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1
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Cui X, Li M, Jing A, Zhang Y, Zheng L, Li T, Hao T, Lang J, Guo Z, Cong H, Zhang Y. Associations Between the Atherogenic Index of Plasma and Triglyceride-Glucose Index With Coronary Microvascular Dysfunction in Hypertensive Patients. Diabetes Metab Syndr Obes 2025; 18:1061-1072. [PMID: 40226440 PMCID: PMC11992995 DOI: 10.2147/dmso.s510851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 03/24/2025] [Indexed: 04/15/2025] Open
Abstract
Background The triglyceride-glucose (TyG) index is a reliable marker of insulin resistance, and the atherogenic index of plasma (AIP) reflects atherosclerosis. However, the relationship between these biomarkers-particularly AIP-and coronary microvascular dysfunction (CMD) in hypertensive patients has not been systematically studied. This study investigates the association between TyG, AIP, and CMD in hypertensive individuals. Methods We included 155 hypertensive patients with coronary anatomy confirmed by coronary angiography (CAG) or computed tomography angiography (CTA) within six months of SPECT imaging. CMD was diagnosed with a summed stress score (SSS) ≥4 and a summed difference score (SDS) ≥2. Patients were stratified into tertiles by TyG index and AIP. Logistic regression, adjusted for traditional cardiovascular risk factors, was used to explore the relationship with CMD. The predictive value of TyG and AIP was assessed using receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) evaluated their clinical benefit. Results Logistic regression revealed that both TyG and AIP were independently associated with coronary artery disease (CAD) (P<0.05 for both). The area under the ROC curve (AUC) for TyG, AIP, and their combined predictive capacity for CMD was 0.744, 0.707, and 0.748, respectively (P<0.001 for all). The optimal cutoff values for TyG and AIP were 7.012 and 0.5175, respectively. Combining both biomarkers enhanced clinical decision-making and patient benefit. Conclusion Higher levels of TyG and AIP are significantly associated with an increased risk of CMD in hypertensive patients. Both biomarkers exhibit strong predictive value, with AIP showing greater specificity and TyG higher sensitivity. Their combined use can improve clinical decision-making and patient outcomes.
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Affiliation(s)
- Xiaodong Cui
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, People’s Republic of China
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China
| | - Mingyang Li
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, People’s Republic of China
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China
| | - Anran Jing
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, People’s Republic of China
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China
| | - Yan Zhang
- Tianjin Union Medical Center, Tianjin Medical University, Tianjin, 300122, People’s Republic of China
| | - Liuying Zheng
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China
| | - Ting Li
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China
| | - Tianxu Hao
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, People’s Republic of China
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China
| | - Jiachun Lang
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, People’s Republic of China
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China
| | - Zhihao Guo
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, People’s Republic of China
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China
- Department of Cardiology, Cangzhou Center Hospital, Cangzhou, Hebei Province, People’s Republic of China
| | - Hongliang Cong
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, People’s Republic of China
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China
| | - Yingyi Zhang
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, People’s Republic of China
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China
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Wan B, Wang S, Hu S, Han W, Qiu S, Zhu L, Ruan L, Wei Y, Xu J. The comprehensive effects of high-sensitivity C-reactive protein and triglyceride glucose index on cardiometabolic multimorbidity. Front Endocrinol (Lausanne) 2025; 16:1511319. [PMID: 40235659 PMCID: PMC11996647 DOI: 10.3389/fendo.2025.1511319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 03/10/2025] [Indexed: 04/17/2025] Open
Abstract
Background The triglyceride-glucose index (TyG index) is one of the surrogate markers of insulin resistance, and high-sensitivity C-reactive protein (hsCRP) reflects systemic inflammation. Existing studies suggest that insulin resistance or systemic inflammation may be indicative of cardiometabolic disease, but few of the existing studies have combined the TyG index and inflammation levels before assessing cardiometabolic multimorbidity. Our study data came from the China Health and Retirement Longitudinal Study (CHARLS). Participants in this data were followed for 9 years, and we used these data to conduct a long-term analysis to assess the combined effects of the TyG index and hsCRP on cardiometabolic multimorbidity in Chinese adults over 45 years of age. Purpose To study the combined effect of TyG index and hsCRP on cardiometabolic multimorbidity in middle-aged as well as elderly Chinese. Method The study data came from the China Health and Retirement Longitudinal Study (CHARLS), which included a total of 4,483 middle-aged and elderly participants who did not have cardiovascular metabolic diseases at baseline, which was from CHARLS 2011, and the last survey was in 2020. A total of five cardiometabolic diseases were considered in this study: diabetes, hypertension, hyperlipidemia, heart disease and stroke. A person was defined as having cardiometabolic multimorbidity when he/she had two or more cardiometabolic diseases at the same time. TyG index (median as cut-off) and hsCRP (1mg/L as cut-off) were each divided into two groups and combined into four groups (Group L-L: TyG index=median & hsCRP<1mg/L; Group L-H: TyG index=1mg/L; Group H-H: TyG index>=median & hsCRP>=1mg/L). Multiple regression equations were fitted to analyse the combined influence of TyG index and hsCRP on cardiometabolic multimorbidity. Results TyG index increases the risk of CMM events independently of hsCRP, as does the reverse. When the TyG index is elevated and hsCRP is also elevated, this condition significantly increases the danger of cardiometabolic multimorbidity in middle-aged and elderly Chinese. Conclusion High levels of TyG index and hsCRP can enhance the danger of cardiometabolic multimorbidity in Chinese middle-aged and elderly people, and the joint use of hsCRP and TyG index assessment may be a better way to achieve primary prevention of cardiometabolic multimorbidity in Chinese middle-aged and elderly people.
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Affiliation(s)
| | | | | | | | | | | | | | - Yiping Wei
- Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Jianjun Xu
- Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
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Calligaris M, Aleksova A, Fluca AL, Janjusevic M, Carpi G, Stefanizzi D, Carnevali S, Curcio F, Puca AA, Cattaneo M, Beltrami AP. Protective role of the longevity-associated BPIFB4 gene on cardiac microvascular cells and cardiac aging. Vascul Pharmacol 2025; 158:107470. [PMID: 39909151 DOI: 10.1016/j.vph.2025.107470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/31/2025] [Accepted: 02/01/2025] [Indexed: 02/07/2025]
Abstract
In recent years, the role of the cardiac microvasculature in modulating the symptoms and disease progression of patients affected by cardiac pathology has been reconsidered. The term cardiac microvascular disease (CMD) describes the set of functional and/or structural alterations of the cardiac microvasculature that reduce the ability of the heart to adequately increase its coronary blood flow to keep up with increased metabolic demand. CMD is involved in the evolution of heart disease of both ischemic and non-ischemic origin as well as in cardiac aging. The primary actors involved in this process are the cells of the stromal compartment, whose nature and biology are now investigated to a new level of detail thanks to single-cell omics studies. Recent studies on the genetics of extreme longevity have identified a polymorphic haplotype variant of the BPIFB4 gene that confers prolonged life span and health span, atheroprotective advantages, and an improved immune response. The aim of this review was to focus on the beneficial effects of the longevity-associated variant (LAV) of BPIFB4 on cardiac microvascular cell biology, providing novel and exciting mechanisms of its action directed against the development or progression of many age-related cardiovascular diseases, thus emphasizing its translational therapeutic potential.
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Affiliation(s)
| | - Aneta Aleksova
- Department of Medical Surgical and Health Sciences of University of Trieste, Trieste, Italy; Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy
| | - Alessandra Lucia Fluca
- Department of Medical Surgical and Health Sciences of University of Trieste, Trieste, Italy
| | - Milijana Janjusevic
- Department of Medical Surgical and Health Sciences of University of Trieste, Trieste, Italy
| | - Giada Carpi
- Department of Medicine (DMED), University of Udine, Udine, Italy
| | | | | | - Francesco Curcio
- Department of Medicine (DMED), University of Udine, Udine, Italy; Laboratory Medicine Department, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
| | - Annibale Alessandro Puca
- IRCCS MultiMedica, Milan, Italy; Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", Università degli Studi di Salerno, Salerno, Italy.
| | | | - Antonio Paolo Beltrami
- Department of Medicine (DMED), University of Udine, Udine, Italy; Laboratory Medicine Department, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy.
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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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Abusnina W, Merdler I, Cellamare M, Chitturi KR, Chaturvedi A, Feuerstein IM, Zhang C, Ozturk ST, Deksissa T, Sawant V, Lopez K, Lupu L, Haberman D, Ben‐Dor I, Satler LF, Waksman R, Hashim HD, Case BC. Epicardial Fat Tissue: A Potential Marker for Coronary Microvascular Dysfunction. J Am Heart Assoc 2025; 14:e038484. [PMID: 39895522 PMCID: PMC12074709 DOI: 10.1161/jaha.124.038484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 10/28/2024] [Indexed: 02/04/2025]
Abstract
BACKGROUND Coronary microvascular dysfunction (CMD), which mimics symptoms of obstructive coronary artery disease, has significant prognostic implications. While epicardial adipose tissue normally has a protective role, increased epicardial adipose tissue is associated with inflammation and may contribute to CMD. However, a direct correlation remains unclear. We aimed to investigate this association. METHODS AND RESULTS The CMDR (Coronary Microvascular Disease Registry) is a prospective, 2-center registry that is enrolling patients with angina and nonobstructive coronary artery disease who underwent invasive hemodynamic assessment of the coronary microvasculature. Patients with chest computed tomography within 1 year of CMD evaluation were included. We measured epicardial fat volume (EFV) and calculated the EFV index. Logistic regression analysis was used to investigate the association between EFV and EFV index to CMD. Our study included 130 CMDR patients with associated chest CT; 35 were diagnosed with CMD. The CMD-negative patients were younger than the CMD-positive patients (58.52±11.97 versus 63.37±9.56 years; P=0.033), with numerically fewer women (64.2% versus 74.3%; P=0.279). Univariate regression analysis demonstrated a statistically significant association between EFV index and CMD diagnosis (odds ratio, 1.037 [95% CI, 1.014-1.063]; P=0.003), while no significance was observed for EFV (odds ratio, 1.006 [95% CI, 0.995-1.017]; P=0.292). CONCLUSIONS Our results suggest a strong association between EFV index (a significant risk factor) and the presence of CMD. Future studies involving larger cohorts are needed to confirm the association of epicardial adipose tissue with CMD and investigate therapeutic targets to prevent CMD. REGISTRATION URL: https://www.clinicaltrials.gov; unique identifier: NCT05960474.
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Affiliation(s)
- Waiel Abusnina
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Ilan Merdler
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Matteo Cellamare
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Kalyan R. Chitturi
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Abhishek Chaturvedi
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | | | - Cheng Zhang
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Sevket Tolga Ozturk
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Teshome Deksissa
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Vaishnavi Sawant
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Kassandra Lopez
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Lior Lupu
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Dan Haberman
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Itsik Ben‐Dor
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Lowell F. Satler
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Ron Waksman
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Hayder D. Hashim
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Brian C. Case
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
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6
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Aleksova A, Fluca AL, Janjusevic M, Padoan L, Pierri A, Chiaradia V, Munaretto L, Merro E, Barbati G, Hiche C, Gabrielli M, Lovadina S, Beltrame D, D'Errico S, Saw J, Fabris E, Di Lenarda A, Sinagra G. Differences between MINOCA and type 2 myocardial infarction: An ITALIAN observational study. Int J Cardiol 2025; 420:132745. [PMID: 39592072 DOI: 10.1016/j.ijcard.2024.132745] [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: 09/19/2024] [Revised: 11/07/2024] [Accepted: 11/14/2024] [Indexed: 11/28/2024]
Abstract
BACKGROUND Myocardial infarction with non-obstructive coronary arteries (MINOCA) and type 2 myocardial infarction (MI), both presenting as non-ST-elevation MI (NSTEMI), are often grouped together due to overlapping symptoms. The aim of our study is to compare their characteristics and prognosis to distinguish between them. METHODS Among 7815 patients with NSTEMI who underwent coronary angiography between 2005 and 2022 we identified 538 patients with diagnosis of MINOCA (n = 301; 3,9 %) and type 2 MI (n = 237; 3 %). The outcome was a composite of all-cause mortality, non-fatal MI, hospitalisation for heart failure (HF) and transitory ischemic attack or non-fatal stroke. RESULTS The mean age of the entire cohort was 68 (11.5) years, with women being the most frequently represented group (65 %). Comparing the sub-cohorts, MINOCA patients were younger (66.3 (11.7) Vs. 70.6 (11) years, p < 0.01), and less likely to have typical cardiovascular risk than type 2 MI patients. At multivariable analysis different clinical (age, heart rate, typical chest pain, palpitations, postmenopausal status), and instrumental (cardiac rhythm, ST-segment changes, diastolic dysfunction, hypo/akinesia with non-coronary distribution) variables were independent predictors of MINOCA with AUC of 0.83 [95 % CI, 0.78-0.88], p < 0.01 at ROC analysis. At a median follow-up of 61 (IQR 34-100) months, MINOCA patients had significantly lower rate of the composite endpoint compared to type 2 MI (20 % Vs. 32 %, p < 0.01). CONCLUSIONS MINOCA cohort was associated with different characteristics compared to type 2 MI and had a better prognosis despite the number of events was not negligible.
