Risk assessment for aortic dissection in Turner syndrome: The role of the aortic growth rate.

OBJECTIVE: The risk of aortic dissection (AoD) is increased in Turner syndrome (TS) but predicting those at risk is difficult. Based on scarce evidence, preventive aortic surgery is recommended when aortic diameter increases >5 mm/year. To investigate the aortic growth rate in TS and TS-related conditions associated with aortic growth. We also reported our experience of women who suffered aortic dissection (AoD), and who had preventive aortic replacement. METHODS: 151 adult TS were retrospectively identified. Women who had more than one transthoracic echocardiogram (TTE) after age 16 years were included in the aortic growth study. Aortic diameters at sinuses of Valsalva (SoV) and ascending aorta (AA) were analysed by two experts. RESULTS: 70/151 women had more than one TTE (interscan interval 4.7 years). Mean aortic growth was 0.13 ± 0.59 mm/year at SoV and 0.23 ± 0.82 mm/year at AA. Known risk factors for aortic dilatation and TS-related conditions were not associated with aortic growth. 4/151 women experienced AoD (age 25±8 years): two had paired scans for aortic growth, which was 0.67 mm/year at both SoV and AA in the first woman, and 11 mm/year (SoV) and 4 mm/year (AA) in the second. Only 1/4 of women with AoD survived; she used a TS cardiac-alert card to inform emergency personnel about her risk of AoD. 5/151 had a preventive aortic replacement, but one died post-operatively. CONCLUSIONS: Mean aortic growth in our TS population was increased compared to non-TS women and was not associated with currently known risk factors for AoD, suggesting that aortic growth rate itself could be a useful variable to stratify who is at risk for AoD.

Arterial tortuosity in pediatric Loeys-Dietz syndrome patients.

Loeys-Dietz syndrome (LDS) is an autosomal connective tissue disorder commonly presenting with hypertelorism, bifid uvula, aortic aneurysms, and arterial tortuosity. The aim of the present study was to investigate differences in tortuosity index (TI) between genotypes of LDS, possible progression over time and its use as an adjunctive prognostic tool alongside aortic dimensions to aid timely surgical planning in pediatric patients. A retrospective observational study of pediatric LDS patients referred to our center (November 2012-February 2021) was conducted. Using magnetic resonance angiography (MRA) with 3D maximum intensity projection volume-rendered angiogram, arterial TI was measured. Twenty three patients had genetically confirmed LDS with at least one head and neck MRA and 19 had no less than one follow-up MRA available. All patients presented arterial tortuosity. Patients with TGFBR2 variants had greater values of TI compared to patients with TGFB2 variants (p = 0.041). For patients who did not undergo surgery (n = 18), z-scores at the level of the sinus of Valsalva showed a significant correlation with vertebral TI (rs = 0.547). There was one death during follow-up. This study demonstrates that patients with LDS and TGFBR2 variants have greater values of TI than patients with TGFB2 variants and that greatest values of TI are associated with increased aortic root z-scores. Furthermore, as TI decreases over time, less frequent neuroimaging follow-up can be considered. Nevertheless, additional studies are needed to better define more accurate risk stratification and long-term surveillance in these patients.

Working towards risk stratification for ascending aortic dilatation in pediatric Turner syndrome patients: results of a longitudinal echocardiographical observation.

This study aimed to longitudinally evaluate aortic root dimensions and elasticity in pediatric Turner syndrome (TS) in relation to known cardiac implications such as coarctation of the aorta (CoA) and bicuspid aortic valves (BAV) in order to create an improved risk profile for the presumed underlying vessel pathology in childhood. We report on the longitudinal findings of our pediatric TS outpatient clinic over a period of up to 7.6 years. Forty-nine TS patients (median age at baseline 9.7 ± 5.9 years, range 0-19.8) were followed-up for on average 2.9 ± 1.1 examinations and a median time of 3.4 ± 1.6 years. Aortic root (AoR) diameters and corresponding Z-scores were determined echocardiographically, and elasticity parameters as well as annual progression rates were calculated. At baseline, 16.3% of patients showed Z-scores > 2 at one or more levels of the AoR (35.7% of patients with BAV, odds ratio of 4.2). There was net progression to be noted at all measuring levels, leading to 28.6% of patients (50% of patients with BAV) exhibiting aortic dilatation at the end of follow-up. Progression correlated with the presence of BAV, non-mosaic monosomy, and age. A levelling-off of progression was seen with the onset of adolescence. CONCLUSIONS: Marked progression of aortic diameters leading to the development of dilatation can be observed in TS patients during childhood and stresses the importance of close surveillance during childhood. Main risk factors are BAV and complete monosomy 45X0. A beneficial influence of estrogen substitution can be suspected but needs further investigation. WHAT IS KNOWN: • Patients with Turner syndrome are at an increased risk for aortic dilatation and dissection. • The presence of BAV and complete monosomy 45X are additional risk factors. WHAT IS NEW: • Aortic dilatation can be detected in pediatric patients with Turner syndrome. • Relevant progression in childhood is possible in at-risk individuals and warrants close surveillance.

