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Khandkar C, Rehan R, Ravindran J, Yong A. An updated review on therapeutic strategies in coronary microvascular dysfunction. Int J Cardiol 2025; 428:133128. [PMID: 40068789 DOI: 10.1016/j.ijcard.2025.133128] [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: 09/02/2024] [Revised: 12/18/2024] [Accepted: 03/05/2025] [Indexed: 03/14/2025]
Abstract
Coronary microvascular dysfunction (CMD) is well-known cause of angina, yet treatment options remain limited. This systematic review and meta-analysis examines the current literature and provides a contemporary evaluation of treatments using a stringent definition for CMD with accurate methods of microvascular assessment in accordance with recent consensus guidelines. Methods and Results: A search strategy was conducted independently by two authors (CK and RR). Studies were required to be prospective trials in adult patients with documented CMD by IC doppler wire, thermodilution techniques, or perfusion imaging via PET/MRI. CMD was defined as either coronary flow reserve (CFR)/myocardial perfusion reserve (MPR) < 2.5, and/or index of microvascular resistance (IMR) > 25. Methodological quality of studies was assessed via the Cochrane Risk of Bias tool. The primary and secondary endpoints were change in CFR/MPR/IMR and change in Seattle Angina Questionnaire (SAQ) scores respectively. Two-sided p-values were used and considered significant if p < 0.05. A total of 11,360 records were identified, from which 14 were included in this review covering 9 different treatments. Two treatments (quinapril and ranolazine) showed significant improvement in both CFR and angina. Three ranolazine trials were pooled in meta-analysis. The standardised mean difference showed a weak positive effect (0.24) with wide intervals (-0.21 to 0.26) which was not statistically significant (p = 0.20). We subsequently reviewed all treatments as mentioned in recent European consensus statements. Conclusions: The overall quality of evidence surrounding treatments for CMD is of "low", with lack of robust data highlighting the dire need for higher quality trials in this area.
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Affiliation(s)
- Chinmay Khandkar
- Concord Hospital, Concord 2139, NSW, Australia; University of Sydney, Camperdown 2050, NSW, Australia; Royal Prince Alfred Hospital, Camperdown 2050, NSW, Australia.
| | - Rajan Rehan
- Concord Hospital, Concord 2139, NSW, Australia; University of Sydney, Camperdown 2050, NSW, Australia; Royal Prince Alfred Hospital, Camperdown 2050, NSW, Australia
| | - Jayant Ravindran
- Concord Hospital, Concord 2139, NSW, Australia; University of Sydney, Camperdown 2050, NSW, Australia
| | - Andy Yong
- Concord Hospital, Concord 2139, NSW, Australia; University of Sydney, Camperdown 2050, NSW, Australia
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2
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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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3
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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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Khansari N, Salehi AM, Mohammadi N, Yazdi AH, Sanaei Z. Evaluation of changes in the global longitudinal strain for left ventricular function before and after eight weeks of taking high dose of atorvastatin in patients with coronary slow flow phenomenon. BMC Cardiovasc Disord 2024; 24:522. [PMID: 39333856 PMCID: PMC11429084 DOI: 10.1186/s12872-024-04198-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 09/16/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Coronary Slow Flow Phenomenon (CSFP) is a well-recognized clinical entity characterized by delayed opacification of coronary arteries in the presence of a normal coronary angiogram. The objective of this study was determined and compared left ventricle (LV)strain in patients with CSFP before and after receiving a high-dose atorvastatin. MATERIALS AND METHODS This cross-sectional study was conducted on 51 patients with CSFP from the beginning of 2021 to the end of September 2022. Trans-thoracic Echocardiogram (TTE) was performed by an echocardiography specialist. Thereafter, the patient's basic information was entered into the researcher's checklist after treatment with atorvastatin 40 mg daily for eight consecutive weeks. After eight weeks, the patients were subjected again to TTE. The data were analyzed in SPSS statistical software. RESULTS The mean LV-GLS before taking atorvastatin was - 16.53%±3.63%. The mean LV-GLS after taking atorvastatin was 17.57%±3.53% (P.value = 0.01). The mean LV function before taking atorvastatin was 48.82%±9.19%. Meanwhile, the mean LV function after taking atorvastatin was 50.59%±7.91% (P = 0.01). There was no significantly change in left atrium volume (49.88 ± 0.68 vs. 49.9 + 0.67) after 8 weeks taking atorvastatin (P = 0.884). CONCLUSION The plasma ET-1 levels are elevated in CSFP patients, and atorvastatin improves coronary flow and endothelial function. As evidenced by the results of this study, the daily intake of 40 mg of oral atorvastatin during eight consecutive weeks in patients with CSFP significantly improved LV strain and LV function, however atorvastatin does not have a significant effect on improving the right ventricular function and pulmonary artery systolic pressure.
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Affiliation(s)
- Nakisa Khansari
- Cardiovascular Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Amir Mohammad Salehi
- Student Research Committee, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Niloofar Mohammadi
- Cardiovascular Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Amir Hossein Yazdi
- Cardiovascular Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Zahra Sanaei
- Department of Community Medicine, School of Medicine, Farshchian Cardiovascular Subspecialty Medical Center, Hamadan University of Medical Sciences, Hamadan, Iran
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Pompei G, Ganzorig N, Kotanidis CP, Alkhalil M, Collet C, Sinha A, Perera D, Beltrame J, Kunadian V. Novel diagnostic approaches and management of coronary microvascular dysfunction. Am J Prev Cardiol 2024; 19:100712. [PMID: 39161975 PMCID: PMC11332818 DOI: 10.1016/j.ajpc.2024.100712] [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: 04/27/2024] [Revised: 07/04/2024] [Accepted: 07/21/2024] [Indexed: 08/21/2024] Open
Abstract
The mechanism underlying ischaemic heart disease (IHD) has been primarily attributed to obstructive coronary artery disease (CAD). However, non-obstructive coronary arteries are identified in >50% of patients undergoing elective coronary angiography, recently leading to growing interest in the investigation and management of angina/ischaemia with non-obstructive coronary arteries (ANOCA/INOCA). INOCA is an umbrella term encompassing a multiple spectrum of possible pathogenetic entities, including coronary vasomotor disorders which consist of two major endotypes: coronary microvascular dysfunction (CMD) and vasospastic angina. Both conditions can coexist and be associated with concomitant obstructive CAD. Particularly, CMD refers to myocardial ischaemia due to reduced vasodilatory capacity of coronary microcirculation secondary to structural remodelling or impaired resting microvascular tone (functional) or a combination of both. CMD is not a benign condition and is more prevalent in women presenting with chronic coronary syndrome compared to men. In this setting, an impaired coronary flow reserve has been associated with increased risk of major adverse cardiovascular events. ANOCA/INOCA patients also experience impaired quality of life and associated increased healthcare costs. Therefore, research in this scenario has led to better definition, classification, and prognostic stratification based on the underlying pathophysiological mechanisms. The development and validation of non-invasive imaging modalities, invasive coronary vasomotor function testing and angiography-derived indices provide a comprehensive characterisation of CMD. The present narrative review aims to summarise current data relating to the diagnostic approach to CMD and provides details on the sequence that therapeutic management should follow.
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Affiliation(s)
- Graziella Pompei
- Translational and Clinical Research Institute, Faculty of Medical Sciences, NewcastleUniversity, Newcastle upon Tyne, UK
- Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona, FE, Italy
| | - Nandine Ganzorig
- Translational and Clinical Research Institute, Faculty of Medical Sciences, NewcastleUniversity, Newcastle upon Tyne, UK
| | - Christos P. Kotanidis
- Translational and Clinical Research Institute, Faculty of Medical Sciences, NewcastleUniversity, Newcastle upon Tyne, UK
- Cardiothoracic Centre, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom
| | - Mohammad Alkhalil
- Translational and Clinical Research Institute, Faculty of Medical Sciences, NewcastleUniversity, Newcastle upon Tyne, UK
- Cardiothoracic Centre, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom
| | - Carlos Collet
- Cardiovascular Center Aalst, OLV Clinic, Aalst, Belgium
| | - Aish Sinha
- School of Cardiovascular Medicine and Sciences, British Heart Foundation Centre of Excellence and National Institute for Health Research Biomedical Research Centre, King's College London, London, UK
| | - Divaka Perera
- School of Cardiovascular Medicine and Sciences, British Heart Foundation Centre of Excellence and National Institute for Health Research Biomedical Research Centre, King's College London, London, UK
| | - John Beltrame
- Basil Hetzel Institute for Translational Health Research, Adelaide Medical School, University of Adelaide and Royal Adelaide Hospital & The Queen Elizabeth Hospital, Adelaide, Australia
| | - Vijay Kunadian
- Translational and Clinical Research Institute, Faculty of Medical Sciences, NewcastleUniversity, Newcastle upon Tyne, UK
- Cardiothoracic Centre, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom
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Toprak K, Karataş M, Kaplangoray M, Dursun A, Taşcanov MB, Altıparmak İH, Biçer A, Demirbağ R. Comparison of the Effect of Non-HDL-C/HDL-C Ratio on Coronary Slow Flow with Other Non-Traditional Lipid Markers. ACTA CARDIOLOGICA SINICA 2024; 40:388-401. [PMID: 39045373 PMCID: PMC11261365 DOI: 10.6515/acs.202407_40(4).20240419a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 04/19/2024] [Indexed: 07/25/2024]
Abstract
Background Coronary slow flow (CSF) is a microvascular disease characterized by delayed opacification of the epicardial coronary arteries during angiography. The main pathogenesis of CSF is endothelial dysfunction caused by diffuse atherosclerosis. Dyslipidemia is one of the primary factors raising the risk of atherosclerosis. Compared to conventional lipid profiles, non-traditional lipid profiles more accurately reflect dyslipidemic status. In this work, we compared the non-high density lipoprotein-cholesterol (HDL-C)/HDL-C ratio (NHHR) with other conventional and non-conventional lipid profiles in order to determine its impact on CSF. Methods A total of 9112 subjects who underwent coronary angiography were screened retrospectively, of whom 130 subjects with CSF and 130 subjects with normal CF were included. Multivariate regression analysis was used to identify independent predictors of CSF. Additionally, in order to predict CSF, the diagnostic accuracies of NHHR and other non-traditional lipid profiles were examined. Results There were significantly higher non-traditional lipid profiles in the CSF group (all p < 0.001). Compared to other non-traditional lipid profiles, NHHR had a stronger association with thrombolysis in myocardial infarction frame count (r = 0.3593, p < 0.0001). In addition to NHHR, non-HDL-C, Castelli's risk index-II, atherogenic index of plasma, plasma glucose, dyslipidemia, smoking, and body mass index were identified as independent predictors of CSF. The ability of NHHR to detect CSF was superior to other non-traditional lipid profiles (area under the curve: 0.785; confidence interval: 0.730-0.840; p < 0.001). Conclusions NHHR was found to be a potent and reliable predictor of CSF. This indicates that NHHR can be used as a reliable biomarker for risk stratification of CSF.
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Affiliation(s)
- Kenan Toprak
- Department of Cardiology, Faculty of Medicine, Harran University, Sanliurfa
| | - Mesut Karataş
- Kartal Koşuyolu High Specialization Training and Research Hospital, Istanbul
| | | | - Ayten Dursun
- Nursing Department, Şanlıurfa Provincial Health Directorate, Sanliurfa, Turkey
| | | | | | - Asuman Biçer
- Department of Cardiology, Faculty of Medicine, Harran University, Sanliurfa
| | - Recep Demirbağ
- Department of Cardiology, Faculty of Medicine, Harran University, Sanliurfa
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Bland A, Chuah E, Meere W, Ford TJ. Targeted Therapies for Microvascular Disease. Cardiol Clin 2024; 42:137-145. [PMID: 37949535 DOI: 10.1016/j.ccl.2023.07.002] [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: 11/12/2023]
Abstract
Coronary microvascular dysfunction (CMD) is a common cause of ischemia but no obstructive coronary artery disease that results in an inability of the coronary microvasculature to meet myocardial oxygen demand. CMD is challenging to diagnose and manage due to a lack of mechanistic research and targeted therapy. Recent evidence suggests we can improved patient outcomes by stratifying antianginal therapies according to the diagnosis revealed by invasive assessment of the coronary microcirculation. This review article appraises the evidence for management of CMD, which includes treatment of cardiovascular risk, antianginal therapy and therapy for atherosclerosis.
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Affiliation(s)
- Adam Bland
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Eunice Chuah
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - William Meere
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Thomas J Ford
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia; University of Glasgow, ICAMS, G12 8QQ Glasgow, UK.
