Cardiovascular Intervention in Neonates Using an Umbilical Vein Approach.

Cardiovascular catheterization has been applied in infant treatment for several decades. To date, considerable research attention has been paid to cardiovascular catheterization in small neonates. However, peripheral vascular routes of catheterization are possible obstacles for interventionists. Umbilical vein catheterization has been reported as a route for neonates, although few attempts have been made to investigate this approach. This study aimed to retrospectively review cardiovascular intervention using the umbilical vein approach as applied to infants admitted to a tertiary center from 2017 to 2020. Details including the perinatal variables, indication diagnoses, and procedure devices were collected. The enrollment included a total of 16 cases representing 17 intervention events, with infants born at a gestation age of 22-39 weeks and body weight ranging from 478 to 3685 g at the time of the procedure. The postnatal age ranged from 1 to 27 days. The catheter sizes ranged from 4 to 11 Fr. Indications included being admitted for patent ductus arteriosus occlusion (n = 15), balloon pulmonary valvuloplasty (n = 3), balloon atrial septostomy (BAS) (n = 3), pulmonary valve (PV) perforation (n = 1), and two interventions for catheter placement for continuous venovenous hemofiltration. The success rate for cardiovascular catheterization was 88.2% (15/17). There were two patients for which cannulation failed due to ductus venosus closure: one intraabdominal hemorrhage complication during continuous venovenous hemofiltration (CVVH), and one cardiac catheterization failure of PV perforation due to failure to insert the guiding catheter into the right ventricular outflow tract. Based on these findings, we conclude that cardiac catheterization and the placement of a large-sized catheter through an umbilical vein in a small infant represents a safe and time-saving method when catheterization is required.

Clinical Experience of Transcatheter Closure for Ventricular Septal Defects in Children Weighing under 15 kg.

BACKGROUND: Failure to thrive and poor weight gain are the main problems associated with ventricular septal defects complicated by heart failure in pediatric patients. Recent advances in transcatheter closure have enabled safe and effective interventions in these patients. OBJECTIVES: The purpose of this study was to describe our experience with transcatheter closure of ventricular septal defects in young children with low weight. METHODS: Pediatric patients weighing < 15 kg who underwent transcatheter closure of ventricular septal defects between January 2018 and December 2019 at our hospital were retrospectively enrolled. RESULTS: Twelve patients were enrolled: one with a muscular defect, two with outlet defects, and nine with perimembranous defects. Their median age was 24 (7-60) months, and their median weight before the procedure was 11.8 kg (4.7-14.9 kg; mean Z-score: -1.3). The median precordial echocardiographic defect diameter was 5.6 (2.0-9.3) mm. Successful transcatheter closure was achieved in 11 cases. The mean weight at 1-month follow-up after defect closure was 13.5 kg (6.2-19.8 kg; mean Z-score: -0.2). The mean length of hospitalization was 2.7 days. CONCLUSIONS: This study highlights the potential safety and therapeutic efficacy of transcatheter ventricular septal defect closure in infants with low weight. Considerable weight gain and heart failure symptom attenuation at 1 month after transcatheter closure were observed.

Transient Congenital Complete Heart Block: A Case Report.

Congenital complete heart block is defined as a complete atrioventricular block occurring prenatally, at birth, or within the first month of life. Congenital complete heart block has a high mortality rate, and in infants with normal heart morphology, it is often associated with maternal connective tissue disease. In these latter cases, neonatal congenital complete heart block is usually irreversible. We present a rare case of a female neonate who had bradycardia noted at a gestational age of 37 weeks. Her mother had no autoimmune disease history. She had no structural heart disease, and the serology surveys for autoantibodies including SSA/Ro and SSB/La were all negative. Without intervention or medication, her congenital complete heart block completely recovered to a normal sinus rhythm within 5 days. The cause of the transient congenital complete heart block was unknown in this case.

Respiratory Trajectory after Invasive Interventions for Patent Ductus Arteriosus of Preterm Infants.

