Comparison of clinical characteristics and prognosis in Taiwanese patients with coronary vasospastic angina pectoris without significant fixed coronary artery disease versus patients with significant fixed coronary artery disease and either stable angina pectoris or acute coronary syndromes

BACKGROUND: Limited information is available comparing the clinical characteristics and prognosis for patients with coronary vasospastic angina in the absence of hemodynamically significant coronary artery disease (CAD) (defined as >50% stenosis) versus patients with significant fixed CAD presenting with either stable angina pectoris (SAP) or acute coronary syndromes (ACS). METHODS: Patients who underwent cardiac catheterization for suspected ischemic heart disease between August 1999 and February 2003 were followed clinically. For patients without hemodynamically significant CAD, a provocation test for coronary vasospasm was undertaken using a step-wise dose of intracoronary ergonovine administration. RESULTS: A total of 1134 patients were enrolled in the final analysis and stratified into 4 diagnostically distinct groups: control group (n = 239; mild CAD without coronary vasospasm); vasospasm group (n = 284; coronary vasospastic angina pectoris without hemodynamically significant CAD); SAP group (n = 110; hemodynamically significant CAD with SAP); ACS group (n = 501; hemodynamically significant CAD with ACS). Comparison of these 4 groups revealed that the ACS patients were more likely to be male, current smokers, and have hypercholesterolemia. In addition, this group had a significantly higher incidence of typical angina pectoris, 3-vessel CAD, and lower left ventricular ejection fraction. Between-group comparison revealed that vasospasm patients had a significantly higher incidence of early morning angina pectoris. Multivariate analysis showed that current smoking was the most independent risk factor associated with the diagnosis of coronary vasospastic angina pectoris in patients without hemodynamically significant CAD. During a median follow-up period of 49 months, recurrent angina pectoris was noted in patients from the control (n = 6; 3%), SAP (n = 9; 8%), vasospasm (n = 30, 11%), and ACS groups (n = 92; 18%); with nonfatal myocardial infarction identified during follow-up in the SAP (n = 5; 5%), vasospasm (n = 3; 1%), and ACS groups (n = 37; 7%). In addition, 29 and 3 cardiac deaths occurred in the ACS and SAP groups, respectively, whereas there were no such mortalities in the control and vasospasm groups. CONCLUSIONS: Early morning angina pectoris and cigarette smoking were the most common clinical characteristics in patients with coronary vasospasm. These patients had an excellent prognosis despite the possibility of recurrences of vasospastic angina pectoris.     

Long-term prognosis of medically treated patients with vasospastic angina and no fixed significant coronary atherosclerosis

The clinical course of 48 consecutive patients with vasospastic angina and minor coronary atherosclerosis (no stenoses greater than 50%) was analyzed during an average follow-up period of 47 months. The study group consisted of 37 men and 11 women. Patients were treated with usual doses of calcium antagonists. One patient died (2%) and three had myocardial infarctions (6%). Seventy-one percent were asymptomatic or had infrequent angina; 13% had recurrences but had periods of remission lasting at least 10 months. Only 16% had persistent angina. None of the clinical or angiographic findings at the time of diagnosis were predictive of myocardial infarction or death, and they could not separate angina-free patients from those with recurrences. Thus, vasospastic angina without fixed coronary narrowing has a good prognosis despite the possibility of recurrences. However, there is a slight risk of myocardial infarction and death. This fact should be considered if there are plans to discontinue treatment.     

Comparison of risk factors in vasospastic angina without significant fixed coronary narrowing to significant fixed coronary narrowing and no vasospastic angina

To determine the importance of usual risk factors of coronary artery disease (CAD) in patients with coronary artery spasm, 40 patients with vasospastic angina (VA), normal or nearly normal coronary arteries and without previous myocardial infarction were compared with 2 control groups of 40 patients each, matched for age and sex: 1 group with CAD and 1 without heart disease. Ninety percent of patients with VA were cigarette smokers and 70% were heavy smokers (more than 20 cigarettes daily), compared with 53% and 33% in patients with CAD (p less than 0.001) and 30% and 15% in those without heart disease (p less than 0.001). Except for cigarette smoking, the risk factor profile of patients with VA appeared more like the profile of patients without heart disease than that of patients with CAD. The results suggest that cigarette smoking may play a role in CAD independent of atherosclerosis and possibly favoring coronary artery spasm.     

