Accuracy of Shunt Volume Measured by Three-Dimensional Echocardiography and Cardiac Magnetic Resonance in Patients With an Atrial Septal Defect and a Dilated Right Ventricle.

BACKGROUND: The accuracy of right ventricular (RV) quantification by three-dimensional echocardiography (3DE) has been reported mainly in patients with a normal right ventricle (RV). However, there are no data regarding the accuracy of 3DE in patients with a dilated RV, as in shunt diseases. In this study, we evaluated the accuracy of 3DE and that of volumetric (Vol) cardiac magnetic resonance (CMR) for assessment of RV and left ventricular (LV) stroke volume (SV) and the pulmonary (Qp)/systemic (Qs) blood flow ratio in patients with an atrial septal defect (ASD) using the two-dimensional phase contrast (2DPC) method as the gold standard. METHODS: We retrospectively investigated 83 patients with ASD who underwent transcatheter closure and clinically indicated CMR and 3DE examinations. The ratio Qp/Qs was calculated using RV and LV SV measured by full-volume volumetric 3DE (Vol-3DE) and CMR (Vol-CMR) and by two-dimensional pulsed Doppler quantification (2D-Dop); the parameters were compared using 2DPC-CMR as the gold standard. RESULTS: There was no significant difference in the Qp/Qs value between 2DPC-CMR and Vol-3DE (2.29 ± 0.70 vs 2.21 ± 0.63, P = .79) and 2D-Dop (vs 2.21 ± 0.65, P = 1.00); however, a significant difference was found between 2DPC-CMR and Vol-CMR (P < .001). The Qp/Qs value obtained using Vol-3DE showed the best correlation with 2DPC-CMR (r = 0.93, P < .001). The RV and LV SV values obtained by Vol-3DE showed the best correlation with 2DPC-CMR (RV SV, r = 0.82, P < .001; LV SV, r = 0.73, P < .001), although the absolute values were underestimated. CONCLUSION: Qp/Qs was more accurately evaluated by Vol-3DE than by Vol-CMR or 2D-Dop. Three-dimensional echocardiography assessment was feasible and reproducible even in a dilated RV.

Cardioembolism after thoracoscopic left atrial appendage clipping in a patient on oral anticoagulation therapy.

Cardioembolism associated with atrial fibrillation is a major cause of ischemic stroke. Left atrial appendage occlusion in atrial fibrillation patients undergoing cardiac surgery reduces the risk of postoperative stroke. A 78-year-old man with a history of atrial fibrillation and severe mitral regurgitation underwent thoracoscopic mitral valve repair with left atrial appendage clipping and the cryo-maze procedure 4 years previously. He was taking a direct oral anticoagulant for stroke prevention because his atrial fibrillation had recurred. He presented with acute onset disturbed consciousness, omnidirectional gaze palsy, left facial palsy, severe dysarthria, bilateral limb ataxia, and sensory disturbance. National Institutes of Health Stroke Scale score was 16. Although non-contrast computed tomography showed no early ischemic changes, computed tomography angiography revealed occlusion of the basilar artery. Intravenous thrombolysis was performed, which resulted in recanalization. Transesophageal echocardiography showed left atrial spontaneous echo contrast and thrombus in the left atrial appendage. Contrast-enhanced chest computed tomography confirmed incomplete left atrial appendage occlusion. Cardioembolic stroke was diagnosed, and warfarin was initiated. Cardioembolism may occur after thoracoscopic left atrial appendage clipping despite direct oral anticoagulant therapy, particularly if appendage occlusion is incomplete. Occlusion status should be evaluated after thoracoscopic clipping. Learning objective: To illustrate, incomplete left atrial appendage closure may increase the risk of ischemic stroke even after thoracoscopic left atrial appendage clipping is performed to prevent embolism.

Relationship between masseter muscle activity during wakefulness and temporomandibular disorder-related symptoms.

