Coronary Vasospasm In Patients Research Articles

Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients With Nonobstructive Coronary Artery Disease: Systematic Review and Meta-Analysis.

BackgroundA relevant proportion of patients with suspected coronary artery disease undergo invasive coronary angiography showing normal or nonobstructive coronary arteries. However, the prevalence of coronary microvascular disease (CMD) and coronary spasm in patients with nonobstructive coronary artery disease remains to be determined. The objective of this study was to determine the prevalence of coronary CMD and coronary vasospastic angina in patients with no obstructive coronary artery disease.Methods and ResultsA systematic review and meta‐analysis of studies assessing the prevalence of CMD and vasospastic angina in patients with no obstructive coronary artery disease was performed. Random‐effects models were used to determine the prevalence of these 2 disease entities. Fifty‐six studies comprising 14 427 patients were included. The pooled prevalence of CMD was 0.41 (95% CI, 0.36–0.47), epicardial vasospasm 0.40 (95% CI, 0.34–0.46) and microvascular spasm 24% (95% CI, 0.21–0.28). The prevalence of combined CMD and vasospastic angina was 0.23 (95% CI, 0.17–0.31). Female patients had a higher risk of presenting with CMD compared with male patients (risk ratio, 1.45 [95% CI, 1.11–1.90]). CMD prevalence was similar when assessed using noninvasive or invasive diagnostic methods.ConclusionsIn patients with no obstructive coronary artery disease, approximately half of the cases were reported to have CMD and/or coronary spasm. CMD was more prevalent among female patients. Greater awareness among physicians of ischemia with no obstructive coronary arteries is urgently needed for accurate diagnosis and patient‐tailored management.

The Role of Mental Stress in Ischaemia with No Obstructive Coronary Artery Disease and Coronary Vasomotor Disorders.

Ischaemic heart disease has been estimated to affect 126.5 million people globally. Approximately 70% of patients with angina and suspected myocardial ischaemia show no signs of obstructed coronary arteries after coronary angiography, but may still demonstrate ischaemia. Ischaemia with no obstructive coronary artery disease (INOCA) is increasingly acknowledged as a serious condition because of its association with poor quality of life and elevated risk for cardiovascular events. The negative effects of psychological stress on INOCA are gaining more attention. Psychological stress is associated with adverse cardiovascular outcomes such as mental stress-induced myocardial ischaemia. Psychological stress includes anxiety, depression, anger and personality disturbances. Coronary microvascular dysfunction and coronary arterial spasm are phenotypes of coronary vasomotor disorders that are triggered by psychological distress and depression, thereby increasing cardiovascular disease risk. Coronary vasomotor disorders are often co-existent in INOCA patients and might be considered as a contributing factor to mental stress-associated adverse cardiovascular outcomes. Additionally, psychological stress induces endothelial dysfunction more often in (young) women with INOCA than in men. Overall, many studies demonstrate an association between mental stress, coronary microvascular dysfunction and coronary vasospasm in patients with INOCA – especially women. Future research on stress-reducing therapies that target coronary vasomotor disorders in patients with INOCA is needed. This is particularly the case in young adolescents, in whom this type of ischaemic heart disease is increasing.

Pericoronary adipose tissue inflammation on coronary computed tomography in patients with vasospastic angina

