Invasive Endotyping in Patients With Angina and No Obstructive Coronary Artery Disease: A Randomized Controlled Trial.

BACKGROUND: We investigated the usefulness of invasive coronary function testing to diagnose the cause of angina in patients with no obstructive coronary arteries. METHODS: Outpatients referred for coronary computed tomography angiography in 3 hospitals in the United Kingdom were prospectively screened. After coronary computed tomography angiography, patients with unobstructed coronary arteries, and who consented, underwent invasive endotyping. The diagnostic assessments included coronary angiography, fractional flow reserve (patient excluded if ≤0.80), and, for those without obstructive coronary artery disease, coronary flow reserve (abnormal <2.0), index of microvascular resistance (abnormal ≥25), and intracoronary infusion of acetylcholine (0.182, 1.82, and 18.2 µg/mL; 2 mL/min for 2 minutes) to assess for microvascular and coronary spasm. Participants were randomly assigned to disclosure of the results of the coronary function tests to the invasive cardiologist (intervention group) or nondisclosure (control group, blinded). In the control group, a diagnosis of vasomotor angina was based on medical history, noninvasive tests, and coronary angiography. The primary outcome was the between-group difference in the reclassification rate of the initial diagnosis on the basis of coronary computed tomography angiography versus the final diagnosis after invasive endotyping. The Seattle Angina Questionnaire summary score and Treatment Satisfaction Questionnaire for Medication were secondary outcomes. RESULTS: Of 322 eligible patients, 250 (77.6%) underwent invasive endotyping; 19 (7.6%) had obstructive coronary disease, 127 (55.0%) had microvascular angina, 27 (11.7%) had vasospastic angina, 17 (7.4%) had both, and 60 (26.0%) had no abnormality. A total of 231 patients (mean age, 55.7 years; 64.5% women) were randomly assigned and followed up (median duration, 19.9 [12.6-26.9] months). The clinician diagnosed vasomotor angina in 51 (44.3%) patients in the intervention group and in 55 (47.4%) patients in the control group. After randomization, patients in the intervention group were 4-fold (odds ratio, 4.05 [95% CI, 2.32-7.24]; P<0.001) more likely to be diagnosed with a coronary vasomotor disorder; the frequency of this diagnosis increased to 76.5%. The frequency of normal coronary function (ie, no vasomotor disorder) was not different between the groups before randomization (51.3% versus 50.9%) but was reduced in the intervention group after randomization (23.5% versus 50.9%, P<0.001). At 6 and 12 months, the Seattle Angina Questionnaire summary score in the intervention versus control groups was 59.2±24.2 (2.3±16.2 change from baseline) versus 60.4±23.9 (4.6±16.4 change) and 63.7±23.5 (4.7±14.7 change) versus 66.0±19.3 (7.9±17.1 change), respectively, and not different between groups (global P=0.36). Compared with the control group, global treatment satisfaction was higher in the intervention group at 12 months (69.9±22.8 versus 61.7±26.9, P=0.013). CONCLUSIONS: For patients with angina and no obstructive coronary arteries, a diagnosis informed by invasive functional assessment had no effect on long-term angina burden, whereas treatment satisfaction improved. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03477890.

Successful Use of Continuous Erector Spinae Plane Blocks in a Patient With Variant Angina After Large Ventral Hernia Repair.

Coronary artery spasm constitutes the primary underlying pathology of variant angina. Because provocation of coronary artery spasm may occur with both excess sympathetic and excess parasympathetic stimulation, patients with this disorder have extremely limited options for perioperative pain control. This is especially true for procedures involving extensive abdominal incision/manipulation. Whereas neuraxial analgesia might otherwise be appropriate in these cases, several studies have demonstrated that coronary artery spasm can occur as a result of epidural placement, and therefore, that this may not be an optimal choice for patients with variant angina. This report discusses the case of a patient with a preexisting diagnosis of variant angina who underwent an exploratory laparotomy with large ventral hernia repair and for whom continuous erector spinae plane blocks were successfully used as analgesic adjuncts without triggering coronary artery spasm.

Spontaneous Multivessel Coronary Spasm During Diagnostic Coronary Angiography.

Acute vasospastic angina, formerly known as Prinzmetal angina, is characterized by transient electrocardiographic changes that are not related to exertion. Its atypical presentation makes it difficult to establish the diagnosis, so it is probably underrecognized and therefore mismanaged. We treated a 49-year-old woman who presented with a 2-day history of chest pain associated with palpitations. Abnormal radionuclide stress test results prompted diagnostic coronary angiography, during which the patient reported chest pain and became hemodynamically unstable. Active coronary vasospasm at multiple sites was treated with intracoronary nitroglycerin and nicardipine, leading to immediate recovery. Our case highlights the importance of accurate, timely diagnosis of vasospastic angina, and of early recognition and management of spontaneous coronary spasm during angiography.

