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Gananandan K, Wiese S, Møller S, Mookerjee RP. Cardiac dysfunction in patients with cirrhosis and acute decompensation. Liver Int 2024; 44:1832-1841. [PMID: 38712826 DOI: 10.1111/liv.15896] [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: 01/22/2024] [Revised: 02/25/2024] [Accepted: 03/04/2024] [Indexed: 05/08/2024]
Abstract
The prevalence of cirrhotic cardiomyopathy (CCM) has been reported as high as 60%-70% in patients with liver cirrhosis and is associated with various negative outcomes. There has been a growing understanding of CCM over recent years. Indeed, the development of imaging techniques has enabled new diagnostic criteria to be proposed by the Cirrhotic Cardiomyopathy Consortium. However, important unanswered questions remain over pathophysiological mechanisms, optimal diagnostic modalities and potential treatment options. While there has been an increasing volume of literature evaluating CCM, there is a lack of clarity on its implications in acute decompensation, acute-on-chronic liver failure and following interventions such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. This review aims to summarise the literature in these challenging domains and suggest where future research should focus. We conclude that systemic inflammation and structural myocardial changes are likely to be crucial in the pathophysiology of the disease, but the relative contribution of different components remains elusive. Furthermore, future studies need to use standardised diagnostic criteria for CCM as well as incorporate newer imaging techniques assessing both myocardial structure and function. Finally, while specific treatments are currently lacking, therapeutics targeting systemic inflammation, microbial dysbiosis and bacterial translocation are promising targets and warrant further research.
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Affiliation(s)
- Kohilan Gananandan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, London, UK
| | - Signe Wiese
- Centre of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, University of Copenhagen, Copenhagen, Denmark
- Gastroenterology Unit, Medical Division, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Søren Møller
- Centre of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Rajeshwar P Mookerjee
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, London, UK
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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Kalambokis G, Christaki M, Tsiakas I, Despotis G, Lakkas L, Tsiouris S, Xourgia X, Markopoulos GS, Dova L, Milionis H. Association of left ventricular diastolic dysfunction with inflammatory activity, renal dysfunction, and liver-related mortality in patients with cirrhosis and ascites. Eur J Gastroenterol Hepatol 2024; 36:775-783. [PMID: 38526935 DOI: 10.1097/meg.0000000000002762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/27/2024]
Abstract
Left ventricular diastolic dysfunction (LVDD) is the predominant cardiac abnormality in cirrhosis. We investigated the association of LVDD with systemic inflammation and its impact on renal function, occurrence of hepatorenal syndrome (HRS) and survival in patients with cirrhosis and ascites. We prospectively enrolled 215 patients with cirrhosis and ascites. We evaluated the diagnosis and grading of LVDD by Doppler echocardiography, inflammatory markers, systemic hemodynamics, vasoactive factors, radioisotope-assessed renal function and blood flow, HRS development and liver-related mortality. LVDD was diagnosed in 142 (66%) patients [grade 2/3: n = 61 (43%)]. Serum lipopolysaccharide-binding protein (LBP), plasma renin activity (PRA) and glomerular filtration rate (GFR) were independently associated with the presence of grade 2/3 LVDD and the severity of diastolic dysfunction. Serum tumor necrosis factor-α, cardiac output and plasma noradrenaline were also independently associated with the presence of grade 2/3 LVDD. The diastolic function marker E / e ' was strongly correlated with serum LBP ( r = 0.731; P < 0.001), PRA ( r = 0.714; P < 0.001) and GFR ( r = -0.609; P < 0.001) among patients with LVDD. The 5-year risk of HRS development and death was significantly higher in patients with grade 2/3 LVDD compared to those with grade 1 (35.5 vs. 14.4%; P = 0.01 and 53.3 vs. 28.2%; P = 0.03, respectively). The occurrence and severity of LVDD in patients with cirrhosis and ascites is closely related to inflammatory activity. Advanced LVDD is associated with baseline circulatory and renal dysfunction, favoring HRS development, and increased mortality.
