Myocardial strain and strain rate in monitoring subclinical heart failure in asymptomatic long-term survivors of childhood cancer.

We studied the role of global myocardial strain and strain rate in monitoring subclinical heart failure in a large group of asymptomatic long-term survivors of childhood cancer. Global strain (rate) parameters of survivors were compared with those in healthy controls and were related to conventional echocardiographic parameters, N-terminal-pro-natriuretic peptide (NT-pro-BNP) levels and clinical parameters. Two-dimensional (2-D) echocardiography was performed in 111 survivors and 107 healthy controls. Blood samples were taken from survivors to determine NT-pro-BNP levels. We showed that global myocardial strain, strain rate and time to peak systolic strain in asymptomatic survivors of childhood cancer were significantly lower compared with healthy controls (p values <0.0001) and were significantly related to several systolic and diastolic left ventricular parameters. Whether myocardial strain and strain rate are superior to conventional echocardiography in the early detection of subclinical heart failure needs to be explored in further longitudinal prospective studies.

Abnormal NT-pro-BNP levels in asymptomatic long-term survivors of childhood cancer treated with anthracyclines.

BACKGROUND: Anthracycline-induced cardiotoxicity can cause serious health problems for an increasing number of survivors of childhood malignancies. The aims of this study were to document plasma concentrations of cardiac troponin T (cTnT) and NT-pro-brain natriuretic peptide (NT-pro-BNP) in a large group of asymptomatic long-term survivors of childhood cancer treated with anthracyclines, and to study the relation of the abnormal biomarker levels with different risk factors for anthracycline-induced cardiotoxicity and conventional echocardiographic parameters. PROCEDURES: One hundred twenty-two asymptomatic survivors of childhood cancer underwent a detailed echocardiography. Blood samples were taken to determine the levels of NT-pro-BNP and cTnT. RESULTS: None of the survivors had abnormal cTnT levels. Thirteen percent of the survivors (n = 16) had abnormal NT-pro-BNP levels. Abnormal NT-pro-BNP levels were significantly related to cumulative anthracycline dosage (P < 0.003). Eleven of 31 survivors (35%) treated with cumulative anthracycline dose of 300 mg/m(2) or more, had abnormal NT-pro-BNP levels which were significantly related to end-diastolic left ventricular internal diameter (LVIDd) indexed for body surface area (BSA) (P < 0.01). CONCLUSION: Cardiac TnT does not contribute to the early detection of late onset anthracycline-induced cardiotoxicity. Abnormal levels of NT-pro-BNP were detected in 13% of 122 asymptomatic, long-term survivors of childhood cancer. Follow-up of these survivors is essential to answer the question whether NT-pro-BNP is an early marker for late onset anthracycline-induced cardiotoxicity.

Interobserver, intraobserver and intrapatient reliability scores of myocardial strain imaging with 2-d echocardiography in patients treated with anthracyclines.

Myocardial strain imaging with 2-D echocardiography is a relatively new noninvasive method to assess myocardial deformation. To determine the interobserver, intraobserver and intrapatient reliability scores, we evaluated myocardial strain measurements of 10 asymptomatic survivors of childhood cancer. Ten patients were selected randomly out of a follow-up cohort of childhood cancer survivors. All 10 patients underwent a transthoracic echocardiographic examination. Two-dimensional gray scale images were made in parasternal apical four-chamber, apical two-chamber, midcavity short-axis and basal short-axis views. Offline analysis was performed using software for echocardiographic quantification (Echopac 6.1.0, GE Medical Systems, Horten, Norway). All echocardiographic studies were analyzed offline by three observers, separately (A.M., G.W., M.P.). A custom-made software package was designed for averaging the strain curves of three consecutive cardiac cycles. Values of peak systolic strain, time-to-peak strain and time-to-end systole of the different segments of the left ventricle were used for statistical analysis. Interobserver, intraobserver and intrapatient reliability were expressed as intraclass correlation coefficients (ICCs). Interobserver ICCs of peak strain, time to peak strain and time to aortic valve closure (AVC) were generally good to very good in all views and segments, except for in the two-chamber view. Intraobserver ICCs were rated as very good for almost all segments, except for the longitudinal peak strain values of the two-chamber view. Intrapatient ICCs were generally good for the two-chamber, four-chamber and midcavity short-axis views, but fair to moderate for the segments of the basal short-axis view (SaxMV). We recommend use of the four-chamber view for longitudinal peak strain values, and the basal and midcavity short-axis views for radial and circumferential peak strain values. Furthermore, we strongly recommend using the average of three cardiac cycles for peak strain values in clinical studies.

