Contrast-enhanced Coronary Computed Tomography Angiography Research Articles

Development and first implementation of a novel multi-modality cardiac motion and dosimetry phantom for radiotherapy applications.

Cardiac applications in radiation therapy are rapidly expanding including magnetic resonance guided radiation therapy (MRgRT) for real-time gating for targeting and avoidance near the heart or treating ventricular tachycardia (VT). This work describes the development and implementation of a novel multi-modality and magnetic resonance (MR)-compatible cardiac phantom. The patient-informed 3D model was derived from manual contouring of a contrast-enhanced Coronary Computed Tomography Angiography scan, exported as a Stereolithography model, then post-processed to simulate female heart with an average volume. The model was 3D-printed using Elastic50A to provide MR contrast to water background. Two rigid acrylic modules containing cardiac structures were designed and assembled, retrofitting to an MR-safe programmable motor to supply cardiac and respiratory motion in superior-inferior directions. One module contained a cavity for an ion chamber (IC), and the other was equipped with multiple interchangeable cavities for plastic scintillation detectors (PSDs). Images were acquired on a 0.35 T MR-linac for validation of phantom geometry, motion, and simulated online treatment planning and delivery. Three motion profiles were prescribed: patient-derived cardiac (sine waveform, 4.3mm peak-to-peak, 60 beats/min), respiratory (cos4 waveform, 30mm peak-to-peak, 12 breaths/min), and a superposition of cardiac (sine waveform, 4mm peak-to-peak, 70 beats/min) and respiratory (cos4 waveform, 24mm peak-to-peak, 12 breaths/min). The amplitude of the motion profiles was evaluated from sagittal cine images at eight frames/s with a resolution of 2.4mm × 2.4mm. Gated dosimetry experiments were performed using the two module configurations for calculating dose relative to stationary. A CT-based VT treatment plan was delivered twice under cone-beam CT guidance and cumulative stationary doses to multi-point PSDs were evaluated. No artifacts were observed on any images acquired during phantom operation. Phantom excursions measured 49.3±25.8%/66.9±14.0%, 97.0±2.2%/96.4±1.7%, and 90.4±4.8%/89.3±3.5% of prescription for cardiac, respiratory, and cardio-respiratory motion profiles for the 2-chamber (PSD) and 12-substructure (IC) phantom modules respectively. In the gated experiments, the cumulative dose was<2% from expected using the IC module. Real-time dose measured for the PSDs at 10Hz acquisition rate demonstrated the ability to detect the dosimetric consequences of cardiac, respiratory, and cardio-respiratory motion when sampling of different locations during a single delivery, and the stability of our phantom dosimetric results over repeated cycles for the high dose and high gradient regions. For the VT delivery, high dose PSD was<1% from expected (5-6 cGy deviation of 5.9Gy/fraction) and high gradient/low dose regions had deviations<3.6% (6.3 cGy less than expected 1.73Gy/fraction). A novel multi-modality modular heart phantom was designed, constructed, and used for gated radiotherapy experiments on a 0.35 T MR-linac. Our phantom was capable of mimicking cardiac, cardio-respiratory, and respiratory motion while performing dosimetric evaluations of gated procedures using IC and PSD configurations. Time-resolved PSDs with small sensitive volumes appear promising for low-amplitude/high-frequency motion and multi-point data acquisition for advanced dosimetric capabilities. Illustrating VT planning and delivery further expands our phantom to address the unmet needs of cardiac applications in radiotherapy.

Coronary Artery Calcium Scoring Using Virtual Versus True Noncontrast Images From Photon-Counting Coronary CT Angiography.

Background Coronary artery calcium scoring (CACS) for coronary artery disease requires true noncontrast (TNC) CT alongside contrast-enhanced coronary CT angiography (CCTA). Photon-counting CT provides an algorithm (PureCalcium) for reconstructing virtual noncontrast images from CCTA specifically for CACS. Purpose To assess CACS differences based on PureCalcium images derived from contrast-enhanced photon-counting CCTA compared with TNC images and evaluate the impact of these differences on the clinically relevant classification of patients into plaque burden groups. Materials and Methods Photon-counting CCTA images acquired between August 2022 and May 2023 were retrospectively identified. Agatston scores were derived from both TNC and PureCalcium images and tested for differences with use of the Wilcoxon signed-rank test. The agreement was assessed with use of equivalence tests, Bland-Altman analysis, and intraclass correlation coefficient. Plaque burden groups were established based on Agatston scores, and agreement was evaluated using weighted Cohen kappa. The dose-length product was analyzed. Results Among 170 patients (mean age, 63 years ± 13 [SD]; 92 male), 111 had Agatston scores higher than 0. Median Agatston scores did not differ between TNC and PureCalcium images (4.8 [IQR, 0-84.4; range, 0.0-2151.8] vs 2.7 [IQR, 0-90.7; range, 0.0-2377.1]; P = .99), with strong correlation (intraclass correlation coefficient, 0.98 [95% CI: 0.97, 0.99]). The equivalence test was inconclusive, with a 95% CI of 0.90, 1.19. Bland-Altman analysis showed wide repeatability limits, indicating low agreement between the two scores. With use of the PureCalcium algorithm, 125 of 170 patients (74%) were correctly classified into plaque burden groups (excellent agreement, κ = 0.88). Patients without plaque burden were misclassified at higher than normal rates (P < .001). TNC image acquisition contributed a mean of 19.7% ± 8.8 of the radiation dose of the entire examination. Conclusion PureCalcium images show potential to replace TNC images for measuring Agatston scores, thereby reducing radiation dose in CCTA. There was strong correlation in calcium scores between TNC and PureCalcium, but limited agreement. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Sakuma in this issue.

