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Three-dimensional (3D) time-resolved phase-contrast cardiac magnetic resonance (4D flow CMR) allows for unparalleled quantification of blood velocity. Despite established potential in aortic diseases, the analysis is time-consuming and requires expert knowledge, hindering clinical application. The present research aimed to develop and test a fully automatic machine learning-based pipeline for aortic 4D flow CMR analysis.Four hundred and four subjects were prospectively included. Ground-truth to train the algorithms was generated by experts. The cohort was divided into training (323 patients) and testing (81) sets and used to train and test a 3D nnU-Net for segmentation and a Deep Q-Network algorithm for landmark detection. In-plane (IRF) and through-plane (SFRR) rotational flow descriptors and axial and circumferential wall shear stress (WSS) were computed at ten planes covering the ascending aorta and arch.Automatic aortic segmentation resulted in a median Dice score (DS) of 0.949 and average symmetric surface distance of 0.839 (0.632-1.071) mm, comparable with the state of the art. Aortic landmarks were located with a precision comparable with experts in the sinotubular junction and first and third supra-aortic vessels (p = 0.513, 0.592 and 0.905, respectively) but with lower precision in the pulmonary bifurcation (p = 0.028), resulting in precise localisation of analysis planes. Automatic flow assessment showed excellent (ICC0.9) agreement with manual quantification of SFRR and good-to-excellent agreement (ICC0.75) in the measurement of IRF and axial and circumferential WSS.Fully automatic analysis of complex aortic flow dynamics from 4D flow CMR is feasible. Its implementation could foster the clinical use of 4D flow CMR.• 4D flow CMR allows for unparalleled aortic blood flow analysis but requires aortic segmentation and anatomical landmark identification, which are time-consuming, limiting 4D flow CMR widespread use. • A fully automatic machine learning pipeline for aortic 4D flow CMR analysis was trained with data of 323 patients and tested in 81 patients, ensuring a balanced distribution of aneurysm aetiologies. • Automatic assessment of complex flow characteristics such as rotational flow and wall shear stress showed good-to-excellent agreement with manual quantification.

This study sought to assess the predictive value of wall shear stress (WSS) for colocalized ascending aorta (AAo) growth rate (GR) in patients with bicuspid aortic valve (BAV).BAV is associated with AAo dilation, but there is limited knowledge about possible predictors of aortic dilation in patients with BAV. An increased WSS has been related to aortic wall damage in patients with BAV, but no previous prospective study tested its predictive value for dilation rate. Recently, a registration-based technique for the semiautomatic mapping of aortic GR has been presented and validated.Forty-seven patients with BAV free from valvular dysfunction prospectively underwent 4-dimensional flow cardiac magnetic resonance to compute WSS and subsequent follow-up with 2 electrocardiogram-gated high-resolution contrast-enhanced computed tomography angiograms for GR assessment.During a median follow-up duration of 43 months, mid AAo GR was 0.24 mm/year. WSS and its circumferential component showed statistically significant association with mid AAo GR in bivariate (P = 0.049 and P = 0.014, respectively) and in multivariate analysis corrected for stroke volume and either baseline AAo diameter (P = 0.046 and P = 0.014, respectively) or z-score (P = 0.036 and P = 0.012, respectively). GR mapping further detailed that GR was heterogeneous in the AAo and that circumferential WSS, but not WSS magnitude, showed statistically significant positive associations with GR in the regions with the fastest growth.4D flow cardiac magnetic resonance-derived WSS and, in particular, its circumferential component predict progressive dilation of the ascending aorta in patients with BAV. Thus, the assessment of WSS may be considered in the follow-up of these patients.