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8
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Bland A, Chuah E, Meere W, Ford TJ. Targeted Therapies for Microvascular Disease. Heart Fail Clin 2024; 20:91-99. [PMID: 37953025 DOI: 10.1016/j.hfc.2023.06.003] [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: 11/14/2023]
Abstract
Coronary microvascular dysfunction (CMD) is a common cause of ischemia but no obstructive coronary artery disease that results in an inability of the coronary microvasculature to meet myocardial oxygen demand. CMD is challenging to diagnose and manage due to a lack of mechanistic research and targeted therapy. Recent evidence suggests we can improved patient outcomes by stratifying antianginal therapies according to the diagnosis revealed by invasive assessment of the coronary microcirculation. This review article appraises the evidence for management of CMD, which includes treatment of cardiovascular risk, antianginal therapy and therapy for atherosclerosis.
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Affiliation(s)
- Adam Bland
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Eunice Chuah
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - William Meere
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Thomas J Ford
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia; University of Glasgow, ICAMS, G12 8QQ Glasgow, UK.
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9
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Vuorio A, Kovanen PT, Raal FJ. Coronary microcirculatory dysfunction in hypercholesterolemic patients with COVID-19: potential benefit from cholesterol-lowering treatment. Ann Med 2023; 55:2199218. [PMID: 37068045 PMCID: PMC10116911 DOI: 10.1080/07853890.2023.2199218] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/18/2023] Open
Abstract
Patients with hypercholesterolemia often have coronary microvascular dysfunction (CMD). Viral infections, such as the SARS-CoV-2 infection, may also result in CMD. Three non-randomized studies have shown significant beneficial effects of statins on CMD in non-infected patients. Similarly, in SARS-CoV-2 - infected patients one beneficial mechanism of action of statins may be the amelioration of endothelial dysfunction, which is a major driver of CMD. Apart from statins, lipoprotein apheresis and PCSK9 inhibitors can also improve or even reverse CMD. The potential reversal of CMD by using effective cholesterol-lowering medications during and after COVID-19 infection, especially in hypercholesterolemic COVID-19 patients, is important.KEY MESSAGESCoronary microvascular dysfunction (CMD) is common in patients hospitalized with SARS-CoV-2 infectionThree nonrandomized studies in non-infected patients are showing the beneficial effects of statin treatment on CMDEffective cholesterol-lowering medication during and after SARS-CoV-2 infection, especially in hypercholesterolemic COVID-19 patients, is of great significance.
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Affiliation(s)
- Alpo Vuorio
- Forensic Medicine, Mehiläinen Airport Health Centre, Vantaa, Finland
- Department of Forensic Medicine, University of Helsinki, Helsinki, Finland
| | - Petri T Kovanen
- Atherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland
| | - Frederick J Raal
- Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
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Tong J, Bei GG, Zhang LB, Yang BQ. Coronary slow flow research: a bibliometric analysis. Eur J Med Res 2023; 28:398. [PMID: 37794429 PMCID: PMC10548595 DOI: 10.1186/s40001-023-01326-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 08/27/2023] [Indexed: 10/06/2023] Open
Abstract
BACKGROUND Studies on coronary slow flow are receiving increasing attention, but objective evaluations are still lacking. The purpose of this study was to visualize the current status and research hotspots of coronary slow flow through bibliometric analysis. METHODS All relevant publications on coronary slow flow from 2003 to 2022 were extracted from the Web of Science Core Collection database and analyzed by VOSviewer and CiteSpace visualization software. Year of publication, journal, country/region, institution, and first author of each paper, as well as research hotspots were identified. RESULTS A total of 913 publications were retrieved. The journal with the most publications was Coronary Artery Disease. The country/region with the most publications was Turkey, followed by China and the United States. The institution with the largest publication volume was Turkey Specialized Higher Education Research Hospital. The author with the largest publication volume was Chun-Yan Ma from China. Keyword analysis indicated that "treatment and prognosis", "pathogenesis and risk factors" and "diagnosis" were the clustering centers of coronary slow flow, and the research hotspots gradually changed with time, from pathogenesis to treatment and prognosis. CONCLUSION Future research will focus on the search for effective and non-invasive detection indicators and treatments of coronary slow flow. Collaboration needs to be enhanced between different institutions or countries/regions, which would improve clinical outcomes for patients with coronary slow flow.
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Affiliation(s)
- Jing Tong
- Department of Radiology, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, 110016, Liaoning, China
| | - Gui-Guang Bei
- Department of Radiology, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, 110016, Liaoning, China
| | - Li-Bo Zhang
- Department of Radiology, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, 110016, Liaoning, China
| | - Ben-Qiang Yang
- Department of Radiology, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, 110016, Liaoning, China.
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Smilowitz NR, Prasad M, Widmer RJ, Toleva O, Quesada O, Sutton NR, Lerman A, Reynolds HR, Kesarwani M, Savage MP, Sweeny JM, Janaszek KB, Barseghian El-Farra A, Holoshitz N, Park K, Albadri A, Blair JA, Jeremias A, Kearney KE, Kobayashi Y, Miner SES, Samuels BA, Shah SM, Taqueti VR, Wei J, Fearon WF, Moses JW, Henry TD, Tremmel JA. Comprehensive Management of ANOCA, Part 2-Program Development, Treatment, and Research Initiatives: JACC State-of-the-Art Review. J Am Coll Cardiol 2023; 82:1264-1279. [PMID: 37704316 DOI: 10.1016/j.jacc.2023.06.044] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 06/15/2023] [Indexed: 09/15/2023]
Abstract
Centers specializing in coronary function testing are critical to ensure a systematic approach to the diagnosis and treatment of angina with nonobstructive coronary arteries (ANOCA). Management leveraging lifestyle, pharmacology, and device-based therapeutic options for ANOCA can improve angina burden and quality of life in affected patients. Multidisciplinary care teams that can tailor and titrate therapies based on individual patient needs are critical to the success of comprehensive programs. As coronary function testing for ANOCA is more widely adopted, collaborative research initiatives will be fundamental to improve ANOCA care. These efforts will require standardized symptom assessments and data collection, which will propel future large-scale clinical trials.
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Affiliation(s)
- Nathaniel R Smilowitz
- Leon H. Charney Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA; Cardiology Section, Department of Medicine, VA New York Harbor Healthcare System, New York, New York, USA
| | - Megha Prasad
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York City, New York, USA
| | | | - Olga Toleva
- Department of Medicine, Emory University, Atlanta, Georgia, USA
| | - Odayme Quesada
- Women's Heart Center, The Christ Hospital Heart and Vascular Institute, Cincinnati, Ohio, USA; The Carl and Edyth Lindner Center for Research and Education, The Christ Hospital, Cincinnati, Ohio, USA
| | - Nadia R Sutton
- Department of Internal Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA
| | - Amir Lerman
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Harmony R Reynolds
- Sarah Ross Soter Center for Women's Cardiovascular Research, Leon H. Charney Division of Cardiology, NYU Grossman School of Medicine, New York, New York, USA
| | - Manoj Kesarwani
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis School of Medicine, Sacramento, California, USA
| | - Michael P Savage
- Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Joseph M Sweeny
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | | | - Noa Holoshitz
- Ascension Columbia St Mary's, Milwaukee, Wisconsin, USA
| | - Ki Park
- Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida, USA
| | - Ahmed Albadri
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - John A Blair
- Department of Medicine, University of Chicago Medicine, Chicago, Illinois, USA
| | - Allen Jeremias
- St Francis Hospital & Heart Center, Roslyn, New York, USA
| | - Kathleen E Kearney
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Yuhei Kobayashi
- New York Presbyterian Brooklyn Methodist Hospital/Weill Cornell Medical College, New York, New York, USA
| | - Steven E S Miner
- Southlake Regional Medical Centre, Newmarket, Ontario, Canada, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Bruce A Samuels
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Samit M Shah
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut USA
| | - Viviany R Taqueti
- Cardiovascular Imaging Program, Departments of Radiology and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Janet Wei
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - William F Fearon
- Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Jeffery W Moses
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York City, New York, USA; St Francis Hospital & Heart Center, Roslyn, New York, USA
| | - Timothy D Henry
- Carl and Edyth Lindner Center for Research and Education, The Christ Hospital Heart and Vascular Institute, Cincinnati, Ohio, USA
| | - Jennifer A Tremmel
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA.
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12
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Marano P, Wei J, Merz CNB. Coronary Microvascular Dysfunction: What Clinicians and Investigators Should Know. Curr Atheroscler Rep 2023; 25:435-446. [PMID: 37338666 PMCID: PMC10412671 DOI: 10.1007/s11883-023-01116-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2023] [Indexed: 06/21/2023]
Abstract
PURPOSE OF REVIEW Abnormal structure and function of the coronary microvasculature have been implicated in the pathophysiology of multiple cardiovascular disease processes. This article reviews recent research progress related to coronary microvascular dysfunction (CMD) and salient clinical takeaways. RECENT FINDINGS CMD is prevalent in patients with signs and symptoms of ischemia and no obstructive epicardial coronary artery disease (INOCA), particularly in women. CMD is associated with adverse outcomes, including most frequently the development of heart failure with preserved ejection fraction. It is also associated with adverse outcomes in patient populations including hypertrophic cardiomyopathy, dilated cardiomyopathy, and acute coronary syndromes. In patients with INOCA, stratified medical therapy guided by invasive coronary function testing to define the subtype of CMD leads to improved symptoms. There are invasive and non-invasive methodologies to diagnose CMD that provide prognostic information and mechanistic information to direct treatment. Available treatments improve symptoms and myocardial blood flow; ongoing investigations aim to develop therapy to improve adverse outcomes related to CMD.
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Affiliation(s)
- Paul Marano
- Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, USA
| | - Janet Wei
- Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, USA
- Cedars-Sinai Medical Center, Barbra Streisand Women's Heart Center, Smidt Heart Institute, 127 S. San Vicente Blvd, Los Angeles, CA, 90048, USA
| | - C Noel Bairey Merz
- Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, USA.
- Cedars-Sinai Medical Center, Barbra Streisand Women's Heart Center, Smidt Heart Institute, 127 S. San Vicente Blvd, Los Angeles, CA, 90048, USA.
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13
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Maurina M, Benedetti A, Stefanini G, Condorelli G, Collet C, Zivelonghi C, Smits PC, Paradies V. Coronary Vascular (DYS) Function and Invasive Physiology Assessment: Insights into Bolus and Continuous Thermodilution Methods. J Clin Med 2023; 12:4864. [PMID: 37510979 PMCID: PMC10381553 DOI: 10.3390/jcm12144864] [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: 06/06/2023] [Revised: 07/19/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023] Open
Abstract
A considerable number of patients with angina or myocardial ischemia have no significant coronary artery disease on invasive angiography. In recent years, several steps towards a better comprehension of the pathophysiology of these conditions, angina or ischemia with non-obstructive coronary arteries (ANOCA/INOCA), have been made. Nevertheless, several gaps in knowledge still remain. This review is intended to provide a comprehensive overview of ANOCA and INOCA, with a particular focus on pathophysiology, recent diagnostic innovations, gaps in knowledge and treatment modalities.
