The Great Masquerade: Not All Coronary Artery Stenosis Are Created Equal.

We present the case of a 60-year-old male, with active smoking and cocaine use disorder, who reported progressive chest pain. Various anatomical and functional cardiac imaging, performed to further evaluate chest pain etiology, revealed changing severity and distribution of left main artery (LMA) stenosis, raising suspicion for vasospasm. Intracoronary nitroglycerin relieved the vasospasm, with resolution of the LMA pseudostenosis. A diagnosis of vasospastic angina (VA) led to starting appropriate medical therapy with lifestyle modification counselling. This case highlights VA, a frequently underdiagnosed etiology of angina pectoris. We discuss when to suspect VA, its appropriate work-up, and management.

[Angina and no obstruction on coronary angiography : New approaches to the diagnosis and treatment of vasomotor disorders]. / Angina pectoris ohne Stenosen in der Koronarangiographie : Neue Wege zur Diagnose und Therapie von Vasomotionsstörungen.

BACKGROUND: Clinical management of patients with angina and no obstructive coronary artery disease (ANOCA) is still challenging. This scenario affects up to 50% of patients undergoing diagnostic coronary angiography due to suspected coronary artery disease. Many patients report a long and debilitating history before adequate diagnostics and management are initiated. OBJECTIVES: This article describes the current recommendations for diagnostic assessments and treatment in patients with ANOCA. Focus is placed on invasive diagnostics in the catheter laboratory, pharmacological/interventional treatment as well as the patient journey. RESULTS: In patients with ANOCA, the current European Society of Cardiology (ESC) guidelines suggest that invasive assessments using acetylcholine and adenosine for the diagnosis of an underlying coronary vasomotor disorder should be considered. Acetylcholine is used to diagnose coronary spasm, whereas adenosine is used in conjunction with a wire-based assessment for the measurement of coronary flow reserve and microvascular resistance. The invasive assessments allow the determination of what are referred to as endotypes (coronary spasm, impaired coronary flow reserve, enhanced microvascular resistance or a combination thereof). Establishing a diagnosis is helpful to: (a) initiate targeted treatment to improve quality of life, (b) reassure the patient that a cardiac cause is found and (c) to assess individual prognosis. CONCLUSIONS: Currently, patients with ANOCA are often not adequately managed. Referral to specialised centres is recommended to prevent long and debilitating patient histories until expertise in diagnosis and treatment becomes more widespread.

Post-partum myocardial ischemia due to intramuscular methylergonovine-induced coronary vasospasm: case report.

BACKGROUND: Methylergonovine is a vasoconstrictive agent historically used as a provocative agent in the lab for coronary vasospasm; it is also a first line uterotonic agent for management of postpartum hemorrhage. CASE PRESENTATION: A 29-year-old female with history of smoking and idiopathic thrombocytopenia received intramuscular methylergonovine after delivery of twins for intrauterine hemorrhage management. Subsequently, she had episodes of chest pain with high sensitivity Troponin I elevation to 1509 ng/L with accompanying septal T wave inversions, decreased left ventricular ejection fraction to 49% and basal septal wall hypokinesis. Computed tomography (CT) coronary angiogram showed patent coronary arteries and no coronary arterial dissection. The patient was conservatively managed with aspirin and metoprolol, and on follow up had fully recovered left ventricular function with resolution of wall motion abnormalities. Given this, coronary vasospasm due to intramuscular methylergonovine is the most likely cause of patient's chest pain and associated myocardial ischemia. CONCLUSIONS: Intramuscular, intrauterine, intravenous, and even oral methylergonovine can rarely cause coronary vasospasm leading to myocardial ischemia. Cardiologists caring for postpartum patients should be aware of these potential lethal complications; prompt identification and administration of sublingual nitroglycerin can prevent severe complications of arrythmias, heart block, or cardiac arrest.

Efficacy of Diltiazem to Improve Coronary Vasomotor Dysfunction in ANOCA: The EDIT-CMD Randomized Clinical Trial.

