Background and Objectives: Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure. However, in pediatric and congenital heart disease (CHD) patients, current adult indications cannot be directly applied because of heterogeneity in anatomy and diagnosis. Therefore, CRT responses and clinical outcomes in these patients were investigated to derive possible candidates for CRT. Methods: This study retrospectively analyzed 16 pediatric and CHD patients who underwent CRT implantation at a single center in early (0.7±0.2 year) and late (4.7±0.3 years) follow-up period after CRT. Results: The median age at CRT implantation was 2.5 (0.3–37.2) years, and median follow-up duration was 6.3 (0.1–13.6) years. Thirteen had non-transvenous CRT. Two had congenital complete atrioventricular (AV) block with previous right ventricular pacing, 5 had dilated cardiomyopathy (DCM) with left bundle branch block, and 9 had CHD. The mean ejection fraction of the systemic ventricle increased from 28.1±10.0% to 44.3±21.0% (p=0.003) in early and 51.8±16.3% (p=0.012) in late outcome. The mean functional class improved from 3.1±0.9 to 1.8±1.1 after CRT (p=0.003). Twelve patients (75%) showed improvement in ventricular function or functional class after CRT. Proportion of responders differed between patients without CHD (2/2 patients with complete AV block and 5/5 with DCM, 100%) and those with CHD (5/9, 56%), although statistical significance was not reached (p=0.088). Conclusions CRT improved ventricular function and functional status according to the underlying condition in pediatric and CHD patients. However, further large and longer-term studies are needed to establish the guideline for the patient selection of CRT in these patients.

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.

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.

Background and Objectives: Liver cirrhosis is accompanied by abnormal vascular shunts. The Wnt pathway is essential for endothelial cell survival and proliferation. C-reactive protein (CRP), which is produced by hepatocyte, activates angiogenesis in cardiovascular diseases. Methods: and Results: The expression of CRP in CCl 4 -injured rat livers was detected using qRT-PCR and Western blotting after transplantation of placenta-derived mesenchymal stem cells (PD-MSCs) into rats. To determine whether CRP functions in hepatic regeneration by promoting angiogenesis through the Wnt pathway, we detected VEGF and β-catenin in liver tissues and BrdU and β-catenin in hepatocytes by immunofluorescence. The expression levels of CRP, Wnt pathway-related and angiogenic factors were increased in CCl 4 -injured and PD-MSCs transplanted rat livers. In vitro, the expression levels of Wnt signaling and angiogenic factors were decreased in siRNA-CRP-transfected rat hepatocytes. Conclusions CRP upregulation by PD-MSCs participates in vascular remodeling to promote liver regeneration via the Wnt signaling pathway during hepatic failure.

Background: In February 2020, a coronavirus disease 2019 (COVID-19) outbreak was reported in fitness centers in Cheonan, Korea. Methods: From February 24 to March 13, an epidemiological investigation was conducted on the fitness center outbreak. All those who were screened were tested for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using real-time reverse transcriptase polymerase chain reaction. Contacts were traced and self-isolated for 14 days. We determined the epidemiological characteristics of confirmed cases of SARS-CoV-2 infection, and estimated the time-dependent reproduction number to assess the transmission dynamics of the infection. Results: A total of 116 cases were confirmed, and 1,687 contacts were traced. The source cases were 8 Zumba instructors who led aerobics classes in 10 fitness centers, and had the largest average number of contacts. A total of 57 Zumba class participants, 37 of their family members, and 14 other contacts were confirmed as cases. The attack rate was 7.3%. The contacts at Zumba classes and homes had a higher attack rate than other contacts. The mean serial interval (± standard deviation) were estimated to be 5.2 (± 3.8) days. The time-dependent reproduction number was estimated to be 6.1 at the beginning of the outbreak, but it dropped to less than 1, 2 days after the epidemiological investigation was launched. Conclusion The results suggest that the COVID-19 outbreak was effectively contained with rigorous contact tracing, isolating, and testing in combination with social distancing without a lock-down.

Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by d(CH₂)₅[Tyr(Me)²,Dab⁵] AVP, a vasopressin-1a (V1a) receptor antagonist, but not by desGly-NH₂-d(CH₂)₅[DTyr², Thr⁴]OVT, an oxytocin receptor antagonist. Single cell RT-PCR analysis revealed that V1a receptor, compared to oxytocin, vasopressin-1b and vasopressin-2 receptors, was more profoundly expressed in dorsal root ganglion (DRG) neurons and the expression of V1a receptor was predominant in transient receptor potential vanilloid 1 (TRPV1)-expressing DRG neurons. Fura-2 based calcium imaging experiments showed that capsaicin-induced calcium transient was significantly inhibited by oxytocin and that such inhibition was reversed by V1a receptor antagonist. Additionally, whole cell patch clamp recording demonstrated that oxytocin significantly increased potassium conductance via V1a receptor in DRG neurons. Taken together, our findings suggest that analgesic effects produced by peripheral administration of oxytocin were attributable to the activation of V1a receptor, resulting in reduction of TRPV1 activity and enhancement of potassium conductance in DRG neurons.
Analgesia* ; Calcium ; Diagnosis-Related Groups ; Electrophysiology ; Fura-2 ; Ganglia, Spinal* ; Humans ; Injections, Intraperitoneal ; Neurons ; Oxytocin* ; Potassium* ; Receptors, Oxytocin ; Receptors, Vasopressin ; Rodentia ; Spinal Nerve Roots*

BACKGROUND/AIMS: Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL). METHODS: The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP. RESULTS: The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. CONCLUSION: CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.
Angiogenic Proteins/genetics/metabolism ; Animals ; Bile Ducts/surgery ; C-Reactive Protein/*analysis/genetics/metabolism ; Cells, Cultured ; Disease Models, Animal ; Hepatic Veins/abnormalities ; Hepatocytes/cytology/metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Lithocholic Acid/pharmacology ; Liver/metabolism/pathology ; Liver Cirrhosis/etiology ; Liver Diseases/metabolism/*pathology ; Male ; Microscopy, Fluorescence ; Mitochondria/drug effects/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Serum Albumin/genetics/metabolism

Unguarded tricuspid regurgitation (TR) due to a flail tricuspid leaflet is a rare condition of newborn cyanosis. A high perinatal mortality has been associated with this fatal condition. But, there are feasible surgical repairs to improve survival. We report the case of a male full-term neonate with intractable hypoxia. He had profound tricuspid insufficiency and leaflet prolapse caused by a ruptured papillary muscle supporting the anterior leaflet of the tricuspid valve. He presented with severe cyanosis and respiratory distress immediately after birth. Despite medical management, the pulmonary vascular resistance was not decreased and a low cardiac output persisted. Initial stabilization was accomplished with nitric oxide and extracorporeal membrane oxygenation. The tricuspid valve repair surgery was successfully performed subsequently. TR resulting from papillary muscle rupture is a potentially lethal condition. Timely diagnosis and proper surgical treatment can be lifesaving.
Anoxia ; Cardiac Output, Low ; Cyanosis ; Diagnosis ; Extracorporeal Membrane Oxygenation ; Female ; Humans ; Infant, Newborn* ; Male ; Nitric Oxide ; Papillary Muscles* ; Parturition ; Perinatal Mortality ; Persistent Fetal Circulation Syndrome* ; Prolapse ; Rupture ; Thoracic Surgery ; Tricuspid Valve Insufficiency ; Tricuspid Valve* ; Vascular Resistance

