Long-term cardiotoxicity in germ cell cancer survivors after platinum-based chemotherapy: cardiac MR shows impaired systolic function and tissue alterations

Antonia Beitzen-Heineke; Christina Charlotte Rolling; Christoph Seidel; Jennifer Erley; Isabel Molwitz; Kai Muellerleile; Dennis Saering; Juliana Senftinger; Niklas Börschel; Nils Wolfgang Engel; Carsten Bokemeyer; Gerhard Adam; Enver Tahir; Hang Chen

doi:10.1007/s00330-023-10420-w

Long-term cardiotoxicity in germ cell cancer survivors after platinum-based chemotherapy: cardiac MR shows impaired systolic function and tissue alterations

Eur Radiol. 2023 Nov 20. doi: 10.1007/s00330-023-10420-w. Online ahead of print.

Affiliations

¹ Department for Oncology, Hematology and Bone Marrow Transplantation with the Section of Pneumology, University Medical Center Hamburg Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. a.beitzen-heineke@uke.de.
² Department for Oncology, Hematology and Bone Marrow Transplantation with the Section of Pneumology, University Medical Center Hamburg Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
³ Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg Eppendorf, Hamburg, Germany.
⁴ Department of General and Interventional Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany.
⁵ Information Technology and Image Processing, University of Applied Sciences Wedel, Wedel, Germany.

^# Contributed equally.

PMID: 37982836
DOI: 10.1007/s00330-023-10420-w

Abstract

Objectives: Long-term toxicities of germ cell cancer (GCC) treatment are of particular importance in young men with a life expectancy of several decades after curative treatment. This study aimed to investigate the long-term effects of platinum-based chemotherapy on cardiac function and myocardial tissue in GCC survivors by cardiac magnetic resonance (CMR) imaging.

Methods: Asymptomatic GCC survivors ≥ 3 years after platinum-based chemotherapy and age-matched healthy controls underwent CMR assessment, including left ventricular (LV) and right ventricular (RV) ejection fraction (EF), strain analysis, late gadolinium enhancement (LGE) imaging, and T1/T2 mapping.

Results: Forty-four survivors (age 44 [interquartile range, IQR 37-52] years; follow-up time 10 [IQR 5-15] years after chemotherapy) and 21 controls were evaluated. LV- and RVEF were lower in GCC survivors compared to controls (LVEF 56 ± 5% vs. 59 ± 5%, p = 0.017; RVEF 50 ± 7% vs. 55 ± 7%, p = 0.008). Seven percent (3/44) of survivors showed reduced LVEF (< 50%), and 41% (18/44) showed borderline LVEF (50-54%). The strain analysis revealed significantly reduced deformation compared to controls (LV global longitudinal strain [GLS] -13 ± 2% vs. -15 ± 1%, p < 0.001; RV GLS -15 ± 4% vs. -19 ± 4%, p = 0.005). Tissue characterization revealed focal myocardial fibrosis in 9 survivors (20%) and lower myocardial native T1 times in survivors compared to controls (1202 ± 25 ms vs. 1226 ± 37 ms, p = 0.016). Attenuated LVEF was observed after two cycles of platinum-based chemotherapy (54 ± 5% vs. 62 ± 5%, p < 0.001).

Conclusion: Based on CMR evaluation, combination chemotherapy with cumulative cisplatin ≥ 200 mg/m² is associated with attenuated biventricular systolic function and myocardial tissue alterations in asymptomatic long-term GCC survivors.

Clinical relevance statement: Platinum-based chemotherapy is associated with decreased systolic function, non-ischemic focal myocardial scar, and decreased T1 times in asymptomatic long-term germ cell cancer survivors. Clinicians should be particularly aware of the risk of cardiac toxicity after platinum-based chemotherapy.

Key points: • Platinum-based chemotherapy is associated with attenuation of biventricular systolic function, lower myocardial T1 relaxation times, and non-ischemic late gadolinium enhancement. • Decreased systolic function and non-ischemic late gadolinium enhancement are associated with a cumulative cisplatin dose of ≥ 200 mg/m². • Cardiac MRI can help to identify chemotherapy-associated changes in cardiac function and tissue in asymptomatic long-term germ cell cancer survivors.

Keywords: Cardiotoxicity; Multiparametric magnetic resonance imaging; Platinum; Survivorship; Testicular neoplasms.