User-defined outcomes of the Danish cardiovascular screening (DANCAVAS) trial: A post hoc analyses of a population-based, randomised controlled trial.

BACKGROUND: The Danish cardiovascular screening (DANCAVAS) trial, a nationwide trial designed to investigate the impact of cardiovascular screening in men, did not decrease all-cause mortality, an outcome decided by the investigators. However, the target group may have varied preferences. In this study, we aimed to evaluate whether men aged 65 to 74 years requested a CT-based cardiovascular screening examination and to assess its impact on outcomes determined by their preferences. METHODS AND FINDINGS: This is a post hoc study of the randomised DANCAVAS trial. All men 65 to 74 years of age residing in specific areas of Denmark were randomised (1:2) to invitation-to-screening (16,736 men, of which 10,471 underwent screening) or usual-care (29,790 men). The examination included among others a non-contrast CT scan (to assess the coronary artery calcium score and aortic aneurysms). Positive findings prompted preventive treatment with atorvastatin, aspirin, and surveillance/surgical evaluation. The usual-care group remained unaware of the trial and the assignments. The user-defined outcome was based on patient preferences and determined through a survey sent in January 2023 to a random sample of 9,095 men from the target group, with a 68.0% response rate (6,182 respondents). Safety outcomes included severe bleeding and mortality within 30 days after cardiovascular surgery. Analyses were performed on an intention-to-screen basis. Prevention of stroke and myocardial infarction was the primary motivation for participating in the screening examination. After a median follow-up of 6.4 years, 1,800 of 16,736 men (10.8%) in the invited-to-screening group and 3,420 of 29,790 (11.5%) in the usual-care group experienced an event (hazard ratio (HR), 0.93 (95% confidence interval (CI), 0.88 to 0.98; p = 0.010); number needed to invite at 6 years, 148 (95% CI, 80 to 986)). A total of 324 men (1.9%) in the invited-to-screening group and 491 (1.7%) in the usual-care group had an intracranial bleeding (HR, 1.17; 95% CI, 1.02 to 1.35; p = 0.029). Additionally, 994 (5.9%) in the invited-to-screening group and 1,722 (5.8%) in the usual-care group experienced severe gastrointestinal bleeding (HR, 1.02; 95% CI, 0.95 to 1.11; p = 0.583). No differences were found in mortality after cardiovascular surgery. The primary limitation of the study is that exclusive enrolment of men aged 65 to 74 renders the findings non-generalisable to women or men of other age groups. CONCLUSION: In this comprehensive population-based cardiovascular screening and intervention program, we observed a reduction in the user-defined outcome, stroke and myocardial infarction, but entail a small increased risk of intracranial bleeding. TRIAL REGISTRATION: ISRCTN Registry number, ISRCTN12157806 https://www.isrctn.com/ISRCTN12157806.

Artificial Intelligence-Enabled Quantitative Coronary Plaque and Hemodynamic Analysis for Predicting Acute Coronary Syndrome.

BACKGROUND: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. OBJECTIVES: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). METHODS: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. RESULTS: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. CONCLUSIONS: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328).

Effects of vitamins K2 and D3 supplementation in patients with severe coronary artery calcification: a study protocol for a randomised controlled trial.

INTRODUCTION: Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction and cardiovascular mortality. Supplementation with vitamin K2 and D3 has been suggested to have a protective role in the progression of CAC. In this study, we will examine the effect of vitamins K2 and D3 in men and women with severe CAC. We hypothesise that supplementation with vitamins K2 and D3 will slow down the calcification process. METHOD AND ANALYSIS: In this multicentre and double-blinded placebo-controlled study, 400 men and women with CAC score≥400 are randomised (1:1) to treatment with vitamin K2 (720 µg/day) and vitamin D3 (25 µg/day) or placebo treatment (no active treatment) for 2 years. Among exclusion criteria are treatment with vitamin K antagonist, coagulation disorders and prior coronary artery disease. To evaluate progression in coronary plaque, a cardiac CT-scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is progression in CAC score from baseline to follow-up at 2 years. Among secondary outcomes are coronary plaque composition and cardiac events. Intention-to-treat principle is used for all analyses. ETHICS AND DISSEMINATION: There are so far no reported adverse effects associated with the use of vitamin K2. The protocol was approved by the Regional Scientific Ethical Committee for Southern Denmark and the Data Protection Agency. It will be conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported. TRIAL REGISTRATION NUMBER: NCT05500443.

