Distinguishing type 1 and type 2 MI: JAMA study explores the role of biomarkers.
Differentiating between type 1 [due to coronary plaque rupture] and type 2 myocardial infarction (MI) [demand-supply mismatch] is clinically important because their treatments differ. However, this distinction is challenging clinically as most of the risk factors for these two varieties of MI overlap. In the latest issue of JAMA Cardiology, Nestelberger et al explore the role of biomarkers quantifying endothelial dysfunction, microvascular dysfunction, and/or hemodynamic stress in this differentiation and found that these markers modestly aid in diagnosis of T2MI vs T1MI.
Most patients presenting with spontaneous MI tend to have type 1 MI, characterized by coronary plaque rupture or erosion and superimposed thrombosis. But a substantial proportion have type 2 MI, characterized by an imbalance between myocardial oxygen supply and demand, precipitated by an extracardiac stressor, such as hypertension, tachycardia, or hypotension.
The treatment strategies differ for both conditions. For patients with type 1 MI, the focus is on aggressive antithrombotic therapy and consideration of urgent coronary angiography and revascularization. For patients with type 2 MI, the focus is on treating the extracardiac stressor precipitating the myocardial oxygen supply and demand imbalance.
Symptoms and electrocardiogram changes that are routinely used are only modest discriminators, each with an area under the receiver operator characteristic curve (AUC) of approximately 0.60. Researchers have therefore turned to circulating biomarkers to see if they can offer additional discriminatory value.
Studies have shown that levels of high-sensitivity cardiac troponin (hsTn) are typically several times higher in those with type 1 MI than in those with type 2 MI. Unfortunately, there is still considerable overlap in the ranges, such that the AUC is typically on the order of 0.65.
This international, multicenter prospective diagnostic study enrolled patients presenting with acute chest discomfort to the emergency departments. The study quantified the discrimination of hs-cTn T, hs-cTn I, and 17 novel cardiovascular biomarkers measured in subsets of consecutively enrolled patients against a reference standard (final diagnosis), centrally adjudicated by 2 independent cardiologists according to the fourth universal definition of MI, using all information, including cardiac imaging and serial measurements of hs-cTnT or hs-cTnI.
The study had the following findings:
1. Among 1106 patients with an adjudicated final diagnosis of MI; 77.8% had T1MI, and 22.2% had T2MI.
2. Patients with T2MI (vs those with T1MI) had lower concentrations of biomarkers quantifying cardiomyocyte injury hs-cTnT, hs-cTnI, and cardiac myosin-binding protein C.
3. But these Type 2 MI patients had higher concentrations of biomarkers quantifying endothelial dysfunction, microvascular dysfunction, and/or hemodynamic stress as evidenced by C-terminal proendothelin, midregional proadrenomedullin, midregional pro–A-type natriuretic peptide, and growth differentiation factor 15 values.
4. Discrimination for these biomarkers, as quantified by the area under the receiver operating characteristics curve, was only modest.
Nestelberger et al have added to this literature by examining a broad array of cardiovascular biomarkers in a larger cohort. They, too, found that MRproANP and C-terminal proendothelin-1 levels were higher in those with type 2 MI than in those with type 1 MI. But ultimately, no biomarkers were convincingly superior to hsTn at 2 hours after presentation.
Thus, for now, the differentiation between type 1 and type 2 MI still requires the clinician to integrate all of the available data for each patient and make an informed, albeit imperfect, judgment.
Source: JAMA cardiology: Nestelberger T, Boeddinghaus J, Lopez-Ayala P, et al; APACE Investigators. Cardiovascular biomarkers in the early discrimination of type 2 myocardial infraction. JAMA Cardiol. Published online April 21, 2021. doi:10.1001/jamacardio.2021.0669