• Journal of The Korean Society of Inherited Metabolic disease
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• v.21 no.1
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• pp.22-27
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• 2021

Propionic acidemia (PA) is an inherited autosomal recessive disorder, due to the deficiency of propionyl-CoA carboxylase (PCC). PCC is the enzyme which catalyzes the conversion of propionyl-CoA to D-methylmalonyl-CoA, and it is critical for the metabolism of amino acids, odd-chain fatty acids, and side chains of cholesterol. The clinical manifestations present mostly at the neonatal period with life-threatening metabolic acidosis and hyperammonemia. Here, we described a case of a 16-year-old Korean boy with late-onset PA who presented with embolic cerebral infarction due to dilated cardiomyopathy (DCMP) with left ventricular noncompaction. And he has family history of sudden cardiac death, so we performed metabolic screening and genetic tests. Elevated levels of 3-hydroxypropionic acid, methylcitric acid and propionylglycerine were detected in urine. Plasma acylcarnitine profile showed elevated propionylcarnitine (C3). Diagnosis of PA was confirmed by genetic analysis, which revealed compound heterozygous mutations, c.[1151T>G] (p.[Phe384Cys]) and c.[1228C>T] (p.[Arg410Trp]) in PCCB gene. His heart function is in improving state and the results of biochemical analysis are stable with heart failure medication and metabolic managements. We present a case of patient without episodes of metabolic decompensation who manifests DCMP as the first symptom of PA.

• Genomics & Informatics
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• v.20 no.4
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• pp.44.1-44.13
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• 2022

Brugada syndrome (BS) is an autosomal dominant inheritance cardiac arrhythmia disorder associated with sudden death in young adults. Thailand has the highest prevalence of BS worldwide, and over 60% of patients with BS still have unclear disease etiology. Here, we performed a new viral metagenome analysis pipeline called VIRIN and validated it with whole genome sequencing (WGS) data of HeLa cell lines and hepatocellular carcinoma. Then the VIRIN pipeline was applied to identify viral integration positions from unmapped WGS data of Thai males, including 100 BS patients (case) and 100 controls. Even though the sample preparation had no viral enrichment step, we can identify several virus genes from our analysis pipeline. The predominance of human endogenous retrovirus K (HERV-K) viruses was found in both cases and controls by blastn and blastx analysis. This study is the first report on the full-length HERV-K assembled genomes in the Thai population. Furthermore, the HERV-K integration breakpoint positions were validated and compared between the case and control datasets. Interestingly, Brugada cases contained HERV-K integration breakpoints at promoters five times more often than controls. Overall, the highlight of this study is the BS-specific HERV-K breakpoint positions that were found at the gene coding region "NBPF11" (n = 9), "NBPF12" (n = 8) and long non-coding RNA (lncRNA) "PCAT14" (n = 4) region. The genes and the lncRNA have been reported to be associated with congenital heart and arterial diseases. These findings provide another aspect of the BS etiology associated with viral genome integrations within the human genome.

• Korean Circulation Journal
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• v.53 no.12
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• pp.843-854
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• 2023

Background and Objectives: We evaluated the effect of diabetes on the relationship between body mass index (BMI) and clinical outcomes in patients following percutaneous coronary intervention (PCI) with drug-eluting stent implantation. Methods: A total of 6,688 patients who underwent PCI were selected from five different registries led by Korean Multicenter Angioplasty Team. They were categorized according to their BMI into the following groups: underweight (<18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight to obese (≥25.0 kg/m²). Major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of death, nonfatal myocardial infarction, stroke, and target-vessel revascularization, were compared according to the BMI categories (underweight, normal and overweight to obese group) and diabetic status. All subjects completed 1-year follow-up. Results: Among the 6,688 patients, 2,561 (38%) had diabetes. The underweight group compared to normal weight group had higher 1-year MACCE rate in both non-diabetic (adjusted hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.04-4.84; p=0.039) and diabetic patients (adjusted HR, 2.86; 95% CI, 1.61-5.07; p<0.001). The overweight to obese group had a lower MACCE rate than the normal weight group in diabetic patients (adjusted HR, 0.67 [0.49-0.93]) but not in non-diabetic patients (adjusted HR, 1.06 [0.77-1.46]), with a significant interaction (p-interaction=0.025). Conclusions: Between the underweight and normal weight groups, the association between the BMI and clinical outcomes was consistent regardless of the presence of diabetes. However, better outcomes in overweight to obese over normal weight were observed only in diabetic patients. These results suggest that the association between BMI and clinical outcomes may differ according to the diabetic status.