Abstract Background A recent study has demonstrated that coronary spasm is associated with inflammation of peri-coronary adipose tissue (PAT) by using the combination of 18F-fluorodeoxyglucose positron emission tomography and computed tomography (CT). PAT attenuation (FAI) on CT angiography (CTA) has been reported to reflect PAT inflammation. We sought to investigate if FAI on CTA was associated with coronary vasospasm in patients with suspected vasospastic angina (VSA). Methods A total of 88 patients who underwent CTA and acetylcholine provocation test (SPT) for suspected VSA were retrospectively investigated. FAI was assessed by the crude analysis of the mean CT attenuation value of 3 major coronary arteries on CTA. FAI was evaluated for the proximal reference diameter (FAI-Ref) and inner 2mm adipose tissue layer (FAI-2mm) from the vessel wall. Diagnosis of VSA (VSA group) was made by SPT and the subjects with negative SPT without organic coronary lesions served as non-VSA group. Association between VSA diagnosis and FAI was assessed and the predictors of VSA was explored by univariable and multivariable analyses. Results In 45 patients (51.1%), VSA was diagnosed (VSA group). There were no significant differences in baseline characteristics between the VSA and non-VSA groups. RCA-FAI was significantly higher in patients of VSA group than in non-VSA group. RCA-FAI-2mm provided significantly better diagnostic performance for VSA than RCA-FAI-Ref and LCA-derived FAI values. Furthermore, RCA-FAI-2mm showed a significant relationship with the severity of spasm evaluated by most stenotic segment diameter during SPT. (r=−0.28, p<0.001) Multivariable logistic regression analysis revealed that RCA-FAI-2mm was an independent predictor of predicting VSA (P<0.001). Conclusion Coronary spasm may be linked with PAT inflammation detected by CTA-derived RCA-FAI, particularly by inner PAT assessment close to the vessel wall. Representative cases for FAI analyses Funding Acknowledgement Type of funding source: None

Unrecognized coronary vasospasm in patients referred for percutaneous coronary intervention: Intracoronary nitroglycerin, the forgotten stepchild of cardiovascular guidelines.

The goal of this study was to demonstrate the importance of intracoronary nitroglycerin (IC NTG) administration during diagnostic coronary angiography and prior to percutaneous coronary intervention (PCI). PCI has been a mainstay treatment for patients with symptomatic coronary artery disease. While current guidelines emphasize the importance of periprocedural antithrombotic medications, they fail to mention the use of nitroglycerin prior to PCI. Retrospective chart and angiographic review was performed to identify patients referred for PCI who had significant angiographic stenoses that resolved after administration of IC NTG. The study group consisted of 6 patients (3 men, 3 women) with mean age 52 ± 4years (range 46-57 years). All had anginal symptoms and significant (>70%) stenosis on diagnostic coronary angiography. None had documented ST segment elevation. The median interval between diagnostic and staged PCI procedures was 3 days. IC NTG was not administered to any of the patients at the time of diagnostic coronary angiography. In each case, repeat coronary angiography following administration of IC NTG (155 ± 46 mcg) before planned PCI demonstrated resolution of the target stenosis. PCI was deferred and all patients were successfully managed medically. Coronary artery spasm is an under-recognized cause of chest pain in patients with significant angiographic lesions. Coronary spasm should be suspected especially in younger patients (less than 60 years old) with apparent single vessel disease. IC NTG should be routinely administered during diagnostic angiography and before PCI to avert unnecessary coronary interventions. © 2017 Wiley Periodicals, Inc.

Eosinophilia-Associated Coronary Artery Vasospasm in Patients with Aspirin-Exacerbated Respiratory Disease

Eosinophilia is known to be associated with coronary artery vasoconstriction that does not respond to conventional vasodilator treatment but does respond to eosinophil-suppressing treatment. The prevalence of eosinophilia-associated coronary vasospasm in patients with aspirin-exacerbated respiratory disease (AERD), an inflammatory disease characterized by blood and respiratory tissue eosinophilia, is unknown. We observed that some patients with AERD report angina-type chest pain that responds to corticosteroid therapy. We sought to understand the cause of and determine the most appropriate treatment for such chest pain. A retrospective chart review of patients with AERD followed at Brigham and Women’s Hospital was performed. Patients who reported chest pain were assessed for presence of cardiac risk factors, eosinophilia, and chest pain response to conventional and unconventional treatments. One hundred fifty three patients were reviewed; 10 had a history of angina-like chest pain. Eight of the 10 patients had undergone aspirin desensitization and initiated high-dose aspirin; of those, 6 reported an increase in the frequency or severity of chest pain while on high-dose aspirin with improvement after aspirin discontinuation or dose reduction. Most patients had no traditional cardiac risk factors but did have significant eosinophilia. Their chest pain did not improve with typical anti-anginal treatments but did respond to corticosteroid therapy. Though uncommon, patients with AERD can develop eosinophilia-associated coronary artery vasospasm, which is occasionally worsened by high-dose aspirin. AERD patients who present with chest pain, particularly if they are on high-dose aspirin, should be screened for eosinophilia as early treatment with corticosteroids could be life saving.

