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• In GCA patients with aortic dilation, scarce data exist on the evolution of aortic morphology. • More than 25 % of GCA patients with aortic dilation showed a fast progression of aorta caliber. • More than 90 % of the aortic dilations on the abdominal portion of the aorta progressed. • Among patients with aortitis, aortic dilation developed on an inflammatory segment in 85 % of them. • Available histologies of patients with fast progression and aortic surgery showed active vasculitis. To identify factors associated with the progression of giant cell arteritis (GCA)-related or associated aortic dilations. In this retrospective study, 47 GCA patients with aortic dilation were longitudinally analyzed. Each patient underwent ≥2 imaging scans of the aorta during the follow-up. Three progression statuses of aortic dilations were distinguished: fast-progressive (FP) defined by a progression of the aortic diameter ≥5 mm/year or ≥1 cm/2 years, slow progressive (SP) by a progression of the aortic diameter >1 mm during the follow-up, and not progressive (NP) when aortic diameter remained stable. Among the 47 patients with aortic dilation, the thoracic section was involved in 87 % of patients. Within a total follow-up of 89 [6–272] months, we identified 13 (28 %) patients with FP dilations, and 16 (34 %) and 18 (38 %) patients with SP and NP dilations, respectively. No differences regarding baseline characteristics, cardiovascular risk factors or treatments were observed among the 3 groups. However, FP patients more frequently showed atheromatous disease (p = 0.04), with a more frequent use of statins (p = 0.04) and antiplatelet agents (p = 0.02). Among the 27 (57 %) patients with aortitis, aortic dilation developed on an inflammatory segment in 23 (85 %). Among the FP patients who underwent aortic surgery with available histology (n = 3), all presented active vasculitis. This study suggests that aortic inflammation, as well as atheromatous disease, might participate in the fast progression of aortic dilation in GCA. [ABSTRACT FROM AUTHOR]

Turner syndrome (TS) is a genetic disorder presenting in phenotypic females with total or partial monosomy of the X chromosome. Cardiovascular abnormalities are common, including congenital heart defects (CHD) and aortic dilation. Although mosaic TS is suspected to have less severe phenotype as compared to non-mosaic TS, differences in cardiovascular manifestations between karyotypes are not well studied. This is a single-center retrospective cohort study including patients with TS seen from 2000 to 2022. Demographic data, chromosomal analysis, and imaging were reviewed. Karyotypes were categorized as monosomy X (45X), 45X mosaicism, isochromosome Xq, partial X deletions, ring X (r(X)), TS with Y material, and others. Prevalence of CHD and aortic dilation were compared between monosomy X and other subtypes using Pearson's chi-square test and Welch two-sample t-test. We included 182 TS patients with median age 18 (range 4–33) years. CHD was more common in monosomy X as compared with others (61.4% vs. 26.8%, p < 0.001), including bicuspid aortic valve (44.3% vs. 16.1%, p < 0.001), partial anomalous pulmonary venous return (12.9% vs. 2.7%, p = 0.023), persistent left superior vena cava (12.9% vs. 1.8%, p = 0.008), and coarctation of the aorta (20.0% vs. 4.5%, p = 0.003). Cardiac surgery (24.3% vs. 8.9%, p = 0.017) was more prevalent in the monosomy X group. There was no statistically significant difference for presence of aortic dilation (7.1% vs 1.8%, p = 0.187). Although CHD and need for cardiac surgery are more common in TS with monosomy X as compared to others, all TS subtypes may have similar risk of developing aortic dilation. All TS patients should have similar cardiovascular surveillance testing to monitor for aortic dilation. [ABSTRACT FROM AUTHOR]

Advances in both imaging techniques and genetics have led to the recognition of a wide variety of aortic anomalies that can be grouped under the term 'hereditary thoracic aortic diseases'. The present review aims to summarize this very heterogeneous population's clinical, genetic, and imaging characteristics and to discuss the implications of the diagnosis for clinical counselling (on sports activity or pregnancy), medical therapies and surgical management. [ABSTRACT FROM AUTHOR]

Background: Neonatal Marfan syndrome is a rare disease with mortality in the first year of life reported as high as 95% predominantly due to progressive heart failure from valvar regurgitation and cardiomyopathy. Multisystem involvement and uncertain prognosis have historically precluded transplant candidacy, and current management options are of limited success. Case Report: We present a baby girl with a postnatal diagnosis of neonatal Marfan syndrome who at 1 year of age underwent mitral valve and tricuspid valve repair with postoperative profound left ventricular and moderate right ventricular dysfunction necessitating biventricular assist device (BiVAD) support and subsequent heart transplant. A number of noncardiac issues persisted in our patient; however, she enjoyed a good quality of life for the initial 3 years posttransplant. Unfortunately, she subsequently developed rapidly progressive coronary allograft vasculopathy (CAV) with progressive deterioration in function and cardiac arrest. Conclusion: To our best knowledge, this is only the second case of neonatal Marfan syndrome to undergo heart transplant reported in the literature and the first with BiVAD support as a bridge to candidacy. This is also the first case of neonatal Marfan syndrome associated with intragenic duplication. This case though demonstrating that earlier listing, ventricular assist device (VAD) support and even primary transplant as treatment in neonatal Marfan syndrome should all be considered viable options but also portends a cautionary tale given the spectrum of comorbidities in this rare and severe disorder. [ABSTRACT FROM AUTHOR]

Background: Coarctation of the aorta (COA) is associated with reduced aortic distensibility and systemic hypertension (HTN). 60–85% of COA patients have a bicuspid aortic valve (BAV). It is not known if the presence of a BAV accentuates the aortopathy and HTN in CoA patients. We examined whether patients with COA and a BAV had lower aortic distensibility by CMR, and a higher prevalence of systemic HTN compared with COA patients with a tricuspid aortic valve (TAV). Methods: In successfully repaired COA patients excluding those with residual COA, ascending aorta (AAO) and descending aorta (DAO) distensibility was calculated by CMR. HTN was assessed using standard pediatric and adult criteria. Results: Among 215 COA patients (median age 25.3 years), 67% had a BAV, and 33% had a TAV. Median AAO distensibility z-score was lower in the BAV group (− 1.2 versus − 0.7; p = 0.014) but DAO distensibility was similar in BAV and TAV patients. HTN prevalence was similar in BAV (32%) and TAV groups (36%, p = 0.56). On multivariable analysis controlling for confounders, HTN was not associated with BAV but was associated with male gender (p = 0.003) and older age at follow-up (p = 0.004). Conclusions: In young adults with treated COA, those with a BAV had stiffer AAO compared to those with a TAV, but DAO stiffness was similar. HTN was not related to BAV. These results suggest that although the presence of a BAV in COA exacerbates the AAO aortopathy, it does not exacerbate the more generalized vascular dysfunction and associated HTN. [ABSTRACT FROM AUTHOR]

Background: Aortic dilation (AoD) is commonly reported in patients with bicuspid aortic valve (BAV) and has been related to flow abnormalities and genetic predisposition. AoD-related complications are reported to be extremely rare in children. Conversely, an overestimate of AoD related to body size may lead to excess diagnoses and negatively impact quality of life and an active lifestyle. In the present study, we compared the diagnosis performance of the newly introduced Q-score (based on a machine-learning algorithm) versus the traditional Z-score in a large consecutive pediatric cohort with BAV. Materials and methods: Prevalence and progression of AoD were evaluated in 281 pediatric patients ages > 5 and < 18 years at first observation, 249 of whom had isolated BAV and 32 had BAV associated with aortic coarctation (CoA–BAV). An additional group of 24 pediatric patients with isolated CoA was considered. Measurements were made at the level of the aortic annulus, Valsalva sinuses, sinotubular aorta, and proximal ascending aorta. Both Z-scores using traditional nomograms and the new Q-score were calculated at baseline and at followup (mean 4.5 years). Results: A dilation of the proximal ascending aorta was suggested by traditional nomograms (Z-score > 2) in 31.2% of patients with isolated BAV and 18.5% with CoA–BAV at baseline and in 40.7% and 33.3%, respectively, at followup. No significant dilation was found in patients with isolated CoA. Using the new Q-score calculator, ascending aorta dilation was detected in 15.4% of patients with BAV and 18.5% with CoA–BAV at baseline and in 15.8% and 3.7%, respectively, at followup. AoD was significantly related to the presence and degree of aortic stenosis (AS) but not to aortic regurgitation (AR). No AoD-related complications occurred during the followup. Conclusions: Our data confirm the presence of ascending aorta dilation in a consistent subgroup of pediatric patients with isolated BAV, with progression during followup, while AoD was less common when CoA was associated with BAV. A positive correlation was found with the prevalence and degree of AS, but not with AR. Finally, the nomograms used may significantly influence the prevalence of AoD, especially in children, with a possible overestimation by traditional nomograms. This concept requires prospective validation in long-term followup. [ABSTRACT FROM AUTHOR]

