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Aims Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood. Methods and results We included patients <21 years old with MFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram–CMR agreement. Bland–Altman and intraclass correlation coefficients (ICCs) assessed inter-rater and inter-modality reliability. Univariable mixed-effects linear regression was used to evaluate longitudinal changes of MAD. MAD was detected in 60% (110/185) eligible patients. MVP was present in 48% (53/110) of MAD and MAD in 90% (53/59) of MVP. MAD detection by CMR and echocardiography had 96% overall agreement (Kappa = 0.89, P < 0.001) and a 0.32 mm estimate bias (95% CI 0.00, 0.65). ICC by echocardiography, CMR, and between modalities were 0.97 (95% CI 0.93, 0.98), 0.92 (95% CI 0.79, 0.97), and 0.91 (95% CI 0.85, 0.94), respectively. MAD was associated with aortic root dilation (P < 0.001). MAD was found in children of all ages, increased +0.18 mm/year (95% CI +0.14, +0.22) during a median duration of 5.5 years (IQR 3.1, 7.5 years). MAD indexed by height yielded a constant value +0.0002 mm/m/year (95% CI −0.0002, +0.0005 mm/m/year). Conclusion MAD was common in pediatric MFS and was associated with aortic root dilation. MAD detection by echocardiography and CMR was highly reliable, suggesting that routine assessment in MFS is feasible. MAD was present in neonates and progressed over time but remained constant when indexing by height. Further studies are needed to evaluate MAD as a biomarker for clinical outcomes in pediatric MFS. [ABSTRACT FROM AUTHOR]

Background: Cantu syndrome is a rare and complex multisystem disorder characterized by hypertrichosis, facial dysmorphism, osteochondroplasia and cardiac abnormalities. With only 150 cases reported worldwide, Cantu syndrome is now gaining wider recognition due to molecular testing and a growing body of literature that further characterizes the syndrome and some of its most important features. Cardiovascular pathology previously described in the literature include cardiomegaly, pericardial effusion, vascular dilation and tortuosity, and other congenital heart defects. However, cardiovascular involvement is highly variable amongst individuals with Cantu syndrome. In some instances, it can be extensive and severe requiring surgical management and long term follow up. Case presentation: Herein we report a case of a fourteen-year-old female who presented with worsening pericardial effusion of unknown etiology, and echocardiographic findings of concentric left ventricular hypertrophy, a mildly dilated aortic root and ascending aorta. Her medical history was notable for hemoptysis and an episode of pulmonary hemorrhage secondary to multiple aortopulmonary collaterals that were subsequently embolized in early childhood. She was initially managed with Ibuprofen and Colchicine but continued to worsen, and ultimately required a pericardial window for the management of refractory pericardial effusion. Imaging studies obtained on subsequent visits revealed multiple dilated and tortuous blood vessels in the head, neck, chest, and pelvis. A cardiomyopathy molecular studies panel was sent, and a pathogenic variant was identified in the ABCC9 gene, confirming the molecular diagnosis of autosomal dominant Cantu syndrome. Conclusions: Vascular anomalies and significant cardiac involvement are often present in Cantu syndrome, however there are currently no established screening recommendations or surveillance protocols in place. The triad of hypertrichosis, facial dysmorphism, and unexplained cardiovascular involvement in any patient should raise suspicion for Cantu syndrome and warrant further investigation. Initial cardiac evaluation and follow up should be indicated in any patient with a clinical and/or molecular diagnosis of Cantu syndrome. Furthermore, whole body imaging should be utilized to evaluate the extent of vascular involvement and dictate long term monitoring and care. [ABSTRACT FROM AUTHOR]

BackgroundDefective connective tissue structure may cause individuals with hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorders (HSD) to develop cardiac defects.MethodsWe conducted a retrospective chart review of adult patients treated in the EDS Clinic from November 1, 2019, to June 20, 2022 to identify those with cardiac defects. Echocardiogram data were collected using a data collection service. All EDS Clinic patients were evaluated by a single physician and diagnosed according to the 2017 EDS diagnostic criteria. Patient demographic, family and cardiac history were extracted from self-reported responses from a REDCap clinical intake questionnaire. Patients with at least 1 available echocardiogram (ECHO) were selected for the study (n = 568).ResultsThe prevalence of aortic root dilation in patients with hEDS was 2.7% and for HSD was 0.6%, with larger measurements for males than females and with age. Based on self-reported cardiac history that was verified from the medical record, patients with hEDS with bradycardia (p = 0.034) or brain aneurysm (p = 0.015) had a significantly larger average adult aortic root z-score. In contrast, patients with HSD that self-reported dysautonomia (p = 0.019) had a significantly larger average aortic root z-score. The prevalence of diagnosed mitral valve prolapse in patients with hEDS was 3.5% and HSD was 1.8%. Variants of uncertain significance were identified in 16 of 84 patients that received genetic testing based on family history.ConclusionsThese data reveal a low prevalence of cardiac defects in a large cohort of well-characterized hEDS and HSD patients. Differences in cardiovascular issues were not observed between patients with hEDS vs. HSD; and our findings suggest that cardiac defects in patients with hEDS or HSD are similar to the general population.

