|
1
|
Namba HF, Boerhout CKM, Damman P, Kunadian V, Escaned J, Ong P, Perera D, Berry C, van de Hoef TP, Piek JJ. Invasive coronary function testing in clinical practice: Implementing the 2024 ESC guidelines on chronic coronary syndromes. Int J Cardiol 2025; 430:133176. [PMID: 40122215 DOI: 10.1016/j.ijcard.2025.133176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 02/11/2025] [Accepted: 03/17/2025] [Indexed: 03/25/2025]
Abstract
Angina with non-obstructive coronary arteries (ANOCA) is increasingly recognized as a significant aspect of chronic coronary syndromes. These patients frequently experience recurrent angina, resulting in high healthcare costs and impaired quality of life. Invasive coronary function testing (ICFT) is able to identify ANOCA endotypes, which can guide treatment and improve quality of life. Despite Class II recommendations for invasive microvascular assessments in the previous 2019 European Society of Cardiology (ESC) Guidelines, ICFT has yet to translate into widespread clinical practice. Patients with ANOCA experience poor quality of life and reduced functional capacity, highlighting the need for earlier ICFT implementation. The 2024 ESC Guidelines now strongly recommend ICFT (Class I, level of evidence B) for patients with non-obstructive coronary arteries and persistent angina despite optimal medical therapy, and for confirming or excluding ANOCA in patients with uncertain diagnoses on non-invasive testing (Class I, level of evidence B). Consequently, a standardized approach to optimize the management of ANOCA patients is warranted. Therefore, this review aims to provide interventional cardiologists with a contemporary review of the literature and a practical guideline on implementation of ICFT. It will discuss the following subjects: the definitions of the different endotypes, an example of an ICFT protocol, discontinuation of medication prior to ICFT, use of radial cocktail, target vessel for testing, acetylcholine injection techniques and rechallenge, adenosine injection techniques, the order of testing, the interpretation of ICFT, safety and feasibility, and the pharmacological treatment.
Collapse
Affiliation(s)
- Hanae F Namba
- Department of Cardiology, Amsterdam UMC, Amsterdam, the Netherlands.
| | | | - Peter Damman
- Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Vijay Kunadian
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
| | - Javier Escaned
- Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos and Complutense University of Madrid, Madrid, Spain
| | - Peter Ong
- Robert-Bosch-Krankenhaus, Department of Cardiology and Angiology, Stuttgart, Germany
| | - Divaka Perera
- School of Cardiovascular Medicine and Sciences, St Thomas' Hospital Campus, King's College London, London, United Kingdom
| | - Colin Berry
- School Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom; NHS Golden Jubilee National Hospital, Glasgow, United Kingdom
| | | | - Jan J Piek
- Department of Cardiology, Amsterdam UMC, Amsterdam, the Netherlands
| |
Collapse
|
|
2
|
Burgess S, Cader FA, Gulati M, Sutton NR, Appelman Y, Banerjee S. Challenges in diagnosing coronary microvascular dysfunction and coronary vasospasm. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2025:S1553-8389(25)00176-9. [PMID: 40312200 DOI: 10.1016/j.carrev.2025.04.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 04/12/2025] [Accepted: 04/15/2025] [Indexed: 05/03/2025]
Abstract
Chronic coronary syndromes (CCS) include 2 overlapping subgroups of patients - those with angina with nonobstructive coronary arteries (ANOCA), or ischaemia with non-obstructive coronary arteries (INOCA). A diagnosis of ANOCA-INOCA, is common and should be considered where angina is present and/or ischaemia is found on functional imaging in the absence of obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CCTA) or invasive coronary angiography (ICA) (Ford and Berry, 2019). This review aims to provide an overview of contemporary challenges in the diagnosis of coronary microvascular dysfunction (CMD) and vasospastic disease, with a focus on recent guideline changes and current controversies. CMD and vasospastic angina (VSA) are increasingly acknowledged as an important and frequently overlooked, under investigated, and undertreated entities that contribute to ANOCA-INOCA (Samuels et al., 2023; Kunadian et al., 2020; Ford and Berry, 2019; Burgess and Mamas, 2024).
Collapse
Affiliation(s)
- Sonya Burgess
- Department of Cardiology, Nepean Hospital, Sydney, Australia; University of Sydney, NSW, Australia
| | - F Aaysha Cader
- Department of Cardiology, Kettering General Hospital, United Kingdom
| | - Martha Gulati
- Barbra Streisand Women's Heart Center Smidt Heart Institute, Cedars-Sinai Medical Center Los Angeles CA, USA; The Baim Institute for Clinical Research, Boston, MA, USA
| | - Nadia R Sutton
- Department of Internal Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA
| | - Yolande Appelman
- Department of Cardiology, Amsterdam UMC Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Shrilla Banerjee
- Department of Cardiology, Surrey and Sussex Healthcare, United Kingdom
| |
Collapse
|
|
3
|
Sueda S, Hayashi Y. Importance of provoked spasms at the sites of nonobstructive stenosis as well as at the sites of obstructive stenosis in patients with obstructive coronary arteries and coronary spasm. Coron Artery Dis 2024; 35:650-658. [PMID: 38829306 DOI: 10.1097/mca.0000000000001398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
OBJECTIVES There are few reports regarding the prognosis in patients with obstructive coronary artery disease (OCAD) and vasospastic angina (VSA). This study investigated the clinical characteristics and clinical outcomes in patients with VSA and OCAD, especially regarding provoked spasm phenotypes and sites. METHODS This was a retrospective, observational, single-center study of 403 patients with typical or atypical angina-like chest pain undergoing acetylcholine (ACH) spasm provocation testing and OCAD. An obstructed coronary artery was defined as ≥50% luminal narrowing. We defined positive epicardial spasm as ≥90% transient stenosis and usual chest symptoms or ischemic ECG changes. RESULTS Among these 403 patients with OCAD, positive spasm by intracoronary ACH testing was observed in 196 patients (49%), whereas negative spasm was found in the remaining 207 patients (51%). The clinical outcomes in the patients with OCAD and provoked spasm were not different according to the provoked-spasm phenotypes. Furthermore, the clinical outcomes were unsatisfactory in the patients with spasm at the site of nonobstructive lesion alone compared with those with spasm at the site of obstructive and nonobstructive lesions. CONCLUSION We should precisely diagnose patients with OCAD who have provoked spasm by using intracoronary ACH testing and medicate the nonobstructive vessels in patients with OCAD and VSA under optimal coronary vasodilators.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Minami Matsuyama Hospital, Matsuyma, Japan
| | | |
Collapse
|
|
4
|
Sueda S, Hayashi Y, Ono H, Sakaue T, Ikeda S. Safety and Usefulness of Intracoronary Acetylcholine 200 μg Into the Left Coronary Artery as Vasoreactivity Testing: Comparisons With Intracoronary Acetylcholine Maximum 100 μg. Clin Cardiol 2024; 47:e70001. [PMID: 39355891 PMCID: PMC11445603 DOI: 10.1002/clc.70001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 07/27/2024] [Accepted: 08/05/2024] [Indexed: 10/03/2024] Open
Abstract
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.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Minami Matsuyama Hospital, Matsuyama, Japan
| | - Yutaka Hayashi
- Department of Cardiology, Minami Matsuyama Hospital, Matsuyama, Japan
| | - Hiroki Ono
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Niihama, Japan
| | - Tomoki Sakaue
- Department of Cardiology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Shuntaro Ikeda
- Department of Cardiology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| |
Collapse
|
|
5
|
Sueda S, Sakaue T. The Need for Separate Testing with Acetylcholine for the Assessment of Endothelial Dysfunction and Coronary Artery Spasm. Eur Cardiol 2024; 19:e17. [PMID: 39449721 PMCID: PMC11499973 DOI: 10.15420/ecr.2022.16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 05/04/2022] [Indexed: 10/26/2024] Open
Abstract
Intracoronary acetylcholine (ACH) testing is clinically useful to diagnose the presence of the coronary vasomotor disorders coronary endothelial dysfunction and coronary epicardial/microvascular spasm. In Western countries, continuous intracoronary injection of ACH for 2-3 minutes without a pacemaker is the usual method, while rapid injection of ACH for 20-30 seconds with a pacemaker is the traditional procedure in Japan. Coronary microvascular spasm is often observed in Western populations, whereas coronary epicardial spasm is frequently seen in Japanese subjects. Methodological differences between Western and Japanese protocols may lead to the opposite prevalence of coronary vasomotor disorders. This article discusses the optimal method for diagnosing endothelial dysfunction and epicardial/microvascular spasm based on previous reports, and compares intracoronary ACH testing performed by Western cardiologists with that by Japanese physicians.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Ehime Niihama Prefectural HospitalNiihama, Japan
| | - Tomoki Sakaue
- Department of Cardiology, Yawatahama City General HospitalYawatahama, Japan
| |
Collapse
|
|
6
|
Denby KJ, Zmaili M, Datta S, Das T, Ellis S, Ziada K, Lerman A, Raphael CE. Developments and Controversies in Invasive Diagnosis of Coronary Microvascular Dysfunction in Angina With Nonobstructive Coronary Arteries. Mayo Clin Proc 2024; 99:1469-1481. [PMID: 39232622 DOI: 10.1016/j.mayocp.2024.04.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 03/18/2024] [Accepted: 04/23/2024] [Indexed: 09/06/2024]
Abstract
Approximately half of all coronary angiograms performed for angina do not show obstructive coronary artery disease, and many of these patients have coronary microvascular dysfunction (CMD). Invasive testing for CMD has increased with the advent and wider availability of thermodilution systems. We review CMD pathophysiology and invasive diagnostic testing using the Doppler and thermodilution systems. We report the results of a PubMed search of invasive microvascular testing and discuss limitations of current diagnostic algorithms in the diagnosis of CMD, including controversies regarding the optimal cutoff value for abnormal coronary flow reserve, use of microvascular resistance indices, and options for increasing sensitivity of testing.