Can prediabetes diagnosed using HemoglobinA1c or oral glucose tolerance test predict presence and severity of coronary artery disease in symptomatic patients?

We investigated whether prediabetes diagnosed by hemoglobinA1c (HbA1c) or oral glucose tolerance test (OGTT) could predict presence and severity of coronary artery disease (CAD) in symptomatic patients. The presence of plaque, stenosis, plaque characteristics, and coronary artery calcium (CAC) were evaluated by coronary CT angiography in 702 patients with suspicion of CAD. Patients were classified by glycemic status using the American Diabetes Association criteria for HbA1c and OGTT, and compared to their respective normal ranges. Prediabetes was observed in 24% by HbA1c and 72% by OGTT. Both prediabetes classifications were associated with increased presence of plaque, stenosis, calcified plaques, CAC >400, and a lower frequency of zero CAC compared to their respective normal range (all, p < 0.05). After adjusting for potential confounders, patients with HbA1c-prediabetes had an odds ratio of 2.1 (95% CI: 1.3-3.5) for CAC >400 and 1.5 (95% CI: 1.0-2.4) for plaque presence, while none of the associations for OGTT-prediabetes were significant. The receiver operating characteristic-curve for HbA1c-prediabetes showed an area under the curve of 0.81 for CAC >400 and 0.77 for plaque presence. Prediabetes defined by HbA1c predicts presence and severity of CAD. Although OGTT identified more patients with prediabetes, their risk of CAD were not explained by prediabetes using these diagnostic-criteria.

Liraglutide treatment is associated with progression of coronary artery fibrous plaque: a prospective 1-year follow-up study in asymptomatic patients with type 2 diabetes.

OBJECTIVE: The objective of this study was to assess the association between clinically indicated liraglutide treatment and coronary artery plaque progression during 1-year follow-up in asymptomatic diabetes. METHODS: Patients were divided into a group receiving liraglutide (Lira+) and a group not receiving liraglutide (Lira-). Coronary computed tomography angiography (CCTA) was performed to assess total atheroma volume (TAV) and subtypes of plaque volumes (dense calcium, fibrous, fibrous-fatty, and necrotic core plaque) and the plaque progression during one year follow-up. RESULTS: Fifty-five patients (27%) receiving liraglutide and 149 (73%) how did not were included. Changes in TAV during 1-year of follow-up were similar in the two groups (38 ± 180 (Lira+) vs. -1 ± 160 mm3 (Lira-), P = 0.13). A greater increase in fibrous plaque volume was seen in the Lira + vs. the Lira- group (34 ± 129 vs. -2 ± 101 mm3, P = 0.04). Changes over 1-year in the other plaque subtypes were similar in the two groups. Treatment duration of liraglutide was not associated with changes in TAV. CONCLUSION: In patients with T2D without known prior coronary artery disease, liraglutide treatment was associated with a significant increase in coronary artery fibrous plaque volume during 1-year follow-up.

The association between diabetes and abdominal aortic aneurysms in men: results of two Danish screening studies, a systematic review, and a meta-analysis of population-based screening studies.

