In spite of tremendous progress in the medical and surgical treatment of children with congenital heart disease and dilated cardiomyopathy achieved during the past few decades, for some children a heart transplant remains the only option. Clinically relevant benefits of intracoronary injection of autologous stem cells on cardiac function and remodelling have been demonstrated in adult patients with acute myocardial infarction. Experience with autologous stem cell therapy in children with severe congenital or acquired pump failure is limited to a small number of case reports.

Between 2006 and 2010, nine severely ill children were treated with intracoronary infusion of autologous bone marrow-derived mononuclear cells as part of a compassionate therapy in our centre. No procedure-related unexpected adverse events occurred. There was one patient on extracorporeal membrane oxygenation who died of haemorrhage unrelated to the procedure; three patients proceeded to heart transplantation once a donor heart became available. The other five patients showed an improvement with respect to New York Heart Association classification (greater than or equal to 1), brain natriuretic peptide serum levels, and ejection fraction.

Similar to adults, intracoronary injection of autologous bone marrow cell is technically feasible and safe for children. On the basis of our data, we propose to perform a pilot study for children with congestive heart failure, to formally assess the efficacy of intracoronary autologous bone marrow cell therapy.

Propranolol was recently discovered to be an effective treatment for infantile haemangiomas, and varying doses and monitoring regimens have been proposed. Adverse events, although uncommon, have been reported.

This was a retrospective chart review of infants with haemangiomas who were started on propranolol at a dose of 3 milligrams per kilogram per day on an outpatient basis. After a baseline cardiac evaluation including an electrocardiogram and an echocardiogram, treatment was initiated during 6 hours of observation.

A total of 15 patients were identified; however, only 13 returned for at least one follow-up visit. This cohort was followed up for a median of 2.8 months with a range from 0.2 to 10.0. No hypotension, hypoglycaemia, bronchospasm, or clinically significant bradycardia occurred during treatment. All patients had clinical improvement of their haemangiomas.

This study suggests that initiating treatment during outpatient observation may be a reasonable alternative to inpatient admission. In addition, expensive testing may not be necessary during pre-treatment screening when the physical examination is normal.

The incidence of Myocardial Infarction (MI) in patients under the age of 30 has been rarely addressed. Moreover, it is not understood why these patients develop symptomatic Coronary Artery Disease (CAD) at such an early age. Traditional risk factor assessment has not been successful in identifying these patients before they present with MI.

Retrospective, single cohort, observational study of 14,704 cardiac catheterizations performed in a community hospital between January 2006–January 2010 identified 12 cases age <30 with MI secondary to a fixed atherosclerotic lesion requiring angioplasty and stenting. The angiograms and charts were reviewed to assess the incidence and frequency of traditional risk factors such as smoking, dyslipidemia and diabetes and family history.

All the patients had single vessel disease. Many of the patients were noted to have traditional CAD risk factors. 2 patients had an intervention and then months later sustained another acute MI secondary to a new culprit lesion despite aggressive risk factor modification.

Evaluating patients for premature CAD by screening for traditional risk factors has not effectively identified at risk patients prior to presentation with MI. There is a role for studies evaluating new and novel risk factors and imaging modalities so that these patients can be identified prior to experiencing MI.

There are concerns over the outcome of device closure of secundum atrial septal defect with special reference to erosions and aortic regurgitation.

To assess the medium-term outcome of device closure of atrial septal defects with special reference to complications.

A total of 205 patients with secundum atrial septal defects underwent transcatheter closure from October, 1999 to April, 2009. The median age was 18 (1.4–55) years. Amplatzer Septal Occluder was used in all the patients. Medium-term follow-up was available in 176 of 200 (88%) patients.

Device closure was successful in 200 out of 205 (98%) patients. The device embolised in four patients and was associated with short inferior caval vein margin (p = 0.003). Balloon sizing in 71 patients (35%) resulted in implantation of a larger device (p = 0.002). Early complications included pericardial effusion, 2:1 heart block, and infective endocarditis (1 patient each). There were eight patients who reported migraine (3.9%). At median follow-up of 5.8 (0.6–10.3) years, complete closure occurred in 197 out of 200 patients. Short superior caval vein margin was associated with a residual shunt (p < 0.001). There were two patients who developed mild aortic regurgitation (1%), which correlated with a device-to-defect ratio of >1.3:1 (p = 0.001). There were no erosions, late embolisation, or thromboembolism. Atrial fibrillation occurred in three adults (1.5%).

