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

BACKGROUND: The prognosis of myocardial ischaemia with no obstructive coronary artery disease (INOCA) and its underlying vasomotor disorders, vasospastic angina (VSA) and microvascular angina (MVA), is not well defined. The aim of this study was to perform a systematic review and meta-analysis of studies evaluating the long-term prognosis of patients with INOCA. METHODS: We included studies evaluating the prognosis of patients with INOCA published between January 1984 and August 2023 in Medline, Embase, Web of Science and Cochrane databases. Studies were selected if they included patients who fulfilled the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria for either possible or definitive VSA or MVA. The primary outcomes were composite of all-cause death and myocardial infarction (MI), and major adverse cardiovascular event (MACE) at annual intervals up to 5-year follow-up. The incidence of primary outcomes for INOCA, each INOCA endotype and by method used to determine the diagnosis was calculated using the random effects model. RESULTS: Fifty-four studies (17 302 patients) meeting the eligibility criteria were selected. The rate of all-cause death and MI with VSA was 0.7 (95% CI 0.4 to 1.0)/100 patient-years and with MVA was 1.1 (95% CI 0.7 to 1.5)/100 patient-years (p>0.05). The rate of MACE with VSA was 1.1 (95% CI 0.5 to 1.9)/100 patient-years and with MVA was 2.5 (95% CI 1.6 to 3.6)/100 patient-years (p=0.025). Patients with reduced coronary flow reserve (CFR) had higher all-cause death and MI rates than patients whose diagnosis of MVA was established based on an abnormal exercise or imaging stress test (4.7 (95% CI 2.0 to 8.4) vs 0.5 (95% CI 0.1 to 1.1) vs 1.1 (95% CI 0.5 to 2.0)/100 patient-years, p=0.001). CONCLUSIONS: Overall, patients with INOCA have a low rate of MACEs, but patients with MVA, especially those with reduced CFR, have a significantly higher rate of MACE than other subgroups, although there is high heterogeneity among the included studies. PROSPERO REGISTRATION NUMBER: CRD42021275070.

Unusual Recurrent Multivessel Coronary Artery Spasm: A Case Report and Literature Review.

Coronary artery spasms (CAS) can manifest in various forms, from silent ischemia to severe cardiac events like myocardial infarction and sudden death. This case involves a 56-year-old male with recurrent ischemic chest pain and varying ECG signs. Cardiac catheterization revealed multiple coronary spasms that resolved spontaneously or with intracoronary nitroglycerin. The report emphasizes the severe presentations of multiple CAS and the importance of thorough diagnostic evaluation to avoid unnecessary interventions, highlighting the diagnostic challenges in managing such cases.

Safety and Usefulness of Intracoronary Acetylcholine 200 µg Into the Left Coronary Artery as Vasoreactivity Testing: Comparisons With Intracoronary Acetylcholine Maximum 100 µg.

OBJECTIVES: We retrospectively analyzed the usefulness and safety of intracoronary acetylcholine (ACh) 200 µg into the left coronary artery (LCA) as vasoreactivity testing compared with intracoronary ACh 100 µg. METHODS: We recruited 1433 patients who had angina-like chest pain and intracoronary ACh testing in the LCA, including 1234 patients with a maximum ACh 100 µg and 199 patients with a maximum ACh 200 µg. ACh was injected in incremental doses of 20/50/100/200 µg into the LCA. Positive spasm was defined as ≥ 90% stenosis, usual chest pain, and ischemic electrocardiogram (ECG) changes. RESULTS: The incidence of coronary constriction ≥ 90%, usual chest pain, and ischemic ECG changes with a maximum ACh of 100 µg was markedly higher than that with a maximum ACh of 200 µg. The frequency of unusual chest pain in patients with a maximum ACh of 200 µg was higher than that in those with a maximum ACh of 100 µg (13% vs. 3%, p < 0.001). In patients with rest angina, positive spasm of maximum ACh 100 µg was significantly higher than that of maximum ACh 200 µg, whereas there was no difference regarding positive spasm in patients with atypical chest pain between the two ACh doses. Major complications (1.38% vs. 1.51%, p = 0.8565) and the occurrence of paroxysmal atrial fibrillation (1.81% vs. 2.63%, p = 0.6307) during ACh testing in the LCA were not different between the two maximum ACH doses. CONCLUSIONS: Intracoronary ACh 200 µg into the LCA is clinically useful and safe for vasoreactivity testing when intracoronary ACh 100 µg dose not provoke spasms.