Left ventricular noncompaction (LVNC) is a heterogeneous entity with uncertain prognosis. This study sought to develop and validate a prediction model of major adverse cardiovascular events (MACE) and to identify LVNC cases without events during long-term follow-up. This is a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance. MACE were defined as heart failure (HF), ventricular arrhythmias (VAs), systemic embolisms, or all-cause mortality. A total of 585 patients were included (45 ± 20 years of age, 57% male). LV ejection fraction (LVEF) was 48% ± 17%, and 18% presented late gadolinium enhancement (LGE). After a median follow-up of 5.1 years, MACE occurred in 223 (38%) patients: HF in 110 (19%), VAs in 87 (15%), systemic embolisms in 18 (3%), and 34 (6%) died. LVEF was the main variable independently associated with MACE (P < 0.05). LGE was associated with HF and VAs in patients with LVEF >35% (P < 0.05). A prediction model of MACE was developed using Cox regression, composed by age, sex, electrocardiography, cardiovascular risk factors, LVEF, and family aggregation. C-index was 0.72 (95% confidence interval: 0.67-0.75) in the derivation cohort and 0.72 (95% confidence interval: 0.71-0.73) in an external validation cohort. Patients with no electrocardiogram abnormalities, LVEF ≥50%, no LGE, and negative family screening presented no MACE at follow-up. LVNC is associated with an increased risk of heart failure and ventricular arrhythmias. LVEF is the variable most strongly associated with MACE; however, LGE confers additional risk in patients without severe systolic dysfunction. A risk prediction model is developed and validated to guide management. The project was partially funded by a grant from the Catalan Society of Cardiology (Barcelona, Spain). Hospital Universitario Virgen de la Arrixaca (Murcia, Spain) was supported by a grant from the Foundation Marató TV3 (218/C/2015) (Barcelona, Spain). Hospital Universitario y Politécnico La Fe (Valencia, Spain) was partially supported by Fondo Europeo de Desarrollo Regional (“Unión Europea, Una forma de hacer Europa”) (Madrid, Spain) and the Instituto de Salud Carlos III (La Fe Biobank PT17/0015/ 0043) (Madrid, Spain). Dr Guala was supported by funding from the Spanish Ministry of Science, Innovation and Universities (IJC2018-037349-I) (Madrid, Spain). Dr La Mura was supported by a research grant from the Cardiopath PhD program (Naples, Italy). Prof de la Pompa was supported by grants PID2019-104776RB-I00 and CB16/11/00399 (CIBER CV) from the Spanish Ministry of Science, Innovation and Universities. Dr Bayes-Genis was supported by grants from CIBER Cardiovascular (CB16/11/00403 and 16/11/00420) (Madrid, Spain) and AdvanceCat 2014-2020 (Barcelona, Spain); and has received advisory board and lecture fees from Novartis, Boehringer Ingelheim, Vifor, Roche Diagnostics, and Critical Diagnostics. Dr Pontone has received speaker honorarium and/or institutional research grants from GE Healthcare, Bracco, Boehringer Ingelheim, and HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sí

Bicuspid aortic valve (BAV), the most common congenital valve defect, is associated with increased risk of aortic dilation and related complications; however, current risk assessment is not effective. Most of BAV have three leaflets with a fusion between two of them of variable length. This study aimed to ascertain whether the extent of leaflet fusion (often called raphe) is related to aortic dilation and flow abnormalities in BAV with no significant valvular dysfunction. One hundred and twenty BAV patients with no significant valvular dysfunction or history of surgical repair or aortic valve replacement were consecutively and prospectively enrolled (September 2014–October 2018). Cardiac magnetic resonance protocol included a 4D flow sequence for haemodynamic assessment. Moreover, a stack of double-oblique cine images of the aortic valve were used to quantify fusion length (in systole) and leaflet length (diastole). Inter- and intra-observer reproducibility was tested in 30 randomly selected patients. Aortic valve leaflet fusion was measurable in 112 of 120 (93%) cases with good reproducibility (ICC = 0.826). Fusion length varied greatly (range: 2.3–15.4 mm; mean: 7.8 ± 3.2 mm). After correction for demographic and clinical conditions, fusion length was independently associated with diameter and z-score at the sinus of Valsalva (p = 0.002 and p = 0.002, respectively) and ascending aorta (p = 0.028 and p = 0.046). Fusion length was positively related to flow asymmetry, vortices and circumferential wall shear stress, thereby possibly providing a pathophysiological link with aortic dilation. Aortic valve fusion length is related to aortic dilation and flow abnormalities in BAV patients. • The length of the fusion between leaflets in non-dysfunctional bicuspid aortic valves varies substantially and can be reliably measured by cine CMR. • Aortic valve leaflet fusion length is independently related to aortic sinus and ascending aorta diameter. • Increased flow asymmetry, circumferential wall shear stress and presence of vortices are positively related to aortic valve leaflet fusion length.

