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Boerhout CKM, Namba HF, Liu T, Beijk MAM, Damman P, Meuwissen M, Ong P, Sechtem U, Appelman Y, Berry C, Escaned J, Lerman A, Henry TD, van der Harst P, Delewi R, Piek JJ, van de Hoef TP. Rationale and design of the ILIAS ANOCA clinical trial: A blinded-arm controlled trial for routine ad-hoc coronary function testing. Am Heart J 2025; 286:1-13. [PMID: 40068714 DOI: 10.1016/j.ahj.2025.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 02/19/2025] [Accepted: 03/05/2025] [Indexed: 04/04/2025]
Abstract
BACKGROUND Angina with nonobstructive coronary arteries (ANOCA) is a major cause of chronic coronary syndromes, affecting nearly half of patients with anginal symptoms who undergo invasive coronary angiography. ANOCA may lead to substantial symptom burden, increased risk of adverse cardiac events, increased healthcare utilization due to ongoing symptoms, repeat hospitalizations, and invasive testing. The pathophysiology of ANOCA often involves a variety of coronary disorders, such as coronary microvascular dysfunction, epicardial or microvascular vasospasm and endothelial dysfunction. While coronary function testing (CFT) can identify each of these specific endotypes, in current practice it is used as a second- or third-line diagnostic tool, delaying diagnosis which contributes to persistent symptoms and diminished quality of life. The ILIAS ANOCA clinical trial aims to enhance understanding and management of ANOCA through early routine CFT-guided management. METHODS After exclusion of obstructive coronary artery disease, eligible patients undergo comprehensive CFT, and will be randomized to blinding of the CFT results (control group) or disclosure of the CFT results combined with a tailored medical therapy escalation plan (intervention group). The control group will be unblinded after 1 year. The primary outcome is the mean difference in the within-subject change in Seattle Angina Questionnaire (SAQ) summary score between the groups at 6 months from baseline. Secondary outcomes include differences in SAQ-summary score and additional health-status and quality of life questionnaires at 12 and 24 months from baseline. CLINICAL TRIAL REGISTRATION International Clinical Trials Registry Platform identifier NL-OMON20739.
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Affiliation(s)
- Coen K M Boerhout
- Department of Cardiology, Amsterdam University Medical Center, Location AMC, Amsterdam, The Netherlands
| | - Hanae F Namba
- Department of Cardiology, Amsterdam University Medical Center, Location AMC, Amsterdam, The Netherlands
| | - Tommy Liu
- Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands; HartKliniek Rijswijk, Rijswijk, The Netherlands
| | - Marcel A M Beijk
- Department of Cardiology, Amsterdam University Medical Center, Location AMC, Amsterdam, The Netherlands
| | - Peter Damman
- Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - Peter Ong
- Department of Cardiology, Robert Bosch Krankenhaus, Stuttgart, Germany
| | - Udo Sechtem
- Department of Cardiology, Robert Bosch Krankenhaus, Stuttgart, Germany
| | - Yolande Appelman
- Department of Cardiology, Amsterdam University Medical Center, Location VUmc, Amsterdam, The Netherlands
| | - Colin Berry
- British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland; The West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, Scotland
| | - Javier Escaned
- Cardiology Department, Hospital Clínico San Carlos, IDISSC Universidad Complutense de Madrid Spain
| | - Amir Lerman
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Timothy D Henry
- The Carl and Edyth Lindner Center for Research and Education, The Christ Hospital, Cincinnati, OH
| | - Pim van der Harst
- Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Ronak Delewi
- Department of Cardiology, Amsterdam University Medical Center, Location AMC, Amsterdam, The Netherlands
| | - Jan J Piek
- Department of Cardiology, Amsterdam University Medical Center, Location AMC, Amsterdam, The Netherlands
| | - Tim P van de Hoef
- Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
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Berry C, Camici PG, Crea F, George M, Kaski JC, Ong P, Pepine CJ, Pompa A, Sechtem U, Shimokawa H, Zeitz C, Escaned J, van de Hoef TP, Beltrame JF, Merz CNB. Clinical standards in angina and non-obstructive coronary arteries: A clinician and patient consensus statement. Int J Cardiol 2025; 429:133162. [PMID: 40088955 DOI: 10.1016/j.ijcard.2025.133162] [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: 01/04/2025] [Revised: 03/02/2025] [Accepted: 03/12/2025] [Indexed: 03/17/2025]
Abstract
Patients with angina and non-obstructive coronary arteries (ANOCA) or myocardial ischaemia with non-obstructive coronary arteries (INOCA) comprise a relatively large subgroup within those with ischaemic heart disease. Advances in the understanding of disease mechanisms, diagnostic tests and multidisciplinary care are improving awareness of the needs of affected individuals. However, practice variations and suboptimal management promulgate the health burden and increase health care resource consumption. Clinical standards represent a limited number of quality statements that describe the care patients should be offered by health professionals and providers for a specific clinical condition or defined clinical pathway in line with current best evidence. Clinical standards should address implementation of this evidence along with education of patients and healthcare professionals, multidisciplinary care networks, and research. In this consensus statement, we highlight contemporary evidence and stakeholder views, including clinicians and patients, to provide an international perspective for developing clinical standards for services involving ANOCA/INOCA patients. A clinical service for ANOCA/INOCA should "consider the whole patient" and provide a multidisciplinary, patient-centred service.
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Affiliation(s)
- Colin Berry
- British Heart Foundation Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, UK; West of Scotland Heart and Lung Centre, NHS Golden Jubilee hospital, Clydebank, UK.
| | | | - Filippo Crea
- Ospedale Isola Tiberina - Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | - Juan Carlos Kaski
- Molecular and Clinical Sciences Research Institute, St George's, University of London, UK
| | - Peter Ong
- Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus, Stuttgart, Germany
| | - Carl J Pepine
- Division of Cardiovascular Medicine, University of Florida, College of Medicine, Gainesville, Florida, USA
| | - Annette Pompa
- International Heart Spasms Alliance, Lehigh Valley, USA
| | - Udo Sechtem
- Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus, Stuttgart, Germany
| | - Hiroaki Shimokawa
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Graduate School, International University of Health and Welfare, Narita, Japan
| | - Christopher Zeitz
- Department of Cardiology, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Adelaide, Australia
| | - Javier Escaned
- Hospital Clínico San Carlos IDISSC, Complutense University of Madrid and CIBERCV, Madrid, Spain
| | - Tim P van de Hoef
- Division Heart and Lung, Cardiology, University Medical Center Utrecht, the Netherlands
| | - John F Beltrame
- The Discipline of Medicine, University of Adelaide, Basil Hetzel Institute, Central Adelaide Local Health Network, Adelaide, South Australia, Australia
| | - C Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
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Takahashi T, Wei J, Iribarren AC, Gulati M, Cook-Wiens G, Nelson MD, Sharif B, Handberg EM, Anderson RD, Petersen J, Berman DS, Pepine CJ, Merz CNB. Rationale and design of the women's ischemia syndrome evaluation mechanisms of coronary microvascular dysfunction leading to preheart failure with preserved ejection fraction (WISE Pre-HFPEF). Am Heart J 2025; 284:47-56. [PMID: 40010584 PMCID: PMC11952140 DOI: 10.1016/j.ahj.2025.02.017] [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: 12/16/2024] [Revised: 02/17/2025] [Accepted: 02/18/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND There is increasing recognition that the pathophysiology of coronary microvascular dysfunction (CMD) plays a pivotal role in the development of heart failure with preserved ejection fraction (HFpEF). However, the mechanisms underlying this role are not known. STUDY DESIGN AND METHODS The Women's Ischemia Syndrome Evaluation Mechanisms of Coronary Microvascular Dysfunction Leading to Pre-Heart Failure With Preserved Ejection Fraction (WISE Pre-HFpEF) is a prospective cohort study enrolling 180 women and men undergoing clinically indicated invasive coronary angiography for suspected ischemia with no obstructive coronary artery disease. The study aims to investigate (1) CMD-related ischemia contribution to myocellular damage and impaired left ventricular (LV) relaxation as determined invasively by ultra-high sensitivity cardiac troponin I (u-hs-cTnI) measurements in the coronary sinus/great cardiac vein and LV pressure-volume loops, respectively, during provocative stress testing with isometric handgrip, and (2) CMD-related ischemic myocellular damage contribution to LV diastolic dysfunction progression as assessed using cardiac magnetic resonance imaging obtained at enrollment and 1-2 years later, along with prospectively repeated ambulatory u-hs-cTnI measurements. CONCLUSIONS The WISE pre-HFpEF study is designed to investigate whether ischemic myocardial damage secondary to CMD contributes to the progression of LV diastolic dysfunction. The findings from this study will provide new understanding of the role of CMD in HFpEF development as well as the potential benefits of CMD-directed therapies for the prevention and treatment of HFpEF. TRIAL REGISTRATION ClilicalTrial.gov, NCT03876223.
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Affiliation(s)
| | - Janet Wei
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Ana C Iribarren
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Martha Gulati
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Galen Cook-Wiens
- Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Michael D Nelson
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Behzad Sharif
- Krannert Cardiovascular Research Center, Indiana University School of Medicine, Indianapolis, IN
| | - Eileen M Handberg
- Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL
| | - R David Anderson
- Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL
| | - John Petersen
- Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL
| | - Daniel S Berman
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Carl J Pepine
- Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL
| | - C Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
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Liu Y, Wang Z, Collins SP, Testani J, Safdar B. Sex differences in proteomics of cardiovascular disease - Results from the Yale-CMD registry. IJC HEART & VASCULATURE 2025; 58:101667. [PMID: 40224648 PMCID: PMC11987697 DOI: 10.1016/j.ijcha.2025.101667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 03/20/2025] [Accepted: 03/22/2025] [Indexed: 04/15/2025]
Abstract
Aims This study assessed sex-specific proteomic profiles by cardiovascular disease (CVD) phenotype (coronary artery disease [CAD] vs coronary microvascular dysfunction [CMD]) and describe their role in sex-specific pathways. METHODS In a secondary biobank analysis of the Yale-CMD registry, adults with ischemic symptoms who underwent cardiac positron emission test/computed tomography were categorized as a) controls (normal coronary flow reserve (CFR) > 2 without perfusion defect or coronary calcification), b) having CMD (CFR < 2 without defect or calcification), or c) having CAD (known CAD or new perfusion defect). Using proximity extension assays (Olink® Explore 3072), we examined 2944 proteins. Differential protein expression was assessed using linear regression models, adjusting for age, race, body mass index, diabetes, dyslipidemia, hypertension, or smoking. RESULTS Of 190 patients, 91 provided blood samples (mean age, 56 years; 66 %, females; 48 %, controls; 24 %, CAD; 27 %, CMD). Among controls, 15 proteins showed sex differences (5 proteins upregulated in females, 10 in males; false discovery rate [FDR < 0.05]). Upregulated in CAD patients were FSHB in females and INSL3 and EDDM3B in males (FDR < 0.05). Among CMD patients, SCGB3A1 and HGFAC were higher in females; INSL3, SPINT3, EDDM3B, and KLK3 were higher in males (FDR < 0.05). Per pathway analysis, females showed upregulation of immune pathways in CAD and lipid and glucose metabolism pathways in CMD. Males showed upregulated endothelial regulation of blood flow in CAD and increased angiogenesis in CMD. CONCLUSIONS Sex differences exist in the proteomic profiles of CAD and CMD patients, highlighting a need for precision medicine.
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Affiliation(s)
- Yihan Liu
- Program in Computational Biology & Biomedical informatics, Yale University, New Haven, CT, USA
- Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA
| | - Zuoheng Wang
- Program in Computational Biology & Biomedical informatics, Yale University, New Haven, CT, USA
- Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA
- Department of Biomedical Informatics & Data Science, Yale University School of Medicine, New Haven, CT, USA
| | - Sean P. Collins
- Department of Emergency Medicine, Vanderbilt University Medical Center, and Veterans Affairs Tennessee Valley Healthcare System, Geriatric Research, Education and Clinical Center (GRECC), Nashville, TN, USA
| | - Jeffery Testani
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Basmah Safdar
- Department of Emergency Medicine, Yale University School of Medicine, New Haven, CT, USA
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Chilian WM, Ahmed T, Merz CNB, Pepine CJ, Domingo CN, Mehta PK. A chronology of basic and clinical research in the coronary microcirculation. J Mol Cell Cardiol 2025; 203:59-66. [PMID: 40209982 DOI: 10.1016/j.yjmcc.2025.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 04/02/2025] [Accepted: 04/07/2025] [Indexed: 04/12/2025]
Affiliation(s)
- William M Chilian
- Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, United States
| | - Taha Ahmed
- Emory Cardiovascular Disease Fellowship Training Program, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States
| | - C Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, CA, United States
| | - Carl J Pepine
- Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL, United States
| | - Catherine Nicole Domingo
- Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, United States
| | - Puja K Mehta
- Emory Clinical Cardiovascular Research Institute and Emory Women's Heart Center, Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States.
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Seshadri H, Gunasekaran D, Mohammad A, Rachoori S, Rajakumar HK. Myocardial ischemia in nonobstructive coronary arteries: A review of diagnostic dilemmas, current perspectives, and emerging therapeutic innovations. World J Cardiol 2025; 17:106541. [DOI: 10.4330/wjc.v17.i5.106541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/27/2025] [Accepted: 05/07/2025] [Indexed: 05/23/2025] Open
Abstract
Myocardial infarction with nonobstructive coronary arteries is a unique presentation of acute coronary syndrome occurring in patients without significant coronary artery disease. Its pathophysiology involves atherosclerotic and nonatherosclerotic mechanisms such as plaque erosion, coronary microvascular dysfunction, vasospasm, spontaneous coronary artery dissection, autoimmune and inflammatory diseases, and myocardial oxygen supply-demand imbalance. A systematic approach to diagnosis is needed due to the diverse range of underlying causes. Cardiac troponins confirm the myocardial injury and coronary angiography rules out significant obstruction. Cardiac magnetic resonance imaging differentiates ischemic from nonischemic causes, and additional investigations, such as intravascular ultrasound, optical coherence tomography, and provocative testing, play a role in identifying the etiology to guide management strategies. Atherosclerotic cases require antiplatelet therapy and statins, vasospastic cases respond to calcium channel blockers, spontaneous coronary artery dissection is typically managed conservatively, and coronary microvascular dysfunction may require vasodilators. Lifestyle modifications and cardiac rehabilitation are essential for improving outcomes. The prognosis of patients experiencing recurrent events despite treatment is uncertain, but long-term outcomes depend on the etiology, highlighting the need for personalized management. Future research should focus on refining diagnostic protocols and identifying optimal therapeutic strategies. Randomized controlled trials are necessary to establish evidence-based treatments for different subtypes of myocardial infarction with nonobstructive coronary arteries.
