Acetylcholine Provocation Test Research Articles

Usefulness of temporary pacemaker during acetylcholine provocation testing

Usefulness of temporary pacemaker during acetylcholine provocation testing

Genetic associations of cardiovascular risk genes in European patients with coronary artery spasm.

Coronary artery spasm (CAS) is a frequent finding in patients presenting with angina pectoris. Although the pathogenesis of CAS is incompletely understood, previous studies suggested a genetic contribution. Our study aimed to elucidate genetic variants in a cohort of European patients with angina and unobstructed coronary arteries who underwent acetylcholine (ACh) provocation testing. A candidate association analysis of 208 genes previously associated with cardiovascular conditions was performed using genotyped and imputed variants in patients grouped in epicardial (focal, diffuse) CAS (n = 119) and microvascular CAS (n = 87). Patients with a negative ACh test result (n = 45) served as controls. We found no association below the genome-wide significance threshold of p < 5 × 10-8, thus not confirming variants in ALDH2, NOS3, and ROCK2 previously reported in CAS patients of Asian ancestry. However, the analysis identified suggestive associations (p < 10-05) for the groups of focal epicardial CAS (CDH13) and diffuse epicardial CAS (HDAC9, EDN1). Downstream analysis of the potential EDN1 risk locus showed that CAS patients have significantly increased plasma endothelin-1 levels (ET-1) compared to controls. An EDN1 haplotype comprising rs9349379 and rs2070698 was significantly associated to ET-1 levels (p = 0.01). In summary, we suggest EDN1 as potential genetic risk loci for patients with diffuse epicardial CAS, and European ancestry. Plasma ET-1 levels may serve as a potential cardiac marker.

Relation of Vasoreactivity in the Left and Right Coronary Arteries During Acetylcholine Spasm Provocation Testing

The diagnosis of vasospastic angina (VSA) according to Japanese guidelines involves an initial intracoronary acetylcholine (ACh) provocation test in the left coronary artery (LCA) followed by testing in the right coronary artery (RCA). However, global variations in test protocols often lead to the omission of ACh provocation in the RCA, potentially resulting in the underdiagnosis of VSA. This study assessed the validity of the LCA-only ACh provocation approach for the VSA diagnosis and whether vasoreactivity in the LCA aids in determining further provocation in the RCA. A total of 273 patients who underwent sequential intracoronary ACh provocation testing in the LCA and RCA were included. Patients with a positive ACh provocation test in the LCA were excluded. Relations between vasoreactivity in the LCA and ACh test outcomes (positivity and adverse events) in the RCA were evaluated. In patients with negative ACh test results in the LCA, subsequent ACh testing was positive in the RCA in 23 out of 273 (8.4%) patients. Among patients with minimal LCA vasoconstriction (<25%), only 3.0% had a positive ACh test in the RCA, while the ACh test in the RCA was positive in 13.5% of those with LCA constriction of 25-90% (p=0.002). No major adverse events occurred during ACh testing in the RCA. In conclusion, for the VSA diagnosis, the omission of ACh provocation in the RCA may be clinically acceptable, particularly when vasoconstriction induced by ACh injection was minimal in the LCA. Further studies are needed to define ACh provocation protocols worldwide.