Collapse
Affiliation(s)
- Kara J Denby
- Department of Cardiovascular Medicine, Saint Alphonsus Regional Medical Center, Boise, ID
| | - Mohammad Zmaili
- Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Sudarshana Datta
- Memorial Hermann Heart & Vascular Institute, Texas Medical Center, Houston
| | - Thomas Das
- Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Stephen Ellis
- Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Khaled Ziada
- Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Amir Lerman
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Claire E Raphael
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.
| |
Collapse
|
|
7
|
Sueda S, Hayashi Y, Ono H, Okabe H, Sakaue T, Ikeda S. Lack of Class I Vasoreactivity Testing for Diagnosing Patients With Coronary Artery Spasm. Clin Cardiol 2024; 47:e70004. [PMID: 39192815 PMCID: PMC11350217 DOI: 10.1002/clc.70004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 07/30/2024] [Indexed: 08/29/2024] Open
Abstract
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.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of CardiologyMinami Matsuyama HospitalMatsuyma CityEhimeJapan
| | - Yutaka Hayashi
- Department of CardiologyMinami Matsuyama HospitalMatsuyma CityEhimeJapan
| | - Hiroki Ono
- Department of CardiologyEhime Prefectural Niihama HospitalNiihamaEhimeJapan
| | - Hikaru Okabe
- Department of CardiologyEhime Prefectural Niihama HospitalNiihamaEhimeJapan
| | - Tomoki Sakaue
- Department of CardiologyEhime University Graduate School of MedicineTouon‐shiEhimeJapan
| | - Shuntaro Ikeda
- Department of CardiologyEhime University Graduate School of MedicineTouon‐shiEhimeJapan
| |
Collapse
|
|
8
|
Okuya Y, Saito Y, Kitahara H, Kobayashi Y. Relation of Vasoreactivity in the Left and Right Coronary Arteries During Acetylcholine Spasm Provocation Testing. Am J Cardiol 2024; 219:71-76. [PMID: 38522651 DOI: 10.1016/j.amjcard.2024.03.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 02/10/2024] [Accepted: 03/11/2024] [Indexed: 03/26/2024]
Abstract
The diagnosis of vasospastic angina (VSA) according to Japanese guidelines involves an initial intracoronary acetylcholine (ACh) provocation test in the left coronary artery (LCA) followed by testing in the right coronary artery (RCA). However, global variations in test protocols often lead to the omission of ACh provocation in the RCA, potentially resulting in the underdiagnosis of VSA. This study assessed the validity of the LCA-only ACh provocation approach for the VSA diagnosis and whether vasoreactivity in the LCA aids in determining further provocation in the RCA. A total of 273 patients who underwent sequential intracoronary ACh provocation testing in the LCA and RCA were included. Patients with a positive ACh provocation test in the LCA were excluded. Relations between vasoreactivity in the LCA and ACh test outcomes (positivity and adverse events) in the RCA were evaluated. In patients with negative ACh test results in the LCA, subsequent ACh testing was positive in the RCA in 23 of 273 (8.4%) patients. In patients with minimal LCA vasoconstriction (<25%), only 3.0% had a positive ACh test in the RCA, whereas the ACh test in the RCA was positive in 13.5% of those with LCA constriction of 25% to 90% (p = 0.002). No major adverse events occurred during ACh testing in the RCA. In conclusion, for the VSA diagnosis, the omission of ACh provocation in the RCA may be clinically acceptable, particularly when vasoconstriction induced by ACh injection was minimal in the LCA. Further studies are needed to define ACh provocation protocols worldwide.
Collapse
Affiliation(s)
- Yoshiyuki Okuya
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Yuichi Saito
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
| | - Hideki Kitahara
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Yoshio Kobayashi
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| |
Collapse
|
|
9
|
Woudstra J, Feenstra RGT, Vink CEM, Marques KMJ, Boerhout CKM, de Jong EAM, de Waard GA, van de Hoef TP, Chamuleau SAJ, Eringa EC, Piek JJ, Appelman Y, Beijk MAM. Comparison of the Diagnostic Yield of Intracoronary Acetylcholine Infusion and Acetylcholine Bolus Injection Protocols During Invasive Coronary Function Testing. Am J Cardiol 2024; 217:49-58. [PMID: 38417650 DOI: 10.1016/j.amjcard.2024.01.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 01/09/2024] [Accepted: 01/19/2024] [Indexed: 03/01/2024]
Abstract
Coronary endothelial dysfunction (CED) and coronary artery spasm (CAS) are causes of angina with no obstructive coronary arteries in patients. Both can be diagnosed by invasive coronary function testing (ICFT) using acetylcholine (ACh). This study aimed to evaluate the diagnostic yield of a 3-minute ACh infusion as compared with a 1-minute ACh bolus injection protocol in testing CED and CAS. We evaluated 220 consecutive patients with angina and no obstructive coronary arteries who underwent ICFT using continuous Doppler flow measurements. Per protocol, 110 patients were tested using 3-minute infusion, and thereafter 110 patients using 1-minute bolus injections, because of a protocol change. CED was defined as a <50% increase in coronary blood flow or any epicardial vasoconstriction in reaction to low-dose ACh and CAS according to the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria, both with and without T-wave abnormalities, in reaction to high dose ACh. The prevalence of CED was equal in both protocols (78% vs 79%, p = 0.869). Regarding the endotypes of CAS according to COVADIS, the equivocal endotype was diagnosed less often in the 3 vs 1-minute protocol (24% vs 44%, p = 0.004). Including T-wave abnormalities in the COVADIS criteria resulted in a similar diagnostic yield of both protocols. Hemodynamic changes from baseline to the low or high ACh doses were comparable between the protocols for each endotype. In conclusion, ICFT using 3-minute infusion or 1-minute bolus injections of ACh showed a similar diagnostic yield of CED. When using the COVADIS criteria, a difference in the equivocal diagnosis was observed. Including T-wave abnormalities as a diagnostic criterion reclassified equivocal test results into CAS and decreased this difference. For clinical practice, we recommend the inclusion of T-wave abnormalities as a diagnostic criterion for CAS and the 1-minute bolus protocol for practicality.
Collapse
Affiliation(s)
- Janneke Woudstra
- Department of Cardiology, Amsterdam UMC Heart Centre, Amsterdam, The Netherlands.
| | - Rutger G T Feenstra
- Department of Cardiology, Amsterdam UMC Heart Centre, Amsterdam, The Netherlands
| | - Caitlin E M Vink
- Department of Cardiology, Amsterdam UMC Heart Centre, Amsterdam, The Netherlands
| | - Koen M J Marques
- Department of Cardiology, Amsterdam UMC Heart Centre, Amsterdam, The Netherlands
| | - Coen K M Boerhout
- Department of Cardiology, Amsterdam UMC Heart Centre, Amsterdam, The Netherlands
| | - Elize A M de Jong
- Department of Cardiology, Amsterdam UMC Heart Centre, Amsterdam, The Netherlands; Department of Cardiology, University Medical Center Utrecht, The Netherlands
| | - Guus A de Waard
- Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Tim P van de Hoef
- Department of Cardiology, University Medical Center Utrecht, The Netherlands
| | - Steven A J Chamuleau
- Department of Cardiology, Amsterdam UMC Heart Centre, Amsterdam, The Netherlands
| | - Etto C Eringa
- Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Amsterdam, The Netherlands; Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - Jan J Piek
- Department of Cardiology, Amsterdam UMC Heart Centre, Amsterdam, The Netherlands
| | - Yolande Appelman
- Department of Cardiology, Amsterdam UMC Heart Centre, Amsterdam, The Netherlands
| | - Marcel A M Beijk
- Department of Cardiology, Amsterdam UMC Heart Centre, Amsterdam, The Netherlands
| |
Collapse
|
|
10
|
Gurgoglione FL, Vignali L, Montone RA, Rinaldi R, Benatti G, Solinas E, Leone AM, Galante D, Campo G, Biscaglia S, Porto I, Benenati S, Niccoli G. Coronary Spasm Testing with Acetylcholine: A Powerful Tool for a Personalized Therapy of Coronary Vasomotor Disorders. Life (Basel) 2024; 14:292. [PMID: 38541619 PMCID: PMC10970947 DOI: 10.3390/life14030292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 02/18/2024] [Accepted: 02/19/2024] [Indexed: 11/11/2024] Open
Abstract
Coronary vasomotor disorders (CVD) are characterized by transient hypercontraction of coronary vascular smooth muscle cells, leading to hypercontraction of epicardial and/or microvascular coronary circulation. CVDs play a relevant role in the pathogenesis of ischemia, angina and myocardial infarction with non-obstructive coronary arteries. Invasive provocative testing with intracoronary Acetylcholine (ACh) administration is the gold standard tool for addressing CVD, providing relevant therapeutic and prognostic implications. However, safety concerns preclude the widespread incorporation of the ACh test into clinical practice. The purpose of this review is to shed light on the pathophysiology underlying CVD and on the clinical role of the ACh test, focusing on safety profile and prognostic implications. We will also discuss contemporary evidence on the management of CVD and the role of the ACh test in driving a personalized approach of patients with CVD.
Collapse
Affiliation(s)
| | - Luigi Vignali
- Division of Cardiology, Parma University Hospital, 43126 Parma, Italy; (L.V.); (G.B.); (E.S.)
| | - Rocco Antonio Montone
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy;
| | - Riccardo Rinaldi
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy;
| | - Giorgio Benatti
- Division of Cardiology, Parma University Hospital, 43126 Parma, Italy; (L.V.); (G.B.); (E.S.)
| | - Emilia Solinas
- Division of Cardiology, Parma University Hospital, 43126 Parma, Italy; (L.V.); (G.B.); (E.S.)
| | - Antonio Maria Leone
- Center of Excellence in Cardiovascular Sciences, Ospedale Isola Tiberina, Gemelli Isola Roma, 00186 Rome, Italy; (A.M.L.); (D.G.)
| | - Domenico Galante
- Center of Excellence in Cardiovascular Sciences, Ospedale Isola Tiberina, Gemelli Isola Roma, 00186 Rome, Italy; (A.M.L.); (D.G.)
| | - Gianluca Campo
- Cardiology Unit, Azienda Ospedaliero Universitaria di Ferrara, 44124 Ferrara, Italy; (G.C.); (S.B.)
| | - Simone Biscaglia
- Cardiology Unit, Azienda Ospedaliero Universitaria di Ferrara, 44124 Ferrara, Italy; (G.C.); (S.B.)
| | - Italo Porto
- Department of Internal Medicine, University of Genoa, 16126 Genoa, Italy; (I.P.); (S.B.)
- Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino—Italian IRCCS Cardiology Network, 16126 Genoa, Italy
| | - Stefano Benenati
- Department of Internal Medicine, University of Genoa, 16126 Genoa, Italy; (I.P.); (S.B.)
| | - Giampaolo Niccoli
- Division of Cardiology, Parma University Hospital, University of Parma, 43126 Parma, Italy;
| |
Collapse
|
|
11
|
Teragawa H, Oshita C, Uchimura Y. Do changes in intracoronary pressure aid coronary spasm diagnosis using the spasm provocation test? World J Cardiol 2024; 16:16-26. [PMID: 38313387 PMCID: PMC10835468 DOI: 10.4330/wjc.v16.i1.16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/11/2023] [Accepted: 12/28/2023] [Indexed: 01/19/2024] Open
Abstract
BACKGROUND Although the spasm provocation test (SPT) can diagnose coronary spasms, it would be helpful if it could also predict their occurrence. AIM To investigate whether coronary spasms can be predicted using changes in intracoronary artery pressure measured using a pressure wire during the SPT. METHODS Seventy patients underwent SPTs with pressure-wire measurement of intracoronary artery pressure. During each SPT, the pressure wire was advanced into the distal portion of the right coronary artery (RCA) and left anterior descending coronary artery, and the ratio of intracoronary pressure to aortic pressure (Pd/Pa) was monitored. Coronary spasm was defined as an arterial narrowing of > 90% in response to the administration of acetylcholine (ACh), with chest symptoms and/or ischemic electrocardiographic changes. ACh was administered to the RCA at low, moderate, or high doses of 20, 50, or 80 µg, respectively, and to the left coronary artery (LCA) at low, moderate, or high doses of 50, 100, or 200 µg, respectively. Coronary arteries with coronary spasms at low doses of ACh were defined as group L, and those with coronary spasms at moderate or high doses were defined as group MH. Those who did not occur coronary spasms at any ACh dose were designated as group N. RESULTS Among the 132 coronary arteries assessed using a pressure wire, there were 49 in group N, 25 in group L, and 58 in group MH. Baseline Pd/Pa was the lowest in group L (P = 0.001). The decrease in the Pd/Pa between baseline to low doses of ACh was lower in group MH than in group N (P < 0.001). A receiver-operating characteristics analysis showed that the cutoff baseline Pd/Pa value for predicting group L was 0.95, with a sensitivity of 0.600 (15/25) and a specificity of 0.713 (76/107) and that the cutoff value of Pd/Pa from baseline to low doses of ACh for predicting group MH was -0.04, with a sensitivity of 0.741 (43/58) and a specificity of 0.694 (34/49). CONCLUSION These findings suggest that indices of intracoronary pressure during SPT may be useful means for predicting the occurrence of coronary spasms.