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Affiliation(s)
- Aneta Aleksova
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Laboratory of Molecular Cardiology, Department of Medical Surgical and Health Sciences, Cattinara Hospital, University of Trieste, Trieste, Italy.
| | - Alessandra Lucia Fluca
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Laboratory of Molecular Cardiology, Department of Medical Surgical and Health Sciences, Cattinara Hospital, University of Trieste, Trieste, Italy
| | - Milijana Janjusevic
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Laboratory of Molecular Cardiology, Department of Medical Surgical and Health Sciences, Cattinara Hospital, University of Trieste, Trieste, Italy
| | - Laura Padoan
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiology Department, Gorizia-Monfalcone, Gorizia, Italy
| | - Alessandro Pierri
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Cardiology Department and Intensive Coronary Care UTIC, San Paolo Hospital, Bari, Italy
| | | | - Laura Munaretto
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Laboratory of Molecular Cardiology, Department of Medical Surgical and Health Sciences, Cattinara Hospital, University of Trieste, Trieste, Italy
| | - Enzo Merro
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Laboratory of Molecular Cardiology, Department of Medical Surgical and Health Sciences, Cattinara Hospital, University of Trieste, Trieste, Italy
| | | | - Cristina Hiche
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy
| | - Marco Gabrielli
- Laboratory of Molecular Cardiology, Department of Medical Surgical and Health Sciences, Cattinara Hospital, University of Trieste, Trieste, Italy
| | - Stefano Lovadina
- Department of General and Thoracic Surgery, Cattinara University Hospital, Trieste, Italy
| | - Daria Beltrame
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy
| | - Stefano D'Errico
- Laboratory of Molecular Cardiology, Department of Medical Surgical and Health Sciences, Cattinara Hospital, University of Trieste, Trieste, Italy
| | - Jacqueline Saw
- Division of Cardiology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Enrico Fabris
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Laboratory of Molecular Cardiology, Department of Medical Surgical and Health Sciences, Cattinara Hospital, University of Trieste, Trieste, Italy
| | - Andrea Di Lenarda
- Cardiovascular Center, University Hospital and Health Services of Trieste, Trieste, Italy
| | - Gianfranco Sinagra
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Laboratory of Molecular Cardiology, Department of Medical Surgical and Health Sciences, Cattinara Hospital, University of Trieste, Trieste, Italy
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7
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Chitturi KR, Bhogal S, Kassaian SE, Merdler I, Abusnina W, Chaturvedi A, Ben-Dor I, Waksman R, Case BC, Barac A, Hashim HD. Coronary microvascular dysfunction and cancer therapy-related cardiovascular toxicity. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2024; 68:45-49. [PMID: 38789343 DOI: 10.1016/j.carrev.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 05/01/2024] [Indexed: 05/26/2024]
Abstract
BACKGROUND Coronary microvascular dysfunction (CMD) has been implicated as a potential mechanism in the pathophysiology of different clinical presentations, including ischemia and no obstructive coronary artery disease (INOCA), myocardial infarction and nonobstructive coronary arteries (MINOCA), stress cardiomyopathy, heart failure, and myocarditis. There are limited data about the role of CMD in cancer therapy-related cardiovascular toxicities. CASE PRESENTATIONS Four women with a diagnosis of active cancer receiving treatment who developed subsequent MINOCA or INOCA presented for cardiac catheterization. Upon coronary angiography showing no obstructive coronary arteries, coronary function testing was performed to evaluate for CMD. METHODS Coronary physiology was assessed measuring non-hyperemic (resting full-cycle ratio [RFR]) and hyperemic (fractional flow reserve [FFR]) indices using a physiologic pressure wire. The wire also measured coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and RFR using thermodilution technology. CMD was confirmed if the CFR was <2.5 and the IMR was >25. RESULTS Among 4 patients with diagnosis of active cancer presenting with chest pain, there was no evidence of obstructive coronary artery disease, leading to separate diagnoses of INOCA, MINOCA, stress cardiomyopathy, and myocarditis. We found CMD in 2 patients (1 with INOCA and 1 with immune checkpoint inhibitor-related myocarditis). CONCLUSIONS CMD may play a role in cardiovascular toxicities. Further coronary physiology studies are needed to understand the mechanisms of cancer therapy-related cardiovascular toxicity and CMD, as well as optimal preventive and treatment options.
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Affiliation(s)
- Kalyan R Chitturi
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
| | - Sukhdeep Bhogal
- Section of Cardiology, Sovah Health, Martinsville, VA, United States of America
| | | | - Ilan Merdler
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
| | - Waiel Abusnina
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
| | - Abhishek Chaturvedi
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
| | - Itsik Ben-Dor
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
| | - Ron Waksman
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America.
| | - Brian C Case
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
| | - Ana Barac
- Section of Cardio-Oncology, Inova Schar Heart and Vascular, Falls Church, VA, United States of America
| | - Hayder D Hashim
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, United States of America
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8
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Smati H, Sellke FW, Bourque JM, Qadeer YK, Niccoli G, Montone RA, Krittanawong C. Coronary Microvascular Dysfunction: A Guide for Clinicians. Am J Med 2024; 137:810-817. [PMID: 38723930 DOI: 10.1016/j.amjmed.2024.04.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 04/26/2024] [Accepted: 04/29/2024] [Indexed: 09/01/2024]
Abstract
Dysfunction of the coronary microvasculature has become increasingly recognized as an important mechanism of myocardial ischemia in patients without obstructive coronary artery disease. The causes and management of coronary microvascular dysfunction remain poorly understood and are still largely based on extrapolation of epicardial coronary artery disease data. Quantification of myocardial blood flow and flow reserve have improved diagnosis, though important questions remain. In this review, we explain current understanding of the spectrum of pathophysiology of coronary microvascular dysfunction, summarize current diagnostic techniques to assess for coronary microvascular dysfunction, and appraise the limited data on management options specifically for patients with coronary microvascular dysfunction.
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Affiliation(s)
- Hannah Smati
- Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Frank W Sellke
- Division of Cardiothoracic Surgery, Cardiovascular Research Center, Brown University Warren Alpert School of Medicine, Providence, RI
| | - Jamieson M Bourque
- Division of Cardiovascular Medicine and Radiology, University of Virginia Health System, Charlottesville
| | - Yusuf Kamran Qadeer
- Division of Cardiology, Department of Medicine, Henry Ford Hospital, Detroit, Mich
| | - Giampaolo Niccoli
- Department of Medicine and Surgery, University of Parma, Italy; Division of Cardiology, Parma University Hospital, Italy
| | - Rocco A Montone
- Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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9
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Cecere A, Perazzolo Marra M, Zanatta E, Civieri G, Iliceto S, Tona F. Coronary microvascular dysfunction in autoimmune rheumatic diseases: beyond coronary flow velocity reserve. Front Cardiovasc Med 2024; 11:1372703. [PMID: 39234606 PMCID: PMC11371758 DOI: 10.3389/fcvm.2024.1372703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 07/31/2024] [Indexed: 09/06/2024] Open
Abstract
Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of disorders characterized by an inappropriate immune reactivity against different body tissues. Patients affected by ARDs present increased cardiovascular morbidity and mortality, which significantly impacts long-term prognosis. Endothelial dysfunction, inflammation, oxidative stress, and autoimmunity are strictly involved in atherosclerosis progression and coronary microvascular dysfunction (CMD), both of which contribute to increased cardiovascular risk. CMD represents the inability of the coronary microvasculature to respond with vasodilation to increased cardiac metabolic demands and can be assessed by non-invasive and invasive imaging tests. Coronary flow velocity reserve assessed by echocardiography has been demonstrated to accurately identify ARDs patients with CMD. However, stress cardiac magnetic resonance (CMR) accurately assesses myocardial ischemia, perfusion, and viability in ARDs patients. The myocardial perfusion reserve index (MPRI) is a robust semiquantitative imaging marker that represents the vasodilatory capacity of the coronary microcirculation in response to a vasodilator stress. In the absence of significant coronary stenosis, ARDs patients revealed a reduced MPRI in comparison with the general population, regardless of the presence of myocardial fibrosis. Identification of CMD in asymptomatic patients could be crucial to precociously start targeted medical therapy, avoiding major adverse cardiac events in this clinical setting. This review aims to summarize the current evidence regarding CMD in ARDs patients, focusing on the role of stress CMR and the promising myocardial perfusion analysis.
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Affiliation(s)
- Annagrazia Cecere
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Martina Perazzolo Marra
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Elisabetta Zanatta
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
- Department of Medicine, University of Padova, Padova, Italy
| | - Giovanni Civieri
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Sabino Iliceto
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Francesco Tona
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
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10
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Liu B, Zeng H, Su H, Williams QA, Besanson J, Chen Y, Chen J. Endothelial Cell-Specific Prolyl Hydroxylase-2 Deficiency Augments Angiotensin II-Induced Arterial Stiffness and Cardiac Pericyte Recruitment in Mice. J Am Heart Assoc 2024; 13:e035769. [PMID: 39056332 PMCID: PMC11963933 DOI: 10.1161/jaha.124.035769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 06/18/2024] [Indexed: 07/28/2024]
Abstract
BACKGROUND Endothelial prolyl hydroxylase-2 (PHD2) is essential for pulmonary remodeling and hypertension. In the present study, we investigated the role of endothelial PHD2 in angiotensin II-mediated arterial stiffness, pericyte recruitment, and cardiac fibrosis. METHODS AND RESULTS Chondroitin sulfate proteoglycan 4 tracing reporter chondroitin sulfate proteoglycan 4- red fluorescent protein (DsRed) transgenic mice were crossed with PHD2flox/flox (PHD2f/f) mice and endothelial-specific knockout of PHD2 (PHD2ECKO) mice. Transgenic PHD2f/f (TgPHD2f/f) mice and TgPHD2ECKO mice were infused with angiotensin II for 4 weeks. Arterial thickness, stiffness, and histological and immunofluorescence of pericytes and fibrosis were measured. Infusion of TgPHD2f/f mice with angiotensin II resulted in a time-dependent increase in pulse-wave velocity. Angiotensin II-induced pulse-wave velocity was further elevated in the TgPHD2ECKO mice. TgPHD2ECKO also reduced coronary flow reserve compared with TgPHD2f/f mice infused with angiotensin II. Mechanistically, knockout of endothelial PHD2 promoted aortic arginase activity and angiotensin II-induced aortic thickness together with increased transforming growth factor-β1 and ICAM-1/VCAM-1 expression in coronary arteries. TgPHD2f/f mice infused with angiotensin II for 4 weeks exhibited a significant increase in cardiac fibrosis and hypertrophy, which was further developed in the TgPHD2ECKO mice. Chondroitin sulfate proteoglycan 4 pericyte was traced by DsRed+ staining and angiotensin II infusion displayed a significant increase of DsRed+ pericytes in the heart, as well as a deficiency of endothelial PHD2, which further promoted angiotensin II-induced pericyte increase. DsRed+ pericytes were costained with fibroblast-specific protein 1 and α-smooth muscle actin for measuring pericyte-myofibroblast cell transition. The knockout of endothelial PHD2 increased the amount of DsRed+/fibroblast-specific protein 1+ and DsRed+/α-smooth muscle actin+ cells induced by angiotensin II infusion. CONCLUSIONS Knockout of endothelial PHD2 enhanced angiotensin II-induced cardiac fibrosis by mechanisms involving increasing arterial stiffness and pericyte-myofibroblast cell transitions.
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Affiliation(s)
- Bo Liu
- Department of Pharmacology and ToxicologyUniversity of Mississippi Medical Center, School of MedicineJacksonMS
| | - Heng Zeng
- Department of Pharmacology and ToxicologyUniversity of Mississippi Medical Center, School of MedicineJacksonMS
| | - Han Su
- Department of Pharmacology and ToxicologyUniversity of Mississippi Medical Center, School of MedicineJacksonMS
| | - Quinesha A. Williams
- Department of Pharmacology and ToxicologyUniversity of Mississippi Medical Center, School of MedicineJacksonMS
| | - Jessie Besanson
- Department of Pharmacology and ToxicologyUniversity of Mississippi Medical Center, School of MedicineJacksonMS
| | - Yingjie Chen
- Department of Physiology and BiophysicsUniversity of Mississippi Medical Center, School of MedicineJacksonMS
| | - Jian‐Xiong Chen
- Department of Pharmacology and ToxicologyUniversity of Mississippi Medical Center, School of MedicineJacksonMS
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11
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Lembo M, Strisciuglio T, Fonderico C, Mancusi C, Izzo R, Trimarco V, Bellis A, Barbato E, Esposito G, Morisco C, Rubattu S. Obesity: the perfect storm for heart failure. ESC Heart Fail 2024; 11:1841-1860. [PMID: 38491741 PMCID: PMC11287355 DOI: 10.1002/ehf2.14641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 11/27/2023] [Accepted: 12/05/2023] [Indexed: 03/18/2024] Open
Abstract
Obesity condition causes morphological and functional alterations involving the cardiovascular system. These can represent the substrates for different cardiovascular diseases, such as atrial fibrillation, coronary artery disease, sudden cardiac death, and heart failure (HF) with both preserved ejection fraction (EF) and reduced EF. Different pathogenetic mechanisms may help to explain the association between obesity and HF including left ventricular remodelling and epicardial fat accumulation, endothelial dysfunction, and coronary microvascular dysfunction. Multi-imaging modalities are required for appropriate recognition of subclinical systolic dysfunction typically associated with obesity, with echocardiography being the most cost-effective technique. Therapeutic approach in patients with obesity and HF is challenging, particularly regarding patients with preserved EF in which few strategies with high level of evidence are available. Weight loss is of extreme importance in patients with obesity and HF, being a primary therapeutic intervention. Sodium-glucose co-transporter-2 inhibitors have been recently introduced as a novel tool in the management of HF patients. The present review aims at analysing the most recent studies supporting pathogenesis, diagnosis, and management in patients with obesity and HF.
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Affiliation(s)
- Maria Lembo
- Department of Advanced Biochemical SciencesFederico II UniversityNaplesItaly
| | - Teresa Strisciuglio
- Department of Advanced Biochemical SciencesFederico II UniversityNaplesItaly
| | - Celeste Fonderico
- Department of Advanced Biochemical SciencesFederico II UniversityNaplesItaly
| | - Costantino Mancusi
- Department of Advanced Biochemical SciencesFederico II UniversityNaplesItaly
| | - Raffaele Izzo
- Department of Advanced Biochemical SciencesFederico II UniversityNaplesItaly
| | - Valentina Trimarco
- Department of Advanced Biochemical SciencesFederico II UniversityNaplesItaly
| | - Alessandro Bellis
- Emergenza Accettazione DepartmentAzienda Ospedaliera ‘Antonio Cardarelli’NaplesItaly
| | - Emanuele Barbato
- Department of Clinical and Molecular MedicineSapienza University of RomeRomeItaly
| | - Giovanni Esposito
- Department of Advanced Biochemical SciencesFederico II UniversityNaplesItaly
| | - Carmine Morisco
- Department of Advanced Biochemical SciencesFederico II UniversityNaplesItaly
| | - Speranza Rubattu
- Department of Clinical and Molecular MedicineSapienza University of RomeRomeItaly
- IRCCS NeuromedPozzilliItaly
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12
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Borkowski P, Maliha M, Borkowski M, Borkowska N, Singh N, Chauhan A, Chowdhury I, Yakkali S, Satish V, Choi H. Myocardial Infarction With Non-obstructive Coronary Arteries (MINOCA): A Case Report and Comprehensive Discussion of Pathophysiology and Risk Factors. Cureus 2024; 16:e67144. [PMID: 39161551 PMCID: PMC11332960 DOI: 10.7759/cureus.67144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/18/2024] [Indexed: 08/21/2024] Open
Abstract
Myocardial infarction with non-obstructive coronary arteries (MINOCA) refers to the occurrence of myocardial infarction symptoms and signs despite angiographic findings showing normal or near-normal coronary arteries. Unlike the more commonly recognized myocardial infarction with coronary artery disease (MICAD), MINOCA often has a better prognosis; however, it is not without risk, as it is associated with increased mortality. We present a 72-year-old female who presented to the hospital with acute chest pain. Following a thorough diagnostic workup, including laboratory tests, left heart catheterization, and cardiac imaging, she was diagnosed with MINOCA. This case report provides a comprehensive review of the pathophysiological mechanisms underlying MINOCA, such as plaque disruption without significant stenosis, microvascular dysfunction, coronary artery spasm, coronary thrombosis or embolism, and spontaneous coronary artery dissection. Additionally, we explore the associated risk factors, highlighting the unconventional risk factors. MINOCA represents a diverse clinical condition with various causes and complex pathophysiology. The variability underscores the necessity for further research to deepen our understanding of this condition. Enhanced knowledge will lead to better diagnostic and treatment strategies, ultimately improving patient outcomes.
