Role of advanced cardiovascular imaging in chemotherapy-induced cardiotoxicity

Abstract

The development of cardiotoxicity induced by cancer treatments has emerged as a significant clinical problem, both in the short run, as it may influence drug administration in chemotherapeutic protocols, and in the long run, because it may determine adverse cardiovascular outcomes in survivors of various malignant diseases. Therefore, early detection of anticancer drug-related cardiotoxicity is an important clinical target to improve prevention of adverse effects and patient care. Today, echocardiography is the first-line cardiac imaging techniques used for identifying cardiotoxicity. Cardiac dysfunction, clinical and subclinical, is generally diagnosed by the reduction of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). However, myocardial injury detected by echocardiography is preceded by other alterations, such as myocardial perfusion and mitochondrial and metabolic dysfunction, that can only be recognized by second-level imaging techniques, like cardiac magnetic resonance (CMR) and nuclear imaging, which, using targeted radiotracers, may help to provide information on the specific mechanisms of cardiotoxicity. In this review, we focus on the current and emerging role of CMR, as a critical diagnostic tool of cardiotoxicity in the very early phase, due to its availability and because it allows the contemporary detection of functional alterations, tissue alterations (mainly performed using T1, T2 mapping with the evaluation of extracellular volume-ECV) and perfusional alteration (evaluated with rest-stress perfusion) and, in the next future, even metabolic changes. Moreover, in the subsequent future, the use of Artificial Intelligence and big data on imaging parameters (CT, CMR) and oncoming molecular imaging datasets, including differences for gender and countries, may help predict cardiovascular toxicity at its earliest stages, avoiding its progression, with precise tailoring of patients' diagnostic and therapeutic pathways.

Keywords: Advanced cardiac imaging; Cardiac magnetic resonance; Cardiotoxicity.

Fig. 1

GLS (global longitudinal strain) evaluated by speckle tracking technique in 3, 4 and 2-chamber apical view: GLS alteration in a patient with HL (Hodgkin Lymphoma) after six cycles of chemotherapy.

Fig. 2

Atrial function-Artificial Intelligence by software Circle Cardiovascular Imaging (CVI) detected left ventricle, left atrial and right atrial contours on all phases of the selected 2CV and 4CV slices.

Fig. 3

Assessment of myocardial deformation by Circle Cardiovascular Imaging, reprocess of multiplanar cine bright blood with semi-automated Feature Tracking: Artificial Intelligence icon tools generate strain curve (a), polar maps (b) about longitudinal (GLS) and circumferential strain (GCS) for left and right ventricles (c,d).

Fig. 4

Inversion recovery T1 weighted with gadolinium-Delayed enhancement (DE): a,b short and 4-chamber long axis evidence subepicardial-mesocardial DE in the context of myo-pericarditis due to acute cardiotoxicity in a patient undergoing the first cycle of anthracyclines for leukaemia; c short axis shows mesocardial DE due to chronic cardiotoxicity by Trastuzumab, located along the ventricular lateral wall.

Fig. 5

T1 mapping (native/enhanced) post-processing with maps and results for segmentation along 1 out of 3 main plans acquired (middle left ventricle): diffuse increase of T1 native and ECV (extracellular volume) as interstitial remodelling with oedema and fibrosis in a patient with HL (Hodgkin Lymphoma) two months after chemotherapy with anthracyclines.

Fig. 6

(a, d): axial T1 W after gadolinium contrast in a patient subjected to Anthracycline chemotherapy and radiotherapy with acute mediastinitis and perimyocarditis; (b,c,e,f): follow-up CMR 4 months after acute cardiotoxicity with evidence of chronic effusive-constrictive pericarditis with thickened pericardium>4 mm (b axial black blood T1 W), S-shaped intraventricular septal motion during the cardiac cycle (c short axis bSSFP Cine), fibrotic thickening of the leaflets (e long axis four chambers late gadolinium enhancement-LGE) and areas of ongoing inflammation (f short axis early gadolinium enhancement).

Fig. 7

Potential applications of cardiac computed tomography in visualising the entire spectrum of cardiovascular disease induced by cancer treatments. Coro CTA: (a, c) baseline and postcontrast scans for morphological evaluation of aortic valve with calcium quantification by Agatston score; (b) MPR-curved and 3D volume in calcific atheromasia of LAD (left anterior descendent); (d) Angio-CT: extensive aortic vascular disease in patients monitored in the long term after chemotherapy (tyrosine kinase inhibitors).

Fig. 8

Detection of CTRCD (cancer treatment-related cardiac dysfunction) using non-invasive imaging. The progress of CTRCD can be divided into three phases: early, intermediate and late. The early phase is characterised by perfusion and mitochondrial dysfunction; in this phase, CMR allows Tissue characterisation for oedema and fibrosis (especially T1 and T2 mapping) and perfusion CMR (Rest/Stress) for microvascular dysfunction. The intermediate phase exhibits a metabolic dysfunction, with impaired diastolic and strain parameters, that can be practically evaluated with Echo and CMR techniques. In the late stage, reduced LVEF represents only the tip of the iceberg and is correlated to consolidated tissue damage.