Coronary Microvascular Disease Registry (CMDR): Study design and rationale

BackgroundCoronary microvascular dysfunction (CMD) is a prevalent condition among patients with cardiovascular risk factors, leading to a reduced quality of life and an increased risk of major adverse cardiovascular events. Novel invasive techniques have emerged to more accurately diagnose CMD. However, CMD's natural history remains poorly understood due to limited data. To address this knowledge gap, the Coronary Microvascular Disease Registry (CMDR) was established with the primary aim of standardizing comprehensive coronary functional testing and understanding of CMD. DesignCMDR is a prospective, multicenter registry enrolling an unlimited number of consecutive subjects who undergo comprehensive invasive hemodynamic assessment of the entire coronary arterial vasculature. Patients undergoing acetylcholine provocation test for coronary vasospasm will also be included. Follow-up assessments will be conducted at 30 days and annually for up to 5 years. The primary endpoint is Canadian Cardiovascular Society angina grade over time. Secondary endpoints, including all-cause mortality, cardiovascular death, acute myocardial infarction, stroke, hospitalizations, medication changes, and subsequent coronary interventions, will be analyzed to establish long-term safety and clinical outcomes in patients undergoing invasive CMD assessment. SummaryCMDR aims to characterize the clinical and physiologic profile of patients undergoing comprehensive invasive coronary functional testing, simultaneously providing crucial longitudinal information on the natural history and outcomes of these patients. This will shed light on CMD's course and clinical implications, which, in turn, holds the potential to significantly improve diagnostic and treatment strategies for CMD patients, ultimately leading to the enhancement of their overall prognosis and quality of life. Clinical trial registrationclinicaltrials.gov, NCT05960474

Long-term prognostic factors for cardiovascular events in patients with chest pain without diabetes mellitus nor significant coronary stenosis.

Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD nor DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of total death, myocardial infarction (MI), revascularization, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5years. Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal antianginal medication therapy. However, a recurrent chest pain remains a problem even with continuous antianginal medication therapy. Up to 5 years, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia (HR: 2.010, 95% CI 1.166-3.466, P = 0.012), mild-moderate (30-70%) coronary stenosis (HR: 2.369, 95% CI 1.118-5.018, P = 0.024), the use of aspirin (HR: 2.885, 95% CI 1.588-5.238, P < 0.001), and the use of nitrates (HR: 1.938, 95% CI 1.094-3.433, P = 0.023) were independent risk factors for MACCE. Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with antianginal medications.

The invasive investigation of INOCA in the coronary catheterization lab

Over half of all patients with angina have no angiographically demonstratable obstructive coronary disease, with a significant proportion of these patients having undiagnosed microvascular dysfunction and/or vasospastic angina. In chronic coronary syndrome, ischemia with non-obstructive coronary artery disease (INOCA) often remains undiagnosed, or uninvestigated. INOCAmay occur due to vasospastic angina and microvascular dysfunction and require invasive assessment in the coronary catheterization lab. To evaluate INOCA coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are used to assess microvascular dysfunction before acetylcholine provocation testing for coronary spasm. This review provides an overview of the invasive investigation of INOCA in the coronary catheterization lab for patients with angina to be optimally managed.

Safety and potential usefulness of sequential intracoronary acetylcholine and ergonovine administration for spasm provocation testing.

Although guidelines recommend intracoronary acetylcholine (ACh) and ergonovine (ER) provocation testing for diagnosis of vasospastic angina, the feasibility and safety of sequential (combined) use of both pharmacological agents during the same catheterization session remain unclear. In this study, we investigated the feasibility and safety of sequential intracoronary ACh and ER administration for coronary spasm provocation testing. The study included 235 patients who showed positive results on ACh and ER provocation testing. Initial intracoronary ACh administration was followed by ER administration for left coronary artery (LCA) spasm provocation testing. Subsequently, the right coronary artery (RCA) was subjected to sequential ACh and ER administration for provocation testing. The primary outcome of the study was the safety of sequential intracoronary ACh and ER provocation testing, which was assessed based on a composite of all-cause death, sustained ventricular tachycardia and fibrillation, and cardiogenic shock. Even in patients with negative results on sequential intracoronary ACh and ER provocation testing in the LCA and only ACh administration into the RCA, additional administration of ER into the RCA showed a positive provocation test result in 33 of 235 (14.0%) patients; three (1.3%) patients developed adverse effects (cardiogenic shock occurred in all cases) during LCA provocation testing. We observed no deaths attributable to spasm provocation testing. Sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of vasospastic angina.

Utility of Intracoronary Acetylcholine Provocation Testing in Inducing Atrial Fibrillation with Preexcitation Followed by Ventricular Fibrillation in a Patient with Wolff-Parkinson-White Syndrome: A Case Report.