Background: Bicuspid aortic valve (BAV) disease is associated with increased risk of aortopathy. In addition to current intervention guidelines, BAV mediated changes in aortic 3D hemodynamics have been considered as risk stratification measures. We aimed to evaluate the association of 4D flow cardiovascular magnetic resonance (CMR) derived voxel-wise aortic reverse flow with aortic dilation and to investigate the role of aortic valve regurgitation (AR) and stenosis (AS) on reverse flow in systole and diastole. Methods: 510 patients with BAV (52 ± 14 years) and 120 patients with trileaflet aortic valve (TAV) (61 ± 11 years) and mid-ascending aorta diameter (MAAD) > 35 mm who underwent CMR including 4D flow CMR were retrospectively included. An age and sex-matched healthy control cohort (n = 25, 49 ± 12 years) was selected. Voxel-wise reverse flow was calculated in the aorta and quantified by the mean reverse flow in the ascending aorta (AAo) during systole and diastole. Results: BAV patients without AS and AR demonstrated significantly increased systolic and diastolic reverse flow (222% and 13% increases respectively, p < 0.01) compared to healthy controls and also had significantly increased systolic reverse flow compared to TAV patients with aortic dilation (79% increase, p < 0.01). In patients with isolated AR, systolic and diastolic AAo reverse flow increased significantly with AR severity (c = − 83.2 and c = − 205.6, p < 0.001). In patients with isolated AS, AS severity was associated with an increase in both systolic (c = − 253.1, p < 0.001) and diastolic (c = − 87.0, p = 0.02) AAo reverse flow. Right and left/right and non-coronary fusion phenotype showed elevated systolic reverse flow (> 17% increase, p < 0.01). Right and non-coronary fusion phenotype showed decreased diastolic reverse flow (> 27% decrease, p < 0.01). MAAD was an independent predictor of systolic (p < 0.001), but not diastolic, reverse flow (p > 0.1). Conclusion: 4D flow CMR derived reverse flow associated with BAV was successfully captured even in the absence of AR or AS and in comparison to TAV patients with aortic dilation. Diastolic AAo reverse flow increased with AR severity while AS severity strongly correlated with increased systolic reverse flow in the AAo. Additionally, increasing MAAD was independently associated with increasing systolic AAo reverse flow. Thus, systolic AAo reverse flow may be a valuable metric for evaluating disease severity in future longitudinal outcome studies. [ABSTRACT FROM AUTHOR]

Objectives : Aortic dilatation and regurgitation after surgical repair of tetralogy of Fallot (TOF) is known, and beside other factors, mainly addressed to an intrinsic aortopathy. In 2011, we reported the influence of realingement of the left ventricular outflow tract (LVOT) by (partial) direct closure of the ventricular septal defect (VSD) in TOF on aortic structures and function. We now evaluated the further follow-up of this cohort and compared the results to a matched group of TOF patients with classical VSD patch closure. Patients and Methods : Forty patients with TOF treated between 2003 and 2008 are included in the study, with 20 patients each in the VSD (a) (partial) direct closure and (b) patch closure group. Follow-up time after surgery was 12.3 years (11.3-13.0). Results : Patient characteristics, echocardiographic measurements, and surgical and intensive care unit parameters were not significantly different between both groups. After surgery and during long-term follow-up, realignement of the LVOT, shown by the angle between the interventricular septum and the anterior aortic annulus in long axis view in echocardiography, was lower in Group A (34 vs. 45°, P < 0.0001). No differences in LVOT or aortic annulus size, aortic regurgitation, or dilation of the ascending aorta and right ventricular outflow tract gradients were found. Transient rhythm disturbances were found in 3 patients in each group, with only one persistent complete atrioventricular block in Group B. Conclusion : (Partial) direct closure of the VSD in TOF leads to a better realignement of the LVOT and showed comparable short- and long-term results without higher risk for rhythm disturbances during follow-up. [ABSTRACT FROM AUTHOR]

• Aortic flow coherence is quantifiable in vivo using 4D flow MRI. • Network science is used to quantify the persistence length of aortic flow coherence. • Physiological aortic flow coherence is reduced in dilated aortas and BAV patients. • High average blood flow rates promote flow coherence in healthy and diseased aortas. • Increasing relative ascending aorta dilation exacerbates flow coherence disruption. The evidence on the role of hemodynamics in aorta pathophysiology has yet to be robustly translated into clinical applications, to improve risk stratification of aortic diseases. Motivated by the need to enrich the current understanding of the pathophysiology of the ascending aorta (AAo), this study evaluates in vivo how large-scale aortic flow coherence is affected by AAo dilation and aortic valve phenotype. A complex networks-based approach is applied to 4D flow MRI data to quantify subject-specific AAo flow coherence in terms of correlation between axial velocity waveforms and the aortic flow rate waveform along the cardiac cycle. The anatomical length of persistence of such correlation is quantified using the recently proposed network metric average weighted curvilinear distance (AWCD). The analysis considers 107 subjects selected to allow an ample stratification in terms of aortic valve morphology, absence/presence of AAo dilation and of aortic valve stenosis. The analysis highlights that the presence of AAo dilation as well as of bicuspid aortic valve phenotype breaks the physiological AAo flow coherence, quantified in terms of AWCD. Of notice, it emerges that cycle-average blood flow rate and relative AAo dilation are main determinants of AWCD , playing opposite roles in promoting and hampering the persistence of large-scale flow coherence in AAo, respectively. The findings of this study can contribute to broaden the current mechanistic link between large-scale blood flow coherence and aortic pathophysiology, with the prospect of enriching the existing tools for the in vivo non-invasive hemodynamic risk assessment for aortic diseases onset and progression. [ABSTRACT FROM AUTHOR]

Introduction: Beta-aminopropionitrile (BAPN) administration is a chemically induced model for preclinical aortic pathologies research. Angiotensin II (AngII) has been widely used to promotes aortic dissections in mice. Here, we provide insight on a modified aortic dissection model in rats. The effect of smooth muscle cell (SMC) relaxation with vasodilators is studied in this model. Methods: Forty Sprague-Dawley rats were divided in 4 groups: control, isosorbide dinitrate (ISDN, 30 mg/kg/day) in the drinking water, BAPN (0.02%) in the food, BAPN + ISDN (same doses). Thoracic and abdominal aortic diameters were evaluated through transthoracic ultrasound echography. After 6 weeks, all rats were infused with AngII (1 mg/kg/day) subcutaneously. Survival and type of aortic events were numbered. Histological and histochemical analyses of aorta were performed. Results: Initial telesystolic ascending aorta diameters were equal in all groups and became significantly larger in the BAPN + ISDN group compared to the BAPN group (control: 3.37 ± 0.17 mm, ISDN: 3.49 ± 0.16 mm, BAPN: 3.53 ± 0.13 mm, BAPN + ISDN: 3.61 ± 0.16 mm, analysis of variance p < 0.0001). BAPN followed by AngII infusion showed a significant lower survival rate (p = 0.029) and produced a large panel of aortic events. Association of ISDN and BAPN significantly reduces survival (p = 0.001) and provides more aortic events compared to BAPN alone (p = 0.031). In both BAPN-treated groups, orcein staining revealed split and dissected elastic fibers in the media, alcian blue staining showed mucoid degeneration of the aortic wall, and Perls-diaminobenzidine staining revealed an accumulation of Fe2+. Conclusion: SMC relaxation with ISDN increases aortic dilatation, worsens aortic prognosis, and reproduces human histological findings in a low-dose BAPN/AngII-induced aortic dissection model in rats. [ABSTRACT FROM AUTHOR]

