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指定難病 — No.215

ファロー四徴症

検索語 Tetralogy of Fallot ・ 最終更新 2026-09-17 15:27 ・ 最新に更新

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指定 No.215
Src PubMed · CT.gov · jRCT

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( 01 )EVIDENCE / PUBMED · 5件

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観察研究
MK-01 · PMID 42744273

Velocity Vector Analysis for Slowly Conducting Anatomical Isthmuses in Patients with Tetralogy of Fallot

Abstract / 原文

BACKGROUND: Slowly conducting anatomical isthmuses (SCAI) represent the main substrate for ventricular arrhythmias (VAs) in tetralogy of Fallot (TOF). However, the optimal conduction velocity (CV) threshold and the best approach for measurements remain to be determined. OBJECTIVE: This study aimed at evaluating a new method for CV analysis. METHODS: This single-center retrospective study included consecutive patients with TOF undergoing right ventricular electroanatomic activation mapping. CV across anatomical isthmus 3 was assessed using both automated Local Activation Time Velocity Vector (LVV) analysis and conventional manual measurements. The primary outcome was inducibility of sustained monomorphic ventricular tachycardia (SMVT). RESULTS: A total of 44 patients were included (mean age 44.6±13.8 years, 56.8% males). Overall, a SMVT was inducible in 23 (52.3%) patients, including 12/14 (85.7%) patients referred for catheter ablation of VT (history of clinical VT) and 11/30 (36.7%) patients referred for EPS without spontaenous VT. LVV-CV demonstrated a strong correlation with manual measurements (r = 0.81). The optimal cutoff value of LVV-CV based on the Youden index was 0.5 m/s. AUC, sensitivity, and specificity were 0.81, 0.96, and 0.71 using LVV-CV vs. 0.75, 0.57, and 0.81 using manual CV measurements, respectively. LVV analysis reduced the number of classification errors from 14 (31.8%) cases with manual CV measurement to 7 (15.9%) cases when LVV-CV was used. CONCLUSION: This novel, reproductible, and easy-to-use LVV-based approach to CV measurement for substrate evaluation in patients with TOF suggest that LVV-CV provides superior discriminative performance compared with manual CV measurements for identifying SCAIs associated with SMVT inducibility. Further studies are warranted to evaluate this approach in larger populations.

Journal
Heart rhythm(2026 Sep)
Authors
11名
Type
Journal Article
PubMedで原文を見る
観察研究
MK-02 · PMID 42739592

Clinical Course and Surgical Outcomes of Patients with Tetralogy of Fallot with Absent Pulmonary Valve Syndrome: A Single-Center Retrospective Study

Abstract / 原文

Background: Tetralogy of Fallot with absent pulmonary valve syndrome (TOF-APVS) is a rare variant of tetralogy of Fallot marked by aneurysmal pulmonary artery dilatation and variable tracheobronchial compression. The identification of clinical indicators that predict perioperative risk in this patient population remains challenging. We aimed to review the surgical outcomes and reintervention requirements of patients with TOF-APVS over a 15-year single-center experience, with particular focus on two indicators of disease severity: preoperative mechanical ventilation (MV) and computed tomography (CT)-detected airway compression. Methods: We retrospectively reviewed 27 patients with TOF-APVS who underwent surgical repair at a single center between January 2010 and January 2025. Airway compression was assessed by CT in 20 patients. The primary outcome was the need for any reintervention during follow-up. Secondary outcomes comprised early and overall mortality and postoperative duration of intubation, ICU stay, and hospital stay. Subgroup comparisons were performed using the Fisher exact test and the Mann-Whitney U test. Results: The median age at surgery was 8 months (IQR, 4.5-16). Preoperative MV was required in 5 patients (18.5%), and CT revealed airway compression in 13 of 20 patients (65.0%). Early postoperative mortality was 7.4%, and overall mortality during follow-up was 18.5%. At least one reintervention was required in 9 patients (33.3%). Preoperative MV was significantly associated with early mortality (40.0% vs. 0%; p = 0.028) and with prolonged ICU stay (median 15 vs. 4 days; p = 0.008). CT-detected airway compression was not significantly associated with either mortality or reintervention. Conclusions: In this 15-year single-center experience with 27 patients, preoperative mechanical ventilation was associated with markedly higher early postoperative mortality and prolonged ICU stay, and may thus serve as a practical clinical indicator of disease severity in TOF-APVS. CT-detected airway compression was a frequent and often severe finding, but its association with early mortality and reintervention could not be statistically confirmed, likely reflecting the selective use of CT and small subgroup size. These findings support the integration of preoperative ventilation status into perioperative risk assessment and highlight the need for larger, preferably multicenter, studies with standardized airway assessment to clarify the prognostic role of anatomical airway compression.

