日本循環器学会．2023年JCS/CVIT/JCC ガイドライン フォーカスアップデート版 冠攣縮性狭心症と冠微小循環障害の診断と治療（日本循環器学会/ 日本心血管インターベンション治療学会/ 日本心臓病学会合同ガイドライン）．https://www.j-circ.or.jp/cms/wp-ontent/uploads/2023/03/JCS2023_hokimoto.pdf.
Vijay Kunadian, Alaide Chieffo, Paolo G Camici, Colin Berry, Javier Escaned, Angela H E M Maas, Eva Prescott, Nicole Karam, Yolande Appelman, Chiara Fraccaro, Gill Louise Buchanan, Stephane Manzo-Silberman, Rasha Al-Lamee, Evelyn Regar, Alexandra Lansky, J Dawn Abbott, Lina Badimon, Dirk J Duncker, Roxana Mehran, Davide Capodanno, Andreas Baumbach
An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group.
Eur Heart J. 2020 Oct 1;41(37):3504-3520. doi: 10.1093/eurheartj/ehaa503.
Abstract/Text
This consensus document, a summary of the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), appraises the importance of ischaemia with non-obstructive coronary arteries (INOCA). Angina pectoris affects approximately 112 million people globally. Up to 70% of patients undergoing invasive angiography do not have obstructive coronary artery disease, more common in women than in men, and a large proportion have INOCA as a cause of their symptoms. INOCA patients present with a wide spectrum of symptoms and signs that are often misdiagnosed as non-cardiac leading to under-diagnosis/investigation and under-treatment. INOCA can result from heterogeneous mechanism including coronary vasospasm and microvascular dysfunction and is not a benign condition. Compared to asymptomatic individuals, INOCA is associated with increased incidence of cardiovascular events, repeated hospital admissions, as well as impaired quality of life and associated increased health care costs. This consensus document provides a definition of INOCA and guidance to the community on the diagnostic approach and management of INOCA based on existing evidence from research and best available clinical practice; noting gaps in knowledge and potential areas for further investigation.
The article has been co-published with permission in the European Heart Journal and EuroIntervention. All rights reserved. © 2020 the Author(s). These articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.
Juhani Knuuti, William Wijns, Antti Saraste, Davide Capodanno, Emanuele Barbato, Christian Funck-Brentano, Eva Prescott, Robert F Storey, Christi Deaton, Thomas Cuisset, Stefan Agewall, Kenneth Dickstein, Thor Edvardsen, Javier Escaned, Bernard J Gersh, Pavel Svitil, Martine Gilard, David Hasdai, Robert Hatala, Felix Mahfoud, Josep Masip, Claudio Muneretto, Marco Valgimigli, Stephan Achenbach, Jeroen J Bax, ESC Scientific Document Group
2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes.
Eur Heart J. 2020 Jan 14;41(3):407-477. doi: 10.1093/eurheartj/ehz425.
Abstract/Text
Doyeon Hwang, Sang-Hyeon Park, Bon-Kwon Koo
Ischemia With Nonobstructive Coronary Artery Disease: Concept, Assessment, and Management.
JACC Asia. 2023 Apr;3(2):169-184. doi: 10.1016/j.jacasi.2023.01.004. Epub 2023 Apr 18.
Abstract/Text
In daily clinical practice, physicians often encounter patients with angina or those with evidence of myocardial ischemia from noninvasive tests but not having obstructive coronary artery disease. This type of ischemic heart disease is referred to as ischemia with nonobstructive coronary arteries (INOCA). INOCA patients often suffer from recurrent chest pain without adequate management and are associated with poor clinical outcomes. There are several endotypes of INOCA, and each endotype should be treated based on its specific underlying mechanism. Therefore, identifying INOCA and discriminating its underlying mechanisms are important issues and of clinical interest. Invasive physiologic assessment is the first step in the diagnosis of INOCA and discriminating the underlying mechanism; additional provocation tests help physicians identify the vasospastic component in INOCA patients. Comprehensive information acquired from these invasive tests can provide a template for mechanism-specific management for patients with INOCA.
© 2023 The Authors.
Lasse Jespersen, Anders Hvelplund, Steen Z Abildstrøm, Frants Pedersen, Søren Galatius, Jan K Madsen, Erik Jørgensen, Henning Kelbæk, Eva Prescott
Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events.
Eur Heart J. 2012 Mar;33(6):734-44. doi: 10.1093/eurheartj/ehr331. Epub 2011 Sep 11.
Abstract/Text
AIMS: Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus.
METHODS AND RESULTS: We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively.
CONCLUSION: Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.
Rocco A Montone, Giampaolo Niccoli, Francesco Fracassi, Michele Russo, Filippo Gurgoglione, Giulia Cammà, Gaetano A Lanza, Filippo Crea
Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests.
Eur Heart J. 2018 Jan 7;39(2):91-98. doi: 10.1093/eurheartj/ehx667.
