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Spontaneous echocardiographic contrast (SEC) in the left atrium can occur with transcatheter edge-to-edge repair (TEER), but the clinical significance is unknown.The authors examined the clinical association of the procedural appearance of SEC in 316 patients (median age, 82 years; interquartile range, 76-86 years; 43.4% women) undergoing TEER with the MitraClip for mitral regurgitation. Acute, 30-day, and 2-year clinical outcomes were analyzed.SEC was common, occurring following device implantation in 106 patients (34%). Although the occurrence of SEC was not related to clinical characteristics, such as atrial fibrillation, anticoagulant use, or left ventricular function, there was a strong relation to beneficial outcomes with TEER. The frequency of optimal reduction in mitral regurgitation was higher in patients who had SEC (99.1% vs 72.9%, P .001). Survival was greater, with a 2-year estimate for freedom from all-cause mortality of 88.4% versus 71.5% (log-rank P = .004). Importantly, the higher survival observed in patients with SEC was present without increased rates of procedural complications or stroke and remained significant in multivariate analyses that adjusted for baseline clinical and echocardiographic variables (P = .01).The occurrence of SEC in patients with TEER is associated with beneficial acute and intermediate-term outcomes.

Prediction of the clinical response to transcatheter edge-to-edge repair (TEER) remains a vexing challenge.This study sought to examine the relation between hemodynamic profiles and outcomes following mitral TEER.Among 378 patients (median age 82 years; 43.9% women), 3 hemodynamic profiles using residual left atrial pressure (LAP) and mitral regurgitation (MR) were defined: type I (optimal), grade ≤1 MR and mean LAP (mLAP) ≤15 mm Hg; type II (mixed), MR grade1 or mLAP15 mm Hg; and type III (poor), MR grade1 and mLAP15 mm Hg. The discrimination of these profiles for predicting outcomes was examined. A positive clinical response to TEER was defined as improvement in New York Heart Association functional class ≥I grade at 1 year without heart failure rehospitalization or death.There were 148 (39.0%) patients classified as optimal (type I), 187 (49.0%) patients as mixed (type II), and 43 (11.0%) patients as poor (type III). For all-cause mortality, survival at 1 year was 91.6%, 82.6%, and 67.9% for types I, II, and III, respectively (HR: 2.13; 95% CI: 1.44-3.15; P 0.001). For the composite endpoint of all-cause mortality and rehospitalization for heart failure, event-free survival at 1 year was 84.1%, 70.7%, and 53.2% for types I, II, and III, respectively (HR: 1.93; 95% CI: 1.41-2.65; P 0.001). Hemodynamic profiling was strongly associated with a positive response to TEER, occurring in 73.9%, 57.0%, 35.0%, for types I, II, and III, respectively (P 0.001).In patients undergoing mitral TEER, hemodynamic profiling is prognostic, with superior survival occurring among patients with optimal reduction in MR and normal postprocedural LAP.

Chronic aortic regurgitation (AR) causes left ventricular (LV) volume overload, which results in progressive LV remodeling negatively affecting outcomes. Whether cardiac magnetic resonance (CMR) volumetric quantification can provide incremental risk stratification over standard clinical and echocardiographic evaluation in patients with chronic moderate or severe AR is unknown.To compare LV remodeling measurements by CMR and echocardiography between patients with and without heart failure symptoms and to verify the association of remodeling measurements of patients with chronic moderate or severe AR but no or minimal symptoms with clinical outcomes receiving medical management.This multicenter retrospective cohort study included consecutive patients with at least moderate chronic native AR evaluated by 2-dimensional transthoracic echocardiography and CMR examination within 90 days from each other between January 2012 and February 2020 at Allina Health System. Data were analyzed from June 2021 to January 2022.Clinical evaluation and risk stratification by CMR.The end point was a composite of death, heart failure hospitalization, or progression of New York Heart Association functional class while receiving medical management, censoring patients at the time of aortic valve replacement (when performed) or at the end of follow-up.Of the 178 included patients, 119 (66.9%) were male, 158 (88.8%) presented with no or minimal symptoms (New York Heart Association class I or II), and the median (IQR) age was 58 (44-69) years. Compared with patients with no or minimal symptoms, symptomatic patients had greater LV end-systolic volume index (LVESVi) by CMR (median [IQR], 66 [46-85] mL/m2 vs 42 [30-58] mL/m2; P .001), while there were no significant differences by echocardiography (LVESVi: median [IQR], 38 [30-58] mL/m2 vs 27 [20-42] mL/m2; P = .07; LV end-systolic diameter index: median [IQR], 21 [17-25] mm/m2 vs 18 [15-22] mm/m2; P = .17). During the median (IQR) follow-up of 3.3 (1.6-5.8) years, 50 patients with no or minimal symptoms receiving medical management developed the composite end point, which, in multivariate analysis adjusted for age and EuroSCORE II, was independently associated with LVESVi of 45 mL/m2 or greater and aortic regurgitant fraction of 32% or greater, the latter adding incremental prognostic value to CMR volumetric assessment.In patients with chronic moderate or severe AR, patients presenting with heart failure symptoms have greater LVESVi by CMR than those with no or minimal symptoms. In patients with no or minimal symptoms, CMR quantification of LVESVi and AR severity may identify those at risk of death or incident heart failure and therefore should be considered in the clinical evaluation and decision-making of these patients.