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Affiliation(s)
- Pawel Borkowski
- Internal Medicine, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, USA
| | - Maisha Maliha
- Internal Medicine, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, USA
| | | | - Natalia Borkowska
- Pediatrics, Samodzielny Publiczny Zakład Opieki Zdrowotnej (SPZOZ), Krotoszyn, POL
| | - Nikita Singh
- Internal Medicine, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, USA
| | - Abhyuday Chauhan
- Internal Medicine, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, USA
| | - Ishmum Chowdhury
- Internal Medicine, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, USA
| | - Shreyas Yakkali
- Internal Medicine, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, USA
| | - Vikyath Satish
- Internal Medicine, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, USA
| | - Hansol Choi
- Internal Medicine, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, USA
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13
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Chien SC, Wang SY, Tsai CT, Shiau YC, Wu YW. Significant Association of Serum Albumin With the Severity of Coronary Microvascular Dysfunction Using Dynamic CZT-SPECT. Microcirculation 2024; 31:e12853. [PMID: 38690605 DOI: 10.1111/micc.12853] [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: 10/02/2023] [Revised: 04/02/2024] [Accepted: 04/10/2024] [Indexed: 05/02/2024]
Abstract
OBJECTIVE Both low serum albumin (SA) concentration and coronary microvascular dysfunction (CMD) are risk factors for the development of heart failure (HF). We hypothesized that SA concentration is associated with myocardial flow reserve (MFR) and implicated in pathophysiological mechanism of HF. METHODS We retrospectively studied 454 patients undergoing dynamic cardiac cadmium-zinc-telluride myocardial perfusion imaging from April 2018 to February 2020. The population was categorized into three groups according to SA level (g/dL): Group 1: >4, Group 2: 3.5-4, and Group 3: <3.5. Myocardial blood flow (MBF) and myocardial flow reserve (MFR, defined as stress/rest MBF ratio) were compared. RESULTS The mean age of the whole cohort was 66.2 years, and 65.2% were men. As SA decreased, stress MBF (mL min-1 g-1) and MFR decreased (MBF: 3.29 ± 1.03, MFR: 3.46 ± 1.33 in Group 1, MBF: 2.95 ± 1.13, MFR: 2.51 ± 0.93 in Group 2, and MBF: 2.64 ± 1.16, MFR: 1.90 ± 0.50 in Group 3), whereas rest MBF (mL min-1 g-1) increased (MBF: 1.05 ± 0.42 in Group 1, 1.27 ± 0.56 in Group 2, and 1.41 ± 0.61 in Group 3). After adjusting for covariates, compared with Group 1, the odds ratios for impaired MFR (defined as MFR < 2.5) were 3.57 (95% CI: 2.32-5.48) for Group 2 and 34.9 (95% CI: 13.23-92.14) for Group 3. The results would be similar if only regional MFR were assessed. The risk prediction for CMD using SA was acceptable, with an AUC of 0.76. CONCLUSION Low SA concentration was associated with the severity of CMD in both global and regional MFR as well as MBF.
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Affiliation(s)
- Shih-Chieh Chien
- Cardiovascular Division, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Shan-Ying Wang
- Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Cheng-Ting Tsai
- Cardiovascular Division, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Yu-Chien Shiau
- Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Yen-Wen Wu
- Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- Division of Cardiology, Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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14
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Yao L, Ta S, Wang J, Han C, Lei C, Li W, Li J, Wang B, Zhao X, Liu L. Myocardial perfusion improvement and mechanism after percutaneous intramyocardial septal radiofrequency ablation in obstructive hypertrophic cardiomyopathy: a study of myocardial contrast echocardiography. THE INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING 2024; 40:1483-1492. [PMID: 38709352 DOI: 10.1007/s10554-024-03126-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 04/28/2024] [Indexed: 05/07/2024]
Abstract
The data on myocardial perfusion of the percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for obstructive hypertrophic cardiomyopathy (HOCM) are still lacking, although PIMSRA have been proved to be of great safety and efficacy. The aim of this study was to quantitatively analyze the changes in myocardial perfusion after PIMSRA using myocardial contrast echocardiography (MCE). 27 HOCM patients treated with PIMSRA were retrospectively analyzed, and their echocardiographic parameters and perfusion parameters of MCE were collected before and 12 months after PIMSRA. A reperfusion curve was used to quantify microvascular blood volume (A), microvascular flux rate (β), and microvascular blood flow (MBF) of each segment. Then the value difference (Δ) of parameters between post- and pre-operation were calculated. Finally, the correlation between the changes in MBF and in each echocardiographic parameter was analyzed. (1) Compared with baseline, the global A, β and MBF were significantly increased in HOCM patients after PIMSRA (all P < 0.001). The β, MBF were increased in the interventricular septum (P < 0.001, respectively), and the A, β, MBF were increased in the left ventricular wall (all P < 0.001). (2) Correlation analysis showed that the ΔMBF of interventricular septum was mainly negatively correlated with the maximum interventricular septum thickness (ΔIVSTmax, r=-0.670, P < 0.001), mean interventricular septum thickness (ΔIVSTmean, r=-0.690, P < 0.001), and left ventricular mass index (ΔLVMI, r=-0.774, P < 0.001), while the ΔMBF of left ventricular wall was positively correlated with left ventricular end-diastolic volume index (ΔLVEDVI, r = 0.621, P = 0.001) and stroke volume index (ΔSVI, r = 0.810, P < 0.001). Myocardial perfusion was improved at both interventricular septum and ventricular wall in HOCM patients after PIMSRA. MCE can provide a new dimension for the efficacy evaluation to PIMSRA procedure.
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Affiliation(s)
- Lu Yao
- Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Air Force Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China
| | - Shengjun Ta
- Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Air Force Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China
| | - Jing Wang
- Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Air Force Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China
| | - Chao Han
- Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Air Force Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China
| | - Changhui Lei
- Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Air Force Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China
| | - Wenxia Li
- Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Air Force Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China
| | - Jing Li
- Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Air Force Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China
| | - Bo Wang
- Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Air Force Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China
| | - Xueli Zhao
- Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Air Force Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China
| | - Liwen Liu
- Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Air Force Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China.
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15
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Reiner Ž. Are Traditional Risk Factors for Cardiovascular Diseases Also Risk Factors for Microvascular Disease? Cardiology 2024; 149:463-465. [PMID: 38885620 DOI: 10.1159/000539328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 05/08/2024] [Indexed: 06/20/2024]
Affiliation(s)
- Željko Reiner
- Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
- Department of Cardiology and Adult Congenital Heart Diseases, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland
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16
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Tsuda T, Patel G. Coronary microvascular dysfunction in childhood: An emerging pathological entity and its clinical implications. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2024; 42:100392. [PMID: 38680649 PMCID: PMC11046079 DOI: 10.1016/j.ahjo.2024.100392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 04/07/2024] [Indexed: 05/01/2024]
Abstract
Coronary microvascular dysfunction (CMD) encompasses a spectrum of structural and functional alterations in coronary microvasculature resulting in impaired coronary blood flow and consequent myocardial ischemia without obstruction in epicardial coronary artery. The pathogenesis of CMD is complex involving both functional and structural alteration in the coronary microcirculation. In adults, CMD is predominantly discussed in context with anginal chest pain or existing ischemic heart disease and its risk factors. The presence of CMD suggests increased risk of adverse cardiovascular events independent of coronary atherosclerosis. Coronary microvascular dysfunction is also known in children but is rarely recognized due to paucity of concommitent coronary artery disease. Thus, its clinical presentation, underlying mechanism of impaired microcirculation, and prognostic significance are poorly understood. In this review article, we will overview variable CMD reported in children and delineate its emerging clinical significance.
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Affiliation(s)
- Takeshi Tsuda
- Nemours Cardiac Center, Nemours Children's Health, Wilmington, DE 19803, USA
- Department of Pediatrics, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Gina Patel
- Nemours Cardiac Center, Nemours Children's Health, Wilmington, DE 19803, USA
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17
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Zhang W, Liu L, Yin G, Mohammed AQ, Xiang L, Lv X, Shi T, Galip J, Wang C, Mohammed AA, Mareai RM, Yu F, Abdu FA, Che W. Triglyceride-glucose index is associated with myocardial ischemia and poor prognosis in patients with ischemia and no obstructive coronary artery disease. Cardiovasc Diabetol 2024; 23:187. [PMID: 38822373 PMCID: PMC11140859 DOI: 10.1186/s12933-024-02230-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 04/09/2024] [Indexed: 06/03/2024] Open
Abstract
BACKGROUND Ischemia and no obstructive coronary artery disease (INOCA) is increasingly recognized and associated with poor outcomes. The triglyceride-glucose (TyG) index is a reliable alternative measure of insulin resistance significantly linked to cardiovascular disease and adverse prognosis. We investigated the association between the TyG index and myocardial ischemia and the prognosis in INOCA patients. METHODS INOCA patients who underwent both coronary angiography and myocardial perfusion imaging (MPI) were included consecutively. All participants were divided into three groups according to TyG tertiles (T1, T2, and T3). Abnormal MPI for myocardial ischemia in individual coronary territories was defined as summed stress score (SSS) ≥ 4 and summed difference score (SDS) ≥ 2. SSS refers to the sum of all defects in the stress images, and SDS is the difference of the sum of all defects between the rest images and stress images. All patients were followed up for major adverse cardiac events (MACE). RESULTS Among 332 INOCA patients, 113 (34.0%) had abnormal MPI. Patients with higher TyG index had a higher rate of abnormal MPI (25.5% vs. 32.4% vs. 44.1%; p = 0.012). Multivariate logistic analysis showed that a high TyG index was significantly correlated with abnormal MPI in INOCA patients (OR, 1.901; 95% CI, 1.045-3.458; P = 0.035). During the median 35 months of follow-up, 83 (25%) MACE were recorded, and a higher incidence of MACE was observed in the T3 group (T3 vs. T2 vs. T1: 36.9% vs. 21.6% vs. 16.4%, respectively; p = 0.001). In multivariate Cox regression analysis, the T3 group was significantly associated with the risk of MACE compared to the T1 group (HR, 2.338; 95% CI 1.253-4.364, P = 0.008). CONCLUSION This study indicates for the first time that the TyG index is significantly associated with myocardial ischemia and poor prognosis among INOCA patients.
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Affiliation(s)
- Wen Zhang
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Lu Liu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Guoqing Yin
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Abdul-Quddus Mohammed
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Lanqing Xiang
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Xian Lv
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Tingting Shi
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Jassur Galip
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Chunyue Wang
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Ayman A Mohammed
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Redhwan M Mareai
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Fei Yu
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Fuad A Abdu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China.
| | - Wenliang Che
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China.
- Department of Cardiology, Shanghai Tenth People's Hospital Chongming branch, Shanghai, China.
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18
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Zhu C, Pan L, Zhou F, Mao R, Hong Y, Wan R, Li X, Jin L, Zou H, Zhang H, Chen QM, Li S. Urocortin2 attenuates diabetic coronary microvascular dysfunction by regulating macrophage extracellular vesicles. Biochem Pharmacol 2024; 219:115976. [PMID: 38081372 DOI: 10.1016/j.bcp.2023.115976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 11/27/2023] [Accepted: 12/06/2023] [Indexed: 12/26/2023]
Abstract
Diabetic patients develop coronary microvascular dysfunction (CMD) and exhibit high mortality of coronary artery disease. Methylglyoxal (MGO) largely accumulates in the circulation due to diabetes. We addressed whether macrophages exposed to MGO exhibited damaging effect on the coronary artery and whether urocortin2 (UCN2) serve as protecting factors against such diabetes-associated complication. Type 2 diabetes was induced by high-fat diet and a single low-dose streptozotocin in mice. Small extracellular vesicles (sEV) derived from MGO-treated macrophages (MGO-sEV) were used to produce diabetes-like CMD. UCN2 was examined for a protective role against CMD. The involvement of arginase1 and IL-33 was tested by pharmacological inhibitor and IL-33-/- mice. MGO-sEV was capable of causing coronary artery endothelial dysfunction similar to that by diabetes. Immunocytochemistry studies of diabetic coronary arteries supported the transfer of arginase1 from macrophages to endothelial cells. Mechanism studies revealed arginase1 contributed to the impaired endothelium-dependent relaxation of coronary arteries in diabetic and MGO-sEV-treated mice. UCN2 significantly improved coronary artery endothelial function, and prevented MGO elevation in diabetic mice or enrichment of arginase1 in MGO-sEV. Diabetes caused a reduction of IL-33, which was also reversed by UCN2. IL-33-/- mice showed impaired endothelium-dependent relaxation of coronary arteries, which can be mitigated by arginase1 inhibition but can't be improved by UCN2 anymore, indicating the importance of restoring IL-33 for the protection against diabetic CMD by UCN2. Our data suggest that MGO-sEV induces CMD via shuttling arginase1 to coronary arteries. UCN2 is able to protect against diabetic CMD via modulating MGO-altered macrophage sEV cargoes.
