Cardiovascular disease risk factors in congenital heart disease survivors are associated with heart failure.

BACKGROUND: Despite advances in treatment and survival, individuals with congenital heart defects (CHD) have a higher risk of heart failure (HF) compared to the general population. OBJECTIVE: To evaluate comorbidities associated with HF in patients with CHD with a goal of identifying potentially modifiable risk factors that may reduce HF-associated morbidity and mortality. METHODS: Five surveillance sites in the United States linked population-based healthcare data and vital records. Individuals with an ICD-9-CM code for CHD aged 11-64 years were included and were stratified by presence of HF diagnosis code. Prevalence of death and cardiovascular risk factors based on diagnosis codes were compared by HF status using log-linear regression. RESULTS: A total of 25,343 individuals met inclusion/exclusion criteria. HF was documented for 2.2% of adolescents and 12.9% of adults with CHD. Adolescents and adults with HF had a higher mortality than those without HF. In both age groups, HF was positively associated with coronary artery disease, hypertension, obesity, diabetes, and increased healthcare utilization compared to those without HF. CONCLUSIONS: Within this population-based cohort, over 1 in 50 adolescents and 1 in 8 adults with CHD had HF, which was associated with increased mortality. Modifiable cardiovascular comorbidities were associated with HF. IMPACT: Five sites in the United States linked population-based healthcare data and vital records to establish surveillance network for identifying the factors which influence congenital heart disease (CHD) outcomes. Survivors of CHD frequently develop heart failure across the lifespan. Over 1 in 50 adolescent and 1 in 8 adult survivors of CHD have heart failure which is associated with increased mortality compared to CHD survivors without heart failure. Heart failure development is associated with potentially modifiable cardiovascular risk factors such as hypertension, coronary artery disease, and diabetes. Controlling modifiable cardiovascular risk factors may serve to lower the risk of heart failure and mortality in survivors of congenital heart disease of all ages.

De Novo Brain Vascular Malformations in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND: Approximately 10% of people with hereditary hemorrhagic telangiectasia (HHT) have brain vascular malformations (VMs). Few reports describe de novo brain VM formation. International HHT Guidelines recommend initial brain VM screening upon HHT diagnosis in children but do not address rescreening. We aimed to confirm whether brain VMs can form de novo in patients with HHT. METHODS: The Brain Vascular Malformation Consortium HHT project is a 17-center longitudinal study enrolling patients since 2010. We analyzed the database for de novo VMs defined as those detected (1) on follow-up neuroimaging in a patient without previous brain VMs or (2) in a location distinct from previously identified brain VMs and reported those in whom a de novo VM could be confirmed on central neuroimaging review. RESULTS: Of 1909 patients enrolled, 409 (21%) had brain VMs. Seven patients were recorded as having de novo brain VMs, and imaging was available for central review in four. We confirmed that three (0.7% of individuals with brain VMs) had de novo brain VMs (two capillary malformations, one brain arteriovenous malformation) with intervals of six, nine, and 13 years from initial imaging. Two with de novo brain VMs were <18 years. The fourth patient, a child, did not have a de novo brain VM but had a radiologically confirmed increase in size of an existing brain arteriovenous malformation. CONCLUSIONS: Brain VMs can, albeit rarely, form de novo in patients with HHT. Given the potential risk of hemorrhage from brain VMs, regular rescreening in patients with HHT may be warranted.

Helix-fixed leadless pacemaker implantation through a valve-in-valve tricuspid prosthesis via the femoral approach.

Leadless pacemakers offer the opportunity to avoid transvenous hardware among patients with tricuspid valve prostheses. We present the first case of a helix-based fixation leadless pacemaker implanted through valve-in-valve tricuspid prostheses in a 43-year-old female with extensive prior cardiac history. At the time of presentation, epicardial pacing was no longer a viable option in the setting of pacemaker dependence. Placement of a helix-fixed, leadless right ventricular pacemaker was performed as a bridge to dual-chamber leadless pacing. This was safely and effectively performed and highlighted favorable procedural characteristics that included RV cavity dimensions and prosthesis type.

