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Shouman WA, Najmeddine S, Sinno L, Dib Nehme R, Ghawi A, Ziade JA, Altara R, Amin G, Booz GW, Zouein FA. Hepatokines and their role in cardiohepatic interactions in heart failure. Eur J Pharmacol 2025; 992:177356. [PMID: 39922419 PMCID: PMC11862882 DOI: 10.1016/j.ejphar.2025.177356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 01/29/2025] [Accepted: 02/05/2025] [Indexed: 02/10/2025]
Abstract
Heart failure is one of the leading causes of death and disease worldwide. It is a condition that affects multiple systems within the body. There is a large body of evidence supporting that the liver is a major organ involved in the pathogenesis of heart failure. Cardiac hepatopathy and cirrhotic cardiomyopathy are two conditions that are associated with poor clinical outcomes in patients with heart failure. Despite the extensive proposed explanations of the mechanisms entailing heart failure, there remains a gap in the role of proteins and metabolic regulators produced by hepatocytes and their effect on the development, progression, and prognosis of heart failure, including adverse cardiac remodeling, fibrosis, cardiac cachexia, and renal dysfunction associated with heart failure. The aim of this review is to identify the major hepatokines being studied (adropin, fetuin-A, fetuin-B, FGF-21, selenoprotein P and α1-microglobulin) as modulators of metabolic homeostasis and cardiac dysfunction in heart failure. Research suggests that these factors play a role in modulating oxidative stress, fibrosis, apoptosis, inflammatory responses, immune cell activation, mitochondrial dysfunction, and cellular migration. The exact role of each of these hepatokines is under on-going research and requires more investigations for future clinical use.
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Affiliation(s)
- Wael A Shouman
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Sarah Najmeddine
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Lilas Sinno
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Ryan Dib Nehme
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Alaa Ghawi
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Joanna A Ziade
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Raffaele Altara
- Department of Pathology, School of Medicine, University of Mississippi Medical Center, 14, Jackson, MS, USA; Department of Anatomy & Embryology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - Ghadir Amin
- Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - George W Booz
- Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - Fouad A Zouein
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon; The Cardiovascular, Renal, and Metabolic Diseases Research Center of Excellence, American University of Beirut Medical Center, Riad El-Solh, Beirut, Lebanon; Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
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Wu HHL, Rakisheva A, Ponnusamy A, Chinnadurai R. Hepatocardiorenal syndrome in liver cirrhosis: Recognition of a new entity? World J Gastroenterol 2024; 30:128-136. [PMID: 38312119 PMCID: PMC10835518 DOI: 10.3748/wjg.v30.i2.128] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 12/05/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome (HRS), outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context. In the absence of established heart disease, cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease. It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities. Despite the clinical description of these potential cardiac-related complications of the liver, the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS. Yet from a physiological sense, temporality (prior onset) of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients. In this review, we discuss current concepts surrounding how the heart may influence the development and progression of HRS, and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting. The temporality of heart and kidney dysfunction in HRS will be discussed. For a subgroup of patients who receive portosystemic shunting, the dynamics of cardiorenal interactions following treatment is reviewed. Continued research to determine the unknowns in this topic is anticipated, hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.
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Affiliation(s)
- Henry H L Wu
- Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital & The University of Sydney, St. Leonards (Sydney) 2065, New South Wales, Australia
| | - Amina Rakisheva
- Department of Cardiology, City Cardiological Center, Almaty 050000, Kazakhstan
| | - Arvind Ponnusamy
- Department of Renal Medicine, Royal Preston Hospital, Preston PR2 9HT, United Kingdom
| | - Rajkumar Chinnadurai
- Donal O’Donoghue Renal Research Centre & Department of Renal Medicine, Northern Care Alliance National Health Service Foundation Trust, Salford M6 8HD, United Kingdom
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Rosseel Z, Cortoos PJ, Jonckheer J, Cools W, Vinken M, Reynaert H, De Waele E. Parenteral Nutrition, Sepsis, Acute Heart Failure and Hepatotoxic Drugs Are Related to Liver Test Disturbances in Critically Ill Patients. Nutrients 2023; 15:nu15112612. [PMID: 37299575 DOI: 10.3390/nu15112612] [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: 04/26/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND Parenteral nutrition (PN) is often associated with liver dysfunction in the ICU, although other factors such as sepsis, acute heart failure (AHF), and hepatotoxic drugs can be equally present. The relative impact of PN on liver dysfunction in critically ill patients is largely unknown. METHODS We recorded the presence of pre-existing liver disturbances, AHF, sepsis, daily PN volume, and commonly used hepatotoxic drugs in adult ICU patients, together with daily aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), alkalic phosphatase (AP), total bilirubin (TB), and INR values in patients with three or more PN treatment days. A linear mixed-effects model was used to assess the relative contribution of each liver parameter. Nutritional adequacy was defined as intake/needs. RESULTS We included 224 ICU patients with PN treatment lasting more than 3 days between 1 January 2017 and 31 December 2019. For AST, pre-existing liver disturbances (+180% ± 11%) and the presence of AHF (+75% ± 14%) were the main predictors of deterioration, whereas PN volume caused only a limited increase of 14% ± 1%/L. Similar results were observed for ALT. GGT, INR, and TB are mainly influenced by the presence of sepsis/septic shock and pre-existing liver disturbances, with no impact of PN or hepatotoxic drugs. Carbohydrate intake exceeded recommendations, and protein and lipid intake were insufficient in this study cohort. CONCLUSIONS Liver test disturbances in ICU patients on PN are multifactorial, with sepsis and AHF having the highest influence, with only limited impact from PN and hepatotoxic drugs. Feeding adequacy can be improved.
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Affiliation(s)
- Zenzi Rosseel
- Department of Pharmacy, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium
- Department of Clinical Nutrition, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium
| | - Pieter-Jan Cortoos
- Department of Pharmacy, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium
- Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium
| | - Joop Jonckheer
- Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium
- Department of Intensive Care, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium
| | - Wilfried Cools
- Department of Support for Quantitative and Qualitative Research (SQUARE), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium
| | - Mathieu Vinken
- Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium
| | - Hendrik Reynaert
- Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium
- Department of Gastro-Enterology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium
| | - Elisabeth De Waele
- Department of Clinical Nutrition, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium
- Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium
- Department of Intensive Care, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium
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Ho FK, Ferguson LD, Celis-Morales CA, Gray SR, Forrest E, Alazawi W, Gill JMR, Katikireddi SV, Cleland JGF, Welsh P, Pell JP, Sattar N. Association of gamma-glutamyltransferase levels with total mortality, liver-related and cardiovascular outcomes: A prospective cohort study in the UK Biobank. EClinicalMedicine 2022; 48:101435. [PMID: 35706481 PMCID: PMC9112033 DOI: 10.1016/j.eclinm.2022.101435] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 04/08/2022] [Accepted: 04/14/2022] [Indexed: 02/09/2023] Open
Abstract
BACKGROUND Gamma-glutamyltransferase (GGT) levels in the blood can be a sensitive marker of liver injury but the extent to which they give insight into risk across multiple outcomes in a clinically useful way remains uncertain. METHODS Using data from 293,667 UK Biobank participants, the relationship of GGT concentrations to self-reported alcohol intake and adiposity markers were investigated. We next investigated whether GGT predicted liver-related, cardiovascular (CV) or all-cause mortality, and potentially improved CV risk prediction. FINDINGS Higher alcohol intake and greater waist circumference (WC) were associated with higher GGT; the association was stronger for alcohol with evidence of a synergistic effect of WC. Higher GGT concentrations were associated with multiple outcomes. Compared to a GGT of 14.5 U/L (lowest decile), values of 48 U/L for women and 60 U/L for men (common upper limits of 'normal') had hazard ratios (HRs) for liver-related mortality of 1.83 (95% CI 1.60-2.11) and 3.25 (95% CI 2.38-4.42) respectively, for CV mortality of 1.21 (95% CI 1.14-1.28) and 1.43 (95% CI 1.27-1.60) and for all-cause mortality of 1.15 (95% CI 1.12-1.18) and 1.31 (95% CI 1.24-1.38). Adding GGT to a risk algorithm for CV mortality reclassified an additional 1.24% (95% CI 0.14-2.34) of participants across a binary 5% 10-year risk threshold. INTERPRETATION Our study suggests that a modest elevation in GGT levels should trigger a discussion with the individual to review diet and lifestyle including alcohol intake and consideration of formal liver disease and CV risk assessment if not previously done. FUNDING British Heart Foundation Centre of Research Excellence Grant (grant number RE/18/6/34217), NHS Research Scotland (grant number SCAF/15/02), the Medical Research Council (grant number MC_UU_00022/2); and the Scottish Government Chief Scientist Office (grant number SPHSU17).
