Four-dimensional flow cardiovascular magnetic resonance aortic cross-sectional pressure changes and their associations with flow patterns in health and ascending thoracic aortic aneurysm.

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is a silent and threatening dilation of the ascending aorta (AscAo). Maximal aortic diameter which is currently used for ATAA patients management and surgery planning has been shown to inadequately characterize risk of dissection in a large proportion of patients. Our aim was to propose a comprehensive quantitative evaluation of aortic morphology and pressure-flow-wall associations from four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) data in healthy aging and in patients with ATAA. METHODS: We studied 17 ATAA patients (64.7 ± 14.3 years, 5 females) along with 17 age- and sex-matched healthy controls (59.7 ± 13.3 years, 5 females) and 13 younger healthy subjects (33.5 ± 11.1 years, 4 females). All subjects underwent a CMR exam, including 4D flow and three-dimensional anatomical images of the aorta. This latter dataset was used for aortic morphology measurements, including AscAo maximal diameter (iDMAX) and volume, indexed to body surface area. 4D flow MRI data were used to estimate 1) cross-sectional local AscAo spatial (∆PS) and temporal (∆PT) pressure changes as well as the distance (∆DPS) and time duration (∆TPT) between local pressure peaks, 2) AscAo maximal wall shear stress (WSSMAX) at peak systole, and 3) AscAo flow vorticity amplitude (VMAX), duration (VFWHM), and eccentricity (VECC). RESULTS: Consistency of flow and pressure indices was demonstrated through their significant associations with AscAo iDMAX (WSSMAX:r = -0.49, p < 0.001; VECC:r = -0.29, p = 0.045; VFWHM:r = 0.48, p < 0.001; ∆DPS:r = 0.37, p = 0.010; ∆TPT:r = -0.52, p < 0.001) and indexed volume (WSSMAX:r = -0.63, VECC:r = -0.51, VFWHM:r = 0.53, ∆DPS:r = 0.54, ∆TPT:r = -0.63, p < 0.001 for all). Intra-AscAo cross-sectional pressure difference, ∆PS, was significantly and positively associated with both VMAX (r = 0.55, p = 0.002) and WSSMAX (r = 0.59, p < 0.001) in the 30 healthy subjects (48.3 ± 18.0 years). Associations remained significant after adjustment for iDMAX, age, and systolic blood pressure. Superimposition of ATAA patients to normal aging trends between ∆PS and WSSMAX as well as VMAX allowed identifying patients with substantially high pressure differences concomitant with AscAo dilation. CONCLUSION: Local variations in pressures within ascending aortic cross-sections derived from 4D flow MRI were associated with flow changes, as quantified by vorticity, and with stress exerted by blood on the aortic wall, as quantified by wall shear stress. Such flow-wall and pressure interactions might help for the identification of at-risk patients.

Deep Learning-Based Analysis of Aortic Morphology From Three-Dimensional MRI.

BACKGROUND: Quantification of aortic morphology plays an important role in the evaluation and follow-up assessment of patients with aortic diseases, but often requires labor-intensive and operator-dependent measurements. Automatic solutions would help enhance their quality and reproducibility. PURPOSE: To design a deep learning (DL)-based automated approach for aortic landmarks and lumen detection derived from three-dimensional (3D) MRI. STUDY TYPE: Retrospective. POPULATION: Three hundred ninety-one individuals (female: 47%, age = 51.9 ± 18.4) from three sites, including healthy subjects and patients (hypertension, aortic dilation, Turner syndrome), randomly divided into training/validation/test datasets (N = 236/77/78). Twenty-five subjects were randomly selected and analyzed by three operators with different levels of expertise. FIELD STRENGTH/SEQUENCE: 1.5-T and 3-T, 3D spoiled gradient-recalled or steady-state free precession sequences. ASSESSMENT: Reinforcement learning and a two-stage network trained using reference landmarks and segmentation from an existing semi-automatic software were used for aortic landmark detection and segmentation from sinotubular junction to coeliac trunk. Aortic segments were defined using the detected landmarks while the aortic centerline was extracted from the segmentation and morphological indices (length, aortic diameter, and volume) were computed for both the reference and the proposed segmentations. STATISTICAL TESTS: Segmentation: Dice similarity coefficient (DSC), Hausdorff distance (HD), average symmetrical surface distance (ASSD); landmark detection: Euclidian distance (ED); model robustness: Spearman correlation, Bland-Altman analysis, Kruskal-Wallis test for comparisons between reference and DL-derived aortic indices; inter-observer study: Williams index (WI). A WI 95% confidence interval (CI) lower bound >1 indicates that the method is within the inter-observer variability. A P-value <0.05 was considered statistically significant. RESULTS: DSC was 0.90 ± 0.05, HD was 12.11 ± 7.79 mm, and ASSD was 1.07 ± 0.63 mm. ED was 5.0 ± 6.1 mm. A good agreement was found between all DL-derived and reference aortic indices (r >0.95, mean bias <7%). Our segmentation and landmark detection performances were within the inter-observer variability except the sinotubular junction landmark (CI = 0.96;1.04). DATA CONCLUSION: A DL-based aortic segmentation and anatomical landmark detection approach was developed and applied to 3D MRI data for achieve aortic morphology evaluation. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Increase in intracellular and extracellular myocardial mass in patients with acromegaly: a cardiac magnetic resonance imaging study.