• Korean Circulation Journal
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• v.53 no.10
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• pp.693-707
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• 2023

Background and Objectives: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. Methods: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. Results: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). Conclusions: There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

• Korean Circulation Journal
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• v.54 no.7
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• pp.409-421
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• 2024

Background and Objectives: The recent developments in chronic thromboembolic pulmonary hypertension (CTEPH) are emphasizing the multidisciplinary team. We report on the changes in clinical practice following the development of a multidisciplinary team, based on our 7 years of experience. Methods: Multidisciplinary team was established in 2015 offering both balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) with technical upgrades by internal and external expertise. For operable cases, PEA was recommended as the primary treatment modality, followed by pulmonary angiography and right heart catheterization after 6 months to evaluate treatment effect and identify patients requiring further BPA. For patients with inoperable anatomy or high surgical risk, BPA was recommended as the initial treatment modality. Patient data and clinical outcomes were closely monitored. Results: The number of CTEPH treatments rapidly increased and postoperative survival improved after team development. Before the team, 38 patients were treated by PEA for 18 years; however, 125 patients were treated by PEA or BPA after the team for 7 years. The number of PEA performed was 64 and that of BPA 342 sessions. World Health Organization functional class I or II was achieved in 93% of patients. The patients treated with PEA was younger, male dominant, higher pulmonary artery pressure, and smaller cardiac index, than BPA-only patients. In-hospital death after PEA was only 1 case and none after BPA. Conclusions: The balanced development of BPA and PEA through a multidisciplinary team approach proved synergistic in increasing the number of actively treated CTEPH patients and improving clinical outcomes.

• Neonatal Medicine
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• v.18 no.2
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• pp.221-227
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• 2011

Purpose: The objectives were to identify the characteristics of neonates with hydrops fetalis, and to identify the risk factors associated with mortality. Methods: A retrospective review of AMC (Asan Medical Center) dataset was performed from January 1990 to June 2009. The characteristics of 71 patients with hydrops fetalis were investigated and they were divided into two groups: the survived group and the expired group. Various perinatal and neonatal factors in two groups were compared to find out risk factors associated with mortality based on univariate analysis, followed by multiple regression analyses (SPSS version 18.0). Results: Of those 71 neonates (average gestational age: 33 weeks, birth weight: 2.6 kg), 38 survived, 33 died, resulting in overall mortality rate of 46.5%. The most common etiology was idiopathic followed by chylothorax, cardiac anomalies, twin-to-twin transfusion, meconium peritonitis, cardiac arrythmias, and congenital infections. Factors that were associated independently with mortality in logistic regression analyses were low 5-minutes Apgar score, hyaline membrane disease and delayed in achieving 50th percentile ideal body weight for appropriate gestational age by 10 days. Conclusion: In this study, 5-minutes Apgar score, hyaline membrane disease and delayed in achieving 50th percentile ideal body weight for appropriate gestational age by 10 days were significant risk factors associated with mortality in hydrops fetalis. Therefore, the risk of death among neonates with hydrops fetalis depends on the illness immediately after birth and severity of hydrops fetalis. Informations from this study may prove useful in prediction of prognosis to neonates with hydrops fetalis.

