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Background Bicuspid aortic valve (BAV), a congenital heart defect, is associated with ascending aorta (AAo) dilation. Whether the high prevalence of dilation in BAV patients is related to alteration of aortic blood flow and thus in wall shear stress (WSS) [1,2], which have been associated with aortic wall degeneration [3], or intrinsic abnormalities of the aortic wall, such as altered aortic stiffness [4], has not been established. Recently, a technique for the semi-automatic quantification of progressive aortic dilation maps via image registration has been introduced [5]. Purpose To test whether ascending aorta WSS predicts co-localized progressive dilation in BAV patients. Methods Forty BAV patients free from moderate and severe aortic valve regurgitation (regurgitant fraction Results Demographic and clinical characteristics of the patients are shown in Table 1. WSS and growth rate maps are shown in Figure 1. Follow-up duration was 44.8±2.6 months. Growth rate (Figure 1A) was heterogeneously distributed, being highest (up to 0.26 mm/year) in the outer region of the mid AAo and in the inner region of the proximal-mid AAo. Circumferential WSS showed highest values in the outer region of the mid AAo (Figure 1C) while WSS (magnitude) and its axial component (Figure 1B and D) presented maximum values in the right region of the mid AAo. Maps of statistically significant association between GR and WSS values showed circumferential WSS to be correlated with GR in regions where progressive dilation was fastest, while WSS magnitude and its axial component resulted in limited associations with GR maps. Conclusions Circumferential wall shear stress predicts location-matched progressive dilation in bicuspid aortic valve patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study has received funding from the Instituto de Salud Carlos III (PI17/00381). Guala A. has received funding from Spanish Ministry of Science, Innovation and Universities (IJC2018-037349-I). Table 1. DemographicsFigure 1. GR and WSS maps and correlations

Introduction Accurate assessment of aortic diameters and growth rates is key for clinical management of patients with aortic aneurysms [1]. Manual assessment on multiplanar reformatted views of computed tomography angiograms (CTA) is recommended [1], although its reproducibility in the assessment of growth rates has not been reported [2]. Image registration has been proposed to provide 3D maps of aortic diameters and growth [3], but its accuracy and reproducibility have not been established. Purpose To quantify accuracy and inter-observer reproducibility of aortic root and thoracic aorta diameters and growth rate by registration of serial CTAs compared to current standard. Methods Forty non-operated patients with ≥2 contrast-enhanced ECG-gated CTA acquired at least 6 months apart were included. Aortic diameters and growth rates were measured in the aortic root and thoracic aorta by two independent observers, both with the current standard and with the registration-based technique. To perform registration-based assessment, each observer semi-automatically segmented the aorta at baseline and located typical anatomical landmarks (Fig. 1A). Then, deformable image registration was used to map baseline and follow-up CT scans and deformation was applied to the baseline aortic surface points to obtain their location at follow-up (Fig. 1B). Finally, aortic root diameters and growth rate and 3D maps of thoracic aortic diameters and growth rate were automatically obtained (Fig. 1C). Agreement between techniques and their inter-observer reproducibility were calculated. Results Follow-up duration was 3.3±1.5 years (range 0.52–6.2). Compared with manual assessment, registration-based aortic diameters presented low bias and excellent agreement in the aortic root (0.42 mm, ICC=0.99) and the thoracic aorta (0.55 mm, ICC=0.99), and similar inter-observer reproducibility (ICC=0.99 for both). Compared with manual assessment, registration-based growth rates presented low bias and good agreement in the aortic root (0.12 mm/y, ICC=0.84) and the thoracic aorta (0.03 mm/y, ICC=0.77) (Fig. 2A), and much higher inter-observer reproducibility (ICC=0.96 vs 0.68 in the aortic root, ICC=0.96 vs 0.80 in the thoracic aorta) (Fig. 2B and C). Registration-based aortic growth rates reproducibility at 6 months follow-up was comparable to that obtained by manual assessment at 2.7 years (LoA = [−0.01, 0.33] and LoA = [−0.13, 0.21], respectively). Aortic diameters and growth rate 3D maps were highly reproducible (ICC>0.9) in the whole thoracic aorta. Conclusions Progressive aortic dilation assessment via registration of CTAs is accurate and more reproducible than the current standard even over follow-ups as short as 6 months, and further provides robust 3D mapping of aortic diameters and growth rates. Its application may provide new insights in aneurysms pathophysiology and improve the clinical management of these patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study has received funding from the Instituto de Salud Carlos III (PI17/00381). Guala A. has received funding from Spanish Ministry of Science, Innovation and Universities (IJC2018-037349-I). Figure 1. Methodology.Figure 2. Growth rate comparison.

Background Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS) and related heritable thoracic aortic diseases (HTAD) are well-known for their aortic complications. Myocardial dysfunction and arrhythmia are less known in this setting but have been increasingly reported as additional causes of morbidity and mortality. Related to the rarity of the disorders, data on the prevalence of these features and clinical characteristics of the patients are difficult to obtain, calling for a multicentre initiative. Purpose To study the prevalence of myocardial dysfunction and arrhythmia in patients with HTAD and describe their clinical and genetic profile. Methods Nine centres from seven countries participated in this multicentre retrospective study. Medical records of patients 12 years or older carrying a (likely) pathogenic variant in the FBN1 gene, LDS genes (TGFBR1, TGFBR2, TGFB2, TGFB3 and SMAD3) or ACTA2 gene were screened. Patients presenting myocardial dysfunction and/or arrhythmia were identified, and clinical and genetic data were collected. Myocardial dysfunction included (a)symptomatic reduced ejection fraction (EF Results In total, 3219 patients with HTAD were screened: 2761 with a variant in FBN1, 385 with a variant in one of the LDS genes (TGFBR1, TGFBR2, TGFB2, TGFB3 and SMAD3) and 73 carrying a variant in ACTA2. Myocardial dysfunction and arrhythmia were not reported in patients carrying an ACTA2 variant. Myocardial dysfunction was observed in patients with a variant in FBN1 and the LDS genes, without significant differences in prevalence (2.3% vs. 1.8%, p=0.563). Patients with a variant in the LDS genes presenting myocardial dysfunction were younger than patients carrying a variant in FBN1 (25±11 years vs. 39±17 years, p=0.034). The prevalence of VT/VF/SCD was similar in patients with a variant in one of the LDS genes compared to those with a variant in FBN1 (1.6% vs. 0.8%, p=0.132) and there was no difference in age at time of event (26±13 years vs. 33±14 years, p=0.289). Among patients with a variant in the LDS genes, the prevalence of VT/VF/SCD was highest in patients carrying a variant in the TGFBR2 gene and was significantly higher compared to patients with a variant in FBN1 (3.4% vs. 0.8%, p=0.017). In contrast, AF/AFL was significantly more often reported in patients with a variant in FBN1 compared to those with a variant in one of the LDS genes (1.7% vs. 0.3%, p=0.033). Conclusions Myocardial dysfunction and arrhythmia are rare features in patients with HTAD. They occur predominantly in patients with a variant in FBN1 and LDS genes, but were not reported in patients carrying a variant in the ACTA2 gene. Further analysis to identify other contributing factors is necessary. Funding Acknowledgement Type of funding sources: None. Figure 1

