Acute pulmonary hypertension and pulmonary hypertensive crisis may result in adverse clinical outcomes if unsuccessfully treated. Inhaled nitric oxide has long been considered as the standard pharmacotherapy for acute pulmonary hypertension, but lack of feasibility in some settings and evidences challenging its benefits lead to the use of alternative treatment, amongst which is nitroglycerin inhalation. The purpose of this review article is to discuss available data on the use of nitroglycerin inhalation for acute treatment of pulmonary hypertension in children with CHD and its potential benefit in post-operative setting.

Literatures included in this review were acquired by searching in PubMed online database. Keywords used were “Pulmonary Hypertension”, “Congenital heart defects”, “Pediatrics”, “Inhaled nitroglycerin”, and its synonyms.

Title and abstract were screened to select relevant literatures including the three paediatric clinical trials on nitroglycerin inhalation. Critical appraisal of the clinical trials was then done using the University of Oxford Centre of Evidence-Based Medicine Critical Appraisal Tools.

Paediatric studies showed the benefit of nitroglycerin inhalation in uncorrected cases of CHD during catheterisation procedures. Until recently, there have been no studies conducted in paediatric post-operative CHD cases. Further study is required to provide evidence for inhaled nitroglycerin use in this setting including the appropriate dosing and potential side effects with repeated administration,

Phrenic nerve injury is a common complication of cardiac and thoracic surgical procedures, with potentially severe effects on the health of a child. This review aims to summarise the available literature on the diagnosis and management of PNI post-cardiac surgery in paediatric patients with CHD.

The presence of injury post-surgery can be difficult to detect and may present with non-specific symptoms, emphasising the importance of an effective diagnostic strategy. Chest X-ray is usually the first investigation for a suspected diagnosis of PNI, which is usually confirmed using fluoroscopy, ultrasound scan, or phrenic nerve stimulation (gold standard). Management options include supportive ventilation and/or invasive diaphragmatic plication surgery. While the optimal timing of plication surgery remains controversial, it is now the most widely accepted treatment for PNI in children post-CHD surgery, especially for very young patients who cannot be weaned off supportive ventilation. Further research is needed to determine the optimal timing of surgical intervention for positive outcomes and to explore the benefits of using minimally invasive surgical techniques in children.

PNI is a common and serious complication of CHD surgery, therefore, its diagnosis and management in the paediatric population are of major importance. Further research is needed to determine the optimal timing of surgical intervention for positive outcomes and to explore the benefits of using minimally invasive surgical techniques in children.

Milrinone is a phosphodiesterase type 3 inhibitor that results in a positive inotropic effect in the heart through an increase in cyclic adenosine monophosphate. The purpose of this study was to evaluate circulating cyclic adenosine monophosphate and milrinone concentrations in milrinone treated paediatric patients undergoing congenital heart surgery.

Single-centre prospective observational pilot study from January 2015 to December 2017 including children aged birth to 18 years. Milrinone and circulating cyclic adenosine monophosphate concentrations were measured at four time points through the first post-operative day and compared between patients with and without low cardiac output syndrome, defined using clinical and laboratory criteria.

Fifty patients were included. Nine (18%) developed low cardiac output syndrome. For all patients, 22% had single ventricle heart disease. The density and distribution of cyclic adenosine monophosphate concentrations varied between those with and without low cardiac output syndrome but were not significantly different. Milrinone concentrations increased in all patients. Paired t-tests demonstrated an increase in circulating cyclic adenosine monophosphate concentrations during the post-operative period among patients without low cardiac output syndrome.

In this prospective observational study, circulating cyclic adenosine monophosphate concentrations increased in those without low cardiac output syndrome during the first 24 post-operative hours and milrinone concentrations increased in all patients. Further study of the utility of cyclic adenosine monophosphate concentrations in milrinone treated patients is necessary.

To evaluate the discriminative ability of hyperlactataemia for early morbidity and mortality in neonates with CHD following cardiac surgery.

Retrospective, observational study of neonates who underwent cardiac surgery on cardiopulmonary bypass at a tertiary care children’s hospital from June 2015 to June 2019. The primary predictor was lactate. The primary composite outcome was defined as ≥1 of the following: cardiac arrest or extracorporeal membrane oxygenation within 72 hours or 30-day mortality post-operatively. The secondary outcome was the presence of major residual lesions, according to the Technical Performance Score.

