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Wang YT, Moura AK, Zuo R, Roudbari K, Hu JZ, Khan SA, Wang Z, Shentu Y, Wang M, Li PL, Hao J, Zhang Y, Li X. Cardiovascular dysfunction and altered lysosomal signaling in a murine model of acid sphingomyelinase deficiency. J Mol Med (Berl) 2025; 103:599-617. [PMID: 40232391 DOI: 10.1007/s00109-025-02542-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 03/18/2025] [Accepted: 04/02/2025] [Indexed: 04/16/2025]
Abstract
Niemann-Pick Disease (NPD) is a rare autosomal recessive lysosomal storage disorder (LSD) caused by the deficiency of acid sphingomyelinase (ASMD), which is encoded by the Smpd1 gene. ASMD impacts multiple organ systems in the body, including the cardiovascular system. This study is the first to characterize cardiac pathological changes in ASMD mice under baseline conditions, offering novel insights into the cardiac implications of NPD. Using histological analysis, biochemical assays, and echocardiography, we assessed cardiac pathological changes and function in Smpd1-/- mice compared to Smpd1+/+ littermate controls. Immunofluorescence and biochemical assays demonstrated that ASMD induced lysosomal dysfunction, as evidenced by the accumulation of lysosomal-associated membrane proteins, lysosomal protease, and autophagosomes in pericytes and cardiomyocytes. This lysosomal dysfunction was accompanied by pericytes and cardiomyocytes inflammation, characterized by increased expression of caspase1 and inflammatory cytokines, and infiltration of inflammatory cells in the cardiac tissues of Smpd1-/- mice. In addition, histological analysis revealed increased lipid deposition and cardiac steatosis, along with pericyte-to-myofibroblast transition (PMT) and interstitial fibrosis in Smpd1-/- mice. Moreover, echocardiography further demonstrated that Smpd1-/- mice developed coronary microvascular dysfunction (CMD), as evidenced by decreased coronary blood flow velocity and increased coronary arteriolar wall thickness. Additionally, these mice exhibited significant impairments in systolic and diastolic cardiac function, as shown by a reduced ejection fraction and prolonged left ventricular relaxation time constant (Tau value). These findings suggest that ASMD induces profound pathological changes and vascular dysfunction in the myocardium, potentially driven by mechanisms involving lysosomal dysfunction as well as both pericytes and cardiac inflammation. KEY MESSAGES: Lysosomal dysfunction in ASMD leads to impaired autophagic flux in cardiac pericytes ASMD causes cardiac inflammation with leukocyte and M2 macrophage infiltration Lipid buildup in the pericytes, fibroblasts and myocardium lead to cardiac steatosis Enhanced cardiac fibrosis in ASMD links to pericyte-to-myofibroblast transition ASMD results in coronary microvascular and diastolic and systolic cardiac dysfunction.
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Affiliation(s)
- Yun-Ting Wang
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA
| | - Alexandra K Moura
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA
| | - Rui Zuo
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA
| | - Kiana Roudbari
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA
| | - Jenny Z Hu
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA
| | - Saher A Khan
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA
| | - Zhengchao Wang
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA
- Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, China
| | - Yangping Shentu
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Mi Wang
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Pin-Lan Li
- Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Jiukuan Hao
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA
| | - Yang Zhang
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA.
| | - Xiang Li
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204 - 5056, USA.
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Wang YT, Moura AK, Zuo R, Roudbari K, Hu JZ, Khan SA, Wang Z, Shentu Y, Wang M, Li PL, Hao J, Zhang Y, Li X. Cardiovascular Dysfunction and Altered Lysosomal Signaling in a Murine Model of Acid Sphingomyelinase Deficiency. RESEARCH SQUARE 2025:rs.3.rs-5154105. [PMID: 40166006 PMCID: PMC11957194 DOI: 10.21203/rs.3.rs-5154105/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Niemann-Pick Disease (NPD) is a rare autosomal recessive lysosomal storage disorder (LSD) caused by the deficiency of acid sphingomyelinase (ASMD), which is encoded by the Smpd1 gene. ASMD impacts multiple organ systems in the body, including the cardiovascular system. This study is the first to characterize cardiac pathological changes in ASMD mice under baseline conditions, offering novel insights into the cardiac implications of NPD. Using histological analysis, biochemical assays, and echocardiography, we assessed cardiac pathological changes and function in Smpd1 -/- mice compared to Smpd1 +/+ littermate controls. Immunofluorescence and biochemical assays demonstrated that ASMD induced lysosomal dysfunction, as evidenced by the accumulation of lysosomal-associated membrane proteins, lysosomal protease, and autophagosomes in pericytes and cardiomyocytes. This lysosomal dysfunction was accompanied by pericytes and cardiomyocytes inflammation, characterized by increased expression of caspase1 and inflammatory cytokines, and infiltration of inflammatory cells in the cardiac tissues of Smpd1 -/- mice. In addition, histological analysis revealed increased lipid deposition and cardiac steatosis, along with pericyte-to-myofibroblast transition (PMT) and interstitial fibrosis in Smpd1 -/- mice. Moreover, echocardiography further demonstrated that Smpd1 -/- mice developed coronary microvascular dysfunction (CMD), as evidenced by decreased coronary blood flow velocity and increased coronary arteriolar wall thickness. Additionally, these mice exhibited significant impairments in systolic and diastolic cardiac function, as shown by a reduced ejection fraction and prolonged left ventricular relaxation time constant (Tau value). These findings suggest that ASMD induces profound pathological changes and vascular dysfunction in the myocardium, potentially driven by mechanisms involving lysosomal dysfunction as well as both pericytes and cardiac inflammation.
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Badmus OO, da Silva AA, Li X, Taylor LC, Greer JR, Wasson AR, McGowan KE, Patel PR, Stec DE. Cardiac lipotoxicity and fibrosis underlie impaired contractility in a mouse model of metabolic dysfunction-associated steatotic liver disease. FASEB Bioadv 2024; 6:131-142. [PMID: 38706754 PMCID: PMC11069051 DOI: 10.1096/fba.2023-00139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 02/20/2024] [Accepted: 02/23/2024] [Indexed: 05/07/2024] Open
Abstract
The leading cause of death among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is cardiovascular disease. A significant percentage of MASLD patients develop heart failure driven by functional and structural alterations in the heart. Previously, we observed cardiac dysfunction in hepatocyte-specific peroxisome proliferator-activated receptor alpha knockout (Ppara HepKO), a mouse model that exhibits hepatic steatosis independent of obesity and insulin resistance. The goal of the present study was to determine mechanisms that underlie hepatic steatosis-induced cardiac dysfunction in Ppara HepKO mice. Experiments were performed in 30-week-old Ppara HepKO and littermate control mice fed regular chow. We observed decreased cardiomyocyte contractility (0.17 ± 0.02 vs. 0.24 ± 0.02 μm, p < 0.05), increased cardiac triglyceride content (0.96 ± 0.13 vs. 0.68 ± 0.06 mM, p < 0.05), collagen type 1 (4.65 ± 0.25 vs. 0.31 ± 0.01 AU, p < 0.001), and collagen type 3 deposition (1.32 ± 0.46 vs. 0.05 ± 0.03 AU, p < 0.05). These changes were associated with increased apoptosis as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining (30.9 ± 4.7 vs. 13.1 ± 0.8%, p < 0.006) and western blots showing increased cleaved caspase-3 (0.27 ± 0.006 vs. 0.08 ± 0.01 AU, p < 0.003) and pro-caspase-3 (5.4 ± 1.5 vs. 0.5 ± 0.3 AU, p < 0.02), B-cell lymphoma protein 2-associated X (0.68 ± 0.07 vs. 0.04 ± 0.04 AU, p < 0.001), and reduced B-cell lymphoma protein 2 (0.29 ± 0.01 vs. 1.47 ± 0.54 AU, p < 0.05). We further observed elevated circulating natriuretic peptides and exercise intolerance in Ppara HepKO mice when compared to controls. Our data demonstrated that lipotoxicity, and fibrosis underlie cardiac dysfunction in MASLD.
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Affiliation(s)
- Olufunto O. Badmus
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Alexandre A. da Silva
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Xuan Li
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Lucy C. Taylor
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Jennifer R. Greer
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Andrew R. Wasson
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Karis E. McGowan
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Parth R. Patel
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - David E. Stec
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
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Oneglia AP, Szczepaniak LS, Zaha VG, Nelson MD. Myocardial steatosis across the spectrum of human health and disease. Exp Physiol 2024; 109:202-213. [PMID: 38063136 PMCID: PMC10841709 DOI: 10.1113/ep091566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 11/15/2023] [Indexed: 02/02/2024]
Abstract
Preclinical data strongly suggest that myocardial steatosis leads to adverse cardiac remodelling and left ventricular dysfunction. Using 1 H cardiac magnetic resonance spectroscopy, similar observations have been made across the spectrum of health and disease. The purpose of this brief review is to summarize these recent observations. We provide a brief overview of the determinants of myocardial triglyceride accumulation, summarize the current evidence that myocardial steatosis contributes to cardiac dysfunction, and identify opportunities for further research.
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Affiliation(s)
- Andrew P. Oneglia
- Applied Physiology and Advanced Imaging Laboratory, Department of Kinesiology, College of Nursing and Health InnovationUniversity of Texas at ArlingtonArlingtonTexasUSA
| | | | - Vlad G. Zaha
- Division of Cardiology, Internal MedicineUniversity of Texas Southwestern Medical CenterDallasTexasUSA
- Advanced Imaging Research CenterUniversity of Texas Southwestern Medical CenterArlingtonTexasUSA
| | - Michael D. Nelson
- Applied Physiology and Advanced Imaging Laboratory, Department of Kinesiology, College of Nursing and Health InnovationUniversity of Texas at ArlingtonArlingtonTexasUSA
- Clinical Imaging Research CenterUniversity of Texas at ArlingtonArlingtonTexasUSA
- Center for Healthy Living and LongevityUniversity of Texas at ArlingtonArlingtonTexasUSA
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Zoico E, Giani A, Saatchi T, Rizzatti V, Mazzali G, Fantin F, Benfari G, Onorati F, Urbani S, Zamboni M. Myocardial Fibrosis and Steatosis in Patients with Aortic Stenosis: Roles of Myostatin and Ceramides. Int J Mol Sci 2023; 24:15508. [PMID: 37958492 PMCID: PMC10648018 DOI: 10.3390/ijms242115508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 10/16/2023] [Accepted: 10/20/2023] [Indexed: 11/15/2023] Open
Abstract
Aortic stenosis (AS) involves progressive valve obstruction and a remodeling response of the left ventriculum (LV) with systolic and diastolic dysfunction. The roles of interstitial fibrosis and myocardial steatosis in LV dysfunction in AS have not been completely characterized. We enrolled 31 patients (19 women and 12 men) with severe AS undergoing elective aortic valve replacement. The subjects were clinically evaluated, and transthoracic echocardiography was performed pre-surgery. LV septal biopsies were obtained to assess fibrosis and apoptosis and fat deposition in myocytes (perilipin 5 (PLIN5)), or in the form of adipocytes within the heart (perilipin 1 (PLIN1)), the presence of ceramides and myostatin were assessed via immunohistochemistry. After BMI adjustment, we found a positive association between fibrosis and apoptotic cardiomyocytes, as well as fibrosis and the area covered by PLIN5. Apoptosis and PLIN5 were also significantly interrelated. LV fibrosis increased with a higher medium gradient (MG) and peak gradient (PG). Ceramides and myostatin levels were higher in patients within the higher MG and PG tertiles. In the linear regression analysis, increased fibrosis correlated with increased apoptosis and myostatin, independent from confounding factors. After adjustment for age and BMI, we found a positive relationship between PLIN5 and E/A and a negative correlation between septal S', global longitudinal strain (GLS), and fibrosis. Myostatin was inversely correlated with GLS and ejection fraction. Fibrosis and myocardial steatosis altogether contribute to ventricular dysfunction in severe AS. The association of myostatin and fibrosis with systolic dysfunction, as well as between myocardial steatosis and diastolic dysfunction, highlights potential therapeutic targets.
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Affiliation(s)
- Elena Zoico
- Division of Geriatric Medicine, Department of Medicine, University of Verona, 37126 Verona, Italy; (A.G.)
| | - Anna Giani
- Division of Geriatric Medicine, Department of Medicine, University of Verona, 37126 Verona, Italy; (A.G.)
| | - Tanaz Saatchi
- Division of Geriatric Medicine, Department of Medicine, University of Verona, 37126 Verona, Italy; (A.G.)
| | - Vanni Rizzatti
- Division of Geriatric Medicine, Department of Medicine, University of Verona, 37126 Verona, Italy; (A.G.)
| | - Gloria Mazzali
- Division of Geriatric Medicine, Department of Medicine, University of Verona, 37126 Verona, Italy; (A.G.)
| | - Francesco Fantin
- Division of Geriatric Medicine, Department of Medicine, University of Verona, 37126 Verona, Italy; (A.G.)
| | - Giovanni Benfari
- Division of Cardiology, Department of Medicine, University of Verona, 37126 Verona, Italy
| | - Francesco Onorati
- Division of Cardiac Surgery, Department of Surgery, Dentistry, Pediatric and Gynecology, University of Verona, 37126 Verona, Italy
| | - Silvia Urbani
- Division of Geriatric Medicine, Department of Medicine, University of Verona, 37126 Verona, Italy; (A.G.)
| | - Mauro Zamboni
- Division of Geriatric Medicine, Department of Surgery, Dentistry, Pediatric and Gynecology, University of Verona, 37126 Verona, Italy
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Quarta S, Santarpino G, Carluccio MA, Calabriso N, Maffia M, Siculella L, Damiano F, Madonna R, Massaro M. Exploring the significance of epicardial adipose tissue in aortic valve stenosis and left ventricular remodeling: Unveiling novel therapeutic and prognostic markers of disease. Vascul Pharmacol 2023; 152:107210. [PMID: 37611727 DOI: 10.1016/j.vph.2023.107210] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 08/11/2023] [Accepted: 08/18/2023] [Indexed: 08/25/2023]
Abstract
Aortic stenosis (AS) is a dynamic degenerative process that shares many pathophysiological features with atherogenesis, from initial proinflammatory calcification and focal thickening of the valve leaflets to obstruction of left ventricular outflow due to superimposed of severe calcification and immobilization of the valve leaflets. As the prevalence increases with age, AS is expected to become one of the most common heart diseases worldwide. In both obese and nonobese patients, persistent thickening of epicardial adipose tissue (EAT) is associated with a shift in its normal metabolic functions toward a dysmetabolic and proatherogenic phenotype that may impair the physiology of adjacent coronary arteries and promote the occurrence of coronary atherosclerosis. In tight analogy with atherosclerosis, recent clinical evidence indicates that EAT may also exert a deleterious role in promoting AS and contributing to myocardial dysfunction, leading to increased health risk for elderly patients with AS and an economic burden on the health care system. This review discusses the clinical and pathologic evidence for the association between EAT and AS and concomitant left ventricular hypertrophy, and provides new insights for the future direction of AS diagnosis and treatment.
