Successful Multimodal Treatment of Intracranial Growing Teratoma Syndrome with Malignant Features.

Molecular analysis of the growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

Clinical and molecular analyses of isolated central congenital hypothyroidism based on a survey conducted in Japan.

Central congenital hypothyroidism (CH) can occur as an isolated deficiency or as part of combined pituitary hormone deficiency. Unlike primary CH, central CH cannot be detected by newborn screening (NBS) using dry filter paper blood TSH levels, and early diagnosis remains challenging. In this study, the clinical and genetic backgrounds of patients with isolated central CH were determined through a questionnaire-based survey among members of the Japanese Society for Pediatric Endocrinology. The known causes of isolated central CH were studied in 14 patients, including six with previously reported patient data. The results revealed IGSF1 and TBL1X pathogenic variants in nine and one patient, respectively. All six patients with low free thyroxine (FT4) levels detected in NBS carried IGSF1 pathogenic variants. Five patients with isolated central CH diagnosed after 3 months of age were variant-negative, except for one female patient with a heterozygous IGSF1 variant. Two of the four variant-negative patients and a variant-positive patient were diagnosed with pituitary hypoplasia. One and two patients with IGSF1 variant had obesity and intellectual disability, respectively. Left amblyopia was identified in the patient with a TBL1X variant. The study revalidated that IGSF1 variants comprise the most frequent pathogenic variant in patients with isolated central CH in Japan. The neonatal period is the optimal time for the diagnosis of central CH, particularly IGSF1 abnormalities, and the introduction of T4 screening should be considered in the future, taking cost-effectiveness into consideration.

Reliable detection of genetic alterations in cyst fluid DNA for the diagnosis of brain tumors.

PURPOSE: Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was performed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) of cyst fluid in cystic brain tumors. METHODS: Cyst fluid was obtained from 22 patients undergoing surgery for a cystic brain tumor with confirmed genetic alterations in tumor DNA. Pathological diagnoses based on WHO 2021 classification and diagnostic alterations in the tumor DNA, such as IDH1 R132H and TERT promoter mutation for oligodendrogliomas, were detected by Sanger sequencing. The same alterations were analyzed by both droplet digital PCR (ddPCR) and Sanger sequencing in cyst fluid cfDNA. Additionally, multiplex ligation-dependent probe amplification (MLPA) assays were performed to assess 1p/19q status, presence of CDKN2A loss, PTEN loss and EGFR amplification, to assess whether differentiating between astrocytomas and oligodendrogliomas and grading is possible from cyst fluid cfDNA. RESULTS: Twenty-five genetic alterations were found in 22 tumor samples. All (100%) alterations were detected in cyst fluid cfDNA by ddPCR. Twenty of the 25 (80%) alterations were also detected by Sanger sequencing of cyst fluid cfDNA. Variant allele frequency (VAF) in cyst fluid cfDNA was comparable to that of tumor DNA (R = 0.62, Pearson's correlation). MLPA was feasible in 11 out of 17 (65%) diffuse gliomas, with close correlation of results between tumor DNA and cyst fluid cfDNA. CONCLUSION: Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diagnosing brain tumors.

Incidence and Risk Factors for Adrenal Crisis in Pediatric-onset Adrenal Insufficiency: A Prospective Study.

PURPOSE: To determine the incidence and risk factors for adrenal crisis (AC) in patients with pediatric-onset adrenal insufficiency (AI). MATERIALS AND METHODS: This multicenter, prospective cohort study conducted in Japan enrolled patients diagnosed with AI at ≤ 15 years of age. The incidence of AC was calculated as events per person-year (PY), and risk factors for AC were assessed using Poisson regression multivariable analysis. RESULTS: The study population comprised 349 patients (164 male, 185 female) with a total follow-up of 961 PY. The median age at enrollment was 14.3 years (interquartile range [IQR] 8.5-21.2 years), and the median follow-up was 2.8 years (IQR 2.2-3.3 years). Of these patients, 213 (61%) had primary AI and 136 (39%) had secondary AI. Forty-one AC events occurred in 31 patients during the study period. The calculated incidence of AC was 4.27 per 100 PY (95% confidence interval [CI] of 3.15-5.75). Poisson regression analysis identified younger age at enrollment (relative risk [RR] 0.93 [95% CI 0.89-0.97]) and increased number of infections (RR 1.17 [95% CI 1.07-1.27]) as significant risk factors. Female sex (RR 0.99 [95% CI 0.53-1.86]), primary AI (RR 0.65 [95 % CI 0.30-1.41]), or equivalent dosage of hydrocortisone per square meter of body area (RR 1.02 [95% CI 0.96-1.08]) was not a significant risk factor. CONCLUSION: A substantial proportion of patients with pediatric-onset AI experience AC. Younger age and an increased number of infections are independent risk factors for developing AC in these patients.