BACKGROUND: A paradoxical protective effect of diabetes on the development and progression of abdominal aortic aneurysms (AAA) has been known for years. This study aimed to investigate whether the protective role of diabetes on AAAs has evolved over the years. METHODS: A cross-sectional study, a systematic review and meta-analysis. This study was based on two large, population-based, randomised screening trials of men aged 65-74; VIVA (2008-2011) and DANCAVAS (2014-2018), including measurement of the abdominal aorta by ultrasound or CT, respectively. Analyses were performed using multiple logistic regressions to estimate the odds ratios (ORs) for AAAs in men with diabetes compared to those not having diabetes. Moreover, a systematic review and meta-analysis of population-based screening studies of AAAs to visualise a potential change of the association between diabetes and AAAs. Studies reporting only on women or Asian populations were excluded. RESULTS: In VIVA, the prevalence of AAA was 3.3%, crude OR for AAA in men with diabetes 1.04 (95% confidence interval, CI, 0.80-1.34), and adjusted OR 0.64 (CI 0.48-0.84). In DANCAVAS, the prevalence of AAA was 4.2%, crude OR 1.44 (CI 1.11-1.87), and adjusted OR 0.78 (CI 0.59-1.04). Twenty-three studies were identified for the meta-analysis (N = 224 766). The overall crude OR was 0.90 (CI 0.77-1.05) before 2000 and 1.16 (CI 1.03-1.30) after 1999. The overall adjusted OR was 0.63 (CI 0.59-0.69) before 2000 and 0.69 (CI 0.57-0.84) after 1999. CONCLUSION: Both the crude and adjusted OR showed a statistically non-significant trend towards an increased risk of AAA by the presence of diabetes. If this represents an actual trend, it could be due to a change in the diabetes population. TRIAL REGISTRATION: DANCAVAS: Current Controlled Trials: ISRCTN12157806. VIVA: ClinicalTrials.gov NCT00662480.

COMBINING HI-RESOLUTION SCAN MODE WITH DEEP LEARNING RECONSTRUCTION ALGORITHMS IN CARDIAC CT.

To investigate the impact of combining the high-resolution (Hi-res) scan mode with deep learning image reconstruction (DLIR) algorithm in CT. Two phantoms (Catphan600® and Lungman, small, medium, large size) were CT scanned using combinations of Hi-res/standard mode and high-definition (HD)/standard kernels. Images were reconstructed with ASiR-V and three levels of DLIR. Spatial resolution, noise and contrast-to-noise ratio (CNR) were assessed. The radiation dose was recorded. The spatial resolution increased using Hi-res & HD. Image noise in the Catphan600® (69%) and the Lungman (10-70%) significantly increased when Hi-res & HD was applied. DLIR reduced the mean noise (54%). The CNR was reduced (64%) for Hi-res & HD. The radiation dose increased for both small (+70%) and medium (+43%) Lungman phantoms but decreased slightly for the large ones (-3%) when Hi-res was applied. In conclusion, the Hi-res scan mode improved the spatial resolution. The HD kernel significantly increased the image noise. DLIR improved the image noise and CNR and did not affect the spatial resolution.

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 AIMS: Insulin 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. METHODS: All 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. RESULTS: Four-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 (ß 0.37 [95% CI 0.10-0.65], p = 0.008), pack-years (ß 0.07 [95% CI 0.007-0.14], p = 0.03) and total atheroma volume (TAV) (ß 0.47 [95% CI 0.36-0.57], p < 0.001) remained associated with necrotic plaque volume in the multivariable linear regression model. CONCLUSIONS: IR 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.

Is There Any Improvement in Image Quality in Obese Patients When Using a New X-ray Tube and Deep Learning Image Reconstruction in Coronary Computed Tomography Angiography?

Deep learning image reconstruction (DLIR) is a technique that should reduce noise and improve image quality. This study assessed the impact of using both higher tube currents as well as DLIR on the image quality and diagnostic accuracy. The study consisted of 51 symptomatic obese (BMI > 30 kg/m2) patients with low to moderate risk of coronary artery disease (CAD). All patients underwent coronary computed tomography angiography (CCTA) twice, first with the Revolution CT scanner and then with the upgraded Revolution Apex scanner with the ability to increase tube current. Images were reconstructed using ASiR-V 50% and DLIR. The image quality was evaluated by an observer using a Likert score and by ROI measurements in aorta and the myocardium. Image quality was significantly improved with the Revolution Apex scanner and reconstruction with DLIR resulting in an odds ratio of 1.23 (p = 0.017), and noise was reduced by 41%. A total of 88% of the image sets performed with Revolution Apex + DLIR were assessed as good enough for diagnosis compared to 69% of the image sets performed with Revolution Apex/CT + ASiR-V. In obese patients, the combination of higher tube current and DLIR significantly improves the subjective image quality and diagnostic utility and reduces noise.

Five-Year Outcomes of the Danish Cardiovascular Screening (DANCAVAS) Trial.

