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Pompei G, Ganzorig N, Kotanidis CP, Alkhalil M, Collet C, Sinha A, Perera D, Beltrame J, Kunadian V. Novel diagnostic approaches and management of coronary microvascular dysfunction. Am J Prev Cardiol 2024; 19:100712. [PMID: 39161975 PMCID: PMC11332818 DOI: 10.1016/j.ajpc.2024.100712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 07/04/2024] [Accepted: 07/21/2024] [Indexed: 08/21/2024] Open
Abstract
The mechanism underlying ischaemic heart disease (IHD) has been primarily attributed to obstructive coronary artery disease (CAD). However, non-obstructive coronary arteries are identified in >50% of patients undergoing elective coronary angiography, recently leading to growing interest in the investigation and management of angina/ischaemia with non-obstructive coronary arteries (ANOCA/INOCA). INOCA is an umbrella term encompassing a multiple spectrum of possible pathogenetic entities, including coronary vasomotor disorders which consist of two major endotypes: coronary microvascular dysfunction (CMD) and vasospastic angina. Both conditions can coexist and be associated with concomitant obstructive CAD. Particularly, CMD refers to myocardial ischaemia due to reduced vasodilatory capacity of coronary microcirculation secondary to structural remodelling or impaired resting microvascular tone (functional) or a combination of both. CMD is not a benign condition and is more prevalent in women presenting with chronic coronary syndrome compared to men. In this setting, an impaired coronary flow reserve has been associated with increased risk of major adverse cardiovascular events. ANOCA/INOCA patients also experience impaired quality of life and associated increased healthcare costs. Therefore, research in this scenario has led to better definition, classification, and prognostic stratification based on the underlying pathophysiological mechanisms. The development and validation of non-invasive imaging modalities, invasive coronary vasomotor function testing and angiography-derived indices provide a comprehensive characterisation of CMD. The present narrative review aims to summarise current data relating to the diagnostic approach to CMD and provides details on the sequence that therapeutic management should follow.
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Affiliation(s)
- Graziella Pompei
- Translational and Clinical Research Institute, Faculty of Medical Sciences, NewcastleUniversity, Newcastle upon Tyne, UK
- Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona, FE, Italy
| | - Nandine Ganzorig
- Translational and Clinical Research Institute, Faculty of Medical Sciences, NewcastleUniversity, Newcastle upon Tyne, UK
| | - Christos P. Kotanidis
- Translational and Clinical Research Institute, Faculty of Medical Sciences, NewcastleUniversity, Newcastle upon Tyne, UK
- Cardiothoracic Centre, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom
| | - Mohammad Alkhalil
- Translational and Clinical Research Institute, Faculty of Medical Sciences, NewcastleUniversity, Newcastle upon Tyne, UK
- Cardiothoracic Centre, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom
| | - Carlos Collet
- Cardiovascular Center Aalst, OLV Clinic, Aalst, Belgium
| | - Aish Sinha
- School of Cardiovascular Medicine and Sciences, British Heart Foundation Centre of Excellence and National Institute for Health Research Biomedical Research Centre, King's College London, London, UK
| | - Divaka Perera
- School of Cardiovascular Medicine and Sciences, British Heart Foundation Centre of Excellence and National Institute for Health Research Biomedical Research Centre, King's College London, London, UK
| | - John Beltrame
- Basil Hetzel Institute for Translational Health Research, Adelaide Medical School, University of Adelaide and Royal Adelaide Hospital & The Queen Elizabeth Hospital, Adelaide, Australia
| | - Vijay Kunadian
- Translational and Clinical Research Institute, Faculty of Medical Sciences, NewcastleUniversity, Newcastle upon Tyne, UK
- Cardiothoracic Centre, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom
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Bland A, Chuah E, Meere W, Ford TJ. Targeted Therapies for Microvascular Disease. Cardiol Clin 2024; 42:137-145. [PMID: 37949535 DOI: 10.1016/j.ccl.2023.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Coronary microvascular dysfunction (CMD) is a common cause of ischemia but no obstructive coronary artery disease that results in an inability of the coronary microvasculature to meet myocardial oxygen demand. CMD is challenging to diagnose and manage due to a lack of mechanistic research and targeted therapy. Recent evidence suggests we can improved patient outcomes by stratifying antianginal therapies according to the diagnosis revealed by invasive assessment of the coronary microcirculation. This review article appraises the evidence for management of CMD, which includes treatment of cardiovascular risk, antianginal therapy and therapy for atherosclerosis.
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Affiliation(s)
- Adam Bland
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Eunice Chuah
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - William Meere
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Thomas J Ford
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia; University of Glasgow, ICAMS, G12 8QQ Glasgow, UK.
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González A, López B, Ravassa S, San José G, Latasa I, Butler J, Díez J. Myocardial Interstitial Fibrosis in Hypertensive Heart Disease: From Mechanisms to Clinical Management. Hypertension 2024; 81:218-228. [PMID: 38084597 DOI: 10.1161/hypertensionaha.123.21708] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2024]
Abstract
Hypertensive heart disease (HHD) can no longer be considered as the beneficial adaptive result of the hypertrophy of cardiomyocytes in response to pressure overload leading to the development of left ventricular hypertrophy. The current evidence indicates that in patients with HHD, pathological lesions in the myocardium lead to maladaptive structural remodeling and subsequent alterations in cardiac function, electrical activity, and perfusion, all contributing to poor outcomes. Diffuse myocardial interstitial fibrosis is probably the most critically involved lesion in these disorders. Therefore, in this review, we will focus on the histological characteristics, the mechanisms, and the clinical consequences of myocardial interstitial fibrosis in patients with HHD. In addition, we will consider the most useful tools for the noninvasive diagnosis of myocardial interstitial fibrosis in patients with HHD, as well as the most effective available therapeutic strategies to prevent its development or facilitate its regression in this patient population. Finally, we will issue a call to action for the need for more fundamental and clinical research on myocardial interstitial fibrosis in HHD.
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Affiliation(s)
- Arantxa González
- Program of Cardiovascular Disease, Centro de Investigación Médica Aplicada Universidad de Navarra (CIMA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Insitituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Center for Biomedical Research in Cardiovascular Diseases Network (CIBERCV), Carlos III Institute of Health, Madrid, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Department of Pathology, Anatomy and Physiology, Universidad de Navarra, Pamplona, Spain (A.G.)
| | - Begoña López
- Program of Cardiovascular Disease, Centro de Investigación Médica Aplicada Universidad de Navarra (CIMA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Insitituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Center for Biomedical Research in Cardiovascular Diseases Network (CIBERCV), Carlos III Institute of Health, Madrid, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
| | - Susana Ravassa
- Program of Cardiovascular Disease, Centro de Investigación Médica Aplicada Universidad de Navarra (CIMA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Insitituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Center for Biomedical Research in Cardiovascular Diseases Network (CIBERCV), Carlos III Institute of Health, Madrid, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
| | - Gorka San José
- Program of Cardiovascular Disease, Centro de Investigación Médica Aplicada Universidad de Navarra (CIMA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Insitituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Center for Biomedical Research in Cardiovascular Diseases Network (CIBERCV), Carlos III Institute of Health, Madrid, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
| | - Iñigo Latasa
- Program of Cardiovascular Disease, Centro de Investigación Médica Aplicada Universidad de Navarra (CIMA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Insitituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Center for Biomedical Research in Cardiovascular Diseases Network (CIBERCV), Carlos III Institute of Health, Madrid, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
| | - Javed Butler
- Baylor Scott and White Research Institute, Dallas, TX (J.B.)
- Department of Medicine, University of Mississippi, Jackson (J.B.)
| | - Javier Díez
- Program of Cardiovascular Disease, Centro de Investigación Médica Aplicada Universidad de Navarra (CIMA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Insitituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
- Center for Biomedical Research in Cardiovascular Diseases Network (CIBERCV), Carlos III Institute of Health, Madrid, Spain (A.G., B.L., S.R., G.S.J., I.L., J.D.)
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Bland A, Chuah E, Meere W, Ford TJ. Targeted Therapies for Microvascular Disease. Heart Fail Clin 2024; 20:91-99. [PMID: 37953025 DOI: 10.1016/j.hfc.2023.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2023]
Abstract
Coronary microvascular dysfunction (CMD) is a common cause of ischemia but no obstructive coronary artery disease that results in an inability of the coronary microvasculature to meet myocardial oxygen demand. CMD is challenging to diagnose and manage due to a lack of mechanistic research and targeted therapy. Recent evidence suggests we can improved patient outcomes by stratifying antianginal therapies according to the diagnosis revealed by invasive assessment of the coronary microcirculation. This review article appraises the evidence for management of CMD, which includes treatment of cardiovascular risk, antianginal therapy and therapy for atherosclerosis.
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Affiliation(s)
- Adam Bland
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Eunice Chuah
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - William Meere
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Thomas J Ford
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia; University of Glasgow, ICAMS, G12 8QQ Glasgow, UK.
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Hwang D, Park SH, Koo BK. Ischemia With Nonobstructive Coronary Artery Disease: Concept, Assessment, and Management. JACC. ASIA 2023; 3:169-184. [PMID: 37181394 PMCID: PMC10167523 DOI: 10.1016/j.jacasi.2023.01.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 01/03/2023] [Accepted: 01/06/2023] [Indexed: 05/16/2023]
Abstract
In daily clinical practice, physicians often encounter patients with angina or those with evidence of myocardial ischemia from noninvasive tests but not having obstructive coronary artery disease. This type of ischemic heart disease is referred to as ischemia with nonobstructive coronary arteries (INOCA). INOCA patients often suffer from recurrent chest pain without adequate management and are associated with poor clinical outcomes. There are several endotypes of INOCA, and each endotype should be treated based on its specific underlying mechanism. Therefore, identifying INOCA and discriminating its underlying mechanisms are important issues and of clinical interest. Invasive physiologic assessment is the first step in the diagnosis of INOCA and discriminating the underlying mechanism; additional provocation tests help physicians identify the vasospastic component in INOCA patients. Comprehensive information acquired from these invasive tests can provide a template for mechanism-specific management for patients with INOCA.
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Affiliation(s)
- Doyeon Hwang
- Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea
| | - Sang-Hyeon Park
- Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea
| | - Bon-Kwon Koo
- Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea
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Rizzoni D, Agabiti-Rosei C, De Ciuceis C. State of the Art Review: Vascular Remodeling in Hypertension. Am J Hypertens 2023; 36:1-13. [PMID: 35961002 DOI: 10.1093/ajh/hpac093] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 07/29/2022] [Accepted: 08/08/2022] [Indexed: 01/05/2023] Open
Abstract
Although the gold-standard method for the assessment of structural alteration in small resistance arteries is the evaluation of the MLR by micromyography in bioptic tissues, new, noninvasive techniques are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles. These approaches represent a promising and interesting future perspective. Appropriate antihypertensive treatment is able to prevent the development of microvascular alterations or to induce their regression. Also, conductance arteries may be affected by a remodeling process in hypertension, and a cross-talk may exist between structural changes in the small and large arteries. In conclusion, the evaluation of microvascular structure is ready for clinical prime time, and it could, in the future, represent an evaluation to be performed in the majority of hypertensive patients, to better stratify cardiovascular risk and better evaluate the effects of antihypertensive therapy. However, for this purpose, we need a clear demonstration of the prognostic relevance of noninvasive measures of microvascular structure, in basal conditions and during treatment. Vascular remodeling may be frequently observed in hypertension, as well as in obesity and diabetes mellitus. An increased media to lumen ratio (MLR) or wall to lumen ratio (WLR) in microvessels is the hallmark of hypertension, and may impair organ flow reserve, being relevant in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage/cardiovascular events. The molecular mechanisms underlying the development of vascular remodeling are only partly understood.
