Pediatric Extracorporeal Membrane Oxygenation in Korea: A Multicenter Retrospective Study on Utilization and Outcomes Spanning Over a Decade.

BACKGROUND: Over the last decade, extracorporeal membrane oxygenation (ECMO) use in critically ill children has increased and is associated with favorable outcomes. Our study aims to evaluate the current status of pediatric ECMO in Korea, with a specific focus on its volume and changes in survival rates based on diagnostic indications. METHODS: This multicenter study retrospectively analyzed the indications and outcomes of pediatric ECMO over 10 years in patients at 14 hospitals in Korea from January 2012 to December 2021. Four diagnostic categories (neonatal respiratory, pediatric respiratory, post-cardiotomy, and cardiac-medical) and trends were compared between periods 1 (2012-2016) and 2 (2017-2021). RESULTS: Overall, 1065 ECMO runs were performed on 1032 patients, with the annual number of cases remaining unchanged over the 10 years. ECMO was most frequently used for post-cardiotomy (42.4%), cardiac-medical (31.8%), pediatric respiratory (17.5%), and neonatal respiratory (8.2%) cases. A 3.7% increase and 6.1% decrease in pediatric respiratory and post-cardiotomy cases, respectively, were noted between periods 1 and 2. Among the four groups, the cardiac-medical group had the highest survival rate (51.2%), followed by the pediatric respiratory (46.4%), post-cardiotomy (36.5%), and neonatal respiratory (29.4%) groups. A consistent improvement was noted in patient survival over the 10 years, with a significant increase between the two periods from 38.2% to 47.1% (P = 0.004). Improvement in survival was evident in post-cardiotomy cases (30-45%, P = 0.002). Significant associations with mortality were observed in neonates, patients requiring dialysis, and those treated with extracorporeal cardiopulmonary resuscitation (P < 0.001). In pediatric respiratory ECMO, immunocompromised patients also showed a significant correlation with mortality (P < 0.001). CONCLUSION: Pediatric ECMO demonstrated a steady increase in overall survival in Korea; however, further efforts are needed since the outcomes remain suboptimal compared with global outcomes.

Reference Intervals of Thromboelastometric Evaluation of Coagulation in Pediatric Patients with Congenital Heart Diseases: A Retrospective Investigation.

BACKGROUND Rotational thromboelastometry (ROTEM®) is a point-of-care test for coagulation, enabling physicians to make a swift decision. The aim of this investigation was to establish reference intervals of thromboelastometric evaluation for coagulation in pediatric patients with congenital heart diseases (CHD). MATERIAL AND METHODS As baseline data, 3 assays of ROTEM® (INTEM, EXTEM, and FIBTEM) were measured after anesthesia induction. ROTEM® parameters were clotting time (CT), amplitude at 10 min (A10), clot formation time (CFT), a angle, maximal clot firmness (MCF), clot lysis index at 60 min (LI60), and maximal clot elasticity (MCE). As age is a well-known factor for maturation, age groups were determined as follows; 1) <1 month, 2) 1-3 months, 3) 4-12 months, 4) 1-3 years, 5) 4-6 years, 6) 7-12 years, and 7) 13-16 years. Reference limits representing 95% of distribution of ROTEM® parameters and 90% confidence intervals of upper and lower reference limits were calculated. RESULTS The data of 413 patients were analyzed. Although INTEM CT was prolonged, significantly shorter CT and CFT, steeper α, and greater A10, MCF, and MCE were shown in patients age <3 months compared to older children. CONCLUSIONS Reference intervals of thromboelastometric evaluation for coagulation from pediatric patients with CHD were shown to have similar pattern to those obtained from healthy pediatric patients. Pediatric patients with CHD, even with cyanosis, were demonstrated to have functionally intact coagulation profile before surgery.

Successful Heart Transplantation Despite Rhesus Blood Type Mismatch: A Case Report.

