Noninvasive imaging of cardiovascular injury related to the treatment of cancer

Abstract

The introduction of multiple treatments for cancer, including chemotherapeutic agents and radiation therapy, has significantly reduced cancer-related morbidity and mortality. However, these therapies can promote a variety of toxicities, among the most severe being the ones involving the cardiovascular system. Currently, for many surviving cancer patients, cardiovascular (CV) events represent the primary cause of morbidity and mortality. Recent data suggest that CV injury occurs early during cancer treatment, creating a substrate for subsequent cardiovascular events. Researchers have investigated the utility of noninvasive imaging strategies to detect the presence of CV injury during and after completion of cancer treatment because it starts early during cancer therapy, often preceding the development of chemotherapy or cancer therapeutics related cardiac dysfunction. In this State-of-the-Art Paper, we review the utility of current clinical and investigative CV noninvasive modalities for the identification and characterization of cancer treatment-related CV toxicity.

Keywords: cardiovascular imaging; chemotherapy-related cardiotoxicity; noninvasive imaging.

Figure 1. 2D Speckle tracking Echocardiogram-based strain in patient with invasive ductal carcinoma (ER-, PR-, Her2-neu+), treated with TCH Regimen (Docetaxel, Carboplatinum and trastuzumab). Baseline EF was 65%. EF after 3 months of therapy was 58%

Panels A and B utilize color to illustrate the global longitudinal strain (GLS) and regional strain values obtained at baseline (pre-chemotherapy) and 3 months after the initiation of trastuzumab-based regimen. The Septal and anteroseptal segments exhibit abnormal regional strain after treatment. (Courtesy of Dr. Juan Carlos Plana, MD, FACC. Co-Director Cardio-Oncology Center. Cleveland Clinic. Cleveland, Ohio)

Figure 2. Pulse wave velocity assessments of aortic stiffness after cancer treatment

Sagittal magnitude image of the thoracic aorta was used to select the axial plane at the level of pulmonary artery and perpendicular to aortic flow (solid white line). The distance between ascending and descending thoracic aorta was obtained by tracing the centerline of the aortic lumen (red line). The two velocity–time curves are shown across the thoracic aorta. The sagittal magnitude image demonstrates the velocity–time curves for the ascending and descending thoracic aorta. Transit time of the flow wave was computed on the basis of the upstroke time difference of the velocity–time curve at two different regions (blue line). The location of the best cross-correlation of two partial upstroke velocity curves was used to estimate the time delay. Pulse wave velocity (PWV) was calculated by dividing the distance between the ascending and descending thoracic aorta by the transit time of the flow wave. CMR-derived aortic stiffness by the measurement of pulse wave velocity (PWV) between control participants without cancer (Panel A) and participants who are receiving cancer therapy (Panel B) at the baseline and after 4 months of treatment. As shown, the PWV increased in participants receiving anthracycline-based therapy. The magnitude of the increase in PWV is equivalent in other populations to an aortic stiffness age associated increase of 15 years.Reprinted with Permission. Chaosuwannakit N, et al. J Clin Oncol. 2012;28:166-72. (118).

Figure 3. Sequential antimyosin (A, B, C) and MIBG (A', B', C') studies before chemotherapy (A, A') at 240-300mg/m ² (B, B') and at 420-600 mg/rn2of doxorubicin

There is a pattern of increasing myocardial antimyosin uptake with decreasing myocardial MIBG uptake both reflecting ongoing myocellular injury from anthracycline-based chemotherapy. Reprinted with permission. This research was originally published in JNM. Carrió I, Estorch M, Berná L, López-Pousa J, Torres G. Indium-111-antimyosin and iodine-123-MIBG studies in early assessment of doxorubicin cardiotoxicity. J Nucl Med. 1995;36:2044-2049. © by the Society of Nuclear Medicine and Molecular Imaging, Inc. (28).

Figure 4. Clinical & Developmental Imaging of Cardiovascular Injury after cancer treatment

Opportunities for utilizing existing (black boxed) and developmental (red boxed) noninvasive imaging technologies for identifying processes associated with myocellular, myofibroblast, myocardial conduction and vascular injuries associated with the administration of cancer therapies that may adversely impact the cardiovascular system. As shown, existing technologies identify mainly clinically evident manifestations of CV injury while developmental technologies may facilitate assessment of biomolecular pathways that precede end organ damage.