Although both were studied before the added value of Hs-cTn to BNPs is an area that is still under scrutiny (21,22,23). The study shed lights on the value of adding one to another in further predicting hard endpoints of heart failure related death and re-hospitalization. There are no “perfect” tests but in this scenario Hs-cTns were “perfect” with sensitivity of 96%. The depicted ROC (receiver operator curves) speaks to this effect very illustratively.
We believe the findings of this trial is unique and may be practice changing for treating patients with acute heart failure. We have selected extremely high-risk patients with quite elevated level of pro Bnp >1000 and we further stratify them using Hs-cTns and radiological evidence of pulmonary edema, both biomarkers are measured in the laboratories and their blood levels are pathophysiologically explained. BNPs are produced due to stretching effect of the myocardial tissue while high sensitivity troponins are released in blood stream in response to direct damage to the myocardium, (24, 25). Translating the laboratories finding to clinical practice was in keeping with the clinical outcomes of patients in this trial, as myocardial damage (measured by high sensitivity Troponins) is more of a surrogate marker compared to the stretching effect causing (Pro BNP elevation).
Despite the novel finding of the trial, there are quite few limitations of the study that need to be highlighted, including small numbers of patients in both groups leading to wide confidence intervals and reducing the power of the study, the selection bias related to open label protocol, and potential lab errors related to sample drawn.
The study seems to touch upon major factors of increasing risk of deaths in patients with heart failure including risk factors of ischemic heart disease, reduced ejection fraction, elevated filling pressure by echo criteria and radiological evidence of pulmonary edema, however the study was not powered to look at the impact of all these factors in the small size sample of patients recruited, making it very difficult to compare its utility in addition to Hs-cTns. We did not repeat cardiac troponin level in post recruitment presentations to avoid dilutional effect of intervention on blood level of pro BNPs and troponins.
Focusing on predicting outcomes is important aspects of proper management of patient with heart failure as outlined in most recent guidelines, where class A is defined as patient at risk of heart failure but not yet diagnosed to have heart failure (26), adding Hs-Ctn to the paradigm of heart failure management may be of value to tailor more aggressive surveillance and more strict management protocol that will help improve survival and outcomes.
The trial served its purpose very well, the drop-out rate was 5%, and results were clinically significant even with the inherited limitations we have alluded to. Further study with large numbers of patients is needed to address the same question but in the setup of other factors or other novel markers, the later may be better in refining the risk assessment tool of patient with first time presentation of heart failure.