Matching for the rhesus (Rh) blood group is currently not taken into account in the organ allocation system. However, in Rh-mismatched transplantation, the primary concern is the potential for RhD-negative recipients to develop sensitization and produce anti-D anti-bodies if they receive a transfusion of RhD-positive blood. It is estimated that over 80% of RhD-negative recipients may experience Rh allosensitization when exposed to RhD-positive blood, although this occurrence is less common in recipients of solid organs. In theory, RhD-negative recipients who receive organs from RhD-positive donors are at risk of alloimmunization and the production of anti-D antibodies, which could complicate future blood product transfusions. However, our understanding of the impact of donor-recipient Rh mismatch on transplant outcomes, particularly in heart transplantation, is limited. We report a case of successful Rh-mismatched heart transplantation, which was effectively managed through the use of preoperative RhD immunoglobulin and plasmapheresis.

Successful Bridge to Heart Transplantation through Ventricular Assist Device Implantation and Concomitant Fontan Completion in a Patient with Glenn Physiology: A Case Report.

A 3-year-old boy with Glenn physiology exhibited refractory heart failure with reduced ejection fraction. To improve the patient's oxygen saturation, he underwent ventricular assist device (VAD) implantation with concomitant Fontan completion. The extracardiac conduit Fontan operation was performed with a 4-mm fenestration. For VAD implantation, Berlin Heart cannulas were positioned at the left ventricular apex and the neo-aorta. Following weaning from cardiopulmonary bypass, a temporary continuous-flow VAD, equipped with an oxygenator, was utilized for support. After a stabilization period of 1 week, the continuous-flow VAD was replaced with a durable pulsatile-flow device. Following 3 months of support, the patient underwent transplantation without complications. The completion of the Fontan procedure at the time of VAD implantation, along with the use of a temporary continuous-flow device with an oxygenator, may aid in stabilizing post-operative hemodynamics. This approach could contribute to a safe transition to a durable pulsatile VAD in patients with Glenn physiology.

Successful Heart Transplant in Dilated Cardiomyopathy Associated With Alström Syndrome: A Case Report.

Alström syndrome is a rare, multisystemic genetic disorder, and dilated cardiomyopathy occurs in approximately two-thirds of patients with this condition. Because of donor organ shortage and unfavorable prognosis of multiple organ dysfunction, heart transplant is not the most desirable therapeutic option for patients with dilated cardiomyopathy with Alström syndrome. However, eliminating heart dysfunction elements at an appropriate time itself plays a pivotal role in preventing or even reversing other organ failures. Herein, we report the case of a 17-year-old boy who underwent successful isolated heart transplant despite severe liver dysfunction.

Platelet Reactivity and Outcomes after Off-Pump Coronary Surgery in Acute Coronary Syndrome Patients.

Ischemic and hemorrhagic complications are major determinants of survival in acute coronary syndrome (ACS) patients undergoing coronary surgery. We investigated the association of preoperative platelet reactivity to P2Y12 antagonists with ischemic and hemorrhagic complications after Off-Pump Coronary Artery Bypass surgery (OPCAB) in ACS patients who received dual anti-platelet therapy (DAPT) within 5 days prior to surgery. This prospective, observational study with 177 patients compared the incidence of perioperative major bleeding and major adverse cardiac events (MACEs) in relation to the tertile distribution of the % inhibitory response to P2Y12 antagonists, as measured by a thromboelastography platelet mapping assay. The incidences of perioperative major bleeding and MACEs were similar in relation to the tertile distribution of inhibitory response to P2Y12 antagonists. The % inhibitory responses to P2Y12 antagonists between patients who did or did not exhibit MACEs, and with or without major bleeding, were 58 ± 20% and 56 ± 20% (p = 0.578) and 57 ± 19% and 56 ± 21% (p = 0.923), respectively. In ACS patients who received DAPT close to OPCAB, the platelet inhibitory response to P2Y12 antagonists was not associated with ischemic or hemorrhagic complications. OPCAB may obviate the need for routine platelet function testing for ACS patients requiring DAPT and surgical revascularization. Clinical Registration Number: NCT02184884.

