Alternative causes of myocardial ischemia in women: An update on spontaneous coronary artery dissection, vasospastic angina and coronary microvascular dysfunction.

Although coronary obstruction due to atherosclerosis is the most common cause of myocardial ischemia, a significant proportion of patients have myocardial ischemia in the absence of obstructive epicardial coronary artery disease (CAD). This finding is more common among women and alternative causes can mediate myocardial ischemia. Abnormalities in vascular structure, alterations in coronary vasomotion and dysfunction of the coronary microcirculation can all cause ischemia in the absence of obstructive CAD due to atherosclerosis. In this review, we provide an update on three alternative causes of myocardial ischemia: spontaneous coronary artery dissection (SCAD), vasospastic angina (VSA) and coronary microvascular dysfunction (CMVD). We review pathophysiology, clinical presentation, diagnosis, treatment and outcomes related to these important clinical entities. There is increasing interest in better defining this patient population with use of advanced imaging and testing tools. Despite the increased associated risk with future cardiac events, evidence-based treatments for these diagnoses remain under-studied and poorly defined. These alternative diagnoses should be kept in mind when evaluating women with myocardial ischemia without obstructive CAD due to atherosclerosis.

Maximal acetylcholine dose of 200 µg into the left coronary artery as a spasm provocation test: comparison with 100 µg of acetylcholine.

As a spasm provocation test of acetylcholine (ACH), incremental dose up (20/50/100 µg) into the left coronary artery (LCA) is recommended in the guidelines established by Japanese Circulation Society. Recently, Ong et al. reported the ACOVA study which maximal ACH dose was 200 µg in the LCA. We compared the angiographic findings between ACH 100 µg and ACH 200 µg in the LCA and also examined the usefulness and safety of ACH 200 µg in Japanese patients without variant angina. As a spasm provocation test, we performed intracoronary injection of ACH 200 µg after ACH 100 µg in 88 patients (55 males, 68.4 ± 11.7 years old) including 59 ischemic heart disease (IHD) patients and 29 non-IHD patients. Positive spasm was defined as >99 % transient stenosis (focal spasm) or 90 % severe diffuse vasoconstriction (diffuse spasm). Positive spasm by ACH 200 µg was significantly higher than that by ACH 100 µg (36 pts: 40.9 % vs. 17 pts: 19.3 %, p < 0.01). Diffuse distal spasm on the left anterior descending artery was more recognized in ACH 200 µg than in ACH 100 µg (30.7 vs. 13.6 %, p < 0.01). In 29 rest angina patients, positive spasm by ACH 200 µg (19 pts) was significantly higher than that by ACH 100 µg (7 pts) (65.5 vs. 24.1 %, p < 0.01). No serious irreversible complications were found during ACH 200 µg. Administration of ACH 200 µg into the LCA was safe and useful. We may reexamine the maximal ACH dose into the LCA.

Persistent coronary artery spasm documented by follow-up coronary angiography in patients with symptomatic remission of variant angina.

For patients with variant angina it is very important to start medical therapy using calcium-channel blockers. However, the decision of physicians regarding whether to decrease the dose of the drug or discontinue it is controversial. We investigated whether the nature of spasm is remissive and whether the termination of medications is safe. The subjects studied were included in the Vasospastic Angina in Catholic Medical Center Registry from March 2001 to December 2009. We analyzed 37 patients (62 lesions) with variant angina, diagnosed using coronary angiography (CAG) and he acetylcholine provocation test, without any organic coronary stenosis, whose symptoms were well controlled after medication. The follow-up CAG with provocation test was performed at a median interval of 44 months. The characteristics of spasm were analyzed on each pair of CAGs. The study group consisted of 23 men (62.2 %) and 14 women (37.8 %) with a mean age of 59 ± 11.1 years. The follow-up CAG with provocation test showed that the characteristics of the spasmodic nature were consistent with the first test in all patients. Although the patients with variant angina had no chest pain after medical treatment, the spasmodic nature of coronary arteries still remained. We may decrease the drug dosage after carefully checking the patient's symptoms but recommend not discontinuing therapy, even if the patient is asymptomatic.

Clinical outcome of coronary stenting in patients with variant angina refractory to medical treatment: a consecutive single-center analysis.

