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

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

Elevated white blood cell count and long-term clinical outcomes of patients with vasospastic angina.

OBJECTIVES: Inflammation is known as one of key pathophysiologic mechanisms of coronary artery disease. We aimed to investigate the relationship between white blood cell (WBC) count and long-term clinical outcomes of patients with vasospastic angina (VA). METHODS: A total of 823 patients who were diagnosed as VA without significant coronary lesion by coronary angiography with ergonovine provocation test were enrolled for analysis. Patients were divided according to WBC count tertile at the time of diagnosis: group I, tertile 1 and 2 (n = 546, <7490/ml); group II, tertile 3 (n = 277, ≥7490/ml). Primary outcome was defined as major adverse cardiovascular events (MACE), a composite outcome of all-cause death, cardiac death, myocardial infarction (MI), readmission due to cardiac symptoms, and revascularization. RESULTS: Median follow-up duration was 4.3 years. No significant difference of primary outcome was observed between group I and group II (14.7% vs. 20.2%, hazard ratio (HR) 1.29, confidence interval (CI) 0.90-1.83, P  = 0.162), while incidence of cardiac death and MI was significantly higher in group II (1.5% vs. 4.3%, HR 2.86, CI 1.14-7.17), P  = 0.025). In multivariate Cox regression model, elevated WBC count at the time of diagnosis of VA was an independent predictor of MI (HR 3.43, CI 1.02-11.59, P  = 0.047). CONCLUSION: Elevated WBC count at the time of diagnosis was associated with a significantly increased risk of cardiac death and MI during long-term follow-up in VA patients.

Sex differences in clinical characteristics and long-term outcomes in patients with vasospastic angina: results from the VA-Korea registry, a prospective multi-center cohort.

BACKGROUND: Sex differences in clinical characteristics and prognosis of vasospastic angina (VA) have not been well elucidated. This study was performed to investigate sex-specific characteristics and predictors for long-term clinical outcomes in patients with VA. METHODS: We analyzed 1838 patients (55 years and 62% male) who were diagnosed with definite (n = 680) or intermediate (n = 1212) VA in ergonovine provocation test from a nation-wide VA registry. The primary study end-point was composite events including cardiac death, acute coronary syndrome, ventricular tachycardia or fibrillation, and atrioventricular block during clinical follow-up. RESULTS: Male patients were younger, and there were more smokers and alcohol drinkers in male patients than in female patients. During the median follow-up period of 760 days (interquartile range, 336-1105 days), there were 73 cases (3.97%) of composite events. There was no sex difference in the occurrence of composite events (log-rank p = 0.649). Concomitant significant (≥ 50%) organic coronary stenosis was associated with worse clinical outcomes in both male (hazard ration [HR], 1.97; 95% confidence interval [CI], 1.01-3.85; p = 0.047) and female (HR, 3.26; 95% CI, 1.07-9.89; p = 0.037) patients. Obesity (body mass index ≥ 25 kg/m2) was associated with better prognosis in female VA patients (HR, 0.22; 95% CI, 0.07-0.68; p = 0.008). Even when only patients with definite diagnosis of VA were considered, there was no significant sex difference in clinical outcomes (log-rank p = 0.876). CONCLUSIONS: In VA patients, there were several different clinical characteristics according to sex; however, long-term clinical outcome was similar between sexes. Significant organic coronary stenosis in both sexes and low body mass index (< 25 kg/m2) in females were associated with worse prognosis in VA patients.

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

OBJECTIVES: The 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. BACKGROUND: Coronary artery spasm can be found in up to 60% of patients with symptoms of myocardial ischemia despite unobstructed coronary arteries. METHODS: Consecutive 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). RESULTS: In 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). CONCLUSIONS: In 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.

Questionnaire in patients with aborted sudden cardiac death due to coronary spasm in Japan.

