Acetylcholine Test Research Articles

Age-related differences and vascular function test findings in patients with vasospastic angina

Abstract Background Vasospastic angina (VSA) accounts for the majority of angina cases with no epicardial stenosis and develops amongawide range of age, which is reportedly induced by coronary functional abnormalities including endothelial dysfunction and smooth muscle hypercontraction. However, the relation of noninvasive vascular function tests to VSA remains to be fully elucidated. Purpose The aim of this study was to assess differences in clinical characteristics and findings from noninvasive vascular function tests among groups by age in patients with VSA. Methods We enrolled a total of 732 patients with angina who underwent intracoronary acetylcholine provocation test. VSA was defined as total or subtotal occlusion of epicardial coronary arteries accompanied by chest pain and/or ischemic electrocardiographic changes in response to acetylcholine administration. Patients with VSA were divided into 3 groups by age (young [<50 years], intermediate [50–64 years], and elderly group [≥65 years]). Noninvasive vascular function test findings such as ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), andpercentage of mean arterial pressure (%MAP) were compared among groups by age in patients with VSA. Results Of all patients, 367 (50.1%) were diagnosed as VSA with intracoronary acetylcholine test, including 66 (18.0%), 113 (30.8%), and 188 (51.2%) patients in the young, intermediate, and elderly groups. Among groups by age, there was no significant difference in gender (female, 31.8% vs. 40.7% vs. 44.7%, P=0.19). Patients in the young group were more often smokers and alcohol drinkers than those in the intermediate and elderly groups, while the prevalence of hypertension, dyslipidemia, and diabetes were lower in younger patients. A history of percutaneous coronary intervention was less frequently found in the young group compared tothe intermediate and elderly groups (7.6% vs. 16.8% vs. 20.7%, P=0.033). The baPWV was higher in the elderly group (1424±232 vs. 1537±247 vs. 1774±358 cm/s, P<0.0001), while there was no difference in ABI between the 3 groups. %MAP at arms was significantly and progressively decreased with an increase in age (54.0±4.5% vs. 53.0±2.6% vs. 51.2±2.8%, P<0.0001). Conclusion Our study demonstrated that there were distinct age-related differences in clinical characteristics of patients with VSA. The higher %MAP in younger patients suggests that more impaired endothelial dysfunction may play a role in the development of VSA in this age group. Funding Acknowledgement Type of funding source: None

Sex differences in patients with ischemia and no obstructive coronary disease subjected to intracoronary acetylcholine test in a multicenter registry

Abstract Background Ischemia with no obstructive coronary disease (INOCA) is increasingly diagnosed because of wide performance of coronary angiography. Prevalence of INOCA is higher in women than in men, however the exact pathophysiological mechanisms which may explain this phenomenon are still not very well understood. Objective To evaluate differences in clinical and procedural characteristics between men and women with INOCA subjected to intracoronary acetylcholine test (Ach). Methods A total of 210 women and 148 men with INOCA diagnosed with coronary angiography, were prospectively enrolled in a multicenter, observational registry. Ach test was performed according to clinical indications in all included patients. After 1-year patients were re-evaluated for major cardiovascular events, angina symptoms and prescribed medical treatment. Results Mean age of 60.6±13.6 years old was similar in both populations, but differences were observed in the prevalence of risk factors: active smoking was more frequent among men (43% vs. 17%, p<0.001), who had also a higher number of associated risk factors (≥3 risk factors were present in 31.2% of men vs. 20.2% of women, p<0.01) and more frequent history of percutaneous coronary revascularization (14.2% vs. 6.7%, p=0.03). Women were more prone to have dyspnea than men (35.5% vs. 20.8%, p=0.01). Men had more coronary atherosclerosis in angiography (57.9% vs. 43.7%, p=0.01) and more slow flow in the left anterior descending artery (21.6% vs. 9.0%, p=0.001). Ach was positive in 36.5% of patients, similar in both sexes, with no differences in the type of induced coronary spasm. Among those with a positive Ach test, at one-year, 36% of women vs. 43.6% of men were on optimal medical treatment for vasospasm although the difference was not statistically significant. Importantly, 41.5% of women and 38.1% of men experienced severe symptoms of angina during follow-up. Conclusions Although men with INOCA have a higher risk profile than women and more coronary atherosclerosis, one third of patients present endothelial dysfunction, similar in both groups, indicating that probably other pathophysiological mechanisms are responsible for it in females. Treatment in these patients remains suboptimal and associated with highly impaired quality of life. Funding Acknowledgement Type of funding source: None