A Rare Case of Cardiogenic Shock Following Severe Multivessel Coronary Vasospasm.

Prinzmetal's angina occurs following spasms in a single or multiple vascular beds, resulting in a typical chest pain and an ST-segment elevation in electrocardiography (ECG). It can lead to life-threatening arrhythmias and sudden cardiac death. We describe a 37-year-old woman who was admitted with a typical chest pain and hypotension. Her initial ECG showed an ST-segment elevation in the inferior and precordial leads. She was transferred to the catheterization unit, where coronary angiography illustrated multivessel spasms. The spasms were relieved with a nitroglycerin injection. She was discharged with stable hemodynamics 7 days later, and at 1 month's follow-up, no recurrent attack was detected.

Noninvasive detection of coronary vasospastic angina using a double-acquisition coronary CT angiography protocol in the presence and absence of an intravenous nitrate: a pilot study.

OBJECTIVES: To evaluate the feasibility of a double-acquisition coronary CT angiography (CCTA) protocol in the presence and absence of an intravenous (IV) vasodilator infusion for detecting vasospastic angina. METHODS: Twenty patients with a high clinical probability of vasospastic angina were enrolled. All subjects underwent baseline CCTA without a vasodilator in the early morning followed by a catheterized coronary angiography with ergonovine provocation test. Within 3 days, all subjects underwent repeat CCTA during a continuous IV infusion of nitrate. Vasospastic angina as detected by CCTA was defined as significant stenosis (≥50 %) with negative remodelling without definite plaques or diffuse small diameter (<2 mm) of a major coronary artery with a beaded appearance on baseline CT that completely dilated on IV nitrate CT. The CCTA results were compared to the catheterized ergonovine provocation test as the reference standard. RESULTS: Among 20 patients, the catheterized ergonovine provocation test detected vasospasm in 15 patients. The sensitivity, specificity, positive predictive value and negative predictive value of CCTA in a per-patient-based analysis were 73, 100, 100 and 56 %, respectively. CONCLUSIONS: Double-acquisition CCTA in the presence and absence of IV infusion of nitrate allows noninvasive detection of vasospastic angina with moderate sensitivity and high specificity. KEY POINTS: • Limited data exist regarding the efficacy of CCTA in detecting vasospastic angina. • We propose a double-acquisition CCTA protocol with and without IV nitrate injections. • This protocol provides 100% specificity and moderate sensitivity (73%) in spasm detection.

Life Threatening Complication of Self-made Remedy for Controlling High Blood Pressure-Coronary Artery Vasospasm Associated with Iatrogenic Thyrotoxicosis.

We report the case of a middle aged woman who was previously diagnosed with hypertension. She had been drinking a kelp concentrate solution daily for her hypertension instead of taking the prescribed medicine due to her personal beliefs about the kelp solution. As a consequence, she experienced vasospastic angina complicated by myocardial infarction and cardiogenic syncope resulting from iatrogenic thyrotoxicosis. Complementary medicine is widely used by the general population. However, there is still a lack of evidence regarding their efficacy and safety. This case shows that inadequate use of complementary medicine could have no effect and may even be harmful. In patients with chronic diseases such as hypertension, self-care in the form of life style modification, home blood pressure monitoring and medial adherence are important for disease management.

Life Threatening Complication of Self-made Remedy for Controlling High Blood Pressure-Coronary Artery Vasospasm Associated with Iatrogenic Thyrotoxicosis

We report the case of a middle aged woman who was previously diagnosed with hypertension. She had been drinking a kelp concentrate solution daily for her hypertension instead of taking the prescribed medicine due to her personal beliefs about the kelp solution. As a consequence, she experienced vasospastic angina complicated by myocardial infarction and cardiogenic syncope resulting from iatrogenic thyrotoxicosis. Complementary medicine is widely used by the general population. However, there is still a lack of evidence regarding their efficacy and safety. This case shows that inadequate use of complementary medicine could have no effect and may even be harmful. In patients with chronic diseases such as hypertension, self-care in the form of life style modification, home blood pressure monitoring and medial adherence are important for disease management.

Biventricular takotsubo cardiomyopathy: case report and general discussion.