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Affiliation(s)
- Hariharan Seshadri
- Institute of Internal Medicine, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai 600003, Tamil Nadu, India
| | - Dhaiyanitha Gunasekaran
- Department of General Surgery, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | | | - Srinivas Rachoori
- Department of General Surgery, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | - Hamrish Kumar Rajakumar
- Department of General Surgery, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
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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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Qian W, Lingli X, Dexue L, Yangwen C, Yongyan S, Weihua W. Influence of fluctuations in fasting blood glucose on left ventricular function in patients with type 2 diabetes mellitus and coronary microcirculation dysfunction: a prospective cohort study. Acta Diabetol 2025:10.1007/s00592-025-02514-2. [PMID: 40332563 DOI: 10.1007/s00592-025-02514-2] [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: 12/31/2024] [Accepted: 04/16/2025] [Indexed: 05/08/2025]
Abstract
AIMS To examine the effects of fluctuations in fasting blood glucose (FBG) levels on left ventricular function in patients with T2DM and coronary microcirculation dysfunction (CMD). METHODS A total of 290 patients with T2DM who received glucose-lowering therapy during hospitalization and were subsequently followed up for 18 months at the First Affiliated Hospital of Harbin Medical University, were enrolled in this study. 135 were diagnosed with CMD and were assigned to the CMD group, whereas 155 patients without CMD were allocated to the non-CMD group. The fasting blood glucose coefficient of variation (FBG-CV) was calculated for all participants. The CMD group was further stratified into three subgroups based on their FBG-CV values: CMD1 (FBG-CV > 25%), CMD2 (FBG-CV 15% ~ 25%), and CMD3 (FBG-CV < 15%). The left ventricular function, assessed by left ventricular ejection fraction (LVEF) and the E/e' ratio, was compared within each group before and after the follow-up period. This study was registered in the Chinese Clinical Trial Register, ChiCTR-ORC-16009800. RESULTS After the end of follow-up, the E/e' ratio in CMD1 was significantly higher than that in CMD2 and CMD3 (14.35 vs 8.57; p < 0.01; 14.35 vs 6.61; p < 0.01), and the E/e' ratio in CMD2 was significantly higher than that in CMD3 (8.57 vs 6.61; p < 0.01). Compared to the baseline measurements, the E/e' ratio in CMD1 showed a significant increase after an average 17.8 months of follow up (14.35 vs 8.44; p < 0.001). We found elevated E/e' ratio was associated with an increased FBG-CV level (odds ratio [OR]: 2.571; 95% CI 1.819-3.634; p < 0.001). In multivariate logistic analysis, course of diabetes (OR:1.062; 1.016-1.11; P = 0.007) and CMD (OR:2.231; 1.303-3.819; P = 0.003), were significantly associated with elevated E/e' ratio, while oral stains drugs (OR = 0.412 95% CI 0.237-0.715; P = 0.002) and insulin injections (OR = 0.536 95% CI 0.311-0.924; P = 0.025) behaved as a protective factor. CONCLUSIONS Our study clarified the association between FBG-CV levels and the E/e' ratio in a prospective cohort study. In T2DM patients with CMD, FBG-CV > 25% may adversely affect left ventricular diastolic function, whereas an optimal FBG-CV is considered to be less than 15%.
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Affiliation(s)
- Wang Qian
- Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China
- Department of Endocrinology, Shenzhen Third People's Hospital, Shenzhen, 518112, Guangdong Province, China
| | - Xie Lingli
- Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China
| | - Lu Dexue
- Department of Endocrinology, Shenzhen Third People's Hospital, Shenzhen, 518112, Guangdong Province, China
| | - Chen Yangwen
- Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China
| | - Shan Yongyan
- Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China
| | - Wu Weihua
- Department of Endocrinology, Shenzhen Third People's Hospital, Shenzhen, 518112, Guangdong Province, China.
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Tas A, Alan Y, Kara Tas I, Umman S, Parker KH, van de Hoef TP, Sezer M, Piek JJ. The impact of high microvascular resistance on coronary wave energetics depends on coronary microvascular functionality. EUROPEAN HEART JOURNAL OPEN 2025; 5:oeaf050. [PMID: 40417173 PMCID: PMC12100483 DOI: 10.1093/ehjopen/oeaf050] [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: 02/14/2025] [Revised: 04/20/2025] [Accepted: 04/30/2025] [Indexed: 05/27/2025]
Abstract
Aims The pathophysiological relevance of high hyperemic microvascular resistance (hMR) in stable coronary artery disease is controversial. Using wave intensity analysis (WIA, defined as the product of the time derivatives of the coronary pressure and velocity), we aim to compare the impact of high hMR on coronary wave energetics with respect to coronary microvascular dysfunction (CMD), defined as reduced coronary flow reserve (CFR < 2.5), in unobstructed arteries. Methods and results The study population (n = 258, mean age = 68 ± 10 years, 73% male) had a high cardiovascular risk profile including dyslipidemia (88%), hypertension (70%), smoking (55%) and diabetes (28%). The mean fractional flow reserve was 0.89 ± 0.05. Vessels (n = 312) were divided into four endotypes: no CMD-low hMR (CFR ≥ 2.5, hMR < 2.5 mmHg.s.cm-1), Functional CMD (CFR < 2.5, hMR < 2.5 mmHg.s.cm-1), Structural CMD (CFR < 2.5, hMR ≥ 2.5 mmHg.s.cm-1), and no CMD-high hMR (CFR ≥ 2.5, hMR ≥ 2.5 mmHg.s.cm-1). The no CMD-high hMR endotype had the lowest mean resting velocity (bAPV = 10 ± 3 cm.s-1 P < 0.001), highest mean basal microvascular resistance (bMR = 9 ± 2 mmHg/cm.s-1 P < 0.001) amongst all endotypes, yet, it had reference-level CFR, microvascular resistance reserve and resistive reserve ratio (P > 0.05 for all compared to no CMD-low hMR), unlike CMD endotypes (P < 0.05 compared to CMD endotypes). The no CMD-high hMR endotype exhibited the highest hyperemic increase in the accelerating wave energy proportion (AEP) (13% ± 13%, P = 0.042), indicating an intact autoregulatory response. Only in the CMD endotypes, high hMR was associated with reduced AEP (r = -0.229, P < 0.001), unlike no CMD endotypes (P = 0.383). Conclusion High hMR alone is not a definitive CMD marker. In line with the adaptive high hMR hypothesis, increased hMR does not necessarily limit augmentation of AEP, and is associated with robust autoregulatory capacity in vessels with preserved CFR. Cardiologists should be alert to a potential adaptive no CMD-high hMR endotype to avoid misdiagnosis. Registration NCT02328820.
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Affiliation(s)
- Ahmet Tas
- Department of Cardiology, Amsterdam UMC, Heart Centre, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Department of Emergency Medicine, Gomec State Hospital, Ayanoglu Str. No:14, 10715 Gomec, Balikesir, Turkey
| | - Yaren Alan
- Faculty of Medicine, Istanbul University, Turgut Ozal Millet Str, 34093 Fatih, Istanbul, Turkey
| | - Ilke Kara Tas
- Department of Emergency Medicine, Gomec State Hospital, Ayanoglu Str. No:14, 10715 Gomec, Balikesir, Turkey
| | - Sabahattin Umman
- Faculty of Medicine, Istanbul University, Turgut Ozal Millet Str, 34093 Fatih, Istanbul, Turkey
- Department of Cardiology, Istanbul University, Istanbul, Turgut Ozal Millet Str, 34093 Fatih, Turkey
| | - Kim H Parker
- Department of Bioengineering, Imperial College, SW7 2AZ, London, UK
| | - Tim P van de Hoef
- Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Murat Sezer
- Department of Cardiology, Acibadem International Hospital, Yesilkoy Istanbul Str. No:82, 34149 Bakirkoy, Istanbul, Turkey
| | - Jan J Piek
- Department of Cardiology, Amsterdam UMC, Heart Centre, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
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10
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Barrio Alonso AI, Broncano Cabrero J, Villán González AM, López Suárez Y, López Muñiz C, Luna Alcalá A. Thoracic pain: From guidelines to clinical practice. RADIOLOGIA 2025; 67:399-412. [PMID: 40412854 DOI: 10.1016/j.rxeng.2024.05.007] [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: 12/29/2023] [Accepted: 05/03/2024] [Indexed: 05/27/2025]
Abstract
Thoracic pain is the most prevalent symptom in patients with cardiovascular diseases. Diagnosis and patient management are guided by the pain attributes, analytical parameters, and several different imaging modalities. Invasive imaging tests and cardiac magnetic resonance are highly relevant in this context, as set out in the 2023 European guidelines for the management of acute coronary syndromes, the 2023 American guidelines for the management of patients with chronic coronary disease, and the 2021 American guidelines for the evaluation and diagnosis of chest pain. This article focuses on the role that these guidelines attribute to non-invasive cardiac imaging (computed tomography and cardiac magnetic resonance) in the management of both acute and chronic coronary syndrome.
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Affiliation(s)
- A I Barrio Alonso
- Hospital Universitario de Cabueñes, Gijón, Asturias, Spain; HT Médica Gijón-Hospital Covadonga, Gijón, Asturias, Spain.
| | | | | | - Y López Suárez
- Hospital Universitario de Cabueñes, Gijón, Asturias, Spain
| | - C López Muñiz
- Hospital Universitario de Cabueñes, Gijón, Asturias, Spain
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11
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Velollari O, Rommel KP, Kresoja KP, Lurz P, Gori T. Focusing on microvascular function in heart failure with preserved ejection fraction. Heart Fail Rev 2025; 30:493-503. [PMID: 39804445 PMCID: PMC11992002 DOI: 10.1007/s10741-024-10479-7] [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] [Accepted: 12/20/2024] [Indexed: 04/12/2025]
Abstract
Heart failure is a prevalent global health issue. Heart failure with preserved ejection fraction (HFpEF), which already represents half of all heart cases worldwide, is projected to further increase, driven by aging populations and rising cardiovascular risk factors. Effective therapies for HFpEF remain limited, particularly due to its pathophysiological heterogeneity and incomplete understanding of underlying pathomechanisms and implications. Coronary microvascular dysfunction (CMD), characterized by structural and functional changes in the coronary microcirculation, is increasingly recognized as a significant factor in HFpEF even though the exact nature of their causal relationship is still unclear. This review explores prevalence, prognostic implications, and potential therapeutic targets for CMD in HFpEF. CMD's role in HFpEF might involve impaired coronary blood flow regulation, leading to myocardial ischemia, impaired relaxation, and/or adverse remodeling. Vice versa, increased wall stress in patients with HFpEF might elevate coronary resistances, further worsening microvascular perfusion. Finally, abnormalities in substrate metabolism might cause both CMD and HFpEF. Current treatments, including pharmacotherapy and device-based therapies, show limited success, highlighting the need for more targeted approaches. New possible therapies, such as the coronary sinus reducer device, may show promise in improving myocardial perfusion and function. However, further large-scale studies are required to elucidate the mechanistic links between CMD and HFpEF and to develop specialized treatments for distinct heart failure phenotypes.
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Affiliation(s)
- Ornela Velollari
- Department of Cardiology, Cardiology I, University Medical Center Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
- German Centre for Cardiovascular Research (DZHK), Standort Rhein-Main, Frankfurt, Germany
| | - Karl-Philipp Rommel
- Department of Cardiology, Cardiology I, University Medical Center Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
- German Centre for Cardiovascular Research (DZHK), Standort Rhein-Main, Frankfurt, Germany
| | - Karl-Patrik Kresoja
- Department of Cardiology, Cardiology I, University Medical Center Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
- German Centre for Cardiovascular Research (DZHK), Standort Rhein-Main, Frankfurt, Germany
| | - Philipp Lurz
- Department of Cardiology, Cardiology I, University Medical Center Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
- German Centre for Cardiovascular Research (DZHK), Standort Rhein-Main, Frankfurt, Germany
| | - Tommaso Gori
- Department of Cardiology, Cardiology I, University Medical Center Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.
- German Centre for Cardiovascular Research (DZHK), Standort Rhein-Main, Frankfurt, Germany.
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12
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Urtasun-Iriarte C, Ezponda A, Barrio-Piqueras M, Bastarrika G. State of the Art in Imaging of Acute Coronary Syndrome with Nonobstructed Coronary Arteries. Radiographics 2025; 45:e240079. [PMID: 40179023 DOI: 10.1148/rg.240079] [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: 04/05/2025]
Abstract
Acute chest pain is a common concern for which patients present to the emergency department. Nonetheless, many patients with acute chest pain indicative of acute coronary syndrome (ACS) show nonobstructed coronary arteries at invasive coronary angiography or coronary CT angiography (CCTA), which is a clinical conundrum in day-to-day practice. Guidelines recommend that the initial course of action for patients experiencing acute chest pain is to exclude extracardiac and cardiac conditions that could cause nonischemic myocardial damage, including aortic dissection, pulmonary embolism, or septic shock. The generic term troponin-positive with nonobstructed coronary arteries (TpNOCA) was coined to refer to patients with nonobstructed coronary arteries who present with clinical symptoms and signs of ACS and increased cardiac troponin levels, electrocardiographic changes, or both. The causes of TpNOCA may be ischemic (eg, myocardial infarction with nonobstructed coronary arteries [MINOCA] or ischemia with nonobstructed coronary arteries [INOCA]) or nonischemic (eg, extracardiac and cardiac entities). MINOCA and INOCA are working diagnostic terms used until a definitive cause is established (eg, coronary plaque rupture, coronary artery dissection, or coronary microvascular disease). Noninvasive cardiac imaging techniques, notably CCTA and cardiac MRI, and ischemia testing are pivotal in evaluating and treating these patients through accurate identification of the underlying cause, improvement in risk stratification, and guidance for clinicians in decision making for treatment and follow-up. ©RSNA, 2025.
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Affiliation(s)
- César Urtasun-Iriarte
- From the Department of Radiology, Clínica Universidad de Navarra, Avenida Pío XII No. 36, Pamplona 31008, Spain
| | - Ana Ezponda
- From the Department of Radiology, Clínica Universidad de Navarra, Avenida Pío XII No. 36, Pamplona 31008, Spain
| | - Miguel Barrio-Piqueras
- From the Department of Radiology, Clínica Universidad de Navarra, Avenida Pío XII No. 36, Pamplona 31008, Spain
| | - Gorka Bastarrika
- From the Department of Radiology, Clínica Universidad de Navarra, Avenida Pío XII No. 36, Pamplona 31008, Spain
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13
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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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14
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Pintea Bentea G, Awada A, Berdaoui B. Should We Revisit the Clinical Value of Fractional Flow Reserve in the Era of Coronary Microvascular Dysfunction? Biomedicines 2025; 13:1086. [PMID: 40426914 DOI: 10.3390/biomedicines13051086] [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: 03/31/2025] [Revised: 04/27/2025] [Accepted: 04/28/2025] [Indexed: 05/29/2025] Open
Abstract
The understanding of coronary artery disease is evolving, with more attention given currently to the microcirculation compartment. Coronary microvascular dysfunction (CMD) is defined by any structural or functional alteration of the coronary microcirculation, and is prevalent in current clinical practice, being associated with pejorative cardiovascular prognosis. CMD can exist by itself as primary microvascular angina, or in association with a variety of cardiovascular diseases. On the other hand, fractional flow reserve (FFR) represents the gold standard for estimating the hemodynamic impact of moderate coronary artery stenosis, and as such guiding coronary revascularization in clinical practice. The fundamental clinical trials that introduced and validated the use of FFR in current clinical practice were published before acquiring more in-depth knowledge on CMD and the impact it can have on FFR measurements. However, in the setting of CMD, studies have shown that FFR can underestimate the severity of coronary stenosis. In addition, recent findings underline the limitations of FFR to guide revascularization in terms of clinical outcome in specific conditions associated with CMD, such as acute coronary syndrome or multivessel coronary artery disease. As such, new research efforts must be made to investigate the reliability of FFR or to reposition its use in guiding coronary revascularization in the context of CMD, in order to define the clinical value of FFR in this particular setting.
