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Marzoog BA, Chomakhidze P, Gognieva D, Parunova AY, Demchuk SN, Silantyev A, Kuznetsova N, Kostikova A, Podgalo D, Nagornov E, Gadzhiakhmedova A, Kopylov P. Updates in breathomics behavior in ischemic heart disease and heart failure, mass-spectrometry. World J Cardiol 2025; 17:102851. [DOI: 10.4330/wjc.v17.i2.102851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/18/2024] [Accepted: 01/23/2025] [Indexed: 02/25/2025] Open
Abstract
BACKGROUND Cardiovascular disease (CVD) and associated sequalae remain the leading cause of disability worldwide. Ischemic heart disease (IHD) and heart failure are the most common etiologies of morbidity and mortality worldwide. This is due to the poor diagnostic and management methods for heart failure and IHD. Early detection of related risk factors through modern strategies is underestimated and requires further research.
AIM To interpret data from the published literature on volatile organic compounds (VOC), including all the methods used to analyze exhaled breath in patients with IHD and heart failure.
METHODS Searches for specific keywords were performed on Scopus and PubMed. A total of 20 studies were identified in breath analysis and IHD and heart failure. The study is registered in PROSPERO (Registration No. CRD42023470556).
RESULTS Considering the articles found, more research is required to gain a full understanding of the role of VOCs in IHD and heart failure. However, the existing literature demonstrates that cardiac metabolic changes can be expressed in exhaled air. The number of papers found is extremely low, making interpretation extremely difficult.
CONCLUSION Exhaled breath analysis can be a novel biomarker for the diagnosis and prevention of heart failure and IHD. Exhaled breath analysis can be used as a mirror to reflect the metabolic changes related to IHD and heart failure.
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Affiliation(s)
| | - Peter Chomakhidze
- Department of Cardiology, Sechenov University, Moscow 119991, Moskva, Russia
| | - Daria Gognieva
- Department of Cardiology, Sechenov University, Moscow 119991, Moskva, Russia
| | - Alena Yurievna Parunova
- Undergraduate Student, National Research Ogarev Mordovia State University, Saransk 430005, Russia
| | | | - Artemiy Silantyev
- Department of Cardiology, Sechenov University, Moscow 119991, Moskva, Russia
| | - Natalia Kuznetsova
- Department of Cardiology, Sechenov University, Moscow 119991, Moskva, Russia
| | | | - Dmitrii Podgalo
- Department of Cardiology, Sechenov University, Moscow 119991, Moskva, Russia
| | - Evgeny Nagornov
- Department of Cardiology, Sechenov University, Moscow 119991, Moskva, Russia
| | | | - Philipp Kopylov
- Department of Cardiology, Sechenov University, Moscow 119991, Moskva, Russia
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Marzoog BA, Chomakhidze P, Gognieva D, Gagarina NV, Silantyev A, Suvorov A, Fominykha E, Mustafina M, Natalya E, Gadzhiakhmedova A, Kopylov P. Machine Learning Model Discriminate Ischemic Heart Disease Using Breathome Analysis. Biomedicines 2024; 12:2814. [PMID: 39767720 PMCID: PMC11673773 DOI: 10.3390/biomedicines12122814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 11/11/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Ischemic heart disease (IHD) impacts the quality of life and is the most frequently reported cause of morbidity and mortality globally. Aims: To assess the changes in the exhaled volatile organic compounds (VOCs) in patients with vs. without ischemic heart disease (IHD) confirmed by stress computed tomography myocardial perfusion (CTP) imaging. Objectives: IHD early diagnosis and management remain underestimated due to the poor diagnostic and therapeutic strategies including the primary prevention methods. Materials and Methods: A single center observational study included 80 participants. The participants were aged ≥ 40 years and given an informed written consent to participate in the study and publish any associated figures. Both groups, G1 (n = 31) with and G2 (n = 49) without post stress-induced myocardial perfusion defect, passed cardiologist consultation, anthropometric measurements, blood pressure and pulse rate measurements, echocardiography, real time breathing at rest into PTR-TOF-MS-1000, cardio-ankle vascular index, bicycle ergometry, and immediately after performing bicycle ergometry repeating the breathing analysis into the PTR-TOF-MS-1000, and after three minutes from the end of the second breath, repeat the breath into the PTR-TOF-MS-1000, then performing CTP. LASSO regression with nested cross-validation was used to find the association between the exhaled VOCs and existence of myocardial perfusion defect. Statistical processing performed with R programming language v4.2 and Python v.3.10 [^R], STATISTICA program v.12, and IBM SPSS v.28. Results: The VOCs specificity 77.6% [95% confidence interval (CI); 0.666; 0.889], sensitivity 83.9% [95% CI; 0.692; 0.964], and diagnostic accuracy; area under the curve (AUC) 83.8% [95% CI; 0.73655857; 0.91493173]. Whereas the AUC of the bicycle ergometry 50.7% [95% CI; 0.388; 0.625], specificity 53.1% [95% CI; 0.392; 0.673], and sensitivity 48.4% [95% CI; 0.306; 0.657]. Conclusions: The VOCs analysis appear to discriminate individuals with vs. without IHD using machine learning models. Other: The exhaled breath analysis reflects the myocardiocytes metabolomic signature and related intercellular homeostasis changes and regulation perturbances. Exhaled breath analysis poses a promise result to improve the diagnostic accuracy of the physical stress tests using machine learning models.
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Affiliation(s)
- Basheer Abdullah Marzoog
- World-Class Research Center «Digital Biodesign and Personalized Healthcare», I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, 119991 Moscow, Russia
| | - Peter Chomakhidze
- World-Class Research Center «Digital Biodesign and Personalized Healthcare», I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, 119991 Moscow, Russia
| | - Daria Gognieva
- World-Class Research Center «Digital Biodesign and Personalized Healthcare», I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, 119991 Moscow, Russia
| | - Nina Vladimirovna Gagarina
- University Clinical Hospital Number 1, Radiology Department, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, 119991 Moscow, Russia
| | - Artemiy Silantyev
- World-Class Research Center «Digital Biodesign and Personalized Healthcare», I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, 119991 Moscow, Russia
| | - Alexander Suvorov
- World-Class Research Center «Digital Biodesign and Personalized Healthcare», I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, 119991 Moscow, Russia
| | - Ekaterina Fominykha
- University Clinical Hospital Number 1, Radiology Department, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, 119991 Moscow, Russia
| | - Malika Mustafina
- World-Class Research Center «Digital Biodesign and Personalized Healthcare», I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, 119991 Moscow, Russia
| | - Ershova Natalya
- World-Class Research Center «Digital Biodesign and Personalized Healthcare», I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, 119991 Moscow, Russia
| | - Aida Gadzhiakhmedova
- World-Class Research Center «Digital Biodesign and Personalized Healthcare», I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, 119991 Moscow, Russia
| | - Philipp Kopylov
- World-Class Research Center «Digital Biodesign and Personalized Healthcare», I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, 119991 Moscow, Russia
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Zhang N, Liu D, Zhao J, Tse G, Zhou J, Zhang Q, Lip GYH, Liu T. Circulating ketone bodies, genetic susceptibility, with left atrial remodeling and atrial fibrillation: A prospective study from the UK Biobank. Heart Rhythm 2024:S1547-5271(24)03454-4. [PMID: 39433077 DOI: 10.1016/j.hrthm.2024.10.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 10/11/2024] [Accepted: 10/12/2024] [Indexed: 10/23/2024]
Abstract
BACKGROUND Ketone bodies (KBs) are an important cardiac metabolic energy source. Metabolic remodeling has recently been found to play an important role in the pathological process of atrial fibrillation (AF). OBJECTIVE The purpose of this study was to evaluate the associations of circulating KB levels with incident AF risk in the general population. METHODS We studied 237,163 participants [mean age, 56.5 years; 129,472 women (55%)] from the UK Biobank who were free of AF at baseline and had data on circulating β-hydroxybutyrate (β-OHB), acetoacetate, and acetone. The associations of KBs with new-onset AF were evaluated using Cox regression in the general population and across the 3 genetic risk groups: low, moderate, and high polygenic risk score of AF. RESULTS During a median follow-up of 14.8 (13.8, 15.5) years, 16,638 participants (7.0%) developed AF. There was a U-shaped association of total KBs and β-OHB with incident AF, with nadirs at 60.6 and 40.8 μmol/L, respectively (Pnonlinear < .05), whereas there was a positive association of acetoacetate and acetone with AF (Poverall < .001; Pnonlinear > .05). Consistently, there was a U-shaped association of total KBs and β-OHB with left atrial (LA) volume parameters, including LA maximum volume, LA minimum volume, and their body surface area-indexed counterparts, and there was an inverted U-shaped association of total KBs and β-OHB with LA ejection fraction (Pnonlinear < .05 for all). The associations of KBs with AF were stronger in individuals with low genetic risk (Pinteraction < .05), while the highest AF risk was in those with high genetic risk with high KB levels. Significant mediation effects of inflammatory markers on the associations between KBs and AF were identified. CONCLUSION There was a U-shaped association of circulating total KBs and β-OHB with incident AF as well as a positive association of acetoacetate and acetone levels with AF risk in the general population.
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Affiliation(s)
- Nan Zhang
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Daiqi Liu
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Jinhua Zhao
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Gary Tse
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China; School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China; Cardiovascular Analytics Group, PowerHealth Research Institute, Hong Kong, China
| | - Jiandong Zhou
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China
| | - Qingpeng Zhang
- School of Data Science, City University of Hong Kong, Hong Kong, China
| | - Gregory Y H Lip
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China; Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom.
| | - Tong Liu
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.
