Vnitr Lek 2006, 52(4):328-338

Late cardiotoxicity in patients with malignant lymphoma treated with doxorubicin chemotherapy

L. Elbl^1,*, I. Vášová², M. Navrátil², I. Tomášková¹, F. Jedlička¹, V. Chaloupka¹, J. Vorlíček²

¹ Oddělení funkčního vyšetřování FN Brno, pracoviště Bohunice, přednosta doc. MUDr. Václav Chaloupka, CSc.

² Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Vorlíček, CSc.

Aim of the study:
Chronic cardiotoxicity of doxorubicin occurs at least one year after the chemotherapy is finished. As such, it is a serious late complication in patients with malignant lymphomas. The aim of the study was to identify the incidence of late clinical and subclinical doxorubicin cardiotoxicity and cardiopulmonary performance of patients being in remission for five and more years from the initial therapy.


Group of patients:
We worked with 96 patients (47 men and 49 women) aged 43 ± 15 (median 41, 23-79) years. Average period of monitoring was 6.2 ± 1.5 (median 6.5-10) years. On the basis of therapy protocol, the patients were administered a maximum doxorubicin cumulative dose (CD DOX) of 377 ± 147 (median 300, 50-880) mg/m2. Additional treatment after initial conventional therapy was performed in 32 patients (33%) due to high risk, progression or relapse of tumour.


Examination methods:
Patients were examined by resting echocardiography before and after initial therapy, and during follow-up examination after 5 years. Also, dynamic stress echocardiography and spiroergometry were performed during follow-up examination. Left ventricle ejection fraction (LVEF) decrease below 50 %, progressive decrease of LVEF > 10 % as compared with initial value, and decreased peak oxygen intake pVO2 < 20 ml/kg/min were considered as pathological. We also evaluated systolic function and index of myocardial performance (Tei-index).

Results:
Clinical cardiotoxicity was observed in 4 % of patients, subclinical in 31 % of patients. Diastolic dysfunction was found in 38 % of patients; pathological values of Tei-index were noted in 31 % of patients. Value of stress increment of LVEF was 13 ± 4 % (median 12; 5-25). Decreased pVO2 was observed in 15 % of patients. Cardiovascular disease and age > 60 years represent a higher risk of left ventricular dysfunction. Additional treatment after initial therapy represents a higher risk only if diastolic dysfunction is found (OR = 2.37, p < 0.05). Multi-dimensional regression analysis proved the relationship between pathological EF, CD DOX ≥ 300 mg/m2, age > 60 years and cardiovascular disease (for CD DOX p < 0.05; age p < 0.01; concomitant cardiovascular disease p < 0.01, with r = 0.57 and p < 0.02 values for the overall model).

Conclusions:
The above-mentioned findings should positively influence the approach of oncologists and haematologists to long-term cardiological monitoring (at least with the help of resting echocardiography) in adult patients treated with antracyclines during initial chemotherapy.

Keywords: late cardiotoxicity; malignant lymphomas; doxorubicin; echocardiography

Received: December 19, 2005; Accepted: January 10, 2006; Published: April 1, 2006  Show citation