Diastolic Function and Left Atrial Strain in Young Patients with History of Aortic Coarctation Repair.

Aortic coarctation (AoCo) leads to long-term sequelae that may impair heart function. Data regarding new echocardiographic function parameters such as atrial strain, in affected patients, are scarce. This study aims to describe these parameters in AoCo patients and define their association with severity measures. 53 AoCo patients and 31 healthy controls, aged 12-40 years, were evaluated. Effectively corrected AoCo (cAoCo) was defined as aortic trans-isthmic corrected Doppler gradient (Dgrad) ≤ 20 mmHg (n = 36), and recoarctation (rAoCo) as Dgrad > 20 mmHg (n = 17). Dependent variables were: E/E'; atrial reservoir strain (Ares); and atrial conduit strain (Acd). T-tests/Mann-Whitney U tests were used to compare these among groups. Multivariable regression was used to test correlation with systolic blood pressure (SBP), indexed LV mass (ILVM), Dgrad, and the ratio between the narrowest diameter of aortic arch and aorta at diaphragm level (Aoratio). In cAoCo and rAoCo patients, E/E' was higher (p < 0.001), Ares, and Acd were lower (p < 0.001 for both) comparing with controls. Acd was higher in cAoCo than rAoCo (p = 0.045). Higher Ares was associated with higher Aoratio (p = 0.002), and lower Acd with higher Dgrad (0.014). EF and GLS were not different among groups. Young patients with effectively corrected aortic coarctation have persistent changes in diastolic function parameters (E/E' and atrial strain), and these are affected by anatomical sequelae. These patients' physiology is closer to patients with recoarctation, than to healthy individuals. This provides rationale for a stronger prevention, and treatment, of arterial dysfunction and high left ventricular afterload in these patients.

Investigation of atrial mass by multi-imaging and biopsy.

The authors describe the case of a child with a history of relapsed acute lymphoblastic leukaemia with a giant intra-auricular lymphomatous mass, submitted to investigation by multiple imaging methods and biopsy.

Azacitidine-induced massive pericardial effusion in a child with myelodysplastic syndrome.

INTRODUCTION: Pericardial effusions are rare yet potentially fatal conditions in children. Azacitidine is a DNA-hypomethylating agent used in the treatment of myelodysplastic syndrome. Although seldomly described in adults, no cases of azacitidine-induced pericardial effusion have been reported in children. CASE REPORT: A 7-year-old boy with myelodysplastic syndrome presented with a large pericardial effusion with risk for cardiac tamponade after his first azacitidine cycle. MANAGEMENT & OUTCOME: The patient was admitted to a pediatric ICU, antibiotic and steroid therapy were initiated. Pericardiocentesis was done due to hemodynamic instability. Serum and pericardial fluid complementary evaluation excluded infectious and malignant causes. The pericardial effusion did not reappear and additional pleural and ascitic slight effusions responded well to diuretics. Follow-up azacitidine cycles were administered by tapering daily dosages and using adjunctive steroid therapy, with no additional adverse events. DISCUSSION: We report the first pediatric case of large pericardial effusion secondary to azacitidine therapy in a child with MDS. This adverse reaction has not been described in pediatric patients, in which this therapeutic option has been increasingly used. We seek to raise awareness on the potential life-threatening cardiotoxicity of azacitidine in pediatric patients.

Spontaneous thrombosis of the arterial duct in a newborn with alloimmune thrombocytopaenia.

We present an uncommon challenging case of spontaneous thrombosis of the arterial duct and with alloimmune thrombocytopaenia in a full-term newborn who presented with respiratory distress, hypoglycaemia dispersed petechiae on the trunk, and significant haemorrhage of the umbilical venous catheter.

The Influence of Atrial Strain on Functional Capacity in Patients with the Fontan Circulation.

