Role of Echocardiography in Patients Treated with Cardiotoxic Drugs

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8 Role of Echocardiography in Patients Treated with Cardiotoxic Drugs

Basic Principles

• Several anti-neoplastic agents are associated with significant cardiotoxicity.

• Agents most commonly associated with cardiotoxic risk include anthracyclines (doxorubicin), as well as the tyrosine kinase inhibitors trastuzumab, sunitinib, and sorafenib (Table 8-1).

• Cardiotoxicity associated with anti-cancer therapy is typically associated with a global decline in left ventricular ejection fraction (LVEF), although early manifestations may include diastolic dysfunction.

• Radiation therapy is also associated with significant cardiotoxic effects.

• Echocardiography is important to assess both systolic and diastolic cardiac function, extent of valvular disease, and evidence for any pericardial disease.

TABLE 8-1 COMMON CHEMOTHERAPY AND ANTI-CANCER AGENTS ASSOCIATED WITH SIGNIFICANT CARDIOTOXICITY

Type of Agent	Potential Cardiac Complication
Anthracyclines
Doxorubicin	Early postinfusion, transient, often reversible decline in LVEF; arrhythmias, myopericarditis; more commonly, a decline in LVEF > 1 year after therapy
Tyrosine Kinase Inhibitors
Trastuzumab	Potentially reversible, significant decline in LVEF
Bevacizumab	Hypertension, arterial thrombosis
Sunitinib	Decline in LVEF, hypertension
Sorafenib	Myocardial infarction, hypertension
Imatinib	Diastolic dysfunction, pericardial effusion
Alkylating Agents
Cisplatin	Hypertension, vascular dysfunction
Cyclophosphamide	Pericarditis/myocarditis, decline in LVEF with high doses
Antimetabolites
5-Fluorouracil	Coronary vasospasm, myocardial ischemia
Antimicrotubules
Paclitaxel	Arrhythmia, heart failure

Anthracycline Cardiotoxicity

• Anthracyclines (e.g., doxorubicin) are widely known to be associated with cardiotoxic effects.

• Doxorubicin cardiotoxicity can occur early or late during therapy. Early changes occur acutely or within the first year of therapy. Late dysfunction occurs months or many years after the initial exposure.

• Overall, doxorubicin cardiotoxicity is indistinguishable from other forms of heart failure with LV dilatation, wall thinning, and decreased contractility (Figure 8-1).

• An increased risk of cardiotoxicity is associated with higher cumulative dosages of doxorubicin (particularly > 550 mg/m²) and with pre-existing cardiac disease, including hypertension, valvular disease, and ischemic heart disease.

Figure 8-1 A, An example of a dilated cardiomyopathy secondary to doxorubicin exposure. B, This same patient also suffered from severe functional mitral regurgitation secondary to annular dilatation.

Trastuzumab Cardiotoxicity

• Trastuzumab is a humanized monoclonal antibody targeting the ErbB2 receptor.

• Cardiotoxicity risk is increased in the setting of prior exposure to anthracyclines as well as concomitant cardiovascular disease such as hypertension or coronary disease.

• Cardiotoxicity is often observed during the treatment phase and can be reversible with cessation of therapy or institution of cardioprotective medications.

• Trastuzumab cardiotoxicity is also echocardiographically indistinguishable from other forms of systolic heart failure (Figure 8-2).

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