Coronary Artery Spasm Research Articles

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.

Reverse Remodeling of Methamphetamine-Associated Cardiomyopathy: An Update on Mechanisms for Recovery

Methamphetamine (MA) use continues to rise worldwide. The adverse effects of MA on the cardiovascular system include cardiomyopathy, dysrhythmias, coronary arterial vasospasm, and atherosclerosis. Methamphetamine-associated cardiomyopathy (MACM) affects predominantly younger male patients and is responsible for an increasing proportion of heart failure emergency department visits, hospital admissions/readmissions, morbidity, and mortality. Reverse remodeling of MACM and full cardiac recovery is achievable in patients who cease using MA and remain abstinent with self-direction, cognitive behavioral therapy, brief interventions, contingency management, motivational interviewing, and residential rehabilitation. Recovery is further enhanced by the addition of an exercise program and guideline-based pharmacotherapy for heart failure, which includes β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors. Alternative heart failure treatment with isosorbide dinitrate plus hydralazine, ivabradine, vericiguat, and omecamtiv mecarbil represent further adjuncts which may promote reverse remodeling. Antioxidant compounds such as coenzyme-Q10, omega-3 polyunsaturated fatty acids, resveratrol, and cannabidiol may aid in cardiac restoration. Diet changes, metformin and glucose control, stem cell therapy, melatonin, and sleep quality improvement are further steps on the road to recovery. In this article we review the cardiotoxicity of MA, pathogenesis of MACM, and evidence behind pharmacologic and lifestyle interventions to reverse its progression.

A Case of Refractory Vasospastic Angina Complicated by Bronchial Asthma with Eosinophilia1.

A 48-year-old woman with a history of bronchial asthma and allergic rhinitis presented with cardiac arrest due to ventricular fibrillation and was resuscitated by defibrillation. Coronary angiography revealed coronary vasospasm. Various antispastic agents were unable to control recurrent coronary spasms. We searched for other points of intervention and found a significant increase in the eosinophil count. The patient received mepolizumab for bronchial asthma with eosinophilia, which normalized the eosinophil count. Since then, the patient has remained free from coronary vasospasm, suggesting that mepolizumab may be a viable option for treating refractory coronary angina associated with bronchial asthma and eosinophilia.

Safety and potential usefulness of sequential intracoronary acetylcholine and ergonovine administration for spasm provocation testing.

Although guidelines recommend intracoronary acetylcholine (ACh) and ergonovine (ER) provocation testing for diagnosis of vasospastic angina, the feasibility and safety of sequential (combined) use of both pharmacological agents during the same catheterization session remain unclear. In this study, we investigated the feasibility and safety of sequential intracoronary ACh and ER administration for coronary spasm provocation testing. The study included 235 patients who showed positive results on ACh and ER provocation testing. Initial intracoronary ACh administration was followed by ER administration for left coronary artery (LCA) spasm provocation testing. Subsequently, the right coronary artery (RCA) was subjected to sequential ACh and ER administration for provocation testing. The primary outcome of the study was the safety of sequential intracoronary ACh and ER provocation testing, which was assessed based on a composite of all-cause death, sustained ventricular tachycardia and fibrillation, and cardiogenic shock. Even in patients with negative results on sequential intracoronary ACh and ER provocation testing in the LCA and only ACh administration into the RCA, additional administration of ER into the RCA showed a positive provocation test result in 33 of 235 (14.0%) patients; three (1.3%) patients developed adverse effects (cardiogenic shock occurred in all cases) during LCA provocation testing. We observed no deaths attributable to spasm provocation testing. Sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of vasospastic angina.