BACKGROUND: Acromegaly is associated with an increased left ventricular (LV) mass, as reported in echo-based and, more recently, in a few cardiac magnetic resonance imaging (MRI) studies. One possible explanation for this increased LV mass could be water retention and subsequent myocardial edema. METHODS: In this prospective cross-sectional study, 26 patients with active acromegaly before and after treatment and 31 controls of comparable age and sex were investigated using cardiac MRI. Cardiac morphology, function, and myocardial tissue characteristics were evaluated. Myocardial T2 relaxation time was used as the main outcome measure of myocardial edema. The study was registered with clinicaltrials.gov (NCT02948322). RESULTS: Patients compared to controls had greater LV mass indexes (58.1 [54.7-68.6] vs 46.0 [41.3-49.8] g/m2; P < .001) and end-diastolic volume (EDV) indexes (97.3 [88-101.2] vs 81.6 [78.1-96.2] mL/m2; P = .0069) and had comparable global contractile function. T2 values were not different between patients and controls. Both intracellular (43.83 [41.0-50.0] vs 34.32 [28.9-38.7] g/m2; P < .001) and extracellular (15.06 [13.5-17.1] vs 11.6 [10.8-12.7] g/m2; P < .001) LV mass indexes were higher in patients compared to controls. Log growth hormone correlated with myocardial mass (r = 0.75; P < .001). Sex, systolic blood pressure (BP), and the presence of acromegaly were predictors of the LV mass index. The extracellular LV mass index was associated with sex and the presence of acromegaly, whereas the intracellular LV mass index was associated with sex, systolic BP, and high-density lipoprotein (HDL) cholesterol. Acromegaly treatment reduced EDV and total and intracellular LV mass indexes without significantly affecting extracellular mass. CONCLUSION: Acromegaly results in a disease-specific form of LV hypertrophic remodeling, characterized by an increase in both intra- and extracellular mass. The LV mass index and intracellular mass were decreased by treatment.

Association between Biomarkers of Inflammation and 10-Year Changes in Aortic Stiffness: The Multi-Ethnic Study of Atherosclerosis.

Background. Chronic inflammation is associated with incident cardiovascular events. We study the association between biomarkers of inflammation and subclinical vascular dysfunction measured as proximal aortic stiffness. Methods. MRI imaging was performed in the Multi-Ethnic Study of Atherosclerosis (MESA) at baseline (2000) and at the 10-year follow-up. Aortic arch pulse wave velocity (PWV) and ascending and descending aorta distensibility (AAD, DAD) were measured in 1223 asymptomatic individuals at both exams. Linear regression was used to study the association of baseline inflammation-C-reactive protein (CRP), interleukin-6 (IL6), and fibrinogen (Fib)-with baseline and 10-year changes in aortic stiffness (PWV, AAD, DAD). Results. The mean age of the participants was 59 ± 9 years, 47.8% of them were men, 32.6% were hypertensive at baseline, and 7.6% were diabetic. At baseline and follow-up, the mean AAD values were, respectively, 1.73 × 10-3 mmHg-1 and 1.57 × 10-3 mmHg-1, the mean DAD values were 2.19 × 10-3 mmHg-1 and 1.99 × 10-3 mmHg-1, and the mean PWV values were 8.10 m/s and 8.99 m/s. At baseline, the AAD (in 10-3 mmHg-1) and DAD (in 10-3 mmHg-1) were inversely associated with CRP (in mg/L) (AAD coeff: -0.047, p-value: 0.011, DAD coeff: -0.068, p-value: <0.001) and IL6 (in pg/mL) (AAD coeff: -0.098, p-value: 0.003, DAD coeff: -0.14, p-value: <0.001) in a univariable analysis but not after adjustment for demographic variables or cardiovascular risk factors. The baseline DAD was inversely associated with Fib (in mg/dL) (coeff: -0.334, p-value: 0.001). The baseline PWV (in m/s) was positively associated with IL6 (in pg/mL) in a univariable analysis (coeff: 0.054, p-value: 0.014). In a longitudinal analysis, the 10-year changes in DAD were inversely associated with CRP, even after adjustment for demographics and risk factors (DAD coeff: -0.08, p-value 0.044). Conclusions. Higher CRP levels at baseline were independently associated with a 10-year increase in aortic stiffness, measured as decreased aortic distensibility.

