Uncovering a hidden danger: a case report of diffuse coronary spasm concealing spontaneous coronary artery dissection.

BACKGROUND: Over recent years, spontaneous coronary artery dissection (SCAD) has emerged as a no longer rare cause of acute coronary syndrome (ACS). On the other hand, coronary artery spasm (CAS) is the main cause of ischemic heart disease with non-obstructive coronary lesions. Clinical manifestations of both vary from stable angina to ACS or, rarely, sudden cardiac death. These entities may be underdiagnosed on a coronary angiography. CASE PRESENTATION: We report the case of a young woman presenting with acute chest pain and no coronary risk factors. Angiography revealed a focal subcritical stenosis of the right coronary artery. Coronary wiring resulted in diffuse and critical spasm. However, optical coherence tomography (OCT) and intravascular ultrasound (IVUS) showed extensive SCAD. She was therefore treated conservatively. On the fourth day, cardiac computed tomography angiography (CCTA) excluded disease progression, and then she was discharged on medical therapy. CONCLUSIONS: Combined IVI plays a vital role in providing accurate and detailed visualization of the coronary anatomy and thus allowing for more precise diagnosis, risk stratification, and treatment planning. CCTA can be considered a valuable tool in the noninvasive follow-up of SCAD.

Psychological burden in patients with angina and unobstructed coronary arteries-underestimated, underexplored, undertreated.

Patients with angina and unobstructed coronary arteries (ANOCA) are frequently encountered in clinical practice. These cases represent a diagnostic and therapeutic challenge and are often characterized by a long patient journey until a diagnosis of coronary vasomotor disorders is established. Moreover, the unsatisfactory management of such patients leads to insecurity, ongoing symptoms, and psychological sequelae such as anxiety or depression. Currently, the psychological burden in patients with ANOCA is underestimated, underexplored, and undertreated. This review gives a new perspective on the pathophysiology of coronary vasomotor disorders including psychological risk factors and calls for comprehensive care by interdisciplinary ANOCA clinics.

New avenues for the assessment of stable ischemic heart disease.

Myocardial ischemia is a complex condition which may result from epicardial and/or microvascular causes involving functional and structural mechanisms. These mechanisms may overlap in a given patient illustrating the difficulties for appropriate management. Assessment of myocardial ischemia can be performed using noninvasive and invasive tools. However, despite living in the era of individualized precision medicine, these tools are not yet used in a broader fashion. Emerging noninvasive techniques such as quantitative perfusion cardiac magnetic resonance imaging (CMR) and stress perfusion computed tomography (CT) or photon-counting CT techniques may contribute to new standards in the assessment of stable angina patients. Invasive evaluation of myocardial ischemia should not only focus on hemodynamically relevant epicardial disease but also involve coronary vasomotor function testing (coronary spasm, coronary flow reserve, and microvascular resistance) where appropriate. Optimal patient management will depend on accurate and comprehensive diagnostic evaluation of myocardial ischemia and development of new treatment options in the future.

Severe multifocal coronary artery spasms after cessation of vasodilators in a patient with a spontaneous coronary artery dissection: a case report.

Background: Vasospastic angina (VSA) and spontaneous coronary artery dissection (SCAD) are challenging causes of non-atherosclerotic acute coronary syndromes (ACS). Here, we report a unique ACS case with coexisting VSA and SCAD, highlighting specific strategies in diagnosis and management of these poorly studied conditions. Case summary: A woman in her mid-60s with a history of suspected microvascular angina and no atherosclerosis in a previously performed coronary computed tomography angiography presented with worsening chest pain. Invasive coronary angiography revealed a focal SCAD with a resulting high-degree stenosis of the right coronary artery. Shortly after successful percutaneous coronary intervention with stent implantation and stopping her previous vasodilator therapy with nitroglycerine and molsidomine, the patient developed recurrent anterior non-ST-segment elevation myocardial infarction. Surprisingly, repeat coronary angiography revealed severe multifocal coronary artery spasms that were successfully treated with intracoronary nitroglycerine. Vasospastic angina was subsequently managed with diltiazem, molsidomine, and nitrates. Discussion: Our report underscores the challenges in diagnosing and managing SCAD and VSA in ACS. The possible interplay between SCAD and VSA highlights the need for careful vasodilator therapy management, as seen in our patient, where therapy discontinuation led to severe multifocal VSA. This emphasizes the need for a comprehensive approach for optimal outcomes in complex ACS cases.

Prevalence of Coronary Vasomotor Disorders in Patients With Angina and Nonobstructive Coronary Arteries: A Sydney Experience.