Brain AVM compactness score in children with hereditary hemorrhagic telangiectasia.

OBJECTIVE: The brain arteriovenous malformation (BAVM) nidus compactness score (CS), determined on angiography, predicts BAVM recurrence after surgical resection among children with sporadic BAVMs. We measured the angiographic CS for BAVMs among children with hereditary hemorrhagic telangiectasia (HHT) to determine CS characteristics in this population. METHODS: A pediatric interventional neuroradiologist reviewed angiograms to determine the CS of BAVMs in children with HHT recruited to the BVMC. CS is based on overall nidus and perinidal anomalous vessel compactness. CS categories included 1 = diffuse nidus, 2 = intermediate nidus, and 3 = compact nidus. RESULTS: Forty-eight of 78 children (61.5%) with HHT and brain vascular malformations had a conventional angiogram; 47 (97.9%) angiograms were available. Fifty-four BAVMs were identified in 40 of these 47 children (85.1%). Of 54 BAVMs in children with HHT, CS was 1 in 7 (13%), 2 in 29 (53.7%), and 3 in 18 BAVMs (33.3%) compared with CS of 1 in six (26.1%), 2 in 15 (65.2%), and 3 in 2 BAVMs (8.7%) among 23 previously reported children with sporadic BAVMs, p = 0.045 (Fisher's exact). Seven children with HHT had intracranial hemorrhage: 4 had CS = 3, 1 had CS = 2, and 2 had CS = 1. CONCLUSIONS: A range of CSs exists across HHT BAVMs, suggesting it may be an angiographic measure of interest for future studies of BAVM recurrence and hemorrhage risk. Children with HHT may have more compact niduses compared to children with sporadic BAVMs. Additional research should determine whether CS affects hemorrhage risk or post-surgical recurrence risk in HHT-associated BAVMs, which could be used to direct BAVM treatment.

Cardiac magnetic resonance predictors for successful primary biventricular repair of unbalanced complete common atrioventricular canal.

BACKGROUND: Patients with unbalanced common atrioventricular canal can be difficult to manage. Surgical planning often depends on pre-operative echocardiographic measurements. We aimed to determine the added utility of cardiac MRI in predicting successful biventricular repair in common atrioventricular canal. METHODS: We conducted a retrospective cohort study of children with common atrioventricular canal who underwent MRI prior to repair. Associations between MRI and echocardiographic measures and surgical outcome were tested using logistic regression, and models were compared using area under the receiver operator characteristic curve. RESULTS: We included 28 patients (median age at MRI: 5.2 months). The optimal MRI model included the novel end-diastolic volume index (using the ratio of left ventricular end-diastolic volume to total end-diastolic volume) and the left ventricle-right ventricle angle in diastole (area under the curve 0.83, p = 0.041). End-diastolic volume index ≤ 0.18 and left ventricle-right ventricle angle in diastole ≤ 72° yield a sensitivity of 83% and specificity of 81% for successful biventricular repair. The optimal multimodality model included the end-diastolic volume index and the echocardiographic atrioventricular valve index with an area under the curve of 0.87 (p = 0.026). CONCLUSIONS: Cardiac MRI can successfully predict successful biventricular repair in patients with unbalanced common atrioventricular canal utilising the end-diastolic volume index alone or in combination with the MRI left ventricle-right ventricle angle in diastole or the echocardiographic atrioventricular valve index. A prospective cardiac MRI study is warranted to better define the multimodality characteristic predictive of successful biventricular surgery.

Reply to Eker et al. Comment on "Kilian et al. Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT. J. Clin. Med. 2023, 12, 2704".

We are grateful to Eker et al. for their thoughtful analysis and response to our publication titled Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT [...].

Nonsense Variant PRDM16-Q187X Causes Impaired Myocardial Development and TGF-ß Signaling Resulting in Noncompaction Cardiomyopathy in Humans and Mice.