There is controversy on how to address mild aortic root dilation during concomitant aortic valve replacement: composite aortic valve conduit replacement or separate ascending aorta and aortic valve replacement. We reviewed our experience to address the issue. We retrospectively reviewed 778 adult nonsyndromic patients with aortic root diameter 55 mm or less who received replacement of the ascending aorta and aortic valve from January 1994 to June 2017. Patients were divided into 2 groups based on the type of aortic root intervention: composite aortic valve conduit replacement in 406 patients (52%) and separate ascending aorta and aortic valve replacement in 372 patients (48%). Propensity matching was used to mitigate differences in baseline patient characteristics and produced 188 matched pairs. Sinus of Valsalva diameter was 43 mm (39-47). Operative mortality occurred in 3 patients (2%) in the composite aortic valve conduit replacement group and in 5 patients (3%) in the separate ascending aorta and aortic valve replacement group (P =.470). Median follow-up was 9.6 years (8.4-10.1). Long-term mortality was similar in the 2 groups (P =.083). Repeat operation was performed in 13 patients (7%) in the composite aortic valve conduit replacement group and in 19 patients (10%) in the separate ascending aorta and aortic valve replacement group (P =.365). Sinus of Valsalva diameter decreased 2 mm (−4-0; median follow-up 41 months) in the propensity-matched separate ascending aorta and aortic valve replacement group. In patients with mild aortic root dilation, separate ascending aorta and aortic valve replacement results in a similar risk of repeat operation and mortality in comparison with composite aortic valve replacement. Separate ascending aorta and aortic valve replacement is not associated with subsequent aortic root dilation on medium-term echocardiography follow-up. Important operative outcomes, need for repeat operation, and survival. [Display omitted] [ABSTRACT FROM AUTHOR]

A 39-year-old man was admitted with acute heart failure due to severe aortic regurgitation induced by annuloaortic ectasia associated with Takayasu's arteritis. Because of the active inflammatory phase associated with Takayasu's arteritis, surgery is typically performed following immune suppression by steroid therapy. Herein, we report a favorable recovery in the active inflammatory phase. Steroid therapy was initiated shortly following surgery. The decision to perform aortic root replacement without prior steroid therapy was made because the patient's risk of subsequent heart failures was deemed high and was complicated by other comorbidities. [ABSTRACT FROM AUTHOR]

We report the case of an 11-year-old girl who complained about severe asthenia, orthostatic dizziness and abdominal pain for 4 weeks. The primary investigation concluded on febrile urinary tract infection treated by antibiotics. Symptom persistence prompted cardiological and endocrinological investigations. A fluctuation in blood pressure, long QT interval, dilation of the aortic root and left ventricular hypertrophy were documented. Elevated levels of urinary catecholamines together with the presence of a right-sided adrenal mass shown via abdominal ultrasound and magnetic resonance imaging were highly suggestive of a pheochromocytoma. This was confirmed by through iodine-123-metaiodobenzylguathdine ([123I]-mIBG) scintigraphy. Genetic analysis allowed for the exclusion of pathogenic mutations in genes implicated in hereditary paragangliomas and pheochromocytomas but showed a rare somatic mutation in exon 3 of the von Hippel-Lindau gene. The patient was treated with a β-blocker and calcium channel antagonist and underwent laparoscopic right-sided adrenalectomy. Cardiac manifestations resolved soon after surgery indicating that they were secondary to the pheochromocytoma. After 5 years of follow-up, the patient remains asymptomatic without any sign of tumor recurrence. The presence of aortic root dilation, a prolonged QT-interval and left ventricular hypertrophy may be early cardiac manifestations of a pheochromocytoma in a child and should prompt this diagnosis to be evoked.

Purpose: Aortic dilation and valvar regurgitation can develop in transposition of the great arteries (TGA) after the arterial switch operation (ASO). Variation in aortic root rotational position affects flow dynamics in patients without congenital heart disease. The aim of this study was to assess neo-aortic root (neo-AoR) rotational position and its association with neo-AoR dilation, ascending aorta (AAo) dilation, and neo-aortic valvar regurgitation in TGA following ASO. Methods: Patients with TGA repaired by ASO who underwent cardiac magnetic resonance (CMR) were reviewed. Neo-AoR rotational angle, neo-AoR and AAo dimensions indexed (to height), indexed left ventricular end diastolic volume (LVEDVI), and neo-aortic valvar regurgitant fraction (RF) were obtained from CMR. Results: Among 36 patients, the median age at CMR was 17.1 years (12.3, 21.9). Neo-AoR rotational angle (range − 52 to + 78°) was clockwise (≥ + 15°) in 50%, counterclockwise (<-9°) in 25%, and central (-9 to + 14°) in 25% of patients. A quadratic term for neo-AoR rotational angle, indicating increasing extremes of counterclockwise and clockwise angles, was associated with neo-AoR dilation (R2 = 0.132, p = 0.03), AAo dilation (R2 = 0.160, p = 0.016), and LVEDVI (R2 = 0.20, p = 0.007). These associations remained statistically significant on multivariable analyses. Rotational angle was negatively associated with neo-aortic valvar RF on univariable (p < 0.05) and multivariable analyses (p < 0.02). Rotational angle was associated with smaller bilateral branch pulmonary arteries (p = 0.02). Conclusion: In patients with TGA after ASO, neo-AoR rotational position likely affects valvar function and hemodynamics, leading to a risk of neo-AoR and AAo dilation, aortic valvar incompetence, increasing left ventricular size, and smaller branch pulmonary arteries. [ABSTRACT FROM AUTHOR]

We report the case of an 11-year-old girl who complained about severe asthenia, orthostatic dizziness and abdominal pain for 4 weeks. The primary investigation concluded on febrile urinary tract infection treated by antibiotics. Symptom persistence prompted cardiological and endocrinological investigations. A fluctuation in blood pressure, long QT interval, dilation of the aortic root and left ventricular hypertrophy were documented. Elevated levels of urinary catecholamines together with the presence of a right-sided adrenal mass shown via abdominal ultrasound and magnetic resonance imaging were highly suggestive of a pheochromocytoma. This was confirmed by through iodine-123-metaiodobenzylguathdine ([123I]-mIBG) scintigraphy. Genetic analysis allowed for the exclusion of pathogenic mutations in genes implicated in hereditary paragangliomas and pheochromocytomas but showed a rare somatic mutation in exon 3 of the von Hippel-Lindau gene. The patient was treated with a β-blocker and calcium channel antagonist and underwent laparoscopic right-sided adrenalectomy. Cardiac manifestations resolved soon after surgery indicating that they were secondary to the pheochromocytoma. After 5 years of follow-up, the patient remains asymptomatic without any sign of tumor recurrence. The presence of aortic root dilation, a prolonged QT-interval and left ventricular hypertrophy may be early cardiac manifestations of a pheochromocytoma in a child and should prompt this diagnosis to be evoked. [ABSTRACT FROM AUTHOR]