Is increased myocardial triglyceride content associated with early changes in left ventricular function? A 1H-MRS and MRI strain study.

Background: Type 2 diabetes (T2D) and obesity induce left ventricular (LV) dysfunction. The underlying pathophysiological mechanisms remain unclear, but myocardial triglyceride content (MTGC) could be involved. Objectives: This study aimed to determine which clinical and biological factors are associated with increased MTGC and to establish whether MTGC is associated with early changes in LV function. Methods: A retrospective study was conducted using five previous prospective cohorts, leading to 338 subjects studied, including 208 well-phenotyped healthy volunteers and 130 subjects living with T2D and/or obesity. All the subjects underwent proton magnetic resonance spectroscopy and feature tracking cardiac magnetic resonance imaging to measure myocardial strain. Results: MTGC content increased with age, body mass index (BMI), waist circumference, T2D, obesity, hypertension, and dyslipidemia, but the only independent correlate found in multivariate analysis was BMI (p=0.01; R²=0.20). MTGC was correlated to LV diastolic dysfunction, notably with the global peak early diastolic circumferential strain rate (r=-0.17, p=0.003), the global peak late diastolic circumferential strain rate (r=0.40, p<0.0001) and global peak late diastolic longitudinal strain rate (r=0.24, p<0.0001). MTGC was also correlated to systolic dysfunction via end-systolic volume index (r=-0.34, p<0.0001) and stroke volume index (r=-0.31, p<0.0001), but not with longitudinal strain (r=0.009, p=0.88). Interestingly, the associations between MTGC and strain measures did not persist in multivariate analysis. Furthermore, MTGC was independently associated with LV end-systolic volume index (p=0.01, R²=0.29), LV end-diastolic volume index (p=0.04, R²=0.46), and LV mass (p=0.002, R²=0.58). Conclusions: Predicting MTGC remains a challenge in routine clinical practice, as only BMI independently correlates with increased MTGC. MTGC may play a role in LV dysfunction but does not appear to be involved in the development of subclinical strain abnormalities.

Aortic Stiffness Measured from Either 2D/4D Flow and Cine MRI or Applanation Tonometry in Coronary Artery Disease: A Case-Control Study.

BACKGROUND AND OBJECTIVE: Aortic stiffness can be evaluated by aortic distensibility or pulse wave velocity (PWV) using applanation tonometry, 2D phase contrast (PC) MRI and the emerging 4D flow MRI. However, such MRI tools may reach their technical limitations in populations with cardiovascular disease. Accordingly, this work focuses on the diagnostic value of aortic stiffness evaluated either by applanation tonometry or MRI in high-risk coronary artery disease (CAD) patients. METHODS: 35 patients with a multivessel CAD and a myocardial infarction treated 1 year before were prospectively recruited and compared with 18 controls with equivalent age and sex distribution. Ascending aorta distensibility and aortic arch 2D PWV were estimated along with 4D PWV. Furthermore, applanation tonometry carotid-to-femoral PWV (cf PWV) was recorded immediately after MRI. RESULTS: While no significant changes were found for aortic distensibility; cf PWV, 2D PWV and 4D PWV were significantly higher in CAD patients than controls (12.7 ± 2.9 vs. 9.6 ± 1.1; 11.0 ± 3.4 vs. 8.0 ± 2.05 and 17.3 ± 4.0 vs. 8.7 ± 2.5 m·s-1 respectively, p < 0.001). The receiver operating characteristic (ROC) analysis performed to assess the ability of stiffness indices to separate CAD subjects from controls revealed the highest area under the curve (AUC) for 4D PWV (0.97) with an optimal threshold of 12.9 m·s-1 (sensitivity of 88.6% and specificity of 94.4%). CONCLUSIONS: PWV estimated from 4D flow MRI showed the best diagnostic performances in identifying severe stable CAD patients from age and sex-matched controls, as compared to 2D flow MRI PWV, cf PWV and aortic distensibility.

Associations of aortic stiffness and intra-aortic flow parameters with epicardial adipose tissue in patients with type-2 diabetes.