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Affiliation(s)
- Stefano Quarta
- Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy; Department of Surgical, Medical, Molecular Pathology and Critical Care Sciences, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
| | - Giuseppe Santarpino
- Cardiovascular Center, Paracelsus Medical University, 90471 Nuremberg, Germany; GVM Care & Research, Città di Lecce Hospital, 73100 Lecce, Italy; Cardiac Surgery Unit, Department of Experimental and Clinical Medicine, University "Magna Graecia", 88100 Catanzaro, Italy.
| | | | - Nadia Calabriso
- Institute of Clinical Physiology (IFC), National Research Council (CNR), 73100 Lecce, Italy.
| | - Michele Maffia
- Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy.
| | - Luisa Siculella
- Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy.
| | - Fabrizio Damiano
- Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy.
| | - Rosalinda Madonna
- Cardiology Division, Cardio-Thoracic and Vascular Department, Azienda Ospedaliero-Universitaria Pisana, Via Paradisa, Edificio 10, primo piano, 56124 Pisa, Italy.
| | - Marika Massaro
- Institute of Clinical Physiology (IFC), National Research Council (CNR), 73100 Lecce, Italy.
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Monga S, Valkovič L, Myerson SG, Neubauer S, Mahmod M, Rider OJ. Role of Cardiac Energetics in Aortic Stenosis Disease Progression: Identifying the High-risk Metabolic Phenotype. Circ Cardiovasc Imaging 2023; 16:e014863. [PMID: 37847766 PMCID: PMC10581424 DOI: 10.1161/circimaging.122.014863] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 09/01/2023] [Indexed: 10/19/2023]
Abstract
BACKGROUND Severe aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and cardiac metabolic alterations with evidence of steatosis and impaired myocardial energetics. Despite this common phenotype, there is an unexplained and wide individual heterogeneity in the degree of hypertrophy and progression to myocardial fibrosis and heart failure. We sought to determine whether the cardiac metabolic state may underpin this variability. METHODS We recruited 74 asymptomatic participants with AS and 13 healthy volunteers. Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to adenosine triphosphate ratio. Myocardial lipid content was determined using proton spectroscopy. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging. RESULTS Phosphocreatine/adenosine triphosphate was reduced early and significantly across the LV wall thickness quartiles (Q2, 1.50 [1.21-1.71] versus Q1, 1.64 [1.53-1.94]) with a progressive decline with increasing disease severity (Q4, 1.48 [1.18-1.70]; P=0.02). Myocardial triglyceride content levels were overall higher in all the quartiles with a significant increase seen across the AV pressure gradient quartiles (Q2, 1.36 [0.86-1.98] versus Q1, 1.03 [0.81-1.56]; P=0.034). While all AS groups had evidence of subclinical LV dysfunction with impaired strain parameters, impaired systolic longitudinal strain was related to the degree of energetic impairment (r=0.219; P=0.03). Phosphocreatine/adenosine triphosphate was not only an independent predictor of LV wall thickness (r=-0.20; P=0.04) but also strongly associated with myocardial fibrosis (r=-0.24; P=0.03), suggesting that metabolic changes play a role in disease progression. The metabolic and functional parameters showed comparable results when graded by clinical severity of AS. CONCLUSIONS A gradient of myocardial energetic deficit and steatosis exists across the spectrum of hypertrophied AS hearts, and these metabolic changes precede irreversible LV remodeling and subclinical dysfunction. As such, cardiac metabolism may play an important and potentially causal role in disease progression.
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Affiliation(s)
- Shveta Monga
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom (S.M., L.V., S.G.M., S.N., M.M., O.J.R.)
| | - Ladislav Valkovič
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom (S.M., L.V., S.G.M., S.N., M.M., O.J.R.)
- Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia (L.V.)
| | - Saul G. Myerson
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom (S.M., L.V., S.G.M., S.N., M.M., O.J.R.)
| | - Stefan Neubauer
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom (S.M., L.V., S.G.M., S.N., M.M., O.J.R.)
| | - Masliza Mahmod
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom (S.M., L.V., S.G.M., S.N., M.M., O.J.R.)
| | - Oliver J. Rider
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom (S.M., L.V., S.G.M., S.N., M.M., O.J.R.)
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Soghomonian A, Dutour A, Kachenoura N, Thuny F, Lasbleiz A, Ancel P, Cristofari R, Jouve E, Simeoni U, Kober F, Bernard M, Gaborit B. Is increased myocardial triglyceride content associated with early changes in left ventricular function? A 1H-MRS and MRI strain study. Front Endocrinol (Lausanne) 2023; 14:1181452. [PMID: 37424866 PMCID: PMC10323751 DOI: 10.3389/fendo.2023.1181452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 06/06/2023] [Indexed: 07/11/2023] Open
Abstract
Background Type 2 diabetes (T2D) and obesity induce left ventricular (LV) dysfunction. The underlying pathophysiological mechanisms remain unclear, but myocardial triglyceride content (MTGC) could be involved. Objectives This study aimed to determine which clinical and biological factors are associated with increased MTGC and to establish whether MTGC is associated with early changes in LV function. Methods A retrospective study was conducted using five previous prospective cohorts, leading to 338 subjects studied, including 208 well-phenotyped healthy volunteers and 130 subjects living with T2D and/or obesity. All the subjects underwent proton magnetic resonance spectroscopy and feature tracking cardiac magnetic resonance imaging to measure myocardial strain. Results MTGC content increased with age, body mass index (BMI), waist circumference, T2D, obesity, hypertension, and dyslipidemia, but the only independent correlate found in multivariate analysis was BMI (p=0.01; R²=0.20). MTGC was correlated to LV diastolic dysfunction, notably with the global peak early diastolic circumferential strain rate (r=-0.17, p=0.003), the global peak late diastolic circumferential strain rate (r=0.40, p<0.0001) and global peak late diastolic longitudinal strain rate (r=0.24, p<0.0001). MTGC was also correlated to systolic dysfunction via end-systolic volume index (r=-0.34, p<0.0001) and stroke volume index (r=-0.31, p<0.0001), but not with longitudinal strain (r=0.009, p=0.88). Interestingly, the associations between MTGC and strain measures did not persist in multivariate analysis. Furthermore, MTGC was independently associated with LV end-systolic volume index (p=0.01, R²=0.29), LV end-diastolic volume index (p=0.04, R²=0.46), and LV mass (p=0.002, R²=0.58). Conclusions Predicting MTGC remains a challenge in routine clinical practice, as only BMI independently correlates with increased MTGC. MTGC may play a role in LV dysfunction but does not appear to be involved in the development of subclinical strain abnormalities.
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Affiliation(s)
- Astrid Soghomonian
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Marseille, France
| | - Anne Dutour
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Marseille, France
| | - Nadjia Kachenoura
- Sorbonne Université, INSERM, CNRS, Laboratoire d’Imagerie Biomédicale, Paris, France
| | - Franck Thuny
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
- Intensive Care Unit, Department of Cardiology, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Aix-Marseille University, Marseille, France
| | - Adele Lasbleiz
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Marseille, France
| | - Patricia Ancel
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
| | | | - Elisabeth Jouve
- UPCET, Clinical Pharmacology, Assistance-Publique Hôpitaux de Marseille, Marseille, France
| | - Umberto Simeoni
- Division of Pediatrics & DOHaD Laboratory, CHUV University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Frank Kober
- Aix-Marseille Université, CNRS, CRMBM, Marseille, France
| | | | - Bénédicte Gaborit
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Marseille, France
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Steyer A, Mas-Peiro S, Leistner DM, Puntmann VO, Nagel E, Dey D, Goeller M, Koch V, Booz C, Vogl TJ, Martin SS. Computed tomography-based pericoronary adipose tissue attenuation in patients undergoing TAVR: a novel method for risk assessment. Front Cardiovasc Med 2023; 10:1192093. [PMID: 37288259 PMCID: PMC10242002 DOI: 10.3389/fcvm.2023.1192093] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 04/27/2023] [Indexed: 06/09/2023] Open
Abstract
OBJECTIVES This study aims to assess the attenuation of pericoronary adipose tissue (PCAT) surrounding the proximal right coronary artery (RCA) in patients with aortic stenosis (AS) and undergoing transcatheter aortic valve replacement (TAVR). RCA PCAT attenuation is a novel computed tomography (CT)-based marker for evaluating coronary inflammation. Coronary artery disease (CAD) in TAVR patients is common and usually evaluated prior to intervention. The most sensible screening method and consequential treatment approach are unclear and remain a matter of ceaseless discussion. Thus, interest remains for safe and low-demand predictive markers to identify patients at risk for adverse outcomes postaortic valve replacement. METHODS This single-center retrospective study included patients receiving a standard planning CT scan prior to TAVR. Conventional CAD diagnostic tools, such as coronary artery calcium score and significant stenosis via invasive coronary angiography and coronary computed tomography angiography, were determined in addition to RCA PCAT attenuation using semiautomated software. These were assessed for their relationship with major adverse cardiovascular events (MACE) during a 24-month follow-up period. RESULTS From a total of 62 patients (mean age: 82 ± 6.7 years), 15 (24.2%) patients experienced an event within the observation period, 10 of which were attributed to cardiovascular death. The mean RCA PCAT attenuation was higher in patients enduring MACE than that in those without an endpoint (-69.8 ± 7.5 vs. -74.6 ± 6.2, P = 0.02). Using a predefined cutoff of >-70.5 HU, 20 patients (32.3%) with high RCA PCAT attenuation were identified, nine (45%) of which met the endpoint within 2 years after TAVR. In a multivariate Cox regression model including conventional CAD diagnostic tools, RCA PCAT attenuation prevailed as the only marker with significant association with MACE (P = 0.02). After dichotomization of patients into high- and low-RCA PCAT attenuation groups, high attenuation was related to greater risk of MACE (hazard ration: 3.82, P = 0.011). CONCLUSION RCA PCAT attenuation appears to have predictive value also in a setting of concomitant AS in patients receiving TAVR. RCA PCAT attenuation was more reliable than conventional CAD diagnostic tools in identifying patients at risk for MACE .
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Affiliation(s)
- Alexandra Steyer
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Frankfurt, Germany
- Institute for Experimental and Translational Cardiovascular Imaging, Goethe University, University Hospital Frankfurt, Frankfurt, Germany
| | - Silvia Mas-Peiro
- Department of Cardiology, University Hospital Frankfurt, Frankfurt, Germany
- German Centre for Cardiovascular Research (DZHK), Berlin, Germany
- Cardiopulmonary Institute (CPI), Frankfurt am Main, Germany
| | - David M. Leistner
- Department of Cardiology, University Hospital Frankfurt, Frankfurt, Germany
| | - Valentina O. Puntmann
- Institute for Experimental and Translational Cardiovascular Imaging, Goethe University, University Hospital Frankfurt, Frankfurt, Germany
| | - Eike Nagel
- Institute for Experimental and Translational Cardiovascular Imaging, Goethe University, University Hospital Frankfurt, Frankfurt, Germany
- German Centre for Cardiovascular Research (DZHK), Berlin, Germany
| | - Damini Dey
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Markus Goeller
- Department of Cardiology, Friedrich-Alexander-University Hospital Erlangen, Erlangen, Germany
| | - Vitali Koch
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Frankfurt, Germany
- Institute for Experimental and Translational Cardiovascular Imaging, Goethe University, University Hospital Frankfurt, Frankfurt, Germany
| | - Christian Booz
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Frankfurt, Germany
| | - Thomas J. Vogl
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Frankfurt, Germany
| | - Simon S. Martin
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Frankfurt, Germany
- Institute for Experimental and Translational Cardiovascular Imaging, Goethe University, University Hospital Frankfurt, Frankfurt, Germany
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10
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Monga S, Valkovič L, Tyler D, Lygate CA, Rider O, Myerson SG, Neubauer S, Mahmod M. Insights Into the Metabolic Aspects of Aortic Stenosis With the Use of Magnetic Resonance Imaging. JACC Cardiovasc Imaging 2022; 15:2112-2126. [PMID: 36481080 PMCID: PMC9722407 DOI: 10.1016/j.jcmg.2022.04.025] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 02/25/2022] [Accepted: 04/29/2022] [Indexed: 01/13/2023]
Abstract
Pressure overload in aortic stenosis (AS) encompasses both structural and metabolic remodeling and increases the risk of decompensation into heart failure. A major component of metabolic derangement in AS is abnormal cardiac substrate use, with down-regulation of fatty acid oxidation, increased reliance on glucose metabolism, and subsequent myocardial lipid accumulation. These changes are associated with energetic and functional cardiac impairment in AS and can be assessed with the use of cardiac magnetic resonance spectroscopy (MRS). Proton MRS allows the assessment of myocardial triglyceride content and creatine concentration. Phosphorous MRS allows noninvasive in vivo quantification of the phosphocreatine-to-adenosine triphosphate ratio, a measure of cardiac energy status that is reduced in patients with severe AS. This review summarizes the changes to cardiac substrate and high-energy phosphorous metabolism and how they affect cardiac function in AS. The authors focus on the role of MRS to assess these metabolic changes, and potentially guide future (cellular) metabolic therapy in AS.