Collapse
Affiliation(s)
- Hiroki Teragawa
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima 732-0057, Japan.
| | - Chikage Oshita
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima 732-0057, Japan
| | - Yuko Uchimura
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima 732-0057, Japan
| |
Collapse
|
|
12
|
Sueda S, Kurokawa K, Sakaue T, Ikeda S. What is the meaning of provoked spasm phenotypes by vasoreactivity testing? J Cardiol 2024; 83:1-7. [PMID: 37453595 DOI: 10.1016/j.jjcc.2023.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/15/2023] [Accepted: 06/29/2023] [Indexed: 07/18/2023]
Abstract
Coronary artery epicardial spasm is involved in the pathogenesis of many cardiac disorders. Vasoreactivity testing, such as intracoronary injection of acetylcholine (ACH) or ergonovine (ER), is the gold standard method for the diagnosis of vasospastic angina. Provoked epicardial spasm phenotypes are classified as focal spasm and diffuse spasm. Multiple factors, including sex, ethnicity, and use of coronary vasoactive stimulators, are related to the provoked phenotypes of epicardial spasm. Diffuse-provoked spasm is often observed in females, where focal-provoked spasm is markedly more common in males. ACH provokes more diffuse and distal spasms, whereas ER induces more focal and proximal spasms. Yellow plaque and coronary thrombi are often observed in lesions with focal spasms, and intimal thickness with a sonolucent zone is significantly more common in lesions with focal spasm. Furthermore, clinical outcomes in patients with focal spasm are unsatisfactory compared with those in patients with diffuse spasm. However, the reproducibility and eternality of provoked spasm phenotypes by vasoreactivity testing is uncertain. Coronary atherosclerosis or endothelial damage may affect coronary vasomotor tone. Although coronary artery spasm may persist in the same coronary artery, provoked coronary spasm phenotypes may exhibit a momentary coronary reaction by intracoronary ACH or ER testing.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Pulmonology, Hypertension & Nephrology, Ehime University Graduate School of Medicine, Toon City, Japan; Department of Cardiology, Ehime Prefectural Niihama Hospital, Niihama City, Japan.
| | - Keisho Kurokawa
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Niihama City, Japan
| | - Tomoki Sakaue
- Department of Cardiology, Pulmonology, Hypertension & Nephrology, Ehime University Graduate School of Medicine, Toon City, Japan
| | - Shuntaro Ikeda
- Department of Cardiology, Pulmonology, Hypertension & Nephrology, Ehime University Graduate School of Medicine, Toon City, Japan
| |
Collapse
|
|
13
|
Rehan R, Beltrame J, Yong A. Insights into the invasive diagnostic challenges of coronary artery vasospasm - A systematic review. J Cardiol 2024; 83:8-16. [PMID: 37541429 DOI: 10.1016/j.jjcc.2023.07.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 07/27/2023] [Accepted: 07/28/2023] [Indexed: 08/06/2023]
Abstract
Coronary provocation testing is an essential diagnostic procedure when evaluating vasospastic angina. Invasive methods using acetylcholine or ergonovine are considered the current gold standard. Despite efforts from global cardiovascular institutions, current protocols vary in dosage, administration time, and procedural approach. In addition, concerns over the specificity of findings and potential complications have limited routine uptake of this procedure in clinical practice. This systematic review evaluates current diagnostic protocols, focusing on invasive provocation testing. We included studies using intracoronary provocation testing with acetylcholine or ergonovine for the assessment of coronary artery vasospasm that detailed specific elements of the procedure (dosage, administration time, etc.) and included ≥50 patients. A total of 28 articles met strict inclusion criteria. Our review highlights the heterogeneity between current diagnostic protocols for invasive provocation testing. We believe standardization of a diagnostic protocol will encourage both current and future cardiologists to incorporate such procedures in the evaluation of variant angina.
Collapse
Affiliation(s)
- Rajan Rehan
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Department of Cardiology, Concord Hospital, Sydney, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - John Beltrame
- Discipline of Medicine, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Central Adelaide Local Health Network, Adelaide, South Australia, Australia; Basil Hetzel Institute for Translational Health Research, Adelaide, South Australia, Australia
| | - Andy Yong
- Department of Cardiology, Concord Hospital, Sydney, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
| |
Collapse
|
|
14
|
Teragawa H, Uchimura Y, Oshita C, Hashimoto Y, Nomura S. Which Coronary Artery Should Be Preferred for Starting the Coronary Spasm Provocation Test? Life (Basel) 2023; 13:2072. [PMID: 37895453 PMCID: PMC10608489 DOI: 10.3390/life13102072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 10/14/2023] [Accepted: 10/14/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND The spasm provocation test (SPT) is a critical test for diagnosing vasospastic angina (VSA). However, the choice of vessel to be preferred for initiating the SPT-the right coronary artery (RCA) or the left coronary artery (LCA)-is unclear. This study aimed to assess SPT results including SPT-related complications while initiating the SPT in the RCA and LCA. METHODS We enrolled 225 patients who underwent coronary angiography and SPTs. The SPT was first performed in the RCA in 133 patients (RCA group) and the LCA in 92 patients (LCA group). We defined VSA as >90% narrowing of the coronary artery during the SPT, accompanied by chest pain and/or ST-T changes on the electrocardiogram. When coronary spasm occurs in two or more major coronary arteries, it is referred to as a multivessel spasm (MVS). SPT-related complications comprised atrial fibrillation, ventricular fibrillation, and unstable hemodynamics following catecholamine use. Analyses using propensity score matching (PSM) were performed in 120 patients. RESULTS No significant differences in the frequencies of VSA and complications were observed between the two groups (RCA: 79% and 19%, respectively; LCA: 85% and 22%, respectively). In both groups, spasms were most frequently provoked in the left anterior descending coronary artery (both p < 0.001) whereas spasms in the left circumflex coronary artery (LCX) were higher in the LCA group than in the RCA group (p = 0.015). Furthermore, no significant difference in the frequency of MVS was observed between both groups (RCA: 50%, LCA: 62%; p = 0.122). After PSM, no significant difference in the frequencies of VSA and complications were observed between the two groups (RCA: 82% and 15%, respectively; LCA: 88% and 18%, respectively). The frequencies of LCX spasms (RCA: 8%, LCA: 23%; p = 0.022) and MVS (RCA: 40%, LCA: 62%; p = 0.020) were higher in the LCA group than in the RCA group. CONCLUSIONS Although the diagnostic rate of VSA and frequency of SPT-related complications were similar in the two groups, the frequency of MVS was higher in the LCA group than in the RCA group because of the increase in the number of LCX spasms. A routine SPT may be started from the LCA.
Collapse
Affiliation(s)
- Hiroki Teragawa
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, 3-1-36, Futabanosato, Higashi-ku, Hiroshima 732-0057, Japan; (Y.U.); (C.O.); (Y.H.); (S.N.)
| | | | | | | | | |
Collapse
|
|
15
|
Hokimoto S, Kaikita K, Yasuda S, Tsujita K, Ishihara M, Matoba T, Matsuzawa Y, Mitsutake Y, Mitani Y, Murohara T, Noda T, Node K, Noguchi T, Suzuki H, Takahashi J, Tanabe Y, Tanaka A, Tanaka N, Teragawa H, Yasu T, Yoshimura M, Asaumi Y, Godo S, Ikenaga H, Imanaka T, Ishibashi K, Ishii M, Ishihara T, Matsuura Y, Miura H, Nakano Y, Ogawa T, Shiroto T, Soejima H, Takagi R, Tanaka A, Tanaka A, Taruya A, Tsuda E, Wakabayashi K, Yokoi K, Minamino T, Nakagawa Y, Sueda S, Shimokawa H, Ogawa H. JCS/CVIT/JCC 2023 guideline focused update on diagnosis and treatment of vasospastic angina (coronary spastic angina) and coronary microvascular dysfunction. J Cardiol 2023; 82:293-341. [PMID: 37597878 DOI: 10.1016/j.jjcc.2023.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/21/2023]
Affiliation(s)
| | - Koichi Kaikita
- Division of Cardiovascular Medicine and Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Japan
| | - Satoshi Yasuda
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Japan
| | - Kenichi Tsujita
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan
| | - Masaharu Ishihara
- Department of Cardiovascular and Renal Medicine, School of Medicine, Hyogo Medical University, Japan
| | - Tetsuya Matoba
- Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Japan
| | - Yasushi Matsuzawa
- Division of Cardiology, Yokohama City University Medical Center, Japan
| | - Yoshiaki Mitsutake
- Division of Cardiovascular Medicine, Kurume University School of Medicine, Japan
| | - Yoshihide Mitani
- Department of Pediatrics, Mie University Graduate School of Medicine, Japan
| | - Toyoaki Murohara
- Department of Cardiology, Nagoya University Graduate School of Medicine, Japan
| | - Takashi Noda
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Japan
| | - Koichi Node
- Department of Cardiovascular Medicine, Saga University, Japan
| | - Teruo Noguchi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Japan
| | - Hiroshi Suzuki
- Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Japan
| | - Jun Takahashi
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Japan
| | - Yasuhiko Tanabe
- Department of Cardiology, Niigata Prefectural Shibata Hospital, Japan
| | - Atsushi Tanaka
- Department of Cardiovascular Medicine, Wakayama Medical University, Japan
| | - Nobuhiro Tanaka
- Division of Cardiology, Tokyo Medical University Hachioji Medical Center, Japan
| | - Hiroki Teragawa
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Japan
| | - Takanori Yasu
- Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center, Japan
| | - Michihiro Yoshimura
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Japan
| | - Yasuhide Asaumi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Japan
| | - Shigeo Godo
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Japan
| | - Hiroki Ikenaga
- Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Japan
| | - Takahiro Imanaka
- Department of Cardiovascular and Renal Medicine, School of Medicine, Hyogo Medical University, Japan
| | - Kohei Ishibashi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Japan
| | - Masanobu Ishii
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan
| | | | - Yunosuke Matsuura
- Division of Cardiovascular Medicine and Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Japan
| | - Hiroyuki Miura
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Japan
| | - Yasuhiro Nakano
- Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Japan
| | - Takayuki Ogawa
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Japan
| | - Takashi Shiroto
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Japan
| | | | - Ryu Takagi
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Japan
| | - Akihito Tanaka
- Department of Cardiology, Nagoya University Graduate School of Medicine, Japan
| | - Atsushi Tanaka
- Department of Cardiovascular Medicine, Saga University, Japan
| | - Akira Taruya
- Department of Cardiovascular Medicine, Wakayama Medical University, Japan
| | - Etsuko Tsuda
- Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Japan
| | - Kohei Wakabayashi
- Division of Cardiology, Cardiovascular Center, Showa University Koto-Toyosu Hospital, Japan
| | - Kensuke Yokoi
- Department of Cardiovascular Medicine, Saga University, Japan
| | - Toru Minamino
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Japan
| | - Yoshihisa Nakagawa
- Department of Cardiovascular Medicine, Shiga University of Medical Science, Japan
| | - Shozo Sueda
- Department of Cardiology, Pulmonology, Hypertension & Nephrology, Ehime University Graduate School of Medicine, Japan
| | - Hiroaki Shimokawa