The measurement of aortic dimensions and their evolution are key in the management of patients with aortic diseases. Manual assessment, the current guideline-recommended method and clinical standard, is subjective, poorly reproducible, and time-consuming, limiting the capacity to track aortic growth in everyday practice. Aortic geometry mapping (AGM) via image registration of serial computed tomography angiograms outperforms manual assessment, providing accurate and reproducible 3D maps of aortic diameter and growth rate. This observational study aimed to evaluate the accuracy and reproducibility of AGM on non-gated contrast-enhanced (CE-) and cardiac- and respiratory-gated (GN-) magnetic resonance angiographies (MRA). Patients with thoracic aortic disease followed with serial CE-MRA (n = 30) or GN-MRA (n = 15) acquired at least 1 year apart were retrospectively and consecutively identified. Two independent observers measured aortic diameters and growth rates (GR) manually at several thoracic aorta reference levels and with AGM. Agreement between manual and AGM measurements and their inter-observer reproducibility were compared. Reproducibility for aortic diameter and GR maps assessed with AGM was obtained. Mean follow-up was 3.8 ± 2.3 years for CE- and 2.7 ± 1.6 years for GN-MRA. AGM was feasible in the 93% of CE-MRA pairs and in the 100% of GN-MRA pairs. Manual and AGM diameters showed excellent agreement and inter-observer reproducibility (ICC>0.9) at all anatomical levels. Agreement between manual and AGM GR was more limited, both in the aortic root by GN-MRA (ICC=0.47) and in the thoracic aorta, where higher accuracy was obtained with GN- than with CE-MRA (ICC=0.55 vs 0.43). The inter-observer reproducibility of GR by AGM was superior compared to manual assessment, both with CE- (thoracic: ICC= 0.91 vs 0.51) and GN-MRA (root: ICC=0.84 vs 0.52; thoracic: ICC=0.93 vs 0.60). AGM-based 3D aortic size and growth maps were highly reproducible (median ICC >0.9 for diameters and >0.80 for GR). Mapping aortic diameter and growth on MRA via 3D image registration is feasible, accurate and outperforms the current manual clinical standard. This technique could broaden the possibilities of clinical and research evaluation of patients with aortic thoracic diseases. [ABSTRACT FROM AUTHOR]

Background: Aortic dilatation is a cardiovascular complication in pediatric renal transplant recipients and may have an increased risk of aortic dissection, aortic rupture, and death. Studies failed to show an association between blood pressure and aortic dilatation; however, 24‐hours ambulatory blood pressure monitoring (ABPM) was not performed. There was also no comparison between preemptive transplantation and dialysis. Methods: After ethics approval, a retrospective cross‐sectional study was performed on all prevalent pediatric renal transplant recipients from a single tertiary care center. The presence of aortic dilatation was determined using standard echocardiographic measurements, and those with other risk factors for aortic dilatation were excluded. Associations between 24‐hours ABPM, renal function, dialysis history, and aortic dimensions were determined. Results: We enrolled 37 participants with the following characteristics: 46% female, mean age 14.5 ± 3.7 years, 16% preemptive transplantation, and median end‐stage renal disease (ESRD) combined vintage (time from ESRD onset to echocardiogram) 597 days (range 289‐1290 days). We found 16/37 patients (43%) with aortic dilatation at any level, mostly mild. There was no association between 24‐hours ABPM measurements and aortic dilatation. None of the preemptively transplanted children had aortic dilatation. Conclusion: This study confirms a high prevalence of aortic dilatation among pediatric renal transplant recipients, which appears to be independent of hypertension on 24‐hour ABPM. Patients with preemptive renal transplantation did not have aortic dilatation, suggesting that the effects of dialysis may contribute to the high prevalence of this complication. Pediatric cardiologists need to carefully assess aortic dimensions in these at‐risk patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the size and geometry of the aorta in patients with 7q11.23 duplication (Dup7) to healthy controls. We retrospectively reviewed all echocardiograms in all patients with Dup7 evaluated at our institutions from June 2017 through September 2019. All standard aortic diameter measurements were made and recorded. Z-scores for the measurements were calculated. For comparison, a set of control echocardiograms was developed by randomly selecting 24 normal echocardiograms in age-matched patients who had undergone echocardiograms for an indication of either chest pain or syncope. In 58 echocardiograms from 21 Dup7 patients, all aortic measurements were increased compared to controls (p < 0.0001). Effacement of the sinotubular junction (STJ) of the aorta was present in all Dup7 patients. Our novel STJ-to-aortic annulus ratio of ≥ 1.15 had a 98.28% sensitivity (95% CI 90.76–99.96) and 100% specificity (95% CI 85.75–100) for distinguishing Dup7 from controls with a positive predictive value of 100% and a negative predictive value of 96.00% (95% CI 77.47–99.41). All patients in our study with Dup7 had echocardiographic evidence of aortopathy. Effacement of the STJ was present in all Dup7 patients. The STJ-to-annulus ratio is a better indicator of aortopathy in Dup7 than the aortic Z-score. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve (BAV) aortopathy remains of difficult clinical management due to its heterogeneity and further assessment of related aortic hemodynamics is necessary. The aim of this study was to assess systolic hemodynamic indexes and wall stresses in patients with diverse BAV phenotypes and dilated ascending aortas. The aortic geometry was reconstructed from patient-specific images while the aortic valve was generated based on patient-specific measurements. Physiologic material properties and boundary conditions were applied and fully coupled fluid-structure interaction (FSI) analysis were conducted. Our dilated aortic models were characterized by the presence of abnormal hemodynamics with elevated degrees of flow skewness and eccentricity, regardless of BAV morphotype. Retrograde flow was also present. Both features, predicted by flow angle and flow reversal ratios, were consistently higher than those reported for non-dilated aortas. Right-handed helical flow was present, as well as elevated wall shear stress (WSS) on the outer ascending aortic wall. Our results suggest that the abnormal flow associated with BAV may play a role in aortic enlargement and progress it further on already dilated aortas. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We present a patient with Phelan‐McDermid syndrome, a rare neurodevelopmental disorder caused by a 22q13 deletion, with the previously undescribed finding of progressive dilation of the great arteries. While congenital heart defects have been identified in patients previously, dilation of the great arteries has not been described to our knowledge. We present a patient with Phelan‐McDermid syndrome, a rare neurodevelopmental disorder caused by a 22q13 deletion, with the previously undescribed finding of progressive dilation of the great arteries. While congenital heart defects have been identified in patients previously, dilation of the great arteries has not been described to our knowledge. [ABSTRACT FROM AUTHOR]

Background Quadricuspid aortic valve (QAV) is a rare and poorly understood congenital cardiac abnormality. This study aims to evaluate the clinical features and surgical outcomes of dysfunctional QAV. Methods From January 2011 to May 2017, 36 (mean age 50.7 ± 11.9 y, 19 males) of a total of 3855 patients who underwent aortic valve surgery were identified as having dysfunctional QAV (frequency 0.9%). All patients presented moderate or severe aortic regurgitation, and nine patients (25.0%) had concomitant aortic stenosis. The ascending aortic diameter was over 40 mm in seven patients (19.4%) and over 45 mm in two patients (5.6%). The most common QAV morphology was type B ( n = 12, 33.3%) according to the Hurwitz-Roberts classification. Results All patients underwent aortic valve replacement and two required concomitant ascending aortic replacement. The mean follow-up time was 20.6 ± 14.2 mo. There was no early or late postoperative mortality or major complications. Pathological analysis of dilated ascending aorta demonstrated a relatively normal appearance. The ascending aorta did not grow after surgery (37.3 ± 4.1 mm versus 36.1 ± 2.5 mm, P = 0.084). Both the end-diastolic (58.1 ± 7.0 mm versus 50.0 ± 6.3 mm, P < 0.001) and end-systolic (37.7 ± 6.7 mm versus 32.8 ± 6.0 mm, P < 0.001) left ventricular dimensions were significantly decreased. Conclusions Aortic insufficiency is the predominant pathology in dysfunctional QAV patients. The incidence and extent of aortic dilation is not significant in QAV and not associated with aortic valve phenotypes. Short- and mid-term surgical outcomes were found to be satisfactory in this study. [ABSTRACT FROM AUTHOR]