Intracoronary imaging assessment of atherosclerosis in vasomotor dysfunction and phenotypes of non-obstructive coronary artery disease

Abstract Background A consistent portion of patients with stable angina is affected by coronary vasomotor dysfunction, in the form of epicardial vasospasm (VSA) or coronary microvascular dysfunction (CMD). Although available data suggest a worse prognosis compared to normal population, anatomical background and associations with atherosclerosis are still uncertain. Purpose To define specific morphological features in patients with stable angina and coronary vasomotor dysfunction. Methods We enrolled all patients referred to our laboratory in the first half of 2019 for coronary reactivity testing (CRT) for stable angina and suspected vasomotor dysfunction. After confirming non-obstructive coronary artery disease by angiography, CRT consisted of acetylcholine test and physiology assessment with resting and hyperemic indexes. In addition, optical coherence tomography (OCT) was performed. All tests were performed in the left anterior descending artery. Patients were divided in 3 groups: VSA, CMD and control group (no CMD/VSA), according to international COVADIS consensus documents. Two independent reviewers assessed the OCTs to identify markers of atherosclerosis. Results We enrolled 48 patients. Mean age was 55.19±7.71 years. 46 (96%) were females. 3 patients were removed due to mixed VSA and CMD, resulting in 45 subjects eligible for analysis: 17 had VSA, 22 CMD and 6 were controls. Baseline characteristics, resting and hyperemic indexes were similar in the groups, except for the index of microvascular resistance (IMR), being higher in CMD group. Moving from control group, to CMD, to VSA, OCT suggested a trend of increasing prevalence of fibroatheromas (0% in controls, 36% in CMD, 47% in VSA, p 0.12), thin-cap fibroatheromas (0% vs 18% vs 29%, respectively, p 0.29) and neovascularisation (17% vs 23% vs 47%, p 0.19). On the other hand, macrophage infiltration was higher in CMD group (55% in CMD, vs 47% in VSA, vs 33% in controls, p 0.64). Plaques covered 43% of the vessel in VSA group (34% being lipid-rich), 35% in CMD (lipid: 36%) and 30% in controls (p 0.69; 17% lipid). Lipid pools showed a different distribution across the groups. Control group had small pools (mean/max lipid arc 56/65°, length: 5.5 mm), CMD showed intermediate width (arc 82/106°), but long extension (11.5 mm), while VSA had large pools (94/127°, p 0.05/0.08), with intermediate length (7 mm, p 0.58). Lipid index (mean arc x lipid length) was similar in VSA (632) and CMD (642), but lower in control group (203, p 0.35). Conclusions This study hints at atherosclerosis as an underlying pathophysiology in VSA and CMD. A trend to increasing burden, both in terms of extension and vulnerability, was observed across patients with normal arteries, CMD and VSA. Peculiar patterns of atherosclerosis may be associated with specific phenotypes of vasomotor dysfunction, with larger lipid pools and neovascularization being associated with VSA and macrophage infiltration being more common in CMD. Funding Acknowledgement Type of funding source: None

Coronary microvascular dysfunction in patients with mild-to-moderate aortic stenosis – Insights from intracoronary acetylcholine testing

Coronary microvascular dysfunction in patients with mild-to-moderate aortic stenosis – Insights from intracoronary acetylcholine testing

Assessment of coronary vasomotor responses to acetylcholine in German and Japanese patients with epicardial coronary spasm-more similarities than differences?