Genotype and clinical phenotype of children with Marfan syndrome in Southeastern Anatolia.

The cardinal phenotypic hallmarks of Marfan syndrome (MFS) include cardiac, ocular, and skeletal abnormalities. Since the clinical phenotype of MFS is highly heterogeneous, with certain symptoms appearing as children age, the diagnostic process and establishing a genotype-phenotype association in childhood MFS can be challenging. The lack of sufficient childhood studies also makes it difficult to interpret the subject. This study aims to evaluate the relationship between clinical symptoms used as diagnostic criteria and FBN1 variations in children with MFS. This study investigated the relationships between genotypes and phenotypes in 131 children suspected of having Marfan syndrome (MFS). Diagnosis of MFS was made according to the revised Ghent nosology. FBN1 variants were categorized based on exon regions, type of variant, and pathogenicity classes. These FBN1 variants were then correlated with the clinical manifestations including cardiovascular, ocular, facial, and skeletal abnormalities. Out of the children, 43 were diagnosed with MFS. FBN1 variant was identified in 32 (74.4%) of the MFS children. MFS diagnosis could not be made in five (15.6%) FBN1 variant-positive children. The most common cardinal finding is cardiac anomalies n = 38 (88.3%). The most common FBN1 pathogenic variant was c.1786 T > C/p.Cys596Arg n = 4 (12.5%). The distribution of pathogenic variants was as follows: 29 (90.6%) missense, 2 (6.3%) frameshift, and 1 (3.1%) nonsense. The numbers of AD and EL of the variant-positive children were 16 (50%) and 14 (43.7%), respectively. Ocular abnormalities were more common in children with FBN1-positive MFS (p = 0.009). There was no difference in the number of cardiac abnormalities between FBN1-positive and FBN1-negative MFS patients (p = 0.139).   Conclusion: This study examines the relationship between FBN1 variants and clinical features used as diagnostic criteria in MFS children. The findings emphasize the importance of long-term monitoring of heterogeneous clinical phenotypes and bioinformatic reanalysis in determining the genotype-phenotype relationship in children, as MFS symptoms can vary with age. What is Known: • Marfan syndrome has highly variable phenotypic heterogeneity. • The genotype-phenotype relationship in childhood Marfan syndrome is not clear enough due to the variation in the time of onset of the findings. What is New: • This article provides regional data for the field of research on genotype-phenotype relationships in childhood Marfan syndrome. • Long-term follow-up of clinical findings and bioinformatics reanalysis is an important requirement for a well-established genotype-phenotype relationship in childhood Marfan syndrome.

Assessment of aortic dilatation in Chinese children and adolescents with Turner syndrome: a single center experience.

BACKGROUND: Patients with Turner syndrome (TS) face an increased risk of developing aortic dilatation (AD), but diagnosing AD in children presents greater complexity compared to adults. This study aimed to investigate the application of various assessment indicators of AD in Chinese children and adolescents with TS. METHODS: This study included TS patients admitted to Shenzhen Children's Hospital from 2017 to 2022. Cardiovascular lesions were diagnosed by experienced radiologists. Patients without structural heart disease were divided into different body surface area groups, then the Chinese TS population Z-score (CHTSZ-score) of the ascending aorta was calculated and compared with other indicators such as aortic size index (ASI), ratio of the ascending to descending aortic diameter (A/D ratio), and TSZ-score (Quezada's method). RESULTS: A total of 115 TS patients were included, with an average age of 10.0 ± 3.7 years. The incidences of the three most serious cardiovascular complications were 9.6% (AD), 10.4% (coarctation of the aorta, CoA), and 7.0% (bicuspid aortic valve, BAV), respectively. The proportion of developing AD in TS patients aged ≥ 10 years was higher than that in those < 10 years old (16.6% vs. 1.8%, P = 0.009), and the proportion of patients with CoA or BAV who additionally exhibited AD was higher than those without these conditions (31.6% vs. 5.2%, P < 0.001). The ASI, A/D ratio, TSZ-score, and CHTSZ-score of the 11 patients with AD were 2.27 ± 0.40 cm/m2, 1.90 ± 0.37, 1.28 ± 1.08, and 3.07 ± 2.20, respectively. Among the AD patients, only 3 cases had a TSZ-score ≥ 2, and 2 cases had a TSZ-score ≥ 1. However, based on the assessment using the CHTSZ-score, 6 patients scored ≥ 2, and 5 patients scored ≥ 1. In contrast, the TSZ-score generally underestimated the aortic Z-scores in Chinese children with TS compared to the CHTSZ-score. CONCLUSIONS: The applicability of ASI and A/D ratio to children with TS is questionable, and racial differences can affect the assessment of TSZ-score in the Chinese population. Therefore, establishing the CHTSZ-score specifically tailored for Chinese children and adolescents is of paramount importance.