Objectives Large-vessel involvement (LVI) can occur in giant-cell arteritis (GCA) and may represent a distinct disease subgroup with a higher risk for aortic dilation. This study aimed to better characterize the presentation and evolution of LVI in patients with GCA. Patients and methods A retrospective multicenter study enrolled 248 GCA patients with LVI and 301 GCA patients without LVI on imaging. Factors associated with aortic dilation were identified in a multivariable model. Results The patients with LVI were younger (p < 0.0001), more likely to be women (p = 0.01), and showed fewer cephalic symptoms (p < 0.0001) and polymyalgia rheumatica (p = 0.001) but more extracranial vascular symptoms (p = 0.05) than the patients without LVI. Glucocorticoids (GC) management did not differ between the two groups, but the GC discontinuation rate was lower in the patients with LVI (p = 0.0003). Repeated aortic imaging procedures were performed at 19 months [range: 5–162 months] and 17 months [range: 6–168 months] after diagnosis in 154 patients with LVI and 123 patients without LVI, respectively, of whom 21% and 7%, respectively, presented new aortic dilations (p = 0.0008). In the patients with LVI, aortic dilation occurred on an aorta segment shown to be inflammatory on previous imaging in 94% of patients. In the multivariate analysis, LVI was the strongest predictor of aortic dilation (hazard ratio: 3.16 [range: 1.34–7.48], p = 0.009). Conclusions LVI represents a distinct disease pattern of GCA with an increased risk of aortic dilation. Control of the aortic morphology during follow-up is required. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve (BAV) is the most common congenital heart defect. BAV is associated with aortic stenosis and insufficiency, and aortic dilation in adult groups, but data in pediatric groups are limited. We sought to assess the impact of BAV morphology on aortic valve disease and aortic dilation in pediatric patients. We performed a retrospective review of all echocardiograms in patients with isolated BAV who were followed at our institution from July 2002 to July 2012. BAV morphology, aortic valve stenosis and/or insufficiency, and aortic dimensions were measured manually. Comparisons were made between right-left cusp fusion (RL) and right-noncoronary cusp fusion (RN) BAV morphologies. Generalized least square models were fit to analyze the impact of specific variables on aortic dilation. There were 1075 echocardiograms in 366 patients (72% male) with isolated BAV. Aortic valve insufficiency and stenosis were more common in RN (p < 0.001 for both). The median aortic sinus Z score was higher in the RL (0.47; IQR − 0.31 to 1.44) than in the RN group (0.02; − 0.83 to 0.82) (p < 0.001). There was no difference in median ascending aorta Z score between groups. Patients with the highest weights had larger aortas (p < 0.001), but the absolute difference between the highest and lowest weight groups was small (1.5 mm). The impact of BAV morphology on aortic valve disease and aortic dilation in pediatric patients presages that seen in adults. Patient body weight does not make significant clinical impacts on aortic diameters, suggesting that Z scores for aortic diameters should be based on ideal body weights. [ABSTRACT FROM AUTHOR]

Background Body surface area ( BSA)-indexed Z-scores are used to assess the ascending aorta ( AAo) and diagnose aortic dilation (AoD) in children. BSA is directly related to body weight and corresponds to body mass index ( BMI). We hypothesized extremes in BMI alter interpretation of aortic size in pediatric patients with AoD. Methods We reviewed all echocardiograms with a diagnosis of AoD performed at our institution from January 2013 through June 2013. Those with an age <2 or >20 years, history of aortic root surgery, or inadequate images were excluded. The aorta was measured by standard methods at the sinus of Valsalva, sinotubular junction, and proximal AAo. Using subject age, height, and gender, hypothetical weights for each subject were calculated to provide BMIs corresponding to the 5th, 50th, 85th, and 95th percentiles. The derived weights were then used to determine hypothetical BSA, and Z-scores were calculated for the subject's aortic diameters in each BMI group. Results A total of 153 patients met inclusion criteria. Mean age was 11.1±4.6 years (68% male). Mean height was 142.7±27.9 cm, mean weight 44.6±24.8 kg, and mean true BMI was the 62nd centile. Significant differences in all aortic dimension Z-scores were found among normal and underweight, overweight, and obese BMI groups ( P<.001 for all comparisons), respectively. Conclusion Using current recommended methods, AoD will be missed in overweight and obese patients and overdiagnosed in underweight patients. For children of normal weight, a Z-score based on BSA may be reliable. As obesity rates increase, weight-independent Z-scores must be developed. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the circulating miRNA expression profile associated with BAV and aortic dilation to provide diagnostic and prognostic biomarkers for BAV and/or aortic dilation.Methods and Results: We applied a miRNome-wide microarray approach using plasma samples (n = 24) from healthy tricuspid aortic valve individuals, BAV patients and BAV patients with aortic dilation to compare and identify the specific miRNAs associated with BAV and aortic dilation. In a second stage, the expression patterns of the miRNA candidates were validated by RT-qPCR in an independent cohort (n = 43). The miRNA microarray data and RT-qPCR analyses revealed that the expression levels of circulating miR-122, miR-130a and miR-486 are significantly influenced by the morphology of the aortic valve (bicuspid/tricuspid) and could be functionally involved in the regulation of TGF-β1 signalling. Furthermore, the expression pattern of miR-718 in the plasma was strongly influenced by dilation of the ascending aorta. miR-718 expression was inversely correlated with the aortic diameter (R = -0.63, p = 3.1 × 10-5) and was an independent predictor of aortic dilation (β = -0.41, p = 0.022). The genes targeted by miR-718 are involved in the regulation of vascular remodelling.Conclusions: We propose that miR-122, miR-130a, miR-486 and miR-718 are new molecular features associated with BAV and aortic dilation principally by the activation of TGF-β1 pathway and vascular remodelling mediated by VEGF signalling pathways. [ABSTRACT FROM AUTHOR]

Background Bicuspid aortic valve is the most common cardiovascular congenital malformation affecting 2% of the general population. The incidence of life-threatening complications, the high heritability, and familial clustering rates support the interest in identifying risk or protective genetic factors. The main objective of the present study was to identify population-based genetic variation associated with bicuspid aortic valve and concomitant ascending aortic dilation. Materials and methods A cross-sectional exome-wide association study was conducted in 565 Spanish cases and 484 controls. Single-marker and gene-based association analyses enriched for low frequency and rare genetic variants were performed on this discovery stage cohort and for the subsets of cases with and without ascending aortic dilation. Discovery-stage association signals and additional markers indirectly associated with bicuspid aortic valve, were genotyped in a replication cohort that comprised 895 Caucasian cases and 1483 controls. Results Although none of the association signals were consistent across series, the involvement of HMCN2 in calcium metabolism and valve degeneration caused by calcium deposit, and a nominal but not genome-wide significant association, supported it as an interesting gene for follow-up studies on the genetic susceptibility to bicuspid aortic valve. Conclusions The absence of a genome-wide significant association signal shows this valvular malformation may be more genetically complex than previously believed. Exhaustive phenotypic characterization, even larger datasets, and collaborative efforts are needed to detect the combination of rare variants conferring risk which, along with specific environmental factors, could be causing the development of this disease. [ABSTRACT FROM AUTHOR]

Background/objectives The mechanisms underlying aortic dilation in bicuspid aortic valve (BAV) disease are unknown. Circulating endothelial microparticles (EMPs) have emerged as biomarkers of endothelial damage. We sought to evaluate the relationships among EMPs, BAV disease, and aortic dilation. Methods Four evaluations were used. Circulating EMPs (PECAM + , E-selectin + ) were compared between BAV patients and tricuspid aortic valve (TAV) control subjects. The variables related to circulating EMPs were investigated in BAV patients. Circulating EMP levels were compared between BAV and TAV patients with a dilated aorta. Finally, circulating EMPs in BAV patients were evaluated over time with respect to aortic valve surgery (AVS) or aortic surgery. Results We observed higher levels of circulating PECAM + EMPs in the BAV patients than in the control subjects (3.98 ± 0.2 vs. 2.39 ± 0.4 per log PECAM + EMPs/μl, p = 0.001). Aortic dilation was the most significant variable that correlated with the PECAM + EMP levels in the BAV patients (β = 0.321, p = 0.008). The BAV patients with aortic dilation exhibited higher PECAM + EMP levels than the TAV patients with dilated aortas, and this correlation was independent of aortic valve function. We observed a drastic decrease in the circulating PECAM + EMPs following AVS and aortic root replacement (4.27 ± 0.6 and 1.75 ± 0.3 per log PECAM + EMPs/μl, p = 0.002). Conclusion The observed pattern of higher circulating PECAM + EMP levels links BAV disease to endothelial damage and aortic dilation. Circulating PECAM + EMPs were identified as a biological variable related to aortic dilation in patients with BAV disease. [ABSTRACT FROM AUTHOR]