Device closure of secundum atrial septal defects using Amplatzer Septal Occluder is safe and effective in the medium term. Short inferior caval vein margin correlates with increased risk of embolisation and short superior caval vein margin with a residual shunt. The risk of developing aortic regurgitation is low and correlates with increased device-to-defect ratio.

To describe the evolution of ventricular septal defects in infants from intra-uterine diagnosis to the age of 3 years or until documented echocardiographic closure of the defect, as well as any relationship between closure rate, time and foetal echocardiographic features.

Between January, 2004 and December, 2006, 268 cases of congenital cardiac defect were detected in 14,993 pregnancies referred to our hospital for routine foetal echocardiography; of these cases, 125 had isolated ventricular septal defect. The mothers were scheduled for regular ultrasonography every 2 weeks from diagnosis until the ventricular septal defect closed or 3 years postnatally.

Of the 125 cases of ventricular septal defects, the pregnancy was terminated in 25, four resulted in death, two defects closed spontaneously in utero, 55 closed at a mean age of 13.7 months postnatally, 17 were treated with surgery, nine remained unclosed, and 13 cases were lost to follow-up. Only 7.7% of muscular ventricular septal defects remained patent as compared with 35.7% of perimembranous ventricular septal defects (p is less than 0.01). Muscular ventricular septal defects closed earlier than perimembranous ventricular septal defects. All the ventricular septal defects less than or equal to 3 millimetres closed, whereas only 79.5% of the defects greater than 3 millimetres closed before the age of 3 years; 60.9% of the defects less than or equal to 3 millimetres closed before the age of 1 year as compared with 41.7% of the defects greater than 3 millimetres. The velocity of right-to-left flow was negatively correlated with closure rate but not related to closure period.

Ventricular septal defects can close in utero or during the postnatal period, and both the size and site play a role in the natural history, with small and muscular ventricular septal defects having a high closure rate and early closure.

To analyse the outcome of children with left ventricular dysfunction placed on Highly Active Antiretroviral Therapy.

This study is a retrospective review of records of Human Immunodeficiency Virus-positive children with left ventricular dysfunction. Demographic data were collected. Left ventricular fractional shortening, CD4 percentage, viral load, and nutritional status were compared before and during antiretroviral therapy.

We reviewed the records of 34 Human Immunodeficiency Virus-positive children with left ventricular dysfunction. In all, 18 patients received antiretroviral therapy (group one) and 16 were antiretroviral therapy naive (group two). The median age of group one at initial visit was 94 months, with a male-to-female ratio of 1:1. Of those, 17 children showed improved left ventricular function on treatment, with an increase in fractional shortening (median: 17–33.5%; p less than 0.0001). There was no significant statistical difference between the groups regarding initial fractional shortening. In group one, the CD4 percentage improved (median: 12% to 30.5%; p less than 0.0001), with viral load suppression (median: 24,900 copies per millilitre to less than 25 copies per millilitre; p less than 0.0001). There was weight gain in group one (median z-score: −1.70 to −1.32; p equal to 0.0083). Proper statistical analysis in group two was not possible because of poor follow-up of patients.

The findings are in keeping with other reports that have shown improvement in left ventricular function in patients with Human Immunodeficiency Virus-associated cardiomyopathy treated with Highly Active Antiretroviral Therapy. Recovery of myocardial function is associated with improvement in immunological and nutritional statuses.

Familial Mediterranean fever may carry a potential for cardiovascular disorders because of sustained inflammation during its course; however, there has been a limited number of studies investigating the cardiac functions in children. The aim of this study was to assess both ventricular diastolic functions using conventional echocardiography and tissue Doppler imaging in children with familial Mediterranean fever.

The study population included 25 patients with familial Mediterranean fever – mean age was 11.8 plus or minus 5.30 years – and 23 healthy patients as controls – mean age was 9.88 plus or minus 3.69 years. Both ventricular functions were measured using echocardiography comprising standard M-mode and conventional Doppler and tissue Doppler imaging during an attack-free period.

The conventional echocardiographic parameters with myocardial performance index were in normal ranges and similar in patients with familial Mediterranean fever and controls, with a p-value more than 0.05. However, right ventricular diastolic dysfunction was observed in patients with familial Mediterranean fever documented by tissue Doppler imaging, with a p-value less than 0.05 for E't and A't wave ratio.

Using tissue Doppler imaging, we have demonstrated that although left ventricular functions were comparable in the patients and healthy children, right ventricular diastolic function indices were impaired in patients with familial Mediterranean fever during childhood. Impaired right ventricular diastolic function may be an early manifestation of cardiac involvement in children with familial Mediterranean fever.

The association between long QT interval and sudden infant death syndrome has been clearly established. Several studies have been conducted to determine the evolution of the QT interval in childhood from birth, but only in full-term newborns. However, data on the QT interval in pre-term infants are extremely scarce. The objective was to describe the development of the QT interval in premature infants.

In a prospective monocentric study in a neonatal intensive care unit, pre-term newborns born before 37 weeks of gestation without congenital heart disease, family history of long QT, unstable haemodynamic status, or administration of drugs inducing QT interval prolongation were included with parental consent. An electrocardiogram was recorded in similar conditions weekly until discharge in each child. The corrected QT was calculated with Bazett's formula.

In all, 309 echocardiograms were recorded in 87 children, with gestational age ranging from 24–36 weeks. QT first increased after birth in very premature infants – less than 30 weeks of gestation – and then started to decrease, whereas it only decreased in more mature infants. When plotted against postmenstrual age, QT first increased, and then decreased after 32 weeks.

Our data suggest that the QT interval varies with postmenstrual age in very premature infants, reaching a peak at 32 weeks. These developmental changes may induce specific vulnerability to QT-lengthening medications in premature infants. This study underlines the need for specific pharmacological studies in this population.

To describe the gross motor development of infants who had undergone cardiac surgery in the neonatal or early infant period.

Gross motor performance was assessed when infants were 4, 8, 12, and 16 months of age with the Alberta Infant Motor Scale. This scale is a discriminative gross motor outcome measure that may be used to assess infants from birth to independent walking. Infants were videotaped during the assessment and were later evaluated by a senior paediatric physiotherapist who was blinded to each infant's medical history, including previous clinical assessments. Demographic, diagnostic, surgical, critical care, and medical variables were considered with respect to gross motor outcomes.

A total of 50 infants who underwent elective or emergency cardiac surgery at less than or up to 8 weeks of age, between July 2006 and January 2008, were recruited to this study and were assessed at 4 months of age. Approximately, 92%, 84%, and 94% of study participants returned for assessment at 8, 12, and 16 months of age, respectively. Study participants had delayed gross motor development across all study time points; 62% of study participants did not have typical gross motor development during the first year of life. Hospital length of stay was associated with gross motor outcome across infancy.

Active gross motor surveillance of all infants undergoing early cardiac surgery is recommended. Further studies of larger congenital heart disease samples are required, as are longitudinal studies that determine the significance of these findings at school age and beyond.

Heterotaxy syndrome is caused by left–right asymmetry disturbances and is associated with abnormal lateralisation of the abdominal and thoracic organs. The heart is frequently involved and the severity of the abnormality usually determines the outcome.

We performed a direct sequence analysis of the coding sequence of genes including Zinc Finger Protein of the Cerebellum 3, Left–Right Determination Factor 2, Activin A Receptor Type IIB, and Cryptic in 47 patients with laterality defects and congenital cardiac disease.

Of the 47 patients, 31 (66%) had atrioventricular septal defects, 34 (72%) had abnormal systemic venous return, 25 (53%) had transposed or malposed great arteries, and 20 (43%) had pulmonary venous abnormalities. We identified two novel genetic changes in Zinc Finger Protein of the Cerebellum 3, and these variants were not present in 100 ethnically matched control samples. One previously reported missense mutation in Activin A Receptor Type IIB was identified in two unrelated subjects. The genetic changes identified in this study are all located in conserved regions and are predicted to affect protein function in left–right axis formation and cardiovascular development.

Mutations in Zinc Finger Protein of the Cerebellum 3 and Activin A Receptor Type IIB were identified in 4 of the 47 patients with heterotaxy syndrome for a yield of approximately 8.5%. Our results expand the mutation spectrum of monogenic heterotaxy syndrome with associated cardiac anomalies and suggest that there are other causes of heterotaxy yet to be identified.

To evaluate the effect of a continuous infusion of basic fibroblast growth factor on the adaptive potential of the right ventricular myocardium after 30 days of mechanically induced overload in rats.

We banded the pulmonary trunk, so as to increase the systolic workload of the right ventricle, in six Lewis/HanHsd rats at the age of 11 weeks, using six adult rats as controls. The six adult rats were also banded and received an additional continuous infusion of basic fibroblastic growth factor, using six rats with a continuous infusion of basic fibroblastic growth factor only as controls. We analysed the functional adaptation and structural changes of the right ventricular myocardium, blood vessels, and interstitial tissue 30 days after the increased afterload.