Family screening for bicuspid aortic valve and aortic dilatation: a meta-analysis.

AIMS: International guidelines recommend screening of first-degree relatives (FDR) of people with bicuspid aortic valves (BAVs). However, the prevalence of BAV and of aortic dilatation amongst family members is uncertain. METHODS AND RESULTS: A systematic review and meta-analysis of original reports of screening for BAV. Databases including MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to December 2021 using relevant search terms. Data were sought on the screened prevalence of BAV and aortic dilatation. The protocol was specified prior to the searches being performed, and standard meta-analytic techniques were used. Twenty-three observational studies met inclusion criteria (n = 2297 index cases; n = 6054 screened relatives). The prevalence of BAV amongst relatives was 7.3% [95% confidence interval (CI) 6.1%-8.6%] overall and per family was 23.6% (95% CI 18.1%-29.5%). The prevalence of aortic dilatation amongst relatives was 9.4% (95% CI 5.7%-13.9%). Whilst the prevalence of aortic dilatation was particularly high in relatives with BAV (29.2%; 95% CI 15.3%-45.1%), aortic dilatation alongside tricuspid aortic valves was a more frequent finding, as there were many more family members with tricuspid valves than BAV. The prevalence estimate amongst relatives with tricuspid valves (7.0%; 95% CI 3.2%-12.0%) was higher than reported in the general population. CONCLUSION: Screening family members of people with BAV can identify a cohort substantially enriched for the presence of bicuspid valve, aortic enlargement, or both. The implications for screening programmes are discussed, including in particular the substantial current uncertainties regarding the clinical implications of aortic findings.

Ten-year follow-up of dilatation of aortic structures in Fallot-type anomalies.

OBJECTIVES: Dilatation of the aortic root structures or ascending aorta is often observed in patients with Fallot-type anomalies. We aimed to determine the dilation rate of the aortic structures and investigate strategies for managing this phenomenon. METHODS: In this retrospective study, we enrolled 66 out of 801 patients who underwent corrective surgery for Fallot-type anomalies (tetralogy of Fallot [TOF] and Fallot-type double outlet right ventricle [DORV]) between 2004 and 2020. These 66 patients had follow-up cardiac computed tomography (CT) angiography images taken at least 5 years after the initial CT study. We analyzed the diameters and aortic cross-sectional area/height ratio (AH) of the aortic annulus, sinus of Valsalva, sinotubular junction, and ascending aorta between the initial and follow-up CT scans. "Dilatation" was defined as a z-score over 2 for each aortic structure. RESULTS: The median age at the initial and follow-up CT scans was 5.9 years (interquartile range [IQR]: 0.4 ~ 12.4) and 15.9 years (IQR 9.3 ~ 23.4), respectively. The median CT interval (from initial to latest CT) was 9.5 years (IQR 6.6 ~ 12.0). The sinus of Valsalva exhibited the most significant dilation (32.8 mm at follow-up CT) over the study period. The AH ratio increased significantly in all four aortic structures. The patient's age was significantly associated with higher AH in the follow-up CT. Aortic dilatation was present in 74.2% of patients at the initial CT and increased to 86.4% at the follow-up CT. CONCLUSION: In Fallot-type anomalies, the AH ratio of aortic root structures significantly increased over an average period of approximately 9.5 years. The number of patients diagnosed with aortic dilatation also increased. Based on our observations in this study, these patients' group should be considered for more frequent follow-up examinations, as significant dilatation could occur in their mid-20 s.

Echocardiographic and radiographic aortic remodeling in cats with confirmed systemic hypertension.