Background Mitral annular disjunction (MAD) is a structural abnormality of the mitral annular fibrosus characterized by a separation between the atrial wall-mitral valve junction, and the left ventricular attachment (1). It has been associated with mitral valve prolapse (MVP) (2) but also, with arrhythmias and sudden cardiac death (SCD) (3). There is no evidence of its prevalence and clinical significance in patients with syndromic hereditary aortopathies. Purpose To evaluate the prevalence of MAD, PMV, and the combination of both in patients with syndromic hereditary thoracic aortic disease (HTAD) including Marfan (MFS), Loeys-Dietz (LDS) and vascular Ehlers-Danlos syndromes (vEDS), and its relationship with arrhythmias, SCD, mitral regurgitation (MR) severity and the need for mitral surgery at the follow-up. Methods Adult patients with syndromic HTAD seen at our specialized unit were retrospectively included. The presence of MAD, MVP, and significant MR at first echocardiogram were evaluated. Electronic medical records were reviewed to register the occurrence of arrhythmic events and the need of mitral surgery. Last echocardiogram available was also assessed to evaluate MR progression. Results A total of 295 patients were included (235 MFS, 42 LDS and 18 vEDS). Mean age at baseline was 39.0±14.4 and 52.9% were female. MAD was present in 87 (37.0%) of MFS, 6 (14.3%) of LDS and was not present in vEDS (p In MFS, the presence of MAD was significantly associated with MVP (p≤0.001) (Table 1). However, 14 (6.0%) of patients had isolated MAD (Table 2). At baseline, significant MR was observed in 18 (24.7%) of patients with concurrent MAD and MVP and was not present in patients with isolated MAD (Table 2). MVP (OR 16.85 IC 4.43 – 64.07) but not MAD (p=0.607), was associated with significant MR in the multivariate analysis. A second echocardiogram was available in 220 patients at ≥1 year (mean 4.1±1.4 years). Overall, 25 (11.4%) presented significant progression of MR, 0 in the isolated MAD group, 13 (19.4%) in the MAD/MVP group and 6 (20.0%) of the isolated MVP (p=0.007). After a mean clinical follow-up of 7.5±3.2 years, 10 patients required mitral surgery (6 prosthesis, 4 valvuloplasty), 22 (9.4%) presented atrial fibrillation, flutter or supraventricular tachycardia (SVT), and 2 (0.9%) SCD. After adjustment for the presence of MVP and time of follow-up, MAD was not associated with progression of MR (p=0.529) need for mitral surgery (p=0.096), atrial fibrillation-flutter or SVT (p=0.510) nor SCD. (p=0.997). Conclusions The prevalence of MAD in syndromic HTAD is high, especially in Marfan syndrome, and absent in vEDS. In this retrospective observational study, the presence of MAD in Marfan was not associated with mitral regurgitation evolution or arrhythmic events. Funding Acknowledgement Type of funding sources: None. Characteristics of MFS patientsPresence of significant MR by groups.

Thanks to a better knowledge of the genetic causes of many diseases and an improvement in genetic testing techniques, genetics has gained an important role in the multidisciplinary approach to diagnosis and management of congenital heart disease and aortic pathology. With the introduction of strategies for precision medicine, it is expected that this will only increase further in the future. Because basic knowledge of the indications, the opportunities as well as the limitations of genetic testing is essential for correct application in clinical practice, this consensus document aims to give guidance to care-providers involved in the follow-up of adults with congenital heart defects and/or with hereditary aortic disease. This paper is the result of a collaboration between the ESC Working Group of Grown-Up Congenital Heart Disease, the ESC Working Group on Aorta and Peripheral Vascular Disease and the European Society of Human Genetics. Throughout the document, the importance of correct counseling in the process of genetic testing is emphasized, indications and timing for genetic studies are discussed as well as the technical modalities of genetic testing. Finally, the most important genetic diseases in adult congenital heart disease and aortic pathology are also discussed., SCOPUS: ar.j, info:eu-repo/semantics/published

