Fully Automatic Coronary Calcium Score Software Empowered by Artificial Intelligence Technology:Validation Study Using Three CT Cohorts

Objective@#This study aimed to validate a deep learning-based fully automatic calcium scoring (coronary artery calcium [CAC]_auto) system using previously published cardiac computed tomography (CT) cohort data with the manually segmented coronary calcium scoring (CAC_hand) system as the reference standard. @*Materials and Methods@#We developed the CAC_auto system using 100 co-registered, non-enhanced and contrast-enhanced CT scans. For the validation of the CAC_auto system, three previously published CT cohorts (n = 2985) were chosen to represent different clinical scenarios (i.e., 2647 asymptomatic, 220 symptomatic, 118 valve disease) and four CT models. The performance of the CAC_auto system in detecting coronary calcium was determined. The reliability of the system in measuring the Agatston score as compared with CAC_hand was also evaluated per vessel and per patient using intraclass correlation coefficients (ICCs) and Bland-Altman analysis. The agreement between CAC_auto and CAC_hand based on the cardiovascular risk stratification categories (Agatston score: 0, 1–10, 11–100, 101–400, > 400) was evaluated. @*Results@#In 2985 patients, 6218 coronary calcium lesions were identified using CAC_hand. The per-lesion sensitivity and falsepositive rate of the CAC_auto system in detecting coronary calcium were 93.3% (5800 of 6218) and 0.11 false-positive lesions per patient, respectively. The CAC_auto system, in measuring the Agatston score, yielded ICCs of 0.99 for all the vessels (left main 0.91, left anterior descending 0.99, left circumflex 0.96, right coronary 0.99). The limits of agreement between CAC_auto and CAC_hand were 1.6 ± 52.2. The linearly weighted kappa value for the Agatston score categorization was 0.94. The main causes of false-positive results were image noise (29.1%, 97/333 lesions), aortic wall calcification (25.5%, 85/333 lesions), and pericardial calcification (24.3%, 81/333 lesions). @*Conclusion@#The atlas-based CAC_auto empowered by deep learning provided accurate calcium score measurement as compared with manual method and risk category classification, which could potentially streamline CAC imaging workflows.

Tricuspid Valve Imaging and Right Ventricular Function Analysis Using Cardiac CT and MRI

Cardiac computed tomography (CT) and cardiac magnetic resonance imaging (CMR) can reveal the detailed anatomy and function of the tricuspid valve and right ventricle (RV). Quantification of tricuspid regurgitation (TR) and analysis of RV function have prognostic implications. With the recently available transcatheter treatment options for diseases of the tricuspid valve, evaluation of the tricuspid valve using CT and CMR has become important in terms of patient selection and procedural guidance. Moreover, CT enables post-procedural investigation of the causes of valve dysfunction, such as pannus or thrombus. This review describes the anatomy of the tricuspid valve and CT and CMR imaging protocols for right heart evaluation, including RV function and TR analyses. We also demonstrate the pre-procedural planning for transcatheter treatment of TR and imaging of postoperative complications using CT.

Late Gadolinium Enhancement of Left Ventricular Papillary Muscles in Patients with Mitral Regurgitation