BACKGROUND: Limited data suggest a benefit of population-based screening for cardiovascular disease with respect to the risk of death. METHODS: We performed a population-based, parallel-group, randomized, controlled trial involving men 65 to 74 years of age living in 15 Danish municipalities. The participants were randomly assigned in a 1:2 ratio to undergo screening (the invited group) or not to undergo screening (the control group) for subclinical cardiovascular disease. Randomization was based on computer-generated random numbers and stratified according to municipality. Only the control group was unaware of the trial-group assignments. Screening included noncontrast electrocardiography-gated computed tomography to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation, ankle-brachial blood-pressure measurements to detect peripheral artery disease and hypertension, and a blood sample to detect diabetes mellitus and hypercholesterolemia. The primary outcome was death from any cause. RESULTS: A total of 46,611 participants underwent randomization. After exclusion of 85 men who had died or emigrated before being invited to undergo screening, there were 16,736 men in the invited group and 29,790 men in the control group; 10,471 of the men in the invited group underwent screening (62.6%). In intention-to-treat analyses, after a median follow-up of 5.6 years, 2106 men (12.6%) in the invited group and 3915 men (13.1%) in the control group had died (hazard ratio, 0.95; 95% confidence interval [CI], 0.90 to 1.00; P = 0.06). The hazard ratio for stroke in the invited group, as compared with the control group, was 0.93 (95% CI, 0.86 to 0.99); for myocardial infarction, 0.91 (95% CI, 0.81 to 1.03); for aortic dissection, 0.95 (95% CI, 0.61 to 1.49); and for aortic rupture, 0.81 (95% CI, 0.49 to 1.35). There were no significant between-group differences in safety outcomes. CONCLUSIONS: After more than 5 years, the invitation to undergo comprehensive cardiovascular screening did not significantly reduce the incidence of death from any cause among men 65 to 74 years of age. (Funded by the Southern Region of Denmark and others; DANCAVAS ISRCTN Registry number, ISRCTN12157806.).

Cost effectiveness of population screening vs. no screening for cardiovascular disease: the Danish Cardiovascular Screening trial (DANCAVAS).

AIMS: A recent trial has shown that screening of men for cardiovascular disease (CVD) may reduce all-cause mortality. This study assesses the cost effectiveness of such screening vs. no screening from the perspective of European healthcare systems. METHODS AND RESULTS: Randomized controlled trial-based cost-effectiveness evaluation with a mean 5.7 years of follow-up. Screening was based on low-dose computed tomography to detect coronary artery calcification and aortic/iliac aneurysms, limb blood pressure measurement to detect peripheral artery disease and hypertension, telemetric assessment of the heart rhythm to detect atrial fibrillation, and measurements of the cholesterol and HgbA1c levels. Censoring-adjusted incremental costs, life years (LY), and quality-adjusted LY (QALY) were estimated and used for cost-effectiveness analysis. The incremental cost of screening for the entire health care sector was €207 [95% confidence interval (CI) -24; 438, P = 0.078] per invitee for which gains of 0.019 LY (95% CI -0.007; 0.045, P = 0.145) and 0.023 QALY (95% CI -0.001; 0.046, P = 0.051) were achieved. The corresponding incremental cost-effectiveness ratios were of €10 812 per LY and €9075 per QALY, which would be cost effective at probabilities of 0.73 and 0.83 for a willingness to pay of €20 000. Assessment of population heterogeneity showed that cost effectiveness could be more attractive for younger men without CVD at baseline. CONCLUSIONS: Comprehensive screening for CVD is overall cost effective at conventional thresholds for willingness to pay and also competitive to the cost effectiveness of common cancer screening programmes. The screening target group, however, needs to be settled.

Diagnostic and Clinical Value of FFRCT in Stable Chest Pain Patients With Extensive Coronary Calcification: The FACC Study.