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Guala A. received funding from the Spanish Ministry of Science, Innovation and Universities Introduction The heterogeneous characteristic of the thoracic aorta implies that all biomarkers with potential for risk stratification need to be references to a specific location. This is the case, for example, of diameter [1], stiffness [2] and wall shear stress [3]. This is normally achieved by the manual identification of a limited number of key anatomic landmarks [4], which is a time-demanding task and may impact biomarkers accuracy and reproducibility. Automatic identification of these anatomic landmarks may speed-up the analysis and allow for the creation of fully automatic image analysis pipelines. Machine learning (ML) algorithms might be suitable for this task. Purpose The aim of this study was to test the performance of a ML algorithm in localizing key thoracic anatomical landmarks on phase-contrast enhanced magnetic resonance angiograms (PC-MRA). Methods PC-MRA of 323 patients with native aorta and aortic valve and a variety of aortic conditions (141 bicuspid aortic valve patients, 60 patients with degenerative aortic aneurysms, 82 patients with genetic aortopathy and 40 healthy volunteers) were included in this study. Four anatomical landmarks were manually identified on PC-MRA by an experienced researcher: sinotubular junction, the pulmonary artery bifurcation and the first and third supra-aortic vessel braches. A reinforcement learning algorithm (DQN), combining Q-learning with deep neural networks, was trained. The algorithm was tested in a separate set of 30 PC-MRA with similar distribution of aortic conditions in which human intra-observer reproducibility was quantified. The distance between points was used as quality metric and human annotation was considered as ground-truth. Repeated-measures ANOVA was used for statistical testing. Results ML algorithm resulted in performance similar to the intra-observer variability obtained by the experienced human reader in the identification of the sinotubular junction (11.1 ± 8.6 vs 11.0 ± 8.1 mm, p = 0.949) and first (6.8 ± 5.6 vs 6.6 ± 3.9 mm, p = 0.886) and third (8.4 ± 7.4 vs 6.8 ± 4.0 mm, p = 0.161) supra-aortic vessels branches. However, the algorithm did not reach human-level performance in the localization of the pulmonary artery bifurcation (15.2 ± 13.1 vs 10.2 ± 7.0 mm, p = 0.008). The time needed to the ML algorithm to locate all points ranged between 0.8 and 1.6 seconds on a standard computer while manual annotation required around two minutes to be performed. Conclusions The rapid identification of key aortic anatomical landmarks by a reinforced learning algorithm is feasible with human-level performance. This approach may thus be used for the design of fully-automatic pipeline for 4D flow CMR analysis.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Guala A. received funding from the Spanish Ministry of Science, Innovation and Universities Background Phase-contrast (PC) enhanced magnetic resonance (MR) angiography (MRA) is a class of angiogram exploiting velocity data to increase the signal-to-noise ratio, thus avoiding the administration of external contrast agent, normally used to segment 4D flow MR data. To train deep-learning algorithms to segment PC-MRA a large amount of manually annotated data is needed: however, the relatively novelty of the sequence, its rapid evolution and the extensive time needed to manually segment data limit its availability. Purpose The aim of this study was to test a deep learning algorithm in the segmentation of multi-center and multi-vendor PC-MRA and to test if transfer learning (TL) improves performance. Methods A large dataset (LD) of 262 and a small one (SD) of 22 PC-MRA, acquired without contrast agent at 1.5 T in a General Electric and a Siemens scanner, respectively, were manually annotated and divided into training (232 and 15 cases) and testing (30 and 7) sets. They both included PC-MRA of healthy subjects and patients with aortic diseases (excluding dissections) and native aorta. A convolutional neural networks (CNN) based on nnU-Net framework [1] was trained in the LD and another in the SD. The left ventricle was removed semi-automatically from the DL segmentations of the LD as it was not relevant for this application. Networks were then tested on the test sets of the dataset there were trained and the other dataset to assess generalizability. Finally, a fine-tuning transfer learning approach was applied to LD network and the performance on both test sets were tested. Dice score, Hausdorff distance, Jaccard score and Average Symmetrical Surface Distance were used as segmentation quality metrics. Results LD network achieved good performance in LD test set, with a DS of 0.904, ASSD of 1.47, J of 0.827 and HD of 6.35, which further improve after removing the left ventricle in the post-processing to a DS of 0.942, ASSD of 0.93, J of 0.892 and HD of 3.32. SD network results in an average DS of 0.895, ASSD of 0.59, J of 0.812 and HD of 2.05. Once tested on the testing set of the other dataset, LD network resulted in a DS of 0.612 while SD network in DS of 0.375, thus showing limited generalizability. However, the application of transfer learning to LD network resulted in the improvement of the evaluation metrics on the SD from a DS of 0.612 to 0.858, while slightly worsening in the first one without post-processing to 0.882. Conclusions nnU-net framework is effective for fast automatic segmentation of the aorta from multi-center and multi-vendor PC-MRA, showing performance comparable with the state of the art. The application of transfer learning allows for increased generalization to data from center not included in the original training. These results unlock the possibility for fully-automatic analysis of multi-vendor multi-center 4D flow MR.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Guala A. received funding from the Spanish Ministry of Science, Innovation and Universities. Background Bicuspid aortic valve (BAV), a congenital heart defect, is associated with ascending aorta dilation, possibly via alteration of aortic blood flow [1]. In BAV abnormal flow condition have been associated with aortic extracellular matrix dysregulation and elastic fiber degeneration [2]. Current morphological classification of BAV patients with aortic valve with a single fusion between two adjacent leaflets does not allow for risk stratification. Purpose This research work tested whether the extent of fusion between leaflets is related to AAo diameter and flow alterations. Methods Ninety BAV patients free from moderate and severe aortic valve disease and with no previous aortic or aortic valve surgery or replacement were prospectively enrolled. A comprehensive magnetic resonance protocol comprised a stack of double-oblique 2D balanced steady-state free-precession (bSSFP) cine CMR of the aortic valve, which was used to measure the length of the fusion between leaflets, a cine CMR at the level of the pulmonary bifurcation to assess aortic diameter and 4D flow MRI sequence to assess flow characteristics and regional stiffness [3]. Jet angle and flow radial displacement, quantifying the extent of flow eccentricity, and systolic flow reversal ratio (SFRR), assessing the relative amount of backward flow during systole, were computed at 8 equidistant planes in the ascending aorta and 4 equidistant planes in the aortic arch [4]. A two-tailed p-value < 0.05 was considered statistically significant. Results The length of leaflet fusion varied widely (median 7.7 mm, inter-quartile range [5.5; 10.2]), Table 1). In bivariate analysis, fusion length was also associated to ascending aortic diameter (R = 0.391, p Conclusions Bicuspid aortic valve fusion extent varies greatly and it is associated with aortic diameter, possibly through flow alterations. Prospective longitudinal studies are needed to establish whether fusion length may allow for risk stratification in bicuspid aortic valve patients.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): La Marató de TV3, Instituto de Salud Carlos III through the project and Spanish Ministry of Science, Innovation and Universities. BACKGROUND Loeys-Dietz (LDS) and Marfan (MFS) syndromes are rare genetic connective tissue disorders associated with progressive aortic dilation, however, aortic dissections have been observed at lower aortic root diameters in LDS than in MFS. Recent CMR studies in MFS patients reported increased aortic stiffness (1–3) and altered rotational flow (4), but research on aortic flow dynamics and biomechanics in LDS is lacking. PURPOSE The aim of this study was to assess rotational aortic flow and aortic stiffness in LDS compared to healthy volunteers (HV) and MFS patients, using 4Dflow CMR. METHODS Twenty-one LDS and 44 MFS patients, without previous aortic dissection or surgery, and 43 HV underwent a non-contrast-enhanced 4D flow CMR. Aortic stiffness was quantified at the AAo and DAo using pulse wave velocity (PWV). In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR) (5) and local aortic diameters were obtained at 20 equidistant planes from the ascending (AAo) to the proximal descending aorta (DAo). RESULTS LDS patients had lower IRF at the distal AAo and proximal DAo compared to HV (p = 0.053 and 0.004, respectively), once adjusted for age, stroke volume and local aortic diameter; but no differences were found with respect to MFS (Figure). Although SFRR at the proximal DAo was increased in LDS patients compared to both HV (p = 0.037) and MFS populations (p = 0.015), once adjusted for age and aortic diameter, the difference in magnitude was small (Figure). On the other hand, AAo and DAo PWV revealed stiffer aortas in LDS patients compared to HV but no differences versus MFS patients (Table). CONCLUSIONS Patients with Loeys-Dietz syndrome showed decreased in-plane rotational flow and abnormally-high regional aortic stiffness compared to healthy controls, and similar hemodynamics and aortic stiffness with respect to patients with Marfan syndrome.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science, Innovation and Universities; La Marató de TV3 Introduction Automatic analysis of medical imaging data may improve their clinical impact by reducing analysis time and improving reproducibility. Many medical imaging data, like 4D-flow magnetic resonance imaging (MRI), are often quantified regionally, implying the need for anatomical landmark identification to locate correspondences in the extracted data and compare among patients. Machine learning (ML) techniques hold potential for automatic analysis of medical imaging. Phase-contrast enhanced magnetic resonance angiography (PC-MRA) is a class of angiograms not requiring the administration of contrast agents. Purpose We aimed to test whether a machine learning algorithm can be trained to identify key anatomical cardiovascular landmarks on PC-MRA images and compare its performance with humans. Methods Three-hundred twenty-three aortic PC-MRA were manually annotated with the location of 4 landmarks: sinotubular junction, pulmonary artery bifurcation and first and third supra-aortic vessels (Figure 1), often used to separate the aorta in sub-regions. Patients included in the training dataset comprised healthy volunteers (40), bicuspid aortic valve patients (141), patients with degenerative aortic disease (60) and patients with genetically-triggered aortic disease (82), all without previous aortic surgery and with native aortic valve. PC-MRA images and manual annotations were used to train a DQN, a reinforcement learning algorithm that combines Q-learning with deep neural networks. The agents can navigate the images and optimally find the landmarks by following the policies learned during training. Data from thirty patients, distributed in terms of aortic condition as the training set, unseen by the algorithm in the training phase, were used to quantify intra-observer reproducibility and to assess ML algorithm performance. Distance between points was used as metric for comparisons, original human annotation was used as ground-truth and repeated-measures ANOVA was used for statistical testing. Results Human and machine learning performed similarly in the identification of the sinotubular junction (distance between points of 11.0 ± 8.1 vs. 11.1 ± 8.6 mm, respectively, p = 0.949) and first (6.6 ± 3.9 vs. 6.8 ± 5.6 mm, p = 0.886) and third (6.8 ± 4.0 vs. 8.4 ± 7.4 mm, p = 0.161) supra-aortic vessels branches but human annotation outperformed ML landmark detection in the identification of the pulmonary artery bifurcation (10.2 ± 7.0 vs. 15.2 ± 13.1 mm, p = 0.008). Computation time for landmark detection by ML was between 0.8 and 1.6 seconds on a standard computer while human annotation took approximatively two minutes. Conclusions ML-based aortic landmarks detection from phase-contrast enhanced magnetic resonance angiography is feasible and fast and performs similarly to human. Reinforced learning anatomical landmark identification unlock automatic extraction of a variety of regional aortic data, including complex 4D flow parameters. Abstract Figure