The prevalence of mitral valve disease with mitral annular calcification (MAC) and its clinical outcomes remain uncertain. This study sought to evaluate the prevalence of significant mitral disease due to MAC, and the impact of intervention on the clinical outcomes in these patients. All patients who underwent transthoracic echocardiography (TTE) between January 2014 and December 2015 in our health care system were reviewed and identified for having MAC with significant mitral valve disease (i.e., either≥moderate mitral regurgitation (MR) or mitral stenosis (MS)). The primary endpoints of the study were all-cause mortality and a composite outcome of mortality or heart failure hospitalization at 3-year follow-up. Of 41,136 patients who underwent TTE, MAC was identified in 2,855 (6.9%) patients, including 434 (1.1% of total) patients who had significant MR and/or MS (median age [IQR], 80 [73 to 87] years; 63% women). MAC predominately involved the posterior annulus (95%), with the majority having calcification of both trigones (55%), the leaflets (71%), and circumferential involvement (67%). During 3-year follow-up, 59 (14%) patients underwent surgical or transcatheter MV intervention. Patients who did not undergo mitral intervention had higher all-cause mortality (HR 2.80, 95% CI 1.60 to 4.92; p0.001) and a greater risk of the composite outcome (HR 1.43, 1.00 to 2.04; p = 0.05) than those treated. Survival at 3-year follow-up was markedly greater in those with mitral intervention (78% vs 50%; p0.001). This survival benefit remained after multivariable adjustment. In conclusion, MAC affects approximately % of patients who undergo echocardiography. Those with significant mitral valve disease due to any degree of MAC have poor survival, which may be ameliorated with transcatheter or surgical intervention.

Although cardiac computed tomography angiography (CCTA) assessment of right ventricular dysfunction (RVD) is feasible, the incremental prognostic value remains uncertain in patients undergoing transcatheter aortic valve replacement (TAVR) evaluation. This study sought to determine the incremental clinical utility of RVD identification by CCTA while accounting for clinical and echocardiographic parameters.Patients who underwent multiphasic ECG-gated functional CCTA using dual-source system for routine TAVR planning were evaluated. Biphasic contrast protocol injection allowed for biventricular contrast enhancement. CCTA-based RVD was defined as right ventricular ejection fraction (RVEF) ​ ​50%. The association of CCTA-RVD with all-cause mortality and the composite outcome of death or heart failure hospitalization after TAVR was evaluated and examined for its incremental utility beyond clinical risk assessment and echocardiographic parameters.A total of 502 patients were included (median [IQR] age, 82 [77 to 87] years; 56% men) with a median follow-up of 22 [16 to 32] months. Importantly, 126 (25%) patients were identified as having RVD by CCTA that was not identified by echocardiography. CCTA-defined RVD predicted death and the composite outcome in both univariate analyses (HR for mortality, 2.15; 95% CI, 1.44-3.22; p ​ ​0.001; HR for composite outcome, 2.11; 95% CI, 1.48-3.01; p ​ ​0.001) and in multivariate models that included clinical risk factors and echocardiographic findings (HR for mortality, 1.74; 95% CI, 1.11-2.74; p ​= ​0.02; HR for composite outcome, 1.63; 95% CI, 1.09-2.44; p ​= ​0.02).Functional CCTA assessment pre-TAVR correctly identified 25% of patients with RVD that was not evident on 2D echocardiography. The presence of RVD on CCTA independently associates with clinical outcomes post-TAVR.