Coronary spasm is an established cause for angina pectoris. Ethnic differences have been suggested among Asian compared to Caucasian patients regarding prevalence, gender distribution, and angiographic patterns of coronary spasm. The aim of this study was to compare contemporary German and Japanese patients with coronary spasm. Between 2011 and 2015, 149 patients with resting angina and unobstructed coronary arteries with acetylcholine-induced epicardial spasm were enrolled in Stuttgart, Germany (n = 69) and Sendai, Japan (n = 80). All patients underwent intracoronary acetylcholine testing according to a standardized protocol. Comprehensive analysis included type of spasm (focal/diffuse), dose of acetylcholine leading to spasm, and frequency of multivessel spasm. Patients in this study were 61 ± 11years old, predominantly female (54%), and had normal left ventricular ejection fraction (73 ± 9%). Diffuse spasm was the most prevalent type of spasm (85%) whereas focal spasm was found in the remaining 15% of patients. 31% of patients had multivessel spasm. Comparing the German with the Japanese patients, distribution of spasm type (focal/diffuse, p = 0.19) and frequency of multivessel spasm (p = 0.22) were comparable. Moreover, when Japanese patients were compared with German patients and diffuse spasm with focal spasm patients, respectively, no significant differences were observed regarding the acetylcholine dose required to induce spasm (p = 0.078 and p = 0.46, respectively). In conclusion, diffuse epicardial coronary spasm is the most frequent finding among German and Japanese patients with resting angina, unobstructed coronary arteries, and epicardial spasm on acetylcholine testing. Japanese and German patients share several similarities including comparable types of spasm and frequency of multivessel spasm.

Vasospastic angina and overlapping cardiac disorders in patients resuscitated from cardiac arrest.

Vasospastic angina (VSA) reportedly accounts for one form of sudden cardiac arrest (SCA). Intracoronary acetylcholine (ACh) testing is useful for diagnosing VSA although invasive provocation testing after SCA is a clinical challenge. In addition, even if the ACh test is positive, any causal relationship between VSA and SCA is often unclear because patients with VSA may have other underlying cardiac disorders. A total of 20 patients without overt structural heart disease who had been fully resuscitated from SCA were included. All patients underwent the ACh provocation test and scrutiny such as cardiac computed tomography or magnetic resonance imaging. Patients were followed up for all-cause death or recurrent SCA including appropriate implantable cardioverter defibrillator therapy. An ACh provocation test was performed 20 ± 17days after cardiac arrest. Fifteen out of 20 (75.0%) patients had a positive ACh test and 2 (10.0%) had adverse events such as ventricular tachycardia and transient cardiogenic shock during the test. In patients with a positive ACh test, 6 of 15 (40.0%) patients had other overlapping cardiac disorders such as long QT syndrome, Brugada syndrome, cardiac sarcoidosis, myocarditis, or cardiomyopathy. Long-term prognosis was not different regardless of a positive ACh test or the presence of other cardiac disorders overlapping with VSA. Three-quarters of the patients who had been resuscitated from SCA had a positive ACh test. Further examinations revealed other overlapping cardiac disorders in addition to VSA in 40% of patients with a positive ACh test.

Long-Term Follow-Up in Patients With Stable Angina and Unobstructed Coronary Arteries Undergoing Intracoronary Acetylcholine Testing

ObjectivesThe aim of this study was to investigate the prognosis of a large cohort of patients with stable angina and unobstructed coronaries undergoing acetylcholine spasm testing. BackgroundCoronary artery spasm can be found in up to 60% of patients with symptoms of myocardial ischemia despite unobstructed coronary arteries. MethodsConsecutive symptomatic patients with unobstructed coronary arteries undergoing acetylcholine testing to detect epicardial or microvascular coronary spasm were prospectively enrolled. After a median follow-up period of 7.2 years (6.5 to 7.9 years), data regarding mortality, nonfatal myocardial infarction, stroke, repeat coronary angiography, recurrent symptoms, and quality of life were obtained in 736 patients (57% women, mean age 62 ± 12 years). ResultsIn total, 55 deaths (7.5%), 8 nonfatal myocardial infarctions (1.4%), and 12 strokes (2.2%) occurred during the follow-up period. Recurrent symptoms were reported by 64% of patients, and repeat coronary angiography was performed in 12% of cases. Multivariate analysis revealed epicardial spasm as a predictor of nonfatal myocardial infarction (hazard ratio: 14.469; 95% confidence interval: 1.735 to 120.646) and repeat angiography (hazard ratio: 1.703; 95% confidence interval: 1.062 to 2.732), whereas patients with microvascular spasm more often had recurrent angina at follow-up (hazard ratio: 1.311; 95% confidence interval: 1.013 to 1.697). ConclusionsIn this long-term follow-up study, the overall prognosis of patients with coronary spasm was favorable. Patients with epicardial spasm were at increased risk for myocardial infarction and repeat angiography, while microvascular spasm was associated with recurrent angina. Acetylcholine testing may help identify patients at increased risk for adverse cardiac events among this overall low-risk population.