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Affiliation(s)
- Frederick K Ho
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Lyn D Ferguson
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | - Carlos A Celis-Morales
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | - Stuart R Gray
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | - Ewan Forrest
- Gastroenterology Unit, Glasgow Royal Infirmary and University of Glasgow, Glasgow, UK
| | - William Alazawi
- Blizard Institute – Faculty of Medicine and Dentistry, Queen Mary University of London, UK
| | - Jason MR Gill
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | | | - John GF Cleland
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
- Robertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Paul Welsh
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | - Jill P Pell
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
- Corresponding author.
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5
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Zhang J, Xu M, Chen T, Zhou Y. Correlation Between Liver Stiffness and Diastolic Function, Left Ventricular Hypertrophy, and Right Cardiac Function in Patients With Ejection Fraction Preserved Heart Failure. Front Cardiovasc Med 2021; 8:748173. [PMID: 34901210 PMCID: PMC8655684 DOI: 10.3389/fcvm.2021.748173] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 10/28/2021] [Indexed: 12/31/2022] Open
Abstract
Objective: Ejection fraction preserved heart failure (HFpEF) is a common clinical syndrome with a high morbidity, accounting for ~50% of all heart failure patients, and a mortality comparable to that of ejection fraction reduced heart failure (HFrEF). The relationship between liver stiffness (LS) and HFpEF remains unclear. The purpose of this study was to explore the correlation between LS and the severity of HFpEF. Methods: We performed a prospective observational study. After accepting liver transient elastography on admission, consecutive 150 hospitalized HFpEF patients were divided into three groups based on their liver elasticity value: first-third quartiles. Left ventricular diastolic function, left ventricular hypertrophy degree, right cardiac function and short-term prognosis (≤1 year) were compared among the three groups, and the correlation between liver elasticity and each indicator was analyzed. Results: The elasticity of the liver was abnormally high in more than two-thirds of cases. The proportion of NYHA class III-IV in the third quartile group was significantly higher than that in the first quartile group (96 vs. 70%, P = 0.013). Significant differences were discovered in the level of lgNT-proBNP between the three groups (2.63 ± 0.65 vs. 2.84 ± 0.44 vs. 3.05 ± 0.71, P = 0.027). In terms of diastolic function and left ventricular hypertrophy, the ventricular septal e′ (5.01 ± 2.69 vs. 6.48 ± 2.29, P = 0.025), lateral wall e′ (6.63 ± 3.50 vs. 8.62 ± 2.73, P = 0.013), mean E/e′ (20.06 ± 7.53 vs. 13.20 ± 6.05, P = 0.001), left atrial volume index (43.53 ± 10.94 vs. 35.78 ± 13.86, P = 0.008), tricuspid regurgitation (TR) peak flow rate (3.16 ± 0.44 vs. 2.75 ± 0.50, P < 0.001), left ventricular mass index (LVMI) in male (163.2 ± 47.6 vs. 131.3 ± 38.0, P = 0.015) and in female (147.4 ± 48.6 vs. 110.6 ± 24.3, P = 0.036) was significantly different between the third quartile and the first quartile. The proportion of patients with diastolic dysfunction in the third quartile was significantly higher than that in the first quartile (70 vs. 36%, P = 0.017). In terms of right cardiac function, right ventricular fractional area change (RVFAC) (30.3 ± 5.4 vs. 36.5 ± 6.8, P < 0.001), tricuspid annular plane systolic excursion (TAPSE) (7.7 ± 5.2 vs. 14.8 ± 5.9, P = 0.010), pulmonary systolic pressure (38.0 ± 10.5 vs. 32.4 ± 10.3, P = 0.005), TR peak flow rate (3.16 ± 0.44 vs. 2.75 ± 0.50, P < 0.001), and inferior vena cava diameter (2.53 ± 0.51 vs. 1.98 ± 0.41, P < 0.001) were significantly different between the third quartile and the first quartile. More than half of HFpEF patients were combined with right ventricular dysfunction (RVD). Compared to HFpEF without RVD, HFpEF with RVD had higher male sex (53.6 vs. 30.3%, P < 0.001), higher NYHA class (3.2 ± 0.6 vs. 2.8 ± 0.6, P = 0.010), higher proportion of atrial fibrillation (45.2 vs. 18.2%, P < 0.001), and higher liver elasticity value (7.95 ± 0.60 vs. 7.31 ± 0.84, P = 0.003). In terms of short-term prognosis, the incidence of adverse cardiovascular events was significantly higher in the third quartile than in the first quartile (P = 0.003) and the second quartile (P = 0.008). Multivariate Cox proportional hazard analysis showed that adverse cardiovascular events were independently associated with NYHA class, atrial fibrillation, lgNT-proBNP and liver elasticity value (HR = 1.208, 95% CI 1.115–1.352, P = 0.002). Conclusion: Increase of liver stiffness is common in HFpEF patients. Increased LS in HFpEF patients was significantly associated with worsen left diastolic function, left ventricular hypertrophy, and the right cardiac function. LS in HFpEF patients may be more than the result of right ventricular dysfunction. Male, atrial fibrillation, poorer NYHA class and increased liver elasticity value were significantly associated with HFpEF combined with RVD. Atrial fibrillation, poorer NYHA class, higher NT-proBNP, and increased liver elasticity value were independent predictors of poor short-term prognosis of HFpEF patients.
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Affiliation(s)
- Junyi Zhang
- Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China
| | - Mingzhu Xu
- Department of Anesthesia, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China
| | - Tan Chen
- Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China
| | - Yafeng Zhou
- Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China
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6
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Salah HM, Pandey A, Soloveva A, Abdelmalek MF, Diehl AM, Moylan CA, Wegermann K, Rao VN, Hernandez AF, Tedford RJ, Parikh KS, Mentz RJ, McGarrah RW, Fudim M. Relationship of Nonalcoholic Fatty Liver Disease and Heart Failure With Preserved Ejection Fraction. JACC Basic Transl Sci 2021; 6:918-932. [PMID: 34869957 PMCID: PMC8617573 DOI: 10.1016/j.jacbts.2021.07.010] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/27/2021] [Accepted: 07/27/2021] [Indexed: 12/17/2022]
Abstract
Although there is an established bidirectional relationship between heart failure with reduced ejection fraction and liver disease, the association between heart failure with preserved ejection fraction (HFpEF) and liver diseases, such as nonalcoholic fatty liver disease (NAFLD), has not been well explored. In this paper, the authors provide an in-depth review of the relationship between HFpEF and NAFLD and propose 3 NAFLD-related HFpEF phenotypes (obstructive HFpEF, metabolic HFpEF, and advanced liver fibrosis HFpEF). The authors also discuss diagnostic challenges related to the concurrent presence of NAFLD and HFpEF and offer several treatment options for NAFLD-related HFpEF phenotypes. The authors propose that NAFLD-related HFpEF should be recognized as a distinct HFpEF phenotype.
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Key Words
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- AV, arteriovenous
- BCAA, branched-chain amino acid
- GLP, glucagon-like peptide
- HF, heart failure
- HFpEF
- HFpEF, heart failure with preserved ejection fraction
- HFrEF, heart failure with reduced ejection fraction
- IL, interleukin
- LV, left ventricular
- LVEF, left ventricular ejection fraction
- NAFLD
- NAFLD, nonalcoholic fatty liver disease
- NASH, nonalcoholic steatohepatitis
- NT-proBNP, N terminal pro–B-type natriuretic peptide
- RAAS, renin-angiotensin aldosterone system
- SGLT2, sodium-glucose cotransporter 2
- SPSS, spontaneous portosystemic shunt(s)
- TNF, tumor necrosis factor
- cardiomyopathy
- heart failure
- liver
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Affiliation(s)
- Husam M. Salah
- Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Ambarish Pandey
- Division of Cardiology, Department of Medicine, University of Texas Southwestern, and Parkland Health and Hospital System, Dallas, Texas, USA
| | - Anzhela Soloveva
- Department of Cardiology, Almazov National Medical Research Centre, Saint Petersburg, Russian Federation
| | - Manal F. Abdelmalek
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina, USA
| | - Anna Mae Diehl
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina, USA
| | - Cynthia A. Moylan
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina, USA
| | - Kara Wegermann
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina, USA
| | - Vishal N. Rao
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Adrian F. Hernandez
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Ryan J. Tedford
- Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Kishan S. Parikh
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
| | - Robert J. Mentz
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Robert W. McGarrah
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
| | - Marat Fudim
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Durham, North Carolina, USA
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7
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Nickel NP, Galura GM, Zuckerman MJ, Hakim MN, Alkhateeb H, Mukherjee D, Austin ED, Heresi GA. Liver abnormalities in pulmonary arterial hypertension. Pulm Circ 2021; 11:20458940211054304. [PMID: 34707859 PMCID: PMC8544777 DOI: 10.1177/20458940211054304] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 09/13/2021] [Indexed: 12/17/2022] Open
Abstract
Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease with high mortality. In recent years, it has been recognized that PAH is a multi-organ system disease, involving the systemic circulation, kidneys, skeletal muscles, and the central nervous system, among others. Right heart failure produces congestive hepatopathy, a disease state that has direct consequences on liver biochemistry, histology, and systemic glucose and lipid metabolism. This article aims to summarize the consequences of congestive hepatopathy with an emphasis on liver biochemistry, histology, and PAH-targeted therapy. Furthermore, PAH-specific changes in glucose and lipid metabolism will be discussed.
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Affiliation(s)
- Nils P. Nickel
- Division of Pulmonary and Critical Care Medicine, Texas Tech
University Health Sciences Center, El Paso, TX, USA
| | - Gian M. Galura
- Division of Gastroenterology, Texas Tech University Health
Sciences Center, El Paso, TX, USA
| | - Marc J. Zuckerman
- Division of Gastroenterology, Texas Tech University Health
Sciences Center, El Paso, TX, USA
| | - M. Nawar Hakim
- Department of Pathology, Texas Tech University Health Sciences
Center, El Paso, TX, USA
| | - Haider Alkhateeb
- Division of Cardiovascular Medicine, Texas Tech University
Health Sciences Center, El Paso, TX, USA
| | - Debabrata Mukherjee
- Division of Cardiovascular Medicine, Texas Tech University
Health Sciences Center, El Paso, TX, USA
| | - Eric D. Austin
- Division of Pediatric Pulmonary Medicine, Vanderbilt University,
Nashville, TN, USA
| | - Gustavo A. Heresi
- Division of Pulmonary and Critical Care Medicine, Cleveland
Clinic, OH, USA
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8
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Liang W, He X, Wu D, Xue R, Dong B, Owusu-Agyeman M, Zhao J, Cai L, You Z, Dong Y, Liu C. Prognostic Implication of Liver Function Tests in Heart Failure With Preserved Ejection Fraction Without Chronic Hepatic Diseases: Insight From TOPCAT Trial. Front Cardiovasc Med 2021; 8:618816. [PMID: 34055924 PMCID: PMC8153182 DOI: 10.3389/fcvm.2021.618816] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 03/29/2021] [Indexed: 02/04/2023] Open
Abstract
Background: Liver dysfunction is prevalent in patients with heart failure (HF), but the prognostic significance of liver function tests (LFTs) remains controversial. Heart failure with preserved ejection fraction (HFpEF) had been introduced for some time, but no previous study had focused on LFTs in HFpEF. Thus, we aim to evaluate the prognostic significance of LFTs in well-defined HFpEF patients. Methods and Results: We conveyed a post-hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). The primary outcome was the composite of cardiovascular mortality, HF hospitalization, and aborted cardiac arrest, and the secondary outcomes were cardiovascular mortality and HF hospitalization. In Cox proportional hazards models, aspartate transaminase (AST) and alanine transaminase (ALT) were not associated with any of the outcomes. On the contrary, increases in total bilirubin (TBIL) and alkaline phosphatase (ALP) were associated with increased risks of the primary outcome [TBIL: adjusted hazard ratio (HR), 1.17; 95% confidence interval (CI) 1.08-1.26; ALP: adjusted HR, 1.12; 95% CI 1.04-1.21], cardiovascular mortality (TBIL: adjusted HR, 1.16; 95% CI 1.02-1.31; ALP: adjusted HR, 1.16; 95% CI 1.05-1.28), and HF hospitalization (TBIL: adjusted HR, 1.22; 95% CI 1.12-1.33; ALP: adjusted HR, 1.12; 95% CI 1.03-1.23). Conclusion: Elevated serum cholestasis markers TBIL and ALP were significantly associated with a poor outcome in HFpEF patients without chronic hepatic diseases, while elevated ALT and AST were not.
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Affiliation(s)
- Weihao Liang
- Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China
| | - Xin He
- Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China
| | - Dexi Wu
- Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China
| | - Ruicong Xue
- Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China
| | - Bin Dong
- Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China
| | - Marvin Owusu-Agyeman
- Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China
| | - Jingjing Zhao
- Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China
| | - Linnuan Cai
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Zhiyao You
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Yugang Dong
- Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China
| | - Chen Liu
- Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China
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9
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Quantification of Hepatic and Splenic Stiffness After Fontan Procedure in Children and Clinical Implications. Ultrasound Q 2020; 36:350-356. [PMID: 33298772 DOI: 10.1097/ruq.0000000000000541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
We aimed to investigate Fontan associated liver disease in children by shear wave elastography (SWE). This is a single-center, prospective case-control study included 41 patients with Fontan physiology and 30 healthy controls. Hepatic and splenic shear wave elasticity values were exhibited both as kPa and m/s. The mean hepatic SWE values of Fontan patients (n = 41; 15.8 ± 3.2 kPa or 2.5 ± 1.8 m/s) were significantly higher than the control group (n = 30; 5.59 ± 0.6 kPa or 1.37 ± 0.07 m/s) (P < 0.001). The mean splenic SWE values of Fontan patients were (25.6 ± 4.61 kPa or 2.85 ± 0.22 m/s) significantly higher than the control group (15.9 ± 1.44 kPa or 2.29 ± 0.1 m/s) (P < 0.001). There were statistically significant positive correlations among the follow-up duration after the Fontan procedure with NT-proBNP (P = 0.008, r = 1) and prothrombin time (P = 0.009, r = 0.4) as well as the hepatic SWE values with alanine aminotransferase (P = 0.039, r = 0.32), gamma-glutamyl transferase (P = 0.045, r = 0.31), and PT (P = 0.011, r = 0.39). There has been statistically significant moderate positive correlations of splenic stiffness values with PT (P = 0.047, r = 0.34), and INR (P = 0.038, r = 0.35). The sensitivity and specificity of liver stiffness cutoff value as 11.1 kPa for detection of Fontan associated liver disease were 95% and 100%, respectively. The hepatic and splenic stiffness increase independently in Fontan patients due to parenchymal disease. Hepatic SWE is a reliable and noninvasive predictor of early hepatic alterations that could not be detected only by biochemical results or routine ultrasound examinations.