A Study of Maternal Patients Diagnosed with Inborn Errors of Metabolism Due to Positive Newborn Mass Screening in Their Newborns.

BACKGROUND: There are reports of mothers being diagnosed with inborn errors of metabolism (IEM) via positive newborn screening (NBS) of their newborns. Mothers with IEM are often considered to have mild cases of little pathological significance. Based in Niigata Prefecture, this study aimed to investigate mothers newly diagnosed with IEM via positive NBS in their newborns using tandem mass spectrometry, and to clarify the disease frequency and severity. METHODS: This was a single-institution, population-based, retrospective study. The subjects were mothers whose newborns had false-positive NBS, among 80,410 newborns who underwent NBS between April 2016 and May 2021. RESULT: there were 3 new mothers were diagnosed with IEM (2 with primary systemic carnitine deficiency (PCD) and 1 with 3-methylcrotonyl-CoA carboxylase deficiency) out of 5 who underwent examination among 18 false positives. The opportunity for diagnosis was low C0 and high C5-OH acylcarnitine levels in their newborn. Two novel SLC22A5 variants (c.1063T > C/c.1266A > G) were identified in patients with PCD. None of the patients had any complications at the time of diagnosis, but two patients showed improvement in fatigue and headache after taking oral carnitine. CONCLUSION: New mothers with IEM cannot be considered as mild cases and need to be treated when necessary. The two novel SLC22A5 variants further expand the variant spectrum of PCD.

Ability of Left Atrial Distensibility After Radiofrequency Catheter Ablation to Predict Recurrence of Atrial Fibrillation.

This study sought to assess the left atrial (LA) functional recovery after radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) and to evaluate the determining factor of procedural success of RFCA, using a novel preload stress echocardiography. A total of 111 patients with AF were prospectively recruited. The echocardiographic parameters were obtained during the leg-positive pressure (LPP) maneuver, both at baseline and midterm after RFCA. As an index of LA distensibility, the LA expansion index was calculated as (LAVmax - LAVmin) × 100 / LAVmin. During a median follow-up period of 14.2 months, AF recurrence was observed in 23 patients (20.7%). In LA functional parameters at baseline, only the Δ LA expansion index was significantly larger in the success group (16 ± 11% vs 4 ± 9%, p <0.05). At midterm follow-up, the Δ LA expansion index significantly increased to 32 ± 19% (p <0.05), together with structural LA reverse remodeling only in the success group. Moreover, the Δ stroke volume index during the LPP stress test significantly increased only in the success group (from 2.3 ± 1.3 ml/m2 to 3.1 ± 4.8 ml/m2, p <0.05). In a multivariate analysis, left ventricular ejection fraction (hazard ratio 0.911, p <0.05) and baseline Δ LA expansion index (hazard ratio 0.827, p <0.001) were independent predictors of AF recurrence. In conclusion, the baseline Δ LA expansion index during LPP stress is a reliable marker for predicting procedural success after RFCA. Moreover, maintenance of sinus rhythm resulted in an improvement of the preload reserve after RFCA.

Peripheral precocious puberty in a girl with an intracranial hCG-producing tumor: case report and literature review.