Noninvasive surrogates are poor predictors of liver fibrosis in patients with Fontan circulation.

OBJECTIVES: Patients with Fontan circulation exhibit a high incidence of liver fibrosis and cirrhosis. Transient elastography (TE) and the enhanced liver fibrosis (ELF) test have proven useful as noninvasive surrogate markers of liver fibrosis for other chronic liver diseases. We evaluated whether TE and the ELF score can predict the degree of liver fibrosis in patients with Fontan circulation. METHODS: We retrospectively reviewed the medical records of 45 adult patients with at least 10 years of Fontan duration who had undergone liver biopsy and investigated the relation between the fibrosis stage and TE and the ELF test results. Additionally, the association of these variables and other biochemical and hemodynamic parameters was assessed. RESULTS: The mean age was 25.9 years and the mean Fontan duration was 20.8 years. Advanced liver fibrosis was present in 36 (80.0%) patients. TE or ELF score are comparable for patients with and without advanced liver fibrosis (mean 23.3 vs 24.8 kPa [P = .85] for TE; mean 8.94 vs 9.25 [P = .44] for the ELF score). However, N-terminal pro-brain natriuretic peptide level and ventricular end-diastolic pressure were higher in patients with advanced liver fibrosis (mean 224 vs 80 pg/mL [P < .01]; and mean 12 vs 9 mm Hg [P = .04], respectively). No independent predictor of advanced liver fibrosis was found in multivariate analysis. CONCLUSIONS: TE and the ELF score were unable to predict the degree of liver fibrosis in Fontan patients. Liver biopsy remains as the only valid method to assess fibrotic burden in this population.

Influence of Mild Thyroid Dysfunction on Outcomes after Off-Pump Coronary Artery Bypass Surgery.

We retrospectively evaluated the association between preoperative mild thyroid dysfunction (subclinical hypothyroidism [SCH] or low triiodothyronine [T3] syndrome) and outcomes in patients who underwent off-pump coronary surgery (OPCAB). Further, 800 patients (2015−2020) were divided into euthyroid, low T3, and SCH groups. The primary outcome assessed the association with composite endpoints (myocardial infarction, prolonged mechanical ventilation [>24 h], acute kidney injury, and 30-day/in-hospital mortality). The secondary outcome assessed the association with long-term mortality and 10% and 8% of the patients exhibited low T3 and SCH, respectively. Incidences of composite endpoints were significantly higher in the low T3 and SCH groups versus the euthyroid group (50.6%, 45.2%, 17.4%, respectively, p < 0.001). Multivariable regression analysis revealed chronic kidney disease, anemia, EuroSCORE, low T3, and SCH as independent risk factors of composite endpoints. The long-term mortality rate (median follow-up, 30 months) was higher in the low T3 and SCH groups than in the euthyroid group (9.6%, 11.3%, 2.4%, respectively, p < 0.001). In the absence of overt thyroid dysfunction, low T3 and SCH were associated with increased risk of adverse outcomes after OPCAB. Moreover, the adverse influences of low T3 and SCH seem to extend to long-term mortality, implying that routine thyroid function tests may enhance accurate risk stratification.

Clinical significance of right ventricular-pulmonary arterial coupling in patients with tricuspid regurgitation before closure of atrial septal defect.