Journal
Journal of clinical medicine(2026 Aug)
Authors
12名
Type
Journal Article
PubMedで原文を見る
観察研究
MK-03 · PMID 42739244

Confounder-Matched Deep Learning on Cardiac CT for the Diagnosis of Tetralogy of Fallot: A Proof of Concept

Abstract / 原文

Background/Objectives: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect, and cardiac computed tomography (CT) is increasingly central to its anatomical and pre-procedural assessment. Artificial-intelligence research in TOF is dominated by MRI; deep learning on cardiac CT in congenital heart disease exists but addresses multi-class diagnosis and segmentation, and the one binary TOF-versus-control CT study used slice-level validation without confounder control, and, to our knowledge, no CT study reports controlling the confounding intrinsic to a TOF-versus-control comparison. This confounding is structural: TOF is imaged predominantly in infancy, so a naive classifier can learn age, body size, and acquisition protocol rather than pathology. We develop and internally evaluate a confounder-matched, anatomy-guided deep-learning pipeline for TOF on cardiac CT. Methods: Contrast-enhanced cardiac CT from a single scanner was de-identified and restricted to one reconstruction (FC15 kernel, 0.5 mm), then matched 1:1 on age and sex, yielding 42 TOF and 42 controls (n = 84); controls were children imaged for suspected but excluded cardiovascular disease, so scan indication, unlike age and sex, was not matched. Standardized volumes were decomposed into four fixed sub-volumes positioned to approximate the components of the diagnostic tetrad: malalignment ventricular septal defect (VSD), overriding aorta, right-ventricular outflow tract (RVOT), and right-ventricular hypertrophy (RVH). Whether each sub-volume contains its named target was audited against independent physician region-of-interest annotations. Per region, a 2.5D transfer-learning classifier (ImageNet ResNet18) and a 3D CNN (DenseNet121) were trained with leak-free patient-level five-fold cross-validation and the branches fused. Optimism was assessed by repeated cross-validation and, for model selection, by nested cross-validation with the component subset and operating point chosen inside an inner loop. Discrimination was reported with bootstrap 95% confidence intervals (CIs); AUROCs were compared by DeLong test, with Benjamini-Hochberg correction applied to a seven-member family (the four within-component comparisons, two hybrid-versus-VSD contrasts, and hybrid versus whole-heart) and other comparisons reported uncorrected. Results: Matching removed the age difference (median 0.33 years, IQR 0.17-0.92 vs. 0.33, IQR 0.27-0.73; p = 0.86) with balanced sex (p = 1.00). The pre-specified four-component hybrid reached AUROC 0.829 (95% CI 0.74-0.91); the VSD region alone reached 0.828 (0.74-0.91), so the tetrad decomposition did not improve accuracy, and the containment audit shows it does not deliver the intended anatomical interpretability either. The 2.5D model exceeded the 3D CNN for every component (0.769-0.828 vs. 0.573-0.656; raw DeLong p = 0.007-0.037, Benjamini-Hochberg q up to 0.065 under a seven-member family, the weakest comparison (RVH) not surviving correction). Repeated cross-validation gave 0.811 ± 0.026 and nested cross-validation 0.787 ± 0.029; a stronger backbone with multi-phase data, handcrafted radiomics, and a large CT foundation model did not significantly improve on the matched pipeline. Grad-CAM maps were sensitive to both model weights and labels and superior to a centred-blob null in all eight comparisons and significantly so in seven, but not consistently superior to a resolution-matched random attribution, so no localization claim is made. Calibration was imperfect (slope 0.67) and recalibration gave no net gain; at an in-sample Youden threshold sensitivity was 0.93 and specificity 0.64. Occlusion sensitivity on the whole-heart baseline model showed it relies on the physician-marked septal, aortic and right-ventricular sites 1.8-4.1 times more than distance-matched surrounding tissue, while gross morphometry alone reached 0.651-0.663. Two of the four sub-volumes did not contain their target: the RVOT prior contained the physician annotation in 48.1% of cases and, because the model samples only the central band, excluded it in 99.4%; the RVH box was offset toward the midline, containing the marked target in 43.4% of annotations. Repositioning the priors, leak-free and derived from controls only, did not change discrimination (all p ≥ 0.10), and boxes placed at random positions inside the standardized heart reached 0.765 on average against 0.796 for the published priors, a difference this cohort cannot resolve. Conclusions: As a proof of concept, confounder-matched deep learning can recognize TOF on cardiac CT. Increasing model capacity did not significantly improve on the matched pipeline; the separate contribution of matching itself was not isolated against an unmatched comparator. Given the small, single-centre sample and the absence of external validation, these findings are hypothesis-generating and require external, multi-centre confirmation before any clinical use.

