Analysis of Important Medical Adverse Events and Signals Related with Cyclosporine and Tacrolimus Using the FDA Adverse Event Reporting System (FAERS) Database

Objective@#This study aimed to analyze the important medical adverse events (IMEs) of cyclosporine and tacrolimus using the reports in US FDA adverse event reporting system (FAERS) and to detect related signals. @*Methods@#The FAERS database was used to analyze the IMEs reported for cyclosporine or tacrolimus during 2017-2021. Reporting odds ratio (ROR) and information component were used to analyze signals for adverse events of both drugs. It was investigated whether the detected signals were present on drug labels in Korea and the United States. @*Results@#Among the total 24,688 reports, the reports on tacrolimus accounted 75.8%. Mean age of the patients was 47.9 years old and median number of adverse events was 2.0 per report. The number of patients hospitalized for adverse events was 7,979 (25.3%). Among the adverse reactions reported on the cyclosporine and tacrolimus, 576 and 1,363 events were detected as signals for cyclosporine and tacrolimus, respectively, and of these, IMEs accounted for 44.8 and 59.2%, respectively. The IMEs related with infections/infestations, renal/urinary disorders, and blood and lymphatic system disorders were reported frequently for both drugs. The most frequently detected IMEs were renal impairment for cyclosporine and acute kidney injury for tacrolimus. Among the top 3 IMEs for each reported SOC for cyclosporine and tacrolimus, 9 and 2 unexpected adverse events were identified, respectively. @*Conclusion@#This study identified the IMEs and signals of cyclosporine and tacrolimus, and detected unidentified adverse events in a drug information database.

Long-term Outcome of Fontan-Associated Protein-Losing Enteropathy: Treatment Modality and Predictive Factor of Mortality

Background and Objectives@#Protein-losing enteropathy (PLE) is a devastating complication after the Fontan operation. This study aimed to investigate the clinical characteristics, treatment response, and outcomes of Fontan-associated PLE. @*Methods@#We reviewed the medical records of 38 patients with Fontan-associated PLE from 1992 to 2018 in 2 institutions in Korea. @*Results@#PLE occurred in 4.6% of the total 832 patients after the Fontan operation. After a mean period of 7.7 years after Fontan operation, PLE was diagnosed at a mean age of 11.6years. The mean follow-up period was 8.9 years. The survival rates were 81.6% at 5 years and 76.5% at 10 years. In the multivariate analysis, New York Heart Association Functional classification III or IV (p=0.002), low aortic oxygen saturation (<90%) (p=0.003), and ventricular dysfunction (p=0.032) at the time of PLE diagnosis were found as predictors of mortality. PLE was resolved in 10 of the 38 patients after treatment. Among medical managements, an initial heparin response was associated with survival (p=0.043). Heparin treatment resulted in resolution in 4 patients. We found no evidence on pulmonary vasodilator therapy alone. PLE was also resolved after surgical Fontan fenestration (2/6), aortopulmonary collateral ligation (1/1), and transplantation (1/1). @*Conclusions@#The survival rate of patients with Fontan-associated PLE has improved with the advancement of conservative care. Although there is no definitive method, some treatments led to the resolution of PLE in one-fourth of the patients. Further investigations are needed to develop the best prevention and therapeutic strategies for PLE.

Association between the Use of Diuretics and Size Reduction in Pediatric Atrial Septal Defect

Background and Objectives@#While diuretics are sometimes used in atrial septal defect (ASD) treatment, their effect on ASD size reduction remains unclear. We aimed to evaluate the efficacy of diuretics in ASD size reduction in pediatric patients. @*Methods@#We retrospectively reviewed the medical records of patients with secundum ASD (size ≥10 mm), between 2005 and 2019. Patients were divided into two groups based on the diuretic administration. @*Results@#Of the 73 enrolled patients, 40 received diuretics. The initial age at ASD diagnosis (2.8±1.7 vs. 2.5±2.0 years, p=0.526) and follow-up duration (22.3±11.4 vs. 18.7±13.2 months, p=0.224) were not significantly different between the groups. The ASD diameter at the initial diagnosis (13.7±2.0 vs. 13.5±3.4 mm, p=0.761) and the indexed ASD diameter (25.5±5.9 vs. 26.9±10.3 mm/m2 , p=0.493) were also not significantly different between two groups. The ASD diameter significantly increased in the non-diuretic group during follow-up (0.0±2.9 vs. +2.6±2.0 mm, p<0.001). The indexed ASD diameter significantly decreased in the diuretic group during follow-up (−5.7±6.5 vs. +0.2±3.9 mm/m 2 , p<0.001). In the linear mixed model analysis, diuretic use was associated with ASD diameter decrease (p<0.001) and indexed ASD diameter reduction (p<0.001) over time. Device closure was more frequently performed in the diuretic (75.0%) than in the non-diuretic group (39.4%). @*Conclusions@#Patients receiving diuretics are less likely to undergo surgery. The diuretics administration may be associated with the use of smaller ASD devices for transcatheter treatment through ASD size reduction.