BackgroundDiffuse myocardial fibrosis (DMF) quantified by extracellular volume (ECV) may represent a vulnerable phenotype and associate with life threatening ventricular arrhythmias more than focal myocardial fibrosis. This principle remains important because 1) risk stratification for implantable cardioverter defibrillators (ICD) remains challenging, and 2) DMF may respond to current or emerging medical therapies (reversible substrate).ObjectivesTo evaluate the association between quantified by ECV in myocardium without focal fibrosis by late gadolinium enhancement (LGE) with time from ICD implantation to 1) appropriate shock, or 2) shock or anti-tachycardia pacing.MethodsAmong patients referred for cardiovascular magnetic resonance (CMR) without congenital disease, hypertrophic cardiomyopathy, or amyloidosis who received ICDs (n=215), we used Cox regression to associate ECV with incident ICD therapy.ResultsAfter a median of 2.9 (IQR 1.5-4.2) years, 25 surviving patients experienced ICD shock and 44 experienced shock or anti-tachycardia pacing. ECV ranged from 20.2% to 39.4%. No patient with ECVConclusionsDMF measured by ECV associates with ventricular arrhythmias requiring ICD therapy in a dose-response fashion, even adjusting for potential confounding variables, focal fibrosis by LGE, and GLS. ECV-based risk stratification and DMF representing a therapeutic target to prevent ventricular arrhythmia warrant further investigation.Condensed AbstractAnalogous to heart failure and mortality outcomes, diffuse myocardial fibrosis (DMF) quantified by extracellular volume (ECV) may represent a more vulnerable phenotype for life-threatening ventricular arrhythmia than focal myocardial fibrosis. In patients referred for cardiovascular magnetic resonance, we identified 215 subsequently receiving implantable cardioverter defibrillators (ICD). After a median of 2.9 (IQR 1.5-4.2) years, 25 patients experienced ICD shock and 44 experienced shock or anti-tachycardia pacing. ECV associated with ICD therapy in Cox regression models. Focal fibrosis variables or global longitudinal strain did not. ECV-based risk stratification and DMF representing a therapeutic target to prevent ventricular arrhythmia warrant further investigation.

Background: Consensus-driven criteria have recently been proposed for prediction of mitral transcatheter edge-to-edge repair outcomes, yet validation for response to therapy is needed. We examined the relation between contemporary criteria and outcomes with mitral transcatheter edge-to-edge repair therapy. Methods: Mitral transcatheter edge-to-edge repair patients were classified according to anatomic and clinical criteria (1) Heart Valve Collaboratory criteria for nonsuitability; (2) commercial indications (suitable); and (3) neither (ie, intermediate). Analyses for Mitral Valve Academic Research Consortium–defined outcomes of reduction in mitral regurgitation and survival were performed. Results: Among 386 patients (median age, 82 years; 48% women), the most common classification was intermediate (46%), with 138 patients (36%) and 70 patients (18%) in the suitable and nonsuitable categories, respectively. Nonsuitable classification was related to prior valve surgery, smaller mitral valve area, type IIIa morphology, larger coaptation depth, and shorter posterior leaflet. Nonsuitable classification was associated with less technical success ( P P Conclusions: Contemporary classification criteria identify patients less suitable for mitral transcatheter edge-to-edge repair with respect to acute procedural success and survival, though patients most commonly fit an intermediate category. In experienced centers, sufficient mitral regurgitation reduction can be achieved safely in the selected patients even with challenging anatomy.