Of 432 neonates, 28 (6.5%) sustained the composite outcome. On univariate analysis, peak lactate within 48 hours, increase in lactate from ICU admission through 12 hours, and single ventricle physiology were significantly associated with the composite outcome. The peak lactate occurred at a median of 2.9 hours (interquartile range: 1, 35) before the event. Through multi-variable analysis, a multi-variable risk algorithm was created. Predicted probabilities demonstrated an increasing risk based on single ventricle status and delta lactate, ranging from 1.8% (95% CI: 0.9, 3.9) to 52.4% (95% CI: 32.4, 71.7). The model had good discriminative ability for the composite outcome on receiver operating characteristic analysis (area under the curve = 0.79; 95% CI: 0.75, 0.89). Moreover, a peak lactate of 7.3 mmol/l or greater was significantly associated with the presence of a major residual lesion (odds ratios: 5.16, 95% CI: 3.01, 8.87).

We present a simple, two-variable model, including delta lactate in the immediate post-operative period and single ventricle status, to prognosticate the risk of early morbidity and mortality in neonates undergoing cardiac surgery for potential intervention.

Three-dimensional printing is increasingly utilised for congenital heart defect procedural planning. CT or MR datasets are typically used for printing, but similar datasets can be obtained from three-dimensional rotational angiography. We sought to assess the feasibility and accuracy of printing three-dimensional models of CHD from rotational angiography datasets.

Retrospective review of CHD catheterisations using rotational angiography was performed, and patient and procedural details were collected. Imaging data from rotational angiography were segmented, cleaned, and printed with polylactic acid on a Dremel® 3D Idea Builder (Dremel, Mount Prospect, IL, USA). Printing time and materials’ costs were captured. CT scans of printed models were compared objectively to the original virtual models. Two independent, non-interventional paediatric cardiologists provided subjective ratings of the quality and accuracy of the printed models.

Rotational angiography data from 15 catheterisations on vascular structures were printed. Median print time was 3.83 hours, and material costs were $2.84. The CT scans of the printed models highly matched with the original digital models (root mean square for Hausdorff distance 0.013 ± 0.003 mesh units). Independent reviewers correctly described 80 and 87% of the models (p = 0.334) and reported high quality and accuracy (5 versus 5, p = NS; κ = 0.615).

Imaging data from rotational angiography can be converted into accurate three-dimensional-printed models of CHD. The cost of printing the models was negligible, but the print time was prohibitive for real-time use. As the speed of three-dimensional printing technology increases, novel future applications may allow for printing patient-specific devices based on rotational angiography datasets.

Arrhythmias are common in the post-operative course of patients with hypoplastic left heart syndrome. We sought to determine the types, incidence, risk factors, and impact of arrhythmias in patients with HLHS and anatomic variants.

We performed a retrospective chart review of 120 consecutive patients with HLHS and anatomical variants, who had single-ventricle palliation at our institution from January, 2006 to December, 2016.

A total of thirty-one patients (26%) had 37 episodes of arrhythmias over a median follow-up period of 3.5 years. Of the 37 episodes, 12 (32.4%) were ectopic atrial tachycardia, 9 (24.3%) were paroxysmal supraventricular tachycardia, 4 (10.8%) were junctional ectopic tachycardia, 5 (13.6%) were sinus node dysfunction, 3 (8.1%) were heart block, 2 (5.4%) were atrial flutter, and 2 (5.4%) were ventricular tachycardia. Twenty-four (65%) of the arrhythmias occurred at post-stage 1 surgery. Most (64.8%) of the arrhythmias were resolved. Arrhythmias that occurred at post-stage 1 surgery were more likely to resolve compared to post-stages 2 or 3 (p = 0.006). No anatomical, surgical, or clinical variables were associated with arrhythmia except for age (OR per unit decrease in age at stage 1 palliation: 1.12 (95% CI 1.003, 1.250); p = 0.0439). Arrhythmias were not associated with length of hospital stay or mortality.

Arrhythmias are common in patients with HLHS and anatomic variants, with EAT and PSVT being the most common types. Arrhythmias were associated with younger age at surgery, but did not affect mortality or length of hospital stay.