The Pediatric Heart Network (PHN) trial showed similar efficacy of β-blockers (BB) and angiotensin receptor blockers (ARB) for aortic root dilation in Marfan syndrome, but the impact on prescription practices is unknown. We hypothesized BB and ARB prescriptions would increase after the trial results were published (2014). Prescription data (2007–2016) were obtained from outpatient encounters (IBM Marketscan) for Marfan syndrome patients (6 months–25 years old). Excluding 2014 as a washout period, we analyzed two intervals: 2007–2013 and 2015–2016. Medication categories included BB, ARB, angiotensin converting enzyme inhibitors (ACEI), combination (BB/ARB and/or BB/ACEI), and no drug. Interrupted time-series analysis assessed immediate level change after publication and change in slope for the trend pre- and post-publication. Odds ratios (OR) and 95% confidence intervals from logistic regressions and generalized estimating equation methods accounted for correlation of prescriptions within patients. In 1499 patients (age 14.1 ± 6.1 years, 59% female) seen 2007–2013, BB trended lower [OR 0.91 (0.89, 0.93), p < 0.001] and ARB trended higher [OR 1.12 (1.07, 1.18), p < 0.001], while combination, ACEI, and no drug remained stable. This trend persisted, but was not significant, for BB [OR 0.54 (0.27, 1.08), p = 0.37] and ARB [OR 1.91 (0.55, 6.69), p = 0.31] in 2015–2016. Combination, ACEI, and no drug remained similar. In short term follow-up, changes in prescription practices following publication of the PHN trial were not statistically significant. This may be due to a change seen prior to publication with early adoption of ARBs that was maintained after confirmation of their effectiveness. [ABSTRACT FROM AUTHOR]

Background: Aortic root dilation (ARD) has been described in 22q11.2DS, even without congenital heart disease (CHD). However, the clinical implications and longitudinal course are unclear. In this study, we evaluated aortic root (AR) dimensions in 22q112.DS adolescents/adults without major intracardiac CHDs, analyzed the progression over time and investigated correlations with extracardiac comorbidities. Methods: AR dimensions were evaluated in 74 patients, measuring the sinus of Valsalva (VS) and proximal ascending aorta (AA), using Z-score to define mild, moderate and severe degrees. Changes in AR dimensions during longitudinal echocardiographic follow-up were investigated. Phenotypic characteristics have been collected. Results: Twenty-four patients (32.4%) showed ARD in terms of VS Z-score (2.43; IQR 2.08–3.01), eight (33.3%) of a moderate/severe degree. Thirteen (54.2%) had concomitant AAD (Z-score 2.34; IQR 1.60–2.85). The risk of ARD was significantly directly related to skeletal/connective tissue disorders (OR 12.82, 95% CI 1.43–115.31; p = 0.023) and inversely related to BMI (OR 0.86, 95% CI 0.77–0.97; p = 0.011). A significant increase in AR diameter's absolute value (p = 0.001) over time has been detected. Conclusion: Isolated ARD is common in 22q11.2DS. Although some clinical risk factors have been identified, pathogenetic mechanisms and risk of complications are undefined. Regular cardiac evaluations should be part of the 22q11.2DS follow-up, and also in non-CHDs patients, to improve long-term outcome. [ABSTRACT FROM AUTHOR]

Abstract Background Linkeropathies refers to a series of extremely rare hereditary connective tissue diseases affected by various glycosyltransferases in the biosynthesis of proteoglycans. We report for the first time two heterozygous variants of B3GAT3 in a Chinese infant, in whom Marfan syndrome was suspected at birth. Case presentation A 2-month-old boy from a non-consanguineous Chinese family without a family history presented severe phenotypes of joint dislocation, obvious flexion contractures of the elbow, arachnodactyly with slightly adducted thumbs, cranial dysplasia, foot abnormalities and aortic root dilation; Marfan syndrome was suspected at birth. Our patient was the youngest, at the age of 2 months, to experience aortic root dilation. Two B3GAT3 variants, NM_012200.2, c.752T>C, p.V251A and c.47C>A, p.S16*, with heterozygosity were identified in the patient by whole-exome sequencing; the variants were inherited from his parents. During close follow-up, significant changes in the cranial profile and obvious external hydrocephalus were present at the age of 7 months, which differs from previously reported cases. Conclusion We diagnosed a patient with congenital heart defects at an early age with a B3GAT3-related disorder instead of Marfan syndrome and expanded the spectrum of B3GAT3-related disorders. We also provide a literature review of reported B3GAT3 cases; for at least one of the variants, this is the first report of genotype–phenotype correlations in individuals with cardiovascular defects being related to the acceptor substrate-binding subdomain of B3GAT3.