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10
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Shear Wave Dispersion Predicts Liver Fibrosis and Adverse Outcomes in Patients with Heart Failure. J Clin Med 2020; 9:jcm9123953. [PMID: 33291248 PMCID: PMC7762121 DOI: 10.3390/jcm9123953] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 12/01/2020] [Accepted: 12/04/2020] [Indexed: 02/06/2023] Open
Abstract
Background: It has been recently reported that liver stiffness assessed by transient elastography reflects right atrial pressure (RAP) and is associated with worse outcomes in patients with heart failure (HF). However, the relationship between shear wave dispersion (SWD, a novel indicator of liver viscosity) determined by abdominal ultrasonography and RAP, and the prognostic impact of SWD on HF patients have not been fully examined. We aimed to clarify the associations of SWD with parameters of liver function test (LFT) and right heart catheterization (RHC), as well as with cardiac events such as cardiac death and worsening HF, in patients with HF. Methods: We performed abdominal ultrasonography, LFT and RHC in HF patients (n = 195), and followed up for cardiac events. We examined associations between SWD and parameters of LFT and RHC. Results: There were significant correlations between SWD and circulating levels of direct bilirubin (R = 0.222, p = 0.002), alkaline phosphatase (R = 0.219, p = 0.002), cholinesterase (R = −0.184, p = 0.011), and 7S domain of collagen type IV (R = 0.177, p = 0.014), but not with RAP (R = 0.054, p = 0.567) or cardiac index (R = −0.015, p = 0.872). In the Kaplan–Meier analysis, cardiac event rate was significantly higher in the high SWD group (SWD ≥ 10.0 (m/s)/kHz, n = 103) than in the low SWD group (SWD < 10.0 (m/s)/kHz, n = 92; log-rank, p = 0.010). In the Cox proportional hazard analysis, high SWD was associated with high cardiac event rates (hazard ratio, 2.841; 95% confidence interval, 1.234–6.541, p = 0.014). In addition, there were no interactions between SWD and all subgroups, according to the subgroup analysis. Conclusions: SWD assessed by abdominal ultrasonography reflects liver fibrosis rather than liver congestion, and is associated with adverse prognosis in HF patients.
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11
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Yoshihisa A, Ishibashi S, Matsuda M, Yamadera Y, Ichijo Y, Sato Y, Yokokawa T, Misaka T, Oikawa M, Kobayashi A, Yamaki T, Kunii H, Takeishi Y. Clinical Implications of Hepatic Hemodynamic Evaluation by Abdominal Ultrasonographic Imaging in Patients With Heart Failure. J Am Heart Assoc 2020; 9:e016689. [PMID: 32750309 PMCID: PMC7792279 DOI: 10.1161/jaha.120.016689] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Background It has been reported that liver stiffness assessed by transient elastography are correlated with right atrial pressure, which is associated with worse outcome in patients with heart failure (HF). We aimed to clarify clinical implications of hepatic hemodynamic evaluation (liver congestion and hypoperfusion) by abdominal ultrasonography in patients with HF. Methods and Results We performed abdominal ultrasonography, right-heart catheterization, and echocardiography, then followed up for cardiac events such as cardiac death or worsening HF in patients with HF. Regarding liver congestion, liver stiffness assessed by shear wave elastography (SWE) of the liver was significantly correlated with right atrial pressure determined by right-heart catheterization (R=0.343; P<0.01), right atrial end-systolic area, and inferior vena cava diameter determined by echocardiography. Regarding liver hypoperfusion, peak systolic velocity (PSV) of the celiac artery was correlated with cardiac index determined by right-heart catheterization (R=0.291; P<0.001) and tricuspid annular plane systolic excursion determined by echocardiography. According to the Kaplan-Meier analysis, HF patients with high SWE and low PSV had the highest cardiac event rate (log-rank P=0.033). In the Cox proportional hazard analysis, high SWE and low PSV were associated with high cardiac event rate (high SWE: hazard ratio [HR], 2.039; 95% CI, 1.131-4.290; low PSV: HR, 2.211; 95% CI, 1.199-4.449), and the combination of high SWE and low PSV was a predictor of cardiac events (HR, 4.811; 95% CI, 1.562-14.818). Conclusions Intrahepatic congestion and hypoperfusion determined by abdominal ultrasonography (liver SWE and celiac PSV) are associated with adverse prognosis in patients with HF.
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Affiliation(s)
- Akiomi Yoshihisa
- Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan.,Department of Advanced Cardiac Therapeutics Fukushima Medical University Fukushima Japan
| | - Shinji Ishibashi
- Department of Clinical Laboratory Medicine Fukushima Medical University Hospital Fukushima Japan
| | - Mitsuko Matsuda
- Department of Clinical Laboratory Medicine Fukushima Medical University Hospital Fukushima Japan
| | - Yukio Yamadera
- Department of Clinical Laboratory Medicine Fukushima Medical University Hospital Fukushima Japan
| | - Yasuhiro Ichijo
- Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan
| | - Yu Sato
- Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan
| | - Tetsuro Yokokawa
- Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan.,Department of Pulmonary Hypertension 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
| | - Masayoshi Oikawa
- Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan
| | - Atsushi Kobayashi
- Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan
| | - Takayoshi Yamaki
- Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan
| | - Hiroyuki Kunii
- Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan
| | - Yasuchika Takeishi
- Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan
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12
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Borovac JA, Glavas D, Susilovic Grabovac Z, Supe Domic D, Stanisic L, D’Amario D, Duplancic D, Bozic J. Right Ventricular Free Wall Strain and Congestive Hepatopathy in Patients with Acute Worsening of Chronic Heart Failure: A CATSTAT-HF Echo Substudy. J Clin Med 2020; 9:jcm9051317. [PMID: 32370248 PMCID: PMC7290588 DOI: 10.3390/jcm9051317] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 04/25/2020] [Accepted: 04/27/2020] [Indexed: 12/20/2022] Open
Abstract
Right ventricular (RV) function is an important predictor of prognosis in patients with heart failure. However, the relationship of the RV free wall longitudinal strain (RV FWS) and the degree of hepatic dysfunction during the acute worsening of heart failure (AWHF) is unknown. We sought to determine associations of RV FWS with laboratory liver function tests and parameters of RV function including tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV FAC), maximal tricuspid jet velocity (TR Vmax), RV S′ velocity, and estimated RV systolic pressure (RVSP). A total of 42 AWHF patients from the CATSTAT-HF study were stratified in two groups by the RV FWS median (−16.5%). Patients < RV FWS median had significantly prolonged international normalized ratio (INR; p = 0.002), increased total bilirubin (p < 0.001) and alkaline phosphatase (ALP; p = 0.020), and decreased albumin (p = 0.005) and thrombocytes (p = 0.017) compared to patients > RV FWS median. RV FWS independently correlated to total bilirubin (β = 0.457, p = 0.004), ALP (β = 0.556, p = 0.002), INR (β = 0.392, p = 0.022), albumin (β = −0.437, p = 0.013), and thrombocytes (β = −404, p = 0.038). Similarly, TAPSE, RV FAC, and RV S′ significantly correlated with RV FWS. In conclusion, RV impairment, reflected in reduced RV FWS, is independently associated with a higher degree of hepatic dysfunction among patients with AWHF (CATSTAT-HF ClinicalTrials gov number, NCT03389386).
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Affiliation(s)
- Josip A. Borovac
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia;
- Institute of Emergency Medicine of Split-Dalmatia County, Spinciceva 1, 21000 Split, Croatia
- Clinic for Cardiovascular Diseases, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (D.G.); (Z.S.G.); (D.D.)
| | - Duska Glavas
- Clinic for Cardiovascular Diseases, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (D.G.); (Z.S.G.); (D.D.)
- Department of Internal Medicine, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia
| | - Zora Susilovic Grabovac
- Clinic for Cardiovascular Diseases, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (D.G.); (Z.S.G.); (D.D.)
| | - Daniela Supe Domic
- Department of Medical Laboratory Diagnostics, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (D.S.D.); (L.S.)
- Department of Health Studies, University of Split, Rudjera Boskovica 35 P.P. 464, 21000 Split, Croatia
| | - Lada Stanisic
- Department of Medical Laboratory Diagnostics, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (D.S.D.); (L.S.)