Patent Foramen Ovale and Coronary Artery Spasm: A New Patent Foramen Ovale-associated Condition that May Explain the Mechanism of Vasospastic Angina.

Patent foramen ovale (PFO) may be an underlying factor in the pathogenesis of migraine, vasospastic angina, and Takotsubo cardiomyopathy. This article reviews the role that PFO may play in each of these clinical entities and discusses potential interventions. It also proposes a novel clinical syndrome wherein PFO may be the unifying link among migraine, coronary vasospasm, and Takotsubo cardiomyopathy in predisposed individuals.

Familial catamenial coronary spasms.

Coronary artery spasms represent important causes of myocardial ischaemia and infarction in patients with non-obstructive coronary artery disease. They are notably seen in younger people and occur almost equally in men and women. Besides traditional risk factors (ie, smoking), female hormones might also play a role.We report of two young sisters who presented with myocardial infarction caused by catamenial coronary spasms (CS), that is, during menstruation. In one of these women, this resulted in heart failure with a severely reduced ejection fraction and ultimately a heart transplant because of intractable ventricular arrhythmias.CS might result from changing hormone levels (especially oestrogen) during menstruation. Increased awareness of the occurrence of catamenial CS is essential for diagnosis and consequent treatment with coronary vasodilators and/or specific oestrogen/progesterone regimens.

[Vasospastic angina : an underdiagnosed pathology]. / Vasospasme coronarien : une pathologie sous-diagnostiquée.

Vasospastic angina (VSA) was first described in 1959 by Myron Prinzmetal as "the variant form of angina pectoris" on the sole basis of medical history and ECG. This condition is currently categorized as an endotype of myocardial infarction without coronary obstruction (Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA)). Diagnostic criteria have been suggested by expert consensus. Provocative testing during coronary angiography is the gold standard test but is rarely used. The clinical presentation is often neglected, and the diagnosis is missed. However, VSA may lead to life-threatening arrhythmias. There are simple and effective therapies that are markedly different from those for the atherosclerotic coronary artery disease.

Le vasospasme coronarien (VC) a été décrit pour la première fois en 1959 par Myron Prinzmetal comme « la forme variante de l'angine de poitrine ¼ sur la seule base de l'anamnèse et de l'ECG. Le VC est actuellement classé comme un endotype de l'infarctus du myocarde sans obstruction coronaire (Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA)). Des critères diagnostiques ont été proposés par des consensus d'experts. Le test de provocation lors de la coronarographie est l'examen de choix mais est rarement employé. La symptomatologie est souvent méconnue et le diagnostic n'est pas suffisamment évoqué. Pourtant, le VC peut conduire à des arythmies potentiellement fatales. Nous disposons de moyens thérapeutiques simples et efficaces, qui diffèrent sensiblement de ceux de la maladie coronarienne athérosclérotique.

Diagnostic Yield and Clinical Utility of Coronary Angiography Versus Coronary Function Testing in Women With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Approximately 50% of women referred for invasive coronary angiography have angina and nonobstructive coronary arteries, which includes coronary microvascular dysfunction, vasospastic angina, and other vasomotor disorders. We sought to determine the real-world diagnostic yield of invasive coronary angiography and coronary function testing in women with angina and nonobstructive coronary arteries. METHODS AND RESULTS: From 2018 to 2023, we enrolled 198 women who underwent either coronary angiography (CA) alone (n=99) or coronary function testing (CFT; n=99). Mean±SD age was 62±10 years (CA alone) compared with 57±10 years (CFT). Coronary angiography was interpreted as nonobstructive coronary artery disease more frequently after CA alone (79% versus 52%). Of the women who underwent CFT, 82% (N=81) were found to have vasomotor disorders, including coronary microvascular dysfunction (27%), vasospastic angina (32%), mixed coronary microvascular dysfunction/vasospastic angina (16%), endothelial dysfunction (10%; without spasm), elevated resting flow (2%), or symptomatic myocardial bridging (4%). Compared with women undergoing CA alone, medications were changed more frequently after CFT at 24 hours (41% versus 65%; P=0.001) and between 24 hours and 30 days (30% versus 44%; P=0.04) with intensification of antianginal therapy (79% versus 92%; P<0.0001) and increased use of calcium channel blockers (36% versus 63%; P<0.0001). CONCLUSIONS: Our findings demonstrate that women presenting with suspected ischemic heart disease undergoing CA alone only received an anatomic diagnosis, whereas >80% of women undergoing CFT received a specific diagnosis of a coronary vasomotor disorder and greater intensification of antianginal therapy.