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.     

Prognostic value of I-123 metaiodobenzylguanidine imaging in vasospastic angina without significant coronary stenosis.

BACKGROUND: Myocardial imaging is widely used to detect coronary artery disease and to assess its prognosis. In vasospastic angina (VA), cardiac imaging can provide information on disease activity, which is related to cardiac events. The aim of this study was to clarify whether exercise thallium-201 imaging (Tl-SPECT) and 123I-metaiodobenzylguanidine imaging (MIBG) have prognostic value for patients with VA, but without significant coronary artery stenosis. METHODS AND RESULTS: One hundred and 5 patients who showed acetylcholine-induced coronary spasm, normal left ventricular function and no significant stenosis (<50%) underwent both symptom-limited Tl-SPECT and MIBG within 1 month. All patients were prescribed calcium antagonist during the follow-up period (mean 4.7 years). Exercise-induced ischemia was detected by Tl-SPECT in 53 patients and multivessel coronary spasm by coronary angiography in 33 patients. During the follow-up period, 1 patient died suddenly and another died of acute myocardial infarction (MI). Two patients developed nonfatal acute MI and 7 patients underwent emergency coronary angiography because of unstable angina. According to the baseline characteristics, VA with cardiac events showed a significantly higher heart-to-mediastinum ratio (H/M ratio) and a significantly lower MIBG washout rate than those without cardiac events (p<0.03 and p<0.02, respectively). Among 8 clinical variables, including coronary risk factors, exercise parameters and exercise-induced ischemia on Tl-SPECT and the MIBG delayed H/M ratio and washout rate, univariate Cox proportional hazard regression analysis showed that the high H/M ratio and reduced washout rate of MIBG were significant predictors of future cardiac events (relative risk (RR) =4, confidence interval (CI) =1.21-13.29, p<0.02 for H/M ratio and RR 0.92, CI 0.85-0.99, p<0.02 for washout rate). However, exercise-induced ischemia did not show any statistical significance. By multivariate Cox proportional hazard regression analysis, a reduced MIBG washout rate was the only significant predictor of future cardiac events (odds ratio =0.90, CI =0.82-1.00, p<0.04). CONCLUSION: MIBG imaging can identify high-risk patients, even among those with VA who were previously regarded as low risk. This result strongly supports the idea that cardiac sympathetic dysfunction contributes to coronary artery spasm leading to cardiac events.     

Cardiac events in vasospastic angina: site and morphology of coronary artery spasm is related to the long-term prognosis of vasospastic angina

To determine whether the site and morphology of coronary artery spasm provoked with acetylcholine can predict the long-term prognosis of vasospastic angina, coronary artery spasm (more than 90% narrowing) provoked with acetylcholine was studied in 66 consecutive patients (56 males, 10 females, mean age 56 +/- 9 years) with vasospastic angina. All patients were followed for 6.7 +/- 0.9 years and the incidence of cardiac events such as sudden death, myocardial infarction or worsened unstable angina was compared with the site and morphology of provoked spasm. The site of spasm was regarded as proximal when spasm occurred in the proximal site of 3 major coronary arteries which was designated as segment 1, 6 or 11, according to the classification of the American Heart Association, and distal in other segments. The morphology of spasm was classified into 3 types, focal (12 cases, localized more than 90% narrowing with adjoining parts constricting less than 25%), diffuse (17 cases, diffuse more than 90% narrowing), and intermediate (37 cases, localized more than 90% narrowing with adjoining parts constricting 25-90%). The site of spasm was classified into 2 types, the proximal group (24 cases) and the distal group (42 cases). Cardiac events occurred in 7 patients during the follow-up period: sudden death in 2, myocardial infarction in 2, and worsened unstable angina in 3. As to the site of spasm, the incidence of cardiac events was 21% (5/24 patients) in the proximal group, significantly higher than 5% (2/42) in the distal group (p < 0.05). As to the site of spasm, the incidence of cardiac events was 41% (5/12) in the focal group, significantly higher than 3% (1/37) in the intermediate group and 6% (1/17) in the diffuse group (p < 0.001). The presence of proximal and focal coronary artery spasm was associated with a significantly higher incidence of cardiac events. The site and morphology of coronary artery spasm provoked with acetylcholine is related to the long-term prognosis of vasospastic angina.     