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Affiliation(s)
- Matteo Maurina
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy
- Cardio Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
- Department of Cardiology, Maasstad Hospital, 3079 DZ Rotterdam, The Netherlands
| | - Alice Benedetti
- HartCentrum, Antwerpen Hospital Network (ZNA) Middelheim, 2020 Antwerp, Belgium
| | - Giulio Stefanini
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy
- Cardio Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
| | - Gianluigi Condorelli
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy
- Cardio Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
| | - Carlos Collet
- Cardiovascular Center Aalst, OLV Clinic, 9300 Aalst, Belgium
| | - Carlo Zivelonghi
- HartCentrum, Antwerpen Hospital Network (ZNA) Middelheim, 2020 Antwerp, Belgium
| | - Pieter C. Smits
- Department of Cardiology, Maasstad Hospital, 3079 DZ Rotterdam, The Netherlands
| | - Valeria Paradies
- Department of Cardiology, Maasstad Hospital, 3079 DZ Rotterdam, The Netherlands
- Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, 3015 GD Rotterdam, The Netherlands
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14
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Afrăsânie I, Matei IT, Leancă SA, Chetran A, Costache AD, Afrăsânie VA, Dmour BA, Crișu D, Bădescu MC, Șerban LI, Costache II. Ischemia with Nonobstructive Coronary Artery Disease and Atrial Cardiomyopathy-Two Sides of the Same Story? Life (Basel) 2023; 13:life13020443. [PMID: 36836800 PMCID: PMC9963666 DOI: 10.3390/life13020443] [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: 12/28/2022] [Revised: 01/28/2023] [Accepted: 02/01/2023] [Indexed: 02/08/2023] Open
Abstract
Ischemia with nonobstructive coronary artery disease (INOCA) is increasingly recognized as a significant cause of angina, myocardial remodeling, and eventually heart failure (HF). Coronary microvascular dysfunction (CMD) is a major endotype of INOCA, and it is caused by structural and functional alterations of the coronary microcirculation. At the same time, atrial cardiomyopathy (ACM) defined by structural, functional, and electrical atrial remodeling has a major clinical impact due to its manifestations: atrial fibrillation (AF), atrial thrombosis, stroke, and HF symptoms. Both these pathologies share similar risk factors and have a high comorbidity burden. CMD causing INOCA and ACM frequently coexist. Thus, questions arise whether there is a potential link between these pathologies. Does CMD promote AF or the reverse? Which are the mechanisms that ultimately lead to CMD and ACM? Are both part of a systemic disease characterized by endothelial dysfunction? Lastly, which are the therapeutic strategies that can target endothelial dysfunction and improve the prognosis of patients with CMD and ACM? This review aims to address these questions by analyzing the existing body of evidence, offering further insight into the mechanisms of CMD and ACM, and discussing potential therapeutic strategies.
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Affiliation(s)
- Irina Afrăsânie
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Correspondence: (I.A.); (D.C.); Tel.: +40-76988633 (I.A. & D.C.)
| | - Iulian Theodor Matei
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Sabina Andreea Leancă
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Adriana Chetran
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Alexandru Dan Costache
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Department of Cardiovascular Rehabilitation, Clinical Rehabilitation Hospital, 700661 Iași, Romania
| | - Vlad-Adrian Afrăsânie
- Department of Medical Oncology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Department of Oncology, The Regional Institute of Oncology, 700483 Iași, Romania
| | - Bianca-Ana Dmour
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Daniela Crișu
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Correspondence: (I.A.); (D.C.); Tel.: +40-76988633 (I.A. & D.C.)
| | - Minerva Codruța Bădescu
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Internal Medicine Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Lăcrămioara Ionela Șerban
- Department of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Irina Iuliana Costache
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
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15
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Ueng KC, Chiang CE, Chao TH, Wu YW, Lee WL, Li YH, Ting KH, Su CH, Lin HJ, Su TC, Liu TJ, Lin TH, Hsu PC, Wang YC, Chen ZC, Jen HL, Lin PL, Ko FY, Yen HW, Chen WJ, Hou CJY. 2023 Guidelines of the Taiwan Society of Cardiology on the Diagnosis and Management of Chronic Coronary Syndrome. ACTA CARDIOLOGICA SINICA 2023; 39:4-96. [PMID: 36685161 PMCID: PMC9829849 DOI: 10.6515/acs.202301_39(1).20221103a] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 11/03/2022] [Indexed: 01/24/2023]
Abstract
Coronary artery disease (CAD) covers a wide spectrum from persons who are asymptomatic to those presenting with acute coronary syndromes (ACS) and sudden cardiac death. Coronary atherosclerotic disease is a chronic, progressive process that leads to atherosclerotic plaque development and progression within the epicardial coronary arteries. Being a dynamic process, CAD generally presents with a prolonged stable phase, which may then suddenly become unstable and lead to an acute coronary event. Thus, the concept of "stable CAD" may be misleading, as the risk for acute events continues to exist, despite the use of pharmacological therapies and revascularization. Many advances in coronary care have been made, and guidelines from other international societies have been updated. The 2023 guidelines of the Taiwan Society of Cardiology for CAD introduce a new concept that categorizes the disease entity according to its clinical presentation into acute or chronic coronary syndromes (ACS and CCS, respectively). Previously defined as stable CAD, CCS include a heterogeneous population with or without chest pain, with or without prior ACS, and with or without previous coronary revascularization procedures. As cardiologists, we now face the complexity of CAD, which involves not only the epicardial but also the microcirculatory domains of the coronary circulation and the myocardium. New findings about the development and progression of coronary atherosclerosis have changed the clinical landscape. After a nearly 50-year ischemia-centric paradigm of coronary stenosis, growing evidence indicates that coronary atherosclerosis and its features are both diagnostic and therapeutic targets beyond obstructive CAD. Taken together, these factors have shifted the clinicians' focus from the functional evaluation of coronary ischemia to the anatomic burden of disease. Research over the past decades has strengthened the case for prevention and optimal medical therapy as central interventions in patients with CCS. Even though functional capacity has clear prognostic implications, it does not include the evaluation of non-obstructive lesions, plaque burden or additional risk-modifying factors beyond epicardial coronary stenosis-driven ischemia. The recommended first-line diagnostic tests for CCS now include coronary computed tomographic angiography, an increasingly used anatomic imaging modality capable of detecting not only obstructive but also non-obstructive coronary plaques that may be missed with stress testing. This non-invasive anatomical modality improves risk assessment and potentially allows for the appropriate allocation of preventive therapies. Initial invasive strategies cannot improve mortality or the risk of myocardial infarction. Emphasis should be placed on optimizing the control of risk factors through preventive measures, and invasive strategies should be reserved for highly selected patients with refractory symptoms, high ischemic burden, high-risk anatomies, and hemodynamically significant lesions. These guidelines provide current evidence-based diagnosis and treatment recommendations. However, the guidelines are not mandatory, and members of the Task Force fully realize that the treatment of CCS should be individualized to address each patient's circumstances. Ultimately, the decision of healthcare professionals is most important in clinical practice.
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Affiliation(s)
- Kwo-Chang Ueng
- Division of Cardiology, Department of Internal Medicine, Chung Shan Medical University Hospital; School of Medicine, Chung Shan Medical University, Taichung
| | - Chern-En Chiang
- General Clinical Research Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
| | - Ting-Hsing Chao
- Department of Internal Medicine, National Cheng Kung University Hospital; College of Medicine, National Cheng Kung University, Tainan
| | - Yen-Wen Wu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Division of Cardiology, Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City
| | - Wen-Lieng Lee
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Cardiovascular Center, Taichung Veterans General Hospital, Taichung
| | - Yi-Heng Li
- Department of Internal Medicine, National Cheng Kung University Hospital; College of Medicine, National Cheng Kung University, Tainan
| | - Ke-Hsin Ting
- Division of Cardiology, Department of Internal Medicine, Yunlin Christian Hospital, Yunlin
| | - Chun-Hung Su
- Division of Cardiology, Department of Internal Medicine, Chung Shan Medical University Hospital; School of Medicine, Chung Shan Medical University, Taichung
| | - Hung-Ju Lin
- Cardiovascular Center, Department of Internal Medicine, National Taiwan University Hospital
| | - Ta-Chen Su
- Cardiovascular Center, Department of Internal Medicine, National Taiwan University Hospital
- Department of Environmental and Occupational Medicine, National Taiwan University College of Medicine, Taipei
| | - Tsun-Jui Liu
- Cardiovascular Center, Taichung Veterans General Hospital, Taichung
| | - Tsung-Hsien Lin
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
| | - Po-Chao Hsu
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
| | - Yu-Chen Wang
- Division of Cardiology, Asia University Hospital, Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung
| | - Zhih-Cherng Chen
- Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan
| | - Hsu-Lung Jen
- Division of Cardiology, Cheng Hsin Rehabilitation Medical Center, Taipei
| | - Po-Lin Lin
- Division of Cardiology, Hsinchu MacKay Memorial Hospital, Hsinchu
| | - Feng-You Ko
- Cardiovascular Center, Kaohsiung Veterans General Hospital, Kaohsiung
| | - Hsueh-Wei Yen
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
| | - Wen-Jone Chen
- Division of Cardiology, Department of Internal Medicine, Min Sheng General Hospital, Taoyuan
| | - Charles Jia-Yin Hou
- Cardiovascular Center, Department of Internal Medicine, MacKay Memorial Hospital; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
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16
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Bland A, Chuah E, Meere W, Ford TJ. Targeted Therapies for Microvascular Disease. Interv Cardiol Clin 2023; 12:131-139. [PMID: 36372457 DOI: 10.1016/j.iccl.2022.09.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
Coronary microvascular dysfunction (CMD) is a common cause of ischemia but no obstructive coronary artery disease that results in an inability of the coronary microvasculature to meet myocardial oxygen demand. CMD is challenging to diagnose and manage due to a lack of mechanistic research and targeted therapy. Recent evidence suggests we can improved patient outcomes by stratifying antianginal therapies according to the diagnosis revealed by invasive assessment of the coronary microcirculation. This review article appraises the evidence for management of CMD, which includes treatment of cardiovascular risk, antianginal therapy and therapy for atherosclerosis.
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Affiliation(s)
- Adam Bland
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Eunice Chuah
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - William Meere
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Thomas J Ford
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia; University of Glasgow, ICAMS, G12 8QQ Glasgow, UK.
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17
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Luu JM, Wei J, Shufelt CL, Asif A, Tjoe B, Theriot P, Bairey Merz CN. Clinical Practice Variations in the Management of Ischemia With No Obstructive Coronary Artery Disease. J Am Heart Assoc 2022; 11:e022573. [PMID: 36172938 DOI: 10.1161/jaha.121.022573] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Ischemia with no obstructive coronary artery disease is a condition associated with major adverse cardiovascular outcomes. To date, there are no specific American Heart Association or American College of Cardiology guidelines. The objective of this survey is to better understand the clinical practice and knowledge gaps that exist nationally. Methods and Results Participant-specific links for a survey with 11 questions and 3 reminders were sent between September and October 2020 to the American College of Cardiology CardioSurve Panel. The panel consist of randomly selected cardiologists (n=437) who represent the current profile of the American College of Cardiology US membership. The survey received a 30% response rate. Of the 172 respondents, 130 (76%) indicated that they have treated patients with ischemia with no obstructive coronary artery disease. Although the majority (69%) are generally confident in their ability to manage this condition, 1 of 3 report lack of confidence or are neutral. The American College of Cardiology/American Heart Association Chronic Stable Angina Guidelines are the most commonly used reference for treating ischemia with no obstructive coronary artery disease (81%), with most cardiologists wanting additional clinical guidance, such as randomized controlled trials (61%). More than 4 of 5 cardiologists rarely or never order advanced imaging modalities to assess coronary flow reserve. Approximately 2 of 3 of respondents frequently prescribe statins (68%), aspirin (66%), calcium channel blockers (63%), and β blockers or α/β blockers (55%). However, nearly 70% never prescribe angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Conclusions This survey demonstrates heterogeneity in the management of ischemia with no obstructive coronary artery disease among US cardiologists, identifies support for guideline development, and outlines knowledge gaps for research and education in the therapeutic management of this condition.
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Affiliation(s)
- Judy M Luu
- Barbra Streisand Women's Heart Center, Smidt Heart Institute Cedars-Sinai Medical Center Los Angeles CA
| | - Janet Wei
- Barbra Streisand Women's Heart Center, Smidt Heart Institute Cedars-Sinai Medical Center Los Angeles CA
| | - Chrisandra L Shufelt
- Barbra Streisand Women's Heart Center, Smidt Heart Institute Cedars-Sinai Medical Center Los Angeles CA
| | - Anum Asif
- Barbra Streisand Women's Heart Center, Smidt Heart Institute Cedars-Sinai Medical Center Los Angeles CA
| | - Benita Tjoe
- Barbra Streisand Women's Heart Center, Smidt Heart Institute Cedars-Sinai Medical Center Los Angeles CA
| | | | - C Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Smidt Heart Institute Cedars-Sinai Medical Center Los Angeles CA
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18
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Zhang W, Dai J, Shen L, Jiang Y, Zheng X, Xu K, Yang X, Wang X, Hao Z, Zhao Y, Wang D, Jiang L, Qiu X, Shen L, He B. Alprostadil vs. isosorbide dinitrate in ameliorating angina episodes in patients with coronary slow flow phenomenon: A randomized controlled trial. Front Cardiovasc Med 2022; 9:965364. [PMID: 36158840 PMCID: PMC9493040 DOI: 10.3389/fcvm.2022.965364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 08/26/2022] [Indexed: 12/04/2022] Open
Abstract
Background The optimum therapy for coronary slow flow phenomenon (CSFP) stays debatable. This study compared the effectiveness of alprostadil with isosorbide dinitrate in alleviating angina episodes in CSFP patients. Methods In this prospective, randomized controlled study, 102 patients with CSFP without severe coronary artery stenosis that exhibited stable angina were allocated randomly in a ratio of 1:1 to either the alprostadil group (40 μg, three times per day, n = 51) or the isosorbide dinitrate group (5 mg, three times per day, n = 51). Frequency of angina events, intensity of suffering, and the Canadian Cardiovascular Society (CCS) grading of angina pectoris were evaluated at baseline and one month after. Additionally, the Seattle Angina Questionnaire (SAQ) was assessed. Results Baseline characteristics were comparable between the two groups. At 1-month follow-up, patients administered with alprostadil experienced fewer angina episodes [episodes per week, 1 (2) vs. 2 (2), P < 0.001] and less pain intensity [self-evaluated pain score, 2 (3) vs. 3 (4), P < 0.001] than those with isosorbide dinitrate. In the alprostadil group, 78.4% of patients were classified as CCS class I, significantly higher than the 47.1% seen in the isosorbide dinitrate group (P = 0.001). Furthermore, treatment of alprostadil led to a significant improvement in the SAQ score (7.09 U, 95% CI: 4.22–9.96, P < 0.001) compared to isosorbide dinitrate. Additionally, fewer patients suffered headaches when receiving alprostadil (7.8% vs. 19.6%, P = 0.084). Conclusion Alprostadil was more effective in ameliorating angina symptoms in CSFP patients than isosorbide dinitrate. Clinical trial registration [www.chictr.org.cn], identifier [ChiCTR2000033233].