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Journal
Diagnostics (Basel, Switzerland)(2026 Sep)
Authors
3名
Type
Journal Article
PubMedで原文を見る
観察研究
MK-04 · PMID 42734858

Repaired tetralogy of Fallot across adulthood: from right ventricular remodelling to targeted intervention

Abstract / 原文

Adults with repaired tetralogy of Fallot (rTOF) constitute a rapidly growing adult congenital heart disease population with excellent early survival but substantial late morbidity. Chronic pulmonary regurgitation and/or residual right ventricular outflow tract obstruction drive progressive right ventricular dilatation, dysfunction, dyssynchrony, and myocardial fibrosis, predisposing to heart failure and ventricular arrhythmias. This review summarizes contemporary concepts in the surveillance and management of adults with rTOF, focusing on multimodality imaging, pulmonary valve replacement (PVR), arrhythmia risk stratification, aortopathy, and emerging pharmacological strategies. Echocardiography remains the first-line modality for assessing residual lesions and aortic dimensions, while cardiac magnetic resonance is central for quantifying right ventricular volumes, regurgitant fraction, and fibrosis; computed tomography complements anatomical evaluation when magnetic resonance imaging is not feasible. PVR, increasingly performed using transcatheter techniques, is a cornerstone intervention, with guideline-based decisions integrating symptoms, right ventricular volumes, functional testing, and ventricular function. Arrhythmia management combines risk stratification, catheter ablation, implantable cardioverter-defibrillators in selected patients, and individualized medical and pacing therapies. Aortic root dilatation is common, but dissection is rare; surveillance and surgery are guided by diameter thresholds and growth rate. Evidence for routine renin-angiotensin-aldosterone inhibition to improve right ventricular function remains limited, although selected agents and exercise-based interventions are under investigation. Infective endocarditis risk differs by pulmonary valve replacement modality and valve type, being generally higher after transcatheter than surgical replacement, and warrants individualized antiplatelet therapy and vigilant surveillance after implantation. Lifelong multidisciplinary follow-up in specialized adult congenital heart disease centers is essential to optimize reintervention timing and reduce arrhythmic and aortic complications in adults with rTOF. Graphical abstract summarises the overall pathophysiology and long-term management of repaired tetralogy of Fallot.

Journal
Heart failure reviews(2026 Sep)
Authors
6名
Type
Journal Article, Review
PubMedで原文を見る
症例報告
MK-05 · PMID 42733126

Expansion of the Clinical and Molecular Spectrum of LINS1-Associated Disease

Abstract / 原文

LINS1 gene plays a role in cognition and brain development. Mutations in this gene have been identified as the cause of a neurodevelopmental disorder as well as dysmorphisms, motor symptoms, behavioral problems, seizures, microcephaly, mitral valve prolapse, and Q-T prolongation. We recruited two related families with a total of four children affected by LINS1-associated neurodevelopmental disorder. All four subjects have global developmental delay. Congenital heart disease is prominent: Tetralogy of Fallot in two (one with a discontinuous left pulmonary artery), left-sided cardiac hypoplasia with bicuspid aortic valve and membranous VSD in one, and transient aortic dilation with residual mild annular dilation and a small coronary fistula in one. Hyperopia is present in three; the fourth, younger than 2 years, is not yet tested. Dysmorphic features include a long face in two, midface hypoplasia in one, and frontal bossing with prominent eyes in one. All subjects are homozygous for a canonical splice acceptor variant in LINS1 (NM_001040616.3:c.490-1G>C); parents are heterozygous carriers. We extend the phenotypic spectrum of LINS1-associated neurodevelopmental disorder to include significant structural cardiac anomalies and refractive errors. These observations support consideration of cardiac and ophthalmologic evaluation in individuals with biallelic pathogenic LINS1 variants.

Journal
American journal of medical genetics. Part A(2026 Sep)
Authors
7名
Type
Case Reports, Journal Article
PubMedで原文を見る
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