To evaluate the reliability of balloon coronary compression testing during percutaneous pulmonary valve implantation.

Despite the widespread use of the ‘balloon coronary test’ as the preferable method to rule out the risk of coronary compression, this adverse event has been described after pulmonary valve implantation where coronary balloon test suggested no risk or low risk, calling into question the accuracy of the test.

We performed a retrospective chart review of 84 patients who underwent pulmonary valve implantation between January 2018 and December 2019 and selected 36 patients whose archived imaging was suitable to perform quantitative analysis of the ‘balloon coronary test’. We focused on the spatial disparity between the right ventricular outflow tract position defined by the inflated testing balloon and the eventual implanted valve position, to classify the test as inaccurate or accurate.

In total, 36.1% of cases were classified as having an inaccurate coronary balloon test. Among the baseline characteristics, right ventricular outflow tract substrate was identified as a significant predictor of test accuracy. Related to this characteristic, the type of testing balloon used and the size of the eventually implanted valve were found to be associated with test accuracy.

Based on our findings, balloon coronary testing is not an accurate method of predicting final valve position with respect to fixed structures in the thorax. This may translate to a high false positive rate for the likelihood of coronary compression in pulmonary valve implantation.

Poor growth is common in children with pulmonary hypertension; however, skeletal muscle deficits have not been described and the association between muscle deficits and functional status is unknown.

Patients aged 8–18 years with pulmonary hypertension (diagnostic Groups 1, 2, or 3) and World Health Organization functional class I or II underwent dual-energy absorptiometry to measure leg lean mass Z-score (a surrogate for skeletal muscle). Muscle strength was assessed using dynamometry. Physical activity questionnaires were administered. Clinical data, including 6-minute walk distance, were reviewed. Relationships between skeletal muscle, physical activity score, and 6-minute walk distance were assessed by correlations and linear regression.

Sixteen patients (12.1 ± 3.2 years, 50% female, 56% Group 1, 56% functional class II) were enrolled. Leg lean mass Z-score was significantly less than reference data (−1.40 ± 1.12 versus 0.0 ± 0.9, p < 0.001) and worse in those with functional class II versus I (−2.10 ± 0.83 versus −0.50 ± 0.73, p < 0.01). Leg lean mass Z-score was positively associated with right ventricular systolic function by tricuspid annular plane systolic Z-score (r = 0.54, p = 0.03) and negatively associated with indexed pulmonary vascular resistance (r = −0.78, p < 0.001). Leg lean mass Z-score and forearm strength were positively associated with physical activity score. When physical activity score was held constant, leg lean mass Z-score independently predicted 6-minute walk distance (R2 = 0.39, p = 0.03).

Youth with pulmonary hypertension demonstrate marked skeletal muscle deficits in association with exercise intolerance. Future studies should investigate whether low leg lean mass is a marker of disease severity or an independent target that can be improved.

Preliminary animal and human data suggest that angiotensin-converting enzyme inhibition has a role in pulmonary vascular remodelling. We sought to assess the effect of ACEi versus placebo on pulmonary artery pressure and transpulmonary gradient amongst infants undergoing single-ventricle palliation.

Using the publicly available Pediatric Heart Network Infant Single-Ventricle trial dataset, we compared mean PA pressure at pre-superior cavopulmonary connection catheterisation (primary outcome), transpulmonary gradient, pulmonary-to-systemic flow ratio, and post-SCPC oxygen saturation (secondary outcomes) in infants receiving enalapril versus placebo.

A total of 179 infants underwent pre-SCPC catheterisation, of which 85 (47%) received enalapril. There was no difference between the enalapril and placebo group in the primary and the secondary outcomes. Mean PA pressure in the enalapril group was 13.1 ± 2.9 compared to 13.7 ± 3.4 mmHg in the placebo group. The transpulmonary gradient was 6.7 ± 2.5 versus 6.9 ± 3.2 mmHg in the enalapril and placebo groups, respectively. The pulmonary-to-systemic flow ratio was 1.1 ± 0.5 in the enalapril group versus 1.0 ± 0.5 in the placebo group and the post-SCPC saturation was 83.1 ± 5.0% in the enalapril group versus 82.2 ± 5.3% in the placebo group. In the pre-specified subgroup analyses comparing enalapril and placebo according to ventricular morphology and shunt type, there was no difference in the primary and secondary outcomes.

