Plasma copeptin and markers of arterial disorder in patients with type 2 diabetes, a cross-sectional study.

OBJECTIVES: There is currently limited understanding of the relationship between copeptin, the midregional portion of proadrenomedullin (MRproADM) and the midregional fragment of the N-terminal of proatrial natriuretic peptide (MRproANP), and arterial disorders. Toe brachial index (TBI) and aortic pulse wave velocity (aPWV) are established parameters for detecting arterial disorders. This study evaluated whether copeptin, MRproADM, and MRproANP were associated with TBI and aPWV in patients with type 2 diabetes with no history of cardiovascular disease (CVD). METHODS: In the CARDIPP study, a cross-sectional analysis of 519 patients with type 2 diabetes aged 55-65 years with no history of CVD at baseline, had complete data on copeptin, MRproADM, MRproANP, TBI, and aPWV was performed. Linear regression analysis was used to investigate the associations between conventional CVD risk factors, copeptin, MRproADM, MRproANP, TBI, and aPWV. RESULTS: Copeptin was associated with TBI (ß-0.0020, CI-0.0035- (-0.0005), p = 0.010) and aPWV (ß 0.023, CI 0.002-0.044, p = 0.035). These associations were independent of age, sex, diabetes duration, mean 24-hour ambulatory systolic blood pressure, glycated hemoglobin A1c, total cholesterol, estimated glomerular filtration rate, body mass index, and active smoking. CONCLUSIONS: Plasma copeptin may be a helpful surrogate for identifying individuals at higher risk for arterial disorders. TRIAL REGISTRATION:  ClinicalTrials.gov identifier NCT010497377.

Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.

BACKGROUND: Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population. METHODS: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50-64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease. RESULTS: We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0-29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6-66.0%), stress (31.6-76.8%), respiratory disease (20.1-37.1%), depression (17.1-26.6%), cardiac disease (6.3-12.7%), anemia (0.8-3.3%), and peripheral arterial disease (0.3-0.8%). Stress was the main factor in women and current smokers. CONCLUSION: Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting-supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

Diastolic function assessment with four-dimensional flow cardiovascular magnetic resonance using automatic deep learning E/A ratio analysis.

BACKGROUND: Diastolic left ventricular (LV) dysfunction is a powerful contributor to the symptoms and prognosis of patients with heart failure. In patients with depressed LV systolic function, the E/A ratio, the ratio between the peak early (E) and the peak late (A) transmitral flow velocity, is the first step to defining the grade of diastolic dysfunction. Doppler echocardiography (echo) is the preferred imaging technique for diastolic function assessment, while cardiovascular magnetic resonance (CMR) is less established as a method. Previous four-dimensional (4D) Flow-based studies have looked at the E/A ratio proximal to the mitral valve, requiring manual interaction. In this study, we compare an automated, deep learning-based and two semi-automated approaches for 4D Flow CMR-based E/A ratio assessment to conventional, gold-standard echo-based methods. METHODS: Ninety-seven subjects with chronic ischemic heart disease underwent a cardiac echo followed by CMR investigation. 4D Flow-based E/A ratio values were computed using three different approaches; two semi-automated, assessing the E/A ratio by measuring the inflow velocity (MVvel) and the inflow volume (MVflow) at the mitral valve plane, and one fully automated, creating a full LV segmentation using a deep learning-based method with which the E/A ratio could be assessed without constraint to the mitral plane (LVvel). RESULTS: MVvel, MVflow, and LVvel E/A ratios were strongly associated with echocardiographically derived E/A ratio (R2 = 0.60, 0.58, 0.72). LVvel peak E and A showed moderate association to Echo peak E and A, while MVvel values were weakly associated. MVvel and MVflow EA ratios were very strongly associated with LVvel (R2 = 0.84, 0.86). MVvel peak E was moderately associated with LVvel, while peak A showed a strong association (R2 = 0.26, 0.57). CONCLUSION: Peak E, peak A, and E/A ratio are integral to the assessment of diastolic dysfunction and may expand the utility of CMR studies in patients with cardiovascular disease. While underestimation of absolute peak E and A velocities was noted, the E/A ratio measured with all three 4D Flow methods was strongly associated with the gold standard Doppler echocardiography. The automatic, deep learning-based method performed best, with the most favorable runtime of ∼40 seconds. As both semi-automatic methods associated very strongly to LVvel, they could be employed as an alternative for estimation of E/A ratio.

Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry.

Rationale: Postbronchodilator spirometry is used for the diagnosis of chronic obstructive pulmonary disease. However, prebronchodilator reference values are used for spirometry interpretation. Objectives: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or postbronchodilator reference values generated within SCAPIS (Swedish CArdioPulmonary bioImage Study) when interpreting postbronchodilator spirometry in a general population. Methods: SCAPIS reference values for postbronchodilator and prebronchodilator spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or postbronchodilator reference values, with respiratory burden in the SCAPIS general population (28,851 individuals). Measurements and Main Results: Bronchodilation resulted in higher predicted medians and lower limits of normal (LLNs) for FEV1/FVC ratios. The prevalence of postbronchodilator FEV1/FVC ratio lower than the prebronchodilator LLN was 4.8%, and that of postbronchodilator FEV1/FVC lower than the postbronchodilator LLN was 9.9%, for the general population. An additional 5.1% were identified as having an abnormal postbronchodilator FEV1/FVC ratio, and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%; P < 0.001), and self-reported physician-diagnosed chronic obstructive pulmonary disease (2.8% vs. 0.5%, P < 0.001) than subjects with a postbronchodilator FEV1/FVC ratio greater than the LLN for both pre- and postbronchodilation. Conclusions: Pre- and postbronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of postbronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using postbronchodilator reference values when interpreting postbronchodilator spirometry might enable the identification of individuals with mild disease and be clinically relevant.

Haemodynamic effects of hypertension and type 2 diabetes: Insights from a 4D flow MRI-based personalized cardiovascular mathematical model.

Type 2 diabetes (T2D) and hypertension increase the risk of cardiovascular diseases mediated by whole-body changes to metabolism, cardiovascular structure and haemodynamics. The haemodynamic changes related to hypertension and T2D are complex and subject-specific, however, and not fully understood. We aimed to investigate the haemodynamic mechanisms in T2D and hypertension by comparing the haemodynamics between healthy controls and subjects with T2D, hypertension, or both. For all subjects, we combined 4D flow magnetic resonance imaging data, brachial blood pressure and a cardiovascular mathematical model to create a comprehensive subject-specific analysis of central haemodynamics. When comparing the subject-specific haemodynamic parameters between the four groups, the predominant haemodynamic difference is impaired left ventricular relaxation in subjects with both T2D and hypertension compared to subjects with only T2D, only hypertension and controls. The impaired relaxation indicates that, in this cohort, the long-term changes in haemodynamic load of co-existing T2D and hypertension cause diastolic dysfunction demonstrable at rest, whereas either disease on its own does not. However, through subject-specific predictions of impaired relaxation, we show that altered relaxation alone is not enough to explain the subject-specific and group-related differences; instead, a combination of parameters is affected in T2D and hypertension. These results confirm previous studies that reported more adverse effects from the combination of T2D and hypertension compared to either disease on its own. Furthermore, this shows the potential of personalized cardiovascular models in providing haemodynamic mechanistic insights and subject-specific predictions that could aid in the understanding and treatment planning of patients with T2D and hypertension. KEY POINTS: The combination of 4D flow magnetic resonance imaging data and a cardiovascular mathematical model allows for a comprehensive analysis of subject-specific haemodynamic parameters that otherwise cannot be derived non-invasively. Using this combination, we show that diastolic dysfunction in subjects with both type 2 diabetes (T2D) and hypertension is the main group-level difference between controls, subjects with T2D, subjects with hypertension, and subjects with both T2D and hypertension. These results suggest that, in this relatively healthy population, the additional load of both hypertension and T2D affects the haemodynamic function of the left ventricle, whereas each disease on its own is not enough to cause significant effects under resting conditions. Finally, using the subject-specific model, we show that the haemodynamic effects of diastolic dysfunction alone are not sufficient to explain all the observed haemodynamic differences. Instead, additional subject-specific variations in cardiac and vascular function combine to explain the complex haemodynamics of subjects affected by hypertension and/or T2D.