BACKGROUND: Masseter muscle activity during wakefulness may be associated with temporomandibular disorder (TMD)-related symptoms, psychosocial status and pain-related disability; however, this relationship is unclear. OBJECTIVES: This study aimed to determine the relationship between masseter muscle electromyography (EMG) burst/duration during wakefulness and TMD-related symptoms, psychosocial status and pain-related disability. METHODS: Sixty participants were assessed masseter muscle activity during wakefulness using a data-logger-type ultraminiature EMG system and TMD-related symptoms, psychosocial status and pain-related disability through Axis I and II of the diagnostic criteria for TMD (DC/TMD). EMG bursts lasting longer than 0.25 s but less than 2.0 s and those lasting longer than 2.0 s were classified as phasic and tonic bursts, respectively. RESULTS: Participants with palpation-related pain in the temporalis and masseter muscles, as assessed through the DC/TMD examination form in Axis I, had more bursts (number/h) (p = .035 and p = .009, respectively) and longer duration (time/h) (p = .013 and p = .004, respectively) of tonic bursts of the masseter muscle during wakefulness. Participants with palpation-related pain in the masseter muscles had higher oral behaviour scores during wakefulness using Axis II (p = .001), which affected the number and duration of tonic bursts of the masseter muscle activity during wakefulness (p = .011 and p = .007, respectively). CONCLUSION: As tonic bursts mainly reflect clenching, individuals with pain in the masseter muscles by palpation may have a high frequency and longer duration of clenching, as well as a high frequency of oral behaviours during wakefulness.

Prognostic Predictors of Tricuspid Regurgitation Worsening after Mitral Regurgitation Surgery with Mild Tricuspid Regurgitation.

We aimed to investigate the prevalence and predictors of postoperative tricuspid regurgitation (TR) worsening in patients with mitral regurgitation (MR) and concomitant ≤mild TR. A total of 620 patients underwent surgery for MR from 2013 to 2017. Of these, 260 had ≤mild preoperative TR and no concomitant tricuspid valve surgery and were enrolled in this single-center retrospective study. The primary endpoint was postoperative worsening of ≥moderate TR. The primary endpoint occurred in 28 of 260 patients (11%) during the follow-up period [median: 4.1 years (interquartile range: 2.9-6.1 years)]. In the multivariable analysis, age, female sex, and left atrial volume index (LAVI) were significant predictors of the primary outcome during intermediate-term follow-up (age: hazard ratio [HR] 1.05 per 1-year increment, 95% confidence interval [CI] 1.02-1.10, P = 0.003; female sex: HR 3.53, 95% CI 1.61-7.72, P = 0.002; LAVI: HR 1.17 per 10-mL/m2 increment, 95% CI 1.07-1.26, P < 0.001). The optimal LAVI cut-off value for predicting postoperative TR worsening was 79 mL/m2 (area under the curve: 0.69). A high LAVI (>79 mL/m²) was significantly associated with a low rate of freedom from postoperative TR worsening compared with a low LAVI (≤79 mL/m²) (82.6% vs 93.9% at 5 years, respectively; log-rank P = 0.008). In patients with ≤mild preoperative TR and no concomitant tricuspid surgery, the rate of postoperative TR worsening was 11% during intermediate-term follow-up. LA enlargement in patients with MR and ≤mild preoperative TR was significantly associated with postoperative TR worsening.

Clinical application of artificial intelligence algorithm for prediction of one-year mortality in heart failure patients.