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Affiliation(s)
| | | | | | | | | | | | | | - Georgios S Markopoulos
- Hematology Laboratory, Unit of Molecular Biology and Translational Flow Cytometry, Medical School, University of Ioannina, Ioannina, Greece
| | - Lefkothea Dova
- Hematology Laboratory, Unit of Molecular Biology and Translational Flow Cytometry, Medical School, University of Ioannina, Ioannina, Greece
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3
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Kosuta I, Premkumar M, Reddy KR. Review article: Evaluation and care of the critically ill patient with cirrhosis. Aliment Pharmacol Ther 2024; 59:1489-1509. [PMID: 38693712 DOI: 10.1111/apt.18016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 03/21/2024] [Accepted: 04/12/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND The increase in prevalence of liver disease globally will lead to a substantial incremental burden on intensive care requirements. While liver transplantation offers a potential life-saving intervention, not all patients are eligible due to limitations such as organ availability, resource constraints, ongoing sepsis or multiple organ failures. Consequently, the focus of critical care of patients with advanced and decompensated cirrhosis turns to liver-centric intensive care protocols, to mitigate the high mortality in such patients. AIM Provide an updated and comprehensive understanding of cirrhosis management in critical care, and which includes emergency care, secondary organ failure management (mechanical ventilation, renal replacement therapy, haemodynamic support and intensive care nutrition), use of innovative liver support systems, infection control, liver transplantation and palliative and end-of life care. METHODS We conducted a structured bibliographic search on PubMed, sourcing articles published up to 31 March 2024, to cover topics addressed. We considered data from observational studies, recommendations of society guidelines, systematic reviews, and meta-analyses, randomised controlled trials, and incorporated our clinical expertise in liver critical care. RESULTS Critical care management of the patient with cirrhosis has evolved over time while mortality remains high despite aggressive management with liver transplantation serving as a crucial but not universally available resource. CONCLUSIONS Implementation of organ support therapies, intensive care protocols, nutrition, palliative care and end-of-life discussions and decisions are an integral part of critical care of the patient with cirrhosis. A multi-disciplinary approach towards critical care management is likely to yield better outcomes.
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Affiliation(s)
- Iva Kosuta
- Department of Intensive Care Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, 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: 0] [Impact Index Per Article: 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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Karagiannakis DS, Karakousis ND, Androutsakos T. B-Blockers in Liver Cirrhosis: A Wonder Drug for Every Stage of Portal Hypertension? A Narrative Review. Biomedicines 2023; 12:57. [PMID: 38255164 PMCID: PMC10813395 DOI: 10.3390/biomedicines12010057] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 12/20/2023] [Accepted: 12/21/2023] [Indexed: 01/24/2024] Open
Abstract
In cirrhotic patients, non-selective b-blockers (NSBBs) constitute the reference treatment of choice as monotherapy or combined with band ligation for the prevention of first variceal bleeding and rebleeding, respectively. Furthermore, the last Baveno VII guidelines recommended carvedilol, a b-blocker with additional anti-a1 receptor activity, in all compensated cirrhotics with clinically significant portal hypertension, to prevent liver decompensation. Interestingly enough, NSBBs have been reported to have a potentially positive impact on the short-term mortality of patients with acute-on-chronic liver failure. However, concerns remain about the use of b-blockers in the presence of severe complications, such as refractory ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, or established cirrhotic cardiomyopathy. In addition, it has not been verified yet whether carvedilol supersedes all the other NSBBs in every stage of liver disease, even when severe complications have developed. Therefore, this review aims to illustrate recent data regarding the potential role of b-blockers across all stages of liver disease, beyond the primary and secondary prophylaxis of variceal bleeding, and address the authors' proposals on the use of NSBBs concerning the severity of liver disease and the patient's performance status.