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Affiliation(s)
- Shveta Monga
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Ladislav Valkovič
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Damian Tyler
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
| | - Craig A Lygate
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Centre for Human Genetics, Oxford, United Kingdom
| | - Oliver Rider
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Saul G Myerson
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Stefan Neubauer
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Masliza Mahmod
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
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11
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Peereboom SM, Kozerke S. Metabolite-cycled echo-planar spectroscopic imaging of the human heart. Magn Reson Med 2022; 88:1516-1527. [PMID: 35666820 PMCID: PMC9544353 DOI: 10.1002/mrm.29333] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 04/30/2022] [Accepted: 05/13/2022] [Indexed: 11/12/2022]
Abstract
Purpose Spectroscopic imaging could provide insights into regional cardiac triglyceride variations, but is hampered by relatively long scan times. It is proposed to synergistically combine echo‐planar spectroscopic imaging (EPSI) with motion‐adapted gating, weighted acquisition and metabolite cycling to reduce scan times to less than 10 min while preserving spatial‐spectral quality. The method is compared to single‐voxel measurements and to metabolite‐cycled EPSI with conventional acquisition for assessing triglyceride‐to‐water (TG/W) ratios in the human heart. Methods Measurements were performed on 10 healthy volunteers using a clinical 1.5T system. EPSI data was acquired both without and with motion‐adapted gating in combination with weighted acquisition to assess TG/W ratios and relative Cramér‐Rao lower bounds (CRLB) of TG. For comparison, single‐voxel (PRESS) spectra were acquired in the interventricular septum. Results Bland–Altman analyses did not show a significant bias in TG/W when comparing both metabolite‐cycled EPSI methods to PRESS for any of the cardiac segments. Scan time was 8.05 ± 2.06 min and 17.91 ± 3.93 min for metabolite‐cycled EPSI with and without motion‐adapted gating and weighted acquisition, respectively, while relative CRLB of TG did not differ significantly between the two methods for any of the cardiac segments. Conclusions Metabolite‐cycled EPSI with motion‐adapted gating and weighted acquisition allows detecting TG/W ratios in different regions of the in vivo human heart. Scan time is reduced by more than 2‐fold to less than 10 min as compared to conventional acquisition, while keeping the quality of TG fitting constant. Click here for author‐reader discussions
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Affiliation(s)
- Sophie M Peereboom
- Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland
| | - Sebastian Kozerke
- Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland
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12
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Microvesicular Steatosis and Severe Cardiac Allograft Dysfunction. Transplant Direct 2022; 8:e1290. [PMID: 35187215 PMCID: PMC8843365 DOI: 10.1097/txd.0000000000001290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 11/30/2021] [Accepted: 12/15/2021] [Indexed: 11/26/2022] Open
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13
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Tanacli R, Hassel JH, Gebker R, Berger A, Gräfe M, Schneeweis C, Doeblin P, Fleck E, Stehning C, Tacke F, Pieske B, Spranger J, Plöckinger U, Ziagaki A, Kelle S. Cardiac Magnetic Resonance Reveals Incipient Cardiomyopathy Traits in Adult Patients With Phenylketonuria. J Am Heart Assoc 2021; 10:e020351. [PMID: 34423658 PMCID: PMC8649272 DOI: 10.1161/jaha.120.020351] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Phenylketonuria is the most common inborn error of amino acid metabolism, where oxidative stress and collateral metabolic abnormalities are likely to cause cardiac structural and functional modifications. We aim herein to characterize the cardiac phenotype of adult subjects with phenylketonuria using advanced cardiac imaging. Methods and Results Thirty-nine adult patients with phenylketonuria (age, 30.5±8.7 years; 10-year mean phenylalanine concentration, 924±330 µmol/L) and 39 age- and sex-matched healthy controls were investigated. Participants underwent a comprehensive cardiac magnetic resonance and echocardiography examination. Ten-year mean plasma levels of phenylalanine and tyrosine were used to quantify disease activity and adherence to treatment. Patients with phenylketonuria had thinner left ventricular walls (septal end-diastolic thickness, 7.0±17 versus 8.8±1.7 mm [P<0.001]; lateral thickness, 6.1±1.4 versus 6.8±1.2 mm [P=0.004]), more dilated left ventricular cavity (end-diastolic volume, 87±14 versus 80±14 mL/m2 [P=0.0178]; end-systolic volume, 36±9 versus 29±8 mL/m2 [P<0.001]), lower ejection fraction (59±6% versus 64±6% [P<0.001]), reduced systolic deformation (global circumferential strain, -29.9±4.2 % versus -32.2±5.0 % [P=0.027]), and lower left ventricular mass (38.2±7.9 versus 47.8±11.0 g/m2 [P<0.001]). T1 native values were decreased (936±53 versus 996±26 ms [P<0.001]), with particular low values in patients with phenylalanine >1200 µmol/L (909±48 ms). Both mean phenylalanine (P=0.013) and tyrosine (P=0.035) levels were independently correlated with T1; and in a multiple regression model, higher phenylalanine levels and higher left ventricular mass associate with lower T1. Conclusions Cardiac phenotype of adult patients with phenylketonuria reveals some traits of an early-stage cardiomyopathy. Regular cardiology follow-up, tighter therapeutic control, and prophylaxis of cardiovascular risk factors, in particular dyslipidemia, are recommended.
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Affiliation(s)
- Radu Tanacli
- Department of Cardiology German Heart Centre Berlin Berlin Germany.,Department of Cardiology Charité University Medicine Berlin Berlin Germany
| | | | - Rolf Gebker
- Department of Cardiology German Heart Centre Berlin Berlin Germany
| | - Alexander Berger
- Department of Cardiology German Heart Centre Berlin Berlin Germany
| | - Michael Gräfe
- Department of Cardiology German Heart Centre Berlin Berlin Germany
| | | | - Patrick Doeblin
- Department of Cardiology German Heart Centre Berlin Berlin Germany
| | - Eckart Fleck
- Department of Cardiology German Heart Centre Berlin Berlin Germany
| | | | - Frank Tacke
- Department of Hepatology and Gastroenterology Charité University Medicine Berlin Berlin Germany.,Interdisziplinäres Stoffwechsel-Centrum Charité-Universitätsmedizin BerlinCampus Virchow Klinikum Berlin Germany
| | - Burkert Pieske
- Department of Cardiology German Heart Centre Berlin Berlin Germany.,Department of Cardiology Charité University Medicine Berlin Berlin Germany.,German Centre for Cardiovascular Research DZHK, Partner Site Berlin Berlin Germany
| | - Joachim Spranger
- Department of Endocrinology, Diabetes, and Nutrition Charité University Medicine Berlin Berlin Germany.,Interdisziplinäres Stoffwechsel-Centrum Charité-Universitätsmedizin BerlinCampus Virchow Klinikum Berlin Germany
| | - Ursula Plöckinger
- Interdisziplinäres Stoffwechsel-Centrum Charité-Universitätsmedizin BerlinCampus Virchow Klinikum Berlin Germany
| | - Athanasia Ziagaki
- Interdisziplinäres Stoffwechsel-Centrum Charité-Universitätsmedizin BerlinCampus Virchow Klinikum Berlin Germany
| | - Sebastian Kelle
- Department of Cardiology German Heart Centre Berlin Berlin Germany.,Department of Cardiology Charité University Medicine Berlin Berlin Germany.,German Centre for Cardiovascular Research DZHK, Partner Site Berlin Berlin Germany
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14
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Ding B, Peterzan M, Mózes FE, Rider OJ, Valkovič L, Rodgers CT. Water-suppression cycling 3-T cardiac 1 H-MRS detects altered creatine and choline in patients with aortic or mitral stenosis. NMR IN BIOMEDICINE 2021; 34:e4513. [PMID: 33826181 PMCID: PMC8243349 DOI: 10.1002/nbm.4513] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 02/23/2021] [Accepted: 03/03/2021] [Indexed: 05/06/2023]
Abstract
Cardiac proton spectroscopy (1 H-MRS) is widely used to quantify lipids. Other metabolites (e.g. creatine and choline) are clinically relevant but more challenging to quantify because of their low concentrations (approximately 10 mmol/L) and because of cardiac motion. To quantify cardiac creatine and choline, we added water-suppression cycling (WSC) to two single-voxel spectroscopy sequences (STEAM and PRESS). WSC introduces controlled residual water signals that alternate between positive and negative phases from transient to transient, enabling robust phase and frequency correction. Moreover, a particular weighted sum of transients eliminates residual water signals without baseline distortion. We compared WSC and the vendor's standard 'WET' water suppression in phantoms. Next, we tested repeatability in 10 volunteers (seven males, three females; age 29.3 ± 4.0 years; body mass index [BMI] 23.7 ± 4.1 kg/m2 ). Fat fraction, creatine concentration and choline concentration when quantified by STEAM-WET were 0.30% ± 0.11%, 29.6 ± 7.0 μmol/g and 7.9 ± 6.7 μmol/g, respectively; and when quantified by PRESS-WSC they were 0.30% ± 0.15%, 31.5 ± 3.1 μmol/g and 8.3 ± 4.4 μmol/g, respectively. Compared with STEAM-WET, PRESS-WSC gave spectra whose fitting quality expressed by Cramér-Rao lower bounds improved by 26% for creatine and 32% for choline. Repeatability of metabolite concentration measurements improved by 72% for creatine and 40% for choline. We also compared STEAM-WET and PRESS-WSC in 13 patients with severe symptomatic aortic or mitral stenosis indicated for valve replacement surgery (10 males, three females; age 75.9 ± 6.3 years; BMI 27.4 ± 4.3 kg/m2 ). Spectra were of analysable quality in eight patients for STEAM-WET, and in nine for PRESS-WSC. We observed comparable lipid concentrations with those in healthy volunteers, significantly reduced creatine concentrations, and a trend towards decreased choline concentrations. We conclude that PRESS-WSC offers improved performance and reproducibility for the quantification of cardiac lipids, creatine and choline concentrations in healthy volunteers at 3 T. It also offers improved performance compared with STEAM-WET for detecting altered creatine and choline concentrations in patients with valve disease.
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Affiliation(s)
- Belinda Ding
- Wolfson Brain Imaging CentreUniversity of CambridgeCambridgeUK
- Oxford Centre for Clinical Magnetic Resonance Research (OCMR)University of OxfordOxfordUK
| | - Mark Peterzan
- Oxford Centre for Clinical Magnetic Resonance Research (OCMR)University of OxfordOxfordUK
| | - Ferenc E. Mózes
- Oxford Centre for Clinical Magnetic Resonance Research (OCMR)University of OxfordOxfordUK
| | - Oliver J. Rider
- Oxford Centre for Clinical Magnetic Resonance Research (OCMR)University of OxfordOxfordUK
| | - Ladislav Valkovič
- Oxford Centre for Clinical Magnetic Resonance Research (OCMR)University of OxfordOxfordUK
- Department of Imaging Methods, Institute of Measurement ScienceSlovak Academy of SciencesBratislavaSlovakia
| | - Christopher T. Rodgers
- Wolfson Brain Imaging CentreUniversity of CambridgeCambridgeUK
- Oxford Centre for Clinical Magnetic Resonance Research (OCMR)University of OxfordOxfordUK
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15
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Bakermans AJ, Boekholdt SM, de Vries DK, Reckman YJ, Farag ES, de Heer P, Uthman L, Denis SW, Zuurbier CJ, Houtkooper RH, Koolbergen DR, Kluin J, Planken RN, Lamb HJ, Webb AG, Strijkers GJ, Beard DA, Jeneson JAL, Nederveen AJ. Quantification of Myocardial Creatine and Triglyceride Content in the Human Heart: Precision and Accuracy of in vivo Proton Magnetic Resonance Spectroscopy. J Magn Reson Imaging 2021; 54:411-420. [PMID: 33569824 PMCID: PMC8277665 DOI: 10.1002/jmri.27531] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 01/10/2021] [Accepted: 01/11/2021] [Indexed: 12/26/2022] Open
Abstract
Background Proton magnetic resonance spectroscopy (1H‐MRS) of the human heart is deemed to be a quantitative method to investigate myocardial metabolite content, but thorough validations of in vivo measurements against invasive techniques are lacking. Purpose To determine measurement precision and accuracy for quantifications of myocardial total creatine and triglyceride content with localized 1H‐MRS. Study type Test–retest repeatability and measurement validation study. Subjects Sixteen volunteers and 22 patients scheduled for open‐heart aortic valve replacement or septal myectomy. Field Strength/Sequence Prospectively ECG‐triggered respiratory‐gated free‐breathing single‐voxel point‐resolved spectroscopy (PRESS) sequence at 3 T. Assessment Myocardial total creatine and triglyceride content were quantified relative to the total water content by fitting the 1H‐MR spectra. Precision was assessed with measurement repeatability. Accuracy was assessed by validating in vivo 1H‐MRS measurements against biochemical assays in myocardial tissue from the same subjects. Statistical Tests Intrasession and intersession repeatability was assessed using Bland–Altman analyses. Agreement between 1H‐MRS measurements and biochemical assay was tested with regression analyses. Results The intersession repeatability coefficient for myocardial total creatine content was 41.8% with a mean value of 0.083% ± 0.020% of the total water signal, and 36.7% for myocardial triglyceride content with a mean value of 0.35% ± 0.13% of the total water signal. Ex vivo myocardial total creatine concentrations in tissue samples correlated with the in vivo myocardial total creatine content measured with 1H‐MRS: n = 22, r = 0.44; P < 0.05. Likewise, ex vivo myocardial triglyceride concentrations correlated with the in vivo myocardial triglyceride content: n = 20, r = 0.50; P < 0.05. Data Conclusion We validated the use of localized 1H‐MRS of the human heart at 3 T for quantitative assessments of in vivo myocardial tissue metabolite content by estimating the measurement precision and accuracy. Level of Evidence 2 Technical Efficacy Stage 2
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Affiliation(s)
- Adrianus J Bakermans
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - S Matthijs Boekholdt
- Department of Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Dylan K de Vries
- Department of Experimental Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Yolan J Reckman
- Department of Experimental Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Emile S Farag
- Department of Cardiothoracic Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Paul de Heer
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.,C.J. Gorter Center for High Field MR, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Laween Uthman
- Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Simone W Denis
- Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Coert J Zuurbier
- Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Riekelt H Houtkooper
- Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - David R Koolbergen
- Department of Cardiothoracic Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Jolanda Kluin
- Department of Cardiothoracic Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - R Nils Planken
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Hildo J Lamb
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Andrew G Webb
- C.J. Gorter Center for High Field MR, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Gustav J Strijkers
- Biomedical Engineering and Physics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Daniel A Beard
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA
| | - Jeroen A L Jeneson
- Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Aart J Nederveen
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
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16
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CMR in Evaluating Valvular Heart Disease: Diagnosis, Severity, and Outcomes. JACC Cardiovasc Imaging 2020; 14:2020-2032. [PMID: 33248967 DOI: 10.1016/j.jcmg.2020.09.029] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 09/04/2020] [Accepted: 09/14/2020] [Indexed: 01/20/2023]
Abstract
Cardiac magnetic resonance (CMR) is a versatile imaging tool that brings much to the assessment of valvular heart disease. Although it is best known for myocardial imaging (even in valve disease), it provides excellent assessment of all 4 heart valves, with some distinct advantages, including a free choice of image planes and accurate flow and volumetric quantification. These allow the severity of each valve lesion to be characterized, in addition to optimal visualization of the surrounding outflow tracts and vessels, to deliver a comprehensive package. It can assess each valve lesion separately (in multiple valve disease) and is not affected by hemodynamic status. The accurate quantitation of regurgitant lesions and the ability to characterize myocardial changes also provides an ability to predict future clinical outcomes in asymptomatic patients. This review outlines how CMR can be used in cardiac valve disease to compliment echocardiography and enhance the patient assessment. It covers the main CMR methods used, their strengths and limitations, and the optimal way to apply them to evaluate valve disease.
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17
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Shariya MA, Ustyuzhanin DV, Lepilin PM, Imaev TE, Komlev AE, Belyaevskaya AA, Ternovoy SK. [Role of magnetic resonance imaging in patients with aortic stenosis before and after replacement of the valve]. TERAPEVT ARKH 2020; 92:70-76. [PMID: 33346434 DOI: 10.26442/00403660.2020.09.000657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 10/13/2020] [Indexed: 11/22/2022]
Abstract
Risk stratification among patients with aortic stenosis remains inadequate, and there is a clinical need for the correct identification of high-risk patients who would benefit from aortic valve intervention before developing left ventricular decompensation. Since the publication of the results of the PARTNER study, transcatheter aortic valve implantation (TAVI) has become the method of choice for aortic valve stenosis in inoperable patients and is a real alternative to conventional surgical replacement of the aortic valve in high-risk patients. In planning TAVI and postoperative monitoring of a patient from imaging methods, the leading role is played by echocardiography and multispiral computed tomography. However, in recent years, the interest of researchers in the use of magnetic resonance imaging in this category of patients has increased. The review article examines the potential role of magnetic resonance imaging in patients with aortic stenosis before and after TAVI.
