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

Abstract

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. 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. 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. 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.