In recent years, our understanding of the physiologic mechanisms of transient takotsubo cardiomyopathy has improved because of the growing use of emergent heart catheterization in patients who present with severe ischemic syndromes. However, even this procedure has revealed only that, in most patients with takotsubo syndrome, the sudden onset of ventricular dysfunction is not due to fixed coronary artery occlusions. We present a case of transient takotsubo cardiomyopathy with an exceptional feature--uneven impairment of both right and left ventricular function, or biventricular takotsubo--and we discuss a novel, comprehensive theory that we have devised to explain the pathophysiology of this syndrome's many manifestations.

Significant response to lower acetylcholine dose is associated with worse clinical and angiographic characteristics in patients with vasospastic angina.

BACKGROUND AND OBJECTIVES: The intracoronary injection of acetylcholine (Ach) has been shown to induce coronary spasms in patients with variant angina. Clinical significance and angiographic characteristics of patients with a significant response to lower Ach dosages are as-yet non-clarified compared with patients responding to higher Ach doses. SUBJECTS AND METHODS: A total of 3034 consecutive patients underwent coronary angiography with Ach provocation tests from January 2004 to August 2010. Ach was injected in incremental doses of 20, 50, 100 µg into the left coronary artery. Significant coronary artery spasm was defined as focal or diffuse severe transient luminal narrowing (>70%) with/without chest pain or ST-T change on the electrocardiogram (ECG). We compared the clinical and angiographic characteristics of patients who responded to a lower Ach dose (20 or 50 µg, n=556) to those that responded to a higher Ach dose (100 µg, n=860). RESULTS: The baseline clinical and procedural characteristics are well balanced between the two groups, except diabetes was higher in the lower Ach dose group and there were differences in medication history. After adjusting for confounding factors, the lower Ach dose group showed more frequent temporary ST elevation and atrioventricular block on the ECG. Furthermore, the group of patients who responded to the lower Ach dose was associated with a higher incidence of baseline and severe spasm than those who responded to a higher Ach dose. CONCLUSION: Patients with a significant response to a lower Ach dose were associated with more frequent ST elevation, baseline spasm, and more severe spasm compared with those who responded to a higher Ach dose, suggesting more intensive medical therapy with close clinical follow-up is required for those patients.

C-type natriuretic Peptide as a surrogate marker in variant angina pectoris.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the value of C-type natriuretic peptide (CNP) as a surrogate marker for detection of coronary artery spasm in variant angina pectoris (VAP). SUBJECTS AND METHODS: Sixty-six patients (mean age: 51±11 years, M : F=40 : 26) who underwent coronary angiography on suspicion of angina and who were diagnosed with VAP by the acetylcholine-induced spasm provocation test (SPT) were enrolled and divided into a SPT (-) group (n=23) and a SPT (+) group (n=43). Concentrations of CNP and other markers were determined by immunoassay in both groups. RESULTS: Plasma CNP and creatine kinase myoglobin band (CK-MB) concentrations were significantly increased in the SPT (+) group relative to the SPT (-) group (CNP, 5.268±1.800 pg/mL vs. 3.342±1.150 pg/mL, p=0.002; CK-MB, 2.54±1.03 ng/dL vs. 1.86±0.96 ng/dL, p=0.019, respectively) while plasma high sensitivity C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT pro-BNP) concentrations were not significantly different between the SPT (-) group and SPT (+) group (hs-CRP, 2.76±4.99 mg/L vs. 3.13±4.88 mg/L, p=0.789; NT pro-BNP, 49±47 pg/mL vs. 57±63 pg/mL, p=0.818, respectively). Plasma CNP concentration was independently associated with the VAP via SPT {odds ratio: 2.014 (95% confidence interval: 1.016-3.992), p=0.045}. A CNP cut-off value of 4.096 pg/mL was found to have a sensitivity of 68.2% and a specificity of 40.0% for predicting the probability of VAP via SPT. CONCLUSION: Increased plasma CNP concentration in patients with VAP may have an impact on the regulation of endothelial function in accordance with the progression of atherosclerosis. Further analysis is warranted to develop clinical applications of this finding.

Does a negative ergonovine provocation test truly predict freedom from variant angina?

Ergonovine provocation test is known to be very sensitive for diagnosing variant angina. The patient described in this study initially presented with atypical chest pain and underwent coronary angiography and ergonovine provocation tests, which were negative. The patient was subsequently prescribed a proton pump inhibitor and prokinetics for pain relief, but then presented with acute myocardial infarction and cardiogenic shock due to coronary artery vasospasm 5 years later. This case suggests that ergonovine provocation test generates false negative results, which can lead to unwanted outcomes. Even with a negative ergonovine provocation test, prescription of calcium channel blockers or nitrates should be considered in patients with a clinical history suggestive of variant angina.