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science, Innovation and Universities ; Instituto de Salud Carlos III Introduction The aorta is a 3D hollow, curvilinear elastic structure whose diseases have life-threatening consequences. Despite much effort has been paid to study aortic diameter, diameter is a poor predictor of events. Conversely, much less is known about aortic curvature, its distribution in the thoracic aorta and the potential impact of risk factors in aneurysms associated with different conditions. Currently, 4D flow magnetic resonance imaging (4D flow CMR) allows to obtain 3D geometry, 4D flow data and regional aortic stiffness. Purpose We aim to study regional aortic curvature in thoracic aorta aneurysms of different aetiologies and define its relationship with established risk factors. Methods One-hundred twenty patients (40 for each group, selected out of prospective cohorts of 156 bicuspid aortic valve – BAV-, 77 Marfan –MFS- and 67 patients with a degenerative aneurysm – TAVdeg-) were matched for age, sex and BSA via propensity score with 40 healthy volunteers (HV). The thoracic aorta was semi-automatically segmented from angiograms and the centreline was computed. Local curvature was assessed at 20 planes covering the thoracic aorta from the sinotubular junction to the proximal descending aorta (DAo) at the level of the pulmonary artery bifurcation. Local curvature was normalized by subject mean thoracic aorta curvature. Length was measured as centreline length. Aortic stiffness was measured in the DAo by pulse wave velocity (PWV). Aneurysm was defined by z-score ≥ 2 using diameters measured by double-oblique cine CMR. Results Matching was successful in all groups with the exception of a residual age difference between HV and TAVdeg. Curvature in HV showed a fairly smooth transition between the straighter ascending aorta (AAo) and DAo to a more curved aortic arch, with a peak in the mid aortic arch (Figure 1A). Conversely, all patients’ groups presented a peak in curvature in the proximal DAo and a decreased local curvature in the aortic arch and mid DAo close to the level of the pulmonary artery. BAV and TAVdeg patients showed also increased curvature in the mid AAo, were dilation is prevalent. Conversely, in the same area MFS showed a reduced curvature and limited prevalence of aneurysm. In the overall population, age, AAo and root diameters, mean blood pressure, DAo PWV and aortic length, all established risk factors for aortic events, were inversely related to curvature in the distal AAo and aortic arch (Figure 1B). Conclusions Aneurysms related to different aetiologies show similar abnormalities in aortic curvature, with limited curvature in the aortic arch and a peak soon after the third supra-aortic vessel. Age, aortic diameter, length, stiffness and blood pressure, all known risk factors, are all related to reduced curvature in the distal ascending aorta and aortic arch. Abstract Figure.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science, Innovation and Universities; Instituto de Salud Carlos III Introduction In Marfan syndrome (MFS) patients reduced longitudinal strain of the ascending aorta (AAo) as measured by applying feature-tracking on cine cardiac magnetic resonance (CMR) images predicts aortic root dilation and aortic events during the follow-up. Speckle-tracking is well established for cardiac deformation assessment but proximal aorta applications are challenging due to limited wall thickness and substantial cardiac motion. Moreover, echocardiography is widely used in the clinical assessment aortic diseases. Purpose We aimed to test a speckle-tracking tool for root longitudinal strain analysis in terms of comparison with CMR-derived AAo longitudinal strain and reproducibility and as predictor of dilation in MFS patients. Methods Thirty-five MFS patients diagnosed by original GHENT criteria, with maximum aortic root diameter of 45 mm and free from previous aortic dissection or cardiac/aortic surgery and non-severe aortic regurgitation were consecutive enrolled and followed-up. CMR and echocardiography were performed less than 2 months apart. Baseline and final aortic root diameter were measured on CMR images. To quantify aortic root cyclic elongation by echocardiography, two regions of interests were manually created covering both walls in a parasternal long-axis view and tracked along the cardiac cycle (Figure 1). Longitudinal strain was computed as the average of maximum increase in relative distance of several sub-regions covering both walls. CMR-derived AAo longitudinal strain was available in 29 patients. Intra-observer reproducibility was tested in 15 patients via intraclass correlation coefficient (ICC) for single-rater absolute agreement. Results Aortic root longitudinal strain by echocardiography was mildly related to CMR-derived AAo longitudinal strain (R = 0.27) and was larger compared to CMR-derived values (16.2 ± 6.0 vs 11.3 ± 4.3). Reproducibility was high, with ICC of 0.811, R = 0.802, p Conclusions The measurement of aortic root longitudinal strain by speckle-tracking echocardiography is feasible. Aortic root longitudinal strain is an independent predictor of progressive dilation in MFS patients. This may permit the improvement of risk-stratification in aortic diseases in large scale studies. Abstract Figure 1

