
Full-text · Article · Feb 2012 · European Heart Journal Cardiovascular Imaging
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The usual diagnostic work-up of chest pain patients includes clinical risk profiling and exercise-ECG, possibly followed by additional tests. Recently cardiac computed tomographic angiography (CCTA) has been employed. We evaluated the prognostic value of the combined use of exercise-ECG and CCTA for the development of cardiovascular endpoints. METHODS: In 283 patients (143 male, mean age 54±10years) with intermediate pre-test probability for coronary artery disease presenting with stable chest pain, exercise-ECG, CCTA and calcium score were performed. Patients were followed-up for combined endpoint of acute coronary syndrome (ACS) and revascularization. RESULTS: After a median follow-up of 769days (interquartile range 644-1007), 6 ACS and 9 revascularizations were recorded. A positive exercise-ECG predicted for the combined endpoint, [hazard ratio (HR) 5.14 (95% confidence interval (CI) 1.64-16.13), p=0.005], as well as a positive calcium score [HR 4.59 (95% CI 1.30-16.28), p=0.02] and a ≥50% stenosis on CCTA [HR 45.82 (95% CI 6.02-348.54), p<0.001]. ROC-analysis showed an area under the curve (AUC) of 0.79 (95% CI 0.67-0.90) for exercise-ECG, which increased significantly when CCTA was added: 0.91 (95% CI; 0.86-0.97; p=0.006). Multivariable Cox regression showed exercise-ECG predicted independently [HR 3.6, (95% CI 1.1-11.2), p=0.03], as well as CCTA [HR 31.4 (95% CI 4.0-246.6), p=0.001], but not calcium score [HR 0.6 (95% CI 0.2-2.3), p=0.5]. CONCLUSIONS: The combined subsequent use of exercise-ECG for functional information and CCTA for anatomical information provides a high diagnostic yield in stable chest pain patients with an intermediate pre-test probability for coronary artery disease.
No preview · Article · Jan 2012 · International journal of cardiology
[Show abstract][Hide abstract] ABSTRACT: Objective Validation of methods to assess the area at risk (AAR) in patients with ST elevation myocardial infarction is limited. A study was undertaken to test different AAR methods using established physiological concepts to provide a reference standard.
Main outcome measured In 78 reperfused patients with first ST elevation myocardial infarction, AAR was measured by electrocardiographic (Aldrich), angiographic (Bypass Angioplasty Revascularization Investigation (BARI), APPROACH) and cardiovascular magnetic resonance methods (T2-weighted hyperintensity and delayed enhanced endocardial surface area (ESA)). The following established physiological concepts were used to evaluate the AAR methods: (1) AAR size is always ≥ infarct size (IS); (2) in transmural infarcts AAR size=IS; (3) correlation between AAR size and IS increases as infarct transmurality increases; and (4) myocardial salvage ((AAR-IS)/AAR×100) is inversely related to infarct transmurality.
Results Overall, 65%, 87%, 76%, 87% and 97% of patients using the Aldrich, BARI, APPROACH, T2-weighted hyperintensity and ESA methods obeyed the concept that AAR size is ≥IS. In patients with transmural infarcts (n=22), Bland–Altman analysis showed poor agreement (wide 95% limits of agreement) between AAR size and IS for the BARI, Aldrich and APPROACH methods (95% CI −22.9 to 29.6, 95% CI −28.3 to 21.3 and 95% CI −16.9 to 20.0, respectively) and better agreement for T2-weighted hyperintensity and ESA (95% CI −6.9 to 16.6 and 95% CI −4.3 to 18.0, respectively). Increasing correlation between AAR size and IS with increasing infarct transmurality was observed for the APPROACH, T2-weighted hyperintensity and ESA methods, with ESA having the highest correlation (r=0.93, p<0.001). The percentage of patients within a narrow margin (±30%) of the inverse line of identity between salvage extent and infarct transmurality was 56%, 76%, 65%, 77% and 92% for the Aldrich, BARI, APPROACH, T2-weighted hyperintensity and ESA methods, respectively, where higher percentages represent better concordance with the concept that the extent of salvage should be inversely related to infarct transmurality.
Conclusions For measuring AAR, cardiovascular magnetic resonance methods are better than angiographic methods, which are better than electrocardiographic methods. Overall, ESA performed best for measuring AAR in vivo.
[Show abstract][Hide abstract] ABSTRACT: Cardiologists are often confronted with patients presenting with chest pain, in whom clinical risk profiling is required. We studied four frequently used risk scores in their ability to predict for coronary artery disease (CAD) and major adverse cardiovascular events in patients presenting with stable chest pain at the cardiology outpatient clinic.
