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On Behalf SADS-TW BrS registry Background Brugada syndrome (BrS) is an inheritable arrhythmic disease responsible for sudden cardiac death. Information on the prevalence and role of SCN10A variants in BrS is limited and equivocal. Purpose We aimed to investigate the prevalence and role of SCN10A variants in BrS in Han Chinese. Methods From 2000 to 2017, we prospectively and consecutively enrolled 176 unrelated BrS patients from the Han Chinese population in Taiwan (the SADS-TW BrS registry). Thirty-four BrS-related genes were screened by next-generation sequencing, using Taiwan Biobank as the population reference. The pathogenicity was evaluated by literature review and in silico analyses, including the SKAT-O algorithm. Results The SKAT-O algorithm showed that rare variants of SCN10A, but not common variants, were significantly different between BrS patients and healthy controls in the additive and dominant models (p-value Conclusions SCN10A likely pathogenic variants were present in 3.4% of Han Chinese BrS patients. Rare SCN10A variants may play a role in BrS, and may have impact on clinical and electrocardiographic manifestations. Table 1. Patient Nucleotide Amino acid TWB gnomAD_EA REVEL CADD PHRED SIFT Polyphen-2 GERP++ 1 c.5789A > T p.D1930V 0.001318 0.0008700 0.479 24.5 Damaging Possibly damaging 4.22 2 c.2341G > A p.G781R 0 0.00005301 0.866 33 Damaging Probably damaging 4.83 3 c.5587C > T p.R1863W 0.000502 0 0.832 27.8 Damaging Probably damaging 1.97 4 c.2161C > T p.P721S 0.000989 0.0009016 0.933 28.5 Damaging Probably damaging 4.19 5 c.3749G > A p.R1250Q 0 0 0.907 31 Damaging Probably damaging 4.23 6 c.1825A > T p.R609W 0.000659 0.0001591 0.811 32 Damaging Probably damaging 4.28 Clinical and predicted functional characteristics of 6 likely pathogenic SCN10A variants. EA = East Asian; GERP = Genomic Evolutionary Rate Profiling; TWB = Taiwan Biobank. Transcript: NM_006514.3. Abstract 299 Figure. Location of the SCN10A variants

Solder-based die-attach processes used to affix GaAs devices to heat spreading carriers were investigated. The microstructures of the solder materials were assessed, with a focus on void formation, and the response of the solder and backsurface metallization and carrier plating to the temperature cycles of die attachment and reflow processes. Voided regions were found in all solder joints, with a dramatic sensitivity to temperature cycles. Gold-tin alloy phases were found to dominate the microstructure of the solder for all configurations evaluated. The total thermal budget was a critical issue in the formation and transformation of various phases, as expected for low melting point alloys. NiVAu and TiPtAu backmetal systems were investigated to determine their suitability for die attachment.

Diastolic heart failure (DHF) refers to an abnormality of diastolic distensibility, filling or relaxation of the left ventricle. The genetic study of DHF is scarce in the literature. The association of renin-angiotensin system (RAS) and DHF are well known. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a case-control study to prove the hypothesis.A total of 1452 consecutive patients were analysed and 148 patients with a diagnosis of DHF confirmed by echocardiography were recruited. We had two control populations. The first controls consisted of 286 normal subjects while the second were 148 matched controls selected on a 1-to-1 basis by age, sex, hypertension, diabetes and medication use. The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; multilocus polymorphisms of the angiotensinogen gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT(1)R) gene were genotyped.In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype and the AT(1)R 1166 CC plus AC genotype. In addition, the concomitant presence of ACE DD and AT(1)R 1166 CC/AC genotypes synergistically increased the predisposition to DHF.Genetic variants in the RAS genes may determine an individual's risk to develop DHF. There is also a synergistic gene-gene interaction between the RAS genes in the development of DHF.

Idiopathic ventricular fibrillation (VF) is extremely rare in children who have not previously undergone cardiac surgery. Patients resuscitated from idiopathic VF remain at risk for recurrence. The use of an implantable cardioverter-defibrillator (ICD) effectively prevents such recurrences. We report the case of a 12-year-old girl who had a history of recurrent syncope and had survived an episode of VF. Serial studies after prolonged but successful resuscitation, including echocardiography, an electrocardiogram (ECG), and coronary angiography failed to reveal abnormal cardiac structures responsible for VF. No abnormal conduction pathways or abnormal early or late after depolarization were found on electrophysiologic study. The ST segments of the 12-lead ECG remained normal after procainamide challenge. The patient underwent ICD implantation 2 weeks after admission and syncope did not recur during a follow-up of 14 months. This report emphasizes that idiopathic VF may be responsible for syncope in children. ICD therapy prevents the recurrence of idiopathic VF and the associated risk of sudden death.

