Jaana Pihkala

Recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of febrile neutropenia: a double blind placebo-controlled study in children.

In a double blind study of 58 episodes of fever and profound neutropenia, children with cancer received either recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or placebo, combined with identical antimicrobial therapy, i.e. imipenem, on admission. The criteria for discontinuation of therapy were identical. A difference was demonstrated both in the number of hospital days, totaling 252 days in the rhGM-CSF group and 354 in the placebo group, days receiving antibiotics (220 vs. 322), and in the resolution of neutropenia (4.5 days vs. 6.0 days; P < 0.05). The number of episodes requiring antimicrobial therapy for longer than 10 days was 5 of 28 (12%) in the rhGM-CSF group as opposed to 15 of 30 (50%) in the placebo group (P = 0.01). rhGM-CSF was well-tolerated. We conclude that rhGM-CSF was efficacious in accelerating myeloid recovery and reducing the length of hospitalization in febrile neutropenia.

Myocardial function in children and adolescents after therapy with anthracyclines and chest irradiation

Cardiotoxicity is a potential adverse effect of anthracycline (A) therapy. Radiotherapy (XRT) may also cause a variety of cardiac complications. The purpose of the present study was to evaluate these cardiac side-effects in children and adolescents treated for cancer. We assessed the cardiac status of 91 patients, divided into three groups: Group A (n = 53) had anthracyclines at a mean cumulative dose of 410 mg/m2, group A+XRT (n = 26) had both chest irradiation (XRT) and A (mean 360 mg/m2), and group XRT (n = 12) had XRT alone. The patients differed from the controls in both systolic and diastolic indices of myocardial function. In echocardiography, the left ventricular (LV) contractility was abnormal in 32% in group A, in 50% in group A+XRT, and in 8% in group XRT. In radionuclide cineangiography, the LV ejection fraction was subnormal in 19% in group A, in 24% in group A+XRT, and in 1 patient in group XRT. A higher cumulative dose of A predicted decreased contractility. Treatment with A and/or XRT often leads to cardiotoxicity. Although in most cases this cardiotoxicity seems to be mild and subclinical, the long-term clinical sequelae merit further evaluation.

Excellent functional result in children after correction of anomalous origin of left coronary artery from the pulmonary artery – a population-based complete follow-up study☆

Surgical strategy to construct a two-coronary system for a patient with anomalous origin of left coronary artery from pulmonary artery (ALCAPA) has evolved with time. Limited long-term follow-up data are available on these children. We report population-based follow-up in children operated on for ALCAPA. In total, 29 patients underwent aortic reimplantation of ALCAPA between 1979 and 2006. Twenty (69%) children were repaired with direct aortic implantation, five (17%) with a modified tubular extension technique, and four (14%) patients with an intrapulmonary baffling technique. Early postoperative mortality (<30 days) was 17%. No late mortality (>30 days) was detected. The median length of follow-up was 11 years (range 10 months-27 years). Global left ventricular function by echocardiography (M-mode) was within normal limits (>30%) in all patients one year after operation. Functionally, 80% of patients were classified in NYHA class I, 20% in NYHA II, and 0% in NYHA classes III/IV at the time of the last examination. Excellent results with good long-term outcome can be achieved in infants with ALCAPA using reimplantation techniques. Normalization of cardiac function is expected within the first year in all operative survivors with a patent coronary system.

Hemodynamic improvement is faster after percutaneous ASD closure than after surgery

Objectives: Hemodynamic effects of surgical and percutaneous closure of atrial septal defect (ASD) were evaluated. Background: ASD causes volume overload of right ventricle (RV) and is associated with distortion and dysfunction of left ventricle (LV). The amount and timing of hemodynamic changes after ASD closure are not well known. Methods: The study group consisted of 7 children treated surgically and 17 treated in the catheterization laboratory. In the control group, there were 51 healthy children. RV size and LV end‐diastolic and systolic dimensions, volumes, and function were examined by two‐ and three‐ dimensional echocardiography and serum concentrations of natriuretic peptides measured prior to ASD closure, and 1, 6, and 12 months thereafter. Results: In all children with ASD, during the 1‐year follow‐up, the z score of RV end‐diastolic diameter decreased from a median 5.00 SD to 2.25 SD (P < 0.001). Dilatation of RV did not resolve entirely during 1‐year follow‐up in either treatment group. End‐diastolic LV diameter increased from −1.50 to −0.50 SD (P < 0.001). LV size increased slower in the surgical subgroup but reached control levels in both groups. Concentrations of natriuretic peptides increased during the first month after ASD closure and normalized thereafter in patients treated percutaneously but remained higher than in controls in patients treated surgically. Conclusions: During 1‐year follow‐up after ASD closure, RV size decreases but does not normalize in all patients. The size of the LV normalizes after ASD closure but the increase in LV size is slower in patients treated surgically. Serum levels of ANPN and proBNP are elevated prior to ASD closure but decrease thereafter to control levels in patients treated with the percutaneous technique but not in those treated surgically.