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Affiliation(s)
- Chao Zhu
- Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China.
| | - Lihua Pan
- Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China
| | - Feier Zhou
- Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China
| | - Rongchen Mao
- Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China
| | - Yali Hong
- Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China
| | - Rong Wan
- Jiangxi Key Laboratory of Molecular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China
| | - Xu Li
- Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China
| | - Lai Jin
- Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China
| | - Huayiyang Zou
- Department of Cardiology, the First Affiliated Hospital, Nanjing Medical University, Nanjing 211166, China
| | - Hao Zhang
- Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing 211166, China
| | - Qin M Chen
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA
| | - Shengnan Li
- Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China.
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Zdravkovic M, Popadic V, Klasnja S, Klasnja A, Ivankovic T, Lasica R, Lovic D, Gostiljac D, Vasiljevic Z. Coronary Microvascular Dysfunction and Hypertension: A Bond More Important than We Think. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:2149. [PMID: 38138252 PMCID: PMC10744540 DOI: 10.3390/medicina59122149] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 12/01/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023]
Abstract
Coronary microvascular dysfunction (CMD) is a clinical entity linked with various risk factors that significantly affect cardiac morbidity and mortality. Hypertension, one of the most important, causes both functional and structural alterations in the microvasculature, promoting the occurrence and progression of microvascular angina. Endothelial dysfunction and capillary rarefaction play the most significant role in the development of CMD among patients with hypertension. CMD is also related to several hypertension-induced morphological and functional changes in the myocardium in the subclinical and early clinical stages, including left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction. This indicates the fact that CMD, especially if associated with hypertension, is a subclinical marker of end-organ damage and heart failure, particularly that with preserved ejection fraction. This is why it is important to search for microvascular angina in every patient with hypertension and chest pain not associated with obstructive coronary artery disease. Several highly sensitive and specific non-invasive and invasive diagnostic modalities have been developed to evaluate the presence and severity of CMD and also to investigate and guide the treatment of additional complications that can affect further prognosis. This comprehensive review provides insight into the main pathophysiological mechanisms of CMD in hypertensive patients, offering an integrated diagnostic approach as well as an overview of currently available therapeutical modalities.
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Affiliation(s)
- Marija Zdravkovic
- Clinic for Internal Medicine, University Clinical Hospital Center Bezanijska Kosa, 11000 Belgrade, Serbia; (M.Z.); (S.K.); (A.K.); (T.I.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (R.L.); (D.G.); (Z.V.)
| | - Viseslav Popadic
- Clinic for Internal Medicine, University Clinical Hospital Center Bezanijska Kosa, 11000 Belgrade, Serbia; (M.Z.); (S.K.); (A.K.); (T.I.)
| | - Slobodan Klasnja
- Clinic for Internal Medicine, University Clinical Hospital Center Bezanijska Kosa, 11000 Belgrade, Serbia; (M.Z.); (S.K.); (A.K.); (T.I.)
| | - Andrea Klasnja
- Clinic for Internal Medicine, University Clinical Hospital Center Bezanijska Kosa, 11000 Belgrade, Serbia; (M.Z.); (S.K.); (A.K.); (T.I.)
| | - Tatjana Ivankovic
- Clinic for Internal Medicine, University Clinical Hospital Center Bezanijska Kosa, 11000 Belgrade, Serbia; (M.Z.); (S.K.); (A.K.); (T.I.)
| | - Ratko Lasica
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (R.L.); (D.G.); (Z.V.)
- Clinic of Cardiology, Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Dragan Lovic
- Clinic for Internal Diseases Inter Medica, 18000 Nis, Serbia;
- School of Medicine, Singidunum University, 18000 Nis, Serbia
| | - Drasko Gostiljac
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (R.L.); (D.G.); (Z.V.)
- Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Zorana Vasiljevic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (R.L.); (D.G.); (Z.V.)
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Chen W, Ni M, Huang H, Cong H, Fu X, Gao W, Yang Y, Yu M, Song X, Liu M, Yuan Z, Zhang B, Wang Z, Wang Y, Chen Y, Zhang C, Zhang Y. Chinese expert consensus on the diagnosis and treatment of coronary microvascular diseases (2023 Edition). MedComm (Beijing) 2023; 4:e438. [PMID: 38116064 PMCID: PMC10729292 DOI: 10.1002/mco2.438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 11/11/2023] [Accepted: 11/16/2023] [Indexed: 12/21/2023] Open
Abstract
Since the four working groups of the Chinese Society of Cardiology issued first expert consensus on coronary microvascular diseases (CMVD) in 2017, international consensus documents on CMVD have increased rapidly. Although some of these documents made preliminary recommendations for the diagnosis and treatment of CMVD, they did not provide classification of recommendations and levels of evidence. In order to summarize recent progress in the field of CMVD, standardize the methods and procedures of diagnosis and treatment, and identify the scientific questions for future research, the four working groups of the Chinese Society of Cardiology updated the 2017 version of the Chinese expert consensus on CMVD and adopted a series of measures to ensure the quality of this document. The current consensus has raised a new classification of CMVD, summarized new epidemiological findings for different types of CMVD, analyzed key pathological and molecular mechanisms, evaluated classical and novel diagnostic technologies, recommended diagnostic pathways and criteria, and therapeutic strategies and medications, for patients with CMVD. In view of the current progress and knowledge gaps of CMVD, future directions were proposed. It is hoped that this expert consensus will further expedite the research progress of CMVD in both basic and clinical scenarios.
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Affiliation(s)
- Wenqiang Chen
- The National Key Laboratory for Innovation and Transformation of Luobing TheoryThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical ScienceDepartment of CardiologyQilu Hospital of Shandong UniversityJinanShandongChina
| | - Mei Ni
- The National Key Laboratory for Innovation and Transformation of Luobing TheoryThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical ScienceDepartment of CardiologyQilu Hospital of Shandong UniversityJinanShandongChina
| | - He Huang
- Department of CardiologySir Run Run Shaw Hospital affiliated with Zhejiang University School of MedicineHangzhouChina
| | - Hongliang Cong
- Department of CardiologyTianjin Chest Hospital, Tianjin UniversityTianjinChina
| | - Xianghua Fu
- Department of CardiologyThe Second Hospital of Hebei Medical UniversityShijiazhuangHebeiChina
| | - Wei Gao
- Department of CardiologyPeking University Third HospitalBeijingChina
| | - Yuejin Yang
- Department of CardiologyFuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Mengyue Yu
- Department of CardiologyFuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xiantao Song
- Department of CardiologyBeijing Anzhen Hospital, Capital Medical UniversityBeijingChina
| | - Meilin Liu
- Department of GeriatricsPeking University First HospitalBeijingChina
| | - Zuyi Yuan
- Department of CardiologyThe First Affiliated Hospital of Xian Jiaotong UniversityXianChina
| | - Bo Zhang
- Department of CardiologyFirst Affiliated Hospital, Dalian Medical UniversityDalianLiaoningChina
| | - Zhaohui Wang
- Department of CardiologyUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Yan Wang
- Department of CardiologyXiamen Cardiovascular Hospital, Xiamen UniversityXiamenChina
| | - Yundai Chen
- Senior Department of Cardiology, Sixth Medical Center of Chinese PLA General Hospital, Beijing, China; for the Basic Research Group, Atherosclerosis and Coronary Heart Disease Group, Interventional Cardiology Group, and Women's Heart Health Group of the Chinese Society of Cardiology
| | - Cheng Zhang
- The National Key Laboratory for Innovation and Transformation of Luobing TheoryThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical ScienceDepartment of CardiologyQilu Hospital of Shandong UniversityJinanShandongChina
| | - Yun Zhang
- The National Key Laboratory for Innovation and Transformation of Luobing TheoryThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical ScienceDepartment of CardiologyQilu Hospital of Shandong UniversityJinanShandongChina
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21
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Mohammed AA, Zhang H, Li S, Liu L, Mareai RM, Xu Y, Abdu FA, Che W. Prognostic value of coronary microvascular dysfunction in patients with aortic stenosis and nonobstructed coronary arteries. J Cardiovasc Med (Hagerstown) 2023; 24:891-899. [PMID: 37942790 DOI: 10.2459/jcm.0000000000001561] [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: 11/10/2023]
Abstract
BACKGROUND Patients with aortic valve stenosis have been postulated to have coronary microvascular dysfunction (CMD) contributing to the clinical symptoms and adverse outcomes. The coronary angiography (CAG)-derived index of microcirculatory resistance (caIMR) is proposed as a novel, less invasive and pressure-wire-free index to assess CMD. This study aimed to quantify CMD assessed by caIMR and investigate its prognostic impact in patients with aortic valve stenosis. METHODS This study included 77 moderate or severe aortic valve stenosis patients with no obstructive coronary disease (defined as having no stenosis more than 50% in diameter) who underwent caIMR measurement. CMD was defined by caIMR at least 25. Major adverse cardiovascular events (MACE) were the clinical outcomes during the median 40 months of follow-up. RESULTS The incidence of CMD was 47.7%. Seventeen MACE occurred during the follow-up duration. CMD was associated with an increased risk of MACE (log-rank P < 0.001) and an independent predictor of clinical outcomes [hazard ratio 5.467, 95% confidence interval (CI) 1.393-21.458; P = 0.015]. The receiver-operating characteristic (ROC) curve analysis demonstrated that caIMR could provide a significant predictive value for MACE in aortic valve stenosis patients (AUC 0.785, 95% CI 0.609-0.961, P < 0.001). In addition, the risk of MACE was higher in CMD patients with severe aortic valve stenosis (log-rank P < 0.001) and no aortic valve replacement (log-rank P = 0.003) than in other groups. CONCLUSION Aortic valve stenosis patients demonstrated markedly impaired caIMR. CMD assessed by caIMR increases the risk of MACE and is an independent predictor of adverse outcomes in aortic valve stenosis patients. This finding suggests that using caIMR in the clinical assessment may help identify high-risk groups and stimulate earlier intervention.
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Affiliation(s)
- Ayman A Mohammed
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine; Shanghai, China
- Department of Internal Medicine, Faculty of Medicine and Health Science, Taiz University, Yemen
| | - Hengbin Zhang
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine; Shanghai, China
| | - Siqi Li
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine; Shanghai, China
| | - Lu Liu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine; Shanghai, China
| | - Redhwan M Mareai
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine; Shanghai, China
| | - Yawei Xu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine; Shanghai, China
| | - Fuad A Abdu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine; Shanghai, China
| | - Wenliang Che
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine; Shanghai, China
- Department of Cardiology, Shanghai Tenth People's Hospital Chongming Branch, Shanghai, China
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Mohammed AQ, Abdu FA, Liu L, Yin G, Mareai RM, Mohammed AA, Xu Y, Che W. Coronary microvascular dysfunction and myocardial infarction with non-obstructive coronary arteries: Where do we stand? Eur J Intern Med 2023; 117:8-20. [PMID: 37482469 DOI: 10.1016/j.ejim.2023.07.016] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 06/15/2023] [Accepted: 07/11/2023] [Indexed: 07/25/2023]
Abstract
In the past decade, scientific and clinical research has provided a translational perspective on myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA). MINOCA is characterized by clinical documentation of an acute MI but angiography shows no significant coronary artery obstruction (stenosis <50%). The prevalence of MINOCA is estimated to range from approximately 6 to 10% among MI patients, and those with this condition have a poor prognosis, experiencing high rates of mortality, rehospitalization, and socioeconomic burden. MINOCA represents a major unmet need in cardiovascular medicine, with uncertain clinical management. It is a complex condition that can be caused by various factors, including atherosclerosis, plaque rupture, coronary vasospasm, and microvascular dysfunction. Effective management of MINOCA depends on identifying the underlying mechanism of the infarction, thus a systematic diagnostic approach is recommended. Contemporary data shows that a significant number of patients exhibit structural and functional abnormalities in coronary microcirculation, which is referred to as coronary microvascular dysfunction (CMD). CMD plays a crucial role in patients with signs and symptoms of myocardial ischemia and non-obstructive coronary artery stenosis, including MINOCA. Furthermore, conducting a thorough evaluation of coronary function can have significant prognostic and therapeutic implications, since personalized patient management strategies based on this assessment have been shown to improve symptoms and prognosis. Therefore, an accurate and timely diagnosis of CMD is essential for effective patient management, which can be achieved through various invasive and non-invasive methods. This review will discuss the pathophysiological understanding, current diagnostic techniques, and management strategies of patients with MINOCA and CMD.
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Affiliation(s)
- Abdul-Quddus Mohammed
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Fuad A Abdu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lu Liu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Guoqing Yin
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Redhwan M Mareai
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ayman A Mohammed
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yawei Xu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wenliang Che
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Cardiology, Shanghai Tenth People's Hospital Chongming Branch, Shanghai, China.
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Allbritton-King JD, García-Cardeña G. Endothelial cell dysfunction in cardiac disease: driver or consequence? Front Cell Dev Biol 2023; 11:1278166. [PMID: 37965580 PMCID: PMC10642230 DOI: 10.3389/fcell.2023.1278166] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 10/09/2023] [Indexed: 11/16/2023] Open
Abstract
The vascular endothelium is a multifunctional cellular system which directly influences blood components and cells within the vessel wall in a given tissue. Importantly, this cellular interface undergoes critical phenotypic changes in response to various biochemical and hemodynamic stimuli, driving several developmental and pathophysiological processes. Multiple studies have indicated a central role of the endothelium in the initiation, progression, and clinical outcomes of cardiac disease. In this review we synthesize the current understanding of endothelial function and dysfunction as mediators of the cardiomyocyte phenotype in the setting of distinct cardiac pathologies; outline existing in vivo and in vitro models where key features of endothelial cell dysfunction can be recapitulated; and discuss future directions for development of endothelium-targeted therapeutics for cardiac diseases with limited existing treatment options.
