Manifestations of Rheumatic Carditis, Regression of Valvular Regurgitation, and Independent Predictors of Mitral Regurgitation Improvement After Rheumatic Carditis in Thai Children.

Background: Acute rheumatic fever (ARF) with carditis can lead to the development of rheumatic heart disease in children and young adults. Objective: This study aimed to investigate the manifestations of rheumatic carditis, clinically significant regression of valvular regurgitation as assessed by echocardiography, and the independent predictors of mitral regurgitation (MR) improvement after rheumatic carditis in Thai children. Method: Children diagnosed with rheumatic carditis during 2005-2020 at Siriraj Hospital (Bangkok, Thailand) were retrospectively enrolled. Trivial, and mild regurgitation were grouped as non-clinically significant (NCS) regurgitation. Valvular regression was defined moderate-severe regurgitation improving to NCS regurgitation. Results: Eighty-one patients (mean age: 10 years, range: 8-12 years) were included. At presentation, 59 (72.8%) patients had combined mitral regurgitation (MR) and aortic regurgitation (AR), 20 (24.6%) patients had MR alone, and 2 (2.4%) patients had AR alone. Concerning severity, 28 (34.6%) and 30 (37%) patients presented with severe and moderate MR, respectively. Severe and moderate AR was found in 9 (11.1%) and 16 (19.8%) patients, respectively. At the one-year follow-up, 43.4% of moderate-severe MR, and 41.7% of moderate-severe AR improved to NCS regurgitation. Multivariate analysis revealed high erythrocyte sedimentation rate (ESR) (p = 0.01) and severe carditis (p = 0.05) at presentation to be independent predictors of MR improvement. Conclusion: Thai children with rheumatic carditis had a high incidence of valvular regurgitation; however, the valvular damage was improved in most patients. High ESR and severe carditis independently predict MR improvement.

Aortic Root Dilatation Measured by Cardiac Magnetic Resonance in Patients with Repaired Tetralogy of Fallot.

BACKGROUND: Aortic root dilatation (AoD) frequently occurs following repaired tetralogy of Fallot (rTOF). The objective of this study was to assess aortic dimensions, investigate the prevalence of AoD, and identify predictors of AoD in rTOF patients. METHODS: A cross-sectional retrospective study was conducted in repaired TOF patients from 2009 to 2020. Aortic root diameters were measured by cardiac magnetic resonance (CMR). Severe AoD of the aortic sinus (AoS) was defined as a Z-score (z) of >4, reflecting a mean percentile ≥99.99%. RESULTS: Two hundred forty-eight patients, with a median age of 28.2 years (10.2-65.3 years), were included in the study. The median age at the time of repair was 6.6 years (0.8-40.5 years) and the median interval between the repair and CMR study was 18.9 years (2.0-54.8 years). The prevalence of severe AoD was found to be 35.2% when defined by an AoS z greater than 4 and 27.6% when defined by a AoS diameter ≥40 mm, respectively. A total of 101 patients (40.7%) had aortic regurgitation (AR), with 7 patients (2.8%) having moderate AR. Multivariate analysis revealed that severe AoD was only associated with the left ventricular end diastolic volume index (LVEDVi) and a longer duration after repair. The age at the time of repair for TOF was found not to be correlated with the development of AoD. CONCLUSIONS: After repair of TOF, severe AoD was found to be prevalent, but no fatal complications were observed in our study. Mild AR was also commonly observed. Larger LVEDVi and a longer duration after repair were identified as factors associated with the development of severe AoD. Therefore, routine monitoring of AoD is recommended.

Major infections following pediatric cardiac surgery pre- and post-CLABSI bundle implementation.