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Affiliation(s)
- Weifeng Zhang
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jinjie Dai
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Lan Shen
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
- Clinical Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Yue Jiang
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaowen Zheng
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ke Xu
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaoxiao Yang
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaolei Wang
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Ziyong Hao
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yu Zhao
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Dong Wang
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Lisheng Jiang
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Xingbiao Qiu
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Linghong Shen
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Ben He
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
- *Correspondence: Ben He,
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19
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Aldiwani H, Mahdai S, Alhatemi G, Bairey Merz CN. Microvascular Angina: Diagnosis and Management. Eur Cardiol 2021; 16:e46. [PMID: 34950242 PMCID: PMC8674627 DOI: 10.15420/ecr.2021.15] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 07/16/2021] [Indexed: 01/18/2023] Open
Abstract
Recognition of suspected ischaemia with no obstructive coronary artery disease – termed INOCA – has increased over the past decades, with a key contributor being microvascular angina. Patients with microvascular angina are at higher risk for major adverse cardiac events including MI, stroke, heart failure with preserved ejection fraction and death but to date there are no clear evidence-based guidelines for diagnosis and treatment. Recently, the Coronary Vasomotion Disorders International Study Group proposed standardised criteria for diagnosis of microvascular angina using invasive and non-invasive approaches. The management strategy for remains empirical, largely due to the lack of high-levelevidence- based guidelines and clinical trials. In this review, the authors will illustrate the updated approach to diagnosis of microvascular angina and address evidence-based pharmacological and non-pharmacological treatments for patients with the condition.
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Affiliation(s)
- Haider Aldiwani
- Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center Los Angeles, California, US.,Scripps Health Institution Chula Vista Hospital, Department of Internal Medicine San Diego, US
| | - Suzan Mahdai
- Scripps Health Institution Chula Vista Hospital, Department of Internal Medicine San Diego, US
| | - Ghaith Alhatemi
- St Mary Mercy Hospital, Department of Internal Medicine Livonia, Michigan, US
| | - C Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center Los Angeles, California, US
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20
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Schroder J, Prescott E. Doppler Echocardiography Assessment of Coronary Microvascular Function in Patients With Angina and No Obstructive Coronary Artery Disease. Front Cardiovasc Med 2021; 8:723542. [PMID: 34778394 PMCID: PMC8585781 DOI: 10.3389/fcvm.2021.723542] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 09/22/2021] [Indexed: 01/18/2023] Open
Abstract
Echocardiographic evaluation is an essential part of the diagnostic work-up in patients with known or suspected cardiovascular disease. Transthoracic Doppler echocardiography (TTDE) enables straightforward and reliable visualization of flow in the left anterior descending artery. In the absence of obstructive coronary artery disease, low TTDE-derived coronary flow velocity reserve (CFVR) is considered a marker of coronary microvascular dysfunction (CMD). TTDE CFVR is free from ionizing radiation and widely available, utilizing high-frequency transducers, pharmacologic vasodilator stress, and pulsed-wave Doppler quantification of diastolic peak flow velocities. European Society of Cardiology guidelines recommend TTDE CFVR evaluation only following preceding anatomic invasive or non-invasive coronary imaging excluding obstructive CAD. Accordingly, clinical use of TTDE CFVR is limited and CMD frequently goes undiagnosed. An evolving body of evidence underlines that low CFVR is an important and robust predictor of adverse prognosis and continuing symptoms in angina patients both with and without obstructive CAD. The majority of angina patients have no obstructive CAD, particularly among women. This has led to the suggestion that there may be a gender-specific female atherosclerotic phenotype with less epicardial obstruction, and a low CFVR signifying CMD instead. Nevertheless, available evidence indicates low CFVR is an equally important prognostic marker in both men and women. In this review, TTDE CFVR was evaluated regarding indication, practical and technical aspects, and interpretation of results. Association with symptoms and prognosis, comparison with alternative invasive and non-invasive imaging modalities, and possible interventions in angina patients with low CFVR were discussed, and key research questions were proposed.
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Affiliation(s)
- Jakob Schroder
- Department of Cardiology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
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Aciksari G, Cetinkal G, Kocak M, Atici A, Celik FB, Caliskan M. The relationship between triglyceride/high-density lipoprotein cholesterol ratio and coronary slow-flow phenomenon. Int J Cardiovasc Imaging 2021; 38:5-13. [PMID: 34453654 DOI: 10.1007/s10554-021-02387-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 08/19/2021] [Indexed: 10/20/2022]
Abstract
In this study, we aimed to investigate the relationship between high triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio and coronary slow flow phenomenon (CSFP) in patients undergoing elective coronary angiography for suspected coronary artery disease. This prospective study included a total of 84 CSFP patients and 83 controls with normal coronary flow, as evidenced by coronary angiography. The Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) was used to measure the coronary blood flow velocity. The lipid profiles were analyzed and TG/HDL-C ratio were calculated dividing absolute TG levels by absolute HDL-C levels in peripheral blood. The median TG/HDL-C ratio was higher in the CSFP group than the control group (3.4 [2.6 to 4.9] vs. 2.3 [1.8 to 3], respectively; p < 0.001). The multivariate logistic regression analysis revealed that TG/HDL-C ratio was an independent predictor of CSFP (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.59-2.32; p = 0.001) and TG/HDL-C ratio was positively correlated with the TFC in the CSFP group (r = 0.311, p < 0.001). The area under the receiver operating characteristic curve of TG/HDL-C for the diagnosis of CSFP was 0.73 (95% CI 0.65-0.81; p < 0.001). If a cut-off value of 2.75 was used, higher levels of TG/HDL-C ratio could predict the presence of CSFP with 72% sensitivity and 71% specificity. Our study results suggest that TG/HDL-C ratio is associated with CSFP and may be a useful biomarker for predicting CSFP and its severity.
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Affiliation(s)
- Gonul Aciksari
- Department of Cardiology, Istanbul Medeniyet University, Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey.
| | - Gokhan Cetinkal
- Department of Cardiology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
| | - Mehmet Kocak
- Department of Emergency Medicine, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
| | - Adem Atici
- Department of Cardiology, Istanbul Medeniyet University, Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey
| | - Fatma Betul Celik
- Department of Cardiology, Istanbul Medeniyet University, Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey
| | - Mustafa Caliskan
- Department of Cardiology, Istanbul Medeniyet University, Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey
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Pacheco C, AlBadri A, Anderson R, Petersen J, Marpuri S, Cook-Wiens G, Pepine C, Mancini G, Merz CB, Wei J. Coronary atheroma burden predicts flow reserve in women with ischemia and nonobstructive coronary artery disease. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2021; 6:100027. [PMID: 38560556 PMCID: PMC10976284 DOI: 10.1016/j.ahjo.2021.100027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/10/2021] [Accepted: 06/10/2021] [Indexed: 04/04/2024]
Abstract
Background Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD) with reduced coronary flow reserve (CFR), and compensatory coronary remodeling. Angiographic measurements of epicardial coronary anatomy (AMCA) may improve understanding of relations between CFR and atherosclerosis. We investigated AMCA and CFR in women evaluated for CMD. Methods Women consecutively enrolled in the Women's Ischemia Syndrome Evaluation CVD Continuation (NCT00832702) were included. All underwent clinically indicated coronary function testing measuring CFR. AMCA included coronary angiographic atheroma burden (AB), percent diameter stenosis (PDS), and tapering reference diameter Z score (RDZ), derived for the left main and left anterior descending coronary epicardial segments. Results The 51 women were aged 55.8 ± 10.8 years, with 19(38%) hypertensive, 10(20.4%) hyperlipidemic, 4(7.8%) diabetic, 13(25.5%) prior smokers, and mean CFR 3.0 ± 0.8. Both average and maximal AB negatively correlated with CFR (r = -0.30 and -0.31, with p = 0.04 for both), as did average and maximal PDS (r = -0.38 and -0.41 with p = 0.009 and p = 0.005) while average RDZ was directly related (r = 0.37, p = 0.01). Multiple linear regression analyses revealed that both average PDS (Units of CFR -0.03 95% CI: -0.06, -0.002, p = 0.023) and maximal PDS (-0.04 95% CI -0.07, -0.01, p = 0.007) were negatively related to CFR. Conclusions Measures of epicardial coronary atheroma burden, size and tapering are related to CFR, suggesting that atherosclerotic anatomical findings may contribute to or be a consequence of CMD, with further work is needed to investigate these measures as treatment targets.
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Affiliation(s)
- C. Pacheco
- Hôpital Pierre-Boucher, Centre Hospitalier de l'Université de Montréal, Université de Montreal, QC, Canada
| | - A. AlBadri
- Emory University, Atlanta, GA, United States of America
| | - R.D. Anderson
- University of Florida, Gainesville, FL, United States of America
| | - J. Petersen
- University of Florida, Gainesville, FL, United States of America
| | - S. Marpuri
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America
| | - G. Cook-Wiens
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America
| | - C.J. Pepine
- University of Florida, Gainesville, FL, United States of America
| | | | - C.N. Bairey Merz
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America
| | - J. Wei
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America
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Atorvastatin improves the proliferation and migration of endothelial progenitor cells via the miR-221/VEGFA axis. Biosci Rep 2021; 40:226426. [PMID: 32936287 PMCID: PMC7689653 DOI: 10.1042/bsr20193053] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 08/18/2020] [Accepted: 09/10/2020] [Indexed: 02/07/2023] Open
Abstract
The present study was aimed at investigating the detailed functions of atorvastatin, a lipid-lowering agent, in the pathogenesis of coronary slow flow (CSF), a clinical disease characterized by delayed angiographic coronary opacity without obstructive coronary disease. In the present study, we successfully identified isolated endothelial progenitor cells (EPCs) from the peripheral blood of patients with CSF. Their vascular endothelial growth factor-A (VEGFA) protein levels were determined using immunoblotting analyses. We determined cell viability using MTT assays, cell migration capacity using Transwell assays, and the angiogenic capacity using a tube formation assay. The target association between miR-221 and VEGFA was validated with a luciferase reporter assay. Atorvastatin treatment increased EPC VEGFA protein levels, proliferation, migration, and angiogenesis. miR-221 expression was down-regulated after atorvastatin treatment; miR-221 overexpression exerted an opposing effect to atorvastatin treatment on VEGFA protein, EPC proliferation, migration, and angiogenesis. The protective effects of atorvastatin treatment on VEGFA protein and EPCs could be significantly suppressed by miR-221 overexpression. miR-221 directly bound the VEGFA 3'UTR to inhibit its expression. In conclusion, atorvastatin improves the cell proliferation, migration, and angiogenesis of EPCs via the miR-221/VEGFA axis. Thus, atorvastatin could be a potent agent against CSF, pending further in vivo and clinical investigations.
