An Hypothesis: Disproportion Between Cardiac Troponin and B-Type Natriuretic Peptide Levels—A High Risk and Poor Prognostic Biomarker in Patients With Fulminant Myocarditis?

Abstract

In our clinical practice, we recently found some patients with severe fulminant myocarditis (FM) who showed persistently elevated cardiac troponin (cTn) levels and "seemingly normal" B-type natriuretic peptide (BNP) level, and who subsequently progressed to poor outcomes. Indeed, this sounds contrary to conventional wisdom, but it is not an accidental phenomenon. Fulminant myocarditis is a rapidly progressive disease associated with high mortality. Recent studies have shown that patients with FM are significantly more likely to require heart transplantation than those without FM. Prompt diagnosis of FM and the institution of advanced cardiac life support will save more lives. Cardiac troponin and BNP are widely used diagnostic markers. Cardiac troponin is a specific marker of cardiac injury and its level correlates with the severity of cardiac injury. However, plasma BNP has a dual identity; it is not only a marker of cardiac pressure/volume overload, but it is also a cardioprotective factor that provides effective neurohormonal compensation to maintain homeostasis. Similar to fulminant hepatitis (characterised by diffuse inflammation and massive parenchymal cell necrosis) sometimes showing disproportion between transaminase level and bilirubin level, the disproportion between cTn and BNP levels in FM seems to be consistent with its severe histopathological changes, including diffuse infiltration of the myocardium by inflammatory cells, as well as severe cardiomyocyte injury and necrosis. Moreover, in previous studies, a lower BNP level was found to be an adverse prognostic marker in end-stage heart failure. All these findings indicate that in patients with FM with a persistently high cTn level and ominous clinical presentation, a "seemingly normal" BNP level is not a friendly signal. We hypothesise that the combination of a persistently elevated cTn level and low BNP level in patients with FM indicates worse myocardial injury and poor prognosis.

PD-1/PD-L1 Inhibitor-Associated Myocarditis: Epidemiology, Characteristics, Diagnosis, Treatment, and Potential Mechanism

“…According to the characteristics of troponins, the type of cardiac troponin I and T are the new isoforms that are present in adult cardiac tissues ( Yu et al, 2021 ). About 46–97% of patients with immune myocarditis have increased serum troponin levels ( Escudier et al, 2017 ; Mahmood et al, 2018 ; Mir et al, 2018 ; Awadalla et al, 2020 ; Finke et al, 2021 ).…”

“…BNP is a specific biomarker reflecting the pressure or overload. BNP can indirectly tell us the function of the left ventricular (LV) strain in patients with heart failure or myocarditis ( Yu et al, 2021 ). All the pathogenesis which can lead to dysfunction of LV can also result in elevated BNP levels.…”

Correlation of rheumatoid and cardiac biomarkers with cardiac anatomy and function in rheumatoid arthritis patients without clinically overt cardiovascular diseases: A cross-sectional study

“…hsTropT was correlated with cardiac structure and function to a greater extent than NT-proBNP. This may be explained by the findings of a previous study in which hsTropT was related to an abnormal myocardium, irrespective of causative factors, whereas NT-proBNP was mostly related to the compensatory cardiac ventricular response to pressure and volume overload [45] . In addition, a previous study showed that patients with high LVMI had low capillary density and high LV mass, which were related to microvascular dysfunction, resulting in an ischemic myocardium and the release of hsTropT [15] .…”

Myoglobin and left ventricular ejection fraction as predictive markers for death in children with fulminant myocarditis

“…According to Xu et al LAd [OR: 1.226; 95% CI: 1.016–1.478; P = 0.034] and eGFR level [OR: 0.928; 95% CI: 0.87–0.989; P = 0.022] were predictors of FM ( 6 ). Besides, a combination of high cTn levels and low BNP levels, which suggested poor outcomes of the patient with FM ( 16 ). Liu et al found that the ACEF score, which was correlated with age, creatinine, and LVEF, [OR: 4.499; 95% CI: 0.960–1.061; p < 0.001] was a strong independent predictor of in-hospital mortality in children with FM, with an area under the ROC curve of.871 ( 7 ).…”