- Graduate School, International University of Health and Welfare, Japan
| | | |
Collapse
|
|
16
|
Hokimoto S, Kaikita K, Yasuda S, Tsujita K, Ishihara M, Matoba T, Matsuzawa Y, Mitsutake Y, Mitani Y, Murohara T, Noda T, Node K, Noguchi T, Suzuki H, Takahashi J, Tanabe Y, Tanaka A, Tanaka N, Teragawa H, Yasu T, Yoshimura M, Asaumi Y, Godo S, Ikenaga H, Imanaka T, Ishibashi K, Ishii M, Ishihara T, Matsuura Y, Miura H, Nakano Y, Ogawa T, Shiroto T, Soejima H, Takagi R, Tanaka A, Tanaka A, Taruya A, Tsuda E, Wakabayashi K, Yokoi K, Minamino T, Nakagawa Y, Sueda S, Shimokawa H, Ogawa H. JCS/CVIT/JCC 2023 Guideline Focused Update on Diagnosis and Treatment of Vasospastic Angina (Coronary Spastic Angina) and Coronary Microvascular Dysfunction. Circ J 2023; 87:879-936. [PMID: 36908169 DOI: 10.1253/circj.cj-22-0779] [Citation(s) in RCA: 85] [Impact Index Per Article: 42.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/11/2023]
Affiliation(s)
| | - Koichi Kaikita
- Division of Cardiovascular Medicine and Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
| | - Satoshi Yasuda
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Kenichi Tsujita
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
| | - Masaharu Ishihara
- Department of Cardiovascular and Renal Medicine, School of Medicine, Hyogo Medical University
| | - Tetsuya Matoba
- Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences
| | | | - Yoshiaki Mitsutake
- Division of Cardiovascular Medicine, Kurume University School of Medicine
| | - Yoshihide Mitani
- Department of Pediatrics, Mie University Graduate School of Medicine
| | - Toyoaki Murohara
- Department of Cardiology, Nagoya University Graduate School of Medicine
| | - Takashi Noda
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Koichi Node
- Department of Cardiovascular Medicine, Saga University
| | - Teruo Noguchi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center
| | - Hiroshi Suzuki
- Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital
| | - Jun Takahashi
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Yasuhiko Tanabe
- Department of Cardiology, Niigata Prefectural Shibata Hospital
| | - Atsushi Tanaka
- Department of Cardiovascular Medicine, Wakayama Medical University
| | - Nobuhiro Tanaka
- Division of Cardiology, Tokyo Medical University Hachioji Medical Center
| | - Hiroki Teragawa
- Department of Cardiovascular Medicine, JR Hiroshima Hospital
| | - Takanori Yasu
- Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center
| | - Michihiro Yoshimura
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine
| | - Yasuhide Asaumi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center
| | - Shigeo Godo
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Hiroki Ikenaga
- Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences
| | - Takahiro Imanaka
- Department of Cardiovascular and Renal Medicine, School of Medicine, Hyogo Medical University
| | - Kohei Ishibashi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center
| | - Masanobu Ishii
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
| | | | - Yunosuke Matsuura
- Division of Cardiovascular Medicine and Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
| | - Hiroyuki Miura
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center
| | | | - Takayuki Ogawa
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine
| | - Takashi Shiroto
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | | | - Ryu Takagi
- Division of Cardiology, Tokyo Medical University Hachioji Medical Center
| | - Akihito Tanaka
- Department of Cardiology, Nagoya University Graduate School of Medicine
| | | | - Akira Taruya
- Department of Cardiovascular Medicine, Wakayama Medical University
| | - Etsuko Tsuda
- Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center
| | - Kohei Wakabayashi
- Division of Cardiology, Cardiovascular Center, Showa University Koto-Toyosu Hospital
| | - Kensuke Yokoi
- Department of Cardiovascular Medicine, Saga University
| | - Toru Minamino
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine
| | - Yoshihisa Nakagawa
- Department of Cardiovascular Medicine, Shiga University of Medical Science
| | - Shozo Sueda
- Department of Cardiology, Pulmonology, Hypertension & Nephrology, Ehime University Graduate School of Medicine
| | | | | |
Collapse
|
|
17
|
Woudstra J, Vink CEM, Schipaanboord DJM, Eringa EC, den Ruijter HM, Feenstra RGT, Boerhout CKM, Beijk MAM, de Waard GA, Ong P, Seitz A, Sechtem U, Piek JJ, van de Hoef TP, Appelman Y. Meta-analysis and systematic review of coronary vasospasm in ANOCA patients: Prevalence, clinical features and prognosis. Front Cardiovasc Med 2023; 10:1129159. [PMID: 36993994 PMCID: PMC10041338 DOI: 10.3389/fcvm.2023.1129159] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 02/17/2023] [Indexed: 03/16/2023] Open
Abstract
Background Coronary artery spasm (CAS), encompassing epicardial and microvascular spasm, is increasingly recognized as cause of angina in patients with non-obstructive coronary artery disease (ANOCA). However, various spasm provocation testing protocols and diagnostic criteria are used, making diagnosis and characterization of these patients difficult and interpretation of study results cumbersome. This review provides a structured overview of the prevalence, characterization and prognosis of CAS worldwide in men and women. Methods A systematic review identifying studies describing ANOCA patients with CAS was performed. Multiple outcomes (prevalence, clinical features, and prognosis) were assessed. Data, except for prognosis were pooled and analysed using random effects meta-analysis models. Results Twenty-five publications (N = 14.554) were included (58.2 years; 44.2% women). Percentages of epicardial constriction to define epicardial spasm ranged from >50% to >90%. Epicardial spasm was prevalent in 43% (range 16-73%), with a higher prevalence in Asian vs. Western World population (52% vs. 33%, p = 0.014). Microvascular spasm was prevalent in 25% (range 7-39%). Men were more likely to have epicardial spasm (61%), women were more likely to have microvascular spasm (64%). Recurrent angina is frequently reported during follow-up ranging from 10 to 53%. Conclusion CAS is highly prevalent in ANOCA patients, where men more often have epicardial spasm, women more often have microvascular spasm. A higher prevalence of epicardial spasm is demonstrated in the Asian population compared to the Western World. The prevalence of CAS is high, emphasizing the use of unambiguous study protocols and diagnostic criteria and highlights the importance of routine evaluation of CAS in men and women with ANOCA. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=272100.
Collapse
Affiliation(s)
- Janneke Woudstra
- Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Caitlin E M Vink
- Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Diantha J M Schipaanboord
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Etto C Eringa
- Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Department of Physiology, Maastricht University, Cardiovascular Research Institute Maastricht, Maastricht, Netherlands
| | - Hester M den Ruijter
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Rutger G T Feenstra
- Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands
| | - Coen K M Boerhout
- Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands
| | - Marcel A M Beijk
- Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands
| | - Guus A de Waard
- Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Peter Ong
- Department of Cardiology, Robert Bosch Hospital, Stuttgart, Germany
| | - Andreas Seitz
- Department of Cardiology, Robert Bosch Hospital, Stuttgart, Germany
| | - Udo Sechtem
- Department of Cardiology, Robert Bosch Hospital, Stuttgart, Germany
| | - Jan J Piek
- Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands
| | - Tim P van de Hoef
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Yolande Appelman
- Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| |
Collapse
|
|
18
|
Perera D, Berry C, Hoole SP, Sinha A, Rahman H, Morris PD, Kharbanda RK, Petraco R, Channon K. 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; 109:88-95. [PMID: 35318254 PMCID: PMC9811089 DOI: 10.1136/heartjnl-2021-320718] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/17/2022] [Indexed: 02/04/2023] Open
Abstract
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.
Collapse
Affiliation(s)
- Divaka Perera
- British Heart Foundation Centre of Excellence and National Institute for Health Research Biomedical Research Centre, School of Cardiovascular Medicine and Sciences, King's College London, London, UK
| | - Colin Berry
- BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
- Cardiology, Golden Jubilee National Hospital, Clydebank, UK
| | | | - Aish Sinha
- British Heart Foundation Centre of Excellence and National Institute for Health Research Biomedical Research Centre, School of Cardiovascular Medicine and Sciences, King's College London, London, UK
| | - Haseeb Rahman
- British Heart Foundation Centre of Excellence and National Institute for Health Research Biomedical Research Centre, School of Cardiovascular Medicine and Sciences, King's College London, London, UK
| | - Paul D Morris
- Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield, UK
| | | | - Ricardo Petraco
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Keith Channon
- Department of Cardiovascular Medicine, University of Oxford, Oxford, UK
| |
Collapse
|
|
19
|
Sex Difference in Coronary Artery Spasm Tested by Intracoronary Acetylcholine Provocation Test in Patients with Nonobstructive Coronary Artery Disease. J Interv Cardiol 2022; 2022:5289776. [PMID: 36131847 PMCID: PMC9481410 DOI: 10.1155/2022/5289776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 07/13/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction Cardiovascular diseases manifest differently in men and women. The purpose of this study is to compare the sex difference in the characteristics of coronary artery spasm (CAS) in patients with nonobstructive cardiovascular disease (NOCVD) and the clinical outcomes in accordance with sex in CAS patients. Methods The study analysed 5,491 patients with NOCVD who underwent an acetylcholine provocation test from November 2004 to May 2014 for evaluation of chest pain. CAS was defined as greater than 70% of luminal narrowing of the artery during the acetylcholine provocation test. Results The patients were divided into men (n = 2,506) and women (n = 2,985). Mean follow-up days were 1,218 ± 577 days. To adjust for confounding factors, the propensity score matching (PSM) analysis was performed in all patients and among the CAS patients. After PSM analysis, a total of 1,201 pairs in all patients and a total of 713 pairs in CAS patients were generated. In all patients, women showed significantly less incidence of CAS compared with men (62.3% vs 50.9%, P < 0.01). Myocardial bridge (MB) and moderate stenosis were less prevalent in women, while transient ST elevation and ischemic chest pain during provocation were more frequent in women. In CAS patients, men had a higher incidence of multivessel spasm than women (35.7% vs. 29.7%, P < 0.01). Old age, dyslipidemia, and MB were independent risk factors of CAS in both men and women. In CAS patients, there was no statistical differences for various individual and composite major outcomes up to five years in either men or women. In men with CAS, old age was a risk factor of a 5-year major adverse cardiac event (MACE), and moderate stenosis was a risk factor of both 5-year MACE and 5-year recurrent angina. In women with CAS, mild stenosis was a risk factor of 5-year MACE, while myocardial bridge was a risk factor of 5-year recurrent angina. Conclusions In this study, there were sex differences in the angiographic and clinical parameters during the acetylcholine provocation test, incidence of CAS, risk factors of CAS, 5-year MACE, and recurrent angina. Old age, dyslipidemia, and MB were independent risk factors of CAS in both sexes. However, major clinical outcomes up to five years in CAS patients were not different according to sex.