Significance of coronary artery tone in patients with vasospastic angina

To investigate the relation between basal coronary artery diameter and development of coronary artery spasm, the diameters of the proximal, middle and distal segments of the three major coronary artery branches, together with that of the left main trunk, were measured on a control angiogram and after ergonovine and nitrate administration in 30 patients with vasospastic angina without significant organic stenosis, and in 35 patients without ischemic heart disease. The percent change in coronary diameter after ergonovine and nitrate administration compared with the control diameter was used as an index of coronary vasoreactivity. In patients with vasospastic angina, coronary artery responses to both ergonovine and nitrate were greater in the spastic segments than in the other segments (p less than 0.05), and those of the coronary arteries without spasm were greater than those of the coronary arteries in patients without ischemic heart disease (p less than 0.01). There were no significant differences between the coronary artery diameters in the two groups after nitrate administration, and the control diameters were less in patients with vasospastic angina than in patients without ischemic heart disease. These observations indicate that a coronary vasomotion disorder, which involves increased basal coronary artery tone and hypersensitivity to vasoconstrictive stimuli, not only at a localized segment but also in the entire coronary artery tree, is present in patients with vasospastic angina. Clinically, evaluation of basal coronary artery tone may be useful for predicting the occurrence and location of coronary artery spasm.     

Biochemical markers of vasospastic coronary artery disease

OBJECTIVE: The risk factors for vasospastic angina pectoris (VSA) have not yet been well defined. We compared the plasma levels of lipids, apo(lipo)proteins, remnants of triglyceride (TG)-rich lipoproteins, oxidized low density lipoprotein (Ox-LDL), cholesteryl ester transfer protein (CETP) [which transfers esterified cholesterol (EC) from HDL to TG-rich lipoproteins and reduces plasma HDL levels], high-sensitivity C-reactive protein (hs-CRP), homocysteine and plasminogen-activator inhibitor (PAI)-1 in background-matched groups of controls, and patients with VSA or coronary atherosclerotic disease (CAD) (n=50 subjects each). METHODS AND RESULTS: The cholesterol levels of remnant-like particles (RLP), which are equivalent to the remnants of TG-rich lipoproteins, were measured using a precipitation method. Ox-LDL, CETP and PAI-1 were measured by means of sandwich ELISA; hs-CRP by means of nephelometry; and homocysteine by means of HPLC. Plasma LDL-C levels were high only in the CAD group, and plasma apo E and PAI-1 levels were high only in the VSA group. The plasma levels of TG, apo CII and RLP-C were highest in the VSA group, followed by the CAD group. The plasma levels of apoB, apo CIII, Ox-LDL, CETP, hs-CRP and homocysteine were equally increased in both the VSA and CAD groups. The increases in plasma RLP-C, CETP, hs-CRP and homocysteine were not significantly different between stable and unstable states of angina pectoris in either the VSA or CAD group. CONCLUSION: The increases in plasma TG-rich lipoproteins and their remnants were more significant markers of VSA than of CAD. The increases in plasma CETP, Ox-LDL, hs-CRP and homocysteine were equally important markers of VAS and CAD.     