OBJECTIVES: We investigated the medical or mechanical therapy, and the present knowledge of Japanese cardiologists about aborted sudden cardiac death (ASCD) due to coronary spasm. METHODS: A questionnaire was developed regarding the number of cases of ASCD, implantable cardioverter-defibrillator (ICD), and medical therapy in ASCD patients due to coronary spasm. The questionnaire was sent to the Japanese general institutions at random in 204 cardiology hospitals. RESULTS: The completed surveys were returned from 34 hospitals, giving a response rate of 16.7%. All SCD during the 5 years was observed in 5726 patients. SCD possibly due to coronary spasm was found in 808 patients (14.0%) and ASCD due to coronary spasm was observed in 169 patients (20.9%). In 169 patients with ASCD due to coronary spasm, one or two coronary vasodilators was administered in two-thirds of patients [113 patients (66.9%)], while more than 3 coronary vasodilators were found in 56 patients (33.1%). ICD was implanted in 117 patients with ASCD due to coronary spasm among these periods including 35 cases with subcutaneous ICD. Majority of cause of ASCD was ventricular fibrillation, whereas pulseless electrical activity was observed in 18 patients and complete atrioventricular block was recognized in 7 patients. Mean coronary vasodilator number in ASCD patients with ICD was significantly lower than that in those without ICD (2.1 ± 0.9 vs. 2.6 ± 1.0, p < 0.001). Although 16 institutions thought that the spasm provocation tests under the medications had some clinical usefulness of suppressing the next fatal arrhythmias, spasm provocation tests under the medication were performed in just 4 institutions. CONCLUSIONS: In the real world, there was no fundamental strategy for patients with ASCD due to coronary spasm. Each institution has each strategy for these patients. Cardiologists should have the same strategy and the same knowledge about ASCD patients due to coronary spasm in the future.

Clinical impact of statin therapy on vasospastic angina: data from a Korea nation-wide cohort study.

The effect of statin therapy on reducing adverse cardiovascular events in vasospastic angina (VSA) has been inconsistent. Therefore, we investigated the association between statin therapy and adverse cardiovascular events in a large, prospective VSA cohort. The Variant Angina Korea registry consecutively enrolled 2960 patients suspected VSA. Among them, we included 1713 patients who were diagnosed with VSA based on coronary provocation test. We divided the patients into the statin (n = 744) and no-statin group (n = 914) according to the medication prescribed at discharge. The primary outcome was a composite of cardiac death, acute coronary syndrome, and new-onset life-threatening arrhythmia during a 3-year follow-up period. The primary outcome occurred in 32 patients (4.3%) in the statin and 28 patients (3.1%) in the no-statin group. In Kaplan-Meier analysis before and after propensity score matching, there was no significant difference in the cumulative incidence of primary outcomes between both groups. Multivariate Cox regression analysis demonstrated that the focal type of VSA was independent predictor of primary outcomes, but statin therapy was not. Furthermore, the lack of benefit of statin therapy for primary outcomes was consistently observed across the statin intensity and spasm characteristics. In conclusion, the present study demonstrated that statin therapy did not reduce adverse cardiovascular events in patients with VSA.

Occurrence and mortality of vasospastic angina pectoris hospitalised patients in Finland: a population-based registry cohort study.

OBJECTIVES: The occurrence and mortality of vasospastic angina pectoris (VAP) is largely unknown in western countries. Our objective was to clarify the occurrence, gender-distribution and mortality of VAP in Finland using a population-based hospital registry. METHODS: We studied consecutive patients aged ≥18 years hospitalized with VAP as the primary cause of admission in Finland during 2004-2014. The data were collected from obligatory nationwide registries. During the study period 1762 admissions were recorded. RESULTS: Majority of all VAP patients were male (59.7%) and mean age was 65.7±12.0 years. Annual admission rate for VAP was 2.29/100 000 person-years. Men were in higher risk for VAP than women (admission rate 3.00/100 000 vs 1.68/100 000; RR 1.70; p<0.0001). Gender difference was not modified by age. Likelihood of VAP was highest in population aged 70-84 years. Admission rate for VAP decreased notably during the study period. One-year all-cause mortality was 8.0% and 3-year mortality was 15.5% (cardiac mortality 11.1%). Mortality was associated with increasing age, comorbidity burden and lack of detected coronary artery obstruction, but was similar between genders and during the study period. CONCLUSIONS: Men have higher risk for vasospastic angina caused admissions. Likelihood of vasospastic angina admission was highest in aged population. The 3-year all-cause mortality was 15.5%. Mortality was associated with increasing age, comorbidities and non-obstructive VAP diagnosis but was similar between genders.