The Impact of Subclinical Hypothyroidism or Thyroid Autoimmunity on Coronary Vasospasm in Patients without Associated Cardiovascular Risk Factors.

Background and ObjectivesSubclinical hypothyroidism is associated with endothelial dysfunction and impaired coronary flow reserve. However, the effect of subclinical hypothyroidism or thyroid autoimmunity on variant angina has yet to be determined.Subjects and MethodsAmong 385 consecutive patients without associated cardiovascular risk factors who underwent coronary angiography with the ergonovine provocation test (EPT), 165 had a positive EPT {EPT(+)} and 220 had a negative EPT {EPT(-)}. The relationship between coronary artery spasm and the presence of subclinical thyroid dysfunction as well as serum thyroid peroxidase autoantibody (TPO Ab) was evaluated.ResultsThe proportion of patients with subclinical hypothyroidism among those who were EPT(+) was significantly higher than that in those who were EPT(-) (18% vs. 11%, p=0.001). However, there was no significant difference in the proportion of patients with subclinical hyperthyroidism between the groups. Moreover, EPT(+) patients showed significantly more positive TPO Ab (33% vs. 14%, p<0.001) than those with EPT(-). There was a positive correlation between EPT(+) and TPO positivity (r=0.226, p<0.001), subclinical hypothyroidism (r=0.112, p=0.033), and body mass index (r=0.123, p=0.018). Binary logistic regression analysis revealed that the significant predictors of EPT(+) were body mass index {adjusted odds ratio (OR)=1.042, 95% confidence interval (CI)=1.005-1.080}, presence of subclinical hypothyroidism (OR=3.047, 95% CI=1.083-8.572), TPO Ab titer (OR=1.028, 95% CI=1.015-1.041), and the presence of TPO Ab (OR=4.904, 95% CI=1.544-15.567).ConclusionSubclinical hypothyroidism and the presence of TPO Ab are significantly associated with coronary vasospasm in patients without cardiovascular risk factors.

Chronic kidney disease stage is a modulator on the association between high-sensitivity C-reactive protein and coronary vasospastic angina.

The prevalence of coronary vasospasm and also the factors associated with coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859 consecutive CKD patients with angina pectoris received coronary catheterization, we evaluated the factors associated with coronary vasospasm. Patients with vasospasm were older and had higher peripheral blood white cell counts, higher peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP levels, and lower levels of serum creatinine than patients without vasospasm. The results of multivariate logistic regression analysis revealed that peripheral blood monocyte count and hs-CRP level were independently associated with coronary vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but not hs-CRP was independently associated with coronary vasospasm in patients with stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is independently associated with coronary vasospasm in patients with stage 1–3 CKD, whereas hs-CRP is only independently associated with coronary vasospasm in patients with stage 1 CKD.

Interaction Between Cigarette Smoking and High-Sensitivity C-Reactive Protein in the Development of Coronary Vasospasm in Patients Without Hemodynamically Significant Coronary Artery Disease

BackgroundInteraction between 2 major risk factors, cigarette smoking and high-sensitivity C-reactive protein (hs-CRP), has not been evaluated in patients with coronary vasospasm (CV) without hemodynamically significant coronary artery disease. MethodsFrom 1999 to 2005, patients undergoing diagnostic coronary angiography with or without proven CV and without coronary stenosis >50% were evaluated. A total of 621 subjects (335 and 286 with and without CV, respectively) were enrolled in the study. The levels of hs-CRP, measured immediately before coronary angiography, were examined in a subset of 314 patients. ResultsSubjects with CV were likely to be older, men, current smokers, and have high hs-CRP levels. The most significant factors for CV were smoking and hs-CRP. In the nonsmoker group, elevated risk of developing CV was only demonstrated in patients with the highest hs-CRP tertile (>5.01mg/L, P=0.012). In the smoker group, however, a positively monotonic trend of association was demonstrated between hs-CRP tertile and CV risk, with multivariate-adjusted odds ratios of 1.11, 3.09 (P=0.012), and 4.12 by the hs-CRP tertiles, suggesting that smokers developed CV at a lower hs-CRP level than nonsmokers and there was a positive interaction between smoking and hs-CRP. ConclusionsThe smokers developed CV at a lower hs-CRP level compared with the nonsmokers. A positive interaction between smoking and hs-CRP was demonstrated for this disease in our study population.