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Spanish Ministry of Science, Innovation and Universities Instituto de Salud Carlos III Background. Dilation of the aortic root is a key feature of Marfan syndrome and it is related to the occurrence of aortic events and death. On top of maximum diameter, rapid annual growth rate is suggested by guidelines for indication of aortic root replacement. Current gold-standard for aortic root diameter assessment is manual quantification on multiplanar reformatted 3D computed tomography (CT) or magnetic resonance angiogram. However, inter- and intra-observer reproducibility are limited and different measurement methods, i.e. cusp-to-cusp and cusp-to-commissure, may be used in different clinical centres, leading to difficulties in the clinical assessment of progressive dilation. Purpose. We aimed to test whether aortic root growth rate during follow-up can be reliably quantified by semi-automatic co-registration of two CT angiograms. Methods. Seven Marfan syndrome patients, free from previous aortic surgery, with a total of 11 pairs of CT were identified. Manual assessment of six aortic root diameters (right-non coronary -RN- , right-left -RL- and left-non coronary -LN- cusp-to-cusp and R, L and N cusp-to-commissure) was obtained from all CTs by an experienced researcher blind to semi-automatic results. The thoracic aorta and the outflow tract were semi-automatically segmented in the baseline CT and commissure and cusps were manually located. A 10 mm-thick region of interest containing the aortic wall was automatically generated from segmentation boundary. Co-registration was obtained with three, fully-automatic steps. Firstly, baseline and follow-up CT scans were aligned by means of a rigid registration. Then, scans were co-registered with multi-resolution affine followed by b-spline non-rigid registrations based on mutual information metric. The transformation pertaining to the location of baseline commissure and cusps points was used to locate the same points in the follow-up scan (Fig. 1 top). Results. Follow-up duration was 35 ± 22 (range 12-70.3) months. Automatic quantification of diameter growth during the follow-up was obtained in 62 out of 66 (94%) diameter comparisons. High Pearson correlation coefficients (R) and ICC were found between manual and semi-automatic assessment of growth rate, both for cusp-to-cusp and cusp-to-commissure diameters: R = 0.727 and ICC = 0.678 for RN; R = 0.822 and ICC = 0.602 for RL; R = 0.648 and ICC = 0.668 for LN; R = 0.726 and ICC = 0.711 for R; R = 0.911 and ICC = 0.895 for L and R = 0.553 and ICC = 0.482 for N. Scatter and Bland-Altman plots for all growth rates (Fig. 1) confirmed very good correlation (R = 0.810) but a slight tendency (R=-0.270) for underestimation at high growth rate. No correlation was found between follow-up duration and difference between techniques (R = 0.06). Conclusions. Semi-automatic quantification of aortic root growth rate by co-registration of pairs of CT angiograms is feasible for follow-up as short as one year. Larger studies are needed to confirm these preliminary data. Abstract Figure. CT measurements. Automatic vs manual.