Objective@#Arrhythmogenic mitral valve prolapse (MVP) is an important cause of sudden cardiac death characterized by fibrosis of the papillary muscles or left ventricle (LV) wall, and an association between late gadolinium enhancement (LGE) of the LV papillary muscles and ventricular arrhythmia in MVP has been reported. However, LGE of the papillary muscles may be observed in other causes of mitral regurgitation, and it is not limited to patients with MVP. This study was to evaluate the association of LGE of the LV papillary muscles or ventricular wall on cardiac magnetic resonance imaging (CMR) and ventricular arrhythmia in patients with mitral regurgitation. @*Materials and Methods@#This study included 88 patients (mean age ± standard deviation, 58.3 ± 12.0 years; male, 42%) with mitral regurgitation who underwent CMR. They were allocated to the MVP (n = 43) and non-MVP (n = 45) groups, and their LGE images on CMR, clinical characteristics, echocardiographic findings, and presence of arrhythmia were compared. @*Results@#LV myocardial wall enhancement was more frequent in the MVP group than in the non-MVP group (28% vs. 11%, p = 0.046). Papillary muscle enhancement was observed in 7 (7.9%) patients. Of the 43 patients with MVP, 15 (34.8%) showed LGE in the papillary muscles or LV myocardium, including 12 (27.9%) with LV myocardial wall enhancement and 4 (9.3%) with papillary muscle enhancement. One patient with bilateral diffuse papillary muscle enhancement experienced sudden cardiac arrest due to ventricular fibrillation. Univariable logistic regression analysis showed that high systolic blood pressure (BP; odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01–1.09; p = 0.027) and ventricular arrhythmia (OR, 6.84; 95% CI, 1.29–36.19; p = 0.024) were significantly associated with LGE of the papillary muscles. @*Conclusion@#LGE of the papillary muscles was present not only in patients with MVP, but also in patients with other etiologies of mitral regurgitation, and it was associated with high systolic BP and ventricular arrhythmia. Papillary muscle enhancement on CMR should not be overlooked.

Novel Resectable Myocardial Model Using Hybrid Three-Dimensional Printing and Silicone Molding for Mock Myectomy for Apical Hypertrophic Cardiomyopathy

Objective@#We implemented a novel resectable myocardial model for mock myectomy using a hybrid method of threedimensional (3D) printing and silicone molding for patients with apical hypertrophic cardiomyopathy (ApHCM). @*Materials and Methods@#From January 2019 through May 2020, 3D models from three patients with ApHCM were generated using the end-diastolic cardiac CT phase image. After computer-aided designing of measures to prevent structural deformation during silicone injection into molding, 3D printing was performed to reproduce anatomic details and molds for the left ventricular (LV) myocardial mass. We compared the myocardial thickness of each cardiac segment and the LV myocardial mass and cavity volumes between the myocardial model images and cardiac CT images. The surgeon performed mock surgery, and we compared the volume and weight of the resected silicone and myocardium. @*Results@#During the mock surgery, the surgeon could determine an ideal site for the incision and the optimal extent of myocardial resection. The mean differences in the measured myocardial thickness of the model (0.3, 1.0, 6.9, and 7.3 mm in the basal, midventricular, apical segments, and apex, respectively) and volume of the LV myocardial mass and chamber (36.9 mL and 14.8 mL, 2.9 mL and -9.4 mL, and 6.0 mL and -3.0 mL in basal, mid-ventricular and apical segments, respectively) were consistent with cardiac CT. The volume and weight of the resected silicone were similar to those of the resected myocardium (6 mL [6.2 g] of silicone and 5 mL [5.3 g] of the myocardium in patient 2; 12 mL [12.5 g] of silicone and 11.2 mL [11.8 g] of the myocardium in patient 3). @*Conclusion@#Our 3D model created using hybrid 3D printing and silicone molding may be useful for determining the extent of surgery and planning surgery guided by a rehearsal platform for ApHCM.

Prognostic Implication of Right Ventricle Parameters Measured on Preoperative Cardiac MRI in Patients with Functional Tricuspid Regurgitation