BACKGROUND: PRDM16 plays a role in myocardial development through TGF-ß (transforming growth factor-beta) signaling. Recent evidence suggests that loss of PRDM16 expression is associated with cardiomyopathy development in mice, although its role in human cardiomyopathy development is unclear. This study aims to determine the impact of PRDM16 loss-of-function variants on cardiomyopathy in humans. METHODS: Individuals with PRDM16 variants were identified and consented. Induced pluripotent stem cell-derived cardiomyocytes were generated from a proband hosting a Q187X nonsense variant as an in vitro model and underwent proliferative and transcriptional analyses. CRISPR (clustered regularly interspaced short palindromic repeats)-mediated knock-in mouse model hosting the Prdm16Q187X allele was generated and subjected to ECG, histological, and transcriptional analysis. RESULTS: We report 2 probands with loss-of-function PRDM16 variants and pediatric left ventricular noncompaction cardiomyopathy. One proband hosts a PRDM16-Q187X variant with left ventricular noncompaction cardiomyopathy and demonstrated infant-onset heart failure, which was selected for further study. Induced pluripotent stem cell-derived cardiomyocytes prepared from the PRDM16-Q187X proband demonstrated a statistically significant impairment in myocyte proliferation and increased apoptosis associated with transcriptional dysregulation of genes implicated in cardiac maturation, including TGF-ß-associated transcripts. Homozygous Prdm16Q187X/Q187X mice demonstrated an underdeveloped compact myocardium and were embryonically lethal. Heterozygous Prdm16Q187X/WT mice demonstrated significantly smaller ventricular dimensions, heightened fibrosis, and age-dependent loss of TGF-ß expression. Mechanistic studies were undertaken in H9c2 cardiomyoblasts to show that PRDM16 binds TGFB3 promoter and represses its transcription. CONCLUSIONS: Novel loss-of-function PRDM16 variant impairs myocardial development resulting in noncompaction cardiomyopathy in humans and mice associated with altered TGF-ß signaling.

Cerebral Blood Flow, Brain Injury, and Aortic-Pulmonary Collateral Flow After the Fontan Operation.

Patients with a single ventricle develop aortopulmonary collaterals (APCs) whose flow has been shown to be inversely proportional to cerebral blood flow (CBF) in a previous cross-sectional study. Longitudinal CBF and APC flow in patients with Fontan physiology adjusting for brain injury (BI) has never been reported. Decreased CBF and BI may adversely impact neurodevelopment. A prospective longitudinal cohort of 27 patients with Fontan physiology (aged 10 ± 1.9 years, 74% male) underwent cardiac and brain magnetic resonance imaging 3 to 9 months and 6.0 ± 1.86 years after Fontan operation to measure the CBF and APC flow and to reassess the BI (focal BI, generalized insult, and hemorrhage). CBF was measured using jugular venous flow and APC flow was measured by the difference between aortic flow and caval return. Multivariate modeling was used to assess the relation between the change in APC flow and BI. A strong inverse relation was found between CBF/aortic flow change and APC flow/aortic flow and APC flow/body surface area change (R2 = 0.70 and 0.72 respectively, p <0.02). Overall, the CBF decreased by 9 ± 11% and the APC flow decreased by 0.73 ± 0.67 l/min/m2. The evolution of CBF and APC flow were significantly and inversely related when adjusting for time since Fontan operation, gender, and BI on the multivariate modeling. Every unit increase in APC flow change was associated with an 8% decrease in CBF change. In conclusion, CBF and APC flow change are inversely related across serial imaging, adjusting for time from Fontan operation, gender, and BI. CBF and APC aortic flow decrease over a 6-year period. This may adversely impact neurodevelopment. Because APCs can be embolized, this may be a modifiable risk factor. Clinical trials numbers: NCT02135081 and NCT02919956.

Cardiac Magnetic Resonance Imaging to Determine Single Ventricle Function in a Pediatric Population is Feasible in a Large Trial Setting: Experience from the Single Ventricle Reconstruction Trial Longitudinal Follow up.