BackgroundA proportion of de novo variants in patients affected by genetic disorders, particularly those with autosomal dominant (AD) inheritance, could be the consequence of somatic mosaicism in one of the progenitors. There is growing evidence that germline and somatic mosaicism are more common and play a greater role in genetic disorders than previously acknowledged. In Marfan syndrome (MFS), caused by pathogenic variants in the fibrillin-1 gene (FBN1) gene, approximately 25% of the disease-causing variants are reported as de novo. Only a few cases of parental mosaicism have been reported in MFS.MethodsEmploying an amplicon-based deep sequencing (ADS) method, we carried out a systematic analysis of 60 parents of 30 FBN1 positive, consecutive patients with MFS with an apparently de novo pathogenic variant.ResultsOut of the 60 parents studied (30 families), the majority (n=51, 85%) had a systemic score of 0, seven had a score of 1 and two a score of 2, all due to minor criteria common in the normal population. We detected two families with somatic mosaicism in one of the progenitors, with a rate of 6.6% (2/30) of apparently de novo cases.ConclusionsThe search for parental somatic mosaicism should be routinely implemented in de novo cases of MFS, to offer appropriate genetic and reproductive counselling as well as to reveal masked, isolated clinical signs of MFS in progenitors that may require specific follow-up.

Periodontitis is an inflammatory condition caused by a bacterial plaque and characterized by progressive destruction of the tooth-supporting apparatus. Patients with Marfan syndrome (MFS) exhibit a connective tissue disorder, which can also affect oral soft and hard tissue. Thus, the aims of this cross-sectional study were to assess the association between periodontitis and MFS and secondly, to compare periodontal parameters and prevalence of disease with a control group (CG) without MFS. 152 patients ( MFS = 76 , CG = 76 ) were recruited to evaluate the following periodontal parameters: probing depth, gingival margin, clinical attachment level, plaque index, and bleeding on probing. The 2017 World Workshop guideline was followed for the diagnosis of the periodontal status. A multivariate analysis was performed using a multinomial logistic regression adjusted for age, gender, and smoking. The level of significance required was p < 0.05 . Patients with MFS did not show a higher prevalence of periodontitis compared to the CG. However, patients with MFS did have higher values in probing depth, gingival recession, clinical attachment level, and plaque index compared to the CG patients ( p < 0.05 ). In conclusion, although similar prevalence of periodontitis was found among the studied groups, MFS patients showed worse periodontal parameters.

Resumen Introduccion y objetivos El sindrome aortico agudo (SAA) tiene una alta mortalidad que obliga a un tratamiento precoz. El proposito del presente estudio es analizar los cambios en el abordaje y el tratamiento del SAA a lo largo de 20 anos. Metodos Se incluyo prospectivamente a 451 pacientes (336 varones; media de edad, 60,9 ± 12,4 anos) diagnosticados de SAA, 270 con el tipo A y 181 con el tipo B, desde 1999 hasta 2018. Se analizaron variables clinicas, diagnosticas y del tratamiento y las complicaciones hospitalarias. Resultados El uso de la tomografia computarizada (TC) como primera tecnica diagnostica se incremento del 62,8 al 94,2% (p Conclusiones El diagnostico y el tratamiento del SAA han presentado importantes cambios en las ultimas 2 decadas. La TC se ha consolidado como la tecnica diagnostica de eleccion. La mortalidad del SAA tipo A ha disminuido de manera muy importante debido a la mejora de los resultados del tratamiento quirurgico. En el SAA tipo B, el tratamiento medico solo se ha reducido debido a la aparicion del tratamiento endovascular, pero la mortalidad hospitalaria no ha disminuido de manera significativa.

Supplemental Digital Content is available in the text., Objective: To assess the relationship between regional wall shear stress (WSS) and oscillatory shear index (OSI) and aortic dilation in patients with bicuspid aortic valve (BAV). Approach and Results: Forty-six consecutive patients with BAV (63% with right-left-coronary-cusp fusion, aortic diameter ≤ 45 mm and no severe valvular disease) and 44 healthy volunteers were studied by time-resolved 3-dimensional phase-contrast magnetic resonance imaging. WSS and OSI were quantified at different levels of the ascending aorta and the aortic arch, and regional WSS and OSI maps were obtained. Seventy percent of BAV had ascending aorta dilation. Compared with healthy volunteers, patients with BAV had increased WSS and decreased OSI in most of the ascending aorta and the aortic arch. In both BAV and healthy volunteers, regions of high WSS matched regions of low OSI and vice versa. No regions of both low WSS and high OSI were identified in BAV compared with healthy volunteers. Patients with BAV with dilated compared with nondilated aorta presented low and oscillatory WSS in the aortic arch, but not in the ascending aorta where dilation is more prevalent. Furthermore, no regions of concomitant low WSS and high OSI were identified when BAV were compared according to leaflet fusion pattern, despite the well-known differences in regional dilation prevalence. Conclusions: Regions with low WSS and high OSI do not match those with the highest prevalence of dilation in patients with BAV, thus providing no evidence to support the low and oscillatory shear stress theory in the pathogenesis of proximal aorta dilation in the presence of BAV.