Evaluation of prosthesis-patient mismatch (P-PM) after transcatheter aortic valve replacement (TAVR) by transthoracic echocardiography (TTE) has provided conflicting results regarding its impact on outcomes. Whether post-TAVR computed tomography angiography (CTA) evaluation of P-PM can improve our understanding is unknown. We aimed to evaluate the inter-modality (TTE vs. CTA) agreement, inter-valve platform (balloon-expanding valve [BEV] vs. self-expandable valve [SEV]) differences in P-PM severity, and outcomes related to P-PM after TAVR.We analyzed patients with both CTA and TTE before and after TAVR. Indexed effective orifice area was calculated using two methods: TTE-derived left ventricular outflow tract (LVOT) area from measured diameter and post-TAVR CTA-measured area. Body size specific cut-offs for P-PM severity were used: for body mass index (BMI) ​ ​30 ​kg/mA total of 447 patients were included (median age, 83 years; 54% male). The prevalence of P-PM (moderate or severe) was lower with CTA vs. TTE (3.5% vs. 19.5%, p ​ ​0.001). The prevalence of P-PM measured by TTE was more common in BEV compared to SEV (p ​= ​0.002), while CTA assessment showed no difference in P-PM incidence and severity between TAVR platforms (p ​= ​0.40). In multivariable analysis, CTA-defined but not TTE-defined P-PM was associated with mortality after TAVR (HR:3.97; 95%CI,1.55-10.2; p ​= ​0.004). Both CTA-defined and TTE-defined P-PM were associated with the composite of death and heart failure rehospitalization.Although post-TAVR CTA substantially downgraded the prevalence of P-PM compared to TTE, it identified a subset of patients with clinically relevant P-PM which associated with outcomes.

Objectives Iodine deficiency and excess both cause thyroid dysfunction. Few data describe the relationship between iodine status and outcomes of congenital hypothyroidism (CH) in iodine-sufficient areas. We investigated urinary iodine (UI) concentration and its relationship with the clinical course of CH. Methods We reviewed and retrospectively analyzed patients with positive newborn screening (NBS) for CH from January 2012 to June 2019 in Japan, obtaining UI and UI-urine creatinine ratio (UI/Cr), serum TSH, free T4, free T3 and thyroglobulin (Tg) at the first visit, TSH at NBS, levothyroxine (LT4) dose, and subsequent doses. A UI value of 100–299 μg/L was considered adequate. Results Forty-eight patients were included. Median UI and UI/Cr were 325 μg/L and 3,930 µg/gCr, respectively. UI was high (≥300 μg/L) in 26 (54%) and low (≤99 μg/L) in 11 (23%). LT4 was administered to 34 patients. Iodine status was not related to the need for treatment. We found a U-shaped relationship between Tg and UI/Cr. Patients with high Tg (≥400 ng/mL) and abnormal UI levels required significantly lower LT4 doses (≤20 µg/day) at three years of age. Even if they showed severe hypothyroidism initially, they did not need subsequent dose increments. Conclusions Abnormal UI levels with Tg elevation were associated with lower LT4 dose requirements. The evaluation of iodine status and Tg concentrations were considered useful in patients suspected of CH.

Background: Although transcatheter aortic valve replacement (TAVR) therapy continues to grow, there have been concerns about the occurrence of hypoattenuating leaflet thickening (HALT), which may affect prosthesis function or durability. This study aimed to examine prosthesis frame factors and correlate their extent to the frequency of HALT and clinical outcomes. Methods: We prospectively examined 565 patients with cardiac computed tomography screening for HALT at 30 days after balloon-expandable SAPIEN3 and self-expanding EVOLUT TAVR. Deformation of the TAVR prostheses, asymmetric prosthesis leaflet expansion, prosthesis sinus volumes, and commissural alignment were analyzed on the postprocedural computed tomography. For descriptive purposes, an index of prosthesis deformation was calculated, with values >1.00 representing relative midsegment underexpansion. A time-to-event model was performed to evaluate the association of HALT with the clinical outcome. Results: Overall, HALT was present in 21% of SAPIEN3 patients and in 16% of EVOLUT patients at 30 days after TAVR. The occurrence of HALT was directly associated with greater prosthesis frame deformation ( P P P P P =0.001), cardiac death (hazard ratio, 4.58 [95% CI, 1.81–11.6]; P =0.001), and a composite outcome of all-cause mortality and heart failure hospitalization (hazard ratio, 1.94 [95% CI, 1.14–3.30]; P =0.02) with adjustment for age, sex, and comorbidities. Conclusions: Nonuniform expansion of TAVR prostheses resulting in frame deformation, asymmetric leaflet, and smaller neosinus volume is related to occurrence of HALT in patients who undergo TAVR. These data may have implications for both prosthesis valve design and deployment techniques to improve clinical outcomes for these patients.

