Abstract Body (Do not enter title and authors here): BACKGROUND
The common preconception is that non-obstructive coronary artery disease(NOCAD) predominantly affects females with little to no cardiac risk factors. However, it is unclear whether there is a significant difference in baseline characteristics between those with a positive vs negative coronary reactivity testing(CRT) result. Furthermore, CRT explores multiple pathophysiological mechanisms which make a positive result nuanced. This study identifies 5 different endotypes based on CRT results, aiming to identify phenotypic characteristics that correlate with these endotypes.

METHODS
409 patients were included in a cohort study, representing all patients referred for CRT to a tertiary referral centre for NOCAD, between 2016-2024. Patients underwent protocol CRT of coronary flow reserve(CFR) and index of microvascular resistance(IMR) measurements following adenosine infusion(140mcg/kg/min) and bolus acetylcholine(100mcg).
Results were compared by positive vs negative CRT, normal vs abnormal CFR/IMR, and by 5 different endotypes identified from CRT result combinations.

RESULTS
There was no significant difference in clinical characteristics between the positive vs negative CRT result groups.
However, with further stratification, there were significant sex differences and cardiac risk profile differences in CFR and IMR results. There was a greater proportion of females in the abnormal (low) CFR group(p<0.001), and higher burden of cardiac risk factors in the abnormal (high) IMR group(p<0.001). The highest burden of cardiac risk factors was seen in the 'Traditional Coronary Microvascular Dysfunction (CMD)' endotype, defined as those with abnormal(low) CFR and abnormal(high) IMR. The 'Functional CMD' endotype was characterised by younger females, whilst the 'Compensated CMD' and 'Coronary spasm' endotype showed no sex difference. The normal CFR and normal IMR endotype reflected the referred population(Figure 1).

CONCLUSION
There is an emergence of clinical phenotypes according to the five coronary reactivity testing endotypes. Lower CFR appears to be a more “female pattern” of microvascular dysfunction. Endotypes reflect underlying pathology and may provide mechanistic explanations for sex differences in the microvascular dysfunction types of NOCAD, whilst explaining the lack of sex differences in other types. Further detailed understanding of CRT endotypes will allow us to understand the mechanistic differences in cardiovascular outcomes between males and females.