Implications of elevated resting microvascular resistance: results from MICRO-SNAPE

Background Coronary microvascular dysfunction (CMD), a mismatch between oxygen supply and demand, is associated with higher symptomatic burden, impaired quality of life and adverse cardiovascular outcomes. Beyond hyperemic functional parameters such as coronary flow reserve (CFR) and hyperemic microvascular resistance (IMR), the significance of elevated resting IMR remains unclear. This study aims to investigate the clinical relevance of elevated resting IMR in patients with angina and non-obstructive coronary arteries (ANOCA). Methods 1001 ANOCA patients (62±11 years old, 56% female) underwent invasive assessment of coronary flow, pressure, resistance and spasm provocation using a standardized protocol (NCT06125392) across nine international centers. The upper reference limit for resting coronary resistances was defined as the 95th percentile of the values measured in a subgroup with normal hemodynamic responses to adenosine and acetylcholine and no history of stenting, myocardial infarction or heart failure. An independent ANOCA cohort (N=154) served as external validation. Results Overall, 130 (13%, 64±11 years old) patients had an elevated resting IMR (>112 U). When compared with patients with normal resting IMR, these had a higher prevalence of hypertension [78% vs. 60%; p<0.001] and were more often male [59% vs. 42%; p<0.001]. Patients with elevated resting IMR had lower heart rate at rest (68±13 vs. 74±13, p<0.001) accompanied by a lower rate-pressure product (6836±1733mmHg*b/min vs. 7353±1678; p<0.001). Resting (1.5±0.4s vs. 0.7±0.3s, p<0.001) and hyperemic coronary flow (0.4±0.2s vs. 0.2±0.15s, p<0.001) were reduced, while CFR was higher (4.7±2.2 vs. 3.3±1.7, p<0.001). Similarly, IMR was higher during adenosine (33±18U vs. 19±11U) and acetylcholine infusion (52±32U vs. 30±19U; both p<0.001). In univariate analysis, hypertension (2.39 [1.54-3.72]; p<0.001), use of Angiotensin receptor blockers (1.58 [1.05-2.37]; p=0.029), hyperlipidaemia (1.52 [1.02-2.26]; p=0.041), a history of rest symptoms (1.59 [1.04-2.43]; p=0.031) were associated with elevated resting IMR, while female sex showed a negative association (OR=0.49 [0.34-0.71]; p<0.001). These findings were confirmed in an external cohort. Elevated resting IMR was associated with larger left atrial area (ß* = 0.19; p=0.03) and impaired left atrial function (ß* = -0.28; p=0.002), higher pulmonary arterial pressure (ß* = 0.23; p=0.03), smaller end-diastolic left ventricular volume (ß* = -0.19; p=0.03), left ventricular hypertrophy (ß* = 0.41; p<0.001), and reduced global longitudinal strain (ß* = 0.20; p=0.03). Conclusion Elevated resting IMR is associated with younger age, hypertension, abnormalities in cardiac structure and function, and reduced external cardiac work while CFR (and therefore vascular responsiveness) is preserved. Assessing resting IMR may provide additional diagnostic and prognostic insights in ANOCA beyond established hyperemic parameters.