Multiparametric Early Detection and Prediction of Cardiotoxicity Using Myocardial Strain, T1 and T2 Mapping, and Biochemical Markers: A Longitudinal Cardiac Resonance Imaging Study During 2 Years of Follow-Up

Sorin Giusca, Grigorios Korosoglou, Moritz Montenbruck, Blaž Geršak, Arne Kristian Schwarz, Sebastian Esch, Sebastian Kelle, Pia Wülfing, Susan Dent, Daniel Lenihan, Henning Steen, Sorin Giusca, Grigorios Korosoglou, Moritz Montenbruck, Blaž Geršak, Arne Kristian Schwarz, Sebastian Esch, Sebastian Kelle, Pia Wülfing, Susan Dent, Daniel Lenihan, Henning Steen

Abstract

Background: Our goal was to evaluate the ability of cardiovascular magnetic resonance for detecting and predicting cardiac dysfunction in patients receiving cancer therapy. Left ventricular ejection fraction, global and regional strain utilizing fast-strain-encoded, T1 and T2 mapping, and cardiac biomarkers (troponin and BNP [brain natriuretic peptide]) were analyzed.

Methods: Sixty-one patients (47 with breast cancer, 11 with non-Hodgkin lymphoma, and 3 with Hodgkin lymphoma) underwent cardiovascular magnetic resonance scans at baseline and at regular intervals during 2 years of follow-up. The percentage of all left ventricular myocardial segments with strain ≤-17% (normal myocardium [%]) was analyzed. Clinical cardiotoxicity (CTX) and sub-CTX were defined according to standard measures.

Results: Nine (15%) patients developed CTX, 26 (43%) had sub-CTX. Of the 35 patients with CTX or sub-CTX, 24 (69%) were treated with cardioprotective medications and showed recovery of cardiac function. The amount of normal myocardium (%) exhibited markedly higher accuracy for the detection of CTX and sub-CTX compared with left ventricular ejection fraction, T1, and T2 mapping as well as troponin I (Δareas under the curve=0.20, 0.24, and 0.46 for normal myocardium (%) versus left ventricular ejection fraction, troponin I, and T1 mapping, P<0.001 for all). In addition, normal myocardium (%) at baseline accurately identified patients with subsequent CTX (P<0.001), which was not achieved by any other markers.

Conclusions: Normal myocardium (%) derived by fast-strain-encoded cardiovascular magnetic resonance, is an accurate and sensitive tool that can establish cardiac safety in patients with cancer undergoing cardiotoxic chemotherapy not only for the early detection but also for the prediction of those at risk of developing CTX. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03543228.

Keywords: biomarker; cardiotoxicity; mortality; myocardium; troponin.

Figures

Figure 1.
Figure 1.
Evolution of the studied parameters over time in patients without clinical cardiotoxicity (no CTX), those with CTX without recovery from cardiotoxicity (CTX wo REC) and those who achieved REC. (A) Normal myocardium (%), (B) left ventricular ejection fraction. wo indicates without.
Figure 2.
Figure 2.
Correlation between strain, left ventricular ejection fraction (EF), and normal myocardium (%). (A) Correlation between circumferential strain and normal myocardium (%). (B) Correlation between longitudinal strain and normal myocardium (%). (C) Correlation between left ventricular EF and normal myocardium. CTX indicates clinical cardiotoxicity; and sub-CTX, subclinical cardiotoxicity.
Figure 3.
Figure 3.
Evaluation of the baseline values of normal myocardium (%) and left ventricular ejection fraction and prediction of cardiotoxicity (CTX) and recovery (REC).A, Differences between baseline values of (A) normal myocardium (%) and (B) left ventricular ejection fraction (LVEF) in patients with versus without CTX. C, Receiver operating characteristic (ROC) analysis for CTX prediction based on baseline cardiovascular magnetic resonance (CMR) values. D, ROC analysis for the prediction of REC in patients who had CTX and received cardioprotective treatment with β-blockers, ACE (angiotensin-converting enzyme)/angiotensin II receptor blockers or combination of both (Note that pooled data were used for this analysis, derived from CMR examinations just before the initiation of the cardioprotective therapies). AUC indicates areas under the curve.
Figure 4.
Figure 4.
Normal myocardium (%) as predictor of cardiotoxicity. Normal myocardium<80% (A) at baseline and <55% (B) during follow-up cardiovascular magnetic resonance scans both accurately differentiated patients with from those without subsequent clinical cardiotoxicity (CTX) and patients with recovery from cardiotoxicity (REC) versus non-REC after CTX occurrence and initiation of cardioprotective treatment, respectively. Normal myo. (%) indicates normal myocardium (%); and ROC, receiver operating characteristic.
Figure 5.
Figure 5.
The role of normal myocardium (%) in the diagnostic evaluation of cancer patients.A, Additional diagnostic window provided by normal myocardium (%) versus left ventricular (LV) ejection fraction for the prediction of clinical cardiotoxicity (CTX) and for its early identification, allowing monitoring of cardiac safety during chemotherapy. B, Proposed clinical algorithm incorporating clinical and cardiovascular magnetic resonance (CMR) data for the management of patients who undergo chemotherapy. CAD indicates coronary artery disease; REC, recovery from cardiotoxicity; and ROC, recovery from cardiotoxicity.

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