UNASSIGNED: Thoracic aortic aneurysms are often an accidental finding and result from a degenerative process. Medical therapy includes pharmacological control of arterial hypertension and smoking cessation, that slows the growth of aneurysms. An association between the dilatation of the ascending and abdominal aorta has been already reported. The aim of the study was to identify possible demographic and clinical factors that may implicate further imaging diagnostics in patients with ascending aorta dilatation.
UNASSIGNED: There were 181 (93 (53%) males and 88 (47%) females) patients with a median age of 54 (41-62) years who underwent cardiac magnetic resonance due to non-vascular diseases, were enrolled into retrospective analysis.
UNASSIGNED: Multivariable analysis revealed ascending aorta dilatation (odds ratios (OR) = 7.45, 95% confidence interval (CI): 1.98-28.0, p = 0.003) and co-existence of coronary artery disease (OR = 8.68, 95% CI: 2.15-35.1, p = 0.002) as significant predictors for thoracic descending aorta dilatation. In patients with abdominal aorta dilatation, the multivariable analysis showed a predictive value of ascending aortic dilatation (OR = 14.8, 95% CI: 2.36-92.8, p = 0.004) and age (OR = 1.04, 95% CI: 1.00-1.08, p = 0.027). In addition, cut-off values were established for age groups determining the risk of thoracic aorta dilatation over 49 years and abdominal aorta dilatation over 54 years.
UNASSIGNED: The results of our analysis showed predictive factors, including ascending aorta dilatation and co-existence of coronary artery disease, particularly over 49 years of age for thoracic, while ascending aorta dilatation and age, particularly over 54 years, for abdominal aorta dilatation. These features may be considered to increase clinical vigilance in patients with aortic diameter abnormalities.

暂无摘要。

Tatton-Brown-Rahman syndrome (TBRS) is a rare congenital genetic disorder caused by autosomal dominant pathogenic variants in the DNA methyltransferase DNMT3A gene. Typical TBRS clinical features are overgrowth, intellectual disability, and minor facial anomalies. However, since the syndrome was first described in 2014, a widening spectrum of abnormalities is being described. Cardiovascular abnormalities are less commonly reported but can be a major complication of the syndrome. This article describes a family of three individuals diagnosed with TBRS in adulthood and highlights the variable expression of cardiovascular features. A 34-year-old proband presented with progressive aortic dilatation, mitral valve (MV) regurgitation, left ventricular (LV) dilatation, and ventricular arrhythmias. The affected family members (mother and brother) were diagnosed with MV regurgitation, LV dilatation, and arrhythmias. Exome sequencing and computational protein analysis suggested that the novel familial DNMT3A mutation Ser775Tyr is located in the methyltransferase domain, however, distant from the active site or DNA-binding loops. Nevertheless, this bulky substitution may have a significant effect on DNMT3A protein structure, dynamics, and function. Analysis of peripheral blood cfDNA and transcriptome showed shortened mononucleosome fragments and altered gene expression in a number of genes related to cardiovascular health and of yet undescribed function, including several lncRNAs. This highlights the importance of epigenetic regulation by DNMT3A on cardiovascular system development and function. From the clinical perspective, we suggest that new patients diagnosed with congenital DNMT3A variants and TBRS require close examination and follow-up for aortic dilatation and valvular disease because these conditions can progress rapidly. Moreover, personalized treatments, based on the specific DNMT3A variants and the different pathways of their function loss, can be envisioned in the future.

OBJECTIVE: Ascending aorta (AA) dilatation in patients with bicuspid aortic valve (AV) is related both to genetic and haemodynamic factors. The aim of this study is to compare late progression of AA dilatation in bicuspid AV patients undergoing surgical aortic valve replacement (SAVR) versus transcatheter aortic valve implantation (TAVI).
METHODS: Data of 189 consecutive patients who underwent AV replacement for severe bicuspid AV stenosis were prospectively collected. Patients who underwent SAVR were compared to patients who underwent TAVI. Indication to the procedure was validated by the institutional Heart Team. Aortic diameters were evaluated by transthoracic echocardiogram. Differences between preoperative and long-term follow-up AA diameters were compared in the 2 groups.
RESULTS: Between January 2015 and December 2021, 143 (76%) patients underwent SAVR and 46 (24%) patients underwent TAVI. At 4.6 (standard deviation 1.7) years follow-up, patients in the TAVI group showed significantly lower survival (P = 0.00013) and event-free survival (P < 0.0001). AA diameter progression was lower in surgical compared to transcatheter patients, 0.95 (0.60, 1.30) vs 1.65 (0.67, 2.63) mm, P = 0.02. AA diameter progression indexed for body surface area and height was lower in the surgical group: 0.72 (0.38, 1.05) vs 1.05 (0.39, 1.71) mm/m2, P = 0.02, and 0.59 (0.36, 0.81) vs 1.11 (0.44, 1.78) mm/m, P = 0.001, respectively. At multivariable linear regression analysis transcatheter procedure, baseline aortic diameter and paravalvular leak were significantly associated with increased postoperative AA dilatation.
CONCLUSIONS: Bicuspid AV patients who underwent SAVR, showed significantly less long-term AA diameter progression than patients who underwent transcatheter procedure.

