Indications for and outcomes of interstage catheter interventions following the Norwood procedure: A single-institution study.

Aims: The aim of this study was to document the incidence, types, and outcome of interstage catheter interventions following the Norwood surgical palliation. Patients and Methods: A retrospective single-center study of all patients surviving the Norwood operation was performed. All data concerning interstage catheter interventions up to the completion of the superior cavopulmonary shunt were collected. Results: Catheter interventions were performed in 62 of 94 patients (66%; 38 males). These included interventions on the aortic arch (n = 44), the branch pulmonary arteries (PAs) (n = 17), and the Sano shunt (n = 14). Multiple interventions and repeat interventions were common. The minimum aortic arch diameter (pre- versus posttreatment) increased from median 3.1 (2.3-3.3) mm to 5.1 (4.2-6.2) mm (P < 0.001). The catheter pullback gradient decreased from 40 (36-46) mmHg to 9 (5-10) mmHg (P < 0.001), and the echocardiographic gradient from 54 (45-64) mmHg to 12 (10-16) mmHg (P < 0.001). The branch PA diameters increased from 2.4 (2.1-3.0) mmHg to 4.7 (4.2-5.1) mmHg (P < 0.001). The minimum Sano shunt diameters increased from 2.0 (1.5-2.1) mm to 5.9 (5.8-6.0) mm (P < 0.001); this was associated with an improvement in systemic saturation from 63% (60%-65%) to 80% (79-82%) (P < 0.001). Unexpected interstage death at home occurred in two patients who had received no interventions. The remainder received a superior cavopulmonary shunt palliation. Conclusions: Catheter interventions were common. Systematic follow-up and a low threshold for reintervention are essential to the success of staged surgical palliation for this patient cohort.

De novo missense variants in RRAGC lead to a fatal mTORopathy of early childhood.

PURPOSE: Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) regulates cell growth in response to nutritional status. Central to the mTORC1 function is the Rag-GTPase heterodimer. One component of the Rag heterodimer is RagC (Ras-related GTP-binding protein C), which is encoded by the RRAGC gene. METHODS: Genetic testing via trio exome sequencing was applied to identify the underlying disease cause in 3 infants with dilated cardiomyopathy, hepatopathy, and brain abnormalities, including pachygyria, polymicrogyria, and septo-optic dysplasia. Studies in patient-derived skin fibroblasts and in a HEK293 cell model were performed to investigate the cellular consequences. RESULTS: We identified 3 de novo missense variants in RRAGC (NM_022157.4: c.269C>A, p.(Thr90Asn), c.353C>T, p.(Pro118Leu), and c.343T>C, p.(Trp115Arg)), which were previously reported as occurring somatically in follicular lymphoma. Studies of patient-derived fibroblasts carrying the p.(Thr90Asn) variant revealed increased cell size, as well as dysregulation of mTOR-related p70S6K (ribosomal protein S6 kinase 1) and transcription factor EB signaling. Moreover, subcellular localization of mTOR was decoupled from metabolic state. We confirmed the key findings for all RRAGC variants described in this study in a HEK293 cell model. CONCLUSION: The above results are in line with a constitutive overactivation of the mTORC1 pathway. Our study establishes de novo missense variants in RRAGC as cause of an early-onset mTORopathy with unfavorable prognosis.

Respiration Dependency of Caval Blood Flow in Patients with Fontan Circulation: Quantification Using 5D Flow MRI.

PURPOSE: To measure respiration-dependent blood flow in the total cavopulmonary connection (TCPC) of patients with Fontan circulation by using free-running, fully self-gated five-dimensional (5D) flow MRI. MATERIALS AND METHODS: From July to November 2018, 10 volunteers (six female volunteers, mean age, 25.1 years ± 4.4 [standard deviation]) and six patients with Fontan circulation (two female patients, mean age, 19.7 years ± 7.5) with a TCPC were examined by using a cardiac- and respiration-resolved three-directional and three-dimensional phase-contrast MRI sequence (hereafter, 5D flow MRI). This prospective study was conducted with approval of the local ethics committee, and written informed consent was obtained from all participants and/or their representative. 5D flow data were acquired during free breathing. Data were reconstructed into 15-20 heart phases and four respiratory phases: end-expiration, inspiration, end-inspiration, and expiration. Respiration-dependent stroke volumes (SVs) and particle traces were analyzed from the caval circulation of volunteers and patients with Fontan circulation. Statistical analysis was performed by using parametric tests and scatterplots. RESULTS: The respiration dependency of caval blood flow was evaluated in all participants and was significantly elevated in patients with Fontan circulation as compared with volunteers. In patients, SV in the inferior vena cava (IVC) showed variations of 120% between inspiration and expiration (P = .002). The flow distribution in the IVC and superior vena cava among the four respiratory phases was differentiated by 20% (range, 9%-30%) and 4% (range, 0%-13%), respectively. CONCLUSION: Hemodynamic parameters (volume flow and blood flow distribution) throughout the cardiac and respiratory cycle can be measured using a single scan, potentially providing further insights into the Fontan circulation.© RSNA, 2019Supplemental material is available for this article.