Mental Health Status in Patients Undergoing Intracoronary Acetylcholine Provocation Test.

Previous studies showed the relation of mental distress such as anxiety and depression to coronary vasoconstriction and myocardial ischemia. However, the mental health status of patients suspected to have vasospastic angina is unclear. A total of 99 patients underwent intracoronary acetylcholine (ACh) provocation tests for the diagnosis of vasospastic angina and mental health assessment using the 12-item General Health Questionnaire (GHQ-12) and State-Trait Anxiety Inventory Form Y (STAI Y-2). Patients with binary GHQ-12 ≥ 4 were defined as having poor mental health. Median GHQ-12 and STAI Y-2 were 3 [1, 6] and 44 [36, 50]. Forty-one (41%) patients had binary GHQ-12 ≥ 4, and 48 (48%) had positive ACh provocation tests. The number of provoked vasospasms and rate of electrocardiographic change and chest pain during ACh tests were not significantly different between patients with and without GHQ-12 ≥ 4. The incidence of positive ACh provocation test was similar between the two groups (49% vs. 48%, p = 1.00). The multivariable analysis indicated that younger age, no history of percutaneous coronary intervention and no diabetes mellitus were factors associated with higher GHQ-12 and/or STAI Y-2 scores. More than 40% of patients who underwent ACh provocation tests had poor mental condition. No impact of mental distress on positive ACh tests was found in this study.

Safety assessment and results of coronary spasm provocation testing in patients with myocardial infarction with unobstructed coronary arteries compared to patients with stable angina and unobstructed coronary arteries.

Coronary spasm is an established cause for myocardial infarction with unobstructed coronary arteries, and can be diagnosed using intracoronary acetylcholine testing. However, it has been questioned whether such testing is feasible and safe in the acute phase. The aim of this study was to assess the frequency of coronary spasm and the safety of the acetylcholine test in patients with myocardial infarction with unobstructed coronary arteries compared to patients with stable angina and unobstructed coronaries. One hundred and eighty selected patients (52% women, mean age 62±13 years) with either myocardial infarction with unobstructed coronary arteries (n=80) or stable angina and unobstructed coronaries (n=100) were enrolled from 2007-2018. All patients underwent the acetylcholine test according to a standardised protocol immediately after diagnostic angiography. Apart from assessment of clinical, demographic and risk factor data, side effects and complications during the acetylcholine test were recorded. Overall, epicardial spasm was found in 26% with a higher prevalence among the myocardial infarction with unobstructed coronary arteries compared to the stable angina patients (35% vs 19%, p=0.017). Microvascular spasm was found in 42% with a higher prevalence among the stable patients compared to the myocardial infarction with unobstructed coronary arteries cohort (53% vs 29%, p=0.0014). There were no statistically significant differences in the rate of side effects (16% vs 14%, p=0.674) or complications (1% vs 2.5%, p=0.438) between the two groups. None of the patients experienced irreversible complications. Coronary spasm is a frequent cause for myocardial infarction with unobstructed coronary arteries. Spasm provocation testing using acetylcholine is feasible in such patients in the acute phase. The complication rate during acetylcholine testing in myocardial infarction with unobstructed coronary arteries patients is low and comparable to patients with stable angina.

