Risk Factors for Cardiac Adverse Events in Infants and Children with Complex Heart Disease Scheduled for Bi-ventricular Repair: Prognostic Value of Pre-operative B-Type Natriuretic Peptide and High-Sensitivity Troponin T.

Few reports have described the prognostic value of measuring both B-type natriuretic peptides (BNP) and high-sensitivity troponin T (hs-TnT) in pediatric patients with complex congenital heart disease (CHD) undergoing surgery. We assessed demographic, hemodynamic, and laboratory data, including BNP and hs-TnT levels, for the prediction of cardiac adverse events in 85 patients. Cardiac adverse events were defined as death, cardiac arrest, worsening heart failure requiring inotropic agents and/or respiratory support, and unscheduled surgery/intervention either within or after 12 months of surgery. There were 17 cardiac adverse events. Of the demographic variables, low birth weight (< 2500 g: Odds ratio [OR], 5.97; 95% confidential interval [CI] 1.48-24.0; p = 0.001) and Ross/New York Heart Association [NYHA] class (≥ 2.0) (OR 12.7; 95% CI 3.08-52.7; p = 0.0004) were strongly association with cardiac adverse events. Among hemodynamic and laboratory variables, preoperative BNP (OR 14.04; 95% CI 2.15-91.7; p = 0.001) and hs-TnT levels (OR 16.66; 95% CI 2.27-122; p = 0.002) were found to be independent risk factors. Receiver operating characteristic analysis determined BNP and hs-TnT levels of 60.9 pg/mL and 0.025 ng/mL, respectively, to be markers of high risk. Kaplan-Meier analysis demonstrated significant differences in the freedom from cardiac adverse events between Group A (BNP or hs-TnT elevated, n = 26) and Group B (both biomarkers elevated, n = 19; log-rank, p < 0.001). In conclusion, low birth weight (< 2500 g) and Ross/NYHA class ≥ 2.0 are strongly associated with cardiac adverse events. Preoperative BNP and hs-TnT also provide prognostic information in patients with complex CHD scheduled for surgery. Using both markers in combination predicts cardiac adverse events better than using either separately.

The Self-Construal Scale: A Potential Tool for Predicting Subjective Well-Being of Individuals With Autism Spectrum Disorder.

Despite accumulating evidence that culture shapes the symptoms of autism spectrum disorder (ASD), no studies have yet applied the Self-Construal Scale to individuals with ASD. We compared the self-construals (measured using the Self-Construal Scale) of 31 high-functioning Japanese individuals with ASD with those of 60 typically developing (TD) individuals. We also examined how the self-construals of individuals with ASD related to their intelligence quotient, adverse childhood experiences, attention deficit hyperactivity disorder, ASD symptoms during adulthood and preschool years, and subjective well-being. Individuals with ASD were more likely to display independent self-construals than were TD individuals; unexpectedly, however, a substantial proportion of individuals with ASD (43.8%) displayed relatively interdependent self-construals. Among individuals with ASD, self-construals were significantly associated with ASD symptoms during preschool years, and with satisfaction of the need for autonomy and frustration of the need for relatedness. Evaluating self-construals can help predict the subjective well-being of high-functioning individuals with ASD. Moreover, the Self-Construal Scale may be useful for understanding the heterogeneous phenotypes of ASD, based on its association with autistic symptoms during preschool years, suggesting that the scale is a potential tool to develop efficient interventions for high-functioning individuals with ASD. Autism Res 2020, 13: 947-958. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism Spectrum Disorders (ASD) are a group of disorders presenting a variety of symptoms and biological origins that can complicate choosing an intervention best suited for improving well-being. Results indicate that a self-construal scale could help understand individuals with high-functioning ASD by independent and interdependent self-construals that are associated with ASD symptoms during preschool years and adult subjective well-being. Our findings suggest that this scale can help understand ASD and select appropriate interventions.

[Infective Endocarditis in Right Ventricle( RV)-Pulmonary Artery( PA) Conduit Late after the Ross Procedure;Report of a Case].