The aortic root dilation in tetralogy of Fallot (TOF) is a long-term clinical problem, because a severely dilated aorta can lead to aortic regurgitation, dissection, or rupture, which can be fatal, necessitating surgical intervention. The details of the mechanism of aortic root dilation, however, are unclear. We have shown that aortic stiffness is increased in patients with repaired TOF, and may mirror the histological abnormality of elastic fiber disruption and matrix expansion. This aortic stiffness is related closely to the aortic dilation, indicating that aortic stiffness may be a predictor of outcome of aortic dilation. Furthermore, the aortic volume overload is a very important determinant of aortic diameter in TOF patients before corrective surgery. In addition, a chromosomal abnormality and the transforming growth factor-β signaling pathway, a major contributor to aortic dilation in Marfan syndrome, also affect this mechanism. In this way, aortic dilation in TOF patients is suggested to be a multifactorial disorder. The aim of this review was therefore to clarify the mechanism of aortic dilation in TOF, focusing on recent research findings. Studies linking histopathology, mechanical properties, molecular/cellular physiology, and clinical manifestations of aortic dilation facilitate appropriate treatment intervention and improvement of long-term prognosis of TOF. [ABSTRACT FROM AUTHOR]

Unlabelled: Aortic dilation at the level of the aortic root can be caused by a variety of congenital or acquired conditions that lead to weakening of the aortic wall. In this retrospective study, we sought to determine the frequency of different associated diagnoses from children with aortic dilation seen at a single institution. A total of 377 children (68 % male) met study inclusion criteria. Patients were classified based on the suspected or confirmed associated diagnosis in one of the following categories: congenital heart disease (241/377, 64 %), chromosomal (34/377, 9 %), Marfan syndrome (26/377, 7 %), other genetic and non-genetic (22/377, 6 %), Loeys-Dietz syndrome (6/377, 2 %), and unknown (48/377, 13 %). Bicuspid aortic valve was by far the most prevalent congenital heart defect (206/241, 85 %), while Turner syndrome was the most frequent chromosomal abnormality (12/34, 35 %). Patients with Marfan syndrome were more likely to have severe dilation of the ascending aorta (p = 0.002) and to require aortic root replacement surgery (p < 0.001) compared to those in other diagnosis categories.Conclusion: The differential diagnosis of aortic dilation is broad and requires a careful assessment of cardiac anatomy. Evaluation by a clinical geneticist in this setting should be strongly considered given the high frequency of associated genetic conditions.What Is Known: • Aortic dilation is frequent in bicuspid aortic valve and other congenital heart defects. • Aortic dilation can be seen in several connective tissue disorders. Limited information is available in regard to the differential diagnosis of aortic dilation in children.What Is New: • In patients with aortic dilation concurrent congenital heart disease is frequently diagnosed. • Almost 18 % of cases in the present study had a defined presumptive or confirmed genetic diagnosis. We suggest considering a genetics evaluation in the setting of aortic dilation. [ABSTRACT FROM AUTHOR]

Accurate and reproducible aortic measurements are essential in aortopathy patients. Transthoracic echocardiography (TTE) is commonly used but has several limitations. Cardiac magnetic resonance (CMR) can offset these limitations but has not been directly compared with TTE. We compared the reproducibility of CMR and TTE measurements at multiple aortic levels. Patients with a connective tissue disorder (CTD) or bicommissural aortic valve (BAV) ( n = 41; 22 CTD, 19 BAV; mean age 18.8 ± 8.9 years) with TTE and CMR imaging performed within 3 months of each other were randomly selected. Two blinded observers measured the aorta at multiple anatomic levels. Intra- and interobserver variability and agreement between techniques were assessed. Aortic root diameter measurements by TTE and CMR were equally reproducible (% error 4-10 %), but TTE measurements were systematically smaller by 5-7 % ( p < 0.0001). Systematic differences were larger in BAV (11-12 %, p < 0.0001) due to root asymmetry. CMR measurements of aortic root cross-sectional area were feasible and highly reproducible (% error 5-8 %). Compared with CMR, ascending aorta measurements by TTE were less reproducible, especially in BAV (% error 21-24 vs. 6-7 %, p = 0.01). Distal aortic measurements by TTE were 14-29 % smaller and had poor reproducibility compared with CMR (% error 24-42 vs. 9-10 %; p < 0.0001). CMR measurement of the largest aortic root dimension is more reliable than TTE, especially when the root is asymmetric. Measurements of the thoracic aorta distal to the root by CMR are more accurate and reproducible than by TTE. These data support a role for CMR in aortopathy patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to characterize the cardiovascular and musculoskeletal systems of elite volleyball players, including aortic dimensions. Previous studies have shown that the upper limit of normal aortic sinus diameter for male and female athletes is 4 and 3.4 cm, respectively. Design: Cross-sectional analysis. Setting: United States Olympic Volleyball Training Facility and Rady Children's Hospital San Diego. Participants: Seventy (37 male) members of the US national volleyball team. Main Outcome Measures: Athletes underwent evaluation that included medical and family histories, targeted physical examinations specifically focusing on abnormalities present in Marfan syndrome (MFS), and transthoracic echocardiograms. Cardiac chamber and great artery size, valve function, and coronary artery origins were assessed. Results: Three male athletes (8%) had an aortic sinus diameter ≥4 cm, one of whom also had an ascending aorta >4 cm. Two female athletes (6%) had aortic sinus diameter ≥3.4 cm, and another had an ascending aorta of 3.4 cm. There were no other intracardiac or arterial abnormalities. Individual musculoskeletal characteristics of MFS were common among the athletes but not more frequent or numerous in those with aortic dilation. Conclusions: The prevalence of aortic root dilation in this population of athletes was higher than what has previously been reported in other similar populations. Further study is needed to determine whether these represent pathological changes or normal variations in tall athletes. Clinical Relevance: This study adds to the existing knowledge base of athlete's heart, with specific attention to aortic dimensions in elite volleyball players. The data are relevant to similar athletes' medical care and to preparticipation cardiac screening in general. [ABSTRACT FROM AUTHOR]

Background—Aortic diameter is an imperfect predictor of aortic complications in connective tissue disorders (CTDs). Novel indicators of vascular phenotype severity such as aortic stiffness and vertebral tortuosity index have been proposed. We assessed the relation between aortic stiffness by cardiac MRI, surgical root replacement, and rates of aortic root dilation in children and young adults with CTDs. Methods and Results—Retrospective analysis of cardiac MRI data on children and young adults with a CTD was performed to derive aortic stiffness measures (strain, distensibility, and β-stiffness index) at the aortic root, ascending aorta, and descending aorta. Vertebral tortuosity index was calculated as previously described. Rate of aortic root dilation before cardiac MRI was calculated as change in echocardiographic aortic root diameter z score per year. In 83 CTD patients (median age, 24 years; range, 1–55; 17% <18 years of age; 60% male), ascending aorta distensibility was reduced in comparison with published normative values: median z score, –1.93 (range, –8.7 to 1.3; P<0.0001 versus normals). Over a median follow-up period of 2.7 years, there were no aortic dissections or deaths, but 16 of 83 (19%) patients underwent surgical aortic root replacement. In multivariable analysis, lower aortic root strain (P=0.05) and higher vertebral tortuosity index (P=0.01) were independently associated with aortic root replacement. Lower ascending aorta strain (P=0.02) was associated with a higher rate of aortic root dilation. Conclusions—Higher aortic stiffness is associated with higher rates of surgical aortic replacement and aortic root dilation in children and young adults with CTDs. [ABSTRACT FROM AUTHOR]