The Single Ventricle Reconstruction (SVR) Trial was a randomized prospective trial designed to determine survival advantage of the modified Blalock-Taussig-Thomas shunt (BTTS) vs the right ventricle to pulmonary artery conduit (RVPAS) for patients with hypoplastic left heart syndrome. The primary aim of the long-term follow-up (SVRIII) was to determine the impact of shunt type on RV function. In this work, we describe the use of CMR in a large cohort follow up from the SVR Trial as a focused study of single ventricle function. The SVRIII protocol included short axis steady-state free precession imaging to assess single ventricle systolic function and flow quantification. There were 313 eligible SVRIII participants and 237 enrolled, ages ranging from 10 to 12.5 years. 177/237 (75%) participants underwent CMR. The most common reasons for not undergoing CMR exam were requirement for anesthesia (n = 14) or ICD/pacemaker (n = 11). A total of 168/177 (94%) CMR studies were diagnostic for RVEF. Median exam time was 54 [IQR 40-74] minutes, cine function exam time 20 [IQR 14-27] minutes, and flow quantification time 18 [IQR 12-25] minutes. There were 69/177 (39%) studies noted to have intra-thoracic artifacts, most common being susceptibility artifact from intra-thoracic metal. Not all artifacts resulted in non-diagnostic exams. These data describe the use and limitations of CMR for the assessment of cardiac function in a prospective trial setting in a grade-school-aged pediatric population with congenital heart disease. Many of the limitations are expected to decrease with the continued advancement of CMR technology.

Frequency of epistaxis and telangiectasia in patients with hereditary hemorrhagic telangiectasia (HHT) in comparison with the general population: Curaçao diagnostic criteria revisited.

PURPOSE: The Curaçao criteria are well-established diagnostic criteria for hereditary hemorrhagic telangiectasia (HHT), but they lack details regarding a predictive presentation of epistaxis and telangiectasias. This study collects and compares data in HHT and population cohorts to inform the application of these criteria. METHODS: In-person interviews regarding epistaxis and targeted examination for telangiectases in a general population cohort (n = 204) and an HHT cohort (n = 432) were conducted. RESULTS: Frequency of epistaxis, rather than intensity or duration, was the best discriminator of HHT. A cutoff of ≥4 nosebleeds per year alone yielded a diagnostic sensitivity of 97%, and specificity of 84%. The mean number of telangiectases at the sites investigated was 0.4 in the general population cohort and 26.5 in the HHT cohort. The most distinctive sites for telangiectases in HHT were lips and palmar fingers, whereas telangiectases of the face and dorsum of the hand were comparable in both cohorts. CONCLUSION: We propose that the Curaçao criteria be modified to include the following cutoffs: (1) epistaxis frequency of ≥4 nosebleeds per year and (2) telangiectasia count of at least 2 in characteristic locations (palmar aspect of fingers, lips, and oral cavity), and that cutaneous telangiectases at other sites not be considered relevant for diagnostic purposes.

Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease characterized by the development of vascular malformations (VMs) in organs such as the brain and lungs, as well as telangiectases on mucosal surfaces. Prophylactic treatment of organ VMs may prevent potential complications, such as hemorrhage. However, brain VM treatment-surgical resection, embolization, and/or radiosurgery-is not recommended for all patients due to the associated risks. Given the scarcity of data regarding HHT-related brain VM presentation and treatment trends in pediatric patients, we aim to describe the clinical presentations and the patterns of treatment of HHT-related brain VMs in a pediatric cohort, and compare pediatric trends to those of adults. Demographic and clinical data were analyzed in 114 pediatric patients with HHT-related brain VMs and compared with a cohort of 253 adult patients enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. Our data demonstrated that a higher proportion of pediatric patients with HHT-related brain VMs were symptomatic at presentation (p = 0.004). Moreover, a higher proportion of pediatric patients presented with intracranial hemorrhage (p < 0.001) and seizure (p = 0.002) compared to adult patients. Surgical resection was the most common brain VM treatment modality in both children and adults. We conclude that pediatric patients may be more likely to present with symptoms and complications from brain VMs, supporting the case for screening for brain VMs in children with HHT.