Objective@#To investigate the prognostic value of preoperative cardiac magnetic resonance imaging (MRI) for long-term major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing tricuspid valve (TV) surgery for functional tricuspid regurgitation (TR). @*Materials and Methods@#The preoperative cardiac MR images, New York Heart Association functional class, comorbidities, and clinical events of 78 patients (median [interquartile range], 59 [51–66.3] years, 28.2% male) who underwent TV surgery for functional TR were comprehensively reviewed. Cox proportional hazards analyses were performed to assess the associations of clinical and imaging parameters with MACCEs and all-cause mortality. @*Results@#For the median follow-up duration of 5.4 years (interquartile range, 1.2–6.6), MACCEs and all-cause mortality were 51.3% and 23.1%, respectively. The right ventricular (RV) end-systolic volume index (ESVI) and the systolic RV mass index (RVMI) were higher in patients with MACCEs than those without them (77 vs. 68 mL/m2 , p = 0.048; 23.5 vs. 18.0%, p = 0.011, respectively). A high RV ESVI was associated with all-cause mortality (hazard ratio [HR] per value of 10 higher ESVI = 1.10, p = 0.03). A high RVMI was also associated with all-cause mortality (HR per increase of 5 mL/m2 RVMI = 1.75, p < 0.001).After adjusting for age and sex, only RVMI remained a significant predictor of MACCEs and all-cause mortality (p < 0.05 for both). After adjusting for multiple clinical variables, RVMI remained significantly associated with all-cause mortality (p = 0.005). @*Conclusion@#RVMI measured on preoperative cardiac MRI was an independent predictor of long-term outcomes in patients who underwent TV surgery for functional TR.

Cardiac Behçet's Disease Presenting with Right Ventricular Endomyocardial Fibrosis and Intracardiac Thrombosis: a Case Report

Behçet’s disease is a chronic inflammatory disorder involving vessels of various sizes and organs, including the skin, joints, gastrointestinal tract, lungs, and cardiovascular system. The etiology of Behçet’s disease is unclear, and clinical diagnosis is important in the absence of definitive laboratory or pathological findings diagnostic of Behçet’s disease. Cardiac involvement is rare but might present as endocarditis, myocarditis, pericarditis, or intracardiac thrombosis. This report presents a case of Behçet’s disease involving the heart in a 22-year-old man with unusual manifestations of right ventricular fibrosis and intracardiac thrombosis. Cardiac magnetic resonance imaging revealed multiple intracardiac thrombi and delayed diffuse subendocardial enhancement involving the right ventricle. No peripheral eosinophilia was detected. Endomyocardial biopsy showed mixed inflammatory cell infiltrates. Based on the patient’s clinical history of oral ulcer and arthritis, a diagnosis of Behçet’s disease was made considering the clinical, radiological, and histological findings. Intracardiac thrombi and endomyocardial fibrosis are rare manifestations of Behçet’s disease, and the diagnosis is often a clinical challenge. Early diagnosis is important for appropriate management. Behçet’s disease should be considered in the differential diagnosis of patients with intracardiac thrombosis and endomyocardial fibrosis of the right chamber.

Late Gadolinium Enhancement of Left Ventricular Papillary Muscles in Patients with Mitral Regurgitation

Objective@#Arrhythmogenic mitral valve prolapse (MVP) is an important cause of sudden cardiac death characterized by fibrosis of the papillary muscles or left ventricle (LV) wall, and an association between late gadolinium enhancement (LGE) of the LV papillary muscles and ventricular arrhythmia in MVP has been reported. However, LGE of the papillary muscles may be observed in other causes of mitral regurgitation, and it is not limited to patients with MVP. This study was to evaluate the association of LGE of the LV papillary muscles or ventricular wall on cardiac magnetic resonance imaging (CMR) and ventricular arrhythmia in patients with mitral regurgitation. @*Materials and Methods@#This study included 88 patients (mean age ± standard deviation, 58.3 ± 12.0 years; male, 42%) with mitral regurgitation who underwent CMR. They were allocated to the MVP (n = 43) and non-MVP (n = 45) groups, and their LGE images on CMR, clinical characteristics, echocardiographic findings, and presence of arrhythmia were compared. @*Results@#LV myocardial wall enhancement was more frequent in the MVP group than in the non-MVP group (28% vs. 11%, p = 0.046). Papillary muscle enhancement was observed in 7 (7.9%) patients. Of the 43 patients with MVP, 15 (34.8%) showed LGE in the papillary muscles or LV myocardium, including 12 (27.9%) with LV myocardial wall enhancement and 4 (9.3%) with papillary muscle enhancement. One patient with bilateral diffuse papillary muscle enhancement experienced sudden cardiac arrest due to ventricular fibrillation. Univariable logistic regression analysis showed that high systolic blood pressure (BP; odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01–1.09; p = 0.027) and ventricular arrhythmia (OR, 6.84; 95% CI, 1.29–36.19; p = 0.024) were significantly associated with LGE of the papillary muscles. @*Conclusion@#LGE of the papillary muscles was present not only in patients with MVP, but also in patients with other etiologies of mitral regurgitation, and it was associated with high systolic BP and ventricular arrhythmia. Papillary muscle enhancement on CMR should not be overlooked.