Relation of High-Sensitivity C-Reactive Protein Level With Coronary Vasospastic Angina Pectoris in Patients Without Hemodynamically Significant Coronary Artery Disease

We prospectively investigated the relation of high-sensitivity C-reactive protein (hs-CRP) to coronary vasospasm and no hemodynamically significant coronary artery disease (CAD) in a sample of 428 patients who underwent coronary angiography. These patients were assigned to 1 of 3 groups. The control group consisted of 66 patients who had no coronary vasospasm and no hemodynamically significant CAD. The vasospasm group consisted of 116 patients who had coronary vasospasm and no hemodynamically significant CAD. The acute coronary syndrome (ACS) group consisted of 246 patients who had ACS and hemodynamically significant CAD. Serum hs-CRP was measured immediately before coronary angiography. Patients were followed for subsequent cardiac events and mortality. Median hs-CRP levels in the control, vasospasm, and ACS groups were 1.0, 5.5, and 8.2 mg/L, respectively. The proportion of hs-CRP increased from the lowest to the highest tertile in the control, vasospasm, and ACS groups, respectively. In the control and vasospasm groups, multivariate analysis showed that hs-CRP was independently associated with a diagnosis of coronary vasospastic angina pectoris (odds ratio 68.74, 95% confidence interval 8.03 to 588.71, p<0.001). During a median follow-up period of 26 months (range 0.4 to 48), 27 cardiac deaths occurred in the ACS group, whereas no cardiac death occurred in the control and vasospasm groups. In conclusion, serum hs-CRP level measured immediately before coronary angiography was an independent marker of coronary vasospasm in patients who had no hemodynamically significant CAD.

Cardiac toxicity of 5FU: Does prophylactic telemetry monitoring of patients at increased risk for cardiac toxicity improve safety? A 10-year experience

8107 Background: 5FU can cause cardiac toxicity as a result of induced coronary artery spasm. This risk appears to be amplified in patients with histories of coronary artery disease. Coronary vasospasm manifests as ST segment elevations during continuous ECG monitoring. The incidence of reported cardiac events has varied from less than 1% to as high as 8%. In the absence of established evidence-based guidelines, management practices vary. At our center selected patients felt to be at high risk have been prophylactically admitted to receive 5FU with inpatient telemetry monitoring. We now report a retrospective analysis of this practice. Our objectives were (1) to evaluate the incidence of cardiac events in high-risk patients admitted for telemetry during 5FU administration, and (2) to determine the utility of telemetry as a guide for coronary vasospasm in patients with cardiac risk. Methods: A retrospective chart review was conducted using the database at Memorial Sloan-Kettering Cancer Center to identify patients who received concurrent 5FU and telemetry as an inpatient between 10/93 and 1/03. Cardiac events were considered to be the development of any symptoms or telemetric ST changes consistent with vasospasm. Results: A total of 88 patients comprising of 463 telemetry days were evaluated. 82/88 (93%) patients had either 1 or more cardiac risk factors or a history of an arrhythmia or abnormal ECG. 3 patients were admitted for advanced age and 3 had no clearly identifiable risk factors. Of 88 patients, 4 patients (CI 1.2%–11.2%) developed chest pain while receiving 5FU. There were no patients in whom telemetric ST changes consistent with coronary vasospasm were found (CI 0–4.1%). In total, there were 0 events attributable to vasospasm in 463 telemetry days (CI 0–0.01 events/day) that were picked up by telemetry. Conclusions: Over a 10 year period, there were no patients in whom telemetry monitoring led to the detection of coronary vasospasm in selected high risk patients. Our experience does not support the routine use of elective telemetric monitoring in patients with significant cardiac risk factors receiving 5FU. No significant financial relationships to disclose.