BACKGROUND: The influence of extensive coronary calcifications on the diagnostic and prognostic value of coronary computed tomography angiography-derived fractional flow reserve (FFRCT) has been scantily investigated. OBJECTIVES: The purpose of this study was to investigate the diagnostic and short-term role of FFRCT in chest pain patients with Agatston score (AS) >399. METHODS: This was a prospective multicenter study of 260 stable patients with suspected coronary artery disease (CAD) and AS >399. FFRCT was measured blinded by an independent core laboratory. All patients underwent invasive coronary angiography (ICA) and FFR if indicated. The agreement of FFRCT ≤0.80 with hemodynamically significant CAD on ICA/FFR (≥50% left main or ≥70% epicardial artery stenosis and/or FFR ≤0.80) was assessed. Patients undergoing FFR had colocation FFRCT measured, and the lowest per-patient FFRCT was registered in all patients. The association among per-patient FFRCT, coronary revascularization, and major clinical events (all-cause mortality, myocardial infarction, or unstable angina hospitalization) at 90-day follow-up was evaluated. RESULTS: Median age and AS were 68.5 years (IQR: 63-74 years) and 895 (IQR: 587-1,513), respectively. FFRCT was ≤0.80 in 204 patients (78%). Colocation FFRCT (n = 112) showed diagnostic accuracy, sensitivity, and specificity to identify hemodynamically significant CAD of 71%, 87%, and 54%. The area under the receiver-operating characteristics curve (AUC) was 0.75. When using the lowest FFRCT (n = 260), per-patient accuracy, sensitivity, and specificity were 57%, 95%, and 32%, respectively. The AUC was 0.84. A total of 85 patients underwent revascularization, and FFRCT was ≤0.80 in 96% of these. During follow-up, major clinical events occurred in 3 patients (1.2%), all with FFRCT ≤0.80. CONCLUSIONS: Most patients with AS >399 had FFRCT ≤0.80. Using ICA/FFR as the reference revealed a moderate diagnostic accuracy of colocation FFRCT. Compared with the lowest per-patient FFRCT, colocation FFRCT measurement improved diagnostic accuracy and specificity. The 90-day follow-up was favorable with few coronary revascularizations and no major clinical events occurring in patients with FFRCT >0.80. (Use of FFR-CT in Stable Intermediate Chest Pain Patients With Severe Coronary Calcium Score [FACC]; NCT03548753).

Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.

BACKGROUND: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis. METHODS: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events. RESULTS: From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225-326 AU) and 292 AU (95% CI, 246-338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, -86 to 53 AU; P=0.64). The mean change in aortic valve area was 0.02 cm2 (95% CI, -0.09 to 0.12 cm2; P=0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, -0.11 to 0.02 m/s; P=0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P=0.99), all-cause death (1 versus 4 patients; P=0.37), or cardiovascular events (10 versus 10 patients; P=0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (-212 pmol/L versus 45 pmol/L; P<0.001). CONCLUSIONS: In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03243890.

Association of Left Atrial Size Measured by Non-Contrast Computed Tomography with Cardiovascular Risk Factors-The Danish Cardiovascular Screening Trial (DANCAVAS).

Left atrium (LA) size is associated with adverse cardiovascular events. The purpose of this study was to investigate the association of LA enlargement measured by non-contrast CT (NCCT) with traditional cardiovascular risk factors. Individuals aged 60-75 years from the population-based multicentre Danish Cardiovascular Screening (DANCAVAS) trial were included in this cross-sectional study. The LA was manually traced on the NCCT scans, and the largest cross-section area was indexed to body surface area. All traditional risk factors were recorded, and a subgroup received an echocardiographic examination. We enrolled 14,987 individuals. Participants with known cardiovascular disease or lacking measurements of LA size or body surface area were excluded, resulting in 10,902 men for the main analysis and 616 women for a sensitivity analysis. Adjusted multivariable analysis showed a significantly increased indexed LA size by increasing age and pulse pressure, while smoking, HbA1c, and total cholesterol were associated with decreased indexed LA size. The findings were confirmed in a supplementary analysis including left ventricle ejection fraction and mass. In this population-based cohort of elderly men, an association was found between age and pulse pressure and increasing LA size. Surprisingly, smoking, HbA1c, and total cholesterol were associated with a decrease in LA size. This indicates that the pathophysiology behind atrial cardiomyopathy is not only reflected by enlargement, but also shrinking.

Mitral Annulus Calcification and Cardiac Conduction Disturbances: A DANCAVAS Sub-study.