Invasive interventions have been conducted in preterm infants with significant patent ductus arteriosus (PDA) when medical treatment has failed, and methods of invasive intervention have been reported. Surgical ligation via lateral thoracotomy has been a well-established procedure for decades. Recently, transcatheter occlusion has been safely and feasibly applied to the premature population. However, little research has been conducted on the benefits of transcatheter occlusion in very-low-birth-weight (VLBW) infants compared to surgical ligation. This study compared transcatheter and surgical techniques in VLBW infants in terms of short-term respiratory outcomes. The medical records of 401 VLBW infants admitted to a tertiary hospital between September 2014 and January 2019 were retrospectively reviewed. Patients who were diagnosed with a congenital anomaly, a chromosomal anomaly, or congenital heart disease, except for an inter-atrial shunt, were excluded. The perinatal conditions, neonatal morbidities, periprocedural vital signs, and respiratory support trajectories were compared between the transcatheter-treated and surgically ligated group. A total of 31 eligible VLBW infants received invasive intervention: 14 were treated with transcatheter occlusion (Group A), and 17 infants were treated with surgical ligation (Group B). Respiratory outcomes were not statistically significant between the two groups, despite Group A showing a trend toward early improvement in post-intervention respiratory trajectory. In this small case study, a different trend in post-intervention respiratory trajectories was observed. Future research with larger case numbers should be conducted to address our preliminary observations in more detail.

Reappraisal of the Subtropical Guidelines on Palivizumab Prophylaxis in Congenital Heart Disease.

Objective: To define the impact of associated abnormalities on the efficacy of the novel subtropical guidelines for palivizumab prophylaxis on respiratory syncytial virus (RSV)-related hospitalizations in patients with hemodynamically significant congenital heart disease (hsCHD). Method: This prospective study enrolled every patient seen at a tertiary care center for hsCHD, who was born between 2014 and 2018 and received at least 1 dose of palivizumab, according to the subtropical guidelines. The patients were followed until the age of 2 years. Results: A total of 772 patients (49% male) were enrolled. Cyanotic CHD was seen in 46% of patients, of whom 23% had associated abnormalities. Lung/airway abnormalities (14%) were the most common followed by the genetic syndromes associated with CHD (7.3%). Among the 772 patients, RSV-related hospitalizations occurred in 3.2 and 2.2% children aged ≤ 12 and 13-24 months, respectively. Most of the RSV infections occurred in patients no longer satisfying the criteria for palivizumab prophylaxis. The patients with associated abnormalities but not the type of CHD, patient age, and patient sex were risk factors for RSV-related hospitalizations. The rates of RSV-related hospitalizations, admission to the intensive care unit, and endotracheal intubation were higher for patients with associated anomalies than for other patients before 24 months of age (10.2 vs. 4.0%, 67 vs. 33%, and 39 vs. 4.2%, p = 0.004, 0.06, 0.013, respectively). Conclusion: Children with abnormalities, especially genetic syndromes and lung/airway problems associated with CHD, are at high risk for RSV-related hospitalization. Our current subtropical guidelines for palivizumab prophylaxis in patients with hsCHD, should be revised to include the results of this study.

Diastolic and systolic right ventricular diameters for predicting pulmonary hypertension in children with congenital heart disease.

Prospective electrocardiography (ECG)-gated cardiac computed tomography angiography (CTA) is widely used for pediatric patients with congenital heart disease (CHD) due to the lower radiation dose compared with the ECG-gated technique. However, functional parameters acquired using ECG-gated cardiac CT to predict pulmonary hypertension (PH) in children with CHD have not yet been reported. This study aimed to investigate the potential of diastolic and systolic right ventricular diameters (RVD) on prospective ECG-gated cardiac CTA to predict PH in children with CHD. A total of 44 children with CHD were divided into two groups: CHD with PH (n = 22) and CHD without PH (n = 22). The association between ECG-gated CTA parameters and PH was evaluated by logistic regression. The receiver operating characteristic curve (ROC) was used to find the best cut-off point for the parameters measured by Youden's index. Patients with higher RVD-BSA [aOR (95% CI) diastolic: 2.76 (1.23-6.23); systolic: 6.15 (1.72-22.06)] had higher risk of PH after adjusting for age and patent ductus arteriosus. The area under the curve (AUC) of D-RVD-BSA was 0.907 and the AUC of S-RVD-BSA was 0.917. Logistic regression showed that patients with D-RVD-BSA over 6.86 or S-RVD-BSA over 5.87 had significantly higher risk of PH after adjustments (aOR = 23.52, 95% CI = 2.89-191.03; aOR = 31.14, 95% CI = 2.75-352.85). In conclusion, in children with CHD, measurements of diastolic or systolic BSA-modified RVDs on prospective ECG-gated CTA are non-invasive markers of PH. BSA-modified D-RVD of 6.86 or BSA-modified S-RVD of 5.87 may be used to identify PH in children with CHD.