Tatton-Brown-Rahman (TBRS) syndrome is a recently described overgrowth syndrome caused by loss of function variants in the DNMT3A gene. This gene encodes for a DNA methyltransferase 3 alpha, which is involved in epigenetic regulation, especially during embryonic development. Somatic variants in DNMT3A have been widely studied in different types of tumors, including acute myeloid leukemia, hematopoietic, and lymphoid cancers. Germline gain-of-function variants in this gene have been recently implicated in microcephalic dwarfism. Common clinical features of patients with TBRS include tall stature, macrocephaly, intellectual disability (ID), and a distinctive facial appearance. Differential diagnosis of TBRS comprises Sotos, Weaver, and Malan Syndromes. The majority of these disorders present other clinical features with a high clinical overlap, making necessary a molecular confirmation of the clinical diagnosis. We here describe seven new patients with variants in DNMT3A, four of them with neuropsychiatric disorders, including schizophrenia and psychotic behavior. In addition, one of the patients has developed a brain tumor in adulthood. This patient has also cerebral atrophy, aggressive behavior, ID, and abnormal facial features. Clinical evaluation of this group of patients should include a complete neuropsychiatric assessment together with psychological support in order to detect and manage abnormal behaviors such as aggressiveness, impulsivity, and attention deficit-hyperactivity disorder. TBRS should be suspected in patients with overgrowth, ID, tall stature, and macrocephaly, who also have some neuropsychiatric disorders without any genetic defects in the commonest overgrowth disorders. Molecular confirmation in these patients is mandatory., This project was supported by ISCII, FEDER funds grant: FIS-PI15/01481.

BACKGROUND There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS). OBJECTIVES This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey. METHODS Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention. RESULTS A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001). CONCLUSIONS A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians. (J Am Coll Cardiol 2021;78:2131-2143) (c) 2021 by the American College of Cardiology Foundation.

Bicuspid aortic valve (BAV) patients are at high risk of developing progressive aortic valve dysfunction and ascending aorta dilation. However, the progression of the disease is not well defined. We aimed to assess mid-long-term aorta dilation and valve dysfunction progression and their predictors. Patients were referred from cardiac outpatient clinics to the echocardiographic laboratories of 10 tertiary hospitals and followed clinically and by echocardiography for &gt, 5 years. Seven hundred and eighteen patients with BAV (median age 47.8 years [IQR 33–62], 69.2% male) were recruited. BAV without raphe was observed in 11.3%. After a median follow-up of 7.2 years [IQR5–8], mean aortic root growth rate was 0.23 ± 0.15 mm/year. On multivariate analysis, rapid aortic root dilation (&gt, 0.35 mm/year) was associated with male sex, hypertension, presence of raphe and aortic regurgitation. Annual ascending aorta growth rate was 0.43 ± 0.32 mm/year. Rapid ascending aorta dilation was related only to hypertension. Variables associated with aortic stenosis and regurgitation progression, adjusted by follow-up time, were presence of raphe, hypertension and dyslipidemia and basal valvular dysfunction, respectively. Intrinsic BAV characteristics and cardiovascular risk factors were associated with aorta dilation and valvular dysfunction progression, taking into account the inherent limitations of our study-design. Strict and early control of cardiovascular risk factors is mandatory in BAV patients.

Ascending aorta diameters have important clinical value in the diagnosis, follow-up, and surgical indication of many aortic diseases. However, there is no uniformity among experts regarding ascending aorta diameter quantification by echocardiography. The aim of this study was to compare maximum aortic root and ascending aorta diameters determined by the diastolic leading edge (DLE) and the systolic inner edge (SIE) conventions in adult and pediatric patients with inherited cardiovascular diseases. Transthoracic echocardiograms were performed in 328 consecutive patients (260 adults and 68 children). Aorta diameters were measured twice at the root and ascending aorta by the DLE convention following the 2015 American Society of Echocardiography (ASE) adult guidelines and the SIE convention following the 2010 ASE pediatric guidelines. Comparison of the diameters measured by the two conventions in the overall population showed a non-significant underestimation of the diameter measured by the SIE convention at root level of 0.28 mm (CI -1.36, 1.93) and at tubular ascending aorta level of 0.17 mm (CI-1.69, 2.03). Intraobserver and interobserver variability were excellent. Maximum aorta diameter measured by the leading edge convention in end-diastole and the inner edge convention in mid-systole had similar values to a mild non-significant underestimation of the inner-to-inner method that permits them to be interchangeable when used in clinical practice.