BACKGROUND: Due to its location very close to the bundle of His, mitral annulus calcification (MAC) might be associated with the development of atrioventricular (AV) conduction disturbances. This study assessed the association between MAC and AV conduction disturbances identified by cardiac implantable electronic device (CIED) use and electrocardiographic parameters. The association between MAC and traditional cardiovascular risk factors was also assessed. METHODS: This cross-sectional study analyzed 14,771 participants, predominantly men aged 60-75 years, from the population-based Danish Cardiovascular Screening trial. Traditional cardiovascular risk factors were obtained. Using cardiac non-contrast computed tomography imaging, MAC scores were measured using the Agatston method and divided into absent versus present and score categories. CIED implantation data were obtained from the Danish Pacemaker and Implantable Cardioverter Defibrillator Register. A 12-lead electrocardiogram was available for 2,107 participants. Associations between MAC scores and AV conduction disturbances were assessed using multivariate regression analyses. RESULTS: MAC was present in 22.4% of the study subjects. Participants with pacemakers for an AV conduction disturbance had significantly higher MAC scores (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.01-1.23) than participants without a CIED, whereas participants with a CIED for other reasons did not. Prolonged QRS-interval was significantly associated with the presence of MAC (OR, 1.45; 95% CI, 1.04-2.04), whereas prolonged PQ-interval was not. Female sex and most traditional cardiovascular risk factors were significantly associated with high MAC scores. CONCLUSIONS: MAC was associated with AV conduction disturbances, which could improve our understanding of the development of AV conduction disturbances.

Dual-energy CT plaque characteristics of post mortem thin-cap fibroatheroma in comparison to infarct-related culprit lesions.

Improvement of non-invasive identification of high-risk plaque may increase the preventive options of acute coronary syndrome. To describe the characteristics of thin-cap fibroatheroma (TCFA) in a post mortem model in comparison to characteristics of culprit lesions in patients with non-ST-elevation-myocardial-infarction (NSTEMI) using the dual energy computed tomography (DECT). Three post mortem hearts were prepared with iodine-contrast, inserted in a Kyoto phantom and scanned by DECT. Six TCFA were identified using histopathological analysis (cap thickness < 65 µm and necrotic core > 10% of the plaque area). In the NSTEMI group, 29 patients were scheduled to DECT prior to coronary angiography and invasive treatment. Culprit lesions were identified blinded for the patient history by two independent invasive cardiologists using the coronary angiography. The DECT analysis of TCFA and culprit lesions was performed retrospectively with determination of effective atomic number (Effective-Z), Hounsfield Unit (HU), plaque type (non-calcified, predominantly non-calcified, predominantly calcified or calcified), spotty calcification,, plaque length, plaque volume and plaque burden and the remodeling index. The Effective-Z, HU and plaqueburden were significantly different between TCFA and culprit lesions (P < 0.05).The TCFA plaques were more calcified in comparison to culprit lesions (P < 0.05). No significant difference in the other plaque characteristics was observed. The use of DECT demonstrated different Effective-Z values and different characteristics of post mortem TCFA in comparison to in vivo culprit lesions. This finding may highlight, that not all TCFA should be considered as vulnerable.

Aortic valve calcification among elderly males from the general population, associated echocardiographic findings, and clinical implications.