A 20-year-old man was resuscitated after ventricular fibrillation (VF). Electrocardiography revealed Wolff-Parkinson-White (WPW) syndrome. Intracoronary acetylcholine provocation testing was performed to induce VF secondary to the coronary vasospasm. The administration of acetylcholine to the coronary artery induced atrial fibrillation (AF) with pre-excitation, followed by VF without coronary vasospasm. Electrophysiological studies revealed an accessory pathway managed by catheter ablation. Subsequent intracoronary acetylcholine provocation testing (ACH test) induced the occurrence of AF without preexcitation. To our knowledge, this case report is the first to demonstrate the utility of the ACH test in confirming WPW syndrome as a cause of VF.

Thrombolysis in Myocardial Infarction Frame Count for Coronary Blood Flow Evaluation during Interventional Diagnostic Procedures.

Background and Objectives: An interventional diagnostic procedure (IDP), including intracoronary acetylcholine (ACh) provocation and coronary physiological testing, is recommended as an invasive diagnostic standard for patients suspected of ischemia with no obstructive coronary arteries (INOCA). Recent guidelines suggest Thrombolysis In Myocardial Infarction frame count (TFC) as an alternative to wire-based coronary physiological indices for diagnosing coronary microvascular dysfunction. We evaluated trajectories of TFC during IDP and the impact of ACh provocation on TFC. Materials and Methods: This was a single-center, retrospective study. Patients who underwent IDP to diagnose INOCA were included and divided into two groups according to the positive or negative ACh provocation test. Wire-based invasive physiological assessment was preceded by ACh provocation tests and intracoronary isosorbide dinitrate (ISDN). We evaluated TFC at three different time points during IDP; pre-ACh, post-ISDN, and post-hyperemia. Results: Of 104 patients, 58 (55.8%) had positive ACh provocation test. In the positive ACh group, resting mean transit time (Tmn) and baseline resistance index were significantly higher than in the negative ACh group. Post-ISDN TFC was significantly correlated with resting Tmn (r = 0.31, p = 0.002). Absolute TFC values were highest at pre-ACh, followed by post-ISDN and post-hyperemia in both groups. All between-time point differences in TFC were statistically significant in both groups, except for the change from pre-ACh to post-ISDN in the positive ACh group. Conclusions: In patients suspected of INOCA, TFC was modestly correlated with Tmn, a surrogate of coronary blood flow. The positive ACh provocation test influenced coronary blood flow assessment during IDP.

A long-term prognostic factor for cardiovascular risk in patients with chest pain without diabetes mellitus and significant coronary stenosis

Abstract Background Chest pain is the most common symptom of coronary artery disease (CAD); diabetes mellitus (DM) is a well-known single largest risk factor for cardiovascular diseases and survival worldwide. So, the impact of CAD and DM on long-term clinical effects is reported widely. This study aimed to evaluate the long-term prognostic factor for major adverse cardiac and clinical events (MACCE) in patients with chest pain without DM and CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation test. Methods A total of 1,046 patients with chest pain without DM and significant CAD who underwent CAG and ACH tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. All subjects were followed clinically for up to 5 years. Results Coronary spasm (CAS) seems the most common cause of chest pain. However, long-term MACCE of CAS is not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal anti-anginal medication therapy. However, a repeated chest pain remains a problem even with continuous anti-anginal medication therapy. Up to 5-year follows, MACCE has occurred 7.3%, including recurrent angina of 6.9%. Dyslipidemia, mild to moderate CAD, and the use of aspirin/nitrates are associated with long-term MACCE. Conclusions Among the patients with chest pain without DM and significant CAD, the occurring major adverse cardiac events, including death, MI, and de novo CAD, are rare, but recurrent angina is still a challenging problem who had the treatment by anti-anginal medications.

