Left ventricular myocardial strain and tissue characterization by cardiac magnetic resonance imaging in immune checkpoint inhibitor associated cardiotoxicity

Abstract

Background Immune checkpoint inhibitors (ICIs) are highly effective in treating cancer; however, cardiotoxicity can occur, including myocarditis. Cardiac magnetic resonance (CMR) imaging is useful for evaluation of myocarditis, although it has not been well studied in ICI cardiotoxicity. Methods We identified patients referred for CMR evaluation of ICI cardiotoxicity from September 2015 through September 2019. We assessed structural and functional parameters, feature tracking (FT) left ventricular and atrial strain, T2- weighted ratios and quantitative late gadolinium enhancement (LGE). We also applied the Updated Lake Louise Criteria for diagnosis of myocarditis. Results Of the 20 patients referred, the median left ventricular ejection fraction (LVEF) was 52.5% ± 19.1 and 50% had a normal LVEF (≥53%). FT strain analysis revealed an average abnormal global longitudinal strain (GLS) of −9.8%± 4.2%. In patients with a normal LVEF, the average GLS remained depressed at −12.3%± 2.4%. In all patients, GLS demonstrated a significant negative correlation with LVEF (rs = −0.64, p 0.002). Sixteen patients (80%) had presence of LGE (14 non-ischemic pattern and 2 ischemic). Percent LGE did not correlate with any CMR parameters and notably did not correlate with LVEF (rs = −0.29, p = 0.22) or GLS (rs = 0.10, p = 0.67), highlighting the value of tissue characterization beyond functional assessment. Nine patients (45%) met full Updated Lake Louise Criteria and 85% met at least one criterion, suggestive of myocarditis in the correct clinical context. Thirteen patients (65%) were treated for ICI-associated myocarditis and, of these, 54% (n = 7) had recovery of LVEF to normal. There was no correlation between LVEF (p = 0.47), GLS (0.89), or % LGE (0.15) and recovery of LVEF with treatment. Conclusion In patients with suspected ICI cardiotoxicity, CMR is an important diagnostic tool, even in the absence of overt left ventricular dysfunction, as abnormalities in left ventricular strain, T2 signal and LGE can identifying disease.

Early evaluation of subclinical cardiotoxicity in patients with lung cancer receiving immune checkpoint inhibitors by cardiovascular magnetic resonance: a prospective observational study

“…Cardiac dysfunction is a long-established adverse effect in patients receiving cancer therapy, and it has been reported in patients receiving ICI therapy (19). The baseline LVEF value in our study was lower than that in a another CMR study conducted by Faron et al, but was similar to that in the CMR study conducted by Higgins et al (14,20). We speculated that this may be due to the baseline characteristics of the patient cohort in our study [with lung cancer, older age (60.7±9.2 years old), and a large proportion (77.8%) of patients with at least 1 CV risk factor].…”

Echocardiographic and Cardiac MRI Comparison of Longitudinal Strain and Strain Rate in Cancer Patients Treated with Immune Checkpoint Inhibitors

“…EMB was not performed on our patients; however, 37.5% ( n = 3) of our patients presented with abnormal LGE patterns on CMR, similar to the findings reported by Zhang et al [ 17 ]. Current literature has only one study analyzing strain indices on CMR [ 25 ]. Our study thus adds to the existing literature by elucidating the utility of these diagnostic modalities.…”

“…Endomyocardial biopsy (EMB) is the gold standard for confirmation; however, at least six biopsies from different regions are needed given the patchy T cell myocardial infiltration, even so there is a high false negative rate [ 12 ]. A retrospective study conducted CMR strain analysis, indicating that despite normal left ventricular function, strain imaging was abnormal, thus highlighting its importance [ 25 ].…”

Cardiac Magnetic Resonance Imaging in Immune Check-Point Inhibitor Myocarditis: A Systematic Review

“…As per prespecified criteria, case reports were excluded from the analysis. After screening for eligibility, 6 studies were finally selected [12][13][14][15][16][17]. Two of these [15,16] enrolled patients within a same multicenter registry, albeit providing partly different information (e.g., T1 and T2 mapping in one); for this reason, they were both included in the analysis.…”