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Affiliation(s)
- Jules D. Allbritton-King
- Department of Pathology, Center for Excellence in Vascular Biology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, United States
| | - Guillermo García-Cardeña
- Department of Pathology, Center for Excellence in Vascular Biology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, United States
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24
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Piaserico S, Papadavid E, Cecere A, Orlando G, Theodoropoulos K, Katsimbri P, Makavos G, Rafouli-Stergiou P, Iliceto S, Alaibac M, Tona F, Ikonomidis I. Coronary Microvascular Dysfunction in Asymptomatic Patients with Severe Psoriasis. J Invest Dermatol 2023; 143:1929-1936.e2. [PMID: 37739764 DOI: 10.1016/j.jid.2023.02.037] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 01/31/2023] [Accepted: 02/22/2023] [Indexed: 09/24/2023]
Abstract
Severe psoriasis is associated with an increased cardiovascular risk, which may be independent of the traditional risk factors. Coronary microvascular dysfunction (CMD) has been shown to predict a poor cardiovascular prognosis in the general population and in patients with psoriasis. In this study, we assessed the prevalence and predictors of CMD in a large cohort of patients with psoriasis without clinical cardiovascular disease. A total of 503 patients with psoriasis were enrolled and underwent transthoracic Doppler echocardiography to evaluate coronary microcirculation. Of these, 55 patients were excluded from the analyses because of missing data. Of the 448 patients in this study, 31.5% showed CMD. Higher PASI, longer disease duration, the presence of psoriatic arthritis, and hypertension were independently associated with CMD. An increase of 1 point of PASI and 1 year of psoriasis duration were associated with a 5.8% and 4.6% increased risk of CMD, respectively. In our study, CMD was associated with the severity and duration of psoriasis. This supports the role of systemic inflammation in CMD and suggests that the coronary microcirculation may represent an extracutaneous site involved in the immune-mediated injury of psoriasis. We should diagnose and actively search for CMD in patients with severe psoriasis.
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Affiliation(s)
- Stefano Piaserico
- Dermatology Unit, Department of Medicine, University of Padova, Padova, Italy.
| | - Evangelia Papadavid
- Department of Dermatology and Venereology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Annagrazia Cecere
- Division of Cardiology, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy
| | - Gloria Orlando
- Dermatology Unit, Department of Medicine, University of Padova, Padova, Italy
| | - Konstantrinos Theodoropoulos
- Department of Dermatology and Venereology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Pelagia Katsimbri
- Department of Dermatology and Venereology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - George Makavos
- 2(nd) Cardiology Department, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Penelope Rafouli-Stergiou
- 2(nd) Cardiology Department, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Sabino Iliceto
- Division of Cardiology, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy
| | - Mauro Alaibac
- Dermatology Unit, Department of Medicine, University of Padova, Padova, Italy
| | - Francesco Tona
- Division of Cardiology, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy
| | - Ignatios Ikonomidis
- 2(nd) Cardiology Department, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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Almeida AG. MINOCA and INOCA: Role in Heart Failure. Curr Heart Fail Rep 2023; 20:139-150. [PMID: 37198520 PMCID: PMC10256635 DOI: 10.1007/s11897-023-00605-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/26/2023] [Indexed: 05/19/2023]
Abstract
PURPOSE OF REVIEW Infarction (MINOCA) and ischaemia (INOCA) with non-obstructive coronary disease are recent non-conventional presentations of coronary syndromes that are increasingly recognised in the clinical arena, particularly with the availability of new cardiovascular imaging techniques. Both are related to heart failure (HF). MINOCA is not associated with benign outcomes, and HF is among the most prevalent events. Regarding INOCA, microvascular dysfunction has also been found to associate with HF, particularly with preserved ejection fraction (HFpEF). RECENT FINDINGS Regardless of the several aetiologies underlying HF in MINOCA, it is likely related to LV dysfunction, where secondary prevention is not yet clearly established. Regarding INOCA, coronary microvascular ischaemia has been associated to endothelial dysfunction leading ultimately to diastolic dysfunction and HFpEF. MINOCA and INOCA are clearly related to HF. In both, there is a lack of studies on the identification of the risk factors for HF, diagnostic workup and, importantly, the appropriate primary and secondary prevention strategies.
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Affiliation(s)
- Ana G Almeida
- Cardiology, Heart and Vessels Department, University Hospital Santa Maria, Faculty of Medicine of Lisbon University, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal.
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26
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Li Y, Ye Z, Guo Z, Xie E, Wang M, Zhao X, Liu M, Li P, Yu C, Gao Y, Zheng J. Ticagrelor vs. clopidogrel for coronary microvascular dysfunction in patients with STEMI: a meta-analysis of randomized controlled trials. Front Cardiovasc Med 2023; 10:1102717. [PMID: 37273883 PMCID: PMC10233131 DOI: 10.3389/fcvm.2023.1102717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 04/17/2023] [Indexed: 06/06/2023] Open
Abstract
Purpose Approximately half of ST-segment elevation myocardial infarction (STEMI) patients who undergo revascularization present with coronary microvascular dysfunction. Dual antiplatelet therapy, consisting of aspirin and a P2Y12 inhibitor (e.g., clopidogrel or ticagrelor), is recommended to reduce rates of cardiovascular events after STEMI. The present study performed a pooled analysis of randomized controlled trials (RCTs) to compare effects of ticagrelor and clopidogrel on coronary microcirculation dysfunction in STEMI patients who underwent the primary percutaneous coronary intervention. Methods The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible RCTs up to September 2022, with no language restriction. Coronary microcirculation indicators included the corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), myocardial blush grade (MBG), TIMI myocardial perfusion grade (TMPG), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). Results Seven RCTs that included a total of 957 patients (476 who were treated with ticagrelor and 481 who were treated with clopidogrel) were included. Compared with clopidogrel, ticagrelor better accelerated microcirculation blood flow [cTFC = -2.40, 95% confidence interval (CI): -3.38 to -1.41, p < 0.001] and improved myocardial perfusion [MBG = 3, odds ratio (OR) = 1.99, 95% CI: 1.35 to 2.93, p < 0.001; MBG ≥ 2, OR = 2.57, 95% CI: 1.61 to 4.12, p < 0.001]. Conclusions Ticagrelor has more benefits for coronary microcirculation than clopidogrel in STEMI patients who undergo the primary percutaneous coronary intervention. However, recommendations for which P2Y12 receptor inhibitor should be used in STEMI patients should be provided according to results of studies that investigate clinical outcomes.
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Affiliation(s)
- Yike Li
- Department of Cardiology, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zixiang Ye
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Ziyu Guo
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, China
| | - Enmin Xie
- Department of Cardiology, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Min Wang
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, China
| | - Xuecheng Zhao
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Mei Liu
- Department of Cardiology, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Peizhao Li
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Changan Yu
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, China
| | - Yanxiang Gao
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, China
| | - Jingang Zheng
- Department of Cardiology, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, China
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Zhang W, Liu L, Chen H, Li S, Wan M, Mohammed AQ, Xu B, Yin G, Lv X, Shi T, Galip J, Mohammed AA, Mareai RM, Xu Y, Abdu FA, Che W. Association between the triglyceride-glucose index and the presence and prognosis of coronary microvascular dysfunction in patients with chronic coronary syndrome. Cardiovasc Diabetol 2023; 22:113. [PMID: 37179333 PMCID: PMC10183136 DOI: 10.1186/s12933-023-01846-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Accepted: 04/29/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. METHODS CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography‑derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). RESULTS Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014-2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066-4.261; P = 0.032). CONCLUSION TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.
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Affiliation(s)
- Wen Zhang
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Lu Liu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Huiying Chen
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Siqi Li
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Minying Wan
- Department of Cardiology, Shanghai Tenth People's Hospital Chongming Branch, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Abdul-Quddus Mohammed
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Bin Xu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Guoqing Yin
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Xian Lv
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Tingting Shi
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Jassur Galip
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Ayman A Mohammed
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Redhwan M Mareai
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Yawei Xu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China
| | - Fuad A Abdu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China.
| | - Wenliang Che
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China.
- Department of Cardiology, Shanghai Tenth People's Hospital Chongming Branch, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China.
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Hung MJ, Yeh CT, Kounis NG, Koniari I, Hu P, Hung MY. Coronary Artery Spasm-Related Heart Failure Syndrome: Literature Review. Int J Mol Sci 2023; 24:ijms24087530. [PMID: 37108691 PMCID: PMC10145866 DOI: 10.3390/ijms24087530] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 04/04/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
Although heart failure (HF) is a clinical syndrome that becomes worse over time, certain cases can be reversed with appropriate treatments. While coronary artery spasm (CAS) is still underappreciated and may be misdiagnosed, ischemia due to coronary artery disease and CAS is becoming the single most frequent cause of HF worldwide. CAS could lead to syncope, HF, arrhythmias, and myocardial ischemic syndromes such as asymptomatic ischemia, rest and/or effort angina, myocardial infarction, and sudden death. Albeit the clinical significance of asymptomatic CAS has been undervalued, affected individuals compared with those with classic Heberden's angina pectoris are at higher risk of syncope, life-threatening arrhythmias, and sudden death. As a result, a prompt diagnosis implements appropriate treatment strategies, which have significant life-changing consequences to prevent CAS-related complications, such as HF. Although an accurate diagnosis depends mainly on coronary angiography and provocative testing, clinical characteristics may help decision-making. Because the majority of CAS-related HF (CASHF) patients present with less severe phenotypes than overt HF, it underscores the importance of understanding risk factors correlated with CAS to prevent the future burden of HF. This narrative literature review summarises and discusses separately the epidemiology, clinical features, pathophysiology, and management of patients with CASHF.
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Affiliation(s)
- Ming-Jui Hung
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital Keelung, Chang Gung University College of Medicine, Keelung City 24201, Taiwan
| | - Chi-Tai Yeh
- Department of Medical Research and Education, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Continuing Education Program of Food Biotechnology Applications, College of Science and Engineering, National Taitung University, Taitung 95092, Taiwan
| | - Nicholas G Kounis
- Department of Cardiology, University of Patras Medical School, 26221 Patras, Greece
| | - Ioanna Koniari
- Cardiology Department, Liverpool Heart and Chest Hospital, Liverpool L14 3PE, UK
| | - Patrick Hu
- Department of Internal Medicine, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA
- Department of Cardiology, Riverside Medical Clinic, Riverside, CA 92506, USA
| | - Ming-Yow Hung
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No.291, Zhongzheng Rd., Zhonghe District, New Taipei City 23561, Taiwan
- Taipei Heart Institute, Taipei Medical University, Taipei City 110301, Taiwan
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, New Taipei City 23561, Taiwan
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Awen A, Hu D, Gao D, Wang Z, Wu Y, Zheng H, Guan L, Mu Y, Sheng Z. Dual-modal molecular imaging and therapeutic evaluation of coronary microvascular dysfunction using indocyanine green-doped targeted microbubbles. Biomater Sci 2023; 11:2359-2371. [PMID: 36883518 DOI: 10.1039/d2bm02155b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
Coronary microvascular dysfunction (CMD), which causes a series of cardiovascular diseases, seriously endangers human health. However, precision diagnosis of CMD is still challenging due to the lack of sensitive probes and complementary imaging technologies. Herein, we demonstrate indocyanine green-doped targeted microbubbles (named T-MBs-ICG) as dual-modal probes for highly sensitive near-infrared (NIR) fluorescence imaging and high-resolution ultrasound imaging of CMD in mouse models. In vitro results show that T-MBs-ICG can specifically target fibrin, a specific CMD biomarker, via the cysteine-arginine-glutamate-lysine-alanine (CREKA) peptide modified on the surface of microbubbles. We further employ T-MBs-ICG to achieve NIR fluorescence imaging of injured myocardial tissue in a CMD mouse model, leading to a signal-to-background ratio (SBR) of up to 50, which is 20 fold higher than that of the non-targeted group. Furthermore, ultrasound molecular imaging of T-MBs-ICG is obtained within 60 s after intravenous injection, providing molecular information on ventricular and myocardial structures and fibrin with a resolution of 1.033 mm × 0.466 mm. More importantly, we utilize comprehensive dual-modal imaging of T-MBs-ICG to evaluate the therapeutic efficacy of rosuvastatin, a cardiovascular drug for the clinical treatment of CMD. Overall, the developed T-MBs-ICG probes with good biocompatibility exhibit great potential in the clinical diagnosis of CMD.
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Affiliation(s)
- Alimina Awen
- Department of Echocardiography, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Ultrasound Medicine, Urumqi, Xinjiang, 830011, P. R. China.
| | - Dehong Hu
- Paul C. Lauterbur Research Center for Biomedical Imaging, CAS Key Laboratory of Health Informatics, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, P. R. China.
| | - Duyang Gao
- Paul C. Lauterbur Research Center for Biomedical Imaging, CAS Key Laboratory of Health Informatics, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, P. R. China.
| | - Zihang Wang
- Department of Echocardiography, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Ultrasound Medicine, Urumqi, Xinjiang, 830011, P. R. China.
| | - Yayun Wu
- Paul C. Lauterbur Research Center for Biomedical Imaging, CAS Key Laboratory of Health Informatics, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, P. R. China.
| | - Hairong Zheng
- Paul C. Lauterbur Research Center for Biomedical Imaging, CAS Key Laboratory of Health Informatics, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, P. R. China.
| | - Lina Guan
- Department of Echocardiography, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Ultrasound Medicine, Urumqi, Xinjiang, 830011, P. R. China.
| | - Yuming Mu
- Department of Echocardiography, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Ultrasound Medicine, Urumqi, Xinjiang, 830011, P. R. China.
| | - Zonghai Sheng
- Paul C. Lauterbur Research Center for Biomedical Imaging, CAS Key Laboratory of Health Informatics, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, P. R. China.
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Liu J, Wang Y, Zhang J, Li X, Tan L, Huang H, Dai Y, Shang Y, Shen Y. Dynamic evolution of left ventricular strain and microvascular perfusion assessed by speckle tracking echocardiography and myocardial contrast echocardiography in diabetic rats: Effect of dapagliflozin. Front Cardiovasc Med 2023; 10:1109946. [PMID: 36910521 PMCID: PMC9996187 DOI: 10.3389/fcvm.2023.1109946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 02/06/2023] [Indexed: 02/25/2023] Open
Abstract
Background This experimental study aimed to determine the dynamic changes in myocardial strain and microvascular perfusion in diabetic rats by comprehensive echocardiography while evaluating the effect of dapagliflozin (DAPA). Materials and methods Male Sprague-Dawley rats (n = 128) were randomly divided into four groups based on the presence or absence of a high-fat diet and streptozotocin-induced diabetes with or without DAPA treatment (n = 32/group). Serial conventional ultrasound, two-dimensional speckle tracking echocardiography (2D-STE) and myocardial contrast echocardiography (MCE) were performed at 2, 4, 6, and 8 weeks, and left ventricular global longitudinal strain (GLS), myocardial blood flow velocity (MBFV), myocardial blood flow (MBF), and myocardial blood volume (MBV) were determined. All animals were sacrificed immediately after the last echo measurement for histopathological assessment. Results Despite similar conventional Doppler-echo indexes among the groups at 2, 4, 6, and 8 weeks (p > 0.05), left ventricular GLS, MBFV, MBF, and MBV were decreased at 8 weeks in diabetic rats (p < 0.05) as detected by both 2D-STE and MCE. These indexes were significantly improved at 6 and 8 weeks after treatment with DAPA for diabetic rats (p < 0.05), reaching similar values observed in non-diabetic controls. DAPA treatment was associated with increased myocardial vacuolization and microvessel density and reduced interstitial fibrosis in diabetic rats. Conclusions Combined 2D-STE and MCE is sensitive for detecting left ventricular deformity and impaired microvascular perfusion in prediabetes and the early stage of diabetes mellitus. DAPA exerts a beneficial effect on protecting myocardial perfusion in diabetic rats.