Human chorionic gonadotropin (hCG)-producing tumors cause peripheral precocious puberty (PP) in boys, but generally not in girls. Homology between LH and hCG activates the LH receptor in testicular Leydig cells, increases testosterone production, and causes virilization. However, since FSH action is required for follicle development, hCG action alone does not increase estradiol (E2) production and does not cause feminization. Only a few cases of peripheral PP with hCG tumors in girls have been reported. We describe the case of a 7-year-old Japanese girl with peripheral PP associated with an hCG-producing tumor. She had prolonged vomiting, loss of appetite, and Tanner stage III breast development. Although no apparent increase in growth rate, bone age was advanced at 9.8 years. Serum E2 was slightly elevated and LH and FSH were below the measurement sensitivity, and abdominal ultrasonography and computed tomography images showed no abnormal findings in the uterus or ovaries. Subsequently, she developed visual field disturbance and loss of consciousness, and brain magnetic resonance imaging revealed an intracranial tumor. Based on pathological findings and abnormally high serum hCG-ß level (48,800 IU/L), intracranial choriocarcinoma was diagnosed. 2.5 months after the start of chemotherapy, the hCG-ß level became almost negative and the breast development disappeared synchronously. Tissue immunostaining of the tumor showed strong positivity for aromatase and hCG, indicating that the choriocarcinoma cells themselves may have produced estrogen via aromatase. This unique case highlights the possibility that hCG-producing tumors can cause peripheral PP in girls as well as boys.

Re-Evaluation of the Prevalence of Permanent Congenital Hypothyroidism in Niigata, Japan: A Retrospective Study.

Although newborn screening (NBS) for congenital hypothyroidism (CH) in Japan started more than 40 years ago, the prevalence of CH remains unclear. Prevalence estimations among NBS-positive CH individuals include those with transient hypothyroidism and transient hyperthyrotropinemia, and re-evaluation with increasing age is necessary to clarify the actual incidence. Thus, we re-evaluated the incidence of permanent CH. Of the 106,114 patients who underwent NBS in the Niigata Prefecture, Japan, between April 2002 and March 2006, 116 were examined further due to high thyroid-stimulating hormone levels (>8 mIU/L) and were included in the study. We retrospectively evaluated their levothyroxine sodium (LT4) replacement therapy status from the first visit to 15 years of age. Of the 116 NBS-positive patients, 105 (91%) were initially examined in our department. Of these, 72 (69%) started LT4 replacement therapy on the first visit. Subsequently, 27 patients continued LT4 replacement until 15 years of age after multiple re-evaluations. The prevalence of permanent CH in the Niigata Prefecture during this period was 1 in 2500-3500 children. Ultimately, 62.5% of patients on LT4 replacement discontinued treatment by 15 years of age. This is the first study to clarify the true prevalence of permanent CH in Japan.

Easy-to-use preload stress echocardiography by using combined dynamic postural stress can identify high-risk patients with heart failure with reduced ejection fraction.

AIMS: Haemodynamic assessment during stress testing is not commonly performed in patients with heart failure with reduced ejection fraction (HFrEF) because of its invasiveness, lower feasibility, and safety concerns. This study aimed to assess the haemodynamic characteristics of patients with HFrEF in response to non-invasive preload stress during dynamic postural alterations achieved by combining both semi-sitting position and passive leg-lifting and to evaluate whether combined postural stress could be used for risk stratification in these patients. METHODS AND RESULTS: For this study, 101 patients with HFrEF and 35 age-matched and sex-matched healthy controls were prospectively recruited. After all standard echocardiographic measurements were obtained in the left decubitus position, all subjects underwent postural stress testing, which consisted of changing from semi-sitting position to passive leg-lifting. During a median follow-up period of 12.2 months, 21 (21%) patients developed adverse cardiovascular events. In patients without adverse cardiovascular events, the stroke volume index (SVi) significantly changed from 28 ± 8 to 35 ± 10 mL/m2 (P < 0.001) during combined postural stress. By contrast, ΔSVi during combined dynamic postural stress was significantly smaller in patients with cardiovascular events than in those without events (ΔSVi 3.4 ± 4.0 vs. 6.4 ± 3.8 mL/m2 , P = 0.002), which indicated severely diseased heart operated on a relatively flat portion of the Frank-Starling curve. In a multivariate Cox proportional hazard analysis, ΔSVi (hazard ratio 0.81, P = 0.02) was an independent predictor of future adverse cardiovascular events. CONCLUSIONS: The combined assessment of dynamic postural stress is a non-invasive, simple, quick, and easy-to-use clinical tool for assessing preload reserve and risk stratification in HFrEF patients.

"Accelerated aging" of the heart as heart failure with preserved ejection fraction-analysis using leg-positive pressure stress echocardiography.