Significant Response to Lower Acetylcholine Dose Is Associated with Worse Clinical and Angiographic Characteristics in Patients with Vasospastic Angina

BACKGROUND AND OBJECTIVES: The intracoronary injection of acetylcholine (Ach) has been shown to induce coronary spasms in patients with variant angina. Clinical significance and angiographic characteristics of patients with a significant response to lower Ach dosages are as-yet non-clarified compared with patients responding to higher Ach doses. SUBJECTS AND METHODS: A total of 3034 consecutive patients underwent coronary angiography with Ach provocation tests from January 2004 to August 2010. Ach was injected in incremental doses of 20, 50, 100 microg into the left coronary artery. Significant coronary artery spasm was defined as focal or diffuse severe transient luminal narrowing (>70%) with/without chest pain or ST-T change on the electrocardiogram (ECG). We compared the clinical and angiographic characteristics of patients who responded to a lower Ach dose (20 or 50 microg, n=556) to those that responded to a higher Ach dose (100 microg, n=860). RESULTS: The baseline clinical and procedural characteristics are well balanced between the two groups, except diabetes was higher in the lower Ach dose group and there were differences in medication history. After adjusting for confounding factors, the lower Ach dose group showed more frequent temporary ST elevation and atrioventricular block on the ECG. Furthermore, the group of patients who responded to the lower Ach dose was associated with a higher incidence of baseline and severe spasm than those who responded to a higher Ach dose. CONCLUSION: Patients with a significant response to a lower Ach dose were associated with more frequent ST elevation, baseline spasm, and more severe spasm compared with those who responded to a higher Ach dose, suggesting more intensive medical therapy with close clinical follow-up is required for those patients.

C-Type Natriuretic Peptide as a Surrogate Marker in Variant Angina Pectoris

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the value of C-type natriuretic peptide (CNP) as a surrogate marker for detection of coronary artery spasm in variant angina pectoris (VAP). SUBJECTS AND METHODS: Sixty-six patients (mean age: 51+/-11 years, M : F=40 : 26) who underwent coronary angiography on suspicion of angina and who were diagnosed with VAP by the acetylcholine-induced spasm provocation test (SPT) were enrolled and divided into a SPT (-) group (n=23) and a SPT (+) group (n=43). Concentrations of CNP and other markers were determined by immunoassay in both groups. RESULTS: Plasma CNP and creatine kinase myoglobin band (CK-MB) concentrations were significantly increased in the SPT (+) group relative to the SPT (-) group (CNP, 5.268+/-1.800 pg/mL vs. 3.342+/-1.150 pg/mL, p=0.002; CK-MB, 2.54+/-1.03 ng/dL vs. 1.86+/-0.96 ng/dL, p=0.019, respectively) while plasma high sensitivity C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT pro-BNP) concentrations were not significantly different between the SPT (-) group and SPT (+) group (hs-CRP, 2.76+/-4.99 mg/L vs. 3.13+/-4.88 mg/L, p=0.789; NT pro-BNP, 49+/-47 pg/mL vs. 57+/-63 pg/mL, p=0.818, respectively). Plasma CNP concentration was independently associated with the VAP via SPT {odds ratio: 2.014 (95% confidence interval: 1.016-3.992), p=0.045}. A CNP cut-off value of 4.096 pg/mL was found to have a sensitivity of 68.2% and a specificity of 40.0% for predicting the probability of VAP via SPT. CONCLUSION: Increased plasma CNP concentration in patients with VAP may have an impact on the regulation of endothelial function in accordance with the progression of atherosclerosis. Further analysis is warranted to develop clinical applications of this finding.

Does a Negative Ergonovine Provocation Test Truly Predict Freedom from Variant Angina?

Ergonovine provocation test is known to be very sensitive for diagnosing variant angina. The patient described in this study initially presented with atypical chest pain and underwent coronary angiography and ergonovine provocation tests, which were negative. The patient was subsequently prescribed a proton pump inhibitor and prokinetics for pain relief, but then presented with acute myocardial infarction and cardiogenic shock due to coronary artery vasospasm 5 years later. This case suggests that ergonovine provocation test generates false negative results, which can lead to unwanted outcomes. Even with a negative ergonovine provocation test, prescription of calcium channel blockers or nitrates should be considered in patients with a clinical history suggestive of variant angina.