Rethinking respiratory function laboratories in the era of coronavirus disease 2019: Considerations for today and the day after

Rethinking respiratory function laboratories in the era of coronavirus disease 2019: Considerations for today and the day after

Short- and mid-term influence of drug-coated stent implantation on structural and functional vascular healing response: An optical coherence tomography and acetylcholine testing study.

This study investigated the effect of a drug-coated stent (DCS) that has a novel microporous abluminal surface without a polymer on 1-month and 1-year functional and morphological healing response as assessed using acetylcholine (Ach) testing and optical coherence tomography (OCT). DCS is expected to induce favorable morphological and physiological arterial healing after its implantation. A total of 11 patients who underwent vascular response examinations 1-month and 1-year after the index PCI with DCS implantation were enrolled. The vascular response was evaluated by the functional response test by acetylcholine infusion, the morphological response test by OCT. Although 94.5% of the DCS struts were covered by homogeneous smooth neointima at 1 month, the percentage of neointimal coverage increased to 98.5% at 1 year (p = .02). Conversely, the proportion of uncovered struts and malapposed struts at 1 year were 1.2 and 0.7%, respectively. Furthermore, the coronary vasomotor response to incremental doses of Ach were impaired especially in the distal segments at each period, although the responses to Ach at 10-6 mol/L in the distal segment tended to improve over time from baseline to 1 month and 1 year later (-19 ± 20%, -9 ± 17%, and -5 ± 14%, respectively; p = .27). The morphological assessment of DCS with OCT revealed a high degree of strut coverage and apposition at 4 weeks after implantation. The impaired endothelium-dependent vasomotor response tended to improve chronologically from baseline to 1 month and 1 year later.

Pharmacological spasm provocation testing in 2500 patients: provoked spasm incidence, complications and cardiac events

Pharmacological spasm provocation tests such as acetylcholine (ACh) and ergonovine (ER) had been performed in the clinic. We retrospectively analyzed the incidence of provoked spasm, complications during testing and the cardiac events after these tests. From January 1991 and October 2018, we performed pharmacological spasm provocation tests in 2500 patients: 1810 ACh tests, 1232 ER tests, 542 both tests, and 310 ACh added after ER tests. ACh was injected in incremental doses of 20/50/100/200μg into the LCA and 20/50/80μg into the RCA. ER was administered as a total dose of 64μg into the LCA and 40μg into the RCA. When adding ACh after ER, the total dose was 50/80μg into the RCA and 100/200μg into the LCA. Positive spasm was defined as ≥ 90% stenosis and usual chest pain or ischemic ECG changes. Mean follow-up duration was 47.5 ± 29.9months. Overall, provoked positive spasm was found in 1095 patients (43.8%). The incidence of positive provoked spasm during ACh testing was significantly higher than that during other tests (ACh: 48.7% vs. ER: 28.9%, Both: 24%, ACh added after ER: 33.5%, p < 0.001). Multiple spasms were remarkably more frequent during ACh testing compared with the other 3 types of testing (ACh: 28.2% vs. ER: 7.4%, Both: 4.1%, ACh added after ER: 13.2%, p < 0.001). No death or acute myocardial infarction was observed, while major complications during ACh testing were significantly more frequent than during ER testing. Readmission due to recurrent angina pectoris in spasm-positive patients was remarkably more frequent than in spasm-negative patients. The incidence of sudden cardiac death, ventricular fibrillation, and acute coronary syndrome were not different between the spasm-positive and spasm-negative groups during the follow-up periods. We could perform all spasm provocation tests without any irreversible complications. All sequential spasm provocation tests were useful for documenting coronary spasm.

