Acetylcholine versus cold pressor testing for evaluation of coronary endothelial function

Abstract

BackgroundAssessment of coronary endothelial function with intracoronary acetylcholine (IC-Ach) provides diagnostic and prognostic data in patients with suspected coronary microvascular dysfunction (CMD), but is often not feasible due in part to the time and expertise needed for pharmacologic mixing. Cold pressor testing (CPT) is a simple and safe stimulus useful for either invasive or non-invasive endothelial function testing and myocardial perfusion imaging but has not been specifically evaluated among symptomatic women with signs of ischemic heart disease (IHD) who have no obstructive coronary artery disease (CAD).Methods163 women with signs and symptoms of IHD and no obstructive CAD from the NHLBI- Women’s Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study underwent coronary reactivity testing with a Doppler flow wire (FloWire® Volcano, San Diego, CA) in the proximal left anterior descending artery. Coronary artery diameter and coronary blood flow (CBF) assessed by core lab using QCA before and after IC-Ach (18.2 μg/ml infused over 3 minutes) and during CPT.ResultsMean age was 55 ± 12 years. Rate pressure product (RPP) in response to IC-Ach did not change (baseline to peak, P = 0.26), but increased during CPT (363±1457; P = 0.0028). CBF in response to CPT was poorly correlated to IC-Ach CBF. Change in coronary artery diameter after IC-Ach correlated with change after CPT (r = 0.59, P<0.001). The correlation coefficient was stronger in subjects with coronary dilation to IC-Ach (r = 0.628, P<0.001) versus those without dilation (r = 0.353, P = 0.002), suggesting that other factors may be important to this relationship when endothelium is abnormal.ConclusionsIn women with no obstructive CAD and suspected CMD, coronary diameter changes with IC-Ach and CPT are moderately-well correlated suggesting that CPT testing may be of some use, particularly among patients with normal endothelial function, however, not an alternative to IC-Ach for diagnosis of coronary endothelial dysfunction.

Peripheral Microvascular Function Reflects Coronary Vascular Function

“…We and others have demonstrated that the endothelial reactivity in response to these pharmacologic probes indicative of vasomotion during physiologic stimulation as well. Coronary flow and epicardial responses to pacing, cold pressor testing and mental stress correlate with the responses to acetylcholine 7,[15][16][17] . We also have shown that forearm microvascular dilation in response to exercise mediated by NO release is greater in healthy subjects compared to those with hypercholesterolemia 18 .…”

Endothelial Dysfunction and Coronary Vasoreactivity - A Review of the History, Physiology, Diagnostic Techniques, and Clinical Relevance

“…This method involves wrapping an ice pack around the forearm or placing it on the patient's forehead for two minutes with angiography then repeated. This works via the pathway of sympathetic (and likely also parasympathetic neuro humoral responses) stimulation though this it is postulated that it may be more complex than this as direct trials comparing this technique with intracoronary acetylcholine have demonstrated a greater effect on coronary vessel change with CPT (96,97). In a normal coronary circulation, sympathetic activation provokes endothelium dependent vasodilation.…”

Diagnostic approach in patients with angina and no obstructive coronary artery disease: emphasising the role of the coronary function test

“…Non-invasive methods that assess coronary spams are available, for example the implementation of mental stress, hyperventilation or the cold-pressor technique to provoke spasm. However, besides the lack of experience in most centres, there is little data about the validity and safety of these methods [ 30 ].…”