Patients with Post-COVID-19 Vaccination Myocarditis Have More Favorable Strain in Cardiac Magnetic Resonance Than Those With Viral Myocarditis.

There have been reports of myocarditis following vaccination against COVID-19. We sought to describe cardiac magnetic resonance (CMR) findings among pediatric patients. Retrospective review at a large academic center of patients clinically diagnosed with post-vaccine myocarditis (PVM) undergoing CMR. Data collected included parametric mapping, ventricular function, and degree of late gadolinium enhancement (LGE). Post-processing strain analysis was performed using feature tracking. Strain values, T1/T2 values, and ventricular function were compared to age- and gender-matched controls with viral myocarditis using a Wilcoxon Signed Rank test. Among 12 patients with presumed PVM, 11 were male and 11 presented after the second vaccination dose, typically within 4 days. All presented with chest pain and elevated troponin. 10 met MRI criteria for acute myocarditis. All had LGE typically seen in the lateral and inferior walls; only five had prolonged T1 values. 10 met criteria for edema based on skeletal muscle to myocardium signal intensity ratio and only 5 had prolonged T2 mapping values. Patients with PVM had greater short-axis global circumferential and radial strain, right ventricle function, and cardiac output when compared to those with viral myocarditis. Patients with PVM have greater short-axis global circumferential and radial strains compared to those with viral myocarditis. LGE was universal in our cohort. Signal intensity ratios between skeletal muscle and myocardium may be more sensitive in identifying edema than T2 mapping. Overall, the impact on myocardial strain by CMR is less significant in PVM compared to more classic viral myocarditis.

Longitudinal Trends of Vascular Flow and Growth in Patients Undergoing Fontan Operation.

BACKGROUND: Single ventricle (SV) patients undergo multiple surgeries with subsequent changes in anatomy and hemodynamics. There are little cardiac magnetic resonance (CMR) data on serial changes in these patients. This study aimed to assess longitudinal changes of SV anatomy and hemodynamics in a large cohort. METHODS: Anatomy and flow in SV patients with serial CMRs performed between 2008 and 2019 at a single institution were retrospectively reviewed. Mixed-effects linear regression was used to estimate changes over time at 3 to 9 months, 1 to 5 years, and >5 years after Fontan. RESULTS: A total of 119 patients were included (51% with hypoplastic left heart syndrome; 77% underwent extracardiac Fontan). A total of 88 patients had 3 serial CMRs. Indexed right superior vena cava, inferior vena cava, neoaortic valve, and descending aorta area decreased over time (beta = -0.19, -0.44, and -0.23, respectively; P < .01), as did indexed right superior vena cava, neoaorta and native aorta, and descending aorta flow (beta = -0.49, -0.53, and -0.59, respectively; P < .0001). Inferior vena cava flow and its contribution to total caval flow increased (beta = 0.33; P < .0001). Indexed right and left pulmonary artery flow did not change; however, indexed left pulmonary artery area decreased (beta = -0.16; P = .0014) with time. Systemic-to-pulmonary collateral flow remained unchanged before and early after Fontan (beta = -0.54; P = .42) but decreased with time from Fontan (beta = -0.22; P < .0001). CONCLUSIONS: In this cohort of longitudinally followed SV patients, there are significant trends in vascular size and flow over time from Fontan. These findings can be used as a framework to interpret serial CMR data in the SV and noninvasively identify deviations from expected patterns before the development of clinical symptoms.

Peak Work Rate Increases With Lower Extremity-Focused Exercise Training in Adolescents With Fontan Circulation.