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Monzo L, Kovar J, Borlaug BA, Benes J, Kotrc M, Kroupova K, Jabor A, Franekova J, Melenovsky V. Circulating beta-hydroxybutyrate levels in advanced heart failure with reduced ejection fraction: Determinants and prognostic impact. Eur J Heart Fail 2024; 26:1931-1940. [PMID: 38853653 DOI: 10.1002/ejhf.3324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 05/16/2024] [Accepted: 05/20/2024] [Indexed: 06/11/2024] Open
Abstract
AIMS Patients with heart failure (HF) display metabolic alterations, including heightened ketogenesis, resulting in increased beta-hydroxybutyrate (β-OHB) formation. We aimed to investigate the determinants and prognostic impact of circulating β-OHB levels in patients with advanced HF and reduced ejection fraction (HFrEF). METHODS AND RESULTS A total of 867 patients with advanced HFrEF (age 57 ± 11 years, 83% male, 45% diabetic, 60% New York Heart Association class III), underwent clinical and echocardiographic examination, circulating metabolite assessment, and right heart catheterization (n = 383). The median β-OHB level was 64 (interquartile range [IQR] 33-161) μmol/L (normal 0-74 μmol/L). β-OHB levels correlated with increased markers of lipolysis (free fatty acids [FFA]), higher natriuretic peptides, worse pulmonary haemodynamics, and lower humoral regulators of ketogenesis (insulin/glucagon ratio). During a median follow-up of 1126 (IQR 410-1781) days, there were 512 composite events, including 324 deaths, 81 left ventricular assist device implantations and 107 urgent cardiac transplantations. In univariable Cox regression, increased β-OHB levels (T3 vs. T1: hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.13-1.72, p = 0.002) and elevated FFA levels (T3 vs. T1: HR 1.39, 95% CI 1.09-1.79, p = 0.008) were both predictors of a worse prognosis. In multivariable Cox analysis evaluating the simultaneous associations of FFA and β-OHB levels with outcomes, only FFA levels remained significantly associated with adverse outcomes. CONCLUSIONS In patients with advanced HFrEF, increased plasma β-OHB correlate with FFA levels, worse right ventricular function, greater neurohormonal activation and other markers of HF severity. The association between plasma β-OHB and adverse outcomes is eliminated after accounting for FFA levels, suggesting that increased β-OHB is a consequence reflecting heightened lipolytic state, rather than a cause of worsening HF.
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Affiliation(s)
- Luca Monzo
- Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
- Université de Lorraine, Centre d'Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France
| | - Jan Kovar
- Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
| | - Barry A Borlaug
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
| | - Jan Benes
- Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
| | - Martin Kotrc
- Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
| | - Katerina Kroupova
- Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
| | - Antonin Jabor
- Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
| | - Janka Franekova
- Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
| | - Vojtech Melenovsky
- Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
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Alzaabi MA, Abdelsalam A, Alhammadi M, Bani Hani H, Almheiri A, Al Matrooshi N, Al Zaman K. Evaluating Biomarkers as Tools for Early Detection and Prognosis of Heart Failure: A Comprehensive Review. Card Fail Rev 2024; 10:e06. [PMID: 38915376 PMCID: PMC11194781 DOI: 10.15420/cfr.2023.24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Accepted: 03/19/2024] [Indexed: 06/26/2024] Open
Abstract
There is a high prevalence of heart failure (HF) worldwide, which has significant consequences for healthcare costs, patient death and quality of life. Therefore, there has been much focus on finding and using biomarkers for early diagnosis, prognostication and therapy of HF. This overview of the research presents a thorough examination of the current state of HF biomarkers and their many uses. Their function in diagnosing HF, gauging its severity and monitoring its response to therapy are all discussed. Particularly promising in HF diagnosis and risk stratification are the cardiac-specific biomarkers, B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide. Markers of oxidative stress, extracellular matrix, renal function, inflammation and cardiac peptides have shown promise in evaluating HF severity and prognosis. MicroRNAs and insulin-like growth factor are two emerging biomarkers that have shown potential in helping with HF diagnosis and prognosis.
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Affiliation(s)
- Moza A Alzaabi
- Cardiothoracic Surgery, Heart, Vascular & Thoracic Institute, Cleveland Clinic Abu DhabiAbu Dhabi, United Arab Emirates
| | - Amin Abdelsalam
- Department of Cardiology, Al Qassemi HospitalSharjah, United Arab Emirates
| | - Majid Alhammadi
- College of Medicine, University of SharjahSharjah, United Arab Emirates
| | - Hasan Bani Hani
- College of Medicine, University of SharjahSharjah, United Arab Emirates
| | - Ali Almheiri
- College of Medicine, University of SharjahSharjah, United Arab Emirates
| | - Nadya Al Matrooshi
- Cardiothoracic Surgery, Heart, Vascular & Thoracic Institute, Cleveland Clinic Abu DhabiAbu Dhabi, United Arab Emirates
| | - Khaled Al Zaman
- Cardiothoracic Surgery, Heart, Vascular & Thoracic Institute, Cleveland Clinic Abu DhabiAbu Dhabi, United Arab Emirates
- College of Medicine, University of SharjahSharjah, United Arab Emirates
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Oyetoro RO, Conners KM, Joo J, Turecamo S, Sampson M, Wolska A, Remaley AT, Otvos JD, Connelly MA, Larson NB, Bielinski SJ, Hashemian M, Shearer JJ, Roger VL. Circulating ketone bodies and mortality in heart failure: a community cohort study. Front Cardiovasc Med 2024; 11:1293901. [PMID: 38327494 PMCID: PMC10847221 DOI: 10.3389/fcvm.2024.1293901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 01/11/2024] [Indexed: 02/09/2024] Open
Abstract
Background The relationship between ketone bodies (KB) and mortality in patients with heart failure (HF) syndrome has not been well established. Objectives The aim of this study is to assess the distribution of KB in HF, identify clinical correlates, and examine the associations between plasma KB and all-cause mortality in a population-based HF cohort. Methods The plasma KB levels were measured by nuclear magnetic resonance spectroscopy. Multivariable linear regression was used to examine associations between clinical correlates and KB levels. Proportional hazard regression was employed to examine associations between KB (represented as both continuous and categorical variables) and mortality, with adjustment for several clinical covariates. Results Among the 1,382 HF patients with KB measurements, the median (IQR) age was 78 (68, 84) and 52% were men. The median (IQR) KB was found to be 180 (134, 308) μM. Higher KB levels were associated with advanced HF (NYHA class III-IV) and higher NT-proBNP levels (both P < 0.001). The median follow-up was 13.9 years, and the 5-year mortality rate was 51.8% [95% confidence interval (CI): 49.1%-54.4%]. The risk of death increased when KB levels were higher (HRhigh vs. low group 1.23; 95% CI: 1.05-1.44), independently of a validated clinical risk score. The association between higher KB and mortality differed by ejection fraction (EF) and was noticeably stronger among patients with preserved EF. Conclusions Most patients with HF exhibited KB levels that were consistent with those found in healthy adults. Elevated levels of KB were observed in patients with advanced HF. Higher KB levels were found to be associated with an increased risk of death, particularly in patients with preserved EF.
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Affiliation(s)
- Rebecca O. Oyetoro
- Heart Disease Phenomics Laboratory, Epidemiology and Community Health Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
| | - Katherine M. Conners
- Heart Disease Phenomics Laboratory, Epidemiology and Community Health Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
| | - Jungnam Joo
- Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
| | - Sarah Turecamo
- Heart Disease Phenomics Laboratory, Epidemiology and Community Health Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
| | - Maureen Sampson
- Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States
| | - Anna Wolska
- Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
| | - Alan T. Remaley
- Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
| | - James D. Otvos
- Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
| | | | - Nicholas B. Larson
- Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Suzette J. Bielinski
- Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Maryam Hashemian
- Heart Disease Phenomics Laboratory, Epidemiology and Community Health Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
| | - Joseph J. Shearer
- Heart Disease Phenomics Laboratory, Epidemiology and Community Health Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
| | - Véronique L. Roger
- Heart Disease Phenomics Laboratory, Epidemiology and Community Health Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
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Marzoog B. Breathomics Detect the Cardiovascular Disease: Delusion or Dilution of the Metabolomic Signature. Curr Cardiol Rev 2024; 20:e020224226647. [PMID: 38318837 PMCID: PMC11327829 DOI: 10.2174/011573403x283768240124065853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 01/04/2024] [Accepted: 01/15/2024] [Indexed: 02/07/2024] Open
Abstract
Volatile organic compounds (VOCs) can be subdivided into exogenous and endogenous categories based on their origin. Analyzing the endogenous VOCs can provide insights into maintaining the internal organs' homeostasis. Despite the ongoing development and the current understanding, studies have suggested a link between cardiovascular metabolic alterations in patients with ischemic heart disease and elevated levels of ethane and isoprene detectable through exhaled breath analysis. Conversely, patients with chronic heart failure exhibit elevated acetone and pentane in their exhaled air. These substances originate from disturbances in the heart tissue, including cellular and subcellular modulations. Hypothetically, ethane levels in the exhaled breath analysis can demonstrate the severity of ischemic heart disease and, consequently, the risk of death in the next 10 years due to cardiovascular disease (CVD). Real-time direct mass spectrometry is the preferred method for assessing VOCs in exhaled breath analysis. The accuracy of this analysis depends on several factors, including the selection of the relevant breath fraction, the type of breath collection container (if used), and the pre-concentration technique.