Effects of the Lysine Methyltransferase Inhibitor AZ505 on Bone Metabolism

Background@#Protein methylation has important role in regulating diverse cellular responses, including differentiation, by affecting protein activity, stability, and interactions. AZ505 is an inhibitor of the SET and MYND domain-containing protein 2 lysine methylase. In this study, we investigated the effect of AZ505 on osteoblast and osteoclast differentiation in vitro and evaluated the effect of AZ505 in vivo on the long bones in mice. @*Methods@#Osteoblast differentiation was assessed by alkaline phosphatase (ALP) and Alizarin red staining after culturing calvarial preosteoblasts in an osteogenic medium. Osteoclast differentiation was analyzed by tartrate-resistant acid phosphatase (TRAP) staining in bone marrow-derived macrophages cultured with macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL). For in vivo experiments, mice were intraperitoneally injected with AZ505 and femurs were examined by micro-computed tomography. @*Results@#AZ505 increased ALP and Alizarin red staining in cultured osteoblasts and the expression of osteoblast marker genes, including Runx2 and osteocalcin. AZ505 resulted in decreased TRAP-staining of osteoclasts and expression of c-Fos and nuclear factor of activated T cells transcription factors and osteoclast marker genes, including cathepsin K and dendritic cell-specific transmembrane protein. Unexpectedly, in vivo administration of AZ505 markedly decreased the trabecular bone mass of femurs. In support of this catabolic result, AZ505 strongly upregulated RANKL expression in osteoblasts. @*Conclusions@#The results indicate that AZ505 has a catabolic effect on bone metabolism in vivo despite its anabolic effect in bone cell cultures. The findings indicate that cell culture data should be extrapolated cautiously to in vivo outcomes for studying bone metabolism.

Effect of Pulmonary Valve Replacement in the Repaired Tetralogy of Fallot Patients with Trans-annular Incision:More than 20 Years of Follow-up

Background and Objectives@#We reviewed the long-term outcomes after tetralogy of Fallot (TOF) repair with trans-annular incision; and evaluated the effectiveness of pulmonary valve replacement (PVR) on outcomes. @*Methods@#This was a retrospective review of clinical outcomes of 180 of 196 TOF patients who underwent total correction with trans-annular incision from 1991 to 1997 (PVR group: 81; non-PVR group: 99). @*Results@#The median age of the patients was 14.0 months (interquartile range [IQR], 10.7–19.8 months) at TOF repair. Ten in-hospital deaths (5.1%) occurred. During the followup, 81 patients underwent PVR at the median age of 13.5 years (IQR, 11.2–17.1 years). The patients in PVR group showed better outcomes than non-PVR group in overall survival rate (100% in PVR vs. 88.7% in non-PVR, p=0.007), in all adverse events (arrhythmia, neurologic complications, 95.5% in PVR vs. 74.6% in non-PVR, p=0.024) at 20 years. Age at TOF repair younger than 1 year (hazard ratio [HR], 2.265; p=0.01) and previous shunt history (HR, 2.195; p=0.008) were predictive for requiring PVR. During follow-up, 10 late deaths (5 sudden deaths) occurred in the non-PVR group, mainly due to ventricular arrhythmia and right ventricular failure; there was 1 late death (not a sudden death) in the PVR group. @*Conclusions@#Long-term survival after repair of TOF with trans-annular incision were acceptable. However, arrhythmias were frequently observed during 20 years of follow-up. The patient age <1 year at the time of TOF repair and shunt implantation prior to TOF repair were predictive factors for requiring PVR.