Thyrotoxicosis Related Coronary Artery Spasm Presenting as Acute Coronary Syndrome

Thyrotoxicosis Related Coronary Artery Spasm Presenting as Acute Coronary Syndrome

ACUTE MYOCARDIAL INFARCTION IN A PUERPERA: A CASE REPORT

We report a lethal case of acute myocardial infarction in a puerpera. Cardiovascular diseases rank as the leading causes of mortality during pregnancy and the postpartum period, with myocardial infarction (MI) being a rare yet frequently fatal occurrence. Research indicates that MI typically manifests between 6 to 12 weeks postpartum, though instances may also occur at later stages. The reported case is interesting in terms of the mismatch between the timing of clinical symptoms of acute coronary syndrome (less than 24 hours) in the puerpera and alterations in myocardial infarction (2-3 days), which was diagnosed morphologically. Therefore, we searched for possible causes that led to the clinical and morphological changes described above. At first glance, the main cause of myocardial infarction development is coronary artery dissection with the formation of hematoma in the wall of the blood vessel, which narrows its lumen and leads to necrosis of the heart muscle. A brief analysis of the case has established that ischemic damage to the myocardium preceded the development of spontaneous coronary artery dissection and could be caused by one of the factors or a combination of them: coronary artery spasm caused by ergometrine and anemia due to uterine atony-related postpartum hemorrhage. The formation of intramural hematoma of the vascular wall, which narrowed the lumen of the coronary artery, could be the result of the prescription of antithrombotic therapy, which complicated the health status of the woman and led to death. When providing medical care to puerperas with postpartum hemorrhage, it is necessary to take into account the risk for cardiovascular complications that could develop due to anemia or administration of ergometrine.

'Single-shot' pulmonary vein isolation using a novel lotos pulsed field ablation catheter: a pre-clinical evaluation of feasibility, safety, and 30-day efficacy.

Pulsed field ablation (PFA) is emerging as a non-thermal, tissue-specific technique for pulmonary vein isolation (PVI) in atrial fibrillation therapy. This pre-clinical study aims to investigate the feasibility and safety of PVI using a novel PFA system including a nanosecond-scale PFA generator, a novel lotos PFA catheter, and a customized 12 Fr steerable sheath. A total of 11 Yorkshire swine were included in this study, with 4 in the acute cohort and 7 in the chronic cohort. Under general anaesthesia, transseptal puncture and pulmonary vein (PV) angiography was initially performed. The PFA catheter was navigated to position at the right and left PV antrum after the electroanatomic reconstruction of the left atrium. Biphasic PFA applications were performed on PVs in both the spindle-shaped and the lotos-shaped poses. Pulmonary vein isolation and PFA-associated safety were assessed 30 min after ablation in both cohorts and 30 days later in the chronic cohort. Detailed necropsy and histopathology were performed. Additional intracardiac echocardiography and coronary angiogram were evaluated for safety. All target PVs (n = 20) were successfully isolated on the first attempt. No spasm of coronary artery or microbubble was seen during the procedure. Eleven of 12 PVs (91.6%) remained in isolation at the 30-day invasive study. No evidence of PV stenosis was observed in any targets. However, transient diaphragm capture occurred in 17.6%. Histopathological examinations showed no evidence of collateral injury. This study provides scientific evidence demonstrating the safety and efficacy of the novel PFA catheter and system for single-shot PVI, which shows great potential.

Clinical Utility of Soluble Lectin Type Oxidized Low-Density Lipoprotein Receptor as a Biomarker for Myocardial Infarction and Stable Angina.

Background and objectives Endothelial soluble lectin-type oxidized low-density lipoprotein receptor 1 (sLOX-1) recognizes oxidized low-density lipoprotein (LDL) and triggers downstream signaling leading to atherosclerosis. The objective of this study was to demonstrate the utility of sLOX-1 as a biomarker for detecting acute myocardial infarction (MI) and stable angina (SA) and to develop a diagnostic algorithm for distinguishing coronary vasospasm from coronary plaque rupture. Methods We enrolled 62 patients who underwent diagnostic coronary angiography (CAG) and 30 healthy controls (21 men and nine women) and measured sLOX-1, troponin I, and cardiac myosin-binding protein C (c-MyBPC) using commercial kits. Results Patients with MI exhibited higher sLOX-1 levels (301.55 ± 196.16 pg/ml) than patients with stable angina (220.76 ± 103.65 pg/ml) and healthy controls (121.14 ± 77.10, F: 10.55, p<0.001). Although higher troponin I levels were detected in MI patients (263.00 ± 493.00 vs. 3.19 ± 2.15 ng/ml, p=0.0019), no significant elevation was observed in SA patients (1.91 ± 0.79 ng/ml). Plasma sLOX-1 levels showed a positive association with age (r=0.37, p=0.003), but not with gender (r=0.04, p=0.75). Troponin I showed no association with age (r=0.12, p=0.36) or gender (r=0.06, p=0.62). Receiver operating characteristic (ROC) curves revealed that among the three biomarkers, troponin-I showed a higher area under the curve (AUC) (AUC: 0.941), followed by sLOX-1 (AUC: 0.888), while c-MyBPC showed no clinical utility in the detection of MI (AUC: 0.666). Conclusions A marked elevation of sLOX-1 can detect MI and differentiate the presence or absence of plaque rupture, along with diagnosing stable angina.