Sympathectomy versus conventional treatment for refractory coronary artery spasm.

BACKGROUND: There is no clear consensus on the potential efficacy and indications for sympathectomy to prevent recurrence of vasospasm in patients with refractory coronary artery spasm (CAS). OBJECTIVE: To compare the clinical outcomes of sympathectomy with those of conventional treatment in patients with refractory CAS. PATIENTS AND METHODS: Patients with refractory CAS were randomly assigned to sympathectomy group (n = 37) or conventional treatment group (n = 42). The primary end point was a composite of major adverse cardiac event (MACE) episodes (including cardiac death, nonfatal myocardial infarction, unstable angina, heart failure, and life-threatening arrhythmia), and the secondary end point was death from any cause within 24 months after randomization. RESULTS: During the follow-up period of 24 months, the incidence of MACE in the sympathectomy and conventional treatment groups was 16.22 and 61.90%, respectively (P = 0.0001). All-cause death as the secondary end point occurred in zero and six (14.29%) patients, respectively (P = 0.0272). The Kaplan-Meier curve for MACE and all-cause death showed a significant between-group difference (log-rank test, P = 0.0013 and 0.0176, respectively). CONCLUSION: Compared with conventional treatment, sympathectomy significantly reduced the composite end point of MACE episodes and death from any cause in patients with refractory CAS by effectively preventing recurrence of vasospasm.

Impact of multi-vessel vasospastic angina on cardiovascular outcome.

BACKGROUND AND AIMS: Since clinical characteristics and prognosis of patients with multi-vessel vasospastic angina (VSA) are not clear, we investigated the nature and prognosis of multi-vessel VSA in Koreans. METHODS: Among 2960 patients enrolled in the VA-KOREA (Vasospastic Angina in Korea) registry, 104 definite multi-vessel VSA patients, 163 single vessel VSA patients and 737 non-VSA patients were identified using the intracoronary ergonovine provocation test. RESULTS: Multi-vessel VSA and single vessel VSA groups showed similar baseline characteristics and medical treatment on discharge, but different from the non-VSA group. The primary composite endpoint (cardiac death, acute coronary syndrome, and symptomatic new onset arrhythmia) over a 36-month follow-up period was significantly higher in the multi-vessel VSA group than in the single vessel VSA and non-VSA groups (8.7% vs. 1.8% and 1.1%, each log-rank p < 0.05, respectively). The rate of death and acute coronary syndrome of the multi-vessel VSA group was higher than in the single vessel VSA and non-VSA groups (5.8% vs. 1.2% and 0.9%, each log-rank p < 0.05, respectively). In addition, multi-vessel VSA was an independent predictor of the primary composite endpoint at 36 months (HR 8.5, 95% CI [2.6-27.2], p < 0.0001). CONCLUSIONS: Patients with multi-vessel VSA had worse clinical outcomes than single vessel VSA and non-VSA groups, suggesting that the existence of multi-vessel VSA itself is highly prognostic.

Impact of serum lipoprotein(a) on endothelium-dependent coronary vasomotor response assessed by intracoronary acetylcholine provocation.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic vascular disease. However, there are limited data regarding the impact of Lp(a) levels on the incidence and severity of endothelium-dependent coronary vasomotor response. PATIENTS AND METHODS: A total of 2416 patients without significant coronary artery lesion (<50% stenosis) by coronary angiography and underwent acetylcholine (ACh) provocation test were enrolled and categorized according to their serum Lp(a) level into four quartile groups: less than 6.70, 6.70-13.30, 13.30-26.27, and more than 26.27 mg/dl. The aim of this study is to estimate the incidence and severity of endothelium-dependent positive ACh provocation test in each group; moreover, to access the incidence of major adverse cardiovascular events, the composite of total death, myocardial infarction, and de novo percutaneous coronary intervention were compared between the four groups up to 5 years. RESULTS: The group with higher Lp(a) had a higher incidence of coronary heart disease, myocardial infarction, and peripheral arterial disease history. However, there was no difference among the four groups as regards the incidence of positive ACh provocation test, spasm severity, spasm extent, and location. However, at up to 5 years of clinical follow-up, the higher-Lp(a) group showed higher total death, de novo percutaneous coronary intervention, recurrent angina, and total major adverse cardiovascular events compared with the lower-Lp(a) groups. CONCLUSION: In our study, there was no relationship between the elevated Lp(a) level and the vasospastic response to the intracoronary ACh provocation test; however, higher Lp(a) levels were associated with poor clinical outcomes up to 5 years.

Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests.

Aims: Functional alterations of epicardial coronary arteries or coronary microcirculation represent a frequent cause of myocardial infarction and non-obstructive coronary arteries (MINOCA). We aimed at assessing the prognostic value of intracoronary provocative tests in patients presenting with MINOCA and in which other causes of MINOCA have been excluded. Methods and results: We prospectively evaluated patients with a diagnosis of MINOCA, excluding patients with aetiologies other than suspected coronary vasomotor abnormalities. Immediately after coronary angiography, an invasive provocative test using acetylcholine or ergonovine was performed. The incidence of death from any cause, cardiac death, and recurrence of acute coronary syndrome (ACS) was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires (SAQ). We enrolled 80 consecutive patients [mean age 63.0 ± 10.7 years, 40 (50%) male]. Provocative test was positive in 37 (46.2%) patients without any complication. Among patients with a positive test, epicardial spasm was detected in 24 (64.9%) patients and microvascular spasm in 13 (35.1%) patients. After a median follow-up of 36.0 (range 12.0-60.0) months, patients with a positive test had a significantly higher occurrence of death from any cause [12 (32.4%) vs. 2 (4.7%); P = 0.002], cardiac death [7 (18.9%) vs. 0 (0.0%); P = 0.005], and readmission for ACS [10 (27.0%) vs. 3 (7.0%); P = 0.015] as well as a worse angina status as assessed by SAQ [Seattle score: 88.0 (33.0-100.0) vs. 100.0 (44.0-100.0); P = 0.001] when compared with patients with a negative test. Conclusions: We demonstrate that in patients presenting with MINOCA and suspected coronary vasomotor abnormalities, a positive provocative test for spasm is safe and identifies a high-risk subset of patients.

Impact of different nitrate therapies on long-term clinical outcomes of patients with vasospastic angina: A propensity score-matched analysis.

BACKGROUND: Despite the short-term vasodilatory effects of nitrates, the prognostic effects of long-term nitrate therapy in patients with vasospastic angina (VSA) remains unclear. We investigated the prognostic impact of chronic nitrate therapy in VSA patients. METHODS: Between January 2003 and December 2014, a total of 1154 VSA patients proven by ergonovine provocation tests were classified into nitrate (n=676) and non-nitrate (n=478) groups according to prescriptions for oral nitrates, including isosorbide mononitrate (ISMN) and nicorandil. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, myocardial infarction, any revascularization, or rehospitalization due to recurrent angina. RESULTS: The nitrate group was found to have a higher risk of MACE (22.9% vs. 17.6%, hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.01-1.73, p=0.043) than the non-nitrate group. After propensity score matching, the nitrate group had greater risks of MACE (HR 1.32, 95%CI 1.01-1.73, p=0.049). Patients who received the immediate-release formula of ISMN (HR 1.80, 95%CI 1.35-2.39, p<0.001) or were administered any forms of ISMN other than at bedtime (HR 1.90, 95%CI 1.41-2.57, p<0.001) had a significantly higher risk of MACE compared with the non-nitrate group. Nicorandil was shown to have a neutral effect on VSA patients (HR 1.11, 95%CI 0.73-1.69, p=0.62). CONCLUSIONS: The long-term use of nitrate therapy was associated with increased risk of adverse cardiac events in VSA patients. The use of immediate-release ISMN or the administration of ISMN other than at bedtime was related with poor outcomes of VSA patients.

Five-year major clinical outcomes according to severity of coronary artery spasm as assessed by intracoronary acetylcholine provocation test.