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Affiliation(s)
| | - Ahmad Awada
- Department of Interventional Cardiology, CHU Brugmann, 1020 Brussels, Belgium
| | - Brahim Berdaoui
- Department of Interventional Cardiology, CHU Brugmann, 1020 Brussels, Belgium
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15
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Sarwar S, Ahmed F, Kadoya Y, Hakimjavadi R, Boczar KE. Assessment of Coronary Microvascular Dysfunction in Patients with Systemic Vasculitis. Curr Cardiol Rep 2025; 27:81. [PMID: 40198429 DOI: 10.1007/s11886-025-02231-w] [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] [Accepted: 03/24/2025] [Indexed: 04/10/2025]
Abstract
INTRODUCTION Coronary microvascular dysfunction (CMD) is characterized by impaired coronary blood flow in the absence of obstructive coronary artery disease. CMD primarily involves the microvasculature, leading to myocardial ischemia, angina, and increased cardiovascular risk. Systemic vasculitides (e.g., giant cell arteritis, antineutrophil cytoplasmic antibody-associated vasculitis, and Takayasu arteritis) are a group of autoimmune conditions known to affect the vasculature through inflammation of the blood vessels that have been associated with more prevalent and severe CMD. Although systemic inflammation likely plays a role in the increased risk of cardiovascular events, the underlying pathogenesis is not well understood. PURPOSE OF REVIEW Invasive and non-invasive techniques for assessing coronary microvascular function have been developed to assess for blood flow and coronary flow reserve (CFR), defined as the ratio of the maximum achievable blood flow during stress to the resting blood flow. The purpose of this review is to further explore the relationship between vasculitis and CMD as well as the techniques available for assessing this association. RECENT FINDINGS Studies have shown that CMD is significantly more prevalent in patients with systemic vasculitis compared to the general population. Moreover, in the absence of significant atherosclerotic burden, patients with vasculitis have a lower CFR than controls, indicating more severely impaired coronary vasomotor function. This suggests that systemic inflammation itself is a factor in driving coronary vasomotor abnormalities and CMD development. CMD contributes to cardiovascular morbidity in patients with systemic vasculitis, underscoring the need for early recognition and management. Further studies are needed to determine whether therapies targeting the reduction of systemic inflammation can lead to improved coronary microvascular function and cardiovascular outcomes.
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Affiliation(s)
- Shihab Sarwar
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Canada
| | - Faisal Ahmed
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Canada
| | - Yoshito Kadoya
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Canada
| | - Ramtin Hakimjavadi
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Canada
| | - Kevin Emery Boczar
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Canada.
- School of Epidemiology and Public Health, Department of Medicine, University of Ottawa, Ottawa, Canada.
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16
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Tognola C, Maloberti A, Varrenti M, Mazzone P, Giannattasio C, Guarracini F. Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA): Current Insights into Pathophysiology, Diagnosis, and Management. Diagnostics (Basel) 2025; 15:942. [PMID: 40218292 PMCID: PMC11989022 DOI: 10.3390/diagnostics15070942] [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: 02/18/2025] [Revised: 03/14/2025] [Accepted: 04/01/2025] [Indexed: 04/14/2025] Open
Abstract
Myocardial infarction with nonobstructive coronary arteries (MINOCA) is an increasingly recognized clinical entity characterized by myocardial injury in the absence of a significant coronary artery obstruction. MINOCA encompasses a diverse range of pathophysiological mechanisms, including coronary plaque disruption, coronary vasospasm, coronary microvascular dysfunction, thromboembolism, and spontaneous coronary artery dissection. A systematic diagnostic approach is essential to identify the underlying etiology and guide appropriate management strategies. Advanced imaging techniques, particularly cardiac magnetic resonance, play a pivotal role in distinguishing ischemic from non-ischemic myocardial injury and refining prognosis. Despite growing awareness, standardized treatment protocols remain limited, with current management largely extrapolated from strategies used in obstructive coronary artery disease. Notably, MINOCA is significantly more prevalent in women, emphasizing the need to understand sex-related differences in its pathophysiology, presentation, and clinical outcomes. This narrative review offers a comprehensive and up-to-date overview of MINOCA, including a dedicated chapter on sex-related considerations. It integrates recent advancements and highlights the importance of personalized management strategies.
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Affiliation(s)
- Chiara Tognola
- Clinical Cardiology Unit, De Gasperis Cardio Center, Niguarda Hospital, 20162 Milan, Italy; (A.M.); (C.G.)
| | - Alessandro Maloberti
- Clinical Cardiology Unit, De Gasperis Cardio Center, Niguarda Hospital, 20162 Milan, Italy; (A.M.); (C.G.)
- School of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy
| | - Marisa Varrenti
- Electrophysiology Unit, De Gasperis Cardio Center, Niguarda Hospital, 20162 Milan, Italy; (M.V.); (P.M.); (F.G.)
| | - Patrizio Mazzone
- Electrophysiology Unit, De Gasperis Cardio Center, Niguarda Hospital, 20162 Milan, Italy; (M.V.); (P.M.); (F.G.)
| | - Cristina Giannattasio
- Clinical Cardiology Unit, De Gasperis Cardio Center, Niguarda Hospital, 20162 Milan, Italy; (A.M.); (C.G.)
- School of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy
| | - Fabrizio Guarracini
- Electrophysiology Unit, De Gasperis Cardio Center, Niguarda Hospital, 20162 Milan, Italy; (M.V.); (P.M.); (F.G.)
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17
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Gąsecka A, Szolc P, van der Pol E, Niewiara Ł, Guzik B, Kleczyński P, Tomaniak M, Figura E, Zaremba M, Grabowski M, Kochman J, Legutko J, Kołtowski Ł. Endothelial Cell-Derived Extracellular Vesicles Allow to Differentiate Between Various Endotypes of INOCA: A Multicentre, Prospective, Cohort Study. J Cardiovasc Transl Res 2025; 18:305-315. [PMID: 39638955 PMCID: PMC12043753 DOI: 10.1007/s12265-024-10575-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 11/18/2024] [Indexed: 12/07/2024]
Abstract
Ischemia and non-obstructive coronary artery disease (INOCA) might be due to coronary microvascular dysfunction (CMD), vasospastic angina (VSA) or both. We compared plasma concentration of various extracellular vesicles (EVs) in patients with different INOCA endotypes. Patients were divided into those with INOCA (CMD, VSA, mixed CMD + VSA) and non-anginal chest pain. Plasma concentrations of EVs were measured using flow cytometry. Out of 96 patients included, 34 had CMD (35%), 15 VSA (16%), 24 mixed endotype (25%) and 23 non-anginal chest pain (24%). Patients with INOCA had lower ratio of endothelial EVs (CD144 +) to total EVs, compared to patients with non-anginal pain (p = 0.027). Patients with mixed endotype had lower ratio of endothelial EVs (CD144 +) to total EVs, compared to CMD (p = 0.008), VSA (p = 0.014) and non-anginal pain (p < 0.001). Decreased ratio of endothelial EVs (CD144 +) to total EVs might serve as a "circulating footprint" of the mixed INOCA endotype.
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Affiliation(s)
- Aleksandra Gąsecka
- 1st Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.
- Amsterdam Vesicle Center, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
| | - Piotr Szolc
- Department of Emergency Medicine, Faculty of Health Sciences, Jagiellonian University Medical College, Kraków, Poland
- Clinical Department of Interventional Cardiology, Saint John Paul II Hospital, Krakow, Poland
| | - Edwin van der Pol
- Amsterdam Vesicle Center, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam UMCBiomedical Engineering & PhysicsLaboratory of Experimental Clinical Chemistry, University of Amsterdam, Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Meibergdreef 9, Amsterdam, The Netherlands
| | - Łukasz Niewiara
- Clinical Department of Interventional Cardiology, Saint John Paul II Hospital, Krakow, Poland
- Faculty of Medicine, Institute of Cardiology, Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow, Poland
| | - Bartłomiej Guzik
- Clinical Department of Interventional Cardiology, Saint John Paul II Hospital, Krakow, Poland
- Faculty of Medicine, Institute of Cardiology, Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow, Poland
| | - Paweł Kleczyński
- Clinical Department of Interventional Cardiology, Saint John Paul II Hospital, Krakow, Poland
- Faculty of Medicine, Institute of Cardiology, Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow, Poland
| | - Mariusz Tomaniak
- 1st Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland
| | - Emilia Figura
- 1st Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland
| | - Mateusz Zaremba
- 1st Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland
| | - Marcin Grabowski
- 1st Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland
| | - Janusz Kochman
- 1st Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland
| | - Jacek Legutko
- Clinical Department of Interventional Cardiology, Saint John Paul II Hospital, Krakow, Poland
- Faculty of Medicine, Institute of Cardiology, Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow, Poland
| | - Łukasz Kołtowski
- 1st Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland
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18
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Di Carli MF. Coronary Microvascular Dysfunction: Identification, Special Populations, and Management Strategies. Heart Fail Clin 2025; 21:201-214. [PMID: 40107799 DOI: 10.1016/j.hfc.2025.01.002] [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] [Indexed: 03/22/2025]
Abstract
Coronary microvascular dysfunction (CMD) is a prevalent and often underdiagnosed condition with significant implications for adverse cardiovascular outcomes. The pathophysiology of CMD includes structural and functional abnormalities in the coronary microvasculature and epicardial atherosclerosis contributes to downstream reduction in myocardial perfusion and symptoms. Diagnosis relies on advanced invasive or noninvasive imaging techniques, such as PET and cardiac magnetic resonance, capable of quantifying myocardial perfusion and myocardial blood flow reserve. Effective management includes optimizing cardiovascular risk factors and symptom control. Novel therapeutic strategies recently approved for management of diabetes, obesity, and heart failure with preserved ejection fraction offer potentially powerful options for management of CMD.
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Affiliation(s)
- Marcelo F Di Carli
- Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Departments of Radiology and Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.
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19
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Crooijmans C, Jansen TPJ, Meeder JG, Woudstra J, Meuwissen M, De Vos AM, Paradies V, Olde Bijvank EGM, Winkler P, Vos NS, Arkenbout K, Woudstra P, Stoel MG, Van de Hoef TP, Van den Oord SCH, Widdershoven JWMG, Remkes W, Cetinyurek-Yavuz A, Den Ruijter HM, Onland-Moret NC, Boersma E, Beijk MA, Appelman Y, Piek JJ, Konst RE, Maas AHEM, Van Royen N, Dimitriu-Leen AC, Elias-Smale SE, Damman P. Safety, Feasibility, and Diagnostic Yield of Invasive Coronary Function Testing: Netherlands Registry of Invasive Coronary Vasomotor Function Testing. JAMA Cardiol 2025; 10:384-390. [PMID: 39969865 PMCID: PMC11840684 DOI: 10.1001/jamacardio.2024.5670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 12/20/2024] [Indexed: 02/20/2025]
Abstract
Importance Patients with angina and no obstructive coronary artery disease frequently have coronary vasomotor dysfunction as underlying pathophysiological mechanism, comprising epicardial spasm, microvascular spasm, and/or microcirculatory dysfunction. These endotypes can be diagnosed by invasive coronary function testing which has previously shown to be safe in tertiary and expert centers. Objective To determine the prevalence of vasomotor dysfunction in patients with angina and no obstructive coronary artery disease who were clinically referred for a coronary function test (CFT); and assess safety and feasibility of a CFT. Design, Setting, and Participants This quality improvement study was performed using the Netherlands Registry of Invasive Coronary Vasomotor Function Testing (NL-CFT), a prospective, observational registry, in 15 participating hospitals (2 tertiary and 13 nontertiary). Patients with angina and no obstructive coronary artery disease who were referred for a clinically indicated CFT between December 2020 and January 2024 were included. Main Outcomes and Measures A complete CFT consisted of acetylcholine spasm provocation testing and assessment of microcirculatory function. Prevalence of different endotypes based on test results and overall safety were assessed. Results Among a total of 1207 patients included, 978 (81%) were female; and the mean (SD) age was 60 (10) years. The prevalence of coronary vasomotor dysfunction was very high (78%). There were 11 (0.9%) major and 10 (0.8%) minor complications reported. Of them, 3 major and all minor were definitely related to the coronary function test. No procedural death, myocardial infarction, or stroke was observed. No differences were found in the occurrence of complications between tertiary and nontertiary centers. Conclusions and Relevance This study found that a CFT was feasible and safe to perform in both tertiary and nontertiary centers with a high diagnostic yield.
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Affiliation(s)
- Caïa Crooijmans
- Department of Cardiology Radboudumc, Nijmegen, the Netherlands
| | | | - Joan G. Meeder
- Department of Cardiology VieCuri Medical Center, North Limburg, the Netherlands
| | - Janneke Woudstra
- Department of Cardiology Amsterdam UMC, Amsterdam, the Netherlands
| | | | | | - Valeria Paradies
- Department of Cardiology Maasstad Hospital, Rotterdam, the Netherlands
| | | | - Patty Winkler
- Department of Cardiology Maastricht UMC, Maastricht, the Netherlands
| | - Nicola S. Vos
- Department of Cardiology Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands
| | - Karin Arkenbout
- Department of Cardiology Tergooi Medical Center, Hilversum, the Netherlands
| | - Pier Woudstra
- Department of Cardiology Medical Center Leeuwarden, Leeuwarden, the Netherlands
| | - Martin G. Stoel
- Department of Cardiology Medical Spectrum Twente, Enschede, the Netherlands
| | | | | | | | - Wouter Remkes
- Department of Cardiology VieCuri Medical Center, North Limburg, the Netherlands
| | | | - Hester M. Den Ruijter
- Laboratory of Experimental Cardiology UMC/University Utrecht, Utrecht, the Netherlands
| | | | - Eric Boersma
- Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands
| | | | - Yolande Appelman
- Department of Cardiology Amsterdam UMC, Amsterdam, the Netherlands
| | - Jan J. Piek
- Department of Cardiology Amsterdam UMC, Amsterdam, the Netherlands
| | - Regina E. Konst
- Department of Cardiology Radboudumc, Nijmegen, the Netherlands
| | | | - Niels Van Royen
- Department of Cardiology Radboudumc, Nijmegen, the Netherlands
| | | | | | - Peter Damman
- Department of Cardiology Radboudumc, Nijmegen, the Netherlands
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20
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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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21
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Behr ER, Winkel BG, Ensam B, Alfie A, Arbelo E, Berry C, Cerrone M, Conte G, Crotti L, Corcia CMG, Kaski JC, Nademanee K, Postema PG, Priori S, Probst V, Sarquella-Brugada G, Schulze-Bahr E, Tadros R, Wilde A, Tfelt-Hansen J. The diagnostic role of pharmacological provocation testing in cardiac electrophysiology: a clinical consensus statement of the European Heart Rhythm Association and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC, the ESC Working Group on Cardiovascular Pharmacotherapy, the Association of European Paediatric and Congenital Cardiology (AEPC), the Paediatric & Congenital Electrophysiology Society (PACES), the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS). Europace 2025; 27:euaf067. [PMID: 40165484 PMCID: PMC12018878 DOI: 10.1093/europace/euaf067] [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: 03/19/2025] [Revised: 03/21/2025] [Accepted: 03/21/2025] [Indexed: 04/02/2025] Open
Abstract
The pharmacological provocation test is a pivotal tool in cardiac electrophysiology for the diagnosis of potential causes of sudden cardiac death, sudden cardiac arrest (SCA), arrhythmias, symptoms, or ECG abnormalities. The 2022 European Society of Cardiology Guidelines for the Treatment of Ventricular Arrhythmias and Prevention of Sudden Cardiac Death offered guidance on provocation testing but did not describe the indications and requirements in depth. This clinical consensus statement, led by the European Heart Rhythm Association and approved by major international stakeholders, aims to advise the general cardiologist and the arrhythmia expert who to test and when, where, and how to do it. The statement focuses on current practice for the diagnosis of subclinical arrhythmia syndromes and the causes of SCA, building upon the recommendations of the Guidelines. We address the sodium channel blocker provocation test for patients suspected of Brugada syndrome as well as the use of epinephrine, isoproterenol, adenosine, ergonovine, and acetylcholine.