Efficacy of Intravenous Nitrates for the Prevention of Coronary Artery Spasm During Pulsed Field Ablation of the Mitral Isthmus.

Efficacy of Intravenous Nitrates for the Prevention of Coronary Artery Spasm During Pulsed Field Ablation of the Mitral Isthmus.

Successful recognition and management of life-threatening multivessel coronary artery vasospasm after conventional coronary artery bypass grafting.

Background: The occurrence of native coronary artery vasospasm after coronary artery bypass grafting (CABG) is a rare phenomenon with potentially catastrophic outcomes. The absence of a clear understanding of contributing factors and an undetermined occurrence rate underscores the importance of coronary angiography as the primary diagnostic tool for this condition. Case Presentation: We present the case of a 70-year-old Asian male with a 14-year history of diabetes mellitus, seven years of Giant Cell Arteritis (GCA), and Ischemic Heart Disease (IHD). The patient experienced severe native coronary artery vasospasm following conventional CABG, prompting intervention through coronary angiography. Management &amp; Results: The patient underwent coronary angiography, revealing multivessel coronary artery vasospasm. Intracoronary administration of nitroglycerin and diltiazem was initiated promptly. The swift identification and treatment of vasospasm were instrumental in preventing severe myocardial injury. Conclusion: Coronary artery vasospasm post-CABG poses a significant threat, emphasizing the need for early identification and intervention. The successful management presented in this case underscores the importance of timely recognition and the administration of vasodilators in mitigating potential myocardial damage. This report contributes to the growing understanding of this rare but critical complication, highlighting the necessity for vigilance in post-CABG patient care.

Non-Obstructing Coronary Artery Ischemia, An Underdiagnosed Silent Killer

Dear Madam, Ischemia due to Non-Obstructing Coronary Arteries (INOCA), formerly known as Prinzmetal Angina, is a condition that affects a significant number of people, especially in Pakistan. I have encountered several cases where patients exhibit stable angina symptoms, despite having normal or near-normal coronary angiograms. Among about 400,000 patients with suspected ischemic heart disease, the American College of Cardiology National Cardiovascular Data Registry found that only 37.6% had obstructive coronary artery disease, and 39.2% had no evidence of coronary artery disease. The exact prevalence of INOCA is not well-known. (1) Moreover, a prior research study found that heart failure patients of South Asian origin had a higher prevalence of INOCA compared to other populations. (2) A recent meta-analysis revealed that approximately 50% of the patients with nonobstructive coronary artery disease had coronary microvascular disease (CMD) and/or coronary artery spasms, suggesting that a significant number of INOCA patients are not appropriately diagnosed in routine clinical practice. (3) This shows us the importance of INOCA and also suggests that we need to improve the diagnosis protocols that Pakistani physicians commonly use. INOCA and myocardial infarction with non-obstructive coronary artery disease (MINOCA) are underrecognized and underdiagnosed conditions with cardiovascular health implications. These conditions are associated with a higher risk of death from cardiovascular causes in Pakistan, as well as a greater burden on the healthcare system, due to frequent hospital admissions for persistent chest pain and invasive coronary angiographies that often yield negative results. We have to dive more into Invasive coronary angiography by doing the Comprehensive Physiologic Assessment, using a pressure sensing guidewire to measure FFR (Fractional Flow reserve) and CFR (Coronary Flow Reserve) to evaluate Epicardial Stenosis and Microvascular Angina respectively. Later on, CFT can also be performed to confirm the diagnosis of coronary microvascular dysfunction. (4) To ensure that we do not miss INOCA, we should also consider other tests that do not involve inserting a catheter into the heart. These tests include Transthoracic echocardiography, Cardiac MRI, and Cardiac PET. By doing these tests, we can determine if the patient has INOCA and what type of INOCA they have. These will help us to tailor our management plan in the best possible way and also help us to guide the patients on how to reduce their risk factors.