BACKGROUND: Long-term clinical outcome data according to severity of coronary artery spasm (CAS) as assessed by an intracoronary acetylcholine provocation test are limited in series of Asian patients. AIM: To investigate 5-year clinical outcomes in patients with CAS according to CAS severity. METHODS: In total, 5873 consecutive patients with insignificant coronary artery disease (<70% fixed stenosis) who underwent an acetylcholine provocation test were enrolled and divided into four groups according to CAS severity during the acetylcholine provocation test: negative, borderline positive, moderately positive and severely positive. CAS severity was assessed by quantitative coronary angiography. We investigated 5-year clinical outcomes according to CAS severity. RESULTS: Over a follow-up period of up to 5 years, before adjustment, the severely-positive CAS group showed a significantly higher incidence of major adverse cardiac events (MACE; composite of death, myocardial infarction and de novo revascularization) (hazard ratio [HR]: 1.834, 95% confidence interval [CI]: 1.047-3.211; P=0.033), total death (HR: 3.124, 95% CI: 1.047-9.322; P=0.041), myocardial infarction (HR: 3.190, 95% CI: 1.069-9.519; P=0.037) and recurrent angina (HR: 1.762, 95% CI: 1.363-2.278; P<0.001) compared with the negative group. However, after adjustment for baseline confounders, only the incidence of recurrent angina (HR: 1.323, 95% CI: 1.014-1.726; P=0.039) was significantly higher in the severely-positive CAS group compared with the negative group. CONCLUSIONS: The severity of CAS in the positive group was not associated with an increased incidence of MACE after adjustment for covariates compared with the negative group, but the severely-positive CAS group was associated with a higher incidence of recurrent angina compared with the negative group.

Masked inherited primary arrhythmia syndromes in sudden cardiac death patients accompanied by coronary vasospasm.

BACKGROUND/AIMS: Coronary vasospasms are one of the important causes of sudden cardiac death (SCD). Provocation of coronary vasospasms can be useful, though some results may lead to false positives, with patients potentially experiencing recurrent SCD despite appropriate medical treatments. We hypothesized that it is not coronary vasospasms but inherited primary arrhythmia syndromes (IPAS) that underlie the development of SCD. METHODS: We analyzed 74 consecutive patients (3.8%) who survived out-of-hospital cardiac arrest among 1,986 patients who had angiographically proven coronary vasospasms. Electrical abnormalities were evaluated in serial follow-up electrocardiograms (ECGs) during and after the index event for a 3.9 years median follow-up. Major clinical events were defined as the composite of death and recurrent SCD events. RESULTS: Forty five patients (60.8%) displayed electrocardiographic abnormalities suggesting IPAS: Brugada type patterns in six (8.2%), arrhythmogenic right ventricular dysplasia patterns in three (4.1%), long QT syndrome pattern in one (2.2%), and early repolarization in 38 (51.4%). Patients having major clinical events showed more frequent Brugada type patterns, early repolarization, and more diffuse multivessel coronary vasospasms. Brugada type pattern ECGs (adjusted hazard ratio [HR], 4.22; 95% confidence interval [CI], 1.16 to 15.99; p = 0.034), and early repolarization (HR, 2.97; 95% CI, 1.09 to 8.10; p = 0.034) were ultimately associated with an increased risk of mortality. CONCLUSIONS: Even though a number of aborted SCD survivors have coronary vasospasms, some also have IPAS, which has the potential to cause SCD. Therefore, meticulous evaluations and follow-ups for IPAS are required in those patients.

Clinical implications of low-dose aspirin on vasospastic angina patients without significant coronary artery stenosis; a propensity score-matched analysis.