Cimetidine induces coronary artery spasm in patients with vasospastic angina

We have previously reported that cimetidine, a histamine H2-receptor blocker, augments the histamine-induced coronary vasoconstriction at the site of spastic segments in the atherosclerotic coronary arteries of swine. To elucidate whether cimetidine has a coronary vasoconstrictive effect in humans, 14 patients with vasospastic angina (group 1) and 14 controls with atypical chest pain (group 2) were examined angiographically. Nitroglycerin-effective spontaneous angina with electrocardiographic ST-T changes and ergonovine-induced coronary artery spasm were confirmed in group 1, but not in group 2. Cimetidine was administered intravenously in a dose of 200 mg. Cimetidine induced coronary artery spasm in 4 patients in group 1 but none in group 2(29% vs. 0%, p less than 0.01). The extent of coronary vasoconstriction induced by cimetidine was greater at the site of spastic coronary segments than that at the site of non-spastic segments in group 1 or all segments in group 2 [14% vs. 4%, (p less than 0.01) or 14% vs. 2%, (p less than 0.01)] as well as the extent of ergonovine-induced coronary vasoconstriction [46% vs. 14%, (p less than 0.01) or 46% vs. 14%, (p less than 0.01)] and nitroglycerin-induced coronary vasodilatation [58% vs. 25%, (p less than 0.01) or 58% vs. 17%, (p less than 0.01)]. As it was suggested that cimetidine has potential vasoconstrictive effects in patients with coronary artery spasm, it should be administered with caution in patients with the vasospastic angina pectoris.     

Comparison of serum levels of inflammatory markers in patients with coronary vasospasm without significant fixed coronary artery disease versus patients with stable angina pectoris and acute coronary syndromes with significant fixed coronary artery disease

Serum levels of inflammatory markers (interleukin-6, monocyte chemoattractant protein-1, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and C-reactive protein) were measured at baseline in serum samples from 189 patients who were admitted for coronary angiography because of suspected ischemic heart disease. Median duration of follow-up was 28 months. Patients in our sample were enrolled in 4 diagnostic groups: no hemodynamically significant coronary artery disease (CAD) and no coronary vasospasm (control group, n = 32), hemodynamically significant CAD and stable angina pectoris (SAP group, n = 34), coronary vasospastic angina pectoris without hemodynamically significant CAD (vasospasm group, n = 31), and acute coronary syndrome (ACS) and hemodynamically significant CAD (ACS group, n = 92). Overall, the level of serum inflammatory markers was highest in the ACS group and lowest in the control group, with intermediate values observed in the SAP and vasospasm groups, with the exception of soluble intercellular adhesion molecule-1, the level of which was highest in the vasospasm group. Multivariate analysis showed that log (interleukin-6) was independently associated with a diagnosis of coronary vasospastic angina pectoris in patients without hemodynamically significant CAD (odds ratio 8.48, p = 0.027). Patients in the ACS group had a significantly lower survival rate compared with the other 3 groups but without an independent predictor that could be identified in this patient cohort. Recurrent angina pectoris occurred with similar rates in the SAP, vasospasm, and ACS groups. The independent predictor for recurrent angina pectoris was treatment that did not include clopidogrel (odds ratio 3.88, p = 0.007). In conclusion, the results of this study suggest that inflammation can exist in coronary vasospasm without hemodynamically significant CAD.     

Impairment of left ventricular diastolic function during the asymptomatic period in vasospastic angina patients without significant coronary stenosis]

We examined whether recurrent transient ischemia may effect left ventricular systolic and diastolic function or not. Left ventricular systolic and diastolic function during the asymptomatic period was studied by gated radionuclide ventriculography (RNV) in 25 patients with vasospastic angina (VA) who had no significant coronary stenosis, in 25 patients with effort angina (EA), and in 20 controls (C). There was no significant difference among patients in all three groups in regards to systolic indices (Ejection Fraction, Peak Ejection Rate). But diastolic indices (Peak Filling Rate, Time to Peak Filling Rate, 1/3 Mean Filling Rate, 1/3 Filling Fraction) were impaired not only in patients with EA but also in patients with VA. The treatment with nitrates and/or Ca antagonist for 6-24 months did not bring about any changes in these data concerning systolic and diastolic function in patients with VA. Thus, it is suggested that the diastolic function is impaired in patients with VA even during the asymptomatic period, though systolic function remains normal. Recurrent transient ischemia may cause irreversible myocardial injury.     

