Dara Baker is a 2020–2021 Doximity Research Review Fellow. Nothing in this article is intended nor implied to constitute professional medical advice or endorsement. The views expressed in this article are those of the author and do not necessarily reflect the views/position of Doximity.
There is not one universal pathophysiological process that drives MI. In fact, at least two distinct presentations exist, categorized as Type 1 MI (T1MI) and Type 2 MI (T2MI). T1MI follows the classic definition: atherosclerotic inflammation leading to plaque disruption and vessel occlusion. T2MI is considered a “supply-demand mismatch,” demonstrating hemodynamic instability by “hypotension, hypertension, tachycardia, or hypoxemia.” Currently, biomarkers such as high-sensitivity cardiac troponin (hs-cTn) I, which indicates cardiac myocyte injury, are limited in utility because they offer little to differentiate between T1MI and T2MI. Nestelberger et al. hypothesized that T1MI and T2MI might have distinct alternative biomarker profiles that better lend themselves to the task of differentiation.
Of the 5,887 individuals recruited for this study, 246 were diagnosed with T1MI, and 860 were diagnosed with T2MI. For adults who presented to the ED within 12 hours of onset of chest pain, evaluation included a 12-lead ECG with continuous monitoring, pulse oximetry, standard blood tests, chest radiograph if indicated, and hs-cTn at some centers to trend. Exclusion criteria at the time of analysis included presence of chronic kidney disease on hemodialysis, ST elevation (unusual for T2MI), and disagreement of expert cardiologists on the final diagnosis.
In total, 17 individual biomarkers were evaluated, related to seven potential pathways underlying the disease. Individually, no biomarker discriminated T1MI from T2MI significantly better than hs-cTnI. However, the researchers did find that four biomarkers — MR-proANP, CT-proET-1, midregional proadrenomedullin, and GDF-15 — were increased in T2MI as compared to T1MI. Interestingly, these biomarkers relate to pathways in hemodynamic stress, endothelial and microvascular dysfunction, inflammation, and aging.
It is also worth noting that this study had important limitations, including the difficulty of testing for all 17 biomarkers in each patient (due to restriction of the blood sample quantities); the inequality of diagnoses for T1MI versus T2MI; the exclusion of individuals with renal dysfunction; and the applicability of this study only to emergency visits. Additionally, it would have been helpful if the authors had presented ROC curves for individual biomarkers, and the combined biomarker model for visualization of the data.
In terms of clinical practice, it may be too early to anticipate a replacement of hs-cTnI with any of the individually studied biomarkers for categorizing MI, though the aforementioned four biomarkers may prove useful in future research, given their comparable AUC values to hs-cTnI. Nevertheless, the exciting takeaway from this work is the possibility of redefining MI by utilizing novel biomarkers to optimize treatment for patients with a common and life-threatening condition.
Dara Baker is a fourth-year medical student at GW SMHS, returning from her yearlong fellowship at NIH as part of the Medical Research Scholars Program, 2019–2020. She is an aspiring physician-scientist, excited about research in stem cell-based medicine, immunology, small molecule regulatory pathways, and genetics.