Background: It has been shown that increased aortic stiffness is related to type-2 diabetes (T2D) which is considered as a risk factor for cardiovascular disease. Among other risk factors is epicardial adipose tissue (EAT) which is increased in T2D and is a relevant biomarker of metabolic severity and adverse outcome. Purpose: To assess aortic flow parameters in T2D patients as compared to healthy individuals and to evaluate their associations with EAT accumulation as an index of cardiometabolic severity in T2D patients. Materials and methods: Thirty-six T2D patients as well as 29 healthy controls matched by age and sex were included in this study. Participants had cardiac and aortic MRI exams at 1.5 T. Imaging sequences included cine SSFP for left ventricle (LV) function and EAT assessment and aortic cine and phase-contrast imaging for strain and flow parameters quantification. Results: In this study, we found LV phenotype to be characterized by concentric remodeling with decreased stroke volume index despite global LV mass within a normal range. EAT was increased in T2D patients compared to controls (p<0.0001). Moreover, EAT, a biomarker of metabolic severity, was negatively correlated to ascending aortic (AA) distensibility (p=0.048) and positively to the normalized backward flow volume (p=0.001). These relationships remained significant after further adjustment for age, sex and central mean blood pressure. In a multivariate model, presence/absence of T2D and AA normalized backward flow (BF) to forward flow (FF) volumes ratio are both significant and independent correlates of EAT. Conclusion: In our study, aortic stiffness as depicted by an increased backward flow volume and decreased distensibility seems to be related to EAT volume in T2D patients. This observation should be confirmed in the future on a larger population while considering additional biomarkers specific to inflammation and using a longitudinal prospective study design.

Acute stress induces long-term metabolic, functional, and structural remodeling of the heart.

Takotsubo cardiomyopathy is a stress-induced cardiovascular disease with symptoms comparable to those of an acute coronary syndrome but without coronary obstruction. Takotsubo was initially considered spontaneously reversible, but epidemiological studies revealed significant long-term morbidity and mortality, the reason for which is unknown. Here, we show in a female rodent model that a single pharmacological challenge creates a stress-induced cardiomyopathy similar to Takotsubo. The acute response involves changes in blood and tissue biomarkers and in cardiac in vivo imaging acquired with ultrasound, magnetic resonance and positron emission tomography. Longitudinal follow up using in vivo imaging, histochemistry, protein and proteomics analyses evidences a continued metabolic reprogramming of the heart towards metabolic malfunction, eventually leading to irreversible damage in cardiac function and structure. The results combat the supposed reversibility of Takotsubo, point to dysregulation of glucose metabolic pathways as a main cause of long-term cardiac disease and support early therapeutic management of Takotsubo.

Value of aortic volumes assessed by automated segmentation of 3D MRI data in patients with thoracic aortic dilatation: A case-control study.

PURPOSE: The purpose of this study was to investigate the benefit of aortic volumes compared to diameters or cross-sectional areas on three-dimensional (3D) magnetic resonance imaging (MRI) in discriminating between patients with dilated aorta and matched controls. MATERIALS AND METHODS: Sixty-two patients (47 men and 15 women; median age, 66 years; age range: 33-86 years) with tricuspid aortic valve and ascending thoracic aorta aneurysm (TAV-ATAA) and 43 patients (35 men and 8 women; median age, 51 years; age range: 17-76 years) with bicuspid aortic valve and dilated ascending aorta (BAV) were studied. One group of 54 controls matched for age and sex to patients with TAV-ATAA (39 men and 15 women; median age, 68 years; age range: 33-81 years) and one group of 42 controls matched for age and sex to patients with BAV (34 men and 8 women; median age, 50 years; age range: 17-77 years) were identified. All participants underwent 3D MRI, used for 3D-segmentation for measuring aortic length, maximal diameter, maximal cross-sectional area (CSA) and volume for the ascending aorta. RESULTS: An increase in ascending aorta volume (TAV-ATAA: +107%; BAV: +171% vs. controls; P < 0.001) was found, which was three times greater than the increase in diameter (TAV-ATAA: +29%; BAV: +40% vs. controls; P < 0.001). In differentiating patients with TAV-ATAA from their controls, the indexed ascending aorta volume showed better performances (AUC, 0.935 [95% confidence interval (CI): 0.882-0.989]; accuracy, 88.7% [95% CI: 82.9-94.5]) than indexed ascending aorta length (P < 0.001), indexed ascending aorta maximal diameter (P = 0.003) and indexed ascending aorta maximal CSA (P = 0.03). In differentiating patients with BAV from matched controls, indexed ascending aorta volume showed significantly better performances performance (AUC, 0.908 [95% CI: 0.829-0.987]; accuracy, 88.0% [95% CI: 80.9-95.0]) than indexed ascending aorta length (P = 0.02) and not different from indexed ascending aorta maximal diameter (P = 0.07) or from indexed ascending aorta maximal CSA (P = 0.27) CONCLUSION: Aortic volume measured by 3D-MRI integrates both elongation and luminal dilatation, resulting in greater classification performance than maximal diameter and length in differentiating patients with dilated ascending aorta or aneurysm from controls.