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Affiliation(s)
- M A Shariya
- Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology
| | - D V Ustyuzhanin
- Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology
| | - P M Lepilin
- Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology
| | - T E Imaev
- Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology
| | - A E Komlev
- Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology
| | - A A Belyaevskaya
- Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology
| | - S K Ternovoy
- Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology.,Sechenov First Moscow State Medical University (Sechenov University)
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18
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Chang KF, Lin G, Huang PC, Juan YH, Wang CH, Tsai SY, Lin YC, Wu MT, Liao PA, Yang LY, Liu MH, Lin YC, Wang JJ, Ng KK, Ng SH. Left Ventricular Function and Myocardial Triglyceride Content on 3T Cardiac MR Predict Major Cardiovascular Adverse Events and Readmission in Patients Hospitalized with Acute Heart Failure. J Clin Med 2020; 9:jcm9010169. [PMID: 31936313 PMCID: PMC7019990 DOI: 10.3390/jcm9010169] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 01/05/2020] [Accepted: 01/07/2020] [Indexed: 01/11/2023] Open
Abstract
Background: This prospective study was designed to investigate whether myocardial triglyceride (TG) content from proton magnetic resonance spectroscopy (MRS) and left ventricular (LV) function parameters from cardiovascular magnetic resonance imaging (CMR) can serve as imaging biomarkers in predicting future major cardiovascular adverse events (MACE) and readmission in patients who had been hospitalized for acute heart failure (HF). Methods: Patients who were discharged after hospitalization for acute HF were prospectively enrolled. On a 3.0 T MR scanner, myocardial TG contents were measured using MRS, and LV parameters (function and mass) were evaluated using cine. The occurrence of MACE and the HF-related readmission served as the endpoints. Independent predictors were identified using univariate and multivariable Cox proportional hazard regression analyses. Results: A total of 133 patients (mean age, 52.4 years) were enrolled. The mean duration of follow-up in surviving patients was 775 days. Baseline LV functional parameters—including ejection fraction, LV end-diastolic volume, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume (p < 0.0001 for all), and myocardial mass (p = 0.010)—were significantly associated with MACE. Multivariable analysis revealed that LVEDVI was the independent predictor for MACE, while myocardial mass was the independent predictor for 3- and 12-month readmission. Myocardial TG content (lipid resonances δ 1.6 ppm) was significantly associated with readmission in patients with ischemic heart disease. Conclusions: LVEDVI and myocardial mass are potential imaging biomarkers that independently predict MACE and readmission, respectively, in patients discharged after hospitalization for acute HF. Myocardial TG predicts readmission in patients with a history of ischemic heart disease.
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Affiliation(s)
- Kuang-Fu Chang
- Department of Radiology, Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung 20401, Taiwan; (K.-F.C.); (Y.-C.L.)
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan 33305, Taiwan; (G.L.); (P.-C.H.); (Y.-H.J.); (P.-A.L.); (Y.-C.L.); (J.-J.W.)
| | - Gigin Lin
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan 33305, Taiwan; (G.L.); (P.-C.H.); (Y.-H.J.); (P.-A.L.); (Y.-C.L.); (J.-J.W.)
- Imaging Core Lab, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan
- Clinical Metabolomics Core Lab, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Pei-Ching Huang
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan 33305, Taiwan; (G.L.); (P.-C.H.); (Y.-H.J.); (P.-A.L.); (Y.-C.L.); (J.-J.W.)
| | - Yu-Hsiang Juan
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan 33305, Taiwan; (G.L.); (P.-C.H.); (Y.-H.J.); (P.-A.L.); (Y.-C.L.); (J.-J.W.)
| | - Chao-Hung Wang
- Department of Cardiology and Heart Failure Center, Chang Gung Memorial Hospital, Keelung 20401, Taiwan; (C.-H.W.); (M.-H.L.)
| | - Shang-Yueh Tsai
- Graduate Institute of Applied Physics, National Chengchi University, Taipei 11605, Taiwan;
| | - Yu-Ching Lin
- Department of Radiology, Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung 20401, Taiwan; (K.-F.C.); (Y.-C.L.)
| | - Ming-Ting Wu
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan;
| | - Pen-An Liao
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan 33305, Taiwan; (G.L.); (P.-C.H.); (Y.-H.J.); (P.-A.L.); (Y.-C.L.); (J.-J.W.)
| | - Lan-Yan Yang
- Clinical Trial Center, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan;
| | - Min-Hui Liu
- Department of Cardiology and Heart Failure Center, Chang Gung Memorial Hospital, Keelung 20401, Taiwan; (C.-H.W.); (M.-H.L.)
| | - Yu-Chun Lin
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan 33305, Taiwan; (G.L.); (P.-C.H.); (Y.-H.J.); (P.-A.L.); (Y.-C.L.); (J.-J.W.)
- Imaging Core Lab, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan
| | - Jiun-Jie Wang
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan 33305, Taiwan; (G.L.); (P.-C.H.); (Y.-H.J.); (P.-A.L.); (Y.-C.L.); (J.-J.W.)
- Imaging Core Lab, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan
| | - Koon-Kwan Ng
- Department of Radiology, Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung 20401, Taiwan; (K.-F.C.); (Y.-C.L.)
- Correspondence: (K.-K.N.); (S.-H.N.); Tel.: +886-2431-3131 (ext. 2214) (K.-K.N.); +886-3328-1200 (ext. 2575) (S.-H.N.); Fax: +886-2433-2869 (K.-K.N.); +886-3397-1936 (S.-H.N.)
| | - Shu-Hang Ng
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan 33305, Taiwan; (G.L.); (P.-C.H.); (Y.-H.J.); (P.-A.L.); (Y.-C.L.); (J.-J.W.)
- Correspondence: (K.-K.N.); (S.-H.N.); Tel.: +886-2431-3131 (ext. 2214) (K.-K.N.); +886-3328-1200 (ext. 2575) (S.-H.N.); Fax: +886-2433-2869 (K.-K.N.); +886-3397-1936 (S.-H.N.)
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19
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Peereboom SM, Gastl M, Fuetterer M, Kozerke S. Navigator-free metabolite-cycled proton spectroscopy of the heart. Magn Reson Med 2019; 83:795-805. [PMID: 31448841 DOI: 10.1002/mrm.27961] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 07/04/2019] [Accepted: 07/31/2019] [Indexed: 11/07/2022]
Abstract
PURPOSE Respiratory gating in cardiac water-suppressed (WS) proton spectroscopy leads to long and unpredictable scan times. Metabolite cycling allows to perform frequency and phase correction on the water signal and, hence, offers an approach to navigator-free cardiac spectroscopy with fixed scan time. The objective of the present study was to develop and implement navigator-free metabolite-cycled cardiac proton spectroscopy (MC nonav) and compare it with standard navigator-gated WS (WS nav) and navigator-free WS (WS nonav) measurements for the assessment of triglyceride-to-water ratios (TG/W) and creatine-to-water ratios (CR/W) in the intraventricular septum of the in vivo heart. METHODS Navigator-free metabolite-cycled spectroscopy was implemented on a clinical 1.5T system. In vivo measurements were performed on 10 young and 5 older healthy volunteers to assess signal-to-noise ratio efficiency as well as TG/W and CR/W and the relative Cramér-Rao lower bounds for CR. The performance of the metabolite-cycled sequence was verified using simulations. RESULTS On average, scan times of MC nonav were 3.4 times shorter compared with WS nav, while no significant bias for TG/W was observed (coefficient of variation = 14.0%). signal-to-noise ratio efficiency of both TG and CR increased for MC nonav compared with WS nav. Relative Cramér-Rao lower bounds of CR decreased for MC nonav. Overall spectral quality was found comparable between MC nonav and WS nav, while it was inferior for WS nonav. CONCLUSION Navigator-free metabolite-cycled cardiac proton spectroscopy offers 3.4-fold accelerated assessment of TG/W and CR/W in the heart with preserved spectral quality when compared with navigator-gated WS scans.
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Affiliation(s)
- Sophie M Peereboom
- Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland
| | - Mareike Gastl
- Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland
| | - Maximilian Fuetterer
- Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland
| | - Sebastian Kozerke
- Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland
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20
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Antonopoulos AS, Antoniades C. Cardiac Magnetic Resonance Imaging of Epicardial and Intramyocardial Adiposity as an Early Sign of Myocardial Disease. Circ Cardiovasc Imaging 2019; 11:e008083. [PMID: 30354506 DOI: 10.1161/circimaging.118.008083] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- Alexios S Antonopoulos
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom
| | - Charalambos Antoniades
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom
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21
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Gulsin GS, Brady EM, Swarbrick DJ, Athithan L, Henson J, Baldry E, McAdam J, Marsh AM, Parke KS, Wormleighton JV, Levelt E, Yates T, Bodicoat D, Khunti K, Davies MJ, McCann GP. Rationale, design and study protocol of the randomised controlled trial: Diabetes Interventional Assessment of Slimming or Training tO Lessen Inconspicuous Cardiovascular Dysfunction (the DIASTOLIC study). BMJ Open 2019; 9:e023207. [PMID: 30928925 PMCID: PMC6475184 DOI: 10.1136/bmjopen-2018-023207] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
INTRODUCTION Despite their young age and relatively short duration of disease, younger adults with type 2 diabetes (T2D) already have diastolic dysfunction and may be at risk of incipient heart failure. Whether weight loss or exercise training improve cardiac dysfunction in people with T2D remains to be established. METHODS AND ANALYSIS Prospective, randomised, open-label, blind endpoint trial. The primary aim of the study is to determine if diastolic function can be improved by either a meal replacement plan or a supervised exercise programme, compared with guideline-directed care. A total of 90 obese participants with T2D (aged 18-65 years), diabetes duration <12 years and not on insulin treatment will be randomised to either guideline-directed clinical care with lifestyle coaching, a low-energy meal replacement diet (average ≈810 kcal/day) or a supervised exercise programme for 12 weeks. Participants undergo glycometabolic profiling, cardiopulmonary exercise testing, echocardiography and MRI scanning to assesses cardiac structure and function and dual-energy X-ray absorptiometry scanning for body composition. Key secondary aims are to assess the effects of the interventions on glycaemic control and insulin resistance, exercise capacity, blood pressure, changes in body composition and association of favourable cardiac remodelling with improvements in weight loss, exercise capacity and glycometabolic control. ETHICS AND DISSEMINATION The study has full ethical approval, and data collection was completed in August 2018. The study results will be submitted for publication within 6 months of completion. TRIAL REGISTRATION NUMBER NCT02590822; Pre-results.
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Affiliation(s)
- Gaurav Singh Gulsin
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Emer M Brady
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Daniel J Swarbrick
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Lavanya Athithan
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Joseph Henson
- National College of Sport and Exercise Medicine, University of Loughborough, Loughborough, UK
| | - Emma Baldry
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - John McAdam
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Anna-Marie Marsh
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Kelly S Parke
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Joanne V Wormleighton
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Eylem Levelt
- University of Leeds, Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, UK
| | - Thomas Yates
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
- National College of Sport and Exercise Medicine, University of Loughborough, Loughborough, UK
| | - Danielle Bodicoat
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Gerry P McCann
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
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22
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Einarsen E, Saeed S, Cramariuc D, Chambers JB, Midtbø H, Gerdts E. Impact of Obesity on Persistent Left Ventricular Hypertrophy After Aortic Valve Replacement for Aortic Stenosis. Am J Cardiol 2019; 123:942-947. [PMID: 30654925 DOI: 10.1016/j.amjcard.2018.12.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 12/02/2018] [Accepted: 12/07/2018] [Indexed: 10/27/2022]
Abstract
Normalization of left ventricular (LV) hypertrophy is expected after successful aortic valve replacement (AVR) in patients with aortic valve stenosis (AS), but is not always observed. We tested the impact of body mass index (BMI) ≥30 kg/m2 on persistent post-AVR LV hypertrophy. In the present subanalysis of Simvastatin Ezetimibe in Aortic Stenosis study, clinical and echocardiographic data of 399 patients with severe AS who underwent surgical AVR were analyzed. All patients had a standardized pre- and post-AVR echocardiogram. Patients were grouped by BMI categories into BMI <25 kg/m2, BMI 25 to 29.9 kg/m2, and BMI ≥30 kg/m2. LV hypertrophy was defined as LV mass/height2.7 >49.2 g/m2.7 in men and >46.7 g/m2.7 in women. Predictors of persistent LV hypertrophy after AVR were identified in logistic regression analysis. After a median follow-up of 196 days after AVR, LV hypertrophy was more prevalent in patients with BMI ≥30 kg/m2 compared with those with BMI 25 to 29.9 kg/m2 and those patients with BMI <25 kg/m2 (71% vs 47% and 37%, p <0.01). BMI ≥30 kg/m2 patients also remained with lower LV midwall shortening post-AVR compared with patients with normal weight (p <0.01), independent of patient prosthesis mismatch. In multivariable logistic regression analysis, the presence of BMI ≥30 kg/m2 before AVR was associated with an almost fourfold higher prevalence of post-AVR LV hypertrophy independent of significant associations with higher systolic blood pressure and lower LV midwall shortening preoperatively (odds ratio 3.75 [95% confidence interval 2.04 to 6.91], p <0.001). In conclusion, the presence of BMI ≥30 kg/m2 before AVR in patients with severe AS was strongly and independently associated with persistent post-AVR LV hypertrophy.
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23
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Parbhudayal RY, Güçlü A, Zweerink A, Biesbroek PS, Croisille P, Clarysse P, Michels M, Stooker W, Vonk ABA, van der Ven PM, van Rossum AC, van der Velden J, Nijveldt R. Myocardial adaptation after surgical therapy differs for aortic valve stenosis and hypertrophic obstructive cardiomyopathy. Int J Cardiovasc Imaging 2019; 35:1089-1100. [PMID: 30825136 PMCID: PMC6534665 DOI: 10.1007/s10554-019-01563-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 02/12/2019] [Indexed: 11/28/2022]
Abstract
Surgical therapies in aortic valve stenosis (AVS) and hypertrophic obstructive cardiomyopathy (HOCM) aim to relief intraventricular pressure overload and improve clinical outcome. It is currently unknown to what extent myocardial adaptation concurs with restoration of intraventricular pressures, and whether this is similar in both patient groups. The aim of this study was to investigate changes in myocardial adaptation after surgical therapies for AVS and HOCM. Ten AVS and ten HOCM patients were enrolled and underwent cardiac magnetic resonance cine imaging and myocardial tagging prior to, and 4 months after aortic valve replacement (AVR) and septal myectomy, respectively. Global left ventricular (LV) analyses were derived from cine images. Circumferential strain was assessed from myocardial tagging images at the septal and lateral wall of the mid ventricle. Pressure gradients significantly decreased in both AVS and HOCM after surgery (p < 0.01), with a concomitant decrease in left atrial volume (p < 0.05) suggesting lower diastolic filling pressures. Also, LV volumes, mass and septal wall thickness decreased in both, but to a larger extent in AVS than in HOCM patients. AVR improved wall thickening (p < 0.05) and did not change systolic strain rate. Myectomy did not affect wall thickening and reduced septal systolic strain rate (p = 0.03). Both AVR and myectomy induced positive structural remodeling in line with a reduction of pressure overload. A concomitant recovery in systolic function however was found in AVR only. The systolic functional deterioration in HOCM patients seems to be inherent to myectomy and the ongoing and irreversible disease.