Collapse
|
|
20
|
Sinha A, Rahman H, Perera D. Vasospastic Angina: A Contemporary Review of its Pathophysiology, Diagnosis and Management. Heart Int 2022; 16:99-104. [PMID: 36741101 PMCID: PMC9872780 DOI: 10.17925/hi.2022.16.2.99] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 05/30/2022] [Indexed: 12/25/2022] Open
Abstract
Nearly 40% of patients presenting to the catheter laboratory with angina have non-obstructed coronary arteries (ANOCA), an umbrella term that encompasses distinct pathophysiological entities, such as coronary artery spasm. Coronary artery spasm leads to sudden reversible coronary flow attenuation, which clinically manifests as vasospastic angina (VSA). VSA is associated with poor quality of life and an increased risk of major adverse cardiac events. However, the pathophysiological mechanisms underlying this phenomenon are incompletely understood, which has resulted in limited therapeutic options for patients afflicted with this condition. The past decade has seen a surge in new research being conducted in the field of ANOCA and VSA. This review article provides a comprehensive summary of the underlying pathophysiological mechanisms of VSA and the current therapeutic options. We also appraise the current diagnostic approach in patients with suspected VSA.
Collapse
Affiliation(s)
- Aish Sinha
- The British Heart Foundation Centre of Excellence and the National Institute for Health and Care Research Biomedical Research Centre at the School of Cardiovascular Medicine and Sciences, King's College London, London, UK
| | - Haseeb Rahman
- The British Heart Foundation Centre of Excellence and the National Institute for Health and Care Research Biomedical Research Centre at the School of Cardiovascular Medicine and Sciences, King's College London, London, UK
| | - Divaka Perera
- The British Heart Foundation Centre of Excellence and the National Institute for Health and Care Research Biomedical Research Centre at the School of Cardiovascular Medicine and Sciences, King's College London, London, UK
| |
Collapse
|
|
21
|
Nishi T, Kume T, Yamada R, Okamoto H, Koto S, Yamashita M, Ueno M, Kamisaka K, Sasahira Y, Enzan A, Sudo Y, Tamada T, Koyama T, Imai K, Neishi Y, Uemura S. Layered Plaque in Organic Lesions in Patients With Coronary Artery Spasm. J Am Heart Assoc 2022; 11:e024880. [PMID: 35322674 PMCID: PMC9075431 DOI: 10.1161/jaha.121.024880] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background Coronary artery spasm plays a vital role in the pathogenesis of coronary plaques. We sought to investigate the plaque characteristics of co‐existing organic lesions in patients with coronary artery spasm in comparison to those without coronary artery spasm by intracoronary optical coherence tomography (OCT). Methods and Results We included 39 patients who presented with a symptom suspected of coronary spastic angina and had an organic lesion, defined as ≥plaque burden of 50% assessed by OCT. Coronary artery spasm was diagnosed by positive acetylcholine provocation test, or by spontaneous spasm detected during coronary angiography. A total of 51 vessels with an organic lesion were identified. Of these, coronary artery spasm was observed in 30 vessels (spasm), while not in 21 vessels (non‐spasm). Organic lesions in the spasm vessels, compared with those in the non‐spasm vessels, had a higher prevalence of layered plaque (93% versus 38%, P<0.001), macrophages (80% versus 43%, P=0.016), and intraplaque microchannels (73% versus 24%, P<0.001), and lower prevalence of macrocalcification (23% versus 62%, P=0.009) as assessed by OCT. Conclusions Layered plaque, macrophages, and intraplaque microchannels, were frequently observed in organic lesions in patients with coronary artery spasm. These findings suggest that coronary artery spasm induces local thrombus formation as well as active inflammatory response, therefore increasing the risk of rapid plaque progression and ischemic events in patients with coronary artery spasm.
Collapse
Affiliation(s)
- Takeshi Nishi
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | - Teruyoshi Kume
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | - Ryotaro Yamada
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | - Hiroshi Okamoto
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | - Satsohi Koto
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | | | - Masahiko Ueno
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | - Kyo Kamisaka
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | | | - Ayano Enzan
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | - Yasuyuki Sudo
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | - Tomoko Tamada
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | - Terumasa Koyama
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | - Koichiro Imai
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | - Yoji Neishi
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| | - Shiro Uemura
- Department of Cardiology Kawasaki Medical School Kurashiki Japan
| |
Collapse
|
|
22
|
Marrone A, Pavasini R, Scollo E, Gibiino F, Pompei G, Caglioni S, Biscaglia S, Campo G, Tebaldi M. Acetylcholine Use in Modern Cardiac Catheterization Laboratories: A Systematic Review. J Clin Med 2022; 11:jcm11041129. [PMID: 35207403 PMCID: PMC8880288 DOI: 10.3390/jcm11041129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 02/09/2022] [Accepted: 02/18/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The use of acetylcholine for the diagnosis of vasospastic angina is recommended by international guidelines. However, its intracoronary use is still off-label due to the absence of safety studies. We aimed to perform a systematic review of the literature to identify adverse events related to the intracoronary administration of acetylcholine for vasoreactivity testing to fill this gap. METHODS AND RESULTS We conducted a systematic review of observational studies and randomized controlled trials dealing with the intracoronary administration of acetylcholine. Articles were searched in MEDLINE (PubMed) using the MeSH strategy. Three independent reviewers determined whether the studies met the inclusion and exclusion criteria. A total of 434 articles were selected. Data concerning clinical characteristics, study population, acetylcholine dosage, and adverse effects were retrieved from the articles. Overall, 71,566 patients were included, of which only 382 (0.5%) developed one adverse event, and there were no fatal events reported (0%). CONCLUSIONS Intracoronary administration of acetylcholine in the setting of coronary spasm provocation testing is safe and plays a central role in the evaluation of coronary vasomotion disorders, making it worthy of becoming a part of clinical practice in all cardiac catheterization laboratories.
Collapse
|
|
23
|
Feenstra RG, Seitz A, Boerhout CK, Bukkems LH, Stegehuis VE, Teeuwisse PJ, de Winter RJ, Sechtem U, Piek JJ, van de Hoef TP, Ong P, Beijk MA. Principles and pitfalls in coronary vasomotor function testing. EUROINTERVENTION 2022; 17:1271-1280. [PMID: 34278990 PMCID: PMC9725006 DOI: 10.4244/eij-d-21-00402] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Coronary vasomotor dysfunction can be diagnosed in a large proportion of patients with angina in the presence of non-obstructive coronary artery disease (ANOCA) using comprehensive protocols for coronary vasomotor function testing (CFT). Although consensus on diagnostic criteria for endotypes of coronary vasomotor dysfunction has been published, consensus on a standardised study testing protocol is lacking. AIMS In this review we provide an overview of the variations in CFT used and discuss the practical principles and pitfalls of CFT. METHODS For the purposes of this review, we assessed study protocols that evaluate coronary vasomotor response as reported in the literature. We compared these protocols regarding a number of procedural aspects and chose six examples to highlight the differences and uniqueness. RESULTS Currently, numerous protocols co-exist and vary in vascular domains tested, the manner in which to test these domains (e.g., preprocedural discontinuation of medication, provocative agent, solution, infusion time, and target artery) and techniques used for measurements (e.g., Doppler vs thermodilution technique). CONCLUSIONS This lack of consensus on a uniform functional testing protocol hampers both a broader clinical acceptance of the concepts of coronary vasomotor dysfunction, and the widespread adoption of such testing protocols in current clinical practice. Furthermore, the endotype of coronary vasomotor dysfunction might differ among the few specialised centres that perform CFT as a result of the use of different protocols.
Collapse
Affiliation(s)
- Rutger G.T. Feenstra
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Andreas Seitz
- Department of Cardiology, Robert-Bosch-Krankenhaus, Stuttgart, Germany
| | - Coen K.M. Boerhout
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Laura H. Bukkems
- Department of Clinical Pharmacy, Amsterdam UMC, Amsterdam, the Netherlands
| | - Valérie E. Stegehuis
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | | | - Robbert J. de Winter
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Udo Sechtem
- Department of Cardiology, Robert-Bosch-Krankenhaus, Stuttgart, Germany
| | - Jan J. Piek
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Tim P. van de Hoef
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Peter Ong
- Department of Cardiology, Robert-Bosch-Krankenhaus, Stuttgart, Germany
| | - Marcel A.M. Beijk
- AMC Heartcenter, Room B2-250, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| |
Collapse
|
|
24
|
Sueda S, Sakaue T. Intracoronary acetylcholine testing among 746 consecutive Japanese patients with angina-like chest pain and unobstructed coronary artery disease. EUROPEAN HEART JOURNAL OPEN 2021; 2:oeab012. [PMID: 35919663 PMCID: PMC9242056 DOI: 10.1093/ehjopen/oeab012] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/18/2021] [Indexed: 12/22/2022]
Abstract
Aims Intracoronary acetylcholine (ACh) testing is useful for the detection of epicardial spasm (ES) and coronary microvascular spasm (CMS). We retrospectively analysed the incidence of ES and CMS in consecutive Japanese patients with unobstructed coronary artery disease. Methods and results From January 1991 to February 2019, we performed intracoronary ACh testing of 1864 patients. Among these patients, a total of 746 consecutive patients (254 women, mean age 64 ± 11 years) who underwent first diagnostic angiography for suspected myocardial ischaemia and had unobstructed coronary arteries (<50%) were enrolled. Epicardial spasm was defined as ≥90% stenosis and usual chest symptoms and ischaemic ECG changes, while CMS was defined as <75% stenosis and usual chest symptoms and ischaemic ECG changes. We performed intracoronary ACh testing on both coronary arteries in 96% (716/746) of all subjects. Overall, ES was found in 329 patients (44%), whereas CMS was revealed in 40 patients (5%) including 4 patients with coexisting ES. In patients with ES, women made up 22%, and approximately three-quarters of the patients had resting chest pain. In contrast, women composed 65% (26/40) of those with CMS, and 15 patients with CMS had another chest symptom. Coronary microvascular spasm was frequently observed in the left coronary artery (LCA) but not the right coronary artery. Electrical cardioversion was necessary for two patients. Conclusions Coronary microvascular spasm was recognized in only 5% of consecutive Japanese patients with unobstructed coronary artery disease, whereas ES was revealed in 44% of those patients. Coronary microvascular spasm was often observed in women and in the LCA.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Hongou 3 choume 1-1, Ehime Prefecture, Niihama City 792-0042, Japan
| | - Tomoki Sakaue
- Department of Cardiology, Yawatahama City General Hospital, Ohira 1-638, Ehime Prefecture, Yawatahama City 796-8502, Japan
| |
Collapse
|
|
25
|
Beck S, Pereyra VM, Seitz A, McChord J, Hubert A, Bekeredjian R, Sechtem U, Ong P. Invasive Diagnosis of Coronary Functional Disorders Causing Angina Pectoris. Eur Cardiol 2021; 16:e27. [PMID: 34276812 PMCID: PMC8280748 DOI: 10.15420/ecr.2021.06] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 04/26/2021] [Indexed: 01/16/2023] Open
Abstract
Coronary vasomotion disorders represent a frequent cause of angina and/or dyspnoea in patients with non-obstructed coronary arteries. The highly sophisticated interplay of vasodilatation and vasoconstriction can be assessed in an interventional diagnostic procedure. Established parameters characterising adequate vasodilatation are coronary blood flow at rest, and, after drug-induced vasodilation, coronary flow reserve, and microvascular resistance (hyperaemic microvascular resistance, index of microcirculatory resistance). An increased vasoconstrictive potential is diagnosed by provocation testing with acetylcholine or ergonovine. This enables a diagnosis of coronary epicardial and/or microvascular spasm. Ischaemia associated with microvascular spasm can be confirmed by ischaemic ECG changes and the measurement of lactate concentrations in the coronary sinus. Although interventional diagnostic procedures are helpful for determining the mechanism of the angina, which may be the key to successful medical treatment, they are still neither widely accepted nor applied in many medical centres. This article summarises currently well-established invasive methods for the diagnosis of coronary functional disorders causing angina pectoris.
Collapse
Affiliation(s)
- Sascha Beck
- Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus Stuttgart, Germany
| | | | - Andreas Seitz
- Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus Stuttgart, Germany
| | - Johanna McChord
- Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus Stuttgart, Germany
| | - Astrid Hubert
- Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus Stuttgart, Germany
| | - Raffi Bekeredjian
- Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus Stuttgart, Germany
| | - Udo Sechtem
- Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus Stuttgart, Germany
| | - Peter Ong
- Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus Stuttgart, Germany
| |
Collapse
|
|
26
|
Pargaonkar VS, Lee JH, Chow EKH, Nishi T, Ball RL, Kobayashi Y, Kimura T, Lee DP, Stefanick ML, Fearon WF, Yeung AC, Tremmel JA. Dose-Response Relationship Between Intracoronary Acetylcholine and Minimal Lumen Diameter in Coronary Endothelial Function Testing of Women and Men With Angina and No Obstructive Coronary Artery Disease. Circ Cardiovasc Interv 2020; 13:e008587. [PMID: 32279562 PMCID: PMC9205616 DOI: 10.1161/circinterventions.119.008587] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 03/20/2020] [Indexed: 11/16/2022]
Abstract
BACKGROUND Intracoronary acetylcholine (Ach) provocation testing is the gold standard for assessing coronary endothelial function. However, dosing regimens of Ach are quite varied in the literature, and there are limited data evaluating the optimal dose. We evaluated the dose-response relationship between Ach and minimal lumen diameter (MLD) by sex and studied whether incremental intracoronary Ach doses given during endothelial function testing improve its diagnostic utility. METHODS We evaluated 65 men and 212 women with angina and no obstructive coronary artery disease who underwent endothelial function testing using the highest tolerable dose of intracoronary Ach, up to 200 μg. Epicardial endothelial dysfunction was defined as a decrease in MLD >20% after intracoronary Ach by quantitative coronary angiography. We used a linear mixed effects model to evaluate the dose-response relationship. Deming regression analysis was done to compare the %MLD constriction after incremental doses of intracoronary Ach. RESULTS The mean age was 53.5 years. Endothelial dysfunction was present in 186 (68.1%). Among men with endothelial dysfunction, there was a significant decrease in MLD/10 µg of Ach at doses above 50 μg and 100 µg, while this decrease in MLD was not observed in women (P<0.001). The %MLD constriction at 20 μg versus 50 μg and 50 μg versus 100 μg were not equivalent while the %MLD constriction at 100 μg versus 200 μg were equivalent. CONCLUSIONS Women and men appear to have different responses to Ach during endothelial function testing. In addition to having a greater response to intracoronary Ach at all doses, men also demonstrate an Ach-MLD dose-response relationship with doses up to 200 μg, while women have minimal change in MLD with doses above 50 µg. An incremental dosing regimen during endothelial function testing appears to improve the diagnostic utility of the test and should be adjusted based on the sex of the patient.
Collapse
Affiliation(s)
- Vedant S Pargaonkar
- Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford CA, USA
| | - Justin H Lee
- Quantitative Sciences Unit, Department of Medicine, Stanford School of Medicine, Stanford, CA, USA
| | - Eric KH Chow
- Quantitative Sciences Unit, Department of Medicine, Stanford School of Medicine, Stanford, CA, USA
| | - Takeshi Nishi
- Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford CA, USA
| | - Robyn L Ball
- Quantitative Sciences Unit, Department of Medicine, Stanford School of Medicine, Stanford, CA, USA
| | - Yuhei Kobayashi
- Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford CA, USA
| | - Takumi Kimura
- Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford CA, USA
- Department of Cardiology, Iwate Medical University, Morioka, Iwate, Japan
| | - David P Lee
- Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford CA, USA
| | - Marcia L Stefanick
- Stanford Prevention Research Center, Stanford School of Medicine, Stanford, CA, USA
| | - Whaliam F Fearon
- Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford CA, USA
| | - Alan C Yeung
- Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford CA, USA
| | - Jennifer A Tremmel
- Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford CA, USA
| |
Collapse
|
|
27
|
Matsumura M, Oshita C, Fujii Y, Ueda T, Teragawa H. Vasospastic Angina Diagnosed by the Spasm Provocation Test with the Combined Use of the Acetylcholine and Ergonovine Provocation Tests. Intern Med 2019; 58:2377-2381. [PMID: 31118393 PMCID: PMC6746633 DOI: 10.2169/internalmedicine.2710-19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 02/27/2019] [Indexed: 12/12/2022] Open
Abstract
The spasm provocation test (SPT) is important for diagnosing vasospastic angina (VSA), and acetylcholine (ACh) is usually used for this test in Japan. However, some patients with VSA have negative SPT results with the use of the standard ACh regimen alone. We herein report two cases in which VSA was diagnosed by the SPT with the combined use of ACh and ergonovine (EM). VSA could not be diagnosed in either case by the SPT using ACh infusions alone. For patients with negative SPT results, cardiologists should consider performing the SPT using a combination of ACh and EM.
Collapse
Affiliation(s)
- Mirai Matsumura
- Department of Clinical Education, JR Hiroshima Hospital, Japan
| | - Chikage Oshita
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Japan
| | - Yuichi Fujii
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Japan
| | - Tomohiro Ueda
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Japan
| | - Hiroki Teragawa
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Japan
| |
Collapse
|
|
28
|
Teragawa H, Oshita C, Ueda T. Coronary spasm: It’s common, but it’s still unsolved. World J Cardiol 2018; 10:201-209. [PMID: 30510637 PMCID: PMC6259026 DOI: 10.4330/wjc.v10.i11.201] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 09/21/2018] [Accepted: 10/07/2018] [Indexed: 02/06/2023] Open
Abstract
Coronary spasm is caused by a transient coronary narrowing due to the constriction of epicardial coronary artery, which leads to myocardial ischemia. More than 50 years have passed since the first recognition of coronary spasm, and many findings on coronary spasm have been reported. Coronary spasm has been considered as having pivotal roles in the cause of not only rest angina but also exertional angina, acute coronary syndrome, and heart failure. In addition, several new findings of the mechanism of coronary spasm have emerged recently. The diagnosis based mainly on coronary angiography and spasm provocation test and the mainstream treatment with a focus on a calcium-channel blocker have been established. At a glance, coronary spasm or vasospastic angina (VSA) has become a common disease. On the contrary, there are several uncertain or unsolved problems regarding coronary spasm, including the presence of medically refractory coronary spasm (intractable VSA), or an appropriate use of implantable cardioverter defibrillator in patients with cardiac arrest who have been confirmed as having coronary spasm. This editorial focused on coronary spasm, including recent topics and unsolved problems.
Collapse
Affiliation(s)
- Hiroki Teragawa
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima 732-0057, Japan
| | - Chikage Oshita
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima 732-0057, Japan
| | - Tomohiro Ueda
- Department of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima 732-0057, Japan
| |
Collapse
|
|
29
|
Aziz A, Hansen HS, Sechtem U, Prescott E, Ong P. Sex-Related Differences in Vasomotor Function in Patients With Angina and Unobstructed Coronary Arteries. J Am Coll Cardiol 2017; 70:2349-2358. [PMID: 29096805 DOI: 10.1016/j.jacc.2017.09.016] [Citation(s) in RCA: 138] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2017] [Revised: 09/04/2017] [Accepted: 09/06/2017] [Indexed: 01/04/2023]
Abstract
BACKGROUND Coronary vasomotor dysfunction is an important mechanism for angina in patients with unobstructed coronary arteries. OBJECTIVES The purpose of this study was to determine sex differences in the prevalence and clinical presentation of vasomotor dysfunction in a European population and to examine sex differences in the dose of acetylcholine leading to a positive acetylcholine provocation test (ACH test). METHODS Between 2007 and 2014, we included 1,379 consecutive patients with stable angina, unobstructed coronaries and ACH test performed for epicardial vasospasm or coronary microvascular dysfunction (CMD) due to microvascular spasm. The predictive value of sex, risk factors, symptoms, and noninvasive test results was analyzed by means of logistic regression. RESULTS The mean patient age was 62 years, and 42% were male. There were 813 patients (59%) with a pathological ACH test, 33% for CMD and 26% for epicardial vasospasm. A pathological test was more common in females (70% vs. 43%; p < 0.001). In a multivariable logistic regression model the sex difference was statistically significant with a female-male odds ratio for CMD and epicardial vasospasm of 4.2 (95% confidence interval: 3.1 to 5.5; p < 0.001) and 2.3 (95% confidence interval: 1.7 to 3.1; p < 0.001), respectively. Effort-related symptoms, but neither risk factors nor noninvasive stress tests, contributed to predicting a pathological test. Female patients were more sensitive to acetylcholine with vasomotor dysfunction occurring at lower ACH doses compared with male patients. CONCLUSIONS Vasomotor dysfunction is frequent in patients with angina and unobstructed coronaries in a European population. Female patients have a higher prevalence of vasomotor dysfunction (especially CMD) compared with male patients. A pathological ACH test was observed at lower ACH doses in women compared with men.
Collapse
Affiliation(s)
- Ahmed Aziz
- Department of Cardiology, Robert Bosch Krankenhaus, Stuttgart, Germany; Department of Cardiology, Odense University Hospital, Odense, Denmark.
| | | | - Udo Sechtem
- Department of Cardiology, Robert Bosch Krankenhaus, Stuttgart, Germany
| | - Eva Prescott
- Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Peter Ong
- Department of Cardiology, Robert Bosch Krankenhaus, Stuttgart, Germany
| |
Collapse
|
|
30
|
Sueda S, Kohno H. Impact of pharmacological spasm provocation test in patients with a history of syncope. Heart Vessels 2017; 33:126-133. [PMID: 28905210 DOI: 10.1007/s00380-017-1046-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 09/01/2017] [Indexed: 12/15/2022]
Abstract
Coronary artery spasm is involved in the pathogenesis of various cardiac disorders. We investigated patients with a history of syncope who underwent elective coronary angiography. We retrospectively analyzed 5781 consecutive patients who had diagnostic or follow-up angiography during a 26-year period. During this period, we found 95 patients with a history of syncope before elective coronary angiography. Pharmacological spasm provocation testing was performed in 64 patients with a history of syncope (<1 year). Positive pharmacological response was observed in 48 patients, while the remaining 16 patients had negative tests. Positive spasm was defined as a transient ≥90% narrowing with ischemic electrocardiographic changes. Among the 64 patients, definite coronary spastic angina (CSA) was found in 35 patients (54.7%) and suspected CSA was found in 13 patients (20.3%). Among the 35 patients with definite CSA, 22 patients (62.9%) had chest symptoms before syncope, but 13 (37.1%) had no chest symptom before syncope. No difference in clinical characteristics was observed between the two groups. Focal spasm during pharmacological spasm provocation tests was significantly higher in patients with chest symptoms than in those without chest symptoms before syncope (54.3 vs. 12.0%, p < 0.002). CSA was observed in 75.0% of patients with a history of syncope (<1 year). Thirteen patients with definite CSA had neither chest pain nor chest pressure before syncope. We should therefore investigate coronary artery spasm as a potential etiology in patients with a history of syncope.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Hongou 3 Choume 1-1, Niihama, Ehime, 792-0042, Japan.
| | - Hiroaki Kohno
- Department of Cardiology, Tsukazaki Hospital, Himeji, Japan
| |
Collapse
|
|
31
|
Teragawa H, Fujii Y, Uchimura Y, Ueda T. Importance of a second spasm provocation test: Four cases with an initial negative spasm provocation test. World J Cardiol 2017; 9:289-295. [PMID: 28400927 PMCID: PMC5368680 DOI: 10.4330/wjc.v9.i3.289] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2016] [Revised: 10/28/2016] [Accepted: 01/14/2017] [Indexed: 02/06/2023] Open
Abstract
The spasm provocation test (SPT) is an important test in the diagnosis of vasospastic angina (VSA). In many cases, this test is performed as the gold standard test, and VSA is considered not present if the SPT is negative. However, some patients continue to experience chest symptoms despite a negative SPT. In this study, we report four cases in which SPT was repeated to evaluate chest symptoms despite the negative results of the first SPT. Two men in their 70s, one woman in her 60s, and one woman in her 70s, all with chest symptoms, underwent a second SPT at 4, 3, 2, and 3 years, respectively, after the first SPT, which was negative. Three patients had positive results in the second SPT (75%). In conclusion, even when SPT is negative, the diagnosis of VSA should be made with clinical symptoms in consideration. In some cases, a second SPT may be required to confirm the diagnosis of VSA.
Collapse
|
|
32
|
Sueda S, Kohno H. The acetylcholine administration time plays the key role for provoked spasm in the spasm provocation test. J Cardiol 2016; 70:141-146. [PMID: 27988074 DOI: 10.1016/j.jjcc.2016.11.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Revised: 10/22/2016] [Accepted: 10/25/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Acetylcholine (ACh) was administered for 3min in the ENCORE study, while the Japanese Circulation Society guidelines recommended the 20s ACh injection as an ACh test. OBJECTIVES We compared the ischemic findings between ACh administration for 3min and ACh injection for 20s in the same patients and in the same ACh doses without administration of nitrates in the left coronary artery. METHODS We investigated 30 patients with ischemic heart disease (25 men, 67±10 years, ACh 50μg: 3, ACh 100μg: 9, ACh 200μg: 18) by the above two ACh injection procedures. Temporary pacemaker was inserted and set at the rate of 40/min. Positive provoked spasm was defined as transient ≥90% narrowing and typical chest symptoms or ischemic electrocardiographic (ECG) changes. RESULTS Provoked spasm was observed in 22 patients with ACh 20s injection, while 10 patients had provoked spasm by ACh 3min administration (73.3% vs. 33.3%, p<0.05). Ischemic ECG changes (50.0% vs. 23.3%, p<0.05) and chest symptoms (73.3% vs. 43.3%, p<0.05) were significantly higher with ACh 20s injection than ACh 3min administration. Pacemaker rhythm was recognized in 19 patients with ACh 20s injection, whereas 7 patients with ACh 3min administration had a pacemaker rhythm (63.3% vs. 23.3%, p<0.01). Maximal ST elevation by ACh 20s injection was significantly higher than that by ACh 3min administration (0.47±0.94 vs. 0.13±0.51, p<0.05), while maximal ST depression was not different between the two procedures. Coronary artery diameter after ACh 20s injection was significantly lower than that after ACh 3min administration in the left anterior descending artery. CONCLUSIONS ACh administration procedures (3min or 20s injection) may influence the ischemic findings in spasm provocation testing.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Niihama City, Japan.
| | | |
Collapse
|
|
33
|
Sueda S, Kohno H, Yoshino H. The real world in the clinic before and after the establishment of guidelines for coronary artery spasm: a questionnaire for members of the Japanese Cine-angio Association. Heart Vessels 2016; 32:637-643. [PMID: 27921167 DOI: 10.1007/s00380-016-0916-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2016] [Accepted: 10/31/2016] [Indexed: 01/22/2023]
Abstract
We investigated the clinical situations and the present knowledge of Japanese cardiologists about coronary artery spasm before and after the establishment of guidelines for this condition in the real world. A questionnaire was developed regarding the number of cases of coronary angiography, percutaneous coronary intervention, and invasive/non-invasive spasm provocation tests before (2008) and after (2014) the establishment of the Japanese Circulation Society (JCS) guidelines for coronary artery spasm and the status of spasm provocation tests. The questionnaire was sent to members of the Japanese Cine-angio Association in 81 cardiology hospitals in Japan. The completed surveys were returned from 20 hospitals, giving a response rate of 24.7%. Pharmacological spasm provocation tests increased in 2014 and vasospastic angina and variant angina also increased in 2014 compared with 2008, but the increase was not significant. Non-invasive spasm provocation tests such as hyperventilation tests and cold stress tests decreased remarkably in 2014. Spasm provocation tests were initially performed in the left coronary artery was employed in just 30% of the hospitals. The majority of institutions did not perform the spasm provocation testing in patients with unknown causes of heart failure or in survivors of ventricular fibrillation. Although 40% of the hospitals were not satisfied with standard spasm provocation tests, the majority of the hospitals agreed that spasm provocation tests will be necessary in the future. In general, the JCS guidelines contributed to the widespread use of provocative testing for coronary artery spasm in the real world. However, some issues about spasm still remained in the clinic.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Hongou 3 Choume 1-1, Niihama City, Ehime, 792-0042, Japan.
| | - Hiroaki Kohno
- Department of Cardiology, Tsukazaki Hospital, Himeji, Japan
| | - Hideaki Yoshino
- Department of Cardiology, Kyorin University Hospital, Tokyo, Japan
| |
Collapse
|
|
34
|
Saito Y, Kitahara H, Shoji T, Tokimasa S, Nakayama T, Sugimoto K, Fujimoto Y, Kobayashi Y. Feasibility of omitting provocation test with 50 μg of acetylcholine in left coronary artery. Heart Vessels 2016; 32:685-689. [DOI: 10.1007/s00380-016-0926-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 11/18/2016] [Indexed: 01/27/2023]
|
|
35
|
Sueda S, Kohno H, Ochi T, Uraoka T, Tsunemitsu K. Overview of the pharmacological spasm provocation test: Comparisons between acetylcholine and ergonovine. J Cardiol 2016; 69:57-65. [PMID: 27856130 DOI: 10.1016/j.jjcc.2016.09.012] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Revised: 09/15/2016] [Accepted: 09/23/2016] [Indexed: 12/11/2022]
Abstract
The spasm provocation tests of ergonovine and acetylcholine have been employed in the cardiac catheterization laboratory. Ergonovine acts through the serotogenic receptors, while acetylcholine acts through the muscarinic cholinergic receptors. Different mediators may have the potential to cause different coronary responses. However, there are few reports concerning the coronary response between ergonovine and acetylcholine in the same patients. Acetylcholine is supersensitive for females; spasm provoked by ergonovine is focal and proximal, whereas provoked spasm by acetylcholine is diffuse and distal. We should use both tests as supplementary in the clinic because ergonovine and acetylcholine have self-limitations to induce coronary spasms during daily life. The maximal pharmacological doses, administration methods, and the angiographical positive definition are remarkably different for each institution in the world. We recommend the pharmacological spasm provocation tests as Class I in the guidelines in patients with vasospastic angina throughout the world.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Ehime, Japan.
| | - Hiroaki Kohno
- Department of Cardiology, Tsukazaki Hospital, Himeji, Hyogo, Japan
| | - Takaaki Ochi
- Department of Cardiology, Ochi Clinic, Iyogun Masaki Chou, Ehime, Japan
| | - Tadao Uraoka
- Department of Cardiology, Uraoka Clinic, Ozu, Ehime, Japan
| | | |
Collapse
|
|
36
|
Li L, Li Y, Lin J, Jiang J, He M, Sun D, Zhao Z, Shen Y, Xue A. Phosphorylated Myosin Light Chain 2 (p-MLC2) as a Molecular Marker of Antemortem Coronary Artery Spasm. Med Sci Monit 2016; 22:3316-3327. [PMID: 27643564 PMCID: PMC5031170 DOI: 10.12659/msm.900152] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Accepted: 08/02/2016] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND It is not uncommon that only mild coronary artery stenosis is grossly revealed after a system autopsy. While coronary artery spasm (CAS) is the suspected mechanism of these deaths, no specific biomarker has been identified to suggest antemortem CAS. MATERIAL AND METHODS To evaluate the potential of using phosphorylated myosin light chain 2 (p-MLC2) as a diagnostic marker of antemortem CAS, human vascular smooth muscle cells (VSMCs) were cultured and treated with common vasoconstrictors, including prostaglandins F2α (PGF2α), acetylcholine (ACh), and 5-hydroxy tryptamine (5-HT). The p-MLC2 level was examined in the cultured cells using Western blot analysis and in a rat model of spasm provocation tests using immunohistochemistry (IHC). Effects of increased p-MLC2 level on VSMCs contractile activities were assessed in vitro using confocal immunofluorescence assay. Four fatal cases with known antemortem CAS were collected and subject to p-MLC2 detection. RESULTS The p-MLC2 was significantly increased in VSMCs after treatments with vasoconstrictors and in the spasm provocation tests. Myofilament was well-organized and densely stained in VSMCs with high p-MLC2 level, but disarrayed in VSMCs with low p-MLC2 level. Three of the 4 autopsied cases showed strongly positive staining of p-MLC2 at the stenosed coronary segment and the adjacent interstitial small arteries. The fourth case was autopsied at the 6th day after death and showed negative-to-mild positive staining of p-MLC2. CONCLUSIONS p-MLC2 might be a useful marker for diagnosis of antemortem CAS. Autopsy should be performed as soon as possible to collect coronary arteries for detection of p-MLC2.
Collapse
Affiliation(s)
- Liliang Li
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China
- Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Science, Ministry of Justice, Shanghai, P.R. China
| | - Yuhua Li
- School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Junyi Lin
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China
| | - Jieqing Jiang
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China
| | - Meng He
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China
| | - Daming Sun
- Forensic Science Center, East China University of Political Science and Law, Shanghai, P.R. China
| | - Ziqin Zhao
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China
| | - Yiwen Shen
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China
| | - Aimin Xue
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China
- Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Science, Ministry of Justice, Shanghai, P.R. China
| |
Collapse
|
|
37
|
Hoshino M, Yonetsu T, Mizukami A, Matsuda Y, Yoshioka K, Sudo Y, Ninomiya R, Soeda M, Kuroda S, Ono M, Iwatsuka R, Suzuki M, Matsumura A, Hashimoto Y. Moderate vasomotor response to acetylcholine provocation test as an indicator of long-term prognosis. Heart Vessels 2016; 31:1943-1949. [DOI: 10.1007/s00380-016-0827-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Accepted: 02/26/2016] [Indexed: 11/25/2022]
|
|
38
|
Sueda S, Miyoshi T, Sasaki Y, Sakaue T, Habara H, Kohno H. Approximately half of patients with coronary spastic angina had pathologic exercise tests. J Cardiol 2016; 68:13-9. [PMID: 26952355 DOI: 10.1016/j.jjcc.2016.01.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2015] [Revised: 01/03/2016] [Accepted: 01/15/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVES We examined the clinical usefulness of treadmill exercise tests (TETs) in diagnosing coronary spastic angina (CSA). METHODS We performed the TETs and 24-h Holter monitoring in 300 CSA patients consisting of 152 patients with rest angina, 77 patients with effort angina, and 71 patients with rest and effort angina. Organic stenosis (>75%) was observed in 44 patients. Multiple spasms were recognized in 204 patients (68%). RESULTS Positive TETs were recognized in 113 patients (38%) and borderline was observed in 30 patients (10%). Positive response was significantly higher in patients with organic stenosis than those without fixed stenosis (63.6% vs. 33.2%, p<0.001). Moreover, ST elevation was more frequent in patients with organic stenosis than those without fixed stenosis (27.3% vs. 1.2%, p<0.001). Positive response in patients with effort angina (46.8%) was higher than those in patients with rest angina (33.6%) and rest and effort angina (36.6%), but not significant. Positive response was not different between single spasm and multiple spasms. In all 300 patients, ST segment elevation was observed in only four patients (1.3%) on the 24-h Holter monitoring. CONCLUSIONS TET was useful in documenting ischemia in patients with CSA. More than a third of patients with CSA had positive TETs. Moreover, we obtained the pathologic TET response in approximately half of patients with CSA.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Ehime, Japan.
| | - Toru Miyoshi
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Ehime, Japan
| | - Yasuhiro Sasaki
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Ehime, Japan
| | - Tomoki Sakaue
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Ehime, Japan
| | - Hirokazu Habara
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Ehime, Japan
| | - Hiroaki Kohno
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Ehime, Japan
| |
Collapse
|
|
39
|
Abstract
BACKGROUND We encounter a less provoked spasm in the left circumflex artery (LCX) by acetylcholine (ACh) testing compared with left anterior descending artery and right coronary artery (RCA) in the real world. OBJECTIVES We investigated the clinical characteristics of provoked spasm in the LCX by ACh testing. METHODS We retrospectively analyzed consecutive 1392 ACh testing over 20 years (1991-2011). The maximal ACh dose was 100 μg into the left coronary artery and 80 μg into the RCA. Positive spasm was defined as transient of more than or equal to 90% narrowing and usual chest symptoms or ischemic ECG changes. RESULTS Positive provoked spasm was recognized in 622 patients (44.7%) including 456 RCA spasms, 448 left anterior descending artery spasms, and 176 LCX spasms. LCX-provoked spasm was significantly lower than other vessels (P<0.001). LCX-provoked spasm was observed in 176 patients, of whom 113 patients (64.2%) had triple-vessel spasm, 46 patients (26.1%) had double-vessel spasm, and 17 patients (9.7%) had single-vessel spasm. More than 90% patients with LCX-provoked spasm had multiple spasms. Of 17 patients with LCX single-vessel spasm, 15 patients (88.2%) had focal spasm. CONCLUSION Under a maximal ACh dose of 100 μg into the left coronary artery, LCX-provoked spasm was significantly lower than other vessels and more than 90% of patients had multiple spasms.
Collapse
|
|
40
|
Saito Y, Kitahara H, Shoji T, Tokimasa S, Nakayama T, Sugimoto K, Fujimoto Y, Kobayashi Y. Intracoronary Acetylcholine Provocation Testing – Omission of the 20-µg Dose Is Feasible in Patients Without Coronary Artery Spasm in the Other Coronary Artery –. Circ J 2016; 80:1820-3. [DOI: 10.1253/circj.cj-16-0344] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Yuichi Saito
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine
| | - Hideki Kitahara
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine
| | - Toshihiro Shoji
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine
| | - Satoshi Tokimasa
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine
| | - Takashi Nakayama
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine
| | - Kazumasa Sugimoto
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine
| | - Yoshihide Fujimoto
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine
| | - Yoshio Kobayashi
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine
| |
Collapse
|
|
41
|
Sueda S, Miyoshi T, Sasaki Y, Sakaue T, Habara H, Kohno H. Gender differences in sensitivity of acetylcholine and ergonovine to coronary spasm provocation test. Heart Vessels 2014; 31:322-9. [PMID: 25539623 DOI: 10.1007/s00380-014-0614-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 12/01/2014] [Indexed: 12/13/2022]
Abstract
We examined the sex difference concerning the coronary artery response between ACh and ER in this study. We already reported the difference of coronary response between acetylcholine (ACh) and ergonovine (ER). We performed both ACh and ER tests of 461 patients (male 294 patients, female 167 patients, mean age 64.4 ± 11.3 years) during 23 years. Positive coronary spasm was defined as >99 % transient luminal narrowing with usual chest pain and/or ischemic ECG changes. Firstly, ACh was administered in incremental doses of 20/50/(80) μg into the RCA and 20/50/100/(200) μg into the LCA over 20 s. Secondly, ER was administered in a total dose of 40 μg into the RCA and of 64 μg into the LCA over 2-4 min. Intracoronary injection of ACh and ER provoked spasm in 221 patients consisting of 160 male patients and 61 female patients. In female patients, the spasm provoked by ACh was almost perfect except in two patients (59 patients, 96.7 %), while ER provoked spasm in only 20 patients (32.8 %). In male patients, provoked spasm by ACh (129 patients, 80.6 %) was significantly higher than ER (97 patients, 60.6 %). As a spasm provocation test, ACh is more sensitive than ER in both sexes and especially in females. We may select two pharmacological agents by sex differences to provoke coronary artery spasm in the cardiac catheterization laboratory in the future.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan.
| | - Toru Miyoshi
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan
| | - Ysuhiro Sasaki
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan
| | - Tomoki Sakaue
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan
| | - Hirokazu Habara
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan
| | - Hiroaki Kohno
- Department of Cardiology, Ehime Prefectural Niihama Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan
| |
Collapse
|
|
42
|
Sueda S, Miyoshi T, Sasaki Y, Ohshima K, Sakaue T, Habara H, Kohno H. Complete definite positive spasm on acetylcholine spasm provocation tests: comparison of clinical positive spasm. Heart Vessels 2014; 31:143-51. [PMID: 25366988 DOI: 10.1007/s00380-014-0595-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Accepted: 10/17/2014] [Indexed: 02/07/2023]
Abstract
In the clinical grounds, patients with ≥90 % luminal narrowing during acetylcholine (ACh) testing had variable response. We investigated ischemic findings and chest symptoms in patients with ≥90 % luminal narrowing when performing ACh tests, retrospectively. We performed 763 ACh tests over 13 years (2001-2013). We analyzed chest symptoms and positive ischemic ECG changes during ACh tests. More than 90 % luminal narrowing was found in 441 patients (57.8 %) including 355 patients in the right coronary artery (RCA) and 363 patients in the left coronary artery (LCA). Chest symptom was observed in 386 patients (87.5 %) including 293 patients in the RCA and 304 patients in the LCA. ST elevation was found in 161 patients including 110 in the RCA and 85 patients in the LCA, while ST depression was recognized in 146 patients including 119 patients in the RCA and 117 patients in the LCA. Three quarter of patients with ≥90 % luminal narrowing had significant ischemic ECG changes, whereas two-third of patients with ≥90 % luminal narrowing complained usual chest pain accompanied with significant ischemic ECG changes. Unusual chest symptom was complained in 7.3 % patients with ≥90 % luminal narrowing. Neither chest symptom nor ECG changes were found in 30 patients (6.8 %) with ≥90 % luminal narrowing. A third of these patients had ischemic findings on non-invasive tests before catheterization and six patients had subtotal or total occlusion. We should realize some limitation to define positive coronary spasm based on the ischemic ECG change and chest symptom during ACh tests.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama City, Ehime Prefecture, 792-0042, Japan.
| | - Toru Miyoshi
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama City, Ehime Prefecture, 792-0042, Japan
| | - Yasuhiro Sasaki
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama City, Ehime Prefecture, 792-0042, Japan
| | - Kousei Ohshima
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama City, Ehime Prefecture, 792-0042, Japan
| | - Tomoki Sakaue
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama City, Ehime Prefecture, 792-0042, Japan
| | - Hirokazu Habara
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama City, Ehime Prefecture, 792-0042, Japan
| | - Hiroaki Kohno
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama City, Ehime Prefecture, 792-0042, Japan
| |
Collapse
|
|
43
|
Sueda S, Miyoshi T, Sasaki Y, Sakaue T, Habara H, Kohno H. Safety and optimal protocol of provocation test for diagnosis of multivessel coronary spasm. Heart Vessels 2014; 31:137-42. [PMID: 25366987 DOI: 10.1007/s00380-014-0591-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Accepted: 10/03/2014] [Indexed: 01/01/2023]
Abstract
We examined the safety of acetylcholine (ACh) and ergonovine (ER) tests retrospectively and investigated the optimal protocol of provocation test for diagnosis of multivessel coronary spasm. We performed 1546 ACh tests and 1114 ER tests during 23 years. ACh was injected in incremental doses of 20/50/80 μg into the right coronary artery (RCA) and of 20/50/100/200 μg into the left coronary artery (LCA) over 20 s. ER was administered in total doses of 40 μg into the RCA and of 64 μg into the LCA over 2-4 min. When a coronary spasm was induced and did not resolve spontaneously within 3 min after the completion of ACh/ER injection, or when hemodynamic instability due to coronary spasms occurred, 2.5-5.0 mg of nitrate was administered into the responsible vessel. To relive provoked spasm, it is necessary to administer nitrate in 31 cases by ACh and in 76 cases by ER (2.0 vs. 6.8 %, p < 0.01) before another vessel attempts. Multivessel spasms were often observed in LCA testing than in RCA testing on both agents [ACh: 78.6 % (11/14) vs. 11.8 % (2/17), p < 0.001, ER: 37.8 % (14/37) vs. 20.5 % (8/39), ns]. Even after the administration of nitrates, positive coronary spasm was obtained in 21.1 % by ACh and 52.9 % by ER tests on another coronary artery. No irreversible complications were recognized on both tests. We should firstly perform spasm provocation tests in the LCA and we may be able to diagnose another vessel spasm by performing the complete spasm provocation tests after the administration of nitrates to relieve provoked spasm in the first attempt.
Collapse
Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan.
| | - Toru Miyoshi
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan
| | - Yasuhiro Sasaki
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan
| | - Tomoki Sakaue
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan
| | - Hirokazu Habara
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan
| | - Hiroaki Kohno
- Department of Cardiology, Ehime Niihama Prefectural Hospital, Hongou 3 choume 1-1, Niihama, Ehime, 792-0042, Japan
| |
Collapse
|