Abstract 14202: Vasospastic Angina as a Potential Cause of Post-Acute Sequelae of COVID-19

Introduction: Although evidence-based practice of has progressed, little is known about underlying mechanisms of chest pain symptoms in patients with post-acute sequelae of COVID-19 (PASC) and preferred approaches for their assessment. Several mechanisms underlying COVID-19-related endothelial dysfunction have been proposed. The purpose of this study was to explore the prevalence of vasospastic angina as a cause of chest pain in PASC patients. Methods: We retrospectively reviewed 273 consecutive patients who presented to an outpatient unit for cardiovascular PASC between June 2021 and March 2023. After the initial evaluation with electro- and echocardiography, coronary computed tomography angiography or cardiac magnetic resonance imaging were performed to rule out obstructive coronary artery disease and myopericarditis if patients had intermittent chest pain and had no contraindications to these tests. When the patients’ chest pain mainly occurred at night and in the morning or was resolved by nitrates, invasive coronary angiography and acetylcholine provocation testing were performed to diagnose vasospastic angina. Results: Eight of 273 patients with PASC underwent acetylcholine provocation testing. The median time from the diagnosis of SARS-CoV2 infection to acetylcholine provocation testing was 197 (interquartile range, 120-542) days. The mean age of the patients was 37.1 years; two required oxygen support during acute COVID-19; and none had previous history of cardiovascular disease ( Figure ). Five of the 8 patients showed acetylcholine-induced multivessel coronary vasospasm and were diagnosed as vasospastic angina. Their chest pain improved with calcium channel blockers and nitrates, whereas nonfatal myocardial infarction occurred in one patient after the diagnosis of vasospastic angina. Conclusions: Our observational case series suggest that vasospastic angina should be considered as a potential cause of PASC.

Abstract 16620: Long-Term Prognostic Factors for Cardiovascular Events in Patients With Chest Pain Without Diabetes Mellitus and Significant Coronary Stenosis

Background: Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD and DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. Methods: A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiovascular events (MACE) were defined as the composite of total death, myocardial infarction (MI), and revascularization. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of MACE, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Results: Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal anti-anginal medication therapy. However, a recurrent chest pain remains a problem even with continuous anti-anginal medication therapy. Up to 5-year, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia, ICS, the use of aspirin and nitrates were associated with long-term MACCE. Conclusions: Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with anti-anginal medications.

Management of myocardial infarction and ischemia without obstructive coronary arteries: insights from a case series

Acute coronary syndromes typically result from the formation of atherosclerotic lesions in a large epicardial vessel, which restrict blood flow either partially or completely. These lesions can be identified through angiography, an invasive imaging technique that enables visualization of the coronary arteries. However, a small percentage of patients, usually ranging from 5% to 10%, experience symptoms and/or signs of myocardial ischemia, either acute or chronic, without significant obstructive coronary lesions visible on angiography. This condition is particularly prevalent in young women and is characterized by two distinct forms: myocardial infarction with no obstructive coronary arteries (MINOCA) and myocardial ischemia with no obstructive coronary arteries (INOCA). MINOCA can be caused by a variety of heterogeneous mechanisms, including coronary vascular spasm, microvascular disease, spontaneous coronary dissection, and plaque rupture or erosion. Conversely, coronary vasospasm and microvascular dysfunction account for the majority of patients with INOCA. We here present three cases of MINOCA/INOCA that were evaluated using optical coherence tomography, coronary flow reserve, index of microcirculatory resistance, and acetylcholine provocative test. These diagnostic tests allowed us to identify a specific condition and adopt a targeted treatment for each patient.

TCT-654 Coronary Vasomotor Response to Intracoronary Acetylcholine Provocation Test According to the Severity of an Insignificant Coronary Artery Stenosis

TCT-654 Coronary Vasomotor Response to Intracoronary Acetylcholine Provocation Test According to the Severity of an Insignificant Coronary Artery Stenosis

Coronary vasospasms induced by a dexmedetomidine infusion for deep sedation during catheter ablation in a patient with negative findings of an acetylcholine provocation test.

Coronary vasospasms induced by a dexmedetomidine infusion for deep sedation during catheter ablation in a patient with negative findings of an acetylcholine provocation test.