Abstract/Text
AIMS: Functional alterations of epicardial coronary arteries or coronary microcirculation represent a frequent cause of myocardial infarction and non-obstructive coronary arteries (MINOCA). We aimed at assessing the prognostic value of intracoronary provocative tests in patients presenting with MINOCA and in which other causes of MINOCA have been excluded.
METHODS AND RESULTS: We prospectively evaluated patients with a diagnosis of MINOCA, excluding patients with aetiologies other than suspected coronary vasomotor abnormalities. Immediately after coronary angiography, an invasive provocative test using acetylcholine or ergonovine was performed. The incidence of death from any cause, cardiac death, and recurrence of acute coronary syndrome (ACS) was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires (SAQ). We enrolled 80 consecutive patients [mean age 63.0 ± 10.7 years, 40 (50%) male]. Provocative test was positive in 37 (46.2%) patients without any complication. Among patients with a positive test, epicardial spasm was detected in 24 (64.9%) patients and microvascular spasm in 13 (35.1%) patients. After a median follow-up of 36.0 (range 12.0-60.0) months, patients with a positive test had a significantly higher occurrence of death from any cause [12 (32.4%) vs. 2 (4.7%); P = 0.002], cardiac death [7 (18.9%) vs. 0 (0.0%); P = 0.005], and readmission for ACS [10 (27.0%) vs. 3 (7.0%); P = 0.015] as well as a worse angina status as assessed by SAQ [Seattle score: 88.0 (33.0-100.0) vs. 100.0 (44.0-100.0); P = 0.001] when compared with patients with a negative test.
CONCLUSIONS: We demonstrate that in patients presenting with MINOCA and suspected coronary vasomotor abnormalities, a positive provocative test for spasm is safe and identifies a high-risk subset of patients.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.
Ahmed AlBadri, C Noel Bairey Merz, B Delia Johnson, Janet Wei, Puja K Mehta, Galen Cook-Wiens, Steven E Reis, Sheryl F Kelsey, Vera Bittner, George Sopko, Leslee J Shaw, Carl J Pepine, Bina Ahmed
Impact of Abnormal Coronary Reactivity on Long-Term Clinical Outcomes in Women.
J Am Coll Cardiol. 2019 Feb 19;73(6):684-693. doi: 10.1016/j.jacc.2018.11.040.
Abstract/Text
BACKGROUND: Currently as many as one-half of women with suspected myocardial ischemia have no obstructive coronary artery disease (CAD), and abnormal coronary reactivity (CR) is commonly found.
OBJECTIVES: The authors prospectively investigated CR and longer-term adverse cardiovascular outcomes in women with and with no obstructive CAD in the National Heart, Lung, and Blood Institute-sponsored WISE (Women's Ischemia Syndrome Evaluation) study.
METHODS: Women (n = 224) with signs and symptoms of ischemia underwent CR testing. Coronary flow reserve and coronary blood flow were obtained to test microvascular function, whereas epicardial CR was tested by coronary dilation response to intracoronary (IC) acetylcholine and IC nitroglycerin. All-cause mortality, major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, stroke, and heart failure), and angina hospitalizations served as clinical outcomes over a median follow-up of 9.7 years.
RESULTS: The authors identified 129 events during the follow-up period. Low coronary flow reserve was a predictor of increased MACE rate (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.01 to 1.12; p = 0.021), whereas low coronary blood flow was associated with increased risk of mortality (HR: 1.12; 95% CI: 1.01 to 1.24; p = 0.038) and MACE (HR: 1.11; 95% CI: 1.03 to 1.20; p = 0.006) after adjusting for cardiovascular risk factors. In addition, a decrease in cross-sectional area in response to IC acetylcholine was associated with higher hazard of angina hospitalization (HR: 1.05; 95% CI: 1.02 to 1.07; p < 0.0001). There was no association between epicardial IC-nitroglycerin dilation and outcomes.
CONCLUSIONS: On longer-term follow-up, impaired microvascular function predicts adverse cardiovascular outcomes in women with signs and symptoms of ischemia. Evaluation of CR abnormality can identify those at higher risk of adverse outcomes in the absence of significant CAD. (Women's Ischemia Syndrome Evaluation [WISE]; NCT00000554).
Copyright © 2019 American College of Cardiology Foundation. All rights reserved.
Gaetano Antonio Lanza, Filippo Crea, Juan Carlos Kaski
Clinical outcomes in patients with primary stable microvascular angina: is the jury still out?
Eur Heart J Qual Care Clin Outcomes. 2019 Oct 1;5(4):283-291. doi: 10.1093/ehjqcco/qcz029.
