Myocardial performance index and biochemical markers for early detection of doxorubicin-induced cardiotoxicity in children with acute lymphoblastic leukaemia.

BACKGROUND: Despite significant improvements in the prognosis of childhood acute lymphoblastic leukaemia (ALL), the risk of anthracycline-induced cardiovascular disease remains a major concern. This study was designed to investigate the role of the myocardial performance index (MPI) and serum concentrations of biomarkers (cTnT and NT-pro-BNP) in the early detection of subclinical anthracycline-induced functional alterations in children with ALL. METHODS: All children consecutively admitted to our Pediatric Oncologic Department from January 2009 to October 2010 with a diagnosis of ALL were enrolled in this study. cTnT and NT-pro-BNP were evaluated in all patients at diagnosis, before doxorubicin therapy and 2 and 24 h following each anthracycline administration. ECG and echocardiography were performed at diagnosis and 24 h after each anthracycline course. RESULTS: Nineteen children with standard-risk ALL were evaluated. The mean age was 6 years. The cumulative doxorubicin dosage was 240 mg/m(2) according to the AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) ALL 2000 protocol. None of the 19 patients developed congestive heart failure. With increasing cumulative dosages of anthracyclines a significant increase was observed in MPI. This increase was statistically significant starting from the cumulative dosage of 120 mg/m(2) compared to baseline, while the median NT-pro-BNP level did not change significantly during treatment and cTnT levels never exceeded the cut-off value for cardiac injury. CONCLUSION: MPI value is a sensitive and accurate parameter, allowing subclinical cardiac dysfunction to be detected in children receiving anthracyclines. Lifelong cardiac surveillance of these patients is warranted in order to determine the clinical implications of increased MPI on long-term cardiac status.

Kawasaki syndrome and concurrent Coxsackie virus B3 infection.

We describe two previously healthy children who were hospitalized in the same period in different departments of our University with clinical signs of Kawasaki syndrome, which were treated with intravenous immunoglobulins and acetylsalicylic acid: in both cases, Coxsackie virus infection was concurrently demonstrated by enzyme-linked immunosorbent assay, and complement fixation test identified antibodies to serotype B3. In the acute phase, both patients presented hyperechogenic coronary arteries, but no cardiologic sequels in the mid term. The etiological relationship between Kawasaki syndrome and Coxsackie viruses is only hypothetical; however, the eventual identification of ad hoc environmental triggers is advisable in front of children with Kawasaki syndrome, with the aim of optimizing epidemiological surveillance and understanding the intimate biological events of this condition.

Platelet reactivity and endothelial function in children of patients with early acute myocardial infarction.

AIMS: To assess whether platelet reactivity is increased in offspring of patients with early acute myocardial infarction (AMI) and its possible relation with endothelial dysfunction. METHODS AND RESULTS: We studied 23 healthy children (15±3 years, 13 males) of patients with early AMI (≤50 years old; Group 1) and 21 healthy children of healthy subjects without any history of cardiovascular disease (14±3 years, 10 males; Group 2). Platelet reactivity was assessed by flow cytometry as the increase in monocyte-platelet aggregates (MPA) and CD41 and PAC-1 platelet expression in response to exercise stress test (EST), adenosine diphosphate (ADP) stimulation (10(-7) M), or both. Endothelial function was assessed by measuring brachial artery dilation during post-ischaemic forearm hyperaemia [flow-mediated dilation (FMD)]. Both EST and ADP induced a higher percentage increase in platelet receptor expression in Group 1, compared with Group 2, with the most significant difference being shown for the response to the combined stimuli (e.g. MPA, 23.1±12 vs. 5.63±8%, P<0.001; platelet PAC-1, 57.7±47 vs. 13.2±7%, P<0.001). Compared with Group 2, Group 1 children showed lower FMD (10.7±3.1 vs. 8.0±2.9%, respectively; P=0.007). However, no significant association was found between FMD and platelet reactivity. CONCLUSION: Our results show increased platelet reactivity in children of patients with early AMI; the finding was not significantly correlated with endothelial dysfunction, suggesting that other mechanisms are mainly involved in the enhanced platelet response to agonistic stimuli.

