ANOCA/INOCA/MINOCA: Open artery ischemia

Ischemic heart disease continues to represent a major health threat for death, disability, and poor quality of life as it also consumes enormous health-related resources. For over a century, the major clinical phenotype was taken to be obstructive atherosclerosis involving the larger coronary arteries (e.g., coronary artery disease CAD). However, evolving evidence now indicates that nonobstructive CAD is the predominant phenotype. Patients within this phenotype have been termed to have angina with no obstructive CAD (ANOCA), ischemia with no obstructive CAD (INOCA), or myocardial infarction with no obstructive coronary arteries (MINOCA). But as methods to assess cardiomyocyte injury evolve, these phenotypic distinctions have begun to merge, raising concern about their usefulness. Also, considerable evidence has suggested several endotypes that link to potential mechanisms. These include coronary microvascular dysfunction, augmented vasoreactivity (failure to relax appropriately, exaggerated constriction “spasm”, etc.), nonobstructive atherosclerosis, pre-heart failure with preserved ejection fraction, hypercoagulable states, and several others, alone or in combination. This review summarizes these syndromes and their associated clinical outcomes with an emphasis on potential mechanistic signals. These involve the endothelium, the microvasculature, and cardiomyocyte function. Biomarkers of injury/dysfunction involving these structures are discussed along with a hypothetical construct for management being tested in an ongoing trial.