Insulin resistance is associated with high-risk coronary artery plaque composition in asymptomatic men between 65 and 75 years and no diabetes: A DANCAVAS cross-sectional sub-study

Background and aimsInsulin resistance (IR) and pre-diabetes are associated with an increased risk of cardiovascular disease (CVD). We aimed to investigate vulnerable plaque composition in relation to IR and pre-diabetes in asymptomatic non-diabetic men. MethodsAll participants underwent a contrast-enhanced coronary computed tomography angiography (CCTA) to evaluate coronary artery plaque burden and plaque composition (necrotic core, dense calcium, fibrotic and fibrous-fatty volume). Homeostasis model assessment of IR (HOMA-IR) was used, and participants were stratified into tertiles. Participants underwent a standard oral glucose tolerance test (OGTT) and were categorized into 2 groups (normal glucose tolerance (NGT) or pre-diabetes). A multivariable linear regression model was used to evaluate the association between vulnerable plaque composition and IR or glycemic group. ResultsFour-hundred-and-fifty non-diabetic men without known CAD were included. The mean age was 70 ± 3 years. Participants in the higher HOMA-IR tertile (H-IR) had higher median necrotic plaque volume compared to the lower HOMA-IR tertile (L-IR) (18.2 vs. 11.0 mm3, p = 0.02). H-IR tertile (β 0.37 [95% CI 0.10–0.65], p = 0.008), pack-years (β 0.07 [95% CI 0.007–0.14], p = 0.03) and total atheroma volume (TAV) (β 0.47 [95% CI 0.36–0.57], p < 0.001) remained associated with necrotic plaque volume in the multivariable linear regression model. ConclusionsIR was associated with necrotic plaque volume in asymptomatic men without diabetes. Thus, even in asymptomatic men without diabetes, IR seems to have an incremental effect on necrotic plaque volume and vulnerable plaque composition.

Abstract 12542: Prevalence and Characterization of Occult Coronary Atherosclerotic Disease Among Middle Aged Individuals Free of Clinical Cardiovascular Disease - Results From Miami Heart Study (MiHeart) at Baptist Health South Florida

Introduction: While prior population-based cohorts have extensively described burden of coronary artery calcification (CAC) among asymptomatic individuals, there is paucity of occult coronary atherosclerotic disease (CAD) assessment with coronary computed tomography angiography (CCTA) in the general population. The aims were to determine prevalence, burden and coronary plaque characteristics in the ongoing prospective Miami Heart Study (MiHeart) using both CAC and CCTA. Methods: MiHeart enrolled 2,549 middle-aged 40-65 years free of clinical cardiovascular disease participants (49% females, mean age 53, 47% Hispanic/Latino) from general population of Greater Miami Area (Florida, USA). Final study consisted of 2491 (98%) among whom non- cardiac-gated CT for CAC testing and contrast-enhanced CCTA cardiac-gated were performed. Results: In this study 58% had CAC=0, 13% had CAC≥100, and 45% had detectable plaque on CCTA. 143 (6%) participants had significant (≥50%) stenosis and 44 (2%) had severe (≥70%) stenosis. Overall, 26% participants had exclusive non-calcified plaque whereas 7% demonstrated high-risk plaque features (HRP) with positive remodeling being most frequently observed (5%). Among participants with CAC=0, 15% had any plaque on CCTA (62% in 1 segment); 1% had obstructive CAD and 2% any HRP, respectively. Burden of CAD (plaque segmental score, subtype, stenosis) as well as HRP on CCTA was strongly associated with increasing CAC scores (table). Overall, 31% and 20% with CAC≥100 had significant stenosis and HRP, respectively. Conclusions: In the first US general population based CCTA study, we demonstrate high burden of diverse coronary atherosclerotic plaque features in a middle-aged general population free of established CVD. Future studies in MiHeart will focus on biological associations and clinical implications of of coronary atherosclerotic disease severity and features on CCTA among asymptomatic individuals.

