A 14-year-old girl with osteosarcoma of the distal femur has completed 3 cycles of neoadjuvant chemotherapy (doxorubicin, cisplatin, methotrexate). Repeat MRI shows 40% reduction in tumor size. Chest CT is negative for metastases. She is scheduled for wide surgical resection in 2 weeks. During the preoperative assessment, she complains of dyspnea on exertion and has a resting heart rate of 110 bpm. Echocardiography reveals a left ventricular ejection fraction (LVEF) of 42% (baseline 55%). What is the most appropriate next step?

Explanation

## Clinical Context: Doxorubicin Cardiotoxicity This patient has developed **chemotherapy-induced cardiomyopathy (CIC)**, a well-recognized complication of doxorubicin-based regimens used in osteosarcoma. **Key Point:** Doxorubicin causes dose-dependent cardiotoxicity through oxidative stress and mitochondrial damage. A decline in LVEF from 55% to 42% (13-point drop) during treatment is significant and requires intervention. ## Cardiotoxicity Grading & Management | LVEF Decline | Grade | Clinical Significance | Action | |---|---|---|---| | <10% | 1 | Mild | Monitor closely | | 10–20% | 2 | Moderate | Cardiology referral, consider dexrazoxane | | >20% | 3–4 | Severe | Hold chemotherapy, optimize cardiac therapy | This patient has a **13-point decline**, which is Grade 2 (moderate) and requires cardiology evaluation. ## Management Algorithm for Chemotherapy-Induced Cardiomyopathy ```mermaid flowchart TD A[LVEF decline during doxorubicin therapy]:::outcome --> B[Refer to cardiology]:::action B --> C[Optimize cardiac function]:::action C --> D{LVEF recovery or stabilization?}:::decision D -->|Yes| E[Proceed with surgery + remaining chemotherapy]:::action D -->|No| F[Reassess surgical vs. medical risk]:::decision F --> G[Proceed with caution or defer]:::action ``` ## Why Cardiology Referral is Essential 1. **Assess reversibility** — Some cardiotoxicity is reversible with ACE inhibitors, beta-blockers, or aldosterone antagonists 2. **Cardioprotection** — Dexrazoxane (if not already given) can reduce further doxorubicin-induced damage 3. **Risk stratification** — Determine if LVEF is stable or declining further 4. **Surgical safety** — Evaluate perioperative cardiac risk before wide resection (major surgery with blood loss) **High-Yield:** Doxorubicin cardiotoxicity can be: - **Acute/subacute** (during or shortly after therapy) — often reversible - **Chronic** (months to years later) — may be progressive This patient's presentation during active therapy suggests acute cardiotoxicity, which may improve with optimization. **Clinical Pearl:** Dexrazoxane (an iron-chelating agent) is a cardioprotective agent that should be considered if not already administered. It reduces doxorubicin cardiotoxicity without compromising antitumor efficacy. ## Why Each Alternative is Incorrect - **Option A (proceed as planned):** Ignores significant cardiac dysfunction. Perioperative cardiac events are a major risk in patients with LVEF <45%. Not safe. - **Option B (defer surgery, continue chemotherapy):** Continuing doxorubicin with declining LVEF risks further deterioration and acute heart failure. Surgery is the next essential step after neoadjuvant therapy. - **Option D (biomarkers alone):** Troponin and BNP are useful but do not replace echocardiographic assessment of LVEF. Normal biomarkers do not guarantee surgical safety in the setting of reduced ejection fraction.