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Affiliation(s)
- Basheer Marzoog
- World-Class Research Center, Digital Biodesign and Personalized Healthcare, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
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8
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Marzoog BA. Volatilome is Inflammasome- and Lipidome-dependent in Ischemic Heart Disease. Curr Cardiol Rev 2024; 20:e190724232038. [PMID: 39039680 PMCID: PMC11440324 DOI: 10.2174/011573403x302934240715113647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 06/07/2024] [Accepted: 07/08/2024] [Indexed: 07/24/2024] Open
Abstract
Ischemic heart disease (IHD) is a pathology of global interest because it is widespread and has high morbidity and mortality. IHD pathophysiology involves local and systemic changes, including lipidomic, proteomic, and inflammasome changes in serum plasma. The modulation in these metabolites is viable in the pre-IHD, during the IHD period, and after management of IHD in all forms, including lifestyle changes and pharmacological and surgical interventions. Therefore, these biochemical markers (metabolite changes; lipidome, inflammasome, proteome) can be used for early prevention, treatment strategy, assessment of the patient's response to the treatment, diagnosis, and determination of prognosis. Lipidomic changes are associated with the severity of inflammation and disorder in the lipidome component, and correlation is related to disturbance of inflammasome components. Main inflammasome biomarkers that are associated with coronary artery disease progression include IL-1β, Nucleotide-binding oligomerization domain- like receptor family pyrin domain containing 3 (NLRP3), and caspase-1. Meanwhile, the main lipidome biomarkers related to coronary artery disease development involve plasmalogen lipids, lysophosphatidylethanolamine (LPE), and phosphatidylethanolamine (PE). The hypothesis of this paper is that the changes in the volatile organic compounds associated with inflammasome and lipidome changes in patients with coronary artery disease are various and depend on the severity and risk factor for death from cardiovascular disease in the time span of 10 years. In this paper, we explore the potential origin and pathway in which the lipidome and or inflammasome molecules could be excreted in the exhaled air in the form of volatile organic compounds (VOCs).
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Affiliation(s)
- Basheer Abdullah Marzoog
- World-Class Research Center «Digital Biodesign and Personalized Healthcare», I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
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Tang WHW, Tranchito L, Albert C, Gul ZG, Cikach FS, Grove D, Wu Y, Dweik RA. Exhaled Breath Analysis Using Selected Ion Flow Tube Mass Spectrometry and Disease Severity in Heart Failure. Metabolites 2023; 13:1049. [PMID: 37887374 PMCID: PMC10608518 DOI: 10.3390/metabo13101049] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 09/25/2023] [Accepted: 09/27/2023] [Indexed: 10/28/2023] Open
Abstract
Exhaled breath volatile organic compounds (VOCs) are elevated in heart failure (HF). The ability of VOCs to predict long term cardiovascular mortality and morbidity has not been independently verified. In 55 patients admitted with acute decompensated heart failure (ADHF), we measured exhaled breath acetone and pentane levels upon admission and after 48 h of diuresis. In a separate cohort of 51 cardiac patients undergoing cardiopulmonary exercise testing (CPET), we measured exhaled breath acetone and pentane levels before and at peak exercise. In the ADHF cohort, admission acetone levels correlated with lower left ventricular ejection fraction (LVEF, r = -0.297, p = 0.035). Greater weight loss with diuretic therapy correlated with a greater reduction in both acetone levels (r = -0.398, p = 0.003) and pentane levels (r = -0.309, p = 0.021). In patients with above-median weight loss (≥4.5 kg), patients demonstrated significantly greater percentage reduction in acetone (59% reduction vs. 7% increase, p < 0.001) and pentane (23% reduction vs. 2% reduction, p = 0.008). In the CPET cohort, admission acetone and pentane levels correlated with higher VE/VCO2 (r = 0.39, p = 0.005), (r = 0.035, p = 0.014). However, there were no significant correlations between baseline or peak exercise acetone and pentane levels and peak VO2. In longitudinal follow-up with a median duration of 33 months, patients with elevated exhaled acetone and pentane levels experienced higher composite adverse events of death, ventricular assist device implantation, or orthotopic heart transplantation. In patients admitted with ADHF, higher exhaled breath acetone levels are associated with lower LVEF and poorer outcomes, and greater reductions in exhaled breath acetone and pentane tracked with greater weight loss. Exhaled acetone and pentane may be novel biomarkers in heart failure worthy of future investigation.
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Affiliation(s)
- Wai Hong Wilson Tang
- Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Lily Tranchito
- Endocrinology & Metabolism Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Chonyang Albert
- Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Zeynep G. Gul
- Department of Surgery, Washington University School of Medicine at St Louis, St Louis, MO 63110, USA
| | - Frank S. Cikach
- Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - David Grove
- Department of Inflammation and Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; (D.G.); (R.A.D.)
- Respiratory Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Yuping Wu
- Department of Mathematics, Cleveland State University, Cleveland, OH 44195, USA
| | - Raed A. Dweik
- Department of Inflammation and Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; (D.G.); (R.A.D.)
- Respiratory Institute, Cleveland Clinic, Cleveland, OH 44195, USA
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10
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Biagini D, Pugliese NR, Vivaldi FM, Ghimenti S, Lenzi A, De Angelis F, Ripszam M, Bruderer T, Armenia S, Cappeli F, Taddei S, Masi S, Francesco FD, Lomonaco T. Breath analysis combined with cardiopulmonary exercise testing and echocardiography for monitoring heart failure patients: the AEOLUS protocol. J Breath Res 2023; 17:046006. [PMID: 37524075 DOI: 10.1088/1752-7163/acec08] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 07/31/2023] [Indexed: 08/02/2023]
Abstract
This paper describes the AEOLUS pilot study which combines breath analysis with cardiopulmonary exercise testing (CPET) and an echocardiographic examination for monitoring heart failure (HF) patients. Ten consecutive patients with a prior clinical diagnosis of HF with reduced left ventricular ejection fraction were prospectively enrolled together with 15 control patients with cardiovascular risk factors, including hypertension, type II diabetes or chronic ischemic heart disease. Breath samples were collected at rest and during CPET coupled with exercise stress echocardiography (CPET-ESE) protocol by means of needle trap micro-extraction and were analyzed through gas-chromatography coupled with mass spectrometry. The protocol also involved using of a selected ion flow tube mass spectrometer for a breath-by-breath isoprene and acetone analysis during exercise. At rest, HF patients showed increased breath levels of acetone and pentane, which are related to altered oxidation of fatty acids and oxidative stress, respectively. A significant positive correlation was observed between acetone and the gold standard biomarker NT-proBNP in plasma (r= 0.646,p< 0.001), both measured at rest. During exercise, some exhaled volatiles (e.g., isoprene) mirrored ventilatory and/or hemodynamic adaptation, whereas others (e.g., sulfide compounds and 3-hydroxy-2-butanone) depended on their origin. At peak effort, acetone levels in HF patients differed significantly from those of the control group, suggesting an altered myocardial and systemic metabolic adaptation to exercise for HF patients. These preliminary data suggest that concomitant acquisition of CPET-ESE and breath analysis is feasible and might provide additional clinical information on the metabolic maladaptation of HF patients to exercise. Such information may refine the identification of patients at higher risk of disease worsening.
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Affiliation(s)
- Denise Biagini
- Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | - Nicola R Pugliese
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Federico M Vivaldi
- Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | - Silvia Ghimenti
- Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | - Alessio Lenzi
- Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | - Francesca De Angelis
- Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | - Matyas Ripszam
- Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | - Tobias Bruderer
- Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | - Silvia Armenia
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Federica Cappeli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Stefano Taddei
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Stefano Masi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Fabio Di Francesco
- Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | - Tommaso Lomonaco
- Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
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11
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Dyńka D, Kowalcze K, Charuta A, Paziewska A. The Ketogenic Diet and Cardiovascular Diseases. Nutrients 2023; 15:3368. [PMID: 37571305 PMCID: PMC10421332 DOI: 10.3390/nu15153368] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 07/24/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
The most common and increasing causes of death worldwide are cardiovascular diseases (CVD). Taking into account the fact that diet is a key factor, it is worth exploring this aspect of CVD prevention and therapy. The aim of this article is to assess the potential of the ketogenic diet in the prevention and treatment of CVD. The article is a comprehensive, meticulous analysis of the literature in this area, taking into account the most recent studies currently available. The ketogenic diet has been shown to have a multifaceted effect on the prevention and treatment of CVD. Among other aspects, it has a beneficial effect on the blood lipid profile, even compared to other diets. It shows strong anti-inflammatory and cardioprotective potential, which is due, among other factors, to the anti-inflammatory properties of the state of ketosis, the elimination of simple sugars, the restriction of total carbohydrates and the supply of omega-3 fatty acids. In addition, ketone bodies provide "rescue fuel" for the diseased heart by affecting its metabolism. They also have a beneficial effect on the function of the vascular endothelium, including improving its function and inhibiting premature ageing. The ketogenic diet has a beneficial effect on blood pressure and other CVD risk factors through, among other aspects, weight loss. The evidence cited is often superior to that for standard diets, making it likely that the ketogenic diet shows advantages over other dietary models in the prevention and treatment of cardiovascular diseases. There is a legitimate need for further research in this area.