Increased prevalence of premature coronary atherosclerosis after preeclampsia

Abstract Background Women with preeclampsia have increased risk of manifest coronary artery disease later in life. However, it remains unknown if and when premature coronary atherosclerotic stages can be identified. This knowledge could enable early intervention in women considered at high risk for future manifest coronary artery disease. Purpose Using cardiac computed tomography, we aimed to investigate the prevalence of premature coronary atherosclerosis in women with previous preeclampsia in comparison with women from the general population. Methods Women, aged 40–55 years, with previous preeclampsia were recruited in the CPH-PRECIOUS study and compared 1:1 with age- and parity-matched women from the CGPS. Both groups underwent a cardiac computed tomography, including a contrast-enhanced coronary computed tomography angiography and a non-contrast coronary artery calcium scoring, as well as an overall assessment of cardiovascular risk factors imbedded in an extensive questionnaire. Cardiac computed tomography examinations were analysed blindly. The main outcome of the study was the prevalence of any coronary atherosclerosis defined as any plaque at coronary computed tomography angiography or a calcium score &amp;gt;0 in case of a non-diagnostic coronary computed tomography angiography. Results A total of 1,424 women were included (715 women with previous preeclampsia and 709 controls from the general population). Women with previous preeclampsia were more likely to have cardiovascular risk factors (hypertension, dyslipidaemia, diabetes mellitus). The prevalence of any coronary atherosclerosis was significantly higher in the preeclampsia group (27.4% vs. 20.0%) (P=0.001). A calcium score &amp;gt;0 was also more prevalent in the preeclampsia group (16.6% vs. 11.8%) (P=0.009). Preeclampsia remained an independent risk factor for the presence of any coronary atherosclerosis after adjusting for cardiovascular risk factors (age, hypertension, dyslipidaemia, diabetes, smoking, body mass index, parity) (OR=1.37, 95% CI (1.05–1.79), P=0.021). Conclusion Women with previous preeclampsia are more likely show premature signs of coronary atherosclerosis compared with an age- and parity matched control group from the general population. Preeclampsia is an independent risk factor for premature coronary atherosclerosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationSkibsreder Per Henriksen, R og Hustrus FondKong Christian den Tiendes FondBrødrene Hartmanns FondHans og Nora Buchards FondArvid Nilssons FondAnita og Tage Therkelsens FondLægefondenAase og Ejnar Danielsens FondHjertecentrets Forskningsudvalg (Rigshospitalet)Direktør Kurt Bønnelycke og Hustru Fru Grethe Bønnelyckes FondLægeforeningens ForskningsfondTorben &amp; Alice Frimodt FondHenry og Astrid Møllers Fond

A new approach to cardiac fat volume assessment and the correlation with coronary artery calcification.

Coronary artery disease (CAD) is the foremost cause of death in the most developed societies. Plaque formation in epicardial coronary arteries and ensuing inflammation are a known pathophysiologic factor of CAD. We aimed to separately and simultaneously evaluate the correlation between pericardial fat pad volume and overall peri-coronary epicardial adipose tissue (EAT) thickness with coronary calcium score (CCS) to improve risk stratification of CAD. We retrospectively reviewed patients who underwent a non-invasive contrast-enhanced coronary multidetector CT (MDCT) angiography. Peri-coronary EAT thickness, pericardial fat pad volume and CCS were obtained by an expert radiologist from the patients coronary multidetector CT (MDCT) angiography. We included 141 symptomatic patients (86 men, 55 women) with an average age of 53.53 ± 12.92. An increment of overall peri-coronary EAT thickness (1/3 × (left anterior descending artery (LAD) + left circumflex artery (LCx) + right coronary artery (RCA)) was associated with a 49% increase in the odds for the presence of coronary artery calcification (CAC) (P = 0.004). Significant predictability of peri-coronary EAT-average was seen in diagnosing calcified plaque. Pericardial fat pad volume was positively correlated with overall peri-coronary EAT thickness in age and body mass index (BMI)-adjusted linear regression models, (P < 0.001). Our results amplify previous idea that peri-coronary EAT and pericardial fat pad volume might act as useful markers and better indicators of CCS based on Agatston score in comparison with BMI or body weight in order to reveal subsequent CADs.