The aging process is a significant risk factor for heart failure. The incidence of heart failure with preserved ejection fraction (HFpEF) dramatically increases with age. Although HFpEF occurs along a continuum of aging of the cardiovascular system, the pathophysiology that differentiates overt HFpEF from physiological aging is not fully understood. A total of 102 subjects were prospectively recruited: 25 patients with HFpEF and 77 healthy controls. Controls were stratified into three age-groups: young (n = 27, 20-40 years), middle aged (n = 25, 40-65 years), and elderly (n = 25, > 65 years). All participants underwent preload stress echocardiography using a leg-positive pressure (LPP) maneuver. With an increase in age, progressive concentric left ventricular (LV) remodeling was observed in healthy controls, resulting in the hemodynamic consequences of an age-dependent increase in the E/e' ratio (ANOVA, P < 0.001). During LPP stress, the E/e' ratio significantly increased in the middle-aged and elderly groups (from 8 ± 2 to 9 ± 3, from 10 ± 2 to 12 ± 3, P < 0.05, respectively), and this was more pronounced in patients with HFpEF (from 16 ± 5 to 17 ± 7, P < 0.05). Forward stroke volume (SV) significantly increased in each healthy group during LPP stress (all P < 0.001) but failed to increase in the HFpEF group (from 43 ± 13 to 44 ± 14 mL/m2, P = 0.65). In a multivariate analysis, LV mass index (odds ratio [OR] 1.051, P < 0.05), E/e' ratio (OR 1.480; P < 0.05), and change in SV (OR 0.780; P < 0.05) were independent parameters that differentiated HFpEF from physiological aging. Structural remodeling and impaired preload reserve may both be critical features that characterize the pathophysiology of HFpEF.

Preoperative coupling between right ventricle and pulmonary vasculature is an important determinant of residual symptoms after the closure of atrial septal defect.

PURPOSES: The closure of atrial septal defect (ASD) is associated with a significant reduction in right ventricular (RV) overload and an improvement in functional capacity in most adults with ASD. However, a subset of patients remains symptomatic even after closure due to therapeutic delay. To date, no clinically robust preoperative predictor of postoperative residual symptoms has been clearly identified. METHODS: In this study, 120 adult patients with ASD and 39 controls were investigated. As an index of RV myocardial deformation, RV global longitudinal strain (RV-GLS) was evaluated. The degree of coupling between RV and pulmonary artery (PA) was quantified by the tricuspid annular plane systolic excursion (TAPSE) divided by the PA systolic pressure (PASP). RESULTS: Compared to controls, baseline RV-GLS was significantly greater (- 27 ± 7 vs. - 23 ± 5%, P = 0.02) and TAPSE/PASP ratio was severely impaired (0.8 ± 0.3 vs. 2.1 ± 1.6 mm/mmHg, P < 0.01) in ASD patients. At 6 months after closure, 15 patients (12.5%) remained symptomatic. In patients without residual symptoms, TAPSE/PASP ratio significantly improved from 0.9 ± 0.3 to 1.0 ± 0.6 mm/mmHg (P = 0.02), and RV-GLS normalized (from - 28 ± 11 to - 24 ± 7%, P < 0.01) after closure. However, RV-GLS and TAPSE/PASP ratio showed no significant change in ASD patients with residual symptoms. On multivariate analysis, preoperative TAPSE/PASP ratio (odds ratio [OR] 0.034, 95% confidence interval [CI] 0.000-0.604, P = 0.03) and pulmonary vascular resistance index ([PVRI], OR 1.011, 95% CI 1.000-1.021, P < 0.05) were associated with the postoperative symptomatic status. CONCLUSION: In terms of integrated assessment of the RV-PA unit, preoperative TAPSE/PASP ratio and PVRI were important determinants of residual symptoms after ASD closure.

A Japanese Family with DICER1 Syndrome Found in Childhood-Onset Multinodular Goitre.