- Department of Health Studies, University of Split, Rudjera Boskovica 35 P.P. 464, 21000 Split, Croatia
| | - Domenico D’Amario
- Department of Cardiovascular and Thoracic Sciences, IRCCS Fondazione Policlinico A. Gemelli, Università Cattolica Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy;
| | - Darko Duplancic
- Clinic for Cardiovascular Diseases, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (D.G.); (Z.S.G.); (D.D.)
- Department of Internal Medicine, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia;
- Correspondence: ; Tel.: +385-21-557-871
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13
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Patel D, Iqbal AM, Mubarik A, Zafar F, Siddiqui SM, Jupalli A, Mitzov NP, Muddassir S. Spontaneous Fungal Peritonitis as a Rare Complication of Ascites Secondary to Cardiac Cirrhosis: A Case Report. AMERICAN JOURNAL OF CASE REPORTS 2019; 20:1526-1529. [PMID: 31619662 PMCID: PMC6818645 DOI: 10.12659/ajcr.917757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Accepted: 07/15/2019] [Indexed: 11/25/2022]
Abstract
BACKGROUND Spontaneous fungal peritonitis (SFP) is a life-threatening infection which occurs more commonly in patients with liver failure. SFP is not as common as spontaneous bacterial peritonitis (SBP) and has higher mortality rates due to late recognition and difficulty in differentiation between SFP and SBP. Spontaneous fungal peritonitis is extremely uncommon in patients with cardiac ascites due to a high protein content, which predisposes to a low risk of infections. CASE REPORT This report presents a rare case of spontaneous fungal peritonitis in a patient with cardiogenic ascites. To the best of our knowledge, this is the second known case of SFP occurring in a patient with cardiac cirrhosis. The patient did not respond to initiation of SBP treatment and after ascitic fluid grew Candida glabrata, the diagnosis of SFP was made. The patient's clinical status improved after initiation of intravenous caspofungin. CONCLUSIONS SFP should be a differential diagnosis in patients who have cardiac or liver cirrhosis, who are not improving with empirical antibiotic therapy for spontaneous bacterial peritonitis.
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14
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Wei XB, Wang Y, Liu YH, Huang JL, Yu DQ, Chen JY. Effect of conjugated bilirubin on clinical outcomes in infective endocarditis. Eur J Clin Microbiol Infect Dis 2019; 38:2259-2266. [PMID: 31428896 DOI: 10.1007/s10096-019-03670-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 08/05/2019] [Indexed: 01/15/2023]
Abstract
Liver dysfunction is associated with adverse events in infective endocarditis (IE). However, few studies have explored the predictive value of conjugated bilirubin (CB) in IE. We aimed to investigate the nature of the link between CB and adverse prognosis in patients with IE. Consecutive patients with IE between January 2009 and July 2015 were enrolled. Multivariate analysis was performed to confirm whether CB was an independent risk factor for adverse outcomes. In all, 1010 patients were included and divided into two groups according to admission CB level (μmol/L): normal (≤ 7.0, n = 820) and elevated (> 7.0, n = 190) CB groups. In-hospital mortality (5.0% vs. 22.1%, p < 0.001) and major adverse cardiac events (16.8% vs. 36.3%, p < 0.001) were significantly higher in patients with increased CB. A possible J-shaped relationship was found between CB and in-hospital events. Further, CB had more predictive power than total bilirubin in predicting in-hospital death (AUC 0.715 vs. 0.674, p = 0.010). Elevated CB was an independent predictor of in-hospital death (adjusted OR = 2.62, 95%CI 1.40-4.91, p = 0.003). Moreover, CB (increment 1 μmol/L) was independently associated with higher long-term mortality. Kaplan-Meier curves indicated that patients with elevated CB were associated with higher cumulative rate of long-term death (log-rank = 21.47, p < 0.001). CB, a biomarker of liver function, was a relatively powerful predictor of in-hospital and long-term adverse prognosis of IE and could likely comprise a novel risk evaluation strategy.
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Affiliation(s)
- Xue-Biao Wei
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.,Department of Gerontological Critical Care Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
| | - Yu Wang
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
| | - Yuan-Hui Liu
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
| | - Jie-Leng Huang
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
| | - Dan-Qing Yu
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
| | - Ji-Yan Chen
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
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15
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16
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Hepatic Changes in the Fontan Circulation: Identification of Liver Dysfunction and an Attempt to Streamline Follow-up Screening. Pediatr Cardiol 2018; 39:1604-1613. [PMID: 30032312 DOI: 10.1007/s00246-018-1937-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 07/05/2018] [Indexed: 12/27/2022]
Abstract
We tried to identify structural and functional liver aberrances in a palliated Fontan population and sought to determine useful screening modalities, in order to propose a screening protocol to detect patients at risk. Twenty nine patients, median age 23.7 years (interquartile range (IQR) 20.5-27.2) and median Fontan interval 19.7 years (IQR 4.5-21.4), were prospectively studied with echocardiography, blood analysis (including serum fibrosis scores Forns, APRI and FIB4), liver imaging (ultrasound (US), Doppler), and shear wave elastography to determine liver stiffness (LS). Laboratory tests predominantly showed abnormal values for gamma-glutamyltransferase. Forns index indicated moderate fibrosis in 29% of patients and correlated with Fontan interval (p = 0.034). US liver morphology was deviant in 46% of patients, with surface nodularity in 21% and nodular hyperplasia in 29%. Doppler assessment of flow velocities was within normal ranges for most patients. LS (mean 10.4 ± 3.7 kPa) was elevated in 96% of our population and higher LS values were significantly related to longer Fontan interval (p = 0.018). Adolescent and adult Fontan patients show moderate signs of liver dysfunction. Usefulness of serum parameters and fibrosis scores in post-Fontan screening remains ambiguous. The high percentage of morphologic liver changes in palliated patients supports the use of US in periodic follow-up. LS likely overestimates fibrosis due to liver congestion, arguing for the need of validation through sequential measurements. Screening should minimally encompass US assessment in combination with selective liver fibrosis scores. The role of LS measurement in Fontan follow-up and liver screening needs to be further elucidated.
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17
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Holndonner-Kirst E, Nagy A, Czobor NR, Fazekas L, Lex DJ, Sax B, Hartyanszky I, Merkely B, Gal J, Szekely A. Higher Transaminase Levels in the Postoperative Period After Orthotopic Heart Transplantation Are Associated With Worse Survival. J Cardiothorac Vasc Anesth 2018; 32:1711-1718. [DOI: 10.1053/j.jvca.2018.01.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Indexed: 11/11/2022]
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18
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Yoshihisa A, Kimishima Y, Kiko T, Sato Y, Watanabe S, Kanno Y, Abe S, Miyata-Tatsumi M, Sato T, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Ishida T, Takeishi Y. Liver fibrosis marker, 7S domain of collagen type IV, in patients with pre-capillary pulmonary hypertension. Int J Cardiol 2018; 258:269-274. [DOI: 10.1016/j.ijcard.2018.01.138] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Revised: 01/29/2018] [Accepted: 01/31/2018] [Indexed: 02/08/2023]
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19
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Risk prediction in infective endocarditis by modified MELD-XI score. Eur J Clin Microbiol Infect Dis 2018; 37:1243-1250. [PMID: 29594801 DOI: 10.1007/s10096-018-3240-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 03/19/2018] [Indexed: 10/17/2022]
Abstract
The suitability of the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score to predict adverse outcomes in infective endocarditis (IE) patients remains uncertain. This study was performed to explore the prognostic value of the MELD-XI score and modified MELD-XI score for patients with IE. A total of 858 patients with IE were consecutively enrolled and classified into two groups: MELD-XI ≤ 10 (n = 588) and MELD-XI > 10 (n = 270). Multivariate analysis was performed to determine risk factors independent of MELD-XI score. Higher MELD-XI score was associated with higher in-hospital mortality (15.6 vs. 4.8%, p < 0.001) and major adverse clinical events (33.3 vs. 18.4%, p < 0.001). MELD-XI score was an independent predictor of in-hospital death (odds ratio [OR] = 1.06, 95% CI, 1.02-1.10, p = 0.005). Based on a multivariate analysis, NYHA class III or IV (3 points), C-reactive protein > 9.5 mg/L (4 points), and non-surgical treatment (6 points) were added to MELD-XI score. Modified MELD-XI score produced higher predictive power than previous (AUC 0.823 vs. 0.701, p < 0.001). The cumulative incidence of long-term mortality (median 29 months) was significantly higher in patients with modified MELD-XI score > 13 than those without (log-rank = 25.30, p < 0.001). Modified MELD-XI score was independently associated with long-term mortality (hazard ratio = 1.08, 95% CI, 1.04-1.12, p < 0.001). MELD-XI score could be used as a risk assessment tool in IE. Furthermore, modified MELD-XI score remained simple and more effective in predicting poor prognosis.