Speckle-tracking echocardiography has been used to assess atrial function. This analysis is feasible in univentricular hearts. The aim of this study was to characterize the relationship between atrial strain and functional capacity in the Fontan circulation. Apical four-chamber echocardiographic loops of 39 Fontan patients were reviewed. The dominant atrium was assessed for active (εact), conduit (εcon), and reservoir (εres) strain and εact/εres ratio. Cardiopulmonary exercise test was performed on the same day and oxygen uptake (VO2) at ventilatory threshold (VT) and peak VO2 were chosen as the dependent variables. Statistical analysis was performed using SPSS® version 23. Unpaired t test was used for binomial and continuous variable correlation; single and multivariable linear regression were used for continuous variable correlation. Statistical significance was defined as p value < 0.05. VO2 at VT as a percentage of predicted VO2 was 36.8% (SD 10.7). Peak VO2 was 64.7% (SD 18.9) of the predicted value. In univariate analysis, both were associated with age, atrioventricular regurgitation, ejection fraction, εres, εcon, and εact/εres. In multivariate regression, higher VO2 at VT and peak VO2 were associated with younger age (p = 0.003 and p = 0.001, respectively) and higher εcon (p = 0.026 and p = 0.020). Evaluation of heart function is difficult in the Fontan circulation, hindered by complex ventricular morphology and lack of normative data. VO2 provides a good surrogate. Atrial strain parameters are compromised in these patients and associated with VO2. Therefore, whenever possible, atrial strain should be measured as it may provide a new method of risk stratification.

A sudden turner of events.

The authors report the case of an 18-year-old woman with Turner Syndrome and aortic coarctation, who developed aortic dissection after percutaneous stenting. Surgical treatment was necessary as the lesion progressed. This case highlights both the importance of awareness as well as multidisciplinary management of this potential complication.

Functional study of DAND5 variant in patients with Congenital Heart Disease and laterality defects.

BACKGROUND: Perturbations on the Left-Right axis establishment lead to laterality defects, with frequently associated Congenital Heart Diseases (CHDs). Indeed, in the last decade, it has been reported that the etiology of isolated cases of CHDs or cases of laterality defects with associated CHDs is linked with variants of genes involved in the Nodal signaling pathway. METHODS: With this in mind, we analyzed a cohort of 38 unrelated patients with Congenital Heart Defects that can arise from initial perturbations in the formation of the Left-Right axis and 40 unrelated ethnically matched healthy individuals as a control population. Genomic DNA was extracted from buccal epithelial cells, and variants screening was performed by PCR and direct sequencing. A Nodal-dependent luciferase assay was conducted in order to determine the functional effect of the variant found. RESULTS: In this work, we report two patients with a DAND5 heterozygous non-synonymous variant (c.455G > A) in the functional domain of the DAND5 protein (p.R152H), a master regulator of Nodal signaling. Patient 1 presents left isomerism, ventricular septal defect with overriding aorta and pulmonary atresia, while patient 2 presents ventricular septal defect with overriding aorta, right ventricular hypertrophy and pulmonary atresia (a case of extreme tetralogy of Fallot phenotype). The functional analysis assay showed a significant decrease in the activity of this variant protein when compared to its wild-type counterpart. CONCLUSION: Altogether, our results provide new insight into the molecular mechanism of the laterality defects and related CHDs, priming for the first time DAND5 as one of multiple candidate determinants for CHDs in humans.

Benign Presentation of a Potentially Fatal Disease.

Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital cardiovascular defect that can range from being fatal early in life to presenting in adulthood asymptomatically. We report the case of a teenager whose diagnosis was incidental and underwent surgery, consisting in coronary artery button transfer, with excellent result.

A origem anómala da artéria coronária esquerda a partir da artéria pulmonar é uma cardiopatia congénita que pode ser fatal precocemente ou apresentar-se na vida adulta de forma assintomática. Apresentamos o caso clínico de um adolescente cujo diagnóstico foi incidental e que foi submetido a cirurgia, com translocação da artéria coronária, com excelente resultado.

Catch-up growth in term and preterm infants after surgical closure of ventricular septal defect in the first year of life.