Feasibility of a New Regional Myocardial Strain Parameter for the Detection of Wall Motion Abnormalities in Arrhythmogenic Right Ventricular Cardiomyopathy.

Purpose: To evaluate a cardiac MRI feature tracking (FT)-derived parameter that combines right ventricular (RV) longitudinal and radial motions in detecting arrhythmogenic right ventricular cardiomyopathy (ARVC). Materials and Methods: Patients with ARVC (n = 47; median age, 46 [IQR, 30-52] years; 31 men) were compared with controls (n = 39; median age, 46 [IQR, 33-53] years; 23 men) and separated into two groups based on fulfillment of major structural 2020 International criteria. Cine data from 1.5-T cardiac MRI examinations were analyzed using FT, resulting in conventional strain parameters and a novel composite index named the longitudinal-to-radial strain loop (LRSL). Receiver operating characteristic (ROC) analysis was used to assess diagnostic performance of RV parameters. Results: Volumetric parameters differed significantly between patients in the major structural criteria group and controls but not between patients in the no major structural criteria group and controls. Patients in the major structural criteria group had significantly lower magnitudes of all FT parameters than controls, including RV basal longitudinal strain, radial motion fraction, circumferential strain, and LRSL (-15.6% ± 6.4 vs -26.7% ± 13.9; -9.6% ± 4.89 vs -13.8% ± 4.7; -6.9% ± 4.6 vs -10.1% ± 3.8; and 217.0 ± 128.9 versus 618.6 ± 356.3, respectively). Only LRSL differed between patients in the no major structural criteria group and controls (359.5 ± 195.8 vs 618.6 ± 356.3; P < .0001). Parameters with the highest area under the ROC curve values for discriminating patients in the no major structural criteria group from controls were LRSL, RV ejection fraction, and RV basal longitudinal strain (0.75, 0.70, and 0.61, respectively). Conclusion: A new parameter combining RV longitudinal and radial motions showed good diagnostic performance in ARVC, even in patients without major structural abnormalities.Keywords: Arrhythmogenic Right Ventricular Dysplasia, Strain, Wall Motion Abnormalities, Right Ventricle, MRI, Inherited Cardiomyopathy Supplemental material is available for this article. © RSNA, 2023.

Firibastat Versus Ramipril After Acute Mechanical Reperfusion of Anterior Myocardial Infarction: A Phase 2 Study.

BACKGROUND: Preclinical data suggest that central renin-angiotensin system blockade by the brain aminopeptidase-A inhibitor firibastat can improve left ventricular ejection fraction (LVEF) after myocardial infarction (MI). OBJECTIVES: This study aimed to compare the effect of firibastat versus ramipril on post-MI LVEF. METHODS: In this phase 2, randomized, double-blind trial, patients selected within 24 h of first acute anterior MI treated by primary percutaneous coronary intervention were randomly assigned (1:1:1) to firibastat 100 mg, firibastat 500 mg or ramipril 5 mg, each twice daily for 12 weeks. The primary endpoint was change in LVEF on cardiac magnetic resonance imaging (cMRI) from baseline to day 84 in the modified intent-to-treat (mITT) population (at least one dose received and one follow-up cMRI available) for each treatment group. RESULTS: From June 4, 2019 to April 12, 2021, 294 patients were randomized and 229 were evaluable for the mITT analysis. After 12 weeks, mean ± standard deviation (SD) percent change in LVEF was 5.6 ± 1.2 with firibastat 100 mg, 5.3 ± 1.1 with firibastat 500 mg and 5.7 ± 1.1 with ramipril. The absolute ± SE adjusted difference in LVEF change from baseline between firibastat 500 mg and ramipril was - 0.36 ± 1.32% (p = 0.79). Occurrence of treatment-related adverse events was similar in the three groups. CONCLUSIONS: Firibastat was not superior to ramipril for prevention of left ventricular dysfunction after first acute anterior MI, and their safety profiles were similar. REGISTRATION: ClinicalTrials.gov identifier NCT03715998.