Abstract/Text
Several studies have demonstrated that angina chest pain in presence of normal or near normal coronary arteries (NCAs) is mainly related to coronary microvascular dysfunction (CMD). However, controversial findings exist about clinical outcome of these patients. In this article, we critically review characteristics and results of the main clinical studies reporting clinical outcome of stable patients with angina chest pain and non-obstructive coronary artery disease (NO-CAD). Published data indicate that clinical outcomes of these patients are heterogeneous, but those with strict criteria for primary stable microvascular angina (MVA, i.e. typical angina with NCAs mainly related to efforts) do not appear to have an increased mortality or risk of major coronary events. A major determinant of outcome in patients with MVA and NO-CAD seems instead related to non-critical atherosclerotic disease, the presence of which should suggest a more aggressive management of cardiovascular risk factors and preventive management. Future studies should assess whether CMD may have a relevant prognostic role in the latter clinical context and/or in other clinical settings of NO-CAD different from primary stable MVA.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.
Yusuke Takagi, Jun Takahashi, Satoshi Yasuda, Satoshi Miyata, Ryusuke Tsunoda, Yasuhiro Ogata, Atsushi Seki, Tetsuya Sumiyoshi, Motoyuki Matsui, Toshikazu Goto, Yasuhiko Tanabe, Shozo Sueda, Toshiaki Sato, Satoshi Ogawa, Norifumi Kubo, Shin-Ichi Momomura, Hisao Ogawa, Hiroaki Shimokawa, Japanese Coronary Spasm Association
Prognostic stratification of patients with vasospastic angina: a comprehensive clinical risk score developed by the Japanese Coronary Spasm Association.
J Am Coll Cardiol. 2013 Sep 24;62(13):1144-53. doi: 10.1016/j.jacc.2013.07.018. Epub 2013 Jul 31.
Abstract/Text
OBJECTIVES: The present study aimed to develop a comprehensive clinical risk score for vasospastic angina (VSA) patients.
BACKGROUND: Previous studies demonstrated various prognostic factors of future adverse events in VSA patients. However, to apply these prognostic factors in clinical practice, the assessment of their accumulation in individual patients is important.
METHODS: The patient database of the multicenter registry study by the Japanese Coronary Spasm Association (JCSA) (n = 1,429; median 66 years; median follow-up 32 months) was utilized for score derivation.
RESULTS: Multivariable Cox proportional hazard model selected 7 predictors of major adverse cardiac events (MACE). The integer score was assigned to each predictors proportional to their respective adjusted hazard ratio; history of out-of-hospital cardiac arrest (4 points), smoking, angina at rest alone, organic coronary stenosis, multivessel spasm (2 points each), ST-segment elevation during angina, and beta-blocker use (1 point each). According to the total score in individual patients, 3 risk strata were defined; low (score 0 to 2, n = 598), intermediate (score 3 to 5, n = 639) and high (score 6 or more, n = 192). The incidences of MACE in the low-, intermediate-, and high-risk patients were 2.5%, 7.0%, and 13.0%, respectively (p < 0.001). The Cox model for MACE between the 3 risk strata also showed prognostic utility of the scoring system in various clinical subgroups. The average prediction rate of the scoring system in the internal training and validation sets were 86.6% and 86.5%, respectively.
CONCLUSIONS: We developed a novel scoring system, the JCSA risk score, which may provide the comprehensive risk assessment and prognostic stratification for VSA patients.
Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Hiroaki Shimokawa
2014 Williams Harvey Lecture: importance of coronary vasomotion abnormalities-from bench to bedside.
Eur Heart J. 2014 Dec 1;35(45):3180-93. doi: 10.1093/eurheartj/ehu427. Epub 2014 Oct 29.
Abstract/Text
Coronary vasomotion abnormalities play important roles in the pathogenesis of ischaemic heart disease, in which endothelial dysfunction and coronary artery spasm are substantially involved. Endothelial vasodilator functions are heterogeneous depending on the vessel size, with relatively greater role of nitric oxide (NO) in conduit arteries and predominant role of endothelium-derived hyperpolarizing factor (EDHF) in resistance arteries, where endothelium-derived hydrogen peroxide serves as an important EDHF. The functions of NO synthases in the endothelium are also heterogeneous with multiple mechanisms involved, accounting for the diverse functions of the endothelium in vasomotor as well as metabolic modulations. Cardiovascular abnormalities and metabolic phenotypes become evident when all three NO synthases are deleted, suggesting the importance of both NO and EDHF. Coronary artery spasm plays important roles in the pathogenesis of a wide range of ischaemic heart disease. The central mechanism of the spasm is hypercontraction of vascular smooth muscle cells (VSMCs), but not endothelial dysfunction, where activation of Rho-kinase, a molecular switch of VSMC contraction, plays a major role through inhibition of myosin light-chain phosphatase. The Rho-kinase pathway is also involved in the pathogenesis of a wide range of cardiovascular diseases and new Rho-kinase inhibitors are under development for various indications. The registry study by the Japanese Coronary Spasm Association has demonstrated many important aspects of vasospastic angina. The ongoing international registry study of vasospastic angina in six nations should elucidate the unknown aspects of the disorder. Coronary vasomotion abnormalities appear to be an important therapeutic target in cardiovascular medicine.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.
S E Reis, R Holubkov, A J Conrad Smith, S F Kelsey, B L Sharaf, N Reichek, W J Rogers, C N Merz, G Sopko, C J Pepine, WISE Investigators
Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study.