Automatic Time-Resolved Cardiovascular Segmentation of 4D Flow MRI Using Deep Learning.

BACKGROUND: Segmenting the whole heart over the cardiac cycle in 4D flow MRI is a challenging and time-consuming process, as there is considerable motion and limited contrast between blood and tissue. PURPOSE: To develop and evaluate a deep learning-based segmentation method to automatically segment the cardiac chambers and great thoracic vessels from 4D flow MRI. STUDY TYPE: Retrospective. SUBJECTS: A total of 205 subjects, including 40 healthy volunteers and 165 patients with a variety of cardiac disorders were included. Data were randomly divided into training (n = 144), validation (n = 20), and testing (n = 41) sets. FIELD STRENGTH/SEQUENCE: A 3 T/time-resolved velocity encoded 3D gradient echo sequence (4D flow MRI). ASSESSMENT: A 3D neural network based on the U-net architecture was trained to segment the four cardiac chambers, aorta, and pulmonary artery. The segmentations generated were compared to manually corrected atlas-based segmentations. End-diastolic (ED) and end-systolic (ES) volumes of the four cardiac chambers were calculated for both segmentations. STATISTICAL TESTS: Dice score, Hausdorff distance, average surface distance, sensitivity, precision, and miss rate were used to measure segmentation accuracy. Bland-Altman analysis was used to evaluate agreement between volumetric parameters. RESULTS: The following evaluation metrics were computed: mean Dice score (0.908 ± 0.023) (mean ± SD), Hausdorff distance (1.253 ± 0.293 mm), average surface distance (0.466 ± 0.136 mm), sensitivity (0.907 ± 0.032), precision (0.913 ± 0.028), and miss rate (0.093 ± 0.032). Bland-Altman analyses showed good agreement between volumetric parameters for all chambers. Limits of agreement as percentage of mean chamber volume (LoA%), left ventricular: 9.3%, 13.5%, left atrial: 12.4%, 16.9%, right ventricular: 9.9%, 15.6%, and right atrial: 18.7%, 14.4%; for ED and ES, respectively. DATA CONCLUSION: The addition of this technique to the 4D flow MRI assessment pipeline could expedite and improve the utility of this type of acquisition in the clinical setting. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

Arterial stiffness and subclinical atherosclerosis in the coronary arteries at different stages of dysglycaemia.

AIM: Our aim was to investigate in a large population-based cohort study whether increased arterial stiffness and subclinical atherosclerosis in the coronary arteries differ at different stages of dysglycaemia. METHODS: Data were obtained from SCAPIS, a population-based cohort of participants 50-64 years. The study population of 9379 participants was categorised according to glycaemic status: normoglycaemic, pre-diabetes (fasting glucose: 6.1-6.9 mmol/L and/or HbA1c 6%-6.4%) and diabetes. Pulse wave velocity (PWV) was measured by the SphygmoCor XCEL system and arterial stiffness was defined by PWV ≥10 m/s. Coronary artery calcium score (CACS) was assessed by coronary computed tomography and coronary artery calcification was defined by CACS ≥100. RESULTS: We identified 1964 (21%) participants with dysglycaemia, out of which 742 (7.9%) had diabetes mellitus. PWV ≥10 m/s was present in 808 (11%), 191 (16%), 200 (27%) and CACS ≥100 in 801 (11%), 190 (16%), 191 (28%) participants with normoglycaemia, pre-diabetes and diabetes, respectively, all, p < 0.001. The overlap between PWV ≥10 m/s and CACS ≥100 within each glycaemic category was 188 (2.5%), 44 (3.6%) and 77 (10) respectively. There was an association between glycaemic status and increased PWV in the fully adjusted models, but not for glycaemic status and CACS ≥100, where there was no difference for pre-diabetes compared to normoglycaemia, OR 1.2 (95% CI 0.98-1.4). In the total study population, there was an association between HbA1c and PWV after adjustment, p < 0.001. CONCLUSIONS: Our results show that increased arterial stiffness and subclinical coronary artery atherosclerosis are present in the early stages of dysglycaemia, but the overlap between markers of major subclinical vascular damage was small in all glycaemic categories. This could be explained by different pathways in the pathogenesis of arterial stiffness or atherosclerosis in the coronary arteries.

Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population.

BACKGROUND: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population. METHODS: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data. RESULTS: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population. CONCLUSIONS: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.

Accelerometer derived physical activity patterns in 27.890 middle-aged adults: The SCAPIS cohort study.

The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50-64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an "at-risk" behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.

Developmental Differences in Left Ventricular Strain in IUGR vs. Control Children the First Three Months of Life.

BACKGROUND: Intrauterine growth restriction (IUGR) may directly affect cardiovascular function in early life. Longitudinal data on left ventricular longitudinal strain (LVLS), a key measure of cardiac function independent of body size, is not available. We hypothesize impaired cardiac function among IUGR newborns and persistence of the impairment until age 3 months. METHOD: This is a prospective cohort study of consecutive pregnancies where IUGR was identified at 18-38 weeks gestational age (GA) with healthy controls randomly selected at 18-20 weeks GA. Echocardiograms were performed at birth and at age 3-4 months, and then compared. RESULTS: At birth, mean (SD) LVLS did not differ between the IUGR group [N = 19; - 15.76 (3.12) %] and controls [N = 35; - 15.53 (3.56) %]. The IUGR group demonstrated no significant change in LVLS at age 3-4 months [- 17.80 (3.82) %], while the control group [- 20.91 (3.31) %] showed a significant increase (P < 0.001). Thus, LVLS was lower in the IUGR group at age 3-4 months (P = 0.003). CONCLUSION: The lack of increase in LVLS may suggest that IUGR has a direct impact on cardiac function as early as during the first months of life. Trial registration Clinical trials.gov Identifier: NCT02583763, registration October 22, 2015. Retrospectively registered September 2014-October 2015, thereafter, registered prospectively.

Moderately trained male football players, compared to sedentary male adults, exhibit anatomical but not functional cardiac remodelling, a cross-sectional study.

BACKGROUND: Elite athletes have been the subject of great interest, but athletes at an intermediate level of physical activity have received less attention in respect to the presence of cardiac enlargement and/or hypertrophy. We hypothesized that playing football, often defined as demanding less endurance components than running or cycling, would still induce remodelling similar to sports with a dominating endurance component. METHODS: 23 male football players, age 25+/- 3.9 yrs. underwent exercise testing, 2D- and 3D- echocardiography and cardiac magnetic resonance (CMR). The results were compared with a control group of engineering students of similar age. The athletes exercised 12 h/week and the control subjects 1 h/week, p < 0.001. RESULTS: The football players achieved a significantly higher maximal load at the exercise test (380 W vs 300 W, p < 0.001) as well as higher calculated maximal oxygen consumption, (49.7 vs 37.4 mL x kg- 1 x min- 1, p < 0.001) compared to the sedentary group. All left ventricular (LV) volumes assessed by 3DEcho and CMR, as well as CMR left atrial (LA) volume were significantly higher in the athletes (3D-LVEDV 200 vs 154 mL, CMR-LVEDV 229 vs 185 mL, CMR-LA volume 100 vs 89 mL, p < 0.001, p = 0.002 and p = 0.009 respectively). LVEF and RVEF, LV strain by CMR or by echo did not differentiate athletes from sedentary participants. Right ventricular (RV) longitudinal strain, LA and right atrial (RA) strain by CMR all showed similar results in the two groups. CONCLUSION: Moderately trained intermediate level football players showed anatomical but not functional cardiac remodelling compared to sedentary males.

Automated segmentation of the individual branches of the carotid arteries in contrast-enhanced MR angiography using DeepMedic.

