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.

Gene-Edited Human-Induced Pluripotent Stem Cell Lines to Elucidate DAND5 Function throughout Cardiac Differentiation.

(1) Background: The contribution of gene-specific variants for congenital heart disease, one of the most common congenital disabilities, is still far from our complete understanding. Here, we applied a disease model using human-induced pluripotent stem cells (hiPSCs) to evaluate the function of DAND5 on human cardiomyocyte (CM) differentiation and proliferation. (2) Methods: Taking advantage of our DAND5 patient-derived iPSC line, we used CRISPR-Cas9 gene-editing to generate a set of isogenic hiPSCs (DAND5-corrected and DAND5 full-mutant). The hiPSCs were differentiated into CMs, and RT-qPCR and immunofluorescence profiled the expression of cardiac markers. Cardiomyocyte proliferation was analysed by flow cytometry. Furthermore, we used a multi-electrode array (MEA) to study the functional electrophysiology of DAND5 hiPSC-CMs. (3) Results: The results indicated that hiPSC-CM proliferation is affected by DAND5 levels. Cardiomyocytes derived from a DAND5 full-mutant hiPSC line are more proliferative when compared with gene-corrected hiPSC-CMs. Moreover, parallel cardiac differentiations showed a differential cardiac gene expression profile, with upregulated cardiac progenitor markers in DAND5-KO hiPSC-CMs. Microelectrode array (MEA) measurements demonstrated that DAND5-KO hiPSC-CMs showed prolonged field potential duration and increased spontaneous beating rates. In addition, conduction velocity is reduced in the monolayers of hiPSC-CMs with full-mutant genotype. (4) Conclusions: The absence of DAND5 sustains the proliferation of hiPSC-CMs, which alters their electrophysiological maturation properties. These results using DAND5 hiPSC-CMs consolidate the findings of the in vitro and in vivo mouse models, now in a translational perspective. Altogether, the data will help elucidate the molecular mechanism underlying this human heart disease and potentiates new therapies for treating adult CHD.

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.

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.

Intracardiac versus extracardiac shunt in a young man with ischaemic stroke.

A 24-year-old man with a history of recent ischaemic stroke was diagnosed with patent foramen ovale (PFO) and referred for closure at our hospital. At admission, besides low peripheral oxygen saturation (88%), physical examination was otherwise normal. We performed intraprocedural transoesophageal echocardiogram that revealed no PFO, although agitated saline injection demonstrated bubbles lately on the left atrium. The atrial septum could not be crossed. We suspected an extracardiac shunt, so pulmonary angiograms were performed that revealed the presence of a left pulmonary arteriovenous malformation (PAVM). A Konar-MF Occluder was used to occlude the PAVM, with a satisfactory result. At 6 months follow-up, the patient had normal peripheral oxygen saturation and a new pulmonary angiogram showed no residual shunt. Intrapulmonary shunts are a rare and under-recognised cause of paradoxical emboli in young patients; physicians should be aware of this diagnosis as percutaneous occlusion is indicated and critical to avoid recurrent ischaemic episodes.

Congenital long QT syndrome presenting as unexplained bradycardia.

Congenital long QT syndrome (LQTS) is a genetically autosomal heterogeneous disorder of the ion channels and causes about 10% of sudden death infant syndrome in newborns. Its estimated prevalence is approximately 1 in 2500, probably underestimated because of its clinical heterogenicity. Few cases of neonatal LQTS have been reported. In 4% of them, life-threatening arrhythmic events can be the first manifestation of LQTS. The authors report two cases of neonatal LQTS with heterogeneous genetic mutations. Both manifested by bradycardia, one since fetal life. One case had serious arrhythmias during beta blocker therapeutic establishment needing a pacemaker implantation. Genetic mutations found were not the most frequently described in association with neonatal bradycardia, thus the importance of this report. Presentation with bradycardia is relatively frequent in neonatal period, thus LQTS should be actively investigated in neonates with unexplained bradycardia. Beta blocker therapy reduces QTc and avoids arrhythmic events and sudden death.

Long-standing hypoxaemia in complex adult congenital heart disease: anatomical and functional interplay in an uncommon presentation.

We report a case of a 28-year-old man lost to follow-up with chronic hypoxaemia and a history of an uncorrected tricuspid hypoplasia, perimembranous ventricular septal defect (VSD) and pulmonary stenosis. Given this initial diagnosis, chronic hypoxaemia was deemed to result from right-to-left shunt through the VSD driven by elevated right ventricle pressures. However, the further investigation identified an inferior sinus venosus atrial septal defect, unveiling the true mechanism behind the clinical scenario. The patient was submitted to surgical correction with clinical improvement. This case illustrates the defiant evaluation of this type of atrial septal defect through echocardiography and underlines the importance of a multimodal evaluation to reach an accurate diagnosis and optimal management.

