Chemotherapy as second hit in desmoplakin cardiomyopathy. CMR as a key tool in diagnosis.

Description of Clinical Presentation: A 37-year-old woman with no prior cardiovascular history was diagnosed with invasive ductal breast carcinoma with axillary lymph node metastasis. Tumor was ER/PR positive, HER2 negative by FISH, Ki-67 30%. She was scheduled for neoadjuvant epirubicin and docetaxel. Baseline cardio-oncology evaluation showed normal ECG, LVEF 61%, GLS –21.4%, and troponin 6.8 pg/mL. During treatment, LVEF declined to 44% and GLS to –13.8%, with elevated proBNP (419 pg/mL). Cardioprotective therapy with dapagliflozin, enalapril, and bisoprolol was initiated. After quadrantectomy and axillary dissection, HER2 positivity was confirmed and trastuzumab was started. Despite initial recovery to LVEF 50%, further deterioration prompted cardiovascular magnetic resonance, which revealed biventricular systolic dysfunction (LVEF 36%, RVEF 32%), ventricular dilation, high extracellular volume, and extensive ring-like late gadolinium enhancement. These findings were atypical for anthracycline cardiotoxicity, raising suspicion of genetic cardiomyopathy. Genetic testing identified a pathogenic desmoplakin mutation. Anti-HER2 therapy was discontinued and heart failure treatment optimized with eplerenone. At three months, CMR showed partial improvement (LVEF 44%, RVEF 45%). Given the arrhythmic risk associated with desmoplakin mutations, mild reduction in LVEF and extensive fibrosis, an implantable cardioverter-defibrillator was placed for primary prevention of sudden cardiac death. After two years, the patient remains in NYHA class I with complete oncologic remission and free of cardiovascular events under multidisciplinary follow-up.

Diagnostic Techniques and Their Most Important Findings: After an initial decline in LVEF and GLS evidenced on follow-up echocardiography, CMR demonstrated increased biventricular volumes with severe impairment of biventricular ejection fraction (LVEF 36%, RVEF 32%), elevated extracellular volume (ECV 30%), and extensive late gadolinium enhancement with a predominantly lateral subepicardial distribution (subepicardial ring-like pattern) and involvement of the right ventricular free wall. Six months later, follow-up CMR showed persistent left ventricular dilation with partial improvement of LVEF to 44% and RVEF to 45%

Learning Points from this Case: This case underscores the pivotal role of CMR in the evaluation of patients with chemotherapy-induced ventricular dysfunction. Beyond its ability to detect structural and functional impairment, CMR may help identify “second-hit” phenomena in genetically predisposed cardiomyopathies with an previous negative phenotype. Furthermore, it provides a reliable tool for longitudinal follow-up, particularly in assessing the degree of ejection fraction recovery over time.

SSFP sequences in the four-chamber view demonstrated global hypoquinesia, increased ventricular volumes and severe impairment of biventricular ejection fraction (LVEF 36%, RVEF 32%).,
PSIR sequences in the four-chamber view demonstrated extensive subepicardial late gadolinium enhancement involving the lateral wall of the left ventricle.
A ring-like LGE pattern on PSIR short-axis view, which is characteristic of genetic cardiomyopathies.