BACKGROUND: Patients with angina and non-obstructive coronary arteries (ANOCA) frequently have coronary vasomotor disorders (CVaD), characterised by transient pathological vasoconstriction and/or impaired microvascular vasodilatation. Functional coronary angiography is the gold standard for diagnosing CVaD. Despite recommendations, testing is only available at a limited number of Australian and New Zealand centres. This study aimed to determine the prevalence of CVaDs in an Australian ANOCA population and identify predictive factors associated with specific endotypes. METHOD: Functional coronary angiography was performed in patients with suspected ANOCA. Vasoreactivity testing was performed using intracoronary acetylcholine provocation. A pressure-temperature sensor guidewire was used for coronary physiology assessment. Comprehensive clinical data on patient characteristics, cardiac risk factors, and symptom profiles was collected before testing. RESULTS: This prospective observational study at Royal Prince Alfred and Concord Repatriation General Hospital included 110 patients (58±13 years with 63.6% women), with 81.8% (90/110) having a CVaD. Regarding specific ANOCA endotypes, microvascular angina (MVA) occurred in 31.8% (35/110) of cases, vasospastic angina (VSA) in 25.5% (28/110) and a mixed presentation of MVA and VSA in 24.5% (27/110) of patients. Patients with CVaD were found to be older (59±11 vs 51±15, p=0.024), overweight (61.1% vs 15.0%, p<0.001) and had a worse quality of life (EuroQol 5 Dimensions-5 Levels; 0.61 vs 0.67, p=0.043). MVA was associated with being overweight (odds ratio [OR] 4.2 [95% confidence interval [CI] 1.9-9.3]; p=0.015) and ischaemia on stress testing (OR 2.4 [95% CI 1.1-4.3]; p=0.028), while VSA was associated with smoking (OR 9.1 [95% CI 2.21-39.3]; p=0.007). CONCLUSIONS: Coronary vasomotor disorders are highly prevalent among ANOCA patients. This study highlights the importance of increasing national awareness and the use of functional coronary angiography to evaluate and manage this unique cohort.

Effects of Smoking on Major Adverse Cardiovascular Events in Patients With Coronary Artery Spasm: A Systematic Review and Meta-Analysis.

BACKGROUND: Smoking is an established independent risk factor for coronary artery spasm (CAS), but its effects on major adverse cardiovascular events (MACE) in patients with CAS have not been systematically assessed. METHODS: This systematic review and meta-analysis of studies published from January 2000 to July 2023 was conducted to examine the relationship between smoking and MACE in patients with CAS. Data on MACE were obtained from both smoking and non-smoking CAS patient groups. The effects of smoking on MACE in patients with CAS were assessed through meta-analysis, utilising Stata 17.0 software for all statistical analyses. RESULTS: Nine studies, encompassing 9,376 patients, from Japan (5 studies), Korea (4 studies) and Spain (1 study) were included in the final analysis. Meta-analysis revealed that smoking significantly impacted MACE in patients with CAS (RR 1.965; 95% CI 1.348-2.865), a finding further validated by sensitivity analyses. Subgroup analyses identified a stronger correlation between smoking and increased MACE endpoints in Japanese patients and in those with >3 years of follow-up. CONCLUSIONS: This meta-analysis strongly indicates that smoking escalates the risk of MACE in patients with CAS, with a more pronounced association observed in Japanese patients and those with extended follow-up periods.

A case report of refractory multivessel coronary spasm associated with hypereosinophilic syndrome: one cell, one disease?

Background: Hypereosinophilic syndrome (HES) is characterized by moderate to severe eosinophilia, exclusion of neoplastic or secondary origins of eosinophilia, and systemic involvement with end-organ damage. Coronary arteries can be affected to cause vasospastic angina (VSA); however, the association of the two diseases is not well recognized. Case summary: A 55-year-old woman who had a history of multiple allergic disease such as bronchial asthma and chronic sinusitis with nasal polyps was hospitalized due to attacks of chest pain at rest. During a spontaneous attack of chest pain, ECG revealed ST-segment elevation in the inferior leads and emergency coronary angiography showed focal spasms of the right and left anterior descending coronary arteries, both of which were relieved after intracoronary administration of nitroglycerine. She was diagnosed with VSA according to the Japanese Circulation Society guidelines. Despite conventional vasodilator therapies, her resting angina remained refractory. Laboratory findings were notable for moderate eosinophilia. A comprehensive evaluation to uncover the underlying cause of refractory VSA led to the diagnosis of HES, concomitant with eosinophilic pneumonia and eosinophilic chronic rhinosinusitis. Pericoronary inflammation by fat attenuation index (FAI) was increased in the proximal segment of the right coronary artery. Treatment was initiated with oral prednisolone at a starting dose of 30 mg/day. The response to treatment was rapid, with her symptoms disappearing and a regression of eosinophilia observed the following day. Discussion: Hypereosinophilic syndrome manifests with refractory VSA, and eosinophil-suppressing corticosteroid therapy proves effective in improving both conditions along with reduction of the pericoronary inflammation by FAI.