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Affiliation(s)
- Elijah R Behr
- Cardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St. George's, University of London, Cranmer Terrace, London, SW17 0RE, UK
- Cardiology Care Group, St George’s University Hospitals NHS Foundation Trust, Blackshaw Road, London, SW17 0QT, UK
- Mayo Clinic Healthcare, 15 Portland Place, London, W1B 1PT, UK
| | - Bo Gregers Winkel
- Department of Cardiology, Copenhagen University Hospital—Rigshospitalet, Copenhagen, Denmark
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart—ERN GUARD-Heart
| | - Bode Ensam
- Cardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St. George's, University of London, Cranmer Terrace, London, SW17 0RE, UK
- University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - Alberto Alfie
- Electrophysiology Section, Cardiology Division, Hospital Nacional Profesor Alejandro Posadas, Moron, Argentina
| | - Elena Arbelo
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart—ERN GUARD-Heart
- Arrhythmia Section, Cardiology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
- Institut d’Investigació August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
| | - Colin Berry
- Department of Cardiology, Golden Jubilee National Hospital, Glasgow, UK
| | - Marina Cerrone
- The Leon Charney Division of Cardiology, New York University Grossmann School of Medicine, New York, NY, USA
| | - Giulio Conte
- Division of Cardiology, Cardiocentro Ticino Institute Ente Ospedaliero Cantonale, Lugano, Switzerland
| | - Lia Crotti
- Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy
- Department of Medicine and Surgery, Università Milano-Bicocca, Milan, Italy
| | | | - Juan Carlos Kaski
- Cardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St. George's, University of London, Cranmer Terrace, London, SW17 0RE, UK
| | - Koonlawee Nademanee
- Department of Medicine, Center of Excellence in Arrhythmia Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pieter G Postema
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart—ERN GUARD-Heart
- Department of Clinical Cardiology, Heart Centre, Amsterdam University Medical Centre, Location AMC, Amsterdam, The Netherlands
| | - Silvia Priori
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart—ERN GUARD-Heart
- Molecular Cardiology Unit, IRCCS Istituti Clinici Scientifici Maugeri, Pavia, Italy
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Vincent Probst
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart—ERN GUARD-Heart
- Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du Thorax, Nantes, France
| | - Georgia Sarquella-Brugada
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart—ERN GUARD-Heart
- Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
| | - Eric Schulze-Bahr
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart—ERN GUARD-Heart
- Institute for Genetics of Heart Diseases, University Hospital Münster, Münster, Germany
| | - Rafik Tadros
- Department of Medicine, Montreal Heart Institute, Montreal, QC, Canada
| | - Arthur Wilde
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart—ERN GUARD-Heart
- Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du Thorax, Nantes, France
| | - Jacob Tfelt-Hansen
- Department of Cardiology, Copenhagen University Hospital—Rigshospitalet, Copenhagen, Denmark
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart—ERN GUARD-Heart
- Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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22
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Scarica V, Rinaldi R, Animati FM, Manzato M, Montone RA. Coronary microvascular dysfunction: pathophysiology, diagnosis, and therapeutic strategies across cardiovascular diseases. EXCLI JOURNAL 2025; 24:454-478. [PMID: 40376434 PMCID: PMC12078779 DOI: 10.17179/excli2025-8285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Accepted: 03/13/2025] [Indexed: 05/18/2025]
Abstract
Ischemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide, presenting with acute and chronic coronary syndromes. Although coronary atherosclerosis is a major cause of IHD, many patients with angina or myocardial ischemia do not have obstructive coronary heart disease and impairment of the coronary microcirculation has been increasingly implicated as a relevant cause of IHD. Therefore, coronary microvascular dysfunction (CMD) refers to a term covering a wide spectrum of structural and functional alterations which affect the coronary microcirculation leading to myocardial ischemia and angina. The advent of non-invasive and invasive functional tests has exponentially broadened the ability to recognize CMD and delineate related clinical and biochemical features. Despite major advances in diagnosing and stratifying this condition, therapeutic strategies remain limited and poorly defined. In this review, we will provide an overview of the pathophysiology and the diagnostic evaluation of CMD across the spectrum of cardiovascular diseases. Furthermore, we will discuss the novel therapeutic strategies available for these patients in the perspective of a personalized medicine approach.
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Affiliation(s)
- Vincenzo Scarica
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Riccardo Rinaldi
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
- Cardiology Unit, Infermi Hospital, Rimini, Italy
| | - Francesco Maria Animati
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Matteo Manzato
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Rocco A. Montone
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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23
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Souza ACDAH, Troschel AS, Marquardt JP, Hadžić I, Foldyna B, Moura FA, Hainer J, Divakaran S, Blankstein R, Dorbala S, Di Carli MF, Aerts HJWL, Lu MT, Fintelmann FJ, Taqueti VR. Skeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes. Eur Heart J 2025; 46:1112-1123. [PMID: 39827905 DOI: 10.1093/eurheartj/ehae827] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 10/28/2024] [Accepted: 11/12/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND AND AIMS Skeletal muscle (SM) fat infiltration, or intermuscular adipose tissue (IMAT), reflects muscle quality and is associated with inflammation, a key determinant in cardiometabolic disease. Coronary flow reserve (CFR), a marker of coronary microvascular dysfunction (CMD), is independently associated with body mass index (BMI), inflammation and risk of heart failure, myocardial infarction, and death. The relationship between SM quality, CMD, and cardiovascular outcomes is not known. METHODS Consecutive patients (n = 669) undergoing evaluation for coronary artery disease with cardiac stress positron emission tomography demonstrating normal perfusion and preserved left ventricular ejection fraction were followed over a median of 6 years for major adverse cardiovascular events (MACEs), including death and hospitalization for myocardial infarction or heart failure. Coronary flow reserve was calculated as stress/rest myocardial blood flow. Subcutaneous adipose tissue (SAT), SM, and IMAT areas (cm2) were obtained from simultaneous positron emission tomography attenuation correction computed tomography using semi-automated segmentation at the 12th thoracic vertebra level. RESULTS Median age was 63 years, 70% were female, and 46% were nonwhite. Nearly half of patients were obese (46%, BMI 30-61 kg/m2), and BMI correlated highly with SAT and IMAT (r = .84 and r = .71, respectively, P < .001) and moderately with SM (r = .52, P < .001). Decreased SM and increased IMAT, but not BMI or SAT, remained independently associated with decreased CFR (adjusted P = .03 and P = .04, respectively). In adjusted analyses, both lower CFR and higher IMAT were associated with increased MACE [hazard ratio 1.78 (95% confidence interval 1.23-2.58) per -1 U CFR and 1.53 (1.30-1.80) per +10 cm2 IMAT, adjusted P = .002 and P < .0001, respectively], while higher SM and SAT were protective [hazard ratio .89 (.81-.97) per +10 cm2 SM and .94 (.91-.98) per +10 cm2 SAT, adjusted P = .01 and .003, respectively]. Every 1% increase in fatty muscle fraction [IMAT/(SM + IMAT)] conferred an independent 2% increased odds of CMD [CFR <2, odds ratio 1.02 (1.01-1.04), adjusted P = .04] and a 7% increased risk of MACE [hazard ratio 1.07 (1.04-1.09), adjusted P < .001]. There was a significant interaction between CFR and IMAT, not BMI, such that patients with both CMD and fatty muscle demonstrated highest MACE risk (adjusted P = .02). CONCLUSIONS Increased intermuscular fat is associated with CMD and adverse cardiovascular outcomes independently of BMI and conventional risk factors. The presence of CMD and SM fat infiltration identified a novel at-risk cardiometabolic phenotype.
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Affiliation(s)
- Ana Carolina do A H Souza
- Cardiovascular Imaging Program, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA
| | - Amelie S Troschel
- Division of Thoracic Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA
- Medical Department II, Klinikum Wolfsburg, Wolfsburg, Germany
| | - Jan P Marquardt
- Division of Thoracic Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Ibrahim Hadžić
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, MA 02114, USA
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Borek Foldyna
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Filipe A Moura
- Cardiovascular Imaging Program, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA
| | - Jon Hainer
- Cardiovascular Imaging Program, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA
| | - Sanjay Divakaran
- Cardiovascular Imaging Program, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA
| | - Ron Blankstein
- Cardiovascular Imaging Program, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA
| | - Sharmila Dorbala
- Cardiovascular Imaging Program, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA
| | - Marcelo F Di Carli
- Cardiovascular Imaging Program, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA
| | - Hugo J W L Aerts
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, MA 02114, USA
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Michael T Lu
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Florian J Fintelmann
- Division of Thoracic Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Viviany R Taqueti
- Cardiovascular Imaging Program, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA
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24
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el Bouziani A, Witte LS, Feenstra RGT, Renkens MPL, Woudstra J, Tijssen JGP, Vink AS, Appelman Y, Grundeken MJD, Straver B, Piek JJ, Bouma BJ, de Winter RJ, Beijk MAM. Prevalence of Patent Foramen Ovale in Patients with Non-Obstructive Coronary Artery Disease (PROVA) Study. J Cardiovasc Dev Dis 2025; 12:108. [PMID: 40278167 PMCID: PMC12028130 DOI: 10.3390/jcdd12040108] [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: 02/10/2025] [Revised: 03/13/2025] [Accepted: 03/19/2025] [Indexed: 04/26/2025] Open
Abstract
(1) Background: Prevalence of patent foramen ovale (PFO) in the general population is estimated at around 24%. We hypothesized that right-to-left shunting (RLS) resulting from PFO might contribute to angina symptoms in patients with coronary artery spasm (CAS), potentially triggered by vasoactive metabolites. Therefore, the aim of this study was to investigate the prevalence of PFO-related RLS in patients with documented CAS. (2) Methods: This single-center prospective cohort study included patients with documented CAS undergoing transthoracic echocardiography (TTE), including a contrast bubble study between 2021 and 2023. The Seattle Angina Questionnaire (SAQ) and Migraine Disability Assessment (MIDAS) were used to survey patients. (3) Results: RLS (PFO group) was observed in 11 of the 48 patients included (23%). In the PFO group, 64% had epicardial spasm and 36% microvascular spasm. Furthermore, RLS was more prevalent in patients with CAS and concomitant migraine (29%). Remarkably, the density plot of the SAQ summary score showed a worse score for patients with RLS (median of 38 [Q1-Q3: 31-49]) than patients without RLS (median of 49 [Q1-Q3: 41-55]) (p = 0.0282). (4) Conclusions: The prevalence of RLS due to PFO in patients with CAS was in line with the PFO prevalence in the general population, and patients with RLS are more symptomatic according to the SAQ summary score. Whether PFO closure could be beneficial to patients with CAS and concomitant migraine requires further investigation.
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Affiliation(s)
- Abdelhak el Bouziani
- Department of Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
| | - Lars S. Witte
- Department of Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
| | - Rutger G. T. Feenstra
- Department of Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
| | - Mick P. L. Renkens
- Department of Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
| | - Janneke Woudstra
- Department of Cardiology, Heart Center, Amsterdam UMC, Location VU Medical Center, VU University, De Boelelaan 1117, 1081 HV Amsterdam, Noord-Holland, The Netherlands
| | - Jan G. P. Tijssen
- Department of Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
| | - Arja S. Vink
- Department of Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
| | - Yolande Appelman
- Department of Cardiology, Heart Center, Amsterdam UMC, Location VU Medical Center, VU University, De Boelelaan 1117, 1081 HV Amsterdam, Noord-Holland, The Netherlands
| | - Maik J. D. Grundeken
- Department of Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
| | - Bart Straver
- Department of Pediatric Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
| | - Jan J. Piek
- Department of Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
| | - Berto J. Bouma
- Department of Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
| | - Robbert J. de Winter
- Department of Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
| | - Marcel A. M. Beijk
- Department of Cardiology, Heart Center, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Noord-Holland, The Netherlands
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25
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Hoek R, van Diemen PA, Somsen YBO, de Winter RW, Jukema RA, Dahdal JE, Raijmakers PG, Driessen RS, Danad I, Knaapen P. Myocardial perfusion imaging in advanced coronary artery disease. Eur J Clin Invest 2025:e70024. [PMID: 40099580 DOI: 10.1111/eci.70024] [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: 12/31/2024] [Accepted: 02/25/2025] [Indexed: 03/20/2025]
Abstract
Myocardial perfusion imaging (MPI) is widely adapted as a noninvasive technique to assess the presence and extent of ischemia in patients with symptoms suggestive of obstructive coronary artery disease (CAD). However, as CAD advances, several factors can complicate the interpretation of MPI, subsequently impacting clinical decision-making. This review focuses on the utility of MPI by means of cardiac magnetic resonance (CMR) imaging, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) in patients with advanced CAD-the latter characterized by documented CAD (i.e. prior myocardial infarction [MI] and/or percutaneous coronary intervention [PCI]), prior coronary artery bypass grafting (CABG) or the presence of a chronic total occlusion (CTO). It will discuss factors impacting the interpretation of MPI, the diagnostic performance for detecting obstructive CAD and coronary microvascular dysfunction (CMD), as well as the role of MPI in guiding revascularization.
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Affiliation(s)
- Roel Hoek
- Department of Cardiology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Pepijn A van Diemen
- Department of Cardiology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Yvemarie B O Somsen
- Department of Cardiology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Ruben W de Winter
- Department of Cardiology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Ruurt A Jukema
- Department of Cardiology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Jorge E Dahdal
- Department of Cardiology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Departamento de Enfermedades Cardiovasculares, Clínica Alemana de Santiago, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile
| | - Pieter G Raijmakers
- Department of Radiology & Nuclear Medicine, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Roel S Driessen
- Department of Cardiology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Ibrahim Danad
- Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Cardiology, Northwest Clinics, Alkmaar, The Netherlands
| | - Paul Knaapen
- Department of Cardiology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Rinaldi R, Russo M, Torre I, Colucci M, Caffè A, Scarica V, Animati FM, Manzato M, Bonanni A, Lenkowicz J, Tudor AM, Liuzzo G, Sanna T, Lanza GA, Leone AM, Trani C, Burzotta F, Crea F, Montone RA. Prognostic significance of individual COVADIS criteria in patients undergoing acetylcholine provocation testing. EUROINTERVENTION 2025; 21:e296-e306. [PMID: 40091873 PMCID: PMC11891921 DOI: 10.4244/eij-d-24-00832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 11/26/2024] [Indexed: 03/19/2025]
Abstract
BACKGROUND The prognostic significance of the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria during acetylcholine (ACh) provocation testing is uncertain. AIMS The aim of this study was to assess the prognostic impact of COVADIS criteria in patients with myocardial ischaemia (INOCA) or myocardial infarction (MINOCA) and non-obstructive coronary arteries undergoing ACh provocation testing. METHODS We enrolled consecutive INOCA and MINOCA patients undergoing ACh provocation testing. The occurrence of each COVADIS criterion was recorded. The primary outcome was the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) at follow-up. RESULTS Among 519 patients (346 [66.7%] INOCA and 173 [33.3%] MINOCA), 274 (52.8%) exhibited a positive ACh test. Over a median 22-month follow-up, the highest incidence of MACCE occurred in patients with 3 positive criteria (15.4%), followed by those with 2 (10.3%) and 1 (9.2%), while the lowest incidence occurred in patients with 0 (3.1%; p=0.004). Patients with ≥1 positive criteria had significantly higher MACCE rates than those with 0 (12.5% vs 3.1%; p=0.003). MACCE-free survival differed significantly among the four groups, with the best survival for 0 criteria and the worst for 3 (p=0.004). Epicardial coronary diameter reduction ≥90% and MINOCA were independent MACCE predictors. Among patients with a negative test, an epicardial coronary diameter reduction ≥90% was the only independent predictor of MACCE, and the presence of ≥1 criteria in this group was associated with a significantly higher MACCE rate compared to patients without any criteria. CONCLUSIONS Our findings challenge the binary stratification (positive vs negative) of COVADIS criteria, suggesting an added value of a comprehensive analysis of their components to provide prognostic stratification and personalised treatment.