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.

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.

Findings regarding the relation between aortic size and risk factors are heterogeneous. This study aimed to generate new insights from a population-based adult cohort on aortic root dimensions and their association with age, anthropometric measures, and cardiac risk factors and evaluate the incidence of acute aortic events. Participants from the fifth examination round of the Copenhagen City Heart study (aged 20 to 98 years) with applicable echocardiograms and no history of aortic disease or valve surgery were included. Aorta diameter was assessed at the annulus, sinus of Valsalva, sinotubular junction, and the tubular part of the ascending aorta. The study population comprised 1,796 men and 2,316 women; mean age: 56.4 ± 17.0 and 56.9 ± 18.1 years, respectively. Men had larger aortic root diameters than women regardless of height indexing (p <0.01). Age, height, weight, systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, hypertension, diabetes, ischemic heart disease, and smoking were positively correlated with aortic sinus diameter in the crude and gender-adjusted analyses. However, after full adjustment, only height, weight, and diastolic blood pressure remained significantly positively correlated with aortic sinus diameter (p <0.001). For systolic blood pressure and pulse pressure, the correlation was inverse (p <0.001). During follow-up (median 5.4 [quartile 1 to quartile 3 4.5 to 6.3] years), the incidence rate of first-time acute aortic events was 13.6 (confidence interval 4.4 to 42.2) per 100,000 person-years. In conclusion, beyond anthropometric measures, age, and gender, diastolic blood pressure was the only cardiac risk factor that was independently correlated with aortic root dimensions. The number of aortic events during follow-up was low.

UNASSIGNED: Transforming growth factor β (TGFβ) metabolism plays an important role in the pathogenesis of Marfan syndrome (MFS). Accordingly, drug therapy uses TGFβ receptor blockade to slow down the cardiovascular manifestations, above all aortic root dilatation. Angiotensin II type 1 receptor blockers (ARBs) have been shown to reduce TGFβ levels in adults. Data on childhood are lacking and are now being investigated in the TiGer For Kids study presented here.
UNASSIGNED: We examined 125 children without chronic disease and 31 pediatric Marfan patients with a proven FBN1 variant with regard to TGFβ levels. In addition, we measured TGFβ levels during the initiation of ARB therapy in pediatric Marfan patients.
UNASSIGNED: In children without chronic disease, TGFβ levels were found to decrease from childhood to adolescence (p < 0.0125). We could not measure a relevantly increased TGFβ level in pediatric Marfan patients. However, we showed a significant suppression of the TGFβ level after treatment with ARBs (p < 0.0125) and a renewed increase shortly before the next dose.
UNASSIGNED: The TGFβ level in childhood changes in an age-dependent manner and decreases with age. The TGFβ level drops significantly after taking ARBs. Based on our experience and data, a TGFβ receptor blockade in childhood seems reasonable. So far, TGFβ level cannot be used as an MFS screening biomarker.

UNASSIGNED: This diagnostic study assessed the accuracy of radiologists retrospectively, using the deep learning and natural language processing chest algorithms implemented in Clinical Review version 3.2 for: pneumothorax, rib fractures in digital chest X-ray radiographs (CXR); aortic aneurysm, pulmonary nodules, emphysema, and pulmonary embolism in CT images.
UNASSIGNED: The study design was double-blind (artificial intelligence [AI] algorithms and humans), retrospective, non-interventional, and at a single NHS Trust. Adult patients (≥18 years old) scheduled for CXR and CT were invited to enroll as participants through an opt-out process. Reports and images were de-identified, processed retrospectively, and AI-flagged discrepant findings were assigned to two lead radiologists, each blinded to patient identifiers and original radiologist. The radiologist\'s findings for each clinical condition were tallied as a verified discrepancy (true positive) or not (false positive).
UNASSIGNED: The missed findings were: 0.02% rib fractures, 0.51% aortic aneurysm, 0.32% pulmonary nodules, 0.92% emphysema, and 0.28% pulmonary embolism. The positive predictive values (PPVs) were: pneumothorax (0%), rib fractures (5.6%), aortic dilatation (43.2%), pulmonary emphysema (46.0%), pulmonary embolus (11.5%), and pulmonary nodules (9.2%). The PPV for pneumothorax was nil owing to lack of available studies that were analysed for outpatient activity.
UNASSIGNED: The number of missed findings was far less than generally predicted. The chest algorithms deployed retrospectively were a useful quality tool and AI augmented the radiologists\' workflow.
UNASSIGNED: The diagnostic accuracy of our radiologists generated missed findings of 0.02% for rib fractures CXR, 0.51% for aortic dilatation, 0.32% for pulmonary nodule, 0.92% for pulmonary emphysema, and 0.28% for pulmonary embolism for CT studies, all retrospectively evaluated with AI used as a quality tool to flag potential missed findings. It is important to account for prevalence of these chest conditions in clinical context and use appropriate clinical thresholds for decision-making, not relying solely on AI.

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.
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.
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.
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.