Complementary insights into novel biomarkers for acute myocardial infarction: reinforcing the role of a multimarker strategy

I have read with great interest the article by Chen et al., entitled “Kinetics of plasma microRNA-499 expression in acute myocardial infarction”, published in the Journal of Thoracic Disease in 2015 (1). This article constitutes a valuable contribution, demonstrating that circulating microRNA-499 (miR-499) increases exponentially in the first hours of an acute myocardial infarction (AMI), correlating with classic biomarkers of necrosis and with the severity of coronary artery disease. Demonstrating a clear kinetic pattern of miR-499 strengthens its value for early diagnosis and also provides insights for prognostic stratification in patients with acute coronary syndrome.

I consider it pertinent to complement what Chen et al. presented with the growing evidence of other emerging biomarkers that, together, reinforce the multimarker strategy as the future of precision cardiology. First, galactin-3 (Gal-3) has played an important role in post-ischemia inflammation and fibrosis. Bivona et al. observed an early increase in Gal-3 in the days following AMI, associated with ventricular remodeling (2). Similarly, Mueller et al. confirmed in a multicenter prospective study that Gal-3 and soluble suppression of tumorigenicity 2 (sST2) combined have diagnostic and prognostic value in AMI, improving the prediction of adverse outcomes (3).

The prognostic value of Gal-3 is not limited solely to AMI. In patients with heart failure (HF) and severely reduced ejection fraction, according to Zivlas et al., elevated levels of Gal-3 and cystatin C have been shown to correlate with left atrial dilation and echocardiographic parameters indicating worse outcomes (4). This reinforces the idea that these fibrotic biomarkers can predict progression to chronic HF, which is relevant in post-AMI follow-up.

Similarly, in the search for rapidly releasing biomarkers with a faster rate than troponins, high-sensitivity assays for cardiac myosin-binding protein C (cMyC) have been developed. Kaier et al. demonstrated that cMyC appears in plasma earlier and in higher concentrations than troponin after myocardial necrosis, making it important in the early triage of patients with chest pain (5).

Consistent with the dynamic prognostic value, the work of van Vark et al. in patients with acute HF demonstrated that serial sST2 measurements are associated with mortality and rehospitalization, even increasing in the weeks before adverse clinical outcomes (6). This anticipatory pattern warns us of the usefulness of including biomarkers with serial behavior during clinical practice, both in AMI and its complications.

Taken together, the current evidence suggests that integrating miR-499, Gal-3, sST2, cMyC, and other biomarkers into a multimarker panel could optimize the initial evaluation, follow-up, and risk stratification of a patient after an AMI episode. I congratulate the authors for their significant contribution with this work and believe that the next step should be to conduct multicenter studies to validate the combined use of biomarkers, with a view to their implementation in emergency and long-term follow-up protocols.

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