Feasibility, safety and prognostic relevance of acetylcholine provocative testing in patients with myocardial bridge: a prespecified analysis of the RIALTO Registry

Abstract Introduction Myocardial bridge (MB) is the most frequent inborn coronary artery variant. Although MB has long been considered a benign entity, a growing body of evidence has suggested its association with angina and adverse cardiac events. However, to date, no data on long-term prognosis are available, nor on therapies improving cardiovascular outcomes. We are currently conducting an ambispective, observational, multicentre, study in which we enroll patients with a clinical indication to undergo coronary angiography (CA) and evidence of MB, aiming to describe the incidence of symptoms and cardiovascular events at baseline and at long-term follow-up (FUP). The role of invasive full-physiology assessment in modifying the discharge therapy and eventually the perceived quality of life and the incidence of major cardiovascular events will be analysed. Herein, we assessed the safety, feasibility, and the prognostic role of invasiveacetylcholine (Ach) testing in unmasking coronary artery spasm in patients with MB. Materials and Methods A total of 444 patients with MB were consecutively enrolled in the RIALTO registry. 73 underwent intracoronary Ach testing. Both patients with acute and chronic presentations were included. The decision to perform the provocative testing was left to the operator's judgment and performed according to a standardized protocol. The incidence of major and minor complications during Ach testing was recorded. Furthermore, the incidence of major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, and cardiac hospitalization, and the rate of patients with a Seattle Angina Questionnaire (SAQ) Angina Summary Score &amp;lt;70 were compared between patients with and withoutcoronary artery spasm. Results Epicardial spasm was diagnosed in 58.9% of MB patients, whereas microvascular spasm in 6.9% according to COVADIS criteria. The most frequent location of coronary artery spasm (CAS) was the intramural segment. Regarding safety, no fatal or major non-fatal events occurred. The rate of minor side effects was low (12.3%) and comparable between acute and chronic patients. MACE occurred in 12 (18.8%) patients, without significant differences in the rate of MACE between the study groups (18.2% in patients with a positive Ach testing vs. 20% in patients with a negative Ach testing; log-rank = 0.88). However, the rate of significant angina (SAQ &amp;lt; 70) was higher in the Ach+ group compared with the Ach- group (47.7% vs. 25%; log-rank = 0.04). Conclusions CAS often coexists with MB. The execution of Ach testing in this cohort proved to be safe and feasible, identifying a subgroup of patients with a higher angina burden and poor quality of life, although with a comparable rate of MACE at 2 years. In our study, invasive provocative test improved the ability to unmask vasomotor disorders associated with MB and to prescribe a tailored therapy with calcium antagonists, which improved symptoms.

Ruptured sinus of valsalva aneurysm - a rare cause of heart failure, challenges in transcatheter closure and mid-term outcomes