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Affiliation(s)
- Dimitrios S. Karagiannakis
- Academic Department of Gastroenterology, Laiko General Medicine, Medical School of National and Kapodistrian University of Athens, 11527 Athens, Greece
| | | | - Theodoros Androutsakos
- Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece;
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Kalluru R, Gadde S, Chikatimalla R, Dasaradhan T, Koneti J, Cherukuri SP. Cirrhotic Cardiomyopathy: The Interplay Between Liver and Heart. Cureus 2022; 14:e27969. [PMID: 36120195 PMCID: PMC9467492 DOI: 10.7759/cureus.27969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/13/2022] [Indexed: 11/05/2022] Open
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Kaur H, Premkumar M. Diagnosis and Management of Cirrhotic Cardiomyopathy. J Clin Exp Hepatol 2022; 12:186-199. [PMID: 35068798 PMCID: PMC8766707 DOI: 10.1016/j.jceh.2021.08.016] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/13/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Cirrhotic cardiomyopathy refers to the structural and functional changes in the heart leading to either impaired systolic, diastolic, electrocardiographic, and neurohormonal changes associated with cirrhosis and portal hypertension. Cirrhotic cardiomyopathy is present in 50% of patients with cirrhosis and is clinically seen as impaired contractility, diastolic dysfunction, hyperdynamic circulation, and electromechanical desynchrony such as QT prolongation. In this review, we will discuss the cardiac physiology principles underlying cirrhotic cardiomyopathy, imaging techniques such as cardiac magnetic resonance imaging and scintigraphy, cardiac biomarkers, and newer echocardiographic techniques such as tissue Doppler imaging and speckle tracking, and emerging treatments to improve outcomes. METHODS We reviewed available literature from MEDLINE for randomized controlled trials, cohort studies, cross-sectional studies, and real-world outcomes using the search terms "cirrhotic cardiomyopathy," "left ventricular diastolic dysfunction," "heart failure in cirrhosis," "liver transplantation," and "coronary artery disease". RESULTS Cirrhotic cardiomyopathy is associated with increased risk of complications such as hepatorenal syndrome, refractory ascites, impaired response to stressors including sepsis, bleeding or transplantation, poor health-related quality of life and increased morbidity and mortality. The evaluation of cirrhotic cardiomyopathy should also guide the feasibility of procedures such as transjugular intrahepatic portosystemic shunt, dose titration protocol of betablockers, and liver transplantation. The use of targeted heart rate reduction is of interest to improve cardiac filling and improve the cardiac output using repurposed heart failure drugs such as ivabradine. Liver transplantation may also reverse the cirrhotic cardiomyopathy; however, careful cardiac evaluation is necessary to rule out coronary artery disease and improve cardiac outcomes in the perioperative period. CONCLUSION More data are needed on the new diagnostic criteria, molecular and biochemical changes, and repurposed drugs in cirrhotic cardiomyopathy. The use of advanced imaging techniques should be incorporated in clinical practice.
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Key Words
- 2-AG, 2-arachidonylglycerol
- 2D, two-dimensional
- AEA, Anandamide
- ANP, Atrial Natriuretic Peptide
- ASE, the American Society of Echocardiography
- AUC, area under the curve
- BA, bile acid
- BNP, Brain natriuretic peptide
- CAD, coronary artery disease
- CB-1, cannabinoid −1
- CCM, Cirrhotic Cardiomyopathy
- CMR, cardiovascular magnetic resonance imaging
- CO, cardiac output
- CT, computed tomography
- CTP, Child–Turcotte–Pugh
- CVP, central venous pressure
- DT, deceleration Time
- ECG, electrocardiogram
- ECV, extracellular volume
- EF, Ejection fraction
- EMD, electromechanical desynchrony
- ESLD, end-stage liver disease
- FXR, Farnesoid X receptor
- GI, gastrointestinal
- GLS, Global Longitudinal strain
- HCN, Hyperpolarization-activated cyclic nucleotide–gated
- HE, hepatic encephalopathy
- HF, heart failure
- HO, Heme oxygenase
- HPS, hepatopulmonary syndrome
- HR, heart rate
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- HfmrEF, heart failure with mid-range ejection fraction
- HfrEF, heart failure with reduced ejection fraction
- IVC, Inferior Vena Cava
- IVCD, IVC Diameter
- IVS, intravascular volume status
- L-NAME, NG-nitro-L-arginine methyl ester
- LA, left atrium
- LAVI, LA volume index