Congenital heart disease with pulmonary artery hypertension in an Asian cohort-initial report from TACHYON (TAiwan congenital heart disease associated with pulmonarY arterial hypertension) registry.

BACKGROUND: Prospective registry studies of congenital heart disease (CHD)-associated pulmonary artery hypertension (PAH) are rare. We established a multicenter registry of CHD-PAH: the TACHYON (TAiwan Congenital Heart disease associated with pulmonarY arterial hypertension) registry. METHODS: The prospective TACHYON registry was initiated in January 2016. Nine pediatric cardiology centers with 99 patients were included. Using this database, we evaluated clinical characteristics and outcomes. RESULTS: Twelve patients with incomplete data were excluded. For the remaining 87 patients, mean age of enrollment was 37.4(SD 18.2) years, and the male to female ratio was 60:27. PAH after defect closure accounted for 46 (52.9%) and Eisenmenger syndrome for 30 (34.5%) cases. Atrial septal defect was the most common (48.3%) disease, followed by ventricular septal defect. Mean pulmonary artery pressure was 56.7 (SD 19.4) mmHg. PAH-targeted therapy was used in 95.4% of patients. Sildenafil and bosentan were the most common drugs. After mean 23.9 months of follow-up, the 2-year Kaplan-Meier survival rate was 93.2%. According to univariate Cox regression analysis, significant risk factors included right heart failure signs, symptom progression, high-risk baseline N-terminal pro-brain natriuretic peptide (BNP)/BNP, high-risk baseline 6-min walking distance (6MWD), and high baseline hemoglobin/hematocrit level. Using the three noninvasive parameters (functional class, 6MWD, NT-pro BNP/BNP) proposed by the European Society of Cardiology, the total number of high-risk criteria predicted survival rate reliably. CONCLUSIONS: Using the TACHYON registry is feasible, but the physicians' adherences to guidelines are unsatisfactory. Midterm outcomes of PAH-target therapy are favorable and predictable using noninvasive parameters.

Timing of Endotracheal Intubation in Patients with Fulminant Enterovirus 71 Infection.

Background and objective: Enterovirus 71 (EV 71) infections may result in the rapid progression of cardiopulmonary failure. Early endotracheal intubation is considered to be of primary importance. However, the appropriate timing for this is still not known. The aim of this study is to investigate the timing of intubation of children with fulminant EV71 infection. Material and Methods: From March 1998 to May 2012, patients with severe EV71 infection who were admitted to the pediatric intensive care unit of the National Cheng Kung University Hospital were enrolled in this study. Medical records were retrospectively reviewed. The patients were classified into three groups in accordance with the outcome of intubation. We used rhombencephalitis grading to describe the neurological presentation of these patients. The study was approved by the institutional review board. Results: There were a total of 105 patients enrolled. Of these, 77 patients were in Grade I, and only three of them needed intubation, who were, however, soon extubated within 24 h. There were 10 patients in Grade II; nine of them needed intubation. In total, 18 patients belonged to Grade III, and all of them need to be intubated. We then compared the outcome of intubation of grades II and III. There was only one patient out of the nine patients in grade II who experienced failed extubation due to the progression of the disease. Among grade III patients, only four patients were successfully extubated. We also listed clinical parameters to determine which one could be a sign that indicated intubation. Comparing the favorable outcomes, cranial nerve involvement was a good indicator for the timing of intubation. Conclusions: This study showed that early intubation in Grade II provides favorable outcomes and improves morbidity and mortality. We also found that if cranial nerve involvement was present, then early intubation is indicated.