Perioperative multivessel coronary artery spasm and cardiac arrest after cardiac surgery.

Postoperative coronary artery spasm, a rare but potentially fatal complication following cardiac surgery, warrants significant attention. This report discusses a 64-year-old male who suffered a severe coronary artery spasm leading to cardiac arrest following surgery. Initially stable, the patient rapidly developed critical ventricular arrhythmias and hypotension, resulting in cardiac arrest 4 h post-surgery. Emergency coronary angiography revealed extensive spasms, successfully managed with intracoronary nitroglycerine. This case stresses prompt recognition and management of coronary artery spasm after non-coronary cardiac procedures, underscoring coronary angiography's vital role in diagnosis and treatment.

Multivessel Coronary Function Testing Increases Diagnostic Yield in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of multivessel, compared with single-vessel, invasive coronary function testing (CFT) in patients with angina and nonobstructive coronary arteries (ANOCA). METHODS: Multivessel CFT was systematically performed in patients with suspected ANOCA. Vasoreactivity testing was performed using acetylcholine provocation in the left (20 to 200 µg) and right (20 to 80µg) coronary arteries. A pressure-temperature sensor guidewire was used for coronary physiology assessment in all three epicardial vessels. RESULTS: This multicenter study included a total of 228 vessels from 80 patients (57.8 ± 11.8 years of age, 60% women). Compared with single-vessel CFT, multivessel testing resulted in more patients diagnosed with coronary vasomotor dysfunction (86.3% vs 68.8%; P = 0.0005), coronary artery spasm (60.0% vs 47.5%; P = 0.004), and CMD (62.5% vs 36.3%; P < 0.001). Coronary artery spasm (n = 48) predominated in the left coronary system (n = 38), though isolated right coronary spasm was noted in 20.8% (n = 10). Coronary microvascular dysfunction (CMD), defined by abnormal index of microcirculatory resistance and/or coronary flow reserve, was present 62.5% of the cohort (n = 50). Among the cohort with CMD, 27 patients (33.8%) had 1-vessel CMD, 15 patients (18.8%) had 2-vessel CMD, and 8 patients (10%) had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery = 36.3%, left circumflex coronary artery = 33.8%, right coronary artery = 31.3%; P = 0.486). CONCLUSIONS: Multivessel CFT resulted in an increased diagnostic yield in patients with ANOCA compared with single-vessel testing. The results of this study suggest that multivessel CFT has a role in the management of patients with ANOCA.

Genetic associations of cardiovascular risk genes in European patients with coronary artery spasm.

BACKGROUND: Coronary artery spasm (CAS) is a frequent finding in patients presenting with angina pectoris. Although the pathogenesis of CAS is incompletely understood, previous studies suggested a genetic contribution. Our study aimed to elucidate genetic variants in a cohort of European patients with angina and unobstructed coronary arteries who underwent acetylcholine (ACh) provocation testing. METHODS: A candidate association analysis of 208 genes previously associated with cardiovascular conditions was performed using genotyped and imputed variants in patients grouped in epicardial (focal, diffuse) CAS (n = 119) and microvascular CAS (n = 87). Patients with a negative ACh test result (n = 45) served as controls. RESULTS: We found no association below the genome-wide significance threshold of p < 5 × 10-8, thus not confirming variants in ALDH2, NOS3, and ROCK2 previously reported in CAS patients of Asian ancestry. However, the analysis identified suggestive associations (p < 10-05) for the groups of focal epicardial CAS (CDH13) and diffuse epicardial CAS (HDAC9, EDN1). Downstream analysis of the potential EDN1 risk locus showed that CAS patients have significantly increased plasma endothelin-1 levels (ET-1) compared to controls. An EDN1 haplotype comprising rs9349379 and rs2070698 was significantly associated to ET-1 levels (p = 0.01). CONCLUSIONS: In summary, we suggest EDN1 as potential genetic risk loci for patients with diffuse epicardial CAS, and European ancestry. Plasma ET-1 levels may serve as a potential cardiac marker.

