From 60% to 5% in 12 Weeks: A Trastuzumab-Induced Left Ventricular Ejection Fraction Drop

Abstract

Trastuzumab is the first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, trastuzumab is associated with cardiotoxicity. It manifests with an asymptomatic reduction of left ventricular ejection fraction (LVEF) and is reversible after discontinuation. Trastuzumab-induced new-onset acute decompensated heart failure is rare (0.5%). We report a case of a 54-year-old woman who received anthracycline (idarubicin, accumulated dose 400 mg/m² doxorubicin equivalent) for her acute promyelocytic leukocyte 10 years ago, had no relevant comorbidities or other pre-existing cardiovascular diseases, had maintained normal cardiac function, presenting with new-onset dyspnea at rest and bilateral lower extremities swelling 12 weeks after receiving trastuzumab induction chemotherapy for her newly diagnosed early stage HER2-positive breast cancer. Chest X-ray showed severe pulmonary edema. Echocardiography revealed diffuse left ventricular hypokinesis with LVEF 5%. After other possible etiology of cardiomyopathy, including ischemia, infection, substance, or radiation, were excluded by extensive cardiomyopathy workup, a diagnosis of trastuzumab-induced cardiotoxicity was established. Trastuzumab was discontinued, and the patient's symptom was improved with furosemide. Guildline-directed medical therapy was gradually maximized over three months. Repeat transthoracic echocardiography (TTE) at one-year follow-up after the initial diagnosis shows LVEF 33%, and the patient was referred to an advanced heart failure clinic. This case report demonstrated a rare catastrophic cardiac toxicity effect of trastuzumab and its potential association with remote exposure to anthracycline. Studies have investigated the cardiotoxicity in the concurrent use of trastuzumab and anthracycline therapy. However, how trastuzumab affected patients who were exposed to anthracycline for more than eight years had remained unreported. To our knowledge, no previous detailed case report has described the same clinical scenario as in this case. The case also demonstrates the limitation of the commonly used cardio-oncology cardiovascular risk assessment tool and highlights the importance of individualized cardiovascular risk stratification when deciding on chemotherapy plans.

Keywords: anthracycline; breast cancer; cardiotoxicity; congestive heart failure; trastuzumab.

Figure 1. Chest X-ray on 12/5/2023 revealing severe pulmonary edema

Figure 2. TTE on 12/6/2022 showing the end-systole phase with LVEF 5%

TTE: transthoracic echocardiography; LVEF: left ventricular ejection fraction

Figure 3. TTE on 12/6/2022 showing the end-diastole phase with LVEF 5%

TTE: transthoracic echocardiography; LVEF: left ventricular ejection fraction

Figure 4. Timeline for LVEF trend

LVEF: left ventricular ejection fraction