Background Aortic regurgitation (AR) can be evaluated by cardiac magnetic resonance (CMR).The most commonly used method to quantify AR is direct measurement using phase contrast (PC) imaging, at the aortic root (as close as possible to the aortic valve), for the calculation of regurgitant fraction (RF). Aortic distensibility (AD) may affect aortic valve dynamics and, as a result, aortic regurgitation grade. However, the impact of aortic distensibility in this evaluation remains unknown. Purpose The aim of the study was to evaluate the relationship between AD and AR in patients with different aortic valve anatomy. Methods 213 patients with different AR severity grades and aortic valve anatomy (tricuspid (TAV) and bicuspid valve (BAV) patients) were enrolled (32.2% female, 74% BAV, 55.5±15.4 years), excluding connective tissue disease. All patients underwent a CMR study with PC sequences for the evaluation of regurgitant fraction at the aortic valve level. AR was considered as mild (30%) depending on RF value. Furthermore we used cine-sequences to estimate aortic diameters and distensibilities, using Art Fun software. Distensibility was calculated as (change in aortic area between systole and diastole/diastolic area)/brachial pulse pressure. Results 159 (73.7%) AR were mild, 30 (14.1%) moderate and 24 (11.3%) severe. RF significantly correlated with aortic root diameter (r=0.337, p Conclusions In our study, aortic regurgitation is positively related to descending aorta distensibility in BAV patients, regardless of age and aortic root diameter. Thus, AD may play a role in the evaluation of AR in case of bicuspid valves. In contrast, in TAV patients, distensibility does not seem to influence the assessment of AR severity. Descending aorta distensibility Funding Acknowledgement Type of funding source: Other. Main funding source(s): Research grant provided by the Cardiopath PhD program

Background Connective tissue disorders, such as Loeys-Dietz (LDS) and Marfan (MFS) syndromes, are rare genetic diseases associated with progressive aortic dilation. Aortic dissections have been observed at lower aortic root diameters in LDS than in MFS, and research on aortic flow dynamics and biomechanics in LDS is lacking. Purpose To evaluate rotational aortic flow and aortic stiffness in LDS compared to healthy volunteers (HV) and MFS patients, using 4Dflow CMR. Methods Twenty-one LDS and 44 MFS patients, without previous aortic dissection or surgery, and 44 HV underwent a non-contrast-enhanced 4D flow CMR. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR) and local aortic diameters were obtained at 20 equidistant planes from the ascending (AAo) to the proximal descending aorta (DAo). Aortic stiffness was quantified at the AAo and DAo using pulse wave velocity (PWV). Results LDS patients had lower IRF at the distal AAo and proximal DAo compared to HV (p=0.053 and 0.004, respectively), once adjusted for age, stroke volume and local aortic diameter; but no differences were found with respect to MFS (Figure). Although SFRR at the proximal DAo was increased in LDS patients compared to both HV (p=0.037) and MFS populations (p=0.015), once adjusted for age and aortic diameter, the difference in magnitude was small (Figure). On the other hand, AAo and DAo PWV revealed stiffer aortas in LDS patients compared to HV but no differences versus MFS patients (Table). Conclusions LDS patients showed decreased in-plane rotational flow and abnormally-high regional aortic stiffness compared to healthy controls, and similar hemodynamics and aortic stiffness with respect to MFS patients Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III, La Maratό TV3

Background EACVI recommends the use of an “integrative approach”, using several parameters, in aortic regurgitation (AR) quantification. This approach is easily achieved by echocardiography although cardiovascular magnetic resonance (CMR) remains the gold standard for the quantification of regurgitant fraction (RF). Purpose The aim of the study was to analyze the accuracy of descending aorta (DA) diastolic reverse flow in the assessment of chronic AR severity by CMR to identify an additional parameter. Methods 188 patients (34% female, 54.6±15.6 years) with different severity grades of chronic AR were enrolled. All patients underwent a CMR study. Aortic regurgitation was considered as absent (≤1%), mild (≤15%), moderate (≤15%) or severe (≥30%) depending on RF value at valve level. Furthermore, cine-sequences were used to estimate aortic diameters and distensibilities using Art Fun software. Velocity-time integral (VTI) of reverse flow in DA was calculated from maximum velocity curves by an in-house MatLab code. Results AR was absent in 21 (12%) patients, mild in 114 (62.9%), moderate in 23 (12.7%) and severe in 21 (11.6%).DA VTI reverse flow was significantly higher as was the RF at valve level (r=0.805, p Conclusions VTI reverse flow in DA correlates strongly with the degree of AR and may be useful in the assessment of its severity. Neverthless, owing to the influence of other factors (aortic distensibility and aortic root diameter), it cannot be used as a single parameter in the quantification of AR severity by CMR. Scatter Plot graphs Funding Acknowledgement Type of funding source: Other. Main funding source(s): research grant provided by the Cardiopath PhD program

Background Due to improved surgical strategies a growing number of patients survive acute aortic dissection. Patent false lumen (FL) is common in chronic dissection and it has been associated with poor prognosis, which is mainly driven by FL expansion. Several variables indirectly related to flow characteristics have been associated with progressive aortic dilation. We aimed to evaluate whether the maximum systolic flow deceleration rate (MSDR) in the FL, quantified by 4D-flow MR, is related to FL dilation in chronic type B aortic dissection. Methods Twenty-nine patients with a patent FL after aortic dissection and a prior follow-up of at least 3 years underwent contrast-enhanced 4D-flow MR. Marfan patients were excluded. Time-resolved FL flow acceleration was calculated in a 5 cm-long volume of the descending aorta around the level of the pulmonary bifurcation. MSDR was determined as the maximum minus the minimum acceleration in systole over the corresponding time interval (Figure 1a). Aortic growth rate (GR) was measured as the difference between final and initial maximum FL diameters obtained by angio-CT divided by follow-up duration. Population was divided into tertiles based on GR. Results Demographic and clinical variables were similar among GR tertiles (Table). MSDR was lower in patients with a GR Conclusions The MSDR in the FL of chronic type B aortic dissection is linearly related to FL growth rate and discriminated between tertiles of aortic dilation. Prospective longitudinal studies are need to unveil possible prognostic value of this parameter. Table Group 1 (n = 9) Group 2 (n = 10) Group 3 (n = 10) p-value Age (years) 63.44 ±13.54 62.50 ± 13.60 64.56 ± 6.67 0.902 BSA (m2) 2.00 ± 0.18 1.77 ± 0.20 1.94 ± 0.12 0.213 Men 6 (86%) 4 (57%) 4 (100%) 0.210 Hypertension 4 (66%) 5 (71%) 4 (100%) 0.438 Atheroclerosis 1 (17%) 1 (14%) 0 (0%) 0.699 Initial Diameter (mm) 45.00 ± 7.69 36.00 ± 4.20 37.00 ± 6.48 0.078 Final Diameter (mm) 49.50 ± 6.74 44.86 ± 5.70 59.25 ± 9.84 0.049 Follow-up (year) 11.83 ± 8.79 7.82 ± 3.34 8.08 ± 4.05 0.921 GR (mm/year) 0.27 ± 0.29 1.18 ± 0.26 2.64 ± 0.97 Abstract P1600 Figure 1