Background Skeletal muscle deficits are associated with worse exercise performance in the Fontan circulation and may be improved by exercise training. We aimed to assess the change in leg lean mass (a marker of skeletal muscle), exercise performance, and functional health status after a lower extremity-focused exercise intervention in adolescents with Fontan circulation. Methods and Results Densitometry for measurement of leg lean mass, cardiopulmonary exercise test, exercise cardiac magnetic resonance, peripheral vascular testing, physical activity questionnaire, and quality of life assessment were performed at baseline and after a 24-week, hybrid center- and home-based training program. Leg lean mass Z-scores were generated, and exercise parameters were expressed as percentage expected based on reference data. The effect of training was assessed by paired t-tests and simple linear regression. Twenty participants (15.6±1.7 years, 50% male) demonstrated low baseline leg lean mass Z-scores with no significant improvement with training (-1.38±1.02 pre versus -1.31±1.06 post, P=0.33). Maximum and percent predicted work increased from 121.9±29.8 (0.66±0.12) to 131.3±35.1 (0.70±0.15) watts (P=0.02). Peak respiratory exchange ratio increased (1.19±0.02 versus 1.25±0.01, P=0.02) but percent predicted oxygen consumption was unchanged, suggesting higher anaerobic activity after training. Physical activity questionnaire score positively associated with peak work at baseline (ß=18.13 [95% CI, 0.83-35.44], R2=0.21; P=0.04) but physical activity questionnaire, quality of life scores, exercise cardiac magnetic resonance performance, and peripheral vascular function were unchanged with training. Conclusions Peak work rate and anaerobic activity increased with lower extremity-focused training in adolescents with Fontan circulation. Larger studies should test the impact of these changes on functional status and quality of life.

Skeletal muscle deficits are associated with worse exercise performance in pediatric pulmonary hypertension.

Background: Skeletal muscle deficits are associated with worse exercise performance in adults with pulmonary hypertension (PH) but the impact is poorly understood in pediatric PH. Objective: To study muscle deficits, physical inactivity, and performance on cardiopulmonary exercise test (CPET) and exercise cardiac magnetic resonance (eCMR) in pediatric PH. Methods: Youth 8-18 years participated in a prospective, cross-sectional study including densitometry (DXA) for measurement of leg lean mass Z-score (LLMZ), handheld dynamometer with generation of dominant and non-dominant handgrip Z-scores, Physical Activity Questionnaire (PAQ), CPET, and optional eCMR. CPET parameters were expressed relative to published reference values. CMR protocol included ventricular volumes and indexed systemic flow at rest and just after supine ergometer exercise. Relationships between LLMZ, PAQ score, and exercise performance were assessed by Pearson correlation and multiple linear regression. Results: There were 25 participants (13.7 ± 2.8 years, 56% female, 64% PH Group 1, 60% functional class I); 12 (48%) performed both CPET and eCMR. Mean LLMZ (-0.96 ± 1.14) was associated with PAQ score (r = 50, p = 0.01) and with peak oxygen consumption (VO2) (r = 0.74, p = < 0.001), VO2 at anaerobic threshold (r = 0.65, p < 0.001), and peak work rate (r = 0.64, p < 0.01). Higher handgrip Z-scores were associated with better CPET and eCMR performance. On regression analysis, LLMZ and PAQ score were positively associated with peak VO2, while handgrip Z-score and PAQ score were positively associated with peak work rate. Conclusion: Muscle mass and strength are positively associated with exercise performance in pediatric PH. Future studies should determine the effect of rehabilitation programs on muscle properties and exercise performance.

Pulmonary Arteriovenous Malformations: What the Interventional Radiologist Should Know.

Pulmonary arteriovenous malformations (PAVMs) are abnormal connections between the pulmonary artery and pulmonary vein bypassing the normal capillary bed causing a right-to-left shunt. The majority (80-90%) of PAVMs are associated with hereditary hemorrhagic telangiectasia (HHT). PAVMs may be asymptomatic or present with symptoms of hypoxia, shortness of breath, migraines, sequelae of paradoxical embolization, or rupture. Transcatheter embolization has become the standard of care. This article will review the clinical presentation, workup, genetics, imaging findings, embolization, complications, and follow-up for patients with PAVMs.

