Abstract 4146993: Anthracycline-based Chemotherapy in A Patient with Breast Cancer and Left-Ventricular Hypertrabeculation

Introduction: Anthracyclines (AC), a class of chemotherapeutic drugs, are used to treat various cancers, including breast cancer (BC). However, AC cause dose-dependent cardiac toxicity. Practice guidelines list pre-existing cardiomyopathy as a risk factor for cancer therapy-related cardiac dysfunction (CTRCD), but there is a lack of data on cardiotoxicity risk in patients with left ventricular (LV) hypertrabeculation without LV hypertrophy/dilation. We present a patient with LV hypertrabeculation who developed LV dysfunction after AC chemotherapy for BC. Description of Case: A 55-year-old woman diagnosed with multicentric invasive ductal carcinoma (IDC) of the right breast, stage IIA (cT3 cN1 cM0), grade 2, ER+/PR+/HER2-, was treated with neoadjuvant Paclitaxel for 3 months. Before AC-based chemotherapy, stress cardiac MRI due to residual post-COVID-19 dyspnea showed LV hypertrabeculation with a non-compacted/compacted ratio of 2.3, LVEF 56%, and no delayed enhancement. Transthoracic echocardiography (TTE) reported an LVEF of 52% with GLS of -17%. The patient's electrocardiogram (ECG) showed normal sinus rhythm, and NT-pro BNP levels were <20 pg/mL. Genetic testing identified a rare variant in MYH7-encoded myosin heavy chain 7 (p.Arg941Leu-MYH7). She had no cardiovascular (CV) risk factors or family history of CV disease. She then underwent 4 cycles of Doxorubicin (cumulative dose 232.2 mg/m2) and Cyclophosphamide, followed by bilateral mastectomy and adjuvant radiotherapy (5000 cGy in 25 fractions). One year after chemotherapy, follow-up TTE showed LVEF decreased to 45% with GLS of -17%. The patient’s ECG remained normal, and NT-pro BNP levels were <36 pg/mL. Despite an LVEF decline, not all criteria for CTRCD were met, suggesting a gene-environment interplay between her chemotherapy and pre-existing MYH7-mediated non-dilated LV cardiomyopathy (NDLVC) with hypertrabeculation. The patient has remained without symptoms of heart failure and is currently taking Letrozole 2.5 mg daily. Discussion: This case offers a unique perspective on a BC patient treated with AC chemotherapy, who has a possible MYH7-mediated NDLVC with hypertrabeculation, and who experienced an LVEF decline of indeterminate significance. While the association of her possible NDLVC with hypertrabeculation is uncertain, the safety of AC in patients with isolated hypertrabeculation or NDLVC with hypertrabeculation, as introduced by the 2023 ESC cardiomyopathy guidelines, remains to be defined.