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Affiliation(s)
- Rahana Y Parbhudayal
- Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.,Department of Physiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.,The Netherlands Heart Institute, Utrecht, The Netherlands
| | - Ahmet Güçlü
- Department of Cardiology, Isala Klinieken, Zwolle, The Netherlands
| | - Alwin Zweerink
- Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - P Stefan Biesbroek
- Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Pierre Croisille
- Univ Lyon, UJM-Saint-Etienne, INSA, CNRS UMR 5520, Inserm U1206, Creatis, 42023, Sint-Etienne, France
| | - Patrick Clarysse
- Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, Creatis UMR 5220, U1206, 69621, Lyon, France
| | - Michelle Michels
- Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Wim Stooker
- Department of Cardiothoracic Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Alexander B A Vonk
- Department of Cardiothoracic Surgery, VU University Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Peter M van der Ven
- Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
| | - Albert C van Rossum
- Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Jolanda van der Velden
- Department of Physiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.,The Netherlands Heart Institute, Utrecht, The Netherlands
| | - Robin Nijveldt
- Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
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24
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Gastl M, Peereboom SM, Gotschy A, Fuetterer M, von Deuster C, Boenner F, Kelm M, Schwotzer R, Flammer AJ, Manka R, Kozerke S. Myocardial triglycerides in cardiac amyloidosis assessed by proton cardiovascular magnetic resonance spectroscopy. J Cardiovasc Magn Reson 2019; 21:10. [PMID: 30700314 PMCID: PMC6354424 DOI: 10.1186/s12968-019-0519-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 01/04/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Cardiac involvement of amyloidosis leads to left-ventricular (LV) wall thickening with progressive heart failure requiring rehospitalization. Cardiovascular magnetic resonance (CMR) is a valuable tool to non-invasively assess myocardial thickening as well as structural changes. Proton CMR spectroscopy (1H-CMRS) additionally allows assessing metabolites including triglycerides (TG) and total creatine (CR). However, opposing results exist regarding utilization of these metabolites in LV hypertrophy or thickening. Therefore, the aim of this study was to measure metabolic alterations using 1H-CMRS in a group of patients with thickened myocardium caused by cardiac amyloidosis. METHODS 1H-CMRS was performed on a 1.5 T system (Achieva, Philips Healthcare, Best, The Netherlands) using a 5-channel receive coil in 11 patients with cardiac amyloidosis (60.5 ± 11.4 years, 8 males) and 11 age- and gender-matched controls (63.2 ± 8.9 years, 8 males). After cardiac morphology and function assessment, proton spectra from the interventricular septum (IVS) were acquired using a double-triggered PRESS sequence. Post-processing was performed using a customized reconstruction pipeline based on ReconFrame (GyroTools LLC, Zurich, Switzerland). Spectra were fitted in jMRUI/AMARES and the ratios of triglyceride-to-water (TG/W) and total creatine-to-water (CR/W) were calculated. RESULTS Besides an increased LV mass and a thickened IVS concomitant to the disease characteristics, patients with cardiac amyloidosis presented with decreased global longitudinal (GLS) and circumferential (GCS) strain. LV ejection fraction was preserved relative to controls (60.0 ± 13.2 vs. 66.1 ± 4.3%, p = 0.17). Myocardial TG/W ratios were significantly decreased compared to controls (0.53 ± 0.23 vs. 0.80 ± 0.26%, p = 0.015). CR/W ratios did not show a difference between both groups, but a higher standard deviation in patients with cardiac amyloidosis was observed. Pearson correlation revealed a negative association between elevated LV mass and TG/W (R = - 0.59, p = 0.004) as well as GCS (R = - 0.48, p = 0.025). CONCLUSIONS A decrease in myocardial TG/W can be detected in patients with cardiac amyloidosis alongside impaired cardiac function with an association to the degree of myocardial thickening. Accordingly, 1H-CMRS may provide an additional diagnostic tool to gauge progression of cardiac amyloidosis along with standard imaging sequences. TRIAL REGISTRATION EK 2013-0132.
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Affiliation(s)
- Mareike Gastl
- Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, 8092 Zurich, Switzerland
- Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
- Department Cardiology, Pneumology and Angiology, Heinrich Heine University, Düsseldorf, Germany
| | - Sophie M. Peereboom
- Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, 8092 Zurich, Switzerland
| | - Alexander Gotschy
- Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, 8092 Zurich, Switzerland
- Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
| | - Maximilian Fuetterer
- Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, 8092 Zurich, Switzerland
| | - Constantin von Deuster
- Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, 8092 Zurich, Switzerland
| | - Florian Boenner
- Department Cardiology, Pneumology and Angiology, Heinrich Heine University, Düsseldorf, Germany
| | - Malte Kelm
- Department Cardiology, Pneumology and Angiology, Heinrich Heine University, Düsseldorf, Germany
| | - Rahel Schwotzer
- Comprehensive Cancer Center Zürich, University Hospital Zurich, Zurich, Switzerland
| | - Andreas J. Flammer
- Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
| | - Robert Manka
- Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, 8092 Zurich, Switzerland
- Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland
| | - Sebastian Kozerke
- Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, 8092 Zurich, Switzerland
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25
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Mahmod M, Pal N, Rayner J, Holloway C, Raman B, Dass S, Levelt E, Ariga R, Ferreira V, Banerjee R, Schneider JE, Rodgers C, Francis JM, Karamitsos TD, Frenneaux M, Ashrafian H, Neubauer S, Rider O. The interplay between metabolic alterations, diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 2018; 20:88. [PMID: 30580760 PMCID: PMC6304764 DOI: 10.1186/s12968-018-0511-6] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 11/27/2018] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity. METHODS Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-cardiovascular magnetic resonance spectroscopy (1H-CMRS) to measure MTG (lipid/water, %), 31P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate. RESULTS When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45 ± 0.25% vs. 0.64 ± 0.16%, p = 0.009) and reduced PCr/ATP (1.60 ± 0.09 vs. 2.00 ± 0.10, p = 0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max. CONCLUSIONS Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.
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Affiliation(s)
- Masliza Mahmod
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
- National University of Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Nikhil Pal
- Divisions of Experimental Therapeutics and Cardiovascular Medicine, Radcliffe Department of Medicine, Oxford, UK
| | - Jennifer Rayner
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
| | - Cameron Holloway
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
| | - Betty Raman
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
| | - Sairia Dass
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
| | - Eylem Levelt
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
| | - Rina Ariga
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
| | - Vanessa Ferreira
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
| | - Rajarshi Banerjee
- 1st Department of Cardiology, Aristotle University, Thessaloniki, Greece
| | - Jurgen E. Schneider
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
| | - Christopher Rodgers
- Department of Medicine, John Radcliffe Hospital, Oxford, UK
- Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK
| | - Jane M. Francis
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
| | - Theodoros D. Karamitsos
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
- 1st Department of Cardiology, Aristotle University, Thessaloniki, Greece
| | - Michael Frenneaux
- Norwich Medical School, Bob Champion Research and Education Building, James Watson Road, University of East Anglia Norwich Research Park, Norwich, NR4 7UQ UK
| | - Houman Ashrafian
- Divisions of Experimental Therapeutics and Cardiovascular Medicine, Radcliffe Department of Medicine, Oxford, UK
| | - Stefan Neubauer
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
| | - Oliver Rider
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU UK
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Gong IY, Al-Amro B, Prasad GVR, Connelly PW, Wald RM, Wald R, Deva DP, Leong-Poi H, Nash MM, Yuan W, Gunaratnam L, Kim SJ, Lok CE, Connelly KA, Yan AT. Cardiovascular magnetic resonance left ventricular strain in end-stage renal disease patients after kidney transplantation. J Cardiovasc Magn Reson 2018; 20:83. [PMID: 30554567 PMCID: PMC6296102 DOI: 10.1186/s12968-018-0504-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Accepted: 11/09/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Cardiovascular disease is a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD) and kidney transplant (KT) patients. Compared with left ventricular (LV) ejection fraction (LVEF), LV strain has emerged as an important marker of LV function as it is less load dependent. We sought to evaluate changes in LV strain using cardiovascular magnetic resonance imaging (CMR) in ESRD patients who received KT, to determine whether KT may improve LV function. METHODS We conducted a prospective multi-centre longitudinal study of 79 ESRD patients (40 on dialysis, 39 underwent KT). CMR was performed at baseline and at 12 months after KT. RESULTS Among 79 participants (mean age 55 years; 30% women), KT patients had significant improvement in global circumferential strain (GCS) (p = 0.007) and global radial strain (GRS) (p = 0.003), but a decline in global longitudinal strain (GLS) over 12 months (p = 0.026), while no significant change in any LV strain was observed in the ongoing dialysis group. For KT patients, the improvement in LV strain paralleled improvement in LVEF (57.4 ± 6.4% at baseline, 60.6% ± 6.9% at 12 months; p = 0.001). For entire cohort, over 12 months, change in LVEF was significantly correlated with change in GCS (Spearman's r = - 0.42, p < 0.001), GRS (Spearman's r = 0.64, p < 0.001), and GLS (Spearman's r = - 0.34, p = 0.002). Improvements in GCS and GRS over 12 months were significantly correlated with reductions in LV end-diastolic volume index and LV end-systolic volume index (all p < 0.05), but not with change in blood pressure (all p > 0.10). CONCLUSIONS Compared with continuation of dialysis, KT was associated with significant improvements in LV strain metrics of GCS and GRS after 12 months, which did not correlate with blood pressure change. This supports the notion that KT has favorable effects on LV function beyond volume and blood pessure control. Larger studies with longer follow-up are needed to confirm these findings.
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Affiliation(s)
| | - Bandar Al-Amro
- Terrence Donnelly Heart Centre, St. Michael’s Hospital, Toronto, Canada
| | - G. V. Ramesh Prasad
- University of Toronto, Toronto, Canada
- Division of Nephrology, St Michael’s Hospital, Toronto, ON Canada
| | - Philip W. Connelly
- University of Toronto, Toronto, Canada
- Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Canada
| | - Rachel M. Wald
- University of Toronto, Toronto, Canada
- Division of Cardiology, Toronto General Hospital, Toronto, Canada
| | - Ron Wald
- University of Toronto, Toronto, Canada
- Division of Nephrology, St Michael’s Hospital, Toronto, ON Canada
| | - Djeven P. Deva
- University of Toronto, Toronto, Canada
- Department of Medical Imaging, St Michael’s Hospital, Toronto, Canada
| | - Howard Leong-Poi
- University of Toronto, Toronto, Canada
- Terrence Donnelly Heart Centre, St. Michael’s Hospital, Toronto, Canada
| | - Michelle M. Nash
- Division of Nephrology, St Michael’s Hospital, Toronto, ON Canada
| | - Weiqiu Yuan
- Division of Nephrology, St Michael’s Hospital, Toronto, ON Canada
| | - Lakshman Gunaratnam
- Division of Nephrology, Department of Medicine, London Health Sciences Centre, Schulich School of Medicine and Dentistry, Western University, London, Canada
| | - S. Joseph Kim
- University of Toronto, Toronto, Canada
- Department of Medicine, Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Charmaine E. Lok
- Department of Medicine, University Health Network-Toronto General Hospital, Toronto, Canada
| | - Kim A. Connelly
- University of Toronto, Toronto, Canada
- Terrence Donnelly Heart Centre, St. Michael’s Hospital, Toronto, Canada
| | - Andrew T. Yan
- University of Toronto, Toronto, Canada
- Terrence Donnelly Heart Centre, St. Michael’s Hospital, Toronto, Canada
- Division of Cardiology, St. Michael’s Hospital, 30 Bond Street, Rm 6-030 Donnelly, Toronto, M5B 1W8 Canada
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Epicardial Adipose Tissue and Myocardial Fibrosis in Aortic Stenosis Relationship With Symptoms and Outcomes: A Study Using Cardiac Magnetic Resonance Imaging. JACC Cardiovasc Imaging 2018; 12:213-214. [PMID: 30448134 DOI: 10.1016/j.jcmg.2018.06.025] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Revised: 06/13/2018] [Accepted: 06/22/2018] [Indexed: 11/23/2022]
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Podlesnikar T, Delgado V, Bax JJ. Cardiovascular magnetic resonance imaging to assess myocardial fibrosis in valvular heart disease. Int J Cardiovasc Imaging 2017. [PMID: 28642994 PMCID: PMC5797565 DOI: 10.1007/s10554-017-1195-y] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The left ventricular (LV) remodeling process associated with significant valvular heart disease (VHD) is characterized by an increase of myocardial interstitial space with deposition of collagen and loss of myofibers. These changes occur before LV systolic function deteriorates or the patient develops symptoms. Cardiovascular magnetic resonance (CMR) permits assessment of reactive fibrosis, with the use of T1 mapping techniques, and replacement fibrosis, with the use of late gadolinium contrast enhancement. In addition, functional consequences of these structural changes can be evaluated with myocardial tagging and feature tracking CMR, which assess the active deformation (strain) of the LV myocardium. Several studies have demonstrated that CMR techniques may be more sensitive than the conventional measures (LV ejection fraction or LV dimensions) to detect these structural and functional changes in patients with severe left-sided VHD and have shown that myocardial fibrosis may not be reversible after valve surgery. More important, the presence of myocardial fibrosis has been associated with lesser improvement in clinical symptoms and recovery of LV systolic function. Whether assessment of myocardial fibrosis may better select the patients with severe left-sided VHD who may benefit from surgery in terms of LV function and clinical symptoms improvement needs to be demonstrated in prospective studies. The present review article summarizes the current status of CMR techniques to assess myocardial fibrosis and appraises the current evidence on the use of these techniques for risk stratification of patients with severe aortic stenosis or regurgitation and mitral regurgitation.
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Affiliation(s)
- Tomaz Podlesnikar
- Department of Cardiology, Heart and Lung Center, Leiden University Medical Center, Albinusdreef 2 2333 ZA, Leiden, The Netherlands
| | - Victoria Delgado
- Department of Cardiology, Heart and Lung Center, Leiden University Medical Center, Albinusdreef 2 2333 ZA, Leiden, The Netherlands
| | - Jeroen J Bax
- Department of Cardiology, Heart and Lung Center, Leiden University Medical Center, Albinusdreef 2 2333 ZA, Leiden, The Netherlands.