Ross procedure has been found to have a lower incidence of infective endocarditis compared to other aortic replacement procedure using prosthetic valves. We report a case of 25-year-old man who underwent Ross procedure for congenital aortic stenosis and regurgitation when he was 7 years old. He presented with fever and was highly suspected of infective endocarditis. All sets of blood cultures were positive for Heamophilus parainfluenzae. Autologous pericardial pulmonary valve was severely stenotic and computed tomography (CT) scan and radio isotope (RI) scan revealed infection at the stenotic valve. We performed right ventricle (RV)-pulmonary artery (PA) conduit replacement and he was discharged after completion of intravenous antibiotic treatment. We experienced a rare case of infective endocarditis in a patient late after Ross procedure. Prophylaxis against infective endocarditis is mandatory even in patients with infection resistant Ross procedure.

Is the presence of end-diastolic forward flow specific for restrictive right ventricular physiology in repaired tetralogy of Fallot?

BACKGROUND: End-diastolic forward flow (EDFF) is recognized as restrictive right ventricular physiology (r-RVP), but conflicting results have been reported about effects on the clinical outcome in repaired tetralogy of Fallot (r-TOF). OBJECTIVES: We hypothesized that the EDFF by Doppler was not specific for diagnosing r-RVP. METHODS: Sixty-two consecutive patients aged 15.7±11.6years who underwent cardiac catheterization were studied. Patients were divided according to the presence of EDFF (group 1: EDFF+, group 2: EDFF-) and RV size (group A: small RV, group B: large RV [>150ml/m2]). RESULTS: Group 1 (n=23) had higher a right atrial pressure (RAP), pressure gradient between the RAP and pulmonary diastolic pressure (PDP), and atrial natriuretic peptide (ANP) levels than group 2. Four patients (17.4%) in group 1 and 89.7% of patients in group 2 had a normal RAP range (a wave<10mmHg). There were no differences in the RV volume, ejection fraction (EF), B-type natriuretic peptide levels, and severity of pulmonary regurgitation (PR) between groups 1 and 2. Group A had better RV and LVEF than group B, as well as a smaller LV size. The RAP in subgroup 1A was higher than that of the other 3 subgroups. Subgroup 1B had a similar RAP to group 2, and a lower PDP and a more severe PR than subgroup 1A. CONCLUSIONS: Patients with EDFF are associated with increased ANP levels. The presence of EDFF may not be specific for r-RVP, since it is observed in some TOF patients with low PDP (severe PR) and normal RAP.

Plasma Metabolites Predict Severity of Depression and Suicidal Ideation in Psychiatric Patients-A Multicenter Pilot Analysis.

Evaluating the severity of depression (SOD), especially suicidal ideation (SI), is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the Hamilton Rating Scale for Depression (HAMD)-17, and/or self-administered questionnaires such as the Patient Health Questionnaire (PHQ)-9. However, these evaluation systems have relied on a person's subjective information, which sometimes lead to difficulties in clinical settings. To resolve this limitation, a more objective SOD evaluation system is needed. Herein, we collected clinical data including HAMD-17/PHQ-9 and blood plasma of psychiatric patients from three independent clinical centers. We performed metabolome analysis of blood plasma using liquid chromatography mass spectrometry (LC-MS), and 123 metabolites were detected. Interestingly, five plasma metabolites (3-hydroxybutyrate (3HB), betaine, citrate, creatinine, and gamma-aminobutyric acid (GABA)) are commonly associated with SOD in all three independent cohort sets regardless of the presence or absence of medication and diagnostic difference. In addition, we have shown several metabolites are independently associated with sub-symptoms of depression including SI. We successfully created a classification model to discriminate depressive patients with or without SI by machine learning technique. Finally, we produced a pilot algorithm to predict a grade of SI with citrate and kynurenine. The above metabolites may have strongly been associated with the underlying novel biological pathophysiology of SOD. We should explore the biological impact of these metabolites on depressive symptoms by utilizing a cross species study model with human and rodents. The present multicenter pilot study offers a potential utility for measuring blood metabolites as a novel objective tool for not only assessing SOD but also evaluating therapeutic efficacy in clinical practice. In addition, modification of these metabolites by diet and/or medications may be a novel therapeutic target for depression. To clarify these aspects, clinical trials measuring metabolites before/after interventions should be conducted. Larger cohort studies including non-clinical subjects are also warranted to clarify our pilot findings.