OBJECTIVE: To investigate the efficacy of coronary stenting in patients with variant angina refractory to medical treatment. SUBJECTS AND METHODS: Variant angina was diagnosed in 81 patients admitted to the Department of Cardiology between January 2003 and June 2011. However, coronary stenting was performed in 21 patients refractory to medical treatment, but coronary angiography and intravascular ultrasound were performed in all patients, and acetylcholine provocative test was performed in 11 of the 21 patients refractory to medical treatment. Coronary angiography was repeated after 9-12 months in the 21 patients with coronary stents. Clinical follow-up time was 2.5 ± 3.1 years (range 1-8). RESULTS: Of the 81 patients, coronary angiography and intravascular ultrasound did not reveal significant stenosis in 13 (16.0%), but revealed 20-75% fixed stenosis in the remaining 68 (84.0%) patients. The acetylcholine provocative test was positive in the 11 patients. Of the 21 patients with coronary stents, the spasm site was located in the right coronary artery in 16 (76.2%) and in the left anterior descending artery in the remaining 5 (23.8%) patients. During the 1- to 8-year follow-up period, 1 of the 21 patients with stents developed recurrent episodes of variant angina, 5 patients had occasional chest pain, and the other 15 were asymptomatic. Coronary angiography at 9-12 months after initial evaluation demonstrated no stenosis in 3 patients, 20-40% in-stent mild intimal hyperplasia in 15 patients, and 50-80% in-stent restenosis in 3 patients. Coronary stenting was performed again in 2 patients. CONCLUSIONS: The present study showed that coronary stenting for severe refractory coronary vasospasm was effective and without serious complications. It can be an alternative and viable option for some patients who are refractory to medical therapy and at a high risk of acute coronary syndrome recurrence.

[Hyperventilation echocardiography in vasospastic angina pectoris diagnosing]. / Hyperventilacní echokardiografie v diagnostice vazospastické anginy pectoris.

Hyperventilation echocardiography is an established diagnostic test in patients with suspected variant angina pectoris. It has got sufficient sensitivity (60-80%) and specificity (85-100%). Positive hyperventilation test is rarely found, which relates to low prevalence of variant angina. The diagnostic yield of the test depends on the population selected for testing: positive result can be expected in patients with a history of typical burning chest pain, ST segment elevation/depression and/or inversions of U wave during the chest pain episode, arrhythmias related to the chest pain, coronary artery stenosis less than 50% of artery diameter, multi-vessel disease, high activity of illness at the time of hyperventilation test. We present a case of 37 years old man with typical angina pectoris at rest and non-Q myocardial infarction, in whom the coronary angiography was negative. Variant angina pectoris was diagnosed by hyperventilation echocardiography. The ECG tracings showing typical ischemic patterns during the hyperventilation test are included.

Pericarditis as a trigger for Prinzmetal angina - a case report.

Prinzmetal angina is one of the causes of acute coronary syndromes, the exact etiology of which is still unknown. Here we introduce a 27-year-old man with no history of cardiovascular disease, with a history of hospitalization due to acute pericarditis in the previous month, who was discharged with a good response to ibuprofen treatment but had clinical and electrocardiographically recurrence of pericarditis with compressive retrosternal chest pain and electrocardiogram (ECG) changes in favor of acute infero-postero-right ventricular (RV) myocardial infarction (MI). Treatment with vasodilator improved compressive retrosternal chest pain and reversed acute myocardial infarction changes completely and left pleuritic chest pain and pericarditis changes in the ECG. Due to the typical chest pain, he was admitted to the emergency room; ECG revealed generalized ST-segment elevation with acute pericarditis pattern again. Acute infero-posterior and right ventricular acute myocardial infarction pattern was also evident. After treatment with nitroglycerin in the Critical Cardiac Unit (CCU), all ECG ischemic changes returned to baseline, and pericarditis remained in all leads. The patient was discharged with non-steroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers, and a good general condition.

Estimation of coronary flow velocity reserve using transthoracic Doppler echocardiography and cold pressor test might be useful for detecting of patients with variant angina.