Comparison of professional medical society guidelines for appropriate use of coronary computed tomography angiography

BackgroundMultiple appropriate use criteria (AUC) exist for the evaluation of coronary artery disease (CAD), but there is little data on the agreement between AUC from different professional medical societies. The aim of this study is to compare the appropriateness of coronary computed tomography angiography (CCTA) exams assessed using multimodality AUC from the American College of Cardiology Foundation (ACCF) versus the American College of Radiology (ACR). MethodsIn a single-center prospective cohort study from June 2014 to 2016, 1005 consecutive subjects referred for evaluation of known or suspected CAD received a contrast-enhanced CCTA. The primary outcome was the agreement of appropriateness ratings using ACCF and ACR guidelines, measured by the kappa statistic. A secondary outcome was the rate of obstructive CAD by appropriateness rating. ResultsAmong 1005 subjects, the median (5–95th percentile) age was 59 (37–76) years with 59.0% male. The ACCF criteria classified 39.6% (n = 398) appropriate, 24.2% (n = 243) maybe appropriate, and 36.2% (n = 364) rarely appropriate. The ACR guidelines classified 72.3% (n = 727) appropriate, 2.6% (n = 26) maybe appropriate, and 25.1% (n = 252) rarely appropriate. ACCF and ACR appropriateness ratings were in agreement for 55.0% (n = 553). Overall, there was poor agreement (kappa 0.27 [95% confidence interval 0.23–0.31]). By both AUC methods, a low rate of obstructive CAD was observed in the rarely appropriate exams (ACCF 7.1% [n = 26 of 364] and ACR 13.5% [n = 34 of 252]). ConclusionsCompared to ACCF criteria, the ACR guidelines of appropriateness were broader and classified significantly more CCTA exams as appropriate. The poor agreement between appropriateness ratings from the ACCF and ACR AUC guidelines evokes implications for reimbursement and future test utilization.

Circulating levels of cardiac troponin T are associated with coronary noncalcified plaque burden in HIV-infected adults: a pilot study.

HIV infection and/or antiretroviral therapy may increase the risk of subclinical coronary atherosclerosis. However, patients with chronic kidney disease (CKD) and those without IV access cannot undergo contrast-enhanced coronary CT angiography (CCTA). This study was to explore the relationship between cardiac troponin T (cTnT) levels and the extent of coronary plaque burden, as assessed by CCTA in those with HIV infection. Between June and September 2017, 58 HIV-infected participants were recruited and underwent contrast-enhanced CCTA. cTnT was measured with the Elecsys Troponin T Gen 5 STAT assay, and noncalcified plaque burden was quantified using coronary plaque analysis. Robust regression model was employed to perform primary statistical analysis. Univariate robust regression analysis indicated that male gender, cardiovascular risk score defined by the 2013 ACC/AHA cardiovascular risk score algorithm, and cTnT levels were significantly associated with noncalcified plaque volume index (NCPI). Final robust regression analyses showed that only cTnT (log scale) was independently associated with the NCPI (regression coefficient: 0.0453 with 95% CI: 0.0151, 0.0755, p = 0.003). These results of this study suggest that cTnT may be a promising marker for coronary plaque burden, especially in patients with HIV-associated CKD or without IV access.

Automatic aortic valve landmark localization in coronary CT angiography using colonial walk.

The minimally invasive transcatheter aortic valve implantation (TAVI) is the most prevalent method to treat aortic valve stenosis. For pre-operative surgical planning, contrast-enhanced coronary CT angiography (CCTA) is used as the imaging technique to acquire 3-D measurements of the valve. Accurate localization of the eight aortic valve landmarks in CT images plays a vital role in the TAVI workflow because a small error risks blocking the coronary circulation. In order to examine the valve and mark the landmarks, physicians prefer a view parallel to the hinge plane, instead of using the conventional axial, coronal or sagittal view. However, customizing the view is a difficult and time-consuming task because of unclear aorta pose and different artifacts of CCTA. Therefore, automatic localization of landmarks can serve as a useful guide to the physicians customizing the viewpoint. In this paper, we present an automatic method to localize the aortic valve landmarks using colonial walk, a regression tree-based machine-learning algorithm. For efficient learning from the training set, we propose a two-phase optimized search space learning model in which a representative point inside the valvular area is first learned from the whole CT volume. All eight landmarks are then learned from a smaller area around that point. Experiment with preprocedural CCTA images of TAVI undergoing patients showed that our method is robust under high stenotic variation and notably efficient, as it requires only 12 milliseconds to localize all eight landmarks, as tested on a 3.60 GHz single-core CPU.

Sex differences in coronary plaque composition evaluated by coronary computed tomography angiography in newly diagnosed Type 2 diabetes: association with low-grade inflammation.