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Affiliation(s)
| | | | | | - Agnieszka Paziewska
- Institute of Health Sciences, Faculty of Medical and Health Sciences, Siedlce University of Natural Sciences and Humanities, 08-110 Siedlce, Poland; (D.D.); (K.K.); (A.C.)
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12
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Spoladore R, Pinto G, Daus F, Pezzini S, Kolios D, Fragasso G. Metabolic Approaches for the Treatment of Dilated Cardiomyopathy. J Cardiovasc Dev Dis 2023; 10:287. [PMID: 37504543 PMCID: PMC10380730 DOI: 10.3390/jcdd10070287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/25/2023] [Accepted: 06/26/2023] [Indexed: 07/29/2023] Open
Abstract
In dilated cardiomyopathy (DCM), where the heart muscle becomes stretched and thin, heart failure (HF) occurs, and the cardiomyocytes suffer from an energetic inefficiency caused by an abnormal cardiac metabolism. Although underappreciated as a potential therapeutic target, the optimal metabolic milieu of a failing heart is still largely unknown and subject to debate. Because glucose naturally has a lower P/O ratio (the ATP yield per oxygen atom), the previous studies using this strategy to increase glucose oxidation have produced some intriguing findings. In reality, the vast majority of small-scale pilot trials using trimetazidine, ranolazine, perhexiline, and etomoxir have demonstrated enhanced left ventricular (LV) function and, in some circumstances, myocardial energetics in chronic ischemic and non-ischemic HF with a reduced ejection fraction (EF). However, for unidentified reasons, none of these drugs has ever been tested in a clinical trial of sufficient size. Other pilot studies came to the conclusion that because the heart in severe dilated cardiomyopathy appears to be metabolically flexible and not limited by oxygen, the current rationale for increasing glucose oxidation as a therapeutic target is contradicted and increasing fatty acid oxidation is supported. As a result, treating metabolic dysfunction in HF may benefit from raising ketone body levels. Interestingly, treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) improves cardiac function and outcomes in HF patients with or without type 2 diabetes mellitus (T2DM) through a variety of pleiotropic effects, such as elevated ketone body levels. The improvement in overall cardiac function seen in patients receiving SGLT2i could be explained by this increase, which appears to be a reflection of an adaptive process that optimizes cardiac energy metabolism. This review aims to identify the best metabolic therapeutic approach for DCM patients, to examine the drugs that directly affect cardiac metabolism, and to outline all the potential ancillary metabolic effects of the guideline-directed medical therapy. In addition, a special focus is placed on SGLT2i, which were first studied and prescribed to diabetic patients before being successfully incorporated into the pharmacological arsenal for HF patients.
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Affiliation(s)
- Roberto Spoladore
- Department of Cardiology, Heart Failure Clinic, Alessandro Manzoni Hospital, ASST Lecco, 23900 Lecco, Italy
| | - Giuseppe Pinto
- IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Francesca Daus
- Post-Graduate School of Cardiovascular Medicine, Milan-Bicocca University, 20126 Milan, Italy
| | - Sara Pezzini
- Post-Graduate School of Cardiovascular Medicine, Milan-Bicocca University, 20126 Milan, Italy
| | - Damianos Kolios
- Department of Clinical Cardiology, Heart Failure Clinic, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy (G.F.)
| | - Gabriele Fragasso
- Department of Clinical Cardiology, Heart Failure Clinic, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy (G.F.)
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13
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Shemesh E, Chevli PA, Islam T, German CA, Otvos J, Yeboah J, Rodriguez F, deFilippi C, Lima JAC, Blaha M, Pandey A, Vaduganathan M, Shapiro MD. Circulating ketone bodies and cardiovascular outcomes: the MESA study. Eur Heart J 2023; 44:1636-1646. [PMID: 36881667 PMCID: PMC10411932 DOI: 10.1093/eurheartj/ehad087] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 01/01/2023] [Accepted: 02/03/2023] [Indexed: 03/09/2023] Open
Abstract
AIMS Ketone bodies (KB) are an important alternative metabolic fuel source for the myocardium. Experimental and human investigations suggest that KB may have protective effects in patients with heart failure. This study aimed to examine the association between KB and cardiovascular outcomes and mortality in an ethnically diverse population free from cardiovascular disease (CVD). METHODS AND RESULTS This analysis included 6796 participants (mean age 62 ± 10 years, 53% women) from the Multi-Ethnic Study of Atherosclerosis. Total KB was measured by nuclear magnetic resonance spectroscopy. Multivariable-adjusted Cox proportional hazard models were used to examine the association of total KB with cardiovascular outcomes. At a mean follow-up of 13.6 years, after adjusting for traditional CVD risk factors, increasing total KB was associated with a higher rate of hard CVD, defined as a composite of myocardial infarction, resuscitated cardiac arrest, stroke, and cardiovascular death, and all CVD (additionally included adjudicated angina) [hazard ratio, HR (95% confidence interval, CI): 1.54 (1.12-2.12) and 1.37 (1.04-1.80) per 10-fold increase in total KB, respectively]. Participants also experienced an 87% (95% CI: 1.17-2.97) increased rate of CVD mortality and an 81% (1.45-2.23) increased rate of all-cause mortality per 10-fold increase in total KB. Moreover, a higher rate of incident heart failure was observed with increasing total KB [1.68 (1.07-2.65), per 10-fold increase in total KB]. CONCLUSION The study found that elevated endogenous KB in a healthy community-based population is associated with a higher rate of CVD and mortality. Ketone bodies could serve as a potential biomarker for cardiovascular risk assessment.
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Affiliation(s)
- Elad Shemesh
- Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 6423906, Israel
| | - Parag Anilkumar Chevli
- Section on Hospital Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA
| | - Tareq Islam
- Section on Hospital Medicine, Department of Internal Medicine, Geisinger Medical Center, 100 N. Academy Ave, Danville, PA 17822, USA
| | - Charles A German
- Section of Cardiology, Department of Medicine, University of Chicago, 5841 S Maryland Ave, MC 6080, Chicago, IL 60637, USA
| | | | - Joseph Yeboah
- Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA
| | - Fatima Rodriguez
- Section on Cardiovascular Medicine, Department of Internal Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA
| | | | - Joao A C Lima
- Division of Cardiology, Department of Medicine, Johns Hopkins University, 600 N. Wolfe Street, Baltimore, MD 21287, USA
| | - Michael Blaha
- The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University, 600 N. Wolfe Street, Baltimore, MD 21287, USA
| | - Ambarish Pandey
- Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
| | - Muthiah Vaduganathan
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, MA75 Francis Street, Boston, MA 20115, USA
| | - Michael D Shapiro
- Center for the Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA
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14
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Abstract
The ketone bodies beta-hydroxybutyrate and acetoacetate are hepatically produced metabolites catabolized in extrahepatic organs. Ketone bodies are a critical cardiac fuel and have diverse roles in the regulation of cellular processes such as metabolism, inflammation, and cellular crosstalk in multiple organs that mediate disease. This review focuses on the role of cardiac ketone metabolism in health and disease with an emphasis on the therapeutic potential of ketosis as a treatment for heart failure (HF). Cardiac metabolic reprogramming, characterized by diminished mitochondrial oxidative metabolism, contributes to cardiac dysfunction and pathologic remodeling during the development of HF. Growing evidence supports an adaptive role for ketone metabolism in HF to promote normal cardiac function and attenuate disease progression. Enhanced cardiac ketone utilization during HF is mediated by increased availability due to systemic ketosis and a cardiac autonomous upregulation of ketolytic enzymes. Therapeutic strategies designed to restore high-capacity fuel metabolism in the heart show promise to address fuel metabolic deficits that underpin the progression of HF. However, the mechanisms involved in the beneficial effects of ketone bodies in HF have yet to be defined and represent important future lines of inquiry. In addition to use as an energy substrate for cardiac mitochondrial oxidation, ketone bodies modulate myocardial utilization of glucose and fatty acids, two vital energy substrates that regulate cardiac function and hypertrophy. The salutary effects of ketone bodies during HF may also include extra-cardiac roles in modulating immune responses, reducing fibrosis, and promoting angiogenesis and vasodilation. Additional pleotropic signaling properties of beta-hydroxybutyrate and AcAc are discussed including epigenetic regulation and protection against oxidative stress. Evidence for the benefit and feasibility of therapeutic ketosis is examined in preclinical and clinical studies. Finally, ongoing clinical trials are reviewed for perspective on translation of ketone therapeutics for the treatment of HF.