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Chalikias G, Tziakas D. Slow Coronary Flow: Pathophysiology, Clinical Implications, and Therapeutic Management. Angiology 2021; 72:808-818. [PMID: 33779300 DOI: 10.1177/00033197211004390] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Coronary slow flow (CSF) is an angiographic phenomenon with specific epidemiologic characteristics, associated clinical presentation, and prognosis. Although patients with CSF are diagnosed as having "normal coronary arteries," it seems appropriate to consider CSF as a distinct disease entity requiring specific treatment. The patient with CSF is usually male, smoker, obese, with a constellation of risk factors suggestive of metabolic syndrome. Unstable angina is the most common clinical presentation, with recurrent episodes of chest pain at rest associated with electrocardiographic changes often requiring readmission and reevaluation. Regarding definition and diagnosis, interventionists should first exclude possible "secondary" causes of CSF, use objective means for definition and then differentiate from other similar conditions such as microvascular angina. Although the phenomenon is generally benign, patients with CSF are severely symptomatic with recurrent episodes of chest pain and poor quality of life. Furthermore, acute presentation of the phenomenon is commonly life-threatening with ventricular tachyarrhythmias, conduction abnormalities, or cardiogenic shock. Acute treatment of CSF includes, but is not restricted to, intracoronary infusion of dipyridamole, adenosine, or atropine. Chronic management of patients with CSF encompasses dipyridamole, diltiazem, nebivolol, telmisartan, and/or atorvastatin associated with amelioration of angina symptoms, improved quality of life, and good prognosis.
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Affiliation(s)
- George Chalikias
- Cardiology Department, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dimitrios Tziakas
- Cardiology Department, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
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25
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Yong J, Tian J, Yang X, Xing H, He Y, Song X. Effects of Oral Drugs on Coronary Microvascular Function in Patients Without Significant Stenosis of Epicardial Coronary Arteries: A Systematic Review and Meta-Analysis of Coronary Flow Reserve. Front Cardiovasc Med 2020; 7:580419. [PMID: 33195465 PMCID: PMC7661556 DOI: 10.3389/fcvm.2020.580419] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 09/14/2020] [Indexed: 12/27/2022] Open
Abstract
Objective: This study aims to investigate the impact of cardiovascular medications on the coronary flow reserve (CFR) in patients without obstructive coronary artery disease (CAD). Methods: We searched PubMed, EMBASE, and Cochrane databases from inception to 15 November 2019. Studies were included if they reported CFR from baseline to follow-up after oral drug therapy of patients without obstructive CAD. Data was pooled using random-effects modeling. The primary outcome was change in CFR from baseline to follow-up after oral drug therapy. Results: A total of 46 studies including 845 subjects were included in this study. Relative to baseline, the CFR was improved by angiotensin-converting enzymes (ACEIs), aldosterone receptor antagonists (ARBs) [standard mean difference (SMD): 1.12; 95% CI: 0.77–1.47], and statins treatments (SMD: 0.61; 95%CI: 0.36–0.85). Six to 12 months of calcium channel blocker (CCB) treatments improved CFR (SMD: 1.04; 95% CI: 0.51–1.58). Beta-blocker (SMD: 0.24; 95% CI: −0.39–0.88) and ranolazine treatment (SMD: 0.31; 95% CI: −0.39–1.01) were not associated with improved CFR. Conclusions: Therapy with ACEIs, ARBs, and statins was associated with improved CFR in patients with confirmed or suspicious CMD. CCBs also improved CFR among patients followed for 6–12 months. Beta-blocker and ranolazine had no impact on CFR.
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Affiliation(s)
- Jingwen Yong
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Jinfan Tian
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Xueyao Yang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Haoran Xing
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yi He
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiantao Song
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
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Impact of persistent endothelial dysfunction in an infarct-related coronary artery on future major adverse cardiovascular event occurrence in STEMI survivors. Heart Vessels 2020; 36:472-482. [PMID: 33196904 DOI: 10.1007/s00380-020-01723-9] [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: 07/16/2020] [Accepted: 10/30/2020] [Indexed: 10/23/2022]
Abstract
Although coronary endothelial vasomotor dysfunction predicts future coronary events, few human studies have shown the relationship between persistent endothelial vasomotor dysfunction and major adverse cardiovascular events (MACE) using serial assessments in the same coronary artery. This study examined whether persistent endothelial vasomotor dysfunction is related to MACE occurrence in the infarct-related coronary artery (IRA) of ST-segment elevation myocardial infarction (STEMI) survivors using serial assessments of the coronary vasomotor response to acetylcholine (ACh). This study included 169 consecutive patients with a first acute STEMI due to left anterior descending coronary artery (LAD) occlusion and successful reperfusion therapy with percutaneous coronary intervention. Vasomotor response to ACh in the LAD was measured within 2 weeks of acute myocardial infarction (AMI) (first test) and repeated 6 months (second test) after AMI under optimal anti-atherosclerotic therapy. MACE was defined as the composite of all-cause death, non-fatal MI, angina recurrence requiring percutaneous intervention or surgical bypass, and hospitalization for heart failure. We followed up 126 patients for a period of ≤ 60 months until MACE occurrence after second test. Nineteen MACEs occurred during the follow-up. The log-rank test, Kaplan-Meier curves and univariate Cox proportional hazards regression analysis showed that MACE occurrence was significantly associated with the persistent impairment of epicardial coronary artery dilation and coronary blood flow increases in response to ACh (log-rank test, p < 0.001 and p < 0.001, respectively) (Hazard ratio, p = 0.001 and p = 0.002, respectively). Persistent impairment of endothelial vasomotor function in the infarct-related conduit arterial segment and resistance arteriole were the significant predictor of future MACE occurrence in STEMI survivors.
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Bove KB, Nilsson M, Pedersen LR, Mikkelsen N, Suhrs HE, Astrup A, Prescott E. Comprehensive treatment of microvascular angina in overweight women - a randomized controlled pilot trial. PLoS One 2020; 15:e0240722. [PMID: 33151955 PMCID: PMC7644075 DOI: 10.1371/journal.pone.0240722] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 10/01/2020] [Indexed: 01/09/2023] Open
Abstract
AIMS Coronary microvascular dysfunction (CMD) carries a poor cardiovascular prognosis and may explain angina in women without obstructive coronary artery disease (CAD). Currently, no evidence-based treatment for CMD exists. We investigated whether reducing cardiovascular risk factors improves symptoms and microvascular function in women with non-endothelial dependent CMD and no obstructive CAD. METHODS We randomized 62 women aged 40-75, with body mass index (BMI) >25 kg/m2, angina ≥monthly, and coronary flow velocity reserve (CFVR) ≤2.5 to a 24-week intervention comprising low energy diet, exercise training, and optimized treatment of hypertension, dyslipidemia and diabetes or to control. Patients were assessed before randomization and after 24 weeks. Primary outcomes were CFVR assessed by transthoracic Doppler stress-echocardiography and angina burden by Seattle Angina Questionnaire (SAQ). Secondary outcomes were exercise capacity, body composition, glycemic control, myocardial function, and anxiety and depression symptoms. RESULTS Fifty-six participants (90%) completed the study. Median (IQR) age was 65.2 (57.1;70.7) years, BMI was 30.1 (28.4;32.7) kg/m2. The intervention resulted in relevant improvement in angina symptoms (9-21-point increase on SAQ-scales (all p<0.01)) but had no effect on CFVR (p = 0.468). Mean (CI) weight loss was 9.6 (7.80;11.48) kg, (p<0.0001). There was a significant mean (CI) decrease in depression symptoms = 1.16 (0.22;2.12), triglycerides = 0.52 (0.25;0.78) mmol/L, total cholesterol = 0.55 (0.12;0.98) mmol/L, and HbA1c in diabetics = 27.1 (1.60;52.6) mmol/mol but no effect on other secondary outcomes. CONCLUSION A major weight loss and intensified risk factor control resulted in significantly improved angina burden but no improvement of coronary microvascular function among women with microvascular angina.
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Affiliation(s)
- Kira Bang Bove
- Department of Cardiology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Malin Nilsson
- Department of Endocrinology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Lene Rørholm Pedersen
- Department of Cardiology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Nicolai Mikkelsen
- Department of Cardiology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Hannah Elena Suhrs
- Department of Cardiology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Arne Astrup
- Department of Nutrition, Exercise and Sports (NEXS), Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Eva Prescott
- Department of Cardiology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
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28
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Waheed N, Elias-Smale S, Malas W, Maas AH, Sedlak TL, Tremmel J, Mehta PK. Sex differences in non-obstructive coronary artery disease. Cardiovasc Res 2020; 116:829-840. [PMID: 31958135 DOI: 10.1093/cvr/cvaa001] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 12/03/2019] [Accepted: 01/13/2020] [Indexed: 12/31/2022] Open
Abstract
Ischaemic heart disease is a leading cause of morbidity and mortality in both women and men. Compared with men, symptomatic women who are suspected of having myocardial ischaemia are more likely to have no obstructive coronary artery disease (CAD) on coronary angiography. Coronary vasomotor disorders and coronary microvascular dysfunction (CMD) have been increasingly recognized as important contributors to angina and adverse outcomes in patients with no obstructive CAD. CMD from functional and structural abnormalities in the microvasculature is associated with adverse cardiac events and mortality in both sexes. Women may be particularly susceptible to vasomotor disorders and CMD due to unique factors such as inflammation, mental stress, autonomic, and neuroendocrine dysfunction, which predispose to endothelial dysfunction and CMD. CMD can be detected with coronary reactivity testing and non-invasive imaging modalities; however, it remains underdiagnosed. This review focuses on sex differences in presentation, pathophysiologic risk factors, diagnostic testing, and prognosis of CMD.
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Affiliation(s)
- Nida Waheed
- Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Suzette Elias-Smale
- Department of Cardiology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Waddah Malas
- Emory Women's Heart Center, Division of Cardiology, Department of Medicine, Emory University, 1462 Clifton Rd, Suite 505, Atlanta, GA 30329, USA
| | - Angela H Maas
- Department of Cardiology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Tara L Sedlak
- Leslie Diamond Women's Heart Center, University of British Columbia, Vancouver, British Columbia, Canada
| | - Jennifer Tremmel
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA
| | - Puja K Mehta
- Emory Women's Heart Center, Division of Cardiology, Department of Medicine, Emory University, 1462 Clifton Rd, Suite 505, Atlanta, GA 30329, USA
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Manfrini O, Amaduzzi P, Bergami M, Cenko E. Effects of Statin Treatment on Patients with Angina and Normal or Nearly Normal Angiograms. Eur Cardiol 2020; 15:e15. [PMID: 32373188 PMCID: PMC7199123 DOI: 10.15420/ecr.2019.15] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Accepted: 01/08/2020] [Indexed: 11/25/2022] Open
Abstract
This article offers an updated and comprehensive overview of major findings on the effects of statin treatment in patients with chronic angina but without any epicardial coronary artery with obstructive lesion.
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Affiliation(s)
- Olivia Manfrini
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna Bologna, Italy
| | - Peter Amaduzzi
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna Bologna, Italy
| | - Maria Bergami
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna Bologna, Italy
| | - Edina Cenko
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna Bologna, Italy
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30
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Suspected Brugada Phenocopy Secondary to Coronary Slow Flow. Case Rep Cardiol 2019; 2019:9027029. [PMID: 31885934 PMCID: PMC6925924 DOI: 10.1155/2019/9027029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 11/28/2019] [Indexed: 11/30/2022] Open
Abstract
Brugada syndrome (BrS) is a genetic condition that accentuates the risk of potentially lethal ventricular arrhythmias and sudden cardiac death (SCD) in a structurally normal heart. The Brugada electrocardiographic pattern may manifest separately from the syndrome—this clinical scenario has been described as Brugada phenocopy (BrP). Many etiologies of BrP have been reported, but it has not yet been reported as a result of coronary slow flow (CSF) phenomenon. This case report highlights a suspected coronary slow flow-associated Brugada type 1 electrocardiographic pattern, which subsequently normalized following the institution of guideline-directed medical therapy for acute coronary syndrome.