Phelan-McDermid syndrome (PMS) is a rare genetic neurodevelopmental disorder that results from the loss of one functional copy of the SHANK3 gene. While many clinical features of PMS are well-understood, there is currently limited literature on cardiovascular abnormalities in PMS. This report aims to evaluate the prevalence of aortic root dilation (ARD) among individuals with PMS and to understand if underlying genetic variation relates to risk for ARD. We present findings from 59 participants collected from a multisite observational study evaluating the phenotype and natural history of PMS. Individual echocardiographic and genetic reports were analyzed for aortic root measurements and genetic variant data, respectively. Our a priori hypothesis was that participants with chromosome 22 deletions with hg19 start coordinates on or before 49,900,000 (larger deletions) would have more instances of ARD than participants with deletion start coordinates after 49,900,000 (smaller deletions). Eight participants (14%) had ARD, and its presence was statistically significantly associated with large deletions (p = 0.047). Relatedly, participants with ARD had significantly more genes deleted on chromosome 22 than participants without ARD (p = 0.013). These results could aid in the identification of individuals with PMS who are at higher risk for ARD., (© 2024 Wiley Periodicals LLC.)

Abstract Background Left atrial (LA) size is frequently assessed by posterior-anterior linear measurement of LA (LAD P-A) in the parasternal long axis to expedite examination. Aging, changes in body surface area, and several cardiovascular pathologies can affect aortic root (AoR) size, thereby affecting LA anatomical shape. We hypothesized that AoR dilatation influences LAD P-A and consequently correct assessment of LA size. Results We tested our hypothesis in a study of 70 patients with AoR diameter ranging from 2.7 to 4.8 cm. LA size assessed in parasternal long axis view as LAD P-A was compared to that with LA width and length acquired in the apical two and four chamber view. Simpson’s method of discs was used as standard measurement to assess LA volume. We observed that LAD P-A in the parasternal long axis decreases when AoR diameter increases. Thus, the increase in LA size assessed in parasternal long axis did not correlate with the increase of LA volume. Further analysis revealed that a significant positive correlation was observed when LAV was plotted as a function of LAD P-A only for those with a normal size AoR. In contrast, LA volume increase correlated with LA diameters assessed in the apical two and four chamber view regardless of AoR size. Conclusions Our study documents that increases in AoR impact on the linear measurement of LA, resulting in an underestimated LAD P-A. LA size ought to be calculated from the apical two and four chambers view parameters, especially in patients with AoR dilatation.

Background: Linkeropathies refers to a series of extremely rare hereditary connective tissue diseases affected by various glycosyltransferases in the biosynthesis of proteoglycans. We report for the first time two heterozygous variants of B3GAT3 in a Chinese infant, in whom Marfan syndrome was suspected at birth. Case presentation: A 2-month-old boy from a non-consanguineous Chinese family without a family history presented severe phenotypes of joint dislocation, obvious flexion contractures of the elbow, arachnodactyly with slightly adducted thumbs, cranial dysplasia, foot abnormalities and aortic root dilation; Marfan syndrome was suspected at birth. Our patient was the youngest, at the age of 2 months, to experience aortic root dilation. Two B3GAT3 variants, NM_012200.2, c.752T>C, p.V251A and c.47C>A, p.S16*, with heterozygosity were identified in the patient by whole-exome sequencing; the variants were inherited from his parents. During close follow-up, significant changes in the cranial profile and obvious external hydrocephalus were present at the age of 7 months, which differs from previously reported cases. Conclusion: We diagnosed a patient with congenital heart defects at an early age with a B3GAT3-related disorder instead of Marfan syndrome and expanded the spectrum of B3GAT3-related disorders. We also provide a literature review of reported B3GAT3 cases; for at least one of the variants, this is the first report of genotype–phenotype correlations in individuals with cardiovascular defects being related to the acceptor substrate-binding subdomain of B3GAT3. [ABSTRACT FROM AUTHOR]

Aims: Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood., Methods and Results: We included patients <21 years old with MFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram-CMR agreement. Bland-Altman and intraclass correlation coefficients (ICCs) assessed inter-rater and inter-modality reliability. Univariable mixed-effects linear regression was used to evaluate longitudinal changes of MAD. MAD was detected in 60% (110/185) eligible patients. MVP was present in 48% (53/110) of MAD and MAD in 90% (53/59) of MVP. MAD detection by CMR and echocardiography had 96% overall agreement (Kappa = 0.89, P < 0.001) and a 0.32 mm estimate bias (95% CI 0.00, 0.65). ICC by echocardiography, CMR, and between modalities were 0.97 (95% CI 0.93, 0.98), 0.92 (95% CI 0.79, 0.97), and 0.91 (95% CI 0.85, 0.94), respectively. MAD was associated with aortic root dilation (P < 0.001). MAD was found in children of all ages, increased +0.18 mm/year (95% CI +0.14, +0.22) during a median duration of 5.5 years (IQR 3.1, 7.5 years). MAD indexed by height yielded a constant value +0.0002 mm/m/year (95% CI -0.0002, +0.0005 mm/m/year)., Conclusion: MAD was common in pediatric MFS and was associated with aortic root dilation. MAD detection by echocardiography and CMR was highly reliable, suggesting that routine assessment in MFS is feasible. MAD was present in neonates and progressed over time but remained constant when indexing by height. Further studies are needed to evaluate MAD as a biomarker for clinical outcomes in pediatric MFS., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: The aims of this study were to evaluate the 16-year experience with  arterial switch operation at Beijing Children's Hospital and to determine early and late mortality and late morbidity, to explore risk factors for late complications and reintervention, and finally to evaluate whether the neoaortic sinotubular junction reconstruction technique reduces late complications of arterial switch operation., Methods: The clinical data of 185 patients with transposition of the great arteries who underwent arterial switch operation in Beijing Children's Hospital from January 2006 to January 2022 and 30 patients who underwent modified arterial switch operation with neoaortic sinotubular junction reconstruction technique in Fuwai Hospital during the same period were retrospectively analysed. Propensity score matching was also used to match the neoaortic sinotubular junction reconstruction patients in Fuwai Hospital with 30 non-neoaortic sinotubular junction reconstruction patients in Beijing Children's Hospital., Results: There were 13 early deaths (7.03%) and five late deaths (3.01%). Nineteen patients (11.45%) developed new aortic valve regurgitation and 28 patients (16.87%) developed aortic root dilation. Late right ventricular outflow tract obstruction occurred in 33 patients (19.88%). Late reintervention occurred in 18 cases (10.84%). Multivariate analysis showed that aorto-pulmonary diameter mismatch, previous pulmonary artery banding, and mild moderate or above new aortic valve regurgitation at discharge were independent risk factors for late new aortic valve regurgitation and aortic root dilation. Low surgical weight was an independent risk factor specific to new aortic valve regurgitation, and bicuspid native pulmonary valve was an independent risk factor specific to aortic root dilation. Older surgical age and aortic root dilation were independent risk factors for late right ventricular outflow tract obstruction. Older surgical age, operation before 2014, late right ventricular outflow tract obstruction, and late aortic root dilation were independent risk factors for late intervention. Propensity score matching showed that new aortic valve regurgitation and aortic root dilation were not followed up in the neoaortic sinotubular junction reconstruction group, while seven cases of aortic root dilation and five cases of new aortic valve regurgitation occurred in the non-neoaortic sinotubular junction reconstruction group, respectively, and the differences were statistically significant (P = 0.003; P = 0.015)., Conclusions: The increased incidence of new aortic valve regurgitation, aortic root dilation, and right ventricular outflow tract obstruction as children age is a major concern outcome in the future and may mean more late reintervention. neoaortic sinotubular junction reconstruction technique may reduce the incidence of new aortic valve regurgitation and aortic root dilation, and improve the late prognosis of arterial switch operation. Careful follow-up of neo-aortic valve and root function is imperative, especially in patients with aorto-pulmonary diameter mismatch, previous pulmonary artery banding, mild new aortic valve regurgitation at discharge, low surgical weight, and bicuspid native pulmonary valve structures.