Background Bicuspid aortic valves are associated with aortic dilation and dissection. There is a paucity of prospective studies evaluating changes in aortic size over time in adult subjects with bicuspid aortic valves. Methods A total of 115 subjects with asymptomatic bicuspid aortic valves were enrolled from 2003 to 2008 and followed prospectively over 5 years. Clinical and family histories, as well as transthoracic echocardiograms, were obtained at baseline, and echocardiograms were performed annually thereafter. Results The mean age of subjects was 41.8 ± 12.8 years, and 61% were male. Ascending aortic size at baseline averaged 35.5 ± 5.6 mm and increased in 71.1% of subjects (mean, 0.66 ± 0.05 mm/y; range, 0.2-2.3 mm/y) over an average of 4.8 years. In 15.6% of subjects, the rate of change exceeded 1 mm/y. The average rate of ascending aortic dilation for all subjects was 0.47 ± 0.05 mm/y ( P < .001). A family history of aortic valve disease was associated with progression in both unadjusted ( P = .029) and logistic regression analyses adjusted for age, gender, and body surface area (odds ratio, 13.7; P = .021). Multivariate analysis did not find leaflet orientation or moderate to severe aortic valve dysfunction as independent predictors of aortic dilation. Conclusions We found that in subjects with bicuspid aortic valve, studied prospectively, there was an annual rate of ascending aortic dilation of 0.47 mm/y. In contrast to previous reports, leaflet orientation and aortic valve dysfunction were not independent predictors of aortic dilation. A family history of aortic valve disease was associated with a significantly increased risk of increasing ascending aortic size. [ABSTRACT FROM AUTHOR]

This paper aims to update clinicians on "hot topics" in the management of patients with D-loop transposition of the great arteries (D-TGA) in the current surgical era. The arterial switch operation (ASO) has replaced atrial switch procedures for D-TGA, and 90% of patients now reach adulthood. The Adult Congenital and Pediatric Cardiology Council of the American College of Cardiology assembled a team of experts to summarize current knowledge on genetics, pre-natal diagnosis, surgical timing, balloon atrial septostomy, prostaglandin E1 therapy, intraoperative techniques, imaging, coronary obstruction, arrhythmias, sudden death, neoaortic regurgitation and dilation, neurodevelopmental (ND) issues, and lifelong care of D-TGA patients. In simple D-TGA: 1) familial recurrence risk is low; 2) children diagnosed pre-natally have improved cognitive skills compared with those diagnosed post-natally; 3) echocardiography helps to identify risk factors; 4) routine use of BAS and prostaglandin E1 may not be indicated in all cases; 5) early ASO improves outcomes and reduces costs with a low mortality; 6) single or intramural coronary arteries remain risk factors; 7) post-ASO arrhythmias and cardiac dysfunction should raise suspicion of coronary insufficiency; 8) coronary insufficiency and arrhythmias are rare but are associated with sudden death; 9) early- and late-onset ND abnormalities are common; 10) aortic regurgitation and aortic root dilation are well tolerated; and 11) the aging ASO patient may benefit from "exercise-prescription" rather than restriction. Significant strides have been made in understanding risk factors for cardiac, ND, and other important clinical outcomes after ASO. [ABSTRACT FROM AUTHOR]

• The differences in the development of aortic dilation induced by BAV phenotypes remains unclear. We provided a controlled environment consisting of the same non-dilated aorta subjected to the different Type-1BAV phenotypes, and compared the early effect of different phenotypes of BAV on aortic hemodynamics. • The real aorta has the specific curvature, which has an impact on the blood flow pattern. Therefore, we adopted a healthy personalized aortic model and added coronary artery. • In this study, a steady-state CFD simulation is performed and the blood was set to be k-epsilon turbulent flow mode, which has a great impact on the results at peak systolic. The bicuspid aortic valve (BAV) is a major risk factor for the progression of aortic dilation (AD) because of the induced abnormal blood flow environment in aorta. The differences in the development of AD induced by BAV phenotypes remains unclear. Therefore, the objective of this study was to assess the potential locations of AD induced by different phenotypes of BAV. The different effects of opening orifice area and leaflet orientation on ascending aortic hemodynamics in Type-1 BAV was investigated by means of numerical simulation. Finite element dynamic analysis was performed on tricuspid aortic valve (TAV) and BAV models to simulate the motion of the leaflets and obtain the geometrical characteristics of AV at peak systole as a reference, which were used for aortic models. Then, four sets of aortic fluid models were designed according to the leaflet fusion types [TAV; BAV (left-right-coronary cusp fusion, LR; right-non-coronary cusp fusion, RN; left-non-coronary cusp fusion, LN)], and the computational fluid dynamics method was applied to compare the hemodynamic differences within the aorta at peak systole. The maximum opening area of BAV was significantly reduced, resulting in alterations in aortic hemodynamics compared with TAV. The velocity streamlines were essentially parallel to the aortic wall in TAV. The average pressure and wall shear stress in aorta tend to be stable. In contrary, the eccentricity of BAV orifice jet resulted in high-velocity flow directed toward the ascending aorta (AA) wall and aortic arch for LR and LN; RN features an asymmetrical velocity distribution toward the outer bend of the middle AA, and eccentric flow tends to impact the distal AA. As the flow angle is associated with distinct flow impingement locations, different degrees of WSS and pressure concentration occur along the aortic wall from the AA to the aortic arch in three BAV types. The BAV morphotype affects the aortic hemodynamics, and the abnormal blood flow associated with BAV may play a role in AD. The different BAV phenotypes determine the direction of blood flow jet and change the expression of dilation. LR is likely to cause dilation of the tubular AA; RN results in dilation of the middle AA to proximal aortic arch; and LN causes an increased incidence of the tubular AA and the proximal aortic arch. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated predictors for aortic dilation (AD) in patients with repaired tetralogy of Fallot (rTOF) using magnetic resonance angiography (MRA). Background: AD is common in patients with rTOF and may result in increased morbidity and mortality. There are no guidelines for evaluation of AD for rTOF patients. Methods: All adults with rTOF who previously underwent MRA had retrospective aortic measurements at the sinuses of Valsalva (SoV) and ascending aorta (AsAo). Rate of change in diameter was determined in patients with multiple MRAs. Chart review identified risk factors for AD. Univariate and multivariate analyses tested predictors of AD. Results: Of the 87 patients who met the inclusion criteria, 12 (14%) had AD. At baseline, mean diameter was 3.6±0.6cm and 3.1±0.6cm at the SoV and AsAo, respectively. The AsAo was larger than the SoV in 17%. Predictors of AD included male gender, age, right aortic arch, pregnancy, older age at complete repair, smoking, and systemic hypertension. Serial studies were available in 55 patients; the rate of growth was slow: 0.4±0.9mm/year (SoV) and 0.1±0.8mm/year (AsAo). Conclusions: AD is common in rTOF at the SoV and AsAo. Transthoracic echocardiography, which does not always image the AsAo as well as MRA, may not image AD in rTOF in cases in which the AsAo is dilated. Although several risk factors correlate with AD in rTOF, the rate of aortic growth is slow, suggesting that rTOF patients may not require frequent aortic imaging. [ABSTRACT FROM AUTHOR]

Background: The cardiovascular manifestations of Marfan syndrome (MFS) are the main causes of morbidity and mortality. This study describes the clinical and echocardiographic findings in a Mestizo-Mexican population affected by the disease. Methods: A total of 166 patients previously diagnosed with MFS were recruited for the study, 114 of them underwent complete clinical history, with emphasis on Ghent nosology criteria, and transthoracic echocardiography, with 68 patients also undergoing transesophageal study. Results: Major cardiovascular criteria from the Ghent nosology predominated in adults (P < 0.0001), minor criteria in children (P = 0.007). Among pediatric patients, 83% had a New York Heart Association (NYHA) functional class of I; however, 64% of the adult patients had an NYHA class ≥II, (P < 0.0001). Corrected aortic echocardiographic measurements of both groups demonstrated statistically significant differences. Children had a greater prevalence of mitral valve prolapse, while adults more frequently presented with aortic complications. Seven patients died during follow-up from aortic complications, one child and six adults. Conclusions: Based on the data, we can conclude that MFS in the Mestizo-Mexican population has a distinctly different clinical pattern in children and adults, and a graver prognosis in adults. Adult patients with MFS are significantly more likely, than children, to have aortic dilation, aortic aneurysm, aortic regurgitation, aneurysm rupture, aortic dissection, and fatal outcome. Children with MFS are more likely, than adults, to present with asymptomatic mitral and tricuspid prolapse and mitral valve regurgitation. (Echocardiography 2010;27:923-930) [ABSTRACT FROM AUTHOR]