Acute coronary syndrome due to coronary vasospasm: a case report.

Coronary vasospasm can lead to decreased cardiac perfusion and result in acute coronary syndrome. Here is a case of a 49-year-old man presented to the emergency department with epigastric pain and nausea with normal initial electrocardiogram. However, 6 h later, the patient experienced severe chest pain prompting a repeat electrocardiogram demonstrating inferior ST-segment elevation with troponin I levels peaked at 1.2 ng/ml (normal range: 0.00-0.02 ng/ml). Coronary angiography revealed angiographic stenosis in the left circumflex territory of a left dominant system which resolved with intracoronary nitroglycerin administration indicating ischemia with nonobstructive coronary arteries secondary to coronary vasospasm. He was discharged on isosorbide mononitrate and amlodipine therapy and had no recurrence of symptoms during follow-up.

[Box: see text].

The Belgian Registry on Coronary Function Testing (BELmicro Registry): Study Population, Prevalence of Coronary Vascular Dysfunction, and Procedural Safety.

Coronary function testing (CFT) plays a pivotal role in the diagnosis of coronary vascular dysfunction and providing patients with tailored therapy. The Belgian registry on CFT (BELmicro registry) is a prospective, observational, multicenter registry including 14 centers in Belgium. All patients who underwent clinically indicated CFT were included in the registry. Baseline characteristics, CFT data, and clinical outcomes were collected. This analysis aimed to describe the baseline characteristics of a real-world population of patients who underwent CFT, evaluate the prevalence of coronary vascular dysfunction, and assess the safety of CFT in daily clinical practice. Between October 2021 and September 2023, 449 patients were enrolled. The mean age was 65 ± 10 years, and 47.4% of patients were men. A total of 59% of patients had hypertension, 18.7% had diabetes, 69.5% had hypercholesterolemia, and 40.1% had a smoking habit. Angina and nonobstructive coronary arteries (ANOCAs) were identified in 85.1% of the patients. Microvascular physiology assessment was performed in 95.5% of patients, vasoreactivity test in 28.5%, and both in 24.0%. coronary microvascular dysfunction was diagnosed in 23.4% of patients with ANOCA, epicardial vasospasm in 26.3%, and microvascular spasm in 14.9%. Rates of major complications were 0.7% for microvascular physiology assessment and 0% for vasoreactivity test. In conclusion, participants in the BELmicro registry represented a real-world population of patients, characterized by a high burden of cardiovascular risk factors. Coronary microvascular dysfunction and coronary vasospasm were frequent in patients with ANOCA. Performing CFT in daily clinical practice was feasible, with a low rate of complications.

High Detectability of Prehospital 12-Lead Electrocardiogram in Diagnosing Spasm-Induced Acute Coronary Syndrome.

BACKGROUND: The importance of prehospital (PH) electrocardiograms (ECG) recorded by emergency medical services (EMS) for diagnosing coronary artery spasm-induced acute coronary syndrome (CS-ACS) remains unclear. METHODS AND RESULTS: We enrolled 340 consecutive patients with ACS who were transported by EMS within 12 h of symptom onset. According to Japanese Circulation Society guidelines, CS-ACS (n=48) was diagnosed with or without a pharmacological provocation test (n=34 and n=14, respectively). Obstructive coronary artery-induced ACS (OC-ACS; n=292) was defined as ACS with a culprit lesion showing 99% stenosis or >75% stenosis with plaque rupture or thrombosis observed via angiographic and intravascular imaging. Ischemic ECG findings included ST-segment deviation (elevation or depression) and negative T and U waves. In CS-ACS, the prevalence of ST-segment deviation decreased significantly from PH-ECG to emergency room (ER) ECG (77.0% vs. 35.4%; P<0.001), as did the prevalence of overall ECG abnormalities (81.2% vs. 45.8%; P<0.001). Conversely, in OC-ACS, there was a similar prevalence on PH-ECG and ER-ECG of ST-segment deviations (94.8% vs. 92.8%, respectively; P=0.057) and abnormal ECG findings (96.9% vs. 95.2%, respectively; P=0.058). Patients with abnormal PH-ECG findings that disappeared upon arrival at hospital without ER-ECG or troponin abnormalities were more frequent in the CS-ACS than OC-ACS group (20.8% vs. 1.0%; P<0.001). CONCLUSIONS: PH-ECG is valuable for detecting abnormal ECG findings that disappear upon arrival at hospital in CS-ACS patients.