Abstract Introduction The ruptured sinus of valsalva aneurysm (RSOV) portends an important cause for acute heart failure. Closure of the defect either percutaneously or surgically is of paramount importance. We report 38 cases of RSOV who presented with cardiac failure, among which 22 cases were selected and amenable for transcatheter closure.Transcatheter closure of RSOV has favorable outcomes in the short-term and mid-term follow-up. Purpose of the study To assess the short-term and midterm outcomes of transcatheter closure of RSOV. Methods All patients who presented with cardiac failure and diagnosed as RSOV by transthoracic echo, from June 2012 to Dec 2022 were included in the study.Age group was between 12 to 73 years.All the 38subjects (Males -24, Females -14) of RSOV, underwent trans esophageal echo (TEE). 22 casesere selected for device closure..The subjects were classified according to New York Heart Association (NYHA) class III - 82%, class IV- 18 %. Size of the defect was measured at the aortic end by TEE and aortogram, and upsized by 2-4 mm from the aortic end. In 21 subjects, the RSOV was entered from the aorta, and an arterio-venous loop was created, and various devices, duct occluders and atrial septal occluder and muscular ventricular septal occluder were used to close the defects. In one patient the RSOV was acquired following surgical closure of perimembranous ventricular septal defect, which was small measuring 3mm at aortic end and hence closed using 4/6 ADO II without forming the arterio-venous loop. Patients were followed up post discharge 1 week, 1 month, 3 months, 6 months, 1 year and every year till 10 years by clinical examination, ECG, and transthoracic echo. Results All 22 patients who underwent successful RSOV device closure improved to NYHA functional class II within 48 hours post procedure and to functional class I at 3 months of follow-up. 3 female patients underwent successful pregnancy and labor after RSOV device closure without any intrapartum or postpartum complications. Two patients had trivial aortic regurgitation pre-procedure remained the same status on follow up post-procedure. One patient developed) severe right coronary artery spasm, due to inadvertent RCA cannulation while crossing the defect, which cleared with nasal oxygen and intracoronary nitroglycerine. A minimal residual shunt was found in 2 patients which gradually disappeared at 6 months. One patient with a large defect (15mm), an atrial septal occluder - 20mm was deployed, developed hemolysis, and hence referred for surgery. Transient global LV systolic dysfunction was present in two patients due to afterload mismatch, whose LV function recovered after 72 hours. Conclusion Percutaneous device closure of RSOV is a feasible and an enticing alternative to surgery in selected patients, as inferred by the short and mid-term outcomes. The age group 12 to 73 years encompasses the youngest and oldest age group yet reported.PROFILE OF RSOV DEVICE CLOSURE CASESRSOV CASE SELECTION AND OUTCOMES

Induced pluripotent stem cell-derived vascular smooth muscle cells as an in vitro model of coronary spastic angina

Abstract Background Coronary spastic angina (CSA), also known as Prinzmetal’s variant angina, is a form of angina caused by coronary artery spasm. CSA is characterized by enhanced basal tone of coronary artery smooth muscle and hyperreactivity to vasoconstrictor stimuli. The vascular smooth muscle hyperreactivity is likely due to a post-receptorial cellular abnormality in the regulation of myofibril contraction, suggesting the possibility of multiple stimuli acting on various cellular receptors. However, its detailed mechanism is still unclear. To investigate it, various experiments using coronary artery smooth muscle cells obtained from the CSA patients is preferable, but it is impossible to do it clinically and ethically. Purpose The purpose of this study was to establish induced pluripotent stem cell (iPSC)-derived vascular smooth muscle cells (VSMCs) and to characterize this VSMC model for CSA research. Methods Three CSA patients with ST-segment elevation, which is a characteristic of variant angina, were recruited for this study. The isolated skin fibroblasts or peripheral blood mononuclear cells were reprogrammed into iPSCs through electroporation of episomal plasmids encoding the reprogramming genes OCT3/4, SOX2, KLF4, L-MYC, LIN28, and mouse p53DD. We differentiated mesodermal using Glycogen synthase kinase 3 inhibition and Bone morphogenetic protein 4 treatment from iPSCs and resulted in the differentiation of VSMCs by platelet-derived growth factor-BB and Activin A. The differentiation of VSMCs was confirmed by VSMC-specific gene expression in qRT–PCR and fluorescence-activated cell sorting (FACS). We examined biological features and intracellular calcium response to acetylcholine (ACh) in VSMCs obtained from 3 CSA patients and 3 healthy controls. Intracellular free Ca2+ concentration ([Ca2+]i; nM) was measured by fura-2. Results CSA iPSCs were confirmed to have normal karyotypes and pluripotency to differentiate. FACS showed that VSMCs differentiated from iPSCs exhibited smooth muscle cell marker expressions including alpha-smooth muscle actin and SM22-alpha. qRT–PCR showed that VSMCs from iPSCs had expressions of ACTA2 and TAGLN gene similar to the human coronary artery smooth muscle cells. Differentiation induction rate of VSMCs differentiated from iPSCs between CSA and control did not show significant difference. [Ca2+]i at baseline did not differ significantly between them (143 nM in CSA versus 120 nM in control, p=0.63, n=3), but peak increase in [Ca2+]i from baseline after ACh stimulation was significantly increased in CSA group compared with control (372 nM versus 177 nM, p&amp;lt;0.05, n=3). Conclusions iPSC-derived VSMCs obtained from CSA patients showed an enhanced intracellular calcium response to ACh, which is likely responsible for CSA phenotype. Our iPSC-derived VSMC model can be useful for elucidating the mechanism of coronary spasm and developing therapeutic strategy such as drug efficacy.

