Endothelin-1 and cardiac function in anthracycline-treated patients: a 1-year follow-up.
Anthracyclines are widely used chemotherapeutic agents in the treatment of lymphomas known to induce cardiomyopathy in more than 20% of patients. There is increasing experimental evidence that cardiac endothelial cells regulate cardiac performance and that endothelin-1 (ET-1) is a central substance in this regulatory mechanism. Twenty (seven male, aged 20-68 years) patients with Hodgkin's or non-Hodgkin's lymphoma treated with anthracycline were followed-up for 1 year. At baseline, after cessation of anthracycline treatment and at 1 year, the plasma ET-1 level was measured by enzyme-linked immunosorbent assay and cardiac function was estimated by echocardiographic measurement of the ejection fraction, the E/A ratio and the deceleration time. The ET-1 level decreased significantly after therapy (5.47 +/- 3.34 pg/mL versus 3.44 +/- 0.69 pg/mL, P < 0.02), and remained significant at 1 year (3.43 +/- 0.57 pg/mL, P < 0.008). The ejection fraction (57.80 +/- 4.73% versus 48.05 +/- 5.65%, P < 0.0001) and the E/A ratio (1.35 +/- 0.40 versus 1.15 +/- 0.40, P < 0.01) decreased, and the deceleration time (177.00 +/- 44.96 ms versus 209.50 +/- 66.25 ms, P < 0.04) increased significantly after therapy, showing that both systolic and diastolic left ventricular performance were deteriorated. Compared with the baseline, the same significant changes were found at 1 year (ejection fraction, 50.65 +/- 8.87%, P < 0.0007; E/A ratio, 1.10 +/- 0.34, P < 0.003; deceleration time, 223.25 +/- 46.85 ms, P < 0.002). The decrease of the ET-1 concentration might be a result of anthracyclines' direct cytotoxic effect and the decreasing level of ET-1 may play a role in the ejection fraction reduction. The results of 1-year follow-up suggest that, although anthracycline toxicity occurs shortly after treatment, the undesirable effect remains.
Zsáry
András
A
3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. zsaran@kut.sote.hu
Szücs
Szófia
S
Keltai
Katalin
K
Pásztor
Edina
E
Schneider
Tamás
T
Rosta
András
A
Sármán
Pál
P
Jánoskuti
Livia
L
Fenyvesi
Tamás
T
Karádi
István
I
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001761:Bleomycin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D015536:Down-Regulation; D004317:Doxorubicin / Q000008:administration & dosage; D015150:Echocardiography, Doppler; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*; D014747:Vinblastine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
D019332:Endothelin-1; D001761:Bleomycin; D014750:Vincristine; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone