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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.
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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
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Wang J, Hu Y, Yang X, Xu R, Chen Z, Wang Z, Ma L, Zhang F, Leng X, Ge J, Xiang J, Li C. A Novel Angiography-Derived Computational Coronary Flow Reserve to Evaluate Non-Obstructive Coronary Artery Disease. J Cardiovasc Transl Res 2025:10.1007/s12265-025-10608-z. [PMID: 40388093 DOI: 10.1007/s12265-025-10608-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 03/19/2025] [Indexed: 05/20/2025]
Abstract
Coronary flow reserve (CFR) is a key parameter for risk stratification in coronary artery disease but is limited by high cost, prolonged procedure time, and suboptimal reproducibility. We proposed a novel angiography-based method (Angio-CFR) to overcome these challenges and assessed its diagnostic performance. 107 consecutive patients underwent invasive coronary angiography with thermodilution-derived CFR (CFRthermo) were prospectively enrolled. Flow velocity at hyperemia and rest was estimated from angiographic images, and Angio-CFR was calculated as their ratio. Angio-CFR correlated well with CFRthermo (r = 0.72, p < 0.001), and showed good discrimination of CFRthermo < 2.5 (AUC = 0.879, p < 0.001) with an optimal cut-off of 2.5. The accuracy, sensitivity, and specificity of Angio-CFR were 81.71%, 83.33%, and 81.25%, respectively. Angio-CFR provides a pressure-wire-free method for coronary function assessment, demonstrating promising diagnostic accuracy and offering a more accessible approach for CFR measurement in clinical practice.
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Affiliation(s)
- Jingpu Wang
- Department of Cardiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Yumeng Hu
- Arteryflow Research and Development Center for Intelligent Diagnosis and Treatment of Cardiovascular and Cerebrovascular Diseases, 459 Qianmo Road, Hangzhou, 310051, China
| | - Xinyi Yang
- Arteryflow Research and Development Center for Intelligent Diagnosis and Treatment of Cardiovascular and Cerebrovascular Diseases, 459 Qianmo Road, Hangzhou, 310051, China
| | - Rende Xu
- Department of Cardiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Zhangwei Chen
- Department of Cardiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Zhe Wang
- Department of Cardiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Leilei Ma
- Department of Cardiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Feng Zhang
- Department of Cardiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Xiaochang Leng
- Arteryflow Research and Development Center for Intelligent Diagnosis and Treatment of Cardiovascular and Cerebrovascular Diseases, 459 Qianmo Road, Hangzhou, 310051, China
| | - Junbo Ge
- Department of Cardiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Jianping Xiang
- Arteryflow Research and Development Center for Intelligent Diagnosis and Treatment of Cardiovascular and Cerebrovascular Diseases, 459 Qianmo Road, Hangzhou, 310051, China.
| | - Chenguang Li
- Department of Cardiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
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Otsuki H, Yoshida A, Pargaonkar VS, Takahashi K, Honda Y, Fitzgerald P, Schnittger I, Tremmel JA. Comparison of Coronary Physiological Indices in Identifying Functionally Significant Myocardial Bridges in ANOCA. Circ Cardiovasc Interv 2025:e014824. [PMID: 40365677 DOI: 10.1161/circinterventions.124.014824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 03/26/2025] [Indexed: 05/15/2025]
Abstract
BACKGROUND A functionally significant myocardial bridge (MB) is an important cause of angina with nonobstructive coronary arteries. However, distinguishing a functionally significant versus incidental MB remains challenging. Resting and hyperemic intracoronary functional indices are available, but no studies have compared their diagnostic performance in MBs. METHODS We prospectively studied 64 patients with angina and nonobstructive coronary arteries, all of whom had an MB confirmed by intravascular ultrasound. We evaluated the diagnostic performance of instantaneous wave-free ratio (iFR) and resting full-cycle ratio (RFR) under Dobutamine stress, with Dobutamine diastolic fractional flow reserve (dFFR) as a reference standard. Dobutamine iFR and Dobutamine RFR were assessed in the first 18 patients, while only Dobutamine RFR was assessed in the remaining 46. Dobutamine dFFR ≤0.76 was considered indicative of a functionally significant MB. RESULTS There was a strong correlation between Dobutamine iFR (R2=0.67, P<0.001) and Dobutamine RFR (R2=0.80, P<0.001) with Dobutamine dFFR. Receiver operating characteristics curve analysis to identify the cutoff for Dobutamine dFFR ≤0.76 was 0.81 for Dobutamine iFR (area under the curve 0.961) and 0.76 for Dobutamine RFR (area under the curve 0.996). The diagnostic accuracy of Dobutamine iFR was 94.4%, with a sensitivity of 100% and specificity of 85.7%. For Dobutamine RFR, the diagnostic accuracy was 96.9%, with a sensitivity of 95.8% and specificity of 100%. CONCLUSIONS In patients with angina and nonobstructive coronary arteries and an MB confirmed by intravascular ultrasound, Dobutamine iFR and Dobutamine RFR may serve as alternatives to Dobutamine dFFR in identifying a functionally significant MB, with Dobutamine RFR having superior diagnostic accuracy.
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Affiliation(s)
- Hisao Otsuki
- Division of Cardiovascular Medicine, Stanford University School of Medicine, CA
| | - Akihiro Yoshida
- Division of Cardiovascular Medicine, Stanford University School of Medicine, CA
| | | | - Kuniaki Takahashi
- Division of Cardiovascular Medicine, Stanford University School of Medicine, CA
| | - Yasuhiro Honda
- Division of Cardiovascular Medicine, Stanford University School of Medicine, CA
| | - Peter Fitzgerald
- Division of Cardiovascular Medicine, Stanford University School of Medicine, CA
| | - Ingela Schnittger
- Division of Cardiovascular Medicine, Stanford University School of Medicine, CA
| | - Jennifer A Tremmel
- Division of Cardiovascular Medicine, Stanford University School of Medicine, CA
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Tjoe B, Pacheco C, Suppogu N, Samuels B, Rezaeian P, Tamarappoo B, Berman DS, Sharif B, Nelson M, Anderson RD, Petersen J, Pepine CJ, Thomson LE, Merz CNB, Wei J. Intracoronary acetylcholine for vasospasm provocation in women with ischemia and no obstructive coronary artery disease. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2025; 53:100527. [PMID: 40182421 PMCID: PMC11964566 DOI: 10.1016/j.ahjo.2025.100527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 02/21/2025] [Accepted: 03/17/2025] [Indexed: 04/05/2025]
Abstract
Objectives To evaluate the utility of higher dose intracoronary acetylcholine (ACh) during invasive coronary function testing (CFT) in women with suspected ischemia and no obstructive coronary artery disease (INOCA) for detection of epicardial vasospasm, relation to quality of life (QoL) and the presence of scar by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMRI). Background CFT is an established method for diagnosis of coronary microvascular dysfunction (CMD). The utility of epicardial vasospasm provocation testing with higher dose ACh infusion is not fully understood. Methods Women with suspected INOCA undergoing invasive CFT were enrolled in the Women's Ischemia Syndrome Evaluation-Pre-Heart Failure with Preserved Ejection Fraction (WISE Pre-HFpEF) study (NCT03876223). Incremental infusions of 0.364, 36.4 μg and 108 μg ACh were used for vasospasm provocation. Vasospasm was defined as ≥75 % artery diameter reduction compared to post-nitroglycerin diameter and related to QoL and LGE on CMRI. Results Among 73 women (56 ± 11 years), epicardial vasospasm was detected in 17 (23 %). Among women with vasospasm, the vast majority (94 %) had coronary endothelial dysfunction and few (12 %) had other abnormal CFT measures. Those with vasospasm had more nocturnal angina symptoms, calcium channel blocker use, poorer QoL (all p = 0.001) and disease perception (p = 0.02) than those without. LGE scar by CMRI was not associated with vasospasm (p = 0.22). Conclusions Among women with suspected INOCA, intracoronary Ach spasm testing provoked epicardial vasospasm in one fourth. Women with epicardial vasospasm overwhelmingly had concomitant endothelial dysfunction, worse QoL but not more frequent myocardial scar on CMRI.
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Affiliation(s)
- Benita Tjoe
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Christine Pacheco
- Hôpital Pierre-Boucher, Centre intégré de santé et de services sociaux de la Montérégie-Est, Longueuil, QC, Canada
- Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Nissi Suppogu
- Department of Cardiology, University of California Irvine School of Medicine, Orange, CA, USA
| | - Bruce Samuels
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Panteha Rezaeian
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Balaji Tamarappoo
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Daniel S. Berman
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Behzad Sharif
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Indiana University School of Medicine, Indianapolis, USA
| | - Michael Nelson
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Kinesiology, University of Texas, Arlington, USA
| | | | | | | | - Louise E.J. Thomson
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - C. Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Janet Wei
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Bergamaschi L, De Vita A, Villano A, Tremamunno S, Armillotta M, Angeli F, Belmonte M, Paolisso P, Foà A, Gallinoro E, Polimeni A, Sucato V, Morrone D, Tuttolomondo D, Pavon AG, Guglielmo M, Gaibazzi N, Mushtaq S, Perrone Filardi P, Indolfi C, Picano E, Pontone G, Lanza GA, Pizzi C. Non-invasive imaging assessment in angina with non-obstructive coronary arteries (ANOCA). Curr Probl Cardiol 2025; 50:103021. [PMID: 40015352 DOI: 10.1016/j.cpcardiol.2025.103021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Accepted: 02/25/2025] [Indexed: 03/01/2025]
Abstract
Due to its significant prevalence and clinical implications, angina with non-obstructive coronary arteries (ANOCA) has become a major focus in modern cardiology. In fact, diagnosing ANOCA presents a significant challenge. The final diagnosis is often difficult, delayed, and frequently necessitates an invasive assessment through coronary angiography. However, recent improvements in non-invasive cardiac imaging allow a diagnosis of ANOCA using a combination of clinical evaluation, anatomical coronary imaging, and functional testing. This narrative review aims to critically assess various non-invasive diagnostic methods and propose a multimodal approach to diagnose ANOCA and tailor appropriate treatments.
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Affiliation(s)
- Luca Bergamaschi
- Department of Medical and Surgical Sciences - DIMEC; Alma Mater Studiorum, University of Bologna, Bologna, Italy; Cardiovascular Division, Morgagni-Pierantoni University Hospital, Forlì, Italy
| | - Antonio De Vita
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Angelo Villano
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Saverio Tremamunno
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Matteo Armillotta
- Department of Medical and Surgical Sciences - DIMEC; Alma Mater Studiorum, University of Bologna, Bologna, Italy; Cardiovascular Division, Morgagni-Pierantoni University Hospital, Forlì, Italy
| | - Francesco Angeli
- Department of Medical and Surgical Sciences - DIMEC; Alma Mater Studiorum, University of Bologna, Bologna, Italy; Cardiovascular Division, Morgagni-Pierantoni University Hospital, Forlì, Italy
| | - Marta Belmonte
- Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy
| | - Pasquale Paolisso
- Division of University Cardiology, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy
| | - Alberto Foà
- Department of Medical and Surgical Sciences - DIMEC; Alma Mater Studiorum, University of Bologna, Bologna, Italy; Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliera-Universitaria di Bologna; Bologna; Italy
| | - Emanuele Gallinoro
- Division of University Cardiology, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy
| | - Alberto Polimeni
- Division of Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.; Cardiovascular Research Center, Magna Graecia University, Catanzaro, Italy
| | - Vincenzo Sucato
- Division of Cardiology, University Hospital Paolo Giaccone, Via del Vespro 129, 90100 Palermo, Italy
| | - Doralisa Morrone
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine-Cardiology Division, University of Pisa, Italy
| | - Domenico Tuttolomondo
- Department of Cardiology, Parma University Hospital, Via Gramsci 14, Parma, 43126, Italy
| | - Anna Giulia Pavon
- Department of Cardiology, Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Via Tesserete, 48, 6900 Lugano, Switzerland
| | - Marco Guglielmo
- Department of Cardiology, Division of Heart and Lungs, Utrecht University Medical Center, Utrecht, The Netherlands
| | - Nicola Gaibazzi
- Department of Cardiology, Parma University Hospital, Via Gramsci 14, Parma, 43126, Italy
| | - Saima Mushtaq
- Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino IRCCS, Milan, Italy
| | | | - Ciro Indolfi
- Division of Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - Eugenio Picano
- Cardiology Clinic, University Center Serbia, Medical School, University of Belgrade, Serbia
| | - Gianluca Pontone
- Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino IRCCS, Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | - Gaetano Antonio Lanza
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Cardiothoracic Sciences, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Carmine Pizzi
- Department of Medical and Surgical Sciences - DIMEC; Alma Mater Studiorum, University of Bologna, Bologna, Italy; Cardiovascular Division, Morgagni-Pierantoni University Hospital, Forlì, Italy.
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6
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Manolis AJ, Collins P, López-Sendón J. Diagnosing and treating stable angina: a contemporary approach for practicing physicians. Future Cardiol 2025; 21:291-303. [PMID: 40116861 PMCID: PMC11980508 DOI: 10.1080/14796678.2025.2479970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 03/12/2025] [Indexed: 03/23/2025] Open
Abstract
Longer life expectancy and advancements in coronary artery disease management have improved life expectancy and survival, increasing the prevalence of chronic coronary syndromes (CCS). Angina is a common symptom in patients with CCS but remains underdiagnosed and undertreated. Contemporary guidelines provide detailed information on diagnosing and treating angina based on evidence and expert consensus; however, their extensive nature may hinder uptake by non-specialists. This review presents a practical approach to diagnosing stable angina, followed by the three pillars of CCS management: 1) healthy lifestyle including appropriate exercise, diet, and avoiding toxic habits; 2) optimal medical therapy, including treatment recommended to prevent cardiovascular events and drugs for the control of myocardial ischemia and angina tailored to the patient's comorbidities; and 3) myocardial revascularization when indicated. This approach may be useful for practicing physicians but is not intended to substitute more detailed and authoritative documents. Checklists are proposed to help focus patient-physician interactions and make follow-up visits more efficient. This approach seeks to increase the proportion of correct angina diagnoses and patients receiving evidence-based treatments, emphasizing the importance of patient education, managing residual angina, and reducing cardiovascular risk. We include reference to the recently published 2024 ESC guidelines on chronic coronary syndromes.
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Affiliation(s)
| | - Peter Collins
- National Heart & Lung Institute, Imperial College London and Royal Brompton Hospital, London, UK
| | - José López-Sendón
- Cardiology Department, IdiPaz Research Institute, Hospital Universitario La Paz, Universidad Autonoma de Madrid, Madrid, Spain
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7
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Benedetti A, Castaldi G, Vermeersch P, Wilgenhof A, Convens C, Scott B, Verheye S, Agostoni P, Zivelonghi C. Clinical implications of coronary microvascular dysfunction in patients with non-obstructive coronary artery disease and role of the thermodilution method. Minerva Cardiol Angiol 2025; 73:23-37. [PMID: 36939733 DOI: 10.23736/s2724-5683.23.06289-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2023]
Abstract
More than 60% of patients undergoing coronary angiography present no coronary artery disease (CAD). Angina and myocardial ischemia are classically determined by epicardial vascular obstruction, but coronary microvascular dysfunction (CMD) may also represent a possible cause for these phenomena. Two endotypes of CMD have been recognized, with two different pathophysiological mechanisms: structural CMD, characterized by low coronary flow reserve (CFR) and high microvascular resistance (MVR) values; and functional CMD, characterized by low CFR and normal MVR values. According to the present data, almost half of patients with non-obstructive CAD have shown signs of CMD. For this reason, further investigations for microvascular function assessment should be considered when evaluating no-CAD patients complaining of angina or presenting signs of myocardial ischemia. The thermodilution method is currently becoming a widespread invasive technique due to its feasibility and high reproducibility for coronary physiology evaluation. Furthermore, a recently introduced technique - called continuous thermodilution - allows for direct measurement of absolute coronary flow and resistances. The role of this brand-new technique in the clinical scenario is however still to be fully investigated and its use is at present limited to research purposes only. Among no-CAD patients, both structural and functional CMD are related to a worse prognosis in term of mortality and major adverse cardiovascular events (MACE). In this review, we will discuss the present evidence supporting the definition, prevalence and clinical implication of the different forms of CMD and the technical aspects of its invasive assessment.
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Affiliation(s)
- Alice Benedetti
- HartCentrum, Antwerpen Hospital Network (ZNA) Middelheim, Antwerp, Belgium
| | - Gianluca Castaldi
- HartCentrum, Antwerpen Hospital Network (ZNA) Middelheim, Antwerp, Belgium
| | - Paul Vermeersch
- HartCentrum, Antwerpen Hospital Network (ZNA) Middelheim, Antwerp, Belgium
| | - Adriaan Wilgenhof
- HartCentrum, Antwerpen Hospital Network (ZNA) Middelheim, Antwerp, Belgium
| | - Carl Convens
- HartCentrum, Antwerpen Hospital Network (ZNA) Middelheim, Antwerp, Belgium
| | - Benjamin Scott
- HartCentrum, Antwerpen Hospital Network (ZNA) Middelheim, Antwerp, Belgium
| | - Stefan Verheye
- HartCentrum, Antwerpen Hospital Network (ZNA) Middelheim, Antwerp, Belgium
| | | | - Carlo Zivelonghi
- HartCentrum, Antwerpen Hospital Network (ZNA) Middelheim, Antwerp, Belgium -
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8
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Daba M, Bineyam D, Yohannes I, Yohannes B, Waktola R, Bedada E. Myocardial Bridging, Unusual Cause of Myocardial Infarction; Case Report and Review of Literature. Clin Case Rep 2025; 13:e70055. [PMID: 39802361 PMCID: PMC11720737 DOI: 10.1002/ccr3.70055] [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: 07/03/2024] [Revised: 11/13/2024] [Accepted: 12/12/2024] [Indexed: 01/16/2025] Open
Abstract
Myocardial bridging is a common coronary anomaly. Although it is considered to be a benign condition, it can rarely be complicated by myocardial infarction. Clinicians should be suspicious of myocardial bridging as an etiology of myocardial infarction when other more common etiologies have been excluded. High resolution CT angiography is the gold standard for diagnostic evaluation, with the length and depth of the bridge, and response to conservative therapies guiding clinical decision making on surgical correction. Myocardial bridging is a congenital coronary anomaly in which the coronary arteries pass through the heart muscle rather than lying on its surface. It is typically a benign condition, and most patients are asymptomatic. However, some may experience symptoms of angina. In rare cases, patients can present with myocardial ischemia or infarction. In this report, we present the case of a 38-year-old female who presented with a 2-month history of chest pain. Further evaluation with coronary computed tomography angiography (CCTA) revealed myocardial bridging. Subsequently, she developed a myocardial infarction, a rare complication of this condition. We discuss this uncommon complication of a common anomaly.
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Affiliation(s)
- Merga Daba
- Department of Internal MedicineCollege of Health Sciences, Addis Ababa UniversityAddis AbabaEthiopia
| | - Dawit Bineyam
- Department of Internal MedicineCollege of Health Sciences, Addis Ababa UniversityAddis AbabaEthiopia
| | - Ibraist Yohannes
- Department of Internal MedicineCollege of Health Sciences, Addis Ababa UniversityAddis AbabaEthiopia
| | - Beniam Yohannes
- Department of Internal MedicineCollege of Health Sciences, Addis Ababa UniversityAddis AbabaEthiopia
| | - Rabirra Waktola
- Department of Radiology and MRTSt. Paul Hospital Millennium Medical CollegeAddis AbabaEthiopia
| | - Eshetu Bedada
- Cardiology Unit, Department of Internal MedicineCollege of Health Sciences, Addis Ababa UniversityAddis AbabaEthiopia
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9
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Kest M, Ágoston A, Szabó GT, Kiss A, Üveges Á, Czuriga D, Komócsi A, Hizoh I, Kőszegi Z. Angiography-based coronary microvascular assessment with and without intracoronary pressure measurements: a systematic review. Clin Res Cardiol 2024; 113:1609-1621. [PMID: 37987840 PMCID: PMC11579095 DOI: 10.1007/s00392-023-02338-6] [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: 08/18/2023] [Accepted: 10/30/2023] [Indexed: 11/22/2023]
Abstract
BACKGROUND In recent years, several indices have been proposed for quantifying coronary microvascular resistance. We intended to conduct a comprehensive review that systematically evaluates indices of microvascular resistance derived from angiography. OBJECTIVE The objective of this study was to identify and analyze angiography-derived indices of microvascular resistance that have been validated against an invasive reference method. We aimed to compare their limits of agreement with their reference methods and explore their advantages and inherent limitations. METHODS AND RESULTS We searched PubMed from inception until 2022 for studies on different techniques for quantifying microvascular resistance. Seven studies met the inclusion criteria. Five studies included techniques that applied calculations based solely on invasive angiography, and were validated against invasively measured thermodilution-derived index of microvascular resistance. The remaining two studies combined angiography with invasively measured intracoronary pressure data, and were validated against invasive Doppler measurements. We converted the ± 1.96 standard deviation limits of agreement with the reference method from the seven studies into percentages relative to the cut-off value of the reference method. The lower limits of agreement for angiography-based methods ranged from - 122 to - 60%, while the upper limits ranged from 74 to 135%. The range of the limits of agreement was considerably lower for the two combined angiography- and pressure-based methods, standing at - 52 to 60% and - 25 to 27%. CONCLUSION Our findings suggest that combined angiography- and pressure-based methods provide a more reliable assessment of microvascular resistance compared to methods relying solely on angiography.
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Affiliation(s)
- Michael Kest
- Szabolcs-Szatmár-Bereg County Hospitals and University Teaching Hospital, Nyíregyháza, Hungary
| | - András Ágoston
- Szabolcs-Szatmár-Bereg County Hospitals and University Teaching Hospital, Nyíregyháza, Hungary
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary
| | - Gábor Tamás Szabó
- Division of Cardiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary
- Center for Biomedical Research and Translational Surgery, Medical University Vienna, Vienna, Austria
| | - Attila Kiss
- Center for Biomedical Research and Translational Surgery, Medical University Vienna, Vienna, Austria
| | - Áron Üveges
- Szabolcs-Szatmár-Bereg County Hospitals and University Teaching Hospital, Nyíregyháza, Hungary
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary
| | - Dániel Czuriga
- Division of Cardiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary
| | - András Komócsi
- Heart Institute, Medical School, University of Pécs, Pécs, Hungary
| | - István Hizoh
- Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Zsolt Kőszegi
- Szabolcs-Szatmár-Bereg County Hospitals and University Teaching Hospital, Nyíregyháza, Hungary.
- Division of Cardiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary.
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10
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Mejia-Renteria H, Shabbir A, Nuñez-Gil IJ, Macaya F, Salinas P, Tirado-Conte G, Nombela-Franco L, Jimenez-Quevedo P, Gonzalo N, Fernandez-Ortiz A, Escaned J. Feasibility and Improved Diagnostic Yield of Intracoronary Adenosine to Assess Microvascular Dysfunction With Bolus Thermodilution. J Am Heart Assoc 2024; 13:e035404. [PMID: 39508144 DOI: 10.1161/jaha.124.035404] [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: 03/08/2024] [Accepted: 10/08/2024] [Indexed: 11/08/2024]
Abstract
BACKGROUND Bolus thermodilution and intravenous adenosine are established methods for coronary microcirculatory assessment. Yet, its adoption remains low, partly due to procedural time and patient discomfort associated with intravenous adenosine. We investigated differences between intracoronary and intravenous adenosine using bolus thermodilution in terms of microcirculatory indices, procedural time, and side effects associated with adenosine in patients with myocardial ischemia and nonobstructive coronary arteries. METHODS AND RESULTS In this prospective, observational study, 102 patients with suspected myocardial ischemia and nonobstructive coronary arteries underwent measurements of mean transit time, coronary flow reserve, index of microcirculatory resistance, procedure time and patient tolerability with low-dose intracoronary adenosine, high-dose intracoronary adenosine (HDIC), and intravenous adenosine. HDIC induced greater hyperemia compared with low-dose intracoronary IC adenosine and intravenous adenosine with a shorter hyperemic mean transit time, P<0.0001. Coronary flow reserve was higher and index of microcirculatory resistance lowest with HDIC, compared with low-dose intracoronary IC adenosine and intravenous adenosine, P<0.05. Low coronary flow reserve was downgraded from 21% with intravenous adenosine to 10% with HDIC adenosine (P=0.031); high index of microcirculatory resistance was downgraded from 23% with intravenous adenosine to 14% with HDIC (P=0.098). Intracoronary adenosine was associated with lower procedural times (P<0.0001). More patients experienced chest pain with intravenous adenosine (P<0.01) and the chest pain intensity was higher compared with intracoronary adenosine (P<0.0001). CONCLUSIONS In patients with suspected myocardial ischemia and nonobstructive coronary arteries undergoing coronary microcirculatory assessment with bolus thermodilution, the use of HDIC compared with intravenous adenosine was associated with enhanced induction of hyperemia. The use of intracoronary adenosine allowed for a shorter procedure time and was better tolerated. REGISTRATION+ URL: clinicaltrials.gov; Unique Identifier: NCT04827498.
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Affiliation(s)
- Hernan Mejia-Renteria
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
| | - Asad Shabbir
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
| | - Ivan J Nuñez-Gil
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
| | - Fernando Macaya
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
| | - Pablo Salinas
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
| | - Gabriela Tirado-Conte
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
| | - Luis Nombela-Franco
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
| | - Pilar Jimenez-Quevedo
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
| | - Nieves Gonzalo
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
| | - Antonio Fernandez-Ortiz
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
| | - Javier Escaned
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
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11
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Cigarroa N, Latif N, Maayah M, Khokhar A, Kunnirickal S, Schwann A, Maciejewski KR, Odanovic N, Mazure CM, Spatz E, Pfau S, Lansky A, Shah SM. Diagnostic Yield and Clinical Utility of Coronary Angiography Versus Coronary Function Testing in Women With Angina and Nonobstructive Coronary Arteries. J Am Heart Assoc 2024; 13:e035852. [PMID: 39291500 PMCID: PMC11681466 DOI: 10.1161/jaha.124.035852] [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: 05/30/2024] [Accepted: 08/20/2024] [Indexed: 09/19/2024]
Abstract
BACKGROUND Approximately 50% of women referred for invasive coronary angiography have angina and nonobstructive coronary arteries, which includes coronary microvascular dysfunction, vasospastic angina, and other vasomotor disorders. We sought to determine the real-world diagnostic yield of invasive coronary angiography and coronary function testing in women with angina and nonobstructive coronary arteries. METHODS AND RESULTS From 2018 to 2023, we enrolled 198 women who underwent either coronary angiography (CA) alone (n=99) or coronary function testing (CFT; n=99). Mean±SD age was 62±10 years (CA alone) compared with 57±10 years (CFT). Coronary angiography was interpreted as nonobstructive coronary artery disease more frequently after CA alone (79% versus 52%). Of the women who underwent CFT, 82% (N=81) were found to have vasomotor disorders, including coronary microvascular dysfunction (27%), vasospastic angina (32%), mixed coronary microvascular dysfunction/vasospastic angina (16%), endothelial dysfunction (10%; without spasm), elevated resting flow (2%), or symptomatic myocardial bridging (4%). Compared with women undergoing CA alone, medications were changed more frequently after CFT at 24 hours (41% versus 65%; P=0.001) and between 24 hours and 30 days (30% versus 44%; P=0.04) with intensification of antianginal therapy (79% versus 92%; P<0.0001) and increased use of calcium channel blockers (36% versus 63%; P<0.0001). CONCLUSIONS Our findings demonstrate that women presenting with suspected ischemic heart disease undergoing CA alone only received an anatomic diagnosis, whereas >80% of women undergoing CFT received a specific diagnosis of a coronary vasomotor disorder and greater intensification of antianginal therapy.
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Affiliation(s)
| | - Nida Latif
- Section of Cardiovascular Medicine, Department of Internal MedicineYale School of MedicineNew HavenCT
| | - Marah Maayah
- Department of Psychiatry and Women’s Health Research at YaleYale University School of MedicineNew HavenCT
| | | | | | | | | | - Natalija Odanovic
- Yale New Haven Hospital New HavenNew HavenCT
- Institute for Cardiovascular Diseases “Dedinje”BelgradeSerbia
| | - Carolyn M. Mazure
- Department of Psychiatry and Women’s Health Research at YaleYale University School of MedicineNew HavenCT
| | - Erica Spatz
- Section of Cardiovascular Medicine, Department of Internal MedicineYale School of MedicineNew HavenCT
| | - Steven Pfau
- Section of Cardiovascular Medicine, Department of Internal MedicineYale School of MedicineNew HavenCT
- Veterans Affairs Connecticut Healthcare SystemWest HavenCT
| | - Alexandra Lansky
- Section of Cardiovascular Medicine, Department of Internal MedicineYale School of MedicineNew HavenCT
| | - Samit M. Shah
- Section of Cardiovascular Medicine, Department of Internal MedicineYale School of MedicineNew HavenCT
- Veterans Affairs Connecticut Healthcare SystemWest HavenCT
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12
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Odanović N, Schwann AN, Zhang Z, Kapadia SS, Kunnirickal SJ, Parise H, Tirziu D, Ilic I, Lansky AJ, Pietras CG, Shah SM. Long-term outcomes of ischaemia with no obstructive coronary artery disease (INOCA): a systematic review and meta-analysis. Open Heart 2024; 11:e002852. [PMID: 39353703 PMCID: PMC11448144 DOI: 10.1136/openhrt-2024-002852] [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: 07/17/2024] [Accepted: 09/04/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND The prognosis of myocardial ischaemia with no obstructive coronary artery disease (INOCA) and its underlying vasomotor disorders, vasospastic angina (VSA) and microvascular angina (MVA), is not well defined. The aim of this study was to perform a systematic review and meta-analysis of studies evaluating the long-term prognosis of patients with INOCA. METHODS We included studies evaluating the prognosis of patients with INOCA published between January 1984 and August 2023 in Medline, Embase, Web of Science and Cochrane databases. Studies were selected if they included patients who fulfilled the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria for either possible or definitive VSA or MVA. The primary outcomes were composite of all-cause death and myocardial infarction (MI), and major adverse cardiovascular event (MACE) at annual intervals up to 5-year follow-up. The incidence of primary outcomes for INOCA, each INOCA endotype and by method used to determine the diagnosis was calculated using the random effects model. RESULTS Fifty-four studies (17 302 patients) meeting the eligibility criteria were selected. The rate of all-cause death and MI with VSA was 0.7 (95% CI 0.4 to 1.0)/100 patient-years and with MVA was 1.1 (95% CI 0.7 to 1.5)/100 patient-years (p>0.05). The rate of MACE with VSA was 1.1 (95% CI 0.5 to 1.9)/100 patient-years and with MVA was 2.5 (95% CI 1.6 to 3.6)/100 patient-years (p=0.025). Patients with reduced coronary flow reserve (CFR) had higher all-cause death and MI rates than patients whose diagnosis of MVA was established based on an abnormal exercise or imaging stress test (4.7 (95% CI 2.0 to 8.4) vs 0.5 (95% CI 0.1 to 1.1) vs 1.1 (95% CI 0.5 to 2.0)/100 patient-years, p=0.001). CONCLUSIONS Overall, patients with INOCA have a low rate of MACEs, but patients with MVA, especially those with reduced CFR, have a significantly higher rate of MACE than other subgroups, although there is high heterogeneity among the included studies. PROSPERO REGISTRATION NUMBER CRD42021275070.
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Affiliation(s)
- Natalija Odanović
- Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Alexandra N Schwann
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Zhiyuan Zhang
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Sohum S Kapadia
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Steffne J Kunnirickal
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Helen Parise
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Daniela Tirziu
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Ivan Ilic
- Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia
| | - Alexandra J Lansky
- Yale Cardiovascular Research Group, Yale Medical School, New Haven, Connecticut, USA
| | - Cody G Pietras
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Samit M Shah
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
- Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA
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13
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Steinberg RS, Dragan A, Mehta PK, Toleva O. Coronary microvascular disease in women: epidemiology, mechanisms, evaluation, and treatment. Can J Physiol Pharmacol 2024; 102:594-606. [PMID: 38728748 DOI: 10.1139/cjpp-2023-0414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/12/2024]
Abstract
Coronary microvascular dysfunction (CMD) involves functional or structural abnormalities of the coronary microvasculature resulting in dysregulation of coronary blood flow (CBF) in response to myocardial oxygen demand. This perfusion mismatch causes myocardial ischemia, which manifests in patients as microvascular angina (MVA). CMD can be diagnosed non-invasively via multiple imaging techniques or invasively using coronary function testing (CFT), which assists in determining the specific mechanisms involving endothelium-independent and dependent epicardial and microcirculation domains. Unlike traditional coronary artery disease (CAD), CMD can often occur in patients without obstructive atherosclerotic epicardial disease, which can make the diagnosis of CMD difficult. Moreover, MVA due to CMD is more prevalent in women and carries increased risk of future cardiovascular events. Successful treatment of symptomatic CMD is often patient-specific risk factor and endotype targeted. This article aims to review newly identified mechanisms and novel treatment strategies for managing CMD, and outline sex-specific differences in the presentation and pathophysiology of the disease.
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Affiliation(s)
- Rebecca S Steinberg
- Emory University School of Medicine, Department of Medicine,Atlanta, GA, USA
| | - Anamaria Dragan
- Emory University School of Medicine, Department of Medicine,Atlanta, GA, USA
| | - Puja K Mehta
- Emory University School of Medicine, Department of Medicine, Division of Cardiology, Atlanta, GA, USA
| | - Olga Toleva
- Emory University School of Medicine, Department of Medicine, Division of Cardiology, Atlanta, GA, USA
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14
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Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J 2024; 45:3415-3537. [PMID: 39210710 DOI: 10.1093/eurheartj/ehae177] [Citation(s) in RCA: 502] [Impact Index Per Article: 502.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/04/2024] Open
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15
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Chandrasekhar S, Woods E, Bennett J, Newman N, McLean P, Alam M, Jneid H, Sharma S, Khawaja M, Krittanawong C. Coronary Artery Anomalies: Diagnosis & Management. Cardiol Rev 2024:00045415-990000000-00334. [PMID: 39315746 DOI: 10.1097/crd.0000000000000786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/25/2024]
Abstract
Coronary artery anomalies encompass a spectrum of congenital abnormalities affecting the origin, course, or termination of the major epicardial coronary arteries. Despite their rarity, coronary artery anomalies represent a significant burden on cardiovascular health due to their potential to disrupt myocardial blood flow and precipitate adverse cardiac events. While historically diagnosed postmortem, the widespread availability of imaging modalities has led to an increased recognition of coronary artery anomalies, particularly in adults. This review synthesizes current knowledge on the classification, mechanisms, and clinical implications of coronary anomalies, focusing on prevalent variants with significant clinical impact. We discuss strategies for medical and surgical management, as well as contemporary screening recommendations, acknowledging the evolving understanding of these anomalies. Given the breadth of possible variants and the limited data on some presentations, this review provides a framework to aid clinicians in the recognition and management of coronary anomalies, with a particular emphasis on their stratification by anatomical location. By consolidating existing knowledge and highlighting areas of uncertainty, this review aims to enhance clinical decision-making and improve outcomes for individuals with coronary anomalies.
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Affiliation(s)
- Sanjay Chandrasekhar
- From the Division of Internal Medicine, Emory University School of Medicine, Atlanta, GA
| | - Edward Woods
- From the Division of Internal Medicine, Emory University School of Medicine, Atlanta, GA
| | - Josiah Bennett
- From the Division of Internal Medicine, Emory University School of Medicine, Atlanta, GA
| | - Noah Newman
- From the Division of Internal Medicine, Emory University School of Medicine, Atlanta, GA
| | - Patrick McLean
- From the Division of Internal Medicine, Emory University School of Medicine, Atlanta, GA
| | - Mahboob Alam
- Cardiology Division, The Texas Heart Institute, Baylor College of Medicine, Houston, TX
| | - Hani Jneid
- John Sealy Distinguished Centennial Chair in Cardiology, Chief, Division of Cardiology, University of Texas Medical Branch, Houston, TX
| | - Samin Sharma
- Department of Cardiology, Mount Sinai Hospital, New York, NY
| | - Muzamil Khawaja
- Cardiology Division, Emory University School of Medicine, Atlanta, GA
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16
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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.
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Affiliation(s)
- Shozo Sueda
- Department of Cardiology, Ehime Niihama Prefectural HospitalNiihama, Japan
| | - Tomoki Sakaue
- Department of Cardiology, Yawatahama City General HospitalYawatahama, Japan
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17
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Allan TE, Mayer MM, Miner SE, Patel H, Patel AR, Balkhy HH, Paul JD, Shah AP, Nathan S, Blair JE. Prevalence of Coronary Microvascular Dysfunction and Epicardial Spasm in Patients With Angina and Myocardial Bridge. JOURNAL OF THE SOCIETY FOR CARDIOVASCULAR ANGIOGRAPHY & INTERVENTIONS 2024; 3:102196. [PMID: 39575216 PMCID: PMC11576376 DOI: 10.1016/j.jscai.2024.102196] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 05/16/2024] [Accepted: 05/30/2024] [Indexed: 11/24/2024]
Abstract
Background Myocardial bridges (MB) are prevalent but not universally associated with angina. The mechanisms linking MB and angina are poorly defined. The objective of this study was to determine the prevalence of epicardial spasm, microvascular spasm, and/or endothelium-independent coronary microvascular dysfunction (CMD) in patients with MB which might explain symptoms. Methods Patients with known MB and chest pain at the University of Chicago Medical Center between 2020-2023 were included. All patients underwent dobutamine testing with measurement of resting full-cycle ratio to determine hemodynamic significance (resting full-cycle ratio ≤0.76). Endothelium-independent CMD was defined as coronary flow reserve <2.0 or index of microvascular resistance ≥25 on adenosine testing. Microvascular spasm was defined as chest pain and electrocardiogram changes with nonischemic fractional flow reserve with acetylcholine. Epicardial spasm was defined as dynamic stenosis of >90% of the epicardial vessel or ischemic fractional flow reserve (≤0.8) with acetylcholine. Results A total of 30 patients (mean age, 47 ± 10 years; 60% female) with MB were studied. Endothelium-independent CMD, microvascular spasm, and epicardial spasm occurred commonly in 60%, 29%, and 37% of patients respectively, with 77% having at least one abnormality. The MB was hemodynamically significant in 47% of patients, and the prevalence of these coexisting conditions was not affected by hemodynamic significance. Conclusions Epicardial spasm, microvascular spasm, and endothelium-independent CMD are prevalent in patients presenting with known MB and chest pain irrespective of the hemodynamic significance of the bridge. Invasive coronary function testing may play an important role in uncovering alternative explanations for angina in patients with known MB.
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Affiliation(s)
- Tess E. Allan
- Section of Cardiology, Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois
| | - Michael M. Mayer
- Section of Cardiology, Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois
| | - Steven E.S. Miner
- Division of Cardiology, Southlake Regional Health Centre, Newmarket, Ontario, Canada
- School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Hena Patel
- Section of Cardiology, Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois
| | - Amit R. Patel
- Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia
| | - Husam H. Balkhy
- Section of Cardiology, Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois
| | - Jonathan D. Paul
- Section of Cardiology, Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois
| | - Atman P. Shah
- Section of Cardiology, Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois
| | - Sandeep Nathan
- Section of Cardiology, Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois
| | - John E.A. Blair
- Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington
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18
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Mahmoudi Hamidabad N, Kanaji Y, Ozcan I, Sara JDS, Ahmad A, Lerman LO, Lerman A. Prognostic Implications of Resistive Reserve Ratio in Patients With Nonobstructive Coronary Artery Disease With Myocardial Bridging. J Am Heart Assoc 2024; 13:e035000. [PMID: 39082414 PMCID: PMC11964029 DOI: 10.1161/jaha.124.035000] [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: 02/13/2024] [Accepted: 07/08/2024] [Indexed: 08/07/2024]
Abstract
BACKGROUND Myocardial bridging (MB) is accompanied by the dynamic extravascular compression of epicardial coronary arteries, leading to intracoronary hemodynamic disturbance with abnormal coronary flow profiles. We aimed to evaluate the prognostic implications of resistive reserve ratio (RRR), a composite measure of flow and pressure parameters that represents the vasodilatory capacity of the coronary arteries, in patients with angina with nonobstructive coronary artery disease (ANOCA) and MB, in comparison with coronary flow reserve (CFR). METHODS AND RESULTS In this retrospective cohort study, we included patients with ANOCA who underwent coronary reactivity testing, where MB was identified by transient constriction in coronary artery segments between systole and diastole. Abnormal CFR and RRR were defined as <2.5 and <2.62, respectively. Major adverse cardiac events, including cardiovascular death, stroke, myocardial infarction, heart failure, and late revascularization, served as outcomes. Among 1251 patients with ANOCA, 191 (15.3%) had MB. The prevalence of abnormal CFR or RRR was not significantly different between patients with and without MB (P=0.144 and P=0.398, respectively). Over a median follow-up time of 6.9 years, abnormal RRR predicted major adverse cardiac events in patients with MB (hazard ratio [HR], 4.38 [95% CI, 1.71-11.21]; P=0.002) and without MB (HR, 1.91 [95% CI, 1.38-2.64]; P<0.001). Abnormal CFR predicted major adverse cardiac events in patients without MB (HR, 2.15 [95% CI, 1.54-3.00]; P<0.001), whereas it was not predictive of major adverse cardiac events in patients with MB (HR, 2.29 [95% CI, 0.93-5.65]; P=0.073). CONCLUSIONS In patients with ANOCA and MB, impaired RRR was superior to impaired CFR in distinguishing patients at a higher risk of future adverse events, suggesting that RRR may serve as a risk stratification tool in patients with MB and ANOCA.
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Affiliation(s)
| | - Yoshihisa Kanaji
- Department of Cardiovascular MedicineMayo ClinicRochesterMN
- Division of Cardiovascular MedicineTsuchiura Kyodo General HospitalIbarakiJapan
| | - Ilke Ozcan
- Department of Cardiovascular MedicineMayo ClinicRochesterMN
| | | | - Ali Ahmad
- Department of Cardiovascular MedicineMayo ClinicRochesterMN
| | | | - Amir Lerman
- Department of Cardiovascular MedicineMayo ClinicRochesterMN
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19
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Maayah M, Latif N, Vijay A, Gallegos CM, Cigarroa N, Posada Martinez EL, Mazure CM, Miller EJ, Spatz ES, Shah SM. Evaluating Ischemic Heart Disease in Women: Focus on Angina With Nonobstructive Coronary Arteries (ANOCA). JOURNAL OF THE SOCIETY FOR CARDIOVASCULAR ANGIOGRAPHY & INTERVENTIONS 2024; 3:102195. [PMID: 39166160 PMCID: PMC11330936 DOI: 10.1016/j.jscai.2024.102195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/22/2024] [Accepted: 05/29/2024] [Indexed: 08/22/2024]
Abstract
Ischemic heart disease (IHD) is common in women, and cardiovascular disease is a leading cause of morbidity and mortality. While obstructive coronary artery disease is the most common form of IHD, millions of women suffer from angina with nonobstructive coronary arteries (ANOCA), an umbrella term encompassing multiple nonatherosclerotic disorders of the coronary tree. The underlying pathology leading to ischemia in these syndromes may be challenging to diagnose, leaving many women without a diagnosis despite persistent symptoms that impact quality of life and adversely affect long-term cardiovascular prognosis. In the last decade, there have been significant advances in the recognition and diagnostic evaluation of ANOCA. Despite these advances, the standard approach to evaluating suspected IHD in women continues to focus predominantly on the assessment of atherosclerotic coronary artery disease, leading to missed opportunities to accurately diagnose and treat underlying coronary vasomotor disorders. The goal of this review is to describe advances in diagnostic testing that can be used to evaluate angina in women and present a pragmatic diagnostic algorithm to guide evaluation of ANOCA in symptomatic patients. The proposed approach for the assessment of ANOCA is consistent with prior expert consensus documents and guidelines but is predicated on the medical interview and pretest probability of disease to inform a personalized diagnostic strategy.
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Affiliation(s)
- Marah Maayah
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Nida Latif
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Aishwarya Vijay
- Cardiovascular Division, John T. Milliken Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
| | - Cesia M. Gallegos
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Natasha Cigarroa
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | | | - Carolyn M. Mazure
- Department of Psychiatry and Women’s Health Research at Yale, Yale School of Medicine, New Haven, Connecticut
| | - Edward J. Miller
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Erica S. Spatz
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Center for Outcomes Research and Evaluation, Yale New Haven Health System, New Haven, Connecticut
| | - Samit M. Shah
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- VA Connecticut Healthcare System, West Haven, Connecticut
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20
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Pruthi S, Siddiqui E, Smilowitz NR. Beyond Coronary Artery Disease: Assessing the Microcirculation. Rheum Dis Clin North Am 2024; 50:519-533. [PMID: 38942582 DOI: 10.1016/j.rdc.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2024]
Abstract
Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.
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Affiliation(s)
- Sonal Pruthi
- Division of Cardiology, Department of Medicine, NYU Langone Health, 550 First Avenue, New York, NY 10016, USA
| | - Emaad Siddiqui
- Division of Cardiology, Department of Medicine, NYU Langone Health, 550 First Avenue, New York, NY 10016, USA
| | - Nathaniel R Smilowitz
- Division of Cardiology, Department of Medicine, NYU Langone Health, 550 First Avenue, New York, NY 10016, USA; Cardiology Section, Department of Medicine, VA New York Harbor Healthcare System, 423 East 23rd Street, New York, NY 10010, USA; The Leon H. Charney Division of Cardiology, NYU Langone Health, NYU School of Medicine, 423 East 23rd Street, 12-West, New York, NY 10010, USA.
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21
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Toprak K, Karataş M, Kaplangoray M, Dursun A, Taşcanov MB, Altıparmak İH, Biçer A, Demirbağ R. Comparison of the Effect of Non-HDL-C/HDL-C Ratio on Coronary Slow Flow with Other Non-Traditional Lipid Markers. ACTA CARDIOLOGICA SINICA 2024; 40:388-401. [PMID: 39045373 PMCID: PMC11261365 DOI: 10.6515/acs.202407_40(4).20240419a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 04/19/2024] [Indexed: 07/25/2024]
Abstract
Background Coronary slow flow (CSF) is a microvascular disease characterized by delayed opacification of the epicardial coronary arteries during angiography. The main pathogenesis of CSF is endothelial dysfunction caused by diffuse atherosclerosis. Dyslipidemia is one of the primary factors raising the risk of atherosclerosis. Compared to conventional lipid profiles, non-traditional lipid profiles more accurately reflect dyslipidemic status. In this work, we compared the non-high density lipoprotein-cholesterol (HDL-C)/HDL-C ratio (NHHR) with other conventional and non-conventional lipid profiles in order to determine its impact on CSF. Methods A total of 9112 subjects who underwent coronary angiography were screened retrospectively, of whom 130 subjects with CSF and 130 subjects with normal CF were included. Multivariate regression analysis was used to identify independent predictors of CSF. Additionally, in order to predict CSF, the diagnostic accuracies of NHHR and other non-traditional lipid profiles were examined. Results There were significantly higher non-traditional lipid profiles in the CSF group (all p < 0.001). Compared to other non-traditional lipid profiles, NHHR had a stronger association with thrombolysis in myocardial infarction frame count (r = 0.3593, p < 0.0001). In addition to NHHR, non-HDL-C, Castelli's risk index-II, atherogenic index of plasma, plasma glucose, dyslipidemia, smoking, and body mass index were identified as independent predictors of CSF. The ability of NHHR to detect CSF was superior to other non-traditional lipid profiles (area under the curve: 0.785; confidence interval: 0.730-0.840; p < 0.001). Conclusions NHHR was found to be a potent and reliable predictor of CSF. This indicates that NHHR can be used as a reliable biomarker for risk stratification of CSF.
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Affiliation(s)
- Kenan Toprak
- Department of Cardiology, Faculty of Medicine, Harran University, Sanliurfa
| | - Mesut Karataş
- Kartal Koşuyolu High Specialization Training and Research Hospital, Istanbul
| | | | - Ayten Dursun
- Nursing Department, Şanlıurfa Provincial Health Directorate, Sanliurfa, Turkey
| | | | | | - Asuman Biçer
- Department of Cardiology, Faculty of Medicine, Harran University, Sanliurfa
| | - Recep Demirbağ
- Department of Cardiology, Faculty of Medicine, Harran University, Sanliurfa
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22
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Ágoston A, Dorj A, Üveges Á, Tar B, Szabó GT, Barta J, Szűk T, Kest M, Méhész R, Komócsi A, Czuriga D, Csippa B, Piróth Z, Barbato E, Kőszegi Z. The pressure-derived microvascular resistance reserve and its correlation to Doppler MRR measurement-a proof of concept study. Front Cardiovasc Med 2024; 11:1322161. [PMID: 38887446 PMCID: PMC11180812 DOI: 10.3389/fcvm.2024.1322161] [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: 10/15/2023] [Accepted: 05/20/2024] [Indexed: 06/20/2024] Open
Abstract
Background Microvascular resistance reserve (MRR) is a recently introduced specific index of coronary microcirculation. MRR calculation can utilize parameters deriving from coronary flow reserve (CFR) assessment, provided that intracoronary pressure data are also available. The previously proposed pressure-bounded CFR (CFRpb) defines the possible CFR interval on the basis of resting and hyperemic pressure gradients in the epicardial vessel, however, its correlation to the Doppler wire measurement was reported to be rather poor without the correction for hydrostatic pressure. Purpose We aimed to determine the pressure-bounded coronary MRR interval with hydrostatic pressure correction according to the previously established equations of CFRpb adapted for the MRR concept. Furthermore, we also aimed to design a prediction model using the actual MRR value within the pressure-bounded interval and validate the results against the gold-standard Doppler wire technique. Methods Hydrostatic pressure between the tip of the catheter and the sensor of the pressure wire was calculated by height difference measurement from a lateral angiographic view. In the derivation cohort the pressure-bounded MRR interval (between MRRpbmin and MRRpbmax) was determined solely from hydrostatic pressure-corrected intracoronary pressure data. The actual MRR was calculated by simple hemodynamic equations incorporating the anatomical data of the three-dimensionally reconstructed coronary artery (MRRp-3D). These results were analyzed by regression analyses to find relations between the MRRpb bounds and the actual MRRp-3D. Results In the derivation cohort of 23 measurements, linear regression analysis showed a tight relation between MRRpbmax and MRRp-3D (r 2 = 0.74, p < 0.0001). Using this relation (MRRp-3D = 1.04 + 0.51 × MRRpbmax), the linear prediction of the MRR was tested in the validation cohort of 19 measurements against the gold standard Doppler wire technique. A significant correlation was found between the linearly predicted and the measured values (r = 0.54, p = 0.01). If the area stenosis (AS%) was included to a quadratic prediction model, the correlation was improved (r = 0.63, p = 0.004). Conclusions The MRR can be predicted reliably to assess microvascular function by our simple model. After the correction for hydrostatic pressure error, the pressure data during routine FFR measurement provides a simultaneous physiological assessment of the macro- and microvasculature.
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Affiliation(s)
- András Ágoston
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary
- Department of Cardiology, Szabolcs—Szatmár—Bereg Country Hospitals and University Teaching Hospital, Nyíregyháza, Hungary
| | - Azzaya Dorj
- Division of Cardiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Áron Üveges
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary
- Department of Cardiology, Szabolcs—Szatmár—Bereg Country Hospitals and University Teaching Hospital, Nyíregyháza, Hungary
| | - Balázs Tar
- Department of Cardiology, Szabolcs—Szatmár—Bereg Country Hospitals and University Teaching Hospital, Nyíregyháza, Hungary
| | - Gábor Tamás Szabó
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary
- Division of Cardiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Judit Barta
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary
- Division of Cardiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Tibor Szűk
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary
- Division of Cardiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Michael Kest
- Department of Cardiology, Szabolcs—Szatmár—Bereg Country Hospitals and University Teaching Hospital, Nyíregyháza, Hungary
| | - Réka Méhész
- Department of Cardiology, Szabolcs—Szatmár—Bereg Country Hospitals and University Teaching Hospital, Nyíregyháza, Hungary
| | | | - Dániel Czuriga
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary
- Division of Cardiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Benjámin Csippa
- Department of Hydrodynamic Systems, Budapest University of Technology and Economics, Budapest, Hungary
| | - Zsolt Piróth
- Gottsegen National Cardiovascular Center, Budapest, Hungary
| | - Emanuele Barbato
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Zsolt Kőszegi
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, Debrecen, Hungary
- Department of Cardiology, Szabolcs—Szatmár—Bereg Country Hospitals and University Teaching Hospital, Nyíregyháza, Hungary
- Division of Cardiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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23
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Shah SM, Tremmel JA, Henry TD, Smilowitz NR, Prasad M, Kobayashi Y, Henry GA, Samady H, Samuels BA, Lerman A, Moses JW, Pietras C, Zhang Z, Tirziu D, Parise H, Cristea E, Chamié D, Grubman D, Henrici K, Matmusaeva E, Latif N, Cigarroa N, Lansky AJ. Determining the Cause of Coronary Vasomotor Disorders in Patients With Ischemia and Nonobstructive Coronary Arteries: Design and Rationale of the DISCOVER INOCA Prospective, Multicenter Registry. JOURNAL OF THE SOCIETY FOR CARDIOVASCULAR ANGIOGRAPHY & INTERVENTIONS 2024; 3:102046. [PMID: 39132594 PMCID: PMC11308755 DOI: 10.1016/j.jscai.2024.102046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 03/28/2024] [Accepted: 04/03/2024] [Indexed: 08/13/2024]
Abstract
Background Approximately 30% to 50% of patients who are referred for diagnostic coronary angiography are found to have no obstructive coronary artery disease (CAD). Ischemia and nonobstructive coronary arteries (INOCA) is increasingly recognized and encompasses coronary microvascular dysfunction, vasospastic angina, symptomatic myocardial bridging, and other vasomotor disorders. However, the prevalence of these disorders and whether underlying atherosclerotic plaque burden and morphology affect the long-term outcomes of each physiologic phenotype is unknown. Methods The DISCOVER INOCA registry is ongoing at 8 centers in the United States and plans to enroll 500 patients with ischemic heart disease referred for angiography undergoing coronary function testing (CFT). All participants will complete patient-reported outcome measures and undergo protocol-guided angiography, acetylcholine provocation, coronary thermodilution, and intravascular imaging. Follow-up assessments occur at 30 days, 6 months, 1 year, and annually for 5 years. The primary short-term end point is the prevalence of INOCA phenotypes based on physiology and the degree of atherosclerosis based on intravascular ultrasound or optical coherence tomography (intravascular imaging). The primary long-term end point is the incidence of major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, hospitalization for cardiovascular causes, or coronary revascularization at a follow-up of 5 years. At the time of this publication, 100 participants have been enrolled. Conclusions DISCOVER INOCA is the first prospective study of INOCA patients to integrate anatomic and physiologic measures of disease and correlate them with long-term outcomes. DISCOVER INOCA will report on the prevalence of INOCA phenotypes, the safety of comprehensive invasive CFT, and the impact of testing on diagnoses and medical therapy. Symptoms and cardiovascular adverse events at long-term follow-up will be determined in patients with no obstructive CAD undergoing angiography.
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Affiliation(s)
- Samit M. Shah
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
| | - Jennifer A. Tremmel
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California
| | - Timothy D. Henry
- The Christ Hospital Heart and Vascular Institute, Cincinnati, Ohio
- The Carl and Edyth Lindner Research Center at The Christ Hospital, Cincinnati, Ohio
| | - Nathaniel R. Smilowitz
- Leon H. Charney Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, New York
- Cardiology Section, Department of Medicine, VA New York Harbor Healthcare System, New York, New York
| | - Megha Prasad
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, New York
| | - Yuhei Kobayashi
- NewYork-Presbyterian Brooklyn Methodist Hospital/Weill Cornell Medical College, New York, New York
| | - Glen A. Henry
- Northeast Georgia Medical Center, Gainesville, Georgia
| | - Habib Samady
- Northeast Georgia Medical Center, Gainesville, Georgia
| | - Bruce A. Samuels
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Amir Lerman
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
| | - Jeffrey W. Moses
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, New York
- St Francis Hospital & Heart Center, Roslyn, New York
| | - Cody Pietras
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
| | - Zhiyuan Zhang
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
| | - Daniela Tirziu
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
| | - Helen Parise
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
| | - Ecaterina Cristea
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
| | - Daniel Chamié
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
| | - Daniel Grubman
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
| | - Kyna Henrici
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
| | - Elzar Matmusaeva
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
| | - Nida Latif
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
| | - Natasha Cigarroa
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Alexandra J. Lansky
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Yale Cardiovascular Research Group, Yale School of Medicine, New Haven, Connecticut
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24
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AlShaikh S, Rohm CL, Sutton NR, Burgess SN, Alasnag M. INOCA: Ischemia in non-obstructive coronary arteries. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2024; 42:100391. [PMID: 38680648 PMCID: PMC11043816 DOI: 10.1016/j.ahjo.2024.100391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 03/29/2024] [Accepted: 04/01/2024] [Indexed: 05/01/2024]
Abstract
This article provides a summary of the clinical spectrum of no obstructive coronary arteries. We describe the pathologies, invasive and noninvasive assessment, and management strategies.
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Affiliation(s)
- Shereen AlShaikh
- Adult Cardiology Department, Mohammed bin Khalifa Cardiac Centre, Riffa, Bahrain
| | - Charlene L. Rohm
- Department of Internal Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Nadia R. Sutton
- Department of Internal Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
- Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States
| | - Sonya N. Burgess
- Cardiology Department, University of Sydney and Nepean Hospital, Sydney, Australia
| | - Mirvat Alasnag
- Cardiac Center, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia
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25
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Lopez-Candales A, Sawalha K, Asif T. Nonobstructive epicardial coronary artery disease: an evolving concept in need of diagnostic and therapeutic guidance. Postgrad Med 2024; 136:366-376. [PMID: 38818874 DOI: 10.1080/00325481.2024.2360888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 05/23/2024] [Indexed: 06/01/2024]
Abstract
For decades, we have been treating patients presenting with angina and concerning electrocardiographic changes indicative of ischemia or injury, in whom no culprit epicardial coronary stenosis was found during diagnostic coronary angiography. Unfortunately, the clinical outcomes of these patients were not better than those with recognized obstructive coronary disease. Improvements in technology have allowed us to better characterize these patients. Consequently, an increasing number of patients with ischemia and no obstructive coronary artery disease (INOCA) or myocardial infarction in the absence of coronary artery disease (MINOCA) have now gained formal recognition and are more commonly encountered in clinical practice. Although both entities might share functional similarities at their core, they pose significant diagnostic and therapeutic challenges. Unless we become more proficient in identifying these patients, particularly those at higher risk, morbidity and mortality outcomes will not improve. Though this field remains in constant flux, data continue to become available. Therefore, we thought it would be useful to highlight important milestones that have been recognized so we can all learn about these clinical entities. Despite all the progress made regarding INOCA and MINOCA, many important knowledge gaps continue to exist. For the time being, prompt identification and early diagnosis remain crucial in managing these patients. Even though we are still not clear whether intensive medical therapy alters clinical outcomes, we remain vigilant and wait for more data.
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Affiliation(s)
- Angel Lopez-Candales
- Cardiovascular Medicine Division University Health Truman Medical Center, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Khalid Sawalha
- Cardiometabolic Fellowship, University Health Truman Medical Center and the University of Missouri-Kansas City, Kansas City, USA
| | - Talal Asif
- Division of Cardiovascular Diseases, University Health Truman Medical Center and the University of Missouri-Kansas City Kansas City, Kansas City, MO, USA
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26
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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.
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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
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27
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Karakayali M, Altunova M, Yakisan T, Aslan S, Omar T, Artac I, Ilis D, Arslan A, Cagin Z, Karabag Y, Rencuzogullari I. The Relationship between the Systemic Immune-Inflammation Index and Ischemia with Non-Obstructive Coronary Arteries in Patients Undergoing Coronary Angiography. Arq Bras Cardiol 2024; 121:e20230540. [PMID: 38597536 PMCID: PMC12092018 DOI: 10.36660/abc.20230540] [Citation(s) in RCA: 23] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 11/12/2023] [Accepted: 12/13/2023] [Indexed: 04/11/2024] Open
Abstract
BACKGROUND Ischemia with the non-obstructive coronary artery (INOCA) is an ischemic heart disease that mostly includes coronary microvascular dysfunction and/or epicardial coronary vasospasm due to underlying coronary vascular dysfunction and can be seen more commonly in female patients. The systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio) is a new marker that predicts adverse clinical outcomes in coronary artery disease (CAD). OBJECTIVE This study aims to investigate the relationship between INOCA and SII, a new marker associated with inflammation. METHODS A total of 424 patients (212 patients with INOCA and 212 normal controls) were included in the study. Peripheral venous blood samples were received from the entire study population prior to coronary angiography to measure SII and other hematological parameters. In our study, the value of p<0.05' was considered statistically significant. RESULTS The optimal cut-off value of SII for predicting INOCA was 153.8 with a sensitivity of 44.8% and a specificity of 78.77% (Area under the curve [AUC]: 0.651 [95% CI: 0.603-0.696, p=0.0265]). Their ROC curves were compared to assess whether SII had an additional predictive value over components. The AUC value of SII was found to be significantly higher than that of lymphocyte (AUC: 0.607 [95% CI: 0.559-0.654, p = 0.0273]), neutrophil (AUC: 0.559 [95%CI: 0.511-0.607, p=0.028]) and platelet (AUC: 0.590 [95% CI: 0.541-0.637, p = 0.0276]) in INOCA patients. CONCLUSIONS A high SII level was found to be independently associated with the existence of INOCA. The SII value can be used as an indicator to add to the traditional expensive methods commonly used in INOCA prediction.
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Affiliation(s)
- Muammer Karakayali
- Kafkas University School of MedicineDepartment of CardiologyKarsTurquiaKafkas University School of Medicine, Department of Cardiology, Kars – Turquia
| | - Mehmet Altunova
- Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training Research HospitalIstanbulTurquiaMehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training Research Hospital, Istanbul – Turquia
| | - Turab Yakisan
- Yozgat City HospitalYozgatTurquiaYozgat City Hospital, Yozgat – Turquia
| | - Serkan Aslan
- Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training Research HospitalIstanbulTurquiaMehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training Research Hospital, Istanbul – Turquia
| | - Timor Omar
- Kafkas University School of MedicineDepartment of CardiologyKarsTurquiaKafkas University School of Medicine, Department of Cardiology, Kars – Turquia
| | - Inanc Artac
- Kafkas University School of MedicineDepartment of CardiologyKarsTurquiaKafkas University School of Medicine, Department of Cardiology, Kars – Turquia
| | - Doğan Ilis
- Kafkas University School of MedicineDepartment of CardiologyKarsTurquiaKafkas University School of Medicine, Department of Cardiology, Kars – Turquia
| | - Ayca Arslan
- Kafkas University School of MedicineDepartment of CardiologyKarsTurquiaKafkas University School of Medicine, Department of Cardiology, Kars – Turquia
| | - Zihni Cagin
- Kafkas University School of MedicineDepartment of CardiologyKarsTurquiaKafkas University School of Medicine, Department of Cardiology, Kars – Turquia
| | - Yavuz Karabag
- Kafkas University School of MedicineDepartment of CardiologyKarsTurquiaKafkas University School of Medicine, Department of Cardiology, Kars – Turquia
| | - Ibrahim Rencuzogullari
- Kafkas University School of MedicineDepartment of CardiologyKarsTurquiaKafkas University School of Medicine, Department of Cardiology, Kars – Turquia
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28
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Zhou Y, Lu D, Hu Y, Dai C, Yin M, Lu H, Li C, Chen Z, Qian J, Ge J. Coronary slow flow and angiography-derived index of microcirculatory resistance as prognostic predictors in patients with angina and normal coronary arteries: a retrospective cohort study. Acta Cardiol 2024; 79:149-158. [PMID: 38628089 DOI: 10.1080/00015385.2023.2281115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 11/03/2023] [Indexed: 04/19/2024]
Abstract
BACKGROUND This study aims to investigate prognostic implications of coronary slow flow (CSF) and angiography-derived index of microcirculatory resistance (caIMR) in patients with angina and normal coronary arteries. METHODS A total of 582 patients were enrolled with angiographically normal coronary arteries. caIMR was calculated using a commercial software. Patients were followed up for a median of 45 months. The primary endpoint was defined as major adverse cardiovascular events (MACEs) comprising death, myocardial infarction and readmission for angina or heart failure. RESULTS CSF was diagnosed when TIMI grade 2 flow presented in at least one coronary artery. Multivariate analysis indicated TIMI-flow-based determination of CSF was not significantly associated with MACEs [hazard ratio (HR): 2.14; 95% confidence interval (CI): 0.87-5.31; p = 0.099), while caIMR >42 (HR: 2.53; 95% CI: 1.02-6.32; p = 0.047) were independent predictors of MACEs. Incorporation of caIMR improved the area under the curve from 0.587 to 0.642. CONCLUSIONS caIMR was an independent prognostic factor of long-term cardiovascular events in patients with CSF. Evaluation of caIMR improved the risk stratification of patients with angiographically-normal coronary arteries.
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Affiliation(s)
- You Zhou
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, PR China
| | - Danbo Lu
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, PR China
| | - Yiqing Hu
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, PR China
| | - Chunfeng Dai
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, PR China
| | - Ming Yin
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, PR China
| | - Hao Lu
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, PR China
| | - ChenGuang Li
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, PR China
| | - Zhangwei Chen
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, PR China
| | - Juying Qian
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, PR China
| | - Junbo Ge
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, PR China
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Januszek R, Kołtowski Ł, Tomaniak M, Wańha W, Wojakowski W, Grygier M, Siłka W, Jan Horszczaruk G, Czarniak B, Kręcki R, Guzik B, Legutko J, Pawłowski T, Wnęk P, Roik M, Sławek-Szmyt S, Jaguszewski M, Roleder T, Dziarmaga M, Bartuś S. Implementation of Microcirculation Examination in Clinical Practice-Insights from the Nationwide POL-MKW Registry. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:277. [PMID: 38399564 PMCID: PMC10890290 DOI: 10.3390/medicina60020277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 12/10/2023] [Accepted: 01/31/2024] [Indexed: 02/25/2024]
Abstract
Background and Objectives: The assessment of coronary microcirculation may facilitate risk stratification and treatment adjustment. The aim of this study was to evaluate patients' clinical presentation and treatment following coronary microcirculation assessment, as well as factors associated with an abnormal coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) values. Materials and Results: This retrospective analysis included 223 patients gathered from the national registry of invasive coronary microvascular testing collected between 2018 and 2023. Results: The frequency of coronary microcirculatory assessments in Poland has steadily increased since 2018. Patients with impaired IMR (≥25) were less burdened with comorbidities. Patients with normal IMR underwent revascularisation attempts more frequently (11.9% vs. 29.8%, p = 0.003). After microcirculation testing, calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors were added more often for patients with IMR and CFR abnormalities, respectively, as compared to control groups. Moreover, patients with coronary microvascular dysfunction (CMD, defined as CFR and/or IMR abnormality), regardless of treatment choice following microcirculation assessment, were provided with trimetazidine (23.2%) and dihydropyridine CCBs (26.4%) more frequently than those without CMD who were treated conservatively (6.8%) and by revascularisation (4.2% with p = 0.002 and 0% with p < 0.001, respectively). Multivariable analysis revealed no association between angina symptoms and IMR or CFR impairment. Conclusions: The frequency of coronary microcirculatory assessments in Poland has steadily increased. Angina symptoms were not associated with either IMR or CFR impairment. After microcirculation assessment, patients with impaired microcirculation, expressed as either low CFR, high IMR or both, received additional pharmacotherapy treatment more often.
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Affiliation(s)
- Rafał Januszek
- Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Cracow University, 30-705 Kraków, Poland
| | - Łukasz Kołtowski
- 1st Department of Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (Ł.K.); (M.T.)
| | - Mariusz Tomaniak
- 1st Department of Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (Ł.K.); (M.T.)
| | - Wojciech Wańha
- Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, 40-055 Katowice, Poland; (W.W.); (W.W.)
| | - Wojciech Wojakowski
- Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, 40-055 Katowice, Poland; (W.W.); (W.W.)
| | - Marek Grygier
- 1st Department of Cardiology, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.G.); (S.S.-S.)
| | - Wojciech Siłka
- Faculty of Medicine, Jagiellonian University Medical College, 31-008 Kraków, Poland; (W.S.); (S.B.)
| | - Grzegorz Jan Horszczaruk
- Faculty of Medical Science, Collegium Medicum. Cardinal Stefan Wyszyński University in Warsaw, 01-938 Warsaw, Poland;
- Department of Cardiology, Voivodeship Hospital in Łomża, 18-404 Łomża, Poland
| | - Bartosz Czarniak
- Provincial Specialist Hospital in Wloclawek, 87-800 Włocławek, Poland;
| | | | - Bartłomiej Guzik
- Department of Interventional Cardiology, Institute of Cardiology, Jagiellonian University Medical College, św. Anny 12, 31-007 Kraków, Poland; (B.G.); (J.L.)
| | - Jacek Legutko
- Department of Interventional Cardiology, Institute of Cardiology, Jagiellonian University Medical College, św. Anny 12, 31-007 Kraków, Poland; (B.G.); (J.L.)
- Department of Interventional Cardiology, The John Paul II Hospital, Prądnicka 80, 31-202 Kraków, Poland
| | - Tomasz Pawłowski
- Department of Cardiology, National Institute of Medicine of the Ministry of Internal Affairs and Administration, 02-507 Warsaw, Poland;
- Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | - Paweł Wnęk
- Provincial Specialist Hospital in Wroclaw, 51-124 Wrocław, Poland;
| | - Marek Roik
- Department of Internal Medicine and Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland;
| | - Sylwia Sławek-Szmyt
- 1st Department of Cardiology, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.G.); (S.S.-S.)
| | - Miłosz Jaguszewski
- 1st Department of Cardiology, Medical University of Gdańsk, 80-210 Gdańsk, Poland;
| | - Tomasz Roleder
- Department of Cardiology, Wroclaw Medical University, 50-556 Wrocław, Poland;
| | - Miłosz Dziarmaga
- Department of Cardiology-Intensive Therapy and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznań, Poland;
| | - Stanisław Bartuś
- Faculty of Medicine, Jagiellonian University Medical College, 31-008 Kraków, Poland; (W.S.); (S.B.)
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Pruthi S, Siddiqui E, Smilowitz NR. Beyond Coronary Artery Disease: Assessing the Microcirculation. Cardiol Clin 2024; 42:125-135. [PMID: 37949533 PMCID: PMC11090694 DOI: 10.1016/j.ccl.2023.07.003] [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] [Indexed: 11/12/2023]
Abstract
Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.
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Affiliation(s)
- Sonal Pruthi
- Division of Cardiology, Department of Medicine, NYU Langone Health, 550 First Avenue, New York, NY 10016, USA
| | - Emaad Siddiqui
- Division of Cardiology, Department of Medicine, NYU Langone Health, 550 First Avenue, New York, NY 10016, USA
| | - Nathaniel R Smilowitz
- Division of Cardiology, Department of Medicine, NYU Langone Health, 550 First Avenue, New York, NY 10016, USA; Cardiology Section, Department of Medicine, VA New York Harbor Healthcare System, 423 East 23rd Street, New York, NY 10010, USA; The Leon H. Charney Division of Cardiology, NYU Langone Health, NYU School of Medicine, 423 East 23rd Street, 12-West, New York, NY 10010, USA.
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31
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Sakai A, Nagao M, Yamamoto A, Nakao R, Arashi H, Momose M, Sato K, Yamaguchi J. 13N-ammonia positron emission tomography for diagnosis and monitoring of ischemia without obstructive coronary artery disease. Int J Cardiol 2024; 395:131392. [PMID: 37748522 DOI: 10.1016/j.ijcard.2023.131392] [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: 06/27/2023] [Revised: 09/20/2023] [Accepted: 09/22/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND Ischemia with no obstructive coronary arteries (INOCA), a chronic disorder with a poor prognosis, remains challenging to diagnose. 13N-ammonia positron emission tomography (13NH3 PET), which can quantify microcirculation, is its most reliable detection method. We aimed to investigate the differences in 13NH3 PET findings between INOCA and coronary artery disease (CAD). METHODS Overall, consecutive 433 patients with known or suspected CAD underwent adenosine-stress 13NH3 PET. Based on the European Society of Cardiology guidelines, INOCA was defined as typical angina without coronary stenosis (INOCA n = 45, CAD n = 293, no CAD n = 95). Papillary muscle ischemia (PMI) and global myocardial flow reserve (MFR) were examined as microvascular injuries using 13NH3 PET. RESULTS PMI was observed significantly more frequently in patients with INOCA than in those with CAD (40.0% vs. 11.6%, respectively; p = 0.02). Global MFR (1.84 ± 0.54 vs. 2.08 ± 0.66, respectively; p < 0.0001) and reactive hyperemia index were significantly lower in patients with INOCA than in those with CAD. Forty-five major adverse cardiac events (MACE) were recorded in a median follow-up time of 827 days. Kaplan-Meier analysis revealed that the survival rate worsened in patients with INOCA and PMI (log-rank test, p = 0.001). In the Cox proportional hazards model, PMI was an independent predictive factor for MACE (odds ratio, 4.16; 95% confidence interval, 2.13-8.15; p < 0.0001). CONCLUSIONS PMI presence and decreased MFR were 13NH3 PET findings characteristic of INOCA. 13NH3 PET can be used to monitor the treatment course.
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Affiliation(s)
- Akiko Sakai
- Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan.
| | - Michinobu Nagao
- Department of Diagnostic Imaging & Nuclear Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan
| | - Atsushi Yamamoto
- Department of Diagnostic Imaging & Nuclear Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan
| | - Risako Nakao
- Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan
| | - Hiroyuki Arashi
- Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan
| | - Mitsuru Momose
- Department of Diagnostic Imaging & Nuclear Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan
| | - Kayoko Sato
- Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan
| | - Junichi Yamaguchi
- Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan
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32
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Polyak A, Wei J, Gulati M, Merz NB. Clinical aspects of ischemia with no obstructive coronary artery disease (INOCA). AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2024; 37:100352. [PMID: 38222977 PMCID: PMC10785769 DOI: 10.1016/j.ahjo.2023.100352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 12/03/2023] [Indexed: 01/16/2024]
Abstract
Ischemia with no obstructive coronary arteries (INOCA) is defined as patients with evidence of myocardial ischemia without obstructive coronary artery disease. About 3-4 million people in the United States have INOCA, more commonly affecting women, and carries adverse morbidity, mortality, and relatively high healthcare costs. The pathophysiology of INOCA appears to be multi-factorial with a variety of contributing mechanisms. Diagnosis of INOCA is suggested by non-invasive or invasive testing consistent with myocardial ischemia. Due to the high prevalence of coronary risk factors and atherosclerosis in the INOCA population, current treatment strategies target angina, coronary atherosclerosis, and atherosclerotic risk factors, as well as burgeoning treatment of coronary microvascular dysfunction (CMD). Ongoing clinical trials are assessing different options.
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Affiliation(s)
- Alexander Polyak
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Janet Wei
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Martha Gulati
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Jenkins K, Pompei G, Ganzorig N, Brown S, Beltrame J, Kunadian V. Vasospastic angina: a review on diagnostic approach and management. Ther Adv Cardiovasc Dis 2024; 18:17539447241230400. [PMID: 38343041 PMCID: PMC10860484 DOI: 10.1177/17539447241230400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 01/17/2024] [Indexed: 02/15/2024] Open
Abstract
Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels responsible for an inadequate supply of blood and oxygen. Coronary artery spasm is a heterogeneous phenomenon that can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction (MI). VSA was originally described as Prinzmetal angina or variant angina, classically presenting at rest, unlike most cases of angina (though in some patients, vasospasm may be triggered by exertion, emotional, mental or physical stress), and associated with transient electrocardiographic changes (transient ST-segment elevation, depression and/or T-wave changes). Ischaemia with non-obstructive coronary arteries (INOCA) is not a benign condition, as patients are at elevated risk of cardiovascular events including acute coronary syndrome, hospitalization due to heart failure, stroke and repeat cardiovascular procedures. INOCA patients also experience impaired quality of life and associated increased healthcare costs. VSA, an endotype of INOCA, is associated with major adverse events, including sudden cardiac death, acute MI and syncope, necessitating the study of the most effective treatment options currently available. The present literature review aims to summarize current data relating to the diagnosis and management of VSA and provide details on the sequence that treatment should follow.
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Affiliation(s)
- Kenny Jenkins
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Graziella Pompei
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona, Italy
| | - Nandine Ganzorig
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Sarah Brown
- Cardiovascular Care Partnership, British Cardiovascular Society, London, UK
| | - John Beltrame
- Basil Hetzel Institute for Translational Health Research, Adelaide Medical School, University of Adelaide and Royal Adelaide Hospital and The Queen Elizabeth Hospital, Adelaide, SA, Australia
| | - Vijay Kunadian
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University Medical School, 4th Floor William Leech Building, Newcastle upon Tyne NE2 4HH, UK
- Cardiothoracic Centre, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
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34
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Muroya T, Kawano H, Yamamoto F, Maemura K. Coronary microvascular resistance comparison of coronary arteries with and without considering vascular diameter: A retrospective, single-center study. Health Sci Rep 2023; 6:e1714. [PMID: 38093829 PMCID: PMC10716331 DOI: 10.1002/hsr2.1714] [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: 05/16/2023] [Revised: 08/29/2023] [Accepted: 11/02/2023] [Indexed: 10/17/2024] Open
Abstract
Background and Aims Measurement of coronary microvascular resistance (MR) is essential for diagnosing nonocclusive coronary artery ischemia, but whether coronary branches of different diameters can be similarly assessed using hyperemic microvascular resistance index (hMVRI) calculated from average peak velocity (APV) remains unclear. We investigated the relationship between coronary arteries of different diameters and hMVRI. Methods Thirty patients with suspected angina pectoris and nonobstructive coronary stenosis with fractional flow reserve >0.8 underwent evaluation of all coronary arteries using a Doppler velocity and pressure-equipped guidewire. Quantitative coronary angiography (QCA) was used to analyze vessel diameter (DQCA). Coronary blood flow (CBFQCA) was calculated as πDQCA 2/4 (0.5 × APV) and hMVRIQCA as distal coronary pressure divided by CBFQCA during maximal hyperemia. Results The hMVRI was significantly higher for the right coronary artery than for the left anterior descending artery, but no significant differences between arteries were seen for CBFQCA and hMVRIQCA. Although the correlation between CBFQCA and APV was weak, CBFQCA divided into three groups according to DQCA showed very strong correlations with APV. Slopes of the straight line between APV and CBFQCA for small-, middle-, and large-diameter groups were 0.48, 0.30, and 0.21, respectively, with slope decreasing as diameter increased. Conclusions Comparative evaluation of MR in coronary branches with varying vessel diameters requires vessel diameter to be accounted for.
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Affiliation(s)
- Takahiro Muroya
- Division of CirculatorySasebo City General HospitalNagasakiJapan
- Department of CardiologyUreshino Medical CenterUreshinoJapan
| | - Hiroaki Kawano
- Department of Cardiovascular MedicineNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
| | - Fumi Yamamoto
- Department of CardiologyUreshino Medical CenterUreshinoJapan
| | - Koji Maemura
- Department of Cardiovascular MedicineNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
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La S, Tavella R, Wu J, Pasupathy S, Zeitz C, Worthley M, Sinhal A, Arstall M, Spertus JA, Beltrame JF. Angina and Non-Obstructive Coronary Artery (ANOCA) Patients with Coronary Vasomotor Disorders. Life (Basel) 2023; 13:2190. [PMID: 38004330 PMCID: PMC10672683 DOI: 10.3390/life13112190] [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: 10/11/2023] [Revised: 11/02/2023] [Accepted: 11/06/2023] [Indexed: 11/26/2023] Open
Abstract
Angina and Non-Obstructive Coronary Artery (ANOCA) patients often lack a clear explanation for their symptoms, and are frequently discharged with the label of "unspecified chest pain", despite the availability of functional coronary angiography (provocative spasm and microvascular function testing) to identify potential underlying coronary vasomotor disorders. This study compared the outcomes of ANOCA patients with a coronary vasomotor disorder diagnosis post elective coronary angiography to patients discharged with unspecified chest pain. Using the CADOSA (Coronary Angiogram Database of South Australia) registry, consecutive symptomatic patients (n = 7555) from 2012 to 2018 underwent elective angiography; 30% had ANOCA (stenosis <50%). Of this cohort, 9% had documented coronary vasomotor disorders diagnosed, and 91% had unspecified chest pain. Patients with coronary vasomotor disorders were younger and had a similar female prevalence compared with those with unspecified chest pain. New prescriptions of calcium channel blockers and long-acting nitrates were more common for the coronary vasomotor cohort at discharge. In the 3 years following angiography, both groups had similar all-cause mortality rates. However, those with coronary vasomotor disorders had higher rates of emergency department visits for chest pain (39% vs. 15%, p < 0.001) and readmissions for chest pain (30% vs. 10%, p < 0.001) compared with those with unspecified chest pain. This real-world study emphasizes the importance of identifying high-risk ANOCA patients for personalized management to effectively address their symptoms.
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Affiliation(s)
- Sarena La
- School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5000, Australia; (S.L.); (R.T.); (J.W.); (S.P.); (C.Z.); (M.A.); (J.A.S.)
- Central Adelaide Local Health Network, Adelaide, SA 5000, Australia
- Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia
| | - Rosanna Tavella
- School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5000, Australia; (S.L.); (R.T.); (J.W.); (S.P.); (C.Z.); (M.A.); (J.A.S.)
- Central Adelaide Local Health Network, Adelaide, SA 5000, Australia
- Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia
| | - Jing Wu
- School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5000, Australia; (S.L.); (R.T.); (J.W.); (S.P.); (C.Z.); (M.A.); (J.A.S.)
| | - Sivabaskari Pasupathy
- School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5000, Australia; (S.L.); (R.T.); (J.W.); (S.P.); (C.Z.); (M.A.); (J.A.S.)
- Central Adelaide Local Health Network, Adelaide, SA 5000, Australia
- Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia
| | - Christopher Zeitz
- School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5000, Australia; (S.L.); (R.T.); (J.W.); (S.P.); (C.Z.); (M.A.); (J.A.S.)
- Central Adelaide Local Health Network, Adelaide, SA 5000, Australia
- Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia
| | - Matthew Worthley
- School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5000, Australia; (S.L.); (R.T.); (J.W.); (S.P.); (C.Z.); (M.A.); (J.A.S.)
- Central Adelaide Local Health Network, Adelaide, SA 5000, Australia
| | - Ajay Sinhal
- Southern Adelaide Local Health Network, Adelaide, SA 5042, Australia;
- School of Medicine, Faculty of Health Sciences, Flinders University, Adelaide, SA 5042, Australia
| | - Margaret Arstall
- School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5000, Australia; (S.L.); (R.T.); (J.W.); (S.P.); (C.Z.); (M.A.); (J.A.S.)
- Northern Adelaide Local Health Network, Adelaide, SA 5112, Australia
| | - John A. Spertus
- School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5000, Australia; (S.L.); (R.T.); (J.W.); (S.P.); (C.Z.); (M.A.); (J.A.S.)
- Saint Luke’s Mid America Heart Institute, Kansas City, MO 64111, USA
- School of Medicine, Healthcare Institute for Innovations in Quality, The University of Missouri-Kansas City, Kansas City, MO 64110, USA
| | - John F. Beltrame
- School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5000, Australia; (S.L.); (R.T.); (J.W.); (S.P.); (C.Z.); (M.A.); (J.A.S.)
- Central Adelaide Local Health Network, Adelaide, SA 5000, Australia
- Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia
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Mohammed AQ, Abdu FA, Liu L, Yin G, Mareai RM, Mohammed AA, Xu Y, Che W. Coronary microvascular dysfunction and myocardial infarction with non-obstructive coronary arteries: Where do we stand? Eur J Intern Med 2023; 117:8-20. [PMID: 37482469 DOI: 10.1016/j.ejim.2023.07.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 06/15/2023] [Accepted: 07/11/2023] [Indexed: 07/25/2023]
Abstract
In the past decade, scientific and clinical research has provided a translational perspective on myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA). MINOCA is characterized by clinical documentation of an acute MI but angiography shows no significant coronary artery obstruction (stenosis <50%). The prevalence of MINOCA is estimated to range from approximately 6 to 10% among MI patients, and those with this condition have a poor prognosis, experiencing high rates of mortality, rehospitalization, and socioeconomic burden. MINOCA represents a major unmet need in cardiovascular medicine, with uncertain clinical management. It is a complex condition that can be caused by various factors, including atherosclerosis, plaque rupture, coronary vasospasm, and microvascular dysfunction. Effective management of MINOCA depends on identifying the underlying mechanism of the infarction, thus a systematic diagnostic approach is recommended. Contemporary data shows that a significant number of patients exhibit structural and functional abnormalities in coronary microcirculation, which is referred to as coronary microvascular dysfunction (CMD). CMD plays a crucial role in patients with signs and symptoms of myocardial ischemia and non-obstructive coronary artery stenosis, including MINOCA. Furthermore, conducting a thorough evaluation of coronary function can have significant prognostic and therapeutic implications, since personalized patient management strategies based on this assessment have been shown to improve symptoms and prognosis. Therefore, an accurate and timely diagnosis of CMD is essential for effective patient management, which can be achieved through various invasive and non-invasive methods. This review will discuss the pathophysiological understanding, current diagnostic techniques, and management strategies of patients with MINOCA and CMD.
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Affiliation(s)
- Abdul-Quddus Mohammed
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Fuad A Abdu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lu Liu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Guoqing Yin
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Redhwan M Mareai
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ayman A Mohammed
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yawei Xu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wenliang Che
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Cardiology, Shanghai Tenth People's Hospital Chongming Branch, Shanghai, China.
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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
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Takahashi T, Gupta A, Samuels BA, Wei J. Invasive Coronary Assessment in Myocardial Ischemia with No Obstructive Coronary Arteries. Curr Atheroscler Rep 2023; 25:729-740. [PMID: 37682498 PMCID: PMC10564835 DOI: 10.1007/s11883-023-01144-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/21/2023] [Indexed: 09/09/2023]
Abstract
PURPOSE OF REVIEW The purpose of this review is threefold: (i) to give an overview of well-established invasive methods for assessing patients with ischemia with no obstructive coronary arteries (INOCA) in the cardiac catheterization laboratory; (ii) to describe the prognostic and treatment implications based on these findings, and (iii) to discuss current knowledge gaps and future perspectives. RECENT FINDINGS Recent studies have demonstrated that invasive coronary function testing not only allows for risk stratification of patients with INOCA but also guides medical therapy with improvement in symptoms and quality of life. Based on these findings, invasive coronary function assessment is now a class 2a recommendation in the 2021 ACC/AHA chest pain guideline to improve the diagnosis of coronary microvascular dysfunction and to enhance risk stratification. Invasive functional testing for patients with INOCA is well established and easily performed in the catheterization laboratory. Comprehensive invasive assessment is a key to differentiating INOCA endotypes and optimizing both medical therapy and preventive strategies including lifestyle modification.
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Affiliation(s)
| | - Aakriti Gupta
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Bruce A Samuels
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Janet Wei
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd A3212, Los Angeles, CA, 90048, USA.
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Boerhout C, Feenstra R, van de Hoef T, Piek J, Beijk M. Pharmacotherapy in patients with vasomotor disorders. IJC HEART & VASCULATURE 2023; 48:101267. [PMID: 37727753 PMCID: PMC10505589 DOI: 10.1016/j.ijcha.2023.101267] [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: 07/20/2023] [Revised: 08/23/2023] [Accepted: 09/03/2023] [Indexed: 09/21/2023]
Abstract
Background Anginal symptoms in patients with non-obstructive coronary artery disease are frequently related to vasomotor disorders of the coronary circulation. Although frequently overlooked, a distinct diagnosis of different vasomotor disorders can be made by intracoronary function testing. Early detection and treatment seems beneficial, but little evidence is available for the medical treatment of these disorders. Nevertheless, there are several pharmacotherapeutic options available to treat these patients and improve quality of life. Methods & findings We performed an extensive yet non-systematic literature search to explore available pharmacotherapeutic strategies for addressing vasomotor disorders in individuals experiencing angina and non-obstructive coronary artery disease. This article presents a comprehensive overview of therapeutic possibilities for patients exhibiting abnormal vasoconstriction (such as spasm) and abnormal vasodilation (like coronary microvascular dysfunction). Conclusion Treatment of vasomotor disorders can be very challenging, but a general treatment algorithm based on the existing evidence and the best available current practice is feasible.
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Affiliation(s)
| | | | - T.P. van de Hoef
- Heart Center, Amsterdam UMC, Amsterdam, the Netherlands
- Department of Cardiology, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - J.J. Piek
- Heart Center, Amsterdam UMC, Amsterdam, the Netherlands
| | - M.A.M. Beijk
- Heart Center, Amsterdam UMC, Amsterdam, the Netherlands
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40
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Samuels BA, Shah SM, Widmer RJ, Kobayashi Y, Miner SES, Taqueti VR, Jeremias A, Albadri A, Blair JA, Kearney KE, Wei J, Park K, Barseghian El-Farra A, Holoshitz N, Janaszek KB, Kesarwani M, Lerman A, Prasad M, Quesada O, Reynolds HR, Savage MP, Smilowitz NR, Sutton NR, Sweeny JM, Toleva O, Henry TD, Moses JW, Fearon WF, Tremmel JA. Comprehensive Management of ANOCA, Part 1-Definition, Patient Population, and Diagnosis: JACC State-of-the-Art Review. J Am Coll Cardiol 2023; 82:1245-1263. [PMID: 37704315 DOI: 10.1016/j.jacc.2023.06.043] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 06/15/2023] [Indexed: 09/15/2023]
Abstract
Angina with nonobstructive coronary arteries (ANOCA) is increasingly recognized and may affect nearly one-half of patients undergoing invasive coronary angiography for suspected ischemic heart disease. This working diagnosis encompasses coronary microvascular dysfunction, microvascular and epicardial spasm, myocardial bridging, and other occult coronary abnormalities. Patients with ANOCA often face a high burden of symptoms and may experience repeated presentations to multiple medical providers before receiving a diagnosis. Given the challenges of establishing a diagnosis, patients with ANOCA frequently experience invalidation and recidivism, possibly leading to anxiety and depression. Advances in scientific knowledge and diagnostic testing now allow for routine evaluation of ANOCA noninvasively and in the cardiac catheterization laboratory with coronary function testing (CFT). CFT includes diagnostic coronary angiography, assessment of coronary flow reserve and microcirculatory resistance, provocative testing for endothelial dysfunction and coronary vasospasm, and intravascular imaging for identification of myocardial bridging, with hemodynamic assessment as needed.
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Affiliation(s)
- Bruce A Samuels
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Samit M Shah
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA
| | - R Jay Widmer
- Baylor Scott and White Health, Temple, Texas, USA
| | - Yuhei Kobayashi
- New York Presbyterian Brooklyn Methodist Hospital/Weill Cornell Medical College, New York, New York, USA
| | - Steven E S Miner
- Southlake Regional Medical Centre, Newmarket, Ontario, Canada; School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Viviany R Taqueti
- Cardiovascular Imaging Program, Departments of Radiology and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Allen Jeremias
- St Francis Hospital and Heart Center, Roslyn, New York, USA
| | - Ahmed Albadri
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - John A Blair
- Department of Medicine, University of Chicago Medicine, Chicago, Illinois, USA
| | - Kathleen E Kearney
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Janet Wei
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Ki Park
- Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida, USA
| | | | - Noa Holoshitz
- Ascension Columbia St Mary's, Milwaukee, Wisconsin, USA
| | | | - Manoj Kesarwani
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis School of Medicine, Sacramento, California, USA
| | - Amir Lerman
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Megha Prasad
- Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York City, New York, USA
| | - Odayme Quesada
- Women's Heart Center, The Christ Hospital Heart and Vascular Institute, Cincinnati, Ohio, USA; The Carl and Edyth Lindner Center for Research and Education, The Christ Hospital, Cincinnati, Ohio, USA
| | - Harmony R Reynolds
- Sarah Ross Soter Center for Women's Cardiovascular Research, Leon H. Charney Division of Cardiology, NYU Grossman School of Medicine, New York, New York, USA
| | - Michael P Savage
- Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Nathaniel R Smilowitz
- Leon H. Charney Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA; Cardiology Section, Department of Medicine, Veterans Affairs New York Harbor Healthcare System, New York, New York, USA
| | - Nadia R Sutton
- Division of Cardiovascular Medicine, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA
| | - Joseph M Sweeny
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Olga Toleva
- Department of Medicine, Emory University, Atlanta, Georgia, USA
| | - Timothy D Henry
- The Carl and Edyth Lindner Center for Research and Education, The Christ Hospital, Cincinnati, Ohio, USA
| | - Jeffery W Moses
- St Francis Hospital and Heart Center, Roslyn, New York, USA; Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York City, New York, USA
| | - William F Fearon
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Jennifer A Tremmel
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
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Ha ET, Qu YS, Takahashi T, Parikh MA, Kobayashi Y. Challenge in Diagnosis and Management of a Patient With Myocardial Bridge and Coronary Artery Spasm. JACC Case Rep 2023; 20:101950. [PMID: 37614330 PMCID: PMC10442663 DOI: 10.1016/j.jaccas.2023.101950] [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: 06/13/2023] [Accepted: 06/22/2023] [Indexed: 08/25/2023]
Abstract
Positive ischemia by noninvasive imaging studies often results in nonobstructive disease in cardiac catheterization. In this case, we observed ischemia by nuclear stress test in only the anteroseptal area, and the apex is free of ischemia. Coronary angiogram findings were unremarkable, but intravascular ultrasound confirmed the long length of the myocardial bridge. Further testing with spasm provocation and microvascular testing showed diffuse epicardial spasm in this area of myocardial bridge without microvascular dysfunction. We observed the myocardial bridge but no microvascular dysfunction. This case illustrates the coexistence of spasm in the area of a myocardial bridge and the challenges in the medical management of these patients. (Level of Difficulty: Advanced.).
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Affiliation(s)
- Edward T. Ha
- Division of Cardiology, NewYork-Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York, USA
| | - Yongxia S. Qu
- Division of Cardiology, NewYork-Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York, USA
- Weill Cornell Medical College, New York, New York, USA
| | | | - Manish A. Parikh
- Division of Cardiology, NewYork-Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York, USA
- Weill Cornell Medical College, New York, New York, USA
| | - Yuhei Kobayashi
- Division of Cardiology, NewYork-Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York, USA
- Weill Cornell Medical College, New York, New York, USA
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Al-Mohaissen MA. Echocardiographic assessment of primary microvascular angina and primary coronary microvascular dysfunction. Trends Cardiovasc Med 2023; 33:369-383. [PMID: 35192927 DOI: 10.1016/j.tcm.2022.02.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 02/13/2022] [Accepted: 02/14/2022] [Indexed: 01/16/2023]
Abstract
There is an increasing interest in the role of echocardiography in the evaluation of primary microvascular angina, which is attributed to primary coronary microvascular dysfunction. Valid echocardiographic techniques are expected to facilitate the diagnosis and follow-up of these patients and would be valuable for research purposes and therapy evaluation. However, adequate echocardiographic data are lacking, and the interpretation of the limited available literature is hindered by the previous addition of microvascular angina under more inclusive entities, such as cardiac syndrome X. In experienced hands, the assessment of primary coronary microvascular dysfunction in patients with suspected primary microvascular angina, using multiple echocardiographic techniques is feasible, relatively inexpensive, and safe. Exclusion of obstructive epicardial coronary artery disease is, however, a prerequisite for diagnosis. Two-dimensional transthoracic echocardiography, routine stress echocardiography, and speckle-tracking echocardiography indirectly assess primary coronary microvascular dysfunction by evaluating potential impairment in myocardial function and lack diagnostic sensitivity and specificity. Conversely, certain echocardiographic techniques, including Doppler-derived coronary flow velocity reserve and myocardial contrast echocardiography, assess some coronary microvascular dysfunction parameters and have exhibited diagnostic and prognostic potentials. Doppler-derived coronary flow velocity reserve is the best studied and only guideline-approved echocardiographic technique for documenting coronary microvascular dysfunction in patients with suspected microvascular angina. Myocardial contrast echocardiography, by comparison, can detect heterogeneous and patchy myocardial involvement by coronary microvascular dysfunction, which is an advantage over the common practice of coronary flow velocity reserve assessment in a single vessel (commonly the left anterior descending artery) which only reflects regional microvascular function. However, there is no consensus regarding the diagnostic criteria, and expertise performing this technique is limited. Echocardiography remains underexplored and inadequately utilized in the setting of microvascular angina and coronary microvascular dysfunction. Appraisal of the current echocardiographic literature regarding coronary microvascular dysfunction and microvascular angina is important to stay current with the progress in its clinical recognition and create a basis for future research and technological advancements.