Decreased Double Product at Rest in Patients With Severe Vasospasm

Autonomic nerve system and endothelial function play important roles in vasospastic angina. Elevated heart rate (HR), blood pressure (BP), and double product (DP) can increase endothelial-dependent coronary artery dilation and blood flow. However, the impact of HR, BP, and DP on occurrence and severity of VSA in the clinical setting is unclear. A total of 170 patients undergoing intracoronary acetylcholine (ACh) provocation test during hospitalisation was included. Resting HR, BP, and DP were measured at least four times, and their variabilities were evaluated by standard deviations (SD) and coefficient of variations (CVs). Angiographic coronary artery vasospasm was defined as total or subtotal occlusion induced by ACh provocation. Mean±SD HR (65.7±9.1 vs 69.6±7.9 beats per minute; p=0.003), systolic BP (122.3±13.4 vs 127.7±14.6 mmHg; p=0.01), and DP (8,001±1,229 vs 8,903±1,495; p<0.001) were significantly lower in patients with a positive ACh test than the counterpart, whereas SD and CV of both HR and systolic BP were not significantly different between the two groups. Mean HR, BP, and DP progressively decreased with increase in the number of vessels with angiographic vasospasm. Multivariate analysis showed current smoking and lower DP as independent predictors of the greater number of vessels with provoked angiographic vasospasm. Resting HR, BP, and DP were lower in patients with vasospastic angina, especially in those with severe vasospasm.

Necessity of back-up pace maker support during acetylcholine testing as a safe method.

Necessity of back-up pace maker support during acetylcholine testing as a safe method.

Diagnosis of coronary microvascular dysfunction in the clinic.

The coronary microcirculation plays a pivotal role in the regulation of coronary blood flow and cardiac metabolism. It can adapt to acute and chronic pathologic conditions such as coronary thrombosis or long-standing hypertension. Due to the fact that the coronary microcirculation cannot be visualized in human beings in vivo, its assessment remains challenging. Thus, the clinical importance of the coronary microcirculation is still often underestimated or even neglected. Depending on the clinical condition of the respective patient, several non-invasive (e.g. transthoracic Doppler-echocardiography assessing coronary flow velocity reserve, cardiac magnetic resonance imaging, positron emission tomography) and invasive methods (e.g. assessment of coronary flow reserve (CFR) and microvascular resistance (MVR) using adenosine, microvascular coronary spasm with acetylcholine) have been established for the assessment of coronary microvascular function. Individual patient characteristics, but certainly also local availability, methodical expertise and costs will influence which methods are being used for the diagnostic work-up (non-invasive and/or invasive assessment) in a patient with recurrent symptoms and suspected coronary microvascular dysfunction. Recently, the combined invasive assessment of coronary vasoconstrictor as well as vasodilator abnormalities has been titled interventional diagnostic procedure (IDP). It involves intracoronary acetylcholine testing for the detection of coronary spasm as well as CFR and MVR assessment in response to adenosine using a dedicated wire. Currently, the IDP represents the most comprehensive coronary vasomotor assessment. Studies using the IDP to better characterize the endotypes observed will hopefully facilitate development of tailored and effective treatments.

Does Coronary Microvascular Spasm Exist? Objective Evidence from Intracoronary Doppler Flow Measurements During Acetylcholine Testing

A 43-year-old woman with recurrent atypical angina underwent invasive coronary angiography including intracoronary Doppler blood flow assessment and coronary spasm provocation testing. While obstructive epicardial disease could be ruled-out angiographically, the patient experienced reproduction of her angina symptoms after intracoronary administration of acetylcholine (100 µg) during spasm provocation testing. Simultaneously, the ECG showed new-onset ST-segment depression in the absence of epicardial spasm. In addition, coronary flow velocity was significantly reduced after acetylcholine compared to the baseline condition. Following intracoronary administration of nitroglycerine (200 µg), the patient’s symptoms as well as the ECG changes and coronary flow reduction were reversed. Considering the ongoing challenges in appropriate evaluation of the pathophysiological mechanisms of coronary microvascular dysfunction, simultaneous intracoronary Doppler flow measurement during spasm testing – as shown in this case – may provide objective evidence for microvascular spasm in addition to the standardized diagnostic criteria, especially if they are ambiguous.

Sensitivity of bronchial receptors under the effect of tobacco smoke in the conditions of various activity of the thyroid gland in children.