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Affiliation(s)
- Juan Liu
- Department of Ultrasound, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yixuan Wang
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jun Zhang
- Department of Ultrasound, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Xin Li
- Department of Ultrasound, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Lin Tan
- Department of Ultrasound, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Haiyun Huang
- Department of Ultrasound, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yang Dai
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yongning Shang
- Department of Ultrasound, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Ying Shen
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Rajai N, Ahmad A, Toya T, Sara JD, Herrmann J, Lerman LO, Lerman A. Coronary microvascular dysfunction is an independent predictor of developing cancer in patients with non-obstructive coronary artery disease. Eur J Prev Cardiol 2023; 30:209-216. [PMID: 35989450 PMCID: PMC10787540 DOI: 10.1093/eurjpc/zwac184] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 07/22/2022] [Accepted: 08/17/2022] [Indexed: 01/21/2023]
Abstract
AIMS Cardiovascular disease and cancer share common pathogenesis and risk factors. Coronary microvascular dysfunction (CMD), reflecting impaired coronary microvascular dilation in response to stress, is related to a higher risk of major cardiovascular events; however, its association with cancer has not been explored. METHODS AND RESULTS A retrospective study on 1042 patients with non-obstructive coronary artery diseases (NOCADs) was performed. Data regarding demographic, clinical history, diagnostic coronary reactivity test, and cancer occurrence were collected. Coronary microvascular dysfunction was defined as coronary flow reserve (the ratio of hyperaemic blood flow to resting blood flow) ≤2.5. Thirty-four per cent had CMD (67.4% female and the average age was 52.4 ± 12.2 years). Of 917 patients with no history of cancer, 15.5% developed cancer during follow-up [median of 9 (4, 16) years]. Kaplan-Meier analysis showed that CMD patients had lower cancer-free survival compared with those without CMD (log-rank P = 0.005). Cox proportional hazard analyses showed that after adjusting for age, sex, hypertension, diabetes, smoking, and glomerular filtration rate, CMD is independently associated with cancer [hazard ratio, 1.4; 95% confidence interval (CI), 1.09-2.04; P = 0.04]. The rate of major adverse cardiovascular events (MACE) was significantly higher in CMD patients compared with that in non-CMD patients who had a previous history of cancer [odds ratio (OR), 2.5; 95% CI, 1-6.2; P = 0.04] and those with no history of cancer (OR, 1.4; 95% CI, 1.01-1.9; P = 0.044). CONCLUSION Coronary microvascular dysfunction is associated with cancer incidence in patients presenting with NOCADs. This study emphasizes follow-up in patients with CMD to evaluate the risk of MACE as well as potential malignant diseases.
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Affiliation(s)
- Nazanin Rajai
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Ali Ahmad
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
- Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO, USA
| | - Takumi Toya
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
- Division of Cardiology, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Jaskanwal D. Sara
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Joerg Herrmann
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Lilach O. Lerman
- Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, USA
| | - Amir Lerman
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
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Zhang W, Singh S, Liu L, Mohammed AQ, Yin G, Xu S, Lv X, Shi T, Feng C, Jiang R, Mohammed AA, Mareai RM, Xu Y, Yu X, Abdu FA, Che W. Prognostic value of coronary microvascular dysfunction assessed by coronary angiography-derived index of microcirculatory resistance in diabetic patients with chronic coronary syndrome. Cardiovasc Diabetol 2022; 21:222. [PMID: 36309724 PMCID: PMC9618191 DOI: 10.1186/s12933-022-01653-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 10/03/2022] [Indexed: 01/14/2024] Open
Abstract
Background Coronary microvascular dysfunction (CMD) is common and is associated with unfavorable cardiovascular events in patients with diabetes mellitus (DM). Coronary angiography-derived index of microcirculatory resistance (caIMR) is a recently developed wire- and hyperemic agent-free method to assess CMD. We aimed to investigate the prognostic impact of CMD assessed by caIMR on clinical outcomes in patients with DM and chronic coronary syndrome (CCS). Methods CCS patients who underwent coronary angiography between June 2015 to May 2018 were included. Coronary microvascular function was measured by caIMR, and CMD was defined as caIMR ≥ 25U. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between caIMR and the risk of MACE. Results Of 290 CCS patients, 102 patients had DM. Compared with non-diabetic patients, CMD (caIMR ≥ 25U) was higher among DM patients (57.8% vs. 38.3%; p = 0.001). During a mean 35 months follow-up, 40 MACE had occurred. Patients with caIMR ≥ 25 had a higher rate of MACE than patients with caIMR < 25 (20.6% vs. 8.2%, p = 0.002). Of these, the MACE rate was higher among DM patients with caIMR ≥ 25 than those with caIMR < 25 (33.9% vs. 14.0%; p = 0.022). In multivariable Cox analysis, caIMR ≥ 25 was independently associated with MACE in the DM patients but not in non-DM patients (HR, 2.760; 95% CI, 1.066–7.146; P = 0.036). Conclusion CMD assessed by caIMR was common and is an independent predictor of MACE among diabetic patients with CCS. This finding potentially enables a triage of higher-risk patients to more intensive therapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12933-022-01653-y.
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Prakash RO, Chakrala TS, Feuer DS, Valdes CA, Pepine CJ, Keeley EC. Critical role of the coronary microvasculature in heart disease: From pathologic driving force to "innocent" bystander. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2022; 22:100215. [PMID: 38558907 PMCID: PMC10978433 DOI: 10.1016/j.ahjo.2022.100215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 09/30/2022] [Indexed: 04/04/2024]
Abstract
The coronary microvasculature is responsible for providing oxygen and nutrients to myocardial tissue. A healthy microvasculature with an intact and properly functioning endothelium accomplishes this by seemless changes in vascular tone to match supply and demand. Perturbations in the normal physiology of the microvasculature, including endothelial and/or vascular smooth muscle dysfunction, result in impaired function (vasoconstriction, antithrombotic, etc.) and structural (hypertrophic, fibrotic) abnormalities that lead to microvascular ischemia and potential organ damage. While coronary microvascular dysfunction (CMD) is the primary pathologic driving force in ischemia with non-obstructive coronary artery disease (INOCA), angina with no obstructive coronary arteries (ANOCA), and myocardial infarction with non-obstructed coronary arteries (MINOCA), it may be a bystander in many cardiac disorders which later become pathologically associated with signs and/or symptoms of myocardial ischemia. Importantly, regardless of the primary or secondary basis of CMD in the heart, it is associated with important increases in morbidity and mortality. In this review we discuss salient features pertaining to known pathophysiologic mechanisms driving CMD, the spectrum of heart diseases where it places a critical role, invasive and non-invasive diagnostic testing, management strategies, and the gaps in knowledge where future research efforts are needed.
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Affiliation(s)
- Roshni O. Prakash
- Department of Medicine, University of Florida, Gainesville, FL, United States of America
| | - Teja S. Chakrala
- Department of Medicine, University of Florida, Gainesville, FL, United States of America
| | - Daniel S. Feuer
- Department of Medicine, University of Florida, Gainesville, FL, United States of America
| | - Carlos A. Valdes
- Department of Medicine, University of Florida, Gainesville, FL, United States of America
| | - Carl J. Pepine
- Department of Medicine, University of Florida, Gainesville, FL, United States of America
- Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, United States of America
| | - Ellen C. Keeley
- Department of Medicine, University of Florida, Gainesville, FL, United States of America
- Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, United States of America
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From Structural to Functional Hypertension Mediated Target Organ Damage—A Long Way to Heart Failure with Preserved Ejection Fraction. J Clin Med 2022; 11:jcm11185377. [PMID: 36143024 PMCID: PMC9504592 DOI: 10.3390/jcm11185377] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 09/01/2022] [Accepted: 09/08/2022] [Indexed: 11/17/2022] Open
Abstract
Arterial hypertension (AH) is a major risk factor for the development of heart failure (HF) which represents one of the leading causes of mortality and morbidity worldwide. The chronic hemodynamic overload induced by AH is responsible for different types of functional and morphological adaptation of the cardiovascular system, defined as hypertensive mediated target organ damage (HMOD), whose identification is of fundamental importance for diagnostic and prognostic purposes. Among HMODs, left ventricular hypertrophy (LVH), coronary microvascular dysfunction (CMVD), and subclinical systolic dysfunction have been shown to play a role in the pathogenesis of HF and represent promising therapeutic targets. Furthermore, LVH represents a strong predictor of cardiovascular events in hypertensive patients, influencing per se the development of CMVD and systolic dysfunction. Clinical evidence suggests considering LVH as a diagnostic marker for HF with preserved ejection fraction (HFpEF). Several studies have also shown that microalbuminuria, a parameter of abnormal renal function, is implicated in the development of HFpEF and in predicting the prognosis of patients with HF. The present review highlights recent evidence on the main HMOD, focusing in particular on LVH, CMD, subclinical systolic dysfunction, and microalbuminuria leading to HFpEF.
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35
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Pasqua T, Tropea T, Granieri MC, De Bartolo A, Spena A, Moccia F, Rocca C, Angelone T. Novel molecular insights and potential approaches for targeting hypertrophic cardiomyopathy: Focus on coronary modulators. Vascul Pharmacol 2022; 145:107003. [DOI: 10.1016/j.vph.2022.107003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 05/04/2022] [Accepted: 05/30/2022] [Indexed: 11/26/2022]
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González A, Richards AM, de Boer RA, Thum T, Arfsten H, Hülsmann M, Falcao-Pires I, Díez J, Foo RSY, Chan MY, Aimo A, Anene-Nzelu CG, Abdelhamid M, Adamopoulos S, Anker SD, Belenkov Y, Ben Gal T, Cohen-Solal A, Böhm M, Chioncel O, Delgado V, Emdin M, Jankowska EA, Gustafsson F, Hill L, Jaarsma T, Januzzi JL, Jhund PS, Lopatin Y, Lund LH, Metra M, Milicic D, Moura B, Mueller C, Mullens W, Núñez J, Piepoli MF, Rakisheva A, Ristić AD, Rossignol P, Savarese G, Tocchetti CG, Van Linthout S, Volterrani M, Seferovic P, Rosano G, Coats AJS, Bayés-Genís A. Cardiac remodelling - Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2022; 24:927-943. [PMID: 35334137 DOI: 10.1002/ejhf.2493] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/09/2022] [Accepted: 03/21/2022] [Indexed: 11/10/2022] Open
Abstract
Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.
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Affiliation(s)
- Arantxa González
- Program of Cardiovascular Diseases, CIMA Universidad de Navarra, and IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
- CIBERCV, Carlos III Institute of Health, Madrid, Spain
| | - A Mark Richards
- Department of medicine, Yong Loo-Lin School of Medicine, National University of Singapore, Singapore
- Christchurch Heart Institute, University of Otago, Dunedin, New Zealand
| | - Rudolf A de Boer
- University Medical Center Groningen, University of Groningen, Department of Cardiology, Groningen, The Netherlands
| | - Thomas Thum
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and Rebirth Center for Translational Regenerative Therapies, Hannover Medical School, Hannover, Germany
- Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany
| | - Henrike Arfsten
- Clinical Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
- German Centre for Cardiovascular Research (DZHK), Berlin, Germany
| | - Martin Hülsmann
- Clinical Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Inês Falcao-Pires
- Department od Surgery and Physiology, Cardiovascular Research and Development Center, Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Javier Díez
- Program of Cardiovascular Diseases, CIMA Universidad de Navarra, and IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
- CIBERCV, Carlos III Institute of Health, Madrid, Spain
- Departments of Cardiology and Cardiac Surgery, and Nephrology, Clínica Universidad de Navarra, Pamplona, Spain
| | - Roger S Y Foo
- Department of medicine, Yong Loo-Lin School of Medicine, National University of Singapore, Singapore
| | - Mark Y Chan
- Department of medicine, Yong Loo-Lin School of Medicine, National University of Singapore, Singapore
| | - Alberto Aimo
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Chukwuemeka G Anene-Nzelu
- Department of medicine, Yong Loo-Lin School of Medicine, National University of Singapore, Singapore
- Montreal Heart Institute, Montreal, Canada
| | | | - Stamatis Adamopoulos
- 2nd Department of Cardiovascular Medicine, Onassis Cardiac Surgery Center, Athens, Greece
| | - Stefan D Anker
- Department of Cardiology (CVK), and Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin, Berlin, Germany
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
| | | | - Tuvia Ben Gal
- Cardiology Department, Rabin Medical Center, Beilinson, Israel
| | | | - Michael Böhm
- Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Saarland University, Homburg/Saar, Germany
| | - Ovidiu Chioncel
- Emergency Institute for Cardiovascular Diseases 'Prof. C.C. Iliescu' Bucharest, University of Medicine Carol Davila, Bucharest, Romania
| | - Victoria Delgado
- Institut del Cor, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Michele Emdin
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Ewa A Jankowska
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
| | - Finn Gustafsson
- Rigshospitalet-Copenhagen University Hospital, Heart Centre, Department of Cardiology, Copenhagen, Denmark
| | | | | | - James L Januzzi
- Massachusetts General Hospital and Baim Institute for Clinical Research, Boston, MA, USA
| | - Pardeep S Jhund
- BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland
| | - Yuri Lopatin
- Volgograd State Medical University, Volgograd, Russia
| | - Lars H Lund
- Department of Medicine, Karolinska Institutet, and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
| | - Marco Metra
- Cardiology, ASST Spedali Civili; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Davor Milicic
- University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Brenda Moura
- Faculty of Medicine, University of Porto, Porto, Portugal
- Cardiology Department, Porto Armed Forces Hospital, Portugal
| | | | | | - Julio Núñez
- CIBERCV, Carlos III Institute of Health, Madrid, Spain
- Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, Valencia, Spain
| | - Massimo F Piepoli
- Cardiology Division, Castelsangiovanni Hospital, Castelsangiovanni, Italy
| | - Amina Rakisheva
- Scientific Research Institute of Cardiology and Internal Medicine, Almaty, Kazakhstan
| | - Arsen D Ristić
- Department of Cardiology, University Clinical Center of Serbia, Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Patrick Rossignol
- Université de Lorraine, Centre d'Investigations Cliniques- Plurithématique 1433, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT, Nancy, France
| | - Gianluigi Savarese
- Department of Medicine, Karolinska Institutet, and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
| | - Carlo G Tocchetti
- Cardio-Oncology Unit, Department of Translational Medical Sciences, Center for Basic and Clinical Immunology Research (CISI), Interdepartmental Center of Clinical and Translational Sciences (CIRCET), Interdepartmental Hypertension Research Center (CIRIAPA), Federico II University, Naples, Italy
| | - Sophie Van Linthout
- German Centre for Cardiovascular Research (DZHK), Berlin, Germany
- Berlin Institute of Health (BIH) at Charité - Universitätmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany
| | | | - Petar Seferovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Serbian Academy of Sciences and Arts, Belgrade, Serbia
| | - Giuseppe Rosano
- St. George's Hospitals, NHS Trust, University of London, London, UK
| | | | - Antoni Bayés-Genís
- CIBERCV, Carlos III Institute of Health, Madrid, Spain
- Institut del Cor, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
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Merlo AC, Troccolo A, Piredda E, Porto I, Gil Ad V. Myocardial Infarction With Non-obstructive Coronary Arteries: Risk Factors and Associated Comorbidities. Front Cardiovasc Med 2022; 9:895053. [PMID: 35586651 PMCID: PMC9108150 DOI: 10.3389/fcvm.2022.895053] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 04/14/2022] [Indexed: 11/25/2022] Open
Abstract
Myocardial infarction with non-obstructive coronary arteries (MINOCA), despite a lower burden of coronary atherosclerosis, has a non-negligible prognostic impact. The label of MINOCA includes an array of different aetiologies and pathologic conditions, thus the identification of the underlying disease is crucial to patient management. Myocardial infarction with obstructive coronary artery disease and MINOCA share only some risk factors and comorbid conditions. While traditional cardiovascular risk factors have a lower prevalence in MINOCA patients, atypical ones—e.g., anxiety, depression, and autoimmune diseases—are much more frequent in this population. Other conditions—e.g., pregnancy, cancer, and anti-cancer therapy—can predispose to or even induce MINOCA through various mechanisms. The evidence of such risk factors for MINOCA is still scarce and contradicting, as no randomised controlled trials exist in this field. In our work, we performed a review of registries, clinical studies, and case reports of MINOCA, in order to summarise the available data and analyse its possibile pathogenic mechanisms.