BACKGROUND: Non-invasive imaging is of interest for tracking the progression of atherosclerosis in the carotid bifurcation, and segmenting this region into its constituent branch arteries is necessary for analyses. The purpose of this study was to validate and demonstrate a method for segmenting the carotid bifurcation into the common, internal, and external carotid arteries (CCA, ICA, ECA) in contrast-enhanced MR angiography (CE-MRA) data. METHODS: A segmentation pipeline utilizing a convolutional neural network (DeepMedic) was tailored and trained for multi-class segmentation of the carotid arteries in CE-MRA data from the Swedish CardioPulmonsary bioImage Study (SCAPIS). Segmentation quality was quantitatively assessed using the Dice similarity coefficient (DSC), Matthews Correlation Coefficient (MCC), F2, F0.5, and True Positive Ratio (TPR). Segmentations were also assessed qualitatively, by three observers using visual inspection. Finally, geometric descriptions of the carotid bifurcations were generated for each subject to demonstrate the utility of the proposed segmentation method. RESULTS: Branch-level segmentations scored DSC = 0.80 ± 0.13, MCC = 0.80 ± 0.12, F2 = 0.82 ± 0.14, F0.5 = 0.78 ± 0.13, and TPR = 0.84 ± 0.16, on average in a testing cohort of 46 carotid bifurcations. Qualitatively, 61% of segmentations were judged to be usable for analyses without adjustments in a cohort of 336 carotid bifurcations without ground-truth. Carotid artery geometry showed wide variation within the whole cohort, with CCA diameter 8.6 ± 1.1 mm, ICA 7.5 ± 1.4 mm, ECA 5.7 ± 1.0 mm and bifurcation angle 41 ± 21°. CONCLUSION: The proposed segmentation method automatically generates branch-level segmentations of the carotid arteries that are suitable for use in further analyses and help enable large-cohort investigations.

The transluminal attenuation gradient does not add diagnostic accuracy to coronary computed tomography.

BACKGROUND: A method for improving the accuracy of coronary computed tomography angiography (CCTA) is highly sought after as it would help to avoid unnecessary invasive coronary angiographies. Measurement of the transluminal attenuation gradient (TAG) has been proposed as an alternative to other existing methods, i.e. CT perfusion and CT fractional flow reserve (FFR). PURPOSE: To evaluate the incremental value of three types of TAG in high-pitch spiral CCTA with invasive FFR measurements as reference. MATERIAL AND METHODS: TAG was measured using two semi-automatic methods and one manual method. A receiver operating characteristic (ROC) analysis was made to determine the usefulness of TAG alone as well as TAG combined with CCTA for detection of significant coronary artery stenoses defined by an invasive FFR value ≤0.80. RESULTS: A total of 51 coronary vessels in 37 patients were included in this retrospective study. Hemodynamically significant stenoses were found in 13 vessels according to FFR. The ROC analysis TAG alone resulted in areas under the curve (AUCs) of 0.530 and 0.520 for the semi-automatic TAG and 0.557 for the manual TAG. TAG and CCTA combined resulted in AUCs of 0.567, 0.562 for semi-automatic TAG, and 0.569 for the manual TAG. CONCLUSION: The results from our study showed no incremental value of TAG measured in single heartbeat CCTA in determining the severity of coronary artery stenosis degrees.

Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS).

The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (D LCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired D LCO We examined if the GLI LLN for D LCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, D LCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50-64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for D LCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of D LCO GLI LLN but GLI LLN but GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for D LCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with D LCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.

Towards Automated Quantification of Vessel Wall Composition Using MRI.