To determine differences in coronary plaque composition and inflammatory biomarkers between men and women with newly diagnosed Type 2 diabetes without known cardiovascular disease. A total of 88 people with newly diagnosed (<1 year) Type 2 diabetes underwent contrast-enhanced coronary computed tomography angiography. Advanced coronary plaque analysis was performed using semi-automated software. Plasma concentrations of inflammatory biomarkers were determined. There were no significant differences between men (n=60) and women (n=28) regarding age or cardiovascular risk factors (all P>0.05). The median (quartiles) serum levels of fibrinogen [10.9 (9.8-12.6) μmol/l vs 9.7 (8.8-10.9) μmol/l], fibrin d-dimer [0.3 (0.2-0.4) mg/l vs 0.27 (0.2-0.4) mg/l] and C-reactive protein [3.1 (1.1-5.2) mg/l vs (0.8-2.6) 1.6 mg/l] were significantly higher in women (all P<0.05). Overall, men more often had multi-vessel involvement [28 men (47%) vs 4 women (14%)], and higher total plaque burden [median (quartiles) 11.6 (2.3-36.0)% vs 2.0 (0.4-5.4)%; both P<0.05]. The median (quartiles) total plaque volume [269.9 (62.6-641.9) mm3 vs 61.1 (7.6-239.9) mm3 ] and absolute calcified plaque volume [33.5 (8.3-148.3) mm3 vs 4.7 (0.9-17.3) mm3 ] were higher in men (both P<0.05). Women had a lower relative proportion of the calcified plaque component [median (quartiles) 7.8 (4.7-15.4)% vs 23.7 (8.4-31.1)%] and a higher relative proportion (median [quartiles]) of the non-low-density non-calfied plaque component [77.6 (66.0-86.0)% vs 63.6 (54.0-72.9)%; both P<0.05]. In people with newly diagnosed Type 2 diabetes, women had lower absolute coronary plaque volumes but a more unfavourable plaque composition and enhanced systemic inflammation compared with men.

A 72-Year-Old Patient with Longstanding, Untreated Familial Hypercholesterolemia but no Coronary Artery Calcification: A Case Report

Familial hypercholesterolemia (FH) is a genetic disease associated with persistently elevated levels of low-density lipoprotein cholesterol (LDL-C), which ultimately leads to greatly increased rates of atherosclerosis and cardiovascular disease. Atherosclerosis progression can be clinically approximated through measurement of coronary artery calcification (CAC). CAC can be measured via electron beam computed tomography (EBCT), multi-slice computed tomography (MSCT), or contrast-enhanced CT coronary angiography (CTCA). Here, we present the case of a 72-year-old man with known FH and established hypercholesterolemia who has consistently tested negative for any significant CAC.

German cardiac CT registry: indications, procedural data and clinical consequences in 7061 patients undergoing cardiac computed tomography.

Cardiac computed tomography permits quantification of coronary calcification as well as detection of coronary artery stenoses after contrast enhancement. Moreover, cardiac CT offers high-resolution morphologic and functional imaging of cardiac structures which is valuable for various structural heart disease interventions and electrophysiology procedures. So far, only limited data exist regarding the spectrum of indications, image acquisition parameters as well as results and clinical consequences of cardiac CT examinations using state-of-the-art CT systems in experienced centers. Twelve cardiology centers with profound expertise in cardiovascular imaging participated in the German Cardiac CT Registry. Criteria for participation included adequate experience in cardiac CT as well of the availability of a 64-slice or newer CT system. Between 2009 and 2014, 7061 patients were prospectively enrolled. For all cardiac CT examinations, patient parameters, procedural data, indication and clinical consequences of the examination were documented. Mean patient age was 61 ± 12 years, 63% were males. The majority (63%) of all cardiac CT examinations were performed in an outpatient setting, 37% were performed during an inpatient stay. 91% were elective and 9% were scheduled in an acute setting. In most examinations (48%), reporting was performed by cardiologists, in 4% by radiologists and in 47% of the cases as a consensus reading. Cardiac CT was limited to native acquisitions for assessment of coronary artery calcification in 9% of patients, only contrast-enhanced coronary CT angiography was performed in 16.6% and combined native and contrast-enhanced coronary CT angiography was performed in 57.7% of patients. Non-coronary cardiac CT examinations constituted 16.6% of all cases. Coronary artery calcification assessment was performed using prospectively ECG-triggered acquisition in 76.9% of all cases. The median dose length product (DLP) was 42mGycm (estimated effective radiation dose of 0.6mSv). Coronary CT angiography was performed using prospectively ECG-triggered acquisition in 77.3% of all cases. Tube voltage was 120kV in 67.8% of patients and 100kV in 30.7% of patients, with a resultant median DLP of 256mGycm (estimated effective dose of 3.6mSv). Clinical consequences of cardiac CT were as follows: in 46.8% of the cases, invasive coronary angiography could be avoided; ischemia testing was recommended in 4.7% of the cases, invasive coronary angiography was recommended in 16.4% of the cases and change in medication in 21.6% of the examinations. Cardiac CT is performed in the majority of patients for non-invasive evaluation of the coronary arteries. CT frequently resulted in medication change, and otherwise planned downstream testing including invasive angiography could be avoided in a high percentage of patients. Radiation exposure in experienced centers is relatively low.