Novel Resectable Myocardial Model Using Hybrid Three-Dimensional Printing and Silicone Molding for Mock Myectomy for Apical Hypertrophic Cardiomyopathy

Objective@#We implemented a novel resectable myocardial model for mock myectomy using a hybrid method of threedimensional (3D) printing and silicone molding for patients with apical hypertrophic cardiomyopathy (ApHCM). @*Materials and Methods@#From January 2019 through May 2020, 3D models from three patients with ApHCM were generated using the end-diastolic cardiac CT phase image. After computer-aided designing of measures to prevent structural deformation during silicone injection into molding, 3D printing was performed to reproduce anatomic details and molds for the left ventricular (LV) myocardial mass. We compared the myocardial thickness of each cardiac segment and the LV myocardial mass and cavity volumes between the myocardial model images and cardiac CT images. The surgeon performed mock surgery, and we compared the volume and weight of the resected silicone and myocardium. @*Results@#During the mock surgery, the surgeon could determine an ideal site for the incision and the optimal extent of myocardial resection. The mean differences in the measured myocardial thickness of the model (0.3, 1.0, 6.9, and 7.3 mm in the basal, midventricular, apical segments, and apex, respectively) and volume of the LV myocardial mass and chamber (36.9 mL and 14.8 mL, 2.9 mL and -9.4 mL, and 6.0 mL and -3.0 mL in basal, mid-ventricular and apical segments, respectively) were consistent with cardiac CT. The volume and weight of the resected silicone were similar to those of the resected myocardium (6 mL [6.2 g] of silicone and 5 mL [5.3 g] of the myocardium in patient 2; 12 mL [12.5 g] of silicone and 11.2 mL [11.8 g] of the myocardium in patient 3). @*Conclusion@#Our 3D model created using hybrid 3D printing and silicone molding may be useful for determining the extent of surgery and planning surgery guided by a rehearsal platform for ApHCM.

Prognostic Implication of Right Ventricle Parameters Measured on Preoperative Cardiac MRI in Patients with Functional Tricuspid Regurgitation

Objective@#To investigate the prognostic value of preoperative cardiac magnetic resonance imaging (MRI) for long-term major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing tricuspid valve (TV) surgery for functional tricuspid regurgitation (TR). @*Materials and Methods@#The preoperative cardiac MR images, New York Heart Association functional class, comorbidities, and clinical events of 78 patients (median [interquartile range], 59 [51–66.3] years, 28.2% male) who underwent TV surgery for functional TR were comprehensively reviewed. Cox proportional hazards analyses were performed to assess the associations of clinical and imaging parameters with MACCEs and all-cause mortality. @*Results@#For the median follow-up duration of 5.4 years (interquartile range, 1.2–6.6), MACCEs and all-cause mortality were 51.3% and 23.1%, respectively. The right ventricular (RV) end-systolic volume index (ESVI) and the systolic RV mass index (RVMI) were higher in patients with MACCEs than those without them (77 vs. 68 mL/m2 , p = 0.048; 23.5 vs. 18.0%, p = 0.011, respectively). A high RV ESVI was associated with all-cause mortality (hazard ratio [HR] per value of 10 higher ESVI = 1.10, p = 0.03). A high RVMI was also associated with all-cause mortality (HR per increase of 5 mL/m2 RVMI = 1.75, p < 0.001).After adjusting for age and sex, only RVMI remained a significant predictor of MACCEs and all-cause mortality (p < 0.05 for both). After adjusting for multiple clinical variables, RVMI remained significantly associated with all-cause mortality (p = 0.005). @*Conclusion@#RVMI measured on preoperative cardiac MRI was an independent predictor of long-term outcomes in patients who underwent TV surgery for functional TR.