Am Heart J. 2001 May;141(5):735-41. doi: 10.1067/mhj.2001.114198.
Abstract/Text
BACKGROUND: Chest pain in the absence of obstructive coronary artery disease (CAD) is common in women; it is frequently associated with debilitating symptoms and repeated evaluations and may be caused by coronary microvascular dysfunction. However, the prevalence and determinants of microvascular dysfunction in these women are uncertain.
METHODS: We measured coronary flow velocity reserve (coronary velocity response to intracoronary adenosine) to evaluate the coronary microvasculature and risk factors for atherosclerosis in 159 women (mean age, 52.9 years) with chest pain and no obstructive CAD. All women were referred for coronary angiography to evaluate their chest pain as part of the Women's Ischemia Syndrome Evaluation (WISE) study.
RESULTS: Seventy-four (47%) women had subnormal (<2.5) coronary flow velocity reserve suggestive of microvascular dysfunction (mean, 2.02 +/- 0.38); 85 (53%) had normal reserve (mean, 3.13 +/- 0.64). Demographic characteristics, blood pressure, ventricular function, lipid levels, and reproductive hormone levels were not significantly different between women with normal and those with abnormal microvascular function. Postmenopausal hormone use within 3 months was significantly less prevalent among those with microvascular dysfunction (40% vs 60%, P =.032). Age and number of years past menopause correlated with flow velocity reserve (r = -0.18, P =.02, and r = -0.30, P <.001, respectively). No significant associations were identified between flow velocity reserve and lipid and hormone levels, blood pressure, and left ventricular ejection fraction.
CONCLUSIONS: Coronary microvascular dysfunction is present in approximately one half of women with chest pain in the absence of obstructive CAD and cannot be predicted by risk factors for atherosclerosis and hormone levels. Therefore, the diagnosis of coronary microvascular dysfunction should be considered in women with chest pain not attributable to obstructive CAD.
Jae Kwan Song
Coronary Artery Vasospasm.
Korean Circ J. 2018 Sep;48(9):767-777. doi: 10.4070/kcj.2018.0251.
Abstract/Text
Coronary artery vasospasm (CVS) is an important mechanism of myocardial ischemia and produces any of the manifestations of coronary artery disease from silent myocardial ischemia, to effort-induced angina and variant angina, to acute coronary syndrome including myocardial infarction or sudden cardiac death. The pathogenesis, characteristic clinical features, diagnosis, and treatment of CVS are summarized. Emphasis is placed on correct diagnosis of CVS using pharmacological spasm provocation test, either during coronary angiography or with echocardiographic monitoring of ventricular wall motion. Current underutilization of pharmacologic provocative test at the time of coronary angiography cannot be justified, as there is no evidence supporting that the incidence of CVS is declining. Physicians' vigilance for objective documentation of CVS is necessary for appropriate management of patients with various clinical presentations of ischemic heart disease.
Copyright © 2018. The Korean Society of Cardiology.
Shozo Sueda, Hiroaki Kohno, Hiroshi Fukuda, Naoto Ochi, Hiroyuki Kawada, Yutaka Hayashi, Tadao Uraoka
Frequency of provoked coronary spasms in patients undergoing coronary arteriography using a spasm provocation test via intracoronary administration of ergonovine.
Angiology. 2004 Jul-Aug;55(4):403-11. doi: 10.1177/000331970405500407.
Abstract/Text
There are no data concerning the incidence of provoked coronary arterial spasms via intracoronary administration of ergonovine (ER). This study sought to establish the incidence of spasms due to intracoronary injection of ER in Japanese patients who underwent coronary angiography. The subjects were 596 consecutive patients (369 men, mean age 64.2 +/- 10.3 years) who were studied with a selective ER test. ER was administered in total doses of 40 microg into the right coronary artery and 64 microg into the left coronary artery. A positive spasm was defined as a total or subtotal occlusion. Coronary vasospasms were determined in 173 patients (29.0%). Spasms occurred often in patients with ischemic heart disease (43.3%); during effort and rest in patients with angina (46.3%), exertional angina (27.7%), recent myocardial infarction (36.7%), healed myocardial infarction (34.1%), and especially in patients with rest angina (55.5%), but were relatively uncommon in patients with nonischemic heart disease (3.7%). The incidence of provoked coronary spasms in this study was 2.2-2.6 times higher than in previous reports with intravenous ER administration. More spasms were superimposed on significant atherosclerotic lesions than on nonfixed atherosclerotic lesions (42.8% vs 24.0%, p < 0.01). No serious or irreversible complications were observed in this study. In conclusion, intracoronary administration of ER was a safe and reliable test. Compared with Caucasian patients, in Japanese patients, coronary arterial spasms occurred 2-3 times more frequently with various cardiac disorders.
Eduard Shantsila, Benjamin Wrigley, Alena Shantsila, Luke D Tapp, Andrew D Blann, Paramjit S Gill, Gregory Y H Lip
Ethnic differences in macrovascular and microvascular function in systolic heart failure.