Background: Postoperative infection contributes to the worsening of congenital cardiac surgery (CCS) outcomes. Surgical site infection (SSI), bloodstream infection (BSI) and ventilator associated pneumonia (VAP) are common. An additional bundle of preventive measures against central-line associated bloodstream infection (CLABSI) bundle was implemented in April 2019. Objectives: To compare the incidence of major infections after pediatric CCS before and after the implementation of the CLABSI bundle and to identify risk factors for major infections. Methods: We conducted a single-center, retrospective study to assess the incidence of major infections including bloodstream infection (BSI), surgical site infection (SSI), and ventilator-associated pneumonia (VAP) after pediatric CCS one year before and after implementation of the CLABSI bundle during April 2018-March 2020. The demographics and outcomes of the patients were explored, and risk factors for major infections were identified using multivariate analysis. Results: A total of 548 children (53% male) underwent CCS with a median age of 1.9 years (range 0.01-17.5 years). The median Aristotle Basic Complexity score was 7.1 (range 3-14.5). The CLABSI bundle was applied in 262 patients. Overall mortality was 5.5%. 126 patients (23%) experienced major postoperative infections. During the year after the implementation of the CLABSI bundle, BSI was reduced from 8.4% to 3.1% (p = 0.01), with a smaller reduction in VAP (21% to 17.6%; p = 0.33). The incidence of SSI was unchanged (1.7% to 1.9%; p = 0.77). The independent risk factors for major infections were age at surgery <6 months (p = 0.04), postoperative ventilator usage >2 days (p < 0.01), central line usage >4 days (p = 0.04), and surgery during the pre-CLABSI bundle period (p = 0.01). Conclusion: Following the implementation of the CLABSI prevention package in our pediatric CCS unit, the incidence of BSI was significantly reduced. The incidence of VAP tended to decrease, while the SSI was unchanged. Sustainability of the prevention package through nurse empowerment and compliance audits is an ongoing challenge.

Prenatal predisposing factors associated with neonatal lupus erythematosus.

OBJECTIVES: To identify the prenatal predisposing factors related to neonatal lupus erythematosus (NLE). MATERIALS AND METHODS: A retrospective case-control study was made of 131 pregnant women with positive anti-Ro or anti-La autoantibodies and known neonatal outcomes between January 2002 and December 2019 at Siriraj Hospital, Bangkok, Thailand. There were 101 unaffected neonates and 30 NLE cases confirmed postnatally. Demographic and clinical data of the mothers and neonates with and without NLE were statistically compared. RESULTS: NLE was diagnosed in 30 out of 131 cases. A multivariate analysis identified the following significant factors for NLE: maternal anti-La antibodies (odds ratio (OR), 3.591; p = 0.030); and maternal treatment with either hydroxychloroquine (OR, 0.082; p = 0.001) or prednisolone (OR, 0.136; p = 0.017). Of the significant variables examined in the multivariate analysis models, high levels of maternal anti-La antibodies were found to be the strongest predictor of noncardiac NLE (OR, 4.558; p = 0.032), while a female baby was significantly higher in pregnancies complicated by cardiac NLE (OR, 5.374; p = 0.046). Hydroxychloroquine still provided a protective effect for both cardiac and noncardiac NLE (p = 0.039 and 0.032, respectively). CONCLUSIONS: The maternal anti-La antibodies were a beneficial predictor for NLE, especially as their high titers were influentially associated with noncardiac features. A female fetus seemed to present an increased risk for developing a congenital heart block. Nevertheless, the treatment with hydroxychloroquine during the pregnancies demonstrated a potentially protective factor against both cardiac and noncardiac manifestations.

A retrospective cohort study of major adverse cardiac events in children affected by Kawasaki disease with coronary artery aneurysms in Thailand.

Kawasaki disease (KD) is a common form of vasculitis in children that can be complicated by coronary artery aneurysms (CAAs). Data of long-term outcomes and major adverse cardiac events (MACE) in children with CAAs following KD in developing country are limited. Our aims were to determine the rates of MACE and identify risk factors associated with MACE in children with KD and CAAs in Thailand. We performed a retrospective analysis of data from 170 children diagnosed with KD and CAAs in two tertiary hospitals between 1994 and 2019. During a median (range) follow-up of 5.4 years (22 days to 23 years), 19 patients (11.2%) experienced MACE, that included 12 coronary artery bypass grafting, 2 percutaneous coronary intervention and 5 children with evidence of myocardial ischemia and coronary occlusion. Coronary interventions were performed at a median time of 4 years (0.01 to 9.5 years) after KD diagnosis. Forty-nine patients (28.8%) had giant CAAs. No MACE was reported in children with small CAAs. Independent risks of MACE were from the absence of intravenous immunoglobulin treatment (HR 7.22; 95% CI 2.21 to 23.59; p = 0.001), the presence of giant aneurysms (HR 13.59; 95% CI 2.43 to 76.09; p = 0.003), and CAAs that involved bilateral branches of coronary arteries (HR 6.19; 95% CI 1.24 to 30.92; p = 0.026). Among children with giant CAAs, the intervention-free rate was 93.8%, 78.7% and 52.2%, at 1, 5 and 10 years, respectively. Of note, 81% of the small CAAs regressed to a normal size, and for medium CAAs, 50% regressed to normal size. Overall, ~10% of children with CAAs following KD experienced MACE in this cohort. Timely IVIG treatment in children with KD following symptom onset will reduce the risk of MACE. Cautious surveillance to identify cardiac complications should be recommended for children once medium or giant CAAs develop. Trial registration: TCTR20190125004.