• Journal of Chest Surgery
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• v.40 no.12
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• pp.811-816
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• 2007

Background: We analyzed our experience of arrhythmia surgery in patients with congenital heart disease. Material and Method: A retrospective review was performed on 43 consecutive patients with congenital heart disease, who underwent arrhythmia surgery between June 1998 and June 2006. Result: The median age at surgery was 52 years ($4{\sim}75$ years). The most frequent cardiac anomaly was an atrial septal defect (23/43, 53.5%). The types of arrhythmias were atrial flutter-fibrillation, intermittent non-sustainable ventricular tachycardia and others in 37, 2 and 4, respectively. Arrhythmia surgery consisted of a bi-atrial maze operation in 18 patients (modified cox maze III procedure in 5 patients, and a right side maze plus pulmonary vein cryo-isolation in 13), right side maze operation in 18 patients, cavo-tricuspid isthmus cryoablation for benign atrial flutter in 4 patients, right ventricular endocardial cryoablation in 2 patients and extranodal cryoablation for atrioventricular node re-entry tachycardia in 1 patient. The median follow-up was 23.8 months ($1{\sim}95.2$ months). There was no early mortality, and one late non-cardiac related death. The overall rates of restored sinus rhythm before discharge and $3{\sim}6$ months after surgery were 79% and 81%, respectively (bi-atrial maze group: 72% and 83%, right-side maze group: 77%, 77%). Conclusion: Arrhythmias associated with congenital heart disease can be safely treated surgically with an excellent intermediate-term outcome.

• Journal of Chest Surgery
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• v.30 no.3
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• pp.287-292
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• 1997

.Itrial fibrillation is one of the most common cardiac arrhythmias requiring treatment. About 60% of patients with mitral valvular disease have atrial fibrillation and one third of patients with atrial fibrillation may have the past history of thromboembolic events. Between April 1994 and June 1995, 20 patients with organic heart diseases combined with atrial fibrillation underwent open heart surgery including Cox-maze 111 procedure. There were 6 men and 14 women with an average age of 48 years (range, 31 to 66 years). Nineteen patients had valvular heart diseases and 1 ventricular septal defEct (VSD). Mean duration of atrial fibrillation was 36 months (:42 months) (range, 1 to 132 months). T e past medical history of thromboembolic events was positive in 7 patients (35%) and left atrial thrombus was detected in 9 patients (45%). The concomitant procedures were mitral valve replacement (MVR) and aortic valve replacement (AVR) in 5 patients, MVR in 4, MVd and tricuspid annuloplasty(TAP) in 4, mitral valvuloplasty(Mln) in 3, Mln and Tln in 1, MIW and coronary artery bypass surgery in 1, AVR in 1, and patch closure of VSD in 1. Mean aortic cross-clamping time was 175 minutes (range, 116 to 270 minutes). Atrial fibrillation recurred in 16 patients (80%) during the early postoperative period, but, recurrent atrial fibrillation was converted to regular rhythm at postoperative forty-first day in average. There was no early or late death in this series of 20 patients and postoperative complications were inappropriate tachycardia in 5 patients (25%), low cardiac output syndrome in 3 (15%), aggravated hemiplegic in 1, and acute renal failure in 1. Mean follow-up interval of patient was 16.5 months (range, 10.5 to 24 months) and all patients are currently in regular rhythm. Seventeen patients (85%) are in sinus rhythm and 3 (15%) in junctional rhythm. Right atrial contraction was detected in 95% of patients and left atrial contraction in 63% on postoperative transthoracic echocardiogram. The surgical treatment of atrial fibrillation concomitant with open heart surgery is warranted in the recent clinical setting of improved myocardial protection technique, considering the untoward side-effects of atrial fibrillation.