Circ Heart Fail. 2011 Nov;4(6):754-62. doi: 10.1161/CIRCHEARTFAILURE.111.962365. Epub 2011 Sep 13.
Abstract/Text
BACKGROUND: Endothelial dysfunction is implicated in the pathophysiological features of heart failure (HF), and ethnic differences in the presentation of cardiovascular disease are evident, with an excess seen among South Asians (SAs). However, data on ethnic differences in endothelial function in HF are limited.
METHODS AND RESULTS: In a cross-sectional study, we recruited 128 subjects with systolic HF: 50 SAs, 50 whites, and 28 African Caribbeans (ACs). In addition, SAs with systolic HF were compared with 40 SAs with coronary artery disease without HF ("disease controls") and 40 SA healthy controls. Macrovascular endothelial function was assessed by measurement of flow-mediated dilation (FMD) in response to hyperemia, arterial stiffness was assessed by the pulse-wave velocity, and microvascular endothelial function was assessed by forearm laser Doppler flowmetry. CD144-expressing endothelial microparticles were measured by flow cytometry. When compared with disease controls and healthy controls, SAs with HF had an impaired microvascular response to acetylcholine (P=0.001) and reduced FMD (P<0.001). In comparing ethnic groups, SAs with HF had an impaired response to acetylcholine (123±95.5%) compared with whites (258±156%) and ACs (286±173%, P<0.001 for both). Whites had a higher FMD (8.49±4.63%) than SAs (4.76±4.78%, P<0.001) and ACs (4.55±3.56%, P=0.01). No difference in endothelial-independent response was observed between study groups or in pulse-wave velocity. Ethnicity remained associated with microvascular endothelial function even after adjustment for age, presence of hypertension and diabetes mellitus, blood pressure, and glucose levels (P=0.003). There were no differences in numbers of endothelial microparticles.
CONCLUSIONS: The SAs with HF have impaired microvascular and macrovascular endothelial function but preserved arterial elastic properties. Significant ethnic differences in endothelial function are evident in subjects with HF, with ethnicity being associated with microvascular endothelial dysfunction in this disorder.
Divaka Perera, Colin Berry, Stephen P Hoole, Aish Sinha, Haseeb Rahman, Paul D Morris, Rajesh K Kharbanda, Ricardo Petraco, Keith Channon, UK Coronary Microvascular Dysfunction Working Group
Invasive coronary physiology in patients with angina and non-obstructive coronary artery disease: a consensus document from the coronary microvascular dysfunction workstream of the British Heart Foundation/National Institute for Health Research Partnership.
Heart. 2022 Dec 22;109(2):88-95. doi: 10.1136/heartjnl-2021-320718. Epub 2022 Dec 22.
Abstract/Text
Nearly half of all patients with angina have non-obstructive coronary artery disease (ANOCA); this is an umbrella term comprising heterogeneous vascular disorders, each with disparate pathophysiology and prognosis. Approximately two-thirds of patients with ANOCA have coronary microvascular disease (CMD). CMD can be secondary to architectural changes within the microcirculation or secondary to vasomotor dysfunction. An inability of the coronary vasculature to augment blood flow in response to heightened myocardial demand is defined as an impaired coronary flow reserve (CFR), which can be measured non-invasively, using imaging, or invasively during cardiac catheterisation. Impaired CFR is associated with myocardial ischaemia and adverse cardiovascular outcomes.The CMD workstream is part of the cardiovascular partnership between the British Heart Foundation and The National Institute for Health Research in the UK and comprises specialist cardiac centres with expertise in coronary physiology assessment. This document outlines the two main modalities (thermodilution and Doppler techniques) for estimation of coronary flow, vasomotor testing using acetylcholine, and outlines a standard operating procedure that could be considered for adoption by national networks. Accurate and timely disease characterisation of patients with ANOCA will enable clinicians to tailor therapy according to their patients' coronary physiology. This has been shown to improve patients' quality of life and may lead to improved cardiovascular outcomes in the long term.
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.
Jacqueline E Tamis-Holland, Hani Jneid, Harmony R Reynolds, Stefan Agewall, Emmanouil S Brilakis, Todd M Brown, Amir Lerman, Mary Cushman, Dharam J Kumbhani, Cynthia Arslanian-Engoren, Ann F Bolger, John F Beltrame, American Heart Association Interventional Cardiovascular Care Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; and Council on Quality of Care and Outcomes Research
Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association.
Circulation. 2019 Apr 30;139(18):e891-e908. doi: 10.1161/CIR.0000000000000670.
Abstract/Text
Myocardial infarction in the absence of obstructive coronary artery disease is found in ≈5% to 6% of all patients with acute infarction who are referred for coronary angiography. There are a variety of causes that can result in this clinical condition. As such, it is important that patients are appropriately diagnosed and an evaluation to uncover the correct cause is performed so that, when possible, specific therapies to treat the underlying cause can be prescribed. This statement provides a formal and updated definition for the broadly labelled term MINOCA (incorporating the definition of acute myocardial infarction from the newly released "Fourth Universal Definition of Myocardial Infarction") and provides a clinically useful framework and algorithms for the diagnostic evaluation and management of patients with myocardial infarction in the absence of obstructive coronary artery disease.