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20
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Abstract
On rare occasions the first manifestation of heart disease is jaundice, caused by passive congestion of the liver or acute ischaemic hepatitis. We looked for this presentation retrospectively in 661 patients referred over fifty-six months to a ‘jaundice hotline’ (rapid access) service. The protocol included a full clinical history, examination and abdominal ultrasound. Those with no evidence of biliary obstruction had a non-invasive liver screen for parenchymal liver disease and those with suspected heart disease had an electrocardiogram, chest X-ray and echocardiogram. 8 patients (1.2%), bilirubin 31–79 μmol/L, mean 46 μmol/L, had a primary cardiac cause for their jaundice. All had dyspnoea, an increased cardiothoracic ratio on chest X-ray and an abnormal electrocardiogram. The jugular venous pressure was raised in the 3 in whom it was recorded. In 6 patients the jaundice was attributed to hepatic congestion and in 2 to ischaemic hepatitis. All patients had severe cardiac dysfunction. Jaundice due to heart disease tends to be mild, and a key feature is breathlessness. The most common mechanism is hepatic venous congestion; ischaemic hepatitis is suggested by a high aminotransferase.
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Affiliation(s)
- R van Lingen
- Cornwall Gastrointestinal Unit, Royal Cornwall Hospital Trust, Truro TR1 3LJ, UK
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21
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Yoshihisa A, Sato Y, Yokokawa T, Sato T, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Kunii H, Nakazato K, Saitoh S, Takeishi Y. Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction. ESC Heart Fail 2017; 5:262-270. [PMID: 28967709 PMCID: PMC5880657 DOI: 10.1002/ehf2.12222] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2017] [Revised: 07/27/2017] [Accepted: 08/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIMS Heart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects, including stiffness and/or congestion of multiple organs. Poor prognosis is expected in heart failure patients with liver stiffness, which has recently been assessed by non-alcoholic fatty liver disease fibrosis score (NFS; based on aspartate aminotransferase to alanine aminotransferase ratio, platelet counts, and albumin). We aimed to investigate the impact of NFS on prognosis of HFpEF patients, with consideration for the peripheral collagen markers such as procollagen type III peptide (PIIIP), type IV collagen 7S, and hyaluronic acid. METHODS AND RESULTS We performed a prospective observational study. Consecutive 492 hospitalized HFpEF patients were divided into four groups based on their NFS: first-fourth quartiles (n = 123). The fourth quartile group had the highest levels of PIIIP, type IV collagen 7S, hyaluronic acid, and B-type natriuretic peptide (P<0.001 each). In addition, there were significant positive correlations between PIIIP, type IV collagen 7S, hyaluronic acid, B-type natriuretic peptide, and NFS (P < 0.001 each). In the follow-up period (mean 1107 days), 93 deaths occurred. All-cause mortality increased in all four quartiles (8.1%, 12.2%, 23.6%, and 31.7%, P < 0.001). In the multivariable Cox proportional hazard analysis, NFS was an independent predictor of all-cause mortality in the HFpEF patients. CONCLUSIONS NFS, a novel indicator of liver fibrosis, correlates with circulating systemic markers of fibrosis and congestion and is associated with higher all-cause mortality in HFpEF patients. NFS can be calculated simply and may be a useful tool to assess liver stiffness and prognosis in HFpEF patients.
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Affiliation(s)
- Akiomi Yoshihisa
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
| | - Yu Sato
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
| | - Tetsuro Yokokawa
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
| | - Takamasa Sato
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
| | - Satoshi Suzuki
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
| | - Masayoshi Oikawa
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
| | - Atsushi Kobayashi
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
| | - Takayoshi Yamaki
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
| | - Hiroyuki Kunii
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
| | - Kazuhiko Nakazato
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
| | - Shu‐ichi Saitoh
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
| | - Yasuchika Takeishi
- Department of Cardiovascular MedicineFukushima Medical University1 HikarigaokaFukushima960‐1295Japan
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Sato Y, Yoshihisa A, Kanno Y, Watanabe S, Yokokawa T, Abe S, Misaka T, Sato T, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Kunii H, Nakazato K, Saitoh SI, Takeishi Y. Liver stiffness assessed by Fibrosis-4 index predicts mortality in patients with heart failure. Open Heart 2017; 4:e000598. [PMID: 28674631 PMCID: PMC5471867 DOI: 10.1136/openhrt-2017-000598] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 02/14/2017] [Accepted: 02/21/2017] [Indexed: 12/25/2022] Open
Abstract
Objective Liver dysfunction due to heart failure (HF) is known as congestive hepatopathy. It has recently been reported that liver stiffness assessed by transient elastography reflects increased central venous pressure. The Fibrosis-4 (FIB4) index (age (years) × aspartate aminotransferase (IU/L)/platelet count (109/L) × square root of alanine aminotransferase (IU/L)) is expected to be useful for evaluating liver stiffness in patients with non-alcoholic fatty liver disease. We aimed to investigate the impact of the FIB4 index on HF prognosis, with consideration for liver fibrosis markers and underlying cardiac function. Methods Consecutive 1058 patients with HF who were admitted to our hospital were divided into three groups based on their FIB4 index: first (FIB4 index <1.72, n=353), second (1.72≤FIB4 index <3.01, n=353) and third tertiles (3.01≤FIB4 index, n=352). We prospectively followed for all-cause mortality. Results During the follow-up period (mean 1047 days), 246 deaths occurred. In the Kaplan-Meier analysis, all-cause mortality progressively increased from the first to third groups (12.2%, 21.0% and 36.6%, p<0.01). In the Cox proportional hazard analysis, FIB4 index was an independent predictor of all-cause mortality in patients with HF (p<0.05). In comparisons of laboratory and echocardiographic findings, the third tertile had higher levels of type IV collagen 7S, procollagen type III peptide, hyaluronic acid, left atrial volume, mitral valve E/e’, inferior vena cava diameter and right atrial end systolic area (p<0.01, respectively). Conclusion The FIB4 index, a marker of liver stiffness, is associated with higher all-cause mortality in patients with HF.
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Affiliation(s)
- Yu Sato
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Akiomi Yoshihisa
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Yuki Kanno
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Shunsuke Watanabe
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Tetsuro Yokokawa
- 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
| | - Takamasa Sato
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Satoshi Suzuki
- 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
| | - Takayoshi Yamaki
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Hiroyuki Kunii
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Kazuhiko Nakazato
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Shu-Ichi Saitoh
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Yasuchika Takeishi
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
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Abstract
Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases
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Abstract
There is a mutual interaction between the function of the heart and the liver and a broad spectrum of acute and chronic entities that affect both the heart and the liver. These can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. In chronic and acute cardiac hepatopathy, owing to cardiac failure, a combination of reduced arterial perfusion and passive congestion leads to cardiac cirrhosis and cardiogenic hypoxic hepatitis. These conditions may impair the liver function and treatment should be directed towards the primary heart disease and seek to secure perfusion of vital organs. In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities termed cirrhotic cardiomyopathy. Electrophysiological abnormalities include prolonged QT interval, chronotropic incompetance, and electromechanical uncoupling. No specific therapy can be recommended, but it should be supportive and directed against the heart failure. Numerous conditions affect both the heart and the liver such as infections, inflammatory and systemic diseases, and chronic alcoholism. The risk and prevalence of coronary artery disease are increasing in cirrhotic patients and since the perioperative mortality is high, a careful cardiac evaluation of such patients is required prior to orthotopic liver transplantation.
