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Anthracycline‐Induced Cardiomyopathy in Adults

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ABSTRACT

Anthracyclines are one of the most commonly used antineoplastic agent classes, and a core part of the treatment in breast cancers, hematological malignancies, and sarcomas. Their benefit is decreased by their well‐recognized cardiotoxicity. The purpose of this review is to outline the presentation, mechanisms, diagnosis, and treatment of anthracyclines‐induced cardiotoxicity. Symptomatic heart failure occurs in 2% to 5% of patients treated with anthrayclines and may be higher in older patients or patients with cardiovascular risk factors. The mechanisms involved in anthracycline‐induced cardiotoxicity involve myocyte loss by apoptosis in the presence of a limited regenerative capacity. Once symptomatic, anthracycline‐induced cardiotoxicity is associated with markedly decreased survival. Left ventricular ejection fraction (LVEF), mostly determined using echocardiography, is used to monitor patients treated with anthracyclines. As more than 1/3 of patients treated with anthracyclines do not recover their baseline LVEF once it is decreased, more sensitive echocardiographic indices of LV function such as myocardial deformation or biomarkers have been studied in patients monitoring. Cardioprotective treatments such as angiotensin‐converting enzyme inhibitors, beta‐blockers, iron chelators, statins, and metformin are also the topic of research efforts. © 2015 American Physiological Society. Compr Physiol 5:1517‐1540, 2015.

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Figure 1. Figure 1. Three‐dimensional echocardiographic measurement of LVEF in patient receiving anthracycline‐based regimen. LVEF decreased from 61% to 39% (22 point reduction to EF below the lower limit of normal).
Figure 2. Figure 2. Diagnosis of subclinical LV dysfunction. Global longitudinal strain reduction in patient receiving anthracycline‐based regimen. Global longitudinal strain is −20.6% at baseline (Fig. 2a) and −16.3% after receiving 450 mg/m2 of doxorubicin (Fig. 2b), a 21% reduction (20.6 − 16.3/20.6 = 20.8%).
Figure 3. Figure 3. Comparative CMR imaging methods of detection of myocardial fibrosis in a healthy control (A and C) and an asymptomatic subject treated 5 years previously with anthracyclines (B and D). Sequence A and B show standard LGE imaging for detection of replacement myocardial fibrosis and are both normal. Figure C and D show the results from measurement of diffuse myocardial fibrosis and calculation of the ECV using a Look‐Locker sequence. The normal patient had an ECV of 0.27 (C, normal range 0.23‐0.32). The patient with prior anthracycline treatment had an elevated ECV of 0.35 (D).
Figure 4. Figure 4. T‐2 weighted imaging for cardiac edema. Comparative T‐2 weighted cardiac images from a patient after anthracyclines (A) showing regions of increased signal intensity, highlighted using the arrows, as compared to a normal patient (B).
Figure 5. Figure 5. Algorithm proposed in the Expert Consensus for Multimodality Imaging Evaluation of Adult Patients during and after Cancer Therapy of the American Society of Echocardiography and the European Association for Cardiovascular Imaging when a patient is scheduled to be treated with anthracyclines.


Figure 1. Three‐dimensional echocardiographic measurement of LVEF in patient receiving anthracycline‐based regimen. LVEF decreased from 61% to 39% (22 point reduction to EF below the lower limit of normal).


Figure 2. Diagnosis of subclinical LV dysfunction. Global longitudinal strain reduction in patient receiving anthracycline‐based regimen. Global longitudinal strain is −20.6% at baseline (Fig. 2a) and −16.3% after receiving 450 mg/m2 of doxorubicin (Fig. 2b), a 21% reduction (20.6 − 16.3/20.6 = 20.8%).


Figure 3. Comparative CMR imaging methods of detection of myocardial fibrosis in a healthy control (A and C) and an asymptomatic subject treated 5 years previously with anthracyclines (B and D). Sequence A and B show standard LGE imaging for detection of replacement myocardial fibrosis and are both normal. Figure C and D show the results from measurement of diffuse myocardial fibrosis and calculation of the ECV using a Look‐Locker sequence. The normal patient had an ECV of 0.27 (C, normal range 0.23‐0.32). The patient with prior anthracycline treatment had an elevated ECV of 0.35 (D).


Figure 4. T‐2 weighted imaging for cardiac edema. Comparative T‐2 weighted cardiac images from a patient after anthracyclines (A) showing regions of increased signal intensity, highlighted using the arrows, as compared to a normal patient (B).


Figure 5. Algorithm proposed in the Expert Consensus for Multimodality Imaging Evaluation of Adult Patients during and after Cancer Therapy of the American Society of Echocardiography and the European Association for Cardiovascular Imaging when a patient is scheduled to be treated with anthracyclines.
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Timothy C. Tan, Tomas G. Neilan, Sanjeev Francis, Juan Carlos Plana, Marielle Scherrer‐Crosbie. Anthracycline‐Induced Cardiomyopathy in Adults. Compr Physiol 2015, 5: 1517-1540. doi: 10.1002/cphy.c140059