Endothelin-1 and cardiac function in anthracycline-treated patients: a 1-year follow-up

J Cardiovasc Pharmacol. 2004 Nov:44 Suppl 1:S372-5. doi: 10.1097/01.fjc.0000166300.48561.07.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Bleomycin / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Dacarbazine / administration & dosage
  • Down-Regulation
  • Doxorubicin / administration & dosage
  • Echocardiography, Doppler
  • Endothelin-1 / blood*
  • Female
  • Follow-Up Studies
  • Heart Diseases / chemically induced*
  • Heart Diseases / diagnostic imaging
  • Heart Diseases / metabolism
  • Heart Diseases / physiopathology
  • Hodgkin Disease / drug therapy*
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Male
  • Middle Aged
  • Prednisone / administration & dosage
  • Stroke Volume / drug effects
  • Time Factors
  • Treatment Outcome
  • Ventricular Function, Left / drug effects*
  • Vinblastine / administration & dosage
  • Vincristine / administration & dosage

Substances

  • Endothelin-1
  • Bleomycin
  • Vincristine
  • Vinblastine
  • Dacarbazine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • ABVD protocol
  • CHOP protocol