PURPOSE: The cold pressor test (CPT) has been used to detect variant angina, but its sensitivity in predicting vasospasm is low. The aim of this study was to determine whether estimates of the coronary flow velocity reserve (CFVR) in the distal left anterior descending coronary artery (dLAD) using transthoracic echocardiography (TTE) and CPT are useful tool to predict variant angina. METHODS: 65 patients (mean age = 52 +/- 10 years; male:female = 41:24) who had normal coronary artery on angiography and underwent acetylcholine provocation test were enrolled and divided into the spasm group (n = 31) and the no spasm group (n = 34). During CPT, the peak (PDV) and mean diastolic flow velocity (MDV) of the dLAD were estimated using TTE with a high-frequency transducer, and electrocardiography, blood pressures, heart rate, and symptoms were monitored every 30 seconds. CPT%PDV and CPT%MDV were defined as the percentage changes in PDV and MDV during CPT, respectively. RESULTS: CPT%PDV was 4.99 +/- 23.62% in the spasm group and 52.75 +/- 24.78% in the no spasm group (P < 0.001). CPT%MDV was 6.83 +/- 23.81% in the spasm group and 50.22 +/- 27.83% in the no spasm group (P < 0.001). CPT%PDV<31.1% had a sensitivity of 93.5% and a specificity of 82.4% in predicting variant angina (95% confidence interval [CI]: 0.939-0.979, P < 0.001). CPT%MDV<30.55% had a sensitivity of 90% and a specificity of 76.5% in predicting variant angina (95% CI: 0.884-0.950, P < 0.001). CONCLUSION: The measurement of changes in the coronary flow velocity of the dLAD using TTE and CPT might be useful for the estimation of endothelial dysfunction in patients with variant angina.

Persistent regional diastolic dysfunction after myocardial ischemia and the effect of statin treatment: assessment with two-dimensional radial strain rate.

BACKGROUND: Persistence of regional diastolic dysfunction after ischemic insult remains debatable. With speckle tracking echocardiography (STE), we sought to (1) prove the persistence of regional diastolic dysfunction, (2) assess the feasibility of applying persistent regional diastolic dysfunction to differentiating ischemic and nonischemic chest pain, and finally (3) examine statin effects on postischemic regional diastolic dysfunction. METHODS: Nineteen patients with variant angina (VA) and 12 normal subjects were enrolled. Comprehensive echocardiographic examinations were performed before and 1 day after coronary angiography (CAG) with ergonovine provocation. Radial systolic (rSRsys) and diastolic (rSRdia) strain rates were obtained and averaged using standard segmentation models corresponding to the three major coronary territories assigned. RESULTS: No significant changes in rSRsys and rSRdia values were observed for controls and in rSRsys for VA. However, rSRdia for VA demonstrated a weak, but significant, decrease from -2.25 +/- 0.71/sec to -2.04 +/- 0.71/sec (P = 0.003) 1 day after CAG. However, because of the wide overlap between rSRdia values in normal and ischemic segments for VA patients, predictability of remote ischemia based solely on the rSRdia was limited. Subgroup analysis according to statin prescription showed that statin administration contributed to the elimination of rSRdia reduction (-2.28 +/- 0.84/sec on pre-CAG vs. -2.29 +/- 0.77/sec on post-CAG, P = 0.72 for patients without statin premedication; -2.23 +/- 0.64/sec for pre-CAG vs. -1.88 +/- 0.65/sec for post-CAG, P = 0.002 for those without). Expectedly, rSRsys values showed no significant changes in all situations. CONCLUSIONS: The presence and sustained nature of regional diastolic dysfunction can be demonstrated with STE. Statin minimized the persistence of regional diastolic dysfunction after an acute ischemia. Although the clinical usefulness of rSRdia by STE appears to be limited, its clinical utility requires further consideration, given the brevity of the ischemia provoked during CAG with ergonovine and the protracted regional diastolic dysfunction.

Variant angina induced by carbon monoxide poisoning: A CARE compliant case report.

RATIONALE: Carbon monoxide (CO) poisoning can cause severe damage to the nervous system, and can also cause serious damage to organs, such as the heart, kidneys, and lungs. CO damage to myocardial cells has been previously reported. This can lead to serious complications, such as myocardial infarction. PATIENT CONCERNS: A 47-year-old female patient complained of sudden chest pain for 30 minutes. Before admission, the patient had non-radiating burning chest pain after inhalation of soot. DIAGNOSIS: An electrocardiogram showed that myocardial ischemia was progressively aggravated, manifested by progressive ST-segment elevation, and accompanied by T wave inversion and other changes. No obvious coronary stenosis was observed in a coronary angiographic examination. Therefore, the patient was considered to have developed variant angina resulting from CO poisoning-induced coronary artery spasm. INTERVENTIONS: The patient was treated with drugs for improving blood circulation and preventing thrombosis, and underwent hyperbaric oxygen therapy. OUTCOMES: Clinical symptoms relieved after the treatment. LESSONS: Findings from this case suggest that CO can cause coronary artery spasm and it is one of the predisposing factors of variant angina. For these patients, hyperbaric oxygen therapy can improve blood circulation and prevent formation of thrombus and encephalopathy.

Vasospastic angina: A literature review of current evidence.