INTRODUCTION: Germline DICER1 mutations have recently been identified in familial multinodular goitre (MNG). The natural history of thyroid nodules in DICER1 carriers in children is unclear. The purpose of this study was to describe the clinical and genetic findings of childhood-onset MNG with DICER1 carrier in a patient who underwent total thyroidectomy. CASE PRESENTATION: The 6-year-old proband had a thyroid nodule, and the number and size of nodules increased over 3 years. A total thyroidectomy was chosen because of the rapid rise in thyroglobulin levels, discomfort when swallowing, and the mother's history of poorly differentiated thyroid cancer (PDTC). Histopathology revealed adenomatous goitre without malignant cells. Her mother, maternal aunt, and maternal grandmother also had thyroid nodules removed during adolescence. Also, her mother had PDTC with lung metastases, and her maternal aunt had an ovarian germ cell tumour. DICER1 mutation analysis identified a heterozygous novel nonsense mutation (c.4509C>G, p.Y1503X) for the patient, her mother, her maternal grandmother, and her asymptomatic elder brother. Y1503X was identified in all resected thyroid tissues, while heterozygous D1709G, D1810V, and E1813K mutations were identified in individual nodules. DISCUSSION/CONCLUSION: A thyroid nodule was detected in chemotherapy- or radiotherapy-naïve patient with DICER1 carrier aged 6 years, and MNG developed over 3 years. This pedigree highlights the natural history of nodular disease in DICER1 carriers and identifies a possible association between DICER1 and more aggressive malignancies.

Timing of hyponatremia development in patients with salt-wasting-type 21-hydroxylase deficiency.

Newborn screening (NBS) can detect 21-hydroxylase deficiency (21-OHD), allowing for early treatment initiation. However, many patients present with adrenal crises or hyponatremia at their first visit. Age (in days) of hyponatremia development in infants with salt-wasting (SW)-type 21-OHD remains unclear. Therefore, we determined the earliest age of hyponatremia diagnosis in this retrospective observational study using medical records of 40 patients with classic 21-OHD in Niigata Prefecture, Japan, from April 1989 to March 2019. We determined the earliest diagnosis of hyponatremia (serum sodium levels < 130 mEq/L) and created a sodium decrease rate model to estimate hyponatremia development age. Of 23 patients with SW-type 21-OHD, 10 (43.5%) were identified during NBS; the earliest case to present with hyponatremia was at day 7. Serum sodium levels were significantly and negatively correlated with age in days, and hyponatremia was estimated to develop at 6.6 d after birth. Genotype or serum 17-hydroxyprogesterone levels were not associated with sodium decrease rate. Thus, hyponatremia development age is earlier (within 7 d) than the previously described time-point (10-14 d) in infants with SW-type 21-OHD. Efforts to reduce the time lag from obtaining results to consultation may be required in patients with high 17-hydroxyprogesterone levels on NBS.

Noninvasive Leg-Positive Pressure Stress Echocardiography Reveals Preload Reserve in Adult Patients after Complete Repair of Tetralogy of Fallot.

BACKGROUND: Long-term sequelae such as right ventricular dysfunction and reduced hemodynamic reserve are the main determinants of cardiovascular outcomes after repair of tetralogy of Fallot (TOF). Echocardiographic parameters at rest offer only partial information on impaired hemodynamics in these patients, and data during stress testing are lacking. The leg-positive pressure (LPP) maneuver has recently been reported to be able to apply acute preload stress. The aim of this study was to test the hypothesis that preload reserve is impaired and ventricular interaction is exacerbated in patients with TOF. METHODS: In this prospective cross-sectional study, we recruited 44 consecutive patients with TOF and 30 normal control subjects. Echocardiography was performed both at rest and during LPP stress, and preload reserve was defined as the change between baseline stroke volume (SV) and that obtained during LPP stress. The eccentricity index was calculated as the ratio of the left ventricular anteroposterior to septal-lateral dimensions to quantify ventricular interaction. RESULTS: LPP stress significantly increased SV from 73 ± 14 to 83 ± 16 mL (P < .01) in control subjects, while the increase in SV was significantly blunted (from 75 ± 19 to 79 ± 18 mL; P < .01 for interaction) in patients with TOF. The eccentricity index significantly changed during LPP stress in patients with TOF only from 1.07 ± 0.13 to 1.13 ± 0.14 (P < .01 for interaction). Patients with TOF were subdivided into two subgroups on the basis of the median value of increased response in SV (22 with sufficient and 22 with insufficient preload reserve). Multivariate analysis identified significant pulmonary regurgitation as the only independent determinant factor for insufficient preload reserve (odds ratio, 4.57; 95% CI, 1.048-19.90; P = .04). CONCLUSIONS: In patients after repair of TOF, ventricular interaction was exacerbated and preload reserve was impaired, especially in patients with significant pulmonary regurgitation. LPP stress testing may direct tailored treatment approaches, risk stratification, and clinical decision-making, such as more aggressive pharmacologic therapy, meticulous outpatient follow-up, or earlier reintervention.