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.

Despite the absence of clinical complications after an acute aortic dissection (AD) with persistent patent false lumen (FL), a high risk for clinical events may persist.The aim of this study was to assess the natural evolution of noncomplicated AD and ascertain whether different FL flow patterns by magnetic resonance imaging (MRI) have independent prognostic value for AD-related events beyond established morphologic parameters.One hundred thirty-one consecutive patients, 78 with surgically treated type A dissections and 53 with medically treated type B dissections, were followed up prospectively after acute AD with persistent patent FL in the descending aorta. Maximum aortic diameter, true lumen compression, entry tear, and partial FL thrombosis by computed tomography were assessed. Systolic antegrade true lumen and FL flow volumes and diastolic antegrade and retrograde flows were analyzed by MRI during the first year after AD.After a median follow-up period of 8.0 years (IQR: 4.6-10.9 years), 43 patients presented aorta-related events (25 died and 18 required endovascular treatment). FL systolic antegrade flow ≥30% with respect to total systolic antegrade flow and retrograde diastolic flow ≥80% with respect to total diastolic FL flow were predictors of aortic events. In multivariate analysis, aortic diameter45 mm (HR: 2.91), type B dissection (HR: 2.44), and MRI flow pattern (HR: 16.87) were independent predictors of AD-related events.High systolic antegrade flow volume in the FL with significant diastolic retrograde flow assessed by MRI and aortic diameter45 mm identify patients with higher risk for complications in whom more aggressive management would be indicated.

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): 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.

Echocardiography plays an important role in the diagnosis and follow-up of aortic diseases. Evaluation of the aorta is a routine part of the echocardiographic examination. Transthoracic echocardiography (TTE) is an excellent modality for imaging the aortic proximal ascending aorta, which is important in the diagnosis and follow-up of aorta aneurysms. Transoesophageal echocardiography (TEE) overcomes the limitations of TTE in thoracic aorta assessment. Although TEE is the technique of choice in the diagnosis of aortic dissection, TTE may be used as the initial modality in the emergency setting. Intimal flap in proximal ascending aorta, pericardial effusion/tamponade, and left ventricular function can be easily visualized by TTE. However, a negative TTE does not rule out aortic dissection and other imaging techniques must be considered. TEE should define entry tear size and location, mechanisms and severity of aortic regurgitation, and true lumen compression. TEE is essential in selecting and monitoring surgical and endovascular treatment and in detecting possible complications.

Manual assessment of aortic diameters on double-oblique reformatted computed tomography angiograms (CTA) is considered the current standard, although the reproducibility for growth rates has not been reported. Deformable registration of CTA has been proposed to provide 3D aortic diameters and growth maps, but validation is lacking. This study aimed to quantify accuracy and inter-observer reproducibility of registration-based and manual assessment of aortic diameters and growth rates. Forty patients with ≥ 2 CTA acquired at least 6 months apart were included. Aortic diameters and growth rate were obtained in the aortic root and the entire thoracic aorta using deformable image registration by two independent observers, and compared with the current standard at typical anatomical landmarks. Compared with manual assessment, the registration-based technique presented low bias (0.46 mm), excellent agreement (ICC = 0.99), and similar inter-observer reproducibility (ICC = 0.99 for both) for aortic diameters; and low bias (0.10 mm/year), good agreement (ICC = 0.82), and much higher inter-observer reproducibility for growth rates (root: ICC = 0.96 vs 0.68; thoracic aorta: ICC = 0.96 vs 0.80). Registration-based growth rate reproducibility over a 6-month-long follow-up was similar to that obtained by manual assessment after 2.7 years (LoA = [− 0.01, 0.33] vs [− 0.13, 0.21] mm/year, respectively). Mapping of diameter and growth rate was highly reproducible (ICC > 0.9) in the whole thoracic aorta. Registration-based assessment of aortic dilation on CTA is accurate and substantially more reproducible than the current standard, even at follow-up as short as 6 months, and provides robust 3D mapping of aortic diameters and growth rates beyond the pre-established anatomic landmarks. • Registration-based semi-automatic assessment of progressive aortic dilation on CTA is accurate and substantially more reproducible than the current standard. • The registration-based technique allows robust growth rate assessment at follow-up as short as 6 months, with a similar reproducibility to that obtained by manual assessment at around 3 years. • The use of image registration provides robust 3D mapping of aortic diameters and growth rates beyond the pre-established anatomic landmarks.