The role of the initial hormonal profile disorders of the system “pituitary – thyroid” in the emergence of a bronchospasm in response to exogenic stimuli has not been finally determined. The aim of our research was to investigate the character and degree of the relationship between bronchial hypersensitivity in children exposed to smoking and the functional activity of the thyroid gland. The research involved 74 patients aged 10 to 17 years. Sixteen children were not exposed to tobacco smoke, 50 children were passive smokers, and 8 of the children surveyed smoked actively. To investigate the level of bronchial sensitivity, a bronchial provocation test with a non-specific stimulus – bronchoconstrictor acetylcholine was carried out. We assayed the functional state of the thyroid gland by the level of free triiodothyronine (FT3), free thyroxin 4 (FT4) and thyroid stimulating hormone (TSH), identified by Enzyme-linked Immunosorbent Assay (ELISA) (Alkor Bio, Russia). Indicators of hormones of a thyroid gland in most of the examined children did not differ from standard values for healthy children. Analysis of the results of the inhaled bronchial provocation test with acetylcholin showed that the state of non-specific bronchial hypersensitivity was observed in 2 active smokers and in none of the passive smokers and non-smokers (χ2=15,4&gt;χ201=9,21 або р&lt;0,01). According to our data, in children with hypothyroidism, under the effect of tobacco smoke, changes in the functional state of sensitive bronchial receptors do not occur. Among 2 children who had an increased activity of the thyroid gland (hyperthyroidism), one child from the group of smokers had an increased bronchial sensitivity by the results of the acetylcholine test (p&gt;0.05). According to our data, changes in the functional status of sensitive bronchial receptors (cholinergic receptors) resulting from exposure to tobacco smoke in children exposed to tobacco smoke, active or passive, do not depend on the functional state of the thyroid gland (Рχ2&gt;0,05).

Coronary Functional Abnormalities in Patients With Angina and Nonobstructive Coronary Artery Disease

BackgroundApproximately one-half of patients undergoing diagnostic coronary angiography for angina have no significant coronary stenosis, in whom coronary functional abnormalities could be involved. ObjectivesThis study examined the significance of coronary functional abnormalities in a comprehensive manner for both epicardial and microvascular coronary arteries in patients with angina and nonobstructive coronary artery disease (CAD). MethodsThis study prospectively enrolled 187 consecutive patients (male/female 113/74, 63.2 ± 12.3 years), who underwent acetylcholine provocation test for coronary spasm and measurement of index of microcirculatory resistance (IMR) to evaluate coronary microvascular function, and followed them for a median of 893 days. ResultsOf all subjects, acetylcholine test identified 128 patients with vasospastic angina (VSA) (68%), and cardiac events occurred in 10 patients (5.3%) during the follow-up. Multivariable analysis revealed that IMR correlated with the incidence of cardiac events (hazard ratio: 1.05; 95% confidence interval: 1.02 to 1.09; p = 0.002) and receiver-operating characteristics (ROC) curve analysis identified IMR of 18.0 as the optimal cut-off value. Among the 4 groups based on the cut-off value of IMR and the presence of VSA, the Kaplan-Meier survival analysis showed a significantly worse prognosis in the group with high IMR (≥18.0) and VSA compared with other groups (log rank, p = 0.002). Importantly, intracoronary administration of fasudil, a Rho-kinase inhibitor, significantly ameliorated IMR in the VSA patients with increased IMR (p < 0.0001). ConclusionsThese results indicate that in patients with angina and nonobstructive CAD, coexistence of epicardial coronary spasm and increased microvascular resistance is associated with worse prognosis, for which Rho-kinase activation may be involved.

Transitional changes of acetylcholine spasm provocation test procedures.