Cardiac adipose tissue volume assessed by computed tomography is a specific and independent predictor of early mortality and critical illness in COVID-19 in type 2-diabetic patients.

BACKGROUND: Patients with type 2-diabetes mellitus (T2D), are characterized by visceral and ectopic adipose tissue expansion, leading to systemic chronic low-grade inflammation. As visceral adiposity is associated with severe COVID-19 irrespective of obesity, we aimed to evaluate and compare the predictive value for early intensive care or death of three fat depots (cardiac, visceral and subcutaneous) using computed tomography (CT) at admission for COVID-19 in consecutive patients with and without T2D. METHODS: Two hundred and two patients admitted for COVID-19 were retrospectively included between February and June 2020 and distributed in two groups: T2D or non-diabetic controls. Chest CT with cardiac (CATi), visceral (VATi) and subcutaneous adipose tissue (SATi) volume measurements were performed at admission. The primary endpoint was a composite outcome criteria including death or ICU admission at day 21 after admission. Threshold values of adipose tissue components predicting adverse outcome were determined. RESULTS: One hundred and eight controls [median age: 76(IQR:59-83), 61% male, median BMI: 24(22-27)] and ninety-four T2D patients [median age: 70(IQR:61-77), 70% male, median BMI: 27(24-31)], were enrolled in this study. At day 21 after admission, 42 patients (21%) had died from COVID-19, 48 (24%) required intensive care and 112 (55%) were admitted to a conventional care unit (CMU). In T2D, CATi was associated with early death or ICU independently from age, sex, BMI, dyslipidemia, CRP and coronary calcium (CAC). (p = 0.005). Concerning T2D patients, the cut-point for CATi was > 100 mL/m2 with a sensitivity of 0.83 and a specificity of 0.50 (AUC = 0.67, p = 0.004) and an OR of 4.71 for early ICU admission or mortality (p = 0.002) in the fully adjusted model. Other adipose tissues SATi or VATi were not significantly associated with early adverse outcomes. In control patients, age and male sex (OR = 1.03, p = 0.04) were the only predictors of ICU or death. CONCLUSIONS: Cardiac adipose tissue volume measured in CT at admission was independently predictive of early intensive care or death in T2D patients with COVID-19 but not in non-diabetics. Such automated CT measurement could be used in routine in diabetic patients presenting with moderate to severe COVID-19 illness to optimize individual management and prevent critical evolution.

Diastolic Function Assessment of Left and Right Ventricles by MRI in Systemic Sclerosis Patients.

BACKGROUND: Heart involvement is frequent although often clinically silent in systemic sclerosis (SSc) patients. Early identification of cardiac involvement can be improved by noninvasive methods such as MRI, in addition to transthoracic echocardiography (TTE). PURPOSE: To assess the ability of phase-contrast (PC)-MRI to detect subclinical left (LV) and right (RV) ventricular diastolic dysfunction in SSc patients. STUDY TYPE: Prospective. POPULATION: Thirty-five consecutive SSc patients (49 ± 14 years) and 35 sex- and age-matched healthy controls (48.6 ± 13.5 years) who underwent TTE and MRI in the same week. FIELD STRENGTH/SEQUENCE: 5 T/PC-MRI using a breath-hold velocity-encoded gradient echo sequence. ASSESSMENT: LV TTE (E/E') and LV and RV PC-MRI indices of diastolic function (LV early and late transmitral [EM , EfM , AM , AfM ] and RV transtricuspid [ET , EfT , AT , AfT ] peak filling flow velocities and flow rates, as well as LV [ E M ' ] and RV [ E T ' ] peak longitudinal myocardial velocities during diastole) were measured. STATISTICAL TESTS: Two-tailed t-test, Wilcoxon test, or Fischer test for comparison of variables between SSc and healthy control groups; sensitivity, specificity, receiver-operating-characteristic (ROC) area under the curve (AUC) to assess discriminative ability of variables. A P-value <0.05 was considered statistically significant. RESULTS: TTE LV E/E' and MRI EM / E M ' and ET / E T ' were significantly higher in SSc patients than in controls (8.27 ± 1.25 vs. 6.70 ± 1.66; 9.43 ± 2.7 vs. 6.51 ± 1.50; 6.51 [4.70-10.40] vs. 4.13 [3.22-5.75], respectively) and separated SSc patients and healthy controls with good sensitivity (68%, 71%, and 80%), specificity (85%, 94%, and 62%), and AUC (0.787, 0.807, and 0.765). LV EfM was significantly higher in SSc patients than in controls (347.1 ± 113.7 vs. 284.7 ± 94.6) as RVAfT (277 [231-355] vs. 220 [154-253] mL/sec) with impaired relaxation pattern (EfT /AfT , 0.95 [0.87-1.21] vs. 1.12 [0.93-1.47]). DATA CONCLUSION: MRI was able to detect LV and RV diastolic dysfunction in SSc patients with good accuracy in the absence of LV systolic dysfunction at echocardiography. Use of MRI can allow to better assess the early impact of myocardial fibrosis related to SSc. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Deep Learning-based Automated Aortic Area and Distensibility Assessment: the Multi-Ethnic Study of Atherosclerosis (MESA).