UNLABELLED: Growth impairment in infants with unrestrictive ventricular septal defects (VSD) is common, and normalisation of growth has been reported after surgical correction. Literature is inconsistent about growth velocity after surgery in term and preterm infants. We aimed to establish the pattern of catch-up growth in term and preterm infants submitted to VSD surgical correction before 1 year of age. Fifty-two infants (41 term, 11 preterm) were studied. Anthropometric data at birth, surgery and 3, 6, 12 and 24 months after surgery were collected retrospectively. Statistic analyses were performed in SPSS® version 21. At the time of surgery, growth was severely impaired in term and preterm infants. Term infants underwent a period of fast growth within the first 6 months after surgery, achieving posteriorly a normal growth pattern, as both weight and height were not significantly different from the reference population at 24 months after surgery. Preterms caught-up later than term infants but with a significant weight gain within 3 months after surgery. CONCLUSION: Early surgical repair of VSD leads to a significant acceleration of growth within 3 to 6 months after surgery, for both groups. WHAT IS KNOWN: • Growth impairment in infants with unrestrictive ventricular septal defects is well documented in literature. • Surgical correction in the first months of life is the current option for most ventricular septal defects, leading to a more favourable growth pattern. • Rapid growth during infancy may be associated with the development of insulin resistance, metabolic syndrome, obesity and cardiovascular disease later in life. What is New: • Literature is inconsistent about catch-up growth velocities after ventricular correction for term infants. • Preterm infants have never been enrolled in previous studies that aimed to establish a pattern of growth after surgery. • This group of children, who underwent a rapid post-surgery catch-up growth that follows a period of failure to thrive, may be at a higher risk of insulin resistance, metabolic syndrome, obesity and cardiovascular disease.

Percutaneous valve implantation in "tricuspid" position after a Fontan-Björk operation.

BACKGROUND: A 30-year-old female with tricuspid valve atresia, ventricular septal defect, and atrial septal defect had a neonatal modified Blalock Taussig shunt and a Fontan-Björk operation performed at five years of age. She did well initially but progressively developed signs of systemic congestion due to severe homograft stenosis and underwent successful percutaneous implantation of a Melody® pulmonary valve (Medtronic, Minneapolis, MN, USA) in the "tricuspid" position.

Doppler Flow Pattern and Arterial Stiffness in Patients with Aortic Coarctation.

Patients with aortic coarctation (CoAo) often have a diastolic flow in the descending aorta. The effect of arterial stiffness on CoAo flow pattern was described in vitro and with computer models. Study of Doppler flow patterns and arterial stiffness may provide helpful data to support the decision of CoAo treatment. Fifty studies were obtained in 31 patients (14 women, 21.5 ± 15.5 years). In 19 patients, studies were performed before and after percutaneous intervention. Systolic invasive gradients were measured (Sgrad). Doppler parameters included Doppler corrected gradient (Dgrad), diastolic velocity at end of T wave (DVT), end diastolic velocity (DVQ), systolic and diastolic half pressure times (SHPTc and DHPTc) and velocity runoff (VRc). In 19 patients, before intervention, arterial stiffness was assessed by measuring pulsed wave velocity (PWV) between right carotid and radial arteries. Sgrad showed correlation with Dgrad, DVT, DVQ, SHPTc, DHPTc and VRc (p < 0.01). Using multiple regression models, Sgrad variability was best explained by combining the variables Dgrad and DHPTc (R 2 = 0.766). A variable named DTail was obtained with DTail = 1 if DHPTc > 0. In the group with Sgrad below 30 mmHg, a negative correlation was found between DTail and PWV (p = 0.024), suggesting that low aortic stiffness contributes to persistent diastolic flow in the descending aorta. Doppler systolic and diastolic parameters correlated well with severity of CoAo. In mild to moderate CoAo, Doppler diastolic flow in the descending aorta was more likely in patients with lower arterial stiffness.

Genealogical and molecular analysis of a family-based cohort of congenital heart disease patients from the São Miguel Island (Azores, Portugal).

BACKGROUND: Congenital heart disease (CHD) is one common birth malformation, accounting for ∼30% of total congenital abnormalities. AIM: Considering the unknown role of consanguinity in causing CHD, this study hypothesised that consanguineous unions and/or familial aggregation may be frequent in the Azorean Island of São Miguel (Portugal). To that end, a retrospective observational study was performed based on genealogical and molecular analyses. SUBJECTS AND METHODS: The study enrolled 112 CHD patients from São Miguel Island, which allowed the assessment of type of family (simplex or multiplex), parental consanguinity and grandparental endogamy. Based on 15 STR markers, inbreeding coefficients (FIS) in the CHD cohort and healthy control group (n = 114) were estimated. RESULTS: Multiplex families were 37.6% (n = 41/109), a rate considerably higher than previously described in the literature (< 15%). Moreover, 9.2% (n = 10/109) of the CHD families were consanguineous, mostly derived from third cousin unions, and 20.2% (n = 22/109) presented full grandparental endogamy. Higher FIS values were found in patients with parental consanguinity (0.0371) and patent ductus arteriosus (0.0277). CONCLUSION: This study analysed several genealogical and genetic features related with CHD, revealing the presence of parental consanguinity and extensive familial aggregation in the CHD patients from São Miguel Island.