Long-term outcomes of patients with ischemia and no obstructive coronary artery disease (INOCA) - a systematic review and meta-analysis

Abstract Background Myocardial ischemia with no obstructive coronary artery disease (INOCA) is an increasingly recognized syndrome that encompasses coronary vasomotor disorders such as coronary microvascular dysfunction (CMD) and coronary vasospasm. However, the prognosis of patients with INOCA is not well defined. Purpose To perform a systematic review and meta-analysis of previous studies evaluating the long-term prognosis of patients with INOCA stratified by the underlying vasomotor disorder. Methods We searched Medline, Embase, Web of Science, and Cochrane databases combining terms for INOCA and outcomes to identify observational studies evaluating the prognosis of patients with INOCA published between 1984 and 2021. The primary outcomes were composite of all-cause death and MI, and major adverse cardiovascular events (MACE) at annual intervals for up to 5-year follow-up. Meta-analytic averages with 95% confidence intervals (CI) of the incidence of primary outcomes for INOCA, each INOCA endotype, and by method used to determine the diagnosis were calculated using the random effect models. Results We identified a total of 52 studies (19765 patients) meeting eligibility criteria. Of those, 22 included patients with vasospastic angina and 34 with microvascular angina. The rate of all-cause death and MI in the vasospastic angina group was 0.7 (95% CI 0.4-1.0)/100 patient-years [Figure 1] and the rate of MACE was 1.1 (95% CI 0.6-1.9)/100 patient-years [Figure 2]. For patients with microvascular angina the rate of all cause death and MI was 1.2 (95% CI 0.7-1.7)/100 patient-years [Figure 1] and the rate of MACE was 2.8 (95% CI 1.8-4.0)/100 patient-years [Figure 2]. Patients with evidence of microvascular dysfunction by non-invasive (CFR) or invasive (CFR, IMR, TIMI frame count) criteria had 2.7 times higher all-cause death and MI rates than patients whose diagnosis was established solely based on an abnormal exercise or imaging stress test (2.6 (95% CI, 0.8-5.1) vs. 0.7(95% CI, 0.4-1.2)/100 patient-years, p=0.034). Conclusions Overall, patients with INOCA have a low rate of MACE events or death, although there is heterogeneity based on the underlying phenotype. Patients with vasospastic angina have a relatively benign long-term prognosis, whereas patients with microvascular angina have a significantly higher rate of MACE at long-term follow-up. Among patients with microvascular angina, those with objective evidence of abnormal microvascular function (such as reduced CFR) had 2.7 times higher rates of all-cause death and MI.Incidence of all cause death and MIIncidence of MACE

Invasive coronary function testing in patients with INOCA - a single center experience