Funding Acknowledgements ISCIII PI14/0106 and PI17/00381, La Marató de TV3 (20151330), Eur FP7/People 267128 and CIBERCV BACKGROUND Genetic syndromic aortic diseases are rare, with Marfan syndrome (MFS) being the most common. However, less is known of Loeys-Dietz syndrome (LDS) which has much lower prevalence and presumed worse prognosis. Increased aortic stiffness in MFS has been previously described but no studies have evaluated aortic biomechanics in LDS. Pulse wave velocity (PWV) is the gold standard measure for arterial stiffness and can be quantified by 4D flow MRI. We aim to evaluate regional aortic PWV by 4D flow MRI in LDS compared to MFS and healthy volunteers. METHODS Sixteen LDS patients with a pathogenic mutation, 76 MFS and 49 healthy volunteers were prospectively and consecutively included. No patient had previous aortic dissection or surgery. All underwent a 4D flow MRI study in a 1.5 T clinical scanner. Ascending (AAo) and descending (DAo) aorta PWV were computed using wavelet analysis of the systolic upslope for transit time calculation (Figure). Statistical comparison was made with non-parametric analysis to account for the non-normality of data and multivariate analysis was evaluated separately for AAo and DAo PWV. RESULTS Ascending and descending aortic PWV revealed stiffer aortas in LDS patients than in healthy volunteers, even after adjustment for diameter of sinus of Valsalva (SoV) and sex. Conversely, no differences in aortic stiffness were found between LDS and MFS patients (Table). CONCLUSIONS Abnormally high regional aortic stiffness was observed in LDS patients when compared with controls. The severity of increased regional aortic stiffness was found similar to the one affecting MFS patients. Table Controls (N = 49) LDS (N = 16) MFS (N = 76) LDS vs. HV LDS vs. MFN Parameter Unadjusted p-value Adjusted p-value Unadjusted p-value Adjusted p-value Age [years] 39 ± 12 39 ± 16 36 ± 12 0.903 0.599 Men 32 (65%) 6 (37%) 34 (45%) 0.079 0.782 Weight [kg] 72 ± 11 69 ± 13 74 ± 16 0.288 0.194 Height [cm] 172 ± 8 172 ±12 181 ± 11 0.834 0.008 Systolic BP [mmHg] 126 ± 18 125 ± 14 127 ± 17 0.957 0.523 Diastolic BP [mmHg] 70 ± 11 77 ± 6 75 ± 12 0.011 0.318 SoV diameter [mm] 30.6 ± 3.9 35.4 ± 4.6 38.1 ± 5.9 0.001 0.060 AAo diameter [mm] 27.7 ± 3.8 29,0 ± 5.0 29.7 ± 5.4 0.458 0.579 DAo diameter [mm] 20.0 ± 2.0 21.3 ± 3.6 22.9 ± 3.8 0.546 0.124 AAo PWV [m/s] 5.2 ± 1.9 7.6 ± 2.4 7.3 ± 2.8 0.001 0.050* 0.534 NS DAo PWV [m/s] 7.1 ± 2.2 9.4 ± 2.6 10.7 ± 4.6 0.003 0.025** 0.493 NS Abstract P372 Figure

Funding Acknowledgements Spanish Ministry of Economy and Competitiveness RTC-2016-5152-1, ISCIII PI17/00381, La Marató de TV3 (20151330), Eur FP7/People 267128 and CIBERCV Background Histological findings of fibrillin-1 deficiency in bicuspid aortic valve (BAV) ascending aorta (AAo), as observed in Marfan (MFS), supported the existence of intrinsic aortic wall abnormalities, but recent studies reported the absence of an intrinsic impairment in stiffness. A recent study in MFS showed that AAo longitudinal strain was reduced in MFS and predicted dilation and aortic events. This parameter has not been studied in BAV. Purpose We investigated whether ascending aorta longitudinal strain is intrinsically altered in BAV with respect to tricuspid aortic valve (TAV) individuals. Methods 80 BAV, 31 healthy volunteers (HV) and 29 TAV with AAo aneurysm, all without moderate valvular disease, were consecutively included. AAo dilation was defined as a z-score > 2. The 1.5T CMR protocol included a set of 2D cine CMR stacks covering the proximal aorta in saggital, coronal and axial views. AAo longitudinal strain was computed by an in-house Matlab code performing a feature tracking of the aortic valve in each of the cine images. Results Twenty (25%) of BAV had AAo dilation. AAo longitudinal strain was lower in non-dilated BAV compared to HV, but the difference was not significant in multivariate analysis adjusted for AAo diameter and systolic blood pressure. Similarly, the difference between dilated BAV and dilated TAV found in univariate analysis was not confirmed by multivariate analysis. On the other hand, both dilated BAV and TAV showed decreased AAo longitudinal strain compared to HV, which were confirmed in multivariate analyses. Conclusions AAo longitudinal strain, a marker of aortic stiffness with predictive value in MFS, is not altered in BAV patients compared to TAV matched for dilation prevalence. Reduced AAo longitudinal strain was independently associated with dilation in both BAV and TAV. Table 1 HV vs. NON-DILATED BAV DILATED BAV vs DILATED TAV HV vs. DILATED BAV HV vs. DILATED TAV HV NON-DILATED BAV Univariate /multivariate p-value DILATED TAV DILATED BAV Univariate /multivariate p-value Univariate/ Multivariate p-value Univariate p-value N 31 20 29 60 Age [years 35 ± 8 49 ± 16