A unique phenotype in a patient with a rare triplication of the 22q11.2 region and new clinical insights of the 22q11.2 microduplication syndrome: a report of two cases.

BACKGROUND: The rearrangements of the 22q11.2 chromosomal region, most frequently deletions and duplications, have been known to be responsible for multiple congenital anomaly disorders. These rearrangements are implicated in syndromes that have some phenotypic resemblances. While the 22q11.2 deletion, also known as DiGeorge/Velocardiofacial syndrome, has common features that include cardiac abnormalities, thymic hypoplasia, characteristic face, hypocalcemia, cognitive delay, palatal defects, velopharyngeal insufficiency, and other malformations, the microduplication syndrome is largely undetected. This is mainly because phenotypic appearance is variable, milder, less characteristic and unpredictable. In this paper, we report the clinical evaluation and follow-up of two patients affected by 22q11.2 rearrangements, emphasizing new phenotypic features associated with duplication and triplication of this genomic region. CASE PRESENTATION: Patient 1 is a 24 year-old female with 22q11.2 duplication who has a heart defect (ostium secundum atrial septal defect) and supernumerary teeth (hyperdontia), a feature previously not reported in patients with 22q11.2 microduplication syndrome. Her monozygotic twin sister, who died at the age of one month, had a different heart defect (truncus arteriousus). Patient 2 is a 20 year-old female with a 22q11.2 triplication who had a father with 22q11.2 duplication. In comparison to the first case reported in the literature, she has an aggravated phenotype characterized by heart defects (restrictive VSD and membranous subaortic stenosis), and presented other facial dysmorphisms and urogenital malformations (ovarian cyst). Additionally, she has a hemangioma planum on the right side of her face, a feature of Sturge-Weber syndrome. CONCLUSIONS: In this report, we described hyperdontia as a new feature of 22q11.2 microdeletion syndrome. Moreover, this syndrome was diagnosed in a patient who had a deceased monozygotic twin affected with a different heart defect, which corresponds to a phenotypic discordance never reported in the literature. Case 2 is the second clinical report of 22q11.2 triplication and presents an aggravated phenotype in contrast to the patient previously reported.

Programming of Essential Hypertension: What Pediatric Cardiologists Need to Know.

Hypertension is recognized as one of the major contributing factors to cardiovascular disease, but its etiology remains incompletely understood. Known genetic and environmental influences can only explain a small part of the variability in cardiovascular disease risk. The missing heritability is currently one of the most important challenges in blood pressure and hypertension genetics. Recently, some promising approaches have emerged that move beyond the DNA sequence and focus on identification of blood pressure genes regulated by epigenetic mechanisms such as DNA methylation, histone modification and microRNAs. This review summarizes information on gene-environmental interactions that lead toward the developmental programming of hypertension with specific reference to epigenetics and provides pediatricians and pediatric cardiologists with a more complete understanding of its pathogenesis.

Abdominal aorta interruption and CHD.

We report a rare case of CHD and abdominal aorta interruption. Renal hypertension was the first sign of the abdominal aortic malformation. The aetiology of abdominal aortic interruption remains unclear, it could be congenital or acquired.

Recommendations from the Association of European Paediatric Cardiology for training in diagnostic and interventional cardiac catheterisation.

Cardiac catheterisation in congenital heart disease is a developing field. Patients' ages range from foetus to adulthood. This document is a revision and update of the previously published recommendations and summarises the requirements for training in diagnostic and interventional cardiac catheterisation.

Screening of copy number variants in the 22q11.2 region of congenital heart disease patients from the São Miguel Island, Azores, revealed the second patient with a triplication.