The role of biomarkers in the early detection of anthracycline-induced cardiotoxicity in children: a review of the literature.

Anthracycline-induced cardiotoxicity can cause serious health problems for an increasing number of children surviving childhood malignancies. Early detection of cardiac failure is critically important for the prevention and management of anthracycline-induced cardiotoxicity. The aim of this research was to determine the role of biomarkers in the early detection of anthracycline-induced cardiotoxicity in children. A literature review is presented of studies regarding the use of the biomarkers B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-pro-BNP), cardiac troponin T (cTnT), and cardiac troponin I (cTnI) in relation with anthracycline-induced cardiotoxicity in children. Six of 14 studies in children showed a significant relation between elevated biomarkers BNP, NT-pro-BNP, and cTnT and cardiac dysfunction. Six studies, although small, suggest that BNP, NT-pro-BNP, and cTnT might be useful markers in the early detection of anthracycline-induced cardiotoxicity.

Recurrent melanotic neuroectodermal tumor of infancy: a proposal for treatment protocol with surgery and adjuvant chemotherapy.

The case of a 4-month-old male infant treated with combined surgery and chemotherapy for an aggressive recurrent melanotic neuroectodermal tumor of infancy (MNTI) on the top of the alveolar process of the mandible with a long-term follow-up is presented. Initial treatment comprised conservative local excision and curettage of the mandible. After several local recurrences and because radical surgical excision would give gross functional and aesthetic mutilation, finally complete, long-lasting remission was achieved with adjuvant chemotherapy, according to a neuroblastoma protocol (10-year follow-up). The reason for this protocol was because molecular genetic studies of this tumor showed loss of heterozygosity of chromosome 1p and gain of chromosome 7q analogue to neuroblastomas. A combination of surgery and chemotherapy should be the preferred treatment in case of a recurrence MNTI because optimal functional and aesthetic outcome.

Regional cardiac wall motion abnormalities during and shortly after anthracyclines therapy.

BACKGROUND: Tissue Doppler imaging (TDI) is a new non-invasive ultrasound technique that enables quantitative assessment of regional myocardial wall motion. A previous study of survivors of childhood malignancies demonstrated abnormalities of regional diastolic wall motion abnormalities many years after treatment with anthracyclines. The purpose of the present study was to investigate this phenomenon during and shortly after treatment. PROCEDURE: A total of 60 patients, age range 4.4-16.0 years, were included in this study: 43 early survivors, with a mean follow-up duration of 2.1 (range 0.3-5.2) years from end of anthracycline treatment, were evaluated retrospectively. Seventeen other patients were evaluated before, during, and 6 months after the end of anthracycline therapy. All patients received moderate cumulative doses of anthracyclines (range 120-450 mg/m2). Echocardiographic examination was performed using standardized conventional and TDI techniques. RESULTS: Of the early survivors, 26 (60%) demonstrated regional LV free wall motion abnormalities. In the prospective group, serial echocardiographic studies revealed three patients (18%) with regional abnormalities of LV free wall motion before starting chemotherapy, but 14 (82%) at the end of treatment. Six months later, however, the incidence decreased to 61% of the survivors. Subject and treatment characteristics, as well as LV wall diameters and fractional shortening were not significantly different for children with or without free wall motion abnormalities. Regional wall motion abnormalities were also seen in the interventricular septum, although this was less frequent. CONCLUSIONS: Regional diastolic wall motion abnormalities are common during and shortly after anthracyclines therapy but may be transient. The authors recommend simultaneous use of both conventional echocardiography & TDI for the monitoring of anthracycline-induced cardiotoxicity.