ACEi did not impact mean pulmonary artery pressure or transpulmonary gradient amongst infants with single-ventricle physiology prior to SCPC palliation.

Disadvantages of intravenous therapeutic unfractionated heparin, the first-line anti-coagulant agent in children with complex congenital heart disease, include unpredictable pharmacokinetics requiring frequent phlebotomies and the need for continuous intravenous access.

To compare efficacy and safety of low-molecular-weight heparin administered by a subcutaneous indwelling catheter with intravenous unfractionated heparin.

Clinical data from 31 inpatients prospectively enrolled to receive subcutaneous low-molecular-weight heparin were compared with those from a historical group of 44 inpatients receiving intravenous unfractionated heparin. Investigation of parents’ satisfaction by telephone survey.

The percentage of anti-factor Xa levels outside therapeutic range was lower in the subcutaneous low-molecular-weight heparin group compared with the percentage of activated partial thromboplastin times outside therapeutic range in the intravenous unfractionated heparin group (40% versus 90%, p < 0.001). Neither group had a major complication. Transient local reactions occurred in 19% of patients of the subcutaneous low-molecular-weight heparin group. The number of needle punctures and that of placement of indwelling catheters were significantly lower in the subcutaneous low-molecular-weight heparin compared with the intravenous unfractionated heparin group (p < 0.001). In total, 84.2% of parents in the subcutaneous low-molecular-weight heparin group reported a positive experience when asked about comparison with prior intravenous unfractionated heparin treatment.

Subcutaneous low-molecular-weight heparin offers a safe anti-coagulation regimen for children with complex congenital heart disease providing more efficient therapeutic anti-coagulation and a reduction in needle punctures, thus causing less pain and anxiety in this children.

Left ventricular non-compaction has been associated with heart failure, arrhythmia, thromboembolism and sudden death. The prevalence of non-compaction in patients with coarctation of the aorta and its clinical significance remains unknown, although obstructive left heart disease is common in patients with non-compaction. We sought to evaluate the prevalence of left ventricular non-compaction in patients with repaired aortic coarctation as well as its effect on left ventricular size and systolic function.

In total, 268 patients (Mean age 26 (inter-quartile range 21–37) years, 63% male) undergoing cardiac magnetic resonance imaging for clinical follow-up were included from three tertiary centres for adult congenital heart disease. Clinical data was obtained from medical records and correlated with ventricular volumes and function. Left ventricular non-compaction was defined as a diastolic non-compacted:compacted dimension ratio >2.3 in the worst affected segment on a long-axis view. Left ventricular non-compaction was present in 8.2% of patients with repaired coarctation. Left ventricular end-diastolic volumes and stroke volumes were significantly higher in patients with non-compaction compared to those without. There were no significant differences in ventricular mass or ejection fraction in these two groups.

Left ventricular non-compaction is relatively common in patients with repaired coarctation of the aorta and correlates with increased left ventricular end-diastolic volumes.

Previous echocardiographic studies failed to show residual alterations of heart function in paediatric patients that have received treatment for Chagas disease. While the echocardiogram is the fundamental front-line tool for evaluating heart function, the appearance of new techniques allows a more detailed analysis. We aimed to evaluate systolic and diastolic function with new techniques in a paediatric population with Chagas disease several years after treatment completion.

Echocardiograms were obtained from 84 Chagas disease patients (48 female) and 27 healthy controls. All patients had received treatment concluding on average 10 years prior to the study. The prospective analysis considered cardiac dimensions and cardiac function using two-dimensional, M-mode, Doppler and tissue Doppler imaging with emphasis on measuring longitudinal strain in the left ventricle by speckle tracking. Ejection fraction was measured with three-dimensional echocardiography.

Patients had an age of 14.2 ± 5.7 years (6–33) at the time of evaluation. Global and segmental motility of the left ventricle was normal in all patients. Ejection fraction was 59.2 ± 6.5 and 57.4 ± 6.5% (p = 0.31) in patients and controls respectively. Left ventricular global longitudinal systolic strain was −19 ± 2.4% in patients and −19 ± 3.6% (p = 0.91) in controls. No significant differences were found in remaining systolic and diastolic function measurements.