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Affiliation(s)
- Riccardo Rinaldi
- Cardiology Unit, Infermi Hospital, Rimini, Italy
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Michele Russo
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
- Department of Cardiology, S. Maria dei Battuti Hospital, AULSS 2 Veneto, Conegliano, Italy
| | - Ilaria Torre
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Michele Colucci
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Andrea Caffè
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Vincenzo Scarica
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Francesco Maria Animati
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Matteo Manzato
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Alice Bonanni
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Jacopo Lenkowicz
- Gemelli Generator RWD, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Andrada Mihaela Tudor
- Gemelli Generator RWD, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Giovanna Liuzzo
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Tommaso Sanna
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Gaetano A Lanza
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Maria Leone
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
- Center of Excellence in Cardiovascular Sciences, Ospedale Isola Tiberina - Gemelli Isola, Rome, Italy
| | - Carlo Trani
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Francesco Burzotta
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Filippo Crea
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
- Gemelli Generator RWD, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Rocco A Montone
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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Escaned J, Paolucci L. Unveiling the coronary acetylcholine test: can it help us predict future cardiovascular events? EUROINTERVENTION 2025; 21:e288-e289. [PMID: 40091875 PMCID: PMC11891918 DOI: 10.4244/eij-e-25-00005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Affiliation(s)
- Javier Escaned
- Hospital Clinico San Carlos IDISSC, Complutense University of Madrid and CIBERCV, Madrid, Spain
| | - Luca Paolucci
- Hospital Clinico San Carlos IDISSC, Complutense University of Madrid and CIBERCV, Madrid, Spain
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Rinaldi R, Kunadian V, Crea F, Montone RA. Management of angina pectoris. Trends Cardiovasc Med 2025:S1050-1738(25)00033-7. [PMID: 40086653 DOI: 10.1016/j.tcm.2025.03.001] [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: 01/05/2025] [Revised: 03/04/2025] [Accepted: 03/08/2025] [Indexed: 03/16/2025]
Abstract
Angina pectoris, a primary manifestation of ischemic heart disease, imposes a significant clinical and economic burden globally. This review highlights recent advancements in the management of angina, emphasizing a patient-centred approach that integrates pharmacological, interventional, and lifestyle strategies to reduce cardiovascular risk and improve patient outcomes. For obstructive coronary artery disease, optimal medical therapy represents the cornerstone of treatment. Individualized regimens should be tailored to clinical factors such as blood pressure, heart rate, left ventricular function, comorbidities like heart failure and diabetes, concomitant medications, patient preferences, and drug availability. Myocardial revascularization is reserved for select cases to alleviate symptoms or improve prognosis. For angina or ischemia with non-obstructive coronary arteries (ANOCA/INOCA), precise endotype classification, differentiating microvascular angina, vasospastic angina, mixed type and non-coronary chest pain, enables personalized treatment strategies. Lifestyle interventions, including smoking cessation, weight management, adherence to Mediterranean diet, and exercise therapy, are essential components of care, promoting improved cardiovascular outcomes and quality of life. Structured exercise programs, particularly within cardiac rehabilitation settings, have demonstrated efficacy in enhancing functional capacity and reducing adverse events. Emerging therapies, including pharmacological agents and novel interventional approaches such as the coronary sinus reducer, hold promise for addressing unmet needs in refractory angina and challenging ANOCA/INOCA cases. Future directions should prioritize the integration of precision medicine, digital health technologies, and multidisciplinary care to optimize outcomes and advance personalized angina management.
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Affiliation(s)
- Riccardo Rinaldi
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy; Cardiology Unit, Infermi Hospital, Rimini, Italy
| | - Vijay Kunadian
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Newcastle-upon-Tyne NE2 4HH, United Kingdom; Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
| | - Filippo Crea
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy; Center of Excellence of Cardiovascular Sciences, Ospedale Isola Tiberina - Gemelli Isola, Rome, Italy
| | - Rocco A Montone
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy; Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
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Guo J, Xiang ZZ, Ma DD. The Global Immune-Nutrition Inflammation Index for Predicting Coronary Slow Flow Phenomenon in Patients with Angina and No Obstructive Coronary Arteries. Int J Gen Med 2025; 18:1325-1332. [PMID: 40070680 PMCID: PMC11895676 DOI: 10.2147/ijgm.s516108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
Background Chronic inflammatory responses are involved in the initiation and development of the coronary slow flow phenomenon (CSFP). However, as a newly developed immuno-nutritional inflammation indicator, the global immune-nutrition inflammation index (GINI) has not been well elaborated for predicting CSFP in patients with angina and no obstructive coronary arteries (ANOCA). Methods A total of 1422 individuals with ANOCA were consecutively included in this study, of whom 93 developed CSFP (CSFP group). We selected 186 (1:2 matched) age- and sex-matched patients with ANOCA and angiographically proven normal coronary blood flow as the controls (the control group). Multivariate logistic regression analysis was used to investigate predictors of CSFP in patients with ANOCA. The optimal cutoff values for GINI were calculated. Results In total, 93 patients developed CSFP, including 29% (27) in one vessel, 28% (26) in two vessels, and 43% (40) in three vessels. Patients with CSFP had an elevated CRP level, white blood cell (WBC) count, neutrophil count, GINI, fasting blood glucose (FBG) level, and a lower lymphocyte count (P<0.05). Multivariate logistic analysis showed that the GINI and FBG levels were independent predictors of CSFP in patients with ANOCA. Moreover, we found that the more vessels affected by CSFP, the higher the GINI level. The receiver operating characteristic (ROC) showed that GINI had a better predictive value than indicators alone. When the GINI AISI was >84.1, the sensitivity and specificity were 88.2% and 58.7%, respectively [The Area Under the ROC curve (AUC): 0.774; 95% CI: 0.721-0.827; P < 0.001]. Conclusion Elevated GINI is a reliable predictor of CSFP in patients with ANOCA. Moreover, GINI had a superior predictive value compared to the indicators alone. As a newly developed inflammatory indicator, GINI can be used for further risk stratification of patients with ANOCA.
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Affiliation(s)
- Jiang Guo
- Department of Cardiovascular Medicine, Longquan People’s Hospital Affiliated to Lishui University, Lishui, People’s Republic of China
| | - Zhi-zhen Xiang
- Department of Cardiovascular Medicine, Longquan People’s Hospital Affiliated to Lishui University, Lishui, People’s Republic of China
| | - Dan-dan Ma
- Department of Intensive Care Unit, Shenzhen Luohu Hospital Group Luohu People’s Hospital (The Third Affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of China
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Xie Y, Sheng Z, He H, Li Y, Chen Q, Gao Y, Zheng J. Single-Center Analysis of Soluble TREM2 as a Biomarker in Coronary Microvascular Dysfunction: A Cross-Sectional Study. J Clin Med 2025; 14:1816. [PMID: 40142624 PMCID: PMC11942759 DOI: 10.3390/jcm14061816] [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] [Received: 12/29/2024] [Revised: 02/22/2025] [Accepted: 03/05/2025] [Indexed: 03/28/2025] Open
Abstract
Background: The soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is linked to the progression of cardiovascular conditions, but its role in coronary microcirculation dysfunction (CMD) is not yet clear. Methods: A cross-sectional observational study from July 2023 to May 2024 was conducted in the China-Japan Friendship Hospital, after registration in the ClinicalTrials database (Registry Name: Coronary Microvascular Dysfunction in Angina Patients With Non-obstructive Coronary Artery Disease (ANOCA-CMD); Registry Number: NCT06503640; Registry Date: 23 September 2022). This cross-sectional study involved 76 subjects, including 55 patients with CMD and 21 without CMD, admitted to the China-Japan Friendship Hospital. CMD was defined by a coronary flow reserve (CFR) < 2.5 or index of microvascular resistance (IMR) ≥ 25. sTREM2 levels were measured using an enzyme-linked immunosorbent assay. Linear correlation analysis assessed the relationship between sTREM2 levels and CFR, IMR, microvascular resistance reserve (MRR), and the resistive reserve ratio (RRR). Univariate and multivariate regression analyses further examined the association between sTREM2 and CMD. Additionally, receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of plasma sTREM2 for identifying CMD patients. Results: Elevated sTREM2 levels were found in the CMD group. Correlation analysis showed a significant positive relationship with IMR and an inverse correlation with CFR, MRR, and RRR. After adjusting for confounders, sTREM2 was found to be an independent risk factor for CMD [OR = 1.003, 95% CI 1.001-1.007, p = 0.008]. ROC analysis revealed a sensitivity of 59.46%, specificity of 90.48%, and an AUC of 0.7677 (95% CI: 0.6481-0.8872, p = 0.008) for CMD diagnosis at a threshold of 595.5 pg/mL, indicating good diagnostic performance. Conclusions: Elevated sTREM2 levels in CMD patients indicate its potential as a biomarker.
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Affiliation(s)
- Yingying Xie
- Department of Cardiology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Beijing 100029, China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Zhaoxue Sheng
- Department of Cardiology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Beijing 100029, China
| | - Haoming He
- Department of Cardiology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Beijing 100029, China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Yike Li
- Department of Cardiology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Beijing 100029, China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Qiang Chen
- Department of Cardiology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Beijing 100029, China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Yanxiang Gao
- Department of Cardiology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Beijing 100029, China
| | - Jingang Zheng
- Department of Cardiology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Beijing 100029, China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
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Rinaldi R, Russo M, Occhipinti G, Laudani C, Torre I, Colucci M, Gurgoglione FL, Animati FM, Lenkowicz J, Tudor AM, Liuzzo G, Sanna T, Leone AM, Niccoli G, Lanza GA, Trani C, Burzotta F, Crea F, Montone RA. Sex-Related Differences in the Prognostic Role of Acetylcholine Provocation Testing. J Am Heart Assoc 2025; 14:e037942. [PMID: 39996450 DOI: 10.1161/jaha.124.037942] [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: 07/27/2024] [Accepted: 12/31/2024] [Indexed: 02/26/2025]
Abstract
BACKGROUND Intracoronary provocation testing with acetylcholine (ACh) is helpful to diagnose and risk-stratify patients with ischemia with nonobstructed coronary arteries (NOCA) and myocardial infarction with NOCA. This study explored potential sex-related disparities on the prognostic significance of ACh provocative testing. METHODS Consecutive patients with ischemia with NOCA and those with myocardial infarction with NOCA who underwent ACh provocation testing were enrolled. The primary end point was the incidence of major adverse cardiovascular and cerebrovascular events at follow-up. Co-primary end points were angina recurrence and quality of life assessed by 12-month Seattle Angina Questionnaire (SAQ) summary score. RESULTS A total of 519 patients (mean age, 61.4±12.1 years; 275 [53.0%] women and 244 [47%] men) were enrolled: 346 (66.7%) with ischemia with NOCA and 173 (33.3%) with myocardial infarction with NOCA. A positive ACh test was observed in 274 (52.8%) patients, with a lower prevalence of epicardial spasm (82 [56.2%] versus 106 [82.8%]) and a higher prevalence of microvascular spasm (64 [43.8%] versus 22 [17.2%]) in women compared with men (P>0.001). After a median 22-month follow-up, major adverse cardiovascular and cerebrovascular events occurred in 53 (10.2%) patients, without significant sex differences (P>0.05). Men with a positive ACh test had a significantly higher rate of major adverse cardiovascular and cerebrovascular events (22 [17.2%] versus 5 [4.3%], P=0.002) compared with those with a negative test; no difference was observed in women (P>0.05) (P for interaction=0.003). Women with a positive test experienced a higher rate of angina recurrence (61 [41.8%] versus 32 [24.8%], P=0.005) and a lower SAQ summary score (82 [interquartile range, 72-90] versus 86 [interquartile range, 78-100], P<0.001) compared with those with a negative result; no difference was observed in men (P>0.05). CONCLUSIONS This study revealed the importance of recognizing sex-specific differences in the prognostic value of ACh testing for proper management of coronary vasomotor disorders.
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Affiliation(s)
- Riccardo Rinaldi
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
- Cardiology Unit Infermi Hospital Rimini Italy
| | - Michele Russo
- Department of Cardiology S. Maria dei Battuti Hospital, AULSS 2 Veneto Conegliano TV Italy
| | - Giovanni Occhipinti
- Hospital Clínic, Cardiovascular Clinic Institute, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Barcelona Spain
- Division of Cardiology Azienda Ospedaliero Universitaria Policlinico "G. Rodolico-San Marco", University of Catania Catania Italy
| | - Claudio Laudani
- Division of Cardiology Azienda Ospedaliero Universitaria Policlinico "G. Rodolico-San Marco", University of Catania Catania Italy
| | - Ilaria Torre
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
| | - Michele Colucci
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
| | | | - Francesco Maria Animati
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
| | - Jacopo Lenkowicz
- Gemelli Generator RWD Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
| | - Andrada Mihaela Tudor
- Gemelli Generator RWD Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
| | - Giovanna Liuzzo
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
- Department of Cardiovascular Sciences Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
| | - Tommaso Sanna
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
- Department of Cardiovascular Sciences Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
| | - Antonio Maria Leone
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
- Department of Cardiovascular Sciences Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
| | - Giampaolo Niccoli
- Division of Cardiology University of Parma, Parma University Hospital Parma Italy
| | - Gaetano A Lanza
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
- Department of Cardiovascular Sciences Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
| | - Carlo Trani
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
- Department of Cardiovascular Sciences Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
| | - Francesco Burzotta
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
- Department of Cardiovascular Sciences Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
| | - Filippo Crea
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
- Center of Excellence in Cardiovascular Sciences Ospedale Isola Tiberina Rome Italy
| | - Rocco A Montone
- Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart Rome Italy
- Department of Cardiovascular Sciences Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
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Shiromani S, AlBadri A, Lindeke-Myers A, Schwartz A, Vatsa N, Dave E, Rashid F, Jain N, Mehta PK. Reduced retinal microvascular density in women with coronary microvascular dysfunction: A pilot study. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2025; 51:100502. [PMID: 39995513 PMCID: PMC11847120 DOI: 10.1016/j.ahjo.2025.100502] [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: 12/23/2024] [Accepted: 01/16/2025] [Indexed: 02/26/2025]
Abstract
Objective To compare retinal microvascular density among women with ischemia with no obstructive coronary artery disease (INOCA) with and without coronary microvascular dysfunction (CMD). Design Cross-sectional study. Setting Patients with myocardial INOCA often have CMD, possibly indicating systemic vascular dysfunction. While retinal microvasculature relates to many cardiovascular risk factors, its link with CMD remains unknown. Participants Women with INOCA (N = 18) and coronary function testing were enrolled and classified into CMD and non-CMD groups, with CMD defined as coronary flow reserve (CFR) <2.5 in response to adenosine. Interventions Participants underwent retinal optical coherence tomography angiography for noninvasive imaging of the retinal microvasculature. Main outcome measures Vessel density, perfusion density, and area, perimeter, and circularity of the foveal avascular zone (FAZ). Non-parametric statistics were used for comparisons. Results Mean age was 54.7 (SD 12.5) years. The CMD (N = 11) and non-CMD (N = 7) groups were balanced with respect to age, BMI, systemic diseases including diabetes, hypertension, and hyperlipidemia, and medications. Those with CMD had a lower retinal vessel density [20.9 (0.7) vs 21.6(0.8), p = 0.006] and lower inner perfusion density [38.5 (1.6) vs 41.2 (0.8), p = 0.006] as compared to those without CMD. There were no differences in the FAZ area, perimeter, or circularity. Conclusions In this study of women with INOCA, those with CMD showed lower retinal microvascular and perfusion densities than those without CMD. Direct, non-invasive retinal imaging is feasible, affordable, and may reflect coronary microvascular function in INOCA patients. A larger study, including men, is needed to confirm these findings.