Free-running cardiac and respiratory motion-resolved 5D whole-heart coronary cardiovascular magnetic resonance angiography in pediatric cardiac patients using ferumoxytol.

BACKGROUND: Coronary cardiovascular magnetic resonance angiography (CCMRA) of congenital heart disease (CHD) in pediatric patients requires accurate planning, adequate sequence parameter adjustments, lengthy scanning sessions, and significant involvement from highly trained personnel. Anesthesia and intubation are commonplace to minimize movements and control respiration in younger subjects. To address the above concerns and provide a single-click imaging solution, we applied our free-running framework for fully self-gated (SG) free-breathing 5D whole-heart CCMRA to CHD patients after ferumoxytol injection. We tested the hypothesis that spatial and motion resolution suffice to visualize coronary artery ostia in a cohort of CHD subjects, both for intubated and free-breathing acquisitions. METHODS: In 18 pediatric CHD patients, non-electrocardiogram (ECG) triggered 5D free-running gradient echo CCMRA with whole-heart 1 mm3 isotropic spatial resolution was performed in seven minutes on a 1.5T CMR scanner. Eleven patients were anesthetized and intubated, while seven were breathing freely without anesthesia. All patients were slowly injected with ferumoxytol (4 mg/kg) over 15 minutes. Cardiac and respiratory motion-resolved 5D images were reconstructed with a fully SG approach. To evaluate the performance of motion resolution, visibility of coronary artery origins was assessed. Intubated and free-breathing patient sub-groups were compared for image quality using coronary artery length and conspicuity as well as lung-liver interface sharpness. RESULTS: Data collection using the free-running framework was successful in all patients in less than 8 min; scan planning was very simple without the need for parameter adjustments, while no ECG lead placement and triggering was required. From the resulting SG 5D motion-resolved reconstructed images, coronary artery origins could be retrospectively extracted in 90% of the cases. These general findings applied to both intubated and free-breathing pediatric patients (no difference in terms of lung-liver interface sharpness), while image quality and coronary conspicuity between both cohorts was very similar. CONCLUSIONS: A simple-to-use push-button framework for 5D whole-heart CCMRA was successfully employed in pediatric CHD patients with ferumoxytol injection. This approach, working without any external gating and for a wide range of heart rates and body sizes provided excellent definition of cardiac anatomy for both intubated and free-breathing patients.

Determination of Contrast Timing by Time-Resolved Magnetic Resonance Angiography in Patients With Bidirectional Glenn and Hemi-Fontan Anastomoses.