Cardiac toxicity of 5FU: Does prophylactic telemetry monitoring of patients at increased risk for cardiac toxicity improve safety? A 10-year experience

8107 Background: 5FU can cause cardiac toxicity as a result of induced coronary artery spasm. This risk appears to be amplified in patients with histories of coronary artery disease. Coronary vasospasm manifests as ST segment elevations during continuous ECG monitoring. The incidence of reported cardiac events has varied from less than 1% to as high as 8%. In the absence of established evidence-based guidelines, management practices vary. At our center selected patients felt to be at high risk have been prophylactically admitted to receive 5FU with inpatient telemetry monitoring. We now report a retrospective analysis of this practice. Our objectives were (1) to evaluate the incidence of cardiac events in high-risk patients admitted for telemetry during 5FU administration, and (2) to determine the utility of telemetry as a guide for coronary vasospasm in patients with cardiac risk. Methods: A retrospective chart review was conducted using the database at Memorial Sloan-Kettering Cancer Center to identify patients who received concurrent 5FU and telemetry as an inpatient between 10/93 and 1/03. Cardiac events were considered to be the development of any symptoms or telemetric ST changes consistent with vasospasm. Results: A total of 88 patients comprising of 463 telemetry days were evaluated. 82/88 (93%) patients had either 1 or more cardiac risk factors or a history of an arrhythmia or abnormal ECG. 3 patients were admitted for advanced age and 3 had no clearly identifiable risk factors. Of 88 patients, 4 patients (CI 1.2%–11.2%) developed chest pain while receiving 5FU. There were no patients in whom telemetric ST changes consistent with coronary vasospasm were found (CI 0–4.1%). In total, there were 0 events attributable to vasospasm in 463 telemetry days (CI 0–0.01 events/day) that were picked up by telemetry. Conclusions: Over a 10 year period, there were no patients in whom telemetry monitoring led to the detection of coronary vasospasm in selected high risk patients. Our experience does not support the routine use of elective telemetric monitoring in patients with significant cardiac risk factors receiving 5FU. No significant financial relationships to disclose.

Effects of anti-vasospastic agents in Japanese patients with dilated cardiomyopathy and coronary vasospasm.

The pathogenesis of dilated cardiomyopathy (DCM) is unknown, but clinical evidence suggests that coronary vasospasm is associated with the development of DCM in some cases. In the present study, we aimed to clarify the prevalence of coronary vasospasm in patients with DCM, the characteristics of patients with DCM and coronary vasospasm, and the effects of anti-vasospastic agents on patients with DCM and coronary vasospasm. This study included 18 consecutive patients with DCM who underwent cardiac catheterization with ergonovine provocation testing. The patient was diagnosed as having coronary vasospasm if ergonovine induced coronary vasoconstriction > or = 75% diameter narrowing was observed compared to the diameter after nitroglycerin administration. Six (33%) patients were found to have coronary vasospasm and anti-vasospastic agents were added after the cardiac catheterization. The prevalence of atrial fibrillation in the patients with DCM and coronary vasospasm was greater than that in DCM without coronary vasospasm [67% vs 8% (P<0.05)]. The left ventricular end-diastolic dimension decreased from 61 mm (56/64) to 55 mm (53/56) (median, 25th/75th percentile, P<0.05) and the left ventricular ejection fraction increased from 36% (32/40) to 47% (46/48) (median, 25th/ 75th percentile, P<0.05) after the administration of anti-vasospastic agents and 4 of the 6 patients improved symptomatically. Therefore, ergonovine provocation testing is useful in identifying patients with DCM and coronary vasospasm, in whom cardiac performance is expected to be improved with anti-vasospastic agent therapy. DCM patients with atrial fibrillation may be a clue for identifying patients with coronary vasospasm.