The pulmonary artery banding induced an increase in the right ventricular free wall thickness of banded rats when compared with controls, which was mainly justified by an increase in cardiomyocyte area and in the percentage of extracellular fibrosis. The infusion of basic fibroblastic growth factor promotes a more extensive capillary network in banded rats (p < 0.001), which modulates the compensatory response of the right ventricle, promoting the hypertrophy of contractile elements and limiting the areas in which fibrosis develops (p < 0.001).

The subcutaneous infusion with osmotic pumps was a valid and reproducible method of delivering basic fibroblast growth factor to heart tissue. This infusion contributed to better preserve the right ventricular capillary network, hampering the development of interstitial fibrosis.

Cardiovascular complications and vascular changes are common in patients with beta-thalassaemia major. The aim of this study is to investigate the common carotid artery intima-media thickness in children.

The study population was consisted of 33 thalassaemic children (22 boys and 11 girls, with a median age of 8 years) and 30 healthy children for control (12 girls and 18 boys, with a median age of 8 years) who were matched for age and gender. Common carotid artery intima-media thickness of the children was measured.

The patients’ age at diagnosis ranged from 0.25 to 2 years, with a median of 0.6 months. Their disease duration ranged from 4 to 13.75 years, with a median of 6.5 years. The patients’ median common carotid artery intima-media thickness was significantly higher than controls – that is, 0.87 versus 0.74, with a p-value less than 0.005. The mean common carotid artery intima-media thickness value was positively correlated with disease duration (r = 0.535), with a p-value less than 0.01 and ferritin level (r = 0.501), with a p-value less than 0.01.

Owing to the nature of the disease, patients with beta-thalassaemia major should be considered to have an increased risk of early vascular alteration and atherosclerosis. For this reason, common carotid artery intima-media thickness measurement can be recommended as a non-invasive and early diagnostic method.

Treatment of patent foramen ovale in young patients with stroke is not supported by robust scientific evidence. In clinical practice, a pragmatic approach is needed to guide such therapeutic decisions. This study aims at standardising the diagnostic pathway for stroke patients younger than 55 years of age with a patent foramen ovale; elaborating a therapeutic algorithm; discussing every case in regular interdisciplinary counselling meeting; and setting up a follow-up schedule to assess clinical outcomes.

This is a cohort study on the effect of a standardised treatment of stroke patients with a patent foramen ovale. The primary endpoints include occurrence of recurrent ischaemic events, major bleeding, and device-related complications. The secondary endpoints include drug- or procedure-related side effects, persistence of right-to-left shunt, and persistent cardiac arrhythmia of new onset.

A total of 103 patients have been enrolled. In all, 51 patients underwent percutaneous atrial septal repair; of these, one had minor post-procedural bleeding. At 12 months, 25% of this group of patients showed a latent I grade shunt, one patient a latent II degree shunt, and none had a persistent shunt. The remaining 52 patients were addressed to medical therapy; one of them experienced stroke recurrences while on medical therapy.

This model of implementation of available evidence to clinical practice via a group-based, multi-disciplinary counselling provides a shared and coherent decision pathway and yielded a very low rate of recurrent events and therapy-related complications. This approach could be replicated in specific protocols for other complex or neglected clinical problems.

Syncope is common in children and adolescents and most commonly represents neurocardiogenic syncope. No information has been reported regarding the effect of syncope on health-related quality of life in children.

This was a retrospective cohort study of patients seen in the Heart Institute Syncope Clinic at Cincinnati Children's Hospital Medical Center between July, 2009 and June, 2010. Health-related quality of life was assessed using the PedsQL™ tool. PedsQL™ scores were compared with both healthy historical controls and historical controls with chronic illnesses.

A total of 106 patients were included for analysis. In all, 90% were Caucasian and 63% were girls. The median age was 15.1 years (8.2–21.6). Compared with healthy controls, patients had lower PedsQL™ scores: Total score (75.2 versus 83.8, p < 0.0001); Physical Health Summary (78.8 versus 87.5, p < 0.0001); Psychosocial Health Summary (73.9 versus 81.9, p < 0.001), Emotional Functioning (68.9 versus 79.3, p < 0.001); and School Functioning (66.4 versus 81.1, p < 0.001). No difference was seen in Social Functioning (86.2 versus 85.2, p = 0.81). Patients also had lower PedsQL™ Total scores than patients with diabetes mellitus (p < 0.0001) and similar scores to patients with asthma, end-stage renal disease, obesity, and structural heart disease.

Children with syncope, although typically benign in aetiology, can have low health-related quality of life.