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Affiliation(s)
- Timothy R. Matsuura
- Cardiovascular Institute and Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
| | - Patrycja Puchalska
- Department of Medicine, Division of Molecular Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA
| | - Peter A. Crawford
- Department of Medicine, Division of Molecular Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA
- Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA
| | - Daniel P. Kelly
- Cardiovascular Institute and Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
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15
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Gladding PA, Cooper M, Young R, Loader S, Smith K, Zarate E, Green S, Villas Boas SG, Shepherd P, Kakadiya P, Thorstensen E, Keven C, Coe M, Jüllig M, Zhang E, Schlegel TT. Metabolomics and a Breath Sensor Identify Acetone as a Biomarker for Heart Failure. Biomolecules 2022; 13:biom13010013. [PMID: 36671398 PMCID: PMC9856097 DOI: 10.3390/biom13010013] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/13/2022] [Accepted: 12/13/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Multi-omics delivers more biological insight than targeted investigations. We applied multi-omics to patients with heart failure with reduced ejection fraction (HFrEF). METHODS 46 patients with HFrEF and 20 controls underwent metabolomic profiling, including liquid/gas chromatography mass spectrometry (LC-MS/GC-MS) and solid-phase microextraction (SPME) volatilomics in plasma and urine. HFrEF was defined using left ventricular global longitudinal strain, ejection fraction and NTproBNP. A consumer breath acetone (BrACE) sensor validated results in n = 73. RESULTS 28 metabolites were identified by GCMS, 35 by LCMS and 4 volatiles by SPME in plasma and urine. Alanine, aspartate and glutamate, citric acid cycle, arginine biosynthesis, glyoxylate and dicarboxylate metabolism were altered in HFrEF. Plasma acetone correlated with NT-proBNP (r = 0.59, 95% CI 0.4 to 0.7), 2-oxovaleric and cis-aconitic acid, involved with ketone metabolism and mitochondrial energetics. BrACE > 1.5 ppm discriminated HF from other cardiac pathology (AUC 0.8, 95% CI 0.61 to 0.92, p < 0.0001). CONCLUSION Breath acetone discriminated HFrEF from other cardiac pathology using a consumer sensor, but was not cardiac specific.
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Affiliation(s)
- Patrick A. Gladding
- Cardiology Department, Waitemata District Health Board, Auckland 0620, New Zealand; (M.C.); (R.Y.); (S.L.)
- Auckland Bioengineering Institute, Auckland 1142, New Zealand
- Correspondence:
| | - Maxine Cooper
- Cardiology Department, Waitemata District Health Board, Auckland 0620, New Zealand; (M.C.); (R.Y.); (S.L.)
| | - Renee Young
- Cardiology Department, Waitemata District Health Board, Auckland 0620, New Zealand; (M.C.); (R.Y.); (S.L.)
| | - Suzanne Loader
- Cardiology Department, Waitemata District Health Board, Auckland 0620, New Zealand; (M.C.); (R.Y.); (S.L.)
| | - Kevin Smith
- Clinical Laboratory, Waitemata District Health Board, Auckland 0622, New Zealand;
| | - Erica Zarate
- School of Biological Science, University of Auckland, Auckland 1010, New Zealand; (E.Z.); (S.G.); (S.G.V.B.)
| | - Saras Green
- School of Biological Science, University of Auckland, Auckland 1010, New Zealand; (E.Z.); (S.G.); (S.G.V.B.)
| | - Silas G. Villas Boas
- School of Biological Science, University of Auckland, Auckland 1010, New Zealand; (E.Z.); (S.G.); (S.G.V.B.)
| | - Phillip Shepherd
- Grafton Genomics Ltd., Liggins Institute, University of Auckland, Auckland 1010, New Zealand; (P.S.); (P.K.)
| | - Purvi Kakadiya
- Grafton Genomics Ltd., Liggins Institute, University of Auckland, Auckland 1010, New Zealand; (P.S.); (P.K.)
| | - Eric Thorstensen
- Liggins Institute, University of Auckland, Auckland 1010, New Zealand; (E.T.); (C.K.); (M.C.)
| | - Christine Keven
- Liggins Institute, University of Auckland, Auckland 1010, New Zealand; (E.T.); (C.K.); (M.C.)
| | - Margaret Coe
- Liggins Institute, University of Auckland, Auckland 1010, New Zealand; (E.T.); (C.K.); (M.C.)
| | - Mia Jüllig
- Paper Dog Ltd., Waiheke Island, Auckland 1081, New Zealand;
| | - Edmond Zhang
- Precision Driven Health Initiative, Auckland 1021, New Zealand;
| | - Todd T. Schlegel
- Karolinska Institutet, 17177 Stockholm, Sweden;
- Nicollier-Schlegel Sàrl, 1270 Trélex, Switzerland
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16
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Badianyama M, Mpanya D, Adamu U, Sigauke F, Nel S, Tsabedze N. New Biomarkers and Their Potential Role in Heart Failure Treatment Optimisation-An African Perspective. J Cardiovasc Dev Dis 2022; 9:jcdd9100335. [PMID: 36286287 PMCID: PMC9604249 DOI: 10.3390/jcdd9100335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 09/05/2022] [Accepted: 09/13/2022] [Indexed: 11/16/2022] Open
Abstract
Heart failure is a clinical syndrome resulting from various cardiovascular diseases of different aetiologies and pathophysiology. These varying pathologies involve several complex mechanisms that lead to the activation of the neurohumoral system, inflammation, angiogenesis, apoptosis, fibrosis, and eventually adverse cardiac remodelling associated with a progressive decline in cardiac function. Once a diagnosis is made, the cardiac function has a gradual decline characterised by multiple hospital admissions. It is therefore imperative to identify patients at different stages of the heart failure continuum to better risk stratify and initiate optimal management strategies. Biomarkers may play a role in the diagnosis, prognostication, and monitoring response to treatment. This review discusses the epidemiology of heart failure and biomarkers commonly used in clinical practice such as natriuretic peptides and cardiac troponins. In addition, we provide a brief overview of novel biomarkers and genetic coding and non-coding biomarkers used in the management of patients with heart failure. We also discuss barriers that hinder the clinical application of novel biomarkers. Finally, we appraise the value of polygenic risk scoring, focusing on sub-Saharan Africa.
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17
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de Koning MSLY, Westenbrink BD, Assa S, Garcia E, Connelly MA, van Veldhuisen DJ, Dullaart RPF, Lipsic E, van der Harst P. Association of Circulating Ketone Bodies With Functional Outcomes After ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol 2021; 78:1421-1432. [PMID: 34593124 DOI: 10.1016/j.jacc.2021.07.054] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/26/2021] [Accepted: 07/28/2021] [Indexed: 01/25/2023]
Abstract
BACKGROUND Circulating ketone bodies (KBs) are increased in patients with heart failure (HF), corresponding with increased cardiac KB metabolism and HF severity. However, the role of circulating KBs in ischemia/reperfusion remains unknown. OBJECTIVES This study sought to investigate longitudinal changes of KBs and their associations with functional outcomes in patients presenting with ST-segment elevation myocardial infarction (STEMI). METHODS KBs were measured in 369 participants from a randomized trial on early metformin therapy after STEMI. Nonfasting plasma concentrations of KBs (β-hydroxybutyrate, acetoacetate, and acetone) were measured by nuclear magnetic resonance spectroscopy at presentation, at 24 hours, and after 4 months. Myocardial infarct size and left ventricular ejection fraction (LVEF) were determined by cardiac magnetic resonance imaging at 4 months. Associations of circulating KBs with infarct size and LVEF were determined using multivariable linear regression analyses. RESULTS Circulating KBs were high at presentation with STEMI (median total KBs: 520 μmol/L; interquartile range [IQR]: 315-997 μmol/L). At 24 hours after reperfusion, KBs were still high compared with levels at 4-month follow-up (206 μmol/L [IQR: 174-246] vs 166 μmol/L [IQR: 143-201], respectively; P < 0.001). Increased KB concentrations at 24 hours were independently associated with larger myocardial infarct size (total KBs, per 100 μmol/L: β = 1.56; 95% confidence interval: 0.29-2.83; P = 0.016) and lower LVEF (β = -1.78; 95% CI: (-3.17 to -0.39; P = 0.012). CONCLUSIONS Circulating KBs are increased in patients presenting with STEMI. Higher KBs at 24 hours are associated with functional outcomes after STEMI, which suggests a potential role for ketone metabolism in response to myocardial ischemia. (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III): a Randomized Controlled Trial; NCT01217307).
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Affiliation(s)
- Marie-Sophie L Y de Koning
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
| | - B Daan Westenbrink
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Solmaz Assa
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Erwin Garcia
- Laboratory Corporation of America Holdings (Labcorp), Morrisville, North Carolina, USA
| | - Margery A Connelly
- Laboratory Corporation of America Holdings (Labcorp), Morrisville, North Carolina, USA
| | - Dirk J van Veldhuisen
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Robin P F Dullaart
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Erik Lipsic
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Pim van der Harst
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
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18
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Anderson JC, Mattar SG, Greenway FL, Lindquist RJ. Measuring ketone bodies for the monitoring of pathologic and therapeutic ketosis. Obes Sci Pract 2021; 7:646-656. [PMID: 34631141 PMCID: PMC8488448 DOI: 10.1002/osp4.516] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 03/29/2021] [Accepted: 04/11/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND The ketone bodies β-hydroxybutyrate (BOHB) and acetone are generated as a byproduct of the fat metabolism process. In healthy individuals, ketone body levels are ∼0.1 mM for BOHB and ∼1 part per million for breath acetone (BrAce). These levels can increase dramatically as a consequence of a disease process or when used therapeutically for disease treatment. For example, increased ketone body concentration during weight loss is an indication of elevated fat metabolism. Ketone body measurement is relatively inexpensive and can provide metabolic insights to help guide disease management and optimize weight loss. METHODS This review of the literature provides metabolic mechanisms and typical concentration ranges of ketone bodies, which can give new insights into these conditions and rationale for measuring ketone bodies. RESULTS Diseases such as heart failure and ketoacidosis can affect caloric intake and macronutrient management, which can elevate BOHB 30-fold and BrAce 1000-fold. Other diseases associated with obesity, such as brain dysfunction, cancer, and diabetes, may cause dysfunction because of an inability to use glucose, excessive reliance on glucose, or poor insulin signaling. Elevating ketone body concentrations (e.g., nutritional ketosis) may improve these conditions by forcing utilization of ketone bodies, in place of glucose, for fuel. During weight loss, monitoring ketone body concentration can demonstrate program compliance and can be used to optimize the weight-loss plan. CONCLUSIONS The role of ketone bodies in states of pathologic and therapeutic ketosis indicates that accurate measurement and monitoring of BOHB or BrAce will likely improve disease management. Bariatric surgery is examined as a case study for monitoring both types of ketosis.