Preoperative Cardiac Computed Tomography Characteristics Associated with Recurrent Aortic Regurgitation after Aortic Valve Re-Implantation

24 mm² (sensitivity, 76.5%; specificity 64.8%), and the area under the ROC curve (AUC) was 0.72. For ASR(area), the cut-off value was > 1.58 (sensitivity, 76.5%; specificity, 58.0%) and the AUC was 0.64. Multivariable Cox regression showed that ARO > 24 mm² (hazard ratio = 3.79, p = 0.020) was a potential independent parameter for recurrent 3 + AR. ROC for the linear regression model showed that the AUC for both ARO and ASR(area) was 0.73 (95% confidence interval, 0.64–0.81, p < 0.001).CONCLUSION: ARO and ASR(area) detected on preoperative cardiac CT would be potentially helpful for identifying AR patients who may benefit from the David operation.

Comparison of Clinical, Angiographic Features and Outcome in Takayasu's Arteritis and Behçet's Disease With Arterial Involvement

OBJECTIVE: Takayasu's arteritis (TAK) is a vasculitis that primarily involves the aorta and its branches. In Behçet's disease (BD), systemic vasculitis is one of major manifestations. We aimed to compare clinical and angiographic features and outcome between TAK and BD with arterial involvement.METHODS: We retrospectively reviewed medical records of 206 TAK patients and 50 BD patients between 1995 and 2015. Angiographic lesions were evaluated via computed tomography, magnetic resonance imaging, and/or conventional angiography.RESULTS: Fever (30% vs. 9.2%, p<0.001) and arthralgia (36% vs. 7.3%, p<0.001) were more common in BD. C-reactive protein was higher in BD compared with TAK (5.85 mg/dL vs. 2.08 mg/dL, p<0.001). Stenosis (89.8% vs. 60%, p<0.001) and occlusion (65.5% vs. 32%, p<0.001) were more observed in TAK. In contrast, aneurysm was common in BD (62% vs. 20.9%, p<0.001). The carotid artery (73.3% vs. 30%, p<0.001), subclavian artery (71.4% vs. 16%, p<0.001), descending aorta (35% vs. 12%, p=0.002), renal artery (23.8% vs. 10%, p=0.032), superior mesenteric artery (18.4% vs. 4%, p=0.012), and brachiocephalic trunk (13.6% vs. 2%, p=0.020) were more commonly involved in TAK, whereas the femoral artery (10% vs. 2.4%, p=0.027) was more frequently involved in BD. During follow-up, arterial dissection (10% vs. 1.9%, p=0.016), rupture (12% vs. 0.5%, p<0.001), and arterial replacement/resection (66% vs. 9.7%, p<0.001) were more observed in BD.CONCLUSION: TAK differs from BD regarding clinical features and vascular involvement patterns. BD exhibits a higher rate of vascular complications.

Automated Segmentation of Left Ventricular Myocardium on Cardiac Computed Tomography Using Deep Learning