High burden of coronary atherosclerosis in patients with a new diagnosis of type 2 diabetes.

The purposes of this study were to compare the presence, extent and composition of coronary plaques in asymptomatic patients with newly diagnosed type 2 diabetes to age- and sex-matched controls. Patients with newly diagnosed (<1 year) type 2 diabetes ( n = 44) and controls ( n = 44) underwent contrast-enhanced coronary computed tomography angiography. Advanced plaque analysis including total plaque volume and volumes of plaque components (calcified plaque and non-calcified plaque, including low-attenuation [low-density non-calcified plaque]) was performed using validated semi-automated software. Coronary artery calcification was more often seen in patients with type 2 diabetes (66%) versus controls (48%), p < 0.05. Both the absolute volume (median; interquartile range) of low-density non-calcified plaque (7.9 mm3; 0-50.5 mm3 vs 0; 0-34.3 mm3, p < 0.05) and the increase in low-density non-calcified plaque ratio in relation to total plaque volume ( τ = 0.5, p < 0.001) were significantly higher in patients with type 2 diabetes. More patients with type 2 diabetes had spotty calcification (31% vs 0%, p < 0.05). By multivariate analysis, the presence of any low-density non-calcified plaque was higher in males (odds ratio: 4.06, p < 0.05), who also demonstrated a larger low-density non-calcified plaque volume ( p < 0.001). The presence and extent of low-density non-calcified plaque increased with age, smoking, hypertension and hyperglycaemia, all p < 0.05. Asymptomatic patients with newly diagnosed type 2 diabetes had plaque features associated with increased vulnerability as compared with age- and sex-matched controls.

Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO): rationale and design of a multicenter cohort study

BackgroundReproductive disorders, such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and hypertensive pregnancy disorders (HPD) like pre-eclampsia (PE), are associated with an increased risk of cardiovascular disease (CVD). Detection of early signs of cardiovascular disease (CVD), as well as identification of risk factors among women of reproductive age which improve cardiovascular risk prediction, is a challenge and current models might underestimate long-term health risks. The aim of this study is to assess cardiovascular disease in patients with a history of a reproductive disorder by low-dose computed tomography (CT).MethodsWomen of 45 - 55 years, who experienced a reproductive disorder (PCOS, POI, HPD), are invited to participate in this multicenter, prospective, cohort study. Women will be recruited after regular cardiovascular screening, including assessment of classical cardiovascular risk factors. CT of the coronary arteries (both coronary artery calcium scoring (CACS), and contrast-enhanced coronary CT angiography (CCTA)) and carotid siphon calcium scoring (CSC) is planned in 300 women with HPD and 300 women with PCOS or POI. In addition, arterial stiffness (non-invasive pulse wave velocity (PWV)) measurement and cell-based biomarkers (inflammatory circulating cells) will be obtained.DiscussionInitial inclusion is focused on women of 45 - 55 years. However, the age range (40 - 45 years and/or ≥ 55 years) and group composition may be adjusted based on the findings of the interim analysis. Participants can potentially benefit from information obtained in this study concerning their current cardiovascular health and expected future risk of cardiovascular events. The results of this study will provide insights in the development of CVD in women with a history of reproductive disorders. Ultimately, this study may lead to improved cardiovascular prediction models and will provide an opportunity for timely adjustment of preventive strategies. Limitations of this study include the possibility of overdiagnosis and the average radiation dose of 3.5 mSv during coronary and carotid siphon CT, although the increased lifetime malignancy risk is negligible.Trial registrationNetherlands Trial Register, NTR5531. Date registered: October 21st, 2015.

Occult coronary artery disease in middle-aged sportsmen with a low cardiovascular risk score: The Measuring Athlete's Risk of Cardiovascular Events (MARC) study.

Most exercise-related cardiac arrests in men aged ≥45 years are due to coronary artery disease (CAD). The current sports medical evaluation (SME) of middle-aged sportsmen includes medical history, physical examination and resting and exercise electrocardiography (ECG). We investigated the added value of low-dose cardiac computed tomography (CCT) - both non-contrast CT for coronary artery calcium scoring (CACS) and contrast-enhanced coronary CT angiography (CCTA) - in order to detect occult CAD in asymptomatic recreational sportsmen aged ≥45 years without known cardiovascular disease. Following a normal SME (with resting and bicycle exercise ECG), 318 asymptomatic sportsmen underwent CCT and 300 (94%) had a low European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) risk. Occult CAD was defined as a CACS ≥100 Agatston units (AU) or obstructive (≥50%) luminal stenosis on CCTA. The number needed to screen (NNS) in order to prevent one cardiovascular event within 5 years with statin treatment was estimated. Fifty-two (16.4%, 95% confidence interval (CI): 12.7-20.8%) of 318 participants had a CACS ≥100 AU. The CCTA identified an additional eight participants with luminal narrowing ≥50% (and a CACS <100 AU). Taken together, CCT identified CAD in 60 (18.9%, 95% CI: 14.9-23.5%) of 318 participants. The 5-year estimated NNS was 183 (95% CI: 144-236) for CACS and 159 (95% CI: 128-201) for CACS combined with CCTA. Coronary CT detects occult CAD in almost one in five asymptomatic sportsmen aged ≥45 years after a normal SME that included resting and bicycle exercise ECG. CACS reveals most of the relevant CAD with limited additional value of contrast-enhanced CCTA. The NNS in order to prevent one cardiovascular event compares favourably to that of other screening tests.

