Paradoxical ST-segment depression at high blood flow in ANOCA: a hypothesis-generating analysis.

BACKGROUND

Angina with non-obstructive coronary arteries (ANOCA) is increasingly recognized as a common cause of chest pain.

OBJECTIVE

We observed that some ANOCA patients undergoing dipyridamole rubidium-82 positron emission tomography (PET)/computed tomography (CT) myocardial perfusion imaging (MPI) develop ST-segment depression despite preserved or elevated stress myocardial blood flow (MBF). This study sought to characterize this phenomenon.

METHODS

We analyzed patients referred for rubidium-82 PET/CT MPI without obstructive coronary artery disease for evaluation of microvascular function between 2017 and 2023 (ANOCA) and a propensity-matched control group at very low likelihood of obstructive disease. Stress MBF was categorized as low (< 2.0 mL/min/g), normal (2.0-3.5 mL/min/g), or high (> 3.5 mL/min/g). ST-segment depression was defined as ≥ 1 mm horizontal or downsloping depression in two contiguous leads.

RESULTS

The final cohort comprised 136 ANOCA patients and 533 controls. A total of 37 (5.5%) patients presented ST-segment depression, 25 (4.7%) in the control group and 12 (8.8%) in the ANOCA group; all were female. Its prevalence was significantly higher among patients with high vs. normal stress MBF in both the ANOCA group (37.5% vs. 6.1%, p = 0.0016) and the Control group (16.7% vs. 3.4%, p < 0.0001). At any given stress MBF, ANOCA patients had a higher probability of developing ST-segment depression compared with controls (p = 0.0037). In multivariable analyses, ST-segment depression was significantly associated with high stress MBF in ANOCA patients (OR:4.85, 95%CI:1.07-21.93).

CONCLUSIONS

Vasodilator-induced ST-segment depression was observed more frequently at higher stress MBF, particularly in ANOCA, raising the possibility of a paradoxical "high-flow ischemia" phenotype. These observations are hypothesis-generating and highlight the need for further studies to clarify underlying mechanisms and prognostic relevance.