Cardiac troponin I, cardiac troponin-specific autoantibodies and natriuretic peptides in children with hypoplastic left heart syndrome

OBJECTIVES To evaluate serum levels of cardiac troponin I (cTnI), autoantibodies against cardiac troponin (cTnAAbs) and natriuretic peptides during the treatment protocol in children with hypoplastic left heart syndrome (HLHS). METHODS In a prospective study, we had 18 consecutive children with HLHS, for whom serum samples were analysed before the Norwood operation, before the bidirectional Glenn (BDG) operation, at the age of one year and before total cavo-pulmonary connection (TCPC). In addition, we performed a cross-sectional study in 22 children examined before TCPC. Controls comprised 34 healthy children. RESULTS In the prospective study, troponin I was positive in eight children before the Norwood operation. At the next follow-up, six children were positive. Thereafter, in all samples, cTnI was negative. Serum levels of natriuretic peptides decreased during the treatment protocol but remained higher than in controls throughout the study. In the cross-sectional study, cTnI levels were negative, but levels of natriuretic peptides were higher than in controls. Levels of cTnI and natriuretic peptides showed no correlation with oxygen saturation or haemoglobin concentration. Autoantibodies against cardiac troponin appeared in one patient but not in the control children. CONCLUSIONS Cardiac TnI release is common before Norwood and BDG operations; then during the treatment protocol for HLHS, cTnI release resolves and serum levels of natriuretic peptides decrease. This may reflect a reduction of volume overload of the right ventricle during the surgical programme.

Myocardial Function and Postmortem Myocardial Histology in Children Given Anthracycline Therapy for Cancer

In an autopsy series of children with cancer, histopathologic myocardial changes caused by anthracyclines (A) were evaluated. The series comprised three groups: group A, 9 patients given A whose myocardial function had been evaluated before death; group B, 10 patients given A, but no lifetime echocardiographic evaluation; group C, 8 patients treated with chemotherapy regimens not including A. Both the cumulative A dose (P < 0.01) and the age of the patient at death (P < 0.001) were correlated with the pathologic changes in the myocardium. In echocardiography of group A patients, left ventricular (LV) contractility was subnormal in 5 (56%) patients, and the afterload was elevated in 3 (33%); the morphologic changes correlated with the LV wall stress (= afterload) (P < 0.05) and with LV fractional shortening (P < 0.04). We conclude that clinical decisions about A therapy should be based on cumulative A dose and myocardial function tests. Myocardial biopsies should be restricted to selected cases.

Long-term results of the Ross procedure in a population-based follow-up

OBJECTIVES The purpose of this study was to evaluate the long-term outcomes of the Ross procedure in a nationwide follow-up. METHODS This retrospective study involved all children treated with the Ross procedure in Finland between 1994 and 2009. The clinical records were reviewed for demographic and anatomical characteristics, Ross operation data, surgical history and status at the latest follow-up. The median follow-up time was 11.5 (range 2.4-19.2) years. RESULTS Fifty-one patients underwent either the Ross (n = 37) or the Ross-Konno (n = 14) procedure at a median age of 4.8 (range 0.02-16.3) years, including 13 infants (<1 year of age). The indication for the Ross procedure was aortic valve stenosis, regurgitation or both, which was observed in 29, 24 and 47% of patients, respectively. The early mortality (before hospital discharge) rate was 10% (31% in infants) and the late mortality rate 6% (15% in infants). Higher mortality was discovered in patients treated with the Ross-Konno procedure (P = 0.001). The most common cause for reintervention was pulmonary homograft stenosis. The rate of freedom from right ventricular outflow tract reintervention was 98% at 5 years, 83% at 10 years and 59% at 15 years. The rate of freedom from autograft reintervention was 98% at 5 and 10 years, and 81% at 15 years. At the latest follow-up visit, mild-to-moderate aortic root dilatation was reported in 52% of patients, and 4 patients had undergone autograft-related reinterventions. Trivial autograft valve regurgitation was commonly seen, but only 1 patient developed severe autograft regurgitation requiring mechanical valve replacement 15.9 years after the Ross operation. CONCLUSIONS The most common reason for reintervention after the Ross procedure in children is homograft stenosis. Aortic root dilatation and autograft valve regurgitation are relatively common but rarely lead to reinterventions before adulthood. Intraoperative complications and complex cardiac anatomy are associated with high mortality in infants undergoing the Ross-Konno procedure. In our centre, the Ross procedure has provided good long-term results in this challenging group of paediatric patients.