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Affiliation(s)
- Damiano Rizzoni
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.,Division of Medicine, Spedali Civili di Brescia, Montichiari (Brescia), Italy
| | - Claudia Agabiti-Rosei
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.,Second Division of Medicine, Spedali Civili di Brescia, Brescia, Italy
| | - Carolina De Ciuceis
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.,Second Division of Medicine, Spedali Civili di Brescia, Brescia, Italy
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Abstract
Hypertensive heart disease (HHD) is currently the second leading cause of heart failure. The prevalence of HHD and its associated risk of heart failure have increased despite substantial improvement in arterial hypertension treatment and control in the recent decades. Therefore, the prevention of heart failure in patients with HHD represents an unmet medical need, due to its clinical, economic, and social impact. In this conceptual framework, we call to action because the time has come for diagnosis and treatment of patients with HHD not to be limited to assessment of morphological and functional left ventricular changes, blood pressure control, and left ventricular hypertrophy regression. We propose a further perspective incorporating also the detection and reversal of the histological changes that develop in the hypertensive heart and that lead to the structural remodeling of the myocardium. In particular, we focus on the diagnosis and treatment of myocardial interstitial fibrosis, likely the lesion most critically involved in the transition from subclinical HHD to clinically overt heart failure. In this context, it is worth considering whether the use of imaging and circulating biomarkers for the noninvasive diagnosis of myocardial interstitial fibrosis should be incorporated in the medical study of hypertensive patients, especially of those with HHD.
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Affiliation(s)
- Javier Díez
- Center for Applied Medical Research (CIMA), and School of Medicine, Universidad de Navarra, and Center for Network Biomedical Research of Cardiovascular Diseases (CIBERCV), Carlos III Institute of Health, Madrid, Spain (J.D.)
| | - Javed Butler
- Baylor Scott and White Research Institute, Dallas, TX, and Department of Medicine, University of Mississippi School of Medicine, Jackson (J.B.)
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Bland A, Chuah E, Meere W, Ford TJ. Targeted Therapies for Microvascular Disease. Interv Cardiol Clin 2023; 12:131-139. [PMID: 36372457 DOI: 10.1016/j.iccl.2022.09.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
Coronary microvascular dysfunction (CMD) is a common cause of ischemia but no obstructive coronary artery disease that results in an inability of the coronary microvasculature to meet myocardial oxygen demand. CMD is challenging to diagnose and manage due to a lack of mechanistic research and targeted therapy. Recent evidence suggests we can improved patient outcomes by stratifying antianginal therapies according to the diagnosis revealed by invasive assessment of the coronary microcirculation. This review article appraises the evidence for management of CMD, which includes treatment of cardiovascular risk, antianginal therapy and therapy for atherosclerosis.
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Affiliation(s)
- Adam Bland
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Eunice Chuah
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - William Meere
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia
| | - Thomas J Ford
- Department of Cardiology, Gosford Hospital - Central Coast LHD, 75 Holden Street, Gosford, New South Wales 2250, Australia; The University of Newcastle, University Dr, Callaghan, New South Wales 2308, Australia; University of Glasgow, ICAMS, G12 8QQ Glasgow, UK.
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Jacobsen DP, Røysland R, Strand H, Moe K, Sugulle M, Omland T, Staff AC. Circulating cardiovascular biomarkers during and after preeclampsia: Crosstalk with placental function? Pregnancy Hypertens 2022; 30:103-109. [PMID: 36148698 DOI: 10.1016/j.preghy.2022.09.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 09/09/2022] [Accepted: 09/12/2022] [Indexed: 11/15/2022]
Abstract
Cardiovascular disease (CVD) is the leading cause of death in women, yet sex-specific risk factors remain understudied. Preeclampsia and other adverse pregnancy outcomes imply an increased maternal cardiovascular risk. We hypothesized that cardiac troponin T (cTnT), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) are increased in such pregnancies and correlate with markers of placental dysfunction. We also investigated these cardiovascular biomarkers 1 or 3 years postpartum. Prior to delivery, we included serum from 417 pregnant women: 55 early-onset preeclampsia (EO-PE), 63 late-onset preeclampsia (LO-PE), 30 gestational hypertension (GH) and 269 healthy controls. Postpartum, we included 341 women 1 or 3 years after delivery: 26 EO-PE, 107 LO-PE, 61 GH, and 147 healthy pregnancies. Prior to delivery, median cTnT and NT-proBNP concentrations were higher in women with EO-PE, LO-PE, or GH than in controls. Median GDF-15 was higher in EO-PE and LO-PE compared to controls. Postpartum, GDF-15 was elevated in women with previous EO-PE. Markers of placental dysfunction correlated with CVD biomarkers in pregnancy, but not postpartum. Our findings underscore the cardiovascular burden of hypertensive disorders of pregnancy and the crosstalk with placental function. The upregulation of circulating GDF-15 following early-onset preeclampsia is in line with the epidemiological excessive risk of premature CVD in this group of women. GDF-15 may be explored for targeting postpartum women with most to gain from intensified preventive follow-up for CVD.
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Affiliation(s)
- Daniel P Jacobsen
- Division of Obstetrics and Gynaecology, Oslo University Hospital, Norway.
| | - Ragnhild Røysland
- Multidisciplinary Laboratory Medicine and Medical Biochemistry, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
| | - Heidi Strand
- Multidisciplinary Laboratory Medicine and Medical Biochemistry, Akershus University Hospital, Lørenskog, Norway
| | - Kjartan Moe
- Division of Obstetrics and Gynaecology, Oslo University Hospital, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Department of Obstetrics and Gynaecology, Bærum Hospital, Vestre Viken HF, Norway
| | - Meryam Sugulle
- Division of Obstetrics and Gynaecology, Oslo University Hospital, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
| | - Torbjørn Omland
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Division of Medicine, Akershus University Hospital, Lørenskog, Norway
| | - Anne Cathrine Staff
- Division of Obstetrics and Gynaecology, Oslo University Hospital, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
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Laohabut I, Songsangjinda T, Kaolawanich Y, Yindeengam A, Krittayaphong R. Myocardial Extracellular Volume Fraction and T1 Mapping by Cardiac Magnetic Resonance Compared Between Patients With and Without Type 2 Diabetes, and the Effect of ECV and T2D on Cardiovascular Outcomes. Front Cardiovasc Med 2021; 8:771363. [PMID: 34950715 PMCID: PMC8688762 DOI: 10.3389/fcvm.2021.771363] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 11/01/2021] [Indexed: 01/16/2023] Open
Abstract
Background: To investigate the difference in myocardial extracellular volume fraction (ECV) by cardiac magnetic resonance (CMR) T1 mapping between patients with and without type 2 diabetes (T2D), and the effect of ECV and T2D on cardiovascular (CV) outcomes. Methods: All patients aged > 18 years with known or suspected coronary artery disease who underwent CMR for assessment of myocardial ischemia or myocardial viability at the Department of Cardiology of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand from September 2017 to December 2018 were screened for inclusion eligibility. Left ventricular ejection fraction (LVEF), late gadolinium enhancement, and T1 mapping were performed. ECV values were derived from myocardial native T1 and contrast-enhanced T1 values that were obtained using modified Look-Locker inversion recovery at the septum of the mid-cavity short-axis map. Demographic data, clinical characteristics, and CV outcomes were collected by retrospective chart review. Composite CV outcomes included CV death, acute coronary syndrome, heart failure hospitalization, or ventricular tachycardia (VT)/ventricular fibrillation. Results: A total of 739 subjects (mean age: 69.5 ± 14.0 years, 49.3% men) were included. Of those, 188 subjects had T2D (25.4%). ECV was significantly higher in T2D than in non-T2D (30.0 ± 5.9% vs. 28.8 ± 4.7%, p = 0.004). During the mean follow-up duration of 26.2 ± 8.5 months, 43 patients (5.8%) had a clinical composite outcome, as follows: three CV death (0.4%), seven acute coronary syndrome (0.9%), 33 heart failure hospitalization (4.5%), and one VT (0.1%). T2D, low LVEF, and high ECV were all identified as independent predictors of CV events. Patients with T2D and high ECV had the highest risk of CV events. Conclusion: Among patients with known or suspected coronary artery disease, patients with T2D had a higher ECV. T2D and high ECV were both found to be independent risk factors for adverse CV outcomes.
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Affiliation(s)
- Issarayus Laohabut
- Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Thammarak Songsangjinda
- Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Yodying Kaolawanich
- Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Ahthit Yindeengam
- Faculty of Medicine Siriraj Hospital, Her Majesty Cardiac Center, Mahidol University, Bangkok, Thailand
| | - Rungroj Krittayaphong
- Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Osipova OA, Gosteva EV, Golivets TP, Belousova ON, Zemlyansky OA, Pokrovsky MV, Golovin AI, Grigorenko NV, Merezhko AA. Changes of myocardial fibrosis markers with the use of beta-blockers and mineralocorticoid receptor antagonists in patients with heart failure with mid-range ejection fraction of ischemic origin. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2021. [DOI: 10.15829/1728-8800-2021-3068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Aim. To compare the effect of 12-month pharmacotherapy with a betablocker (BB) (bisoprolol and nebivolol) and a combination of BB with a mineralocorticoid receptor antagonist (bisoprolol+eplerenone, nebivolol+eplerenone) on following fibrosis markers: matrix metalloproteinases 1 and 9 (MMP-1, MMP-9) and tissue inhibitor of MMP-1 (TIMP-1) in patients with heart failure with mid-range ejection fraction (HFmrEF) of ischemic origin.Material and methods. The study included 135 patients, including 40 (29,6%) women and 95 (70,4%) men aged 45-60 years (mean age, 53,1±5,7 years). Patients were randomized into subgroups based on pharmacotherapy with BB (bisoprolol or nebivolol) and their combination with eplerenone. The enzyme-linked immunosorbent assay was used to determine the level of MMP-1, MMP-9, TIMP-1 (ng/ml) using the commercial test system “MMP-1 ELISA”, “MMP-9 ELISA”, “Human TIMP-1 ELISA” (“Bender Medsystems “, Austria).Results. In patients with HFmrEF of ischemic origin, there were following downward changes in serum level of myocardial fibrosis markers, depending on the therapy: bisoprolol — MMP-1 decreased by 35% (p<0,01), MMP-9 — by 56,3% (p<0,001), TIMP-1 — by 17,9% (p<0,01); nebivolol — MMP-1 decreased by 45% (p<0,001), MMP-9 — by 57,1% (p<0,001), TIMP-1 — by 30,1% (p<0,01); combination of bisoprolol with eplerenone — MMP-1 decreased by 43% (p<0,001), MMP-9 — by 51,2% (p<0,001), TIMP-1 — by 25,1% (p<0,01); combination of nebivolol with eplerenone — MMP-1 decreased by 53% (p<0,001), MMP-9 — by 64,3% (p<0,001), TIMP-1 — by 39% (p<0,01). In patients with NYHA class I HFmrEF after 12-month therapy, the decrease in MMP-1 level was 39,9% (p<0,01), MMP-9 — 57,5% (p<0,001). In class II, the decrease in MMP-1 level was 47% (p<0,001), MMP-9 — 49,7% (p<0,001). A significant decrease in TIMP-1 level was revealed in patients with class I by 29% (p<0,01), in patients with class II by 27,1% (p<0,01) compared with the initial data.Conclusion. A significant decrease in the levels of myocardial fibrosis markers (MMP-1, MMP-9, TIMP-1) was demonstrated in patients with HFmrEF of ischemic origin receiving long-term pharmacotherapy. The most pronounced effect was determined in patients with NYHA class I HF.