Background: Although transcatheter edge-to-edge repair (TEER) is effective and safe, there is a need for better prediction of optimal outcomes. We aimed to determine predictors of optimal reduction in mitral regurgitation (MR) and survival with TEER. Methods: We examined mitral anatomy and its change with TEER on outcomes in 183 patients (age, 82 [77–87] years; 53% women). Coaptation reserve was measured as the distance of continuous apposition of the A2 and P2 leaflet segments in 2-dimensional apical long-axis imaging at the site of the predominant jet of MR. Augmentation in coaptation was measured as the total amount of leaflet insertion. Addressable coaptation area was calculated using the physical boundaries of the TEER device. Results: Coaptation reserve, its augmentation, and addressable coaptation area were strong predictors of MR reduction (all P 2 , respectively. Receiver operating characteristic analyses determined the best values for optimal MR reduction as a coaptation reserve of >3.0 mm ( P 2 ( P P Conclusions: Coaptation reserve and its augmentation are simple, independent parameters that predict optimal MR reduction and better survival in patients undergoing TEER. These findings may have implications for patient selection and expanded use of the therapy.

Herein, we report two girls with a neonatal screening (NS)-negative 21-hydroxylase deficiency (21-OHD) requiring treatment with hydrocortisone due to virilization that developed in late childhood. Patient 1 was born prematurely on the 30th gestational week with normal external genitalia at birth. She passed the NS for 21-OHD. At 6 yr of age, she was referred to a hospital for evaluation of premature pubarche and clitoromegaly. Her diagnosis was central precocious puberty, and GnRH agonist was initiated. However, her symptoms did not improve despite treatment for over 4 years. She was then referred to our hospital where she was diagnosed with 21-OHD. Although she was started on hydrocortisone therapy, her adult height reached only 140 cm (−3.4 SD). Patient 2 was delivered at 37 weeks of gestation and passed the NS for 21-OHD. She was referred to a hospital because of premature pubarche at the age of 6 yr. She was diagnosed with 21-OHD, and hydrocortisone replacement therapy was initiated. Her present height at 13 yr of age is 148 cm (−1.3 SD). These cases reminded us that the possibility of 21-OHD should be considered when patients show premature pubarche or precocious puberty, even if they passed the NS test for 21-OHD.

We aimed to compare the profile of the Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV) between Japanese schoolchildren born very preterm (VP) and with very low birthweight (VLBW) and those with attention deficit hyperactivity disorder (ADHD), and to identify the specific neurocognitive characteristics of VLBW/VP children.The VLBW/VP group in the present study included 50 (19 male, 31 female) first- to third-grade elementary school children born between January 2008 and February 2013 at Osaka Medical and Pharmaceutical University Hospital and Saiseikai Suita Hospital with birthweights1,500 g and32 gestational weeks. The ADHD group included 18 (13 male, 5 female) first- to third-grade elementary school children who visited Osaka Medical and Pharmaceutical University Hospital between January 2019 and October 2021. Full-scale intelligence quotient scores, four indices, and 12 subtests of the WISC-IV were calculated for all participants and compared between the VLBW/VP and ADHD groups. We assessed whether the patients' clinical history was associated with a low score on the cancellation task in the VLBW/VP group.The WISC-IV profiles showed similar between-group patterns, and the VLBW/VP group had lower cancellation task scores than the ADHD group.This is the first study to compare WISC-IV profiles between VLBW/VP children and those with ADHD. Further investigation is needed on the association between academic performance and the score of the cancellation task, and the neural mechanism of low performance for cancellation tasks in VLBW/VP children.