Omitting 50 μg of intracoronary acetylcholine injection in the left coronary artery during spasm provocation test

BackgroundAlthough guidelines recommend intracoronary administration of acetylcholine (ACh) with incremental doses of 20, 50, and 100 μg into the left coronary artery (LCA) during spasm provocation test for diagnosing vasospastic angina, 50 μg of ACh rarely induced significant coronary vasospasm when no vasoconstriction was observed with 20 μg of ACh in a previous report. The aim of this study was to evaluate the safety and feasibility of omitting 50 μg according to the vasoreactivity by 20 μg of ACh in the LCA. MethodsA total of 556 patients undergoing ACh provocation test with 20 μg followed by 50 and/or 100 μg were retrospectively included. Injection of 50 μg of ACh was primarily omitted when vasoconstriction <25 % was observed with 20 μg, which was left to operator's discretion. Adverse events were defined as a composite of ventricular fibrillation, sustained ventricular tachycardia, and cardiogenic shock during ACh test in the LCA. ResultsPositive ACh test in the LCA was observed in 245 (44.1 %) patients. Overall, patients with LCA constriction <25 % by 20 μg of ACh had a lower rate of positive ACh test than their counterpart (24.0 % vs. 88.4 %, p < 0.001). In patients with LCA constriction ≥25 % by 20 μg, the incidence of adverse events was significantly higher than in those with LCA constriction <25 % during the provocation test at doses of 50 and 100 μg (2.3 % vs. 0 %, p = 0.009). ConclusionsOmitting 50 μg of ACh in the LCA may be safe and feasible when little vasoconstriction was observed with preceding injection of 20 μg of ACh during spasm provocation test for diagnosing vasospastic angina. However, we believe that 50 μg of ACh should not be omitted when 20 μg of ACh induced LCA constriction ≥25 %.

Differences in Clinical and Angiographic Characteristics Following Intracoronary Ergnovine and Acetylcholine Provocation Test in Hypertension Patients

Differences in Clinical and Angiographic Characteristics Following Intracoronary Ergnovine and Acetylcholine Provocation Test in Hypertension Patients

Differences in Clinical and Angiographic Parameters Following Intracoronary Ergonovine and Acetylcholine Provocation Test in Elderly Patients

Differences in Clinical and Angiographic Parameters Following Intracoronary Ergonovine and Acetylcholine Provocation Test in Elderly Patients

Utility of Temporary Pacemaker During Acetylcholine Provocation Testing

Utility of Temporary Pacemaker During Acetylcholine Provocation Testing

Impact of preceding acetylcholine provocation testing on following coronary physiological assessment during an interventional diagnostic procedure

BackgroundIntracoronary acetylcholine (ACh) provocation test and coronary physiological assessment are useful interventional diagnostic procedures for evaluating ischemia with no obstructive coronary arteries (INOCA). However, the appropriate sequential order of the diagnostic procedures has been a matter of debate. We investigated the impact of preceding ACh provocation on following coronary physiological assessment. MethodsPatients suspected of INOCA underwent invasive coronary physiological assessment using thermodilution method and were divided into two groups according to the implementation of ACh provocation test. The ACh group was further divided into the positive and negative ACh groups. In the ACh group, intracoronary ACh provocation was performed before the invasive coronary physiological assessment. The main interest of this study was to compare coronary physiological indices among the no ACh, negative ACh, and positive ACh groups. ResultsOf 120 patients, the no ACh, and negative and positive ACh groups included 46 (38.3 %), 36 (30.0 %), and 38 (31.7 %), respectively. Fractional flow reserve was lower in the no ACh group than in the ACh group. Resting mean transit time was significantly longer in the positive ACh group, followed by the no ACh and negative ACh groups (1.22 ± 0.55 vs. 1.00 ± 0.46 vs. 0.74 ± 0.36 s, p < 0.001). Index of microcirculatory resistance and coronary flow reserve did not differ significantly among the three groups. ConclusionsPreceding ACh provocation influenced following physiological assessment, particularly when ACh test was positive. Further studies are warranted to determine which interventional diagnostic procedure, ACh provocation or physiological assessment, should be preceded in the invasive evaluation of INOCA.