This study aimed to determine the dimensions of the thoracic aorta and the predictors of aortic dimensions in girls and young women with Turner syndrome (TS). A cross-sectional study was performed at a secondary care center. The study compared 41 TS patients with 50 healthy age-matched control subjects. The mean age of the patients was 17 ± 3.3 years. Magnetic resonance imaging was performed for all the patients. The thoracic aortic diameters of the patients were measured at nine positions. Adjustment for body surface area (BSA) was performed. The outcome for the patients was measured in terms of absolute and BSA-adjusted aortic dilation. In TS, both the absolute and the BSA-adjusted mean aortic diameters were smaller than or comparable with those of the control subjects. However, individual aortic dilation at one to four positions was found in four TS patients according to the uncorrected data and in five TS patients after BSA-adjustment. The aortic diameters correlated with height, weight, body mass index (BMI), and BSA at all positions ( R = 0.34–0.60; all p < 0.04). The diameters of the aortic arch and the descending aorta correlated with a history of aortic coarctation ( R = 0.35–0.52; p < 0.03). The presence of bicuspid aortic valves correlated at the descending part of the aorta ( R = 0.38; p < 0.03). The mean thoracic aortic dimensions were not enlarged in girls or young TS patients. The BSA predicted aortic size at all positions. The prevalence of aortic dilation and aneurysm was lower in this population of girls and younger women with TS than in older TS populations. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to examine the relationship between proximal aortic dilation and systemic vascular function in men with bicuspid aortic valve (BAV). Background: Proximal aortic dilation in subjects with BAV is associated with structural and functional abnormalities in the ascending aorta. Methods: We studied 32 men (median age 31 years [range 28 to 32 years]) with nonstenotic BAV categorized into 2 subgroups according to proximal ascending aorta dimensions (nondilated ≤35 mm and dilated ≥40 mm, respectively). Sixteen healthy men were studied as control subjects. Flow-mediated dilation in response to hyperemia (a marker of endothelial dysfunction) and carotid–femoral pulse wave velocity (an index of aortic stiffness) were assessed, and peripheral blood was sampled for matrix metalloproteinases (MMP-2 and -9) and their tissue inhibitors (TIMP-1 and -2), respectively. Cardiac chamber and aortic dimensions were assessed by echocardiography and cardiac magnetic resonance imaging, respectively. Results: Despite the similar severity of aortic stenosis, left ventricular mass, and function, men with dilated aortas had blunted brachial flow-mediated vasodilation to hyperemia (5% [interquartile range (IQR) 4% to 6%] vs. 8% [IQR 7% to 9%] change, p = 0.001), higher carotid–femoral pulse wave velocity (9.3 cm/s [IQR 9 to 10 cm/s] vs. 7 cm/s [IQR 6.9 to 7.4 cm/s], p = 0.001), and significantly higher plasma levels of MMP-2 (1,523 [IQR 1,460 to 1,674] vs. 1,036 [IQR 962 to 1,167], p = 0.001) compared with men with BAV and nondilated aorta. Values for MMP-9, TIMP-1 and -2 levels, and nitroglycerin-induced (endothelium-independent) vasodilation were similar in all 3 groups. Conclusions: Young men with BAV and dilated proximal aortas manifest systemic endothelial dysfunction, increased carotid–femoral pulse wave velocity, and higher plasma levels of MMP-2. These observations could introduce new targets for screening and perhaps for therapeutic intervention. [Copyright &y& Elsevier]

Giant cell arteritis (GCA) is a systemic vasculitis with a direct and indirect increased risk of acute and chronic vascular events, affecting large and medium vessels, and responsible for most of the morbidity and mortality of this disease. We aimed in this review to provide an updated synthesis of knowledge regarding cardiovascular events observed in GCA. By definition, GCA patients are over 50 and often over 70 years old, and subsequently also present age-related cardiovascular risk factors. In addition, the systemic and vascular inflammation as well as glucocorticoids (GC) probably contribute to an accelerated atherosclerosis and to vascular changes leading to arterial stenoses and aortic dilations and/or dissections. GCA-related ischemic complications, especially ophthalmologic events, stroke or myocardial infarcts are mostly observed within the first months after the diagnosis, being mainly linked to the vasculitic process. Conversely, aortic complications, including dilations or dissections, generally occur several months or years after the diagnosis, mainly in patients with large-vessel vasculitis. In these patients, other factors such as atherosclerosis, GC-related endothelial damage and vascular wall remodeling/healing probably contribute to the vascular events. GCA management includes the detection and treatment of these previous and newly induced cardiovascular risk factors. Hence, the use of cardiovascular treatments (e.g., aspirin, anticoagulation, statins, anti-hypertensive treatments) should be evaluated individually. Aortic structural changes require regular morphologic evaluations, especially in patients with previous aortitis. The initial or secondary addition of immunosuppressants, especially tocilizumab, an anti-IL-6 receptor antibody, is discussed in patients with GCA-related cardiovascular complications and, more consensually, to limit GC-mediated comorbidities. [ABSTRACT FROM AUTHOR]

Prenatal ductal constriction and closure usually are related to maternal intake of prostaglandin receptor inhibitors during late gestation but may occur spontaneously. This report describes three live-born infants sharing echocardiographic features of spontaneous intrauterine ductal constriction, closure, or both, although only one had a prenatal diagnosis. Interestingly, in addition to severely hypertrophied right ventricles, all three had hyperechogenic tricuspid valve papillary muscles. Two also had mild ascending aorta dilation. These cases raise mechanistic questions because of intrauterine ductal occlusion, bright papillary muscles, and potential dilated ascending aortas. [ABSTRACT FROM AUTHOR]

Marfan Syndrome and Bicuspid Aortic Valve (BAV) are characterized by the congenital/inherited alteration of the fibrillin proteins of aortic wall extracellular matrix, with higher incidence of aortic dissection/rupture even without aortic dilation. Therefore, early identification and treatment of aortic involvement could improve prognosis. The purpose of this study was to evaluate aortic elastic properties of BAV and Marfan Syndrome patients to identify an index of early aortic involvement. Methods: A Magnetic Resonance Imaging (MRI) study was performed on 38 BAV patients, 20 Marfan patients and 14 healthy volunteers as a control group. A high-resolution gradient-echo sequence was applied in the axial plane at the level of pulmonary artery bifurcation to evaluate aortic distensibility. Results: Aortic distensibility was significantly different among the three groups (ANOVA, p = 0.0001) and was sensibly reduced in BAV (0.0056 ± 0.0048 versus 0.025 ± 0.006 control group) and Marfan (0.0085 ± 0.006 versus 0.025 ± 0.006 control group). Intraobserver and interobserver reproducibility for diastolic measurements were 1.2% and 0.4% respectively and for systolic measurements, they were 1.1% and 0.3% respectively. Conclusion: In BAV or Marfan Syndrome patients, MRI evaluation of abnormal distensibility may provide a reliable index of early aortic involvement, even before aortic dilation occurs. [ABSTRACT FROM AUTHOR]