This study details application of deep learning for automatic segmentation of the ascending and descending aorta from 2D phase-contrast cine magnetic resonance imaging for automatic aortic analysis on the large MESA cohort with assessment on an external cohort of thoracic aortic aneurysm (TAA) patients. This study includes images and corresponding analysis of the ascending and descending aorta at the pulmonary artery bifurcation from the MESA study. Train, validation, and internal test sets consisted of 1123 studies (24,282 images), 374 studies (8067 images), and 375 studies (8069 images), respectively. The external test set of TAAs consisted of 37 studies (3224 images). CNN performance was evaluated utilizing a dice coefficient and concordance correlation coefficients (CCC) of geometric parameters. Dice coefficients were as high as 97.55% (CI: 97.47-97.62%) and 93.56% (CI: 84.63-96.68%) on the internal and external test of TAAs, respectively. CCC for maximum and minimum and ascending aortic area were 0.969 and 0.950, respectively, on the internal test set and 0.997 and 0.995, respectively, for the external test. The absolute differences between manual and deep learning segmentations for ascending and descending aortic distensibility were 0.0194 × 10-4 ± 9.67 × 10-4 and 0.002 ± 0.001 mmHg-1, respectively, on the internal test set and 0.44 × 10-4 ± 20.4 × 10-4 and 0.002 ± 0.001 mmHg-1, respectively, on the external test set. We successfully developed a U-Net-based aortic segmentation and analysis algorithm in both MESA and in external cases of TAA.

Left ventricular diastolic early and late filling quantified from 4D flow magnetic resonance imaging.

PURPOSE: The purpose of this study was to investigate the value of 4D flow MRI for mitral filling measurements, using transthoracic echocardiography (TTE) and 2D flow MRI as references, as well as identify relationships with age and left ventricle (LV) remodeling in healthy volunteers. MATERIAL AND METHODS: Fifty healthy volunteers (22 men, 28 women; mean age, 51.3 ± 16.9 [SD] years; age range: 20-80 years) prospectively underwent TTE and MRI on the same day. 4D flow volume acquisition was done at 3T with reconstructed spatial/temporal resolutions: 1 × 1.48 × 2.38 mm3/34 ms. Early (E) and late (A) flow rate and maximal velocity peaks were measured from 4D flow data with three strategies: static planes at 1) the mitral valve leaflets tip (4DLT) and 2) annulus (4Dann); and 3) while tracking the annulus through time (4Dtrack). RESULTS: 4DLT- and 4Dtrack-derived E/A ratios were in good agreement with 2D flow and TTE estimates with a superiority over maximal velocities (4DLT: r = 0.71 and r = 0.66; 4Dtrack: r = 0.74 and r = 0.71, respectively) of flow rates (4DLT: r = 0.89 and 0.72; 4Dtrack: r = 0.91 and 0.76, respectively). Measurements of 4DLT and 4Dtrack were highly reproducible (ICC = 0.89 and 0.95, respectively) and significantly correlated with age and LV remodeling (4DLT: r = -0.76 and ρ = -0.49; 4Dtrack: r = -0.79 and ρ = -0.51, respectively). CONCLUSION: E/A ratio can be accurately measured using 4D flow MRI either at a fixed mitral leaflet tip location or through annulus plane time-resolved tracking.

Myocardial fibrosis assessed by magnetic resonance imaging in asymptomatic heterozygous familial hypercholesterolemia: the cholcoeur study.