Impaired Left Ventricular Reserve in Childhood Cancer Survivors Treated With Anthracycline Therapy.

BACKGROUND: Childhood cancer survivors show evidence of diffuse myocardial fibrosis that is related to exercise capacity. The mechanism of reduced exercise tolerance in anthracycline cardiotoxicity remains unclear. We explored the determinants of exercise intolerance by evaluating left ventricular (LV) distensibility and functional reserve. METHODS: Patients (n = 22) and healthy controls (n = 10) underwent two-dimensional echocardiography while supine, upright, and during cycle exercise. LV distensibility was measured as the change in end-diastolic cavity area (EDCA) from supine to the upright position. LV functional reserve was assessed during peak exercise, and measured as the exercise-induced change in systolic circumferential strain rate (SR) and early-diastolic SR (EDSR). The peak rate of oxygen consumption was measured by indirect calorimetry. RESULTS: Median age of patients was 16 years (range 8-19) and controls 14 years (range 8-19). Median time since anthracycline therapy was 6 years (range 2-16). Peak oxygen consumption was significantly lower in patients compared to controls (35 ml/kg/min [28-60] vs. 45 ml/kg/min [44-53], P = 0.005). Transitioning from the supine position to the upright position caused a similar reduction in LV EDCA, suggesting similar LV distensibility between patients (-22% [-46 to -4]) and controls (-20% [-46 to -3], P = 0.3). However, during exercise, both systolic SR and EDSR reserve were significantly impaired in patients (∆SR: 93% [14-308], ∆EDSR: -4.5% [-88 to 121]) compared to controls (∆SR: 128% [54-230], P = 0.046; ∆EDSR: 74% [22-234], P = 0.02). CONCLUSIONS: Our findings suggest that impaired LV contractility and functional reserve play a role in the reduced exercise capacity in anthracycline cardiotoxicity rather than LV distensibility.

Insights into the evolution of myocardial dysfunction in the functionally single right ventricle between staged palliations using speckle-tracking echocardiography.

BACKGROUND: The long-term prognosis of hypoplastic left heart syndrome is limited by progressive right ventricular dysfunction. The aim of this study was to determine the trends in single right ventricular systolic function between staged palliative surgeries using speckle-tracking and conventional echocardiography. METHODS: There were 76 patients with functionally single right ventricles at the (1) pre-Norwood (n = 26), (2) pre-bidirectional cavopulmonary anastomosis (BCPA; n = 19), (3) pre-Fontan (n = 16), and (4) post-Fontan (n = 15) stages, compared with 30 controls of similar ages. Speckle-tracking-derived longitudinal and circumferential strain and strain rate, postsystolic strain index, and mechanical dyssynchrony index were compared with conventional measures of ventricular function. Differences between stages were analyzed using analysis of variance (P < .05). RESULTS: Strain rate was highest at the pre-Norwood stage and decreased at the other stages (longitudinal P < .0001, circumferential P = .0002), as opposed to controls, in whom strain rate was maintained. Longitudinal strain was significantly decreased at the pre-BCPA stage compared with the pre-Norwood stage (P = .004), but circumferential strain was maintained, resulting in a corresponding decrease in the ratio of longitudinal to circumferential strain, which failed to resemble that of controls. Longitudinal (P = .003) and circumferential (P = .002) postsystolic strain indices were greatest at the pre-BCPA stage. CONCLUSIONS: A decline in contractility occurred at the pre-BCPA stage. Although there was evidence of adaptation of the single right ventricle, this failed to resemble the normal left ventricle and may be insufficient to handle the chronic volume load or insult from previous surgery. These findings suggest an intrinsic inability of the single right ventricular myocardium to fully adapt to chronic systemic pressures.