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Li X, Li L, Lei W, Chua HZ, Li Z, Huang X, Wang Q, Li N, Zhang H. Traditional Chinese medicine as a therapeutic option for cardiac fibrosis: Pharmacology and mechanisms. Biomed Pharmacother 2021; 142:111979. [PMID: 34358754 DOI: 10.1016/j.biopha.2021.111979] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 07/05/2021] [Accepted: 07/26/2021] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular diseases are one of the leading causes of death worldwide and cardiac fibrosis is a common pathological process for cardiac remodeling in cardiovascular diseases. Cardiac fibrosis not only accelerates the deterioration progress of diseases but also becomes a pivotal contributor for futile treatment in clinical cardiovascular trials. Although cardiac fibrosis is common and prevalent, effective medicines to provide sufficient clinical intervention for cardiac fibrosis are still unavailable. Traditional Chinese medicine (TCM) is the natural essence experienced boiling, fry, and other processing methods, including active ingredients, extracts, and herbal formulas, which have been applied to treat human diseases for a long history. Recently, research has increasingly focused on the great potential of TCM for the prevention and treatment of cardiac fibrosis. Here, we aim to clarify the identified pro-fibrotic mechanisms and intensively summarize the application of TCM in improving cardiac fibrosis by working on these mechanisms. Through comprehensively analyzing, TCM mainly regulates the following pathways during ameliorating cardiac fibrosis: attenuation of inflammation and oxidative stress, inhibition of cardiac fibroblasts activation, reduction of extracellular matrix accumulation, modulation of the renin-angiotensin-aldosterone system, modulation of autophagy, regulation of metabolic-dependent mechanisms, and targeting microRNAs. We also discussed the deficiencies and the development direction of anti-fibrotic therapies on cardiac fibrosis. The data reviewed here demonstrates that TCM shows a robust effect on alleviating cardiac fibrosis, which provides us a rich source of new drugs or drug candidates. Besides, we also hope this review may give some enlightenment for treating cardiac fibrosis in clinical practice.
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Affiliation(s)
- Xiao Li
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Innovation Team of Research on Compound Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Lin Li
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Innovation Team of Research on Compound Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Wei Lei
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Innovation Team of Research on Compound Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Hui Zi Chua
- Evidence-Based Medicine Center, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Zining Li
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Innovation Team of Research on Compound Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Xianglong Huang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China.
| | - Qilong Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Innovation Team of Research on Compound Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Nan Li
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Innovation Team of Research on Compound Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Han Zhang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Innovation Team of Research on Compound Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
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13
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Mahfouz RA, Abdelhamed M, Galal I, Elsanan M. Usefulness of Stress-Derived E/e' Ratio in Asymptomatic Hypertensive Patients. Pulse (Basel) 2021; 8:92-98. [PMID: 34307205 DOI: 10.1159/000511217] [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: 07/14/2020] [Accepted: 08/25/2020] [Indexed: 11/19/2022] Open
Abstract
Purpose We sought to investigate the usefulness of stress echocardiography-derived E/e' in predicting subclinical atherosclerosis in asymptomatic hypertensive patients. Materials and Methods 71 newly diagnosed untreated hypertensive patients (48 ± 13 years, 65% males) and 30 age- and sex-matched healthy controls were recruited. Resting and exercise echocardiography was performed to assess resting diastolic blood pressure and the diastolic stress parameters. Coronary flow reserve (CFR) was evaluated as well. Results Based on CFR values, newly diagnosed, untreated hypertensives were stratified into hypertensives with microvascular dysfunction (MVD; 34 patients had CFR <2.0) and those without MVD (37 patients had CFR ≥2.0). Patients with MVD had a significantly higher C-reactive protein level (p < 0.05) and lower metabolic equivalent values (p < 0.05). With resting echocardiography, only the left atrial volume index (LAVI) was significantly increased in those with MVD compared with those without MVD and controls (p < 0.05). With exercise echo, the E/e' was significantly increased in MVD patients compared with those without MVD and controls (p < 0.001). Importantly, the percentage of subjects with exercise E/e' ≥15 was 76.5% (26 patients in the group with MVD), 4.1% (3 patients in the group without MVD), and 0% in controls. At univariate analysis, high-sensitivity C-reactive protein (p < 0.05), LAVI (p < 0.05), and exercise E/e' (p < 0.001) were independently associated with reduced CFR. On the other hand, at multivariate analysis, only exercise E/e' was the independent predictor of reduced CFR in newly diagnosed hypertensives. Conclusion We have demonstrated significant associations between exercise-derived raised left ventricular pressure and coronary MVD in newly diagnosed untreated hypertensive patients. Herein, we supposed that exercise-derived E/e' could predict subclinical atherosclerosis and might be a risk parameter for newly diagnosed untreated hypertensive patients.
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Affiliation(s)
- Ragab A Mahfouz
- Department of Cardiology, Zagazig University Hospital, Zagazig, Egypt
| | | | - Islam Galal
- Department of Cardiology, Zagazig University Hospital, Zagazig, Egypt
| | - Moataz Elsanan
- Department of Cardiology, Zagazig University Hospital, Zagazig, Egypt
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14
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Najjar RS, Schwartz AM, Wong BJ, Mehta PK, Feresin RG. Berries and Their Polyphenols as a Potential Therapy for Coronary Microvascular Dysfunction: A Mini-Review. Int J Mol Sci 2021; 22:3373. [PMID: 33806050 PMCID: PMC8036956 DOI: 10.3390/ijms22073373] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/19/2021] [Accepted: 03/23/2021] [Indexed: 12/16/2022] Open
Abstract
Ischemia with no obstructive coronary artery disease (INOCA) is a common diagnosis with a higher prevalence in women compared to men. Despite the absence of obstructive coronary artery disease and no structural heart disease, INOCA is associated with major adverse cardiovascular outcomes as well a significant contributor to angina and related disability. A major feature of INOCA is coronary microvascular dysfunction (CMD), which can be detected by non-invasive imaging and invasive coronary physiology assessments in humans. CMD is associated with epicardial endothelial-dependent and -independent dysfunction, diffuse atherosclerosis, and left-ventricular hypertrophy, all of which lead to insufficient blood flow to the myocardium. Inflammatory and oxidative stress signaling, upregulation of the renin-angiotensin-aldosterone system and adrenergic receptor signaling are major drivers of CMD. Treatment of CMD centers around addressing cardiovascular risk factors; however, there are limited treatment options for those who do not respond to traditional anti-anginal therapies. In this review, we highlight the ability of berry-derived polyphenols to modulate those pathways. The evidence supports the need for future clinical trials to investigate the effectiveness of berries and their polyphenols in the treatment of CMD in INOCA patients.
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Affiliation(s)
- Rami S. Najjar
- Department of Nutrition, Georgia State University, Atlanta, GA 30302, USA;
| | - Arielle M. Schwartz
- J. Willis Hurst Internal Medicine Residency Program, Emory University, Atlanta, GA 30322, USA;
| | - Brett J. Wong
- Department of Kinesiology & Health, Georgia State University, Atlanta, GA 30302, USA;
| | - Puja K. Mehta
- Division of Cardiology, Emory Women’s Heart Center, Emory University School of Medicine, Atlanta, GA 30322, USA
- Division of Cardiology, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Rafaela G. Feresin
- Department of Nutrition, Georgia State University, Atlanta, GA 30302, USA;
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15
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Markousis-Mavrogenis G, Bacopoulou F, Vlachakis D, Mavrogeni S. Tissue Characterization in Cardiology: Moving Beyond Function. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1337:89-97. [DOI: 10.1007/978-3-030-78771-4_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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16
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Yong J, Tian J, Yang X, Xing H, He Y, Song X. Effects of Oral Drugs on Coronary Microvascular Function in Patients Without Significant Stenosis of Epicardial Coronary Arteries: A Systematic Review and Meta-Analysis of Coronary Flow Reserve. Front Cardiovasc Med 2020; 7:580419. [PMID: 33195465 PMCID: PMC7661556 DOI: 10.3389/fcvm.2020.580419] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 09/14/2020] [Indexed: 12/27/2022] Open
Abstract
Objective: This study aims to investigate the impact of cardiovascular medications on the coronary flow reserve (CFR) in patients without obstructive coronary artery disease (CAD). Methods: We searched PubMed, EMBASE, and Cochrane databases from inception to 15 November 2019. Studies were included if they reported CFR from baseline to follow-up after oral drug therapy of patients without obstructive CAD. Data was pooled using random-effects modeling. The primary outcome was change in CFR from baseline to follow-up after oral drug therapy. Results: A total of 46 studies including 845 subjects were included in this study. Relative to baseline, the CFR was improved by angiotensin-converting enzymes (ACEIs), aldosterone receptor antagonists (ARBs) [standard mean difference (SMD): 1.12; 95% CI: 0.77–1.47], and statins treatments (SMD: 0.61; 95%CI: 0.36–0.85). Six to 12 months of calcium channel blocker (CCB) treatments improved CFR (SMD: 1.04; 95% CI: 0.51–1.58). Beta-blocker (SMD: 0.24; 95% CI: −0.39–0.88) and ranolazine treatment (SMD: 0.31; 95% CI: −0.39–1.01) were not associated with improved CFR. Conclusions: Therapy with ACEIs, ARBs, and statins was associated with improved CFR in patients with confirmed or suspicious CMD. CCBs also improved CFR among patients followed for 6–12 months. Beta-blocker and ranolazine had no impact on CFR.
