Tuija Poutanen

Long-Term Prospective Follow-Up Study of Cardiac Function After Cardiotoxic Therapy for Malignancy in Children

PURPOSE To evaluate cardiac function by means of conventional and three-dimensional echocardiography (3DE) and measurement of natriuretic peptides in children and adolescents previously treated for childhood malignancy using individual follow-up data and matched control children as reference criteria. PATIENTS AND METHODS Thirty-nine survivors of childhood malignancy were examined in 1994 and 1998. The mean time from the diagnosis was 8.6 (3.9 to 16.8) years and between cardiac evaluations was 4.1 (3.3 to 5.1) years. Patients were divided into two groups according to therapies given (group I (n = 30): no cardiac irradiation, median cumulative anthracycline dose 210 mg/m2; group II (n = 9): irradiation in the cardiac region, median cumulative anthracycline dose 180 mg/m2). RESULTS Fractional shortening (FS) in 1994 was higher than in 1998 (32.5 +/- 4.3 vs. 30.3% +/- 3.3%, P =.009). 33% of patients in group I and 56% in group II in 1994 and 30% of patients in group I and 67% in group II in 1998 had N-terminal of the propeptide-atrial natriuretic peptide (NT-proANP) levels exceeding the 90th percentile of controls. In 1998, both groups (I and II) had lower ejection fraction (EF) measured by 3DE than their matched controls (52.9 +/- 5.2 vs. 58.8% +/- 3.1%, P <.001 and 50.0 +/- 6.6 vs. 60.8% +/- 3.2%, P =.024, respectively). Left atrial maximum volumes/body surface area were smaller in the patients than in controls. B-Type natriuretic peptide values did not differ significantly in either group. CONCLUSION Left ventricular contractility decreases slowly even years after cardiotoxic cancer therapy in children. 3DE and NT-proANP measurements are effective methods to evaluate the cardiac function in these patients.

Cardiac Magnetic Resonance Imaging in the Evaluation of the Late Effects of Anthracyclines Among Long-Term Survivors of Childhood Cancer

OBJECTIVES This study sought to examine the left ventricular (LV) and right ventricular (RV) function and signs of focal fibrosis among long-term survivors of childhood cancer with the use of cardiac magnetic resonance (CMR) imaging. BACKGROUND Increased myocardial fibrosis has been detected in the endomyocardial biopsies of survivors. CMR has established its role in the assessment of both cardiac function and structure, and focal fibrosis of the myocardium is detectable with late gadolinium enhancement (LGE). METHODS Sixty-two anthracycline-exposed long-term survivors of childhood cancer were studied at a mean age of 14.6 years. The LV and RV ejection fractions (EFs) and volumes were measured, and LGE was assessed using CMR. RESULTS An abnormal LV function (EF <45%) was detected in 18% (11 of 62) of the survivors, and an abnormal RV function was detected in 27% (17 of 62) of the survivors. Subnormal (45% ≤ EF <55%) LV function were demonstrated in 61% (38 of 62) and subnormal RV function in 53% (33 of 62) of the survivors, respectively. Both the LV and RV end-systolic and LV end-diastolic volumes were increased compared with reference values. None of the study patients showed LGE. CONCLUSIONS A considerable proportion of the long-term survivors of childhood cancer with anthracycline exposure demonstrate signs of cardiac dysfunction detectable by CMR, with the RV also being involved. Yet, myocardial fibrosis does not seem to be detectable at a median of 7.8 years after anthracycline therapy.

Normal aortic dimensions and flow in 168 children and young adults.

Background: Knowledge of normal aortic dimensions is important while evaluating children with aortic root dilatation.

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.

