Annals of Oncology Advance Access originally published online on August 12, 2005
Annals of Oncology 2006 17(1):173-174; doi:10.1093/annonc/mdj004
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© 2005 European Society for Medical Oncology
letter to the editor |
Reply to "Troponins in prediction of cardiotoxic effects", by D. Cardinale et al.
We have read the interpretation of our study [1
] by Cardinale et al. [2]. We would like to thank the authors for their interest. The increase in serum levels of cardiac troponin I and T (cTnI and cTnT) occur due to myocardial damage and are generally used to detect acute myocardial infarction. Since cardiotoxicity can be a dose-limiting factor during cancer treatment, it is very important to detect chemotherapy-related cardiotoxicity at an early stage. There are several studies assessing the use of both cTnI and cTnT for the early prediction of cardiac damage in patients who have received chemotherapy. However, information obtained from these studies is limited, and use of troponins in subjects who have undergone chemotherapy is not routinely recommended.
Although both cTnI and cTnT are used to detect myocardial damage, measurement of cTnI has an important limitation: there is no standardization of assays measuring cTnI [3]. More than 15 companies presently market assays for cTnI measurements by employing different epitope specificities. On the other hand, a third-generation cTnT assay is commercially available only from a single diagnostic manufacturer, so that result standardization for this marker is not a problem. Point-of-care qualitative testing is available for both of these enzymes, but the assay for cTnT has been more uniform and reliable [4]. The studies by Cardinale et al. evaluate mainly the utility of cTnI rather than cTnT after chemotherapy. However, our conclusion based on limited data was about the value of cTnT after chemotherapy. Although an increase in cTnI or cTnT may be considered equivalent, one should keep in mind that results from different cTnI systems and assay generations may cloud the interpretations of reported data [5].
The second comment by Cardinale et al. [2] was about the threshold level of cTnT. The consensus documents use the 99th percentile of the value distribution of the healthy population as the reference cut-off value. However, unfortunately there is no threshold below which elevations of troponins are harmless and without negative implications for prognosis [5]. In our study, although there was no change in cTnT level, 12 of the 27 patients developed diastolic dysfunction based on the E/A ratio. Taking into account these results and the results of a substudy of GUSTO-IV ACS [6], we speculate that a lower threshold may be appropriate. Although we agree that using a lower threshold may decrease specificity of this marker for detection of myocardial necrosis, we think that the question of whether it has additional clinical advantage requires further study.
We stated the short follow-up period as a limitation of our article. However, we do not think that this undermines our findings of the relationship between increase in cTnT and the development of diastolic dysfunction. However, it is clear that the clinical relevance of this finding requires long-term follow-up.
Two studies about the use of cTnI to reveal chemotherapy-related cardiotoxicity were inconclusive. In one study, 22 patients who were treated with doxorubicin were evaluated [7]. Although the cardiac functions, which were evaluated by using echocardiography, were impaired in three patients, the levels of serum cTnI were found to be within normal range in all subjects. The authors found no relationship between serum cardiac cTnI, the dose of doxorubicin and echocardiographical findings. In another study, Morandi et al. [8] investigated the relationship between cTnI and cardiac function using echocardiography in patients receiving high-dose cyclophosphamide. Early cTnI elevation and cardiac toxicity were not found. They recorded diastolic dysfunction in only two patients.
1 Hacettepe University Institute of Oncology, Department of Medical Oncology, Ankara; 2 Hacettepe University Faculty of Medicine, Department of Cardiology, Ankara, Turkey
* E-mail: skilickap{at}yahoo.com
References
1. Kilickap S, Barista I, Akgul E et al. cTnT can be a useful marker for early detection of anthracycline cardiotoxicity. Ann Oncol 2005; 16: 798–804.
2. Cardinale D, Civelli M, Cipolla CM. Troponins in prediction of cardiotoxic effects. Ann Oncol doi:10.1093/annonc/mdj003.
3. Panteghini M. The measurement of cardiac markers. Where should we focus? Am J Clin Pathol 2002; 118: 354–361.[CrossRef][ISI][Medline]
4. Ohman EM, Armstrong PW, White HD et al. Risk stratification with a point-of-care cardiac troponin T test in acute myocardial infarction. Am J Cardiol 1999; 84: 1281–1286.[CrossRef][ISI][Medline]
5. Panteghini M. Role and importance of biochemical markers in clinical cardiology. Eur Heart J 2004; 25: 1187–1196.
6. Ottervanger JP, Armstrong P, Barnathan ES et al. Association of revascularisation with low mortality in non-ST elevation acute coronary syndrome, a report from GUSTO IV-ACS. Eur Heart J 2004; 25: 1494–1501.
7. Koseoglu V, Berberoglu S, Karademir S et al. Cardiac troponin I: is it a marker to detect cardiotoxicity in children treated with doxorubicin? Turk J Pediatr 2005; 47: 17–22.[ISI][Medline]
8. Morandi P, Ruffini PA, Benvenuto GM et al. Serum cardiac troponin I levels and ECG/Echo monitoring in breast cancer patients undergoing high-dose (7 g/m2) cyclophosphamide. Bone Marrow Transplant 2001; 28: 277–282.[CrossRef][ISI][Medline]
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