Improved low-risk criteria scores for combination therapy of sildenafil and generic bosentan in patients with congenital heart disease with severe pulmonary hypertension: A prospective open label study.

OBJECTIVE: We evaluated the efficacy and safety of the bosentan as a sequential add-on therapy with sildenafil in pulmonary arterial hypertension with congenital heart disease (PAH-CHD) patients. MATERIAL AND METHOD: Twenty patients who were receiving sildenafil were given generic bosentan for up to a year. Hemodynamic data was collected from cardiac catheterization at pretreatment and at three months. Comparisons were made between the total scores of the four, low-risk criteria adapted from the 2015 ESC/ERS pulmonary hypertension guidelines, which are: 1) WHO functional class of I or II, 2) 6MWD of more than 440 m, 3) right atrial pressure of less than 8 mm Hg, and 4) cardiac index ≥2.5 L/min/m2, performed at the beginning of therapy, 3-months, 6-months, and 1 year. RESULTS: Patients' average age was 27 ± 11 years old (12-53). PVRi decreased from 16.7 ± 9.5 to 12.7 ± 10.3 Wood unit (WU) m2 (p = 0.025) and PVRi/SVRi decreased from 0.69 ± 0.33 to 0.49 ± 0.32 (p = 0.001). During the follow-up, the composite scoring of the low risk scores for 19 patients was increased significantly from 1.8 ± 1.0 at baseline to 2.3 ± 0.9 at 3 months, to 2.9 ± 0.8 at 6 months, and 3 ± 0.7 at 1 year (p = 0.001). CONCLUSION: We demonstrated intermediate term benefits for generic bosentan as an add-on therapy to sildenafil in patients with PAH-CHD by improving PVRi, and PVRi/SVRi at three months. A significant improvement was also seen in the combined scores of the low-risk criteria from below 2 to 3 at one year (p = 0.001).Thai Clinical Trials Registry (TCTR): TCTR identification number is TCTR20200506006.

Long-term outcomes of repaired and unrepaired truncus arteriosus: 20-year, single-center experience in Thailand.

BACKGROUND: Truncus arteriosus (TA) is a complex congenital heart disease that carries morbidities in the first year of life. Previous authors have reported an operative mortality of 50%. In this report, we aim to report on the survival of patients with TA in our medical center in the recent era. METHODS: A retrospective review of all patients diagnosed with TA in Siriraj Hospital, Thailand from August 1995 to March 2018 was performed. Patients with single ventricle, hemiTA were excluded. The characteristics and outcomes of repaired and unrepaired TA patients with a known recent functional status in 2018 were reviewed. Operative mortality risks were analyzed using a multivariate model. RESULTS: A total of 74 patients (median age at referral: 70 days) were included in the cohort. One-third of the patients had associated anomalies including DiGeorge syndrome (13.5%). Anatomical repair was not performed in 22 patients (29.7%). The median age at time of repair for the 52 patients was 133 days (range: 22 days to 16.7 years). Complex TA was 10%. Early mortality occurred in 16 patients (30.8%). Five patients (9.6%) had late deaths at 0.3-1.2 years. Significant mortality risk was weight at time of operation <4 kg (HR 3.05, 95% CI [1.05-8.74], p-value 0.041). Of the 31 operation survivors, 17 required re-intervention within 0.4-11.4 years. Eight patients had reoperation at 8.7 years (range: 2.7-14.6 years) post-repair. Freedom from reoperation was 93%, 70.4%, and 31%, at 5, 10, and 15 years, respectively. All late survivors were in functional class I-II. Of the 22 unrepaired TA patients, 11 patients (50%) died (median age: 13.6 years; range: 14 days-32.8 years). Survival of unrepaired TA patients was 68.2%, 68.2%, and 56.8, at 5, 10, and 15 years of age, respectively. At the end of study, 11 survivors of TA with palliative treatment had a recent mean oxygen saturation value of 84.1 ± 4.8% and a mean weight for height of 81.4 ± 12.7%, which were significantly lower than those of 31 late-survivors who had undergone anatomical repair. CONCLUSION: Contemporary survival rates of patients with TA following operation in the center has been gradually improved over time. Most of the operative mortality occurs in the early postoperative period. Compared to patients with TA who had palliative treatment, operative survivors have a better functional status even though they carry a risk for re-intervention.

Current era outcomes of pulmonary atresia with ventricular septal defect: A single center cohort in Thailand.

