Table 2.

Knowledge gaps and future directions in INOCA

Mechanistic research

➢ Are there sex differences in human coronary artery innervation and blood flow regulation

➢ What is the impact on microvascular function with premature estrogen loss?

➢ Sex-differences in myocardial energy utilization

➢ Investigation of pathways that lead to diastolic dysfunction and fibrosis in cardiometabolic inflammation

➢ Chronic psychological stress, coronary inflammation, and immune dysfunction

➢ Is CMD a systemic process: brain, renal, cardiac, retinal, skeletal muscle

➢ Sex-differences in Central pain processing in INOCA syndrome

➢ Are mechanisms of stress-induced abnormal microvascular reactivity in INOCA different than in obstructive CAD?

identification of at risk subsets

➢ Using precision medicine methods – i.e. proteomic profiling

➢ Leveraging electronic health record to better characterize INOCA phenotypes for risk stratification

➢ Clarifying race/ethnic differences in CMD as a contributor to adverse outcomes

Improving diagnostic strategies

➢ Utility & safety of functional testing in the setting of ACS/MINOCA

➢ Improved imaging techniques/cost for radiotracers to detect coronary inflammation

➢ Utility of cardiac sympathetic imaging in INOCA

Improving therapeutics/management

➢ Can microvascular function be restored with angiogenic factors or stem cells?

➢ Can nutraceuticals with flavonoids/polyphenols in berries, beets, dark chocolate, etc. impact microvascular flow reserve?

➢ Will anti-atherosclerotic medications alter outcomes in INOCA?

➢ GLP-1A and impact of weight loss on CMD-ischemia and INOCA symptoms

➢ Use of endothelin receptor antagonists in INOCA

➢ Testing autonomic modulation strategies for improvement in CFR and angina