Inclusion and exclusion criteria.

Background
MicroRNAs (miRNAs) are noncoding RNAs involved in post-transcriptional genetic regulation with a proposed role in intercellular communication. miRNAs are considered promising biomarkers in ischemic heart disease. Invasive physiological evaluation allows a precise assessment of each affected coronary compartment. Although some studies have associated the expression of circulating miRNAs with invasive physiological indexes, their global relationship with coronary compartments has not been assessed. Here, we will evaluate circulating miRNAs profiles according to the coronary pattern of the vascular compartment affectation.
Study and design
This is an investigator-initiated, multicentre, descriptive study to be conducted at three centres in Spain (NCT05374694). The study will include one hundred consecutive patients older than 18 years with chest pain of presumed coronary cause undergoing invasive physiological evaluation, including fractional flow reserve (FFR) and index of microvascular resistance (IMR). Patients will be initially classified into four groups, according to FFR and IMR: macrovascular and microvascular affectation (FFR≤0.80 / IMR≥25), isolated macrovascular affectation (FFR≤0.80 / IMR<25), isolated microvascular affectation (FFR>0.80 / IMR ≥25) and normal coronary indexes (FFR>0.80 / IMR<25). Patients with isolated microvascular affectation or normal indexes will also undergo the acetylcholine test and may be reclassified as a fifth group in the presence of spasm. A panel of miRNAs previously associated with molecular mechanisms linked to chronic coronary syndrome will be analysed using RT-qPCR.
Conclusions
The results of this study will identify miRNA profiles associated with patterns of coronary affectation and will contribute to a better understanding of the mechanistic pathways of coronary pathology.