To the Editor:
We thank Dr Kawada for his interest in our research, which represents a first step toward understanding the relationship of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) to hibernating myocardium in patients with ischemic heart failure.
1
We now reemphasize, as was stated in the report, that this work is a “first step” and further studies are needed.We agree with Dr Kawada that overfitting can be a risk with logistic regression models.
2
We noted that age, left ventricular ejection fraction, and estimated glomerular filtration rate were selected a priori as covariates because these parameters are known to affect the levels of NT-proBNP and hs-cTnT.3
, 4
Because of the clinical importance of the listed covariates and the magnitude of their effects on biomarkers, it was deemed necessary to include them in the model. We did acknowledge the risk of overfitting the logistic regression model in the Discussion (Study Limitations section).1
The smallest subgroup modelled had a reasonable sample size of 29 (Table 4). We also presented the results of the multiple regression model with the covariates (including hibernation and biomarkers) as continuous variables (Table 3), and kept these 4 covariates for the analysis. Furthermore, we also acknowledged in the Discussion that this subgroup analysis was post hoc, and as such, “…should be interpreted with caution. Further studies are required to support these findings and are ongoing.”1
In the multiple regression model, the adjusted R2 was not presented because a model of prediction was not our concern. At this stage, we were simply interested in the relationship with hibernation/scar adjusted for the other variables.In reference to the receiver operating characteristic curve analysis, Dr Kawada correctly notes that the accuracy of NT-proBNP and hs-cTnT predict hibernating myocardium was moderate. That there is some predictive ability for these biomarkers is very provocative, but we agree that confirmatory studies are needed to support this novel observation.
Finally, Dr Kawada raises the important point that a combination of biomarkers for predicting hibernation would be useful; we agree. In the present study, however, NT-proBNP and hs-cTnT were not modelled together, because: (1) of the risk of overfitting that was previously identified; (2) it was more important to first establish their independent association with hibernation and scar; and (3) this important line of investigation should be reserved for higher-powered confirmatory studies, because a substantial increase in sample size would be required. This concept is an important area of our ongoing investigations.
Acknowledgements
Lisa M. Mielniczuk and Rob S. Beanlands are co-supervising/senior authors.
Funding Sources
Roche Diagnostics Global is a partner with the Genome Canada grant to Peter P. Liu.
Disclosures
R.S.B. is or has been a consultant for, and has received grant funding from: GE Healthcare, Lantheus Medical Imaging, and Jubilant DraxImage. The other authors have no conflicts of interest to disclose.
References
- N-terminal pro B-type natriuretic peptide and high-sensitivity cardiac troponin T levels are related to the extent of hibernating myocardium in patients with ischemic heart failure.Can J Cardiol. 2017; 33: 1478-1488
- N-terminal pro B-type natriuretic peptide, high-sensitivity cardiac troponin T, and hibernating myocardium in patients with ischemic heart failure.Can J Cardiol. 2018; 34: 690.e11
- The potential role of natriuretic peptides and other biomarkers in heart failure diagnosis, prognosis and management.Expert Rev Cardiovasc Ther. 2015; 13: 1017-1030
- Use of cardiac biomarkers in end-stage renal disease.J Am Soc Nephrol. 2008; 19: 1643-1652
Article info
Publication history
Published online: February 03, 2018
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© 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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- N-terminal Pro B-Type Natriuretic Peptide, High-Sensitivity Cardiac Troponin T, and Hibernating Myocardium in Patients With Ischemic Heart FailureCanadian Journal of CardiologyVol. 34Issue 5
- PreviewZelt et al. examined the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and the extent of hibernating myocardium and scar tissue in 39 patients with ischemic left ventricular dysfunction and heart failure.1 For the prediction of hibernation, the area under the receiver operating characteristic curve for NT-proBNP and hs-cTnT was 0.76 and 0.78, respectively. The adjusted odds ratio (95% confidence intervals) of Log (NT-proBNP) and Log (hs-cTnT) for > 10% hibernation was 8.83 (0.15-515.59) and 8.57 (0.90-82), respectively.
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- N-Terminal Pro B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin T Levels Are Related to the Extent of Hibernating Myocardium in Patients With Ischemic Heart FailureCanadian Journal of CardiologyVol. 33Issue 11
- PreviewIncreased N-terminal pro b-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) can identify patients with heart failure (HF) who are at increased risk of cardiac events. The relationship of these biomarkers to the extent of hibernating myocardium and scar has not been previously characterized in patients with ischemic left ventricular dysfunction and HF.
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