Electrical and autonomic cardiac function in patients with Dravet syndrome.

Dravet syndrome (DS) is an epileptic encephalopathy related mainly to mutations in the SCN1A gene, encoding for neuronal sodium channels. Patients with DS have a high risk of sudden unexpected death in epilepsy (SUDEP). In this study we investigated whether patients with DS present abnormalities in electrical and autonomic cardiac function. To this aim we assessed ventricular repolarization and heart rate variability (HRV) on standard electrocardiography (ECG) and on 24-h ECG Holter monitoring, respectively, in 20 patients affected by DS (6.8 ± 4 years, 11 female). As age- and sex-matched control groups, we also studied 20 patients with other epileptic syndromes receiving antiepileptic drugs (ES/AED, 6.0 ± 5 years, 12 female), 20 patients with other epileptic syndromes without treatment (ES/no-AED, 6.7 ± 4 years, 10 female), and 20 healthy children (HC, 7.2 ± 5 years, 11 females). Data analysis showed that patients with DS had depressed HRV variables compared to both ES patients (ES/AED and ES/no-AED) and HC control group, whereas no significant differences in HRV variables were found between ES patients (with and without treatment) and HC. There was no significant difference between patients with DS and all the other control groups in RR intervals, QT, and QTc interval analysis. In conclusion, DS patients display an imbalance of cardiac autonomic function toward a relative predominance of adrenergic tone compared to both healthy children and patients with other forms of epilepsy, independent of antiepileptic therapy. Follow-up studies should clarify the clinical significance of this autonomic impairment and whether HRV analysis can be helpful in predicting the risk of sudden death in patients with DS.

Neurogenic stunned myocardium presenting as left ventricular hypertrabeculation in childhood: a variant of Takotsubo cardiomyopathy?

OBJECTIVE: To report the first case of neurogenic stunned myocardium presenting with heart left ventricle noncompaction requiring intensive care in the perioperative period of tension tumor-induced hydrocephalus. METHODS AND DESIGN: Case report and literature review. Our Institutional Review Board waived the need for consent. PATIENT: A 12-yr-old female with intracranial astrocytoma and hypertensive hydrocephalus presented with severe heart dysfunction and life-threatening ventricular ectopies intraoperatively. A severe heart failure developed requiring hemodynamic and ventilatory support for 10 days. Echocardiography showed a transient noncompaction aspect of the left ventricular wall, further confirmed by a cardiac magnetic resonance image. The noncompaction aspect lasted until 15 days postadmission, as was the case for the QT interval prolongation; no life-threatening ectopies were demonstrated on the subsequent Holter electrocardiogram monitoring. CONCLUSIONS: This report describes a unique presentation of myocardial stunning in association with an intracranial illness, namely, a hypertensive hydrocephalus complicating an intracranial neoplasm.

Exercise-induced rhabdomyolysis and transient loss of deambulation as outset of partial carnitine palmityl transferase II deficiency.

We report the case of a 13-year-old boy with an abrupt onset of leg pain and muscle weakness, incapability of deambulation and a laboratory picture of exercise-induced acute rhabdomyolysis. Intravenous hyperhydration and forced diuresis were adopted to avoid renal complications. No evidence of articular or residual muscular damage was appreciated in the short-term. The recurrence of rhabdomyolysis required a muscular biopsy showing a disturbance of fatty acid ß-oxidation pathway.

Neonatal emergencies associated with cardiac rhabdomyomas: an 8-year experience.