BACKGROUND: Familial Hypercholesterolemia (FH) is an underdiagnosed condition with an increased cardiovascular risk. It is unknown whether lipid accumulation plays a role in structural myocardial changes. Cardiovascular Magnetic Resonance (CMR) is the reference technique for the morpho-functional evaluation of heart chambers through cine sequences and for myocardial tissue characterization through late gadolinium enhancement (LGE) and T1 mapping images. We aimed to assess the prevalence of myocardial fibrosis in FH patients. METHODS: Seventy-two asymptomatic subjects with genetically confirmed FH (mean age 49·24, range 40 to 60 years) were prospectively recruited along with 31 controls without dyslipidaemia matched for age, sex, BMI, and other cardiovascular risk factors. All underwent CMR including cine, LGE, pre- and post-contrast T1 mapping. Extracellular volume (ECV) and enhancement rate of the myocardium (ERM = difference between pre- and post-contrast myocardial T1, normalized by pre-contrast myocardial T1) were calculated. FINDINGS: Five FH patients and none of the controls had intramyocardial LGE (p= 0·188). While no changes in Native T1 and ECV were found, post-contrast T1 was significantly lower (430·6 ± 55ms vs. 476·1 ± 43ms, p<0·001) and ERM was higher (57·44± 5·99 % vs 53·04±4·88, p=0·005) in HeFH patients compared to controls. Moreover, low post-contrast T1 was independently associated with the presence of xanthoma (HR 5·221 [1·04-26·28], p= 0·045). A composite score combining the presence of LGE, high native T1 and high ERM (defined as ≥ mean ± 1·5 SD) was found in 20·8% of the HeFH patients vs. 0% in controls (p<0·000, after adjustment for main confounders). INTERPRETATION: CMR revealed early changes in myocardial tissue characteristics in HeFH patients, that should foster further work to better understand and prevent the underlying pathophysiological processes.

Reduction in left atrial and pulmonary vein dimensions after ablation therapy is mediated by scar.

BACKGROUND: Ablative pulmonary vein isolation (PVI) decreases pulmonary vein (PV) and left atrial (LA) dimensions in atrial fibrillation (AF) patients. These changes are attributed to reverse structural remodeling following sinus rhythm restoration but evidence is lacking. We hypothesized that the downsizing is directly caused by the ablative energy and subsequent scar formation. METHODS: We studied cardiac magnetic resonance imaging in 21 paroxysmal AF patients before and 3 months after successful PVI and in healthy sheep (n = 12) before and after PVI of the right PV only. RESULTS: PVI decreased the PV diameter in patients and sheep by 11.0(10.3) and 9.2(11.0)%, (p < 0.001 and p = 0.020), respectively. The control left PV in sheep were unchanged. A linear correlation existed between the extent of PV scar and PVI-induced decrease in PV diameter in patients.After PVI, the LA volume decreased (103(38) vs. 92(31)ml, pre- vs. post-ablation, respectively, p = 0.006), while the right atrial (RA) volume was unchanged in patients. A decrease in active emptying fraction after ablation (26.5(10.7) vs. 21.8(10.6)%, pre- vs. post-ablation, p = 0.031) was associated with reduced contractility of the PV walls (p = 0.004). The contractility of the LA walls was unaltered (p = 0.749). CONCLUSION: The ablation-induced PV diameter reduction was similar in patients with AF and healthy sheep without AF and was associated with PV scar extent. The volume only decreased in LA and not RA after PVI, and wall contractility decreased only in ablated sites. Therefore, the PVI-induced atrial downsizing is caused by the ablative energy and subsequent scar formation.

A left lateral body position increases pulmonary vein stress in healthy humans.

Pulmonary vein (PV) stretch is proarrhythmic for atrial fibrillation (AF). AF patients often report that a left lateral (LL) body position can trigger arrhythmia symptoms. Because the PV myocardium is thought to trigger AF, we hypothesized that the LL compared to the supine body position increases PV wall stress. Functional cardiac magnetic resonance imaging was performed in supine and LL recumbent body position in awake condition in healthy human volunteers (n = 20). Following a change from supine to LL position, the heart moved in an anterior-LL direction in the thorax. The right superior PV diameter was increased by 19% (24.6 ± 3.1 vs. 20.7 ± 3.2 mm, p = 0.009) and left atrial (LA) volume was larger by 17% (61.7[15.4] vs. 51.0[17.8] ml, p = 0.015) in LL than supine position, respectively. The passive LA conduit fraction (normalized difference between maximum and pre-contraction LA volume) increased by 25% in LL compared to supine position (19.6 ± 9.0 vs. 15.7 ± 7.6%, respectively, p = 0.016). Local wall stress in the PV regions increased in LL compared to supine position (overall mean: 1.01 ± 0.12 vs. 1.10 ± 0.10 arb. unit, LL vs. supine, position effect p = 0.041), whereas this was not the case in the LA walls (overall mean: 1.18 ± 0.31 vs. 1.21 ± 0.21 arb. unit, LL vs. supine, position effect p = 0.381). In conclusion, a left lateral body position increases PV myocardial stress during the atrial relaxation phase of healthy volunteers. These results have implications for the mechanisms of posture-triggered AF.