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Affiliation(s)
- Jingwen Yong
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Jinfan Tian
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Xueyao Yang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Haoran Xing
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yi He
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiantao Song
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
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17
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Aguiar Rosa S, Rocha Lopes L, Fiarresga A, Ferreira RC, Mota Carmo M. Coronary microvascular dysfunction in hypertrophic cardiomyopathy: Pathophysiology, assessment, and clinical impact. Microcirculation 2020; 28:e12656. [PMID: 32896949 DOI: 10.1111/micc.12656] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 06/21/2020] [Accepted: 07/13/2020] [Indexed: 12/14/2022]
Abstract
Myocardial ischemia constitutes one of the most important pathophysiological features in hypertrophic cardiomyopathy. Chronic and recurrent myocardial ischemia leads to fibrosis, which may culminate in myocardial dysfunction. Since the direct visualization of coronary microcirculation in vivo is not possible, its function must be studied indirectly. Invasive and noninvasive techniques allow microcirculatory dysfunction to be evaluated, including echocardiography, magnetic resonance, positron emission tomography, and cardiac catheterization. Blunted myocardial blood flow and coronary flow reserve have been suggested to associate with unfavorable prognosis. Microcirculatory dysfunction may be one additional important parameter to take into account for risk stratification beyond the conventional risk factors.
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Affiliation(s)
- Sílvia Aguiar Rosa
- Department of Cardiology, Santa Marta Hospital, Lisbon, Portugal.,Nova Medical School, Lisbon, Portugal
| | - Luís Rocha Lopes
- Inherited Cardiac Disease Unit, Bart's Heart Centre, St Bartholomew's Hospital, London, UK.,Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, UK.,Centro Cardiovascular, Universidade de Lisboa, Lisbon, Portugal
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18
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Han X, Cao Y, Ju Z, Liu J, Li N, Li Y, Liu T, Shi H, Gu J. Assessment of regional left ventricular myocardial strain in patients with left anterior descending coronary stenosis using computed tomography feature tracking. BMC Cardiovasc Disord 2020; 20:362. [PMID: 32770941 PMCID: PMC7414558 DOI: 10.1186/s12872-020-01644-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 07/30/2020] [Indexed: 11/10/2022] Open
Abstract
Background Computed tomography feature tracking (CT-FT) has emerged as a valuable method for the assessment of cardiac function. However, no studies have investigated the usefulness of CT-derived assessments of left ventricular (LV) strain in coronary artery disease (CAD). Our aim was to evaluate regional LV systolic deformation in patients with left anterior descending coronary artery (LAD) stenosis using CT-FT. Methods Seventy-six patients with LAD stenosis were enrolled. The patients were divided into four groups according to the percentage of LAD stenosis: ≤25% was defined as group I (24 patients), 26 to 49% as group II (17 patients), 50 to 74% as group III (21 patients), and ≥ 75% as group IV (14 patients). Thirty-two sex- and age-matched healthy subjects were included as controls. Results No intergroup differences were found between groups I-IV and the controls in terms of the left ventricular ejection fraction, end-diastolic volume and end-systolic volume. However, the longitudinal strain (LS) of the LAD territory was significantly reduced in groups I-IV compared with the controls (− 20.8, − 18.6%, − 18.6%, and − 17.0% vs − 23.7%, respectively). The circumferential strain (CS) of the LAD territory was significantly reduced in groups III and IV compared with the controls and groups I and II (− 22.4% and − 22.1% vs − 25.4, − 24.1%, and − 25.3%, respectively). Compared with the non-LAD territory, the LAD territory in groups II-IV showed significantly increased LS (− 18.6% vs − 21.9%, p = 0.07; − 18.6% vs − 21.9%, p = 0.024; − 17.5% vs − 20%, p = 0.032, respectively). The severity of LAD stenosis was positively correlated with the LS of the LAD territory (r = 0.438, p = 0.002). Conclusion CT-FT can detect decreasing LV systolic function in patients with LAD stenosis. LV regional systolic deformation of the LAD territory was reduced with increasing LAD stenosis severity.
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Affiliation(s)
- Xiaoyu Han
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Yukun Cao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Zhiguo Ju
- College of Medical Imaging, Shanghai University of Medicine & Health Science, Shanghai, China
| | - Jia Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Na Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Yumin Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Tong Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Heshui Shi
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. .,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
| | - Jin Gu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. .,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
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19
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Quarta G, Gori M, Iorio A, D'Elia E, Moon JC, Iacovoni A, Burocchi S, Schelbert EB, Brambilla P, Sironi S, Caravita S, Parati G, Gavazzi A, Maisel AS, Butler J, Lam CSP, Senni M. Cardiac magnetic resonance in heart failure with preserved ejection fraction: myocyte, interstitium, microvascular, and metabolic abnormalities. Eur J Heart Fail 2020; 22:1065-1075. [PMID: 32654354 DOI: 10.1002/ejhf.1961] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 06/22/2020] [Accepted: 06/24/2020] [Indexed: 11/11/2022] Open
Abstract
Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose prevalence continues to rise, with high social and economic burden, but with no specific approved treatment. Patients diagnosed with HFpEF have a high prevalence of comorbidities and exhibit a high misdiagnosis rate. True HFpEF is likely to have multiple pathophysiological causes - with these causes being clinically ill-defined due to limitations of current measurement techniques. Myocyte, interstitium, microvascular, and metabolic abnormalities have been regarded as key components of the pathophysiology and potential therapeutic targets. Cardiac magnetic resonance (CMR) has the capability to look deeper with a number of tissue characterization techniques which are closer to the underlying specific abnormalities and which could be linked to personalized medicine for HFpEF. This review aims to discuss the potential role of CMR to better define HFpEF phenotypes and to infer measurable therapeutic targets.
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Affiliation(s)
- Giovanni Quarta
- Cardiovascular Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Mauro Gori
- Cardiovascular Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Annamaria Iorio
- Cardiovascular Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Emilia D'Elia
- Cardiovascular Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - James C Moon
- University College London and Barts Heart Centre, London, UK
| | - Attilio Iacovoni
- Cardiovascular Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Simone Burocchi
- Cardiovascular Department, Azienda Ospedaliera S. Andrea, Rome, Italy
| | - Erik B Schelbert
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.,UPMC Cardiovascular Magnetic Resonance Center, Heart and Vascular Institute, Pittsburgh, PA, USA.,Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA
| | - Paolo Brambilla
- Diagnostic Radiology, Papa Giovanni XXIII Hospital, University of Milano-Bicocca, Milan, Italy
| | - Sandro Sironi
- Diagnostic Radiology, Papa Giovanni XXIII Hospital, University of Milano-Bicocca, Milan, Italy
| | - Sergio Caravita
- Department of Management, Information and Production Engineering, University of Bergamo, Dalmine (Bergamo), Italy.,Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital IRCCS, Istituto Auxologico Italiano, Milan, Italy
| | - Gianfranco Parati
- Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital IRCCS, Istituto Auxologico Italiano, Milan, Italy.,Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Antonello Gavazzi
- FROM - Fondazione per la Ricerca dell'Ospedale di Bergamo, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Alan S Maisel
- Division of Cardiovascular Medicine, University of California San Diego, La Jolla, CA, USA
| | - Javed Butler
- Department of Medicine, University of Mississippi, Jackson, MS, USA
| | - Carolyn S P Lam
- National Heart Centre, Singapore, Singapore.,Duke-National University of Singapore, Singapore, Singapore.,University Medical Centre Groningen, Groningen, The Netherlands
| | - Michele Senni
- Cardiovascular Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
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Zhou T, Wang J, Xu J, Zheng C, Niu Y, Wang C, Xu F, Yuan L, Zhao X, Liang L, Xu P. A Smart Fluorescent Probe for NO Detection and Application in Myocardial Fibrosis Imaging. Anal Chem 2020; 92:5064-5072. [DOI: 10.1021/acs.analchem.9b05435] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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21
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Bairey Merz CN, Pepine CJ, Shimokawa H, Berry C. Treatment of coronary microvascular dysfunction. Cardiovasc Res 2020; 116:856-870. [PMID: 32087007 PMCID: PMC7061279 DOI: 10.1093/cvr/cvaa006] [Citation(s) in RCA: 121] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 11/18/2019] [Indexed: 12/30/2022] Open
Abstract
Contemporary data indicate that patients with signs and symptoms of ischaemia and non-obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD) with elevated risk for adverse outcomes. Coronary endothelial (constriction with acetylcholine) and/or microvascular (limited coronary flow reserve with adenosine) dysfunction are well-documented, and extensive non-obstructive atherosclerosis is often present. Despite these data, patients with INOCA currently remain under-treated, in part, because existing management guidelines do not address this large, mostly female population due to the absence of evidence-based data. Relatively small sample-sized, short-term pilot studies of symptomatic mostly women, with INOCA, using intense medical therapies targeting endothelial, microvascular, and/or atherosclerosis mechanisms suggest symptom, ischaemia, and coronary vascular functional improvement, however, randomized, controlled outcome trials testing treatment strategies have not been completed. We review evidence regarding CMD pharmacotherapy. Potent statins in combination with angiotensin-converting enzyme inhibitor (ACE-I) or receptor blockers if intolerant, at maximally tolerated doses appear to improve angina, stress testing, myocardial perfusion, coronary endothelial function, and microvascular function. The Coronary Microvascular Angina trial supports invasive diagnostic testing with stratified therapy as an approach to improve symptoms and quality of life. The WARRIOR trial is testing intense medical therapy of high-intensity statin, maximally tolerated ACE-I plus aspirin on longer-term outcomes to provide evidence for guidelines. Novel treatments and those under development appear promising as the basis for future trial planning.
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Affiliation(s)
- C Noel Bairey Merz
- Barbra Streisand Women’s Heart Center, Smidt Heart Institute, Cedars-Sinai, 127 S. San Vicente Blvd, Suite A3600, Los Angeles, CA 90048, USA
| | - Carl J Pepine
- Division of Cardiovascular Medicine, University of Florida, 1329 SW 16th Street, PO Box 100288, Gainesville, FL 32610-0288, USA
| | - Hiroki Shimokawa
- Division of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
| | - Colin Berry
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK
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Optimal Blood Pressure Control Improves Left Ventricular Torsional Deformation and Vascular Function in Newly Diagnosed Hypertensives: a 3-Year Follow-up Study. J Cardiovasc Transl Res 2020; 13:814-825. [DOI: 10.1007/s12265-019-09951-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 12/20/2019] [Indexed: 12/14/2022]
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Halliday BP, Prasad SK. The Interstitium in the Hypertrophied Heart. JACC Cardiovasc Imaging 2019; 12:2357-2368. [DOI: 10.1016/j.jcmg.2019.05.033] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 04/06/2019] [Accepted: 05/07/2019] [Indexed: 12/17/2022]
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Why Clinicians Should Care About the Cardiac Interstitium. JACC Cardiovasc Imaging 2019; 12:2305-2318. [DOI: 10.1016/j.jcmg.2019.04.025] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 04/05/2019] [Accepted: 04/11/2019] [Indexed: 12/12/2022]
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25
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Considerations for Clinical Trials Targeting the Myocardial Interstitium. JACC Cardiovasc Imaging 2019; 12:2319-2331. [DOI: 10.1016/j.jcmg.2019.03.034] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 02/26/2019] [Accepted: 03/07/2019] [Indexed: 01/23/2023]
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26
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Suhrs HE, Michelsen MM, Prescott E. Treatment strategies in coronary microvascular dysfunction: A systematic review of interventional studies. Microcirculation 2019; 26:e12430. [PMID: 29130567 DOI: 10.1111/micc.12430] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 11/06/2017] [Indexed: 12/12/2022]
Abstract
CMD has been associated with a wide spectrum of diseases and conditions, and it has proven to be a strong prognostic marker of morbidity and mortality. Despite increased attention, guideline-based treatment recommendations are lacking. We performed a systematic review of pharmacological and nonpharmacological interventions to improve coronary perfusion, assessed by IC Doppler, TTDE, PET, CMRI, transthoracic contrast perfusion echocardiography, and dilution techniques. No restrictions were made regarding the study design (randomized, placebo-controlled/randomized with active comparators/nonrandomized with or without a control group), the cardiac condition studied, or the coronary microvascular function at baseline. An electronic database search yielded 4485 records of which 80 studies met our inclusion criteria. Included studies were sorted according to intervention and study design. Studies were small and heterogeneous in methodology, and only few were placebo-controlled. Although some treatments looked promising, we found that no specific treatment was sufficiently well documented to be recommended in any patient groups. There is a need for larger well-designed clinical trials, and we suggest that future studies stratify study populations according to pathogenic mechanisms, thereby investigating whether an individualized treatment approach would be more successful.