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Affiliation(s)
- Maha A Al-Mohaissen
- Department of Clinical Sciences (Cardiology), College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
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Marano P, Wei J, Merz CNB. Coronary Microvascular Dysfunction: What Clinicians and Investigators Should Know. Curr Atheroscler Rep 2023; 25:435-446. [PMID: 37338666 PMCID: PMC10412671 DOI: 10.1007/s11883-023-01116-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2023] [Indexed: 06/21/2023]
Abstract
PURPOSE OF REVIEW Abnormal structure and function of the coronary microvasculature have been implicated in the pathophysiology of multiple cardiovascular disease processes. This article reviews recent research progress related to coronary microvascular dysfunction (CMD) and salient clinical takeaways. RECENT FINDINGS CMD is prevalent in patients with signs and symptoms of ischemia and no obstructive epicardial coronary artery disease (INOCA), particularly in women. CMD is associated with adverse outcomes, including most frequently the development of heart failure with preserved ejection fraction. It is also associated with adverse outcomes in patient populations including hypertrophic cardiomyopathy, dilated cardiomyopathy, and acute coronary syndromes. In patients with INOCA, stratified medical therapy guided by invasive coronary function testing to define the subtype of CMD leads to improved symptoms. There are invasive and non-invasive methodologies to diagnose CMD that provide prognostic information and mechanistic information to direct treatment. Available treatments improve symptoms and myocardial blood flow; ongoing investigations aim to develop therapy to improve adverse outcomes related to CMD.
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Affiliation(s)
- Paul Marano
- Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, USA
| | - Janet Wei
- Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, USA
- Cedars-Sinai Medical Center, Barbra Streisand Women's Heart Center, Smidt Heart Institute, 127 S. San Vicente Blvd, Los Angeles, CA, 90048, USA
| | - C Noel Bairey Merz
- Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, USA.
- Cedars-Sinai Medical Center, Barbra Streisand Women's Heart Center, Smidt Heart Institute, 127 S. San Vicente Blvd, Los Angeles, CA, 90048, USA.
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44
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Tomdio AN, McFalls EO, Jovin IS. Editorial commentary: Best imaging modalities to decipher coronary microvascular angina. Trends Cardiovasc Med 2023; 33:384-385. [PMID: 35337960 DOI: 10.1016/j.tcm.2022.03.006] [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] [Received: 03/14/2022] [Accepted: 03/16/2022] [Indexed: 11/23/2022]
Affiliation(s)
- Anna N Tomdio
- Pauley Heart Center, Virginia Commonwealth University Medical Center, Richmond, VA, United States
| | - Edward O McFalls
- McGuire Veterans Affairs Medical Center, 1201 Broad Rock Boulevard, 111J, Richmond, VA 23249, United States
| | - Ion S Jovin
- Pauley Heart Center, Virginia Commonwealth University Medical Center, Richmond, VA, United States; McGuire Veterans Affairs Medical Center, 1201 Broad Rock Boulevard, 111J, Richmond, VA 23249, United States.
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Wang XH, Li MD, Xie FX, Liang H, Yang L, Wei XF, Pang H, Wang ZJ, Jing XG. Prognostic utility of 99mTc-MIBI single photon emission computerized tomography myocardial perfusion imaging in patients with ischemia and non-obstructive coronary artery disease. Front Cardiovasc Med 2023; 10:1115135. [PMID: 37469480 PMCID: PMC10352836 DOI: 10.3389/fcvm.2023.1115135] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Accepted: 06/19/2023] [Indexed: 07/21/2023] Open
Abstract
Objective The aim of our study was to evaluate the prognostic value of gated SPECT MPI in non-obstructed coronary arteries (INOCA) patients, sought to stratify patients more accurately and thus derive more reliable prognostic information. Materials and methods In total, 167 patients with INOCA were enrolled. The patients were divided into two groups according to their SSS. Patients were followed-up regularly in terms of major adverse cardiovascular event (MACE), including cardiac death, nonfatal myocardial infarction, stroke, re-hospitalization with angina pectoris, and recurrent angina pectoris. Kaplan-Meier curves and Cox's proportional hazards models were used to analyze survival and identify predictive factors. Results Adverse cardiac events occurred in 33 cases (19.8%). The rate of MACE was higher in the summed stress score (SSS) ≥4 group than in the SSS 0-3 group (30.1% vs. 9.5%, respectively, P = 0.001) and MACE-free survival was lower (annual MACE-free rates of 87.5% vs. 96.2%, respectively, P = 0.003). Event-free survival was consistently higher in patients with normal arteries than in those with non-obstructive coronary artery disease (annual MACE-free rates of 96.1% and 88.4%, P = 0.035). When the SSS and the CAG results were combined, patients with normal coronary arteries (SSS 0-3) had the best prognosis and those with non-obstructive coronary artery stenosis (SSS ≥ 4) had the worst. However, the early prognosis of patients with non-obstructive coronary artery disease and SSS of 0-3 was comparable to that of patients with normal coronary arteries and SSS ≥ 4 (annual MACE-free rates of 100%, 94.6%, 93.1%, and 78.2%, respectively). Multivariate Cox's regression indicated that the SSS [hazard ratio (HR) = 1.126, 95% confidence interval (CI) 1.042-1.217, P = 0.003] and non-obstructive coronary artery disease (HR = 2.559, 95% CI 1.249-5.246, P = 0.01) were predictors of adverse cardiac events. Conclusion SPECT MPI data were prognostic for INOCA patients, thus identifying groups at high risk. The long-term predictive efficacy of such data exceeded that of CAG data. A combination of the two measures more accurately stratified INOCA patients in terms of risk.
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Zhang H, Caobelli F, Che W, Huang Y, Zhang Y, Fan X, Hu X, Xu C, Fei M, Zhang J, Lv Z, Shi K, Yu F. The prognostic value of CZT SPECT myocardial blood flow (MBF) quantification in patients with ischemia and no obstructive coronary artery disease (INOCA): a pilot study. Eur J Nucl Med Mol Imaging 2023; 50:1940-1953. [PMID: 36786817 PMCID: PMC10199834 DOI: 10.1007/s00259-023-06125-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 01/22/2023] [Indexed: 02/15/2023]
Abstract
BACKGROUND Despite the demonstrated adverse outcome, it is difficult to early identify the risks for patients with ischemia and no obstructive coronary artery disease (INOCA). We aimed to explore the prognostic potential of CZT SPECT in INOCA patients. METHODS The study population consisted of a retrospective cohort of 118 INOCA patients, all of whom underwent CZT SPECT imaging and invasive coronary angiography (ICA). Dynamic data were reconstructed, and MBF was quantified using net retention model. Major adverse cardiovascular events (MACEs) were defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure, late coronary revascularization, or hospitalization for unstable angina. RESULTS During a median follow-up of 15 months (interquartile range (IQR) 11-20), 19 (16.1%) MACEs occurred; both stress myocardial blood flow (sMBF) ([Formula: see text]) and coronary flow reserve (CFR) ([Formula: see text]) were significantly lower in the MACE group. Optimal thresholds of sMBF<3.16 and CFR<2.52 were extracted from the ROC curves, and both impaired sMBF (HR: 15.08; 95% CI 2.95-77.07; [Formula: see text]) and CFR (HR: 6.51; 95% CI 1.43-29.65; [Formula: see text]) were identified as prognostic factors for MACEs. Only sMBF<3.16 (HR: 11.20; 95% CI 2.04-61.41; [Formula: see text]) remained a robust predictor when sMBF and CFR were integrated considered. Compared with CFR, sMBF provides better prognostic model discrimination and reclassification ability (C-index improvement = 0.06, [Formula: see text]; net reclassification improvement (NRI) = 0.19; integrated discrimination improvement (IDI) = 0.10). CONCLUSION The preliminary results demonstrated that quantitative analysis on CZT SPECT provides prognostic value for INOCA patients, which may allow the stratification for early prevention and intervention.
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Affiliation(s)
- Han Zhang
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
- Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai, 200072, China
| | - Federico Caobelli
- Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Wenliang Che
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Yan Huang
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
- Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai, 200072, China
| | - Yu Zhang
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
- Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai, 200072, China
| | - Xin Fan
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
- Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai, 200072, China
| | - Xueping Hu
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
- Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai, 200072, China
| | - Chong Xu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Mengyu Fei
- Department of Radiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Jiajia Zhang
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
- Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai, 200072, China
| | - Zhongwei Lv
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
- Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai, 200072, China
| | - Kuangyu Shi
- Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
- Computer Aided Medical Procedures and Augmented Reality, Institute of Informatics I16, Technical University of Munich, Munich, Germany.
| | - Fei Yu
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
- Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai, 200072, China.
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Abstract
Coronary microvascular disease (CMD) causes myocardial ischemia in a variety of clinical scenarios. Clinical practice guidelines support routine testing for CMD in patients with ischemia with nonobstructive coronary artery disease. Invasive testing to identify CMD requires Doppler or thermodilution measures of flow to determine the coronary flow reserve and measures of microvascular resistance. Acetylcholine coronary reactivity testing identifies concomitant endothelial dysfunction, microvascular spasm, or epicardial coronary spasm. Comprehensive testing may improve symptoms, quality of life, and patient satisfaction by establishing a diagnosis and guiding-targeted medical therapy and lifestyle measures. Beyond ischemia with nonobstructive coronary artery disease, testing for CMD may play a role in patients with acute myocardial infarction, angina following coronary revascularization, heart failure with preserved ejection fraction, Takotsubo syndrome, and after heart transplantation. Additional education and provider awareness of CMD and its role in cardiovascular disease is needed to improve patient-centered outcomes of ischemic heart disease.
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Affiliation(s)
- Nathaniel R Smilowitz
- Division of Cardiology, Department of Medicine, NYU Langone Health, NY (N.R.S.)
- Cardiology Section, Department of Medicine, Veterans Affairs New York Harbor Healthcare System, NY (N.R.S.)
| | | | - Alaide Chieffo
- Interventional Cardiology Unit, San Raffaele Hospital, Milan, Italy (A.C.)
| | - Divaka Perera
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, UK (D.P.)
- Guy's and St Thomas' Hospital, London, UK (D.P.)
| | - Colin Berry
- British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Scotland, UK (C.B.)
- The West of Scotland Heart and Lung Centre, NHS Golden Jubilee, Glasgow, Scotland, UK (C.B.)
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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: 88] [Impact Index Per Article: 44.0] [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
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Caiati C, Stanca A, Lepera ME. Case report: Diagnosis of apical hypertrophic cardiomyopathy that escaped clinical and echocardiographic investigations for twenty years: Reasons and clinical implications. Front Cardiovasc Med 2023; 10:1157599. [PMID: 37168654 PMCID: PMC10165117 DOI: 10.3389/fcvm.2023.1157599] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 04/03/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND Apical hypertrophic cardiomyopathy (ApHCM) is a rare form of hypertrophic cardiomyopathy which predominantly affects the apex of the left ventricle. The diagnosis can be challenging due to several factors, ranging from no typical clinical and electrocardiogram (EKG) findings to potential difficulties in executing and interpreting the echocardiographic examination. CASE PRESENTATION We report the case of an 84-year-old woman who came to our echo-lab to undergo a routine echocardiogram. She had a history of permanent atrial fibrillation, paced rhythm and previous episodes of heart failure (HF), allegedly explained by a diagnosis of hypertensive heart disease that had been confirmed many times over the previous 20 years. The clinical examination and the EKG were unremarkable. The echocardiographic images were poor quality. But a senior cardiologist, expert in imaging and echocardiography, noted the lack of delineation of the endocardial border of the left ventricular (LV) apex region. Contrast echocardiography was performed and severe apical hypertrophy discovered. CONCLUSION ApHCM can be a challenging diagnosis. Contrast echocardiography must always be applied in cases of poor delineation of the LV apical endocardial border at baseline echocardiography. Timely detection and appropriate lifestyle intervention might slow the development of LV hypertrophy, and possibly minimize and delay heart failure (HF) related symptoms and arrhythmias. The prognosis remains relatively benign during long term follow-up.
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Affiliation(s)
- Carlo Caiati
- Unit of Cardiovascular Diseases, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Bari, Italy
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50
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Hung MJ, Yeh CT, Kounis NG, Koniari I, Hu P, Hung MY. Coronary Artery Spasm-Related Heart Failure Syndrome: Literature Review. Int J Mol Sci 2023; 24:ijms24087530. [PMID: 37108691 PMCID: PMC10145866 DOI: 10.3390/ijms24087530] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 04/04/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
Although heart failure (HF) is a clinical syndrome that becomes worse over time, certain cases can be reversed with appropriate treatments. While coronary artery spasm (CAS) is still underappreciated and may be misdiagnosed, ischemia due to coronary artery disease and CAS is becoming the single most frequent cause of HF worldwide. CAS could lead to syncope, HF, arrhythmias, and myocardial ischemic syndromes such as asymptomatic ischemia, rest and/or effort angina, myocardial infarction, and sudden death. Albeit the clinical significance of asymptomatic CAS has been undervalued, affected individuals compared with those with classic Heberden's angina pectoris are at higher risk of syncope, life-threatening arrhythmias, and sudden death. As a result, a prompt diagnosis implements appropriate treatment strategies, which have significant life-changing consequences to prevent CAS-related complications, such as HF. Although an accurate diagnosis depends mainly on coronary angiography and provocative testing, clinical characteristics may help decision-making. Because the majority of CAS-related HF (CASHF) patients present with less severe phenotypes than overt HF, it underscores the importance of understanding risk factors correlated with CAS to prevent the future burden of HF. This narrative literature review summarises and discusses separately the epidemiology, clinical features, pathophysiology, and management of patients with CASHF.
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Affiliation(s)
- Ming-Jui Hung
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital Keelung, Chang Gung University College of Medicine, Keelung City 24201, Taiwan
| | - Chi-Tai Yeh
- Department of Medical Research and Education, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Continuing Education Program of Food Biotechnology Applications, College of Science and Engineering, National Taitung University, Taitung 95092, Taiwan
| | - Nicholas G Kounis
- Department of Cardiology, University of Patras Medical School, 26221 Patras, Greece
| | - Ioanna Koniari
- Cardiology Department, Liverpool Heart and Chest Hospital, Liverpool L14 3PE, UK
| | - Patrick Hu
- Department of Internal Medicine, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA
- Department of Cardiology, Riverside Medical Clinic, Riverside, CA 92506, USA
| | - Ming-Yow Hung
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No.291, Zhongzheng Rd., Zhonghe District, New Taipei City 23561, Taiwan
- Taipei Heart Institute, Taipei Medical University, Taipei City 110301, Taiwan
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, New Taipei City 23561, Taiwan
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