Normal and reference values for cardiovascular magnetic resonance-based pulse wave velocity in the middle-aged general population.

BACKGROUND: Aortic stiffness, assessed through pulse wave velocity (PWV), is an independent predictor for cardiovascular disease risk. However, the scarce availability of normal and reference values for cardiovascular magnetic resonance imaging (CMR) based PWV is limiting clinical implementation. The aim of this study was to determine normal and reference values for CMR assessed PWV in the general population. METHODS: From the 2,484 participants of the Netherlands Epidemiology of Obesity (NEO) study that have available CMR-PWV data, 1,394 participants free from cardiovasculard disease, smokers or treatment for diabetes, hypertension or dyslipidaemia were selected (45-65 years, 51% female). Participants were divided into sex, age and blood pressure (BP) subgroups. Normal values were specified for participants with a BP < 130/80 mmHg and reference values for elevated BP subgroups (≥ 130/80 and < 140/90 mmHg; and ≥ 140/90 mmHg). Differences between groups were tested with independent samples t-test or ANOVA. Due to an oversampling of obese individuals in this study, PWV values are based on a weighted analysis making them representative of the general population. RESULTS: Normal mean PWV was 6.0 m/s [95% CI 5.8-6.1]. PWV increased with advancing age and BP categories (both p < 0.001). There was no difference between sex in normal PWV, however in the BP > 140/90 mmHg women had a higher PWV (p = 0.005). The interpercentile ranges were smaller for participants < 55 years old compared to participants ≥ 55 years, indicating an increasing variability of PWV with age. PWV upper limits were particularly elevated in participants ≥ 55 years old in the high blood pressure subgroups. CONCLUSION: This study provides normal and reference values for CMR-assessed PWV per sex, age and blood pressure category in the general population.

The role of insulin resistance in the relation of visceral, abdominal subcutaneous and total body fat to cardiovascular function.

BACKGROUND AND AIMS: The separate cardiovascular effects of type 2 diabetes and adiposity remain to be examined. This study aimed to investigate the role of insulin resistance in the relations of visceral (VAT), abdominal subcutaneous (aSAT) adipose tissue and total body fat (TBF) to cardiovascular remodeling. METHODS AND RESULTS: In this cross-sectional analysis of the population-based Netherlands Epidemiology of Obesity study, 914 middle-aged individuals (46% men) were included. Participants underwent magnetic resonance imaging. Standardized linear regression coefficients (95%CI) were calculated, adjusted for potential confounding factors. All fat depots and insulin resistance (HOMA-IR), separate from VAT and TBF, were associated with lower mitral early and late peak filling rate ratios (E/A): -0.04 (-0.09;0.01) per SD (54 cm2) VAT; -0.05 (-0.10;0.00) per SD (94 cm2) aSAT; -0.09 (-0.16;-0.02) per SD (8%) TBF; -0.11 (-0.17;-0.05) per 10-fold increase in HOMA-IR, whereas VAT and TBF were differently associated with left ventricular (LV) end-diastolic volume: -8.9 (-11.7;-6.1) mL per SD VAT; +5.4 (1.1;9.7) mL per SD TBF. After adding HOMA-IR to the model to evaluate the mediating role of insulin resistance, change in E/A was -0.02 (-0.07;0.04) per SD VAT; -0.03 (-0.08;0.02) per SD aSAT; -0.06 (-0.13;0.01) per SD TBF, and change in LV end-diastolic volume was -7.0 (-9.7;-4.3) mL per SD VAT. In women, adiposity but not HOMA-IR was related to higher aortic arch pulse wave velocity. CONCLUSION: Insulin resistance was associated with reduced diastolic function, separately from VAT and TBF, and partly mediated the associations between adiposity depots and lower diastolic function.

Is Hepatic Triglyceride Content Associated with Aortic Pulse Wave Velocity and Carotid Intima-Media Thickness? The Netherlands Epidemiology of Obesity Study.

