Table_1_Transfemoral Occlusion of Doubly Committed Subarterial Ventricular Septal Defect Using the Amplatzer Duct Occluder-II in Children.DOCX

BackgroundsThe traditional treatment of doubly committed subarterial ventricular septal defect (dcVSD) is open-heart surgery. This study aimed to evaluate the feasibility, safety, and outcome of transcatheter closure of small dcVSD using Amplatzer duct occluder-II (ADO-II) in children.MethodsBetween January 2016 and April 2021, 24 children (17 male and 7 female patients) with small dcVSD who received transfemoral closure with ADO-II were enrolled retrospectively. All of their available clinical and follow-up data were evaluated.ResultsThe patients' median age was 3.2 years (1.6–12.6 years, 4.2 ± 3.1 years) and body weight was 13.3 kg (10.0–38.5 kg, 16.5 ± 7.7 kg). Left ventricular angiography showed that the median dcVSD size was 2.0 mm (1.5–3.5 mm, 2.1 ± 0.6 mm). The device was successfully implanted in 23 patients (95.8%), and one patient failed to be closed because of the underestimation of defect size due to preoperative aortic valve prolapse, with 16 patients by the antegrade approach and eight patients by retrograde approach. The diameters of the device used were 3/4, 4/4, and 5/4 mm. The median operative time was 40.0 min (20.0–75.0 min, 41.7 ± 13.7 min), and the median fluoroscopic time was 5.0 min (3.0–25.0 min, 6.8 ± 5.0 min). With a follow-up duration of 1+ to 45+ months, only 1 patient presented with new-onset mild aortic regurgitation (AR).ConclusionTransfemoral closure of small dcVSD with ADO-II is technically feasible and safe in the selected children. However, the development or worsening of AR requires long-term follow-up.</p

DataSheet2_Efficacy and Safety of Various First-Line Therapeutic Strategies for Fetal Tachycardias: A Network Meta-Analysis and Systematic Review.PDF

Background: Fetal arrhythmias are common cardiac abnormalities associated with high mortality due to ventricular dysfunction and heart failure, particularly when accompanied by hydrops. Although several types of common fetal tachycardias have been relatively identified medications, such as digoxin, flecainide, and sotalol, there is no first-line drug treatment protocol established for the treatment of various types of fetal tachycardias.Methods: We conducted a network meta-analysis using a Bayesian hierarchical framework to obtain a model for integrating both direct and indirect evidence. All tachycardia types (Total group), supraventricular tachycardia (SVT subgroup), atrial flutter (AF subgroup), hydrops subgroup, and non-hydrops subgroup fetuses were analyzed, and five first-line regimens were ranked according to treatment outcomes: digoxin monotherapy (D), flecainide monotherapy (F), sotalol monotherapy (S), digoxin plus flecainide combination therapy (DF), and digoxin plus sotalol combination therapy (DS). Effectiveness and safety were determined according to the cardioversion rate and intrauterine death rate.Results: The pooled data indicated that DF combination therapy was always superior to D monotherapy, regardless of the tachycardia type or the presence of hydrops: Total, 2.44 (95% CrI: 1.59, 3.52); SVT, 2.77 (95% CrI: 1.59, 4.07); AF, 67.85 (95% CrI: 14.25, 168.68); hydrops, 6.03 (95% CrI: 2.54, 10.68); and non-hydrops, 5.06 (95% CrI: 1.87, 9.88). DF and F had a similar effect on control of fetal tachycardias. No significant differences were observed when comparing S, DS with D therapies across the subgroup analyses for the SVT, hydrops, and non-hydrops groups. No significant differences in mortality risks were among the various treatment regimens for the total group. And no significant differences were found in rates of intrauterine death rates at the same cardioversion amount.Conclusion The flecainide monotherapy and combination of digoxin and flecainide should be considered the most superior therapeutic strategies for fetal tachycardia.Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=288997), identifier (288997).</p

DataSheet4_Efficacy and Safety of Various First-Line Therapeutic Strategies for Fetal Tachycardias: A Network Meta-Analysis and Systematic Review.PDF