Paediatric patients that have received treatment for Chagas disease, evaluated with either conventional techniques or new tools, do not show significant long-term alterations of ventricular function.

Retrospectively apply criteria from Center to Advance Palliative Care to a cohort of children treated in a cardiac ICU and compare children who received a palliative care consultation to those who were eligible for but did not receive one.

Medical records of children admitted to a cardiac ICU between January 2014 and June 2017 were reviewed. Selected criteria include cardiac ICU length of stay >14 days and/or ≥ 3 hospitalisations within a 6-month period.

A consultation occurred in 17% (n = 48) of 288 eligible children. Children who received a consult had longer cardiac ICU (27 days versus 17 days; p < 0.001) and hospital (91 days versus 35 days; p < 0.001) lengths of stay, more complex chronic conditions at the end of first hospitalisation (3 versus1; p < 0.001) and the end of the study (4 vs.2; p < 0.001), and higher mortality (42% versus 7%; p < 0.001) when compared with the non-consulted group. Of the 142 pre-natally diagnosed children, only one received a pre-natal consult and 23 received it post-natally. Children who received a consultation (n = 48) were almost 2 months of age at the time of the consult.

Less than a quarter of eligible children received a consultation. The consultation usually occurred in the context of medical complexity, high risk of mortality, and at an older age, suggesting potential opportunities for more and earlier paediatric palliative care involvement in the cardiac ICU. Screening criteria to identify patients for a consultation may increase the use of palliative care services in the cardiac ICU.

Patent ductus arteriosus stenting in duct-dependent pulmonary circulation is a challenging procedure. Percutaneous carotid artery access for ductal stenting has proven to be feasible; however, comparison with femoral artery access in terms of procedure details and complications either immediate or late is scarce. Therefore, we evaluated carotid artery access in comparison with femoral artery for stenting of patent ductus arteriosus.

Forty neonates were reviewed, 20 were stented via carotid artery access, and 20 via the traditional femoral artery access. Comparison variables were neonatal demographics at the procedure, angiographic ductal anatomy, procedure details, and immediate complications. Follow-up Doppler ultrasound on access site was performed to document late complications.

Median age of included cases was 10.5 (3–28) days with complex ductal anatomy more frequently accessed via carotid artery than femoral. Immediate access-related complications were significantly higher with femoral than carotid artery access; 9 (45%) versus 3 (15%) respectively, p = 0.038. With carotid access, we had only one case with small pseudoaneurysm and acute hemiparesis 3 days after the procedure. Delayed local complications were more common with femoral access (15%) than carotid access (5%), mild stenosis in one case, and severe in another with femoral access; while with transcarotid arterial access, only one case had mild narrowing.

Percutaneous carotid artery access in neonates is a more convenient approach for patent ductus arteriosus stenting especially with complex ductal anatomy. Moreover, local complications are limited and vascular patency is better preserved, in comparison with trans-femoral arterial access. However, the potential for neurological adverse events should not be overlooked.

The aim of this study was to evaluate the safety and efficacy of the Cardi-O-Fix plug used for the treatment of muscular ventricular septal defects.

We retrospectively reviewed the medical records of five patients with muscular ventricular septal defects who underwent transcatheter closure using the Cardi-O-Fix Plug, from November 2017 to August 2019. The median age was 5.1 years (range: 3.2–6.5). Their median body weight was 18.1 kg (range: 13.4–21.8). All the patients underwent detailed two-dimensional Doppler and colour flow imaging by transthoracic echocardiography. The left ventricular median defect size of the muscular ventricular septal defects was 5.6 mm (range: 5.3–7.0). The right ventricular median defect size of the muscular ventricular septal defects was 3.9 mm (range: 3.3–4.7). All the procedures were performed on beating hearts.

All the patients underwent successful device implantation with no displacement or detachment, they have complete echocardiographic closure at the 1-year follow-up. There were no occluder-related arrhythmia, chordae tendineae rupture, tricuspid insufficiency, aortic regurgitation, haemolysis, or embolisation.

Application of the Cardi-O-Fix plug appears to be a feasible, safe, and effective treatment option for patients with muscular ventricular septal defects. Longer follow-up periods are warranted to prove the conclusion for long-term outcomes.