BACKGROUND: Diltiazem is recommended and frequently prescribed in patients with angina and nonobstructive coronary artery disease (ANOCA), suspected of coronary vasomotor dysfunction (CVDys). However, studies substantiating its effect is this patient group are lacking. OBJECTIVES: The randomized, placebo-controlled EDIT-CMD (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial) evaluated the effect of diltiazem on CVDys, as assessed by repeated coronary function testing (CFT), angina, and quality of life. METHODS: A total of 126 patients with ANOCA were included and underwent CFT. CVDys, defined as the presence of vasospasm (after intracoronary acetylcholine provocation) and/or microvascular dysfunction (coronary flow reserve: <2.0, index of microvascular resistance: ≥25), was confirmed in 99 patients, of whom 85 were randomized to receive either oral diltiazem or placebo up to 360 mg/d. After 6 weeks, a second CFT was performed. The primary end point was the proportion of patients having a successful treatment, defined as normalization of 1 abnormal parameter of CVDys and no normal parameter becoming abnormal. Secondary end points were changes from baseline to 6-week follow-up in vasospasm, index of microvascular resistance, coronary flow reserve, symptoms (Seattle Angina Questionnaire), or quality of life (Research and Development Questionnaire 36). RESULTS: In total, 73 patients (38 diltiazem vs 35 placebo) underwent the second CFT. Improvement of the CFT did not differ between the groups (diltiazem vs placebo: 21% vs 29%; P = 0.46). However, more patients on diltiazem treatment progressed from epicardial spasm to microvascular or no spasm (47% vs 6%; P = 0.006). No significant differences were observed between the diltiazem and placebo group in microvascular dysfunction, Seattle Angina Questionnaire, or Research and Development Questionnaire 36. CONCLUSIONS: This first performed randomized, placebo-controlled trial in patients with ANOCA showed that 6 weeks of therapy with diltiazem, when compared with placebo, did not substantially improve CVDys, symptoms, or quality of life, but diltiazem therapy did reduce prevalence of epicardial spasm. (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial [EDIT-CMD]; NCT04777045).

Perioperative coronary artery spasm after off-pump coronary artery bypass grafting in the non-manipulated coronary artery.

BACKGROUND: Perioperative coronary artery spasm (CAS) following coronary artery bypass grafting (CABG) is a severe or lethal condition that is rarely reported. In addition, rare cases with CAS following CABG in the non-manipulated coronary artery are angiographically documented in the perioperative period. We aimed to report our experiences on the diagnosis and treatment of a case with CAS following off-pump CABG in the non-manipulated coronary artery. METHODS: A 57-year old male with coronary heart disease and unstable angina willing to undergo CABG was admitted to our department. CABG was recommended as he showed 90% stenosis in distal left anterior descending artery, 90% stenosis in intermediate branch, 90% stenosis in left circumflex coronary artery, as well as 50% stenosis in proximal right coronary artery (RCA). RESULTS: After CABG, the patient showed Adams-Stokes syndrome and ST-segment elevation. Then CPR was conducted and coronary angiography indicated perioperative CAS in the non-manipulated posterior descending artery. For the treatment, the patient received nitroglycerin injection into the coronary artery by catheter and pumping of diltiazem. Finally, the patient was discharged on day 7 after surgery. A comprehensive literature search was conducted to summarize the studies focused on the diagnosis and treatment of such condition, which indicated that all of the CAS cases occurred in the manipulated vessels, except one study showing CAS in the untouched native coronary artery which was similar with our case. CONCLUSIONS: Perioperative CAS in the non-manipulated coronary artery following CABG is a severe or lethal condition that is rarely reported, which deserves close attention by the clinicians in clinical practice.