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

Objectives This study sought to ascertain whether patients with a bicuspid aortic valve (BAV) have an intrinsic alteration in regional aortic stiffness compared with patients with tricuspid aortic valve (TAV) and Marfan syndrome (MFS) patients with similar aortic sizes, as well as to assess the influence of ascending aorta (AAo) dilation on regional stiffness parameters in BAV patients. Background Imaging biomarkers as predictors of BAV, MFS, and degenerative AAo aneurysms in TAV patients (DA-TAV) are lacking. Biomechanical characterization has been proposed as a possible tool for further aneurysm stratification. Methods A total 234 subjects (136 BAV, 44 MFS, and 18 DA-TAV patients and 36 healthy control subjects) were included. The cardiac magnetic resonance protocol comprised 4-dimensional flow to assess AAo and descending aorta (DAo) pulse wave velocities (PWVs) and double-oblique, 2-dimensional, steady-state free-precession cine cardiac magnetic resonance to compute aortic distensibility (AD). Results On adjusted analysis, nondilated BAV patients had similar PWV and AD as healthy control subjects in both AAo and DAo, whereas dilated BAV did not differ from DA-TAV. In contrast, AAo and DAo stiffness in MFS patients was markedly greater than in BAV patients, increasing slightly with dilation severity. AAo PWV showed a biphasic pattern in BAV patients: it first decreased and then increased throughout AAo dilation, with a clear turning point at 50 mm, whereas distensibility did not discern mildly dilated aorta. In multivariate analysis adjusted for clinical and demographic characteristics, only PWV was related to AAo dilation in BAV patients. Conclusions The mechanical properties of AAo aneurysms are similar in BAV and TAV patients, whereas MFS patients have a stiffer aorta. Aortic stiffness strongly depends on dilation severity. AAo PWV resulted in a potentially clinically useful biphasic trend with respect to aneurysm diameter, whereas distensibility did not discern mildly dilated aorta. Beyond clinical risk factors, PWV but not AD was independently related to AAo dilation in BAV patients.

Transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI) have yielded excellent results in aortic root diameter measurement in patients with tricuspid aortic valve. However, accuracy in bicuspid aortic valve (BAV), often associated with aortic root asymmetry, is not fully defined. The aim of this study was to determine the agreement between TTE and MRI in proximal ascending aortic diameters in patients with BAVs.Seventy-six consecutive patients with BAVs (mean age, 53 ± 15 years; 65% men) who underwent both TTE and MRI for ascending aortic assessment in a follow-up protocol were included in the study. Maximum aortic root and ascending aortic diameters were compared.For the whole population, TTE slightly underestimated aortic root diameter (difference, -0.8 ± 2.9 mm; P = .02). However, agreement was significantly better in BAV with fusion of the left and right coronary cusps than with fusion of the right coronary and noncoronary cusps, both with (type 1) and without (type 0) raphe (mean difference, 0.1 ± 2.5 vs -2.8 ± 2.8 mm, P .001, respectively). In raphe BAV, mean absolute differences of maximum diameters between both techniques were significantly greater in asymmetric versus symmetric aortic roots (3.3 ± 2.2 vs 1.6 ± 1.9 mm, P = .002). BAV type and root asymmetry were independent related to measurement disagreement between both modalities.Although TTE is the technique of choice in the follow-up of patients with BAVs, aortic root diameter measurements may be inaccurate in the presence of root asymmetry and in BAV with fusion of the right coronary and noncoronary cusps. In these cases, cross-sectional imaging, with MRI or computed tomography, to confirm aortic diameters may be advisable.