BACKGROUND AND OBJECTIVES: Milrinone is often used in children to treat acute heart failure and prevent low cardiac output syndrome after cardiac surgery. Due to the lack of studies on the long-term milrinone use in children, the objective of this study was to assess the safety and efficacy of the current patterns of milrinone use for > or =3 days in infants and children with heart diseases. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of patients aged <13 years who received milrinone for > or =3 days from January 2005 to December 2012. Patients' characteristics including age, sex, height, weight, and body surface area were recorded. The following parameters were analyzed to identify the clinical application of milrinone: initial infusion rate, maintenance continuous infusion rate, total duration of milrinone therapy, and concomitantly infused inotropes. The safety of milrinone was determined based on the occurrence of adverse events such as hypotension, arrhythmia, chest pain, headache, hypokalemia, and thrombocytopenia. RESULTS: We assessed 730 admissions (684 patients) during this period. Ventricular septal defects were the most common diagnosis (42.4%) in these patients. Milrinone was primarily used after cardiac surgery in 715 admissions (97.9%). The duration of milrinone treatment varied from 3 to 64.4 days (> or =7 days in 149 admissions). Ejection fraction and fractional shortening of the left ventricle improved in patients receiving milrinone after cardiac surgery. Dose reduction of milrinone due to hypotension occurred in only 4 admissions (0.5%). Although diverse arrhythmias occurred in 75 admissions (10.3%), modification of milrinone infusion to manage arrhythmia occurred in only 3 admissions (0.4%). Multivariate analysis indicated that the development of arrhythmia was not influenced by the pattern of milrinone use. CONCLUSION: Milrinone was generally administered for > or =3 days in children with heart diseases. The use of milrinone for > or =3 days was effective in preventing low cardiac output after cardiac surgery when combined with other inotropes, suggesting that milrinone could be safely employed in pediatric patients with heart diseases.
Arrhythmias, Cardiac ; Body Surface Area ; Cardiac Output, Low ; Chest Pain ; Child ; Diagnosis ; Headache ; Heart Diseases* ; Heart Failure ; Heart Septal Defects, Ventricular ; Heart Ventricles ; Humans ; Hypokalemia ; Hypotension ; Infant ; Medical Records ; Milrinone* ; Multivariate Analysis ; Off-Label Use* ; Retrospective Studies ; Thoracic Surgery ; Thrombocytopenia

We investigated characteristics associated with the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4i) in Korean patients with type 2 diabetes. We reviewed medical records of 477 patients who had taken sitagliptin or vildagliptin longer than 40 weeks. Response to DPP4i was evaluated with HbA1c change after therapy (DeltaHbA1c). The Student's t-test between good responders (GR: DeltaHbA1c > 1.0%) and poor responders (PR: DeltaHbA1c < 0.5%), a correlation analysis among clinical parameters, and a linear multivariate regression analysis were performed. The mean age was 60 yr, duration of diabetes 11 yr and HbA1c was 8.1%. Baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and creatinine were significantly higher in the GR compared to the PR. Duration of diabetes, FPG, HbA1c, C-peptide and creatinine were significantly correlated with DeltaHbA1c. In the multivariate analysis, age (r2 = 0.006), duration of diabetes (r2 = 0.019), HbA1c (r2 = 0.296), and creatinine levels (r2 = 0.024) were independent predictors for the response to DPP4i. Body mass index and insulin resistance were not associated with the response to DPP4i. In conclusion, better response to DPP4i would be expected in Korean patients with type 2 diabetes who have higher baseline HbA1c and creatinine levels with shorter duration of diabetes.
Adamantane/*analogs & derivatives/therapeutic use ; Blood Glucose/analysis ; Body Mass Index ; C-Peptide/analysis ; Creatinine/blood ; Diabetes Mellitus, Type 2/*drug therapy/pathology ; Dipeptidyl-Peptidase IV Inhibitors/*therapeutic use ; Hemoglobin A, Glycosylated/analysis ; Humans ; Insulin Resistance ; Male ; Middle Aged ; Multivariate Analysis ; Nitriles/*therapeutic use ; Pyrazines/*therapeutic use ; Pyrrolidines/*therapeutic use ; Retrospective Studies ; Triazoles/*therapeutic use