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Affiliation(s)
- Sakshi Shiromani
- Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA
| | - Ahmed AlBadri
- Interventional Cardiology, Wellstar Health System, Marietta, GA, USA
| | - Aaron Lindeke-Myers
- Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA
| | - Arielle Schwartz
- Cardiovascular Disease Fellowship Training Program, Emory University School of Medicine, Atlanta, GA, USA
| | - Nishant Vatsa
- Cardiovascular Disease Fellowship Training Program, Emory University School of Medicine, Atlanta, GA, USA
| | - Esha Dave
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - Fauzia Rashid
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - Nieraj Jain
- Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA
| | - Puja K. Mehta
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
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Gerlach RM, Sweitzer B. Special Considerations Related to Race, Sex, Gender, and Socioeconomic Status in the Preoperative Evaluation: Part 2: Sex Considerations and Homeless Patients. Anesthesiol Clin 2025; 43:19-35. [PMID: 39890320 DOI: 10.1016/j.anclin.2024.08.002] [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: 02/03/2025]
Abstract
Preoperative evaluation identifies unique patient characteristics with an impact on perioperative care. Sex-based differences in cardiovascular disease are particularly important. Diseases in women can go unrecognized and yet have long-term implications for cardiovascular risk. Peripartum cardiomyopathy and hypertensive disorders of pregnancy affect cardiovascular risk in young women long after pregnancy. Sex-hormone therapy in women, men, and transgender patients carries minimal perioperative risk, except in select patients at high risk for venous thromboembolism. The unique challenges facing patients experiencing homelessness in accessing care mean underlying comorbidities are common and additional resources may be required to provide effective perioperative care.
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Affiliation(s)
- Rebecca M Gerlach
- Pre-Anesthesia Clinic, Department of Anesthesiology & Critical Care Medicine, University of New Mexico, Albuquerque, NM, USA
| | - BobbieJean Sweitzer
- Preoperative Medicine, Inova Health, Medical Education, University of Virginia, 3300 Gallows Road, Falls Church, VA 22042, USA.
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Osigwe PC, Osigwe IS, Obieze AA, Osigwe E, Agomoh CE. Unusual Presentation of Obstructive Atherosclerotic Coronary Artery Disease With Chronic, Persistent Neck and Shoulder Pain: A Case Report. Cureus 2025; 17:e80298. [PMID: 40201893 PMCID: PMC11978238 DOI: 10.7759/cureus.80298] [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] [Accepted: 03/09/2025] [Indexed: 04/10/2025] Open
Abstract
Ischaemic chest pain or its equivalents are acute-onset in acute coronary syndrome (ACS) and chronic, episodic, and transient in chronic coronary syndrome (CCS). A 56-year-old Caucasian male with a history of premature atherosclerotic coronary artery disease (CAD) presented to secondary care with recurrent presyncope and syncope. He reported a year-long history of persistent left-sided neck and shoulder dull ache/tightness, unrelated to exertion and fluctuating unpredictably. His primary care had diagnosed the pain as musculoskeletal, attributing it to prior physical trauma. However, the pain did not respond to treatment. During his admission for suspected cardiac syncope, he experienced transient chest discomfort, transient inferior ST-segment elevation on electrocardiogram (ECG), and elevated troponin levels, indicating a non-ST-elevation myocardial infarction (NSTEMI). Coronary angiography revealed obstructive atherosclerotic two-vessel disease, with severe proximal stenosis in the right coronary artery (RCA) and moderate-to-severe stenosis in the left anterior descending artery (LAD). His chronic neck and shoulder pain resolved after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) placement in the RCA, confirming it was an anginal equivalent. Although the chronicity of this anginal equivalent may align it more with CCS than ACS, its unremitting nature is inconsistent with CCS. Our patient's history also showed that his ischaemic symptoms changed over time, from remote exertional dyspnoea to persistent neck and shoulder pain, and then to the chest discomfort that preceded his NSTEMI. Our case highlights the importance of heightened clinician awareness of atypical CAD presentations and symptom variability over time. Symptoms initially considered non-anginal should be reassessed for CAD, particularly when alternative treatments prove ineffective. Similar cases like ours, in the future, could prompt updates to CCS diagnostic guidelines to address atypical presentations with persistent pain.
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Affiliation(s)
- Pacelli C Osigwe
- Department of Cardiology, Bronglais General Hospital, Aberystwyth, GBR
| | - Ifunanya S Osigwe
- Department of Medicine, Bronglais General Hospital, Aberystwyth, GBR
| | - Amando A Obieze
- Department of Medicine, Worcestershire Royal Hospital, Worcester, GBR
| | - Ebubechi Osigwe
- Department of General Practice, Improving Health (IH) Medical, Wolverhampton, GBR
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Tang N, Li KM, Li HR, Zhang QD, Hao J, Qi CM. Advances in the diagnosis and management of post-percutaneous coronary intervention coronary microvascular dysfunction: Insights into pathophysiology and metabolic risk interactions. World J Cardiol 2025; 17:103950. [DOI: 10.4330/wjc.v17.i2.103950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/28/2025] [Accepted: 02/10/2025] [Indexed: 02/25/2025] Open
Abstract
Percutaneous coronary intervention (PCI), as an essential treatment for coronary artery disease, has significantly improved the prognosis of patients with large coronary artery lesions. However, some patients continue to experience myocardial ischemic symptoms post-procedure, largely due to coronary microvascular dysfunction (CMD). The pathophysiological mechanisms of CMD are complex and involve endothelial dysfunction, microvascular remodeling, reperfusion injury, and metabolic abnormalities. Moreover, components of metabolic syndrome, including obesity, hyperglycemia, hypertension, and dyslipidemia, exacerbate the occurrence and progression of CMD through multiple pathways. This review systematically summarizes the latest research advancements in CMD after PCI, including its pathogenesis, diagnostic techniques, management strategies, and future research directions. For diagnosis, invasive techniques such as coronary flow reserve and the index of microcirculatory resistance, as well as non-invasive imaging modalities (positron emission tomography and cardiac magnetic resonance), provide tools for early CMD detection. In terms of management, a multi-level intervention strategy is emphasized, incorporating lifestyle modifications (diet, exercise, and weight control), pharmacotherapy (vasodilators, hypoglycemic agents, statins, and metabolic modulators), traditional Chinese medicine, and specialized treatments (enhanced external counterpulsation, metabolic surgery, and lipoprotein apheresis). However, challenges remain in CMD treatment, including limitations in diagnostic tools and the lack of personalized treatment strategies. Future research should focus on the complex interactions between CMD and metabolic risks, aiming to optimize diagnostic and therapeutic strategies to improve the long-term prognosis of patients post-PCI.
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Affiliation(s)
- Nan Tang
- Department of Cardiology, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Kang-Ming Li
- Department of Cardiology, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Hao-Ran Li
- Department of Cardiology, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Qing-Dui Zhang
- Department of Cardiology, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Ji Hao
- Department of Cardiology, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Chun-Mei Qi
- Department of Cardiology, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
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Martins AM, Nobre Menezes M, Alves da Silva P, Almeida AG. Multimodality Imaging in the Diagnosis of Coronary Microvascular Disease: An Update. J Pers Med 2025; 15:75. [PMID: 39997350 PMCID: PMC11856700 DOI: 10.3390/jpm15020075] [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: 12/02/2024] [Revised: 01/18/2025] [Accepted: 02/04/2025] [Indexed: 02/26/2025] Open
Abstract
Coronary microvascular dysfunction (CMD) is characterized by structural and functional abnormalities in the coronary microvasculature which can lead to ischaemia and angina and is increasingly recognized as a major contributor to adverse cardiovascular outcomes. Despite its clinical importance, the diagnosis of CMD remains limited compared with traditional atherosclerotic coronary artery disease. Furthermore, the historical lack of non-invasive methods for detecting and quantifying CMD has hindered progress in understanding its pathophysiology and clinical implications. This review explores advancements in non-invasive cardiac imaging that have enabled the detection and quantification of CMD. It evaluates the clinical utility, strengths and limitation of these imaging modalities in diagnosing and managing CMD. Having improved our understanding of CMD pathophysiology, cardiac imaging can provide insights into its prognosis and enhance diagnostic accuracy. Continued innovation in imaging technologies is essential for advancing knowledge about CMD, leading to improved cardiovascular outcomes and patient care.
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Affiliation(s)
- Ana Margarida Martins
- Cardiology, Heart and Vessels Department, ULS Santa Maria, Centro Cardiovascular da Universidade de Lisboa, 1649-128 Lisboa, Portugal; (M.N.M.); (P.A.d.S.); (A.G.A.)
- Cardiovacular Magnetic Ressonance Services, Royal Brompton and Harefield Hospitals, 6W3 6NP London, UK
| | - Miguel Nobre Menezes
- Cardiology, Heart and Vessels Department, ULS Santa Maria, Centro Cardiovascular da Universidade de Lisboa, 1649-128 Lisboa, Portugal; (M.N.M.); (P.A.d.S.); (A.G.A.)
- Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal
| | - Pedro Alves da Silva
- Cardiology, Heart and Vessels Department, ULS Santa Maria, Centro Cardiovascular da Universidade de Lisboa, 1649-128 Lisboa, Portugal; (M.N.M.); (P.A.d.S.); (A.G.A.)
- Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal
| | - Ana G. Almeida
- Cardiology, Heart and Vessels Department, ULS Santa Maria, Centro Cardiovascular da Universidade de Lisboa, 1649-128 Lisboa, Portugal; (M.N.M.); (P.A.d.S.); (A.G.A.)
- Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal
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Vink CEM, Borodzicz-Jazdzyk S, de Jong EAM, Woudstra J, van de Hoef TP, Chamuleau SAJ, Eringa EC, Götte MJW, Appelman Y. Quantitative perfusion by cardiac magnetic resonance imaging reveals compromised myocardial perfusion in patients with angina with non-obstructive coronary artery disease. Clin Res Cardiol 2025:10.1007/s00392-025-02606-7. [PMID: 39966158 DOI: 10.1007/s00392-025-02606-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 01/16/2025] [Indexed: 02/20/2025]
Abstract
INTRODUCTION Stress perfusion cardiac magnetic resonance (CMR) effectively detects myocardial ischemia. In angina with non-obstructive coronary arteries (ANOCA), visually assessed first-pass perfusion often appears normal. Automated quantitative perfusion (QP) might benefit ANOCA diagnosis, offering absolute quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). AIM We aimed to evaluate the efficacy of QP in detecting ANOCA. METHODS This study compared fully automated QP CMR in ANOCA patients with age- and sex-matched healthy controls. Participants underwent adenosine stress perfusion CMR, including visual assessment and quantification of MBF and MPR. ANOCA patients underwent coronary function testing to identify vasospasm and/or coronary microvascular dysfunction. RESULTS Twenty-four ANOCA patients (83% women, 57 ± 9 years) and 25 healthy controls (80% women, 56 ± 7 years) were included. Visual perfusion assessment did not differ between groups (p = 0.54). Additionally, no differences in resting MBF were observed. However, ANOCA patients had significantly lower global MBF during stress (2.43 ± 0.72 vs 2.99 ± 0.65 ml/g/min, p < 0.01) and a significantly lower global MPR (2.24 ± 0.79 vs 2.68 ± 0.64, p = 0.04) compared to healthy controls. MPR was significantly reduced in the RCA territory in ANOCA patients (2.16 ± 0.71 vs 2.69 ± 0.69, p = 0.01), with no significant differences in other coronary territories. MPR did not significantly differ between ANOCA endotypes. CONCLUSIONS ANOCA patients display reduced global MPR, suggesting compromised perfusion. Variation in MPR across coronary territories highlights the importance of assessing perfusion in all teritories. These findings are promising and support the use of QP for non-invasive detection of vasomotor dysfunction in ANOCA patients. PRE-REGISTERED CLINICAL TRIAL NUMBER The pre-registered clinical trial number is NL-OMON23861.
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Affiliation(s)
- Caitlin E M Vink
- Department of Cardiology (ZH5F020), Amsterdam UMC Heart Centre, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Sonia Borodzicz-Jazdzyk
- Department of Cardiology (ZH5F020), Amsterdam UMC Heart Centre, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
- 1st Department Cardiology, Medical University of Warsaw, Warszawa, Poland
| | - Elize A M de Jong
- Department of Cardiology (ZH5F020), Amsterdam UMC Heart Centre, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
- Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Janneke Woudstra
- Department of Cardiology (ZH5F020), Amsterdam UMC Heart Centre, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Tim P van de Hoef
- Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Steven A J Chamuleau
- Department of Cardiology (ZH5F020), Amsterdam UMC Heart Centre, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Etto C Eringa
- Department of Internal Medicine, Diabetes Center, Amsterdam UMC, Amsterdam, The Netherlands
- Department of Physiology, Amsterdam UMC, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
- Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - Marco J W Götte
- Department of Cardiology (ZH5F020), Amsterdam UMC Heart Centre, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Yolande Appelman
- Department of Cardiology (ZH5F020), Amsterdam UMC Heart Centre, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
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Al Bitar M, Shantouf R, Al Azzoni A, Al Mahmeed W, Atallah B. Ischemia with no obstructed coronary arteries and microvascular testing procedures: a review of utility, pharmacotherapy, and current challenges. Front Cardiovasc Med 2025; 12:1523352. [PMID: 40041175 PMCID: PMC11876165 DOI: 10.3389/fcvm.2025.1523352] [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: 11/05/2024] [Accepted: 02/03/2025] [Indexed: 03/06/2025] Open
Abstract
Ischemia with no obstructive coronary arteries (INOCA) is an increasingly recognized condition in patients presenting with angina and positive stress tests but without significant coronary artery stenosis. This review addresses the pathophysiology, diagnostic approaches, and management strategies associated with INOCA, emphasizing epicardial coronary spasms and coronary microvascular dysfunction (CMD) as underlying mechanisms and myocardial bridging (MB) as a risk factor. Diagnostic modalities include both non-invasive techniques and invasive procedures, such as acetylcholine provocation testing, to differentiate vasospasm from microvascular causes. The paper discusses a potential interference between vasodilators used in trans-radial access and coronary spasm testing. Long-term management approaches for INOCA patients, including pharmacologic therapies and lifestyle interventions, are reviewed.
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Affiliation(s)
- Mohammad Al Bitar
- School of Medicine, Royal College of Surgeons in Ireland, Busaiteen, Ireland
| | | | | | | | - Bassam Atallah
- Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
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Čanković M, Milovančev A, Tadić S, Stefanović M, Petrović M, Kovačević M, Tomas I, Dabović D, Ivanović V, Ilić A, Stojšić-Milosavljević A, Stojšić S, Komazec N, Mihajlović B, Ivanov I. Relationship Between Noninvasive Doppler-Derived Coronary Flow Reserve Measured by Transthoracic Echocardiography and Angiography Thermodilution-Measured Coronary Flow Reserve and the Index of Microcirculatory Resistance in Patients with Non-Obstructive Coronary Arteries. Biomedicines 2025; 13:466. [PMID: 40002879 PMCID: PMC11852765 DOI: 10.3390/biomedicines13020466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 02/05/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: Coronary microvascular dysfunction (CMD) is emerging as a critical factor in patients presenting with anginal symptoms without obstructive coronary artery disease (CAD). This study aims to investigate the relationship between invasive measurements of coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) using thermodilution techniques, compared to non-invasive assessments of CFR with transthoracic Doppler echocardiography (TDE). Methods: In this observational prospective cross-sectional study, a total of 49 patients, clinically characterized as having angina with no obstructive CAD (ANOCA) or ischemia with no obstructive CAD (INOCA), underwent both TDE and invasive coronary angiography (ICA) followed by thermodilution assessment of CFR and IMR. Results: It was found that there is a statistically significant negative correlation between both non-invasive and invasive CFR measurements and IMR. Specifically, a negative moderate correlation was observed between non-invasive CFR and IMR (rs = -0.477, p < 0.01), as well as a high negative correlation between invasive CFR and IMR (r = -0.541, p < 0.01). Receiver operating characteristic (ROC) analysis indicated that both non-invasive and invasive CFRs are effective predictors of CMD, defined as IMR > 25. Conclusions: Both noninvasive and invasive CFR measurements are significant independent predictors of CMD. Our results indicate that noninvasive TDE CFR can be a reliable tool for assessing CMD in patients with ANOCA, potentially facilitating earlier diagnosis and management strategies for this patient population.