Eosinophilic granulomatosis with polyangiitis presenting with repetitive acute coronary syndrome, refractory coronary vasospasm, and spontaneous coronary dissection: a case report.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of eosinophilic vasculitis that is mainly limited to small- and medium-sized arteries. Cardiac involvement is the leading cause of death in patients with EGPA. Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome in middle-aged women with no or few traditional cardiovascular risk factors. EGPA manifesting as repetitive acute coronary syndrome and SCAD has not been reported. A 45-year-old woman presented with recurrent chest pain and cardiogenic shock associated with coronary vasospasm refractory to common vasodilators. Coronary angiography showed SCAD at the proximal right coronary artery. Blood tests showed significant eosinophilia. In addition to sinusitis as shown by nasal computed tomography and abnormal nerve conduction velocity, the diagnosis of EGPA was made and immunosuppression commenced. During a 20-month follow-up, the patient remained free from symptoms and adverse cardiovascular events. EGPA can involve coronary arteries and may rarely manifest as SCAD or vasospasm. We herein review the mechanism underlying coronary involvement of EGPA and emphasize special clues for its detection. Early recognition and initiation of immunosuppression therapy are important.

Features of atherosclerosis in patients with angina and no obstructive coronary artery disease.

BACKGROUND: An association between atherosclerosis and coronary vasospasm has previously been suggested. However, to date, no conclusive data on the whole spectrum of these disorders have been published. AIMS: This study aimed to define specific morphological features of atherosclerosis in patients with angina and no obstructive coronary artery disease (ANOCA) due to coronary vasospasm. METHODS: From February 2019 to January 2020, we enrolled 75 patients referred to our laboratory for a coronary function test (CFT) due to ANOCA and suspected coronary vasomotor dysfunction. The CFT consisted of an acetylcholine test and a physiology assessment with hyperaemic indexes using adenosine. Patients were divided into two groups according to the presence or absence of coronary vasospasm triggered by acetylcholine (ACH+ and ACH-, respectively). In addition, optical coherence tomography (OCT) was performed to assess the lipid index (LI), a surrogate for lipid area, and the prevalence of markers of plaque vulnerability. RESULTS: ACH+ patients had a higher LI than ACH- patients (LI: 819.85 [460.95-2489.03] vs 269.95 [243.50-878.05], respectively, p=0.03), and a higher prevalence of vulnerable plaques (66% vs 38%, p=0.04). Moreover, ACH+ patients showed a higher prevalence of neovascularisation compared to ACH- subjects (37% vs 6%, p=0.02) and a trend towards a higher prevalence of all individual markers, in particular thin-cap fibroatheroma (20% vs 0%, p=0.06). No differences were detected between patterns of coronary vasospasm. CONCLUSIONS: The presence of coronary vasospasm, regardless of its phenotype, is associated with higher lipid burden, plaque vulnerability and neovascularisation.

Perioperative coronary artery spasms in patients undergoing catheter ablation of atrial fibrillation.

PURPOSE: Catheter ablation (CA) is an established treatment for atrial fibrillation (AF). Although coronary artery spasms (CAS) during or after ablation procedures have been described as a rare complication in some case reports, the incidence and characteristics of this complication have not been fully elucidated. The present observational study aimed to clarify the CAS in a large number of patients experiencing AF ablation. METHODS: A total of 2913 consecutive patients (male: 78%, mean 66 ± 10 years) who underwent catheter ablation of AF were enrolled. RESULTS: Nine patients (0.31%, mean 66 ± 10 years, 7 males) had transient ST-T elevation (STE). Eight out of the 9 patients had STE in the inferior leads. STE occurred after the transseptal puncture in 7 patients, after the sheath was pulled out of the left atrium in 1, and 2 h after the ablation procedure in 1. Six patients had definite angiographic CAS without any sign of an air embolization on the emergent coronary angiography. In the3 other patients, the STE improved either directly after an infusion of nitroglycerin or spontaneously before the CAG. The patients with CAS had a higher frequency of a smoking habit (89% vs. 53%; P = .04), smaller left atrial diameter (36 ± 6 vs. 40 ± 7; P = .07), and lower CHADS2 score (0.6 ± 0.5 vs. 1.3 ± 1.1; P = .004) than those without. CONCLUSIONS: Although the incidence was rare (0.31%), CAS should be kept in mind as a potentially life-threatening complication throughout an AF ablation procedure especially performed under conscious sedation.