- LGE, late gadolinium enhancement
- LT, liver transplant
- LV, left ventricle
- LVDD, left ventricular diastolic dysfunction
- LVEDP, left ventricular end-diastolic pressure
- LVEDV, LV end diastolic volume
- LVEF, left ventricular ejection fraction
- LVESV, LV end systolic volume
- LVOT, left ventricular outflow tract
- MAP, mean arterial pressure
- MELD, Model for End-Stage Liver Disease
- MR, mitral regurgitation
- MRI, Magnetic resonance imaging
- MV, mitral valve
- NAFLD, Nonalcoholic fatty liver disease
- NO, nitric oxide
- NOS, Nitric oxide synthases
- NTProBNP, N-terminal proBNP
- PAP, pulmonary artery pressure
- PCWP, pulmonary capillary wedged pressure
- PHT, portal hypertension
- PWD, Pulsed-wave Doppler
- RV, right ventricle
- RVOT, right ventricular outflow tract
- SA, sinoatrial
- SD, standard deviation
- SV, stroke volume
- SVR, Systemic vascular resistance
- TDI, tissue Doppler imaging
- TIPS, transjugular intrahepatic portosystemic shunt
- TR, Tricuspid valve
- TRPV1, transient receptor potential cation channel subfamily V member 1
- TTE, transthoracic echocardiography
- USG, ultrasonography
- VTI, velocity time integral
- beta blocker
- cirrhotic cardiomyopathy
- hemodynamics in cirrhosis
- left ventricular diastolic dysfunction
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Affiliation(s)
| | - Madhumita Premkumar
- Address for correspondence: Dr. Madhumita Premkumar, M.D., D.M., Department of Hepatology, Postgraduate Institute of Medical Education and Research, 60012, Chandigarh, India. Tel.: ++91-9540951061 (mobile)
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Dourakis SP, Geladari E, Geladari C, Vallianou N. Cirrhotic Cardiomyopathy: The Interplay Between Liver and Cardiac Muscle. How Does the Cardiovascular System React When the Liver is Diseased? Curr Cardiol Rev 2021; 17:78-84. [PMID: 31072296 PMCID: PMC8142364 DOI: 10.2174/1573403x15666190509084519] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 04/21/2019] [Accepted: 04/22/2019] [Indexed: 12/03/2022] Open
Abstract
It is widely known that liver cirrhosis, regardless of the etiologies is accompanied by severe hemodynamic changes. The principal pathophysiological mechanisms are the hyperdynamic circulation with increased cardiac output, heart rate along with reduced systemic vascular resistance. Thus, counteractive mechanisms may develop that eventually lead to systolic as well as diastolic dysfunction and rhythm disturbances, in order to keep a steady homeostasis in the human body. Literally, blunted contractile responsiveness to physical or pharmacological stress, impaired diastolic relaxation and electrophysiological changes, primarily QT interval prolongation, do occur progressively in a cirrhotic patient with no known preexisting cardiac disease. This condition is identified as cirrhotic cardiomyopathy (CCM), an entity different from that seen in alcoholic cardiac muscle disease. For the past decades, clinicians did study and attempt to understand the pathophysiology and clinical significance of this process. Indeed, various factors have been identified acting at the molecular and cellular level. Electrocardiography, echocardiography and various serum biomarkers are the main tools that help healthcare practitioners to point to the correct diagnosis. Noteworthy, the subjects that suffer from cirrhotic cardiomyopathy may progress to heart failure during invasive procedures such as surgery, insertion of a transjugular intrahepatic portosystemic shunting (TIPS) and liver transplantation. Besides, several studies have illustrated that CCM is a contributing factor, or even a precipitant, of hepatorenal syndrome (HRS), a conceivable reversible kidney failure in patients with liver cirrhosis and ascites. The treatment is the same as it is in the patients with liver cirrhosis and heart failure and there is no particular treatment for cirrhotic cardiomyopathy. Hence, it is of utmost importance to clearly comprehend the pathophysiology of this disease in order to design more accurate diagnostic tools and definitive treatments in a way to prevent the complications of cirrhosis and overt heart failure. The objective of this review is to describe in a comprehensive way the pathological alterations that occur in the cardiovascular system of cirrhotic patients. It will also point the limitations that remain in the diagnosis and treatment strategies and more importantly, this review will alert the clinicians in the modern era to further observe and record additional pathological changes in this subset of patients.