Diffuse myocardial fibrosis by T1-mapping in children with subclinical anthracycline cardiotoxicity: relationship to exercise capacity, cumulative dose and remodeling.

BACKGROUND: The late cardiotoxic effects of anthracycline chemotherapy influence morbidity and mortality in the growing population of childhood cancer survivors. Even with lower anthracycline doses, evidence of adverse cardiac remodeling and reduced exercise capacity exist. We aim to examine the relationship between cardiac structure, function and cardiovascular magnetic resonance (CMR) tissue characteristics with chemotherapy dose and exercise capacity in childhood cancer survivors. METHODS: Thirty patients (15 ± 3 years), at least 2 years following anthracycline treatment, underwent CMR, echocardiography, and cardiopulmonary exercise testing (peak VO(2)). CMR measured ventricular function, mass, T(1) and T(2) values, and myocardial extracellular volume fraction, ECV, a measure of diffuse fibrosis based on changes in myocardial T1 values pre- and post-gadolinium. Cardiac function was also assessed with conventional and speckle tracking echocardiography. RESULTS: Patients had normal LVEF (59 ± 7%) but peak VO(2) was 17% lower than age-predicted normal values and were correlated with anthracycline dose (r = -0.49). Increased ECV correlated with decreased mass/volume ratio (r = -0.64), decreased LV wall thickness/height ratio (r = -0.72), lower peak VO(2)(r = -0.52), and higher cumulative dose (r = 0.40). Echocardiographic measures of systolic and diastolic function were reduced compared to normal values (p < 0.01), but had no relation to ECV, peak VO(2) or cumulative dose. CONCLUSIONS: Myocardial T1 and ECV were found to be early tissue markers of ventricular remodeling that may represent diffuse fibrosis in children with normal ejection fraction post anthracycline therapy, and are related to cumulative dose, exercise capacity and myocardial wall thinning.

The assessment of atrial function in single ventricle hearts from birth to Fontan: a speckle-tracking study by using strain and strain rate.

BACKGROUND: Single ventricle (SV) exercise performance is impaired and limited by reduced ventricular preload reserve. The atrium modulates ventricular filling, and enhancement of atrial compliance can increase cardiac performance. We aimed to study atrial mechanics in SV hearts across staged surgical palliation compared with healthy children by using novel speckle-tracking echocardiography techniques. METHODS: A cross-sectional study of 81 patients with SV (1 day to 6.5 years) at 4 stages of surgical palliation (presurgery, 22; prebidirectional cavopulmonary anastomosis, 23; pre-Fontan, 22; post-Fontan, 14). The dominant atrium was assessed with speckle-tracking echocardiography for active (εact), conduit (εcon), and reservoir (εres) strain; strain rate (SR); and εact/εres ratio before each stage of surgical palliation. Findings were compared with the left atrium of 51 healthy children (1 day to 5.5 years). RESULTS: Single ventricle atrial size was increased (P < .01), and atrial εres was decreased (P < .01) compared with healthy controls. SV atrial εcon (P < .01) and SRcon (P < .0001) was decreased, increased εact persisted (P < .05), and εact/εres was increased (P < .001) between surgical stages. Although the expected maturational trend of increasing εcon, decreasing εact, and εact/εres occurred in SV, they lagged behind healthy maturational changes (P < .0001). CONCLUSION: Single ventricle atrium is dilated, has deceased compliance, decreased early diastolic emptying, and increased reliance on active atrial contraction for ventricular filling. This deviates from normal early childhood maturational changes and appears to parallel those of an atrium facing early ventricular diastolic dysfunction.

Single right ventricles have impaired systolic and diastolic function compared to those of left ventricular morphology.