Coronary spasm: unpredictability and safety in treatment key role of hybrid setting.

The present case highlights the crucial role of hybrid setting for diagnosis and treatment of refractory coronary spasms.

Vasomotor dysfunction in patients with angina and nonobstructive coronary artery disease is dominated by vasospasm.

BACKGROUND: Coronary vasomotor dysfunction, comprising endotypes of coronary spasm and/or impaired microvascular dilatation (IMD), is common in patients with angina and no obstructive coronary arteries (ANOCA). However, there are discrepant reports regarding the prevalence of these endotypes. The objective of this study was to determine the prevalence of coronary vasomotor dysfunction in patients with ANOCA, underlying endotypes, and differences in clinical characteristics. METHODS: Prospective registry of patients with ANOCA that underwent clinically indicated invasive coronary function testing (CFT), including acetylcholine spasm testing (2-200 µg) to diagnose coronary spasm, and adenosine testing (140 µg/kg/min) to diagnose IMD, defined as an index of microvascular resistance ≥25 and/or coronary flow reserve <2.0. RESULTS: Of the 111 patients that completed CFT (88% female, mean age 54 years), 96 (86%) showed vasomotor dysfunction. The majority 93 (97%) had coronary spasm, 63% isolated and 34% combined with IMD. Isolated IMD was rare, occurring in only 3 patients (3%). Hypertension was more prevalent in patients with vasomotor dysfunction compared to those without (39% vs. 7%, p = 0.02). Obesity and a higher severity of angiographic atherosclerotic disease were more prevalent in patients with coronary spasm compared to those without (61% vs. 28%; 40% vs. 0%, respectively, both p < 0.01). No differences in angina characteristics were observed between patients with and without vasomotor dysfunction or between endotypes. CONCLUSIONS: Coronary vasomotor dysfunction is highly prevalent in patients with ANOCA, especially epicardial or microvascular vasospasm, whereas isolated IMD was rare. Performing a CFT without acetylcholine testing should be strongly discouraged.

Beneficial effects of exercise training on physical performance in patients with vasospastic angina.

AIMS: In vasospastic angina (VSA), coronary vasomotion abnormalities could develop not only in epicardial coronary arteries but also in coronary microvessels, where calcium channel blockers (CCBs) have limited efficacy. However, efficacy of exercise training for VSA remains to be elucidated. We thus aimed to examine whether vasodilator capacity of coronary microvessels is impaired in VSA patients, and if so, whether exercise exerts beneficial effects on the top of CCBs. METHODS: We performed 2 clinical protocols. In the protocol 1, we measured myocardial blood flow (MBF) using adenosine-stress dynamic computed tomography perfusion (CTP) in 38 consecutive VSA patients and 17 non-VSA controls. In the protocol 2, we conducted randomized controlled trial, where 20 VSA patients were randomly assigned to either 3-month exercise training group (Exercise group) or Non-Exercise group (n= 10 each). RESULTS: In the protocol 1, MBF on CTP was significantly decreased in the VSA group compared with the Non-VSA group (138 ± 6 vs 166 ± 10 ml/100 g/min, P = 0.02). In the protocol 2, exercise capacity was significantly increased in the Exercise group than in the Non-Exercise group (11.5 ± 0.5 to 15.4 ± 1.8 vs 12.6 ± 0.7 to 14.0 ± 0.8 ml/min/kg, P < 0.01). MBF was also significantly improved after 3 months only in the Exercise group (Exercise group, 145 ± 12 to 172 ± 8 ml/100 g/min, P < 0.04; Non-Exercise group, 143 ± 14 to 167 ± 8 ml/100 g/min, P = 0.11), although there were no significant between-group differences. CONCLUSIONS: These results provide the first evidence that, in VSA patients, exercise training on the top of CCBs treatment may be useful to improve physical performance, although its effect on MBF may be minimal.