Reduced ovarian reserve relates to monocyte activation and subclinical coronary atherosclerotic plaque in women with HIV.

To investigate differences in subclinical coronary atherosclerotic plaque and markers of immune activation among HIV-infected and non-HIV-infected women categorized by degree of ovarian reserve and menopause status. Cross-sectional evaluation. Seventy-four women (49 HIV-infected, 25 non-HIV-infected) without known cardiovascular disease (CVD) were classified as premenopausal, premenopausal with reduced ovarian reserve, or postmenopausal based on menstrual history and anti-Müllerian hormone (AMH) levels. Participants underwent contrast-enhanced coronary computed tomography angiography and immune phenotyping. Comparisons in coronary atherosclerotic plaque burden and immune markers were made between the HIV-infected and non-HIV-infected women overall and within the HIV-infected and non-HIV-infected women by reproductive classification group. Among the overall group of HIV-infected women, the women with reduced ovarian reserve (undetectable AMH) had a higher prevalence of coronary atherosclerotic plaque (52 versus 6%, P = 0.0007) and noncalcified plaque (48 versus 6%, P = 0.002), as well as higher levels of log sCD163 (P = 0.0004) and log MCP-1 (P = 0.006), compared with the premenopausal women with measurable AMH. Furthermore, reduced ovarian reserve in the HIV-infected group related to noncalcified plaque, controlling for traditional CVD risk factors (P = 0.04) and sCD163 (P = 0.03). HIV-infected women with reduced ovarian reserve have increased subclinical coronary atherosclerotic plaque compared with premenopausal women in whom AMH is measurable. This relationship holds when controlling for CVD risk factors (including age) and immune activation. Our findings demonstrate that reduced ovarian reserve may contribute to CVD burden in HIV-infected women and support a comprehensive assessment of CVD risk prior to completion of menopause in this population.

Coronary calcium scoring from contrast coronary CT angiography using a semiautomated standardized method

BackgroundWhen coronary calcium scoring is performed in patients with suspected coronary artery disease, a separate noncontrast scan is acquired before contrast-enhanced coronary CT angiography (CTA). ObjectiveOur aim was to develop and validate an automated method for calculating the coronary calcium score (CCS) from coronary CTA. MethodsWe analyzed coronary CTA and noncontrast CT data sets of 84 patients (Agatston score >0). The CCS on noncontrast CT was measured using commercial methods. Coronary calcium volume was measured on coronary CTA using an automated standardized method with scan-specific calcium thresholds. Data sets were split into derivation (n = 40) and validation groups (n = 44). To calculate the CCS on coronary CTA, a conversion factor between calcium scores measured in noncontrast CT and the calcium volume measured on coronary CTA was derived by linear regression. ResultsIn the validation group, the median calculated CCS derived from CTA was 277 and 244 on noncontrast images (P = .12). This CCS showed an excellent correlation with the CCS from noncontrast images (Pearson, r = 0.95). In the validation group, 39 of 44 patients (88.6%) were classified into the same standard category (1–10, 11–100, 101–400, or >400) with an excellent agreement (weighted κ of 0.87). ConclusionCCSs can be accurately measured from contrast-enhanced coronary CTA by using an automated, standardized method, obviating the need for a noncontrast scan.