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Affiliation(s)
- Joseph C. Anderson
- Department of BioengineeringUniversity of WashingtonSeattleWashingtonUSA
| | - Samer G. Mattar
- Department of SurgeryBaylor College of MedicineHoustonTexasUSA
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19
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Yurista SR, Nguyen CT, Rosenzweig A, de Boer RA, Westenbrink BD. Ketone bodies for the failing heart: fuels that can fix the engine? Trends Endocrinol Metab 2021; 32:814-826. [PMID: 34456121 DOI: 10.1016/j.tem.2021.07.006] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/20/2021] [Accepted: 07/26/2021] [Indexed: 01/08/2023]
Abstract
Accumulating evidence suggests that the failing heart reverts energy metabolism toward increased utilization of ketone bodies. Despite many discrepancies in the literature, evidence from both bench and clinical research demonstrates beneficial effects of ketone bodies in heart failure. Ketone bodies are readily oxidized by cardiomyocytes and can provide ancillary fuel for the energy-starved failing heart. In addition, ketone bodies may help to restore cardiac function by mitigating inflammation, oxidative stress, and cardiac remodeling. In this review, we hypothesize that a therapeutic approach intended to restore cardiac metabolism through ketone bodies could both refuel and 'repair' the failing heart.
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Affiliation(s)
- Salva R Yurista
- Cardiovascular Research Center, Cardiology Division, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
| | - Christopher T Nguyen
- Cardiovascular Research Center, Cardiology Division, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
| | - Anthony Rosenzweig
- Cardiovascular Research Center, Cardiology Division, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Rudolf A de Boer
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - B Daan Westenbrink
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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20
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Segreti A, Verolino G, Crispino SP, Agostoni P. Listing Criteria for Heart Transplant: Role of Cardiopulmonary Exercise Test and of Prognostic Scores. Heart Fail Clin 2021; 17:635-646. [PMID: 34511211 DOI: 10.1016/j.hfc.2021.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Patients with advanced heart failure (AdHF) have a reduced quality of life and poor prognosis. A heart transplant (HT) is an effective treatment for such patients. Still, because of a shortage of donor organs, the final decision to place a patient without contraindications on the HT waiting list is based on detailed risk-benefit analysis. Cardiopulmonary exercise tests (CPETs) play a pivotal role in guiding selection in patients with AdHF considered for an HT. Furthermore, several validated multivariable predicting scores obtained through various techniques, including the CPETs, are available and part of the decision-making process for HT listing.
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Affiliation(s)
- Andrea Segreti
- Unit of Cardiovascular Science, Campus Bio-Medico University of Rome, Rome, Italy.
| | - Giuseppe Verolino
- Unit of Cardiovascular Science, Campus Bio-Medico University of Rome, Rome, Italy
| | | | - Piergiuseppe Agostoni
- Centro Cardiologico Monzino, IRCCS, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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21
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Yurista SR, Chong CR, Badimon JJ, Kelly DP, de Boer RA, Westenbrink BD. Therapeutic Potential of Ketone Bodies for Patients With Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol 2021; 77:1660-1669. [PMID: 33637354 DOI: 10.1016/j.jacc.2020.12.065] [Citation(s) in RCA: 119] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 12/14/2020] [Indexed: 12/19/2022]
Abstract
Metabolic perturbations underlie a variety of cardiovascular disease states; yet, metabolic interventions to prevent or treat these disorders are sparse. Ketones carry a negative clinical stigma as they are involved in diabetic ketoacidosis. However, evidence from both experimental and clinical research has uncovered a protective role for ketones in cardiovascular disease. Although ketones may provide supplemental fuel for the energy-starved heart, their cardiovascular effects appear to extend far beyond cardiac energetics. Indeed, ketone bodies have been shown to influence a variety of cellular processes including gene transcription, inflammation and oxidative stress, endothelial function, cardiac remodeling, and cardiovascular risk factors. This paper reviews the bioenergetic and pleiotropic effects of ketone bodies that could potentially contribute to its cardiovascular benefits based on evidence from animal and human studies.
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Affiliation(s)
- Salva R Yurista
- University Medical Center Groningen, University of Groningen, Department of Cardiology, Groningen, the Netherlands. https://twitter.com/salvareverentia
| | - Cher-Rin Chong
- Basil Hetzel Institute for Translational Research, The Queen Elizabeth Hospital, Australia; Adelaide Medical School, University of Adelaide, Adelaide, Australia
| | - Juan J Badimon
- AtheroThrombosis Research Unit, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Daniel P Kelly
- Cardiovascular Institute, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Rudolf A de Boer
- University Medical Center Groningen, University of Groningen, Department of Cardiology, Groningen, the Netherlands. https://twitter.com/Rudolf_deboer
| | - B Daan Westenbrink
- University Medical Center Groningen, University of Groningen, Department of Cardiology, Groningen, the Netherlands.
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22
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Karwi QG, Biswas D, Pulinilkunnil T, Lopaschuk GD. Myocardial Ketones Metabolism in Heart Failure. J Card Fail 2020; 26:998-1005. [PMID: 32442517 DOI: 10.1016/j.cardfail.2020.04.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 03/18/2020] [Accepted: 04/09/2020] [Indexed: 02/06/2023]
Abstract
Ketone bodies can become a major source of adenosine triphosphate production during stress to maintain bioenergetic homeostasis in the brain, heart, and skeletal muscles. In the normal heart, ketone bodies contribute from 10% to 15% of the cardiac adenosine triphosphate production, although their contribution during pathologic stress is still not well-characterized and currently represents an exciting area of cardiovascular research. This review focuses on the mechanisms that regulate circulating ketone levels under physiologic and pathologic conditions and how this impacts cardiac ketone metabolism. We also review the current understanding of the role of augmented ketone metabolism as an adaptive response in different types and stages of heart failure. This analysis includes the emerging experimental and clinical evidence of the potential favorable effects of boosting ketone metabolism in the failing heart and the possible mechanisms of action through which these interventions may mediate their cardioprotective effects. We also critically appraise the emerging data from animal and human studies which characterize the role of ketones in mediating the cardioprotection established by the new class of antidiabetic drugs, namely sodium-glucose co-transporter inhibitors.
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Affiliation(s)
- Qutuba G Karwi
- Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada; Department of Pharmacology, College of Medicine, University of Diyala, Diyala, Iraq.
| | - Dipsikha Biswas
- Department of Biochemistry and Molecular Biology, Dalhousie Medicine New Brunswick, Dalhousie University, Saint John, New Brunswick, Canada.
| | - Thomas Pulinilkunnil
- Department of Biochemistry and Molecular Biology, Dalhousie Medicine New Brunswick, Dalhousie University, Saint John, New Brunswick, Canada
| | - Gary D Lopaschuk
- Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada
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23
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Marcondes-Braga FG, Gioli-Pereira L, Bernardez-Pereira S, Batista GL, Mangini S, Issa VS, Fernandes F, Bocchi EA, Ayub-Ferreira SM, Mansur AJ, Gutz IGR, Krieger JE, Pereira AC, Bacal F. Exhaled breath acetone for predicting cardiac and overall mortality in chronic heart failure patients. ESC Heart Fail 2020; 7:1744-1752. [PMID: 32383349 PMCID: PMC7373929 DOI: 10.1002/ehf2.12736] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 03/27/2020] [Accepted: 04/15/2020] [Indexed: 11/11/2022] Open
Abstract
Aims Exhaled breath acetone (EBA) has been described as a new biomarker of heart failure (HF) diagnosis. EBA concentration increases according to severity of HF and is associated with poor prognosis, especially in acute decompensated HF. However, there are no data on chronic HF patients. The aim is to evaluate the role of EBA for predicting cardiac and overall mortality in chronic HF patients. Methods and results In GENIUS‐HF cohort, chronic patients were enrolled between August 2012 and December 2014. All patients had left ventricular ejection fraction ≤ 50%, and the diagnosis was established according to Framingham criteria. After consent, patients were submitted to clinical evaluation and exhaled breath collection. EBA identification and quantitative determination were done by spectrophotometry. The clinical characteristics associated with acetone were identified. All participants were followed for 18 months to assess cardiac and overall mortality. Around 700 participants were enrolled in the current analysis. Patients were 55.4 ± 12.2 years old, 67.6% male patients, and 81% New York Heart Association I/II with left ventricular ejection fraction of 32 ± 8.6%. EBA median concentration was 0.6 (0.3–1.2) ug/L. Acetone levels increased with the number of symptoms of HF and were associated with right HF signs/symptoms and liver biochemical changes. EBA at highest quartile (EBA > 1.2ug/L) was associated with a significantly worse prognosis (log rank test, P < 0.001). Cox proportional multivariable regression model revealed that EBA > 1.20ug/L was an independent predictor of cardiac (P = 0.011) and overall (P = 0.010) mortality in our population. Conclusions This study shows that EBA levels reflect clinical HF features, especially right HF signs/symptoms. EBA is an independent predictor of cardiac and overall mortality in chronic HF patients.