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Affiliation(s)
- Søren Møller
- Centre of Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, The Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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Souza MVLD, Novaes FS. [Serious jaundice and thyrotoxic myocardiopathy with atrial thrombus]. ARQUIVOS BRASILEIROS DE ENDOCRINOLOGIA E METABOLOGIA 2012; 56:456-460. [PMID: 23108751 DOI: 10.1590/s0004-27302012000700008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2012] [Accepted: 06/27/2012] [Indexed: 06/01/2023]
Abstract
Jaundice related to thyrotoxicosis and not as an effect of antithyroid drugs is a rare complication that usually occurs in the presence of heart failure (HF) or hepatitis. We report a case of a 54-year-old white woman with hyperthyroidism caused by Graves's disease and jaundice despite methimazole suspension. Bilirubin fluctuated at high values, between 30.0 and 52.3 mg/dL, transaminases were slightly increased, on admission ALT = 46 U/L and AST = 87 U/L; coagulation indices and serum proteins were on the lower limit of the normal range with PT 68% and albumin = 2.5 g/dL. Serology for hepatitis was negative. After the first radioiodine therapy (RT), bilirubin reached its maximum, which coincided with the worst period of HF exacerbation. Bilirubin normalized 4 weeks after the second RT, with the stabilization of HF and normalization of thyroid hormones. We discuss the possible etiologies of severe jaundice in hyperthyroid patients, as well as the difficult anticoagulant therapy with warfarin.
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Affiliation(s)
- Marcus V Leitão de Souza
- Serviço de Endocrinologia, Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, Rio de Janeiro, RJ, Brasil
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26
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Hepatic dysfunction and survival after orthotopic heart transplantation: application of the MELD scoring system for outcome prediction. J Heart Lung Transplant 2012; 31:591-600. [PMID: 22458996 DOI: 10.1016/j.healun.2012.02.008] [Citation(s) in RCA: 128] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2011] [Revised: 12/10/2011] [Accepted: 02/02/2012] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND The prevalence of heart failure (HF) is rising and the only corrective treatment is cardiac transplantation. Advanced HF is associated with congestive hepatopathy and progressive functional and ultrastructural changes of the liver. We hypothesized that hepatic dysfunction is associated with impaired clinical outcome after heart transplantation. METHODS Data of 617 adult patients (75% men, mean age 53 ± 12 years, mean BMI 25 ± 4, mean ejection fraction 19 ± 9%) undergoing orthotopic heart transplantation (OHT) were analyzed retrospectively. Deviation from institutional normal ranges was used to define abnormal liver function. Standard Model for End-stage Liver Disease (MELD) scores were calculated and a modified MELD score with albumin replacing INR (modMELD) was created to eliminate the confounding effects of anti-coagulation. RESULTS Before OHT, AST, ALT and total bilirubin were elevated in 20%, 18% and 29% of the population, respectively. Total protein and albumin were decreased in 25% and 52% of the population, respectively. By 2 months post-transplantation, percentages of individuals with pathologic values decreased significantly, except for ALT, total protein and albumin, all of which took longer to normalize. Individuals with a higher pre-transplantation MELD or modMELD score had worse outcome 30 days post-transplant and reduced long-term survival over a 10-year follow-up. CONCLUSIONS In this large, single-center retrospective study, we demonstrated the dynamics of liver dysfunction after cardiac transplantation and that elevated MELD scores indicating impaired liver function are associated with poor clinical outcome after OHT. Thus, pre-operative liver dysfunction has a significant impact on survival of patients after cardiac transplantation.
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27
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Poelzl G, Ess M, Mussner-Seeber C, Pachinger O, Frick M, Ulmer H. Liver dysfunction in chronic heart failure: prevalence, characteristics and prognostic significance. Eur J Clin Invest 2012; 42:153-63. [PMID: 21806605 DOI: 10.1111/j.1365-2362.2011.02573.x] [Citation(s) in RCA: 108] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Although abnormal liver morphology and function have long been recognized, characterization and importance of liver dysfunction in heart failure are poorly defined. This study sought to investigate the relevance of circulating liver function tests (LFTs) in an unselected chronic heart failure (CHF) cohort. MATERIALS AND METHODS A total of 1032 consecutive ambulatory patients with CHF were enrolled from 2000 to 2008. Clinical and laboratory variables including LFTs were collected at study entry. Follow-up (median 36 months) was available in 1002 (97·1%) patients. The endpoint was defined as death from any cause or heart transplantation. Hazard ratios (HR) for transplant-free survival were estimated per log unit using Cox proportional hazard regression models for sex-stratified data. RESULTS Sex-specific prevalence of cholestatic enzyme elevation was 19·2% as opposed to elevated transaminases in 8·3%. Cholestatic enzymes, but not transaminases, were significantly associated with severity of heart failure syndrome and backward failure. The endpoint was recorded in 339 patients (33·8%). T-Bil, γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) were associated with adverse outcome in bivariate models. Of these, GGT [HR 1·22 (1·06, 1·41); P = 0·006] and ALP [HR 1·52 (1·09, 2·12); P = 0·014] were independently associated with the endpoint after adjustment for a wide array of clinical and laboratory predictors. CONCLUSIONS Liver dysfunction is frequent in CHF and characterized by a predominantly cholestatic enzyme profile that is associated with disease severity and prognosis. Thus, we propose a cardio-hepatic syndrome in CHF. Future studies are needed to clarify the exact mechanisms of organ interaction.
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Affiliation(s)
- Gerhard Poelzl
- Clinical Division of Cardiology, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria.
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Maleki M, Vakilian F, Amin A. Liver diseases in heart failure. HEART ASIA 2011; 3:143-9. [PMID: 27326014 DOI: 10.1136/heartasia-2011-010023] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Accepted: 09/22/2011] [Indexed: 11/04/2022]
Abstract
Heart failure (HF) is a growing public health concern as a consequence of the ageing of the population and the improved survival of patients with HF. HF is defined as impaired organ perfusion and/or high filling pressure. It is a systemic and chronic disease and as such involves many organs, not least the liver and kidney. The complex vascular system of the liver and its high metabolic activity render it vulnerable to circulation disturbances and trigger many molecular and haemodynamic changes in patients. There are many studies describing the impact of liver disease on patient outcomes. Hepatic dysfunction is commonly seen in HF patients and is closely correlated with a poor outcome. Knowledge about the mechanisms and impacts of liver disease in HF helps us to know the stage of the disease and treat it properly. Moreover, many drugs and toxins that are metabolised in the liver and contribute to drug interactions should also be taken into account when prescribing medication for HF patients. In light of the above-mentioned points, the authors have compiled this review on congestive hepatopathy with the aim of providing physicians and cardiologists with a succinct and useful guide on the role of the liver in HF.