Intravenous ivabradine for control of heart rate during coronary CT angiography: A randomized, double-blind, placebo-controlled trial

BackgroundLow heart rates (HRs) are preferable for coronary CT angiography (CTA). We evaluated the use of an intravenous bolus of ivabradine, a selective sinus node inhibitor, to lower HR before coronary CTA in a prospective, randomized, double-blind, placebo-controlled multicenter trial. MethodsA total of 370 patients scheduled for CTA, with sinus rhythm ≥70 beats/min but ineligible for intravenous beta-blockers, were randomized to an intravenous bolus of 10 mg (HR, 70–79 beats/min) or 15 mg (HR ≥80 beats/min) ivabradine or placebo. Primary end point was the proportion of patients achieving HR ≤65 beats/min at the initiation of coronary CTA (Ta). ResultsBaseline HR was 79 ± 8.5 beats/min. At Ta, HR ≤65 beats/min was achieved in 55% of the ivabradine group vs 23% for placebo (P < .0001) and in 68% vs 16% 1-hour after bolus administration (P < .0001). Contrast-enhanced coronary CTA was performed in 87% of the ivabradine group vs 65% for placebo (P < .0001). Mean HR at Ta was 67 ± 10 beats/min for ivabradine vs 75 ± 10 beats/min for placebo (P < .0001). Procedural convenience was scored better with ivabradine (“good” or “very good” in 79% vs 63% for placebo; P = .0005). The effective radiation dose of contrast-enhanced CTA was 13 ± 7 mSv for ivabradine vs 16 ± 7 mSv for placebo (P < .05). Ivabradine was well tolerated. ConclusionsAn intravenous bolus of ivabradine achieves rapid, safe, and sustained HR lowering during coronary CTA, increasing procedural convenience and reducing radiation exposure vs placebo.

Additive Prognostic Value of Coronary Artery Calcium Score Over Coronary Computed Tomographic Angiography Stenosis Assessment in Symptomatic Patients Without Known Coronary Artery Disease

The objective of this study was to examine the additive prognostic performance of coronary artery calcium score (CACS) over coronary computed tomography angiography (CCTA) stenosis assessment in symptomatic patients suspected for coronary artery disease (CAD) undergoing CCTA. A total of 805 symptomatic patients without known history of CAD who underwent coronary evaluation by multidetector cardiac CT were analyzed. Mean age of the cohort was 58 ± 13 years. A total of 44% (354 of 805) of the patients had a 0 CACS, 27% (215 of 805) had CACS 1 to 100, 14% (111 of 805) had CACS 101 to 400, and 15% (125 of 805) had CACS >400. CCTA showed normal coronary arteries in 43% (349 of 805) of patients, ≤50% stenosis in 42% (333 of 805), and >50% stenosis in 15% (123 of 805). Patients were followed for 2.3 ± 0.9 years. Major adverse cardiac event (MACE) was defined as cardiac death, nonfatal myocardial infarction, and late coronary revascularization. Overall incidence of MACE was 1.4% per year. Both CACS and CCTA stenosis were independently associated with increased MACE (p <0.05 for both). Addition of CACS into the model with clinical risk factors and CCTA stenosis significantly improved predictive performance for MACE from the model with clinical risk factors and CCTA stenosis only (global chi-square score 108 vs 70; p = 0.019). In conclusion; in symptomatic patients without known CAD, both CACS and CCTA stenosis were independently associated with increased cardiac events, and performing non-contrast-enhanced CACS evaluation in addition to contrast-enhanced CCTA improved predictive ability for future cardiac events compared to CCTA stenosis assessment alone.

When Do We Really Need Coronary Calcium Scoring Prior to Contrast-Enhanced Coronary Computed Tomography Angiography? Analysis by Age, Gender and Coronary Risk Factors

AimsTo investigate the value of coronary calcium scoring (CCS) as a filter scan prior to coronary computed tomography angiography (CCTA).Methods and ResultsBetween February 2008 and April 2011, 732 consecutive patients underwent clinically indicated CCTA. During this ‘control phase’, CCS was performed in all patients. In patients with CCS≥800, CCTA was not performed. During a subsequent ‘CCTA phase’ (May 2011–May 2012) another 200 consecutive patients underwent CCTA, and CCS was performed only in patients with increased probability for severe calcification according to age, gender and atherogenic risk factors. In patients where CCS was not performed, calcium scoring was performed in contrast-enhanced CCTA images. Significant associations were noted between CCS and age (r = 0.30, p<0.001) and coronary risk factors (χ2 = 37.9; HR = 2.2; 95%CI = 1.7–2.9, p<0.001). Based on these associations, a ≤3% pre-test probability for CCS≥800 was observed for males <61 yrs. and females <79 yrs. According to these criteria, CCS was not performed in 106 of 200 (53%) patients during the ‘CCTA phase’, including 47 (42%) males and 59 (67%) females. This resulted in absolute radiation saving of ∼1 mSv in 75% of patients younger than 60 yrs. Of 106 patients where CCS was not performed, estimated calcium scoring was indeed <800 in 101 (95%) cases. Non-diagnostic image quality due to calcification was similar between the ‘control phase’ and the ‘CCTA’ group (0.25% versus 0.40%, p = NS).ConclusionThe value of CCS as a filter for identification of a high calcium score is limited in younger patients with intermediate risk profile. Omitting CCS in such patients can contribute to further dose reduction with cardiac CT studies.