Effect of Pulmonary Valve Replacement in the Repaired Tetralogy of Fallot Patients with Trans-annular Incision:More than 20 Years of Follow-up

Background and Objectives@#We reviewed the long-term outcomes after tetralogy of Fallot (TOF) repair with trans-annular incision; and evaluated the effectiveness of pulmonary valve replacement (PVR) on outcomes. @*Methods@#This was a retrospective review of clinical outcomes of 180 of 196 TOF patients who underwent total correction with trans-annular incision from 1991 to 1997 (PVR group: 81; non-PVR group: 99). @*Results@#The median age of the patients was 14.0 months (interquartile range [IQR], 10.7–19.8 months) at TOF repair. Ten in-hospital deaths (5.1%) occurred. During the followup, 81 patients underwent PVR at the median age of 13.5 years (IQR, 11.2–17.1 years). The patients in PVR group showed better outcomes than non-PVR group in overall survival rate (100% in PVR vs. 88.7% in non-PVR, p=0.007), in all adverse events (arrhythmia, neurologic complications, 95.5% in PVR vs. 74.6% in non-PVR, p=0.024) at 20 years. Age at TOF repair younger than 1 year (hazard ratio [HR], 2.265; p=0.01) and previous shunt history (HR, 2.195; p=0.008) were predictive for requiring PVR. During follow-up, 10 late deaths (5 sudden deaths) occurred in the non-PVR group, mainly due to ventricular arrhythmia and right ventricular failure; there was 1 late death (not a sudden death) in the PVR group. @*Conclusions@#Long-term survival after repair of TOF with trans-annular incision were acceptable. However, arrhythmias were frequently observed during 20 years of follow-up. The patient age <1 year at the time of TOF repair and shunt implantation prior to TOF repair were predictive factors for requiring PVR.

TM4SF4 and LRRK2 Are Potential Therapeutic Targets in Lung and Breast Cancers through Outlier Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be ‘some sort of problem.’ Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2). @*Materials and Methods@#Modified Tukey’s fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes. @*Results@#TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines @*Conclusion@#Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.

Radiofrequency catheter ablation of ventricular tachycardia in pediatric patients

Background@#Radiofrequency catheter ablation (RFCA) has been accepted as an efficient therapy for tachycardia, and substantial improvement in the outcomes of RFCA in pediatric patients has been seen. However, there is not enough data on the clinical outcomes of RFCA for ventricular tachycardia (VT) in pediatric patients. The objective of this study was to elucidate the efficacy and safety of RFCA for VT in pediatric patients. @*Methods@#We performed a retrospective study involving 35 consecutive pediatric VT ablation procedures in 28 patients at a single institution. @*Results@#The median age at ablation was 14.0 years (range 6.9–19.2 years). There were 24 patients with a structurally normal heart and four patients with congenital heart disease (CHD). The left ventricular posteroseptal area was the most common site of VT origin (22/28, 78.6%). However, there was an unusual case of VT which involved a papillary muscle as its origin. Acute success was achieved in 30 (85.7%) of 35 procedures. The recurrence rate after successful RFCA was 14.2% (5/35) at a median follow-up of 6.7 years (range 1.0–16.7 years). There were five procedural failures due to the inability to induce VT for complete mapping. Ultimately, long-term success was achieved in 27 patients (96.4%) after repeated procedures and no major complications occurred. Long-term success was associated with VT inducibility (p = < 0.001). @*Conclusions@#Difficulty in inducing VT for precise mapping was a significant obstacle to successful RFCA. RFCA was identified as safe and effective therapy to eliminate VT in the selected pediatric VT patients.

Radiofrequency catheter ablation of ventricular tachycardia in pediatric patients

Background@#Radiofrequency catheter ablation (RFCA) has been accepted as an efficient therapy for tachycardia, and substantial improvement in the outcomes of RFCA in pediatric patients has been seen. However, there is not enough data on the clinical outcomes of RFCA for ventricular tachycardia (VT) in pediatric patients. The objective of this study was to elucidate the efficacy and safety of RFCA for VT in pediatric patients. @*Methods@#We performed a retrospective study involving 35 consecutive pediatric VT ablation procedures in 28 patients at a single institution. @*Results@#The median age at ablation was 14.0 years (range 6.9–19.2 years). There were 24 patients with a structurally normal heart and four patients with congenital heart disease (CHD). The left ventricular posteroseptal area was the most common site of VT origin (22/28, 78.6%). However, there was an unusual case of VT which involved a papillary muscle as its origin. Acute success was achieved in 30 (85.7%) of 35 procedures. The recurrence rate after successful RFCA was 14.2% (5/35) at a median follow-up of 6.7 years (range 1.0–16.7 years). There were five procedural failures due to the inability to induce VT for complete mapping. Ultimately, long-term success was achieved in 27 patients (96.4%) after repeated procedures and no major complications occurred. Long-term success was associated with VT inducibility (p = < 0.001). @*Conclusions@#Difficulty in inducing VT for precise mapping was a significant obstacle to successful RFCA. RFCA was identified as safe and effective therapy to eliminate VT in the selected pediatric VT patients.

