Author + information
- Maria Anastasiou, MD,
- Evangelos Oikonomou, MD, PhD∗ (, )
- Flora Zagouri, MD, PhD,
- Gerasimos Siasos, MD, PhD,
- Alexios S. Antonopoulos, MD, PhD,
- Theodora Psaltopoulou, MD, PhD,
- Aristotelis Bamias, MD, PhD,
- Meletios A. Dimopoulos, MD, PhD and
- Dimitris Tousoulis, MD, PhD
- ↵∗1st Department of Cardiology, ‘Hippokration’ General Hospital, National and Kapodistrian University of Athens, School of Medicine, VasilissisSofias 114, P.O. 11528, Athens, Greece
Recently, Finkelman et al. (1) reported that plasma arginine and nitric oxide (NO) metabolites are strongly associated with the development of doxorubicin cardiotoxicity (2). In the same context, we explored the association of brachial flow- mediated dilation (FMD) as an index of in vivo NO bioavailability, with development of cardiotoxicity after anthracycline treatment. Twenty-five female patients (age 57 ± 12 years) diagnosed with breast cancer and scheduled for anthracycline-based chemotherapy were enrolled. Patients were treated with epirubicin (75 mg/m2) and cyclophosphamide followed by docetaxel and trastuzumab.
A transthoracic echocardiogram was performed at baseline, 3 months, and 6 months after initiation of chemotherapy to evaluate left ventricular ejection fraction (LVEF) and diastolic performance. In vivo NO bioavailability was assessed by using the FMD of the right brachial artery at baseline before treatment initiation.
A reduction in LVEF >5% was observed in 5 and 9 patients at 3 and 6 months, respectively. In the whole study population, LVEF was significantly reduced at 6 months (Figure 1A). There was no change in E/A, E/e′, or RVS′ at 6 months compared with baseline (p = NS). Interestingly, there was a significant association between baseline FMD and delta [LVEF] at 3 months (rho = 0.433; p = 0.044) or 6 months (rho = 0.581; p = 0.023). In patients with lower brachial FMD at baseline (FMD less than the median), LVEF was significantly reduced at 3 and 6 months (p = 0.04); however, that was not the case in patients with higher brachial FMD at baseline (p = 0.12). Βrachial FMD had good discriminative value for the nondevelopment of cardiotoxicity, defined as the nondrop of LVEF at 3 months (Figure 1B). Per 1 SD (2.7%) increase in FMD, there was a 37% less likelihood for LVEF reduction at 3 months (odds ratio: 0.63; 95% confidence interval: 0.41 to 0.95). The change in serum levels of cardiac troponin I and N-terminal pro–B-type natriuretic peptide levels at 3 months were not predictive of LVEF change at 6 months (p = NS).
Because cardiac-specific biomarkers (cardiac troponin I or NT-proBNP) have low sensitivity for cardiotoxicity development, our preliminary data suggest that biomarkers of NO bioavailability, such as FMD, may have a role as a risk-stratification tool for anthracycline-induced cardiotoxicity.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
- Finkelman B.S.,
- Putt M.,
- Wang T.,
- et al.
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- Gori T.,
- Munzel T.