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Affiliation(s)
- Milenko Čanković
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Aleksandra Milovančev
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Snežana Tadić
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Maja Stefanović
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Milovan Petrović
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Mila Kovačević
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Igor Tomas
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Dragana Dabović
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Vladimir Ivanović
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Aleksandra Ilić
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Anastazija Stojšić-Milosavljević
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Snežana Stojšić
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Nikola Komazec
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Bojan Mihajlović
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
| | - Igor Ivanov
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (A.M.); (S.T.); (M.S.); (M.P.); (M.K.); (D.D.); (V.I.); (A.I.); (A.S.-M.); (N.K.); (B.M.); (I.I.)
- Institute for Cardiovascular Diseases of Vojvodina, 21204 Sremska Kamenica, Serbia; (I.T.); (S.S.)
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Abramik J, Mariathas M, Felekos I. Coronary Microvascular Dysfunction and Vasospastic Angina-Pathophysiology, Diagnosis and Management Strategies. J Clin Med 2025; 14:1128. [PMID: 40004660 PMCID: PMC11856034 DOI: 10.3390/jcm14041128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 02/02/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Coronary artery disease is one of the leading public health problems in the world in terms of mortality and economic burden from the disease. Traditionally, the focus of research and clinical pathways leading to the diagnosis and treatment of coronary artery disease was on the more common variant of the disease resulting from atherosclerosis in the epicardial coronary arteries. However, coronary microvasculature, representing the vast majority of the total heart circulation, has the greatest influence on overall coronary resistance and, therefore, blood flow. Coronary microvascular dysfunction (CMD), characterized by structural or functional abnormalities in the microvasculature, significantly impacts myocardial perfusion. Endothelial dysfunction results in inadequate coronary dilation during exercise or spontaneous spasm in the microvasculature or epicardial arteries. A significant proportion of people presenting for coronary angiography in the context of angina have unobstructed epicardial coronary arteries yet are falsely reassured about the benign nature of their condition. Meanwhile, increasing evidence indicates that patients diagnosed with CMD as well as vasospastic angina (VSA) face an increased risk of Major Adverse Cardiovascular Events (MACEs), including death. The aim of this review is to outline the current practice with regard to invasive and non-invasive methods of CMD and VSA diagnosis and assess the evidence supporting the existing treatment strategies. These include endotype-specific pharmacological therapies, a holistic approach to lifestyle modifications and risk factor management and novel non-pharmacological therapies. Furthermore, the review highlights critical gaps in research and suggests potential areas for future investigation, to improve understanding and management of these conditions.
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Affiliation(s)
- Joanna Abramik
- Bristol Heart Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Terrell Street, Bristol BS2 8ED, UK; (J.A.); (M.M.)
- Department for Health, University of Bath, Claverton Down, Bath BA2 7AY, UK
| | - Mark Mariathas
- Bristol Heart Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Terrell Street, Bristol BS2 8ED, UK; (J.A.); (M.M.)
| | - Ioannis Felekos
- Bristol Heart Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Terrell Street, Bristol BS2 8ED, UK; (J.A.); (M.M.)
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Parlati ALM, Nardi E, Sucato V, Madaudo C, Leo G, Rajah T, Marzano F, Prastaro M, Gargiulo P, Paolillo S, Vadalà G, Galassi AR, Perrone Filardi P. ANOCA, INOCA, MINOCA: The New Frontier of Coronary Syndromes. J Cardiovasc Dev Dis 2025; 12:64. [PMID: 39997498 PMCID: PMC11856364 DOI: 10.3390/jcdd12020064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 01/31/2025] [Accepted: 02/06/2025] [Indexed: 02/26/2025] Open
Abstract
The growing prevalence in the diagnosis of INOCA (Ischemia with Non-Obstructive Coronary Arteries), ANOCA (Angina with Non-Obstructive Coronary Arteries), and MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries) highlights the need to reassess their clinical relevance. Historically regarded as benign syndromes, emerging evidence suggests that these conditions may cause serious cardiovascular events and considerable long-term disability. Additionally, emerging studies suggest that non-obstructive coronary artery disease (CAD) may have a higher prevalence compared to traditional obstructive forms of CAD. This leads to the need to better clarify the underlying pathogenic mechanisms as well as the risk factors associated with these syndromes. This is precisely the aim of this review, which focuses on the complex and heterogeneous mechanisms underlying these syndromes as well as the associated risk factors. This review also sums up the diagnostic steps necessary to achieve an accurate diagnosis, along with the interventional and pharmacological approaches to be implemented in light of the latest evidence.
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Affiliation(s)
- Antonio L. M. Parlati
- Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Ermanno Nardi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Vincenzo Sucato
- Division of Cardiology, Department of Excellence of Sciences for Health Promotion and Maternal-Child Care, Internal Medicine and Specialties (ProMISE) “G. D’Alessandro”, Paolo Giaccone Hospital, University of Palermo, 90133 Palermo, Italy
| | - Cristina Madaudo
- Division of Cardiology, Department of Excellence of Sciences for Health Promotion and Maternal-Child Care, Internal Medicine and Specialties (ProMISE) “G. D’Alessandro”, Paolo Giaccone Hospital, University of Palermo, 90133 Palermo, Italy
| | - Giulio Leo
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, 41121 Modena, Italy
| | - Tanisha Rajah
- Birmingham Medical School, University of Birmingham, Birmingham B15 2TT, UK
| | - Federica Marzano
- Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Maria Prastaro
- Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Paola Gargiulo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Stefania Paolillo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Giuseppe Vadalà
- Division of Cardiology, Department of Excellence of Sciences for Health Promotion and Maternal-Child Care, Internal Medicine and Specialties (ProMISE) “G. D’Alessandro”, Paolo Giaccone Hospital, University of Palermo, 90133 Palermo, Italy
| | - Alfredo Ruggero Galassi
- Division of Cardiology, Department of Excellence of Sciences for Health Promotion and Maternal-Child Care, Internal Medicine and Specialties (ProMISE) “G. D’Alessandro”, Paolo Giaccone Hospital, University of Palermo, 90133 Palermo, Italy
| | - Pasquale Perrone Filardi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy
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Toya T. Coronary Endothelial Dysfunction and Vasomotor Dysregulation in Myocardial Bridging. J Cardiovasc Dev Dis 2025; 12:54. [PMID: 39997488 PMCID: PMC11856107 DOI: 10.3390/jcdd12020054] [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: 12/09/2024] [Revised: 01/15/2025] [Accepted: 01/31/2025] [Indexed: 02/26/2025] Open
Abstract
Myocardial bridging (MB), a congenital variant where a coronary artery segment is tunneled within the myocardium, is increasingly recognized as a contributor to coronary endothelial and vasomotor dysfunction. Beyond the hallmark systolic compression observed on angiography, MB disrupts endothelial integrity, impairs the release of vasoactive substances, and induces vasomotor abnormalities. These effects exacerbate ischemic symptoms and predispose to atherosclerosis in the proximal segment, particularly in conditions such as ischemia/myocardial infarction with nonobstructive coronary arteries. Recent studies underscore MB's association with coronary vasospasm, microvascular endothelial dysfunction, and adverse cardiovascular outcomes, including sudden cardiac death. These findings highlight the interplay between MB's structural anomalies and functional impairments, with factors such as the bridge's length, depth, and orientation influencing its hemodynamic significance. Advances in imaging and coronary physiology assessment, including acetylcholine testing and stress diastolic fractional flow reserve/iFR/RFR, have enhanced diagnostic precision. This review explores the multifaceted impact of MB on coronary physiology, emphasizing its role in endothelial dysfunction and vasomotor regulation. Recognizing MB's contribution to cardiovascular disease is essential for accurate diagnosis and tailored management strategies aimed at mitigating ischemic risk and improving patient outcomes.
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Affiliation(s)
- Takumi Toya
- Division of Cardiology, National Defense Medical College, Tokorozawa 359-8513, Japan;
- Department of Cardiovascular Medicine, NHO Tokyo Medical Center, Tokyo 152-8902, Japan
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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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Verma BR, Galo J, Chitturi KR, Chaturvedi A, Hashim HD, Case BC. Coronary microvascular dysfunction endotypes: IMR tips and tricks. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2025; 71:11-15. [PMID: 39890499 DOI: 10.1016/j.carrev.2025.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 01/22/2025] [Indexed: 02/03/2025]
Abstract
Coronary microvascular dysfunction (CMD) is an important clinical disease spectrum which has gained widespread attention due to chronic anginal symptoms, and worse clinical outcomes, with or without obstructive coronary artery disease (CAD). Coronary microcirculatory dysfunction is due to a wide array of mechanisms such as inflammation, platelet aggregation, vessel wall collagen deposition, imbalance of nitric oxide, free radicals, and sympathetic/parasympathetic simulation. As noted in this supplement, CMD can occur as a primary disease or co-exist with multi-array of diverse cardiac conditions such as CAD (old infarct), hypertrophic cardiomyopathy, Takotsubo cardiomyopathy, hypertension, or infiltrative diseases. CMD, which is often under diagnosed, leads to increase in medical expenses, decrease in quality of life, exacerbation of underlying conditions such as heart failure and even increased mortality. CMD presents a challenge for patients as well as physicians to manage. Here, we review CMD and focus on its endotypes, techniques for microcirculatory assessment, associated tips and tricks and available treatment options.
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Affiliation(s)
- Beni Rai Verma
- Department of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
| | - Jason Galo
- Department of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
| | - Kalyan R Chitturi
- Department of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
| | - Abhishek Chaturvedi
- Department of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
| | - Hayder D Hashim
- Department of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
| | - Brian C Case
- Department of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America.
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Johnson NP, Gould KL. Subendocardial ischemia: Does CMD really exist? CARDIOVASCULAR REVASCULARIZATION MEDICINE 2025; 71:31-37. [PMID: 39864971 DOI: 10.1016/j.carrev.2025.01.008] [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: 10/13/2024] [Revised: 01/07/2025] [Accepted: 01/16/2025] [Indexed: 01/28/2025]
Abstract
Patients with angina but without obstructive epicardial coronary disease still require a specific mechanistic diagnosis to enable targeted treatment. The overarching term "coronary microvascular dysfunction" (CMD) has been applied broadly - but is it correct? We present a series of case examples culminating a systematic exploration of our large clinical database to distinguish among four categories of coronary pathophysiology. First, by far the largest group of "no stenosis angina" patients exhibits subendocardial ischemia during intact flow through diffuse epicardial disease during dipyridamole vasodilator stress. Second, rare patients indeed have ischemic signs or symptoms due solely to reduced flow attributable to microvascular dysfunction but without subendocardial hypoperfusion. Third, a previously unrecognized group of patients displays significant ST-segment changes and rare angina but normal high dipyridamole induced coronary flow and intact normal subendocardial uptake, perhaps due to a stretch mechanism from hyperemia. Fourth, ischemia due to reduced flow plus a subendocardial defect can arise as a secondary effect of a variety of global cardiac pathology, for example severe diffuse atherosclerosis, severe aortic stenosis, or a primary cardiomyopathy. Because subendocardial ischemia dominates the pathophysiologic epidemiology of these patient categories, understanding its mechanisms and therefore potential treatment targets will bring the largest clinical benefits to the largest number of patients. However, its diagnosis requires meticulous attention to exclude caffeine that can lead to a "false positive" diagnosis of CMD, absolute flow quantification to avoid confusing high resting flow with normal stress flow from reduced flow capacity, and quantification of subendocardial blood flow.
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Affiliation(s)
- Nils P Johnson
- Weatherhead PET Imaging Center, Division of Cardiology, Department of Medicine, McGovern Medical School at UTHealth and Memorial Hermann Hospital, Houston, TX, United States of America.
| | - K Lance Gould
- Weatherhead PET Imaging Center, Division of Cardiology, Department of Medicine, McGovern Medical School at UTHealth and Memorial Hermann Hospital, Houston, TX, United States of America
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46
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Shetrit A, Zornitzki L, Banai A, Freund O, Shamir RA, Ben-Shoshan J, Szekely Y, Arbel Y, Banai S, Konigstein M. The role of non-invasive stress testing in the diagnosis of coronary microvascular disease. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2025; 71:38-42. [PMID: 39753394 DOI: 10.1016/j.carrev.2024.12.005] [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: 08/11/2024] [Revised: 10/28/2024] [Accepted: 12/18/2024] [Indexed: 05/01/2025]
Abstract
BACKGROUND Angina with non-obstructive coronary artery disease (ANOCA) is commonly observed in patients with stable angina undergoing coronary angiography. Current guidelines recommend non-invasive stress testing as the first step in diagnosing coronary microvascular disease (CMD). This study aims to evaluate the diagnostic value of non-invasive stress testing in patients invasively diagnosed with CMD. METHODS We conducted a retrospective analysis of prospectively collected data. Eligible subjects were patients with angina who underwent NIST evaluation (echocardiography/ electrocardiography stress test or single-photon emission computerized tomography) prior to coronary angiography. All patients underwent invasive evaluation of microvascular function, which included the assessment of Coronary Flow Reserve, Index of Microcirculatory Resistance, and Resistive Reserve Ratio. RESULTS Overall, 140 patients (77 women, 67 ± 10 y/o) underwent NIST evaluation prior to coronary angiography, of whom 81 % were positive for ischemia. There was no difference in the prevalence of positive NIST between patients with abnormal compared with normal microvascular function tested invasively (81 % vs 82 %, p = 0.94). The prevalence of CMD was similar between patients with positive versus negative NIST (51 % vs 50 %, p = 0.94). Among 114 patients with positive NIST, 56 (49.2 %) had normal microvascular function, regardless of the type of stress test used (p = 0.94), the suspected territory of ischemia (p = 0.15), or the estimated severity of the ischemia (p = 0.63). CONCLUSION Non-invasive stress testing may have a limited predictive value in the diagnosis of CMD in ANOCA patients. Larger prospective studies are required for better understanding of the role these tests in the diagnosis and definition of CMD.
