"In the past, we did not have the right tools to make the diagnosis so this used to be called cardiac syndrome X because nobody knew what it was. But now we understand that the majority of these patients have coronary microvascular dysfunction, where it is the small vessels that are unable to fully dilate to increase blood flow due to stress or exercise. Or there is actually constriction or vasospasm, where there can be significant narrowing of the coronary arteries and therefore patients present with chest pain," Wei explained. "There have been decades of under-diagnosis, and therefore under-treatment of women with angina in the setting of non-obstructed coronary arteries. Women were sent home, or told it was fibromyalgia, or it was in their head."  

In some cases, the INOCA condition can lead to a myocardial infarction, which is then known as MINOCA. 

Wei said a subset of MINOCA cases are due to spontaneous coronary artery dissection (SCAD), which is a tear that forms inside a coronary vessel. She said 90% of these cases are in women, but in rare cases can happen in men. 

"In most cases, the presentation may be difficult for the typical coronary angiographer to see. You have to be attuned and consider if this presentation of a myocardial infarction might actually be due to a dissection," Wei explained. 

How to diagnose INOCA or MINOCA

Wei said we have learned in the past decade that the coronary arteries can be interrogated for prognostic information with invasive coronary function testing, or noninvasively using stress cardiac PET nuclear imaging, stress echo with Doppler testing, or stress cardiac MRI. During stress imaging, she said coronary flow reserve can be calculated. This is a measure of how well the blood flow increases during stress, which can help unmask these conditions and show chest pain is not just inside someone's head. 

A non-FDA approved imaging agent acetylcholine also can help assess coronary artery spasm or endothelial  function, Wei said. 

In PET imaging, coronary flow reserve can help determine if a patient cannot increase their blood flow at least two-fold from rest to stress, indicting the patient has microvascular dysfunction.  

"But while we now have the tools to diagnose these conditions, we do not have the large clinical trials to guide therapy," Wei explained. 

However, she said trial evidence is starting to grow with ongoing trials, such as the WARRIOR trial. 

Nitroglycerin and calcium channel blocker's are commonly used for treatment vascular spasm and in some cases microvascular disfunction, she said.