This study applies convolutional neural network (CNN)-based automatic segmentation and distensibility measurement of the ascending and descending aorta from 2D phase-contrast cine magnetic resonance imaging (PC-cine MRI) within the large MESA cohort with subsequent assessment on an external cohort of thoracic aortic aneurysm (TAA) patients. 2D PC-cine MRI images of the ascending and descending aorta at the pulmonary artery bifurcation from the MESA study were included. Train, validation, and internal test sets consisted of 1123 studies (24282 images), 374 studies (8067 images), and 375 studies (8069 images), respectively. An external test set of TAAs consisted of 37 studies (3224 images). A U-Net based CNN was constructed, and performance was evaluated utilizing dice coefficient (for segmentation) and concordance correlation coefficients (CCC) of aortic geometric parameters by comparing to manual segmentation and parameter estimation. Dice coefficients for aorta segmentation were 97.6% (CI: 97.5%-97.6%) and 93.6% (84.6%-96.7%) on the internal and external test of TAAs, respectively. CCC for comparison of manual and CNN maximum and minimum ascending aortic areas were 0.97 and 0.95, respectively, on the internal test set and 0.997 and 0.995, respectively, for the external test. CCCs for maximum and minimum descending aortic areas were 0.96 and 0. 98, respectively, on the internal test set and 0.93 and 0.93, respectively, on the external test set. We successfully developed and validated a U-Net based ascending and descending aortic segmentation and distensibility quantification model in a large multi-ethnic database and in an external cohort of TAA patients., 25 pages, 5 figures

Aortic branch aneurysms are not included in the diagnostic criteria for Marfan syndrome (MFS); however, their prevalence and eventual prognostic significance are unknown.The goal of this study was to assess the prevalence of aortic branch aneurysms in MFS and their relationship with aortic prognosis.MFS patients with a pathogenic FBN1 genetic variant and at least one magnetic resonance or computed tomography angiography study assessing aortic branches were included. Aortic events and those related to aneurysm complications were recorded during follow-up.A total of 104 aneurysms were detected in 50 (26.7%) of the 187 patients with MFS (mean age 37.9 ± 14.4 years; 54% male) included in this study, with the iliac artery being the most common location (45 aneurysms). Thirty-one patients (62%) had1 peripheral aneurysm, and surgery was performed in 5 (4.8%). Patients with aneurysms were older (41.9 ± 12.7 years vs. 36.7 ± 14.8 years; p = 0.040) and had more dilated aortic root (42.2 ± 6.4 mm vs. 38.8 ± 8.0 mm; p = 0.044) and dyslipidemia (31.0% vs. 9.7%; p = 0.001). In a subgroup of 95 patients with no previous aortic surgery or dissection followed up for 3.3 ± 2.6 years, the presence of arterial aneurysms was associated with a greater need for aortic surgery (hazard ratio: 3.4; 95% confidence interval: 1.1 to 10.3; p = 0.028) in a multivariable Cox analysis adjusted for age and aortic diameter.Aortic branch aneurysms are present in one-quarter of patients with MFS and are related to age and aortic dilation, and they independently predict the need for aortic surgery. The systematic use of whole-body vascular assessment is recommended to identify other sites of vascular involvement at risk for complications and to define the subgroup of patients with more aggressive aortic disease.

Imatge de perfusió miocàrdica per TC; Isquèmia miocàrdica; Relació de perfusió transmural CT myocardial perfusion imaging; Myocardial ischaemia; Transmural perfusion ratio Imágenes de perfusión miocárdica por TC; Isquemia miocárdica; Relación de perfusión transmural Purpose To compare performance of visual and quantitative analyses for detecting myocardial ischaemia from single- and dual-energy computed tomography (CT) in patients with suspected coronary artery disease (CAD). Methods Eighty-four patients with suspected CAD were scheduled for dual-energy cardiac CT at rest (CTA) and pharmacological stress (CTP). Myocardial CT perfusion was analysed visually and using three parameters: mean attenuation density (MA), transmural perfusion ratio (TPR) and myocardial perfusion reserve index (MPRI), on both single-energy CT and CT-based iodine images. Significant CAD was defined in AHA-segments by concomitant myocardial hypoperfusion identified visually or quantitatively (parameter < threshold) and coronary stenosis detected by CTA. Single-photon emission CT and invasive coronary angiography were used as reference. Perfusion-parameter cut-off values were calculated in a randomly-selected subgroup of 30 patients. Results The best-performing thresholds for TPR, MPRI and MA were 0.96, 23 and 0.5 for single-energy CT and 0.97, 47 and 0.3 for iodine imaging. For both CT-imaging modalities, TPR yielded the highest area under receiver operating characteristic curve (AUC) (0.99 and 0.97 for single-energy CT and iodine imaging, respectively, in vessel-based analysis) compared to visual analysis, MA and MPRI. Visual interpretation on iodine imaging resulted in higher AUC compared to that on single-energy CT in per-vessel (AUC: 0.93 vs 0.86, respectively) and per-patient (0.94 vs 0.93) analyses. Conclusion Transmural perfusion ratio on both CT-imaging modalities is the best-performing parameter for detecting myocardial ischaemia compared to visual method and other perfusion parameters. Visual analysis on CT-based iodine imaging outperforms that on single-energy CT.