Background: Hypoattenuated leaflet thickening (HALT), identified on functional cardiac computed tomography (CTA), can affect valve function and clinical outcomes. The objective of this study was to assess the impact of HALT on clinical outcomes in patients treated with transcatheter aortic valve replacement (TAVR). Methods: In July 2015, Minneapolis Heart Institute implemented prospective screening of HALT at 30-day post-TAVR with CTA. Patients with evidence of HALT were recommended to initiate anticoagulation for 3 to 6 months with warfarin. Echocardiographic, ischemic, and bleeding outcomes were compared between HALT+ and HALT− patients. Survival rates were compared between HALT+ and HALT− patients using log-rank test, with Cox regression analysis used to identify variables independently associated with long-term death landmarked at time of CTA. This analysis included patients treated from July 1, 2015 to October 31, 2019. Results: Of 856 patients undergoing TAVR during the study period, 638 (75%) underwent CTA post-TAVR (median time 31 [30–37] days). HALT+ was evident in 79 (12.3%). HALT+ patients were more likely prescribed warfarin at 1, 3, and 12 months (all P P =0.001). In Cox regression analysis, presence of HALT (hazard ratio, 1.83 [95% CI, 1.13–2.97]; P =0.014) remained independently associated with long-term mortality. Conclusions: In a large, real-world cohort of patients receiving TAVR followed by systematic screening with CTA 30-days post-procedure, HALT was found in 12% of patients and independently associated with long-term mortality. Findings of this nonrandomized, observational cohort study require independent validation.

Objectives The aim of this study was to describe the anatomic and functional changes in left-sided chambers using computed tomographic angiography (CTA) from baseline to 1 month after transcatheter mitral valve replacement (TMVR) with the Tendyne prosthesis. Background Data on changes in left atrial and left ventricular (LV) volumes after TMVR implantation are very limited. Methods Patients who underwent TMVR with the Tendyne prosthesis between 2015 and 2018 were analyzed. Changes in LV end-diastolic volume, ejection fraction, LV mass, left atrial volume, and global longitudinal strain were assessed at baseline and 1 month after TMVR using CTA. Specific Tendyne implant characteristics were identified and correlated with remodeling changes. Results A total of 36 patients (median age 74 years; interquartile range [IQR]: 69 to 78 years; 78% men; 86% with secondary mitral regurgitation) were included in this study. There were significant decreases in LV end-diastolic volume (281 ml [IQR: 210 to 317 ml] vs. 239 ml [IQR: 195 to 291 ml]; p Conclusions TMVR with Tendyne results in favorable left-sided chamber remodeling in the majority of patients treated, as detected on CTA at 1 month after implantation. CTA identifies favorable post-TMVR changes, which could be related to specific characteristics of the device implantation.

MIRAGE syndrome is a recently identified disorder characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. It is caused by a gain-of-function variant in the SAMD9 gene, but there is limited knowledge regarding the genotype–phenotype correlation. We herein report a Japanese patient with MIRAGE syndrome carrying a novel de novo heterozygous missense variant in the SAMD9 gene (c.4435 G > T; p.Ala1479Ser).

Background We sought to quantify and compare changes in quality of life measures after transcatheter aortic valve replacement (TAVR) in patients with low-flow (LF) and normal-flow (NF) aortic stenosis (AS). Methods We included 297 patients treated with TAVR at Abbott Northwestern Hospital from January 2015 to October 2017. Health status was assessed at baseline and 30 days post-procedure using the Kansas City Cardiomyopathy Questionnaire 12 (KCCQ-12). Overall (KCCQ-OS) and domain-specific (physical limitation, symptom frequency, quality of life, and social limitation) scores were compared in three subsets of patients as defined by stroke volume index (≤ or >35 ml/m2 ), ejection fraction (EF) (≤ or >40%), and mean gradient (≤ or >40 mmHg). Results Of the 297 patients included, 129 (43%) had NF high-gradient (NF AS group) and 168 (56%) had LF severe AS, including 25 (8%) with low EF (8%) ("Classical" low-flow low-gradient LEF [LF-LG-LEF] group) and 143 (48%) with preserved EF ("Paradoxical" LF-LG group). At baseline, patients with LF-LG-LEF AS had more severe impairment in symptoms frequency (p = .06) but similar KCCQ-OS. At 1-month after TAVR, all groups had moderate improvements in quality of life (Delta KCCQ-OS: "Classical" LF-LG-LEF 18 ± 21, paradoxical AS 14 ± 18, and NF AS 15 ± 16, p = .57). During a median follow-up time of 2.4 years, there was no difference in mortality (p = .34) but patients with paradoxical LF-LG AS had a higher risk of rehospitalization for heart failure (p = .01). Conclusions Patients with LF severe AS derive significant improvements in quality of life measures after TAVR, indistinguishable from patients with NF AS.