Niya Mileva, Sakura Nagumo, Takuya Mizukami, Jeroen Sonck, Colin Berry, Emanuele Gallinoro, Giovanni Monizzi, Alessandro Candreva, Daniel Munhoz, Dobrin Vassilev, Martin Penicka, Emanuele Barbato, Bernard De Bruyne, Carlos Collet
Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients With Nonobstructive Coronary Artery Disease: Systematic Review and Meta-Analysis.
J Am Heart Assoc. 2022 Apr 5;11(7):e023207. doi: 10.1161/JAHA.121.023207. Epub 2022 Mar 18.
Abstract/Text
Background A relevant proportion of patients with suspected coronary artery disease undergo invasive coronary angiography showing normal or nonobstructive coronary arteries. However, the prevalence of coronary microvascular disease (CMD) and coronary spasm in patients with nonobstructive coronary artery disease remains to be determined. The objective of this study was to determine the prevalence of coronary CMD and coronary vasospastic angina in patients with no obstructive coronary artery disease. Methods and Results A systematic review and meta-analysis of studies assessing the prevalence of CMD and vasospastic angina in patients with no obstructive coronary artery disease was performed. Random-effects models were used to determine the prevalence of these 2 disease entities. Fifty-six studies comprising 14 427 patients were included. The pooled prevalence of CMD was 0.41 (95% CI, 0.36-0.47), epicardial vasospasm 0.40 (95% CI, 0.34-0.46) and microvascular spasm 24% (95% CI, 0.21-0.28). The prevalence of combined CMD and vasospastic angina was 0.23 (95% CI, 0.17-0.31). Female patients had a higher risk of presenting with CMD compared with male patients (risk ratio, 1.45 [95% CI, 1.11-1.90]). CMD prevalence was similar when assessed using noninvasive or invasive diagnostic methods. Conclusions In patients with no obstructive coronary artery disease, approximately half of the cases were reported to have CMD and/or coronary spasm. CMD was more prevalent among female patients. Greater awareness among physicians of ischemia with no obstructive coronary arteries is urgently needed for accurate diagnosis and patient-tailored management.
Kazuya Otsu, Kazuko Tajiri, Shunsuke Sakai, Masaki Ieda
Vasospastic angina following immune checkpoint blockade.
Eur Heart J. 2020 May 1;41(17):1702. doi: 10.1093/eurheartj/ehz796.
Abstract/Text
Thomas J Ford, Bethany Stanley, Richard Good, Paul Rocchiccioli, Margaret McEntegart, Stuart Watkins, Hany Eteiba, Aadil Shaukat, Mitchell Lindsay, Keith Robertson, Stuart Hood, Ross McGeoch, Robert McDade, Eric Yii, Novalia Sidik, Peter McCartney, David Corcoran, Damien Collison, Christopher Rush, Alex McConnachie, Rhian M Touyz, Keith G Oldroyd, Colin Berry
Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial.
J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2841-2855. doi: 10.1016/j.jacc.2018.09.006. Epub 2018 Sep 25.
Abstract/Text
BACKGROUND: Patients with angina symptoms and/or signs of ischemia but no obstructive coronary artery disease (INOCA) pose a diagnostic and therapeutic challenge.
OBJECTIVES: The purpose of this study was to test whether an interventional diagnostic procedure (IDP) linked to stratified medicine improves health status in patients with INOCA.
METHODS: The authors conducted a randomized, controlled, blinded clinical trial of stratified medical therapy versus standard care in patients with angina. Patients with angina undergoing invasive coronary angiography (standard care) were recruited. Patients without obstructive CAD were immediately randomized 1:1 to the intervention group (stratified medical therapy) or the control group (standard care, IDP sham procedure). The IDP consisted of guidewire-based assessment of coronary flow reserve, index of microcirculatory resistance, fractional flow reserve, followed by vasoreactivity testing with acetylcholine. The primary endpoint was the mean difference in angina severity at 6 months (assessed by the Seattle Angina Questionnaire summary score).
RESULTS: A total of 391 patients were enrolled between November 25, 2016, and November 12, 2017. Coronary angiography revealed obstructive disease in 206 (53.7%). One hundred fifty-one (39%) patients without angiographically obstructive CAD were randomized (n = 76 intervention group; n = 75 blinded control group). The intervention resulted in a mean improvement of 11.7 U in the Seattle Angina Questionnaire summary score at 6 months (95% confidence interval [CI]: 5.0 to 18.4; p = 0.001). In addition, the intervention led to improvements in the mean quality-of-life score (EQ-5D index 0.10 U; 95% CI: 0.01 to 0.18; p = 0.024) and visual analogue score (14.5 U; 95% CI: 7.8 to 21.3; p < 0.001). There were no differences in major adverse cardiac events at the 6-month follow-up (2.6% controls vs. 2.6% intervention; p = 1.00).