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31
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Dong R, Lv Q, Gao Y, He C, Tan S, Zhang M, Zhou T. Carotid artery blood velocity decreases in patients with coronary slow flow: A manifestation of systemic arteriosclerosis. Echocardiography 2019; 36:2234-2240. [PMID: 31755583 DOI: 10.1111/echo.14540] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 10/08/2019] [Accepted: 10/25/2019] [Indexed: 01/31/2023] Open
Abstract
OBJECTIVES Coronary slow flow phenomenon (CSFP) could be a manifestation of systemic arteriosclerosis, as coronary and carotid arteries have similar intimal thickening. However, as an initial cause of arteriosclerosis, hemodynamic changes in carotid arteries have rarely been studied. METHODS Twenty patients with angiography-proven CSFP and 39 patients with normal coronary flow (NCF) were enrolled. TIMI frame counts (CTFC) were investigated. Carotid intima-media thickness (CIMT), peak systolic velocity (PSV), and end-diastolic velocity (EDV) were measured by ultrasonography, and shear rate (SR) and resistance index (RI) were calculated. RESULTS The results showed that PSV, EDV, SR, and RI were significantly lower in patients with CSFP (p<0.01), but CIMT was significantly increased (P < 0.01). PSV, EDV, SR, and RI were negatively correlated with CTFC, while CIMT was positively correlated with CTFC. Logistic regression analysis revealed that PSV (OR = 0.95, P < 0.01) could be an independent protective factor against CSFP, but CIMT (OR = 1.10, P < 0.05) and male gender (OR = 9.89, P < 0.01) could be risk factors for CSFP. CONCLUSIONS The slow flow phenomenon was observed in both coronary and carotid arteries, which could be a characteristic manifestation of systemic arteriosclerosis in CSFP; the lower wall shear stress may be the underlying mechanism. Carotid ultrasound could be applied in the noninvasive diagnosis of CSFP in the future.
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Affiliation(s)
- Rui Dong
- Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Qian Lv
- Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Yannan Gao
- Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Caiyun He
- Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Siyuan Tan
- Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Mingyu Zhang
- Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Tao Zhou
- Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
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Abstract
In recent years, it has become apparent that coronary microvascular dysfunction plays a pivotal pathogenic role in angina pectoris. Functional and structural mechanisms can affect the physiological function of the coronary microvasculature and lead to myocardial ischemia in people without coronary atheromatous disease and also in individuals with obstructive coronary artery disease. Abnormal dilatory responses of the coronary microvessels, coronary microvascular spasm, and extravascular compressive forces have been identified as pathogenic mechanisms in both chronic and acute forms of ischemic heart disease. The condition characterized by anginal symptoms and evidence of myocardial ischemia triggered by coronary microvascular dysfunction, in the absence of obstructive coronary disease, is known as microvascular angina. The concept of microvascular angina, however, may extend further to include patients with obstructive coronary artery disease and individuals with angina after coronary revascularization or heart transplantation because coronary microvascular dysfunction contributes to myocardial ischemia in many such patients. Patients with microvascular angina constitute a sizeable proportion of all cases of stable angina undergoing diagnostic coronary angiography and of those with persisting angina after successful coronary revascularization. Coronary microvascular dysfunction is also often responsible for angina in individuals with cardiomyopathy and heart valve disease as well as acute coronary syndrome cases such as Takotsubo syndrome and myocardial infarction with no obstructive coronary artery disease. Patients with stable microvascular angina present typically with effort or rest chest pain and a reduced coronary flow reserve or microvascular spasm. This condition, which affects women and men, can markedly impair quality of life and prognosis and represents a substantial cost burden to healthcare systems and individuals alike. In recent years, progress in the diagnosis of myocardial ischemia and the use of tests to investigate functional and structural causes for a reduced coronary flow reserve and microvascular spasm have allowed the identification of an increased number of cases of microvascular angina in everyday clinical practice. Although some of the available anti-anginal drugs may be helpful, treatment of coronary microvascular dysfunction remains a major challenge. The present article discusses the fundamental role that coronary microvascular dysfunction plays in the pathogenesis of ischemic heart disease, the clinical characteristics of patients presenting with microvascular angina, and possible diagnostic and therapeutic strategies.
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Affiliation(s)
- Juan-Carlos Kaski
- Molecular and Clinical Sciences Research Institute, St George's, University of London, United Kingdom (J.-C.K)
| | - Filippo Crea
- Institute of Cardiology, Catholic University, Rome, Italy (F.C.)
| | - Bernard J Gersh
- Department of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN (B.J.G.)
| | - Paolo G Camici
- Vita-Salute University and Department of Cardiology San Raffaele Hospital, Milan, Italy (P.G.C.)
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Suhrs HE, Michelsen MM, Prescott E. Treatment strategies in coronary microvascular dysfunction: A systematic review of interventional studies. Microcirculation 2019; 26:e12430. [PMID: 29130567 DOI: 10.1111/micc.12430] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 11/06/2017] [Indexed: 12/12/2022]
Abstract
CMD has been associated with a wide spectrum of diseases and conditions, and it has proven to be a strong prognostic marker of morbidity and mortality. Despite increased attention, guideline-based treatment recommendations are lacking. We performed a systematic review of pharmacological and nonpharmacological interventions to improve coronary perfusion, assessed by IC Doppler, TTDE, PET, CMRI, transthoracic contrast perfusion echocardiography, and dilution techniques. No restrictions were made regarding the study design (randomized, placebo-controlled/randomized with active comparators/nonrandomized with or without a control group), the cardiac condition studied, or the coronary microvascular function at baseline. An electronic database search yielded 4485 records of which 80 studies met our inclusion criteria. Included studies were sorted according to intervention and study design. Studies were small and heterogeneous in methodology, and only few were placebo-controlled. Although some treatments looked promising, we found that no specific treatment was sufficiently well documented to be recommended in any patient groups. There is a need for larger well-designed clinical trials, and we suggest that future studies stratify study populations according to pathogenic mechanisms, thereby investigating whether an individualized treatment approach would be more successful.
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Affiliation(s)
- Hannah E Suhrs
- Department of Cardiology, Bispebjerg University Hospital, Copenhagen NV, Denmark
| | - Marie M Michelsen
- Department of Cardiology, Bispebjerg University Hospital, Copenhagen NV, Denmark
| | - Eva Prescott
- Department of Cardiology, Bispebjerg University Hospital, Copenhagen NV, Denmark
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Clinical Profile and Outcome in Patients with Coronary Slow Flow Phenomenon. Cardiol Res Pract 2019; 2019:9168153. [PMID: 31205785 PMCID: PMC6530115 DOI: 10.1155/2019/9168153] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 03/10/2019] [Accepted: 04/23/2019] [Indexed: 01/20/2023] Open
Abstract
The coronary slow flow phenomenon (CSFP) is a poorly recognized clinical entity characterized by delayed distal vessel opacification in the absence of epicardial coronary stenosis and presently lack of specific data on the clinical profile and outcome. We investigated a cohort of 429 patients who fulfilled the criteria for CSFP to explore the clinical feature, outcome, and risk factor of prognosis. Two teams (clinical center and core lab) were blind to patient data for the assessment of coronary angiograph using corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC). The study cohort consisted of 429 patients (294 men, 68.5%), aged from 30 to 78 years (mean, 54 years). Two hundred patients (46.6%) out of 429 patients had a history of hypertension, 72 (16.8%) had diabetes mellitus, and 222 (51.7%) had dyslipidemia. All the rates of agreement between two teams in evaluating whether normal flow (CTFC ≤ 27 frames) or slow flow (CTFC > 27 frames) were moderate (0.40 < κ < 0.75) for the three arteries. Follow-up (mean, 3.8 years) was done for 421 patients (98.1%). The major adverse cardiovascular events (MACE) occurred in 39 patients (9.3%) out of 421 patients. Multivariate analysis showed that the risk of MACE approximately doubles with age >50 years (hazard ratio (HR) = 2.2, 95% CI: 1.0 to 4.9, and P=0.042), hypertension (HR = 2.1, 95% CI: 1.1 to 4.2, and P=0.021), and dyslipidemia (HR = 2.0, 95% CI: 1.0 to 3.9, and P=0.042). CSFP affects predominantly patients at middle age and above but can occur in any age group; CSFP should be more concerned, particularly in patients >50 years old with hypertension and dyslipidemia.
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Solberg OG, Stavem K, Ragnarsson A, Beitnes JO, Skårdal R, Seljeflot I, Ueland T, Aukrust P, Gullestad L, Aaberge L. Index of microvascular resistance to assess the effect of rosuvastatin on microvascular function in women with chest pain and no obstructive coronary artery disease: A double-blind randomized study. Catheter Cardiovasc Interv 2019; 94:660-668. [PMID: 30790446 DOI: 10.1002/ccd.28157] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 01/19/2019] [Accepted: 02/06/2019] [Indexed: 01/01/2023]
Abstract
INTRODUCTION Many women undergoing coronary angiography for chest pain have no or only minimal coronary artery disease (CAD). However, despite the lack of obstructive CAD, they still have an increased risk of major adverse cardiovascular events. Pleiotropic effects of statins may influence microvascular function, but if statins improve microvascular function in unselected chest pain patients is not well studied. This study assessed microvascular function by using the thermodilution-derived test "the index of microvascular resistance" (IMR) with the aim of determining the (i) IMR level in women with chest pain and non-obstructive CAD and if (ii) IMR is modified by high-dose statin treatment in these patients. Additional objectives were to identify the influence of statins on the health status as assessed with generic health questionnaires and on biomarkers of endothelial activation. MATERIALS AND METHODS The study was a randomized, double-blind, single-center trial comparing 6 months of rosuvastatin treatment with placebo. In total, 66 women without obstructive CAD were included. Mean age was 52.7 years and 55.5 years in the placebo and rosuvastatin group, respectively. Microvascular function was assessed using the IMR, health status was assessed using the SF-36 and EQ-5D questionnaires, and biochemical values were assessed at baseline and 6 months later. RESULTS AND CONCLUSIONS In the placebo group IMR was 14.6 (SD 5.7) at baseline and 14.4 (SD 6.5) at follow-up. In the rosuvastatin group IMR was 16.5 (SD 7.5) at baseline and 14.2 (SD 5.8) at follow-up. IMR did not differ significantly between the two study groups at follow-up controlled for preintervention values. C-reactive protein (CRP) was comparable between the groups at baseline, while at follow-up CRP was significantly lower in the rosuvastatin group compared to placebo [0.6 (±0.5) mg/L vs. 2.6 (±3.0) mg/L; p = 0.002]. Whereas rosuvastatin treatment for 6 months attenuated CRP levels, it did not improve microvascular function as assessed by IMR (Clinical Trials.gov NCT01582165, EUDRACT 2011-002630-39.3tcAZ).
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Affiliation(s)
- Ole Geir Solberg
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Knut Stavem
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Pulmonary Medicine, Akershus University Hospital, Lørenskog, Norway.,Department of Health Services Research, Akershus University Hospital, Lørenskog, Norway
| | - Asgrimur Ragnarsson
- Department of Radiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Jan-Otto Beitnes
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Rita Skårdal
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Ingebjørg Seljeflot
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Thor Ueland
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway.,Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Pål Aukrust
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Lars Gullestad
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,K.G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, Faculty of Medicine, Oslo University Hospital, Oslo, Norway
| | - Lars Aaberge
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Abstract
PURPOSE OF REVIEW When patients are seen for persistent chest pain in the absence of obstructive coronary artery disease, the physician must decide if the symptoms are due to myocardial ischemia in order to guide treatment. RECENT FINDINGS Recent findings indicate that ischemia due to coronary microvascular dysfunction (CMD) is associated with subclinical coronary atherosclerosis and an adverse prognosis. Therapeutic probe trials suggest that antiatherosclerotic and anti-ischemic therapeutic strategies may be useful. A large randomized clinical trial of high-intensity statin, maximally tolerated angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker and low-dose aspirin (WARRIOR NCT#03417388) is in progress. SUMMARY The diagnosis of CMD should be considered in patients with persistent angina, evidence of myocardial ischemia and normal coronary angiogram. Because of the associated adverse prognosis of CMD , conservative empiric treatment or further diagnostic evaluation of the coronary microvasculature can be performed. Diagnosis involves the measurement of coronary blood blow in response to a vasodilator agent invasively or noninvasively. Treatment of CMD can include the use of traditional antianginal and antiatherosclerotic medications. Clinical trials are needed to assess therapeutic strategies on the outcomes of cardiovascular disease and quality of life, in order to develop evidence-based guidelines.