Systemic hypertension (SH) in cats may occur secondary to renal disease, hyperthyroidism, or idiopathic causes. Asymmetric dilation of the sinuses of Valsalva has been recognized in people with systemic hypertension as target organ damage (TOD). Aortic knob formation (lateral bowing of the aortic arch to proximal descending aorta on the posteroanterior/anteroposterior radiographic projection) is recognized as TOD in people due to SH. None of these changes have been reported in feline patients. The first objective of this retrospective case-controlled study was to compare echocardiographic changes in the aorta of 76 cats with systemic hypertension (SH) to those seen in 76 cats with normal blood pressure (NBP). Our second objective was to have blinded reviewers assess heart size and aortic shape and size from available thoracic radiographs of 49/76 cats with SH and 46/76 cats with NBP. A two-way unpaired t-test with significance set at alpha = 0.01 was used to evaluate aortic echocardiographic parameters. The mean of the aortic diameter and length of each aortic cusp was significantly larger in cats with SH than in cats with NBP. The aortic cusps were considered altered in size in 62 of 76 cats with SH, 12/62 ≥ with 0.5 mm, and 50/62 ≥ 1.0 mm. No significant difference in the vertebral heart score (VHS) was noted between groups. The aortic knob to lateral margin of the trachea in cats with SH had an area under the curve (AUC) of 0.74 (95% CI:0.61-0.87) with best cutoff of 1.12 cm with sensitivity of 81% and specificity of 69%.

Abdominal aortic diameter and cardiovascular status in patients with idiopathic retroperitoneal fibrosis.

Although much debated, an exaggerated inflammatory response to advanced atherosclerosis has been implicated in the pathogenesis of idiopathic retroperitoneal fibrosis (RPF). Clinical presentation, infrarenal abdominal aortic diameter and RPF mass thickness were retrospectively analyzed in 166 patients with idiopathic RPF seen at our referral center between April 1998 and December 2019. Patients were stratified to their infrarenal abdominal aortic diameter at presentation (i.e., non-ectatic [< 25 mm]; ectatic [25-29 mm]; and aneurysmal [≥ 30 mm]) to compare characteristics across groups with an undilated or dilated aorta. Ectatic or aneurysmal aortic dilatation was present in 34% of patients. Most clinical characteristics did not differ across abdominal aortic diameter stratified groups, but RPF mass thickness was greater in patients presenting with aortic aneurysmal dilatation compared to that in patients with an undilated aorta (49.0 mm [IQR 34.0-62.0] vs 32.5 mm [IQR 25.3-47.8]; P < 0.001). A positive linear association was found between aortic diameter on a continuous scale and RPF mass thickness (ß 0.32 [95% CI 0.34-0.96]; P < 0.001). This association remained significant after adjusting for age, sex and acute-phase reactant levels (ß 0.28 [95% CI 0.15-0.95]; P < 0.01). Treatment success across aortic diameter stratified groups did not differ (P = 0.98). Treatment induced RPF mass regression was not associated with an increase in aortic expansion rate (P = 0.44). Aortic dilatation was prevalent among patients. Infrarenal abdominal aortic diameter was independently associated with RPF mass thickness. Findings support the concept that at least in a subset of patients, RPF may be secondary to advanced atherosclerosis.

Aortic Elongation in Bicuspid Aortic Valve with Aortic Stenosis Assessed by Thin-Slice Electrocardiogram-Gated Computed Tomography.

Bicuspid aortic valve (BAV) patients with aortic stenosis (AS) are known to develop dilatation of the ascending aorta at a younger age, but the morphology of the aorta in these patients is yet to be investigated. Thus, in this study, we aim to evaluate the aortic morphology of BAV patients with severe AS using thin-slice electrocardiogram (ECG) -gated computed tomography (CT) and identify the possible contributing effect of age.In this retrospective study, 122 BAV and 154 tricuspid aortic valve (TAV) patients who received aortic valve replacement for severe AS were assessed by thin-slice ECG-gated CT and three-dimensional reconstruction. The morphology of the ascending aorta was also evaluated among BAV patients aged < 70 (n = 72) and ≥ 70 (n = 50) years old. As per our findings, BAV patients with severe AS had significantly greater diameter (P < 0.01), elongation (P < 0.01), and tortuosity (P = 0.03) of the ascending aorta; minimum aortic arch angle (P < 0.01); and significantly lower calcified plaque (P < 0.01) compared with those of TAV patients even after adjusting for background. Multiple regression analysis showed that standardized partial regression coefficients (ß) of dilatation (0.5) and elongation (0.35) were higher among other measurements of aortic morphology for BAV patients. BAV patients with severe AS aged ≥ 70 years had significantly greater diameter (42.0 [37.2-46.1] mm versus 40.4 [35.2-44.2] mm, P = 0.049) and elongation (133.8 [123.5-147.3] mm versus 127.0 [111.0-140.0] mm, P = 0.01) of the ascending aorta than those aged < 70 years.BAV patients with severe AS were determined to have greater dilatation and elongation of the ascending aorta. Moreover, BAV patients older than 70 years had greater diameter and elongation of the ascending aorta.