Background: Fetal arrhythmias are common cardiac abnormalities associated with high mortality due to ventricular dysfunction and heart failure, particularly when accompanied by hydrops. Although several types of common fetal tachycardias have been relatively identified medications, such as digoxin, flecainide, and sotalol, there is no first-line drug treatment protocol established for the treatment of various types of fetal tachycardias.Methods: We conducted a network meta-analysis using a Bayesian hierarchical framework to obtain a model for integrating both direct and indirect evidence. All tachycardia types (Total group), supraventricular tachycardia (SVT subgroup), atrial flutter (AF subgroup), hydrops subgroup, and non-hydrops subgroup fetuses were analyzed, and five first-line regimens were ranked according to treatment outcomes: digoxin monotherapy (D), flecainide monotherapy (F), sotalol monotherapy (S), digoxin plus flecainide combination therapy (DF), and digoxin plus sotalol combination therapy (DS). Effectiveness and safety were determined according to the cardioversion rate and intrauterine death rate.Results: The pooled data indicated that DF combination therapy was always superior to D monotherapy, regardless of the tachycardia type or the presence of hydrops: Total, 2.44 (95% CrI: 1.59, 3.52); SVT, 2.77 (95% CrI: 1.59, 4.07); AF, 67.85 (95% CrI: 14.25, 168.68); hydrops, 6.03 (95% CrI: 2.54, 10.68); and non-hydrops, 5.06 (95% CrI: 1.87, 9.88). DF and F had a similar effect on control of fetal tachycardias. No significant differences were observed when comparing S, DS with D therapies across the subgroup analyses for the SVT, hydrops, and non-hydrops groups. No significant differences in mortality risks were among the various treatment regimens for the total group. And no significant differences were found in rates of intrauterine death rates at the same cardioversion amount.Conclusion The flecainide monotherapy and combination of digoxin and flecainide should be considered the most superior therapeutic strategies for fetal tachycardia.Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=288997), identifier (288997).</p

DataSheet1_Efficacy and Safety of Various First-Line Therapeutic Strategies for Fetal Tachycardias: A Network Meta-Analysis and Systematic Review.PDF

Background: Fetal arrhythmias are common cardiac abnormalities associated with high mortality due to ventricular dysfunction and heart failure, particularly when accompanied by hydrops. Although several types of common fetal tachycardias have been relatively identified medications, such as digoxin, flecainide, and sotalol, there is no first-line drug treatment protocol established for the treatment of various types of fetal tachycardias.Methods: We conducted a network meta-analysis using a Bayesian hierarchical framework to obtain a model for integrating both direct and indirect evidence. All tachycardia types (Total group), supraventricular tachycardia (SVT subgroup), atrial flutter (AF subgroup), hydrops subgroup, and non-hydrops subgroup fetuses were analyzed, and five first-line regimens were ranked according to treatment outcomes: digoxin monotherapy (D), flecainide monotherapy (F), sotalol monotherapy (S), digoxin plus flecainide combination therapy (DF), and digoxin plus sotalol combination therapy (DS). Effectiveness and safety were determined according to the cardioversion rate and intrauterine death rate.Results: The pooled data indicated that DF combination therapy was always superior to D monotherapy, regardless of the tachycardia type or the presence of hydrops: Total, 2.44 (95% CrI: 1.59, 3.52); SVT, 2.77 (95% CrI: 1.59, 4.07); AF, 67.85 (95% CrI: 14.25, 168.68); hydrops, 6.03 (95% CrI: 2.54, 10.68); and non-hydrops, 5.06 (95% CrI: 1.87, 9.88). DF and F had a similar effect on control of fetal tachycardias. No significant differences were observed when comparing S, DS with D therapies across the subgroup analyses for the SVT, hydrops, and non-hydrops groups. No significant differences in mortality risks were among the various treatment regimens for the total group. And no significant differences were found in rates of intrauterine death rates at the same cardioversion amount.Conclusion The flecainide monotherapy and combination of digoxin and flecainide should be considered the most superior therapeutic strategies for fetal tachycardia.Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=288997), identifier (288997).</p

DataSheet3_Efficacy and Safety of Various First-Line Therapeutic Strategies for Fetal Tachycardias: A Network Meta-Analysis and Systematic Review.PDF