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Affiliation(s)
- Janet Wei
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, California, USA
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Sanghvi S, Mathur R, Baroopal A, Kumar A. Clinical, demographic, risk factor and angiographic profile of coronary slow flow phenomenon: A single centre experience. Indian Heart J 2018; 70 Suppl 3:S290-S294. [PMID: 30595277 PMCID: PMC6310702 DOI: 10.1016/j.ihj.2018.06.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Revised: 05/06/2018] [Accepted: 06/04/2018] [Indexed: 11/27/2022] Open
Abstract
Background The coronary slow flow phenomenon (CSFP) is an angiographic finding characterized by delayed distal vessel opacification in the absence of significant epicardial coronary stenosis. Although it is well-known to interventional cardiologists for approximately four decades, the etiopathogenesis still remains unclear. Aims and objectives In this study, we aimed to determine the clinical, demographic, risk factor and angiographic profile of patients with CSFP. Methods Clinical, demographic, risk factor and angiographic profile were recorded in all consecutive patients who had undergone coronary angiography between September 2016 and March 2017 and showed features of CSFP and a control group who showed normal coronary flow (NCF). The CSFP was diagnosed on the basis of the corrected thrombolysis in myocardial infarction frame count. Results CSFP was significantly more prevalent in male patients. Among the traditional risk factors, there was significantly more prevalence of hypertension (31.25% versus 6.67%, p < 0.001), dyslipidemia (40% versus 7.5%, p < 0.001) and history of tobacco use (47.5% versus 10.0%, p < 0.001) in CSFP patients as compared to NCF patients. On multivariable regression analysis hypertension, dyslipidemia, history of smoking and tobacco chewing were found to have independent association with CSFP. Acute coronary syndrome (ACS) was the most common mode of presentation in CSFP patients. Conclusion CSFP was relatively common among patients who presented with ACS. Hypertension, dyslipidemia, smoking and tobacco chewing can be considered independent risk factors for this phenomenon. Therefore, CSFP should be considered as a pathological entity and not an entirely benign condition.
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Affiliation(s)
- Sanjeev Sanghvi
- Department of Cardiology, DR. S.N. Medical College, Jodhpur, India
| | - Rohit Mathur
- Department of Cardiology, DR. S.N. Medical College, Jodhpur, India
| | - Anil Baroopal
- Department of Cardiology, DR. S.N. Medical College, Jodhpur, India.
| | - Aditya Kumar
- Department of Cardiology, DR. S.N. Medical College, Jodhpur, India
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Pacheco Claudio C, Quesada O, Pepine CJ, Noel Bairey Merz C. Why names matter for women: MINOCA/INOCA (myocardial infarction/ischemia and no obstructive coronary artery disease). Clin Cardiol 2018; 41:185-193. [PMID: 29498752 DOI: 10.1002/clc.22894] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Accepted: 01/05/2018] [Indexed: 12/19/2022] Open
Abstract
The syndromes of myocardial infarction/myocardial ischemia with No Obstructive Coronary Artery Disease (MINOCA/INOCA) are increasingly evident. A majority of these patients have coronary microvascular dysfunction. These patients have elevated risk for a cardiovascular event (including acute coronary syndrome, myocardial infarction, stroke, and repeated cardiovascular procedures) and appear to be at higher risk for development of heart failure with preserved ejection fraction. Terminology such as coronary artery disease or coronary heart disease is often synonymous with obstructive atherosclerosis in the clinician's mind, leaving one at a loss to recognize or explain the phenomenon of MINOCA and INOCA with elevated risk. We review the available literature regarding stable and unstable ischemic heart disease that suggests that use of the ischemic heart disease (IHD) terminology matters for women, and should facilitate recognition of risk to provide potential treatment targets and optimized health.
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Affiliation(s)
| | - Odayme Quesada
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, California
| | - Carl J Pepine
- Division of Cardiology, University of Florida, Gainesville, Florida
| | - C Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, California
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Niu H, Wei Z, Zhang Y, He J, Jia D. Atorvastatin improves coronary flow and endothelial function in patients with coronary slow flow. Exp Ther Med 2017; 15:904-908. [PMID: 29399097 PMCID: PMC5772870 DOI: 10.3892/etm.2017.5484] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 10/31/2017] [Indexed: 01/16/2023] Open
Abstract
The underlying mechanisms behind the effect of atorvastatin on patients with coronary slow flow (CSF) remain largely unknown. To investigate the possible underlying molecular mechanisms 108 patients were divided into atorvastatin group and control group. Coronary flow was quantified according to corrected TIMI frame count (CTFC). Serum high sensitivity C-reactive protein (hs-CRP), lipids, ET-1, interleukin (IL)-6, NO, circulating endothelial progenitor cell (cEPC) count, adhesion, migration and proliferation were measured in pretreatment and post-treatment. After respective treatment, the atorvastatin group had significantly decreased levels of TC, TG, LDL-C, hs-CRP, ET-1 and IL-6 and increased NO compared to the control group. The atorvastatin group had a more significant improvement of CTFC, effective rate, cEPC number, EPC adhesion, migration and proliferation compared to the control group. In conclusion, atorvastatin can be used in treatment of CSF by suppressing inflammation and improving endothelial function.
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Affiliation(s)
- Hongmei Niu
- Department of Cardiovascular Medicine, Shandong Provincial Third Hospital, Jinan, Shandong 250000, P.R. China
| | - Zhenzhen Wei
- Department of Cardiovascular Medicine, The First People's Hospital of Jinan, Jinan, Shandong 250000, P.R. China
| | - Yanling Zhang
- Department of Cardiovascular Medicine, The First People's Hospital of Jinan, Jinan, Shandong 250000, P.R. China
| | - Jian He
- Digestive Disease Department of Internal Medicine, The First People's Hospital of Jinan, Jinan, Shandong 250000, P.R. China
| | - Danyan Jia
- Jinan First Aid Center, Jinan, Shandong 250000, P.R. China
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Nelson MD. Left ventricular diastolic dysfunction in women with nonobstructive ischemic heart disease: insights from magnetic resonance imaging and spectroscopy. Am J Physiol Regul Integr Comp Physiol 2017; 313:R322-R329. [PMID: 28794105 DOI: 10.1152/ajpregu.00249.2017] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 07/20/2017] [Accepted: 08/03/2017] [Indexed: 02/01/2023]
Abstract
Ischemic heart disease, in the absence of obstructive coronary artery disease, is prevalent in women and constitutes a major risk factor for developing major adverse cardiovascular events, including myocardial infarction, stroke, and heart failure. For decades, diagnosis was considered benign and often minimized; however, it is now known that this etiology carries much risk and is a significant burden to the health care system. This review summarizes the current state of knowledge on nonobstructive ischemic heart disease (NOIHD), the association between NOIHD and left ventricular diastolic dysfunction, potential links between NOIHD and the development of heart failure with preserved ejection fraction (HFpEF), and therapeutic options and knowledge gaps for patients living with NOIHD.
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Affiliation(s)
- Michael D Nelson
- Applied Physiology and Advanced Imaging Laboratory, University of Texas at Arlington, Arlington, Texas
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Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL. Ischemia and No Obstructive Coronary Artery Disease (INOCA): Developing Evidence-Based Therapies and Research Agenda for the Next Decade. Circulation 2017; 135:1075-1092. [PMID: 28289007 PMCID: PMC5385930 DOI: 10.1161/circulationaha.116.024534] [Citation(s) in RCA: 521] [Impact Index Per Article: 65.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The Cardiovascular Disease in Women Committee of the American College of Cardiology, in conjunction with interested parties (from the National Heart, Lung, and Blood Institute, American Heart Association, and European Society of Cardiology), convened a working group to develop a consensus on the syndrome of myocardial ischemia with no obstructive coronary arteries. In general, these patients have elevated risk for a cardiovascular event (including acute coronary syndrome, heart failure hospitalization, stroke, and repeat cardiovascular procedures) compared with reference subjects and appear to be at higher risk for development of heart failure with preserved ejection fraction. A subgroup of these patients also has coronary microvascular dysfunction and evidence of inflammation. This document provides a summary of findings and recommendations for the development of an integrated approach for identifying and managing patients with ischemia with no obstructive coronary arteries and outlines knowledge gaps in the area. Working group members critically reviewed available literature and current practices for risk assessment and state-of-the-science techniques in multiple areas, with a focus on next steps needed to develop evidence-based therapies. This report presents highlights of this working group review and a summary of suggested research directions to advance this field in the next decade.
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Affiliation(s)
- C Noel Bairey Merz
- From Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA (C.N.B.M.); Division of Cardiology, University of Florida, Gainesville (C.J.P.); St. Vincent Heart Transplant, Indianapolis, IN (M.N.W.); and National Heart, Lung, and Blood Institute, Bethesda, MD (J.L.F.).
| | - Carl J Pepine
- From Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA (C.N.B.M.); Division of Cardiology, University of Florida, Gainesville (C.J.P.); St. Vincent Heart Transplant, Indianapolis, IN (M.N.W.); and National Heart, Lung, and Blood Institute, Bethesda, MD (J.L.F.)
| | - Mary Norine Walsh
- From Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA (C.N.B.M.); Division of Cardiology, University of Florida, Gainesville (C.J.P.); St. Vincent Heart Transplant, Indianapolis, IN (M.N.W.); and National Heart, Lung, and Blood Institute, Bethesda, MD (J.L.F.)
| | - Jerome L Fleg
- From Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA (C.N.B.M.); Division of Cardiology, University of Florida, Gainesville (C.J.P.); St. Vincent Heart Transplant, Indianapolis, IN (M.N.W.); and National Heart, Lung, and Blood Institute, Bethesda, MD (J.L.F.)
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Chen C, Wei J, AlBadri A, Zarrini P, Bairey Merz CN. Coronary Microvascular Dysfunction - Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy. Circ J 2016; 81:3-11. [PMID: 27904032 PMCID: PMC8607842 DOI: 10.1253/circj.cj-16-1002] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/20/2023]
Abstract
Angina has traditionally been thought to be caused by obstructive coronary artery disease (CAD). However, a substantial number of patients with angina are found to not have obstructive CAD when undergoing coronary angiography. A significant proportion of these patients have coronary microvascular dysfunction (CMD), characterized by heightened sensitivity to vasoconstrictor stimuli and limited microvascular vasodilator capacity. With the advent of non-invasive and invasive techniques, the coronary microvasculature has been more extensively studied in the past 2 decades. CMD has been identified as a cause of cardiac ischemia, in addition to traditional atherosclerotic disease and vasospastic disease. CMD can occur alone or in the presence obstructive CAD. CMD shares many similar risk factors with macrovascular CAD. Diagnosis is achieved through detection of an attenuated response of coronary blood flow in response to vasodilatory agents. Imaging modalities such as cardiovascular magnetic resonance, positron emission tomography, and transthoracic Doppler echocardiography have become more widely used, but have not yet completely replaced the traditional intracoronary vasoreactivity testing. Treatment of CMD starts with lifestyle modification and risk factor control. The use of traditional antianginal, antiatherosclerotic medications and some novel agents may be beneficial; however, clinical trials are needed to assess the efficacy of the pharmacologic and non-pharmacologic therapeutic modalities. In addition, studies with longer-term follow-up are needed to determine the prognostic benefits of these agents. We review the epidemiology, prognosis, pathogenesis, diagnosis, risk factors and current therapies for CMD.
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Affiliation(s)
- Cheng Chen
- Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center
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Zhuang X, Peng Y, Bardeesi ASA, Bardisi ESA, Liao X, Luo C. Vessel heterogeneity of TIMI frame count and its relation to P-wave dispersion in patients with coronary slow flow. J Thorac Dis 2016; 8:476-81. [PMID: 27076943 DOI: 10.21037/jtd.2016.02.48] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND The vessel heterogeneity of thrombolysis in myocardial infarction (TIMI) frame count (TFC) in patients with coronary slow flow (CSF) remains to be further evaluated, and the correlation between TFC heterogeneity and P-wave dispersion (PWD) has not been elucidated. We aim to investigate the vessel heterogeneity of TFC in coronary arteries, and its relation to PWD in patients with CSF and otherwise normal coronary arteries. METHODS We studied 72 patients with angiographically documented CSF and 66 age- and gender-matched control subjects. The coefficient of variation (CV) and mean TFC of the three vessels were calculated. P-wave duration and PWD were measured on the standard electrocardiograms (ECGs). RESULTS The mean TFC and CV were both significantly higher in CSF patients than in controls (P<0.001 for both comparisons). The maximum P-wave duration (Pmax) and PWD were found to be significantly higher in CSF patients than in controls (P<0.001 for both comparisons). In patients with CSF, both Pmax and PWD were mildly correlated to mean TFC (r=0.318, P=0.009; and r=0.307, P=0.010), and were more significantly correlated to CV (r=0.506, P<0.001; and r=0.579, P<0.001). CONCLUSIONS These data demonstrate that variability of TFC in three coronary arteries is increased in CSF patients, and that the vessel heterogeneity in coronary flow might be intimately associated with PWD.