Background: Functional tricuspid regurgitation (TR) usually decreases after atrial septal defect (ASD) closure; however, it may persist and cause heart failure that requires treatment. We aimed to investigate clinical and echocardiographic factors predicting persistent TR after ASD closure. Methods: Among 348 adults who underwent isolated ASD closure between January 2010 and September 2020, 91 (26.1%) patients with significant TR (at least moderate degree) before ASD closure were included. Persistent TR was defined as significant TR on echocardiography at 6 months to 1 year after ASD correction. We comprehensively analyzed the echocardiogram before ASD closure, including speckle-tracking imaging. Right ventricular (RV)-pulmonary arterial (PA) (RV-PA) coupling was assessed by the ratio of RV global longitudinal strain (RV GLS) and tricuspid annular S' velocity to PA systolic pressure (PASP). Results: Persistent TR was observed in 22 (24.2%) patients. Patients with persistent TR were significantly older and had larger TR jet areas and lower RV-PA coupling parameters than those without persistent TR. On multivariable regression, persistent TR was independently associated with age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01-1.14, p = 0.030) and |RV GLS|/PASP (OR 0.001, 95% CI 0.00-0.017, p = 0.012). ROC curves analysis showed that |RV GLS|/PASP's best cut-off for persistent TR was 0.46 (cut-off 0.46, the area under the curve 0.789, p < 0.001). Conclusion: Persistent TR after ASD closure is not rare. Old age and RV-PA uncoupling could be associated with persistent TR after ASD closure. In older patients with abnormal RV-PA coupling, careful evaluation and concomitant or subsequent TR intervention may be considered.

Chylothorax after Surgery for Congenital Cardiac Disease: A Prevention and Management Protocol.

BACKGROUND: Chylothorax after congenital heart surgery is not an uncommon complication, and it is associated with significant morbidity. However, consensus treatment guidelines are lacking. To improve the treatment outcomes of patients with postoperative chylothorax, we implemented a standardized management protocol at Severance Hospital in September 2014. METHODS: A retrospective review of patients treated at a single center was done. All corrective and palliative operations for congenital heart disease performed at our institution between January 2008 and April 2018 were reviewed. The incidence and treatment outcomes of postoperative chylothorax were analyzed. RESULTS: The incidence of chylothorax was 1.9%. Sixty-one percent of the patients could be managed with a low-fat diet, while 28% of the patients required complete restriction of enteral feeding. Thoracic duct embolization was performed in 2 patients and chest tube drainage decreased immediately after the procedure. No patient required thoracic duct ligation or pleurodesis. After implementation of the institutional management protocol, the number of chest tube drainage days decreased (median, 24 vs. 14 days; p=0.45). CONCLUSION: Implementing a strategy to reduce postoperative chylothorax resulted in an acceptable incidence of postoperative chylothorax. Instituting a clinical practice protocol helped to curtail the treatment duration and to decrease the requirement for surgical treatment. Image-guided embolization of the thoracic duct is an effective treatment for postoperative chylothorax.

The First Pediatric Heart Transplantation Bridged by a Durable Left Ventricular Assist Device in Korea.

Treatment options for children with end-stage heart failure are limited. We report the first case of a successful pediatric heart transplantation bridged with a durable left ventricular assist device in Korea. A 10-month-old female infant with dilated cardiomyopathy and left ventricular non-compaction was listed for heart transplantation. During the waiting period, the patient's status deteriorated. Therefore, we decided to provide support with a durable left ventricular assist device as a bridge to transplantation. The patient was successfully bridged to heart transplantation with effective support and without any major adverse events.

Pediatric Ventricular Assist Device.

There have been great advances in ventricular assist device (VAD) treatment for pediatric patients with advanced heart failure. VAD support provides more time for the patient in the heart transplant waiting list. Augmented cardiac output improves heart failure symptoms, end-organ function, and general condition, and consequently provides beneficial effects on post-transplant outcomes. Miniaturized continuous flow devices are more widely adopted for pediatric patient with promising results. For infants and small children, still paracorporeal pulsatile device is the only option for long-term support. Younger age, congenital heart disease, biventricular support, patient's status and end-organ dysfunction at the time of implantation are risks for poor outcomes. Patient selection, timing of implantation, and selection of device for each patient are critical for optimal clinical outcomes.