BACKGROUND: High-dose aspirin has been reported to exacerbate coronary artery spasm in patients with vasospastic angina. We investigated clinical implications of low-dose aspirin on vasospastic angina patients without significant coronary artery stenosis. METHODS: We included patients without significant coronary artery stenosis on coronary angiography (CAG) and with positive results on intracoronary ergonovine provocation test between January 2003 and December 2014. A total of 777 patients were divided into two groups according to prescription of low-dose aspirin at discharge: aspirin group (n=321) and non-aspirin group (n=456). The major adverse cardiovascular events (MACE), defined as composite outcomes of cardiac death, acute myocardial infarction, revascularization, or rehospitalization requiring CAG or medication change due to recurrent angina were compared. RESULTS: The aspirin group had significantly higher incidence of MACE (22.8% versus 12.1%; p=0.04) and had higher tendency for rehospitalization (20.6% versus 11.2%; p=0.08). All-cause mortality and cardiac death were similar between the two groups. After propensity score matching, the aspirin group had greater risk of MACE (hazard ratio [HR] 1.54; 95% confidence interval [CI], 1.04-2.28; p=0.037) and rehospitalization requiring CAG (HR, 1.33; 95% CI, 1.13-4.20; p=0.03), and a higher tendency for rehospitalization (HR, 1.40; 95% CI, 0.94-2.09; p=0.12). CONCLUSION: In vasospastic angina without significant coronary artery stenosis, patients taking low-dose aspirin are at higher risk of MACE, driven primarily by tendency toward rehospitalization. Low-dose aspirin might be used with caution in vasospastic angina patients without significant coronary artery stenosis.

Impact of aspirin on the prognosis in patients with coronary spasm without significant atherosclerotic stenosis.

BACKGROUND: Coronary spasm is one of the mechanisms of myocardial infarction with nonobstructive coronary arteries (MINOCA). The aim of this study was to investigate the effects of aspirin on future cardiovascular events in patients with coronary vasospastic angina (VSA) with non-significant atherosclerotic stenosis. METHODS: This was the retrospective analysis of the 640 VSA patients with non-significant atherosclerotic stenosis (≤50% stenosis) among 1,877 consecutive patients who underwent acetylcholine (ACh)-provocation testing between January 1991 and December 2010. The patients were divided into 2 groups treated with (n=137) or without (n=503) low-dose aspirin (81-100mg/day). We evaluated major adverse cardiac events (MACE), defined as cardiac death, nonfatal myocardial infarction, and unstable angina. RESULTS: In the study population, 24 patients (3.8%) experienced MACE; there were 6 cases in VSA patients with aspirin and 6 in those without aspirin. Multivariate Cox hazards analysis for correlated factors of MACE indicated that use of statin (HR: 0.11; 95% CI: 0.02 to 0.84; P=0.033), ST-segment elevation during attack (HR: 5.28; 95% CI: 2.19-12.7; P<0.001), but not the use of aspirin as a significant predictor of MACE. After propensity score matching (n=112, each), Kaplan-Meier survival analysis indicated almost identical rate of 5-year survival free from MACE in those with aspirin, compared to those without aspirin in the entire and matched cohort (P=0.640 and P=0.541, respectively). CONCLUSIONS: Low-dose aspirin might not reduce future cardiovascular events in VSA patients with non-significant stenosis.

Acetylcholine-Provoked Coronary Spasm at Site of Significant Organic Stenosis Predicts Poor Prognosis in Patients With Coronary Vasospastic Angina.

BACKGROUND: Coronary artery spasm contributes to the pathogenesis of variant angina and ischemic heart disease and may play a role in the progression of atherosclerosis. It is unclear whether the location of spasm is related to outcome. OBJECTIVES: This study compared the clinical features and prognosis of patients with coronary spasm at the site of significant atherosclerotic stenosis with patients with spasm at sites without stenosis or nonsignificant stenosis. METHODS: This was a retrospective, observational study of 1,877 consecutive patients with typical or atypical angina-like chest pain undergoing acetylcholine (ACh)-provocation testing. A total of 1,760 patients were eligible for analysis. ACh-provoked coronary spasm and significant organic stenosis were observed in 873 and 358 patients, respectively. RESULTS: In patients with significant atherosclerotic stenosis, ACh-positive patients (n = 233) were younger and without diabetes mellitus compared with nonspasm patients (n = 125). In patients without organic stenosis, ACh-positive patients (n = 640) were older, had dyslipidemia, and were more likely to have a family history of ischemic heart disease than nonspasm patients (n = 762). Multiple logistic regression analysis identified ST-segment elevation during anginal attacks, organic stenosis of the left anterior descending artery, and multivessel spasm as correlates of spasm at sites of significant organic stenosis (n = 192). Multivariate analysis identified ACh-provoked spasm at the site of significant stenosis and use of nitrates as the 2 prognostic factors for major adverse cardiac events. CONCLUSIONS: The clinical features and prognosis of patients with ACh-provoked coronary spasm were different when it occurred at the site of significant atherosclerotic stenosis compared with patients with spasm elsewhere. Both spasm at the site of significant organic stenosis and nitrate use were significant predictors of major adverse cardiac events.

