The impact of hyperemic agent selection on the interpretation of invasive coronary microvascular function

Introduction Invasive assessment of coronary microvascular function relies on pharmacologically induced maximum hyperaemia; however, the interpretation of derived physiological indices may be influenced by the choice of hyperaemic agent. Adenosine triphosphate (ATP) and nicorandil are commonly used, but they differ in their systemic haemodynamic effects, including blood pressure changes. Unlike fractional flow reserve, indices of coronary microvascular dysfunction are influenced by haemodynamic conditions; therefore, measured values may vary depending on the hyperaemic agent used. Nevertheless, the effect of different hyperaemic agents on invasively derived microvascular indices has not been adequately evaluated in direct within-patient comparisons. Purpose This study aimed to determine whether the choice of hyperaemic agent influences the interpretation of invasive microvascular function in patients with suspected ischaemia and non-obstructive coronary arteries (INOCA). Methods This prospective observational study enrolled patients with suspected INOCA without significant epicardial stenosis (fractional flow reserve (FFR) ≧0.80). Coronary physiology of the left anterior descending artery was assessed using a pressure wire and bolus thermodilution technique. Maximum hyperaemia was induced by continuous intravenous ATP infusion (180 μg/kg/min) and intracoronary nicorandil (2 mg), with both agents administered in each patient. The sequence of administration was at operator discretion. A ≧5-minute washout period was observed, and the second agent was administered only after confirmation that heart rate and blood pressure had returned to baseline, to minimise potential order effects. Results A total of 47 patients were analysed. In comparison with nicorandil, ATP was associated with a significantly greater reduction in blood pressure (ΔBP) (14.6 ± 9.84 mmHg vs. 7.63 ± 6.12 mmHg; p < 0.001). Coronary flow reserve (CFR) was significantly lower during ATP-induced hyperaemia than during nicorandil-induced hyperaemia (geometric mean ratio (GMR) [ATP/nicorandil] 0.83, 95% CI 0.73–0.95; p=0.007). In contrast, index of microcirculatory resistance (IMR) and microvascular resistance reserve (MRR) exhibited comparable characteristics across the agents (IMR: GMR 1.07, 95% CI 0.94–1.22; p=0.27; MRR: GMR 0.95, 95% CI 0.84–1.07; p=0.386). The FFR values were comparable (0.91 ± 0.03 vs. 0.91 ± 0.03; p=0.33). Conclusions In comparison with intracoronary nicorandil, intravenous ATP resulted in a greater decrease in blood pressure and a lower CFR, while IMR, MRR and FFR were comparable. These findings suggest that systemic blood pressure changes induced by hyperaemic agents may influence the interpretation of CFR and should be taken into consideration when assessing coronary microvascular function. In this context, evaluation using MRR, which accounts for haemodynamic conditions, may provide a complementary approach for microvascular assessment.