Emergency Pulmonary Artery-to-Systemic Artery Shunt to Break the Positive Feedback Loop of a Pulmonary Hypertensive Crisis after Neonatal Coarctation Repair.

A 2.5-kg neonate with coarctation of the aorta and a small left ventricle experienced a severe pulmonary hypertensive crisis. An emergency pulmonary artery-to-systemic artery shunt was placed to break the positive feedback loop caused by pulmonary hypertension and functional mitral stenosis. This shunt provided immediate relief of suprasystemic pulmonary hypertension and the resultant low cardiac output.

Evaluation of Flow Pattern in the Ascending Aorta in Patients with Repaired Tetralogy of Fallot Using Four-Dimensional Flow Magnetic Resonance Imaging.

OBJECTIVE: To evaluate flow pattern characteristics in the ascending aorta (AA) with four-dimensional (4D)-flow MRI and to determine predictors of aortic dilatation late after tetralogy of Fallot (TOF) repair. MATERIALS AND METHODS: This study included 44 patients with repaired TOF (25 males and 19 females; mean age, 28.9 ± 8.4 years) and 11 volunteers (10 males and 1 female, mean age, 33.7 ± 8.8 years) who had undergone 4D-flow MRI. The aortic diameters, velocity, wall shear stress (WSS), flow jet angle (FJA), and flow displacement (FD) at the level of the sinotubular junction (STJ) and mid-AA were compared between the repaired TOF and volunteer groups. The hemodynamic and clinical parameters were also compared between the aortic dilatation and non-dilatation subgroups in the repaired TOF group. RESULTS: The diameters of the sinus of Valsalva, STJ, and AA were significantly higher in the repaired TOF group than in the volunteer group (p = 0.002, p < 0.001, and p = 0.013, respectively). The FJAs at the STJ and AA were significantly greater in the repaired TOF group (p < 0.001 and p = 0.003, respectively), while velocities and WSS parameters were significantly lower. FD showed no statistically significant difference (p = 0.817). In subgroup analysis, age at TOF repair was significantly higher (p = 0.039) and FJA at the level of the AA significantly greater (p = 0.003) and mean WSS were significantly lower (p = 0.039) in the aortic dilatation group. FD were higher in the aortic dilatation group without statistical significance (p = 0.217). CONCLUSION: Patients with repaired TOF have an increased FJA, dilated AA, and secondarily decreased WSS. In addition to known risk factors, flow eccentricity may affect aortic dilatation in patients with repaired TOF.

Simplified Tricuspid Polytetrafluoroethylene Valved Conduit: Midterm Results of Multicenter Study.

BACKGROUND: Conduit survival without significant dysfunction is important when selecting the right ventricular outflow tract conduit. We made an expanded polytetrafluoroethylene tricuspid valved conduit using a simplified technique. We aimed to investigate the midterm functional results and longevity of this conduit. METHODS: Between November 2008 and December 2016, four hospitals in Korea implanted 145 valved conduits. We retrospectively analyzed their functional results and longevity. RESULTS: The patients' median age at operation was 36.6 months; the median body weight was 11.3 kg. The mean follow-up duration was 32.3 ± 24.5 months. There were four inhospital deaths and three late deaths, but there were no conduit-related deaths. The mean peak systolic pressure gradient across the conduit was 14.7 ± 8.3 mm Hg and 31.6 ± 17.7 mm Hg at discharge and last follow-up, respectively. Six patients (4.4%) had moderate or more conduit valve regurgitation at last follow-up. Conduit dysfunction was observed in 30 patients (21.9%), mainly caused by increased pressure gradient (24 of 30, 80%). Freedom from conduit dysfunction was 88.1% and 58.5% at 3 and 5 years, respectively. Lower freedom from conduit dysfunction was observed in small conduits. Eleven patients (7.8%) underwent conduit explantation, and freedom from explantation was 94.8% and 81.7% at 3 and 5 years, respectively. The main cause of explantation was conduit stenosis. Small conduits tended to have lower freedom from explantation. CONCLUSIONS: Functional results and longevity of our expanded polytetrafluoroethylene tricuspid valved conduit are acceptable. Although our conduits tend to have increasing pressure gradient over time, especially in small conduits, they have low incidence of moderate or more regurgitation.