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.

The lack of standardized pipelines for image processing has prevented the application of deep learning (DL) techniques for the segmentation of the aorta in phase-contrast enhanced magnetic resonance angiography (PC-MRA). Furthermore, large, well-curated and annotated datasets, which are needed to create DL-based models able to generalize, are rare. We present the adaptation of the popular nnU-net DL framework to automatically segment the aorta in 4D flow MRI-derived angiograms. The resulting segmentations in a large database (\(> 300\) cases) with normal cases and examples of different pathologies of the aorta provided from a single centre were excellent after post-processing (Dice score of 0.944). Subsequently, we explored the generalisation of the trained network in a small dataset of images (around 20 cases) acquired in a different hospital with another scanner. Without domain adaptation, only with a model trained with the large dataset, the obtained results were substantially worst than with adding a few cases of the small dataset (Dice scores of 0.61 vs 0.86, respectively). The obtained results created good quality segmentations of the aorta in 4D flow MRI, which can later be post-processed to assess blood flow patterns, similarly than with manual annotations. However, advanced domain adaptation schemes are very important in 4D flow MRI due to the large differences in image characteristics between different vendor scanners available in multiple centers.

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: Thoracic endovascular aortic repair (TEVAR) is becoming the preferred treatment option to repair the proximal descending aorta after rupture following blunt traumatic injury. However, hemodynamic and mechanic implications of this intervention are poorly understood. Exploiting the possibilities of 4D flow magnetic resonance imaging, hemodynamics, stiffness and local dilation in the ascending aorta in patients following aortic repair by TEVAR are studied. Methods: Fifteen apparently healthy individuals who underwent TEVAR implantation after traumatic descending aortic injury and 44 healthy volunteers (HV) underwent 4D flow-MRI. Ascending aorta pulse wave velocity was computed [1]. Moreover, at eight planes equally distributed in the ascending aorta systolic flow reversal ratio, i.e. relative amount of backward flow during systole, and in-plane rotational flow, measuring the strength of helical flow, were computed [2,3]. Results: TEVAR patients and HV did not differ in terms of age, sex, BSA and blood pressure (Table). However, compared to HV, TEVAR patients showed reduced in-plane rotational flow in the distal ascending aorta in patients with TEVAR and increased backward systolic flow in the whole ascending aorta (Figure). Patients with TEVAR had a stiffer ascending aorta, with pulse wave velocity higher compared control (7.8 ± 4.2 vs 5.3 ± 1.9, p = 0.004). Finally, aortic root and ascending aorta diameters were larger in TEVAR patients compared to HV (Table). Healthy volunteers TEVAR patients p N 44 15 Age [years] 40 ± 12 43 ± 10 0.392 Sex [% male] 66 80 0.075 Years from intervention [years] N/A 10.3 ± 6.4 N/A Body surface area [m2] 1.87 ± 0.15 1.96 ± 0.23 0.088 Systolic blood pressure [mmHg] 127 ± 19 131 ± 15 0.389 Diastolic blood pressure [mmHg] 70 ± 11 74 ± 9 0.198 Aortic root diameter [mm] 31 ± 4 34 ± 4 0.026 Ascending aorta diameter [mm] 28 ± 4 32 ± 3 0.003 Ascending aorta PWV [m/s] 5.3 ± 1.9 7.8 ± 4.2 0.004 FigureIn-plane rotational flow (IRF, left) and systolic flow reversal ratio (SFRR, right) in healthy volunteers (black) and TEVAR patients (yellow) in the proximal (planes 1 to 4) and distal (planes 5 to 8) ascending aorta. Stars show statistically-significant differences (p < 0.05). Conclusions: The implantation of TEVAR in apparently healthy individuals after traumatic rupture of the proximal descending aorta is associated with altered hemodynamics, higher stiffness and larger aortic diameter in the region proximal to the TEVAR.

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