Bi-allelic Loss-of-Function Mutations in the NPR-C Receptor Result in Enhanced Growth and Connective Tissue Abnormalities.

The natriuretic peptide signaling pathway has been implicated in many cellular processes, including endochondral ossification and bone growth. More precisely, different mutations in the NPR-B receptor and the CNP ligand have been identified in individuals with either short or tall stature. In this study we show that the NPR-C receptor (encoded by NPR3) is also important for the regulation of linear bone growth. We report four individuals, originating from three different families, with a phenotype characterized by tall stature, long digits, and extra epiphyses in the hands and feet. In addition, aortic dilatation was observed in two of these families. In each affected individual, we identified a bi-allelic loss-of-function mutation in NPR3. The missense mutations (c.442T>C [p.Ser148Pro] and c.1088A>T [p.Asp363Val]) resulted in intracellular retention of the NPR-C receptor and absent localization on the plasma membrane, whereas the nonsense mutation (c.1524delC [p.Tyr508∗]) resulted in nonsense-mediated mRNA decay. Biochemical analysis of plasma from two affected and unrelated individuals revealed a reduced NTproNP/NP ratio for all ligands and also high cGMP levels. These data strongly suggest a reduced clearance of natriuretic peptides by the defective NPR-C receptor and consequently increased activity of the NPR-A/B receptors. In conclusion, this study demonstrates that loss-of-function mutations in NPR3 result in increased NPR-A/B signaling activity and cause a phenotype marked by enhanced bone growth and cardiovascular abnormalities.

Clinical characteristics and rate of dilatation in Turner syndrome patients treated for aortic dilatation.

Turner syndrome is associated with an increased risk of aortic aneurysms and dissection. Recent 2017 clinical care guidelines recommend medical therapy to treat aortic dilatation, although whether this slows dilatation is unknown. We aimed to describe a pre-guideline cohort of Turner syndrome patients with aortic dilatation, the rate of dilatation following diagnosis, and post therapy dilatation rates. We conducted a retrospective review of Turner syndrome patients with a dilated aortic root or ascending aorta by current definitions. In total, 40 patients were included with 22 treated patients. Most patients had 45,X karyotype, were white, non-Hispanic, and received both growth hormone and estrogen. Except for hypertension, there were no differences in risk factors among treated and untreated groups. Bicuspid aortic valve was very common. Treatment group patients had significantly more dilated ascending aortas by absolute measurements and aortic size index. In an adjusted model, there was minimal change in aortic measures over time and this was not associated with medication use. In conclusion, in this cohort, Turner syndrome patients with aortic dilatation were more likely to be treated if they had hypertension and if they met multiple dilatation criteria. Further study is needed to establish medical therapy efficacy on dilatation progression.

Measurement accuracy of prototype non-contrast, compressed sensing-based, respiratory motion-resolved whole heart cardiovascular magnetic resonance angiography for the assessment of thoracic aortic dilatation: comparison with computed tomography angiography.

BACKGROUND: Patients with thoracic aortic dilatation who undergo annual computed tomography angiography (CTA) are subject to repeated radiation and contrast exposure. The purpose of this study was to evaluate the feasibility of a non-contrast, respiratory motion-resolved whole-heart cardiovascular magnetic resonance angiography (CMRA) technique against reference standard CTA, for the quantitative assessment of cardiovascular anatomy and monitoring of disease progression in patients with thoracic aortic dilatation.  METHODS: Twenty-four patients (68.6 ± 9.8 years) with thoracic aortic dilatation prospectively underwent clinical CTA and research 1.5T CMRA between July 2017 and November 2018. Scans were repeated in 15 patients 1 year later. A prototype free-breathing 3D radial balanced steady-state free-precession whole-heart CMRA sequence was used in combination with compressed sensing-based reconstruction. Area, circumference, and diameter measurements were obtained at seven aortic levels by two experienced and two inexperienced readers. In addition, area and diameter measurements of the cardiac chambers, pulmonary arteries and pulmonary veins were also obtained. Agreement between the two modalities was assessed with intraclass correlation coefficient (ICC) analysis, Bland-Altman plots and scatter plots. RESULTS: Area, circumference and diameter measurements on a per-level analysis showed good or excellent agreement between CTA and CMRA (ICCs > 0.84). Means of differences on Bland-Altman plots were: area 0.0 cm2 [- 1.7; 1.6]; circumference 1.0 mm [- 10.0; 12.0], and diameter 0.6 mm [- 2.6; 3.6]. Area and diameter measurements of the left cardiac chambers showed good agreement (ICCs > 0.80), while moderate to good agreement was observed for the right chambers (all ICCs > 0.56). Similar good to excellent inter-modality agreement was shown for the pulmonary arteries and veins (ICC range 0.79-0.93), with the exception of the left lower pulmonary vein (ICC < 0.51). Inter-reader assessment demonstrated mostly good or excellent agreement for both CTA and CMRA measurements on a per-level analysis (ICCs > 0.64). Difference in maximum aortic diameter measurements at baseline vs follow up showed excellent agreement between CMRA and CTA (ICC = 0.91). CONCLUSIONS: The radial whole-heart CMRA technique combined with respiratory motion-resolved reconstruction provides comparable anatomical measurements of the thoracic aorta and cardiac structures as the reference standard CTA. It could potentially be used to diagnose and monitor patients with thoracic aortic dilatation without exposing them to radiation or contrast media.