BACKGROUND: The rearrangements in the 22q11.2 chromosomal region, responsible for the 22q11.2 deletion and microduplication syndromes, are frequently associated with congenital heart disease (CHD). The present work aimed to identify the genetic basis of CHD in 87 patients from the São Miguel Island, Azores, through the detection of copy number variants (CNVs) in the 22q11.2 region. These structural variants were searched using multiplex ligation-dependent probe amplification (MLPA). In patients with CNVs, we additionally performed fluorescent in situ hybridization (FISH) for the assessment of the exact number of 22q11.2 copies among each chromosome, and array comparative genomic hybridization (array-CGH) for the determination of the exact length of CNVs. RESULTS: We found that four patients (4.6%; A to D) carried CNVs. Patients A and D, both affected with a ventricular septal defect, carried a de novo 2.5 Mb deletion of the 22q11.2 region, which was probably originated by inter-chromosomal (inter-chromatid) non-allelic homologous recombination (NAHR) events in the regions containing low-copy repeats (LCRs). Patient C, with an atrial septal defect, carried a de novo 2.5 Mb duplication of 22q11.2 region, which could have been probably generated during gametogenesis by NAHR or by unequal crossing-over; additionally, this patient presented a benign 288 Kb duplication, which included the TOP3B gene inherited from her healthy mother. Finally, patient B showed a 3 Mb triplication associated with dysmorphic facial features, cognitive deficit and heart defects, a clinical feature not reported in the only case described so far in the literature. The evaluation of patient B's parents revealed a 2.5 Mb duplication in her father, suggesting a paternal inheritance with an extra copy. CONCLUSIONS: This report allowed the identification of rare deletion and microduplication syndromes in Azorean CHD patients. Moreover, we report the second patient with a 22q11.2 triplication, and we suggest that patients with triplications of chromosome 22q11.2, although they share some characteristic features with the deletion and microduplication syndromes, present a more severe phenotype probably due to the major dosage of implicated genes.

Aortic coarctation repair in the adult.

Aortic coarctation can be repaired surgically or percutaneously. The decision should be made according to the anatomy and location of the coarctation, age of the patient, presence of other cardiac lesions, and other anatomic determinants (extensive collaterals or aortic calcification). This article reviews the different therapeutic options available, explaining the differences between children and adults, describing different approaches to the same disease, exemplified by three cases of nonclassic surgical approach and one percutaneous treatment.

Mitral valve lipomatous hamartoma: a rare entity.

Lipomatous hamartoma of cardiac valves is a very rare entity, with only three reported cases in children. We describe the case of a 9-year-old girl with a mass in the mitral valve, which was detected in an echocardiogram performed for heart murmur investigation. At surgery, a white round-shaped tumour was removed and histopathological examination revealed a lipomatous hamartoma.

Prenatal diagnosis of coarctation: Impact on early and late cardiovascular outcome.

BACKGROUND: Prenatal diagnosis (PND) of aortic coarctation (AoCo) has been associated with a significant improvement in early results, but there is limited information on the long-term cardiovascular outcome. METHODS: We studied 103 patients with simple AoCo, operated in the neonatal period, with a median follow-up of 8,5 years (2 to 23,7 years), with 47% followed for over 10 years. PND was made in 35%. The primary aim was to determine the short and long-term cardiovascular impact of PND of AoCo. RESULTS: Neonates with PND had less preoperative neonatal complications, with only 2,8% incidence of a composite preoperative severe morbidity course, compared to 28% in the postnatal group. PND patients underwent surgery 8 days earlier and had a shorter length of stay in ICU. PND did not impact the incidence of post-operative complications. On the long-term, prevalence of hypertension, left ventricular hypertrophy and rate of recoarctation were not influenced by PND. The PND group had mean 24 h diastolic BP 9 mmHg lower and mean daytime diastolic BP 11 mmHg lower. In the final multivariable model, PND was the single independent variable correlating with daytime diastolic BP. CONCLUSION: PND of AoCo effectively leads to a better pre-operative course with less pre-operative morbidity. We found no significant differences in immediate post-operative cardiovascular outcomes. A better initial course of patients with PND does not have a major long-term impact on cardiovascular outcomes, nevertheless, at late follow-up PND patients had lower diastolic BP values on ambulatory monitoring, which may have an impact on long-term cardiovascular risk.