CONCLUSIONS: Coronary angiography often fails to identify patients with vasospastic and/or microvascular angina. Stratified medical therapy, including an IDP with linked medical therapy, is routinely feasible and improves angina in patients with no obstructive CAD. (CORonary MICrovascular Angina [CorMicA]; NCT03193294).
Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Thomas J Ford, Bethany Stanley, Novalia Sidik, Richard Good, Paul Rocchiccioli, Margaret McEntegart, Stuart Watkins, Hany Eteiba, Aadil Shaukat, Mitchell Lindsay, Keith Robertson, Stuart Hood, Ross McGeoch, Robert McDade, Eric Yii, Peter McCartney, David Corcoran, Damien Collison, Christopher Rush, Naveed Sattar, Alex McConnachie, Rhian M Touyz, Keith G Oldroyd, Colin Berry
1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA).
JACC Cardiovasc Interv. 2020 Jan 13;13(1):33-45. doi: 10.1016/j.jcin.2019.11.001. Epub 2019 Nov 11.
Abstract/Text
OBJECTIVES: The aim of this study was to test the hypothesis that invasive coronary function testing at time of angiography could help stratify management of angina patients without obstructive coronary artery disease.
BACKGROUND: Medical therapy for angina guided by invasive coronary vascular function testing holds promise, but the longer-term effects on quality of life and clinical events are unknown among patients without obstructive disease.
METHODS: A total of 151 patients with angina with symptoms and/or signs of ischemia and no obstructive coronary artery disease were randomized to stratified medical therapy guided by an interventional diagnostic procedure versus standard care (control group with blinded interventional diagnostic procedure results). The interventional diagnostic procedure-facilitated diagnosis (microvascular angina, vasospastic angina, both, or neither) was linked to guideline-based management. Pre-specified endpoints included 1-year patient-reported outcome measures (Seattle Angina Questionnaire, quality of life [EQ-5D]) and major adverse cardiac events (all-cause mortality, myocardial infarction, unstable angina hospitalization or revascularization, heart failure hospitalization, and cerebrovascular event) at subsequent follow-up.
RESULTS: Between November 2016 and December 2017, 151 patients with ischemia and no obstructive coronary artery disease were randomized (n = 75 to the intervention group, n = 76 to the control group). At 1 year, overall angina (Seattle Angina Questionnaire summary score) improved in the intervention group by 27% (difference 13.6 units; 95% confidence interval: 7.3 to 19.9; p < 0.001). Quality of life (EQ-5D index) improved in the intervention group relative to the control group (mean difference 0.11 units [18%]; 95% confidence interval: 0.03 to 0.19; p = 0.010). After a median follow-up duration of 19 months (interquartile range: 16 to 22 months), major adverse cardiac events were similar between the groups, occurring in 9 subjects (12%) in the intervention group and 8 (11%) in the control group (p = 0.803).
CONCLUSIONS: Stratified medical therapy in patients with ischemia and no obstructive coronary artery disease leads to marked and sustained angina improvement and better quality of life at 1 year following invasive coronary angiography. (Coronary Microvascular Angina [CorMicA]; NCT03193294).
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Yuji Mizuno, Eisaku Harada, Sumio Morita, Kenji Kinoshita, Mariko Hayashida, Makoto Shono, Yoshinobu Morikawa, Toyoaki Murohara, Masafumi Nakayama, Michihiro Yoshimura, Hirofumi Yasue
East asian variant of aldehyde dehydrogenase 2 is associated with coronary spastic angina: possible roles of reactive aldehydes and implications of alcohol flushing syndrome.
Circulation. 2015 May 12;131(19):1665-73. doi: 10.1161/CIRCULATIONAHA.114.013120. Epub 2015 Mar 10.
Abstract/Text
BACKGROUND: Coronary spastic angina (CSA) is a common disease among East Asians, including Japanese. The prevalence of alcohol flushing syndrome associated with deficient activity of the variant aldehyde dehydrogenase 2 (ALDH2*2) genotype is prevalent among East Asians. We examined whether CSA is associated with the ALDH2*2 genotype in Japanese.
METHODS AND RESULTS: The study subjects consisted of 202 patients in whom intracoronary injection of acetylcholine was performed by angiography on suspicion of CSA (119 men and 83 women; mean age, 66.2±11.4 years). They were divided into CSA (112 patients) and control groups (90 patients). ALDH2 genotyping was performed by the direct application of the TaqMan polymerase chain reaction system on dried whole blood. Clinical and laboratory data were examined using conventional methods. The frequencies of male sex, ALDH2*2 genotype carriers, alcohol flushing syndrome, tobacco smoking, and the plasma level of uric acid were higher (P<0.001, P<0.001, P<0.001, P<0.001, and P=0.007, respectively) and the plasma high-density lipoprotein cholesterol levels were lower (P<0.001) in the CSA group than in the control group. The multivariable logistic regression analysis revealed that ALDH2*2 genotype and smoking were significantly associated with CSA (P<0.001 and P=0.024, respectively).