Vasospastic angina (VSA) is a variant form of angina pectoris, in which angina occurs at rest, with transient electrocardiogram modifications and preserved exercise capacity. VSA can be involved in many clinical scenarios, such as stable angina, sudden cardiac death, acute coronary syndrome, arrhythmia or syncope. Coronary vasospasm is a heterogeneous phenomenon that can occur in patients with or without coronary atherosclerosis, can be focal or diffuse, and can affect epicardial or microvasculature coronary arteries. This disease remains underdiagnosed, and provocative tests are rarely performed. VSA diagnosis involves three considerations: classical clinical manifestations of VSA; documentation of myocardial ischaemia during spontaneous episodes; and demonstration of coronary artery spasm. The gold standard diagnostic approach uses invasive coronary angiography to directly image coronary spasm using acetylcholine, ergonovine or methylergonovine as the provocative stimulus. Lifestyle changes, avoidance of vasospastic agents and pharmacotherapy, such as calcium channel blockers, nitrates, statins, aspirin, alpha1-adrenergic receptor antagonists, rho-kinase inhibitors or nicorandil, could be proposed to patients with VSA. This review discusses the pathophysiology, clinical spectrum and management of VSA for clinicians, as well as diagnostic criteria and the provocative tests available for use by interventional cardiologists.

Effect of intracoronary adenosine on ergonovine-induced vasoconstricted coronary arteries.

BACKGROUND: This study aimed to evaluate the effect of adenosine on epicardial coronary artery diameter during ergonovine provocation testing. METHODS: A total of 158 patients who underwent an ergonovine provocation test with intracoronary adenosine injection between 2011 and 2014 were selected. Patients were divided into four groups based on the severity of percent diameter stenosis following intracoronary ergonovine administration: Group 1, induced spasm < 50%; Group 2, 50-89%; Group 3, 90-99%; and Group 4, total occlusion. RESULTS: Spasm positivity was observed in 44 (27.8%) cases in the study population (mean age, 57.4 ± ± 10.7 years). Intracoronary adenosine increased the diameter of the ergonovine-induced epicardial artery by 0.51 ± 0.31 mm, 0.73 ± 0.39 mm, 0.44 ± 0.59 mm, and 0.01 ± 0.04 mm in Groups 1, 2, 3, and 4, respectively. Subsequent administration of nitroglycerin further increased vessel diameter by 0.49 ± 0.28 mm, 0.93 ± 0.68 mm, 2.11 ± 1.25 mm, and 2.23 ± 0.69 mm in Groups 1, 2, 3, and 4, respectively. The ratios of adenosine-induced diameter to reference diameter were significantly lower in patients with spasm positive results (0.68 [0.59-0.76] vs. 0.18 [0.00-0.41], p < 0.001 in the study population; 0.60 [0.54-0.67] vs. 0.40 [0.27-0.44], p < 0.001 in Group 2) with the best cut-off value of 0.505 (sensitivity 0.955, specificity 0.921). CONCLUSIONS: Intracoronary administration of adenosine dilated the ergonovine-induced vasoconstricted epicardial coronary artery. The ratio of adenosine-induced diameter to reference diameter was significantly lower in patients with spasm positive results.

Variant angina in an adolescent coexisting with intermittent Wolff-Parkinson-White syndrome.

Chest pain is not an uncommon complaint among adolescents; however, it often leads them to seek emergency medical care. The variant angina (coronary artery spasm) with resulting acute myocardial ischemia is an extremely rare cause of chest pain among the pediatric population, and there are very few cases reported. We describe a 13-year-old boy with underlying intermittent Wolff-Parkinson-White syndrome and who had an acute coronary artery syndrome due to coronary artery vasospasm.

[Prinzmetal's angina: clinical manifestation in a 79-year-old man with atherosclerotic coronary artery disease]. / Dlawica naczynioskurczowa - manifestacja kliniczna u 79-letniego chorego z miazdzyca tetnic wiencowych.

A case of a 79-year-old man with risk factors of ischaemic heart disease is presented. He was admitted to the Cardiology Ward because of recurrent angina pectoris with ST-segment elevation in the anterior electrocardiographic leads. Coronary arteriography revealed 90% stenosis of the marginal branch of the left coronary artery, which was supplied by coronary angioplasty. During hospitalisation recurrent episodes of angina pectoris were noted, only in night hours, with ST-segment elevations in anterior electrocardiographic leads. Pharmacotherapy with calcium blockers and nitrates eliminated the episodes of chest pain in a ten-month follow-up.

A case of suspected vasospastic angina related to S-1 administration.