We investigated the gene expression of calcium-handling genes including L-type calcium channel, sarcoplasmic reticular calcium adenosine triphosphatase (Ca(2+)-ATPase), ryanodine receptor, calsequestrin and phospholamban in human atrial fibrillation.Recent studies have demonstrated that atrial electrical remodeling in atrial fibrillation is associated with intracellular calcium overload. However, the changes of calcium-handling proteins remain unclear.A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The messenger ribonucleic acid (mRNA) amount of the genes was measured by reverse transcription-polymerase chain reaction and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase.The mRNA of L-type calcium channel and of Ca(2+)-ATPase was significantly decreased in patients with persistent atrial fibrillation for more than 3 months (0.36+/-0.26 vs. 0.90+/-0.88 for L-type calcium channel; 0.69+/-0.42 vs. 1.21+/-0.68 for Ca(2+)-ATPase; both p0.05, all data in arbitrary unit). We further demonstrated that there was no spatial dispersion of the gene expression among the four atrial tissue sampling sites. Age, gender and underlying cardiac disease had no significant effects on the gene expression. In contrast, the mRNA levels of ryanodine receptor, calsequestrin and phospholamban showed no significant change in atrial fibrillation.L-type calcium channel and the sarcoplasmic reticular Ca(2+)-ATPase gene were down-regulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation.

We investigated the clinical characteristics and coronary risk factors of Chinese patients with suspected coronary artery disease (CAD) having low serum concentrations of both low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Of 1,450 patients with suspected CAD (age range, 30-92 years; 948 men and 502 women), 760 had established CAD. The patients were divided into three groups according to lipid profile patterns. Group 1 patients (n = 138) had low LDL-C concentrations (100 mg/dL) and low TC concentrations (160 mg/dL). They were characterized by lower triglyceride concentrations, lower frequencies of high TC/high-density lipoprotein cholesterol (HDL-C) ratios (5) and LDL-C/HDL-C ratios (5), and lower frequencies of a family history of CAD and obesity. Group 3 patients (n = 610) had LDL-C concentrations of 130 mg/dL or above and TC concentrations of 200 mg/dL or above, much higher than in group 1. The prevalence of CAD was 41.3% (57/138) in group 1. 46.7% (328/702) in group 2, and 61.5% (375/610) in group 3. Groups with higher TC and LDL-C concentrations had a higher CAD prevalence. Coronary risk factors of group 1 patients appeared to be low HDL-C concentration, high TC/HDL-C ratio, advanced age, cigarette smoking, hypertension, and diabetes mellitus. Among these risk factors, HDL-C and hypertension were independent predictors of CAD. Unlike in the other two groups, hypertension was the only independent nonlipid risk factor. We conclude that in therapy or prevention of CAD, the goals should be to reduce LDL-C concentration to below 100 mg/dL and the TC concentration to below 160 mg/dL. However, other risk factors should also be considered.

In Taiwan over the past decades there has been enormous economic growth and rapid westernization of people's life style, as well as a concomitant rise in coronary heart disease (CHD) mortality and morbidity. Studying the effects of such a degree of socioeconomic development on the coronary risk factors of the Chinese population, an ethnic group long regarded as having a low incidence of CHD, may provide some insight into the etiology of coronary atherosclerosis. Coronary risk factors among 1,449 patients (759 with CHD) were retrospectively studied. Diagnosis was established by angiography or a definite history of myocardial infarction in approximately 60% of the patients, and for the remainder, at least by noninvasive testing. The frequencies of dyslipidemia and nonlipid risk factors in patients with and without CHD were determined and compared. The lipid levels of subjects with or without CHD were close to or approaching those reported from the United States. Socioeconomic development and changes in dietary patterns seem influential in this regard. Among risk factors, high-density lipoprotein cholesterol (HDL-C), smoking, diabetes mellitus, hypertension and family history in males and, in females, total cholesterol, HDL-C, diabetes mellitus and hypertension, were significantly and independently correlated with CHD. These risk factors are similar to those found in the West; however, there is an important association of serum HDL-C concentrations with CHD, irrespective of gender. This issue requires further study in Chinese populations in other Asian countries.

Histiocytosis X is a disease of histiocyte proliferation in response to some unknown etiology. Thyroid involvement is extremely rare in the literature. In this paper, we present an 18-year-old female with histiocytosis X with thyroid involvement. This patient had had a goiter with normal thyroid function since 12 years of age. A thyroidectomy was done under the suspicion of thyroid cancer. Pathology revealed histiocytosis X. Hypoparathyroidism and hypothyroidism were noted after the operation and were treated with thyroid hormone, vitamin D and calcium carbonate. This patient also had lesions on the left side of mandible, in the suprasellar region and possibly in the right mastoid. A curettage biopsy of her mandibular lesion was also compatible with histiocytosis X. She was proven to have hypothalamic and pituitary dysfunction including hypogonadism and hypoadrenalism. Her thyroid lesion did not recur after the thyroidectomy. The toothache that she had also experienced subsided after the curettage biopsy of the mandibular lesion. Hypothalamic and pituitary dysfunction were controlled by hormone replacement. Because her disease had been running a benign clinical course, no chemotherapy was given.