AIMS: Aortic valve calcification (AVC) detected by non-contrast computed tomography (NCCT) associates with morbidity and mortality in patients with aortic valve stenosis. However, the importance of AVC in the general population is sparsely evaluated. We intend to describe the associations between AVC score on NCCT and echocardiographic findings as left atrial (LA) dilatation, left ventricular (LV) hypertrophy, aortic valve area (AVA), peak velocity, mean gradient, and aortic valve replacement (AVR) in a population with AVC scores ≥300 AU. METHODS AND RESULTS: Of 10 471 males aged 65-74 years from the Danish Cardiovascular Screening trial (DANCAVAS), participants with AVC score ≥300 AU were invited for transthoracic echocardiography and 828 (77%) of 1075 accepted the invitation. AVC scores were categorized (300-599, 600-799, 800-1199, and ≥1200 AU). AVR was obtained from registries. AVC was significantly associated with a steady increase in LA dilation (10.5%, 16.3%, 15.8%, 19.6%, P = 0.031), LV hypertrophy (3.9%, 6.6%, 8.9%, 10.1%, P = 0.021), peak velocity (1.7, 1.9, 2.1, 2.8 m/s, P = 0001), mean gradient (6, 8, 11, 19 mmHg, P = 0.0001), and a decrease in AVA (2.0, 1.9, 1.7, 1.3 cm2, P = 0.0001). The area under the curve was 0.79, 0.93, and 0.92 for AVA ≤1.5 cm2, peak velocity ≥3.0 m/s, and mean gradient ≥20 mmHg, respectively, and the associated optimal AVC score thresholds were 734, 1081, and 1019 AU. AVC > 1200 AU was associated with AVR (P < 0.0001). CONCLUSION: Among males from the background population, increasing AVC scores were associated with LA dilatation, LV hypertrophy, AVA, peak aortic velocity, mean aortic gradient, and AVR.

Prognostic value of myocardial perfusion imaging after first-line coronary computed tomography angiography: A multi-center cohort study.

PURPOSE: Further diagnostic testing may be required after a coronary computed tomography angiography (CTA) showing suspected coronary stenosis. Whether myocardial perfusion imaging (MPI) provides further prognostic information post-CTA remains debated. We evaluated the prognosis for patients completing CTA stratified for post-CTA diagnostic work-up using real-world data. METHODS: We identified all patients in our uptake area with angina symptoms undergoing first-time CTA over a 10-year period. Follow-up time was a median of 3.7 years [1.9-5.8]. The primary endpoint was a composite of myocardial infarction or death. The secondary endpoint was late revascularization. RESULTS: During the study period 53,351 patients underwent CTA. Of these, 24% were referred for further down-stream testing, 3,547 (7%) to MPI and 9,135 (17%) to invasive coronary angiography (ICA). The primary and secondary endpoints occurred in 2,026 (3.8%) and 954 (1.8%) patients. Patient-characteristic-adjusted hazard ratios for the primary and secondary endpoint using patients with a normal CTA as reference were 1.37 (1.21-1.55) and 2.50 (1.93-3.23) for patient treated medically, 1.68 (1.39-2.03) and 6.13 (4.58-8.21) for patients referred to MPI and 1.94 (1.69-2.23) and 9.18 (7.16-11.78) for patients referred for ICA, respectively. Adjusted analysis with stratification for disease severity at CTA showed similar hazard ratios for patients treated medically after CTA and patients referred for MPI and treated medically after the MPI. CONCLUSION: In patients completing coronary CTA, second-line MPI testing seems to identify patients at low risk of future events. MPI seems to have the potential to act as gatekeeper for ICA after coronary CTA.

Prevalence and extent of coronary artery calcification in the middle-aged and elderly population.

AIMS: Coronary artery calcification (CAC) measured on cardiac computed tomography (CT) is an important risk marker for cardiovascular disease (CVD) and has been included in the prevention guidelines. The aim of this study was to describe CAC score reference values in the middle-aged and elderly population and to develop a freely available CAC calculator. METHODS AND RESULTS: All participants from two population-based cardiac CT screening cohorts (DanRisk and DANCAVAS) were included. The CAC score was measured as a part of a screening session. Positive CAC scores were log-transformed and non-parametrically regressed on age for each gender, and percentile curves were transposed according to proportions of zero CAC scores. Men had higher CAC scores than women, and the prevalence and extend of CAC increased steadily with age. An online CAC calculator was developed, http://flscripts.dk/cacscore. After entering sex, age, and CAC score, the CAC score percentile and the coronary age are depicted including a figure with the specific CAC score and 25%, 50%, 75%, and 90% percentiles. The specific CAC score can be compared to the entire background population or only those without prior CVD. CONCLUSION: This study provides modern population-based reference values of CAC scores in men and woman and a freely accessible online CAC calculator. Physicians and patients are very familiar with blood pressure and lipids, but unfamiliar with CAC scores. Using the calculator makes it easy to see if a CAC value is low, moderate, or high, when a physician in the future communicate and discusses a CAC score with a patient.