Risk prediction for heart failure (HF) using machine learning methods (MLM) has not yet been established at practical application levels in clinical settings. This study aimed to create a new risk prediction model for HF with a minimum number of predictor variables using MLM. We used two datasets of hospitalized HF patients: retrospective data for creating the model and prospectively registered data for model validation. Critical clinical events (CCEs) were defined as death or LV assist device implantation within 1 year from the discharge date. We randomly divided the retrospective data into training and testing datasets and created a risk prediction model based on the training dataset (MLM-risk model). The prediction model was validated using both the testing dataset and the prospectively registered data. Finally, we compared predictive power with published conventional risk models. In the patients with HF (n = 987), CCEs occurred in 142 patients. In the testing dataset, the substantial predictive power of the MLM-risk model was obtained (AUC = 0.87). We generated the model using 15 variables. Our MLM-risk model showed superior predictive power in the prospective study compared to conventional risk models such as the Seattle Heart Failure Model (c-statistics: 0.86 vs. 0.68, p < 0.05). Notably, the model with an input variable number (n = 5) has comparable predictive power for CCE with the model (variable number = 15). This study developed and validated a model with minimized variables to predict mortality more accurately in patients with HF, using a MLM, than the existing risk scores.

Prevalence and predictive factors for clinical outcomes of isolated functional tricuspid regurgitation.

BACKGROUND: A substantial number of patients have functional tricuspid regurgitation (TR). Isolated functional TR has been undertreated and may be a next target for transcatheter intervention. However, the prevalence, patient characteristics, and predictive factors for prognosis remain unclear. METHODS: From patients in our echocardiographic database (N = 64,242), we extracted those with severe TR and examined prognosis according to etiologies of TR. Thereafter, we focused on two types of isolated functional TR; progressive TR after left-sided valve surgery (postoperative TR) and TR associated with annular dilatation (atrial TR). Composite adverse events were defined as all-cause death or hospitalization for heart failure (HF). RESULTS: Of 1001 patients with severe TR (median age, 77 years; female, 58 %), 71 (7 %) patients were classified as postoperative TR, and 149 (15 %) as atrial TR. During the follow-up period (median, 1.6 years), 30 composite adverse events were observed (postoperative TR, n = 14; atrial TR, n = 16). Composite adverse events were less frequent in these two types of functional TR than TR of other etiologies. Multivariate analysis adjusted for age and sex showed that a history of hospitalization for HF, history of cardiac surgery >2 times, loop diuretics, estimated glomerular filtration rate, blood urea nitrogen, hemoglobin, platelet level, left ventricular ejection fraction, and right ventricular dimension were associated with clinical adverse events (p < 0.05), while B-type natriuretic peptide level was not. CONCLUSIONS: A considerable number of patients had isolated functional TR. Extracardiac factors such as renal function, hemoglobin and platelet are important in determining clinical outcomes.

Substitute parameters of exercise-induced pulmonary hypertension and usefulness of low workload exercise stress echocardiography in mitral regurgitation.

In asymptomatic patients with mitral regurgitation (MR), data of exercise-induced pulmonary hypertension (EIPH) are limited, and feasibility of evaluating EIPH is not high. We aimed to investigate prognostic impact of EIPH and its substitute parameters. Exercise stress echocardiography (ESE) were performed in 123 consecutive patients with moderate to severe degenerative MR. The endpoint was a composite of death, hospitalization for heart failure, and worsening of symptoms. EIPH [tricuspid regurgitation peak gradient (TRPG) at peak workload ≥ 50 mmHg] was shown in 57 patients (46%). TRPG at low workload was independently associated with TRPG at peak workload (ß = 0.67, p < 0.001). Early surgical intervention (within 6 months after ESE) was performed in 65 patients. Of the remaining 58 patients with the watchful waiting strategy, the event free survival was lower in patients with EIPH than in patients without EIPH (48.1 vs. 97.0% at 1-year, p < 0.001). TRPG at low workload ≥ 35.0 mmHg as well as EIPH were associated with poor prognosis in patients with the watchful waiting strategy. In conclusion, the importance of ESE and evaluating EIPH in patients with MR was re-acknowledged. TRPG at peak workload can be predicted by TRPG at low workload, and TRPG at low workload may be useful in real-world clinical settings.

Effects of sex, age, choice of surgical orthodontic treatment, and skeletal pattern on the psychological assessments of orthodontic patients.