Transcatheter Closure of Patent Ductus Arteriosus in Premature Infants With Very Low Birth Weight.

Background: The aim of this study was to describe our experience with transcatheter device closure of patent ductus arteriosus (PDA) in symptomatic low-birth-weight premature infants. Methods: We performed a retrospective study of infants born with a birth body weight of < 2,000 g and admitted to National Cheng Kung University Hospital from September 2014 to December 2019. Basic demographic and clinical information as well as echocardiographic and angiographic data were recorded. Results: Twenty-five premature infants (11 boys and 14 girls) born at gestational ages ranging between 22 and 35 weeks (mean, 25 weeks) were identified. The mean age at procedure was 34.5 ± 5.5 days, and the mean weight was 1,209 ± 94 g (range, 478-1,980 g). The mean diameter of the PDA was 3.4 ± 0.2 mm (range, 2.0-5.4 mm). The following devices were used in this study: Amplatzer Ductal Occluder II additional size (n = 20), Amplatzer Vascular Plug I (n = 1), and Amplatzer Vascular Plug II (n = 4). Complete closure was achieved in all patients. The mean follow-up period was 30.1 ± 17.3 months (range, 6-68 months). In total, 3 patients had left pulmonary artery (LPA) stenosis and 1 patient had coarctation of the aorta during the follow-up period. Younger procedure age and smaller procedure body weight were significantly associated with these obstructions. Conclusions: Performing transcatheter PDA closure in symptomatic premature infants weighing more than 478 g is feasible using currently available devices; moreover, the procedure serves as an alternative to surgery.

Efficacy of a Novel Palivizumab Prophylaxis Protocol for Respiratory Syncytial Virus Infection in Congenital Heart Disease: A Multicenter Study.

OBJECTIVE: To analyze the efficacy of a novel palivizumab protocol for hemodynamically significant congenital heart disease (hsCHD) in subtropical areas without clear respiratory syncytial virus seasonality. STUDY DESIGN: Since July 2013, the National Health Insurance program has provided reimbursement for palivizumab prophylaxis with a novel monthly protocol in selected patients with hsCHD under 1 year of age. We performed a multicenter study to assess the trend of respiratory syncytial virus hospitalizations in patients with hsCHD from 2010 to 2016 during the prepalivizumab, transition, and postpalivizumab periods, and compared treatment and propensity-matched control groups. RESULTS: A total of 747 patients were enrolled in the study group and 809 in the control group. The male:female was 836:720. Cyanotic CHD was observed in 42.9% of patients. The mean age at diagnosis of CHD was 32.9 days. After 516 685 patient-days of follow-up and a mean of 3.9 doses of palivizumab in the treatment group, respiratory syncytial virus hospitalization rates decreased by 53% and 49% before and after match compared with the control group (P = .009 and .029, respectively). Hospitalization days and intensive care unit admission rate also decreased similarly in the treatment group. The efficacy of this protocol was more prominent in patients with cyanotic hsCHD. The annual respiratory syncytial virus-associated hospitalization rates also decreased significantly from the prepalivizumab to the palivizumab period (from 4.8% to 2.0%; P = .038). CONCLUSION: Palivizumab prophylaxis through the novel monthly protocol for patients with hsCHD is effective in reducing respiratory syncytial virus-related hospitalizations.

Hemodynamic, biological, and right ventricular functional changes following intraatrial shunt repair in patients with flow-induced pulmonary hypertension.

