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Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Anna B Catino1, Rebecca A Hubbard1, Julio A Chirinos1
1From the Division of Cardiovascular Medicine (A.B.C., J.C.F.) and Division of Oncology (N.A.), Department of Medicine, University of Utah, Salt Lake City; Department of Biostatistics, Epidemiology and Informatics (R.A.H., B.K.), Division of Cardiology (J.A.C., D.H., A.M.S., T.P., V.E., B.K.), Division of Hematology and Oncology (S.K., N.B.H., V.N.), and Division of Nephrology (R.T.), Department of Medicine, and Abramson Cancer Center (S.K., N.B.H., V.N., B.K.), University of Pennsylvania, Philadelphia; Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY (I.P.); Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison (S.E.); Division of Cardiovascular Medicine, Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH (C.E.); Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (M.G.); and Division of Cardiology, Department of Medicine, Washington University in St Louis, MO (D.L.).
Background:
Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood.
Methods And Results:
In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P=0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P<0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P<0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time.
Conclusions:
In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function.
Insights
Sunitinib treatment for kidney cancer increases blood pressure and arterial stiffness early on. Baseline vascular function impacts diastolic heart function, but not systolic function, during treatment.
Area of Science:
- Cardiovascular research
- Oncology
- Pharmacology
Background:
- Sunitinib is a common treatment for metastatic renal cell carcinoma.
- Sunitinib use is associated with potential cardiovascular side effects like hypertension and heart failure.
- The precise links between vascular changes and cardiac dysfunction due to sunitinib remain unclear.
Purpose of the Study:
- To investigate the relationship between vascular function and cardiac dysfunction in patients receiving sunitinib.
- To assess how sunitinib affects vascular parameters and cardiac function over time.
Main Methods:
- A multicenter prospective study involving 84 patients with metastatic renal cell carcinoma.
- Echocardiography, arterial tonometry, and B-type natriuretic peptide (BNP) measurements were taken at baseline and at multiple time points during sunitinib treatment.
- Statistical analyses, including linear regression, were used to correlate vascular function with cardiac parameters.
Main Results:
- Within 3.5 weeks of sunitinib initiation, significant increases in systolic and diastolic blood pressure were observed.
- Sunitinib led to increased arterial stiffness, resistive load, and pulsatile load.
- No significant associations were found between vascular function and systolic dysfunction (left ventricular ejection fraction, longitudinal strain).
- However, baseline vascular parameters like total peripheral resistance and arterial elastance were linked to worsening diastolic function.
Conclusions:
- Sunitinib treatment rapidly induces significant changes in vascular function, including elevated blood pressure and arterial stiffness.
- Vascular parameters at baseline predict the development of diastolic dysfunction during sunitinib therapy.
- These findings highlight the importance of monitoring vascular and diastolic function in patients treated with sunitinib.
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