Perspective:

The following are 10 points to consider from this review:

1. Several new drugs used to treat malignancies affect cardiovascular signaling pathways, and thus, may have important cardiac side effects, particularly during times of increased cardiac stress or diminished myocardial reserve.

2. Conventional chemotherapeutic agents such as anthracyclines may induce permanent myocardial cell injury (type 1), while signaling inhibitors currently in use—such as inhibitors of human epidermal growth factor receptor 2 (HER2/erB2) and vascular endothelial growth factor (VEGF)—often lead to reversible cardiac dysfunction (type 2).

3. Cumulative doses of doxorubicin above 300 mg/m² lead to exponential increases in cardiotoxicity. Susceptibility to cardiac toxicity is increased in patients with genetic predisposition, arterial hypertension, previous or concurrent mediastinal radiation, and combination chemotherapy with alkylating or antimicrotubule agents.

4. Approaches to mitigate anthracycline toxicity with protective agents, including angiotensin-converting enzyme inhibitors, have been studied, although evidence from large randomized, prospective trials is still needed.

5. Other chemotherapeutic agents that lead to myocyte destruction include mitoxantrone, cyclophosphamide (especially large single doses), cisplatin, and pyrimidine analogues, which may cause ischemia/infarction.

6. Trastuzumab (monoclonal antibody against HER2 receptor) is beneficial in patients with some breast and gastric cancers. Risk factors for trastuzumab-associated cardiotoxicity include anthracycline therapy (severe heart failure occurred in 16% of patients treated with anthracyclines and trastuzumab), even borderline low left ventricular ejection fraction, hypertension, advanced age, and possibly body mass index >25.

7. Angiogenesis inhibitors targeting VEGF (antibodies-bevacizumab or small molecule TKIs – sunitinib, sorafenib) prolong lives of patients with many types of solid tumors. These drugs may also cause cardiac dysfunction/heart failure (3.8% with bevacizumab), presumably due to impaired myocardial VEGF signaling.

8. Other cardiovascular effects of anticancer drugs to be alert for include hypertension (VEGF inhibitors), coronary vasospasm (5-FU), thromboembolism (cisplatin, angiogenesis inhibitors, tamoxifen), dysrhythmia, and prolonged QT (many).

9. Noninvasive imaging techniques (i.e., tissue Doppler/strain) and biomarkers (B-type natriuretic peptide, cardiac troponin) may be useful in managing patients receiving chemotherapy, although clinical trials are needed to assess their efficacy.

10. As therapeutic breakthroughs in cancer chemotherapies continue to emerge, it will become increasingly important to identify patients at increased risk of cardiotoxicity to carefully balance the benefits of lifesaving chemotherapy with cardiovascular complications.