Background: Fetal arrhythmias are common cardiac abnormalities associated with high mortality due to ventricular dysfunction and heart failure, particularly when accompanied by hydrops. Although several types of common fetal tachycardias have been relatively identified medications, such as digoxin, flecainide, and sotalol, there is no first-line drug treatment protocol established for the treatment of various types of fetal tachycardias.Methods: We conducted a network meta-analysis using a Bayesian hierarchical framework to obtain a model for integrating both direct and indirect evidence. All tachycardia types (Total group), supraventricular tachycardia (SVT subgroup), atrial flutter (AF subgroup), hydrops subgroup, and non-hydrops subgroup fetuses were analyzed, and five first-line regimens were ranked according to treatment outcomes: digoxin monotherapy (D), flecainide monotherapy (F), sotalol monotherapy (S), digoxin plus flecainide combination therapy (DF), and digoxin plus sotalol combination therapy (DS). Effectiveness and safety were determined according to the cardioversion rate and intrauterine death rate.Results: The pooled data indicated that DF combination therapy was always superior to D monotherapy, regardless of the tachycardia type or the presence of hydrops: Total, 2.44 (95% CrI: 1.59, 3.52); SVT, 2.77 (95% CrI: 1.59, 4.07); AF, 67.85 (95% CrI: 14.25, 168.68); hydrops, 6.03 (95% CrI: 2.54, 10.68); and non-hydrops, 5.06 (95% CrI: 1.87, 9.88). DF and F had a similar effect on control of fetal tachycardias. No significant differences were observed when comparing S, DS with D therapies across the subgroup analyses for the SVT, hydrops, and non-hydrops groups. No significant differences in mortality risks were among the various treatment regimens for the total group. And no significant differences were found in rates of intrauterine death rates at the same cardioversion amount.Conclusion The flecainide monotherapy and combination of digoxin and flecainide should be considered the most superior therapeutic strategies for fetal tachycardia.Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=288997), identifier (288997).</p

Primer sequences used for real-time quantitative PCR.

Primer sequences used for real-time quantitative PCR.</p

Fetal cardiac malformations induced by maternal Di-(2-ethylhexyl)-phthalate (DEHP) and verapamil exposure from E6.5 to E14.5.

The phenotypes of fetal cardiac malformations included septal defects (B, D, E, G). The magnification used was 4×and 10×.</p

Placental P-glycoprotein inhibition enhances susceptibility to Di-(2-ethylhexyl)-phthalate induced cardiac malformations in mice: A possibly promising target for congenital heart defects prevention - Fig 1

Effect of maternal Di-(2-ethylhexyl)-phthalate (DEHP) and verapamil exposure from E6.5 to E14.5 on maternal bodyweights (A), fetal weights (B) and placental weights (C). Differences among different groups were determined by ANOVA followed by a Student–Newman–Keuls multiple comparisons. N = 10, 15, 20 and 10 for vehicle, 500mg/Kg DEHP, 500mg/Kg DEHP & 3mg/Kg verapamil and 3mg/Kg verapamil group, respectively. Data were expressed as Means±SEM. *PPP<0.001 in comparison with the verapamil group and the vehicle group.</p

Effect of maternal Di-(2-ethylhexyl)-phthalate (DEHP) and verapamil exposure from E6.5 to E14.5 on fetal heart <i>PPARγ/Nkx2</i>.<i>5/Gata4/Tbx5/Mef2c/Chf1</i> mRNA expression at E15.5.

Differences among different groups were determined by ANOVA followed by a Student–Newman–Keuls multiple comparisons. N = 10, 15, 20 and 10 for vehicle, 500mg/Kg DEHP, 500mg/Kg DEHP & 3mg/Kg verapamil and 3mg/Kg verapamil group, respectively. Data were expressed as Means±SEM. *PPP<0.001 in comparison with the verapamil group and the vehicle group.</p

Effect of maternal Di-(2-ethylhexyl)-phthalate (DEHP) and verapamil exposure from E6.5 to E14.5 on fetal heart <i>Nkx2</i>.<i>5/Gata4/Tbx5/Mef2c/Chf1</i> protein expression at E15.5.

Differences among different groups were determined by ANOVA followed by a Student–Newman–Keuls multiple comparisons. N = 10, 15, 20 and 10 for vehicle, 500mg/Kg DEHP, 500mg/Kg DEHP & 3mg/Kg verapamil and 3mg/Kg verapamil group, respectively. Data were expressed as Means±SEM. *PPP<0.001 in comparison with the verapamil group and the vehicle group.</p