Phosphorylated CPI-17 and MLC2 as Biomarkers of Coronary Artery Spasm-Induced Sudden Cardiac Death.

Coronary artery spasm (CAS) plays an important role in the pathogeneses of various ischemic heart diseases and has gradually become a common cause of life-threatening arrhythmia. The specific molecular mechanism of CAS has not been fully elucidated, nor are there any specific diagnostic markers for the condition. Therefore, this study aimed to examine the specific molecular mechanism underlying CAS, and screen for potential diagnostic markers. To this end, we successfully constructed a rat CAS model and achieved in vitro culture of a human coronary-artery smooth-muscle cell (hCASMC) contraction model. Possible molecular mechanisms by which protein kinase C (PKC) regulated CAS through the C kinase-potentiated protein phosphatase 1 inhibitor of 17 kDa (CPI-17)/myosin II regulatory light chain (MLC2) pathway were studied in vivo and in vitro to screen for potential molecular markers of CAS. We performed hematoxylin and eosin staining, myocardial zymogram, and transmission electron microscopy to determine myocardial and coronary artery injury in CAS rats. Then, using immunohistochemical staining, immunofluorescence staining, and Western blotting, we further demonstrated a potential molecular mechanism by which PKC regulated CAS via the CPI-17/MLC2 pathway. The results showed that membrane translocation of PKCα occurred in the coronary arteries of CAS rats. CPI-17/MLC2 signaling was observably activated in coronary arteries undergoing CAS. In addition, in vitro treatment of hCASMCs with angiotensin II (Ang II) increased PKCα membrane translocation while consistently activating CPI-17/MLC2 signaling. Conversely, GF-109203X and calphostin C, specific inhibitors of PKC, inactivated CPI-17/MLC2 signaling. We also collected the coronary artery tissues from deceased subjects suspected to have died of CAS and measured their levels of phosphorylated CPI-17 (p-CPI-17) and MLC2 (p-MLC2). Immunohistochemical staining was positive for p-CPI-17 and p-MLC2 in the tissues of these subjects. These findings suggest that PKCα induced CAS through the CPI-17/MLC2 pathway; therefore, p-CPI-17 and p-MLC2 could be used as potential markers for CAS. Our data provide novel evidence that therapeutic strategies against PKC or CPI-17/MLC2 signaling might be promising in the treatment of CAS.

Unleashing an Underlying Serious Cardiac Arrhythmia: A Case of Coronary Vasospasm With Atypical Presentation.

This case report highlights the atypical presentation of coronary artery vasospasm in a 59-year-old patient presenting with syncope due to ventricular arrhythmia. Despite initially elevated troponin levels and non-significant lesions observed during left heart catheterization, the patient experienced recurrent chest pain and dizziness, prompting further evaluation. Ultimately, coronary vasospasm was identified as the likely differential diagnosis, supported by various diagnostic modalities including electrocardiogram, Zio patch monitoring, transthoracic echocardiogram, cardiac MRI, and CT angiography. Management involved the initiation of calcium channel blocker therapy, leading to a non-eventful follow-up in the cardiology clinic.

Transient changes in the ST-T waveform mimicking myocardial infarction in a child with near-drowning: a case report.

Drowning is a common cause of childhood morbidity and mortality worldwide. Anoxia, hypothermia, and metabolic acidosis are mainly responsible for this morbidity. Drowning may lead to multiple organ damage, especially cardiac damage, in cases in which severe hypothermia and hypoxemia occur. We report a case of a 4-year-old girl who was admitted to our hospital's Emergency Department because of drowning. She had elevated troponin I concentrations and ST-segment elevation with T wave inversion. However, cardiovascular computed tomography showed no obvious abnormalities in the coronary arteries. We suggest that cardiac damage in this situation is caused by coronary artery spasms. To the best of our knowledge, this is the first case of cardiac damage with electrocardiographic changes after drowning in a preschool child.

Recurrent syncope due to ischemia with non-obstructive coronary artery disease: a case report.

BACKGROUND: Ischemia with non-obstructive coronary artery disease is a prevalent form of ischemic heart disease. The majority of ischemia with non-obstructive coronary artery disease cases are attributed to underlying factors such as coronary microvascular dysfunction (CMD) and/or coronary artery spasm. Ischemia with non-obstructive coronary artery disease can present with various clinical manifestations. Recurrent syncope is an atypical complaint in patients with ischemia with non-obstructive coronary artery disease. CASE PRESENTATION: This case report describes the presentation of a 58-year-old Chinese male patient who experienced repeated episodes of syncope. The syncope was found to be caused by concomitant coronary artery spasm and presumptive coronary microvascular dysfunctionc suggested by "slow flow" on coronary angiography. The patient was prescribed diltiazem sustained-release capsules, nicorandil, and atorvastatin. During the three-month follow-up conducted on our outpatient basis, the patient did not experience a recurrence of syncope. CONCLUSION: This study highlights the importance of considering ischemia with non-obstructive coronary artery disease as a potential cause of syncope in the differential diagnosis. It emphasizes the need for early diagnosis of ischemia with non-obstructive coronary artery disease to facilitate more effective management strategies.