This study investigated the impact of coronavirus disease 2019 pandemic school closures on the mental health of school students with chronic diseases.Questionnaires were distributed to students from 4th-9th grade diagnosed with chronic diseases at Osaka Medical College Hospital and their parents or caregivers. Questionnaires from 286 families were returned by mail after the schools reopened. The students were divided into the "psychosomatic disorder" group (group P, n = 42), the "developmental disorder" group (group D, n = 89), and the "other disease" group (group O, n = 155). Using students' self-reports on the Questionnaire for Triage and Assessment with 30 items, we assessed the proportion of students with a high risk of psychosomatic disorder in three groups. We investigated how the students requiring the support of somatic symptom (SS) felt about school during school closure. Further, using parents' and caregivers' answers, SS scores were calculated before and during school closure and after school reopening.The proportion of students with a high risk of developing psychosomatic disorder increased in all groups. For the students in Group P, the response "I did not want to think about school" indicated an increase in SS scores, and for the students in Group O, "I wanted to get back to school soon" indicated a decrease. Furthermore, especially in Group P students, SS scores decreased transiently during school closure and increased after school reopening.The impact of school closure on mental health differed depending on students' diagnoses and feelings about school during school closures.

Aims This study sought to compare cardiac magnetic resonance (CMR) characteristics according to different flow/gradient patterns of aortic stenosis (AS) and to evaluate their prognostic value in patients with low-gradient AS. Methods and results This international prospective multicentric study included 147 patients with low-gradient moderate to severe AS who underwent comprehensive CMR evaluation of left ventricular global longitudinal strain (LVGLS), extracellular volume fraction (ECV), and late gadolinium enhancement (LGE). All patients were classified as followings: classical low-flow low-gradient (LFLG) [mean gradient (MG) < 40 mmHg and left ventricular ejection fraction (LVEF) < 50%]; paradoxical LFLG [MG < 40 mmHg, LVEF ≥ 50%, and stroke volume index (SVi) < 35 ml/m2]; and normal-flow low-gradient (MG < 40 mmHg, LVEF ≥ 50%, and SVi ≥ 35 ml/m2). Patients with classical LFLG (n = 90) had more LV adverse remodelling including higher ECV, and higher LGE and volume, and worst LVGLS. Over a median follow-up of 2 years, 43 deaths and 48 composite outcomes of death or heart failure hospitalizations occurred. Risks of adverse events increased per tertile of LVGLS: hazard ratio (HR) = 1.50 [95% CI, 1.02–2.20]; P = 0.04 for mortality; HR = 1.45 [1.01–2.09]; P < 0.05 for composite outcome; per tertile of ECV, HR = 1.63 [1.07–2.49]; P = 0.02 for mortality; HR = 1.54 [1.02–2.33]; P = 0.04 for composite outcome. LGE presence also associated with higher mortality, HR = 2.27 [1.01–5.11]; P < 0.05 and composite outcome, HR = 3.00 [1.16–7.73]; P = 0.02. The risk of mortality and the composite outcome increased in proportion to the number of impaired components (i.e. LVGLS, ECV, and LGE) with multivariate adjustment. Conclusions In this international prospective multicentric study of low-gradient AS, comprehensive CMR assessment provides independent prognostic value that is cumulative and incremental to clinical and echocardiographic characteristics.