BACKGROUND: Differences in single right ventricle (SRV) and single left ventricles (SLV) function are poorly described, although myocardial dysfunction is an important risk factor for morbidity and mortality. The aims of this study were to compare function between patients with SRVs and those with SLVs using newer echocardiographic techniques and to determine differences across staged palliation. METHODS: In this cross-sectional study comparing 30 patients with SRVs and 30 with SLVs of similar ages (2.5 ± 1.7 vs 2.6 ± 1.6 years), patients were matched for surgical stage (20 pre-bidirectional cavopulmonary anastomosis, 20 pre-Fontan, and 20 post-Fontan patients). Circumferential and longitudinal strain, strain rate (SR), early diastolic SR, postsystolic strain index, and myocardial dyssynchrony index were measured. Comparisons between SRV and SLV parameters were made as a whole group and by subanalysis at each surgical stage. RESULTS: Patients with SRVs had reduced systolic SRs (circumferential: -1.0%/sec vs -1.2%/sec, P = .01; longitudinal: -1.1%/sec vs -1.3%/sec, P = .002), reduced early diastolic SRs (circumferential: 1.4%/sec vs 1.9%/sec, P = .03; longitudinal: 1.6%/sec vs 2.2%/sec, P = .001), and increased circumferential postsystolic strain indexes (8% vs 0%, P < .0001). Subanalysis at each surgical stage showed that the greatest disparity in systolic parameters occurred before bidirectional cavopulmonary anastomosis (longitudinal SR, P = .009; postsystolic strain index, P = .005) and that parity was regained after the Fontan procedure, while traditional diastolic parameters (E velocity, P = .004; E/E' ratio, P = .0003) were reduced in patients with SRVs after the Fontan procedure. CONCLUSIONS: The SRV has reduced contractility and diastolic function compared with the SLV. Ventricular systolic performance in patients with SRVs was poorest before bidirectional cavopulmonary anastomosis, while differences in diastolic function were more prominent after Fontan completion.

Altered left ventricular tissue velocities, deformation and twist in children and young adults with acute myocarditis and normal ejection fraction.

BACKGROUND: Acute myocarditis is a significant cause of sudden death in young adults, and accurate screening for subclinical disease is needed. The aim of this study was to test the hypothesis that newer measures of tissue deformation and twist can detect ventricular dysfunction in patients with myocarditis and preserved left ventricular ejection fractions (LVEFs). METHODS: Twenty-eight consecutive patients (median age, 26.5 years; interquartile range, 19.3-33.8 years) with normal LVEFs and cardiovascular magnetic resonance features of myocarditis were prospectively recruited. Left ventricular tissue velocities, deformation, and twist were measured and compared with values in 64 healthy controls (median age, 25.1 years; interquartile range, 13.5-31.7 years). RESULTS: Patients with myocarditis had reduced annular e' velocity and longitudinal and circumferential strain parameters (P < .01) but similar LVEFs. Reduced lateral e' velocity (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.34-2.34), longitudinal strain (OR, 1.81; 95% CI, 1.38-2.38), circumferential early diastolic strain rate (OR, 1.31; 95% CI, 1.08-1.71), increased twist rate (OR, 1.02; 95% CI, 1.01-1.04), and earlier time to peak twist (OR, 0.80; 95% CI, 0.72-0.88) were identified as independent predictors of myocarditis, with abnormalities in any two of five predictors having 93% sensitivity and 91% specificity. Longitudinal strain parameters and lateral e' velocity were improved at 1 year (P ≤ .03) but remained reduced compared with controls (P ≤ .02). CONCLUSIONS: Patients with acute myocarditis and normal LVEFs had detectable left ventricular systolic and diastolic dysfunction on echocardiography. Tissue velocity, deformation, and twist parameters have the potential to improve the detection of patients with myocarditis and preserved LVEFs.

Novel insights into RV adaptation and function in hypoplastic left heart syndrome between the first 2 stages of surgical palliation.