Aortic dilatation: Value of echocardiography in the systematic assessment of elite rugby players in the French National Rugby League (LNR).

The value of echocardiography in the screening of athletes in addition to the electrocardiogram is debated and still unclear. 336 rugby players in French professional divisions (Top 14, Pro D2) were prospectively assessed with electrocardiogram and echocardiography. 75% were Caucasian, 16.4% Pacific Islanders, and 8.6% Afro-Caribbean. Six (1.8%) players had electrocardiogram abnormalities, exclusively negative T waves. Twenty-one (6.25%) of them had abnormal echocardiography findings: one possible early hypertrophic cardiomyopathy, one anomalous origin of coronary artery, two left ventricular dilatations, one isolated bicuspid aortic valve, two aortic regurgitations, and 14 ascending aortic dilatations. The median aortic diameter was modestly correlated with age: 32 mm [23-48] in players aged ≤25 years vs 33.5 mm [24-50] in those aged >25 years (P = 0.02, correlation coefficient -.01). This tendency increased with cumulative hours of weight training: 34 mm [24-50] in forwards vs 32 mm [25-44] in backs (P = 0.01); and ethnicity, with Pacific Islanders having higher values in both raw data and body surface area or height-indexed data than Afro-Caribbeans and Caucasians: 34 [25-50] vs 32 [27-48] and 33 [23-49] mm (P = 0.017); 15 [12.2-21] vs 14.8 [11-19.9] and 14.8 [10-20.9] mm/m2 (P < 0.0001); 18.5 [14-25] mm/m vs 17.4 [14.8-25] mm/m and 17.6 [12.2-25.3] mm/m (P = 0.0125). In a population of professional rugby players, echocardiography was contributive. The main anomaly was aortic dilatation (14/336, 4.2%). While this is proportionally much higher than in other sports, the cutoffs need to be defined more precisely by including the criterion of ethnicity, as is already the case for electrocardiography.

Elevated levels of short-term blood pressure variability: A marker for ascending aortic dilatation in hypertensive patients.

Background: Ascending aortic aneurysms are one of the primary causes of mortality. However, not much is known about the etiologies of aortic aneurysm. Recently, in hypertensive (HT) patients, blood pressure variability (BPV) has been recommended as a remarkable risk factor for adverse cardiovascular outcomes. This study aimed to explore the association between short-term BPV and ascending aortic dilatation (AAD).Methods: In this study, a total of 53 HT patients with AAD (aortic size index [ASI] ≥21 mm/m2) and 126 HT patients with a normal ascending aortic diameter (ASI <21 mm/m2) were included. Baseline, echocardiographic, and 24-h ambulatory blood pressure (BP) monitoring results were compared between groups. Standard deviation (SD) and coefficient of variation (CV) of BP were used to determine short-term BPV.Results: Except for daytime SBP values, daytime, nighttime, and 24-h mean systolic (SBP) and diastolic (DBP) BP levels were similar between groups. Compared with the HT patients with normal AA, daytime SBP, daytime SD of SBP, 24-h SD of SBP, daytime CV of SBP, and 24-h CV of SBP were significantly higher in HT patients with AAD. Compared with the HT patients with normal AA, the frequency of nondipper pattern was higher and dipper pattern was lower in HT patients with AAD. In multivariate logistic regression analysis, the daytime CV of SBP, daytime SD of SBP, 24-h SD of SBP, daytime SBP, and left ventricular mass index were independently associated with AAD. In receiver operating characteristic curve analysis, the daytime CV of SBP levels of >12.95 had a sensitivity of 61% and a specificity of 59% (area under the curve, 0.659; 95% CI, 0.562-0.756; P= .01); moreover, daytime SD of SBP > 16.4 had sensitivity of 62% and specificity of 61% (AUC, 0.687; 95% CI, 0.591-0.782; P< .001).:Conclusion Increased short-term BPV is independently associated with AAD and may be recommended as a remarkable factor risk for AAD in HT patients.