PURPOSE: Children with single-ventricle congenital heart disease undergo a series of operations to maintain their pulmonary circulation including bidirectional Glenn (BDG) or hemi-Fontan in the second stage to create a superior cavopulmonary anastomosis. We aimed to optimize cardiovascular angiography protocols by determining optimal contrast timing of pulmonary and systemic circulation on magnetic resonance angiography (MRA) performed with the technique of time-resolved imaging with interleaved stochastic trajectories (TWIST). METHODS AND MATERIALS: Cardiac TWIST MRA with lower extremity (LE) contrast injection was analyzed in 92 consecutive patients with a BDG or hemi-Fontan anastomosis. Contrast arrival time to inferior vena cava was set to zero to determine the relative time-to-peak (TTP) of the target vessels. Time-to-peak of each vessel was compared by age (<2 or ≥2 y), ejection fraction (<54% or ≥54%), the median values of heart rate (<111 or ≥111 beats per minute), body surface area (BSA, <0.59 or ≥0.59), cardiac index (<6.04 or ≥6.04), and indexed ascending aorta flow (AscAo_i, <5.3 or ≥5.3). The TTP of the vessels was also correlated with the volumetric parameters. RESULTS: The mean age of 92 patients (32 female, 60 male) was 3.1 years (0.7-5.6 years). With LE injection, the first peak was depicted in AscAo. Time-to-peak of the pulmonary arteries was approximately 9 seconds later than AscAo. The TTP difference between pulmonary arteries and AscAo was shorter in high heart rate group (8.3 vs 10 seconds, P < 0.001). The TTP difference between AscAo and the mean of pulmonary arteries was significantly shorter in high cardiac index group (8.4 vs 9.9 seconds, P < 0.01) and high AscAo_i group (8.7 vs 9.7 seconds, P = 0.03). The TTP differences were not significant by age, ejection fraction, and BSA. Cardiac index and AscAo_i were negatively correlated with all TTPs except AscAo. The ejection fraction, stroke volume, and atrioventricular regurgitation fraction did not correlate with the TTP. CONCLUSIONS: In patients with BDG or hemi-Fontan anastomosis, TTP of the pulmonary arteries on TWIST MRA via LE intravenous injection is approximately 9 seconds later than AscAo, approximately 8 and 10 seconds later in high and low heart rate groups, respectively. Cardiac index and AscAo_i have less effect on the TTP than the heart rate. There was no TTP difference of the pulmonary arteries by age, BSA, and ejection fraction and no correlation with ejection fraction, stroke volume, and atrioventricular regurgitation fraction. These data can be used to guide timing of pulmonary arterial enhancement of single-ventricle patients after BDG or hemi-Fontan anastomosis.

Clinical 3D modeling to guide pediatric cardiothoracic surgery and intervention using 3D printed anatomic models, computer aided design and virtual reality.

BACKGROUND: Surgical and catheter-based interventions for congenital heart disease require precise understanding of complex anatomy. The use of three-dimensional (3D) printing and virtual reality to enhance visuospatial understanding has been well documented, but integration of these methods into routine clinical practice has not been well described. We review the growth and development of a clinical 3D modeling service to inform procedural planning within a high-volume pediatric heart center. METHODS: Clinical 3D modeling was performed using cardiac magnetic resonance (CMR) or computed tomography (CT) derived data. Image segmentation and post-processing was performed using FDA-approved software. Patient-specific anatomy was visualized using 3D printed models, digital flat screen models and virtual reality. Surgical repair options were digitally designed using proprietary and open-source computer aided design (CAD) based modeling tools. RESULTS: From 2018 to 2020 there were 112 individual 3D modeling cases performed, 16 for educational purposes and 96 clinically utilized for procedural planning. Over the 3-year period, demand for clinical modeling tripled and in 2020, 3D modeling was requested in more than one-quarter of STAT category 3, 4 and 5 cases. The most common indications for modeling were complex biventricular repair (n = 30, 31%) and repair of multiple ventricular septal defects (VSD) (n = 11, 12%). CONCLUSIONS: Using a multidisciplinary approach, clinical application of 3D modeling can be seamlessly integrated into pre-procedural care for patients with congenital heart disease. Rapid expansion and increased demand for utilization of these tools within a high-volume center demonstrate the high value conferred on these techniques by surgeons and interventionalists alike.

Choroidal melanoma with synchronous Fuchs' adenoma and novel ATRX mutation.

BACKGROUND: To report a case of Fuchs' adenoma occurring in an eye with a large choroidal melanoma. We have reviewed the literature to describe the clinical presentation, ultrasound characteristics and pathological features of these entities. CASE PRESENTATION: A 69-year-old Caucasian man presented with vision loss from a large choroidal melanoma. Enucleation showed an incidental Fuchs' adenoma in the same eye. Whole-exome sequence analysis was also performed on the patient's blood and melanoma, which showed a rarely-reported ATRX mutation. CONCLUSIONS: Fuchs' adenoma is an under-diagnosed benign age-related hyperplasia of the non-pigmented ciliary epithelium (NPCE). Given its location and characteristics, it can be mistaken for choroidal melanoma and clinicians are reminded how to differentiate between these pathologies and that they may co-exist.