Echocardiography to predict left ventricular filling pressure for long-term paediatric heart transplant patients.

OBJECTIVES: Left ventricular diastolic dysfunction is a recognised sequela following transplantation in paediatric heart transplant patients. Traditional echocardiographic indices do not correlate well with left ventricular filling pressure immediately after transplantation. This study aimed to assess whether these indices have any long-term correlation after transplantation in paediatric patients. METHODS: A retrospective chart review of 41 patients who had a heart transplant before the age of 24 years was performed. The median time since the transplantation was 11 years. Data obtained from surveillance cardiac catheterisation and echocardiographic examination were reviewed. Traditional echocardiographic indices of diastolic function were compared with the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure obtained from cardiac catheterisation. RESULTS: The median age at transplant was 12.1 years, and the median time since transplant was 11 years. Eighteen patients (43%) had a history of at least one rejection episode and 12 patients (29%) had a history of cardiac allograft vasculopathy. There was no correlation between mitral inflow E velocity, mitral E/A ratio, tissue Doppler velocities, mitral E/e' (mitral inflow E velocity to mitral annular velocity), and elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. There was no correlation between mitral valve deceleration time or isovolumetric relaxation time with elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. CONCLUSION: Our findings suggest that traditional echocardiographic indices of diastolic function do not correlate well with elevated invasive pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure in paediatric heart transplant patients' long-term post-transplantation.

Fetal Diagnosis of Scimitar Syndrome in the Presence of Complex Congenital Heart Disease.

Fetal diagnosis of scimitar syndrome requires a high index of suspicion. We present two fetal cases of complex congenital heart disease associated with scimitar syndrome, one of them is diagnosed with scimitar syndrome in utero. We emphasize prenatal echocardiographic findings that may assist with arriving at the correct prenatal diagnosis. We also discuss potential challenges in suspecting the presence of scimitar syndrome in utero. The postnatal echocardiographic findings and course are described for both patients. We reviewed the available literature on prenatal diagnosis of scimitar syndrome in the presence of complex congenital heart disease. We describe a new association of VACTERL, imperforate anus, scimitar syndrome, and double-outlet right ventricle all on the same patient, as well as the first prenatal diagnosis of scimitar syndrome associated with hypoplastic left heart syndrome with restrictive atrial septum. Advanced imaging modalities such as a fetal lung Magnetic Resonance Imaging is suggested as a confirmatory test when scimitar syndrome is suspected in utero in the presence of complex congenital heart disease.

Association between genetic variants in the HIF1A-VEGF pathway and left ventricular regional myocardial deformation in patients with hypertrophic cardiomyopathy.

BACKGROUND: Information on genetic etiology of pediatric hypertrophic cardiomyopathy (HCM) rarely aids in risk stratification and prediction of disease onset. Little data exist on the association between genetic modifiers and phenotypic expression of myocardial performance, hampering an individual precision medicine approach. METHODS: Single-nucleotide polymorphism genotyping for six previously established disease risk alleles in the hypoxia-inducible factor-1α-vascular endothelial growth factor pathway was performed in a pediatric cohort with HCM. Findings were correlated with echocardiographic parameters of systolic and diastolic myocardial deformation measured by two-dimensional (2-D) speckle-tracking strain. RESULTS: Twenty-five children (6.1 ± 4.5 years; 69% male) with phenotypic and genotypic (60%) HCM were included. Out of six risk alleles tested, one, VEGF1 963GG, showed an association with reduced regional systolic and diastolic left ventricular (LV) myocardial deformation. Moreover, LV average and segmental systolic and diastolic strain and strain rate were significantly reduced, as assessed by the standardized difference, in patients harboring the risk allele. CONCLUSIONS: This is the first study to identify an association between a risk allele in the VEGF pathway and regional LV myocardial function, with the VEGF1 963GG allele associated with reduced LV systolic and diastolic myocardial performance. While studies are needed to link this information to adverse clinical outcomes, this knowledge may help in risk stratification and patient management in HCM. IMPACT: Risk allele in the VEGF gene impacts on LV myocardial deformation phenotype in children with HCM. LV 2-D strain is significantly reduced in patients with risk allele compared to non-risk allele patients within HCM patient groups. Describes that deficiencies in LV myocardial performance in children with HCM are associated with a previously identified risk allele in the angiogenic transcription factor VEGF. First study to identify an association between a risk allele in the VEGF pathway and regional LV myocardial deformation measured by 2-D strain in children with HCM.

Custodiol cardioplegia solution compared to cold blood cardioplegia in pediatric cardiac surgery: a single-institution experience.