Spontaneous multivessel coronary artery spasm: a case report.

A 60-year-old male presented to the emergency department of our hospital with persistent dull pain in the lower and middle sternum with generalized sweating after a heated argument with another person, and his symptoms did not resolve after 3 hours of onset.

Comparison of the Diagnostic Yield of Intracoronary Acetylcholine Infusion and Acetylcholine Bolus Injection Protocols During Invasive Coronary Function Testing.

Coronary endothelial dysfunction (CED) and coronary artery spasm (CAS) are causes of angina with no obstructive coronary arteries in patients. Both can be diagnosed by invasive coronary function testing (ICFT) using acetylcholine (ACh). This study aimed to evaluate the diagnostic yield of a 3-minute ACh infusion as compared with a 1-minute ACh bolus injection protocol in testing CED and CAS. We evaluated 220 consecutive patients with angina and no obstructive coronary arteries who underwent ICFT using continuous Doppler flow measurements. Per protocol, 110 patients were tested using 3-minute infusion, and thereafter 110 patients using 1-minute bolus injections, because of a protocol change. CED was defined as a <50% increase in coronary blood flow or any epicardial vasoconstriction in reaction to low-dose ACh and CAS according to the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria, both with and without T-wave abnormalities, in reaction to high dose ACh. The prevalence of CED was equal in both protocols (78% vs 79%, p = 0.869). Regarding the endotypes of CAS according to COVADIS, the equivocal endotype was diagnosed less often in the 3 vs 1-minute protocol (24% vs 44%, p = 0.004). Including T-wave abnormalities in the COVADIS criteria resulted in a similar diagnostic yield of both protocols. Hemodynamic changes from baseline to the low or high ACh doses were comparable between the protocols for each endotype. In conclusion, ICFT using 3-minute infusion or 1-minute bolus injections of ACh showed a similar diagnostic yield of CED. When using the COVADIS criteria, a difference in the equivocal diagnosis was observed. Including T-wave abnormalities as a diagnostic criterion reclassified equivocal test results into CAS and decreased this difference. For clinical practice, we recommend the inclusion of T-wave abnormalities as a diagnostic criterion for CAS and the 1-minute bolus protocol for practicality.

Recurrent syncope driven by unique-variant angina pectoris.

The patient's vasospastic variant angina manifested as syncope with asymptomatic ischemic episodes, and repeated 24-h dynamic electrocardiogram and coronary angiography examinations combined with coronary provocation spasm tests were necessary for its diagnosis and management.

Vasospastic angina: a review on diagnostic approach and management.

Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels responsible for an inadequate supply of blood and oxygen. Coronary artery spasm is a heterogeneous phenomenon that can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction (MI). VSA was originally described as Prinzmetal angina or variant angina, classically presenting at rest, unlike most cases of angina (though in some patients, vasospasm may be triggered by exertion, emotional, mental or physical stress), and associated with transient electrocardiographic changes (transient ST-segment elevation, depression and/or T-wave changes). Ischaemia with non-obstructive coronary arteries (INOCA) is not a benign condition, as patients are at elevated risk of cardiovascular events including acute coronary syndrome, hospitalization due to heart failure, stroke and repeat cardiovascular procedures. INOCA patients also experience impaired quality of life and associated increased healthcare costs. VSA, an endotype of INOCA, is associated with major adverse events, including sudden cardiac death, acute MI and syncope, necessitating the study of the most effective treatment options currently available. The present literature review aims to summarize current data relating to the diagnosis and management of VSA and provide details on the sequence that treatment should follow.

Diagnosis and treatment of epicardial coronary artery spasmVasospastic angina (VSA) refers to chest pain experienced as a consequence of a sudden narrowing of the epicardial coronary arteries. VSA can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction. Reduced blood and oxygen supply in patients with non-obstructive coronary arteries is not a benign condition, as patients are at elevated risk of adverse cardiovascular events. These patients also experience impaired quality of life and associated increased healthcare costs. This review aims to summarise current data relating to the diagnosis of VSA and provides details on treatment strategies.