Three-Dimensional Echocardiography and Cardiac Magnetic Resonance Imaging in the Screening of Long-Term Survivors of Childhood Cancer After Cardiotoxic Therapy

The left ventricular (LV) volumes, ejection fraction (EF), and dyssynchrony indexes for the 16 and 12 cardiac segments (Tmsv16-SD and Tmsv12-SD, respectively) were analyzed among nonadult, anthracycline-exposed long-term survivors of childhood cancer and compared with those of healthy controls using conventional and real-time 3-dimensional echocardiography (RT-3DE) with cardiac magnetic resonance (CMR) imaging in a prospective, cross-sectional, single tertiary center setting. Seventy-one survivors and gender-, body surface area-, and age-matched healthy controls were studied by conventional echocardiography and RT-3DE. Fifty-eight of the 71 survivors underwent also CMR. The survivors were evaluated in 2 groups. Group I consisted of 63 exposed to anthracyclines and group II consisted of 8 also exposed to cardiac irradiation. By RT-3DE, the group I survivors had a lower LVEF (57% vs 60%, respectively, p = 0.003) and larger body surface area-indexed LV end-systolic volume (31 vs 28 ml/m(2), respectively, p = 0.001) than controls. The Tmsv16-SD was higher in group II than in I (1.93% vs 1.39%, respectively, p = 0.003). None of the survivors had an abnormal fractional shortening (<28%), but 10% had an LVEF <50% by RT-3DE. An LVEF <55% was detected in 45 of 58 (78%) of those imaged with CMR. In conclusion, RT-3DE seems to detect more abnormalities in cardiac function than conventional echocardiography following childhood cancer therapy. The LV dyssynchrony indexes derived from RT-3DE appear potentially useful in assessing the early signs of cardiotoxicity between anthracycline and cardiac irradiation exposed long-term survivors of childhood cancer.

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.

Cardiac biomarkers indicate a need for sensitive cardiac imaging among long-term childhood cancer survivors exposed to anthracyclines.

The role that plasma N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and cardiac troponins T (cTnT) and I (cTnI) play in supplementing imaging to screen for cardiac late effects remains controversial and the impact of high‐sensitivity cTnT and troponin‐specific autoantibodies (cTnAAbs) remains unexplored. We studied the role of cardiac biomarkers as indicators of the late effects of anthracyclines among childhood cancer survivors.

Cardiac troponin I in congenital heart defects with pressure or volume overload.

Abstract Objective. To evaluate the prevalence of cardiac troponin I (cTnI) and autoantibodies to cTn in children with congenital heart defects with volume or pressure overload fulfilling the criteria for treatment, and in healthy children. Design. The study groups comprised 78 children with volume overload caused by an atrial septal defect or a patent ductus arteriosus, and 60 children with pressure overload caused by coarctation of the aorta or stenosis of the aortic or the pulmonary valve, and 74 healthy controls. Serum levels of natriuretic peptides, cTnI, and autoantibodies to cTn were analyzed at baseline, prior to treatment and in 64 patients 6 months after treatment. Results. At baseline, one child with volume overload, 12 children with pressure overload, and one healthy control had positive cTnI. Further analysis of the pressure overload subgroup revealed that the children with positive cTnI were younger than those with negative cTnI, and had higher levels of natriuretic peptides. The pressure gradient at the coarctation site or stenotic valve was higher in those with positive TnI. Six months after treatment, 63 of 64 children examined were cTnI negative. Conclusions. The cTnI release is more frequently associated with pressure than volume overload which resolves after treatment in most children.

Bilateral Absence of the Superior Vena Cava

Bilateral absence of the superior vena cava (SVC) is a very rarely detected, mainly asymptomatic congenital vascular anomaly. Though usually innocent, this anomaly may complicate cardiothoracic surgery and certain procedures like central venous catheter insertion. This SVC anomaly is poorly known, and we assume that its incidence in the general population may be higher than detected. In this paper, we summarize current knowledge on this anomaly and its clinical implications. In addition, we present a neonatal case with bilateral absence of the SVC associated with a fetal cystic hygroma. Conclusion. Totally absent SVC can cause unexpected problems during cardiothoracic surgery. Suspicion of SVC absence should arise in basic echocardiography. Our paper suggests that, like other congenital anomalies, bilateral absent SVC may be associated with a fetal cyctic hygroma.

Velocity vector imaging shows normal cardiac systolic function in survivors of severe bronchopulmonary dysplasia at six to 16 years of age

This study evaluated global myocardial function and associations between cardiac function and lung function in very low birth weight (VLBW) children, with and without severe radiographic bronchopulmonary dysplasia (BPD), at six to 14 years of age.