A 58-year-old male with advanced gastric cancer underwent a total gastrectomy after neoadjuvant chemotherapy with paclitaxel and cisplatin. The combination chemotherapy was resumed postoperatively as adjuvant chemotherapy. Although no recurrence was observed after 6 months of adjuvant chemotherapy,the patient elected to receive further adjuvant chemotherapy with an oral drug. On the night of November 9,2006, he began taking S-1 at a dose of 50 mg twice daily. Fifty minutes after taking the first 50 mg of S-1,he experienced a squeezing chest pain at rest that was later accompanied by diaphoresis and nausea. The pain continued for approximately one hour,but had subsided by the time he reached an emergency room. Coronary angiography revealed a 50% eccentric stenosis in the proximal site of the right coronary artery,but there was no coronary lesion which could caused myocardial ischemia. Cardiac scintigraphy using 123I-BMIPP (123I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid) showed a decreased uptake of BMIPP within the posterior wall,which improved one month later,so transient myocardial ischemia was confirmed. Since vasospastic angina related to S-1 administration was highly suspected,re-administration of S-1 was not performed. The patient is not currently receiving chemotherapy and remains under surveillance for relapse.

Prinzmetals angina presenting with non critical lesion with normal FFR -to stent or not to stent.

Variant angina also called Prinzmetals angina is an enigma characterized by transient circadian symptoms of chest pain associated with ECG changes. The patient is symptom free with normal ECG and echo during symptom free periods. We present a case associated with transient ST-segment elevation with non critical lesion with normal FFR.

A woman with recurrent chest pain and ST-segment elevation.

A 32-year-old female presents with recurrent episodes of unprovoked chest pain associated with inferior ST-segment elevation and reciprocal ST-segment depression. Coronary angiography during one of these episodes revealed coronary artery spasm that spontaneously resolved followed by resolution of these electrocardiographic changes. There was no atherosclerotic occlusive disease. Her cardiac markers were normal and echocardiogram showed no regional wall motion abnormalities. Electrocariogram and angiography findings are shown in Fig. 1.

Differential incidence and type of spasm according to coronary arterial location.

BACKGROUND: We encounter a less provoked spasm in the left circumflex artery (LCX) by acetylcholine (ACh) testing compared with left anterior descending artery and right coronary artery (RCA) in the real world. OBJECTIVES: We investigated the clinical characteristics of provoked spasm in the LCX by ACh testing. METHODS: We retrospectively analyzed consecutive 1392 ACh testing over 20 years (1991-2011). The maximal ACh dose was 100 µg into the left coronary artery and 80 µg into the RCA. Positive spasm was defined as transient of more than or equal to 90% narrowing and usual chest symptoms or ischemic ECG changes. RESULTS: Positive provoked spasm was recognized in 622 patients (44.7%) including 456 RCA spasms, 448 left anterior descending artery spasms, and 176 LCX spasms. LCX-provoked spasm was significantly lower than other vessels (P<0.001). LCX-provoked spasm was observed in 176 patients, of whom 113 patients (64.2%) had triple-vessel spasm, 46 patients (26.1%) had double-vessel spasm, and 17 patients (9.7%) had single-vessel spasm. More than 90% patients with LCX-provoked spasm had multiple spasms. Of 17 patients with LCX single-vessel spasm, 15 patients (88.2%) had focal spasm. CONCLUSION: Under a maximal ACh dose of 100 µg into the left coronary artery, LCX-provoked spasm was significantly lower than other vessels and more than 90% of patients had multiple spasms.

Circulating cardiac myosin light chains in patients with angina at rest: identification of a high risk subgroup.

To detect myocardial cell damage, serum samples of 42 consecutive patients with angina at rest were screened for cardiac myosin light chains, which were detected in 22 patients (52%). In 17 of these patients there was a persistent release of myosin light chains lasting until the 4th hospital day, whereas in 7 patients myosin light chains were only detectable during the initial 24 h after admission. The presence of myosin light chains correlated with signs of ischemia in the electrocardiogram (ECG) (p less than 0.05) and with the extent of coronary artery narrowing (p less than 0.05). Cardiac myosin light chains were elevated in serum only if there was a greater than or equal to 75% diameter narrowing in at least one major vessel. In all five patients who developed transmural myocardial infarction during the course of their hospital stay, myosin light chains were detectable greater than or equal to 28 h before the diagnosis of myocardial infarction could be established by ECG criteria and conventional serum enzymes. Thus the detection of circulating cardiac myosin light chains enables one to identify a subgroup of patients with angina at rest having more severe coronary artery disease with a worse outcome.