Recurrent attack of acute myocardial infarction complicated with ventricular fibrillation due to coronary vasospasm within a myocardial bridge: a case report.

BACKGROUND: Myocardial bridge (MB) often an inoffensive condition that goes in one or more of the coronary arteries through the heart muscle instead of lying on its surface. MBs sometimes leads to myocardial ischemic symptoms such as chest pain, even an occurrence of myocardial infarction. However, reports of severe and recurrent cardiac adverse events related to the MBs are rare. CASE PRESENTATION: A 44-year-old male patient who suffered from a four-hour crushing chest pain ten years ago, was diagnosed as acute anterior ST-elevation myocardial infarction (STEMI). The initial findings of coronary angiography (CAG) showed MB was located in the middle part of the left anterior descending coronary artery (LAD). The patient was managed medically. Another re-attack of similar previous chest pain characteristics occured just after 3 days of discharge. Supra-arterial myotomy and CABG were the next adopted management. Postoperative progression was uneventful. However, 32 months after surgical treatment, the patient experienced an abrupt onset of chest pain accompanied by loss of consciousness. The ECG showed ventricular fibrillation (VF). After electrical cardioversion, an immediate CAG followed by CTA was performed which excluded thrombus or acute occlusion in the native coronary artery and an occlusion was observed at the end of the left internal mammary artery. An implantable cardioverter-defibrillator (ICD) was successfully performed for prevention of malignant arrhythmia. During ten years of follow-up, no complications have been identified. CONCLUSIONS: Although MB is mostly benign, it may lead to significant cardiovascular consequences. Supra-arterial myotomy is an appropriate treatment option for this patient who failed to optimal medical therapy. Furthermore, ICD implantation must be considered in order to prevent malignant ventricular arrhythmia caused by continuous spasm resulting in ischemia. Further investigations are required to confirm the clinical effectiveness of these procedures.

Massive coronary spasm of the native coronary system after coronary artery bypass grafting: Two patients with different outcomes.

We report the cases of two patients who developed a massive spasm of the native coronary system in the immediate postoperative period, following a coronary artery bypass grafting operation with different outcomes. The first patient was hemodynamic stable and it was manifested as ischemic electrocardiographic changes in different leads (ST elevation or depression). He was treated with intracoronary and intravenous administration of nitroglycerin and calcium channel blocker and had a favorable outcome. The second patient died due to multiorgan failure and hemorrhagic shock, after the implantation of a central venoarterial extracorporeal membrane oxygenation.

Acute myocardial infarction caused by persistent coronary spasm associated with high-grade macrophage accumulation.

The mechanisms responsible for persistent and lethal coronary spasm remain incompletely understood. Our group treated a patient with non-ST-elevation myocardial infarction (MI) caused by a spontaneously persistent spasm associated with high-grade macrophage accumulation. A 48-year-old man was transferred to an emergency room because of persisted chest tightness. The patient's chest pain subsided without ST elevation when he arrived at the hospital, but he tested positive for fatty acid-binding protein. Emergent coronary angiography revealed a subtotal occlusion in the middle of the right coronary artery. The occluded lesion was released immediately after an injection of isosorbide dinitrate. No disruption, ulceration or erosion was observed at the culprit lesion segment on optical coherence tomography. The only finding was high-grade macrophage accumulation in the segment of the persistent focal coronary spasm. The present case suggests that the early stage of atherosclerosis with high-grade macrophage accumulation was associated with persistent coronary spasm resulting in acute MI.

Clinical, angiographic and echocardiographic correlates of epicardial and microvascular spasm in patients with myocardial ischaemia and non-obstructive coronary arteries.

