Background and Objectives: Up to 40% of patients undergoing a coronary angiogram due to angina pectoris have no obstructive coronary artery disease, also known as angina with non-obstructive coronary arteries (ANOCA). ANOCA is associated with significant impairment in patients’ quality of life, increased risk of myocardial infarction and all-cause mortality. Approximately 25% of patients with ANOCA have persisting symptoms despite optimal medical therapy. There is a lack of in-depth knowledge regarding tailored treatment for patients with ANOCA due to a scarcity of trials designed to assess the effect of treatment modalities. The aim of this systematic review and meta-analysis is to give clinicians an overview of the efficacy of current treatment modalities for patients with ANOCA. Methods: PudMed/MEDLINE, Embase, the Cochrane Library and clinical trial registries were searched for randomised controlled and cohort studies regarding treatment modalities for ANOCA. The main outcome was change in angina pectoris frequency for each treatment modality. Secondary outcomes included changes in exercise capacity, quality of life, Canadian Cardiovascular Society (CCS) class, coronary flow reserve (CFR) and survival. Results: In total, 80 studies were included and used in the meta-analysis, of which ten studies met the current definition of ANOCA. Angina pectoris frequency improved significantly in the majority of the treatment modalities, with neuromodulation resulting in −3.35 standardised mean difference (SMD) (95% CI: −5.13; −1.56), trimetazidine in −1.74 SMD (−2.63; −0.85), traditional Chinese medicine in −1.55 SMD (−2.36; −0.75), beta-blockers in −1.32 SMD (−1.88; −0.77), enhanced external counterpulsation in −1.27 SMD (−2.04; −0.49), stem cell therapy in −1.04 SMD (−1.51; −0.57), lifestyle interventions in −0.86 SMD (−1.15; −0.57), RAAS-inhibitors in −0.83 SMD (−1.31; −0.35) and calcium channel blockers in −0.64 SMD (−0.92; −0.35). Conclusions: This meta-analysis into treatment modalities for patients with ANOCA shows a significant improvement in angina pectoris frequency in the majority of included treatment modalities. However, these results should be interpreted cautiously, as only ten of the studies included in the meta-analysis meet the current definition of ANOCA. This review underlines the importance of undertaking new studies with existing treatment modalities to determine the efficacy in patients with ANOCA.

Background: A coronary function test (CFT) is the recommended diagnostic test to identify coronary vasomotor dysfunction as a cause of symptoms in patients with angina and nonobstructive coronary arteries (ANOCA). Acetylcholine is the commonly used pharmacological agent for spasm provocation. We aimed to investigate an association between severity of symptoms and provocative acetylcholine dose. Methods and Results: We included ANOCA patients undergoing clinically indicated CFT from the Netherlands Registry of Invasive Coronary Vasomotor Function Testing: NL‐CFT. Patients with epicardial spasm (n=251) were divided according to acetylcholine spasm triggering dose: low (2–20 mcg, EpiLOW), middle (100 mcg, EpiMIDDLE) or high (200 mcg, EpiHIGH). Patients with microvascular spasm (n=157) were analyzed irrespective of triggering dose. The patient groups were compared to each other and to a control group with negative CFT results (n=101). We assessed mean Seattle Angina Questionnaire angina frequency and summary scores at baseline and follow‐up and the proportion of patients improving or deteriorating. An inverse relationship between provocation dosage and angina frequency at baseline was found in epicardial spasm: the lower the triggering dose, the more frequently patients experienced angina (EpiLOW 48±20, EpiMIDDLE 53±21, EpiHIGH 57±19, microvascular spasm 61±21, controls 64±21, overall P =0.003). A trend was seen toward most patients improving in the high triggering dose group, and most patients deteriorating in the low triggering dose group. Conclusions: A significant dose‐dependent relationship between spasm provocation and anginal complaints exists. Acetylcholine provocation dose could be incorporated as a risk stratification factor or surrogate outcome in future clinical trials. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06083155.

Continuous infusion thermodilution is an established technique for the assessment of absolute coronary blood flow and microvascular resistance due to its proven accuracy and reproducibility. However, for this technique to yield reliable measurements, direct and homogenous mixing of injected saline and blood is mandatory. This study aimed to assess and compare the mixing properties of two different microcatheters, namely the Rayflow® (with sideholes for infusion) and the Finecross® catheter (single end-hole for infusion), which are commonly used in the catheterization laboratory. The study employed three different methods to evaluate the mixing properties of the catheters. Firstly, a qualitative assessment of mixing was performed using ink injections in an in vitro bench model of a coronary artery. Secondly, in analogy to the human catheterization laboratory, mixing properties over the length of the coronary artery were assessed semi-quantitatively by temperature measurements in the bench model. Lastly, a quantitative assessment was performed by 3D computational fluid dynamics, where the standard deviation and entropy ratio of the temperature over the cross-section in the coronary artery model were calculated for both catheters. All three evaluation methods demonstrated that the Rayflow catheter’s specific design leads to a more optimal, homogeneous mixture of blood and saline over both the cross-section and length of a coronary vessel, as compared with the standard end-hole catheter. Methods and main results are shown for in vitro measurements and 3D computational fluid dynamics.

BACKGROUND: Coronary vasomotor dysfunction is diagnosed by a coronary function testing (CFT). However, protocols vary, and the influence of access site and concomitant vasodilator medication on the diagnostic yield and safety of CFT is unclear. This study assessed the diagnostic yield and safety of CFT by radial access with intraarterial calcium channel blockers compared with CFT by femoral access. METHODS: Data were obtained from the Netherlands Registry of Invasive Coronary Vasomotor Function Testing, a Dutch multicenter collaboration on CFT. Patients who underwent CFT between December 2020 and July 2025 were included. RESULTS: A total of 1885 patients were included, 1436 (76.2%) with primary radial access and 380 (20.2%) with primary femoral access. In 69 (3.7%) patients conversion from radial to femoral access was necessary. The conversion group was analyzed separately. The total diagnostic yield of coronary vasomotor dysfunction was 78.5%. There was no significant difference in the prevalence of coronary vasomotor dysfunction between patients with primary radial versus femoral access (79.2% versus 75.3%; P =0.1). There was also no difference in total diagnostic yield between the group without conversion and the conversion group (78.4% versus 82.6%; P =0.4); however, spasm was more prevalent in the conversion group (67.7% versus 79.4%; P =0.04). There were no differences in CFT complication rates between groups. CONCLUSIONS: Primary radial access with routine administration of calcium channel blockers was not associated with a lower diagnostic yield in CFT than primary femoral access. Procedural safety was comparable.