Polymorphic Ventricular Tachycardia Associated with Coronary Vasospasm in a Patient with Coronavirus Disease 2019 Infection.

A 70-year-old man was admitted to our hospital for restoration of sinus rhythm from atrial fibrillation by direct current counter shocks. On admission, he had a coronavirus disease 2019 (COVID-19) infection and syncope during bed rest. Electrocardiography revealed polymorphic ventricular tachycardia after ST-segment elevation with a normal QT interval. Coronary angiography revealed coronary vasospasm. Coronary vasospasm may be a cause of polymorphic ventricular tachycardia in COVID-19 patients.

Relationship between peripheral and intracoronary blood flow in patients with angina and nonobstructive coronary arteries.

Coronary vasomotor dysfunction, an important underlying cause of angina and nonobstructive coronary arteries (ANOCA), encompassing coronary vasospasm, coronary endothelial dysfunction, and/or coronary microvascular dysfunction, is clinically assessed by invasive coronary function testing (ICFT). As ICFT imposes a high burden on patients and carries risks, developing noninvasive alternatives is important. We evaluated whether coronary vasomotor dysfunction is a component of systemic microvascular endothelial and smooth muscle dysfunction and can be detected using laser speckle contrast analysis (LASCA). Forty-three consecutive patients with ANOCA underwent ICFT, with intracoronary acetylcholine, adenosine, and flow measurements, to assess coronary vasomotor dysfunction. Cutaneous microvascular function was assessed using LASCA in the forearm, combined with vasodilators acetylcholine, sodium nitroprusside, and insulin and using EndoPAT, by measuring the reactive hyperemia index (RHI). Of the 43 included patients with ANOCA (79% women, 59 ± 9 yr old), 38 patients had coronary vasomotor dysfunction, including 28 with coronary vasospasm, 26 with coronary endothelial dysfunction, and 18 with coronary microvascular dysfunction, with overlapping endotypes. Patients with and without coronary vasomotor dysfunction had similar peripheral flow responses to acetylcholine, insulin, and RHI. In contrast, coronary vasomotor dysfunction was associated with lower peripheral flow responses to sodium nitroprusside (P < 0.001). An absolute flow response to sodium nitroprusside of 83.95 APU resulted in 86.1% sensitivity and 80.0% specificity for coronary vasomotor dysfunction (area under the ROC curve, 0.883; P = 0.006). In conclusion, this study provides evidence of systemic vascular smooth muscle dysfunction in patients with ANOCA with coronary vasomotor dysfunction and the diagnostic value of peripheral microvascular function testing as a noninvasive tool for detecting coronary vasomotor dysfunction.NEW & NOTEWORTHY This study provides proof of concept that assessment of the peripheral vasculature, particularly vascular smooth muscle cells measured using the LASCA technology holds potential as a noninvasive tool for detecting coronary vasomotor dysfunction. This finding highlights the potential of the LASCA technology in, for example, medication studies for coronary vasomotor dysfunction, especially when investigating whether medication improves vascular function, as repeated peripheral measurements are less invasive than invasive coronary function testing, the current gold standard.

Out-of-season, multiserotype acute coxsackie B myocarditis with concomitant thyrotoxicity.

Acute viral myocarditis and hyperthyroidism can present with acute coronary syndrome. However, the link between hyperthyroidism and myocarditis has hardly been explored apart from a small collection of published case reports. We report a case where a patient presents with severe chest pain and was found to have concomitant severe coronary vasospasm and acute myocarditis and was diagnosed with Graves' disease.

The Diagnostic Value of ECG Characteristics for Vasospastic and Microvascular Angina: A Systematic Review.