OBJECTIVES: Atrial septal defects may result in pulmonary hypertension and right heart remodeling. We analyzed improvements in patients with flow-induced pulmonary hypertension and the activation of endothelial progenitor cells after flow reduction. DESIGN: This prospective cohort study included 37 patients who were admitted for an occluder implantation. Blood samples were collected before and after the procedure. We determined the number of endothelial progenitor cells in outgrowth colonies and serum Hsp27 concentrations. Daily performance and cardiothoracic ratio were reevaluated later. RESULTS: Closure of the defect significantly reduced the pulmonary pressure and B-type natriuretic peptide levels. The cardiothoracic ratio and daily performance status also improved. The number of endothelial progenitor cell outgrowth colony-forming units significantly increased and was positively correlated with daily performance. In patients with enhanced colony formation, Hsp27 levels were significantly increased. CONCLUSIONS: The implantation of an occluder successfully improved hemodynamic, right ventricular, and daily performance. Qualitative enhancement of colony formation for endothelial progenitor cells was also noted and positively correlated with daily performance. Closure of defects may serve as a valid, reliable model to obtain a deeper understanding of the modulation of endothelial progenitor cell activity and its relationship with pulmonary hypertension prognosis.

Interventional Transcatheter Closure Ameliorates the Leukocyte Rho Kinase Activities among Patients with Patent Ductus Arteriosus.

BACKGROUND: Patent ductus arteriosus (PDA) causes increased pulmonary blood flow, which can lead to pulmonary arterial hypertension (PAH). Rho-associated coiled-coil containing protein kinase (ROCK) may play an important pathophysiological role in PAH. We hypothesized that the increased pulmonary artery (PA) flow from PDA could activate ROCK. METHODS: Patients who received a PDA transcatheter closure in our hospital were consecutively enrolled in this study. Basic demographics and clinical hemodynamic data of the study participants were recorded. Then, ROCK activity was measured before and after the PDA occlusion procedure. ROCK activity was defined as the phosphorylation ratio of myosin-binding subunit by Western blot measurement. We also sub-divided patients into the coil group and occluder group based on the occlusion device used in each patient's procedure. RESULTS: From January 2009 to December 2011, 25 patients with a median age of 2.3 years, ranging from 10 months to 72 years were enrolled. The mean PDA size was 0.31 ± 0.14 cm, the mean Qp/Qs shunt was 1.54 ± 0.41, and the mean systolic pulmonary artery pressure was 26.9 ± 10.3 mmHg. There were 10 patients (one boy and nine girls) in the coil group and 15 patients (four boys and eleven girls) in the occluder group. Following the closure of the PDA, ROCK activity significantly decreased (1.78 ± 2.25 vs. 0.77 ± 0.69, p < 0.01). There was a strong correlation between the leukocyte ROCK activity with the systolic PA pressure (y = 5.4608x + 22.54, R2 = 0.5539, p < 0.05), but not the Qp/Qs value. Both subgroups showed significant changes of ROCK activity after the procedure. Interestingly, when comparing the coil group with the occluder group, the decrease in ROCK activity was more apparent in the occluder group. CONCLUSIONS: The findings of this study indicated that ROCK activity is higher in patients with PDA and correlates with PA pressure. The decrease in ROCK activity following the device closure suggests that ROCK may be an important biomarker for PDA patency. KEY WORDS: Patent ductus arteriosus (PDA); Pulmonary arterial pressure; Rho kinase; Transcatheter closure.

Late recurrence of infra-Hisian complete atrioventricular block.

Acquired complete atrioventricular block that is caused by infectious myocarditis is usually transient and has a favourable outcome. We report the case of a 15-year-old girl who had complete infra-Hisian atrioventricular block due to adeno viral myocarditis and received a permanent pacemaker at the age of 10 months. The pacemaker lost its function at the age of 7 years. However, she experienced a late recurrence of complete atrioventricular block 10 years later. Complete atrioventricular block is rarely recovered if it persisted for 2 weeks. Even in the patients with late recovery, long-term follow-up and pacemaker therapy are still needed.

Tetralogy of Fallot associated with right arch and persistent left dorsal aortic aneurysm.

We described a patient who was diagnosed of Tetralogy of Fallot with right arch. Dorsal aortic aneurysm was found later confirmed by cardiac catheterization and reconstruction of 3D computer tomography. To our knowledge, the combination of Tetralogy of Fallot and dorsal aortic aneurysm had never been reported.

Octreotide therapy in two children with intractable postoperative chylothorax.

Postoperative chylothorax is sometimes difficult to be managed either by conventional therapies or by surgery. Herein, we report the experience of octreotide therapy for intractable postoperative chylothorax in two children (one was severe tetralogy of Fallot received Blalock-Taussing shunt, and the other was a single ventricle received bi-directional Glenn shunt) and review the literature on octreotide efficacy.