End-of-Life Care of Hospitalized Children with Advanced Heart Disease

Background@#Despite improvements in palliative care for critically ill children, the characteristics of end-of-life care for pediatric patients with advanced heart disease are not well-known. We investigated these characteristics among hospitalized children with advanced heart disease in a tertiary referral center in Korea. @*Methods@#We retrospectively reviewed the records of 136 patients with advanced heart disease who died in our pediatric department from January 2006 through December 2013. @*Results@#The median age of patients at death was 10.0 months (range 1 day–28.3 years). The median duration of the final hospitalization was 16.5 days (range 1–690 days). Most patients (94.1%) died in the intensive care unit and had received mechanical ventilation (89.7%) and inotropic agents (91.2%) within 24 hours of death. The parents of 74 patients (54.4%) had an end-of-life care discussion with their physician, and the length of stay of these patients in the intensive care unit and in hospital was longer. Of the 90 patients who had been hospitalized for 7 days or more, the parents of 54 patients (60%) had a documented end-of-life care discussion. The time interval from the end-of-life care discussion to death was 3 days or less for 25 patients. @*Conclusion@#Children dying of advanced heart disease receive intensive treatment at the end of life. Discussions regarding end-of-life issues are often postponed until immediately prior to death. A pediatric palliative care program must be implemented to improve the quality of death in pediatric patients with heart disease.

A Comparative Analysis of Clinical Screening Test and Language Specific Test in Language Delay Children / 전남의대학술지

The aim of this study was to investigate the usefulness of a clinical screening test [the Korean Infant and Child Developmental Test (KICDT)] compared to language specific tests: the sequenced language scale for infant (SELSI) and the Preschool Receptive-Expressive language Scale (PRES) in children with delayed language development. A retrospective chart review was conducted on 615 children who visited the Department of Pediatrics at Chonbuk National University Hospital from January 2013 to December 2016. All patients were evaluated with KICDT as a clinical screening test and SELSI or PRES as a language specific test. Language Developmental Quotients (LDQs) from the KICDT were compared with the Receptive Language Quotient (RLQ) and expressive language quotient (ELQ) from the SELSI or PRES. The sensitivity, specificity and predictive values of LDQ of KICDT were calculated by comparing with SELSI/PRES. Language DQs from the KICDT were significantly correlated with the RLQ (r=0.706), ELQ (r=0.768), and total language quotient (TLQ) (r=0.766) from the SELSI/PRES (p<0.05). In cross tabulation, the patients belonging to the retardation groups in both KICDT and SELSI/PRES were 417 (67.8%). Otherwise, patients belonging to the normal group in KICDT but not in SELSI/PRES were 151 (24.6%). Sensitivity and specificity of LDQ of KICDT relative to SELSI/PRES were 72.3% and 92.2% respectively (p<0.05). Our data suggests that clinical screening tests alone, not cumbersome language specific tests, can determine language developmental delays in children.

Perspectives on Adopting the Guideline for Multi-regional Clinical Trials in Korea: A Multi-stakeholder Survey

BACKGROUND@#With the globalization of drug development, multi-regional clinical trials (MRCTs) have emerged to facilitate rapid availability of medicines to patients worldwide. The present study aimed to has explored attitudes and perceptions towards adopting the Korean MRCT guideline.@*METHODS@#An online survey, consisting of 16 questions, classified into two subjects, was administered to stakeholders in Korea. Most quantitative components were measured using the Likert scales. A content analysis of the qualitative components was carried out to identify the keywords in open-ended responses.@*RESULTS@#A total of 94 survey responses were analyzed: 51 participants from pharmaceutical companies, 11 from clinical research organizations, and 21 from clinical trial centers. The content of the guideline was rated as appropriate for clarity, acceptability, and applicability (96.8, 96.8, and 93.6%, respectively). The local environmental impact of the systemic/political, academic/technical, and industrial/economical aspects of the guideline was rated as appropriate at 95.7, 97.9, and 91.5%, respectively. The suggested adoption period was 1~2 years (40, 42.6%). The concept and individuals' domestic circumstances were the key problems affecting the clarity, applicability, and local environmental impact of the guideline.@*CONCLUSION@#The Korean MRCT guideline was well-developed. Their overall impact on the local environmental impact of MRCTs in Korea was expected to be beneficial, but methods are needed to minimize the negative impacts. The findings of this study can inform the priorities for the future adoption of the guideline in Korea.