Long-term prognosis of Kawasaki disease patients with coronary artery obstruction

Summary The prognosis of coronary artery obstruction was studied in patients with Kawasaki disease. Between May 1973 and December 1987, coronary artery obstruction was diagnosed by coronary angiography in 30 patients (21 males, 9 females), of whom, only 8 (26.7%) had clinical symptoms. One patient died after 9 years of illness. Two complained of frequent chest pain, which disappeared after bypass surgery in one case and spontaneously in the other. Five had symptomatic myocardial infarction. Myocardial ischemia was diagnosed in 31.8% by treadmill stress testing, but was well demonstrated in 85.7% by thallium-201 myocardial tomography. Frequent ventricular premature beats, Wenckebachtype atrioventricular block, and ST-segment depression accompanied by chest pain were recognized by 24-h Holter monitoring. In the past, the methods used to determine the prognosis of Kawasaki disease patients with coronary artery obstruction were not adequate. However, the examinations used in this study revealed an improved ability to determine the prognosis in this disease. Myocardial tomography, in particular, provided a more accurate evaluation of myocardial damage. Ventricular arrhythmias seem to be a serious problem in these patients. Therefore, careful observation using these tests, especially myocardial tomography and Holter monitoring, should be done even if the patients are free of symptoms.     

Hibernating myocardium associated with coronary artery dissection and vasospastic angina.

Hibernating myocardium is an uncommon clinical state involving persistently impaired myocardial function. A 61-year-old man was admitted because of vasospastic angina. Coronary angiography revealed coronary artery dissection in the midportion of the right coronary artery, and segmental vasoconstriction was evoked by acetylcholine. In this patient, hibernating myocardium in the dissected region was clearly demonstrated by dipyridamole thallium-201 imaging. This report describes the first documented case of hibernating myocardium associated with coronary artery dissection, and the usefulness of dipyridamole thallium-201 imaging in the assessment of this state. Coronary artery spasm might be relevant to the etiology of coronary artery dissection.     

多支冠脉病变不完全血运重建的远期预后

目的以残余SYNTAX积分(rSS)定量评价不完全血运重建,探讨其对多支病变患者行经皮冠脉介入(PCI)治疗的远期预后评价。方法入选2010年1月至2011年6月在天津胸科医院经冠状动脉造影证实为多支病变并行PCI治疗患者653例。根据PCI术前和术后冠状动脉造影结果计算SYNTAX积分和残余SYNTAX积分。根据rSS分为:rSS≤4(207例);48(177例)。随访3~4年终点事件发生率。结果 653例患者中失访104例,与rSS≤4组和48组MACCE发生率(x~2=15.347,P<0.05)、心原性死亡率(x~2=7.383,P<0.05)、再次血运重建率(x~2=6.485,P<0.05)均明显升高,全因死亡率也明显增高(x~2=7.742,P<0.05)。Kaplan-Meier生存分析显示,rSS>8组患者长期无事件生存率明显低于rSS≤4和4相似文献   

Role of coronary spasm for a positive noninvasive stress test result in angina pectoris patients without hemodynamically significant coronary artery disease