Functional characteristics and inducibility of atrioventricular nodal re-entry in rabbits of different ages.

AIMS: Many issues regarding atrioventricular nodal re-entry (AVNR) remain unexplored; however, no stable animal model for the study of AVNR has yet been developed. Clinically, AVNR is found more commonly in adults than children. We attempt to characterize AV nodal functional properties and inducibility of AVNRT using rabbits of three different age groups since we hypothesize that the inducibility of AVNR may increase as the subject ages. METHODS AND RESULTS: We evaluated the inducibility of AVNR and the functional characteristics of the AV node in 6-month-old (Group 1), 2-month-old (Group 2), and at 1-week-old (Group 3) rabbits using a well-established rabbit heart model. We found that the inducibility of AVNR was higher in the 2-month-old group, compared with the 1-week-old group (30%). There was no functional difference between the two older groups (6-month-old and 2-month-old groups), however the youngest group (Group 3) showed better AV nodal functional properties. Regarding the correlation between inducibility and nodal functional properties, subgroups with AVNR demonstrated a longer AH maximum (AHmax) compared with the non-re-entry group, although there is no difference in age-adjusted AHmax. Regarding the correlation between inducibility and nodal functional properties, for the 1-week-old rabbits, subgroups with AVNR demonstrated a shorter AH minimum compared with the non-re-entry group (39.0 vs. 61.0, P=0.017). CONCLUSION: Our results demonstrate that both 2-month-old and 6-month-old rabbits represent stable models for AVNR. Longer AH conduction time may lead to greater re-entry inducibility.

Urinary cytokines and renal Doppler study in Kawasaki disease.

OBJECTIVE: To investigate whether renal vasculitis is the sole cause or merely a contributing cause of renal inflammation in Kawasaki disease (KD). STUDY DESIGN: This prospective study in a university medical center in Taiwan enrolled 24 children with KD between June 2004 and November 2005. All patients underwent a technetium-99 m dimercaptosuccinic acid scintigraphy single-photon emission computed tomography scan, the results of which were used to group the patients with KD as with or without renal involvement. Urine samples underwent a cytokine analysis. Renal Doppler ultrasonography was used to evaluate renal vasculitis by measuring the pulsatility index (PI) and resistance index (RI). RESULTS: Ten of the 24 patients (42%) with renal inflammatory foci were the study group; the remainder composed the control group. Urinary interleukin (IL)-6 levels were significantly higher in the study group (496.7 +/- 310.9 vs 115.0 +/- 65.9 ng/g urinary creatinine; P < .01), as were PI values (1.85 +/- 0.70 vs 1.44 +/- 0.53; P < .05). Urinary IL-6 levels and PI values were significantly (P < .05) correlated. CONCLUSIONS: Increased urinary IL-6 and elevated renal Doppler measures suggest that immune-mediated vasculitis is one of the mechanisms causing renal inflammation in KD.

PTPN11 mutations in LEOPARD syndrome: report of four cases in Taiwan.

BACKGROUND/PURPOSE: LEOPARD syndrome (LS) is a rare, autosomal dominant disorder. The typical clinical presentation includes multiple lentigines and cardiac defects. Mutation analysis of the PTPN11 gene is feasible. We report four cases of LS, which were confirmed by molecular genetic study. METHODS: The clinical features and mutations of the four patients were summarized. RESULTS: The diagnosis of all four patients was made when lentigines appeared during childhood. Three cases had hypertrophic cardiomyopathy. No electrocardiographic conduction abnormality was noted in any of the cases. Three patients had hypertelorism and three had short stature. Two patients, identical twins, presented with the atypical phenotype of tongue protrusion and hepatosplenomegaly at birth. Twin B had mild mental retardation. Case 4 had moderate hearing impairment. Point mutation of the PTPN11 gene was found in all patients. CONCLUSION: LS has typical skin manifestations. All patients should undergo a comprehensive examination, especially echocardiography and electrocardiography. The diagnosis can be confirmed by genetic study.