Concomitant Right Ventricular Outflow Tract Cryoablation during Pulmonary Valve Replacement in a Patient with Tetralogy of Fallot.

A 38-year-old female patient with a history of tetralogy of Fallot repair at 10 years of age underwent pulmonary valve replacement with a mechanical prosthesis, tricuspid annuloplasty, and right ventricular outflow tract cryoablation due to pulmonary regurgitation, tricuspid regurgitation, and multiple premature ventricular contractions with sustained ventricular tachycardia. After surgery, she had an uneventful postoperative course with arrhythmia monitoring. She was discharged without incident, and a follow-up Holter examination showed a decrease in the number of ventricular ectopic beats from 702 to 41.

Tricuspid Valve Re-Repair in Ebstein Anomaly Using the Cone Technique.

The management of recurrent tricuspid regurgitation after tricuspid valve repair in patients with Ebstein anomaly is difficult, and tricuspid valve replacement is most commonly performed in such patients. We report two cases of recurrent tricuspid regurgitation in patients with Ebstein anomaly that were successfully re-repaired using the cone technique. The cone repair technique is a useful surgical method for reconstructing a competent tricuspid valve, and can be applied in patients who have undergone previous tricuspid valve repair.

Glutamine up-regulates MAPK phosphatase-1 induction via activation of Ca2+→ ERK cascade pathway.

The non-essential amino acid L-glutamine (Gln) displays potent anti-inflammatory activity by deactivating p38 mitogen activating protein kinase and cytosolic phospholipase A2 via induction of MAPK phosphatase-1 (MKP-1) in an extracellular signal-regulated kinase (ERK)-dependent way. In this study, the mechanism of Gln-mediated ERK-dependency in MKP-1 induction was investigated. Gln increased ERK phosphorylation and activity, and phosphorylations of Ras, c-Raf, and MEK, located in the upstream pathway of ERK, in response to lipopolysaccharidein vitro and in vivo. Gln-induced dose-dependent transient increases in intracellular calcium ([Ca2+]i) in MHS macrophage cells. Ionomycin increased [Ca2+]i and activation of Ras → ERK pathway, and MKP-1 induction, in the presence, but not in the absence, of LPS. The Gln-induced pathways involving Ca2+→ MKP-1 induction were abrogated by a calcium blocker. Besides Gln, other amino acids including L-phenylalanine and l-cysteine (Cys) also induced Ca2+ response, activation of Ras → ERK, and MKP-1 induction, albeit to a lesser degree. Gln and Cys were comparable in suppression against 2, 4-dinitrofluorobenzene-induced contact dermatitis. Gln-mediated, but not Cys-mediated, suppression was abolished by MKP-1 small interfering RNA. These data indicate that Gln induces MKP-1 by activating Ca2+→ ERK pathway, which plays a key role in suppression of inflammatory reactions.

Cytomegalovirus Myocarditis Required Extracorporeal Membrane Oxygenation Support Followed by Ganciclovir Treatment in Infant.

A 7-month-old girl with no medical history was treated with mechanical circulatory support due to myocarditis. Her cardiac contractility did not improve despite more than one week of extracorporeal membrane oxygenation treatment. Thus, we planned a heart transplant. However, a high level of cytomegalovirus was found in blood laboratory results by quantitative polymerase chain reaction. The patient's heart contractility recovered to normal range four days after ganciclovir treatment. She was discharged with slightly decreased cardiac contractility with a left ventricular ejection fraction of 45%.