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Musa TA, Uddin A, Swoboda PP, Fairbairn TA, Dobson LE, Singh A, Garg P, Steadman CD, Erhayiem B, Kidambi A, Ripley DP, McDiarmid AK, Haaf P, Blackman DJ, Plein S, McCann GP, Greenwood JP. Cardiovascular magnetic resonance evaluation of symptomatic severe aortic stenosis: association of circumferential myocardial strain and mortality. J Cardiovasc Magn Reson 2017; 19:13. [PMID: 28173819 PMCID: PMC5297161 DOI: 10.1186/s12968-017-0329-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 01/18/2017] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND It is unknown whether circumferential strain is associated with prognosis after treatment of aortic stenosis (AS). We aimed to characterise strain in severe AS, using myocardial tagging cardiovascular magnetic resonance (CMR), prior to and following Transcatheter Aortic Valve Implantation (TAVI) and Surgical Aortic Valve Replacement (SAVR), and determine whether abnormalities in strain were associated with outcome. METHODS CMR was performed pre- and 6 m post-intervention in 98 patients (52 TAVI, 46 SAVR; 77 ± 8 years) with severe AS. TAVI patients were older (80.9 ± 6.4 vs. 73.0 ± 7.0 years, p < 0.01) with a higher STS score (2.06 ± 0.6 vs. 6.03 ± 3.4, p < 0.001). Tagged cine images were acquired at the basal, mid and apical LV levels with a complementary spatial modulation of magnetization (CSPAMM) pulse sequence. Circumferential strain, strain rate and rotation were calculated using inTag© software. RESULTS No significant change in basal or mid LV circumferential strain, or of diastolic strain rate, was seen following either intervention. However, a significant and comparable decline in LV torsion and twist was observed (SAVR: torsion 14.08 ± 8.40 vs. 7.81 ± 4.51, p < 0.001, twist 16.17 ± 7.01 vs.12.45 ± 4.78, p < 0.01; TAVI: torsion 14.43 ± 4.66 vs. 11.20 ± 4.62, p < 0.001, twist 16.08 ± 5.36 vs. 12.36 ± 5.21, p < 0.001) which likely reflects an improvement towards normal physiology following relief of AS. Over a maximum 6.0y follow up, there were 23 (16%) deaths following valve intervention. On multivariable Cox analysis, baseline mid LV circumferential strain was significantly associated with all-cause mortality (hazard ratio, 1.03; 1.01-1.05; p = 0.009) independent of age, LV ejection fraction and STS mortality risk score. ROC analysis indicated a mid LV circumferential strain > -18.7% was associated with significantly reduced survival. CONCLUSION TAVI and SAVR procedures are associated with comparable declines in rotational LV mechanics at 6 m, with largely unchanged strain and strain rates. Pre-operative peak mid LV circumferential strain is associated with post-operative mortality.
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Affiliation(s)
- Tarique Al Musa
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
| | - Akhlaque Uddin
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
| | - Peter P. Swoboda
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
| | - Timothy A. Fairbairn
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
| | - Laura E. Dobson
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
| | - Anvesha Singh
- Department of Cardiovascular Sciences, and the National Institute of Health Research (NIHR), Cardiovascular Biomedical Research Unit, Glenfield General Hospital, University of Leicester, Leicester, UK
| | - Pankaj Garg
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
| | - Christopher D. Steadman
- Department of Cardiovascular Sciences, and the National Institute of Health Research (NIHR), Cardiovascular Biomedical Research Unit, Glenfield General Hospital, University of Leicester, Leicester, UK
| | - Bara Erhayiem
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
| | - Ananth Kidambi
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
| | - David P. Ripley
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
| | - Adam K. McDiarmid
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
| | - Philip Haaf
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
| | | | - Sven Plein
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
- Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary, Leeds, UK
| | - Gerald P. McCann
- Department of Cardiovascular Sciences, and the National Institute of Health Research (NIHR), Cardiovascular Biomedical Research Unit, Glenfield General Hospital, University of Leicester, Leicester, UK
| | - John P. Greenwood
- Multidisciplinary Cardiovascular Research Centre & The Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT UK
- Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary, Leeds, UK
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Nucifora G, Tantiongco JP, Crouch G, Bennetts J, Sinhal A, Tully PJ, Bradbrook C, Baker RA, Selvanayagam JB. Changes of left ventricular mechanics after trans-catheter aortic valve implantation and surgical aortic valve replacement for severe aortic stenosis: A tissue-tracking cardiac magnetic resonance study. Int J Cardiol 2017; 228:184-190. [DOI: 10.1016/j.ijcard.2016.11.200] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Accepted: 11/06/2016] [Indexed: 11/17/2022]
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Al Musa T, Uddin A, Swoboda PP, Garg P, Fairbairn TA, Dobson LE, Steadman CD, Singh A, Erhayiem B, Plein S, McCann GP, Greenwood JP. Myocardial strain and symptom severity in severe aortic stenosis: insights from cardiovascular magnetic resonance. Quant Imaging Med Surg 2017; 7:38-47. [PMID: 28275558 PMCID: PMC5337186 DOI: 10.21037/qims.2017.02.05] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 01/10/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND Symptomatic severe aortic stenosis (AS) is a class I indication for replacement in patients when left ventricular ejection fraction (LVEF) is preserved. However, symptom reporting is often equivocal and decision making can be challenging. We aimed to quantify myocardial deformation using cardiovascular magnetic resonance (CMR) in patients classified by symptom severity. METHODS Forty-two patients with severe AS referred to heart valve clinic were studied using tagged CMR imaging. All had preserved LVEF. Patients were grouped by symptoms as either "none/mild" (n=21, NYHA class I, II) or "significant" (n=21, NYHA class III, IV, angina, syncope) but were comparable for age (72.8±5.4 vs. 71.0±6.8 years old, P=0.345), surgical risk (EuroSCORE II: 1.90±1.7 vs. 1.31±0.4, P=0.302) and haemodynamics (peak aortic gradient: 55.1±20.8 vs. 50.4±15.6, P=0.450). Thirteen controls matched in age and LVEF were also studied. LV circumferential strain was calculated using inTag© software and longitudinal strain using feature tracking analysis. RESULTS Compared to healthy controls, patients with severe AS had significantly worse longitudinal and circumferential strain, regardless of symptom status. Patients with "significant" symptoms had significantly worse peak longitudinal systolic strain rates (-83.352±24.802%/s vs. -106.301±43.276%/s, P=0.048) than those with "no/mild" symptoms, with comparable peak longitudinal strain (PLS), peak circumferential strain and systolic and diastolic strain rates. CONCLUSIONS Patients with severe AS who have no or only mild symptoms exhibit comparable reduction in circumferential and longitudinal fibre function to those with significant symptoms, in whom AVR is clearly indicated. Given these findings of equivalent subclinical dysfunction, reportedly borderline symptoms should be handled cautiously to avoid potentially adverse delays in intervention.
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Affiliation(s)
- Tarique Al Musa
- Multidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Akhlaque Uddin
- Multidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Peter P. Swoboda
- Multidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Pankaj Garg
- Multidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Timothy A. Fairbairn
- Multidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Laura E. Dobson
- Multidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Christopher D. Steadman
- Department of Cardiovascular Sciences, University of Leicester, Glenfield General Hospital, Leicester, UK
- the National Institute of Health Research (NIHR), Cardiovascular Biomedical Research Unit, Glenfield General Hospital, Leicester, UK
| | - Anvesha Singh
- Department of Cardiovascular Sciences, University of Leicester, Glenfield General Hospital, Leicester, UK
- the National Institute of Health Research (NIHR), Cardiovascular Biomedical Research Unit, Glenfield General Hospital, Leicester, UK
| | - Bara Erhayiem
- Multidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Sven Plein
- Multidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
- Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary, Leeds, UK
| | - Gerald P. McCann
- Department of Cardiovascular Sciences, University of Leicester, Glenfield General Hospital, Leicester, UK
- the National Institute of Health Research (NIHR), Cardiovascular Biomedical Research Unit, Glenfield General Hospital, Leicester, UK
| | - John P. Greenwood
- Multidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
- Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary, Leeds, UK
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Abstract
Although echocardiography remains the mainstay imaging technique for the evaluation of patients with valvular heart disease (VHD), innovations in noninvasive imaging in the past few years have provided new insights into the pathophysiology and quantification of VHD, early detection of left ventricular (LV) dysfunction, and advanced prognostic assessment. The severity grading of valve dysfunction has been refined with the use of Doppler echocardiography, cardiac magnetic resonance (CMR), and CT imaging. LV ejection fraction remains an important criterion when deciding whether patients should be referred for surgery. However, echocardiographic strain imaging can now detect impaired LV systolic function before LV ejection fraction reduces, thus provoking the debate on whether patients with severe VHD should be referred for surgery at an earlier stage (before symptom onset). Impaired LV strain correlates with the amount of myocardial fibrosis detected with CMR techniques. Furthermore, accumulating data show that the extent of fibrosis associated with severe VHD has important prognostic implications. The present Review focuses on using these novel imaging modalities to assess pathophysiology, early LV dysfunction, and prognosis of major VHDs, including aortic stenosis, mitral regurgitation, and aortic regurgitation.
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Ávila-Vanzzini N, Fritche-Salazar JF, Vázquez-Castro NM, Rivera-Lara P, Pérez-Méndez O, Martínez-Herrera H, Gómez-Sánchez M, Aranda-Frausto A, Herrera-Bello H, Luna-Luna M, Arias Godínez JA. Echocardiographic and Histologic Correlations in Patients with Severe Aortic Stenosis: Influence of Overweight and Obesity. J Cardiovasc Ultrasound 2017; 24:303-311. [PMID: 28090258 PMCID: PMC5234343 DOI: 10.4250/jcu.2016.24.4.303] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Revised: 11/20/2016] [Accepted: 11/30/2016] [Indexed: 12/22/2022] Open
Abstract
Background Severe aortic stenosis (AS), leads to pathological left ventricular remodeling that may worsen with concomitant overweight and obesity (OW/O). Methods We aimed to prospectively analyze the impact of OW/O on ventricular remodeling in severe AS, by evaluating the percentage of intraendomyocardial fibrosis (PIEF) and the percentage of infiltrating intraendocardial lipid vacuoles (PIELV) and its relationship to global longitudinal strain (GLS) in patients with OW/O. Results 44 patients with severe AS were included, 13 non-obese (29%) and 31 OW/O (71%), all of them with left ventricular ejection fraction ≥ 55%. GLS was evaluated with 2D speckle tracking. During valve replacement, an endocardial biopsy was obtained, where PIEF and PIELV were analyzed. Patients with higher PIEF and PIELV had greater body mass index (p < 0.0001) and worse GLS (p < 0.0053). A GLS cut-off point < -14% had a sensitivity of 75%, and a specificity of 92.8% to detect important PIEF (AUC: 0.928, 95% confidence interval: 0.798–1.00). On multivariate analysis, OW/O and PIELV were independently associated to the PIEF, and OW/O and PIEF were independently associated to GLS. A high correlation between the amount of PIELV and PIEF were found. Conclusion Patients with severe AS and OW/O have greater PIEF and PIELV, suggesting more pathological remodeling. GLS is useful to detect subclinical myocardial injury and is potentially useful for endomyocardial fibrosis detection. The presence of higher PIELF may be a trigger factor for the development of intraendomyocardial fibrosis.
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Affiliation(s)
- Nydia Ávila-Vanzzini
- Department of Echocardiography, Ignacio Chávez National Cardiology Institute, Mexico City, Mexico
| | | | | | - Pedro Rivera-Lara
- Department of Echocardiography, Ignacio Chávez National Cardiology Institute, Mexico City, Mexico
| | - Oscar Pérez-Méndez
- Department of Molecular Biology, Ignacio Chávez National Cardiology Institute, Mexico City, Mexico
| | | | - Mario Gómez-Sánchez
- Department of Surgery, Ignacio Chávez National Cardiology Institute, Mexico City, Mexico
| | - Alberto Aranda-Frausto
- Department of Pathology, Ignacio Chávez National Cardiology Institute, Mexico City, Mexico
| | | | - María Luna-Luna
- Department of Molecular Biology, Ignacio Chávez National Cardiology Institute, Mexico City, Mexico
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Abstract
While mortality rates related to cardiovascular disease (CVD) have decreased over time among adults with HIV, excess risk of CVD in the HIV-infected population may persist despite highly active antiretroviral therapy (HAART) treatment and aggressive CVD risk factor control. Beyond atherosclerotic CVD, recent studies suggest that HIV infection may be associated with left ventricular systolic and diastolic function, interstitial myocardial fibrosis, and increased cardiac fat infiltration. Thus, with the increasing average age of the HIV-infected population, heart failure and arrhythmic disorders may soon rival coronary artery disease as the most prevalent forms of CVD. Finally, the question of whether HIV infection should be considered in clinical risk stratification has never been resolved, and this question has assumed new importance with recent changes to lipid treatment guidelines for prevention of CVD.
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Levelt E, Rodgers CT, Clarke WT, Mahmod M, Ariga R, Francis JM, Liu A, Wijesurendra RS, Dass S, Sabharwal N, Robson MD, Holloway CJ, Rider OJ, Clarke K, Karamitsos TD, Neubauer S. Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus. Eur Heart J 2016; 37:3461-3469. [PMID: 26392437 PMCID: PMC5201143 DOI: 10.1093/eurheartj/ehv442] [Citation(s) in RCA: 129] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Revised: 07/27/2015] [Accepted: 08/12/2015] [Indexed: 12/12/2022] Open
Abstract
AIMS Patients with type 2 diabetes mellitus (T2DM) are known to have impaired resting myocardial energetics and impaired myocardial perfusion reserve, even in the absence of obstructive epicardial coronary artery disease (CAD). Whether or not the pre-existing energetic deficit is exacerbated by exercise, and whether the impaired myocardial perfusion causes deoxygenation and further energetic derangement during exercise stress, is uncertain. METHODS AND RESULTS Thirty-one T2DM patients, on oral antidiabetic therapies with a mean HBA1c of 7.4 ± 1.3%, and 17 matched controls underwent adenosine stress cardiovascular magnetic resonance for assessment of perfusion [myocardial perfusion reserve index (MPRI)] and oxygenation [blood-oxygen level-dependent (BOLD) signal intensity change (SIΔ)]. Cardiac phosphorus-MR spectroscopy was performed at rest and during leg exercise. Significant CAD (>50% coronary stenosis) was excluded in all patients by coronary computed tomographic angiography. Resting phosphocreatine to ATP (PCr/ATP) was reduced by 17% in patients (1.74 ± 0.26, P = 0.001), compared with controls (2.07 ± 0.35); during exercise, there was a further 12% reduction in PCr/ATP (P = 0.005) in T2DM patients, but no change in controls. Myocardial perfusion and oxygenation were decreased in T2DM (MPRI 1.61 ± 0.43 vs. 2.11 ± 0.68 in controls, P = 0.002; BOLD SIΔ 7.3 ± 7.8 vs. 17.1 ± 7.2% in controls, P < 0.001). Exercise PCr/ATP correlated with MPRI (r = 0.50, P = 0.001) and BOLD SIΔ (r = 0.32, P = 0.025), but there were no correlations between rest PCr/ATP and MPRI or BOLD SIΔ. CONCLUSION The pre-existing energetic deficit in diabetic cardiomyopathy is exacerbated by exercise; stress PCr/ATP correlates with impaired perfusion and oxygenation. Our findings suggest that, in diabetes, coronary microvascular dysfunction exacerbates derangement of cardiac energetics under conditions of increased workload.