BACKGROUND: Coronary vasomotor dysfunction represents an important mechanism responsible for myocardial ischaemia in patients with non-obstructive coronary artery disease (CAD). The use of invasive provocative tests allows identifying patients with epicardial or microvascular spasm. Of note, clinical characteristics associated with the occurrence of epicardial or microvascular spasm have still not completely clarified. METHODS AND RESULTS: We prospectively enrolled consecutive patients undergoing coronary angiography for suspected myocardial ischaemia/necrosis with evidence of non-obstructive CAD and undergoing intracoronary provocative test for suspected vasomotor dysfunction. Patients with a positive provocative test were enrolled. Clinical, echocardiographic and angiographic characteristics of patients were evaluated according to the pattern of vasomotor dysfunction (epicardial vs. microvascular spasm). We included 120 patients [68 patients with stable angina and 52 patients with myocardial infarction and non-obstructive coronary arteries (MINOCA)]. In particular, 77 (64.2%) patients had a provocative test positive for epicardial spasm and 43 (35.8%) patients for microvascular spasm. Patients with epicardial spasm were more frequently males, smokers, had higher rates of diffuse coronary atherosclerosis at angiography and more frequently presented with MINOCA. On the other hand, patients with microvascular spasm presented more frequently diastolic dysfunction. At multivariate logistic regression analysis male sex, smoking, and diffuse coronary atherosclerosis were independent predictors for the occurrence of epicardial spasm. CONCLUSIONS: Our study showed that specific clinical features are associated with different responses to intracoronary provocative test. Epicardial spasm is more frequent in males and in MINOCA patients, whereas microvascular spasm is more frequent in patients with stable angina and is associated with diastolic dysfunction.

Vasoespasmo coronario en un niño alérgico al látex: síndrome de Kounis / Coronary vasospasm in a child allergic to latex: Kounis syndrome

El síndrome de Kounis consiste en la aparición simultánea de anafilaxia y síndrome coronario agudo. Se trata de una entidad poco descrita y que puede estar infradiagnosticada en pediatría. Es crucial, por su presentación variable, atípica e inesperada, y por sus posibles complicaciones graves (arritmias ventriculares, infarto de miocardio, muerte súbita), su reconocimiento y tratamiento precoz, dirigido a la revascularización del miocardio y al tratamiento de la reacción anafiláctica concomitante. Se presenta el caso de un varón de 11 años que, tras el contacto con látex, presentó una reacción anafiláctica asociada a vasoespasmo coronario, con recuperación rápida y completa con la administración de adrenalina intramuscular. El estudio cardiológico descartó patología coronaria como causa del evento. El estudio alergológico puso de manifiesto un síndrome de reactividad cruzada látex-frutas (kiwi y piña). Se diagnosticó síndrome de Kounis tipo i desencadenado por látex, y se recomendó evitar posibles factores desencadenantes.

Kounis syndrome consists of the simultaneous occurrence of anaphylaxis and acute coronary syndrome. It is a rare entity that may be underdiagnosed in paediatrics. The clinical presentation is variable, atypical and usually unexpected, and it carries possible serious complications such as ventricular arrhythmias, myocardial infarction and sudden death. Therefore, an early diagnosis and treatment for myocardial revascularization and the anaphylactic reaction are crucial. We report the case of an 11-year-old male who, after contact with latex, presented an anaphylactic reaction associated with coronary vasospasm, with rapid and complete recovery after administration of intramuscular adrenaline. The cardiological study ruled out coronary pathology as the cause of the event. The allergy study revealed a latex-fruit (kiwi and pineapple) cross-reactivity syndrome. The patient was diagnosed with type I Kounis syndrome triggered by latex, recommending the avoidance of possible triggers.

Successful Management of Unremitting Spasm after Myocardial Revascularization Exclusively with Bilateral Internal Thoracic Arteries in Y-graft Configuration: A Case Report.

Coronary artery spasm (CAS) after coronary artery bypass grafting (CABG) is rare, and in time may be fatal for the patient if undiagnosed. The purpose of the present study is to report the case of a patient who survived after experiencing a persistent spasm of all native coronary arteries following successful arterial myocardial revascularization. Furthermore, we aimed to discuss the therapeutic strategies which may prevent the occurrence of a coronary artery spasm in settings of myocardial revascularization, in the context of reviewed specific literature evidences.