21. Cardio-Oncology and Drug-Induced Cardiotoxicities
Cardio-Oncology focuses on the detection, surveillance, and management of cardiovascular toxicities associated with conventional chemotherapy, targeted therapies, and immune checkpoint inhibitors.
1. Major Antineoplastic Classes & Cardiotoxicity Signatures
| Oncological Drug Class | Specific Agents | Mechanism of Cardiotoxicity | Electrocardiographic & Clinical Signatures | Surveillance & Management Protocols |
|---|---|---|---|---|
| Immune Checkpoint Inhibitors (ICIs) | Pembrolizumab, Nivolumab, Ipilimumab. | T-cell hyperactivation against cardiac autoantigens $\to$ Fulminant Myocarditis. | New PR prolongation, high-grade AV block, complete heart block, diffuse ST-T changes, ventricular arrhythmias. | Immediate discontinuation of ICI; High-dose IV Methylprednisolone ($1000\text{ mg/day}$) for 3 days; Abatacept/Infliximab if refractory. |
| Anthracyclines | Doxorubicin, Daunorubicin. | Topoisomerase II$\beta$ inhibition $\to$ free radical myocyte death $\to$ DCM. | Sinus tachycardia, low voltage QRS, nonspecific ST-T wave changes, progressive LV systolic dysfunction. | Baseline and serial TTE with Global Longitudinal Strain (GLS); ACEi/Beta-blockers for early GLS decline $>15\%$. |
| Tyrosine Kinase Inhibitors (TKIs) | Sunitinib, Sorafenib, Nilotinib, Ibrutinib. | Off-target inhibition of cardiac signaling cascades. | Marked $QTc$ prolongation, Atrial Fibrillation (Ibrutinib: $>10-15\%$ incidence), hypertension. | Serial baseline and post-treatment 12-lead ECGs; maintain $QTc < 500\text{ ms}$. |
| Fluoropyrimidines | 5-Fluorouracil (5-FU), Capecitabine. | Direct coronary vasospasm and endothelial injury. | Angina with transient ST elevation / depression during infusion mimicking acute STEMI. | Immediate cessation of infusion; IV/sublingual Nitrates and Calcium Channel Blockers (Diltiazem). |
2. Drug-Induced $QTc$ Prolongation & The CredibleMeds Framework
- High-Risk $QTc$ Thresholds:
- Baseline $QTc > 500\text{ ms}$ or an increase in $QTc > 60\text{ ms}$ from baseline during therapy mandates urgent dose reduction, drug substitution, and electrolyte optimization ($K^+ > 4.0\text{ mEq/L}, Mg^{2+} > 2.0\text{ mg/dL}$).