Prosthetic aortic valve dehiscence is a rare but potentially life-threatening complication that can occur after aortic valve replacement surgery. This condition occurs when the prosthetic valve becomes detached or dislodged from its original position leading to aortic valve regurgitation and congestive heart failure. The most common risk factors for prosthetic valve dehiscence include infective endocarditis, ascending aortic aneurysm, and severe calcification of the aortic valve. Ankylosing spondylitis, non-infectious aortitis, and accompanying vasculitis can also cause aortic valve dehiscence. Transthoracic echocardiography and transesophageal echocardiography usually reveal an unstable prosthesis with rocking motion and paravalvular regurgitation. Fluoroscopy and cardiac computed tomography (CT) are useful complementary tests, especially in patients with significant artifacts related to a valve prosthesis. Patients with prosthetic valve dehiscence and paravalvular regurgitation eventually develop heart failure and circulatory collapse. Timely diagnosis and early surgical intervention in these patients are crucial to achieve good long-term outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Pamulapati et al.)

[Display omitted] [ABSTRACT FROM AUTHOR]

Aortic root dilation (ARD) has been reported in patients with 22q11.2 deletion syndrome (22q11.2DS) with and without congenital heart defects (CHDs). However, the long-term implications of isolated ARD in 22q11.2DS remain undefined. In this study, we measured aortic root size and estimated the probability of changing between normal aortic root size and ARD during follow up to understand the prevalence, longitudinal course, and clinical risk factors for ARD in patients with 22q11.2DS without intracardiac CHDs. Aortic root size was measured in 251 patients with 432 studies. Forty-one patients (16.3%) had ARD on at least one echocardiogram and the cohort sinus Z-score was increased on the last echocardiogram [mean (1.09, SD 1.24) and median (1.20, min − 1.90 and max 5.40)]. Transition probability analysis showed that 8.1% of patients developed ARD and 45.4% of patients with ARD reverted to normal at the next echocardiogram. The risk of ARD over time was significantly associated with male sex (OR 3.06, 95% CI 1.41–6.65; p = 0.004), but not with age or presence of an aortic arch anomaly. Compared to a sinus Z-score ≥ 2, initial Z-score < 2 was associated with 14.3 times lower risk of developing sinus Z-score ≥ 3 at follow up. Sinus Z-score overall decreased by age, and males had a higher Z-score than females (ß = 0.72, SE = 0.14, p < 0.001). Though only a few patients had a Z-score > 4, and patients with initial Z-scores < 2 seem unlikely to develop clinically significant disease, screening practices remain incompletely defined such that periodic evaluation appears warranted. [ABSTRACT FROM AUTHOR]

Van den Ende‐Gupta syndrome (VDEGS) is a rare autosomal recessive condition characterized by distinctive facial and skeletal features, and in most affected persons, by biallelic pathogenic variants in SCARF2. We review the type and frequency of the clinical features in 36 reported individuals with features of VDEGS, 15 (42%) of whom had known pathogenic variants in SCARF2, 6 (16%) with negative SCARF2 testing, and 15 (42%) not tested. We also report three new individuals with pathogenic variants in SCARF2 and clinical features of VDEGS. Of the six persons without known pathogenic variants in SCARF2, three remain unsolved despite extensive genetic testing. Three were found to have pathogenic ABL1 variants using whole exome sequencing (WES) or whole genome sequencing (WGS). Their phenotype was consistent with the congenital heart disease and skeletal malformations syndrome (CHDSKM), which has been associated with ABL1 variants. Of the three unsolved cases, two were brothers who underwent WGS and targeted long‐range sequencing of both SCARF2 and ABL1, and the third person who underwent WES and RNA sequencing for SCARF2. Because these affected individuals with classical features of VDEGS lacked a detectable pathogenic SCARF2 variant, genetic heterogeneity is likely. Our study shows the importance of performing genetic testing on individuals with the VDEGS "phenotype," either as a targeted gene analysis (SCARF2, ABL1) or WES/WGS. Additionally, individuals with the combination of arachnodactyly and blepharophimosis should undergo echocardiography while awaiting results of molecular testing due to the overlapping physical features of VDEGS and CHDSKM. [ABSTRACT FROM AUTHOR]