Objective@#To evaluate the accuracy of a deep learning-based automated segmentation of the left ventricle (LV) myocardium using cardiac CT. @*Materials and Methods@#To develop a fully automated algorithm, 100 subjects with coronary artery disease were randomly selected as a development set (50 training / 20 validation / 30 internal test). An experienced cardiac radiologist generated the manual segmentation of the development set. The trained model was evaluated using 1000 validation set generated by an experienced technician. Visual assessment was performed to compare the manual and automatic segmentations. In a quantitative analysis, sensitivity and specificity were calculated according to the number of pixels where two three-dimensional masks of the manual and deep learning segmentations overlapped. Similarity indices, such as the Dice similarity coefficient (DSC), were used to evaluate the margin of each segmented masks. @*Results@#The sensitivity and specificity of automated segmentation for each segment (1–16 segments) were high (85.5– 100.0%). The DSC was 88.3 ± 6.2%. Among randomly selected 100 cases, all manual segmentation and deep learning masks for visual analysis were classified as very accurate to mostly accurate and there were no inaccurate cases (manual vs. deep learning: very accurate, 31 vs. 53; accurate, 64 vs. 39; mostly accurate, 15 vs. 8). The number of very accurate cases for deep learning masks was greater than that for manually segmented masks. @*Conclusion@#We present deep learning-based automatic segmentation of the LV myocardium and the results are comparable to manual segmentation data with high sensitivity, specificity, and high similarity scores.

Sinus of Valsalva Thrombosis Detected on Computed Tomography after Transcatheter Aortic Valve Replacement

Background and Objectives@#Leaflet thrombosis after transcatheter aortic valve replacement (TAVR) has been reported recently, whereas thrombus formation in sinus of Valsalva has yet to be fully evaluated. This study describes clinical and cardiac computed tomography (CT) findings of patients with sinus of Valsalva thrombosis. @*Methods@#Between March 2011 and Aug 2019, 192 patients underwent cardiac CT after TAVR. After a retrospective review of CT images, 9 patients (82 years, male:female=2:7) who had sinus of Valsalva thrombosis identified by cardiac CT were selected for this study. Patient demographics, interval between TAVR and cardiac CT scan, location and CT attenuation of sinus of Valsalva thrombosis, and presence of concurrent leaflet thrombosis were evaluated. @*Results@#The median interval between TAVR and cardiac CT was 11 days. Sinus of Valsalva thrombosis was frequently detected in the non-coronary sinus (89%, 8/9), and predominantly located in the bottom of the sinus extending upward towards the sinotubular junction. Three patients had concomitant leaflet thrombosis, and 3 patients had subclinical embolic stroke noted on brain magnetic resonance imaging. All patients had been prescribed aspirin and clopidogrel after TAVR for at least 6 months without anticoagulants. @*Conclusions@#Cardiac CT after TAVR can detect sinus of Valsalva thrombosis, and attention should be paid to this potential source of subsequent systemic embolization.

Extent of Subprosthetic Pannus after Aortic Valve Replacement: Changes Over Time and Relationship with Echocardiographic Findings

Purpose@#This study aimed to evaluate changes of subprosthetic pannus on cardiac CT and determine its relationship to echocardiographic findings in patients with mechanical aortic valve replacement (AVR). @*Materials and Methods@#Between April 2011 and November 2017, 17 AVR patients (56.8 ± 8.9 years, 12% male) who showed pannus formation on CT and had undergone both follow-up CT and echocardiography were included. The mean interval from AVR to the date of pannus detection was 10.5 ± 7.1 years. In the initial and follow-up CT and echocardiography, the pannus extent and echocardiographic parameters were compared using paired t-tests. The relationship between the opening angle of the prosthetic valve and the pannus extent was evaluated using Pearson correlation analysis. @*Results@#The pannus extent was significantly increased on CT (p < 0.05). The peak velocity (3.9 ± 0.8 m/s vs. 4.2 ± 0.8 m/s, p = 0.03) and mean pressure gradient (36.4 ± 15.5 mm Hg vs. 42.1 ± 15.8 mm Hg, p = 0.03) were significantly increased. The mean opening angles of the mechanical aortic leaflets were slightly decreased, but there was no statistical significance (73.1 ± 8.3° vs. 69.4 ± 12.1°, p = 0.12). The opening angle of the prosthetic leaflets was inversely correlated with the pannus extent (r = −0.57, p < 0.001). @*Conclusion@#The pannus extent increases over time, increasing transvalvular peak velocity and the pressure gradient. CT can be used to evaluate the pannus extent associated with hemodynamic changes that need to be managed by surgical intervention.

