Abstract
BackgroundCombined anthracycline-trastuzumab chemotherapy has been associated with LV dysfunction. We aimed to assess early changes in left ventricular (LV) and right ventricular (RV) mechanics associated with combined anthracycline-trastuzumab treatment for breast cancer. As well as explore whether early changes in 2-dimensional (2D)–speckle tracking echocardiography (STE) could predict later chemotherapy-induced cardiotoxicity.MethodsSixty-six patients with breast cancer who received anthracycline-trastuzumab treatment were included (mean [±SD] age, 52 [9] years). Echocardiograms were available for analysis with 2D-STE at the following time points: pretreatment (T0), first cycle (T1), and second cycle (T2) of combined chemotherapy. All patients had a normal pretreatment LV ejection fraction (LVEF). Cardiotoxicity was defined as a decrease in LVEF of at least 10 percentage points from baseline on follow-up echocardiography.ResultsCardiotoxicity developed in 13 of the 66 patients (20%). The mean (±SD) LVEF at T0 was 66% (±6); at T1 60% (±7); and at T2, 54% (±6). For the 53 patients without cardiotoxicity, the LVEF was 65% (±4%) at T0, 63% (±5%) at T1, and 62% (±4) at T2. Global longitudinal strain (GLS) at T1 was the strongest indicator of subsequent cardiotoxicity (area under the curve, 0.85; cutoff value, − 14.06; sensitivity, 91%; specificity, 83%; P = .003). Compared with baseline (T0), left ventricular longitudinal strain, LV circumferential strain, circumferential peak systolic strain rate (SR), circumferential peak early diastolic SR, right ventricular longitudinal strain, and longitudinal peak systolic SR at T1 and T2 were reduced significantly in patients with cardiotoxicity (P < .05).ConclusionsAnthracycline-trastuzumab treatment leads to early deterioration of LV GLS, circumferential strain, and systolic SR. Right ventricular GLS and SR were also affected. Early changes in GLS are good predictors of subsequent development of anthracycline-trastuzumab–induced cardiotoxicity.
Highlights
Combined anthracycline-trastuzumab chemotherapy has been associated with left ventricular (LV) dysfunction
Because of lack of consensus, we followed the definition of cardiotoxicity used in the clinical trials for combined chemotherapy in HER 2 positive patients, where it was defined as an absolute decrease in LV ejection fraction (LVEF) of 10 or more percentage points from baseline echocardiogram [24, 25]
Of the 66 patients, 13 (20%) had cardiotoxicity defined by a decrease in LVEF of 10 or more percentage points from baseline [24, 25]
Summary
Combined anthracycline-trastuzumab chemotherapy has been associated with LV dysfunction. Cardiotoxicity may be silent, yet its prompt diagnosis is important for patients with early structural heart changes but no signs or symptoms of heart failure (stage B heart failure [American Heart Association/American College of Cardiology]) [6]. Combined chemotherapeutic agents, such as anthracycline and trastuzumab have increased survival rates for patients with HER 2 positive breast cancer, and combination therapy has become a well-established therapeutic approach [7]. Recognition and appropriate therapy can improve outcomes and decrease morbidity, mortality, and progression to clinical heart failure [10]
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