Primary Cardiac Hemangioendothelioma in an Infant: A Case Report / 임상소아혈액종양

Primary cardiac tumors are rare, with a prevalence of 0.001–0.2%. Among such tumors, cardiac hemangioendotheliomas are some of the most uncommon. In Korea, there have been no reports of hemangioendothelioma occurring in the heart of infants. We herein report a case of an infant that was admitted to our medical center and presented with cough and a runny nose. The initial diagnosis was acute bronchiolitis. Cardiomegaly was observed on chest radiography. Echocardiography revealed a tumor measuring 3.5×4.0 cm in the right atrium. The infant was transferred to a tertiary medical center for tumor excision. The excised lesion was 3.8×3×3.2 cm in size, and biopsy confirmed a diagnosis of hemangioendothelioma. In this case report, we describe our experience with a rare case involving cardiac tumor in an infant with an upper respiratory tract infection.

Stress Induced Cardiomyopathy Requiring Ventricular Assist Device Support in an 8-Year-Old Girl with Acute Leukemia / 전남의대학술지

No abstract available.

A pediatric case of eosinophilic granulomatosis with polyangiitis accompanied by heart failure mimicking an asthma attack

Eosinophilic granulomatosis with polyangiitis (EGPA, also known as the Churg-Strauss syndrome) is a disorder characterized by asthma, peripheral eosinophilia and systemic vasculitis. It rarely occurs in children, so that physicians may frequently mistake it for a simple uncontrolled asthma. Since a subsequent cardiac involvement is critical for the prognosis, it is important to suspect EGPA in children with severe, uncontrolled asthma. The cardiac manifestations in EGPA are variable from asymptomatic electrocardiogram abnormalities to pericarditis with pericardial effusion, myocarditis with cardiomyopathy, heart failure, and sudden cardiac death. Although delayed treatment may lead to fatal cardiac complications in EGPA, adequate immune suppression can reverse cardiac impairment. We report a 14-year-old girl with persistent asthma refractory to steroids who was eventually diagnosed with an anti-neutrophil cytoplasmic antibody-negative EGPA.

Development of Agenda for Pharmaceutical Care Service Research and Development using the Analytical Hierarchy Process

BACKGROUND: Although the importance of pharmaceutical care service has been growing to meet the needs of customers with the improvement of clinical and humanistic outcomes, there was not a systematic strategy to promote research in Korea. The aim of this study was to suggest the core agendas for pharmaceutical care services research and development (R&D) considering priorities. METHODS: Based on desk researches, we developed R&D agendas for the needs of improving pharmaceutical care services in the area of institution, community, and public health. To determine the priority of agendas in developing pharmaceutical care service, analytic hierarchy process (AHP) analysis was performed by the 14 experts. Criteria and subcriteria were assessed for significance by pairwise comparisons. Then, agendas were evaluated for importance according to each subcriteria, and rank ordered considering the weight calculated by multiplying the importance scores of the criteria and the subcriteria. RESULTS: We derived 25 agendas including 13 for institutional pharmaceutical care service, 8 for community pharmaceutical care service, and 4 for public-health related pharmaceutical care service. AHP model was constructed based on 4 criteria and 8 subcriteria by a hierarchical structure. From the AHP survey, the ‘Development of pharmaceutical care service for metabolic and chronic disease’ agenda accounted for the highest priority. CONCLUSION: We have developed the R&D agendas of the pharmaceutical care service which should be promoted. The results should be utilized by the government to nationally support the development of the standards and relevant regulations related to pharmaceutical care services in Korea.

The Complexity of Pediatric Multifocal Atrial Tachycardia and Its Prognostic Factors