Abstract Background Coronary vasomotion disorders (CVDs) represent a frequent cause of angina in patients with ischemia with non-obstructed coronary arteries (INOCA). Invasive coronary angiography (ICA) often fails to identify patients with vasospastic angina and/or microvascular dysfunction. Purpose Our aim was to describe and characterize CVDs in INOCA patients, using a multi-parametric, invasive, coronary function testing protocol. Methods Patients with INOCA that underwent our protocol for coronary function testing (CFT), between July 2021 and October 2022 were included in this single-center prospective study. The protocol consisted of an invasive assessment of coronary circulation vasorelaxation at rest and during hyperemia, as well as the propensity for coronary vasospasm using increasing doses of intra-coronary acetylcholine. Fractional flow reserve, coronary flow reserve (CFR), and index of microvascular resistance (IMR) were recorded. CVDs were diagnosed based on the criteria proposed by the Coronary Vasomotor Disorders International Study Group. Results A total of 56 patients were included, mean age was 64±12 years and 57.1% were female. At baseline, all patients had either typical angina (82.1%, n=46) or a positive ischemia test (67.9%, n=38). Twenty patients (35.7%) had a history of a previous ICA or computed tomography due to anginal symptoms, while only 8.9% of patients had known structural ischemic heart disease and were subjected to percutaneous coronary intervention. Our CFT protocol was completed in all patients without any serious complications. Isolated epicardial vasospasm was found in 16 (28.6%) patients, isolated coronary microvascular dysfunction (CMD) in 9 (16.1%), and a combination of CMD and coronary vasospasm in 9 (16.1%). Only 1 patient (1.8%) had isolated microvascular spasm. We were able to further identify two distinct endotypes of CMD, using a combined assessment of CFR and IMR, termed structural and functional CMD: Functional CMD - 7 patients (12.5%) had CFR &amp;lt; 2.0 and IMR &amp;lt; 25; Structural CMD - 6 patients (10.7%) had CFR &amp;lt; 2.0 and IMR &amp;gt; 25. Conclusion Coronary vasomotion disorders are a common cause of INOCA. A CFT protocol is safe, can be used in clinical practice, and can provide a definite diagnosis for the underlying cause of angina.

Abstract 16552: Coronary Vasomotor Response to Intracoronary Ergonovine Provocation Test According to the Severity of an Insignificant Coronary Artery Fixed Stenosis

BACKGROUND: Coronary artery spasm (CAS) is a major cause of variant angina in patients with chest pain without significant coronary stenosis. However, whether there are differences in the incidence of CAS according to the severity of underlying coronary artery fixed stenosis is limited. Methods: A total of 608 patients without significant coronary artery disease (CAD) who underwent the ergonovine (ERG) provocation test between January 2018 and December 2021 were enrolled. Significant CAS was defined as having≥70% of temporary narrowing by ERG test. Patients were divided into three groups, based on the presence of coronary artery stenosis: None group (n=456), mild group (30-49%,n=114) and moderate group (50-69%,n=38). Results: In patients with chest pain without significant coronary artery stenosis, mild stenosis was 18.8%, and moderate stenosis was 6.3% in the population. The baseline characteristics of the patients were worse in the mild and moderate group than in the None group, including age, hypertension, diabetes, and smoking habit. In the ERG test, CAS occurred in 44.4% (270/608) of the overall population. The incidence of CAS of the mild (55.3%) and moderate (52.6%) groups were higher than the None group (41.0%). Also, in the case of CAS occurrence, focal CAS (Length&lt;20mm) was more frequent in the mild (14.3%) and moderate (30%) groups than in the no group (8.6%). CONCLUSIONS: In patients with resting chest pain without severe coronary artery stenosis, CAS was observed in a high proportion of nearly half by ergonovine provocation test. Moreover, the mild to moderate coronary artery fixed stenosis showed higher incidence of CAS and focal CAS than patients without fixed stenosis.

Abstract 17720: The Role of Soluble Guanylyl Cyclase/NLRP3/RHOA/ROCK Axis in Coronary Artery Spasm: A Potential Biomarker and Therapeutic Target