Intracoronary acetylcholine (ACh) testing has become popular in the world as a spasm provocation test as well as an ergonovine test. Intracoronary ACh test based on the Japanese Circulation Society guidelines is necessary to insert a temporary pace maker (PM). We analyzed the ACh spasm provocation test procedures retrospectively. We performed 1829 ACh spasm provocation testing during 28years. We investigated the procedural approach sites of artery and vein. Femoral artery and vein approach, brachial artery and femoral vein approach, brachial artery and vein approach, radial artery and brachial vein approach, radial artery and femoral vein approach were performed in 292 patients (16.0%), 498 patients (27.2%), 589 patients (32.2%), 252 patients (13.8%), and 175 patients (9.6%), respectively. We could perform the ACh testing by the femoral artery and brachial artery in all patients, while the success rate of radial artery approach was 97.1%. We could also insert the temporary PM by the brachial vein in 94.8% (841/887) of the study patients, whereas we could insert the temporary PM in all femoral vein approach [100% (965/965)]. We experienced the pulmonary embolism by the femoral artery and vein approach in two patients, while we also had the arterio-venous fistula necessary for surgical repair in two patients by the brachial artery and vein approach. Although there was no difference about the procedure-related major complications among the various procedures, we had no pulmonary embolism or arterio-venous fistula by the radial artery and brachial vein approach. Considering the disinfection with povidone iodine, procedural performance or procedure-related complications by the ACh testing, we recommend that radial artery and brachial vein approach is more comfortable method of the future ACh testing not only for patients but also for operators.

P875Myocardial perfusion reserve assessment in patients with angina pectoris and suspected coronary spasm

Abstract Background Patients with signs and symptoms of myocardial ischemia yet unobstructed coronary arteries represent a diagnostic and therapeutic challenge. Coronary vasomotor disorders such as coronary epicardial or microvascular spasm are frequently found among these patients. They can be diagnosed using intracoronary acetylcholine testing (ACH-test). It has been shown that patients with epicardial spasm have a worse prognosis compared to patients with microvascular spasm. The reasons for this finding are however not apparent. We speculated in this study that patients with epicardial spasm have a worse vasomotor dysfunction compared to patients with microvascular spasm or normal ACH-test. To assess this hypothesis all patients in this study not only underwent ACH-testing but in addition also adenosine stress perfusion cardiac MRI (CMR) with calculation of the myocardial perfusion reserve index (MPRI). The latter method allows for assessment of vasodilatory function compared to the vasoconstrictor assessment using acetylcholine. Methods Between 2012 and 2016, 129 consecutive patients (mean age 64±13 years, 46% female) with signs and symptoms of myocardial ischemia yet unobstructed coronary arteries were enrolled in this study. All patients underwent ACH-testing as well as adenosine stress perfusion CMR. According to the results of the acetylcholine test, patients were allocated to 3 groups: a) epicardial spasm (angina, ischemic ECG changes and &gt;75% coronary diameter reduction), b) microvascular spasm (angina, ischemic ECG changes and &lt;75% coronary diameter reduction) and c) no evidence of coronary artery spasm. CMR-derived MPRI was calculated semiquantitatively from myocardial signal intensity-over-time curves of adenosine stress and rest perfusion. Results Epicardial and microvascular spasm was found in 31 (24%) and 69 (53%) patients, respectively, while 29 (22%) patients had no evidence of coronary spasm on ACH-testing. Women were more likely to have microvascular spasm than men (68% vs. 36%, p&lt;0.001). The prevalence of epicardial spasm did not significantly differ between female and male patients (18% vs. 31%, p=0.08). MPRI was similar in patients with microvascular spasm compared to patients without spasm (1.30 vs. 1.27, p=0.43). However, patients with epicardial spasm had significantly lower MPRI than patients without spasm (1.16 vs. 1.30, p&lt;0.05) or those with microvascular spasm (1.16 vs. 1.27, p&lt;0.05). Conclusion MPRI determined by stress perfusion CMR was significantly reduced in patients with epicardial spasm compared to those with microvascular spasm or normal ACH-test. This could indicate that patients with epicardial spasm have a more generalized coronary vasomotor disorder compared to other patients. This may be the reason for the worse outcome observed and could lead to more aggressive medical therapy and closer follow-up. Acknowledgement/Funding This work was funded by the Robert-Bosch-Stiftung, Stuttgart, Germany and the Berthold-Leibinger-Stiftung, Ditzingen, Germany.