BACKGROUND: MRI can be used to generate fat fraction (FF) and R2* data, which have been previously shown to characterize the plaque compositional features lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in the carotid arteries (CAs). Previously, these data were extracted from CA plaques using time-consuming manual analyses. PURPOSE: To design and demonstrate a method for segmenting the CA and extracting data describing the composition of the vessel wall. STUDY TYPE: Prospective. SUBJECTS: 31 subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). FIELD STRENGTH/SEQUENCES: T1 -weighted (T1 W) quadruple inversion recovery, contrast-enhanced MR angiography (CE-MRA), and 4-point Dixon data were acquired at 3T. ASSESSMENT: The vessel lumen of the CA was automatically segmented using support vector machines (SVM) with CE-MRA data, and the vessel wall region was subsequently delineated. Automatically generated segmentations were quantitatively measured and three observers visually compared the segmentations to manual segmentations performed on T1 w images. Dixon data were used to generate FF and R2* maps. Both manually and automatically generated segmentations of the CA and vessel wall were used to extract compositional data. STATISTICAL TESTS: Two-tailed t-tests were used to examine differences between results generated using manual and automated analyses, and among different configurations of the automated method. Interobserver agreement was assessed with Fleiss' kappa. RESULTS: Automated segmentation of the CA using SVM had a Dice score of 0.89 ± 0.02 and true-positive ratio 0.93 ± 0.03 when compared against ground truth, and median qualitative score of 4/5 when assessed visually by multiple observers. Vessel wall regions of 0.5 and 1 mm yielded compositional information similar to that gained from manual analyses. Using the 0.5 mm vessel wall region, the mean difference was 0.1 ± 2.5% considering FF and 1.1 ± 5.7[1/s] for R2*. LEVEL OF EVIDENCE: 1. TECHNICAL EFFICACY STAGE: 1. J. Magn. Reson. Imaging 2020;52:710-719.

Evaluation of an AI-based, automatic coronary artery calcium scoring software.

OBJECTIVES: To evaluate an artificial intelligence (AI)-based, automatic coronary artery calcium (CAC) scoring software, using a semi-automatic software as a reference. METHODS: This observational study included 315 consecutive, non-contrast-enhanced calcium scoring computed tomography (CSCT) scans. A semi-automatic and an automatic software obtained the Agatston score (AS), the volume score (VS), the mass score (MS), and the number of calcified coronary lesions. Semi-automatic and automatic analysis time were registered, including a manual double-check of the automatic results. Statistical analyses were Spearman's rank correlation coefficient (⍴), intra-class correlation (ICC), Bland Altman plots, weighted kappa analysis (κ), and Wilcoxon signed-rank test. RESULTS: The correlation and agreement for the AS, VS, and MS were ⍴ = 0.935, 0.932, 0.934 (p < 0.001), and ICC = 0.996, 0.996, 0.991, respectively (p < 0.001). The correlation and agreement for the number of calcified lesions were ⍴ = 0.903 and ICC = 0.977 (p < 0.001), respectively. The Bland Altman mean difference and 1.96 SD upper and lower limits of agreements for the AS, VS, and MS were - 8.2 (- 115.1 to 98.2), - 7.4 (- 93.9 to 79.1), and - 3.8 (- 33.6 to 25.9), respectively. Agreement in risk category assignment was 89.5% and κ = 0.919 (p < 0.001). The median time for the semi-automatic and automatic method was 59 s (IQR 35-100) and 36 s (IQR 29-49), respectively (p < 0.001). CONCLUSIONS: There was an excellent correlation and agreement between the automatic software and the semi-automatic software for three CAC scores and the number of calcified lesions. Risk category classification was accurate but showing an overestimation bias tendency. Also, the automatic method was less time-demanding. KEY POINTS: • Coronary artery calcium (CAC) scoring is an excellent candidate for artificial intelligence (AI) development in a clinical setting. • An AI-based, automatic software obtained CAC scores with excellent correlation and agreement compared with a conventional method but was less time-consuming.

Clinical validation of three cardiovascular magnetic resonance techniques to measure strain and torsion in patients with suspected coronary artery disease.