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Affiliation(s)
- Aviel Shetrit
- Department of Cardiology, Tel Aviv Sourasky Medical Center, affiliated with the School of Medicine, Tel Aviv University, Israel.
| | - Lior Zornitzki
- Department of Cardiology, Tel Aviv Sourasky Medical Center, affiliated with the School of Medicine, Tel Aviv University, Israel
| | - Ariel Banai
- Department of Cardiology, Tel Aviv Sourasky Medical Center, affiliated with the School of Medicine, Tel Aviv University, Israel
| | - Ophir Freund
- Department of Cardiology, Tel Aviv Sourasky Medical Center, affiliated with the School of Medicine, Tel Aviv University, Israel
| | - Reut Amar Shamir
- Department of Cardiology, Tel Aviv Sourasky Medical Center, affiliated with the School of Medicine, Tel Aviv University, Israel
| | - Jeremy Ben-Shoshan
- Department of Cardiology, Tel Aviv Sourasky Medical Center, affiliated with the School of Medicine, Tel Aviv University, Israel
| | - Yishay Szekely
- Department of Cardiology, Tel Aviv Sourasky Medical Center, affiliated with the School of Medicine, Tel Aviv University, Israel
| | - Yaron Arbel
- Department of Cardiology, Tel Aviv Sourasky Medical Center, affiliated with the School of Medicine, Tel Aviv University, Israel
| | - Shmuel Banai
- Department of Cardiology, Tel Aviv Sourasky Medical Center, affiliated with the School of Medicine, Tel Aviv University, Israel
| | - Maayan Konigstein
- Department of Cardiology, Tel Aviv Sourasky Medical Center, affiliated with the School of Medicine, Tel Aviv University, Israel
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Chitturi KR, Kumar S, Hill AP, Lorente-Ros M, Cellamare M, Merdler I, Abusnina W, Haberman D, Lupu L, Chaturvedi A, Ozturk ST, Cermak V, Sawant V, Zhang C, Ben-Dor I, Tsimploulis A, Waksman R, Hashim HD, Case BC. Prevalence of Arrhythmias in Patients With Coronary Microvascular Dysfunction. Catheter Cardiovasc Interv 2025; 105:483-490. [PMID: 39660783 DOI: 10.1002/ccd.31324] [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: 10/13/2024] [Revised: 11/14/2024] [Accepted: 11/22/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Coronary microvascular dysfunction (CMD) is an important cause of angina with nonobstructive coronary arteries (ANOCA). It is unclear whether CMD is associated with arrhythmia. AIMS This study aimed to evaluate the prevalence of arrhythmias in patients with ANOCA and CMD compared to those in patients with ANOCA without CMD. METHODS In this observational study of the Coronary Microvascular Disease Registry (NCT05960474), patients with ANOCA who underwent invasive coronary functional assessment for CMD were included. The diagnosis of arrhythmia was based on 12-lead electrocardiography (ECG), or clinical diagnosis accompanied by ECG evidence within 1 year before CMD evaluation. RESULTS The study included 262 patients; 66 (25.2%) were CMD-positive. Patients with CMD were older, and there was no difference in history of heart failure and baseline left ventricular ejection fraction compared to those without CMD. Premature atrial contractions (PACs) (25.8% vs. 5.6%; p < 0.001), supraventricular tachycardia (SVT) (24.2% vs. 6.6%; p < 0.001), premature ventricular complexes (PVCs) (43.9% vs. 10.7%; p < 0.001), nonsustained ventricular tachycardia (NSVT) (28.8% vs. 3.1%; p < 0.001), and accelerated idioventricular rhythm (9.1% vs. 2.6%; = 0.02) were more common in CMD-positive patients. In a multivariate analysis adjusting for baseline differences and other variables clinically associated with arrhythmia, CMD was associated with PACs (odds ratio [OR]: 4.7; 95% confidence interval [CI]: 1.8-11.9), SVT (OR: 3.5; 95% CI: 1.5-8.6), PVCs (OR: 5.9; 95% CI: 2.6-13.0), and NSVT (OR: 9.5; 95% CI: 3.2-27.7). CONCLUSION Patients with ANOCA and CMD have a higher likelihood of arrhythmias, especially ventricular arrhythmias.
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Affiliation(s)
- Kalyan R Chitturi
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Sant Kumar
- Department of Internal Medicine, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Andrew P Hill
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Marta Lorente-Ros
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Matteo Cellamare
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Ilan Merdler
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Waiel Abusnina
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Dan Haberman
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Lior Lupu
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Abhishek Chaturvedi
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Sevket Tolga Ozturk
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Vijoli Cermak
- MedStar Cardiovascular Research Network, MedStar Southern Maryland Hospital Center, Clinton, Maryland, USA
| | - Vaishnavi Sawant
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Cheng Zhang
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Itsik Ben-Dor
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Apostolos Tsimploulis
- Section of Electrophysiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Ron Waksman
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Hayder D Hashim
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Brian C Case
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
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48
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Quarta R, Martino G, Romano LR, Lopes G, Greco FF, Spaccarotella CAM, Indolfi C, Curcio A, Polimeni A. The Role of Circulating Biomarkers in Patients with Coronary Microvascular Disease. Biomolecules 2025; 15:177. [PMID: 40001480 PMCID: PMC11853534 DOI: 10.3390/biom15020177] [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: 12/30/2024] [Revised: 01/16/2025] [Accepted: 01/24/2025] [Indexed: 02/27/2025] Open
Abstract
Coronary microvascular disease (CMD) comprises a spectrum of conditions characterized by the functional and structural abnormalities of coronary microcirculation, affecting vessels typically smaller than 500 μm. Despite its clinical significance as a contributor to myocardial ischemia, CMD frequently remains underdiagnosed due to the limitations of current diagnostic approaches. Invasive testing, including coronary reactivity assessment, is considered the gold standard, but it is resource-intensive and not always accessible. Non-invasive methods, such as positron emission tomography (PET) and transthoracic Doppler echocardiography (TTDE), offer alternatives but are limited by varying accuracy and accessibility. Amid these diagnostic challenges, there is increasing interest in circulating biomarkers as adjuncts in CMD evaluation. Biomarkers associated with endothelial dysfunction, inflammation, and oxidative stress, detectable through routine blood tests, may assist in CMD diagnosis, risk stratification, and therapeutic monitoring. These biomarkers can offer insights into CMD pathogenesis and enable early, non-invasive screening to identify patients who may benefit from more invasive investigations. This narrative review examines studies assessing biomarkers in CMD patients with diagnoses confirmed through invasive techniques. Our objective is to focus on circulating biomarkers linked to the invasive evaluation of coronary microcirculation, aiming to advance the understanding of the underlying mechanisms of this prevalent condition and enhance diagnostic accuracy and the clinical management of affected patients.
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Affiliation(s)
- Rossella Quarta
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
- Division of Cardiology, Annunziata Hospital, 87100 Cosenza, Italy
| | - Giovanni Martino
- Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy
| | - Letizia Rosa Romano
- Division of Cardiology, Annunziata Hospital, 87100 Cosenza, Italy
- Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy
| | - Giovanni Lopes
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
| | | | | | - Ciro Indolfi
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
| | - Antonio Curcio
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
- Division of Cardiology, Annunziata Hospital, 87100 Cosenza, Italy
| | - Alberto Polimeni
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
- Division of Interventional Cardiology, Annunziata Hospital, 87100 Cosenza, Italy
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49
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Crooijmans C, Jansen TPJ, Meeder JG, Paradies V, de Vos AMJ, Woudstra P, Vossenberg TNE, van de Hoef TP, Vos NS, Olde Bijvank EGM, van den Oord SCH, Winkler P, Meuwissen M, Widdershoven JWMG, Arkenbout EK, Stoel MG, Appelman Y, Beijk MAM, Cetinyurek‐Yavuz A, den Ruijter HM, Elias‐Smale SE, van Royen N, Dimitriu‐Leen AC, Damman P, for NL‐CFT. Angina Severity and Symptom Improvement Are Associated With Diagnostic Acetylcholine Provocation Dose in Vasospastic Angina. J Am Heart Assoc 2025; 14:e037913. [PMID: 39818972 PMCID: PMC12054411 DOI: 10.1161/jaha.124.037913] [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: 09/12/2024] [Accepted: 11/08/2024] [Indexed: 01/19/2025]
Abstract
BACKGROUND A coronary function test (CFT) is the recommended diagnostic test to identify coronary vasomotor dysfunction as a cause of symptoms in patients with angina and nonobstructive coronary arteries (ANOCA). Acetylcholine is the commonly used pharmacological agent for spasm provocation. We aimed to investigate an association between severity of symptoms and provocative acetylcholine dose. METHODS AND RESULTS We included ANOCA patients undergoing clinically indicated CFT from the Netherlands Registry of Invasive Coronary Vasomotor Function Testing: NL-CFT. Patients with epicardial spasm (n=251) were divided according to acetylcholine spasm triggering dose: low (2-20 mcg, EpiLOW), middle (100 mcg, EpiMIDDLE) or high (200 mcg, EpiHIGH). Patients with microvascular spasm (n=157) were analyzed irrespective of triggering dose. The patient groups were compared to each other and to a control group with negative CFT results (n=101). We assessed mean Seattle Angina Questionnaire angina frequency and summary scores at baseline and follow-up and the proportion of patients improving or deteriorating. An inverse relationship between provocation dosage and angina frequency at baseline was found in epicardial spasm: the lower the triggering dose, the more frequently patients experienced angina (EpiLOW 48±20, EpiMIDDLE 53±21, EpiHIGH 57±19, microvascular spasm 61±21, controls 64±21, overall P=0.003). A trend was seen toward most patients improving in the high triggering dose group, and most patients deteriorating in the low triggering dose group. CONCLUSIONS A significant dose-dependent relationship between spasm provocation and anginal complaints exists. Acetylcholine provocation dose could be incorporated as a risk stratification factor or surrogate outcome in future clinical trials. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT06083155.
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Affiliation(s)
- C. Crooijmans
- Department of CardiologyRadboud University Medical CentreNijmegenThe Netherlands
| | - Tijn P. J. Jansen
- Department of CardiologyRadboud University Medical CentreNijmegenThe Netherlands
| | - Joan G. Meeder
- Department of CardiologyVieCuri Medical CentreNorth‐LimburgThe Netherlands
| | - Valeria Paradies
- Department of CardiologyMaasstad HospitalRotterdamThe Netherlands
| | | | - Pier Woudstra
- Department of CardiologyMedical Centre LeeuwardenLeeuwardenThe Netherlands
| | | | - Tim P. van de Hoef
- Department of CardiologyUniversity Medical Centre UtrechtUtrechtThe Netherlands
| | - Nicola S. Vos
- Department of CardiologyOnze Lieve Vrouwe GasthuisAmsterdamThe Netherlands
| | | | | | - Patty Winkler
- Department of CardiologyZuyderland HospitalHeerlenThe Netherlands
| | | | | | | | - Martin G. Stoel
- Department of CardiologyMedical Spectrum TwenteEnschedeThe Netherlands
| | - Yolande Appelman
- Department of CardiologyAmsterdam University Medical CenterAmsterdamThe Netherlands
| | - Marcel A. M. Beijk
- Department of CardiologyAmsterdam University Medical CenterAmsterdamThe Netherlands
| | | | - Hester M. den Ruijter
- Laboratory of experimental CardiologyUniversity Medical Centre UtrechtUtrechtThe Netherlands
| | | | - Niels van Royen
- Department of CardiologyRadboud University Medical CentreNijmegenThe Netherlands
| | | | - Peter Damman
- Department of CardiologyRadboud University Medical CentreNijmegenThe Netherlands
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50
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Ang DTY, Carberry J, Ford TJ, Kamdar A, Sykes R, Sidik NP, Carrick D, McCartney PJ, Collison D, Robertson K, Shaukat A, Rocchiccioli JP, McGeoch R, Watkins S, Hood S, McEntegart M, Lindsay M, Eteiba H, Oldroyd KG, Good R, McConnachie A, Berry C. Coronary microvascular function and atherosclerotic plaque burden in ischaemia and no obstructive coronary arteries: a secondary analysis of the CorMicA trial. Heart 2025; 111:117-124. [PMID: 39603791 PMCID: PMC11874308 DOI: 10.1136/heartjnl-2024-324677] [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: 07/01/2024] [Accepted: 11/03/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND The relationship between atherosclerosis and endotypes of myocardial ischaemia with no obstructive coronary artery disease (INOCA) is unclear. We investigated potential associations between cumulative atherosclerotic plaque burden quantified using the Gensini score, novel invasive indices of coronary microvascular function (microvascular resistance reserve (MRR); resistive reserve ratio (RRR)) and related INOCA endotypes. METHODS Coronary angiography and invasive coronary function tests were simultaneously acquired in the CorMicA cohort. A comprehensive physiological assessment was performed using both a thermodilution-based diagnostic guidewire and intracoronary acetylcholine provocation testing. Angiograms were examined for luminal stenosis in each segment of the SYNTAX coronary model. Cumulative plaque burden was quantified using the Gensini score, which incorporated both the number of diseased coronary segments and stenosis severity. Results were compared with indices of microvascular function and INOCA endotypes. Angiographic analyses were performed blind to coronary physiology findings. RESULTS In 151 participants (median age 61 years; 73.5% female) without flow-limiting coronary artery disease, medical history included 41.7% smoking, 63.6% hypertension and 19.2% diabetes mellitus. The left anterior descending artery underwent diagnostic guidewire testing in 85.4%, and 55.0% of participants had abnormal coronary flow reserve (CFR) and/or Index of Microcirculatory Resistance (IMR). The median Gensini score was 6.0 (IQR 2.5-11.0). CFR (p=0.012), MRR (p=0.026) and RRR (p=0.026), but not IMR (p=0.445), were univariably associated with raised Gensini scores. These significant effects persisted in multivariable models controlling for potential confounders. Considering INOCA endotypes, Gensini scores differed among participants with microvascular angina (MVA) (7.0 (2.5-11.0)), vasospastic angina (VSA) (4.5 (2.0-10.0)), mixed MVA/VSA (9.0 (5.0-11.5)) and non-cardiac symptoms (3.5 (1.5-8.0)); Kruskal-Wallis p=0.030. CONCLUSIONS Reduced CFR, MRR and RRR, and MVA were associated with increased coronary atherosclerotic plaque burden, as evidenced by higher Gensini scores. These novel findings provide a mechanistic link between INOCA and cardiovascular events, reinforcing the importance of antiatherosclerosis therapy in patients with MVA.
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Affiliation(s)
- Daniel T Y Ang
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
- School of Cardiovascular and Metabolic Health, University of Glasgow College of Medical Veterinary and Life Sciences, Glasgow, UK
- University Hospital Hairmyres, East Kilbride, South Lanarkshire, UK
| | - Jaclyn Carberry
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
- School of Cardiovascular and Metabolic Health, University of Glasgow College of Medical Veterinary and Life Sciences, Glasgow, UK
| | - Thomas J Ford
- Department of Cardiology, Central Coast Local Health District, Gosford, New South Wales, Australia
| | - Anna Kamdar
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
- School of Cardiovascular and Metabolic Health, University of Glasgow College of Medical Veterinary and Life Sciences, Glasgow, UK
| | - Robert Sykes
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
- School of Cardiovascular and Metabolic Health, University of Glasgow College of Medical Veterinary and Life Sciences, Glasgow, UK
- University Hospital Hairmyres, East Kilbride, South Lanarkshire, UK
| | - Novalia P Sidik
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
- School of Cardiovascular and Metabolic Health, University of Glasgow College of Medical Veterinary and Life Sciences, Glasgow, UK
| | - David Carrick
- University Hospital Hairmyres, East Kilbride, South Lanarkshire, UK
| | - Peter J McCartney
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
| | - Damien Collison
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
| | - Keith Robertson
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
| | - Aadil Shaukat
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
| | - J Paul Rocchiccioli
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
| | - R McGeoch
- University Hospital Hairmyres, East Kilbride, South Lanarkshire, UK
| | - Stuart Watkins
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
| | - Stuart Hood
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
| | | | - Mitchell Lindsay
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
| | - Hany Eteiba
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
| | - Keith G Oldroyd
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
| | - Richard Good
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
- School of Cardiovascular and Metabolic Health, University of Glasgow College of Medical Veterinary and Life Sciences, Glasgow, UK
| | - Alex McConnachie
- Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
| | - Colin Berry
- Cardiology, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
- School of Cardiovascular and Metabolic Health, University of Glasgow College of Medical Veterinary and Life Sciences, Glasgow, UK
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