Cytotoxicity analysis of staphylococcal bi-component ß-pore forming toxins using the CHO cells expressing human lymphocyte receptor CCR5.

CCR5-mediated cytotoxicity of staphylococcal bi-component toxins was investigated using human CCR5-expressing CHO cells. Cytotoxicity of rim domain loop-exchange mutants between LukE and Hlg2 indicated that loop-4 of LukE is essential for cytotoxicity in combination with LukD. Interestingly, Hlg2 showed LukF-dependent CCR5-mediated cytotoxicity, suggesting that the F-components of toxins also play a role in the cell-specific cytotoxicity.

Nonbacterial Thrombotic Endocarditis Concomitant with Repeated Systemic Embolization That Received Palliative Care Based on the Antemortem Diagnosis.

A 67-year-old woman was admitted to our hospital due to an acute onset of consciousness disturbance, aphasia and left hemiplegia. Computed tomography revealed multiple systemic infarctions, including brain, kidney and spleen. Transesophageal echocardiography revealed vegetations attached to the mitral valve leaflets, which was suspected to be the embolic source. Repeated blood cultures were negative, and advanced lung cancer was incidentally revealed by computed tomography. She was then diagnosed with nonbacterial thrombotic endocarditis (NBTE) based on the overall clinical picture. Subsequently, extensive systemic embolization repeatedly occurred, and she eventually died 25 days after admission. The autopsy proved NBTE and advanced-stage lung adenocarcinoma.

Rim domain loops of staphylococcal ß-pore forming bi-component toxin S-components recognize target human erythrocytes in a coordinated manner.

Staphylococcus aureus bi-component pore-forming toxins consist of S- and F-components, and form hetero-octameric beta-barrel pores on target blood cell membranes. Among them, γ-haemolysin (Hlg2 and F-component of Luk (LukF)) and LukED (LukE and LukD) possess haemolytic activity, whereas the Panton-Valentine leukocidin (LukS-PV and LukF-PV) does not lyse human erythrocytes. Here, we focussed on four loop structures in the rim domain of S-component, namely loops -1, -2, -3 and -4, and found that replacement of Loop-4 in both Hlg2 and LukE with that of LukS-PV abolished their haemolytic activity. Furthermore, LukS-PV gained haemolytic activity by Loop-4 exchange with Hlg2 or LukE, suggesting that Loop-4 of these S-components determined erythrocyte specificity. LOOP-1 and -2 enhanced the erythrocytes-binding ability of both components. Although Hlg2 and LukE recognize Duffy antigen receptor for chemokines on human erythrocytes, the ability of Loop-4 was not complementary between Hlg2 and LukE. Exchange of Hlg2 with LukE Loop-4 showed weaker activity than intact Hlg2, and LukE mutant with Hlg2 Loop-4 lost its haemolytic activity in combination of LukD. Interestingly, the haemolytic activities of these Loop-4 exchange mutants were affected by F-component, namely LukF enhanced haemolytic activities of these Hlg2 and LukE Loop-4 mutants, and also haemolytic activity of LukS-PV mutant with LukE Loop-4.

The first case of "locked-in leaflet" after transcatheter aortic valve replacement in a patient with bicuspid aortic stenosis.

This case report is about an 85-year-old woman with bicuspid aortic stenosis (AS). Although preoperative multimodality imaging showed challenging anatomical aspects, transcatheter aortic valve replacement (TAVR) was selected to be performed as a less invasive alternative treatment approach, owing to her comorbidity. Postoperative transesophageal echocardiography and multidetector-row computed tomography revealed the presence of "locked-in leaflet" caused by stent distortion due to pinching by calcified native leaflets, with nodular calcification preventing the full expansion of the valve, which resulted in moderate perivalvular leakage. This is the first reported case of bicuspid AS treated with TAVR that eventually resulted in "locked-in leaflet."