Progression of Vasculopathy in Young Individuals with Turner Syndrome.

Vasculopathy has been identified in young individuals with Turner syndrome (TS). No studies in young individuals with TS have investigated whether this vasculopathy progresses over time. The objective of this study is to describe the changes in vasculopathy over time in a cohort of young individuals with TS. Repeat ultrasound and SphygmoCor CPV® (AtCor Medical) measurements of carotid thickness and peripheral arterial stiffness were performed. Vascular measurements were compared at baseline and follow-up. Follow-up measurements were also compared to historical lean (L) and obese (O) age-, race-, and sex-matched non-TS controls. Thirty-five individuals with TS were studied at a mean age of 19.4 years (range, 13.9-27.5). Mean time to follow-up was 7.2 years (range, 7.1-7.8). Carotid intima media thickness increased by 0.03 ± 0.07 mm (p < 0.01) over time, but was less than L and O controls at follow-up. Pulse wave velocity carotid-femoral increased by 0.51 ± 0.86 m/s (p < 0.01) over time, but was similar to L and less than O controls at follow-up. Augmentation index (AIx) remained unchanged (p = 0.09) over time, but was significantly higher at follow-up than both control groups (p < 0.01 for both). There were no identified differences between 45,X and other TS genotypes. We demonstrate evidence of vascular thickening and stiffening over 7 years in a cohort of young individuals with TS, as well as a persistently increased augmentation index compared to L and O non-TS controls. It is unclear whether the increase in vascular structure and function are related to normal aging or if TS is a risk factor. Higher body mass index seems to be a risk factor. Early estrogen replacement and longer exposure to growth hormone therapy need to be further explored as potential protective factors.

Does the Leaflet Fusion Subtype Affect Pattern and Rate of Growth in BAV Aortopathy?: A Study of 102 BAV Aortopathy Cases With A Literature Review.

BACKGROUND: Bicuspid aortic valves (BAV) and related aortopathy remain an intriguing topic. Not all BAVs get diseased and around 40% would develop aortic dilatation in their lifetime. If haemodynamic theory is to be believed, then leaflet fusion pattern should have an impact. This study sought to compare the association of aortic morphologies and rate of growth in a set of 102 BAV acropathies operated at a single centre, based on the fusion patterns. METHODS: Data on aortic valve replacements over a 10-year period was analysed from a prospectively maintained database. Of the 198 BAV undergoing surgery, 102 had aortic dilatation above 40 mm on echocardiogram. These underwent computed tomography (CT) aortograms and were followed up as a part of a database. The impact of leaflet fusion patterns on aortic dilatation pattern and rate was analysed. RESULTS: Of the 102, two patients had type 0 pathology and one had left-noncoronary (LN) leaflet fusion. Seventy-four (74) had type 1A or left-right (RL) fusion and 25 had type 1B right-noncoronary (RN) fusion. RL fusion had more males, were taller, bigger and had more proportion of aortic stenosis (AS). Aortic diameters, angles and growth rates at root, ascending/descending aorta and arch were not different. Regression analyses for size or growth did not show any significant impact of fusion pattern. CONCLUSIONS: Left-right fusion pattern comprised three-quarters of BAV in this cohort and these patients were bigger, taller and had a greater proportion of males with increased rate of aortic stenosis. Despite these differences, there was no significant impact of fusion pattern on aortic size or rate of growth.

Dilatation of the Ascending Aorta in Turner Syndrome: Influence of Bicuspid Aortic Valve Morphology and Body Composition.