Background: Left atrial (LA) size is frequently assessed by posterior-anterior linear measurement of LA (LAD P-A) in the parasternal long axis to expedite examination. Aging, changes in body surface area, and several cardiovascular pathologies can affect aortic root (AoR) size, thereby affecting LA anatomical shape. We hypothesized that AoR dilatation influences LAD P-A and consequently correct assessment of LA size. Results: We tested our hypothesis in a study of 70 patients with AoR diameter ranging from 2.7 to 4.8 cm. LA size assessed in parasternal long axis view as LAD P-A was compared to that with LA width and length acquired in the apical two and four chamber view. Simpson's method of discs was used as standard measurement to assess LA volume. We observed that LAD P-A in the parasternal long axis decreases when AoR diameter increases. Thus, the increase in LA size assessed in parasternal long axis did not correlate with the increase of LA volume. Further analysis revealed that a significant positive correlation was observed when LAV was plotted as a function of LAD P-A only for those with a normal size AoR. In contrast, LA volume increase correlated with LA diameters assessed in the apical two and four chamber view regardless of AoR size. Conclusions: Our study documents that increases in AoR impact on the linear measurement of LA, resulting in an underestimated LAD P-A. LA size ought to be calculated from the apical two and four chambers view parameters, especially in patients with AoR dilatation. [ABSTRACT FROM AUTHOR]

The prevalence of obstructive sleep apnea (OSA) is increased in children and adults with Marfan syndrome (MFS) compared to the general population and has been shown to be associated with rapid aortic root dilation and dissection in adults. Early diagnosis and treatment of OSA may decrease long-term cardiac morbidity. We therefore studied the utility of noninvasive OSA screening tools in children with MFS. We hypothesized that youth with MFS would have higher OSA screening scores than the general pediatric population. Subjects with confirmed MFS were recruited from a single pediatric center. Data collected included cardiac history, retrospective polysomnogram (PSG) data, and prospectively collected Pediatric Sleep Questionnaire (SRBD-PSQ) and Epworth Sleepiness Scale (ESS-CHAD) scores. Fifty-one individuals aged 2–21 years old were identified. Nineteen subjects completed the surveys, 53% female, median age 16 years. Of those that completed the survey, mean SRBD-PSQ score was 0.24 ± 0.21 and mean ESS-CHAD was 6.4 ± 3.7. Comparatively, published normative data for pediatric control subjects were 0.24 ± 0.21 for SRBD-PSQ and 5.4 ± 3.7 for ESS-CHAD. In conclusions, youth with MFS had similar OSA screening scores compared to published pediatric controls. Given these findings and high prevalence of OSA in MFS youth, standard questionnaires may not be an appropriate tool for identifying children at risk for OSA in this population. In the absence of evidence-based guidelines, physicians caring for children with MFS should consider referral for PSG, even in the absence of classic symptoms. [ABSTRACT FROM AUTHOR]

Objective Evaluating an artificial intelligence (AI) tool (AIATELLA, version 1.0; AIATELLA Oy, Helsinki, Finland) in interpreting cardiac magnetic resonance (CMR) imaging to produce measurements of the aortic root and valve by comparison of accuracy and efficiency with that of three National Health Service (NHS) cardiologists. Methods AI-derived aortic root and valve measurements were recorded alongside manual measurements from three experienced NHS consultant cardiologists (CCs) over three separate sites in the northeast part of the United Kingdom. The study utilised a comprehensive dataset of CMR images, with the intraclass correlation coefficient (ICC) being the primary measure of concordance between the AI and the cardiologist assessments. Patient imaging was anonymised and blinded at the point of transfer to a secure data server.  Results The study demonstrates a high level of concordance between AI assessment of the aortic root and valve with NHS cardiologists (ICC of 0.98). Notably, the AI delivered results in 2.6 seconds (+/- 0.532) compared to a mean of 334.5 seconds (+/- 61.9) by the cardiologists, a statistically significant improvement in efficiency without compromising accuracy. Conclusion AI's accuracy and speed of analysis suggest that it could be a valuable tool in cardiac diagnostics, addressing the challenges of time-consuming and variable clinician-based assessments. This research reinforces AI's role in optimising the patient journey and improving the efficiency of the diagnostic pathway., Competing Interests: AIATELLA has filed for a patent related to the method utilised by the AI tool to determine key landmarks and produce measurements from medical imaging. Patent application 20235369 - Finland - Machine Learning Based Landmark or Segment Detection From Medical Image Data.. Jack Parker is the CEO and co-founder of AIATELLA. He holds a majority shareholding in the company. James Coey is an unpaid advisor to AIATELLA., (Copyright © 2024, Parker et al.)

Background: Defective connective tissue structure may cause individuals with hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorders (HSD) to develop cardiac defects., Methods: We conducted a retrospective chart review of adult patients treated in the EDS Clinic from November 1, 2019, to June 20, 2022 to identify those with cardiac defects. Echocardiogram data were collected using a data collection service. All EDS Clinic patients were evaluated by a single physician and diagnosed according to the 2017 EDS diagnostic criteria. Patient demographic, family and cardiac history were extracted from self-reported responses from a REDCap clinical intake questionnaire. Patients with at least 1 available echocardiogram (ECHO) were selected for the study ( n  = 568)., Results: The prevalence of aortic root dilation in patients with hEDS was 2.7% and for HSD was 0.6%, with larger measurements for males than females and with age. Based on self-reported cardiac history that was verified from the medical record, patients with hEDS with bradycardia ( p  = 0.034) or brain aneurysm ( p  = 0.015) had a significantly larger average adult aortic root z-score. In contrast, patients with HSD that self-reported dysautonomia ( p  = 0.019) had a significantly larger average aortic root z-score. The prevalence of diagnosed mitral valve prolapse in patients with hEDS was 3.5% and HSD was 1.8%. Variants of uncertain significance were identified in 16 of 84 patients that received genetic testing based on family history., Conclusions: These data reveal a low prevalence of cardiac defects in a large cohort of well-characterized hEDS and HSD patients. Differences in cardiovascular issues were not observed between patients with hEDS vs. HSD; and our findings suggest that cardiac defects in patients with hEDS or HSD are similar to the general population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Knight, Bruno, Singh, Munipalli, Gajarawala, Solomon, Kocsis, Darakjian, Jain, Whelan, Kotha, Gorelov, Phillips and Fairweather.)