Prenatal Diagnosis Improves the Postnatal Cardiac Function in a Population-Based Cohort of Infants with Hypoplastic Left Heart Syndrome

BACKGROUND Prenatal diagnosis of hypoplastic left heart syndrome (HLHS) enables planning of perinatal care and is known to be associated with more stable preoperative hemodynamics. The impact on postnatal myocardial function is poorly known. The aim of this study was to determine the impact of prenatal diagnosis of HLHS on postnatal myocardial function. METHODS A consecutively encountered cohort of 66 infants with HLHS born between 2003 and 2010 in Finland was retrospectively reviewed. Twenty-five infants had prenatal diagnoses. Postnatal global and segmental right ventricular fractional area change, strain rate, and myocardial velocity were analyzed from the apical four-chamber view using Velocity Vector Imaging. Preoperative hemodynamic status and end-organ damage measurements were the lowest arterial pH, highest lactate, alanine aminotransferase, and creatinine. Early mortality was studied until 30 days after Norwood procedure. RESULTS Prenatally diagnosed infants had better cardiac function (fractional area change, 27.9 ± 7.4% vs 21.1 ± 6.3%, P = .0004; strain rate, 1.1 ± 0.6/1.3 ± 1.0 vs 0.7 ± 0.2/0.7 ± 0.3 1/sec, P = .004/.003; myocardial velocity, 1.6 ± 0.6/2.0 ± 1.1 vs 1.3 ± 0.4/1.4 ± 0.4 cm/sec, P = .0035/.0009). Mechanical dyssynchrony was similar in both groups (P > .30). Infants diagnosed prenatally had less acidosis (pH = 7.30 vs 7.25, P = .005) and end-organ dysfunction (alanine aminotransferase, 33 ± 38 vs 139 ± 174 U/L, P = .0001; creatinine, 78 ± 18 vs 81 ± 44 mmol/L, P = .05). No deaths occurred among the prenatally diagnosed infants, but four deaths were recorded among postnatally diagnosed infants (P = .15). CONCLUSIONS A prenatal diagnosis of HLHS is associated with improved postnatal right ventricular function, reduced metabolic acidosis, and end-organ dysfunction.

During treatment protocol for univentricular heart serum levels of natriuretic peptides decrease.

OBJECTIVE In children treated for univentricular heart (UVH), prospective evaluation of serum levels of N-terminal proatriopeptide (ANPN) and N-terminal pro-brain natriuretic peptide (NT-proBNP) was performed. METHODS Serum samples were analysed in 19 children before the first operation, before the bi-directional Glenn (BDG) operation, at age 1 year and before total cavopulmonary connection (TCPC). In addition, we performed cross-sectional measurement of peptide levels in 32 children: 22 hypoplastic left ventricle (LV), 10 hypoplastic right ventricle (RV) before; and in 12 children: nine hypoplastic LV, three hypoplastic RV, 2 (range: 0.5-5.3) years after the TCPC operation. Controls comprised 12 children aged less than 6 months and 41 children aged from 6 months to 7 years. RESULTS Between the first and second operations, peptide levels decreased. Before TCPC, further decreases had occurred. Throughout follow-up, peptide levels were higher than in controls. In the cross-sectional study, before TCPC, median ANPN concentration measured 0.37 (range: 0.18-1.00) nmol l(-1) (P=0.059, compared with controls) and NT-proBNP 155 (range: 13-718) ng l(-1) (P<0.001). After TCPC, median ANPN concentration measured 0.39 (range: 0.09-0.98) nmol l(-1) (P=ns) and NT-proBNP 201 (range: 76-1406) ng l(-1) (P<0.001). Before TCPC, levels of NT-proBNP were higher in patients with RV than with LV morphology. CONCLUSIONS Natriuretic peptide levels decreased during treatment protocol for UVH, but NT-proBNP levels remained higher than in controls. These reflect reduction of volume overload of the single ventricle and can prove useful for haemodynamic monitoring.

Right ventricular systolic function in hypoplastic left heart syndrome: a comparison of velocity vector imaging and magnetic resonance imaging

AIMS Velocity vector imaging (VVI) is an echocardiographic technique based on speckle tracking, which has been validated for the left ventricle (LV). It has not been validated to assess the systemic right ventricle (RV) in patients with hypoplastic left heart syndrome (HLHS). The aim of this study was to evaluate whether VVI measurements reliably reflect RV systolic function in patients with HLHS when compared with RV ejection fraction (EF) calculated using magnetic resonance imaging (MRI). METHODS AND RESULTS In this prospective study, 49 children with HLHS underwent transthoracic echocardiography and cardiac MRI under the same general anaesthetic as a part of routine assessment between the different stages of palliative surgery. Global RV fractional area change (FAC-VVI), strain (S), strain rate (SR), and peak systolic velocity (V) were analysed from the apical four-chamber view using the VVI technique. MRI-derived EF was calculated from a short-axis cine stack of images. Intra- and interobserver reproducibility was excellent for all VVI parameters (intraclass correlation coefficient >0.9). All VVI-derived parameters, except myocardial velocity, correlated with MRI-derived EF (FAC-VVI: R = 0.7, P < 0.001; S: R = -0.5, P < 0.001; SR: R = 0.5, P = 0.001, and V: R = 0.1, P = 0.4). CONCLUSIONS All VVI-derived parameters, except V, correlate with MRI-derived EF, with FAC being the best predictor of it. Reproducibility of all VVI parameters is excellent. VVI provides a useful tool for the follow-up of RV function during the staged treatment protocol for HLHS.