BACKGROUND: Aortic dilatation and bicuspid aortic valve (BAV) are frequent in Turner syndrome (TS). Due to short stature, aortic size index (ASI)-ascending aortic diameter (AD)/body surface area (BSA)-is used to identify aortic dilatation in TS patients. We sought to: 1) describe echocardiographic findings in the largest cohort of Australian women with TS; 2) assess if ASI progresses differently with age in TS BAV compared to non-syndromic BAV; and 3) determine whether adjustment of AD for body composition may be superior to BSA indexation. METHODS: Transthoracic echocardiography (TTE) data were retrospectively collected on 125 women with TS. Body composition was quantified by dual energy X-ray absorptiometry (DXA) in 60 women within 6 months of baseline TTE. Age-matched females with non-syndromic BAV (n=170) were used as controls for TS patients with BAV. RESULTS: Mean age of TS women was 28±16 years, and mean height and BSA were 141.6±21.7 cm and 1.4±0.4 m2, respectively. Mean AD was 2.5±0.8 cm, and ASI 2.0±0.6 cm/m2. Aortic dilatation (ASI >2.0 cm/m2) was present in 42 (34%) patients. Turner syndrome women with BAV (n=34; 27%) had a larger ASI than those with tri-leaflet AV (2.2±0.4 cm/m2 vs. 1.7±0.3 cm/m2, p<0.001). In the pooled BAV cohort, TS patients had a higher baseline ASI (2.2±0.4 cm/m2 vs. 2.1±0.3 cm/m2, p=0.02) and greater increase in ASI with age (0.21 mm/m2/year vs. 0.10 mm/m2/year, p=0.01) compared to non-syndromic BAV patients. DXA fat-free mass (r=0.33, p=0.01) and lean mass (r=0.32, p=0.02) correlated with AD, as did BSA (r=0.62, p<0.001). CONCLUSION: Turner syndrome women with BAV have a greater degree of baseline aortic dilatation and a twofold faster increase in aortic dimension with age when compared to matched women with non-syndromic BAV. Several DXA-derived body composition parameters correlate with aortic size in TS, however BSA appears to be the most robust method of indexation.

Heart and Aorta Anomalies in Turner Syndrome and Relation with Karyotype.

OBJECTIVES: Turner Syndrome (TS) is associated with a high risk of cardiac anomalies and cardiovascular disease. We aimed to evaluate patients with TS (n=33) for cardiac and aortic pathology using thorax magnetic resonance angiography (MRA). SUBJECTS AND METHODS: Clinical findings, karyotypes, echocardiogram (ECHO) findings and thorax MRA results were evaluated. Aortic dimensions were measured and standard Z scores of aortic diameters along with aortic size index (ASI) were calculated. RESULTS: Mean age of the patients was 13.7±3.4 years. MRA revealed cardiovascular pathology in 10 patients (30%). CoA (n=4), aberrant right subclavian artery (n=3), dilatation of the ascending aorta (n=1), tortuosity of the descending aorta (n=1) and fusiform dilatation of the left subclavian artery (n=1) were found. Two of the four patients with CoA found on MRA were detected with ECHO. Mean diameter of the sinotubular junction was found to be elevated [mean±SD: 2.4±1.5]. Z scores for the diameters of the isthmus, ascending aorta and descending aorta were in normal ranges. 45,X patients were found to have significantly higher ASI values than non 45,X patients (p=0.036). CONCLUSION: Our findings indicate that patients with TS should be evaluated with MR imaging studies in addition to ECHO to reveal additional subtle cardiac and vascular anomalies. CoA which is very distally located or which has mild nature may not be seen by ECHO. The increase in ASI observed in 45,X patients may herald the development of life-threatening complications. Therefore, frequent follow-up is warranted in these patients.

Phenotypic spectrum of TGFB3 disease-causing variants in a Dutch-French cohort and first report of a homozygous patient.

Disease-causing variants in TGFB3 cause an autosomal dominant connective tissue disorder which is hard to phenotypically delineate because of the small number of identified cases. The purpose of this retrospective cross-sectional multicenter study is to elucidate the genotype and phenotype in an international cohort of TGFB3 patients. Eleven (eight novel) TGFB3 disease-causing variants were identified in 32 patients (17 families). Aortic root dilatation and mitral valve disease represented the most common cardiovascular findings, reported in 29% and 32% of patients, respectively. Dissection involving distal aortic segments occurred in two patients at age 50 and 52 years. A high frequency of systemic features (65% high-arched palate, 63% arachnodactyly, 57% pectus deformity, 52% joint hypermobility) was observed. In familial cases, incomplete penetrance and variable clinical expressivity were noted. Our cohort included the first described homozygous patient, who presented with a more severe phenotype compared to her heterozygous relatives. In conclusion, TGFB3 variants were associated with a high percentage of systemic features and aortic disease (dilatation/dissection) in 35% of patients. No deaths occurred from cardiovascular events or pregnancy-related complications. Nevertheless, homozygosity may be driving a more severe phenotype.