Efficiency of ergonovine echocardiography in detecting angiographically assessed coronary vasospasm

Coronary vasospasm plays a major role in provoking myocardial ischemia in patients with variant angina, but also in some patients with acute coronary syndrome including unstable angina, myocardial infarction, and sudden death. Ergonovine provocation has been used for >20 years for detection of coronary artery spasm. 1 Maseri A. L.’Abbate A. Pesola A. Ballestra A. Marzilli M. Maltinti G. Severi S. De Ness D.M. Parodi O. Biagini A. Coronary vasospasm in angina pectoris. Lancet. 1977; 1: 713-717 Abstract PubMed Scopus (153) Google Scholar , 2 Schroeder J.S. Bolen J.L. Wuint R.A. Clark D.A. Hayden W.G. Higgins C.B. Wexler L. Provocation of coronary spasm with ergonovine maleate. New test with results in 57 patients undergoing coronary arteriography. Am J Cardiol. 1977; 40: 487-491 Abstract Full Text PDF PubMed Scopus (226) Google Scholar , 3 Heupler F.A. Proudfit W.L. Razavi M. Shirey E.K. Greenstreet R. Sheldon W.C. Ergonovine maleate provocative test for coronary arterial spasm. Am J Cardiol. 1978; 41: 631-640 Abstract Full Text PDF PubMed Scopus (270) Google Scholar Most data on ergonovine testing have been reported in the preselected group of patients with variant angina, establishing ergonovine as a test of high diagnostic confidence. 4 Bott-Silverman C. Heupler F.A. Yiannikis J. Variant angina comparison of patients with and without fixed severe coronary artery disease. Am J Cardiol. 1984; 54: 1173-1175 Abstract Full Text PDF PubMed Scopus (19) Google Scholar , 5 Bory M. Pierron F. Panagides J. Bonnet J.L. Yvorra S. Desfossez L. Coronary artery spasm in patients with normal or near-normal coronary arteries. Long-term follow-up of 277 patients. Eur Heart J. 1996; 17: 1015-1021 Crossref PubMed Scopus (157) Google Scholar In current clinical practice, when a marked decline in the use of ergonovine testing in the catheterization laboratory is observed, 6 Song J.K. Park S.W. Kang D.H. Hong M.K. Kim J.J. Lee C.W. Park S.J. Safety and clinical impact of ergonovine stress echocardiography for diagnosis of coronary vasospasm. J Am Coll Cardiol. 2000; 35: 1850-1856 Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar accompanied by promising reports on ergonovine echocardiography, a question remains on the incidence, safety, and usefulness of provocative testing for coronary vasospasm in patients with chest pain syndrome and nonsignificant coronary artery stenosis. Thus, the objectives of our study were to evaluate (1) the incidence of angiographically assessed coronary vasospasm in a consecutive population of patients with nonsignificant coronary artery disease, (2) the efficiency of simultaneously performed ergonovine echocardiography in identifying coronary vasospasm, and (3) the relation between ergonovine echocardiographic and angiographic results.

49-Year-Old Woman With Chest Pain

49-Year-Old Woman With Chest Pain

Frequency of provoked coronary vasospasm in patients undergoing coronary arteriography with spasm provocation test of acetylcholine

This study examines the incidence of spasm by intracoronary injection of acetylcholine in Japanese patients who underwent coronary angiography. The subjects were 685 consecutive patients (477 men, mean age 63.2 ± 7.5 years) who were studied with an acetylcholine test. Acetylcholine was injected in incremental doses of 20, 50, and 80 μg into the right coronary artery and 20, 50, and 100 μg into the left coronary artery. Spasm was defined as total or subtotal occlusion. Coronary vasospasm was determined in 221 patients (32.3%). Spasm occurred often during effort and rest in patients with angina (25 of 51, 49.0%), exertional angina (25 of 74, 33.8%), recent myocardial infarction (30 of 80, 37.5%), healed myocardial infarction (14 of 37, 37.8%), and especially in patients with rest angina (83 of 124, 66.9%), whereas spasm was relatively uncommon in patients with nonischemic heart disease (23 of 252, 9.1%). Spasm was superimposed on significant atherosclerotic lesions in 35.9% of patients as well as on nonfixed atherosclerotic lesions in 30.8% of patients. We conclude that >9% of Japanese patients may have coronary vasospasm with intracoronary injection of acetylcholine and recommend the provocation test for evaluating coronary vasospasm if coronary angiography is undertaken.

Histological evaluation of coronary plaque in patients with variant angina: relationship between vasospasm and neointimal hyperplasia in primary coronary lesions.