During the foetal-neonatal period, rhabdomyomas represent the majority of cardiac tumours and are closely associated with tuberous sclerosis. Cardiac rhabdomyomas may be completely asymptomatic and are incidentally discovered during an echocardiogram, or may cause cardiac dysfunctions requiring medical and/or surgical intervention. During foetal life and the early neonatal period, life-threatening conditions, mostly due to arrhythmias, cardiac failure or obstruction, do occur on rare occasions. We reviewed the medical records of all cases of cardiac rhabdomyomas diagnosed prenatally or postnatally over an 8-year period. The present study reviews 7 cases of life-threatening conditions. Arrhythmic episodes were described in 5 patients, and blood flow obstruction was reported in 2 cases. Antiarrhythmic agents successfully controlled the clinical and electrophysiological conditions. Obstructive conditions were associated with poor outcomes. In conclusion, when prenatal diagnosis of rhabdomyoma is made, appropriate planning at delivery for the management of potential haemodynamic complications may prevent adverse neonatal outcomes. The clinical outcome is more influenced by obstructive rather than by dysrhythmic complications. Appropriate antiarrhythmic treatment is of primary importance. In all cases discovered through prenatal and/or neonatal life-threatening conditions, an accurate follow-up should always be performed to anticipate the development of tuberous sclerosis.

Isolated pericardial agenesis revealed by bradycardia and heart MRI in a healthy 5-year-old child.

We present a five-year-old boy with an unremarkable medical history who was incidentally found to have bradycardia and electrocardiographic signs of right axial deviation. Initial echocardiogram showed left displacement of the cardiac apex with slight enlargement of the right ventricle, while frontal chest radiograph showed a lucent area between the aorta and pulmonary artery. Cardiac magnetic resonance imaging finally revealed a partial left pericardial agenesis and abnormal displacement of the heart into the left hemithorax.

Incomplete Kawasaki syndrome followed by systemic onset-juvenile idiopathic arthritis mimicking Kawasaki syndrome.

A 3-month-old child was first treated for incomplete Kawasaki syndrome with three cycles of intravenous immunoglobulins and aspirin, then with methylprednisolone which led to fever remission. The same child was re-hospitalized after a 10-month-period of well-being for the suspicion of a new episode of Kawasaki syndrome, which appeared to be immunoglobulin-resistant: extensive testing failed to provide an alternative diagnosis of any infectious or infiltrative disease. Diagnosis of systemic onset-juvenile idiopathic arthritis was postulated upon the long persistence of fever and inflammatory signs, which subsided only after starting corticosteroid treatment.

Responsiveness to intravenous immunoglobulins and occurrence of coronary artery abnormalities in a single-center cohort of Italian patients with Kawasaki syndrome.

Clues to predict the response to intravenous immunoglobulins (IVIG) and the development of coronary artery abnormalities (CAA) in children with Kawasaki syndrome (KS) are still undefined. We examined retrospectively the medical charts of children hospitalized between February 1990 and April 2009 with diagnosis of KS. A total of 32 Italian patients with a mean age of 23.8 months were analyzed and all received IVIG according to two schemes: 0.4 g/(kg day) for 5 days or 2 g/kg in a single infusion, combined with oral acetylsalicylic acid. General, clinical and laboratory data were registered. Each patient was evaluated with echocardiography at admission, then with 3-day and weekly frequency, respectively, during hospital stay and for the first 6-8 weeks since onset, and finally with a regular 6-12 month follow-up over time, according to patient risk stratification. Five patients showing significantly higher values of C-reactive protein (CRP) at admission were IVIG-resistant after the first infusion (P = 0.04) in comparison with the remaining 27. Five patients out of 32 developed CAA, with no statistical significance when analyzed for IVIG dosage or IVIG-resistance. The demonstration of CAA was significantly higher in children aged <12 months (P = 0.037). Our experience, limited to a single-center cohort of 32 patients with KS, though treated with two different IVIG schemes, has shown that higher values of CRP and younger age at onset are nodal points in determining, respectively, a failure in the response to IVIG and an increased occurrence of CAA.

Occipital porencephaly in a child with gyrate atrophy of the choroid and retina.

A 4-year-old girl was hospitalized for psychomotor delay, low vision, and horizontal nystagmus. She was found to have bilateral chorioretinal atrophic scars and 2 large occipital porencephalic cavities. High plasma ornithine levels led to the presumed diagnosis of gyrate atrophy of the choroid and retina. After 6 months of arginine-restricted diet and high-dose pyridoxine (300 mg/d), there was no change of plasma ornithine level or ocular findings. To our knowledge, this is the first report showing an association of porencephaly with gyrate atrophy of the choroid and retina.