Background Chronic aortic regurgitation (AR) causes left ventricular (LV) volume overload resulting in progressive LV remodeling, which negatively affect clinical outcome. Clinical Guidelines recommend assessment of LV remodeling by echocardiography, but little is known about comparative remodeling quantification by cardiac magnetic resonance (CMR) and association with outcomes. Purpose To assess LV remodeling in AR by CMR, compared with echocardiographic measures and determine its impact on clinical outcome. Methods Patients with native, ≥moderate, chronic AR by echocardiography who underwent CMR exam within 90 days of diagnosis from January 2012 to February 2020 were enrolled. The endpoint was a composite of death, heart failure hospitalization, and heart failure symptom exacerbation during follow-up. Results The 178 patients included had median age (IQR) of 58 years (44–69), and most (88%, n=158) presented with no or minimal symptoms (NYHA class I/II). At diagnosis symptomatic vs. no/minimal symptoms patients presented with much more advanced LV remodeling by CMR (EDVI 133 [83–151] vs. 96 [80–123] p=0.024, ESVI 66 [46–85] vs. 42 [30–58], P=0.001) while echocardiography showed limited differences (EDVI 76 [57–93] vs. 65 [54–87] p=0.507, ESVI 38 [30–58] vs. 27 [20–42], p=0.072). During follow-up (3.3 years [1.6–5.8]), aortic valve replacement (AVR) was performed in 49 patients. In patients with no/minimal symptoms, the composite endpoint occurred in 54 (34%) patients including eight deaths and 30 heart failure hospitalizations. Patients with LV end-systolic volume index (LVESVi) >45 ml/m2 by CMR had higher likelihood for composite endpoint (Panel A) confirmed in multivariate models, adjusting for age, sex, AVR (time-dependent), EuroSCORE2, and LV End-systolic-dimension-index (LVESDi) >25 mm/2, with adjusted hazard ratio 1.84 [1.02–3.33], p Conclusion Assessment of LV remodeling by CMR in patients with clinically significant AR is feasible in routine clinical practice, detects with high sensitivity LV remodeling associated with development of HF symptoms and is independently predictive of clinical outcome. Hence, CMR provides a powerful tool for evaluation and risk stratification of patients with AR. Funding Acknowledgement Type of funding sources: None. Panel APanel B

Background The clinical utility of comprehensive cardiac magnetic resonance (CMR) for the assessment of myocardial structure and function remains unknown in patients with low gradient (LG) aortic stenosis (AS). Purpose This study sought to compare CMR characteristics of myocardial structure and function according to different flow / gradient patterns of AS: classical low flow LG (LFLG); paradoxical LFLG; normal flow LG; and high gradient, and to evaluate their impact on the outcomes of these patients. Methods International multicentric prospective study included 147 patients with LG moderate to severe AS and 18 patients with high gradient severe AS who underwent comprehensive CMR evaluation of left ventricular global longitudinal strain (LVGLS), extracellular volume fraction (ECV), and late gadolinium enhancement (LGE). Results Patients with classical LFLG (n=90) had more LV adverse remodeling and impaired longitudinal function including higher ECV, and higher LGE and volume, and worst LVGLS, compared to other patterns of AS. Over a median follow-up of 2-years, 43 deaths and 48 composite outcomes of death or heart failure hospitalization occurred in LG AS patients. As LVGLS or ECV worsened, risks of adverse events also increased (per tertile of LVGLS: HR [95% CI] for mortality, 1.50 [1.02–2.20]; p=0.04; HR [95% CI] for composite outcome, 1.45 [1.01–2.09]; p Conclusions In this international multicentric study of LG AS, comprehensive CMR assessment of myocardial structure and function provides independent prognostic value that is cumulative and incremental to clinical and echocardiographic characteristics. Funding Acknowledgement Type of funding sources: None.

The untranslated regions (UTRs) of mRNAs are involved in many posttranscriptional regulatory pathways. The rice OsMac1 mRNA has three splicing variants of the 5’ UTR (UTRa, UTRb, and UTRc), which include a CU-rich region and three upstream open reading frames (uORFs). UTRc contains an additional 38-nt sequence, termed sp38, which acts as a strong translational enhancer of the downstream ORF; reporter analysis revealed translational efficiencies >15-fold higher with UTRc than with the other splice variants. Mutation analysis of UTRc demonstrated that an optimal sequence length of sp38, rather than its nucleotide sequence is essential for UTRc to promote efficient translation. In addition, the 5’ 100 nucleotides of CU-rich region contribute to UTRc translational enhancement. Strikingly, three uORFs did not reveal their inhibitory potential within the full-length leader, whereas deletion of the 5’ leader fragment preceding the leader region with uORFs nearly abolished translation. Computational prediction of UTRc structural motifs revealed stem-loop structures, termed SL1-SL4, and two regions, A and B, involved in putative intramolecular interactions. Our data suggest that SL4 binding to Region-A and base pairing between Region-B and the UTRc 3’end are critically required for translational enhancement. Since UTRc is not capable of internal initiation, we presume that the three-dimensional leader structures can allow translation of the leader downstream ORF, likely allowing the bypass of uORFs.