Background: Coronary artery spasm (CAS) can lead to potentially life-threatening acute coronary syndrome. The second messenger cyclic guanosine 3',5'-monophosphate (cGMP), which is regulated by BNP-pGC-cGMP and nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP pathways, regulate not only vasodilation but also the functions of immune cells. However, the significance of sGC, as a primary receptor for NO, is unclear in CAS. Methods: We investigated sGC and downstream signaling in patient monocyte-derived macrophages (PMDMs) and human coronary artery smooth muscle cells (HCASMCs) using computational biology and bioinformatics to correlate macrophage polarization subsets, Lp(a), and inflammasome signaling axes with CAS. Results: Plasma sGC levels were significantly higher in 30 CAS patients compared to 20 non-CAS controls (P&lt;0.001). RNA-sequencing analysis revealed a significant association of sGC expression with NLR Family Pyrin Domain Containing (NLRP)-3 in HCASMCs and induced expression of inflammatory cytokines-specific surface markers. Lp(a) induction promoted the sGC-NLRP3 mediated lipid metabolism axis in PMDMs at both mRNA and protein levels, with elevated M1 polarization. sGC inhibition in HCASMCs reduced RhoA-GTP activity and its downstream effector ROCK, mitigating the Lp(a) effect, while sGC-specific modulator 1-H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-l-one (ODQ) treatment decreased Lp(a)-induced expression of sGC-NLRP3-inflammasome mediators and induced caspase-1, as well as subsequent cleavage of proIL-1β and proIL-18 in VSMCs. Conclusion: sGC/GC molecule in conjunction with the RHOA/ROCK pathway is an early biomarker for CAS. The sGC-NLRP3-inflammasome mediators signaling axis plays an important role in Lp(a)-regulated macrophage polarization and CAS development.

Abstract 16620: Long-Term Prognostic Factors for Cardiovascular Events in Patients With Chest Pain Without Diabetes Mellitus and Significant Coronary Stenosis

Background: Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD and DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. Methods: A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiovascular events (MACE) were defined as the composite of total death, myocardial infarction (MI), and revascularization. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of MACE, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Results: Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal anti-anginal medication therapy. However, a recurrent chest pain remains a problem even with continuous anti-anginal medication therapy. Up to 5-year, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia, ICS, the use of aspirin and nitrates were associated with long-term MACCE. Conclusions: Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with anti-anginal medications.

Abstract 19084: The Deadly Squeeze - Coronary Vasospasm Complicated by Myocardial Infarction and Cardiac Arrest

Introduction: Acute coronary syndrome (ACS) typically results from atherosclerotic plaque rupture. However, about 6% of ST elevation Myocardial Infarction (STEMI) patients have no obstructive disease. We present a case of STEMI, diagnosed with coronary vasospasm. Hypothesis: Methods: A 54-year-old female with alcohol abuse, smoking and uncontrolled hypertension presented after an out of hospital ventricular fibrillation cardiac arrest. EKG showed anterolateral ST elevation (STE). Left heart catheterization (LHC) showed moderate to severe multi-vessel disease without a definitive culprit lesion. STE resolved. Heart team approach for revascularization was contemplated. Echocardiogram showed systolic dysfunction with ejection fraction (EF) of 25%. Patient had another cardiac arrest and EKG showed recurrent anterolateral STE. Repeat LHC showed severe vasospasm of Left anterior descending (LAD) artery and diagonal branch, which improved with intracoronary (IC) nitroglycerin. Vasospasm was attributed to smoking and catecholamine excess from alcohol withdrawal. She was started on intravenous nitroglycerin and amlodipine. Her hospital course was complicated by high degree AV block requiring temporary pacer. She was eventually extubated with good neurological recovery and recovered systolic function (EF 60%). She was counselled on smoking and alcohol cessation and discharged home on isosorbide dinitrate and Amlodipine with planned surgical revascularization. Results: Coronary vasospasm (CVS) can occur both in normal and diseased coronaries. Risk factors include smoking, alcohol use and withdrawal, cocaine, mental stress, etc. Vasospasm may present as Prinzmetal’s angina, myocardial infarction, AV block, or fatal arrhythmias. IC nitroglycerine during LHC aids in diagnosis of CVS in setting of ACS. IVUS (Intravascular ultrasound) may help diagnose presence or absence of concomitant atherosclerotic disease. Provocative testing with IC ergonovine and acetylcholine may be considered in non-ACS setting. Conclusions: This case emphasizes the need to have a high index of suspicion for vasospasm to prevent associated complications and establish an accurate diagnosis and guide proper management of this potentially fatal disease.