Impact of Diabetes Control on Subclinical Atherosclerosis: Analysis from Coronary Computed Tomographic Angiography Registry

Background@#There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis. @*Methods@#We analyzed 6,434 consecutive asymptomatic individuals without previous history of coronary artery disease who underwent coronary computed tomographic angiography (CCTA) (mean age, 53.7±7.6 years and 4,694 men [73.0%]). The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Study participants were categorized as normal (n=5,319), controlled diabetes (glycosylated hemoglobin [HbA1c] <7%, n=747), or uncontrolled diabetes (HbA1c ≥7%, n=368), respectively. @*Results@#Compared with normal individuals, there were no statistically significant differences in the risk of for any atherosclerotic plaque (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.98 to 1.38; p=0.086) and significant coronary artery stenosis (OR, 1.08; 95% CI, 0.82 to 1.42; p=0.583) in controlled diabetic individuals. In contrast, uncontrolled diabetic individuals had consistently higher risks of any atherosclerotic plaque (OR, 2.16; 95% CI, 1.70 to 2.75; p<0.001) and significant coronary artery stenosis (OR, 3.34; 95% CI, 2.52 to 4.43; p<0.001) than normal individuals. During a follow-up of median 5.4 years, there was no significant difference in cardiac events between normal and controlled diabetic individuals (p=0.365). However, uncontrolled diabetes was associated with an increased risk of cardiac events compared with normal individuals (P<0.001) and controlled diabetic individuals (p=0.023). @*Conclusion@#Asymptomatic uncontrolled diabetes was associated with significant subclinical coronary atherosclerosis with subsequent high risk for cardiac events.

Treatment Outcomes of Vagus Nerve Stimulation in Lennox-Gastaut Syndrome / 대한소아신경학회지

PURPOSE@#Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic encephalopathies and frequently patients with this syndrome respond poorly to antiepileptic drugs. The aim of this study was to evaluate the treatment outcomes of vagus nerve stimulation (VNS) in LGS patients with drug-resistant epilepsy.@*METHODS@#We analyzed the clinical files, collected over 5 years, of children with LGS who received VNS treatment.@*RESULTS@#Seven children were included in this study (four males, three females; mean age of VNS insertion 12.4±3.5 years). All the patients had generalized tonic seizures and there were various other seizure types including myoclonic seizures, atonic seizures, and atypical absence seizures. Although two patients had normal imaging, five patients had abnormalities on imaging, including pachygyria, cortical dysplasia, kernicterus, and a chromosomal anomaly. Comparing the baseline seizure frequency to the frequency after the VNS surgery, the seizure frequency at the last follow-up showed a decrease of 57.2% (0% to 100%) on average (P=0.028) and one patient achieved seizure free status. Only two children were given additional antiepileptic drugs with the aim of managing their seizures. There was no mortality or complications related to the VNS therapy except one case requiring intensive care unit admission due to pneumonia. Comparing the results before and after VNS surgery, the VNS therapy also had a tendency to have a positive effect on quality of life (P=0.066).@*CONCLUSION@#In LGS patients with drug resistant epilepsy who are not candidates for a corpus callosotomy or resective surgery, VNS could be an effective, low-risk adjunct therapy for decreasing seizure frequency.

Twenty-one-year follow-up of variable onset MELAS syndrome with heteroplasmic nt3243A>G mtDNA mutation: A case report

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder of which m.3243A>G is the most commonly associated mutation, resulting in an inability to meet the energy requirements of various organs. MELAS poses a diagnostic challenge owing to its multiple organ involvement and great clinical variability due to its heteroplasmic nature. We report three cases from a family who were initially misdiagnosed with myasthenia gravis or undiagnosed. Although there is no optimal consensus treatment approach for patients with MELAS because of the disease's heterogeneity, our 21-year-long therapy regimen of l-arginine, l-carnitine, and coenzyme Q10 supplementation combined with dietary management appeared to provide noticeable protection from the symptoms and complications. Prompt early diagnosis is important, as optimal multidisciplinary management and early intervention may improve outcomes.

