Chemotherapy-Induced Cardiac Disease

KEY FEATURES

ESSENTIALS OF DIAGNOSIS

• No uniformly accepted definition of cancer therapy–related cardiac dysfunction

• Past or present treatment with chemotherapeutic agents associated with symptomatic or asymptomatic elevation in cardiac biomarkers or abnormalities in left ventricular function

• Patients with arrhythmias, chest pain, or symptoms and signs of congestive heart failure

GENERAL CONSIDERATIONS

• Anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin) are the most common agents, and cardiotoxicity risk increases with increasing cumulative dosage

• Human epidermal growth factor receptor 2 (HER-2) targeted therapies (trastuzumab) lead to left ventricular dysfunction and heart failure symptoms, especially when combined with anthracyclines

• Vascular endothelial growth factor (VEGF) inhibitors have been linked to hypertension, ischemia, systolic dysfunction, and heart failure

• Cyclophosphamide (> 2000 mg/m²) may cause severe cardiomyopathy

CLINICAL PRESENTATION

SYMPTOMS AND SIGNS

• Palpitations

• Chest pain

• Fatigue

• Dyspnea

• Reduced exercise tolerance

• Orthopnea and paroxysmal nocturnal dyspnea

• Syncope

• Weight gain

PHYSICAL EXAM FINDINGS

• Tachypnea

• Tachycardia

• Elevated jugular venous pressure

• Pulmonary rales

• Diffuse, sustained apical impulse

• Murmurs of tricuspid and mitral insufficiency

• S₃ and S₄

• Pericardial rub

• Hepatomegaly; pulsatile liver from tricuspid regurgitation

• Abdominal ascites

• Peripheral edema

• Reduced pulse pressure

DIFFERENTIAL DIAGNOSIS

• Coexistent cardiomyopathy such as ischemic and/or dilated cardiomyopathies should be in the differential diagnosis

DIAGNOSTIC EVALUATION

LABORATORY TESTS

• Electrolytes (hyponatremia portends a poor prognosis)

• Blood urea nitrogen and creatinine

• CBC (anemia should be worked up)

• Liver function tests (elevations may be due to hepatic congestion)

• Cardiac troponin and natriuretic peptide

• Thyroid function tests

ELECTROCARDIOGRAPHY

• Sinus tachycardia or atrial fibrillation

• Varying degrees of atrioventricular block may be present

• Premature ventricular complexes

• ST elevations indicative of acute myocardial infarction

• Nonspecific ST- and T-wave changes

• Q waves

IMAGING STUDIES

• Chest x-ray: enlarged cardiac silhouette; pulmonary vascular congestion; curly B lines; pleural effusions

• Elevated tricuspid regurgitant peak velocity indicates pulmonary hypertension to evaluate left ventricular systolic function and diastolic function. More recent techniques including strain imaging and speckle tracking allow for earlier detection of left ventricular dysfunction

• Cardiac MRI can be used for accurate cardiac chamber volume measurements and to detect cardiac edema, inflammation, and fibrosis

• Noninvasive stress testing with nuclear imaging: can screen for coronary artery disease

DIAGNOSTIC PROCEDURES

• Cardiopulmonary exercise testing with oxygen consumption: used to determine when to list a patient for cardiac transplantation; peak oxygen consumption of < 14 mL/kg/min signifies a poor prognosis and is generally used as the cutoff for listing a patient

• Left heart catheterization with coronary angiography: indicated for patients with acute myocardial infarction or to exclude coronary artery disease; the left ventricular end-diastolic pressure is ...