Myocardial ischemia in nonobstructive coronary arteries: A review of diagnostic dilemmas, current perspectives, and emerging therapeutic innovations

Table 6 Biomarkers of supply-demand mismatch

Biomarker	Description	Clinical significance
MR-proANP	MR-proANP is involved in cardiac stress response and is an indicator of atrial stretch. It is proposed to be elevated in MINOCA due to acute myocardial stress or inflammation	It reflects atrial and ventricular stress, which may arise from microvascular dysfunction, inflammatory processes, or stress-induced myocardial injury, all of which could contribute to MINOCA. It helps in diagnosing myocardial injury when coronary arteries appear unobstructed
CT-proET1	CT-proET-1 is a marker of endothelin-1 precursor, a potent vasoconstrictor involved in vascular tone and cardiac remodeling. Elevated levels suggest endothelial dysfunction	Elevated CT-proET-1 levels in MINOCA indicate impaired endothelial function and increased vasoconstriction, potentially contributing to myocardial ischemia despite normal coronary artery findings. Endothelin-1 can cause vasoconstriction, leading to reduced myocardial perfusion, a mechanism in MINOCA
MR-proADM	MR-proADM is a biomarker related to adrenomedullin, a vasodilator, and marker of endothelial dysfunction. It is elevated in conditions of heart failure, sepsis, and myocardial injury	MR-proADM reflects the systemic vasodilatory response and endothelial dysfunction, which may result from microvascular spasm, inflammation, or altered myocardial perfusion in MINOCA. High levels correlate with worse prognosis and heart failure in these patients
GDF-15	GDF15 is a stress-induced cytokine elevated in response to inflammation, oxidative stress, and myocardial injury. It is thought to be a biomarker of myocardial stress in MINOCA	GDF15 reflects myocardial injury and inflammation, which may result from microvascular dysfunction or myocardial stress in the absence of obstructive coronary disease. Elevated levels suggest a heightened inflammatory response and oxidative stress, both of which can contribute to the pathophysiology of MINOCA. It is related to adverse cardiovascular outcomes

MR-proANP: Mid-region pro-atrial natriuretic peptide; CT-proET1: C-terminal pro-endothelin-1; MR-proADM: Mid-region pro-adrenomedullin; GDF-15: Growth differentiation factor-15; MINOCA: Myocardial infarction with nonobstructive coronary arteries.