Symptoms including chest pain and palpitations are commonly described by pediatric patients with pectus deformity. Cardiac anomalies are thought to be less common in patients with pectus carinatum (PC) than those in patients with pectus excavatum; however, no literature supports this presumption. Echocardiogram (echo) assesses heart structure and function. We hypothesized that a screening echo would 1) determine the relationship between symptoms and echo findings and 2) define the incidence of cardiac defects in patients with PC. This is an institutional review board–approved retrospective review of all patients with PC who received an echo from 2015 to 2019 at a tertiary care children's hospital. Echo findings and patient-reported symptoms were collected from electronic health records. Descriptive statistics were used to assess correlation between findings. We identified 155 patients with PC who received an echo with complete data available for analysis. Of these, 44 (28.4%) reported chest pain and 13 (8.4%) reported palpitations. Echo results showed that five patients (3.2%) had mitral valve prolapse and 11 (7.1%) had aortic root dilation. Patient-reported symptoms were not significantly associated with abnormal echo findings. Chest pain and palpitations frequently occur in the PC population but may not be related to abnormal echo findings. We recommend screening echo in patients with PC regardless of symptoms. • More than one fifth of PC patients have an identified cardiac anomaly. • Nearly one fifth of PC patients report chest pain to their physician. • Symptoms are not predictive of structural abnormalities. • PC patients have notable rates of mitral valve prolapse and aortic root dilation. • Echo is recommended for all patients with PC regardless of symptoms. [ABSTRACT FROM AUTHOR]

Pre-operative planning of valve-sparing aortic root reconstruction relies on the automatic discrimination of healthy and pathologically dilated aortic roots. The basis of this classification are features extracted from 3D ultrasound images. In previously published approaches, handcrafted features showed a limited classification accuracy. However, feature learning is insufficient due to the small data sets available for this specific problem. In this work, we propose transfer learning to use deep learning on these small data sets. For this purpose, we used the convolutional layers of the pretrained deep neural network VGG16 as a feature extractor. To simplify the problem, we only took two prominent horizontal slices throgh the aortic root, the coaptation plane and the commissure plane, into account by stitching the features of both images together and training a Random Forest classifier on the resulting feature vectors. We evaluated this method on a data set of 48 images (24 healthy, 24 dilated) using 10-fold cross validation. Using the deep learned features we could reach a classification accuracy of 84 %, which clearly outperformed the handcrafted features (71 % accuracy). Even though the VGG16 network was trained on RGB photos and for different classification tasks, the learned features are still relevant for ultrasound image analysis of aortic root pathology identification. Hence, transfer learning makes deep learning possible even on very small ultrasound data sets.

We present a case report of a 30-year-old Marfan syndrome patient who underwent a David procedure for severe aortic valve insufficiency and Valsalva aneurysm. Harvested aortic walls were examined by pathologists. Although the tunica media of the ascending aorta contained aligned elastic fibers, the aortic root media lacked aligned elastic fibers.

Aortic root dilation and thoracic aortic aneurysms are relatively rare in young and healthy patient populations. However, a number of observed incidental cases regarding young males and testosterone use raises suspicion of a potential risk factor for aortic root dilation. The authors' patient, a healthy 40-year-old man with a significant history of testosterone use who developed a massively dilated aortic root, is sufficiently alarming to report. Notwithstanding anecdotal cases, there exists a well-known association between elite strength athletes and aortic root dilation. Nevertheless, very little clinical research exists on the relationship between testosterone use and aortic root dilation and/or thoracic aortic aneurysms. Furthermore, a small number of animal studies showed a relationship between testosterone and vascular dilation, particularly the aorta. Although testosterone may play a role in the development of aortic pathologies, further research is necessary to clarify the possible relationship if cases such as these are to be prevented. [ABSTRACT FROM AUTHOR]

Background Aortic root dilation is an increasingly recognized feature in repaired tetralogy of Fallot (TOF) patients. However, the dilation at the aortic root and ascending aorta in unrepaired TOF is rarely studied. This study aims to confirm whether aortic dilation is a common feature in unrepaired TOF and investigate the factors attributed to aortic dilation. Methodology Patients with an echocardiographic diagnosis of TOF undergoing computed tomography angiography were retrospectively studied. Diameters and z scores of aortic annular (Ao1), aortic sinotubular junction (Ao2), ascending aorta (Ao3), and distal transverse aortic arch (Ao4) were measured. Preoperative body surface area (BSA), hemoglobin (Hb), hematocrit (HCT), arterial oxygen saturation (SaO 2 ), and platelet (PLT) count were recorded. Results A total of 101 TOF patients aged 6.8 ± 9.5 years were included in this study, whose mean BSA (m 2 ), Hb (g/L), HCT, SaO 2  (%), and PLT (10 9 /L) were 0.7 ± 0.4, 162.1 ± 3.8, 0.5 ± 0.1, 85.1 ± 9.3, and 238.1 ± 101.1, respectively. The mean z score of Ao1, Ao2, Ao3, and Ao4 were 10.3 ± 3.5, 4.7 ± 2.9, 4.0 ± 2.7, and 4.1 ± 2.4, respectively. Age and BSA were positively correlated with the z scores of Ao1 and Ao2. Preoperative Hb and HCT were positively correlated with the z scores of Ao1, Ao2, Ao3, and Ao4. Preoperative SaO 2  and PLT were negatively correlated with the z scores of Ao1, Ao2, Ao3, and Ao4. Conclusions Aortic dilation is common in unrepaired TOF patients. The dilation of different levels of the aorta was correlated with age, BSA, preoperative Hb, HCT, SaO 2 , and PLT., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Lu et al.)