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.

Coronary artery bypass grafting in a child with Kawasaki disease.

Kawasaki disease (KD) with cardiac involvement can result in the development of coronary aneurysm, stenosis or thrombosis with significant cardiovascular implications. We report the case of a 23-month-old male with a late diagnosis of KD, in whom intravenous immunoglobulin treatment was not feasible. The patient's course was assessed by routine echocardiography. At the age of five years, angiographic assessment revealed an aneurysm of the anterior descending coronary artery measuring 17 mm×7 mm involving the first diagonal branch, 90% post-aneurysmal stenosis, and an aneurysm of the right coronary artery measuring 32 mm×6 mm. Due to the critical anatomy of the anterior descending artery the revascularization method of choice was coronary artery bypass surgery with an internal mammary artery graft, under cardiopulmonary bypass. There were no significant intraoperative or postoperative complications. This confirms coronary artery bypass grafting as a reliable treatment option for patients who present with coronary sequelae from KD, even at a very young age.

Evolution of acute myocarditis in a pediatric population: An MRI based study.

BACKGROUND: Cardiac Magnetic Resonance (CMR) data regarding myocarditis presentation and disease course is still lacking in pediatric patients. We evaluate baseline CMR and evolution of functional and tissue abnormalities in children with acute myocarditis. METHODS: CMR was performed in 125 patients with clinical diagnosis of acute myocarditis. Clinical follow-up was performed for a median of 498 (214-923) days. RESULTS: LVEF was depressed (<55%) in 56 cases (45%) upon baseline CMR. LGE was found in 93 patients (77%) of cases. LGE was exclusively subepicardial in 29 patients (23%), while other LGE patterns (midwall/mixed) were present in 64 (51%). CMR was repeated in 92 (74%) patients. 67% presented recover of function at a median of 170 (70-746) days after onset of symptoms. Midwall/mixed LGE pattern had a statistically significant correlation with absent recover of function (OR 0.20 p 0.036). Thirteen patients (16%) had recovery from LV dysfunction but with persistence of LGE. Sub-epicardial pattern of LGE (OR 3.33, 95% CI 1.08-10.2, p = 0.036) and the presence of fever at admission (OR 4.67, 95% CI 1.16-18.7, p = 0.03) were associated with a significantly higher likelihood of complete normalization while midwall/mixed LGE pattern was associated with non-recovery. CONCLUSIONS: In pediatric myocarditis, midwall/mixed LGE pattern is associated with absent recover of function. Patients with recover of function may still have persistence of LGE, while a complete recovery from functional and tissue abnormalities is found only in a third of patients. Midwall/mixed pattern of LGE at first MRI was associated to worse outcome.

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.

Sports practice predicts better functional capacity in children and adults with Fontan circulation.

BACKGROUND: Peak oxygen uptake (peak VO2) and its decline predict death or serious cardiovascular adverse events in patients with Fontan circulation. Our aim was to study VO2 in a population of Fontan patients with variable age and contemporary surgical correction, and find predictors of functional status which could lead to management changes. METHODS: Prospective cardiopulmonary exercise test was performed on a treadmill. Blood tests and transthoracic echocardiogram were performed on the same day. Dependent variables were defined as: VO2 at ventilatory threshold (VT) as a percentage of the predicted peak VO2 and peak VO2 as a percentage of its predicted value. Statistical analysis was performed on SPSS® version 23 and significance was defined as a p-value < 0.05. RESULTS: Forty-eight patients were included for analysis. All had a lateral or extracardiac conduit. Mean age was 18.2 years (SD 6.2). Mean age at Fontan completion of 6.5 years (SD 2.3) showed no association with functional capacity. Mean percent VO2 at VT was 37.6% (SD 9.4) and percent peak VO2 was 67.8% (SD 16.7). VO2 both at ventilatory threshold and peak was associated with age, weekly sports practice, significant atrioventricular regurgitation and having a pacemaker or being on antiarrhythmic drugs. On multivariate analysis, weekly sports practice was the best predictor for VO2 values. CONCLUSIONS: Sports practice is a modifiable factor that significantly impacts functional capacity in Fontan patients despite their age. Clinicians should actively prescribe and promote physical activity in this population, either with regular sports practice or engagement in cardiac rehabilitation programs.

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.