Using anginal symptoms to predict underlying etiology in patients with angina and no obstructive coronary disease (ANOCA)
Authors: Roca Alvarez Y , Ashokprabhu N , Tapp D , Schmidt C , Kaur S , Fox J , Hamstra M , Henry T D , Quesada O 
Published: October 2024

Abstract

Background
Patients with angina with no obstructive coronary disease (ANOCA) can present with exertional anginal symptoms or angina at rest. Invasive coronary functional angiography (CFA) is used to diagnose endothelial-dependent and independent coronary microvascular dysfunction (CMD), microvascular spasm, and epicardial spasm. Historically, the type of anginal symptoms has been thought to be suboptimal in predicting the etiology of ANOCA. However, the sensitivity, specificity, predictive value, and correlation of angina type related to CFA abnormalities are unknown. We hypothesize that patients with predominantly exertional angina are more likely to have endothelial-independent and dependent CMD, and patients with angina at rest are more likely to have microvascular or epicardial spasm.

Objective
To explore sensitivity, specificity, predictive value, and correlation of angina type with underlying etiology of ANOCA as diagnosed by CFA.

Methods
A prospective registry-based cohort study of consecutive CFA performed in 197 ANOCA patients between 2020 and 2023 using the Doppler-tipped guidewire method. ANOCA was defined as &lt;50% stenosis in any major epicardial artery at time of CFA. Patients were classified based on CFA diagnosis: (1) endothelial-independent CMD (coronary flow reserve [CFR] &lt; 2.5 in response to adenosine), (2) endothelial-dependent CMD (coronary blood flow [CBF] &lt; 50% or no change in vessel diameter in response to 54mcg intracoronary acetylcholine), (3) microvascular (&lt;90% constriction) and epicardial spasm (&gt;90% constriction) to 108 mcg intracoronary acetylcholine. Patients were categorized based on anginal symptoms (exertional angina or at rest angina) documented at cardiologist visit prior to CFA. McNemar’s test and Spearman correlations were performed for both types of angina and the 3 ANOCA underlying diagnoses.

Results
Among 197 ANOCA patients, the average age was 56.5 ± 11.9 years and 91% were female. Angina at rest had a high specificity (91.3%) but a low sensitivity (25.2%) for the diagnosis of spasm with a PPV of 90.5 (Table 1). There was a significant correlation between angina at rest and spasm (p=0.012). Angina at rest had a similarly intermediate sensitivity and specificity for endothelial independent and dependent CMD. Exertional angina had similar sensitivity, specificity, and a high PPV for endothelial independent and dependent CMD. There was a significant correlation between exertional angina and endothelial dependent CMD (p=0.025). McNemar’s test was statistically significant (p&lt;0.001) for all analyses.

Conclusion
ANOCA patients with symptoms of angina at rest had a significant correlation with coronary spasms and exertional angina correlates with endothelial-dependent CMD. We demonstrate that angina at rest can be 90% specific for the diagnosis of spasm. Our findings warrant further investigation but suggest that empiric therapy based on angina type is a reasonable first step before invasive testing.