BACKGROUND: A positive noninvasive stress test result is often considered as a false-positive indicator of coronary artery disease (CAD) when coronary angiography reveals no hemodynamically significant CAD. METHODS: From January 2001 through December 2004, 5474 patients scheduled to undergo exercise electrocardiogram (ECG) [exercise ECG without imaging or exercise ECG with thallium-201 (201Tl) single photon emission tomography (SPECT)] or dipyridamole 201Tl tomography at our outpatient clinic because of chest oppressive sensation were included in this prospective study. Coronary angiography was performed when a noninvasive test result was positive for ischemia or when ischemic chest pain was suspected. Intracoronary methylergonovine testing was performed when spastic angina was suspected and coronary angiography showed no hemodynamically significant CAD. RESULTS: Noninvasive stress testing was positive in 113 (67%) patients with coronary spasm. Of the 53 patients who had positive exercise ECG (exercise ECG with or without imaging), ST depression was found in 50 patients and ST elevationin in 3 patients. Multivessel spasm was found in 6 (15%), 6 (15%), and 7 (21%) of the patients with a positive result on exercise ECG without imaging, exercise ECG with 201Tl SPECT, and dipyridamole 201Tl SPECT, respectively. There was no significant difference in the results of noninvasive stress testing and the number of vessels with coronary spasm (1-vessel spasm versus multivessel spasm) among these 3 noninvasive stress testing groups. CONCLUSION: Intracoronary ergonovine testing induced coronary spasm in over 50% of patients who had suspected ischemic chest pain, a positive noninvasive stress test, and no hemodynamically significant CAD.     

Long-term prognosis of coronary artery spasm

This study analyses the long-term prognosis of 210 patients with coronary spasm documented at coronary angiography. All patients with a previous history of myocardial infarction or who had undergone coronary angioplasty were excluded. The average follow-up was 55 months and only 11 patients were lost to follow-up. The actuarial survival figures showed the 1 year, 2 year and 5 year survival rates to be 95, 92 and 89 per cent respectively. Extracardiac mortality was mainly related to smoking (lung cancer, laryngeal cancer, etc.) and was higher than cardiac mortality. More than half of the cardiovascular events (sudden death, myocardial infarcts) occurred during the first year of follow-up. Ten patients (4.7%) died suddenly. The predictive factors of this event were: previous syncopal episodes or syncopal angina due to coronary spasm, percritical arrhythmias and the documentation of multiple spasms at coronary angiography. Myocardial infarction was observed in 10.6 per cent of patients. Only those with significant coronary arterial lesions developed this complication. At the end of the follow-up period, 75 per cent of patients were asymptomatic or had only atypical chest pain. No significant differences were observed between the two groups treated medically, by aortocoronary bypass or by the association of coronary bypass and plexectomy with the exception of non-lethal myocardial infarcts being significantly less common in patients treated medically. Therefore, the long-term prognosis of patients with coronary spams is relatively satisfactory.     

Exercise-induced thallium-201 myocardial perfusion defects in angina pectoris without significant coronary artery stenosis

We performed exercise thallium-201 myocardial scintigraphy in 32 patients with angina pectoris to study the incidence of perfusion defects, who had no significant organic stenosis on coronary angiography. None of them had myocardial infarction or cardiomyopathy. Thallium-201 myocardial scintigraphy and 12-lead ECG recording were performed during supine bicycle ergometer exercise. Perfusion defects in thallium-201 scintigrams in SPECT images were assessed during visual analysis by two observers. In the coronary angiograms obtained during intravenous infusion of nitroglycerin, the luminal diameter of 75% stenosis or less in the AHA classification was regarded as an insignificant organic stenosis. Myocardial perfusion defects in the thallium-201 scintigrams were detected in eight (25%) of the 32 patients. Six of these eight patients had variant angina documented during spontaneous attacks with ST elevations in standard 12-lead ECGs. Perfusion defects were demonstrated at the inferior or inferoposterior regions in six patients, one of whom had concomitant anteroseptal defect. The defects were not always accompanied by chest pain. All but one patient demonstrating inferior or inferoposterior defects showed ST depression in leads II, III and aVF on their ECGs, corresponding to inferior wall ischemia. The exception was a case with right bundle branch block. Thus, 25% of the patients with angina pectoris, who had no evidence of significant organic stenosis on their coronary angiograms, exhibited exercise-induced perfusion defects in their thallium-201 scintigrams. Coronary spasms might have caused myocardial ischemia in these patients.