The 24-Month Prognosis of Patients With Positive or Intermediate Results in the Intracoronary Ergonovine Provocation Test.

OBJECTIVES: This study was an observational, multicenter registry to determine clinical characteristics and 24-month prognosis of patients who underwent intracoronary ergonovine provocation tests. BACKGROUND: The clinical characteristics and prognosis of patients who underwent the ergonovine provocation for vasospastic angina were not fully elucidated. METHODS: A total of 2,129 patients in the VA-KOREA (Vasospastic Angina in Korea) registry were classified into positive (n = 454), intermediate (n = 982), and negative (n = 693) groups by intracoronary ergonovine provocation tests. The 24-month incidences of cardiac death, new-onset arrhythmia, and acute coronary syndrome were determined (mean 26.7 ± 8.8 months). RESULTS: The number of smokers, frequency of angina before angiography, high-sensitivity C-reactive protein, and triglyceride were higher in the positive group than in other groups. The clinical characteristics of the intermediate and the negative groups were very similar. In the positive group, the incidences of diffuse, focal, and mixed spasm were 65.9%, 23.6%, and 10.6%. Coronary spasm was more frequently provoked on atherosclerotic segments. The 24-month incidences of cardiac death, arrhythmia, and acute coronary syndrome were low (0.9%, 1.6%, and 1.9%, respectively) in the positive group, and there was no cardiac death in the intermediate group (p = 0.02). In the positive group, frequent angina, current smoking, and multivessel spasm were independent predictors for adverse events. CONCLUSIONS: The 24-month prognosis of the positive group in the intracoronary ergonovine provocation test was relatively worse than that of the intermediate group. More intensive clinical attention should be paid to vasospastic angina patients with high-risk factors including frequent angina before angiography, current smoking, and multivessel spasm.

Serious cardiac complications in coronary spasm provocation tests using acetylcholine or ergonovine: analysis of 21 512 patients from the diagnosis procedure combination database in Japan.

BACKGROUND: Previous studies on complications with coronary spasm provocation tests were based on small sample sizes or were limited to high-volume centers. The risk of provocation tests using acetylcholine (ACH) or ergonovine (ER) remains to be fully examined by a large-scale multicenter study. HYPOTHESIS: ACH provocation tests are associated with a higher rate of serious cardiac complications than ER tests. METHODS: Using the Diagnosis Procedure Combination database in Japan, we identified patients aged ≥20 years who underwent a pharmacological provocation test during coronary angiography. We assessed the composite outcome of cardiac complications requiring urgent procedures (defibrillation, chest compression, intra-aortic balloon pumping, or extracorporeal membrane oxygenation) or death on the day of the provocation test, and compared the outcome between ACH and ER tests. RESULTS: Of 21 512 eligible patients in 602 hospitals, 10 628 (49.4%) underwent an ACH test and 10 884 (50.6%) underwent an ER test. The composite outcome occurred in 141 (0.7%) patients. The ACH group was significantly more likely to have the composite outcome than the ER group (0.9% vs 0.4%, P < 0.001). The propensity-score analyses showed consistent results (propensity score-matched, 0.9% vs 0.4%, P = 0.003; inverse probability-weighted, 0.8% vs 0.4%, P < 0.001). In a multivariable logistic regression analysis, ACH tests were significantly associated with a higher rate of the composite outcome than ER tests (odds ratio: 1.75, 95% confidence interval: 1.13-2.69, P = 0.011). CONCLUSIONS: This retrospective cohort study suggested that ACH tests were associated with a higher rate of cardiac complications than ER tests.