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Affiliation(s)
- Eylem Levelt
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
- Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK
| | - Christopher T Rodgers
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
| | - William T Clarke
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
| | - Masliza Mahmod
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
| | - Rina Ariga
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
| | - Jane M Francis
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
| | - Alexander Liu
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
| | - Rohan S Wijesurendra
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
| | - Saira Dass
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
| | | | - Matthew D Robson
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
| | - Cameron J Holloway
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
- Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK
- St. Vincent's Hospital, Sydney, Australia
| | - Oliver J Rider
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
| | - Kieran Clarke
- Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK
| | - Theodoros D Karamitsos
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
- 1st Department of Cardiology, AHEPA Hospital, Aristotle University, Thessaloniki, Greece
| | - Stefan Neubauer
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
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Stoll VM, Clarke WT, Levelt E, Liu A, Myerson SG, Robson MD, Neubauer S, Rodgers CT. Dilated Cardiomyopathy: Phosphorus 31 MR Spectroscopy at 7 T. Radiology 2016; 281:409-417. [PMID: 27326664 PMCID: PMC5084974 DOI: 10.1148/radiol.2016152629] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Cardiac phosphorus spectroscopy is demonstrated to be feasible in patients at 7 T,
giving higher signal-to-noise ratios and more precise quantification of the
phosphocreatine to adenosine triphosphate concentration ratio than at 3 T in a group
of 25 patients with dilated cardiomyopathy. Purpose To test whether the increased signal-to-noise ratio of phosphorus 31
(31P) magnetic resonance (MR) spectroscopy at 7 T improves precision
in cardiac metabolite quantification in patients with dilated cardiomyopathy (DCM)
compared with that at 3 T. Materials and Methods Ethical approval was obtained, and participants provided written informe consent.
In a prospective study, 31P MR spectroscopy was performed at 3 T and 7
T in 25 patients with DCM. Ten healthy matched control subjects underwent
31P MR spectroscopy at 7 T. Paired Student t tests
were performed to compare results between the 3-T and 7-T studies. Results The phosphocreatine (PCr) signal-to-noise ratio increased 2.5 times at 7 T
compared with that at 3 T. The PCr to adenosine triphosphate (ATP) concentration
ratio (PCr/ATP) was similar at both field strengths (mean ± standard
deviation, 1.48 ± 0.44 at 3 T vs 1.54 ± 0.39 at 7 T, P
= .49), as expected. The Cramér-Rao lower bounds in PCr concentration (a
measure of uncertainty in the measured ratio) were 45% lower at 7 T than at 3 T,
reflecting the higher quality of 7-T 31P spectra. Patients with dilated
cardioyopathy had a significantly lower PCr/ATP than did healthy control subjects
at 7 T (1.54 ± 0.39 vs 1.95 ± 0.25, P = .005),
which is consistent with previous findings. Conclusion 7-T cardiac 31P MR spectroscopy is feasible in patients with DCM and
gives higher signal-to-noise ratios and more precise quantification of the PCr/ATP
than that at 3 T. PCr/ATP was significantly lower in patients with DCM than in
control subjects at 7 T, which is consistent with previous findings at lower field
strengths.
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Affiliation(s)
- Victoria M Stoll
- From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Level 0, John Radcliffe Hospital, Oxford OX3 9DU, England
| | - William T Clarke
- From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Level 0, John Radcliffe Hospital, Oxford OX3 9DU, England
| | - Eylem Levelt
- From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Level 0, John Radcliffe Hospital, Oxford OX3 9DU, England
| | - Alexander Liu
- From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Level 0, John Radcliffe Hospital, Oxford OX3 9DU, England
| | - Saul G Myerson
- From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Level 0, John Radcliffe Hospital, Oxford OX3 9DU, England
| | - Matthew D Robson
- From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Level 0, John Radcliffe Hospital, Oxford OX3 9DU, England
| | - Stefan Neubauer
- From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Level 0, John Radcliffe Hospital, Oxford OX3 9DU, England
| | - Christopher T Rodgers
- From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Level 0, John Radcliffe Hospital, Oxford OX3 9DU, England
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Musa TA, Plein S, Greenwood JP. The role of cardiovascular magnetic resonance in the assessment of severe aortic stenosis and in post-procedural evaluation following transcatheter aortic valve implantation and surgical aortic valve replacement. Quant Imaging Med Surg 2016; 6:259-73. [PMID: 27429910 PMCID: PMC4929281 DOI: 10.21037/qims.2016.06.05] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Accepted: 04/02/2016] [Indexed: 01/20/2023]
Abstract
Degenerative aortic stenosis (AS) is the most common valvular disease in the western world with a prevalence expected to double within the next 50 years. International guidelines advocate the use of cardiovascular magnetic resonance (CMR) as an investigative tool, both to guide diagnosis and to direct optimal treatment. CMR is the reference standard for quantifying both left and right ventricular volumes and mass, which is essential to assess the impact of AS upon global cardiac function. Given the ability to image any structure in any plane, CMR offers many other diagnostic strengths including full visualisation of valvular morphology, direct planimetry of orifice area, the quantification of stenotic jets and in particular, accurate quantification of valvular regurgitation. In addition, CMR permits reliable and accurate measurements of the aortic root and arch which can be fundamental to appropriate patient management. There is a growing evidence base to indicate tissue characterisation using CMR provides prognostic information, both in asymptomatic AS patients and those undergoing intervention. Furthermore, a number of current clinical trials will likely raise the importance of CMR in routine patient management. This article will focus on the incremental value of CMR in the assessment of severe AS and the insights it offers following valve replacement.
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Affiliation(s)
- Tarique Al Musa
- Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Sven Plein
- Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - John P Greenwood
- Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
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Sai E, Shimada K, Yokoyama T, Hiki M, Sato S, Hamasaki N, Maruyama M, Morimoto R, Miyazaki T, Fujimoto S, Tamura Y, Aoki S, Watada H, Kawamori R, Daida H. Myocardial triglyceride content in patients with left ventricular hypertrophy: comparison between hypertensive heart disease and hypertrophic cardiomyopathy. Heart Vessels 2016; 32:166-174. [PMID: 27142065 DOI: 10.1007/s00380-016-0844-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2015] [Accepted: 04/22/2016] [Indexed: 12/29/2022]
Abstract
Proton magnetic resonance spectroscopy (1H-MRS) enables the assessment of myocardial triglyceride (TG) content, which is reported to be associated with cardiac dysfunction and morphology accompanied by metabolic disorder and cardiac hemodynamic status. The clinical usefulness of myocardial TG content measurements in patients with left ventricular hypertrophy (LVH) has not been fully investigated. We examined whether myocardial TG content assessed by 1H-MRS was useful for diagnosis in patients with LVH. To quantify myocardial TG content, we conducted 1H-MRS in 35 subjects with LVH. Left ventricular function was measured by cardiac magnetic resonance imaging. Patients were assigned to a hypertensive heart disease (HHD, n = 10) or hypertrophic cardiomyopathy (HCM, n = 25) group based on the histology and/or late gadolinium enhancement pattern. The myocardial TG content was significantly higher in the HHD group than in the HCM group (2.14 ± 1.29 vs. 1.09 ± 0.72 %, P < 0.001). Myocardial TG content were significantly and negatively correlated with LV mass (r = -0.41, P < 0.04) and stroke volume (r = -0.64, P < 0.05) in the HCM group and HHD group, respectively. In a multivariate analysis, LV mass volume and diagnosis of HCM or HHD were independent factors of the myocardial TG content. The results suggest that myocardial metabolism may differ between HCM and HHD patients and that measurement of myocardial TG content by 1H-MRS may be useful for evaluating the myocardial metabolic features of LVH.
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Affiliation(s)
- Eiryu Sai
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, Japan
| | - Kazunori Shimada
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, Japan.
- Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
| | - Takayuki Yokoyama
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, Japan
| | - Makoto Hiki
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, Japan
| | - Shuji Sato
- Department of Radiology, Juntendo University Hospital, Tokyo, Japan
| | - Nozomi Hamasaki
- Department of Radiology, Juntendo University Hospital, Tokyo, Japan
| | - Masaki Maruyama
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, Japan
| | - Ryoko Morimoto
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, Japan
| | - Tetsuro Miyazaki
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, Japan
| | - Shinichiro Fujimoto
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, Japan
| | - Yoshifumi Tamura
- Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Shigeki Aoki
- Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Hirotaka Watada
- Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Ryuzo Kawamori
- Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Hiroyuki Daida
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, Japan
- Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
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Brittain EL, Talati M, Fessel JP, Zhu H, Penner N, Calcutt MW, West JD, Funke M, Lewis GD, Gerszten RE, Hamid R, Pugh ME, Austin ED, Newman JH, Hemnes AR. Fatty Acid Metabolic Defects and Right Ventricular Lipotoxicity in Human Pulmonary Arterial Hypertension. Circulation 2016; 133:1936-44. [PMID: 27006481 DOI: 10.1161/circulationaha.115.019351] [Citation(s) in RCA: 179] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 03/18/2016] [Indexed: 11/16/2022]
Abstract
BACKGROUND The mechanisms of right ventricular (RV) failure in pulmonary arterial hypertension (PAH) are poorly understood. Abnormalities in fatty acid (FA) metabolism have been described in experimental models of PAH, but systemic and myocardial FA metabolism has not been studied in human PAH. METHODS AND RESULTS We used human blood, RV tissue, and noninvasive imaging to characterize multiple steps in the FA metabolic pathway in PAH subjects and controls. Circulating free FAs and long-chain acylcarnitines were elevated in PAH patients versus controls. Human RV long-chain FAs were increased and long-chain acylcarnitines were markedly reduced in PAH versus controls. With the use of proton magnetic resonance spectroscopy, in vivo myocardial triglyceride content was elevated in human PAH versus controls (1.4±1.3% triglyceride versus 0.22±0.11% triglyceride, P=0.02). Ceramide, a mediator of lipotoxicity, was increased in PAH RVs versus controls. Using an animal model of heritable PAH, we demonstrated reduced FA oxidation via failure of palmitoylcarnitine to stimulate oxygen consumption in the PAH RV. CONCLUSIONS Abnormalities in FA metabolism can be detected in the blood and myocardium in human PAH and are associated with in vivo cardiac steatosis and lipotoxicity. Murine data suggest that lipotoxicity may arise from reduction in FA oxidation.
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Affiliation(s)
- Evan L Brittain
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.).
| | - Megha Talati
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - Joshua P Fessel
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - He Zhu
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - Niki Penner
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - M Wade Calcutt
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - James D West
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - Mitch Funke
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - Gregory D Lewis
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - Robert E Gerszten
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - Rizwan Hamid
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - Meredith E Pugh
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - Eric D Austin
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - John H Newman
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
| | - Anna R Hemnes
- From Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (E.L.B.); Vanderbilt Translational and Clinical Cardiovascular Center, Vanderbilt University Medical Center, Nashville, TN (E.L.B.); Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN (M.T., J.P.F., N.P., J.D.W., M.F., M.E.P., J.H.N., A.R.H.); Vanderbilt University Institute of Imaging Science, Nashville, TN (H.Z.); Department of Biochemistry; Vanderbilt University, Nashville, TN (M.W.C.); Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (D.G.L., R.E.G.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., R.E.G.); Broad Institute of MIT and Harvard, Cambridge, MA (R.E.G.); Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (R.H.); and Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN (E.D.A.)
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Liao PA, Lin G, Tsai SY, Wang CH, Juan YH, Lin YC, Wu MT, Yang LY, Liu MH, Chang TC, Lin YC, Huang YC, Huang PC, Wang JJ, Ng SH, Ng KK. Myocardial triglyceride content at 3 T cardiovascular magnetic resonance and left ventricular systolic function: a cross-sectional study in patients hospitalized with acute heart failure. J Cardiovasc Magn Reson 2016; 18:9. [PMID: 26850626 PMCID: PMC4744377 DOI: 10.1186/s12968-016-0228-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2015] [Accepted: 01/25/2016] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Increased myocardial triglyceride (TG) content has been recognized as a risk factor for cardiovascular disease. However, its relation with cardiac function in patients on recovery from acute heart failure (HF) remains unclear. In this cross-sectional study, we sought to investigate the association between myocardial TG content measured on magnetic resonance spectroscopy ((1)H-MRS) and left ventricular (LV) function assessed on cardiovascular magnetic resonance (CMR) in patients who were hospitalized with HF. METHODS A total of 50 patients who were discharged after hospitalization for acute HF and 21 age- and sex-matched controls were included in the study. Myocardial TG content and LV parameters (function and mass) were measured on a 3.0 T MR scanner. Fatty acid (FA) and unsaturated fatty acid (UFA) content was normalized against water (W) using the LC-Model algorithm. The patient population was dichotomized according to the left ventricular ejection fraction (LVEF, <50% or ≥ 50%). RESULTS H-MRS data were available for 48 patients and 21 controls. Of the 48 patients, 25 had a LVEF <50% (mean, 31.2%), whereas the remaining 23 had a normal LVEF (mean, 60.2%). Myocardial UFA/W ratio was found to differ significantly in patients with low LVEF, normal LVEF, and controls (0.79% vs. 0.21% vs. 0.14%, respectively, p = 0.02). The myocardial UFA/TG ratio was associated with LV mass (r = 0.39, p < 0.001) and modestly related to LV end-diastolic volume (LVEDV; r = 0.24, p = 0.039). We also identified negative correlations of the myocardial FA/TG ratio with both LV mass (r = -0.39, p < 0.001) and LVEDV (r = -0.24, p = 0.039). CONCLUSIONS As compared with controls, patients who were discharged after hospitalization for acute HF had increased myocardial UFA content; furthermore, UFA was inversely related with LVEF, LV mass and, to a lesser extent, LVEDV. Our study may stimulate further research on the measure of myocardial UFA content by (1)H-MRS for outcome prediction. TRIAL REGISTRATION ClinicalTrial.gov: NCT02378402 . Registered 27/02/2015.
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Affiliation(s)
- Pen-An Liao
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, 5 Fuhsing Street, Gueishan, Taoyuan, 333, Taiwan.
| | - Gigin Lin
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, 5 Fuhsing Street, Gueishan, Taoyuan, 333, Taiwan.
- Institute for Radiological Research, Chang Gung University, Taoyuan, Taiwan.
| | - Shang-Yueh Tsai
- Graduate Institute of Applied Physics, National Chengchi University, Taipei, Taiwan.
| | - Chao-Hung Wang
- Department of Cardiology and Heart Failure Center, Chang Gung Memorial Hospital, Keelung, Taiwan.
| | - Yu-Hsiang Juan
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, 5 Fuhsing Street, Gueishan, Taoyuan, 333, Taiwan.
| | - Yu-Ching Lin
- Department of Radiology, Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung, Taiwan.
| | - Ming-Ting Wu
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
| | - Lan-Yan Yang
- Clinical Trial Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
| | - Min-Hui Liu
- Department of Cardiology and Heart Failure Center, Chang Gung Memorial Hospital, Keelung, Taiwan.
| | - Tsun-Ching Chang
- Department of Radiology, Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung, Taiwan.
| | - Yu-Chun Lin
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, 5 Fuhsing Street, Gueishan, Taoyuan, 333, Taiwan.
| | - Yu-Chieh Huang
- Department of Radiology, Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung, Taiwan.
| | - Pei-Ching Huang
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, 5 Fuhsing Street, Gueishan, Taoyuan, 333, Taiwan.
| | - Jiun-Jie Wang
- Institute for Radiological Research, Chang Gung University, Taoyuan, Taiwan.
| | - Shu-Hang Ng
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, 5 Fuhsing Street, Gueishan, Taoyuan, 333, Taiwan.
| | - Koon-Kwan Ng
- Department of Radiology, Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung, Taiwan.