Pulmonary atresia with ventricular septal defect (PA/VSD) is a complex cyanotic congenital heart disease with a wide-range of presentations and treatment strategies, depending on the source of pulmonary circulation, anatomy of pulmonary arteries (PAs), and major aortopulmonary collateral arteries (MAPCAs). Data about the outcomes in developing countries is scarce. We therefore conducted a retrospective study to assess survival rates and mortality risks of 90 children with PA/VSD at Siriraj Hospital, Thailand during 2005-2016. Patients with single ventricle were excluded. Survival and mortality risks were analyzed at the end of 2018. The median age of diagnosis was 0.5 (0-13.8) years. The patients' PAs were categorized into four groups: 1) PA/VSD with confluent PAs (n = 40), 2) PA/VSD with confluent PAs and MAPCAs (n = 21), 3) PA/VSD with non-confluent PAs and MAPCAs (n = 12), and 4) PA/VSD with small native PAs and MAPCAs (n = 17). Of the 88 patients who underwent operations, 32 patients had complete repair at 8.4 ± 4.6 years old. During the follow-up [median time of 5.7 years (7 days-13.6 years)], 17 patients (18.9%) died. The survival rates at 1, 5, and 10 years of age were 95%, 83.7%, and 79.6%, respectively. Significant mortality risks were the presence of associated anomalies and non-confluent PAs.

Contemporary outcomes and mortality risks of Ebstein anomaly: A single-center experience in Thailand.

BACKGROUND: The increasing number of patients with Ebstein anomaly (EA) surviving into adulthood implies improvements in the treatments for the complex lesion. We revisited the clinical outcomes of patients with EA to demonstrate their "real world" survival. OBJECTIVES: To identify the survival and predictors of mortality in patients with EA who underwent medical or surgical management in the present era. METHODS: All patients who had EA with atrioventricular concordance between 1994 and 2016 were retrospectively reviewed. Baseline characteristics, initial echocardiographic findings, treatments, and outcomes were explored. The survival analysis was performed at the end of 2017. A multivariate analysis was used to assess mortality risks. RESULTS: A total of 153 patients (25.4 ± 20.4 years, 60% female) were analyzed. Of these, 89 patients had been diagnosed with EA in childhood. During the follow-up [median time of 5.2 years (3 days-23.5 years)], 32 patients (20.9%) died due to major cardiac adverse events. The overall survival at 1, 5, and 10 years were 89%, 82.2%, and 79%, respectively. Of the total 153 patients, 64 patients underwent at least one surgical intervention [median age of 17 years (1 day-64.4 years)]. The survival at 1, 5, and 10 years were 87.5%, 82.4%, and 77.7%, respectively, in patients with EA surgery. This survival is comparable to the survival of 89 nonoperated patients with EA: 89.9%, 87.5%, and 81.8%, at 1, 5, and 10 years, respectively. The significant predictors of mortality were: age at diagnosis ≤2 years, tricuspid valve (TV) z-score >3.80, TV displacement >19.5 mm/m2 , presence of severe tricuspid regurgitation, and absence of forward flow across the pulmonic valve at the initial diagnosis. CONCLUSION: Patients with EA had a moderately good survival in this era. In this paper, we report five simple predictors of death in this patient population.

Genotype and clinical characteristics of congenital long QT syndrome in Thailand.

BACKGROUND: Congenital long QT syndrome (LQTS) is an inheritable arrhythmic disorder which is linked to at least 17 genes. The clinical characteristics and genetic mutations may be variable among different population groups and they have not yet been studied in Thai population. METHODS: Clinical characteristics were retrospectively reviewed from children and young adults with congenital long QT syndrome whose blood samples were sent for genotyping during 1998-2017. Sangers sequencing was used to sequentially identify KCNQ1 or KCNH2 genetic variants. Whole exome sequencing (WES) was used to identify variants in all other known LQTS genes. RESULTS: Of the 20 subjects (17 families), 45% were male, mean QTc was 550.3 ±â€¯68.8 msec (range 470-731 msec) and total Schwartz's score was 5.6 ±â€¯1.2 points (range 3-8 points). Fifty percent of patients had events at rest, 30% had symptoms after adrenergic mediated events, and 20% were asymptomatic. We discovered pathogenic and likely pathogenic genetic variants in KCNQ1, KCNH2, and SCN5A in 6 (35%), 4 (24%), and 2 (12%) families, respectively. One additional patient had variance of unknown significance (VUS) in KCNH2 and another one in ANK2. No pathogenic genetic variant was found in 3 patients (18%). Most patients received beta-blocker and 9 (45%) had ICD implanted. LQT1 patients were either asymptomatic or had stress-induced arrhythmia. Most of the LQT2 and LQT3 patients developed symptoms at rest or during sleep. CONCLUSIONS: Our patients with LQTS were mostly symptomatic at presentation. The genetic mutations were predominantly in LQT1, LQT2, and LQT3 genes.