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Affiliation(s)
- Hannah E Suhrs
- Department of Cardiology, Bispebjerg University Hospital, Copenhagen NV, Denmark
| | - Marie M Michelsen
- Department of Cardiology, Bispebjerg University Hospital, Copenhagen NV, Denmark
| | - Eva Prescott
- Department of Cardiology, Bispebjerg University Hospital, Copenhagen NV, Denmark
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Lewis GA, Schelbert EB, Naish JH, Bedson E, Dodd S, Eccleson H, Clayton D, Jimenez BD, McDonagh T, Williams SG, Cooper A, Cunnington C, Ahmed FZ, Viswesvaraiah R, Russell S, Neubauer S, Williamson PR, Miller CA. Pirfenidone in Heart Failure with Preserved Ejection Fraction-Rationale and Design of the PIROUETTE Trial. Cardiovasc Drugs Ther 2019; 33:461-470. [PMID: 31069575 PMCID: PMC6689029 DOI: 10.1007/s10557-019-06876-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The PIROUETTE (PIRfenidOne in patients with heart failUre and preserved lEfT venTricular Ejection fraction) trial is designed to evaluate the efficacy and safety of the anti-fibrotic pirfenidone in patients with chronic heart failure and preserved ejection fraction (HFpEF) and myocardial fibrosis. HFpEF is a diverse syndrome associated with substantial morbidity and mortality. Myocardial fibrosis is a key pathophysiological mechanism of HFpEF and myocardial fibrotic burden is strongly and independently associated with adverse outcome. Pirfenidone is an oral anti-fibrotic agent, without haemodynamic effect, that leads to regression of myocardial fibrosis in preclinical models. It has proven clinical effectiveness in pulmonary fibrosis. METHODS The PIROUETTE trial is a randomised, double-blind, placebo-controlled phase II trial evaluating the efficacy and safety of 52 weeks of treatment with pirfenidone in patients with chronic HFpEF (symptoms and signs of heart failure, left ventricular ejection fraction ≥ 45%, elevated natriuretic peptides [BNP ≥ 100 pg/ml or NT-proBNP ≥ 300 pg/ml; or BNP ≥ 300 pg/ml or NT-proBNP ≥ 900 pg/ml if in atrial fibrillation]) and myocardial fibrosis (extracellular matrix (ECM) volume ≥ 27% measured using cardiovascular magnetic resonance). The primary outcome measure is change in myocardial ECM volume. A sub-study will investigate the relationship between myocardial fibrosis and myocardial energetics, and the impact of pirfenidone, using 31phosphorus magnetic resonance spectroscopy. DISCUSSION PIROUETTE will determine whether pirfenidone is superior to placebo in relation to regression of myocardial fibrosis and improvement in myocardial energetics in patients with HFpEF and myocardial fibrosis (NCT02932566). CLINICAL TRIAL REGISTRATION clinicaltrials.gov (NCT02932566) https://clinicaltrials.gov/ct2/show/NCT02932566.
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Affiliation(s)
- Gavin A Lewis
- Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
- Manchester University NHS Foundation Trust, Southmoor Road, Wythenshawe, Manchester, M23 9LT, UK
| | - Erik B Schelbert
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- UPMC Cardiovascular Magnetic Resonance Center, Heart and Vascular Institute, Pittsburgh, PA, USA
- Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA
| | - Josephine H Naish
- Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
| | - Emma Bedson
- Clinical Trials Research Centre, 2nd Floor - Institute in the Park, Alder Hey Children's NHS Foundation Trust, University of Liverpool, Member of Liverpool Health Partners, Liverpool, L12 2AP, UK
| | - Susanna Dodd
- Department of Biostatistics, University of Liverpool, Member of Liverpool Health Partners, Block F, Waterhouse Bld, 1-5 Brownlow Street, Liverpool, L69 3GL, UK
| | - Helen Eccleson
- Clinical Trials Research Centre, 2nd Floor - Institute in the Park, Alder Hey Children's NHS Foundation Trust, University of Liverpool, Member of Liverpool Health Partners, Liverpool, L12 2AP, UK
| | - Dannii Clayton
- Clinical Trials Research Centre, 2nd Floor - Institute in the Park, Alder Hey Children's NHS Foundation Trust, University of Liverpool, Member of Liverpool Health Partners, Liverpool, L12 2AP, UK
| | - Beatriz Duran Jimenez
- Manchester University NHS Foundation Trust, Southmoor Road, Wythenshawe, Manchester, M23 9LT, UK
| | | | - Simon G Williams
- Manchester University NHS Foundation Trust, Southmoor Road, Wythenshawe, Manchester, M23 9LT, UK
| | - Anne Cooper
- Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK
| | - Colin Cunnington
- Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
- Manchester University NHS Foundation Trust, Southmoor Road, Wythenshawe, Manchester, M23 9LT, UK
| | - Fozia Zahir Ahmed
- Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
- Manchester University NHS Foundation Trust, Southmoor Road, Wythenshawe, Manchester, M23 9LT, UK
| | - Rajavarma Viswesvaraiah
- Stockport NHS Foundation Trust, Stepping Hill Hospital, Poplar Grove, Hazel Grove, Stockport, SK2 7JE, UK
| | - Stuart Russell
- East Cheshire NHS Trust, Victoria Road, Macclesfield, SK10 3BL, UK
| | - Stefan Neubauer
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Paula R Williamson
- Department of Biostatistics, University of Liverpool, Member of Liverpool Health Partners, Block F, Waterhouse Bld, 1-5 Brownlow Street, Liverpool, L69 3GL, UK
| | - Christopher A Miller
- Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
- Manchester University NHS Foundation Trust, Southmoor Road, Wythenshawe, Manchester, M23 9LT, UK.
- Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
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28
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Ma N, Lu R, Zhao D, Jiang Z, Tang M, Bao C, Mei J. Left Atrial Appendage Fibrosis and 3-Year Clinical Outcomes in Atrial Fibrillation After Endoscopic Ablation: A Histologic Analysis. Ann Thorac Surg 2019; 109:69-76. [PMID: 31302082 DOI: 10.1016/j.athoracsur.2019.05.055] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 04/05/2019] [Accepted: 05/20/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND Interest has been increasing in the study of atrial fibrosis, an important mechanism in atrial matrix remodeling. However, histopathologic evaluation of atrial fibrosis in non-valvular atrial fibrillation (NVAF) has been limited. This study aimed to analyze the histologic relationship between atrial fibrosis and development or recurrence of NVAF after endoscopic ablation. METHODS Patients (n = 136) with NVAF undergoing endoscopic ablation and 10 patients in sinus rhythm were enrolled in this study. Left atrial appendage was harvested from all patients. Collagen volume fraction (CVF) and fibrosis biomarkers were evaluated. Linear regression analysis was performed to determine the correlation between clinical variables and atrial fibrosis. The association between atrial fibrosis and NVAF recurrence was evaluated with the Cox proportional hazards model. RESULTS A significant difference was found in the degree of atrial fibrosis between patients with NVAF and sinus rhythm (CVF: median 15 [interquartile range (IQR), 13-17] vs median 6.5 [IQR, 5-10.25]; P < .001, respectively). Factors independently associated with CVF in multivariate linear regression analysis included longer duration of NVAF and larger left atrial diameter. Among 136 patients with ablation, 19 (13.9%) had recurrent NVAF. In multivariate Cox regression analysis, CVF (hazard ratio [HR] 1.093; 95% confidence interval [CI], 1.007-1.186; P = .033) and left atrial diameter (HR for 3-mm change 1.240; 95% CI, 1.004-1.531; P = .046) were independent risk factors for NVAF recurrence. CONCLUSIONS Atrial fibrosis in NVAF is not only associated with left atrial diameter and duration of atrial fibrillation but also with recurrence after ablation. Atrial fibrosis may be a future therapeutic target for reduction of recurrence after endoscopic ablation.
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Affiliation(s)
- Nan Ma
- Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China
| | - Rongxin Lu
- Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China; Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Dongfang Zhao
- Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan
| | - Zhaolei Jiang
- Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China
| | - Min Tang
- Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China
| | - Chunrong Bao
- Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China
| | - Ju Mei
- Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China.
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Schelbert EB, Fridman Y, Wong TC, Abu Daya H, Piehler KM, Kadakkal A, Miller CA, Ugander M, Maanja M, Kellman P, Shah DJ, Abebe KZ, Simon MA, Quarta G, Senni M, Butler J, Diez J, Redfield MM, Gheorghiade M. Temporal Relation Between Myocardial Fibrosis and Heart Failure With Preserved Ejection Fraction: Association With Baseline Disease Severity and Subsequent Outcome. JAMA Cardiol 2019; 2:995-1006. [PMID: 28768311 DOI: 10.1001/jamacardio.2017.2511] [Citation(s) in RCA: 162] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Importance Among myriad changes occurring during the evolution of heart failure with preserved ejection fraction (HFpEF), cardiomyocyte-extracellular matrix interactions from excess collagen may affect microvascular, mechanical, and electrical function. Objective To investigate whether myocardial fibrosis (MF) is similarly prevalent both in those with HFpEF and those at risk for HFpEF, similarly associating with disease severity and outcomes. Design, Setting, and Participants Observational cohort study from June 1, 2010, to September 17, 2015, with follow-up until December 14, 2015, at a cardiovascular magnetic resonance (CMR) center serving an integrated health system. Consecutive patients with preserved systolic function referred for CMR were eligible. Cardiovascular magnetic resonance was used to exclude patients with cardiac amyloidosis (n = 19). Exposures Myocardial fibrosis quantified by extracellular volume (ECV) CMR measures. Main Outcome and Measures Baseline BNP; subsequent hospitalization for heart failure or death. Results Of 1174 patients identified (537 [46%] female; median [interquartile range {IQR}] age, 56 [44-66] years), 250 were "at risk" for HFpEF given elevated brain-type natriuretic peptide (BNP) level; 160 had HFpEF by documented clinical diagnosis, and 745 did not have HFpEF. Patients either at risk for HFpEF or with HFpEF demonstrated similarly higher prevalence/extent of MF and worse prognosis compared with patients with no HFpEF. Among those at risk for HFpEF or with HFpEF, the actual diagnosis of HFpEF was not associated with significant differences in MF (median ECV, 28.2%; IQR, 26.2%-30.7% vs 28.3%; IQR, 25.5%-31.4%; P = .60) or prognosis (log-rank 0.8; P = .38). Over a median of 1.9 years, 61 patients at risk for HFpEF or with HFpEF experienced adverse events (19 hospitalization for heart failure, 48 deaths, 6 with both). In those with HFpEF, ECV was associated with baseline log BNP (disease severity surrogate) in multivariable linear regression models, and was associated with outcomes in multivariable Cox regression models (eg, hazard ratio 1.75 per 5% increase in ECV, 95% CI, 1.25-2.45; P = .001 in stepwise model) whether grouped with patients at risk for HFpEF or not. Conclusions and Relevance Among myriad changes occurring during the apparent evolution of HFpEF where elevated BNP is prevalent, MF was similarly prevalent in those with or at risk for HFpEF. Conceivably, MF might precede clinical HFpEF diagnosis. Regardless, MF was associated with disease severity (ie, BNP) and outcomes. Whether cells and secretomes mediating MF represent therapeutic targets in HFpEF warrants further evaluation.