Purpose To test the hypothesis that hepatic triglyceride content is associated with subclinical vascular impairment and is not confounded by various cardiometabolic risk factors. Materials and Methods This study was approved by the institutional review board, and all participants gave written informed consent. In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, a population-based cohort study, 1899 participants (52% men; mean age, 55 years ± 6 [standard deviation]) underwent magnetic resonance (MR) spectroscopy and MR imaging to assess hepatic triglyceride content, aortic pulse wave velocity (PWV), and visceral fat. Carotid intima-media thickness (IMT) was acquired and measured by trained research nurses according to standard procedures. Multivariate regression analyses were used to study associations of hepatic triglyceride content with total and regional aortic PWV and carotid IMT while adjusting for several possible confounding factors, including the metabolic syndrome. Results Total aortic PWV (mean difference, 0.5 m/sec; 95% confidence interval [CI]: 0.3, 0.7) and carotid IMT (mean difference, 37 µm; 95% CI: 25, 49) were higher in participants with hepatic steatosis. After adjusting for various covariates, a 10-fold increase in hepatic triglyceride content was associated with an increased mean aortic PWV of 0.19 m/sec (95% CI: 0.03, 0.36) in total and an increased mean aortic PWV of 0.42 m/sec (95% CI: 0.03, 0.81) in the abdominal segment. A 10-fold increase in hepatic triglyceride content was also associated with an increased mean carotid IMT of 15 µm (95% CI: 0, 29) but not after additional adjustments for visceral and total body fat. Conclusion In this relatively large population-based cohort study, hepatic triglyceride content was associated with aortic pulse wave velocity and carotid IMT. These associations were only partly explained by the metabolic syndrome and visceral adiposity, suggesting a possible specific contribution of hepatic steatosis to subclinical vascular impairment. © RSNA, 2017 Online supplemental material is available for this article.

Association between Hepatic Triglyceride Content and Left Ventricular Diastolic Function in a Population-based Cohort: The Netherlands Epidemiology of Obesity Study.

PURPOSE: To investigate the association between hepatic triglyceride content and left ventricular (LV) diastolic function while taking potential confounding factors into account, including the components of the metabolic syndrome. MATERIALS AND METHODS: The study was approved by the institutional review board, and all participants gave informed consent. In this cross-sectional analysis of baseline data from the Netherlands Epidemiology of Obesity study, a population-based, prospective cohort study, participants (45% men; mean age ± standard deviation, 55.3 years ± 6.2) underwent magnetic resonance (MR) spectroscopy and MR imaging to assess hepatic triglyceride content and LV diastolic heart function (ratio of peak filling rates of the early filling phase and atrial contraction [E/A ratio]). Multivariate linear regression analysis was performed while adjusting for confounding factors, and results were additionally stratified according to body mass index. RESULTS: Adjustment for age, sex, heart rate, alcohol consumption, pack-years of smoking, all components of the metabolic syndrome, and visceral adiposity attenuated crude observed associations. A 10-fold increase in hepatic triglyceride content was associated with a change in mean E/A ratio of -0.004 (95% confidence interval [CI]: -0.134, 0.125) in the total study population, -0.194 (95% CI: -0.430, 0.042) in the normal-weight subgroup, 0.079 (95% CI: -0.090, 0.248) in the overweight subgroup, and -0.109 (95% CI: -0.186, -0.032) in the obese subgroup. CONCLUSION: Fatty liver itself could, at least in obesity, pose a risk of myocardial dysfunction above and beyond known cardiovascular risk factors that are clustered within the metabolic syndrome. The association in the obese subgroup was small, and future studies with larger samples sizes are required to investigate to what extent the association exists and differs in normal-weight, overweight, and obese persons to unravel its clinical relevance.

Exercise and type 2 diabetes mellitus: changes in tissue-specific fat distribution and cardiac function.

PURPOSE: To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. MATERIALS AND METHODS: Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. RESULTS: Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P < .01), and subcutaneous abdominal fat volume remained unchanged (P = .9). Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P < .01) and paracardial fat volume from 4.6 mL ± 0.9 to 3.7 mL ± 0.8 (P = .02). Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). CONCLUSION: A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study.

Estimated pulse wave velocity (ePWV) as a potential gatekeeper for MRI-assessed PWV: a linear and deep neural network based approach in 2254 participants of the Netherlands Epidemiology of Obesity study.