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Wei J, Nelson MD, Szczepaniak EW, Smith L, Mehta PK, Thomson LEJ, Berman DS, Li D, Bairey Merz CN, Szczepaniak LS. Myocardial steatosis as a possible mechanistic link between diastolic dysfunction and coronary microvascular dysfunction in women. Am J Physiol Heart Circ Physiol 2016; 310:H14-9. [PMID: 26519031 PMCID: PMC4865076 DOI: 10.1152/ajpheart.00612.2015] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 10/27/2015] [Indexed: 11/22/2022]
Abstract
Women with coronary microvascular dysfunction (CMD) and no obstructive coronary artery disease (CAD) have increased rates of heart failure with preserved ejection fraction (HFpEF). The mechanisms of HFpEF are not well understood. Ectopic fat deposition in the myocardium, termed myocardial steatosis, is frequently associated with diastolic dysfunction in other metabolic diseases. We investigated the prevalence of myocardial steatosis and diastolic dysfunction in women with CMD and subclinical HFpEF. In 13 women, including eight reference controls and five women with CMD and evidence of subclinical HFpEF (left ventricular end-diastolic pressure >12 mmHg), we measured myocardial triglyceride content (TG) and diastolic function, by proton magnetic resonance spectroscopy and magnetic resonance tissue tagging, respectively. When compared with reference controls, women with CMD had higher myocardial TG content (0.83 ± 0.12% vs. 0.43 ± 0.06%; P = 0.025) and lower diastolic circumferential strain rate (168 ± 12 vs. 217 ± 15%/s; P = 0.012), with myocardial TG content correlating inversely with diastolic circumferential strain rate (r = -0.779; P = 0.002). This study provides proof-of-concept that myocardial steatosis may play an important mechanistic role in the development of diastolic dysfunction in women with CMD and no obstructive CAD. Detailed longitudinal studies are warranted to explore specific treatment strategies targeting myocardial steatosis and its effect on diastolic function.
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Affiliation(s)
- Janet Wei
- Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California;
| | - Michael D Nelson
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California; and
| | - Edward W Szczepaniak
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California; and
| | - Laura Smith
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California; and
| | - Puja K Mehta
- Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California
| | - Louise E J Thomson
- S. Mark Taper Foundation Imaging Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Daniel S Berman
- S. Mark Taper Foundation Imaging Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Debiao Li
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California; and
| | - C Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California
| | - Lidia S Szczepaniak
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California; and
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Novel plasma and imaging biomarkers in heart failure with preserved ejection fraction. IJC HEART & VASCULATURE 2015; 9:55-62. [PMID: 28785707 PMCID: PMC5497340 DOI: 10.1016/j.ijcha.2015.07.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 07/25/2015] [Indexed: 12/17/2022]
Abstract
Existing diagnostic guidelines for heart failure with preserved ejection fraction (HFPEF) primarily comprise natriuretic peptides and echocardiographic assessment, highlighting the role of diastolic dysfunction. However, recent discoveries of novel plasma markers implicated in pathophysiology of heart failure and technological advances in imaging provide additional biomarkers which are potentially applicable to HFPEF. The evidence base for plasma extra-cellular matrix (ECM) peptides, galectin-3, ST2, GDF-15 and pentraxin-3 is reviewed. Furthermore, the capabilities of novel imaging techniques to assess existing parameters (e.g. left ventricular ejection fraction, systolic & diastolic function, chamber size) and additional derangements of the ECM, myocardial mechanics and ischaemia evaluation are addressed.
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Hall ME, Harmancey R, Stec DE. Lean heart: Role of leptin in cardiac hypertrophy and metabolism. World J Cardiol 2015; 7:511-524. [PMID: 26413228 PMCID: PMC4577678 DOI: 10.4330/wjc.v7.i9.511] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 06/16/2015] [Accepted: 07/23/2015] [Indexed: 02/06/2023] Open
Abstract
Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin’s role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity.
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Mantovani A, Pernigo M, Bergamini C, Bonapace S, Lipari P, Valbusa F, Bertolini L, Zenari L, Pichiri I, Dauriz M, Zoppini G, Barbieri E, Byrne CD, Bonora E, Targher G. Heart valve calcification in patients with type 2 diabetes and nonalcoholic fatty liver disease. Metabolism 2015; 64:879-87. [PMID: 25957758 DOI: 10.1016/j.metabol.2015.04.003] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2015] [Revised: 04/03/2015] [Accepted: 04/20/2015] [Indexed: 12/22/2022]
Abstract
PURPOSE Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are two powerful predictors of adverse cardiovascular outcomes in patients with type 2 diabetes, but the etiology of valvular calcification is uncertain. Nonalcoholic fatty liver disease (NAFLD) is an emerging cardiovascular risk factor and is very common in type 2 diabetes, but whether NAFLD is associated with valvular calcification in this group of patients is presently unknown. METHODS We undertook a cross-sectional study of 247 consecutive type 2 diabetic outpatients with no previous history of heart failure, valvular heart diseases (aortic stenosis, mitral stenosis, moderate or severe aortic and mitral regurgitation) or hepatic diseases. Presence of MAC and AVS was detected by echocardiography. NAFLD was diagnosed by ultrasonography. RESULTS Overall, 139 (56.3%) patients had no heart valve calcification (HVC-0), 65 (26.3%) patients had one valve affected (HVC-1) and 43 (17.4%) patients had both valves affected (HVC-2). 175 (70.8%) patients had NAFLD and the prevalence of this disease markedly increased in patients with HVC-2 compared with either HVC-1 or HVC-0 (86.1% vs. 83.1% vs. 60.4%, respectively; p < 0.001). NAFLD was significantly associated with AVS and/or MAC (unadjusted-odds ratio 3.51, 95% CI 1.89-6.51, p < 0.001). Adjustments for age, sex, waist circumference, smoking, blood pressure, hemoglobin A1c, LDL-cholesterol, kidney function parameters, medication use and echocardiographic variables did not appreciably weaken this association (adjusted-odds ratio 2.70, 95% CI 1.23-7.38, p < 0.01). CONCLUSIONS Our results show that NAFLD is an independent predictor of cardiac calcification in both the aortic and mitral valves in patients with type 2 diabetes.
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Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Matteo Pernigo
- Section of Cardiology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Corinna Bergamini
- Section of Cardiology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Stefano Bonapace
- Division of Cardiology, "Sacro Cuore" Hospital, Negrar (VR) Italy
| | - Paola Lipari
- Division of Cardiology, "Sacro Cuore" Hospital, Negrar (VR) Italy
| | - Filippo Valbusa
- Division of General Medicine and Diabetes Unit "Sacro Cuore" Hospital, Negrar (VR) Italy
| | - Lorenzo Bertolini
- Division of General Medicine and Diabetes Unit "Sacro Cuore" Hospital, Negrar (VR) Italy
| | - Luciano Zenari
- Division of General Medicine and Diabetes Unit "Sacro Cuore" Hospital, Negrar (VR) Italy
| | - Isabella Pichiri
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Marco Dauriz
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giacomo Zoppini
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Enrico Barbieri
- Division of Cardiology, "Sacro Cuore" Hospital, Negrar (VR) Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Enzo Bonora
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
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van Ewijk PA, Schrauwen-Hinderling VB, Bekkers SCAM, Glatz JFC, Wildberger JE, Kooi ME. MRS: a noninvasive window into cardiac metabolism. NMR IN BIOMEDICINE 2015; 28:747-66. [PMID: 26010681 DOI: 10.1002/nbm.3320] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Revised: 04/02/2015] [Accepted: 04/07/2015] [Indexed: 05/21/2023]
Abstract
A well-functioning heart requires a constant supply of a balanced mixture of nutrients to be used for the production of adequate amounts of adenosine triphosphate, which is the main energy source for most cellular functions. Defects in cardiac energy metabolism are linked to several myocardial disorders. MRS can be used to study in vivo changes in cardiac metabolism noninvasively. MR techniques allow repeated measurements, so that disease progression and the response to treatment or to a lifestyle intervention can be monitored. It has also been shown that MRS can predict clinical heart failure and death. This article focuses on in vivo MRS to assess cardiac metabolism in humans and experimental animals, as experimental animals are often used to investigate the mechanisms underlying the development of metabolic diseases. Various MR techniques, such as cardiac (31) P-MRS, (1) H-MRS, hyperpolarized (13) C-MRS and Dixon MRI, are described. A short overview of current and emerging applications is given. Cardiac MRS is a promising technique for the investigation of the relationship between cardiac metabolism and cardiac disease. However, further optimization of scan time and signal-to-noise ratio is required before broad clinical application. In this respect, the ongoing development of advanced shimming algorithms, radiofrequency pulses, pulse sequences, (multichannel) detection coils, the use of hyperpolarized nuclei and scanning at higher magnetic field strengths offer future perspective for clinical applications of MRS.
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Affiliation(s)
- Petronella A van Ewijk
- Maastricht University Medical Center, Human Biology, Maastricht, the Netherlands
- Maastricht University Medical Center, Radiology, Maastricht, the Netherlands
- Maastricht University Medical Center, NUTRIM - School for Nutrition, Toxicology and Metabolism, Maastricht, the Netherlands
| | - Vera B Schrauwen-Hinderling
- Maastricht University Medical Center, Human Biology, Maastricht, the Netherlands
- Maastricht University Medical Center, Radiology, Maastricht, the Netherlands
- Maastricht University Medical Center, NUTRIM - School for Nutrition, Toxicology and Metabolism, Maastricht, the Netherlands
| | | | - Jan F C Glatz
- Maastricht University Medical Center, Molecular Genetics, Maastricht, the Netherlands
- Maastricht University Medical Center, CARIM - Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands
| | | | - M Eline Kooi
- Maastricht University Medical Center, Radiology, Maastricht, the Netherlands
- Maastricht University Medical Center, NUTRIM - School for Nutrition, Toxicology and Metabolism, Maastricht, the Netherlands
- Maastricht University Medical Center, CARIM - Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands
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47
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Jiang K, Yu X. Quantification of regional myocardial wall motion by cardiovascular magnetic resonance. Quant Imaging Med Surg 2014; 4:345-57. [PMID: 25392821 DOI: 10.3978/j.issn.2223-4292.2014.09.01] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2014] [Accepted: 09/12/2014] [Indexed: 12/12/2022]
Abstract
Cardiovascular magnetic resonance (CMR) is a versatile tool that also allows comprehensive and accurate measurement of both global and regional myocardial contraction. Quantification of regional wall motion parameters, such as strain, strain rate, twist and torsion, has been shown to be more sensitive to early-stage functional alterations. Since the invention of CMR tagging by magnetization saturation in 1988, several CMR techniques have been developed to enable the measurement of regional myocardial wall motion, including myocardial tissue tagging, phase contrast mapping, displacement encoding with stimulated echoes (DENSE), and strain encoded (SENC) imaging. These techniques have been developed with their own advantages and limitations. In this review, two widely used and closely related CMR techniques, i.e., tissue tagging and DENSE, will be discussed from the perspective of pulse sequence development and image-processing techniques. The clinical and preclinical applications of tissue tagging and DENSE in assessing wall motion mechanics in both normal and diseased hearts, including coronary artery diseases, hypertrophic cardiomyopathy, aortic stenosis, and Duchenne muscular dystrophies, will be discussed.
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Affiliation(s)
- Kai Jiang
- 1 Departments of Biomedical Engineering, 2 Case Center for Imaging Research, 3 Radiology, and 4 Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA
| | - Xin Yu
- 1 Departments of Biomedical Engineering, 2 Case Center for Imaging Research, 3 Radiology, and 4 Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA
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Carasso S, Mutlak D, Lessick J, Reisner SA, Rakowski H, Agmon Y. Symptoms in severe aortic stenosis are associated with decreased compensatory circumferential myocardial mechanics. J Am Soc Echocardiogr 2014; 28:218-25. [PMID: 25441330 DOI: 10.1016/j.echo.2014.09.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2014] [Indexed: 12/22/2022]
Abstract
BACKGROUND Symptomatic patients with severe aortic stenosis (AS) demonstrate abnormal left ventricular (LV) mechanics. The aim of this study was to compare mechanics in asymptomatic and symptomatic patients with severe AS using two-dimensional myocardial strain imaging. METHODS One hundred fifty-four patients with severe AS (aortic valve area ≤ 1.0 cm(2)) referred to a heart valve clinic from 2004 to 2011 were studied. Thirty patients were asymptomatic, with normal LV ejection fractions (≥ 55%), without other significant valvular disease or wall motion abnormalities. Thirty-two symptomatic patients who underwent early aortic valve replacement, with similar age, gender, LV ejection fraction, and aortic valve area, were selected for comparison. Both groups were also compared with 32 healthy subjects with similar age and gender distributions and normal echocardiographic results who served as controls. LV longitudinal and circumferential strain and rotation were measured using speckle-tracking software applied to archived echocardiographic studies. Conventional echocardiographic and myocardial mechanical parameters were compared among the study subgroups. RESULTS Patients with asymptomatic severe AS demonstrated smaller reductions in longitudinal strain, higher (supernormal) apical circumferential strain (-38 ± 6% vs -35 ± 4%, P < .05), and extreme (supernormal) apical rotation (12.2 ± 4.9° vs 2.9 ± 1.7°, P < .0005) compared with symptomatic patients. Apical rotation < 6° was the single significant predictor of symptoms in logistic regression analysis of clinical, echocardiographic, and mechanical parameters. Twelve asymptomatic patients underwent eventual aortic valve replacement and showed decreases in strain and apical rotation compared with baseline values. CONCLUSIONS Longitudinal strain was uniformly low in patients with severe AS and lower in those with symptoms. Compensatory circumferential myocardial mechanics (increased apical circumferential strain and rotation) were absent in symptomatic patients. Thus, myocardial mechanics may help in the follow-up of patients with severe AS and timing of valve surgery.
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Affiliation(s)
- Shemy Carasso
- Department of Cardiology, Rambam Health Care Campus, Haifa, Israel; Technion - Israel Institute of Technology, Haifa, Israel.
| | - Diab Mutlak
- Department of Cardiology, Rambam Health Care Campus, Haifa, Israel
| | - Jonathan Lessick
- Department of Cardiology, Rambam Health Care Campus, Haifa, Israel; Technion - Israel Institute of Technology, Haifa, Israel
| | - Shimon A Reisner
- Department of Cardiology, Rambam Health Care Campus, Haifa, Israel; Technion - Israel Institute of Technology, Haifa, Israel
| | - Harry Rakowski
- University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Yoram Agmon
- Department of Cardiology, Rambam Health Care Campus, Haifa, Israel; Technion - Israel Institute of Technology, Haifa, Israel
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Singh A, Steadman CD, McCann GP. Advances in the Understanding of the Pathophysiology and Management of Aortic Stenosis: Role of Novel Imaging Techniques. Can J Cardiol 2014; 30:994-1003. [DOI: 10.1016/j.cjca.2014.03.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2013] [Revised: 02/28/2014] [Accepted: 03/01/2014] [Indexed: 12/17/2022] Open
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Capoulade R, Larose É, Mathieu P, Clavel MA, Dahou A, Arsenault M, Bédard É, Larue-Grondin S, Le Ven F, Dumesnil JG, Després JP, Pibarot P. Visceral Adiposity and Left Ventricular Mass and Function in Patients With Aortic Stenosis: The PROGRESSA Study. Can J Cardiol 2014; 30:1080-7. [DOI: 10.1016/j.cjca.2014.02.007] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 01/27/2014] [Accepted: 02/01/2014] [Indexed: 11/29/2022] Open
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