Right Ventricular Systolic Function Parameters in Hypoplastic Left Heart Syndrome.

Assessment of the systolic function of the right ventricle (RV) in patients with hypoplastic left heart syndrome (HLHS) is important. The asymmetric shape and heavy trabeculations make accurate assessment of RV systolic function challenging. Novel measures of RV function could be helpful in distinguishing reduced versus preserved function in HLHS and may also be worse in HLHS with preserved function compared to normal controls. These novel methods offer promise, but research and clinical applicability is hindered as no cut-off values for normal function have been established. We performed a retrospective comparison of functional assessments from echocardiograms of HLHS patients with preserved and reduced RV function along with a control group of normal patients. Measures of function included fractional area change (FAC), tissue motion annular displacement of the tricuspid (TMAD-TV) and pulmonary valves (TMAD-PV), myocardial performance index (MPI), tricuspid tissue Doppler S' velocity, and RV global longitudinal strain (RVGLS). Comparisons were made between three groups: normal patients, HLHS with preserved function, and HLHS with reduced function defined as FAC < 35%. FAC was chosen as the reference as it is a historical standard. 41 HLHS patients were studied. Of these patients, 20 had HLHS with reduced function, and 21 had preserved function. They were compared with 27 age-matched, normal, controls. Comparison between HLHS and normal controls: in HLHS with preserved RV systolic function, compared to normal controls, tissue Doppler S', MPI, and TMAD-TV were all abnormal (all p < 0.05). RVGLS was not statistically different (20.5 ± 3.6% for normal vs. 17.9 ± 2.6% for HLHS with preserved function). TMAD-PV was similar between groups (16.1 ± 4.6% vs. 16.7 ± 5.1%). All measures were significantly worse (all p < 0.05) in the HLHS with reduced function group compared to normal controls. Comparison between HLHS preserved vs reduced function: in HLHS with reduced function defined by FAC < 35%, all measures were significantly worse compared to HLHS with preserved function (all p < 0.05). The cut-off values that correspond to a FAC of > 35% were 14.5% for TMAD-TV and 16% for RVGLS. All measures except RVGLS and TMAD-PV estimated worse function than controls even for HLHS with preserved function. Each of the functional measures was able to identify preserved vs reduced function in HLHS with FAC as the reference standard. Cut-off values between preserved and reduced function in HLHS were estimated for TMAD-TV and RVGLS based on a relatively small cohort. These cut-off values will aid in the research design of future studies.

Contemporary survival of patients with pulmonary arterial hypertension and congenital systemic to pulmonary shunts.

OBJECTIVE: To compare survival of patients with newly diagnosed pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) according to various clinical classifications with classifications of anatomical-pathophysiological systemic to pulmonary shunts in a single-center cohort. METHODS: All prevalent cases of PAH-CHD with hemodynamic confirmation by cardiac catheterization in 1995-2015 were retrospectively reviewed. Patients who were younger than three months of age, or with single ventricle following surgery were excluded. Baseline characteristics and clinical outcomes were retrieved from the database. The survival analysis was performed at the end of 2016. Prognostic factors were identified using multivariate analysis. RESULTS: A total of 366 consecutive patients (24.5 ± 17.6 years of age, 40% male) with PAH-CHD were analyzed. Most had simple shunts (85 pre-tricuspid, 105 post-tricuspid, 102 combined shunts). Patients with pre-tricuspid shunts were significantly older at diagnosis in comparison to post-tricuspid, combined, and complex shunts. Clinical classifications identified patients as having Eisenmenger syndrome (ES, 26.8%), prevalent left to right shunt (66.7%), PAH with small defect (3%), or PAH following defect correction (3.5%). At follow-up (median = 5.9 years; 0.1-20.7 years), no statistically significant differences in survival rate were seen among the anatomical-pathophysiological shunts (p = 0.1). Conversely, the clinical classifications revealed that patients with PAH-small defect had inferior survival compared to patients with ES, PAH post-corrective surgery, or PAH with prevalent left to right shunt (p = 0.01). Significant mortality risks were functional class III, age < 10 years, PAH-small defect, elevated right atrial pressure > 15 mmHg, and baseline PVR > 8 WU•m.2. CONCLUSION: Patients with PAH-CHD had a modest long-term survival. Different anatomical-pathophysiological shunts affect the natural presentation, while clinical classifications indicate treatment strategies and survival. Contemporary therapy improves survival in deliberately selected patients.