We aimed to examine the effects of sex, age, choice of surgical orthodontic treatment, and skeletal pattern on psychological assessment scores of orthodontic patients before edgewise treatment. They completed the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI)-II, and the psychological domain of the World Health Organization Quality of Life 26 (Psych-QOL) for assessment of anxiety, depression, and body image, respectively. No significant effects on psychological assessment scores due to sex or age differences were found. Surgical orthodontic treatment patients and patients with skeletal Class III had significantly higher STAI-Trait and/or BDI-II scores and lower Psych-QOL score. Based on the linear mixed-effects model, the choice of surgical orthodontic treatment had a significant effect on the STAI-Trait, BDI-II, and Psych-QOL scores. No significant interaction effect was found between the choice of surgical orthodontic treatment and the skeletal pattern by ANB angle. Patients with skeletal Class I or III who chose surgical orthodontic treatment had higher STAI-Trait and/or BDI-II scores and/or lower body image score, respectively. These results suggest that patients who chose surgical orthodontic treatment, particularly those with skeletal Class I and III, may be more prone to experience anxiety and depression and have body image dissatisfaction.

Contemporary Diagnosis and Management of Hypertrophic Cardiomyopathy: The Role of Echocardiography and Multimodality Imaging.

Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease with an estimated prevalence of 0.2-0.5%. Although the prognosis of HCM is relatively good, with an annual general mortality of ~0.7%, some patients have an increased risk of sudden death, or of developing severe heart failure requiring heart transplantation or left ventricular (LV) assist device therapy. Therefore, earlier diagnosis and proper identification of high-risk patients may reduce disease-related morbidity/mortality by promoting timely treatment. Echocardiography is the primary imaging modality for patients with suspected HCM; it plays central roles in differential diagnosis from other causes of LV hypertrophy and in evaluating morphology, hemodynamic disturbances, LV function, and associated valvular disease. Echocardiography is also an essential tool for the continuous clinical management of patients with confirmed HCM. Other imaging modalities, such as cardiac computed tomography (CT) and cardiac magnetic resonance imaging (MRI), can supplement echocardiography in identifying high-risk as well as milder HCM phenotypes. The role of such multimodality imaging has been steadily expanding along with recent advancements in surgical techniques and minimally invasive procedures, and the emergence of novel pharmacotherapies directly targeting pathogenic molecules such as myosin inhibitors. Here we review essential knowledge surrounding HCM with a specific focus on structural and functional abnormalities assessed by imaging modalities, leading to treatment strategies.

Rapidly Progressing Aseptic Abscesses in a Patient with Ulcerative Colitis.

Aseptic abscesses (AAs) are extraintestinal manifestations of inflammatory bowel disease (IBD). IBD-associated AAs are rare in Japan. We treated a 45-year-old man with ulcerative colitis (UC)-associated AAs. During remission, multiple progressive abscesses were detected in the spleen; he underwent splenectomy because an infectious disease was suspected. Although his condition improved temporarily after splenectomy, a large liver abscess was noted, and a diagnosis of UC-associated AAs was made. Granulocytapheresis (GCAP) and infliximab (IFX) administration resolved the abscess. This is the first reported case of UC-associated AAs in a Japanese patient treated by splenectomy, GCAP, and IFX.

The association among enterobacterial flora, dietary factors, and prognosis in patients with ulcerative colitis.

The role of enterobacterial flora in the onset and progression of inflammatory bowel diseases is a topic of considerable interest. Here, we assessed the association among enterobacterial flora, dietary factors, and ulcerative colitis (UC) progression. Forty-six patients with UC who were diagnosed as being in remission were enrolled. We collected each patient's stool sample one or two days before diagnostic colonoscopy. After colonoscopy, we observed the patients for one year and then retrospectively divided them into two groups: remission (n = 39) and relapse (n = 7) groups, depending on whether the relapse occurred during the follow-up period, and analyzed the relationship among patient characteristics, dietary factors, enterobacterial flora, and UC relapse. Overall, there were no significant differences in bacterial community populations between the remission and relapse groups, except that the order Lactobacillales was detected at a significantly higher rate in the relapse than in the remission group (100% vs 71.4%, p<0.05). Vitamin C intake was significantly higher in the remission than in the relapse group (p<0.05). Although there were no obvious differences in enterobacterial flora between the remission and relapse groups, there was a relationship among enterobacterial flora, diet, and UC progression. Given that the enterobacterial flora was only analyzed at the initiation of the study, we conclude that in future analyses, enterobacterial flora should be sampled at numerous time points to examine its role in UC progression. Further long-term longitudinal studies examining enterobacterial flora, dietary factors, and UC progression are also required.