Introduction Patent false lumen (FL) in aortic dissection has been associated with poor prognosis mainly due to aortic expansion. Although morphologic variables have been related to aortic dilatation as expression of high pressure in the FL, they do not reflect flow characteristics. We propose the maximum systolic flow deceleration rate (MSDR) in the FL, quantified by 4Dflow, assuming that flow should be strongly decelerated during systole under high pressure. Methods Twenty-nine patients with a patent FL after aortic dissection (no Marfan syndrome) and with a follow-up of at least 3 years underwent a contrast-enhanced 4D-flow MR. FL acceleration was calculated during the cardiac cycle in a sub-volume of the descending aorta (5 cm around the level of the pulmonary bifurcation). MSDR was determined as the maximum minus the minimum acceleration in systole over the corresponding time interval (Figure 1a). Aortic growth rate (GR) was defined as the difference between final and initial aortic diameters obtained by angio-CT over the period of follow-up. Population was divided into tertiles based on GR. Results Demographic, clinical variables or basal aortic diameter did not show differences among GR groups (Table 1). MSDR was statistically different in patients with a GR Table 1. Demographic and other variables Tertile 1 Tertile 2 Tertile 3 p-value Age (year) 63.4 (±13.5) 62.5 (±13.6) 64.6 (±6.7) 0.902 BSA (m2) 2.0 (±0.2) 1.8 (±0.2) 1.9 (±0.1) 0.213 Men 6 (86%) 4 (57%) 4 (100%) 0.210 Hypertension 4 (66%) 5 (71%) 4 (100%) 0.438 Atherosclerosis 1 (17%) 1 (14%) 0 (0%) 0.699 Initial diameter 45.0 (±7.69) 36.0 (±4.2) 37.0 (±6.5) 0.078 Final diameter 49.5 (±6.74) 44.9 (±5.7) 59.2 (±9.8) 0.049* Follow-up (year) 11.8 (±8.79) 7.9 (±3.3) 8.1 (±4.0) 0.921 Aortic GR (mm/year) 0.3 (±0.3) 1.2 (±0.3) 2.6 (±1.0) 0.001* MSDR (cm/s3) 1212 (±468) 2411 (±1034) 2558 (±1098) 0.005* Values are mean (±SD) or n (%). Conclusion MSDR of flow in the FL derived from 4D-flow RM is related to GR of dissected descending aorta. It is useful to discriminate mild vs. significant aorta enlargement and identify patients who may benefit from earlier therapy.

Aims Longitudinal determinants of aortic stiffness (AS) measured by magnetic resonance imaging (MRI) have not been assessed in a large community-based population. Our aim was to examine the determinants of change in thoracic AS over 10 years of follow-up in a multi-ethnic population of individuals 45 years of age and older measured by MRI. Methods and results We studied 1160 participants (mean age = 60 ± 9 years at baseline, 45% male) with aortic MRI at both the MESA Year 0 and Year 10 examinations. Ascending and descending aorta distensibility (AAD/DAD) and aortic arch pulse-wave velocity (PWV) were measured using MRI. Determinants of the change in AS parameters over 10 years were assessed using linear regression adjusted for baseline values, demographic variables, baseline risk factors and change in risk factors, and chronic risk exposure. AAD and DAD decreased slightly (5% decrease in median for AAD: 1.33–1.26 mmHg−1 · 10−3, P = 0.008; 5% decrease in median for DAD: 1.73–1.64 mmHg−1 · 10−3, P < 0.001), and PWV increased over 10 years (18% increase in median: 6.8–8.0 m/s P < 0.001). Baseline age was related to a reduction in AAD and DAD and an increase in PWV throughout the follow-up period. Baseline and change in mean blood pressure and continued smoking were associated with a reduction in AAD and an increase in PWV. Furthermore, baseline heart rate was also related to a reduction in AAD and DAD. Blood pressure normalization was related to less aortic stiffening throughout the follow-up period. Conclusions In our longitudinal, community-based cohort study of adult individuals aged 45 years or greater, greater mean blood pressure and a history of smoking history were associated with increased aortic stiffening over 10 years as assessed by MRI.

Aims To determine the efficacy of losartan vs. atenolol in aortic dilation progression in Marfan syndrome (MFS) patients. Methods and results A phase IIIb, randomized, parallel, double-blind study was conducted in 140 MFS patients, age range: 5–60 years, with maximum aortic diameter

Aims To assess the test–retest, intra- and inter-reader reliability of thoracic aorta measurements by magnetic resonance imaging (MRI). Methods and results Twenty-five participants underwent aortic MRI twice over 13 ± 7 days. All aortic variables from baseline and repeat MR were analysed using a semi-automated method by the ARTFUN software. To assess the inter-study reproducibility of aortic variables, we calculated intraclass correlation coefficient (ICC) for individual aortic measurements. Intra- and inter-observer variability was also assessed using the baseline MR data. Mean ascending aortic strain had moderate inter-study reproducibility (11.53 ± 6.44 vs. 10.55 ± 6.64, P = 0.443, ICC = 0.53, P < 0.01). Mean descending aortic strain and arch pulse wave velocity (PWV) had good inter-study reproducibility (descending aortic strain: 8.65 ± 5.30 vs. 8.35 ± 5.26, P = 0.706, ICC = 0.74, P < 0.001; PWV: 9.92 ± 4.18 vs. 9.94 ± 4.55, P = 0.968, ICC = 0.77, P < 0.001, respectively). All aortic variables had excellent intra- and inter-observer reproducibility (intra-: ICC range, 0.87–0.99, inter-: ICC range, 0.56–0.99, respectively). Conclusion Inter-study reproducibility of all aortic variables was acceptable. Intra- and inter-observer reproducibility of all aortic variables was excellent. MRI can provide a repeatable method of measuring aortic structural and functional parameters.