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Affiliation(s)
- Fabiana G Marcondes-Braga
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
| | - Luciana Gioli-Pereira
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
| | - Sabrina Bernardez-Pereira
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
| | | | - Sandrigo Mangini
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
| | - Victor S Issa
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
| | - Fabio Fernandes
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
| | - Edimar A Bocchi
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
| | - Silvia M Ayub-Ferreira
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
| | - Alfredo J Mansur
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
| | - Ivano G R Gutz
- Institute of Chemistry (IQ-USP), University of Sao Paulo, Sao Paulo, Brazil
| | - Jose E Krieger
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
| | - Alexandre C Pereira
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
| | - Fernando Bacal
- Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Dr Eneas de Carvalho Aguiar, 44-Cerqueira Cesar, São Paulo, 0540300, Brazil
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24
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Ciuculete DC, Dobrev D, Dan GA. Prognostic value of biomarkers of impaired metabolism in heart failure patients with reduced ejection fraction. IJC HEART & VASCULATURE 2019; 25:100441. [PMID: 31890861 PMCID: PMC6923432 DOI: 10.1016/j.ijcha.2019.100441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 11/08/2019] [Indexed: 11/23/2022]
Affiliation(s)
- Denisa Corina Ciuculete
- University Hospital Colentina, Bucharest, Romania
- “Carol Davila” University of Medicine, Bucharest, Romania
| | - Dobromir Dobrev
- Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany
| | - G.-Andrei Dan
- University Hospital Colentina, Bucharest, Romania
- “Carol Davila” University of Medicine, Bucharest, Romania
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25
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Yokokawa T, Yoshihisa A, Kanno Y, Abe S, Misaka T, Yamada S, Kaneshiro T, Sato T, Oikawa M, Kobayashi A, Nakazato K, Ishida T, Takeishi Y. Circulating acetoacetate is associated with poor prognosis in heart failure patients. IJC HEART & VASCULATURE 2019; 25:100432. [PMID: 31890860 PMCID: PMC6923508 DOI: 10.1016/j.ijcha.2019.100432] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 09/21/2019] [Accepted: 10/09/2019] [Indexed: 12/28/2022]
Abstract
Background Acetoacetate is used as an alternative energy source in the heart, and has the potential to improve cardiac function. However, the prognostic impact of acetoacetate has not been investigated in heart failure. Methods This study enrolled consecutive 615 hospitalized patients with heart failure. We investigated the associations between circulating acetoacetate and clinical characteristics or prognosis in HF patients. Results We divided the patients into two groups based on circulating acetoacetate levels (high group: acetoacetate ≥35 µmoL/L, n = 313; and low group: acetoacetate <35 µmoL/L, n = 302). The high group had an older age (68 vs. 65 years, P = 0.003) and higher log brain natriuretic peptide levels (2.43 vs. 2.23, P < 0.001) compared with the low group. In contrast, there were no significant differences in the prevalence of co-morbidities, including diabetes mellitus, chronic kidney disease, and anemia, between the two groups. During the median follow-up period of 328 days, 66 all-cause deaths occurred. The high group had a worse prognosis compared with the low group (Log rank, P = 0.041). In the Cox proportional hazard analysis, circulating acetoacetate levels (per 10 µmoL/L increase) were associated with all-cause mortality (hazard ratio 1.020, 95% confidence interval 1.010–1.030, P < 0.001). Conclusions Circulating acetoacetate is associated with all-cause mortality in patients with heart failure. These results provide new insights into the role of alternative cardiac metabolism in heart failure patients, and raise the possibility of acetoacetate as a novel biomarker to predict the prognosis of heart failure patients.
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Affiliation(s)
- Tetsuro Yokokawa
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.,Department of Pulmonary Hypertension, Fukushima Medical University, Fukushima, Japan
| | - Akiomi Yoshihisa
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.,Department of Advanced Cardiac Therapeutics, Fukushima Medical University, Fukushima, Japan
| | - Yuki Kanno
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Satoshi Abe
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Tomofumi Misaka
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.,Department of Advanced Cardiac Therapeutics, Fukushima Medical University, Fukushima, Japan
| | - Shinya Yamada
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Takashi Kaneshiro
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Takamasa Sato
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Masayoshi Oikawa
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Atsushi Kobayashi
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Kazuhiko Nakazato
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Takafumi Ishida
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Yasuchika Takeishi
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
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26
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Iskander-Rizk S, van der Steen AFW, van Soest G. Photoacoustic imaging for guidance of interventions in cardiovascular medicine. Phys Med Biol 2019; 64:16TR01. [PMID: 31048573 DOI: 10.1088/1361-6560/ab1ede] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Imaging guidance is paramount to procedural success in minimally invasive interventions. Catheter-based therapies are the standard of care in the treatment of many cardiac disorders, including coronary artery disease, structural heart disease and electrophysiological conditions. Many of these diseases are caused by, or effect, a change in vasculature or cardiac tissue composition, which can potentially be detected by photoacoustic imaging. This review summarizes the state of the art in photoacoustic imaging approaches that have been proposed for intervention guidance in cardiovascular care. All of these techniques are currently in the preclinical phase. We will conclude with an outlook towards clinical applications.
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Affiliation(s)
- Sophinese Iskander-Rizk
- Department of Cardiology, Biomedical Engineering, Erasmus MC University Medical Center Rotterdam, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands
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27
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Bykova AA, Malinovskaya LK, Chomakhidze PS, Trushina OV, Shaltaeva YR, Belyakov VV, Golovin AV, Pershenkov VS, Syrkin AL, Betelin VB, Kopylov PY. [Exhaled Breath Analysis in Diagnostics of Cardiovascular Diseases]. ACTA ACUST UNITED AC 2019; 59:61-67. [PMID: 31322091 DOI: 10.18087/cardio.2019.7.10263] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 07/19/2019] [Indexed: 11/18/2022]
Abstract
Exhaled breath analysis is a novel tool for diagnostics of different diseases. Taking into account the secretory function of the lungs, the composition of exhaled breath is different in physiological and pathological conditions. In this review we consider of some substances which content vary in cardiovascular diseases - pentane, isoprene, carbon monoxide and trimethylamine. Modern technologies allow to move the analysis of exhaled breath from research laboratories into clinical practice. Thus, a new tool for real time of screening various cardiovascular diseases has appeared in the arsenal of physicians.
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Affiliation(s)
- A A Bykova
- Sechenov First Moscow State Medical University (Sechenov University); Scientific Research Institute for System Analysis
| | - L K Malinovskaya
- Sechenov First Moscow State Medical University (Sechenov University)
| | - P Sh Chomakhidze
- Sechenov First Moscow State Medical University (Sechenov University); Scientific Research Institute for System Analysis
| | - O V Trushina
- Sechenov First Moscow State Medical University (Sechenov University)
| | - Y R Shaltaeva
- National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
| | - V V Belyakov
- National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
| | - A V Golovin
- National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
| | - V S Pershenkov
- National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
| | - A L Syrkin
- Sechenov First Moscow State Medical University (Sechenov University); Scientific Research Institute for System Analysis
| | - V B Betelin
- Scientific Research Institute for System Analysis
| | - Ph Yu Kopylov
- Sechenov First Moscow State Medical University (Sechenov University); Scientific Research Institute for System Analysis
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28
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Albert CL, Tang WHW. Following the Scent of Microbes Within: The Heart-Gut Connection. J Card Fail 2019; 25:328-329. [PMID: 30926393 DOI: 10.1016/j.cardfail.2019.03.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 03/21/2019] [Indexed: 01/18/2023]
Affiliation(s)
- Chonyang Lu Albert
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - W H Wilson Tang
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
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Wirtz LM, Kreuer S, Volk T, Hüppe T. Moderne Atemgasanalysen. Med Klin Intensivmed Notfmed 2019; 114:655-660. [DOI: 10.1007/s00063-019-0544-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 11/08/2018] [Accepted: 01/14/2019] [Indexed: 10/27/2022]
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30
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Klos M, Morgenstern S, Hicks K, Suresh S, Devaney EJ. The effects of the ketone body β-hydroxybutyrate on isolated rat ventricular myocyte excitation-contraction coupling. Arch Biochem Biophys 2018; 662:143-150. [PMID: 30543786 DOI: 10.1016/j.abb.2018.11.027] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 11/06/2018] [Accepted: 11/30/2018] [Indexed: 02/08/2023]
Abstract
β-hydroxybutyrate is the primary ketone body produced by the body during ketosis and is used to meet its metabolic demands. The healthy adult heart derives most of its energy from fatty acid oxidation. However, in certain diseases, the heart alters its substrate preference and increases its ketone body metabolism. Little is known about the effects of βOHB on ventricular myocyte excitation-contraction coupling. Therefore, we examined the effects of ketone body metabolism on single cell excitation-contraction coupling during normoxic and hypoxic conditions. Myocytes were isolated from adult rats, cultured for 18 h in RPMI 1640, RPMI 1640 no glucose, and M199, HEPES with/without various amount of βOHB added. To simulate hypoxia, myocytes were incubated at 1%O2, 5% CO2 for 1 h followed by incubation at atmospheric oxygen (21%O2,5% CO2) for 30 min before recordings. Recordings were obtained using an IonOptix system at 36±1ᵒ C. Myocytes were paced at 0.5, 1, 2, 3, and 4 Hz. We found that exposure to βOHB had no effect on excitation-contraction coupling. However, culturing cells with βOHB results in a significant increase in both contraction and calcium in RPMI 1640 media. Dose response experiments demonstrated 0.5 mM βOHB is enough to increase myocyte contraction in the absence of glucose. However, βOHB has no measurable effects on myocytes cultured in a nutrient rich media, M199, HEPES. Therefore, βOHB improves single cell excitation-contraction coupling, is protective against hypoxia, and may be a beneficial adaptation for the heart during periods of nutrient scarcity and or metabolic dysregulation.