We aimed to assess the immediate haemodynamic response and the timing of cardiac remodelling in paediatric secundum atrial septal defect patients who underwent percutaneous transcatheter closure.

In this longitudinal cohort study with 41 paediatric secundum ASD patients who underwent PTC with Amplatzer Occluder device were assessed for immediate post-interventional haemodynamic response measured by catheterisation and was evaluated for right and left cardiac remodelling during a follow-up period of 12 months by transthoracic echocardiography. SPSS 20.0 was used for statistical analyses of pre- and post-interventional invasive haemodynamic parameters of the patients, and pre- and post-interventional TTE data compared with the values of the control group consisted of 39 healthy children.

The mean diameter of ASD was 13.9 ± 4.7 mm. PTC intervention in all patients completed with 100% success and 0% complication rates. All invasive haemodynamic data, except the ratio of pulmonary resistance to systemic resistance, significantly reduced after PTC (p < 0.05). TTE and PW Doppler revealed that right and left cardiac remodelling started as soon as the post-interventional 24th hour and completed in the 12th month.

This study with a very high interventional success rate can be counted as the first example of research on the haemodynamic response and timing of cardiac remodelling after PTC of secundum ASD in children. We suggest that future multicentric studies with larger cohorts and a comprehensive methodology like ours with longer follow-up periods would better serve to further assess the cardiac remodelling in children after PTC of secundum ASD.

After congenital heart surgery, some patients may need long-term mechanical ventilation because of chronic respiratory failure. In this study, we analysed outcomes of the patients who need tracheostomy and home mechanical ventilation.

Amongst 1343 patients who underwent congenital heart surgery between January, 2014 and June, 2018, 45 needed tracheostomy and HMV. The median age of these patients was 6.4 months (12 days–6.5 years). Nineteen patients underwent palliation while 26 patients underwent total repair. Post-operative diaphragm plication was performed in five patients (11%). Median duration of mechanical ventilation before tracheostomy was 32 days (8–154 days). The patients were followed up with their home ventilators in ward and at home. Mean follow-up time was 36.24 ± 11.61 months.

The median duration of ICU stay after tracheostomy was 27 days (range 2–93 days). Follow-up time in ward was median 30 days (2–156 days). A total of 12 patients (26.6%) were separated from the ventilator and underwent decannulation during hospital stay. Thirty-two patients (71.1%) were discharged home with home ventilator support. Of them, 15 patients (46.9%) were separated from the respiratory support in median of 6 weeks (1 week–11 months) and decannulations were performed. Total mortality was 31.1%. in which four patients are still HMV dependent. There was no significant difference for decannulation between total repair and palliation patients.

HMV via tracheostomy is a useful option for the treatment of children who are dependent on long-term ventilation after congenital heart surgery although there are potential risks.

Acute rheumatic fever in childhood continues to cause serious morbidity despite all developments. The objective of this study was to evaluate the clinical and laboratory characteristics of patients with acute rheumatic fever and to determine the frequency of subclinical carditis and the side effects of the drugs used in the treatment.

The data of patients hospitalised between 2008 and 2018 with the diagnosis of acute rheumatic fever were included in the study. The relationship of gender and age with the frequency of major symptoms and the distribution of the drugs used in the treatment and their side effects were evaluated.

Medical records of 102 patients with complete data were reviewed. 56.9% of the patients were male and the mean age was 10.7 ± 1.9 years. The most common distribution of complaints found were arthritis (51%), arthralgia (25.5%) and fever (16.7%). 10.8% of all patients (n = 11) were diagnosed subclinical carditis via echocardiographic evaluation. The frequency of carditis was higher in female patients with a borderline statistical significance (p = 0.05). However, there was no statistically significant difference between gender and arthritis (p = 0.22) and carditis (p > 0.05). Anti-congestive therapy was required in 22% and inotropic treatment was needed in 6.1% cases. Toxic hepatitis developed in four cases during the acetylsalicylic acid treatment.

In a 10-year period, detection of subclinical carditis in 10.8% cases supported that echocardiography should be performed as a standard method for the diagnosis of acute rheumatic fever. Patients should be followed closely in terms of hepatic toxicity due to acetylsalicylic acid used in the treatment.