BACKGROUND AND OBJECTIVES@#Multifocal atrial tachycardia (MAT), in general, has a favorable outcome. However, there are insufficient data regarding MAT in a pediatric population. This study sought to determine the clinical course of MAT and identify potential prognostic factors.@*METHODS@#The medical records of MAT patients from 1997–2015 were reviewed. The arrhythmia control rate and factors for unfavorable outcomes were assessed and compared to those in the literature.@*RESULTS@#Of the 33 included patients (19 boys and 14 girls), 27 were infants less than 1 year of age. The median age at diagnosis was 1.7 months (range, 0 day to 14 years). Fourteen (42%) patients had structural heart disease. Eight (24%) patients had lung disease and 6 (18%) had a syndromic diagnosis belonging to RASopathy. Two patients developed polymorphic ventricular tachycardia, in whom genetic analysis confirmed the presence of the RyR2 mutation several years later. MAT was controlled in 26 patients (84%) within 3.9 months (median; range, 16 days–18.4 years) using an average of 2.4 medications. There were 3 cases of cardiopulmonary mortality. The arrhythmia control rate was higher in the infant group (85%) than in the non-infant group (67%), although this trend was not statistically significant. There was a significantly lower rate of unfavorable outcomes in the idiopathic infant group (n=11) than in the other groups (p=0.008). Considering the findings of previous studies, the mortality rate was significantly higher in patients with structural heart disease than in patients without (21% vs. 5%, p=0.01).@*CONCLUSIONS@#MAT usually affects infants and has a favorable prognosis, particularly in the idiopathic infant group. However, in the presence of other comorbidities, MAT may have a variable clinical course.

2018 KHRS guideline for the evaluation and management of syncope: Part 1

Syncope is a very common symptom that occurs in all age groups, especially in adolescents and elderly people. The cause of syncope is very diverse, and patients with syncope visit various medical departments such as general medicine, cardiology, neurology, and emergency medicine. If we do not perform appropriate diagnostic tests based on detailed history of syncope, we may have some difficulty to identify the cause of syncope. Failure to identify the cause of syncope can lead to physical trauma due to recurrence of syncope or may increase the risk of cardiovascular events in the future. However, there is no Korean guidelines for the diagnosis and treatment of syncope yet. Considering these circumstances in Korea, we prepared writing and publishing committee for evaluation and management guidelines of syncope in the Korean Society for Holter and Noninvasive Electrocardiology (KSHNE) under the Korean Heart Rhythm Society (KHRS). In this guideline, we reviewed the Korean published literatures and European / American guidelines on syncope.

2018 KHRS guideline for the evaluation and management of syncope: Part 2

The general concept and initial approach to syncope patients has been mentioned in the general sections. This special sections have been described the characteristics, diagnosis, and treatment with patient education for the each syncope. It has been described in order of reflex syncope, orthostatic hypotension, postural orthostatic tachycardia syndrome (POTS), cardiac syncope, and unexplained syncope. Several clinical issues will have been dealt with in special issues. Neurological assessment is added when the patients were diagnosed with psychogenic pseudosyncope (PPS). Although many childhood syncope caused by reflex syncope, they are also presented as syncope caused by arrhythmic events in patients with congenital heart disease. In the elderly patients, syncope is because of not only a single cause of syncope but a combination of various conditions. In case of a syncope patient visiting the emergency department, a standardized systematic approach will be required to determine whether hospitalize the patient according to the risk of recurrence and the needs for the syncope management unit. We also mention recommendations on the limits of driving, exercising and social life style that are relevant to syncope in all patients. In this guideline, we reviewed the Korean published literatures and European/American guidelines on syncope. We, writing and publishing committee for evaluation and management guidelines of syncope in the Korean Society for Holter and Noninvasive Electrocardiography (KSHNE) under the Korean Heart Rhythm Society (KHRS) are very pleased to be able to publish this guideline. We also hope this guideline will be a good support to manage the syncope patients and a useful trigger for further research in Korea.

Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A

Long QT syndrome (LQTS) is an inherited cardiac disease characterized by a prolonged heart rate-corrected QT (QTc) interval. We investigated the genetic causes in patients with prolonged QTc intervals who were negative for pathogenic variants in three major LQTS-related genes (KCNQ1, KCNH2, and SCN5A). Molecular genetic testing was performed using a panel including 13 LQTS-related genes and 67 additional genes implicated in other cardiac diseases. Overall, putative genetic causes of prolonged QTc interval were identified in three of the 30 patients (10%). Among the LQTS-related genes, we detected a previously reported pathogenic variant, CACNA1C c.1552C>T, responsible for cardiac-only Timothy syndrome. Among the genes related to other cardiac diseases, a likely pathogenic variant, RYR2 c.11995A>G, was identified in a patient with catecholaminergic polymorphic ventricular tachycardia. Another patient who developed dilated cardiomyopathy with prolonged QTc interval was found to carry a likely pathogenic variant, TAZ c.718G>A, associated with infantile dilated cardiomyopathy. Comprehensive screening of genetic variants using multigene panel sequencing enables detection of genetic variants with a possible involvement in QTc interval prolongation, thus uncovering unknown molecular mechanisms underlying LQTS.