TITLE:
Analysis of Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor-Induced Left Ventricular Dysfunction
AUTHORS:
Yasuhisa Hashino, Kengo Umehara, Shinya Takada, Kuninori Iwayama, Koichi Ohtaki, Hideki Sato
KEYWORDS:
VEGFR-TKI, Left Ventricular Dysfunction, Cardio-Oncology, HFrEF, HFpEF, CTRCD
JOURNAL NAME:
Journal of Biophysical Chemistry,
Vol.14 No.2,
May
29,
2023
ABSTRACT: Vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (VEGFR-TKI), an oral molecular targeted drug, reportedly causes serious adverse cardiovascular events such as hypertension and left ventricular failure. The association between VEGFR-TKI-induced hypertension and heart failure with preserved left ventricular ejection fraction (LVEF) (HFpEF) has been previously studied. Therefore, we investigated the relationship between hypertension onset and associated cardiac diastolic dysfunction due to VEGFR-TKI use. Patients who used VEGFR-TKIs (target drugs: sunitinib, axitinib, sorafenib, pazopanib, and cabozantinib) at the Department of Urology, Hokkaido Cancer Center were recruited between May 2009 and October 2021 and were divided into two groups based on whether their blood pressure was elevated during VEGFR-TKI use. The markers of left ventricular diastolic function (E/A, Dct (ms), mean E/e, septal e') and left ventricular systolic function (LVEF, LVDd, and LVDs) were evaluated. LVEF and mean E/e in the elevated blood pressure group (n = 41) showed significant changes before and after treatment. LVEF values (contractile function markers) in the TKI-HT (+) group significantly decreased from 70.7% ± 6.8% before treatment to 68.3% ± 7.8% after treatment (p = 0.03). Conversely, no significant difference was observed for any ventricular systolic function marker in the TKI-HT (−) group. E/e (diastolic function marker) in the TKI-HT (+) group significantly decreased from 11.9% ± 3.6% before treatment to 10.3% ± 3.0% after treatment (p = 0.02). However, no change was observed in any ventricular diastolic function marker in the TKI-HT (−) group. The results of this study suggest that cardiac function may be affected in patients using VEGFR-TKI. Furthermore, appropriate antihypertensive treatment and early monitoring with regular echocardiography, even in asymptomatic patients, may help prevent VEGFR-TKI-induced deterioration of systolic and diastolic function.