BACKGROUND: Coronary vascular dysfunction comprises VSA and/or MVA and is more common in women than in men with angina without obstructive coronary artery disease (ANOCA). Invasive coronary function testing is considered the reference test for diagnosis, but its burden on patients is large. We aimed to investigate the potential of electrocardiography (ECG) as noninvasive marker for vasospastic angina (VSA) and microvascular angina (MVA) diagnosis. METHODS: We systematically screened Pubmed and EMBASE databases for studies reporting on ECG characteristics in ANOCA patients with (a suspicion of) coronary vascular dysfunction. We assessed study quality using QUADAS-2. We extracted data on diagnostic values of different ECG characteristics and analyzed whether the studies were sex-stratified. RESULTS: Thirty publications met our criteria, 13 reported on VSA and 17 on MVA. The majority addressed repolarization-related ECG parameters. Only 1 of the 13 VSA papers and 4 of the 17 MVA papers showed diagnostic accuracy measures of the ECG characteristics. The presence of early repolarization, T-wave alternans, and inverted U waves showed of predictive value for VSA diagnosis. The QTc interval was predictive for MVA diagnosis in all six studies reporting on QTc interval. Sex-stratified results were reported in only 5 of the 30 studies and 3 of those observed sex-based differences. CONCLUSIONS: ECG features are not widely evaluated in diagnostic studies for VSA and MVA. Those features predictive for VSA and MVA diagnosis mostly point to repolarization abnormalities and may contribute to noninvasive risk stratification.

Lack of Class I Vasoreactivity Testing for Diagnosing Patients With Coronary Artery Spasm.

BACKGROUND: Vasoreactivity testing, such as intracoronary acetylcholine (ACh) or ergometrine (EM), is defined as Class I for the diagnosis of patients with vasospastic angina (VSA) according to recommendations from the Coronary Vasomotion Disorders International Study (COVADIS) group and guidelines from the Japanese Circulation Society (JCS). HYPOTHESIS: Although vasoreactivity testing is a clinically useful tool, it carries some risks and limitations in diagnosing coronary artery spasm. METHODS: Previous reports on vasoreactivity testing for diagnosing the presence of coronary spasm are summarized from the perspective of Class I. RESULTS: There are several problems such as reproducibility, underestimation, overestimation, and inconclusive/nonspecific results associated with daily spasm. Because provoked spasm caused by intracoronary ACh is not always similar to that caused by intracoronary EM, possibly due to different mediators, supplementary use of these vasoreactivity tests is necessary for cardiologists to diagnose VSA when a provoked spasm is not revealed by each vasoactive agent. CONCLUSIONS: Cardiologists should understand the imperfection of these vasoreactivity tests when diagnosing patients with VSA.

Exploring the mechanisms of Guizhifuling pills in the treatment of coronary spastic angina based on network pharmacology combined with molecular docking.

Coronary spastic angina (CSA) is common, and treatment options for refractory vasospastic angina are sometimes limited. Guizhifuling pills (GFP) have demonstrated efficacy in reducing CSA episodes, but their pharmacological mechanism remains unclear. To explore the mechanism of action of GFP in preventing and treating CSA, we employed network pharmacology and molecular docking to predict targets and analyze networks. We searched GFP chemical composition information and related targets from databases. The drug-target and drug-target pathway networks were constructed using Cytoscape. Then the protein-protein interaction was analyzed using the STRING database. Gene Ontology biological functions and Kyoto Encyclopedia of Genes and Genomes pathways were performed by the Metascape database, and molecular docking validation of vital active ingredients and action targets of GFP was performed using AutoDock Vina software. The 51 active components in GFP are expected to influence CSA by controlling 279 target genes and 151 signaling pathways. Among them, 6 core components, such as quercetin, ß-sitosterol, and baicalein, may regulate CSA by affecting 10 key target genes such as STAT3, IL-6, TP53, AKT1, and EGFR. In addition, they are involved in various critical signaling pathways such as apelin, calcium, advanced glycation end product-receptor for advanced glycation end product, and necroptosis. Molecular docking analysis confirms favorable binding interactions between the active components of GFP and the selected target proteins. The effects of GFP in treating CSA involve multiple components, targets, and pathways, offering a theoretical basis for its clinical use and enhancing our understanding of how it works.