Relationships of maxillofacial morphology and malocclusion with handgrip strength in adult women.

OBJECTIVES: Maxillofacial morphology and malocclusion are related to maximum occlusal force (MOF). Although it has been reported that MOF was related to handgrip strength (HS), the relationships between maxillofacial morphology/malocclusion and HS remain unclear. This study aimed to examine the relationships between maxillofacial morphology, malocclusion and HS. SETTING AND SAMPLE POPULATION: Eighty-five women with malocclusion, aged 18-40 years, were selected. MATERIALS AND METHODS: Lateral cephalometric radiographs (SNA, SNB, ANB, mandibular plane-FH, and gonial angles, overjet and overbite), the Peer Assessment Rating (PAR) index and HS were measured. Subjects were classified by the Japanese normal mean value of cephalometric analysis or the reference value which was defined by degree of malocclusion in each PAR index measurement item (small/low: value < mean/reference value, large/high: value ≧ mean/reference value). Measurements were then compared between groups. RESULTS: HS of the large-gonial angle group was lower than that of the small-gonial angle group. In the small-overbite group or high-transverse (PAR index score showing crossbite/scissor bite in the canine and molars) group, HS in the large-gonial angle group was significantly lower than that in the small-gonial angle group. CONCLUSIONS: Our results suggest that gonial angle is the largest factor affecting HS. HS may be especially low in those subjects with a large gonial angle and a small overbite or a crossbite/scissor bite in the molar section.

Treatment Adherence in Patients with Ulcerative Colitis Is Dependent on the Formulation of 5-Aminosalicylic Acid.

BACKGROUND/AIMS: It is unclear whether 5-aminosalicylic acid (5-ASA) formulation is associated with treatment adherence in ulcerative colitis (UC). Thus, we aimed to investigate the adherence rate after switching from 5-ASA tablets to granules. METHODS: This prospective study included 121 UC outpatients treated using 5-ASA tablets. They were grouped based on choice: Group 1 (continued with tablets) and Group 2 (switched to granules without regimen change). Group 2 was further divided into Group 3 (returned to tablets) and Group 4 (continued with granules). The patients completed a self-administered questionnaire regarding the treatment. The primary endpoint was change in adherence after switching to granules. RESULTS: Seventy-nine patients continued with tablets, while 42 patients switched to granules. The adherence rate to the tablet was not significantly different between Group 1 and 2 before switching. In Group 2, switching to granules did not affect adherence. However, in Group 4, adherence significantly improved after switching to granules. Group 3 showed no significant change in adherence before and after switching from tablets. Full-time work and difficulty taking tablets were significant predictors of continuing with granules in Group 4. CONCLUSION: Patients who continued with 5-ASA granules showed significantly increased adherence, suggesting that patient-tailored drug formulations improved treatment adherence.

Validation of the 2014 European Society of Cardiology Sudden Cardiac Death Risk Prediction Model Among Various Phenotypes in Japanese Patients With Hypertrophic Cardiomyopathy.

