Mitral Annular Disjunction and Its Progression during Childhood in Marfan Syndrome.

BACKGROUND: Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. OBJECTIVES: To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood. METHODS: 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 (ICC) assessed interrater and intermodality reliability. Univariable mixed-effects linear regression was used to evaluate longitudinal changes of MAD. RESULTS: 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). CONCLUSIONS: 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.

Computational framework for the generation of one-dimensional vascular models accounting for uncertainty in networks extracted from medical images.

One-dimensional (1D) cardiovascular models offer a non-invasive method to answer medical questions, including predictions of wave-reflection, shear stress, functional flow reserve, vascular resistance, and compliance. This model type can predict patient-specific outcomes by solving 1D fluid dynamics equations in geometric networks extracted from medical images. However, the inherent uncertainty in in-vivo imaging introduces variability in network size and vessel dimensions, affecting hemodynamic predictions. Understanding the influence of variation in image-derived properties is essential to assess the fidelity of model predictions. Numerous programs exist to render three-dimensional surfaces and construct vessel centerlines. Still, there is no exact way to generate vascular trees from the centerlines while accounting for uncertainty in data. This study introduces an innovative framework employing statistical change point analysis to generate labeled trees that encode vessel dimensions and their associated uncertainty from medical images. To test this framework, we explore the impact of uncertainty in 1D hemodynamic predictions in a systemic and pulmonary arterial network. Simulations explore hemodynamic variations resulting from changes in vessel dimensions and segmentation; the latter is achieved by analyzing multiple segmentations of the same images. Results demonstrate the importance of accurately defining vessel radii and lengths when generating high-fidelity patient-specific hemodynamics models.

Vertebral Tortuosity Is Associated With Increased Rate of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome.

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic COL3A1 variant diagnosed at age <50 years were included from 2 institutions and the GenTAC Registry (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions). Height-adjusted vertebral artery tortuosity index (VTI-h) using magnetic resonance or computed tomography angiography was calculated. Associations between VTI-h and outcomes of (1) cardiovascular events (arterial dissection/rupture, aneurysm requiring intervention, stroke), or (2) hollow organ collapse/rupture at age <50 years were evaluated using receiver operator curve analysis (using outcome by age 30 years) and mixed-effects Poisson regression for incidence rate ratios. Of 65 subjects (54% male), median VTI-h was 12 (interquartile range, 8-16). Variants were missense in 46%, splice site in 31%, and null/gene deletion in 14%. Thirty-two subjects (49%) had 59 events, including 28 dissections, 5 arterial ruptures, 4 aneurysms requiring intervention, 4 strokes, 11 hollow organ ruptures, and 7 pneumothoraces. Receiver operator curve analysis suggested optimal discrimination at VTI-h ≥15.5 for cardiovascular events (sensitivity 70%, specificity 76%) and no association with noncardiovascular events (area under the curve, 0.49 [95% CI, 0.22-0.78]). By multivariable analysis, older age was associated with increased cardiovascular event rate while VTI-h ≥15.5 was not (incidence rate ratios, 1.79 [95% CI, 0.76-4.24], P=0.185). However, VTI-h ≥15.5 was associated with events among those with high-risk variants <40 years (incidence rate ratios, 4.14 [95% CI, 1.13-15.10], P=0.032), suggesting effect modification by genotype and age. Conclusions Increased arterial tortuosity is associated with a higher incidence rate of cardiovascular events in Vascular Ehlers-Danlos syndrome. Vertebral tortuosity index may be a useful biomarker for prognosis when evaluated in conjunction with genotype and age.

A computational study of aortic reconstruction in single ventricle patients.

Patients with hypoplastic left heart syndrome (HLHS) are born with an underdeveloped left heart. They typically receive a sequence of surgeries that result in a single ventricle physiology called the Fontan circulation. While these patients usually survive into early adulthood, they are at risk for medical complications, partially due to their lower than normal cardiac output, which leads to insufficient cerebral and gut perfusion. While clinical imaging data can provide detailed insight into cardiovascular function within the imaged region, it is difficult to use these data for assessing deficiencies in the rest of the body and for deriving blood pressure dynamics. Data from patients used in this paper include three-dimensional, magnetic resonance angiograms (MRA), time-resolved phase contrast cardiac magnetic resonance images (4D-MRI) and sphygmomanometer blood pressure measurements. The 4D-MRI images provide detailed insight into velocity and flow in vessels within the imaged region, but they cannot predict flow in the rest of the body, nor do they provide values of blood pressure. To remedy these limitations, this study combines the MRA, 4D-MRI, and pressure data with 1D fluid dynamics models to predict hemodynamics in the major systemic arteries, including the cerebral and gut vasculature. A specific focus is placed on studying the impact of aortic reconstruction occurring during the first surgery that results in abnormal vessel morphology. To study these effects, we compare simulations for an HLHS patient with simulations for a matched control patient that has double outlet right ventricle (DORV) physiology with a native aorta. Our results show that the HLHS patient has hypertensive pressures in the brain as well as reduced flow to the gut. Wave intensity analysis suggests that the HLHS patient has irregular circulatory function during light upright exercise conditions and that predicted wall shear stresses are lower than normal, suggesting the HLHS patient may have hypertension.

Dobutamine stress cardiac MRI is safe and feasible in pediatric patients with anomalous aortic origin of a coronary artery (AAOCA).

BACKGROUND: Risk stratification in anomalous aortic origin of a coronary artery (AAOCA) is challenged by the lack of a reliable method to detect myocardial ischemia. We prospectively studied the safety and feasibility of Dobutamine stress-cardiac magnetic resonance (DSCMR), a test with excellent performance in adults, in pediatric patients with AAOCA. METHODS: Consecutive DSCMR from 06/2014-12/2019 in patients≤20 years old with AAOCA were included. Hemodynamic response and major/minor events were recorded. Image quality and spatial/temporal resolution were evaluated. Rest and stress first-pass perfusion and wall motion abnormalities (WMA) were assessed. Inter-observer agreement was assessed using kappa coefficient. RESULTS: A total of 224 DSCMR were performed in 182 patients with AAOCA at a median age of 14 years (IQR 12, 16) and median weight of 58.0 kg (IQR 43.3, 73.0). Examinations were completed in 221/224 (98.9%), all studies were diagnostic. Heart rate and blood pressure increased significantly from baseline (p < 0.001). No patient had major events and 28 (12.5%) had minor events. Inducible hypoperfusion was noted in 31/221 (14%), associated with WMA in 13/31 (42%). Inter-observer agreement for inducible hypoperfusion was very good (Κ = 0.87). Asymptomatic patients with inducible hypoperfusion are considered high-risk and those with a negative test are of standard risk. CONCLUSIONS: DSCMR is feasible in pediatric patients with AAOCA to assess for inducible hypoperfusion and WMA. It can be performed safely with low incidence of major/minor events. Thus, DSCMR is potentially a valuable test for detection of myocardial ischemia and helpful in the management of this patient population.

Echocardiographic Diagnosis of Left Main Coronary Artery Atresia.

This case describes an infantile presentation of left main coronary artery atresia (LMCAA), which involves complete absence of the left coronary ostium and left main coronary artery. The echocardiographic features of LMCAA that assist in making this diagnosis are detailed. Important imaging features that distinguish LMCAA from anomalous left coronary artery from the pulmonary artery are highlighted.