• Journal of Chest Surgery
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• v.30 no.7
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• pp.663-669
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• 1997

This is a report on the clinical outcome and hemodynamic profile of the ATSwcardiac valve prosthesis, which is a recently introduced pyrolytic carbon bileaflet prosthesis. We retrospectively reviewed the early outcome of 100 consecutive patients who underwent isolated cardiac valve replacement with the ATS(w prosthesis from October 1994 through June 1996 at our hospital. All patients were evaluated with Doppler echocardiography before discharge from the hospital. The mean age of the patients was 48.6 years(range: 2 to 74). A tota of 124 prosthesis were implanted; 71 mitral, 46 aortic, and 7 tricuspid. The two most frequently used sizes were 27 mm(40.8%) and 29 mm(35.2%) in the mitral position, and 23 mm(30.4%) and 21 mm(28.3%) in the aortic position. There was no early or late death. The total follow-up period was 950 patient-months with 99% follow-up rate. Serious late morbidity occurred in three patients; reoperation in two patients for late rupture of Sinus of Valsava in one and for endocarditis with prosthetic dehiscence in the other, and intracranial hemorrhage due to hypertension in one patient. There has been no thromboembolic complication or structural valval deterioration. In the mitral position, the average values of peak and mean transprosthetic pressure gradients and valve area calculated from pressure half time were 6.9$\pm$2.8 mmHg, 2.6$\pm$ 1.5 mmHg, and 2.7 $\pm$0.8 cm2 respectively. In the aortic position, the peak and mean pressure gradients'were 26.4 $\pm$ 15.9 mmHg and 14.2 $\pm$ 7.9 mmHg. For the mitra prostheses larger than 25-mm size, there was no significant difference among prosthetic sizes in terms of transprosthetic gradients, whereas there was a significant negative correlation between the prosthesis size and the transprosthetic gradients for the aortic valves. The peak and mean Pressere pradients were 52.2 $\pm$ 17.6 tmHg and 26.9$\pm$ 7.4 mmHg across the 19-mm aortic Prostheses, and 27.1 $\pm$ 11.9 mmHg and 13.3$\pm$6.6 mmHg across the 21-mm size. Above results can lead to the conclusion that the early clinical outcome of the ATS valve prosthesis is quite satisfactory, And the hemodynamic characteristics are comparable, if not better, with other bileaflet prostheses.

• Journal of Chest Surgery
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• v.41 no.6
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• pp.695-702
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• 2008

Background: The choice between a bioprosthetic and a mechanical valve is an important decision in cardiac valve surgery, and the durability of the tissue valve is a major decision factor. We retrospectively evaluated the midterm results of bioprosthetic valve replacement in the mitral position. Material and Method: The subjects were all patients who had undergone mitral bioprosthesis replacement between July 1989 and August 200.7. Among the 216 patients, there were 236 surgical cases. The mean age was $63{\pm}15$ years, and the male to female ratio was 1 : 3. We retrospectively analyzed hospital and outpatient records such that the total follow-up duration amounted to 760.2 patient-years, and the mean follow-up duration was $41.9{\pm}40.7$ months (range $0{\sim}212$ months). Result: Early death occurred in 18 patients (8.3%), and 13 of these underwent concomitant cardiac procedures. The survival rate after 5 years was $79.9{\pm}3.5%$, and the survival rate after 8 years was $65.5{\pm}5.5%$, while freedom from structural valve deterioration (SVD) was $96.2{\pm}2.2%$ at 5 years and $85.9{\pm}5.3%$ at 8 years. Freedom from reoperation was $90.6{\pm}1.7%$ at 5 years and $90.4{\pm}4.2%$ at 8 years, while freedom from reoperation for SVD was $98.1{\pm}1.2%$ at 5 years and $92.3{\pm}4.1%$ at 8 years. On multivariate analysis of preoperative risk factors, small valve size (between 25mm and 27mm) was a significant risk factor for reoperation, and low LV ejection fraction (<40%) was a significant risk factor for SVD and mortality. Conclusion: Survival and freedom from reoperation for SVD in mitral bioprosthesis replacement had acceptable midterm results, but freedom from SVD Was relatively low. In particular, since SVD increased sharply at the eighth postoperative year, frequent follow-up and echocardiograms around that time will be helpful for the early detection of SVD. It will be necessary to conduct further studies involving long-term follow-up and more patients.