Vascular Endothelial Growth Factor Receptor Inhibitors Impair Left Ventricular Diastolic Functions

• Yokoyama Haruka

  Project of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University

• Shioyama Wataru

  Department of Internal Medicine, Division of Cardiovascular Medicine, Shiga University of Medical Science

• Shintani Takuya

  Department of Pharmacy, Osaka University Hospital

• Maeda Shinichiro

  Project of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University Department of Pharmacy, Osaka University Hospital

• Hirobe Sachiko

  Project of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University Department of Pharmacy, Osaka University Hospital Department of Molecular Pharmaceutical Science, Graduate School of Medicine, Osaka University

• Maeda Makiko

  Project of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University Department of Molecular Pharmaceutical Science, Graduate School of Medicine, Osaka University

• Sakata Yasushi

  Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University

• Fujio Yasushi

  Project of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University

Abstract

Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) frequently induce cardiovascular adverse events, though VEGFR-TKIs contribute to the improvement of the prognosis of patients with malignancies. It is widely accepted that VEGFR-TKIs impair left ventricular systolic functions; however, their effects on diastolic functions remain to be fully elucidated. The purpose of this study was to analyze the impact of VEGFR-TKIs on left ventricular diastolic functions. This study was designed as a retrospective single-center cohort study in Japan. We assessed 24 cases who received VEGFR-TKI monotherapy (sunitinib, sorafenib, pazopanib, axitinib) with left ventricular ejection fraction (LVEF) above 50% during the therapy at the Osaka University Hospital from January 2008 to June 2019. Left ventricular diastolic functions were evaluated by the change in echocardiographic parameters before and after the VEGFR-TKI treatment. Both septal e' and lateral e's decreased after treatment (septal e': before, 6.1 ± 1.8; after, 5.0 ± 1.9; n = 21, P < 0.01; lateral e': before, 8.7 ± 2.8; after, 6.9 ± 2.3; n = 21, P < 0.01). E/A declined after VEGFR-TKIs administration, though not statistically significantly. In 20 cases with at least one risk factor for heart failure with preserved ejection fraction (HFpEF), E/A significantly decreased (0.87 ± 0.34 versus 0.68 ± 0.14; P < 0.05) as well as the septal and lateral e's. These results suggest that treatment with VEGFR-TKIs impairs left ventricular diastolic functions in patients with preserved LVEF, especially in those with risk factors for HFpEF.

Journal

• International Heart Journal

  International Heart Journal 62 (6), 1297-1304, 2021-11-29

  International Heart Journal Association

Keywords

• Cardio-oncology
• Diastolic dysfunction
• HFpEF
• VEGFR-TKIs
• Sunitinib

Details

• CRID: 1390008754690431104
• NII Article ID: 130008122384
• DOI: 10.1536/ihj.21-307
• ISSN: 13493299
• ISSN: 13492365
• Web Site: https://www.jstage.jst.go.jp/article/ihj/62/6/62_21-307/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2022238597
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed