As patients going through cancer therapy live longer, they are at a higher risk of
developing cardiovascular disease. Hence the evolving field of Cardio-Oncology has
garnered much attention and importance. In recent years, immune checkpoint inhibitors
(ICI) have become an essential component of cancer therapy, significantly improving
patient outcomes that were previously considered palliative, e.g. metastatic melanoma,
renal cell or lung cancer, and these therapies have improved survival.
With ICI therapy and especially with combination therapy, patients may develop severe
ICI-related adverse events, e.g. myocarditis (1-5%) which is fatal in 30-50% of the
patients. Another more significant subgroup of patients will develop non-inflammatory
cardiomyopathy or other major cardiac events like cardiovascular death, cardiac arrest
etc. There is also evidence that during ICI treatment atherosclerotic disease may
progress. Identifying patients at risk for both remains a major challenge and is a
knowledge gap in Cardio-Oncology.
Cardiovascular magnetic resonance (CMR) is a unique, highly reproducible, multiparametric
method for non-invasive myocardial tissue characterization for diagnosing myocardial
inflammation. Biomarkers like quantitative cardiac relaxometry (T1/T2-Mapping) with
extracellular volume fraction (ECV), delayed gadolinium enhancement (LGE) or myocardial
strain show insights into myocardial tissue composition. These biomarkers have the
potential to identify early myocardial changes before the risk of clinical myocarditis or
non-inflammatory cardiomyopathy occurs and may therefore help identify early myocardial
tissue changes during ICI treatment and help identify patients at risk early on. Also,
CMR can assess the aorta with high temporal and spatial resolution to identify
atherosclerotic changes.
Only a few retrospective studies and case reports with small numbers of patients have
investigated ICI-related cardiac events during treatment. Evidence shows that many
patients present with heart failure (~80%), but troponin is only elevated in ~45%. This
indicates that ICI-associated left ventricular (LV) dysfunction may exist without
troponin elevation. Other data suggests that the ICI-associated myocardial tissue
inflammation pattern might differ from viral myocarditis. The myocardial T1/T2 relaxation
times may be elevated during ICI-associated myocardial inflammation. There is also
evidence that strain changes are associated with adverse events within 30 days of
treatment. However, all these studies demonstrate CMR findings when patients have already
developed LV dysfunction or myocarditis. The proposed project would be the first
prospective study to get deeper insights into serial, systematic ICI-associated
myocardial tissue changes during treatment and their correlation with serum biomarkers
and clinical symptoms.