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Affiliation(s)
- Matthew Klos
- Department of Pediatric Cardiac Surgery, UH Hospitals Cleveland, Cleveland, OH, 44106, USA; Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA
| | - Sherry Morgenstern
- Department of Pediatric Cardiac Surgery, UH Hospitals Cleveland, Cleveland, OH, 44106, USA
| | - Kayla Hicks
- Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA
| | - Shreyas Suresh
- Case Western Reserve University School of Graduate Studies, Cleveland, OH, 44106, USA
| | - Eric J Devaney
- Department of Pediatric Cardiac Surgery, UH Hospitals Cleveland, Cleveland, OH, 44106, USA; Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
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31
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Yokokawa T, Sato T, Suzuki S, Oikawa M, Yoshihisa A, Kobayashi A, Yamaki T, Kunii H, Nakazato K, Suzuki H, Saitoh SI, Ishida T, Shimouchi A, Takeishi Y. Change of Exhaled Acetone Concentration Levels in Patients with Acute Decompensated Heart Failure. Int Heart J 2018; 59:808-812. [PMID: 29794390 DOI: 10.1536/ihj.17-482] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Exhaled acetone concentration is one of the expected compounds to be a breath biomarker in heart failure. However, it has not been clarified how exhaled acetone concentration changes in clinical course of heart failure.To investigate whether exhaled acetone concentration changes after treatment in acute decompensated heart failure (ADHF).This study included 19 patients with ADHF (ADHF group) and eight patients with stable heart failure (control group). Exhaled acetone was collected from these patients, and the concentration was measured with gas chromatography.The ADHF group had higher heart rates (P = 0.046), higher New York Heart Association class (P < 0.001), higher levels of brain natriuretic peptide (P = 0.026), blood total ketone bodies (P = 0.015), and exhaled acetone concentration (P < 0.001), compared with the control group. In ADHF group, exhaled acetone concentration significantly decreased after treatment (median: 2.40 versus 0.92 ppm, P < 0.001). However, in the control group, exhaled acetone concentration did not significantly change (median: 0.73 versus 0.49 ppm, P = 0.141).In these preliminary findings, exhaled acetone concentration in patients with ADHF drastically decreased by treatment. Serial exhaled acetone measurement might be useful to evaluate the course of ADHF.
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Affiliation(s)
- Tetsuro Yokokawa
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Takamasa Sato
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Satoshi Suzuki
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Masayoshi Oikawa
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Akiomi Yoshihisa
- Department of Cardiovascular Medicine, Fukushima Medical University
| | | | - Takayoshi Yamaki
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Hiroyuki Kunii
- Department of Cardiovascular Medicine, Fukushima Medical University
| | | | - Hitoshi Suzuki
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Shu-Ichi Saitoh
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Takafumi Ishida
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Akito Shimouchi
- Department of Lifelong Sports for Health Biochemical Sciences, College of Life and Health Sciences, Chubu University
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Lomonaco T, Romani A, Ghimenti S, Biagini D, Bellagambi FG, Onor M, Salvo P, Fuoco R, Di Francesco F. Determination of carbonyl compounds in exhaled breath by on-sorbent derivatization coupled with thermal desorption and gas chromatography-tandem mass spectrometry. J Breath Res 2018; 12:046004. [DOI: 10.1088/1752-7163/aad202] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Yokokawa T, Sato T, Suzuki S, Oikawa M, Yoshihisa A, Kobayashi A, Yamaki T, Kunii H, Nakazato K, Ishida T, Takeishi Y. Feasibility of skin acetone analysis in patients with cardiovascular diseases. Fukushima J Med Sci 2018; 64:60-63. [PMID: 30012937 DOI: 10.5387/fms.2018-03] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Breath acetone is reported to be a noninvasive biomarker for heart failure. However, the measurement of this metabolite requires expertize and is not standardized yet. Acetone is also released from the skin; thus, measuring acetone as a skin gas may be easier than breath analysis. METHODS We analyzed skin acetone collected from 41 hospitalized patients with cardiovascular diseases. Passive samplers were used to measure skin acetone emission. Passive sampler was softly fixed on the surface of forearm skin for 10 hour at night. RESULTS Skin acetone emission ranged from 0.00 to 2.70 ng/cm2/h, and was significantly correlated with blood ketone bodies (r = 0.377, p = 0.017). CONCLUSIONS This is the first study to analyze skin gas in patients with cardiovascular diseases. Skin acetone emission was found to reflect blood ketone bodies. It is feasible to measure skin acetone emission for reflecting blood ketone bodies in patients with cardiovascular diseases.
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Affiliation(s)
- Tetsuro Yokokawa
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Takamasa Sato
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Satoshi Suzuki
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Masayoshi Oikawa
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Akiomi Yoshihisa
- Department of Cardiovascular Medicine, Fukushima Medical University
| | | | - Takayoshi Yamaki
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Hiroyuki Kunii
- Department of Cardiovascular Medicine, Fukushima Medical University
| | | | - Takafumi Ishida
- Department of Cardiovascular Medicine, Fukushima Medical University
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Bishop AC, Libardoni M, Choudary A, Misra B, Lange K, Bernal J, Nijland M, Li C, Olivier M, Nathanielsz PW, Cox LA. Nonhuman primate breath volatile organic compounds associate with developmental programming and cardio-metabolic status. J Breath Res 2018; 12:036016. [PMID: 29593130 PMCID: PMC6364675 DOI: 10.1088/1752-7163/aaba84] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Rodent and nonhuman primate studies indicate that developmental programming by reduced perinatal nutrition negatively impacts life course cardio-metabolic health. We have developed a baboon model in which we feed control mothers (CON) ad libitum while nutrient restricted mothers are fed 70% of ad libitum global feed in pregnancy and lactation. Offspring of nutrient restricted mothers are intrauterine growth restricted (IUGR) at term. By 3.5 years IUGR baboons showed signs of insulin resistance, indicating a pre-diabetic phenotype, in contrast to healthy CON offspring. We hypothesized that a novel breath analysis approach would provide markers of the altered cardio-metabolic state in a non-invasive manner. Here we assess whether exhaled breath volatile organic compounds (VOCs) collected from this unique cohort of juvenile baboons with documented cardio-metabolic dysfunction resulting from in utero programming can be detected from their breath signatures. Breath was collected from male and female CON and IUGR baboons at 4.8 ± 0.2 years (human equivalent ~13 years). Breath VOCs were quantified using a two-dimensional gas chromatography mass spectrometer. Two-way ANOVA, on 76 biologically relevant VOCs identified 27 VOCs (p < 0.05) with altered abundances between groups (sex, birthweight, and sex x birthweight). The 27 VOCs included 2-pentanone, 2-octanone, 2,2,7,7-tetramethyloctane and 3-methyl-1-heptene, which have not previously been associated with cardio-metabolic disease. Unsupervised principal component analysis of these VOCs could discriminate the four clusters defining males, females, CON and IUGR. This study, which is the first to assess quantifiable breath signatures associated with cardio-metabolic programing for any model of IUGR, demonstrates the translational value of this unique model to identify metabolites of programmed cardio-metabolic dysfunction in breath signatures. Future studies are required to validate the translatability of these findings to humans.
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Affiliation(s)
- Andrew C Bishop
- Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, United States of America
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Biagini D, Lomonaco T, Ghimenti S, Bellagambi FG, Onor M, Scali MC, Barletta V, Marzilli M, Salvo P, Trivella MG, Fuoco R, Di Francesco F. Determination of volatile organic compounds in exhaled breath of heart failure patients by needle trap micro-extraction coupled with gas chromatography-tandem mass spectrometry. J Breath Res 2017; 11:047110. [PMID: 29052557 DOI: 10.1088/1752-7163/aa94e7] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The analytical performances of needle trap micro-extraction (NTME) coupled with gas chromatography-tandem mass spectrometry were evaluated by analyzing a mixture of twenty-two representative breath volatile organic compounds (VOCs) belonging to different chemical classes (i.e. hydrocarbons, ketones, aldehydes, aromatics and sulfurs). NTME is an emerging technique that guarantees detection limits in the pptv range by pre-concentrating low volumes of sample, and it is particularly suitable for breath analysis. For most VOCs, detection limits between 20 and 500 pptv were obtained by pre-concentrating 25 ml of a humidified standard gas mixture at a flow rate of 15 ml min-1. For all compounds, inter- and intra-day precisions were always below 15%, confirming the reliability of the method. The procedure was successfully applied to the analysis of exhaled breath samples collected from forty heart failure (HF) patients during their stay in the University Hospital of Pisa. The majority of patients (about 80%) showed a significant decrease of breath acetone levels (a factor of 3 or higher) at discharge compared to admission (acute phase) in correspondence to the improved clinical conditions during hospitalization, thus making this compound eligible as a biomarker of HF exacerbation.
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Affiliation(s)
- D Biagini
- Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
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