Few data exist regarding predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome (MFS). To identify independent predictors of the rate of aortic root (AoR) dilation and referral for aortic surgery, we investigated the data from the Pediatric Heart Network randomized trial of atenolol versus losartan in young patients with MFS. Data were analyzed from the echocardiograms at 0, 12, 24, and 36 months read in the core laboratory of 608 trial subjects, aged 6 months to 25 years, who met original Ghent criteria and had an AoR z-score (AoRz) > 3. Repeated measures linear and logistic regressions were used to determine multivariable predictors of AoR dilation. Receiver operator characteristic curves were used to determine cut-points in AoR dilation predicting referral for aortic surgery. Multivariable analysis showed rapid AoR dilation as defined by change in AoRz/year > 90th percentile was associated with older age, higher sinotubular junction z-score, and atenolol use (R2 = 0.01) or by change in AoR diameter (AoRd)/year > 90th percentile with higher sinotubular junction z-score and non-white race (R2 = 0.02). Referral for aortic root surgery was associated with higher AoRd, higher ascending aorta z-score, and higher sinotubular junction diameter:ascending aorta diameter ratio (R2 = 0.17). Change in AoRz of 0.72 SD units/year had 42% sensitivity and 92% specificity and change in AoRd of 0.34 cm/year had 38% sensitivity and 95% specificity for predicting referral for aortic surgery. In this cohort of young patients with MFS, no new robust predictors of rapid AoR dilation or referral for aortic root surgery were identified. Further investigation may determine whether generalized proximal aortic dilation and effacement of the sinotubular junction will allow for better risk stratification. Rate of AoR dilation cut-points had high specificity, but low sensitivity for predicting referral for aortic surgery, limiting their clinical use. Clinical Trial Number ClinicalTrials.gov number, NCT00429364. [ABSTRACT FROM AUTHOR]

Aims It has been hypothesized that in response to dilation of the aortic root, the aortic valve cusps may remodel to prevent aortic regurgitation (AR). The aim of the present study was to evaluate the association between aortic cusp dimensions and aortic root geometry. Methods and results Three-dimensional transoesophageal echocardiography was performed in 40 patients with aortic root dilation (mean age 57±12 years, 75% men, 35% bicuspid aortic valve) and 20 controls with a normal aortic root (mean age 61±13 years, 65% men). Aortic valve geometry was measured, and the ratio between closed cusp area and sinotubular junction (STJ) area as a measure of the aortic cusp remodelling relative to the aortic root dilation was assessed. Patients with aortic root dilation with tricuspid aortic valve (n = 26) showed significant increase in aortic cusp size. However, the closed cusp area to STJ area ratio was smaller in dilated aortic roots [0.88 (95% confidence interval: 0.78-0.98)] compared with normal aortic roots [1.22 (95% confidence interval: 1.02-1.41); P = 0.002]. In addition, in patients with central AR, there was insufficient cusp tissue, as suggested by a closed cusp area to STJ area ratio of 0.75 (95% confidence interval: 0.67-0.82), compared with relative excess of cusp tissue in eccentric AR with a ratio of 1.14 (95% confidence interval: 1.01-1.27; P, 0.001). Conclusion Aortic root dilation was associated with significant increase in aortic valve cusp size. However, this increase seemed insufficient to match aortic root size, particularly in central AR, whereas in eccentric AR, there was relative abundance of cusp tissue resulting in relative cusp prolapse. [ABSTRACT FROM AUTHOR]

Diagnosis and treatment of 22q11.2 deletion syndrome (22q11.2DS) have led to improved life expectancy and achievement of adulthood. Limited data on long-term outcomes reported an increased risk of premature death for cardiovascular causes, even without congenital heart disease (CHD). The aim of this study was to assess the cardiac function in adolescents and young adults with 22q11.2DS without CHDs. A total of 32 patients (20M, 12F; mean age 26.00 ± 8.08 years) and a healthy control group underwent transthoracic echocardiography, including Tissue Doppler Imaging (TDI) and 2-dimensional Speckle Tracking Echocardiography (2D-STE). Compared to controls, 22q11.2DS patients showed a significant increase of the left ventricle (LV) diastolic and systolic diameters (p = 0.029 and p = 0.035 respectively), interventricular septum thickness (p = 0.005), LV mass index (p < 0.001) and aortic root size (p < 0.001). 2D-STE analysis revealed a significant reduction of LV global longitudinal strain (p < 0.001) in 22q11.2DS than controls. Moreover, several LV diastolic parameters were significantly different between groups. Our results suggest that an echocardiographic follow-up in 22q11.2DS patients without CHDs can help to identify subclinical impairment of the LV and evaluate a potential progression of aortic root dilation over time, improving outcomes, reducing long-term complications and allowing for a better prognosis. [ABSTRACT FROM AUTHOR]

We report the first case of a patient with large pericardial cyst occurring concurrently with a very large thoracic aortic aneurysm. There have been no patients reported in the literature with this constellation of syndromes. Additionally, this case was followed through a period of 4 years, enabling the natural evolution of both pathologies to be visualised. [ABSTRACT FROM AUTHOR]