Cardio-oncology imaging tools at the translational interface
Introduction
Cardio-oncology is a growing field at the intersection of cardiovascular medicine, hematology and oncology [1]. Improved survival of cancer patients has led to an increased awareness of cardiac complications due to anticancer therapies [2]. Widely recognized, anthracyclines are associated with an acute or subacute cardiotoxic effect, typically detectable immediately or within the first year after treatment with conventional imaging methods [3], but also with chronic, progressive cardiotoxicity that can lead to impaired left ventricular function, many years after exposure [4,5] However, there are only limited tools to identify patients with late effects at an early stage, and most of them depend on elevated cardiac biomarker indicating myocardial injury or structural abnormalities. And more importantly, there are several novel anticancer therapies that are associated with cardiotoxic effects, such as transient cardiac dysfunction (e.g., kinase inhibitors, proteasome inhibitors, BRAF-inhibitors) [[6], [7], [8], [9]] or inflammation (e.g., immune checkpoint inhibitors) [10], but there are even less data available for detecting early molecular, immune or metabolic cardiotoxic effects of these breakthrough oncological interventions.
In addition to the cardiac risk, cancer survivors with cardiovascular side effects also have reduced progression free- and overall survival [6]. Therefore, early identification of patients at risk and early diagnosis of cardiotoxic events may allow to optimize the overall outcome after cancer treatment. Cardiovascular imaging can be implemented in a cardio-oncological surveillance strategy using established modalities (Table 1) and emerging more specific imaging techniques (Fig. 1, Table 2, Table 3) as a gatekeeper for suitable cardioprotective strategies.
This review is focused on novel imaging techniques that can visualize in new ways cardiovascular structures, biochemical processes and molecular targets and their possible implications for cardio-oncological patients. The literature is selected based on the translational potential and usefulness in preclinical and early clinical applications.
Section snippets
Structural and functional imaging in cardio-oncology
Cardiovascular changes evolve in cardio-oncological patients due to underlying diseases (e.g. cardiac hypertrophy, or accompanying amyloidosis) [11,12] and as a result of cardiotoxic therapies (e.g. cardiac atrophy in patients with anthracycline therapies) [13]. Specific tissue characteristics can be detected by established methods, such as echocardiography or conventional cMRI and PET-tracer based imaging, but all these changes can be understood as an end-stage situation of cancer or
Molecular imaging developments
Pathological cardiac remodeling is associated with fundamental metabolic changes [73]. Preclinical data suggest that such metabolic changes precede adverse cardiac remodeling and could be used as an early or predictive marker for patients at risk [74]. Simplified, pathological cardiac remodeling is based on a number of molecular events that are well accepted to be crucial for the development of left ventricular dysfunction. Many of the underlying molecular mechanisms were initially described in
Limitations of imaging in cardio-oncology
In case of echocardiography, image quality and expertise of the investigator is crucial to allow reliable diagnosis. Especially in case of 3D-echocardiography and strain analysis, investigators need a strong expertise to acquire and interpret novel findings. Semi-automated or AI-based algorithms may reduce this inter-observer problem of echocardiography. Still, in many cancer patients imaging quality and suitable depth of ultrasound is challenged by previous radiation of the chest or thoracic
Patient and imaging method selection
From a clinical standpoint, it is increasingly important to select a suitable imaging modality, based on the patient's history and planned or ongoing oncological therapy. The choice for the imaging modality will have to take in account pathological processes, as well as statistical considerations of prevalence of abnormal results in the subgroup of patients. A certain imaging technology can be recommended only for a small number of oncological therapies. For example, in case of anthracyclines
Future directions
The development and systematic application of cardiovascular imaging tools has the potential to improve overall outcomes in cancer survivors. Observations from translational studies and proof of concept clinical trials open the opportunity to develop larger scale trials to establish the evidence necessary for the systematic application of cardiovascular imaging tools in cardio-oncology. Prospective studies will be required in multiple cancer types involving patients with different classes of
Conclusion
Paradigm-shifting scientific discoveries have driven major transitions in the therapeutic and diagnostic approaches in oncology towards molecular and immunologic targets. Considering the crosstalk between biological systems, new cardiovascular imaging methodologies are also poised to open a more granular understanding of the cardiovascular pathophysiology at the intersection with cancer. A systematic approach in this field may then result in bidirectional application of new knowledge with broad
Acknowledgements
This work was supported by awards from the German Center for Cardiovascular Research (DZHK), German Research Foundation (DFG LE3570/2-1, 3570/3-1) and the Federal Ministry for Education and Research (BMBF 01KC2006B) to LHL, and from the from the Cancer Prevention and Research Institute of Texas (CPRIT RP180404) to VGZ.
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