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Affiliation(s)
- Andrea Carlo Merlo
- Division of Cardiovascular Diseases, Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
| | - Alessandro Troccolo
- Division of Cardiovascular Diseases, Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
| | - Elisa Piredda
- Division of Cardiovascular Diseases, Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
| | - Italo Porto
- Division of Cardiovascular Diseases, Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
- Cardiology Unit, DICATOV - Cardiothoracic and Vascular Department, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, Genoa, Italy
| | - Vered Gil Ad
- Cardiology Unit, DICATOV - Cardiothoracic and Vascular Department, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, Genoa, Italy
- *Correspondence: Vered Gil Ad
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Markousis-Mavrogenis G, Bacopoulou F, Mavragani C, Voulgari P, Kolovou G, Kitas GD, Chrousos GP, Mavrogeni SI. Coronary microvascular disease: The "Meeting Point" of Cardiology, Rheumatology and Endocrinology. Eur J Clin Invest 2022; 52:e13737. [PMID: 34939183 DOI: 10.1111/eci.13737] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/19/2021] [Accepted: 12/20/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Exertional chest pain/dyspnea or chest pain at rest are the main symptoms of coronary artery disease (CAD), which are traditionally attributed to insufficiency of the epicardial coronary arteries. However, 2/3 of women and 1/3 of men with angina and 10% of patients with acute myocardial infarction have no evidence of epicardial coronary artery stenosis in X-ray coronary angiography. In these cases, coronary microvascular disease (CMD) is the main causative factor. AIMS To present the pathophysiology of CMD in Cardiology, Rheumatology and Endocrinology. MATERIALS-METHODS The pathophysiology of CMD in Cardiology, Rheumatology and Endocrinology was evaluated. It includes impaired microvascular vasodilatation, which leads to inability of the organism to deal with myocardial oxygen needs and, hence, development of ischemic pain. CMD, observed in inflammatory autoimmune rheumatic and endocrine/metabolic disorders, brings together Cardiology, Rheumatology and Endocrinology. Causative factors include persistent systemic inflammation and endocrine/metabolic abnormalities influencing directly the coronary microvasculature. In the past, the evaluation of microcirculation was feasible only with the use of invasive techniques, such as coronary flow reserve assessment. Currently, the application of advanced imaging modalities, such as cardiovascular magnetic resonance (CMR), can evaluate CMD non-invasively and without ionizing radiation. RESULTS CMD may present with a variety of symptoms with 1/3 to 2/3 of them expressed as typical chest pain in effort, more commonly found in women during menopause than in men. Atypical presentation includes chest pain at rest or exertional dyspnea,but post exercise symptoms are not uncommon. The treatment with nitrates is less effective in CMD, because their vasodilator action in coronary micro-circulation is less pronounced than in the epicardial coronary arteries. DISCUSSION Although both classic and new medications have been used in the treatment of CMD, there are still many questions regarding both the pathophysiology and the treatment of this disorder. The potential effects of anti-rheumatic and endocrine medications on the evolution of CMD need further evaluation. CONCLUSION CMD is a multifactorial disease leading to myocardial ischemia/fibrosis alone or in combination with epicardial coronary artery disease. Endothelial dysfunction/vasospasm, systemic inflammation, and/or neuroendocrine activation may act as causative factors and bring Cardiology, Rheumatology and Endocrinology together. Currently, the application of advanced imaging modalities, and specifically CMR, allows reliable assessment of the extent and severity of CMD. These measurements should not be limited to "pure cardiac patients", as it is known that CMD affects the majority of patients with autoimmune rheumatic and endocrine/metabolic disorders.
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Affiliation(s)
| | - Flora Bacopoulou
- University Research Institute of Maternal and Child Health and Precision Medicine, UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Athens, Greece
| | - Clio Mavragani
- Pathophysiology Department, University of Athens, Athens, Greece
| | | | - Genovefa Kolovou
- Onassis Cardiac Surgery Hospital, Athens, Greece.,Epidemiology Department, University of Manchester, Manchester, UK
| | - George D Kitas
- Epidemiology Department, University of Manchester, Manchester, UK
| | - George P Chrousos
- University Research Institute of Maternal and Child Health and Precision Medicine, UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Athens, Greece
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Quiroga B, Ortiz A, Navarro-González JF, Santamaría R, de Sequera P, Díez J. From cardiorenal syndromes to cardionephrology: a reflection by nephrologists on renocardiac syndromes. Clin Kidney J 2022; 16:19-29. [PMID: 36726435 PMCID: PMC9871856 DOI: 10.1093/ckj/sfac113] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Indexed: 02/04/2023] Open
Abstract
Cardiorenal syndromes (CRS) are broadly defined as disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. CRS are currently classified into five categories, mostly based on disease-initiating events and their acuity or chronicity. CRS types 3 and 4 (also called renocardiac syndromes) refer to acute and chronic kidney dysfunction resulting in acute and chronic heart dysfunction, respectively. The notion of renocardiac syndromes has broadened interest in kidney-heart interactions but uncertainty remains in the nephrological community's understanding of the clinical diversity, pathophysiological mechanisms and optimal management approaches of these syndromes. This triple challenge that renocardiac syndromes (and likely other cardiorenal syndromes) pose to the nephrologist can only be faced through a specific and demanding training plan to enhance his/her cardiological scientific knowledge and through an appropriate clinical environment to develop his/her cardiological clinical skills. The first must be the objective of the subspecialty of cardionephrology (or nephrocardiology) and the second must be the result of collaboration with cardiologists (and other specialists) in cardiorenal care units. This review will first consider various aspects of the challenges that renocardiac syndromes pose to nephrologists and, then, will discuss those aspects of cardionephrology and cardiorenal units that can facilitate an effective response to the challenges.
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Affiliation(s)
| | | | - Juan F Navarro-González
- RICORS2040, Carlos III Institute of Health, Madrid, Spain,Division of Nephrology and Research Unit, University Hospital Nuestra Señora de Candelaria, and University Institute of Biomedical Technologies, University of La Laguna, Santa Cruz de Tenerife, Spain
| | - Rafael Santamaría
- RICORS2040, Carlos III Institute of Health, Madrid, Spain,Division of Nephrology, University Hospital Reina Sofia, Cordoba, Spain,Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain
| | - Patricia de Sequera
- Department of Nephrology, University Hospital Infanta Leonor, University Complutense of Madrid, Madrid, Spain
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40
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McCutcheon K, Manga P. Human Immunodeficiency Virus and Cardiovascular Disease: Revisiting the Inflammation-Thrombosis Axis. Thromb Haemost 2022; 122:476-479. [PMID: 34689321 DOI: 10.1055/s-0041-1736445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Affiliation(s)
- Keir McCutcheon
- Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
| | - Pravin Manga
- Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
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41
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Han PL, Li XM, Jiang L, Yan WF, Guo YK, Li Y, Li K, Yang ZG. Additive Effects of Obesity on Myocardial Microcirculation and Left Ventricular Deformation in Essential Hypertension: A Contrast-Enhanced Cardiac Magnetic Resonance Imaging Study. Front Cardiovasc Med 2022; 9:831231. [PMID: 35402539 PMCID: PMC8987987 DOI: 10.3389/fcvm.2022.831231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/25/2022] [Indexed: 11/18/2022] Open
Abstract
Objective The combination of hypertension and obesity is a major cause of cardiovascular risk, and microvascular changes and subclinical dysfunction should be considered to illustrate the underlying mechanisms and early identification, thereby developing targeted therapies. This study aims to explore the effect of obesity on myocardial microcirculation and left ventricular (LV) deformation in hypertensive patients by cardiac magnetic resonance (CMR). Methods This study comprised 101 hypertensive patients, including 54 subjects with a body mass index (BMI) of 18.5–24.9 kg/m2 and 47 subjects with a BMI ≥25 kg/m2, as well as 55 age- and sex-matched controls with a BMI of 18.5–24.9 kg/m2. Myocardial perfusion indicators [upslope, time to maximum signal intensity (TTM), maximum signal intensity (Max SI)] and LV strains [radial, circumferential, and longitudinal global peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR)] were measured. Results Upslope was numerically increased in obese patients but statistically decreased in non-obese patients compared with controls. Longitudinal PS deteriorated significantly and gradually from controls to non-obese and obese hypertensive patients. Longitudinal PSSR and PDSR were significantly decreased in obese hypertensive patients compared with the other two groups. BMI was associated with upslope (β = −0.136, P < 0.001), Max SI (β = −0.922, P < 0.001), longitudinal PSSR (β = 0.018, P < 0.001), and PDSR (β = −0.024, P = 0.001). Myocardial perfusion was independently associated with longitudinal PSSR (TTM: β = 0.003, P = 0.017) and longitudinal PDSR (upslope: β = 0.067, P = 0.020) in hypertension. Conclusion Obesity had adverse effects on microvascular changes and subclinical LV dysfunction in hypertension, and BMI was independently associated with both myocardial perfusion and LV deformation. Impaired myocardial perfusion was independently associated with subclinical LV dysfunction in hypertension.
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Affiliation(s)
- Pei-Lun Han
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xue-Ming Li
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Li Jiang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Wei-Feng Yan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Ying-Kun Guo
- Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Yuan Li
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Kang Li
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Kang Li,
| | - Zhi-Gang Yang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Zhi-Gang Yang,
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Tsugu T, Tanaka K, Belsack D, Devos H, Nagatomo Y, Michiels V, Argacha JF, Cosyns B, Buls N, De Maeseneer M, De Mey J. Effects of left ventricular mass on computed tomography derived fractional flow reserve in significant obstructive coronary artery disease. Int J Cardiol 2022; 355:59-64. [DOI: 10.1016/j.ijcard.2022.03.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 02/27/2022] [Accepted: 03/07/2022] [Indexed: 12/13/2022]
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Rizzoni D, De Ciuceis C, Szczepaniak P, Paradis P, Schiffrin EL, Guzik TJ. Immune System and Microvascular Remodeling in Humans. Hypertension 2022; 79:691-705. [PMID: 35098718 DOI: 10.1161/hypertensionaha.121.17955] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Low-grade inflammatory processes and related oxidative stress may have a key role in the pathogenesis of hypertension and hypertension-mediated organ damage. Innate immune cells, such as neutrophils, dendritic cells, monocytes/macrophages, as well as unconventional T lymphocytes like γδ T cells contribute to hypertension and may trigger vascular inflammation. Adaptive immunity has been demonstrated to participate in elevation of blood pressure and in vascular and kidney injury. In particular, effector T lymphocytes (Th1, Th2, and Th17) may play a relevant role in promoting hypertension and microvascular remodeling, whereas T-regulatory lymphocytes may have a protective role. Effector cytokines produced by these immune cells lead to increased oxidative stress, endothelial dysfunction and contribute to target organ damage in hypertension. A possible role of immune cell subpopulations in the development and regression of microvascular remodeling has also been proposed in humans with hypertension. The present review summarizes the key immune mechanisms that may participate in the pathophysiology of hypertension-mediated inflammation and vascular remodeling; advances in this field may provide the basis for novel therapeutics for hypertension.
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Affiliation(s)
- Damiano Rizzoni
- Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Italy (D.R., C.D.C.).,Division of Medicine, Spedali Civili di Brescia, Montichiari, Italy (D.R.)
| | - Carolina De Ciuceis
- Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Italy (D.R., C.D.C.)
| | - Piotr Szczepaniak
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (P.S., T.J.G.).,Department of Medicine, Jagiellonian University Medical College, Krakow, Poland (P.S., T.J.G.)
| | - Pierre Paradis
- Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research, Montreal, Québec, Canada (P.P., E.L.S.)
| | - Ernesto L Schiffrin
- Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research, Montreal, Québec, Canada (P.P., E.L.S.).,Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Québec, Canada (E.L.S.)
| | - Tomasz J Guzik
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (P.S., T.J.G.).,Department of Medicine, Jagiellonian University Medical College, Krakow, Poland (P.S., T.J.G.)