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Affiliation(s)
- Erik B Schelbert
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.,UPMC Cardiovascular Magnetic Resonance Center, Heart and Vascular Institute, Pittsburgh, Pennsylvania.,Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Yaron Fridman
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.,UPMC Cardiovascular Magnetic Resonance Center, Heart and Vascular Institute, Pittsburgh, Pennsylvania
| | - Timothy C Wong
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.,UPMC Cardiovascular Magnetic Resonance Center, Heart and Vascular Institute, Pittsburgh, Pennsylvania.,Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Hussein Abu Daya
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.,UPMC Cardiovascular Magnetic Resonance Center, Heart and Vascular Institute, Pittsburgh, Pennsylvania
| | - Kayla M Piehler
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.,UPMC Cardiovascular Magnetic Resonance Center, Heart and Vascular Institute, Pittsburgh, Pennsylvania.,Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Ajay Kadakkal
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.,UPMC Cardiovascular Magnetic Resonance Center, Heart and Vascular Institute, Pittsburgh, Pennsylvania
| | - Christopher A Miller
- Centre for Imaging Sciences and Biomedical Imaging Institute, University of Manchester, Manchester, England
| | - Martin Ugander
- Department of Clinical Physiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Maren Maanja
- Department of Clinical Physiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Peter Kellman
- National Heart, Lung, and Blood Institute, Bethesda, Maryland
| | - Dipan J Shah
- Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas
| | - Kaleab Z Abebe
- Center for Clinical Trials and Data Coordination, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Marc A Simon
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.,Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Giovanni Quarta
- Department of Cardiology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - Michele Senni
- Department of Cardiology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - Javed Butler
- Cardiology Division, Stony Brook University, Stony Brook, New York
| | - Javier Diez
- Program of Cardiovascular Diseases, Center for Applied Medical Research, Department of Cardiology and Cardiac Surgery, University Clinic, University of Navarra, Pamplona, Spain.,CIBERCV, Carlos III Institute of Health, Madrid, Spain
| | | | - Mihai Gheorghiade
- Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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Fibrosis miocárdica: hacia una nueva aproximación. REVISTA COLOMBIANA DE CARDIOLOGÍA 2019. [DOI: 10.1016/j.rccar.2018.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Bax JJ, Di Carli M, Narula J, Delgado V. Multimodality imaging in ischaemic heart failure. Lancet 2019; 393:1056-1070. [PMID: 30860031 DOI: 10.1016/s0140-6736(18)33207-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 12/01/2018] [Accepted: 12/07/2018] [Indexed: 12/30/2022]
Abstract
In heart failure, extensive evaluation with modern non-invasive imaging modalities is needed to assess causes, pathophysiology, and haemodynamics, to determine prognosis and consider therapeutic options. This systematic evaluation includes a stepwise assessment of left ventricular size and function, the presence and severity of coronary artery disease, mitral regurgitation, pulmonary hypertension, right ventricular dilation and dysfunction, and tricuspid regurgitation. Based on this imaging-derived information, the need for specific therapies besides optimised medical therapy can be determined. The need for revascularisation, implantation of an implantable cardiac defibrillator, and mitral or tricuspid valve repair or replacement, can be (partially) guided by non-invasive imaging. Importantly, randomised controlled trials on the use of non-inasive imaging to guide therapy are scarce in this field and most non-pharmacological therapies are based on expert-consensus, but whenever trials are available, they will be addressed in this paper.
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Affiliation(s)
- Jeroen J Bax
- Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands.
| | - Marcelo Di Carli
- Departments of Radiology and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, NY, USA
| | - Jagat Narula
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Victoria Delgado
- Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands
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Incremental value of extracellular volume assessment by cardiovascular magnetic resonance imaging in risk stratifying patients with suspected myocarditis. Int J Cardiovasc Imaging 2019; 35:1067-1078. [DOI: 10.1007/s10554-019-01552-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 02/02/2019] [Indexed: 01/27/2023]
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Abraham DM, Lee TE, Watson LJ, Mao L, Chandok G, Wang HG, Frangakis S, Pitt GS, Shah SH, Wolf MJ, Rockman HA. The two-pore domain potassium channel TREK-1 mediates cardiac fibrosis and diastolic dysfunction. J Clin Invest 2018; 128:4843-4855. [PMID: 30153110 PMCID: PMC6205385 DOI: 10.1172/jci95945] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 08/23/2018] [Indexed: 01/08/2023] Open
Abstract
Cardiac two-pore domain potassium channels (K2P) exist in organisms from Drosophila to humans; however, their role in cardiac function is not known. We identified a K2P gene, CG8713 (sandman), in a Drosophila genetic screen and show that sandman is critical to cardiac function. Mice lacking an ortholog of sandman, TWIK-related potassium channel (TREK-1, also known Kcnk2), exhibit exaggerated pressure overload-induced concentric hypertrophy and alterations in fetal gene expression, yet retain preserved systolic and diastolic cardiac function. While cardiomyocyte-specific deletion of TREK-1 in response to in vivo pressure overload resulted in cardiac dysfunction, TREK-1 deletion in fibroblasts prevented deterioration in cardiac function. The absence of pressure overload-induced dysfunction in TREK-1-KO mice was associated with diminished cardiac fibrosis and reduced activation of JNK in cardiomyocytes and fibroblasts. These findings indicate a central role for cardiac fibroblast TREK-1 in the pathogenesis of pressure overload-induced cardiac dysfunction and serve as a conceptual basis for its inhibition as a potential therapy.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Howard A Rockman
- Department of Medicine
- Department of Cell Biology, and
- Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA
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Abstract
PURPOSE OF REVIEW When patients are seen for persistent chest pain in the absence of obstructive coronary artery disease, the physician must decide if the symptoms are due to myocardial ischemia in order to guide treatment. RECENT FINDINGS Recent findings indicate that ischemia due to coronary microvascular dysfunction (CMD) is associated with subclinical coronary atherosclerosis and an adverse prognosis. Therapeutic probe trials suggest that antiatherosclerotic and anti-ischemic therapeutic strategies may be useful. A large randomized clinical trial of high-intensity statin, maximally tolerated angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker and low-dose aspirin (WARRIOR NCT#03417388) is in progress. SUMMARY The diagnosis of CMD should be considered in patients with persistent angina, evidence of myocardial ischemia and normal coronary angiogram. Because of the associated adverse prognosis of CMD , conservative empiric treatment or further diagnostic evaluation of the coronary microvasculature can be performed. Diagnosis involves the measurement of coronary blood blow in response to a vasodilator agent invasively or noninvasively. Treatment of CMD can include the use of traditional antianginal and antiatherosclerotic medications. Clinical trials are needed to assess therapeutic strategies on the outcomes of cardiovascular disease and quality of life, in order to develop evidence-based guidelines.
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Affiliation(s)
- Janet Wei
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, California, USA
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Michelsen MM, Rask AB, Suhrs E, Raft KF, Høst N, Prescott E. Effect of ACE-inhibition on coronary microvascular function and symptoms in normotensive women with microvascular angina: A randomized placebo-controlled trial. PLoS One 2018; 13:e0196962. [PMID: 29883497 PMCID: PMC5993253 DOI: 10.1371/journal.pone.0196962] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2018] [Accepted: 04/23/2018] [Indexed: 12/13/2022] Open
Abstract
Objective Studies have suggested a beneficial effect of angiotensin-converting enzyme (ACE) inhibition. To explore whether the ACE inhibitor ramipril has a direct effect on the microvasculature beyond the blood pressure (BP) lowering effect, we investigated whether ramipril improved coronary microvascular function in normotensive women with coronary microvascular dysfunction (CMD). Methods We included 63 normotensive women with angina, no epicardial stenosis>50% and CMD defined as a coronary flow velocity reserve (CFVR)<2.2 assessed by adenosine stress-echocardiography in a randomized double-blinded, superiority trial with 1:1 allocation to placebo or ramipril (maximum dose 10 mg depending on blood pressure) for 24±6 weeks. Primary outcome was CFVR. Secondary outcomes were left ventricular systolic and diastolic function and symptoms evaluated by Seattle Angina Questionnaire (clinicaltrials.gov, NCT02525081). Results Follow-up was available on 55 patients. BP remained unchanged during treatment in both groups. CFVR improved in both the ramipril (p = 0.004) and placebo group (p = 0.026) with no difference between groups (p = 0.63). Symptoms improved in both groups with no significant between-group differences. No changes were detected in parameters of systolic and diastolic function. No serious adverse reactions were reported. Conclusions In normotensive women with angina and CMD, treatment with ramipril had no significant effect on CFVR or symptoms compared with placebo. The effect of ACE inhibition previously reported may be mediated by blood pressure reduction.
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Affiliation(s)
- Marie Mide Michelsen
- Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Anna Bay Rask
- Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Elena Suhrs
- Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | | | - Nis Høst
- Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Eva Prescott
- Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
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Abstract
Heart failure is a growing cardiovascular disease with significant epidemiological, clinical, and societal implications and represents a high unmet need. Strong efforts are currently underway by academic and industrial researchers to develop novel treatments for heart failure. Biomarkers play an important role in patient selection and monitoring in drug trials and in clinical management. The present review gives an overview of the role of available molecular, imaging, and device-derived digital biomarkers in heart failure drug development and highlights capabilities and limitations of biomarker use in this context.