CONCLUSIONS: East Asian variant ALDH2*2 genotypes and, hence, deficient ALDH2 activity were associated with CSA in Japanese. These data support further investigation of treatment targeting aldehydes for CSA.
© 2015 American Heart Association, Inc.
Yuji Mizuno, Seiji Hokimoto, Eisaku Harada, Kenji Kinoshita, Kazuko Nakagawa, Michihiro Yoshimura, Hisao Ogawa, Hirofumi Yasue
Variant Aldehyde Dehydrogenase 2 (ALDH2*2) Is a Risk Factor for Coronary Spasm and ST-Segment Elevation Myocardial Infarction.
J Am Heart Assoc. 2016 May 6;5(5). doi: 10.1161/JAHA.116.003247. Epub 2016 May 6.
Abstract/Text
BACKGROUND: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) plays a key role in removing toxic aldehydes. Deficient variant ALDH2*2 genotype is prevalent in up to 40% of the East Asians and reported to be associated with acute myocardial infarction (AMI). To elucidate the mechanisms underlying the association of ALDH2*2 with AMI, we compared the clinical features of AMI patients with ALDH2*2 to those with wild-type ALDH2*1/*1.
METHODS AND RESULTS: The study subjects consisted of 202 Japanese patients with acute ST-segment elevation myocardial infarction (STEMI) (156 men and 46 women; mean age, 67.3±12.0) who underwent primary percutaneous coronary intervention (PCI). In 85 patients, provocation test for coronary spasm was also done 6 month post-PCI. ALDH2 genotyping was performed by direct application of the TaqMan polymerase chain system. Of the 202 patients, 103 (51.0%) were carriers of ALDH2*2 and 99 (49.0%) those of ALDH2*1/*1. There were no differences in clinical features between ALDH2*2 and ALDH2*1/*1 carrier groups except higher frequencies of coronary spasm and alcohol flush syndrome (AFS) (88.6% vs 56.1%; P=0.001 and 94.3% vs 17.6%; P<0.001), less-frequent alcohol habit (14.6% vs 51.5%; P<0.001), and higher peak plasma creatine phophokinase levels (2224 vs 1617 mg/dL; P=0.002) in the ALDH2*2 than the ALDH2*1/*1 carrier group.
CONCLUSIONS: ALDH2*2 is prevalent (51.0%) among Japanese STEMI patients, and those with ALDH2*2 had higher frequencies of coronary spasm and AFS and more-severe myocardial injury compared to those with ALDH2*1/*1.
© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Yoku Kikuchi, Jun Takahashi, Kiyotaka Hao, Koichi Sato, Jun Sugisawa, Satoshi Tsuchiya, Akira Suda, Tomohiko Shindo, Shohei Ikeda, Takashi Shiroto, Yasuharu Matsumoto, Satoshi Miyata, Yasuhiko Sakata, Hiroaki Shimokawa
Usefulness of intracoronary administration of fasudil, a selective Rho-kinase inhibitor, for PCI-related refractory myocardial ischemia.
Int J Cardiol. 2019 Dec 15;297:8-13. doi: 10.1016/j.ijcard.2019.09.057. Epub 2019 Oct 8.
Abstract/Text
BACKGROUND: Intra-procedural myocardial ischemia as an iatrogenic complication still remains a critical issue in contemporary interventional cardiology. The aim of this study was to examine the usefulness of fasudil, a selective Rho-kinase inhibitor, for percutaneous coronary intervention (PCI)-related myocardial ischemia.
METHODS: Among 448 PCI sessions performed between October 2015 and December 2017, we retrospectively examined 36 patients (69.0 ± 9.1 [SD] yrs., M/F 26/10) who underwent intracoronary administration of fasudil during a procedure to resolve myocardial ischemia that was resistant to intracoronary nitrate administration.
RESULTS: The refractory myocardial ischemia was caused by distal embolization (69%), enhanced vasoconstriction at distal site of chronic total occlusion (11%), coronary spasm (11%), and coronary dissection (8%), most of which occurred immediately after balloon or stent dilatation. Intracoronary fasudil significantly improved corrected TIMI frame count (from 37 [30-56] to 24 [12-36]) and TIMI flow grade (from 2 [1-2.5] to 3 [2-3]) (both P < 0.001). Finally, 86% of all subjects successfully obtained TIMI flow grade 3 at the end of the procedure. Intracoronary fasudil tended to be more effective in patients with an attenuated plaque detected by intravascular ultrasound. Importantly, among the 19 elective cases, fasudil successfully prevented 17 patients from developing post-procedure myocardial infarction. Although fasudil-induced transient hypotension requiring a vasopressor was noted in 22% of the subjects, no other adverse effects were noted.
CONCLUSIONS: These results indicate that fasudil is a useful and safe therapeutic option for PCI-related myocardial ischemia refractory intracoronary nitrate.
Copyright © 2019 Elsevier B.V. All rights reserved.
