Background: The use of acetylcholine for the diagnosis of vasospastic angina is recommended by international guidelines. However, its intracoronary use is still off-label due to the absence of safety studies. We aimed to perform a systematic review of the literature to identify adverse events related to the intracoronary administration of acetylcholine for vasoreactivity testing to fill this gap. Methods and results: We conducted a systematic review of observational studies and randomized controlled trials dealing with the intracoronary administration of acetylcholine. Articles were searched in MEDLINE (PubMed) using the MeSH strategy. Three independent reviewers determined whether the studies met the inclusion and exclusion criteria. A total of 434 articles were selected. Data concerning clinical characteristics, study population, acetylcholine dosage, and adverse effects were retrieved from the articles. Overall, 71,566 patients were included, of which only 382 (0.5%) developed one adverse event, and there were no fatal events reported (0%). Conclusions: Intracoronary administration of acetylcholine in the setting of coronary spasm provocation testing is safe and plays a central role in the evaluation of coronary vasomotion disorders, making it worthy of becoming a part of clinical practice in all cardiac catheterization laboratories.

Aims To investigate the correlation between quantitative flow ratio (QFR), Pd/Pa, diastolic hyperaemia-free ratio (DFR), and fractional flow reserve (FFR, gold standard) in non-culprit lesion (NCL) of patients with non ST-segment elevation myocardial infarction (NSTEMI). The non-hyperemic pressure ratio (NHPR) and the angiography-based indexes have been developed to overcome the limitation of the use of the FFR. Methods and results Between January and December 2019, 184 NCL from 116 NSTEMI patients underwent physiologic assessment and were included in the study. NCLs were investigated with QFR, Pd/Pa, DFR, and FFR. Mean values of QFR, Pd/Pa, DFR, and FFR were 0.85 ± 0.10, 0.92 ± 0.07, 0.93 ± 0.05, and 0.84 ± 0.07, respectively. DFR and FFR showed a good correlation (r = 0.76). Bland and Altman plot showed a mean difference of 0.080. DFR diagnostic accuracy was 88%. The area under the ROC curve (AUC) for DFR was 0.946 (95% CI: 0.90–0.97, P = 0.0001). Similar findings were reported for Pd/Pa [r = 0.73; mean difference 0.095, diagnostic accuracy 84%, AUC 0.909 (95% CI: 0.85–0.94, P = 0.0001)] and QFR [r = 0.68; mean difference: 0.01; diagnostic accuracy: 88%, AUC: 0.964 (95% CI: 0.91–0.98, P = 0.0001)]. FFR, QFR, Pd/Pa, and DFR identified 31%, 32%, 30%, and 32% potentially flow-limiting lesions, respectively. Conclusions In NSTEMI patients, QFR, Pd/Pa, and DFR showed equivalence as compared to gold standard FFR in the discrimination of non-culprit lesions requiring revascularization.

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Purpose Coronary vasomotor dysfunction embraces two specific clinical entities: coronary (micro)vascular spasm and microvascular dysfunction. The clinical manifestations of these entities are respectively called vasospastic angina (VSA) and microvascular angina (MVA). Over the years, these diseases have become more and more prominent and several studies aimed to investigate the best diagnostic and therapeutic strategies. Patients with coronary vasomotor disorders are often undertreated due to the absence of evidence-based guidelines. The purpose of this overview is to illustrate the various therapeutic options available for the optimized management of these patients. Methods A Medline search of full-text articles published in English from 1980 to April 2022 was performed. The main analyzed aspects of vasomotor disorders were treatment options. We also performed research on “Clinicaltrial.gov” for ongoing trials. Conclusion Coronary (micro)vascular spasm and microvascular dysfunction are clinical entities characterized by high prevalence and clinical representation. Several therapeutic strategies, both innovative and established, are available to optimize treatment and improve the quality of life of these patients.

To test whether quantitative flow ratio (QFR)-based trans-stent gradient (TSG) is associated with adverse clinical events at follow-up. A post-hoc analysis of the multi-center HAWKEYE study was performed. Vessels post-PCI were divided into four groups (G) as follows: G1: QFR ≥ 0.90 TSG = 0 (n = 412, 54.8%); G2: QFR ≥ 0.90, TSG > 0 (n = 216, 28.7%); G3: QFR < 0.90, TSG = 0 (n = 37, 4.9%); G4: QFR < 0.90, TSG > 0 (n = 86, 11.4%). Cox proportional hazards regression model was used to analyze the effect of baseline and prognostic variables. The final reduced model was obtained by backward stepwise variable selection. Receiver operating characteristic (ROC) was plotted and area under the curve (AUC) was calculated and reported. Overall, 449 (59.8%) vessels had a TSG = 0 whereas (40.2%) had TSG > 0. Ten (2.2%) vessel-oriented composite endpoint (VOCE) occurred in vessels with TSG = 0, compared with 43 (14%) in vessels with TSG > 0 (p < 0.01). ROC analysis showed an AUC of 0.74 (95% CI: 0.67 to 0.80; p < 0.001). TSG > 0 was an independent predictor of the VOCE (HR 2.95 [95% CI 1.77–4.91]). The combination of higher TSG and lower final QFR (G4) showed the worst long-term outcome while low TSG and high QFR showed the best outcome (G1) while either high TSG or low QFR (G2, G3) showed intermediate and comparable outcomes. Higher trans-stent gradient was an independent predictor of adverse events and identified a subgroup of patients at higher risk for poor outcomes even when vessel QFR was optimal (> 0.90).