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Coronary Microcirculatory Dysfunction in Human Cardiomyopathies: A Pathologic and Pathophysiologic Review. Cardiol Rev 2018; 25:165-178. [PMID: 28574936 DOI: 10.1097/crd.0000000000000140] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Cardiomyopathies are a heterogeneous group of diseases of the myocardium. The term cardiomyopathy involves a wide range of pathogenic mechanisms that affect the structural and functional states of cardiomyocytes, extravascular tissues, and coronary vasculature, including both epicardial coronary arteries and the microcirculation. In the developed phase, cardiomyopathies present with various clinical symptoms: dyspnea, chest pain, palpitations, swelling of the extremities, arrhythmias, and sudden cardiac death. Due to the heterogeneity of cardiomyopathic patterns and symptoms, their diagnosis and therapies are great challenges. Despite extensive research, the relation between the structural and functional abnormalities of the myocardium and the coronary circulation are still not well understood in the various forms of cardiomyopathy. The main pathological characteristics of cardiomyopathies and the coronary microcirculation develop in a progressive manner due to (1) genetic-immunologic-systemic factors; (2) comorbidities with endothelial, myogenic, metabolic, and inflammatory changes; (3) aging-induced arteriosclerosis; and (4) myocardial fibrosis. The aim of this review is to summarize the most important common pathological features and/or adaptations of the coronary microcirculation in various types of cardiomyopathies and to integrate the present understanding of the underlying pathophysiological mechanisms responsible for the development of various types of cardiomyopathies. Although microvascular dysfunction is present and contributes to cardiac dysfunction and the potential outcome of disease, the current therapeutic approaches are not specific for the given types of cardiomyopathy.
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Huelnhagen T, Ku MC, Reimann HM, Serradas Duarte T, Pohlmann A, Flemming B, Seeliger E, Eichhorn C, A Ferrari V, Prothmann M, Schulz-Menger J, Niendorf T. Myocardial Effective Transverse Relaxation Time T 2* is Elevated in Hypertrophic Cardiomyopathy: A 7.0 T Magnetic Resonance Imaging Study. Sci Rep 2018; 8:3974. [PMID: 29507338 PMCID: PMC5838254 DOI: 10.1038/s41598-018-22439-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 02/19/2018] [Indexed: 12/18/2022] Open
Abstract
Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the myocardium and bares the risk of progression to heart failure or sudden cardiac death. Identifying patients at risk remains an unmet need. Recognizing the dependence of microscopic susceptibility on tissue microstructure and on cardiac macromorphology we hypothesized that myocardial T2* might be altered in HCM patients compared to healthy controls. To test this hypothesis, myocardial T2*-mapping was conducted at 7.0 Tesla to enhance T2*-contrast. 2D CINE T2*-mapping was performed in healthy controls and HCM patients. To ensure that T2* is not dominated by macroscopic magnetic field inhomogeneities, volume selective B0 shimming was applied. T2* changes in the interventricular septum across the cardiac cycle were analyzed together with left ventricular radius and ventricular septal wall thickness. The results show that myocardial T2* is elevated throughout the cardiac cycle in HCM patients compared to healthy controls. A mean septal T2* = 13.7 ± 1.1 ms (end-systole: T2*,systole = 15.0 ± 2.1, end-diastole: T2*,diastole = 13.4 ± 1.3 ms, T2*,systole/T2*,diastole ratio = 1.12) was observed in healthy controls. For HCM patients a mean septal T2* = 17.4 ± 1.4 ms (end-systole: T2*,systole = 17.7 ± 1.2 ms, end-diastole: T2*,diastole = 16.2 ± 2.5 ms, T2*,systole/T2*,diastole ratio = 1.09) was found. Our preliminary results provide encouragement that assessment of T2* and its changes across the cardiac cycle may benefit myocardial tissue characterization in HCM.
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Affiliation(s)
- Till Huelnhagen
- Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
| | - Min-Chi Ku
- Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), partner site, Berlin, Germany
| | - Henning Matthias Reimann
- Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
| | - Teresa Serradas Duarte
- Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
| | - Andreas Pohlmann
- Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
| | - Bert Flemming
- Institute of Vegetative Physiology, Charité University Medicine, Berlin, Germany
| | - Erdmann Seeliger
- Institute of Vegetative Physiology, Charité University Medicine, Berlin, Germany
| | - Christina Eichhorn
- Statistical Sciences, Department of Information Technology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
| | - Victor A Ferrari
- Division of Cardiovascular Medicine and Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
| | - Marcel Prothmann
- DZHK (German Centre for Cardiovascular Research), partner site, Berlin, Germany
- Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, Germany
| | - Jeanette Schulz-Menger
- DZHK (German Centre for Cardiovascular Research), partner site, Berlin, Germany
- Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, Germany
| | - Thoralf Niendorf
- Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
- DZHK (German Centre for Cardiovascular Research), partner site, Berlin, Germany.
- Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, Germany.
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Pacheco Claudio C, Quesada O, Pepine CJ, Noel Bairey Merz C. Why names matter for women: MINOCA/INOCA (myocardial infarction/ischemia and no obstructive coronary artery disease). Clin Cardiol 2018; 41:185-193. [PMID: 29498752 DOI: 10.1002/clc.22894] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Accepted: 01/05/2018] [Indexed: 12/19/2022] Open
Abstract
The syndromes of myocardial infarction/myocardial ischemia with No Obstructive Coronary Artery Disease (MINOCA/INOCA) are increasingly evident. A majority of these patients have coronary microvascular dysfunction. These patients have elevated risk for a cardiovascular event (including acute coronary syndrome, myocardial infarction, stroke, and repeated cardiovascular procedures) and appear to be at higher risk for development of heart failure with preserved ejection fraction. Terminology such as coronary artery disease or coronary heart disease is often synonymous with obstructive atherosclerosis in the clinician's mind, leaving one at a loss to recognize or explain the phenomenon of MINOCA and INOCA with elevated risk. We review the available literature regarding stable and unstable ischemic heart disease that suggests that use of the ischemic heart disease (IHD) terminology matters for women, and should facilitate recognition of risk to provide potential treatment targets and optimized health.
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Affiliation(s)
| | - Odayme Quesada
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, California
| | - Carl J Pepine
- Division of Cardiology, University of Florida, Gainesville, Florida
| | - C Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, California
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Increased myocardial extracellular volume assessed by cardiovascular magnetic resonance T1 mapping and its determinants in type 2 diabetes mellitus patients with normal myocardial systolic strain. Cardiovasc Diabetol 2018; 17:7. [PMID: 29301529 PMCID: PMC5755204 DOI: 10.1186/s12933-017-0651-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Accepted: 12/23/2017] [Indexed: 02/07/2023] Open
Abstract
Background Cardiac magnetic resonance (CMR) T1 mapping and tissue-tracking strain analysis are useful quantitative techniques that can characterize myocardial tissue and mechanical alterations, respectively, in patients with early diabetic cardiomyopathy. The purpose of this study was to assess the left ventricular myocardial T1 value, extracellular volume fraction (ECV), and systolic strain in asymptomatic patients with type 2 diabetes mellitus (T2DM) and their underlying relationships with clinical parameters. Methods We recruited 50 T2DM patients (mean age: 55 ± 7 years; 28 males) and 32 sex-, age-and BMI-matched healthy volunteers to undergo contrast-enhanced CMR examinations. The myocardial native T1, post-contrast T1 and ECV values of the left ventricle were measured from T1 and ECV maps acquired using the modified Look-Locker inversion recovery technique. The left ventricular global systolic strain and the strain rates were evaluated using routine cine images and tissue-tracking analysis software. The baseline clinical and biochemical indices were collected before the CMR examination. Results The myocardial ECV and native T1 values were significantly higher in the diabetic patients than in the controls. (ECV: 27.4 ± 2.5% vs. 24.6 ± 2.2%, p < 0.001; native T1: 1026.9 ± 30.0 ms vs. 1011.8 ± 26.0 ms, p = 0.022). However, the left ventricular global systolic strain, strain rate, volume, myocardial mass, ejection fraction, and left atrial volume were similar between the diabetic patients and the healthy controls. In the diabetic patients, the native T1 values were independently correlated with the hemoglobin A1c levels (standardized β = 0.368, p = 0.008). The ECVs were independently associated with the hemoglobin A1c levels (standardized β = 0.389, p = 0.002), angiotensin-converting enzyme inhibitor (ACEI) treatment (standardized β = − 0.271, p = 0.025) and HCT values (standardized β = − 0.397, p = 0.001). Conclusions Type 2 diabetes mellitus patients with normal myocardial systolic strain exhibit increased native T1 values and ECVs indicative of myocardial extracellular interstitial expansion, which might be related to poor glycemic control. The amelioration of myocardial interstitial matrix expansion might be associated with ACEI treatment. A valid assessment of the association of glucose control and ACEI treatment with myocardial fibrosis requires notably larger trials.
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Gyöngyösi M, Winkler J, Ramos I, Do QT, Firat H, McDonald K, González A, Thum T, Díez J, Jaisser F, Pizard A, Zannad F. Myocardial fibrosis: biomedical research from bench to bedside. Eur J Heart Fail 2017; 19:177-191. [PMID: 28157267 PMCID: PMC5299507 DOI: 10.1002/ejhf.696] [Citation(s) in RCA: 287] [Impact Index Per Article: 35.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 09/07/2016] [Accepted: 10/01/2016] [Indexed: 01/05/2023] Open
Abstract
Myocardial fibrosis refers to a variety of quantitative and qualitative changes in the interstitial myocardial collagen network that occur in response to cardiac ischaemic insults, systemic diseases, drugs, or any other harmful stimulus affecting the circulatory system or the heart itself. Myocardial fibrosis alters the architecture of the myocardium, facilitating the development of cardiac dysfunction, also inducing arrhythmias, influencing the clinical course and outcome of heart failure patients. Focusing on myocardial fibrosis may potentially improve patient care through the targeted diagnosis and treatment of emerging fibrotic pathways. The European Commission funded the FIBROTARGETS consortium as a multinational academic and industrial consortium with the primary aim of performing a systematic and collaborative search of targets of myocardial fibrosis, and then translating these mechanisms into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure. This review focuses on those methodological and technological aspects considered and developed by the consortium to facilitate the transfer of the new mechanistic knowledge on myocardial fibrosis into potential biomedical applications.
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Affiliation(s)
| | | | - Isbaal Ramos
- Innovative Technologies in Biological Systems SL (INNOPROT), Bizkaia, Spain
| | | | | | | | - Arantxa González
- Program of Cardiovascular Diseases, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
| | - Thomas Thum
- Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Germany.,National Heart and Lung Institute, Imperial College London, UK
| | - Javier Díez
- Program of Cardiovascular Diseases, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.,Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, University of Navarra, Pamplona, Spain
| | - Frédéric Jaisser
- Centre de Recherche des Cordeliers, Inserm U1138, Université Pierre et Marie Curie, Paris, France
| | - Anne Pizard
- UMRS U1116 Inserm, CIC 1433, Pierre Drouin, CHU, Université de Lorraine, Nancy, France
| | - Faiez Zannad
- UMRS U1116 Inserm, CIC 1433, Pierre Drouin, CHU, Université de Lorraine, Nancy, France
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Banerjee P. Heart failure: a story of damage, fatigue and injury? Open Heart 2017; 4:e000684. [PMID: 29081980 PMCID: PMC5652497 DOI: 10.1136/openhrt-2017-000684] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 08/29/2017] [Accepted: 09/26/2017] [Indexed: 12/16/2022] Open
Abstract
Heart failure has been recognised for years but the complete picture has been difficult to clearly understand. This article aims to try and put forward a proposed mechanistic explanation to encompass all that we see within the clinical heart failure syndrome using supporting published evidence. The aim of the article is to link, using published evidence, all the known varieties of heart failure into a spectrum that is explained by simple interlinked processes. In addition, the concept of routinely looking for reversibility of left ventricular dysfunction is introduced.