We enrolled 1,296 stable chest pain patients, who underwent cardiac computed tomographic angiography (CCTA) to assess CAD (any, significant: stenosis ≥50%). Framingham (FRS), PROCAM, SCORE risk score, and Diamond Forrester pre-test probability were calculated. All patients were followed up for a mean 19 ± 9 months for all cardiovascular events (mortality, acute coronary syndrome, revascularization >90 days after CCTA). In ROC-analysis for prediction of significant CAD, the areas under the curve for FRS; 0.68 (95% confidence interval: 0.64-0.72) and for SCORE; 0.69 (95% confidence interval: 0.65-0.72) were significantly higher than for PROCAM; 0.64 (95% confidence interval: 0.61-0.68; P ≤ .001), as well as marginally higher than for Diamond Forrester; 0.65 (95% confidence interval: 0.61-0.68; P ≤ .05). Low FRS category showed the lowest number of patients with significant CAD, compared to patients with low risk using PROCAM, SCORE or Diamond Forrester (P < .001). Also, low FRS category showed less events (compared to PROCAM and SCORE; P < .001, for Diamond Forrester; P = .14).
Our data show that in a stable chest pain population, the ability of FRS and SCORE to predict for CAD was similar and better compared to PROCAM and Diamond Forrester. The number of low risk patients showing significant CAD or events was lower using FRS. Consequently, risk categorization using FRS seems to be safest to stratify stable chest pain patients prior to CCTA.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE
Patients with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM2) suffer from 2-4 fold higher cardiovascular mortality compared to normoglycaemic patients. We examined the hypothesis that in patients with IGT and DM2 increased amounts of epicardial adipose tissue are associated with more severe coronary artery disease (CAD).
METHOD AND MATERIALS
Coronary plaque burden was assessed in 174 patients referred for imaging of the coronary arteries to rule out CAD. EAT was estimated by measuring the amount of adipose tissue within the pericardium using ImageJ software. CAD was classified in each of 16 coronary artery segments as mild (diameter stenosis <50%; 1 point), moderate (50%-70% stenosis; 2 points), or severe (diameter stenosis >70%; 3 points). Total CAD burden per patient was expressed as the sum of all points divided by the number of assessable segments.
61 patients had normal glucose metabolism, 56 patients had IGT and 57 patients had DM2. Mean (±SD) fat volumes were 76.9±30.4 (normoglycaemia group), 85.4±29.3 (IGT group) and 94.3±33.6 (DM2 group) mL, respectively (p=0.018). Increased EAT was also independently and significantly associated with higher CAD burden (ANOVA; p=0.03), although there was no significant difference with regard to the presence of >50% coronary stenosis (p>0.05). 34% of patients with normoglycaemia, 25% of patients with IGT and 17.5% DM2 were free of CAD (p=0.03).
An increased amount of epicardial adipose tissue is a proxy measure for the presence of an increased coronary atheroma burden in patients with impaired glucose tolerance and type 2 diabetes compared to patients with normoglycaemia.
An increased amount of epicardial adipose tissue is a proxy measure for a higher coronary plaque burden in patients with impaired glucose tolerance and type 2 diabetes mellitus.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE
Patients with severely impaired renal function have a higher risk of coronary artery disease (CAD) and mortality, but little is known about CAD in patients with mild to moderately impaired renal function. We examined the hypothesis that prevalence of CAD in patients with moderately impaired renal function (CKD3; eGFR 30-60) will be increased compared to patients with mildly impaired renal function (CKD 2; eGFR 60-90), and patients with normal renal function (eGFR >90).
METHOD AND MATERIALS
We assessed coronary calcium scores (CCS) as well as coronary plaque burden in 1314 patients (mean age: 57 yrs; 719 males) referred for imaging of coronary arteries to rule out CAD. The coronary artery tree was analyzed for presence and severity of CAD, which was classified as wall irregularities, non-significant (<70%) or significant (≥70%) luminal narrowing. The relative risk of coronary atherosclerosis was assessed for four groups of patients based on their eGFR as determined by the MDRD equation, namely: 1) eGFR<45, 2) 45≤eGFR<60, 3) 60≤eGFR<90, and 4) eGFR≥90.
There were 27, 144, 867 and 276 patients in groups 1-4, respectively. CCS and coronary plaque burden increased with decreasing renal function. The relative risks (95%CI) for CCS>0 were 1.81 (1.45–1.95), 1.40 (1.19–1.61) and 1.13 (0.99–1.29) for patients in groups 1-3, respectively, compared to patients in group 4 (p<0.001 for groups 1-2 versus group 4). Decreasing renal function was also associated with an increased risk for the presence of significant coronary plaques. The relative risks for significant plaque were 3.16 (1.82–4.94), 1.91 (1.27–2.85) and 1.20 (0.86–1.68) for patients in groups 1-3, respectively, compared to patients in group 4 (p<0.001 for groups 1 and 2 versus group 4).
The relative risk of CAD as manifested by elevated CCS or presence of significant coronary plaques is significantly higher in patients with moderately impaired renal function (30≤eGFR<60), compared to patients with normal or mildly impaired renal function (eGFR≥60). These data support the suggestion that impaired renal function plays a role in the pathogenesis of coronary artery disease.
Moderately impaired renal function is associated with an increased coronary plaque burden. This finding supports the suggestion that impaired renal function plays a role in the pathogenesis of CAD.