Predictive Factors for Long-term Clinical Outcomes in Patients with Variant Angina / 대한내과학회지

BACKGROUND/AIMS: The incidence of variant angina (VA) is relatively high in Korea compared with western countries, but its long-term clinical outcomes are not well defined. METHODS: Patients who underwent ergonovine provocation tests at the cardiac catheterization laboratory of Chonnam National University Hospital between 1996 and 2011 were enrolled in this study (n = 1162). Of them, 686 patients with positive ergonovine provocation tests were divided into two groups: patients with cardiac events (Group I: 153 patients, 52.4 +/- 11.0 years, M: F = 103: 50) and those without (Group II: 533 patients, 51.6 +/- 10.7 years, M: F = 350: 183). The mean follow-up duration was 40.2 +/- 38.0 months. Cardiac events were defined as cardiac death, recurrent ischemia, rehospitalization, myocardial infarction, and follow-up angiography. Clinical findings, laboratory and coronary angiographic characteristics were compared between the groups. RESULTS: A history of smoking was more common in Group I than in Group II (45.8% vs. 36.3%, p = 0.037). The levels of low-density lipoprotein cholesterol (119.4 +/- 35.3 vs. 111.1 +/- 32.2 mg/dL, p = 0.010) were higher in Group I than in Group II. According to Cox proportional hazard regression analysis, the major predictive factor for cardiac events during clinical follow-up was smoking (HR 1.80, 95% CI 1.036-3.126, p = 0.037). CONCLUSIONS: A history of smoking was the only independent risk factor for cardiac events during a long-term clinical follow-up in Korean patients with variant angina.

Differential local spasticity in myocardial bridges.

To illustrate the effect of myocardial bridges on coronary vascular tone, we describe the cases of 2 patients with different clinical presentations in the context of reproducible increased spasticity at the site of myocardial bridging. One had an episode of takotsubo cardiomyopathy, and one developed typical Prinzmetal angina while receiving desmopressin treatment for pituitary insufficiency. In both patients, acetylcholine challenge clearly revealed both the presence and the severity of myocardial bridging while producing several recognizable degrees of abnormal spastic tendency.Both baseline functional states and responses to different medications correlate with spastic tendency and enable the characterization of individual cases. Understanding the spectrum of spastic conditions might help to clarify the causes of atypical ischemic events, especially in patients with myocardial bridging.

Metastatic carcinoid disease inducing coronary vasospasm.

Herein, we report a case of progressive coronary vasospasm in a 70-year-old man who had a long-standing history of metastatic gastrointestinal carcinoid tumor. Despite octreotide, nitrate, and calcium channel-blocker therapy, the patient's urinary 5-hydroxy-indole acetic acid level increased, coinciding with an increased frequency of flushing episodes with chest discomfort. In the cardiac catheterization laboratory, we captured an episode that was associated with diffuse right coronary artery spasm, ST-segment elevation, and intense symptoms. We attribute the patient's coronary vasospasm to his metastatic carcinoid disease.

Clinical characteristics of variant angina patients with or without fixed coronary stenosis / 中华全科医师杂志

Seventy-one patients with variant angina (VA) admitted in the Cardiology Department from January 2003 to March 2011,were divided into non-stenosis group (stenosis ＜ 50％,n =43) and stenosis group (stenosis ≥50％,n =28) according to the degree of stenosis.The differences of the risk factors,clinical manifestations,electrocardiogram,echocardiogram and laboratory examinations between these two groups were compared.The average age of patients in stenosis group 58 ± 8 y was higher than that in non-stenosis group (52 ± 9 y,t =2.43,P =0.02).Other risk factors,including male gender,smoking,hypertension,diabetes mellitus and lipid disorder did not show any differences between the two groups.Percentage of patients with angina pectoris lasting less than 5 min was higher in stenosis group (x2 =5.98,P =0.02),while percentage of effort angina,seeking medical consultation ≤ 6 months of onset and hemodynamic disorders showed no difference.Laboratory examinations had no differences.It is difficult to determine whether the VA patient has fixed coronary stenosis by analyzing the risk factors,clinical manifestations and laboratory examinations; to determine the fixed coronary stenosis coronary angiography is necessary.

A case of variant angina developing transient collateral circulation during vasospasm.

Variant angina is characterized by spontaneous episodes of angina, usually occurring in the morning and having ST segment elevation on the electrocardiogram. However, in the case presented here, vasospasm and angina was shown by ergonovine without ST elevation. The patient was a 60-year-old man who presented with a 2-year history of frequent chest pain. There were no abnormalities in coronary angiography. When ergonovine (100 µg) was injected, total occlusion of the proximal right coronary artery was seen, without ST elevation at the electrocardiogram. The cause was collateral from left anterior descending artery to distal right coronary artery at the left coronary angiography. Therefore, in a patient with variant angina without ST elevation, a transient collateral circulation during vasospasm should be considered.