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Keeley EC, Handberg EM, Wei J, Merz CNB, Pepine CJ. Coronary microvascular dysfunction as a chronic inflammatory state: Is there a role for omega-3 fatty acid treatment? AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2022; 13:100098. [PMID: 38560085 PMCID: PMC10978178 DOI: 10.1016/j.ahjo.2022.100098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 01/08/2022] [Indexed: 04/04/2024]
Abstract
Coronary microvascular dysfunction is a ubiquitous pathologic process that is operational in ischemia with no obstructive coronary artery disease and other cardiovascular disorders including heart failure with preserved ejection fraction. It may, in fact, be a manifestation of a multi-systemic condition of small vessel dysfunction that also affects the brain and kidneys. While the pathophysiology driving coronary microvascular dysfunction is multifactorial, chronic inflammation plays an important role. Resolution of inflammation is an active process mediated, in part, by a family of locally active mediators biosynthesized from omega-3 fatty acids, collectively referred to as specialized pro-resolving mediators. Omega-3 fatty acid treatment modulates inflammation and is associated with improved cardiovascular outcomes and attenuation of plaque progression on cardiovascular imaging. Whether omega-3 fatty acid treatment attenuates coronary microvascular dysfunction is unknown.
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Affiliation(s)
- Ellen C. Keeley
- Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, FL, United States of America
| | - Eileen M. Handberg
- Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, FL, United States of America
| | - Janet Wei
- Barbra Streisand Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America
| | - C. Noel Bairey Merz
- Barbra Streisand Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America
| | - Carl J. Pepine
- Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, FL, United States of America
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Mangiacapra F, Viscusi MM, Verolino G, Paolucci L, Nusca A, Melfi R, Ussia GP, Grigioni F. Invasive Assessment of Coronary Microvascular Function. J Clin Med 2021; 11:jcm11010228. [PMID: 35011968 PMCID: PMC8745537 DOI: 10.3390/jcm11010228] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 12/21/2021] [Accepted: 12/29/2021] [Indexed: 01/01/2023] Open
Abstract
The critical role of the coronary microvascular compartment and its invasive functional assessment has become apparent in light of the significant proportion of patients presenting signs and symptoms of myocardial ischemia, despite the absence of epicardial disease, or after the adequate treatment of it. However, coronary microvascular dysfunction (CMD) represents a diagnostic challenge because of the small dimensions of the coronary microvasculature, which prevents direct angiographic visualization. Several diagnostic tools are now available for the invasive assessment of the coronary microvascular function, which, in association with the physiological indices used to investigate the epicardial department, may provide a comprehensive evaluation of the coronary circulation as a whole. Recent evidence suggests that the physiology-guided management of CMD, although apparently costly and time-consuming, may offer a net clinical benefit in terms of symptom improvement among patients with angina and ischemic heart disease. However, despite the results of several observational studies, the prognostic effect of the physiology-driven management of CMD within this population is currently a matter of debate, and therefore represents an unmet clinical need that urgently deserves further investigation.
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Bogatyreva FM, Kaplunova VRY, Kozhevnikova MV, Shakaryants GA, Khabarova NV, Privalova EV, Belenkov YN. [Assessment of the structural and functional state of blood vessels in patients with hypertrophic cardiomyopathy]. KARDIOLOGIIA 2021; 61:16-21. [PMID: 35057717 DOI: 10.18087/cardio.2021.12.n1718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 09/07/2021] [Indexed: 06/14/2023]
Abstract
Aim To evaluate the structural and functional condition of the vasculature using fingertip photoplethysmography and computerized videocapillaroscopy in patients with hypertrophic cardiomyopathy (HCMP).Material and methods The study included patients with HCMP (n=48; 28 (57 %) men; age, 54.3±13.6 years) and healthy volunteers (control group, n=33, 15 (45 %) men; age, 58.2±8.8 years). Standard laboratory and instrumental examination (blood count and biochemistry, electrocardiography, echocardiography, Holter electrocardiogram monitoring) were performed for all HCMP patients. The condition of vascular wall at various levels of the vasculature was evaluated by fingertip photoplethysmography (apparatus Angioscan-01) and computerized nail-fold videocapillaroscopy (apparatus Capillaroscan-01). The photoplethysmography study analyzed structural parameters, including the arterial wall stiffness index (aSI) of large blood vessels and the resistance index (RI) of small muscular arteries. Endothelial dysfunction was evaluated by the occlusion index (OI) and phase shift (PS). The capillaroscopy study assessed structural parameters, including the resting capillary density (rCD) and the capillary density following venous occlusion (voCD), and functional parameters, including the percentage of perfused capillaries (PPC), the percentage of restored capillaries (PRC), and the capillary density after the reactive hyperemia test (rhCD).Results The study showed increases in aSI (8.8 [6.8; 12.2] and RI (32.5 [17.4; 47.9] in the HCMP group. The OI was significantly lower in the HCMP group (1.3 [1.1; 1.5]) than in the control group (1.8 [1.5; 2.7], р<0.001). Also, PS values were significantly decreased in the HCMP group (4.4 [2.3; 8.6]) compared to the control group (8.4 [5.1; 12.1]. p=0.018). Disorders of structural and functional capillary indexes were observed in HCMP patients compared to the control group; rCD and voCD were decreased in the HCMP group (60 [52.6; 68] and 88 [75; 90], respectively) compared to the control group (75.8 [60; 87] and 90 [73; 101]), however, no intergroup difference reached a statistical significance. The rhCD, PPC, and PRC values were decreased in the HCMP group (66.3 [55; 72], 86.7 [70.9; 104.2] and 1.7 [-6.95; 20.3], respectively) compared to the control group (86 [68.6; 100], 103 [96; 114] and 18.4 [8.1; 27.4], respectively); PPC and PRC values were significantly different (р<0.005 and p<0.004, respectively).Conclusion In patients with HCMP, fingertip photoplethysmography and computerized videocapillaroscopy showed increased wall stiffness in both large blood vessels and microvasculature, pronounced endothelial dysfunction, and decreases in capillary density and percentage of restored capillaries following respective tests.
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Affiliation(s)
- F M Bogatyreva
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow
| | - V Ra Yu Kaplunova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow
| | - M V Kozhevnikova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow
| | - G A Shakaryants
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow
| | - N V Khabarova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow
| | - E V Privalova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow
| | - Yu N Belenkov
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow
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Qin XF, Shan YG, Gao JH, Li FX, Guo YX. E3 ubiquitin ligase mind bomb 1 overexpression reduces apoptosis and inflammation of cardiac microvascular endothelial cells in coronary microvascular dysfunction. Cell Signal 2021; 91:110223. [PMID: 34954392 DOI: 10.1016/j.cellsig.2021.110223] [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: 05/24/2021] [Revised: 12/09/2021] [Accepted: 12/19/2021] [Indexed: 11/03/2022]
Abstract
BACKGROUND The apoptosis and inflammation in cardiac microvascular endothelial cells (CMECs) promote the development of coronary microvascular dysfunction (CMD). The present study aimed to explore the role of E3 ubiquitin ligase mind bomb 1 (MIB1) in the apoptosis and inflammation in CMECs during CMD. METHODS In vivo, CMD in rats was induced by sodium laurate injection. In vitro, rat primary CMECs were stimulated by homocysteine (Hcy). The apoptosis of CMECs was measured using flow cytometry. The inflammation of CMECs was evaluated by the level of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β). The interplay between MIB1 and mitogen-activated protein kinase kinase kinase 5 (map3k5, also called ASK1) was measured using Co-immunoprecipitation. RESULTS MIB1 expression was decreased and ASK1 expression was increased in the heart tissues of CMD rats and Hcy-treated CMECs. MIB1 overexpression decreased fibrinogen-like protein 2 (FGL2) secretion, inflammation, and apoptosis induced by Hcy in CMECs. Meanwhile, MIB1 overexpression decreased the protein levels of ASK1 and p38, while not affected ASK1 mRNA levels. The following mechanism experiments revealed that MIB1 downregulated ASK1 expression by increasing its ubiquitination. ASK1 overexpression reversed the inhibitory effect of MIB1 on FGL2 secretion, apoptosis, inflammation, and p38 activation in Hcy-treated CMECs. In CMD rats, MIB1 overexpression partly retarded CMD progression, manifesting as increased coronary capillary density and decreased microthrombi formation. CONCLUSION MIB1 overexpression relieved apoptosis and inflammation of CMECs during CMD by targeting the ASK1/p38 pathway.
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Affiliation(s)
- Xiao-Fei Qin
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
| | - Ying-Guang Shan
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Jing-Hong Gao
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Feng-Xiang Li
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Yu-Xi Guo
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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48
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Abstract
Menopause transition marks an important phase in life when cardiovascular risk in women gradually takes an adverse turn. Although menopausal hormone therapy has gained a negative appreciation over the last decades, its value in the treatment of disabling vasomotor symptoms is still undisputed. Cardiovascular risk assessment has become a matter of precision medicine, which is helpful for safe menopausal hormone therapy prescription. With a multidisciplinary approach the current available hormone regimens can be even given to women at intermediate cardiovascular risk, when risk factors such as hypertension and dyslipidemia are adequately monitored and treated.
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Affiliation(s)
- Angela H E M Maas
- Chair Women's Cardiovascular Health Program, Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.
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49
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Giordano C, Francone M, Cundari G, Pisano A, d'Amati G. Myocardial fibrosis: morphologic patterns and role of imaging in diagnosis and prognostication. Cardiovasc Pathol 2021; 56:107391. [PMID: 34601072 DOI: 10.1016/j.carpath.2021.107391] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 09/21/2021] [Accepted: 09/23/2021] [Indexed: 12/21/2022] Open
Abstract
Myocardial fibrosis is defined as an increased amount of collagen in the myocardium relative to cardiac myocytes. Two main morphologic patterns are recognized: 1) replacement fibrosis, which occurs in response to myocyte necrosis (myocardial scarring); and 2) interstitial fibrosis, which is usually a diffuse process and has been shown to be reversible and treatable. Replacement and interstitial fibrosis often coexist and are a constant feature of pathologic cardiac remodeling. In the last twenty years, there has been significant interest in developing objective non-invasive methods to identify and quantitatively assess myocardial fibrosis in vivo, both for diagnostic purposes and to improve stratification of patients. The present Review focuses on the morphologic patterns of myocardial fibrosis observed either at autopsy and heart transplant, or in vivo by non-invasive imaging techniques. Main aim is to provide clues for the differential diagnosis, with emphasis on entities whose diagnosis may be challenging. An update on the diagnostic and prognostic role of imaging, along with recent data on available biomarkers, is also proposed.
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Affiliation(s)
- Carla Giordano
- Department of Radiology, Oncology and Pathology, Sapienza, University of Rome, Rome, Italy.
| | - Marco Francone
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Humanitas Research Hospital IRCCS, Rozzano, Milan, Italy
| | - Giulia Cundari
- Department of Radiology, Oncology and Pathology, Sapienza, University of Rome, Rome, Italy
| | - Annalinda Pisano
- Department of Radiology, Oncology and Pathology, Sapienza, University of Rome, Rome, Italy
| | - Giulia d'Amati
- Department of Radiology, Oncology and Pathology, Sapienza, University of Rome, Rome, Italy
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50
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Triposkiadis F, Xanthopoulos A, Bargiota A, Kitai T, Katsiki N, Farmakis D, Skoularigis J, Starling RC, Iliodromitis E. Diabetes Mellitus and Heart Failure. J Clin Med 2021; 10:3682. [PMID: 34441977 PMCID: PMC8396967 DOI: 10.3390/jcm10163682] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 08/17/2021] [Accepted: 08/17/2021] [Indexed: 12/12/2022] Open
Abstract
Diabetes mellitus (DM) is a major risk factor for new-onset heart failure (HF) and vice versa. The pathogenesis of new-onset HF in DM is complex and has been largely attributed to the toxic cardiovascular effects of hyperglycemia and relevant metabolic abnormalities (diabetic cardiomyopathy) as well as the frequently coexisting morbidities such as hypertension (HTN), coronary artery disease (CAD), and diabetic nephropathy. In patients with type 1 DM (T1DM), HF develops in the setting of a dysregulated immune response, whereas in most patients with type 2 DM (T2DM), against a background of overweight/obesity. HF prevention in DM is feasible with rigorous treatment of cardiovascular risk factors and selective antidiabetic agents. Conversely, development of new-onset T2DM in HF (cardiogenic DM) is common and has been attributed to an increase in the resistance to insulin, especially in the skeletal muscle, liver, and adipose tissue as well as in diminished insulin secretory response to hyperglycemia by pancreatic β-cells. Cardiogenic DM further deteriorates cardiac dysfunction and adversely affects outcome in HF. Novel lifesaving medications employed in HF management such as sacubitril/valsartan and sodium glucose cotransporter 2 inhibitors (SGLT-2i) have a favorable metabolic profile and lower the incidence of cardiogenic diabetes. Whether mitigation of cardiogenic DM should be a treatment target in HF deserves further investigation.
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Affiliation(s)
- Filippos Triposkiadis
- Department of Cardiology, University General Hospital of Larissa, 411 10 Larissa, Greece; (A.X.); (J.S.)
| | - Andrew Xanthopoulos
- Department of Cardiology, University General Hospital of Larissa, 411 10 Larissa, Greece; (A.X.); (J.S.)
| | - Alexandra Bargiota
- Department of Endocrinology and Metabolic Diseases, University General Hospital of Larissa, 411 10 Larissa, Greece;
| | - Takeshi Kitai
- National Cerebral and Cardiovascular Center, Osaka 564-8565, Japan;
| | - Niki Katsiki
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, 54124 Thessaloniki, Greece;
| | - Dimitrios Farmakis
- University of Cyprus Medical School, P.O. Box 20537, Nicosia 1678, Cyprus;
| | - John Skoularigis
- Department of Cardiology, University General Hospital of Larissa, 411 10 Larissa, Greece; (A.X.); (J.S.)
| | - Randall C. Starling
- Kaufman Center for Heart Failure Treatment and Recovery, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH 44195, USA;
| | - Efstathios Iliodromitis
- Second Department of Cardiology, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece;
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