This study was designed to determine whether coronary vasospasm in patients with variant angina pectoris (VAP) may produce focal organic lesions at the site of vasospasm that would contribute to disease progression. Recent clinical angiographic and experimental studies have demonstrated the potential role of vasospasm in the worsening of organic coronary stenosis. We studied histologically the coronary plaques obtained at atherectomy in 202 patients with moderate to severe coronary stenosis. This population included 22 patients with VAP, 100 patients with chronic stable angina and 80 patients with restenosis following angioplasty or atherectomy. Diagnosis of VAP was based on both the clinical feature of angina at rest associated with ST elevation and a positive response to acetylcholine provocation test. The most common histological appearance in 92% of patients with stable angina was hypocellular fibroatheromatous plaques, whereas neointimal hyperplasia was the characteristic feature of the plaque observed in 90% of patients with restenosis. The coronary specimens at the site of spasm in 15 of the 22 patients (68%) with VAP demonstrated intimal injuries such as neointimal hyperplasia (15), thrombus formation (2), and intimal hemorrhage (3). Neointimal hyperplasia was significantly more common in the patients with VAP as compared with those with stable angina (68% vs. 8%; p < 0.0001). A rapid progression of organic stenosis within three years was angiographically found in 5 of the 22 patients with variant angina. In all five cases, neointimal hyperplasia was the main contributor to the worsening of the organic lesion at the site of spasm. These histological findings in patients with VAP extremely resembled those in restenosis. Except for vasospasm, no factors significantly predicted the presence of neointimal formations in primary coronary lesions. Coronary vasospasm may provoke vascular injury that leads to the formation of neointima in VAP patients similar to that seen with restenosis. Coronary spasm may thus play a key role in the rapid coronary stenosis progression in certain patients with VAP.

Diagnosis of coronary vasospasm in patients with clinical presentation of unstable angina pectoris using ergonovine echocardiography

Although coronary vasospasm can contribute to the development of unstable angina, the definite diagnostic method has not been established. The purpose of this study was to determine if ergonovine echocardiography (detection of regional wall motion abnormality during bedside ergonovine challenge) after angiographic confirmation of insignificant fixed disease would be useful and safe in detecting coronary vasospasm in patients with unstable angina. After control of chest pain with medications in patients admitted to the coronary care unit under the tentative diagnosis of unstable angina, diagnostic coronary angiography was performed. All patients with normal or insignificant fixed disease underwent ergonovine echocardiography after discontinuation of medications for 4 ± 1 days. Among 208 consecutive patients enrolled for this study, 75% (156 of 208) showed significant fixed disease in the angiography. Ergonovine echocardiography was performed in 52 patients with insignificant disease, and coronary vasospasm was documented in 33 (63%, 33 of 52). No serious procedure-related arrhythmia or myocardial infarction occurred. Esophageal motility disorder and hypertrophic cardiomyopathy were diagnosed in 6 and 3 patients, respectively. Chest pain of undetermined etiology was the final diagnosis at discharge in 10 patients (5%, 10 of 208); among them chest pain redeveloped in 2 patients, and repeated ergonovine echocardiography revealed positive results. Our data suggest that among patients with the clinical presentation of unstable angina, coronary vasospasm is the main cause of myocardial ischemia in a considerable number of patients with a normal or near-normal angiogram, and ergonovine echocardiography after confirmation of absence of significant fixed disease is useful and safe for noninvasive diagnosis of coronary vasospasm in this setting.

Disturbed Autonomic Activity Precedes Ischemic Episodes in Patients with Variant Angina