Risk stratification for sudden cardiac death (SCD) is essential in the management of hypertrophic cardiomyopathy (HC). The 2014 European Society of Cardiology SCD risk prediction model (Risk-SCD) is a novel risk scoring system; however, whether it can be applied to Japanese HC and its usefulness among various HC phenotypes remain unclear. The aim of this study was to validate the Risk-SCD model in Japanese HC, and to evaluate its usefulness among various HC phenotypes. We studied 370 consecutive Japanese HC patients evaluated for primary SCD prevention at our tertiary referral center. The Risk-SCD model was validated in 289 HC patients with ejection fraction (EF) ≥50% (including left ventricular outflow tract obstruction [LVOTO], mid ventricular obstruction [MVO], apical hypertrophy, and nonobstructive phenotypes), and 81 end-stage HC patients (EF <50%). The end point of the study was SCD or an equivalent event (appropriate implantable cardioverter defibrillator therapy or successful resuscitation after cardiac arrest). Thirty-one SCD events were observed during a median follow-up of 5.2 (interquartile range 3.5 to 6.9) years. The Risk-SCD model showed improved risk prediction in HC with EF ≥50% compared with the previous 2011 American College of Cardiology Foundation/American Heart Association and 2003 American College of Cardiology/European Society of Cardiology guideline approaches (number needed to treat = 3.8 at Risk-SCD >6%) regardless of phenotypes; LVOTO, MVO, apical, and nonobstructive, but misclassified SCD risk in end-stage HC. In the current external validation of the Risk-SCD model in Japanese HC, the model improved SCD prediction compared with previous approaches, and was also shown to be useful in LVOTO, MVO, apical, and nonobstructive phenotypes.

Endoscopic submucosal resection with an endoscopic variceal ligation device for the treatment of rectal neuroendocrine tumors.

BACKGROUND: Endoscopic resection is recommended for rectal neuroendocrine tumors < 1 cm in diameter; the three techniques (mucosal resection, submucosal dissection, and mucosal resection with variceal ligation device) of endoscopic resection of neuroendocrine tumor were reported; however, the optimal endoscopic technique remains unclear. PURPOSE: We compared the efficacy and safety of three endoscopic rectal neuroendocrine tumor resection methods. METHODS: We retrospectively enrolled 52 patients with rectal neuroendocrine tumors treated by endoscopy at Aichi Medical University Hospital and Nagoya City University Hospital between May 2003 and June 2017. We compared clinical outcomes in three groups based on the endoscopic treatment method. RESULTS: Fifty-two patients underwent endoscopic rectal neuroendocrine tumor treatment (mucosal resection, 14; submucosal dissection, 19; mucosal resection with an endoscopic variceal ligation device, 19). In the endoscopic mucosal resection, submucosal dissection, and mucosal resection with variceal ligation device groups, R0 resection occurred in 50.0, 94.7, and 89.5%, respectively (mucosal resection vs. mucosal resection with variceal ligation device, p < 0.05; mucosal resection vs. submucosal dissection, p < 0.01), while the median procedure times were 6.5, 43, and 6.0 min, respectively (submucosal dissection vs. mucosal resection with variceal ligation device procedure times, p < 0.01; mucosal resection vs. submucosal resection procedure times, p < 0.01). Postoperative bleeding occurred after endoscopic mucosal resection (1/14) and endoscopic submucosal dissection (4/19), but not after endoscopic mucosal resection with a ligation device. CONCLUSION: Endoscopic mucosal resection with an endoscopic variceal ligation device was a safe, effective treatment for rectal neuroendocrine tumors.

NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study.

BACKGROUND: Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs. METHODS: Overall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation. RESULTS: We confirmed the association of NUDT15 p.Arg139Cys with leukopenia and alopecia (p = 2.20E-63, 1.32E-69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms (p = 6.39E-04, OR = 1.89). Time to leukopenia was significantly shorter, and when leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of leukopenia frequency with estimated enzyme activities based on the diplotypes (r2 = 0.926, p = 0.0087), there were no significant differences in the AUCs of diplotypes from those of codon 139 to predict severe AEs (AUC = 0.916, 0.921, for acute severe leukopenia, AUC = 0.990, 0.991, for severe alopecia, respectively). CONCLUSIONS: Genotyping of NUDT15 codon 139 was sufficient to predict acute severe leukopenia and alopecia in Japanese patients with IBD.