Understanding cardiovascular injury after treatment for cancer: an overview of current uses and future directions of cardiovascular magnetic resonance

Abstract

While cancer-free survival has improved over the past 20 years for many individuals with prostate, renal, breast, and hematologic malignancies, the increasingly recognized prevalence of cardiovascular (CV) events in cancer survivors has been an unintended consequence of many of the therapies that have improved these survival rates. The increase in CV events threatens to offset the improvement in cancer related survival. As a result, there is an emerging need to develop methods to identify those individuals treated for cancer at increased risk of cardiovascular events. With its inherent ability to characterize myocardial tissue and identify both cardiac and vascular dysfunction, cardiovascular magnetic resonance (CMR) has the potential to identify both subclinical and early clinical CV injury before the development of an overt catastrophic event such as a myocardial infarction, stroke, or premature cardiac death. Early identification provides an opportunity for the implementation of primary prevention strategies to prevent such events, thereby improving overall cancer survivorship and quality of life. This article reviews the etiology of CV events associated with cancer therapy and the unique potential of CMR to provide early diagnosis of subclinical CV injury related to the administration of these therapies.

Figure 1

Cardiac toxicity by type of structure affected, along with causative cancer therapies is listed below. Valvular, pericardial and myocardial disease is shown in A, while vascular injury pertaining to the coronary, peripheral and aortic circulation is shown in B. Sample cases with a brief description of the images and the specific techniques used are shown.

Figure 2

Imaging of cardiac metastases. Images from a patient with lung cancer with pericardial metastases. Panel A shows an axial slice of the heart acquired by steady-state free precession imaging. The red arrows point to the circumferential pericardial mass, which is hypointense and encases the entire right atrium, right ventricle and left ventricle. Panel B shows a cine image of the pericardial mass in a short-axis orientation (an additional movie file shows the cine series in motion [see Additional file 1]). In addition to the circumferential extent of the mass, the anterolateral wall of the left ventricle and the free wall of the right ventricle are tethered to the mass with reduced wall thickening and motion (arrows). Panel C shows a T2 weighted image in the same short-axis orientation. The red arrows point to the hyperintense mass. Panel D shows a delayed enhancement image of the mass in the short axis orientation. The red arrow points to the areas of hyperenhancement within the mass. The blue arrow points to the necrotic areas within the mass which are hypoenhanced with low signal intensity.

Figure 3

Correlation of T1 signal intensity change after anthracycline exposure with histopathologic changes in the myocardium. Serial histograms and histopathology of the myocardium before and after receipt of anthracycline. On the top portion of the figure are shown 4-week histograms of the number of pixels (y-axes) and intensities (x-axes) in individual animals after receipt of NS (top left), DOX without an EF drop (top middle), and DOX with an EF drop (top right). Below the histograms are 40× hematoxylin and eosin histopathologic images from the same animals. As shown, mean intensity increased in the animals that had a drop in EF corresponding to vacuolization (arrows, bottom right). Reprinted from Lightfoot, et al. Circ Cardiovasc Imaging 2010[77].

Figure 4

Serial changes in LV volumes, myocardial strain and LVEF after anthracycline exposure in human subjects. Time dependent changes in left ventricular (LV) end diastolic volume (left y-axis; panel A) and LV end systolic volume (right y-axis; panel A); in LV ejection fraction (left y-axis; panel B); serum Troponin-I (right y-axis; panel B); pulse wave velocity (PWV) (left y-axis; panel C); and mean mid wall circumferential strain (right y-axis; panel C). The mean ± the standard error are shown. There was a substantive increase in LV end systolic volume, PWV, and serum Troponin-I while at the same time a decrease in LV ejection fraction and mean mid-wall circumferential strain from baseline to six months after administration of low to moderate doses of anthracycline-based chemotherapy. Reprinted from Drafts, et al. JACC-Imaging 2012[96].

Figure 5

Serial changes in aortic stiffness in chemotherapy recipients. Chaosuwannakit, et al. demonstrated that pulse wave velocity (PWV) increased in participants receiving cancer therapy. PWV results for the control participants (A) and the participants receiving cancer therapy (B). The increase in PWV observed in this study is associated with a 3-fold increase in the risk of a future CV event and consistent with a 10 to 20 year age associated increment of the cardiovascular system. Reprinted from Chaosuwannakit, et al. J Clin Oncol 2010[64].