Pulse wave velocity (PWV) assessed by magnetic resonance imaging (MRI) is a prognostic marker for cardiovascular events. Prediction modelling could enable indirect PWV assessment based on clinical and anthropometric data. The aim was to calculate estimated-PWV (ePWV) based on clinical and anthropometric measures using linear ridge regression as well as a Deep Neural Network (DNN) and to determine the cut-off which provides optimal discriminative performance between lower and higher PWV values. In total 2254 participants from the Netherlands Epidemiology of Obesity study were included (age 45-65 years, 51% male). Both a basic and expanded prediction model were developed. PWV was estimated using linear ridge regression and DNN. External validation was performed in 114 participants (age 30-70 years, 54% female). Performance was compared between models and estimation accuracy was evaluated by ROC-curves. A cut-off for optimal discriminative performance was determined using Youden's index. The basic ridge regression model provided an adjusted R2 of 0.33 and bias of < 0.001, the expanded model did not add predictive performance. Basic and expanded DNN models showed similar model performance. Optimal discriminative performance was found for PWV < 6.7 m/s. In external validation expanded ridge regression provided the best performance of the four models (adjusted R2: 0.29). All models showed good discriminative performance for PWV < 6.7 m/s (AUC range 0.81-0.89). ePWV showed good discriminative performance with regard to differentiating individuals with lower PWV values (< 6.7 m/s) from those with higher values, and could function as gatekeeper in selecting patients who benefit from further MRI-based PWV assessment.

Validation and Feasibility of Echocardiographic Assessment of Systemic Right Ventricular Function: Serial Correlation With MRI.

Background: Inherent to its geometry, echocardiographic imaging of the systemic right ventricle (RV) is challenging. Therefore, echocardiographic assessment of systemic RV function may not always be feasible and/or reproducible in daily practice. Here, we aim to validate the usefulness of a comprehensive range of 32 echocardiographic measurements of systemic RV function in a longitudinal cohort by serial assessment of their correlations with cardiac magnetic resonance (CMR)-derived systemic RV ejection fraction (RVEF). Methods: A single-center, retrospective cohort study was performed. Adult patients with a systemic RV who underwent a combination of both CMR and echocardiography at two different points in time were included. Off-line analysis of echocardiographic images was blinded to off-line CMR analysis and vice versa. In half of the echocardiograms, measurements were repeated by a second observer blinded to the results of the first. Correlations between echocardiographic and CMR measures were assessed with Pearson's correlation coefficient and interobserver agreement was quantified with intraclass correlation coefficients (ICC). Results: Fourteen patients were included, of which 4 had congenitally corrected transposition of the great arteries (ccTGA) and 10 patients had TGA late after an atrial switch operation. Eight patients (57%) were female. There was a mean of 8 years between the first and second imaging assessment. Only global systemic RV function, fractional area change (FAC), and global longitudinal strain (GLS) were consistently, i.e., at both time points, correlated with CMR-RVEF (global RV function: r = -0.77/r = -0.63; FAC: r = 0.79/r = 0.67; GLS: r = -0.73/r = -0.70, all p-values < 0.05). The ICC of GLS (0.82 at t = 1, p = 0.006, 0.77 at t = 2, p = 0.024) was higher than the ICC of FAC (0.35 at t = 1, p = 0.196, 0.70 at t = 2, p = 0.051) at both time points. Conclusion: GLS appears to be the most robust echocardiographic measurement of systemic RV function with good correlation with CMR-RVEF and reproducibility.

Endobronchial ultrasound for T4 staging in patients with resectable NSCLC.

BACKGROUND: In lung cancer patients, accurate assessment of mediastinal and vascular tumor invasion (stage T4) is crucial for optimal treatment allocation and to prevent unnecessary thoracotomies. We assessed the diagnostic accuracy of linear endobronchial ultrasound (EBUS) for T4-status in patients with centrally located lung cancer. METHODS: This is a retrospective study among consecutive patients who underwent EBUS for diagnosis and staging of lung cancer in four hospitals in The Netherlands (Amsterdam, Leiden), Italy (Bologna) and Poland (Zakopane) between 04-2012 and 04-2019. Patients were included if the primary tumor was detected by EBUS and subsequent surgical-pathological staging was performed, which served as the reference standard. T4-status was extracted from EBUS and pathology reports. Chest CT's were re-reviewed for T4-status. RESULTS: 104 patients with lung cancer in whom EBUS detected the primary tumour, and who underwent subsequent surgical-pathological staging were included. 36 patients (35 %) had T4-status, based on vascular (n = 17), mediastinal (n = 15), both vascular and mediastinal (n = 3), or oesophageal invasion (n = 1). For EBUS, sensitivity, specificity, PPV and NPV for T4-status were (n = 104): 63.9 % (95 %CI 46.2-79.2 %), 92.6 % (83.7-97.6 %), 82.1 % (65.6-91.7 %), and 82.9 % (75.7-88.2 %), respectively. For chest CT (n = 72): 61.5 % (95 %CI 40.6-79.8 %), 37.0 % (23.2-52.5 %), 35.6 % (27.5-44.6 %), and 63.0 % (47.9-75.9 %), respectively. When combining CT and EBUS with concordant T4 status (n = 33): 90.9 % (95 %CI 58.7-99.8 %), 77.3 % (54.6-92.20 %), 66.7 % (47.5-81.6 %), and 94.4 % (721-99.1%), respectively. CONCLUSION: Both EBUS and CT alone are inaccurate for assessing T4-status as standalone test. However, combining a negative EBUS with a negative CT may rule out T4-status with high certainty.