Objective: The combination of aortic coarctation (CoA) and bicuspid aortic valve (BAV) is assumed to be associated with a higher risk of ascending aortic dilatation and type A dissection, and current European Society of Cardiology (ESC) guidelines advise therefore to operate at a lower threshold in the presence of CoA. The aim of our study is to evaluate whether the coexistence of CoA in BAV patients is indeed associated with a higher risk of ascending aortic events (AAE). Methods: In a retrospective study, all adult BAV patients visiting the outpatient clinic of our tertiary care center between February 2003 and February 2019 were included. The primary end point was an ascending aortic event (AAE) defined as ascending aortic dissection/rupture or preventive surgery. The secondary end points were aortic dilatation and aortic growth. Results: In total, 499 BAV patients (43.7% female, age 40.3 ± 15.7 years) were included, of which 121 (24%) had a history of CoA (cBAV). An aortic event occurred in 38 (7.6%) patients at a mean age of 49.0 ± 13.6 years. In the isolated BAV group (iBAV), significantly more AAE occurred, but this was mainly driven by aortic valve dysfunction as indication for aortic surgery. There was no significant difference in the occurrence of dissection or severely dilated ascending aorta (>50 mm) between the iBAV and cBAV patients (p = 0.56). The aortic diameter was significantly smaller in the cBAV group (30.3 ± 6.9 mm versus 35.7 ± 7.6 mm; p < 0.001). The median aortic diameter increase was 0.23 (interquartile range (IQR): 0.0–0.67) mm/year and was not significantly different between both groups (p = 0.74). Conclusion: Coexistence of CoA in BAV patients was not associated with a higher risk of aortic dissection, preventive aortic surgery, aortic dilatation, or more rapid aorta growth. This study suggests that CoA is not a risk factor in BAV patients, and the advice to operate at lower diameter should be reevaluated. [ABSTRACT FROM AUTHOR]

Aneurysm Outreach Inc. (AOI; ) is a nonprofit volunteer organization founded in 1999 whose aim is to (a) raise public awareness about aneurysms; (b) stimulate and fund genetic research through donations; and (c) coordinate a support network for aneurysm patients and their families. Since abdominal ultrasonography examination of an asymptomatic individual is not presently reimbursed by health insurance in the United States, one of the initiatives supported by AOI is to have free ultrasonography screening for abdominal aortic aneurysm (AAA) for those most at risk. One of the initiatives supported by AOI is to have free ultrasonography screening for abdominal aortic aneurysm (AAA). To meet this goal, a free screening program was initiated in September 2001 and by November 2004 approximately 3,000 participants were screened and 61 (2.0%) participants were confirmed to have a dilated aorta and were referred to their primary care physicians or vascular surgeons for further follow-up and treatment, if indicated. [ABSTRACT FROM AUTHOR]

Large-vessel involvement (LVI) in giant cell arteritis (GCA) includes different clinical and imaging patterns that are rarely described separately at diagnosis and whose specific cardiovascular outcomes are unknown. We conducted a nationwide retrospective study and included GCA patients with LVI demonstrated on imaging at diagnosis between 2007 and 2017. We analyzed the prognosis of three different imaging patterns of LVI present at diagnosis, with some of them overlapping but with the first one present in all patients: 1) inflammation of the aorta and/or its branches; 2) dilation of the aorta; and 3) stenosis of the aortic branches. A control group of GCA patients without LVI was constituted. We included 183 patients with LVI and 105 controls without LVI. Altogether, among the 183 patients who all showed inflammation of the aorta and/or its main branches, concomitant aortic dilation and large-vessel stenosis were observed in 27 (15%) and 55 (30%) patients, respectively. During the follow-up period, new cardiovascular events occurred in 49% and 11% of LVI patients and controls, respectively (p < 0.0001). Inflammation of the aorta and/or its branches (HR: 3.42 [2.09–5.83], p < 0.0001) and large-artery stenosis (HR: 2.75 [1.80–4.15], p < 0.0001) were independent predictive factors of new cardiovascular events. Conversely, the use of an immunosuppressant besides corticosteroids was a protective factor against new cardiovascular events (HR: 0.44 [0.29–0.66], p < 0.0001) and the development of aortic dilation (HR: 0.43 [0.23–0.77], p = 0.005). This study suggests different forms of cardiovascular events according to the initial imaging pattern of LVI. • Large-vessel involvements include aortitis, aorta dilation and vascular stenoses. • These patterns exhibit different outcomes and prognoses. • More cardiovascular events occur in patients with initial large-vessel involvement. • Large-vessel stenosis was associated with the poorest outcomes. • Immunosuppressants might have a protective impact on new cardiovascular events. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve (BAV), the most common congenital heart defect, is associated with an increased prevalence of aortic dilation, aortic rupture and aortic valve calcification. Endothelial cells (ECs) play a major role in vessel wall integrity. Little is known regarding EC function in BAV patients due to lack of patient derived primary ECs. Endothelial colony forming cells (ECFCs) have been reported to be a valid surrogate model for several cardiovascular pathologies, thereby facilitating an in vitro system to assess patient-specific endothelial dysfunction. Therefore, the aim of this study was to investigate cellular functions in ECFCs isolated from BAV patients. Outgrowth and proliferation of ECFCs from patients with BAV (n = 34) and controls with a tricuspid aortic valve (TAV, n = 10) were determined and related to patient characteristics. Interestingly, we were only able to generate ECFCs from TAV and BAV patients without aortic dilation, and failed to isolate ECFC colonies from patients with a dilated aorta. Analyzing EC function showed that while proliferation, cell size and endothelial-to-mesenchymal transition were similar in TAV and BAV ECFCs, migration and the wound healing capacity of BAV ECFCs is significantly higher compared to TAV ECFCs. Furthermore, calcification is blunted in BAV compared to TAV ECFCs. Our results reveal ECs dysfunction in BAV patients and future research is required to unravel the underlying mechanisms and to further validate ECFCs as a patient-specific in vitro model for BAV. [ABSTRACT FROM AUTHOR]

Background: Williams syndrome ([WS], 7q11.23 hemideletion) and 7q11.23 duplication syndrome (Dup7) show contrasting syndromic symptoms. However, within each group there is considerable interindividual variability in the degree to which these phenotypes are expressed. Though software exists to identify areas of copy number variation (CNV) from commonly-available SNP-chip data, this software does not provide non-diploid genotypes in CNV regions. Here, we describe a method for identifying haploid and triploid genotypes in CNV regions, and then, as a proof-of-concept for applying this information to explain clinical variability, we test for genotype-phenotype associations. Methods: Blood samples for 25 individuals with WS and 13 individuals with Dup7 were genotyped with Illumina-HumanOmni5M SNP-chips. PennCNV and in-house code were used to make genotype calls for each SNP in the 7q11.23 locus. We tested for association between the presence of aortic arteriopathy and genotypes of the remaining (haploid in WS) or duplicated (triploid in Dup7) alleles. Results: Haploid calls in the 7q11.23 region were made for 99.0% of SNPs in the WS group, and triploid calls for 98.8% of SNPs in those with Dup7. The G allele of SNP rs2528795 in the ELN gene was associated with aortic stenosis in WS participants (p < 0.0049) while the A allele of the same SNP was associated with aortic dilation in Dup7. Conclusions: Commonly available SNP-chip information can be used to make haploid and triploid calls in individuals with CNVs and then to relate variability in specific genes to variability in syndromic phenotypes, as demonstrated here using aortic arteriopathy. This work sets the stage for similar genotype-phenotype analyses in CNVs where phenotypes may be more complex and/or where there is less information about genetic mechanisms. [ABSTRACT FROM AUTHOR]

Objective: To report the fatal outcome of a woman with Turner syndrome (TS) undergoing assisted reproductive technology (ART). Design: Case report. Setting: Reproductive medicine center. Patient(s): A 33-year-old woman with TS. Intervention(s): Screening before oocyte donation and treatment of aortic dissection occurring at term pregnancy. Main Outcome Measure(s): Evaluation of cardiovascular risk. Result(s): After a normal cardiac screening, a woman with TS got pregnant as a result of oocyte donation. At 16 weeks of gestation, a bicuspid aortic valve was detected and associated with moderate aortic root dilation. Aortic dissection was diagnosed at 38 weeks of gestation, which required emergent cesarean delivery and aortic root replacement. Despite surgical treatment, early maternal death was recorded. Conclusion(s): Careful cardiac screening and close follow-up before and during pregnancy are necessary in patients with TS. [Copyright &y& Elsevier]

An abstract of the article "Turner Syndrome Is an Independent Risk Factor for Aortic Dilation in the Young," by Leo Lopez, Steven D. Colan, Roque Ventura, and Michael Silberbach is presented.