OBJECTIVES: This study sought to examine the changes in ventricular function of hypoplastic left heart syndrome (HLHS) between the first 2 stages of surgical palliation. BACKGROUND: The mortality risk between first and second stages of surgical palliation in HLHS remains high. Right ventricular (RV) dysfunction predicts mortality. Postulated mechanisms include a maladaptive contraction pattern, myocardial ischemia, or contraction asynchrony. Speckle tracking imaging allows accurate measurement of myocardial deformation without geometric assumptions. METHODS: Prospective echocardiography pre-Norwood and pre-bidirectional cavopulmonary anastomosis (BCPA) examinations were performed in 20 HLHS patients, with comparisons made between stages. Measurements of ventricular function included: longitudinal/circumferential strain ratio, reflecting changes in contraction pattern; post-systolic strain index, a potential marker of myocardial ischemia; and mechanical dyssynchrony index. Relationships between echocardiographic variables and magnetic resonance imaging RV parameters before BCPA were examined. RESULTS: Before BCPA, myocardial contractility estimated by isovolumic acceleration and strain rate was reduced, paralleled by an increased in post-systolic strain index (p < 0.01). Right ventricular longitudinal/circumferential strain ratio decreased, becoming similar to a left ventricle-like contraction pattern, and this correlated with decreased mechanical dyssynchrony index (r = 0.65, p < 0.01), magnetic resonance imaging RV end-diastolic volume (r = 0.65, p < 0.05) and mass (r = 0.71, p < 0.01). Ventricular strain (r = -0.72, p < 0.01), strain rate (r = -0.85, p < 0.001), and mechanical dyssynchrony index (r = -0.73, p < 0.01) correlated linearly with magnetic resonance imaging-derived RV ejection fraction. CONCLUSIONS: Reduced RV contractility occurred before BCPA. RV with a left ventricle-like contraction pattern was associated with improved contraction synchrony as well as a reduction in RV size and mass in HLHS. The finding of increased post-systolic strain index before BCPA is novel and its potential link with myocardial ischemia warrants further investigation. RV strain, strain rate, and contraction synchrony measured by speckle tracking imaging correlated closely with ventricular function and might be useful for monitoring ventricular function in HLHS.

Massive pericardial effusion in an early gestational fetus having intrapericardial diaphragmatic hernia.

Intrapericardial diaphragmatic hernia is a very rare phenotype of congenital diaphragmatic hernia. Twelve cases of this condition have been reported under the age of 1 year since 1981, and in only four cases were abnormal findings observed antenatally. We report a case of a fetus with this disease in which pericardial effusion was noted in an earlier gestational age than any other previously reported cases. A 35-year-old pregnant woman was referred to our center at 16 weeks' gestation. Ultrasound revealed that the bilateral lungs of the fetus were very small due to the compression by massive pericardial effusion. Pregnancy was terminated at 18 weeks, and autopsy of the stillborn baby revealed intrapericardial diaphragmatic hernia and cardiac aneurysm of the right ventricle. In conclusion, when pericardial effusion is observed in a fetus, intrapericardial diaphragmatic hernia, a very rare type of congenital diaphragmatic hernia, must be included in a differential diagnosis.

Quantification of right and left ventricular volumes in children with congenital heart disease by multidetector-row computed tomography.

Multidetector-row computed tomography (MDCT) of the heart is a new diagnostic approach for the quantitative evaluation of the coronary artery in adults. However, in children, the quantitative analysis of each cardiac chamber has not been established. We attempt to clarify the feasibility and validation of ECG-gated MDCT as a quantitative diagnostic tool to assess the right and left ventricular volume in children. The study consisted of 16 patients who had definite right and left ventricle. After obtaining multislice images by MDCT, we measured the end diastolic volume of both the right and the left ventricle by direct calculation of the region of interest and calculation from the projected image of three-dimensional reconstruction by traditional formulas. The correlation between the two calculations for both ventricles is excellent (r=0.99 for LV and 0.94 for RV, respectively). The correlations for ventricular volume between calculation of catheterization and calculation of MDCT is also good (r=0.99 for LV 0.99 for RV, respectively). Volume measurement by ECG-gated MDCT of the right and left ventricles is well correlated with that by catheterization in children and can reduce the necessity for cardiac catheterization.