ABSTRACT
THE STUDY OBJECTIVE: The aim of the study was to find out the relationship between plasmatic levels of brain natriuretic peptide (BNP) and echocardiographic indicators of left ventricle (LV) function in patients who were in a long-term remission after the therapy of hematological malignity and examined in order to diagnose the late cardiotoxicity of doxorubicin. METHODS AND PATIENT SAMPLE: We enrolled 55 patients (31 men/24 women) aged 43 +/- 16 (median 41; 21-79) who were treated for historically diagnosed malignant lymphoma. At the time of examination, all patients were in a long-term remission and, at the same time, they completed their initial therapy 6.2 +/- 1.5 (median 5; 5-10) years ago. Patients were examined via resting echocardiography before and after the therapy and during the follow-up examination. We determined the left ventricle ejection fraction (LV EF), parameters of diastolic function and the Doppler parameters of systolic and diastolic function (MPI-Tei index). During the follow-up examination, we measured plasmatic levels of BNP (standard levels were between 0 and 29 pmol/1). RESULTS: Follow-up examination showed that EF of five patients (9 %) decreased below 50% and three patients had symptoms of heart failure. Although EF of another eleven patients (20%) was in the physiological range, it decreased by more than 10% as compared with their pre-treatment EF values. Seventeen patients (30 %) showed higher MPI > 0.55 and twenty patients (36%) demonstrated diastolic dysfunction (impaired relaxation). BNP > 29 pmol/l was observed only in patients with EF < 50% and heart failure symptoms. BNP values significantly correlated only with endsystolic (r = 0.82; p < 0.0001) and enddiastolic (r = 0.72; p < 0.0001) volume of LV. On the other hand, BNP of 11.4 pmol/l showed negative predictive value for the following parameters: 80% for decrease of EF by more than 10%; 72% for detection of MPI > 0.55; and 70% for detection of relaxation disorder, i.e. the diagnostics of subclinical cardiotoxicity. CONCLUSIONS: The present study highlights the practical importance of measuring BNP levels when diagnosing the late changes of LV functions after doxorubicin chemotherapy. Standard cut-off BNP (29 pmol/1) used in diagnostics of heart failures identifies patients with pathological EF and heart failure symptoms. Cut-off BNP of 11.4 pmol/l has sufficient negative predictive value to exclude subclinical damage to the myocardium.
Subject(s)
Antibiotics, Antineoplastic/adverse effects , Biomarkers/blood , Doxorubicin/adverse effects , Natriuretic Peptide, Brain/blood , Ventricular Dysfunction, Left/chemically induced , Ventricular Dysfunction, Left/diagnostic imaging , Echocardiography , Female , Heart Failure/chemically induced , Heart Failure/diagnostic imaging , History, 16th Century , History, 17th Century , History, 18th Century , Humans , Male , Stroke Volume , Ventricular Dysfunction, Left/physiopathologyABSTRACT
Bone marrow and peripheral blood stem cell transplantations, despite their curative potential, still carry significant risks for patients. Toxicity of high-dose chemotherapy is one of the leading causes of peritransplant mortality. Busulfan is a frequently used chemotherapeutic agent in conditioning regimens prior to transplantations. The choice of the optimal busulfan dose and prediction of its clinical effect may be very difficult. Absorption of busulfan from gastrointestinal tract and its metabolism can vary considerably. Several studies published recently showed that the busulfan plasma concentrations correlate better with the clinical effect and extramedullary toxicity caused by this drug than with the actual dose administered to the patient. Approximate target plasma concentrations of busulfan, which meet the optimal balance between the clinical effect and the risk of severe side effects of chemotherapy, were proposed. Almost twenty chromatographic methods were published, which make the quantitative measurement of busulfan possible. The maintenance of certain busulfan plasma concentration during its whole administration with the help of the repeated adjustments of its dosage can reduce the toxicity caused by this agent and improve the results of bone marrow or peripheral blood stem cell transplantations. This method is easily applicable, has low financial and personal demands, and technical appliances, which it requires are usually accessible in most transplant center laboratories.