BackgroundWhile the autonomic nervous system is known to be involved in the pathogenesis of variant angina, the relationship between disturbed autonomic activity and ischemic episodes in patients with variant angina has not been determined.MethodsWe performed 24‐hour Holter monitoring and power spectral analysis of heart rate variability (HRV) in ten patients with variant angina. The low frequency (0.04–0.15 Hz [LF]) and high frequency (0.15–0.40 Hz [HF]) components of HRV were quantified. The ratio of LF to HF (LF/HF) and the coefficient of the RR interval variation (CV) were also calculated. We analyzed HRV every 10 minutes beginning 50 minutes before the onset of ischemic episodes confirmed by ST segment elevation.ResultsThe LF/HF from 40 to 30 minutes before ischemia was decreased compared with the value from 50 to 40 minutes before ischemia (0.80 ± 0.15 vs 1.63 ± 0.44, mean ± SE, P = 0.037). The LF/HF then began to increase, and the value from 20 to 10 minutes (2.91 ± 0.66) was significantly greater than that from 40 to 30 minutes (P &lt; 0.01). The CV was increased from 30 to 20 minutes before ischemia compared with the CV from 50 to 40 minutes (8.5%± 1.6% vs 5.2%± 0.8%, P = 0.033). The LF/HF and the CV remained increased until the onset of ischemia.ConclusionsData suggests that a disturbed autonomic nervous activity plays an important role in the initiation of coronary vasospasm in patients with variant angina. A.N.E. 1997;2(4):313–318

Ergonovine echocardiography as a screening test for diagnosis of vasospastic angina before coronary angiography

In patients with chest pain suggestive of variant angina, we performed this prospective study to test the specificity and diagnostic validity of ergonovine echocardiography (detection of regional wall motion abnormality during bedside ergonovine challenge) as a screening procedure before coronary angiography. Spasm provocation test outside the catheterization room has generally not been accepted as a safe diagnostic method. Ergonovine echocardiography was performed in 80 consecutive patients with chest pain syndrome after confirmation of negative treadmill or normal stress myocardial perfusion scan results using thallium-201. A bolus of ergonovine maleate was injected at 5-min intervals up to a total cumulative dosage of 0.35 mg with echocardiographic monitoring of left ventricular wall motion. A 12-lead electrocardiogram (ECG) was also recorded every 3 min after each ergonovine injection. Positive test results were development of regional wall motion abnormalities or transient ST segment elevation or depression >0.1 mV in any single lead of the 12-lead ECG. Coronary angiography was undertaken within 2 +/- 4 days (mean +/- SD) after ergonovine echocardiography, and the spasm provocation test with acetylcholine or ergonovine was performed in patients with normal angiographic findings or lumen diameter narrowing <70%. On the basis of angiographic criteria, 56 patients had coronary vasospasm; this finding was later ruled out in 19 patients with near-normal angiographic results by a negative response on the spasm provocation test. In the remaining five patients, coronary spasm provocation was not performed because they revealed a high degree of fixed stenosis (lumen diameter narrowing 97 +/- 4%). Ergonovine echocardiography could diagnose coronary vasospasm before angiography, with a sensitivity of 91% (51 of 56 patients, 95% confidence interval [CI] 84% TO 98%) and specificity of 88% (21 of 24 patients, 95% CI 75% to 100%). Of 53 patients showing regional wall motion abnormalities during ergonovine echocardiography, characteristic ST segment elevation in the simultaneously recorded ECG was observed in only 20 (38%). There were no complications, including myocardial infarction or fatal arrhythmia, during the test. Ergonovine echocardiography before coronary angiography is safe and can be used as a reliable diagnostic screening test for coronary vasospasm in patients with negative treadmill or normal stress myocardial perfusion scan results. These findings suggest that invasive coronary angiography can be avoided in selected patients for the diagnosis of vasospastic angina.

Improvement of Coronary Vasomotion With Eicosapentaenoic Acid Does Not Inhibit Acetylcholine-Induced Coronary Vasospasm in Patients With Variant Angina.

Impaired function of the endothelium may be a mechanism of the coronary vasospasm induced by acetylcholine. We examined whether purified eicosapentaenoic acid (EPA), a major component of fish oil, improves the coronary vasomotion in response to acetylcholine, and the effect of purified EPA on acetylcholine (ACh)-induced coronary vasospasm in 22 patients with variant angina. ACh was infused into the coronary artery both before and after 4 months of EPA treatment (EPA 1.8 g/day, n = 12). In the control group (n = 10) that did not receive EPA, the response of the coronary diameter to ACh did not change over time. In the EPA-treated group, the cholinergic response in non-spastic sites changed from vasoconstriction to vasodilation, while ACh-induced coronary vasospasm persisted at the spastic sites. Therefore, EPA treatment improved the coronary vasomotor responsiveness to ACh, but did not inhibit ACh-induced coronary vasospasm.