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Affiliation(s)
- Xiaodong Zhuang
- 1 Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China ; 2 Department of Geriatric, Geriatric Hospital of Hunan Province, Changsha, China ; 3 Department of Surgery, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia ; 4 Department of Surgery, University hospitals Leuven (UZ-Leuven), Leuven, Belgium
| | - You Peng
- 1 Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China ; 2 Department of Geriatric, Geriatric Hospital of Hunan Province, Changsha, China ; 3 Department of Surgery, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia ; 4 Department of Surgery, University hospitals Leuven (UZ-Leuven), Leuven, Belgium
| | - Adham Sameer A Bardeesi
- 1 Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China ; 2 Department of Geriatric, Geriatric Hospital of Hunan Province, Changsha, China ; 3 Department of Surgery, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia ; 4 Department of Surgery, University hospitals Leuven (UZ-Leuven), Leuven, Belgium
| | - Ekhlas Samir A Bardisi
- 1 Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China ; 2 Department of Geriatric, Geriatric Hospital of Hunan Province, Changsha, China ; 3 Department of Surgery, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia ; 4 Department of Surgery, University hospitals Leuven (UZ-Leuven), Leuven, Belgium
| | - Xinxue Liao
- 1 Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China ; 2 Department of Geriatric, Geriatric Hospital of Hunan Province, Changsha, China ; 3 Department of Surgery, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia ; 4 Department of Surgery, University hospitals Leuven (UZ-Leuven), Leuven, Belgium
| | - Chufan Luo
- 1 Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China ; 2 Department of Geriatric, Geriatric Hospital of Hunan Province, Changsha, China ; 3 Department of Surgery, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia ; 4 Department of Surgery, University hospitals Leuven (UZ-Leuven), Leuven, Belgium
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Marinescu MA, Löffler AI, Ouellette M, Smith L, Kramer CM, Bourque JM. Coronary microvascular dysfunction, microvascular angina, and treatment strategies. JACC Cardiovasc Imaging 2015; 8:210-20. [PMID: 25677893 DOI: 10.1016/j.jcmg.2014.12.008] [Citation(s) in RCA: 216] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Revised: 12/16/2014] [Accepted: 12/22/2014] [Indexed: 02/07/2023]
Abstract
Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively-defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded published data. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD.
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Affiliation(s)
- Mark A Marinescu
- Department of Medicine, Cardiovascular Imaging Center, University of Virginia Health System, Charlottesville, Virginia
| | - Adrián I Löffler
- Department of Medicine, Cardiovascular Imaging Center, University of Virginia Health System, Charlottesville, Virginia
| | - Michelle Ouellette
- Department of Medicine, Cardiovascular Imaging Center, University of Virginia Health System, Charlottesville, Virginia
| | - Lavone Smith
- Department of Medicine, Cardiovascular Imaging Center, University of Virginia Health System, Charlottesville, Virginia
| | - Christopher M Kramer
- Department of Medicine, Cardiovascular Imaging Center, University of Virginia Health System, Charlottesville, Virginia; Department of Radiology and Medical Imaging, Cardiovascular Imaging Center, University of Virginia Health System, Charlottesville, Virginia
| | - Jamieson M Bourque
- Department of Medicine, Cardiovascular Imaging Center, University of Virginia Health System, Charlottesville, Virginia; Department of Radiology and Medical Imaging, Cardiovascular Imaging Center, University of Virginia Health System, Charlottesville, Virginia.
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Sani HD, Eshraghi A, Nezafati MH, Vojdanparast M, Shahri B, Nezafati P. Nicorandil Versus Nitroglycerin for Symptomatic Relief of Angina in Patients With Slow Coronary Flow Phenomenon: A Randomized Clinical Trial. J Cardiovasc Pharmacol Ther 2015; 20:401-6. [PMID: 25701829 DOI: 10.1177/1074248415571457] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2014] [Accepted: 12/22/2014] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Patients with the coronary slow flow phenomenon frequently experience angina episodes. The present study aimed to compare the efficacy of nicorandil versus nitroglycerin for alleviation of angina symptoms in slow flow patients. METHODS In a single-center, single-blind, parallel-design, comparator-controlled, randomized clinical trial (NCT02254252), 54 patients with slow flow and normal or near-normal coronary angiography who presented with frequent angina episodes were randomly assigned to 1-month treatment with nicorandil 10 mg, 2 times a day (n = 27) or sustained-release glyceryltrinitrate 6.4 mg 2 times a day (n =27). Frequency of angina episodes, pain intensity, and the Canadian Cardiovascular Society (CCS) grading of angina pectoris were assessed at baseline and after 1 month of treatment. RESULTS In all, 25 patients in the nicorandil arm and 24 patients in the nitroglycerin arm were analyzed. After 1 month, patients treated with nicorandil had fewer angina episodes (adjusted mean number of episodes per week, nicorandil versus nitroglycerin; 1.68 ± 0.15 vs 2.29 ± 0.15, P = .007, effect size = 14.6%). Patients also reported greater reductions in pain intensity with nicorandil versus nitroglycerin (adjusted mean of self-reported pain score; 3.03 ± 0.29 vs 3.89 ± 0.30, P = .046, effect size = 8.4%). A significantly higher proportion of patients in the nicorandil arm were categorized in CCS class I (76% vs 33.3%, P = .004) or class II (16.0% vs 45.8%, P = .032). CONCLUSION In slow flow patients, nicorandil provides better symptomatic relief of angina than nitroglycerin.
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Affiliation(s)
- Hashem Danesh Sani
- Atherosclerosis Prevention Research Center, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Eshraghi
- Atherosclerosis Prevention Research Center, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Hassan Nezafati
- Department of Cardiac Surgery, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Vojdanparast
- Atherosclerosis Prevention Research Center, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Bahram Shahri
- Atherosclerosis Prevention Research Center, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Pouya Nezafati
- Department of Cardiac Surgery, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
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Sadr-Ameli MA, Saedi S, Saedi T, Madani M, Esmaeili M, Ghardoost B. Coronary slow flow: Benign or ominous? Anatol J Cardiol 2014; 15:531-5. [PMID: 25537993 PMCID: PMC5337030 DOI: 10.5152/akd.2014.5578] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Objective: Coronary slow flow phenomenon has been arbitrarily defined as delayed coronary blood flow in the absence of obstructive coronary artery disease. The present study sought to investigate the clinical features, natural history, and outcomes of affected patients. Methods: In this prospective cross-sectional study, 217 consecutive patients who had undergone coronary angiography and showed features of coronary slow flow phenomenon were evaluated for demographic and coronary risk factor profile, as well as clinical outcomes, at baseline and following treatment. Results: The study population consisted of 165 (76%) males and 52 (24%) females. The mean age of patients was 52.6±10 years. Mean ejection fraction was 48.2±5.4, 39.3% had diabetes, 43.3% had hypertension, 49.8% was a cigarette smoker, 41.9% had dyslipidemia, and 15% had a familial history of cardiac disease. Forty-nine percent was detected to have abnormal hsCRP levels. The most prevalent presenting complaint was atypical chest pain. Fifty-four percent of patients had slow blood flow in all three vessels. Thirty-six people had undergone repeat coronary angiography in a follow-up period of 5-7 years due to persisting or worsening clinical symptoms, of whom 6 (16.6%) showed significant coronary artery stenosis. Eight (22.2%) had mild CAD, and the rest still showed coronary slow flow without significant stenosis. The most common complaint during follow-up and after initiation of medical therapy was nonanginal chest pain. Conclusion: Patients with coronary slow flow phenomenon are predisposed to atherosclerosis and obstructive coronary artery disease. Therefore, this pathology should not be considered as a totally benign condition. Primary and secondary cardiovasculature preventive measures should be constituted and seem worthwhile in this patient population.
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Affiliation(s)
- Mohammad Ali Sadr-Ameli
- Department of Cardiology, Shahid Rajaie Cardiovascular, Medical, Research Center, Iran University of Medical Sciences; Tehran-Iran.
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Wang X, Nie SP. The coronary slow flow phenomenon: characteristics, mechanisms and implications. Cardiovasc Diagn Ther 2013; 1:37-43. [PMID: 24282683 DOI: 10.3978/j.issn.2223-3652.2011.10.01] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2011] [Accepted: 10/10/2011] [Indexed: 11/14/2022]
Abstract
The coronary slow flow phenomenon (CSFP) is an important, angiographic entity characterized by delayed progression of the injected contrast medium through the coronary tree. It is a frequent finding, typically observed in patients presenting with acute coronary syndromes. Although it is well known to interventional cardiologists for approximately four decades, the pathogenic mechanisms remain unclear. The clinical implications are significant, with over 80% of patients experiencing recurrent chest pain, resulting in considerable impairment in quality of life. This article will address in detail the characteristics, possible mechanisms, and clinical implications of this entity to provide further insight into its clinical significance and management strategies.
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Affiliation(s)
- Xiao Wang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
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Gan LM, Wikström J, Fritsche-Danielson R. Coronary flow reserve from mouse to man--from mechanistic understanding to future interventions. J Cardiovasc Transl Res 2013; 6:715-28. [PMID: 23877202 PMCID: PMC3790920 DOI: 10.1007/s12265-013-9497-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2013] [Accepted: 07/01/2013] [Indexed: 11/29/2022]
Abstract
Myocardial ischemia is recognized as an important mechanism increasing the risk for cardiovascular events in both symptomatic and asymptomatic patients. In addition to obstructive coronary diseases, systemic inflammation, macro- and microvascular function are additional important mechanisms contributing to the ischemic myocardium. Accumulating evidence indicates that coronary flow reserve (CFR) is a quantitative measurement of ischemia including integrated information on structure and function of the coronary artery at all levels. Not surprisingly, CFR has been shown to confer strong prognostic value for hard cardiovascular (CV) events in a number of relevant patient cohorts. Using high-resolution imaging, it is now possible to study coronary arteries from mouse to man. Therefore, CFR may be an important translational tool to risk-stratify patients and to perform both preclinical and clinical proof-of-concept studies before investing in large-scale outcome trials, thus improving the translational value for novel CV targets.
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Affiliation(s)
- Li-Ming Gan
- Department of Molecular and Clinical Medicine, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Göteborg, Sweden,
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Echeverri D, Cabrales J. Statins and percutaneous coronary intervention: A complementary synergy. CLINICA E INVESTIGACION EN ARTERIOSCLEROSIS 2013; 25:112-22. [DOI: 10.1016/j.arteri.2012.10.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2012] [Accepted: 10/31/2012] [Indexed: 11/15/2022]
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Luo C, Liu D, Wu G, Hu C, Zhang Y, Du Z, Dong Y. Effect of enhanced external counterpulsation on coronary slow flow and its relation with endothelial function and inflammation: a mid-term follow-up study. Cardiology 2012; 122:260-8. [PMID: 22907077 DOI: 10.1159/000339876] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2012] [Accepted: 05/24/2012] [Indexed: 11/19/2022]
Abstract
BACKGROUND Although enhanced external counterpulsation (EECP) showed short-term effects in improving coronary flow in patients with coronary slow flow (CSF), whether such improvement is durable remains uncertain, and the relationships between such improvement and changes in endothelial function as well as inflammatory markers have not been elucidated. OBJECTIVES The aim of the present study was to investigate the effects of EECP on transthoracic coronary flow, flow-mediated dilatation (FMD), and high-sensitivity C-reactive protein (hsCRP) in patients with CSF. METHODS Forty-five patients with documented CSF underwent transthoracic Doppler echocardiography (TTDE) for the assessment of coronary diastolic peak flow velocity (DPFV) and coronary flow reserve (CFR), and measurements of FMD and hsCRP; they were then nonrandomly assigned to two groups. Subjects in the control group (n = 24) received only medical therapy, and those in the EECP group (n = 21) were additionally treated with the 36 one-hour sessions of EECP. After 8 weeks of medical/EECP therapy, TTDE, FMD, and hsCRP examinations were repeated, and TTDE was additionally repeated after the 6-month clinical follow-up. RESULTS In the EECP group, resting DPFV, hyperemic DPFV, and CFR were significantly increased shortly after therapy (p < 0.001) and the improvement was maintained up to the 6-month follow-up, whereas in the control group those variables were not statistically increased. Meanwhile, hsCRP significantly decreased and FMD increased after therapy in the EECP group (p < 0.001). In all subjects, CFR improvement was negatively correlated with hsCRP change and positively correlated with FMD increase (p < 0.001). CONCLUSIONS EECP may have a durable effect in improving coronary flow in patients with CSF. Such improvement is related to the favorable effects of EECP on vascular inflammation and endothelial function.
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Affiliation(s)
- Chufan Luo
- Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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