Abstract Body (Do not enter title and authors here): Background:
Lactate measurement during acetylcholine (ACh) provocation tests can indicate the presence or absence of myocardial ischemia. Despite ACh-provoked spasm, including epicardial coronary artery spasm (CSA) and microvascular spasm (MVS), lactate production from coronary circulation is not observed in some cases. This may be attributable to the severity of myocardial ischemia. The relationship between lactate production due to coronary spasms and myocardial metabolism is not fully understood.

Hypothesis:
We hypothesized that there was a significant difference of ketone bodies concentration between patients with and without lactate production in ACh-provoked spasm patients.

Method:
This retrospective analysis included 81 CSA or MVS patients (excluding myocardial infarction) diagnosed by ACh provocation test from May 2018 to February 2024. During the test, blood sample was collected from aortic root (Ao) and coronary sinus (CS) before and after ACh provocation, in order to measure lactate and ketone bodies, such as acetoacetic acid (AcAc) and 3-hydroxybutyric acid (3-OHBA). The patients were categorized into two groups based on lactate production during ACh provocation test. Lactate extraction ratio was calculated as follows: lactate extraction (%) = {([lactate concentration at Ao] – [lactate concentration at CS]) / [lactate concentration at Ao]} x 100. Ketone bodies concentration from Ao was used before ACh provocation.

Results:
During ACh provocation test, 63 patients had lactate production, and 18 did not. The patients with lactate production had significantly higher concentration of ketone bodies (235.0 [IQR: 120.7-426.4] vs 90.5 [IQR: 62.2-286.7] mmol/L, p value = 0.007), AcAc (87.5 [IQR: 48.9-124.7] vs 44.9 [IQR: 29.8-88.8] mmol/L, p value = 0.006), and 3-OHBA (147.4 [IQR: 70.0-290.9] vs 51.0 [IQR: 35.1-197.4] mmol/L, p value = 0.006). Multiple logistic regression analysis adjusted for brain natriuretic peptide showed that ketone bodies (p = 0.048) and AcAc (p = 0.035) were associated with lactate production, but 3-OHBA (p value = 0.053) was not.

Conclusion:
This study showed that CSA or MVS patients with lactate production during ACh provocation tests have higher levels of ketone bodies concentration. These results implied that there was the differential severity of myocardial ischemia caused by ACh provocation, and that severity might affect the ketone metabolism in myocardium.