Malignant Epithelial Transformation in Phyllodes Tumor: A Population-Based Case Series.

Background Phyllodes tumor (PT) of the breast is an uncommon fibroepithelial neoplasm. Malignant epithelial transformation in PT is rare. This study reports clinicopathologic characteristics and outcomes of patients with malignant epithelial transformation in PT. Methods From an institutional database of 183 patients with newly diagnosed PT referred to a Canadian provincial cancer institution between 1999 and 2014, 11 cases of PT with concomitant in situ or invasive carcinoma were identified. Descriptive analysis was performed to document the characteristics, treatment and outcomes of this cohort. Results Prevalence of malignant epithelial transformation in PT was 6.0%. Median (range) age was 54 (35-75) years. Types of carcinoma were ductal carcinoma in situ (DCIS) (n = 6), lobular carcinoma in situ (n = 4), and invasive ductal carcinoma (IDC) (n = 1). Median PT size was 5 (1-15) cm. Three PTs were classified as benign (27%), five as borderline (45%), and three as malignant (27%). Mastectomy was performed in six (55%) and breast conserving surgery in five (45%) patients. Hormonal therapy was used in two cases: one with a 1 cm, grade 2 DCIS, and one with an 11 cm, grade 1 IDC, the latter also receiving radiotherapy. Mean follow-up duration was 54 (6-175) months. None of the cases showed any evidence of disease after treatment at the time of their last follow-up. Conclusion This case series showed a higher prevalence of malignant epithelial transformation in PT than reported in previous literature. Outcomes were favourable despite the presence of either in situ or invasive carcinoma within PT.

Individual contributions of visceral fat and total body fat to subclinical atherosclerosis: The NEO study.

BACKGROUND: Both overall and abdominal adiposity are established risk factors for cardiovascular disease. Visceral adipose tissue (VAT) and total body fat (TBF) are strongly correlated and previous studies did not make this distinction. OBJECTIVE: We aimed to distinguish individual contributions of TBF, VAT, and the ratio of VAT to abdominal subcutaneous adipose tissue (VAT/SAT) to subclinical atherosclerosis in men and women. METHODS: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity (NEO) study, we assessed VAT and SAT with magnetic resonance imaging, TBF with bio-electrical impendence analysis, and carotid Intima-Media Thickness (cIMT) with ultrasound. We performed linear regression analyses of standardized values of TBF, VAT, VAT/SAT with cIMT. We adjusted the models for confounding factors (age, sex, ethnicity, education, smoking, alcohol, physical activity), and either for VAT or TBF. RESULTS: This analysis included 2451 participants, 53% men with mean (SD) cIMT of 615 (91)µm. After adjustment for confounding factors, the difference in cIMT (95% CI) per SD in VAT was 14 (8,21)µm in men and 18 (13,24)µm in women. After adjustment for TBF, this attenuated to 5 (-3,13)µm in men and 13 (5,20)µm in women. In the full model, differences in cIMT (95% CI) per SD of TBF were 14 (6,22)µm in men and 8 (0,16)µm in women, and per SD of VAT/SAT were 7 (-1,15)µm and 9 (3,16)µm respectively. CONCLUSIONS: In this population-based study, VAT contributed beyond overall adiposity to subclinical atherosclerosis, particularly in women. This implies a specific role of VAT in the early development of atherosclerosis.