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Affiliation(s)
- Prithwish Banerjee
- Department of Cardiology, University Hospitals Coventry and Warwickshire, Coventry, UK
- Faculty of Health and Life Sciences, Coventry University, Coventry, UK
- Warwick Medical School, University of Warwick, Coventry, UK
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Mavrogeni S, Apostolou D, Argyriou P, Velitsista S, Papa L, Efentakis S, Vernardos E, Kanoupaki M, Kanoupakis G, Manginas A. T1 and T2 Mapping in Cardiology: “Mapping the Obscure Object of Desire”. Cardiology 2017; 138:207-217. [DOI: 10.1159/000478901] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 06/21/2017] [Indexed: 12/24/2022]
Abstract
The increasing use of cardiovascular magnetic resonance (CMR) is based on its capability to perform biventricular function assessment and tissue characterization without radiation and with high reproducibility. The use of late gadolinium enhancement (LGE) gave the potential of non-invasive biopsy for fibrosis quantification. However, LGE is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) provide knowledge about pathologies affecting both the myocardium and interstitium that is otherwise difficult to identify. Changes of myocardial native T1 reflect cardiac diseases (acute coronary syndromes, infarction, myocarditis, and diffuse fibrosis, all with high T1) and systemic diseases such as cardiac amyloid (high T1), Anderson-Fabry disease (low T1), and siderosis (low T1). The ECV, an index generated by native and post-contrast T1 mapping, measures the cellular and extracellular interstitial matrix (ECM) compartments. This myocyte-ECM dichotomy has important implications for identifying specific therapeutic targets of great value for heart failure treatment. On the other hand, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset heart failure. Although these indices can significantly affect the clinical decision making, multicentre studies and a community-wide approach (including MRI vendors, funding, software, contrast agent manufacturers, and clinicians) are still missing.
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Saeed M, Liu H, Liang CH, Wilson MW. Magnetic resonance imaging for characterizing myocardial diseases. Int J Cardiovasc Imaging 2017; 33:1395-1414. [PMID: 28364177 DOI: 10.1007/s10554-017-1127-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 03/23/2017] [Indexed: 12/21/2022]
Abstract
The National Institute of Health defined cardiomyopathy as diseases of the heart muscle. These myocardial diseases have different etiology, structure and treatment. This review highlights the key imaging features of different myocardial diseases. It provides information on myocardial structure/orientation, perfusion, function and viability in diseases related to cardiomyopathy. The standard cardiac magnetic resonance imaging (MRI) sequences can reveal insight on left ventricular (LV) mass, volumes and regional contractile function in all types of cardiomyopathy diseases. Contrast enhanced MRI sequences allow visualization of different infarct patterns and sizes. Enhancement of myocardial inflammation and infarct (location, transmurality and pattern) on contrast enhanced MRI have been used to highlight the key differences in myocardial diseases, predict recovery of function and healing. The common feature in many forms of cardiomyopathy is the presence of diffuse-fibrosis. Currently, imaging sequences generating the most interest in cardiomyopathy include myocardial strain analysis, tissue mapping (T1, T2, T2*) and extracellular volume (ECV) estimation techniques. MRI sequences have the potential to decode the etiology by showing various patterns of infarct and diffuse fibrosis in myocarditis, amyloidosis, sarcoidosis, hypertrophic cardiomyopathy due to aortic stenosis, restrictive cardiomyopathy, arrythmogenic right ventricular dysplasia and hypertension. Integrated PET/MRI system may add in the future more information for the diagnosis and progression of cardiomyopathy diseases. With the promise of high spatial/temporal resolution and 3D coverage, MRI will be an indispensible tool in diagnosis and monitoring the benefits of new therapies designed to treat myocardial diseases.
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Affiliation(s)
- Maythem Saeed
- Department of Radiology and Biomedical Imaging, School of Medicine, University of California San Francisco, 185 Berry Street, Suite 350, Campus Box 0946, San Francisco, CA, 94107-5705, USA.
| | - Hui Liu
- Department of Radiology, Guangdong General Hospital, Guangzhou, China
| | - Chang-Hong Liang
- Department of Radiology, Guangdong General Hospital, Guangzhou, China
| | - Mark W Wilson
- Department of Radiology and Biomedical Imaging, School of Medicine, University of California San Francisco, 185 Berry Street, Suite 350, Campus Box 0946, San Francisco, CA, 94107-5705, USA
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Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL. Ischemia and No Obstructive Coronary Artery Disease (INOCA): Developing Evidence-Based Therapies and Research Agenda for the Next Decade. Circulation 2017; 135:1075-1092. [PMID: 28289007 PMCID: PMC5385930 DOI: 10.1161/circulationaha.116.024534] [Citation(s) in RCA: 521] [Impact Index Per Article: 65.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The Cardiovascular Disease in Women Committee of the American College of Cardiology, in conjunction with interested parties (from the National Heart, Lung, and Blood Institute, American Heart Association, and European Society of Cardiology), convened a working group to develop a consensus on the syndrome of myocardial ischemia with no obstructive coronary arteries. In general, these patients have elevated risk for a cardiovascular event (including acute coronary syndrome, heart failure hospitalization, stroke, and repeat cardiovascular procedures) compared with reference subjects and appear to be at higher risk for development of heart failure with preserved ejection fraction. A subgroup of these patients also has coronary microvascular dysfunction and evidence of inflammation. This document provides a summary of findings and recommendations for the development of an integrated approach for identifying and managing patients with ischemia with no obstructive coronary arteries and outlines knowledge gaps in the area. Working group members critically reviewed available literature and current practices for risk assessment and state-of-the-science techniques in multiple areas, with a focus on next steps needed to develop evidence-based therapies. This report presents highlights of this working group review and a summary of suggested research directions to advance this field in the next decade.
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Affiliation(s)
- C Noel Bairey Merz
- From Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA (C.N.B.M.); Division of Cardiology, University of Florida, Gainesville (C.J.P.); St. Vincent Heart Transplant, Indianapolis, IN (M.N.W.); and National Heart, Lung, and Blood Institute, Bethesda, MD (J.L.F.).
| | - Carl J Pepine
- From Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA (C.N.B.M.); Division of Cardiology, University of Florida, Gainesville (C.J.P.); St. Vincent Heart Transplant, Indianapolis, IN (M.N.W.); and National Heart, Lung, and Blood Institute, Bethesda, MD (J.L.F.)
| | - Mary Norine Walsh
- From Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA (C.N.B.M.); Division of Cardiology, University of Florida, Gainesville (C.J.P.); St. Vincent Heart Transplant, Indianapolis, IN (M.N.W.); and National Heart, Lung, and Blood Institute, Bethesda, MD (J.L.F.)
| | - Jerome L Fleg
- From Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA (C.N.B.M.); Division of Cardiology, University of Florida, Gainesville (C.J.P.); St. Vincent Heart Transplant, Indianapolis, IN (M.N.W.); and National Heart, Lung, and Blood Institute, Bethesda, MD (J.L.F.)
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Adam RD, Shambrook J, Flett AS. The Prognostic Role of Tissue Characterisation using Cardiovascular Magnetic Resonance in Heart Failure. Card Fail Rev 2017; 3:86-96. [PMID: 29387459 DOI: 10.15420/cfr.2017:19:1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Despite significant advances in heart failure diagnostics and therapy, the prognosis remains poor, with one in three dying within a year of hospital admission. This is at least in part due to the difficulties in risk stratification and personalisation of therapy. The use of left ventricular systolic function as the main arbiter for entrance into clinical trials for drugs and advanced therapy, such as implantable defibrillators, grossly simplifies the complex heterogeneous nature of the syndrome. Cardiovascular magnetic resonance offers a wealth of data to aid in diagnosis and prognostication. The advent of novel cardiovascular magnetic resonance mapping techniques allows us to glimpse some of the pathophysiological mechanisms underpinning heart failure. We review the growing prognostic evidence base using these techniques.
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Affiliation(s)
- Robert D Adam
- Department of Cardiology, University Hospital Southampton,Southampton, UK
| | - James Shambrook
- Department of Cardiology, University Hospital Southampton,Southampton, UK
| | - Andrew S Flett
- Department of Cardiology, University Hospital Southampton,Southampton, UK
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Chen C, Wei J, AlBadri A, Zarrini P, Bairey Merz CN. Coronary Microvascular Dysfunction - Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy. Circ J 2016; 81:3-11. [PMID: 27904032 PMCID: PMC8607842 DOI: 10.1253/circj.cj-16-1002] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/20/2023]
Abstract
Angina has traditionally been thought to be caused by obstructive coronary artery disease (CAD). However, a substantial number of patients with angina are found to not have obstructive CAD when undergoing coronary angiography. A significant proportion of these patients have coronary microvascular dysfunction (CMD), characterized by heightened sensitivity to vasoconstrictor stimuli and limited microvascular vasodilator capacity. With the advent of non-invasive and invasive techniques, the coronary microvasculature has been more extensively studied in the past 2 decades. CMD has been identified as a cause of cardiac ischemia, in addition to traditional atherosclerotic disease and vasospastic disease. CMD can occur alone or in the presence obstructive CAD. CMD shares many similar risk factors with macrovascular CAD. Diagnosis is achieved through detection of an attenuated response of coronary blood flow in response to vasodilatory agents. Imaging modalities such as cardiovascular magnetic resonance, positron emission tomography, and transthoracic Doppler echocardiography have become more widely used, but have not yet completely replaced the traditional intracoronary vasoreactivity testing. Treatment of CMD starts with lifestyle modification and risk factor control. The use of traditional antianginal, antiatherosclerotic medications and some novel agents may be beneficial; however, clinical trials are needed to assess the efficacy of the pharmacologic and non-pharmacologic therapeutic modalities. In addition, studies with longer-term follow-up are needed to determine the prognostic benefits of these agents. We review the epidemiology, prognosis, pathogenesis, diagnosis, risk factors and current therapies for CMD.
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Affiliation(s)
- Cheng Chen
- Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center
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Frohlich ED. Review: Promise of prevention and reversal of target organ involvement in hypertension. J Renin Angiotensin Aldosterone Syst 2016; 2:S4-S9. [DOI: 10.1177/14703203010020010101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Schelbert EB, Messroghli DR. State of the Art: Clinical Applications of Cardiac T1 Mapping. Radiology 2016; 278:658-76. [DOI: 10.1148/radiol.2016141802] [Citation(s) in RCA: 128] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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