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Affiliation(s)
- Majid Maleki
- Department of Cardiology, Rajai Cardiovascular, Medical and Research Center, Tehran University of Medical Science, Tehran, Iran
| | - Farveh Vakilian
- Cardiology Department, Mashad University of Medical Science, Imam Reza Hospital, Mashad, Iran
| | - Ahmad Amin
- Heart Failure and Transplantation, Rajai Cardiovascular, Medical and Research Center, Iran
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Dhingra R, Gona P, Wang TJ, Fox CS, D'Agostino RB, Vasan RS. Serum gamma-glutamyl transferase and risk of heart failure in the community. Arterioscler Thromb Vasc Biol 2010; 30:1855-60. [PMID: 20539015 PMCID: PMC2924453 DOI: 10.1161/atvbaha.110.207340] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To examine the association of serum gamma-glutamyltransferase (GGT) with incident heart failure. METHODS AND RESULTS We related serum GGT to the incidence of heart failure in 3544 (mean age, 44.5 years; 1833 women and 1711 men) Framingham Study participants who were free of heart failure and myocardial infarction. On follow-up (mean, 23.6 years), 188 participants (77 women) developed new-onset heart failure. In multivariable Cox proportional hazards regression models adjusting for standard risk factors and alcohol consumption as time-varying covariates (updated every 4 years), each SD increase in log-GGT was associated with a 1.39-fold risk of heart failure (95% CI, 1.20 to 1.62). The linearity of the association was confirmed by multivariable-adjusted splines, and the relations remained robust on additional adjustment for hepatic aminotransferases and C-reactive protein. Participants with a serum GGT level at the median or greater had a 1.71-fold risk of heart failure (95% CI, 1.21 to 2.41) compared with individuals with GGT concentrations less than the median. GGT marginally increased the model C-statistic from 0.85 to 0.86 but improved the risk reclassification modestly (net reclassification index, 5.7%; P=0.01). CONCLUSIONS In this prospective study of a large community-based sample, higher serum GGT concentrations within the "normal" range were associated with greater risk of heart failure and incrementally improved prediction of heart failure risk.
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Affiliation(s)
- Ravi Dhingra
- National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA
- Division of Cardiology, Dartmouth Hitchcock Medical Center, Lebanon, NH
- Harvard School of Public Health, Boston, MA
| | - Philimon Gona
- Department of Biostatistics, Boston University School of Public Health, Boston, MA
| | - Thomas J Wang
- National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA
- Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Caroline S Fox
- National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA
- National Heart, Lung and Blood Institute, Bethesda, MD
| | - Ralph B D'Agostino
- National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA
- Department of Biostatistics, Boston University School of Public Health, Boston, MA
| | - Ramachandran S. Vasan
- National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA
- Cardiology Section and the Department of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MA
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Ohno N, Terada N, Ohno S. Histochemical analyses of living mouse liver under different hemodynamic conditions by "in vivo cryotechnique". Histochem Cell Biol 2006; 126:389-98. [PMID: 16601970 DOI: 10.1007/s00418-006-0173-6] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/08/2006] [Indexed: 01/14/2023]
Abstract
Although the morphology and molecular distribution in animal liver tissues have been examined using conventional preparation methods, the findings are always affected by the technical artifacts caused by perfusion-fixation and tissue-resection. Using "in vivo cryotechnique" (IVCT), we have examined living mouse livers with histochemical, immunohistochemical and ultrastructural analyses. In samples prepared by IVCT, widely open sinusoids with many flowing erythrocytes were observed under normal blood circulation, and their collapse or blood congestion was seen in ischemic or heart-arrested mice. In contrast, the sinusoidal cavities were artificially dilated by perfusion-fixation, and collapsed by immersion-fixation and quick-freezing (QF) methods of resected tissues. The immunoreactivity of serum albumin and immunoglobulin G and intensity of periodic acid-Schiff-staining in hepatocytes were well preserved with the QF method and IVCT. Furthermore, following tissue resection, serum proteins were rapidly translocated into hepatocytes as demonstrated by immunoreactions on QF tissues frozen 1 or 5 min after resection. Translocation was not observed in IVCT samples, indicating that IVCT could be useful to examine cell membrane permeability of hepatocytes under different pathological conditions. Both dynamic morphology and immunodistribution of soluble components in living mouse livers, reflecting their physiological and pathological states, can be precisely examined by IVCT with higher time-resolution.
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Affiliation(s)
- Nobuhiko Ohno
- Department of Anatomy, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo-city, Yamanashi, 409-3898, Japan
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31
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van Lingen R, Warshow U, Dalton HR, Hussaini SH. Jaundice as a presentation of heart failure. J R Soc Med 2005. [PMID: 16055900 DOI: 10.1258/jrsm.98.8.357] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
On rare occasions the first manifestation of heart disease is jaundice, caused by passive congestion of the liver or acute ischaemic hepatitis. We looked for this presentation retrospectively in 661 patients referred over fifty-six months to a 'jaundice hotline' (rapid access) service. The protocol included a full clinical history, examination and abdominal ultrasound. Those with no evidence of biliary obstruction had a non-invasive liver screen for parenchymal liver disease and those with suspected heart disease had an electrocardiogram, chest X-ray and echocardiogram. 8 patients (1.2%), bilirubin 31-79 micromol/L, mean 46 micromol/L, had a primary cardiac cause for their jaundice. All had dyspnoea, an increased cardiothoracic ratio on chest X-ray and an abnormal electrocardiogram. The jugular venous pressure was raised in the 3 in whom it was recorded. In 6 patients the jaundice was attributed to hepatic congestion and in 2 to ischaemic hepatitis. All patients had severe cardiac dysfunction. Jaundice due to heart disease tends to be mild, and a key feature is breathlessness. The most common mechanism is hepatic venous congestion; ischaemic hepatitis is suggested by a high aminotransferase.
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Affiliation(s)
- R van Lingen
- Cornwall Gastrointestinal Unit, Royal Cornwall Hospital Trust, Truro TR1 3LJ, UK
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Dichtl W, Vogel W, Dunst KM, Grander W, Alber HF, Frick M, Antretter H, Laufer G, Pachinger O, Pölzl G. Cardiac hepatopathy before and after heart transplantation. Transpl Int 2005; 18:697-702. [PMID: 15910296 DOI: 10.1111/j.1432-2277.2005.00122.x] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Chronic cardiac hepatopathy is a common entity in patients evaluated for heart transplantation (HTX). Hepatic injury is caused by severe heart failure resulting from prolonged recurrent congestion and/or impaired arterial perfusion. No data are available on the reversibility of cardiac hepatopathy in patients undergoing HTX. Data of 56 consecutive adult patients undergoing HTX during 2000-02 at the University Hospital of Innsbruck were analysed retrospectively. The following parameters were evaluated at the time of listing and 3, 6 and 12 months after HTX. Plasma levels of gamma-glutamyl transferase (gamma-GT), alkaline phosphatase (AP), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and total plasma protein. When listed for HTX, only 12% of all patients analysed had physiological values throughout the seven laboratory parameters assessed. Elevated levels of gamma-GT, AP, bilirubin, AST, ALT, LDH and total plasma protein were detected in 66.6%, 29%, 50%, 16.7%, 10%, 40% and 18% of all patients respectively. Accordingly, median plasma levels of gamma-GT, bilirubin and LDH were elevated, whereas the mean plasma level of AP was at the upper normal range. In contrast, median plasma level of AST and mean plasma levels of ALT and total plasma protein were within the normal range: gamma-GT (median, 109.0; range, 634.0 U/l; n = 36), AP (mean, 120.2 +/- 78.9 U/l; n = 29), bilirubin (median, 1.3; range, 16.1 mg/dl; n = 32), LDH (median, 226.0; range, 2355.0 U/l; n = 33), AST (median, 29.0; range, 145.0 U/l; n = 36), ALT (mean, 28.3 +/- 20.8 U/l; n = 36) and total plasma protein (mean, 7.2 +/- 1.1 g/dl; n = 25). Within 3 months after HTX, elevated parameters except LDH significantly ameliorated: gamma-GT (median, 59.0; range, 1160.0 U/l; P = 0.011), AP (92.2 +/- 75.2 U/l; P = 0.016), bilirubin (median, 0.9; range, 8.1 mg/dl; P = 0.004), LDH slightly increased (median, 281.0; range, 543.0 U/l; P = 0.039), but there was a delayed improvement of this parameter after 6 and 12 months post-HTX. End-stage heart failure is characterized by a cholestatic liver enzyme profile with elevated plasma levels of gamma-GT and bilirubin. These parameters significantly improve within 3 months after HTX. Therefore, chronic cardiac hepatopathy seems to be a benign, potentially reversible disease.
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Affiliation(s)
- Wolfgang Dichtl
- Clinical Division of Cardiology, Innsbruck Medical University, Innsbruck, Austria.
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