Calpain-2 as a Treatment Target in Prenatal Stress-induced Epileptic Spasms in Infant Rats

Stress can induce a serious epileptic encephalopathy that occurs during early infancy. Recent studies have revealed that prenatal stress exposure is a risk factor for the development of infantile spasms. Our previous work demonstrates that prenatal stress with betamethasone-induced alterations to the expression of the K⁺/Cl⁻ co-transporter (KCC2) in gamma-aminobutyric acid (GABA) interneurons lowers the seizure threshold in exposed animals. Here, we further investigated the mechanisms involved in this KCC2 dysfunction and explored possible treatment options. We stressed Sprague-Dawley rats prenatally and further treated dams with betamethasone on gestational day 15, which increases seizure susceptibility and NMDA (N-Methyl-D-aspartate)-triggered spasms on postnatal day 15. In this animal model, first, we evaluated baseline calpain activity. Second, we examined the cleavage and dephosphorylation of KCC2. Finally, we checked the effect of a calpain inhibitor on seizure occurrence. The phosphorylated-N-methyl-D-aspartate Receptor 2B (NR2B):non-phosphorylated NR2B ratio was found to be higher in the cortex of the prenatally stressed beta-methasone model. We further found that the betamethasone model exhibited increased phosphorylation of calpain-2 and decreased phosphorylation of KCC2 and Glutamic acid decarboxylase 67 (GAD67). After using a calpain inhibitor in prenatal-stress rats, the seizure frequency decreased, while latency increased. GABAergic depolarization was further normalized in prenatal-stress rats treated with the calpain inhibitor. Our study suggests that calpain-dependent cleavage and dephosphorylation of KCC2 decreased the seizure threshold of rats under prenatal stress. Calpain-2 functions might, thus, be targeted in the future for the development of treatments for epileptic spasms.

Assessment of Tissue Perfusion with Blood Oxygenation Level-Dependent Magnetic Resonance Imaging in Critical Limb Ischemia

No abstract available.

Different Clinical Features and Lower Scores in Clinical Scoring Systems for Appendicitis in Preschool Children: Comparison with School Age Onset / 대한소아소화기영양학회지

PURPOSE: To clarify the clinical features of appendicitis in preschool children and to explore clinical appendicitis scoring systems in this age group. METHODS: We retrospectively collected data on 142 children, aged 10 years or younger, with confirmed diagnosis of appendicitis based on surgical and pathologic findings. Enrolled subjects were divided into two groups: Group 1 (preschool children aged ≤5 years, n=41) and Group 2 (school children aged >5 to ≤10 years, n=101). Data analyzed included clinical presentation, laboratory findings, the pediatric appendicitis score (PAS), and the modified Alvarado score (MAS). RESULTS: The most common presenting symptom was abdominal pain in both groups (92.7% vs. 97.0%). Other presenting symptoms were as follows: fever (65.9%), vomiting (68.3%), right lower quadrant (RLQ) localization (24.4%), anorexia (14.6%), and diarrhea (7.3%) in Group 1, and RLQ localization (74.3%), vomiting (71.3%), anorexia (52.5%), fever (47.5%), and diarrhea (11.9%) in Group 2. Perforation and abscess occurred more frequently in Group 1 than in Group 2 (43.9% vs. 12.9%, p < 0.001; 34.1% vs. 5.0%, p < 0.001; respectively). PAS and MAS were lower in Group 1 than in Group 2 (4.09±1.97 vs. 6.91±1.61, p=0.048; 4.65±1.79 vs. 6.51±1.39, p=0.012; respectively). CONCLUSION: In preschool children, appendicitis often presents with atypical features, more rapid progression, and higher incidence of complications. This age group is more likely to have lower PAS and MAS than those of school children.