OBJECTIVE: Custodiol is an intracellular, crystalloid cardioplegia solution that is a single-dose alternative to multi-dose cold blood cardioplegia; however, there is scarce data regarding its use in infants and children. The objective of this study was to compare its impact on myocardial function in infants. METHODS: Single-center retrospective review including 132 patients <12 months old undergoing biventricular repair. There were 106 patients who received single-dose Custodiol and 27 patients who received multi-dose blood cardioplegia. Demographic and echocardiographic data were compared between the two groups. RESULTS: Patients receiving Custodiol were slightly younger (100 ± 62 days) and lower weight (4.7 ± 1.3 kg) compared to 152 ± 86 days and 5.2 ± 1.3 kg for blood cardioplegia (p < 0.05). The Society of Thoracic Surgeons/European Association for Cardio-Thoracic Surgery Congenital Heart Surgery score was similar between both groups. Average cardiopulmonary bypass time was similar between both groups (Custodiol 93 ± 54 minutes vs. blood 81 ± 44 minutes, p = 0.46) as was aortic cross-clamp time (Custodiol 58 ± 33 minutes vs. cold blood 53 ± 33 minutes, p = 0.62). Pre-operative left ventricular ejection fraction was similar for blood 73 ± 8% versus Custodiol 70 ± 9%, p = 0.21. There was also no intergroup difference in left ventricular ejection fraction 24 hours post op (blood 64 ± 9% vs. Custodiol 65 ± 12%, p = 0.53) or at discharge (blood 66 ± 10% vs. Custodiol 66 ± 11%, p = 0.95). The pre-operative right ventricle function by fractional area change was also similar in blood cardioplegia (46 ± 13%) versus Custodiol (48 ± 9%, p = 0.38) and showed similar drops in parameters in the two groups 24 hours after surgery and at discharge. CONCLUSION: Single-dose Custodiol is as safe as blood cardioplegia for myocardial protection in congenital cardiac surgery for the cross-clamp times evaluated in this study. Evaluation at longer cross-clamp times would be helpful to determine if there is a greater benefit to single-dose Custodiol versus more repeated doses of blood cardioplegia for longer cross-clamp times.

Genetic variations in hypoxia response genes influence hypertrophic cardiomyopathy phenotype.

BACKGROUND: Risk factors for diastolic dysfunction in hypertrophic cardiomyopathy (HCM) are poorly understood. We investigated the association of variants in hypoxia-response genes with phenotype severity in pediatric HCM. METHODS: A total of 80 unrelated patients <21 y and 14 related members from eight families with HCM were genotyped for six variants associated with vascular endothelial growth factor A (VEGFA) downregulation, or hypoxia-inducible factor A (HIF1A) upregulation. Associations between risk genotypes and left-ventricular (LV) hypertrophy, LV dysfunction, and freedom from myectomy were assessed. Tissue expression was measured in myocardial samples from 17 patients with HCM and 20 patients without HCM. RESULTS: Age at enrollment was 9 ± 5 y (follow-up, 3.1 ± 3.6 y). Risk allele frequency was 67% VEGFA and 92% HIF1A. Risk genotypes were associated with younger age at diagnosis (P < 0.001), septal hypertrophy (P < 0.01), prolonged E-wave deceleration time (EWDT) (P < 0.0001) and isovolumic relaxation time (IVRT) (P < 0.0001), and lower freedom from myectomy (P < 0.05). These associations were seen in sporadic and familial HCM independent of the disease-causing mutation. Risk genotypes were associated with higher myocardial HIF1A and transforming growth factor B1 (TGFB1) expression and increased endothelial-fibroblast transformation (P < 0.05). CONCLUSION: HIF1A-upregulation and/or VEGFA-downregulation genotypes were associated with more severe septal hypertrophy and diastolic dysfunction and may provide genetic markers to improve risk prediction in HCM.

Usefulness of the right ventricular systolic to diastolic duration ratio to predict functional capacity and survival in children with pulmonary arterial hypertension.

The objective of this study was to investigate the systolic to diastolic duration ratio (S:D ratio) in children with pulmonary arterial hypertension (PAH) and its association with right ventricular (RV) performance, hemodynamics, 6-minute walk test, clinical outcomes, and survival. We reviewed 503 serial echocardiograms in 47 children with PAH (mean pulmonary artery pressure >or=25 mm Hg) and compared the S:D ratio, assessed from Doppler flow of tricuspid valve regurgitation, to that in 47 age-matched controls. We reviewed echocardiograms, catheterization data, 6-minute walk tests, clinical data, lung transplantation, and death and used univariate linear regression models with a maximum likelihood algorithm for parameter estimation to investigate associations between S:D ratio and RV function, hemodynamics, functional capacity, and clinical outcomes. The S:D ratio was significantly higher in patients than in controls (1.38 +/- 0.61 vs 0.72 +/- 0.16, p <0.001). A higher S:D ratio was associated with worse echocardiographic RV fractional area of change, worse catheterization hemodynamics, shorter 6-minute walk distance, and worse clinical outcomes independent of pulmonary resistance or pressures. An increase of 0.1 in the S:D ratio was associated with a 13% increase in yearly risk for lung transplantation or death (hazard ratio 1.13, p <0.001). An S:D ratio 1.00 to 1.40 was associated with a moderate risk and an S:D ratio >1.40 was associated with a high risk of a negative outcome. In conclusion, in children with PAH, an increased S:D ratio is temporally associated with worse RV function, hemodynamics, exercise capability, clinical status, and survival.