BACKGROUND: Several cardiovascular magnetic resonance (CMR) techniques can measure myocardial strain and torsion with high accuracy. The purpose of this study was to compare displacement encoding with stimulated echoes (DENSE), tagging and feature tracking (FT) for measuring circumferential and radial myocardial strain and myocardial torsion in order to assess myocardial function and infarct scar burden both at a global and at a segmental level. METHOD: 116 patients with a high likelihood of coronary artery disease (European SCORE > 15%) underwent CMR examination including cine images, tagging, DENSE and late gadolinium enhancement (LGE) in the short axis direction. In total, 97 patients had signs of myocardial disease and 19 had no abnormalities in terms of left ventricular (LV) wall mass index, LV ejection fraction, wall motion, LGE or a history of myocardial infarction. Thirty-four patients had myocardial infarct scar with a transmural LGE extent (transmurality) that exceeded 50% of the wall thickness in at least one segment. Global circumferential strain (GCS) and global radial strain (GRS) was analyzed using FT of cine loops, deformation of tag lines or DENSE displacement. RESULTS: DENSE and tagging both showed high sensitivity (82% and 71%) at a specificity of 80% for the detection of segments with > 50% LGE transmurality, and receiver operating characteristics (ROC) analysis showed significantly higher area under the curve-values (AUC) for DENSE (0.87) than for tagging (0.83, p < 0.001) and FT (0.66, p = 0.003). GCS correlated with global LGE when determined with DENSE (r = 0.41), tagging (r = 0.37) and FT (r = 0.15). GRS had a low but significant negative correlation with LGE; DENSE r = - 0.10, FT r = - 0.07 and tagging r = - 0.16. Torsion from DENSE and tagging had a weak correlation (- 0.20 and - 0.22 respectively) with global LGE. CONCLUSION: Circumferential strain from DENSE detected segments with > 50% scar with a higher AUC than strain determined from tagging and FT at a segmental level. GCS and torsion computed from DENSE and tagging showed similar correlation with global scar size, while when computed from FT, the correlation was lower.

The association of body mass index, weight gain and central obesity with activity-related breathlessness: the Swedish Cardiopulmonary Bioimage Study.

INTRODUCTION: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m2) is rapidly increasing globally and its impact on breathlessness is unclear. METHODS: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score ≥1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex. RESULTS: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m2; and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness. CONCLUSION: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

Cardiovascular biomarkers and echocardiographic findings at rest and during graded hypovolemic stress in women with recurrent vasovagal syncope.

INTRODUCTION: Vasovagal reflex is the most common type of syncope but its etiology is not fully elucidated. Venous return and cardiac output are key in hemodynamic control. The aim of the study was to assess cardiovascular biomarkers and echocardiographic measures at rest and during hypovolemia in women with and without a history of vasovagal syncope. METHODS: Fourteen women (aged 18-30) suffering from recurrent vasovagal syncope and 15 age-matched healthy women were included. Graded lower body negative pressure (LBNP) was used to create central hypovolemic stress until signs of presyncope occurred. Echocardiography was applied at rest and throughout LBNP. Cardiovascular biomarkers: copeptin, mid-regional proadrenomedullin, mid-regional pro-ANP, C-terminal proendothelin-1, and plasma norepinephrine were measured both at rest and throughout graded hypovolemia to presyncope. RESULTS: Women prone to vasovagal syncope presented with a narrower right ventricle (RV) (29 ± 1 vs 32 ± 1 mm, P < .05), smaller left atrium (36 ± 2 vs 47 ± 3 cm3 , P < .01) and lower cardiac output at rest (3.1 ± 0.2 vs 3.7 ± 0.2 L/min, P < .05) and during graded hypovolemia (P < .05). Copeptin was elevated at rest (4.3 ± 0.8 vs 2.5 ± 0.2 pmol/L, P < .05) and increased more in women with vasovagal syncope during progression of LBNP (P < .01). At rest, lower C-terminal proendothelin-1 (35 ± 5 vs 46 ± 2 pmol/L, P < .05) and higher norepinephrine levels (1.1 ± 0.1 vs 0.8 ± 0.1 nmol/L, P < .01) were seen in women with vasovagal syncope. CONCLUSION: Women prone to vasovagal syncope demonstrate reduced cardiac preload, lower cardiac output, as well as increased release of vasopressin in rest and during hypovolemic challenge. The results emphasize the importance of venous return and cardiac output in the pathogenesis of vasovagal syncope.