Assessing adriamycin-induced early cardiotoxicity by estimating left ventricular ejection fraction using technetium-99m multiple-gated acquisition scan and echocardiography

Abstract

Background: Adriamycin cardiotoxicity begins with the first dose of therapy. The insult may be subclinical initially, but with continued treatment can result in clinical congestive heart failure. Therefore, a study for the detection of early cardiotoxicity of adriamycin by left ventricular ejection fraction (LVEF) estimation using technetium (Tc)-99m multiple-gated acquisition (MUGA) scan and echocardiography (ECHO) was conducted.

Methods: LVEF was assessed in 42 patients with different cancers, advised to receive adriamycin (average received dose = 95.2 ± 6.82 mg/cycle, protocol dose = 65 ± 10 mg/m) in each of six cycles. The percentage of LVEF (%LVEF) was determined as a baseline after every successive cycle, simultaneously, by a Tc-99m MUGA scan (reference method) and ECHO.

Results: A significant decline of 12.17 ± 5.01 and 9.26 ± 4.82 (P < 0.001) in %LVEF was noted at the end of adriamycin therapy, estimated by a Tc-99m MUGA scan and ECHO respectively. Thirteen of 42 (31%) and six of 42 (14%) patients developed protocol-defined cardiotoxicity, determined by a Tc-99m MUGA scan and ECHO, respectively. The incidence of cardiotoxicity was 2.4, 2.4, 4.8, 16, and 31.2% at the median cumulative adriamycin dose of 210, 380, 450 , 550 , and 615 mg/m, respectively.

Conclusion: Subclinical adriamycin cardiotoxicity was detectable from the third cycle and if not detected earlier continued therapy may progress to severe and irreversible cardiotoxicity. A decline of 5% or more of %LVEF instead of 10% should be considered as a significant marker of subclinical cardiotoxicity. A Tc-99m MUGA scan is more sensitive than ECHO for the estimation of subtle changes in %LVEF. Ideally, %LVEF must be determined at baseline and after every cycle, and if not possible then preferably from the third cycle onwards.