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Affiliation(s)
- Spyros P Dourakis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece
| | - Eleni Geladari
- Internal Medicine Department, Evaggelismos General Hospital, Athens, Greece
| | | | - Natalia Vallianou
- Internal Medicine Department, Evaggelismos General Hospital, Athens, Greece
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Shahvaran SA, Menyhárt O, Csedrik L, Patai ÁV. Diagnosis and Prevalence of Cirrhotic Cardiomyopathy: A Systematic Review and Meta-analysis. Curr Probl Cardiol 2021; 46:100821. [PMID: 34016482 DOI: 10.1016/j.cpcardiol.2021.100821] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 02/17/2021] [Indexed: 01/26/2023]
Abstract
The proposed diagnostic criteria for cirrhotic cardiomyopathy (CCM), defines it as documented echocardiographic findings of systolic or diastolic dysfunction (using conventional 2D echocardiogram), with or without electrophysiological abnormalities or elevated biomarkers in cirrhotic patients. In comparison to 2D echocardiogram, tissue Doppler imaging (TDI) has better sensitivity and specificity, when evaluating for cardiac dysfunction. This meta-analysis of 12 selected cohort studies attempted to estimate the pooled prevalence of CCM using either conventional echocardiography or TDI. Using the 2005 criteria, the pooled prevalence of CCM is 61% (P = 0.106). When TDI is used, the prevalence of CCM is at 45% (P = 0.088). Analyzing data of 615 cirrhotic patients, this study estimates the mean population-specific echocardiographic values of cirrhotic patients, including left ventricle ejection fraction (63.52%), deceleration time (229.04 ms), isovolumetric relaxation time (87.71 ms) and E/A ratio (1.04). In comparison to TDI, using standard 2D echocardiography leads to overdiagnosis of CCM.
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Affiliation(s)
| | - Orsolya Menyhárt
- Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary; Buda Health Center
| | | | - Árpád V Patai
- Interdisciplinary Gastroenterology Working Group, Semmelweis University, Budapest, Hungary; Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary.
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Matyas C, Haskó G, Liaudet L, Trojnar E, Pacher P. Interplay of cardiovascular mediators, oxidative stress and inflammation in liver disease and its complications. Nat Rev Cardiol 2021; 18:117-135. [PMID: 32999450 DOI: 10.1038/s41569-020-0433-5] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/11/2020] [Indexed: 12/11/2022]
Abstract
The liver is a crucial metabolic organ that has a key role in maintaining immune and endocrine homeostasis. Accumulating evidence suggests that chronic liver disease might promote the development of various cardiac disorders (such as arrhythmias and cardiomyopathy) and circulatory complications (including systemic, splanchnic and pulmonary complications), which can eventually culminate in clinical conditions ranging from portal and pulmonary hypertension to pulmonary, cardiac and renal failure, ascites and encephalopathy. Liver diseases can affect cardiovascular function during the early stages of disease progression. The development of cardiovascular diseases in patients with chronic liver failure is associated with increased morbidity and mortality, and cardiovascular complications can in turn affect liver function and liver disease progression. Furthermore, numerous infectious, inflammatory, metabolic and genetic diseases, as well as alcohol abuse can also influence both hepatic and cardiovascular outcomes. In this Review, we highlight how chronic liver diseases and associated cardiovascular effects can influence different organ pathologies. Furthermore, we explore the potential roles of inflammation, oxidative stress, vasoactive mediator imbalance, dysregulated endocannabinoid and autonomic nervous systems and endothelial dysfunction in mediating the complex interplay between the liver and the systemic vasculature that results in the development of the extrahepatic complications of chronic liver disease. The roles of ageing, sex, the gut microbiome and organ transplantation in this complex interplay are also discussed.
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Affiliation(s)
- Csaba Matyas
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health/NIAAA, Bethesda, MD, USA
| | - György Haskó
- Department of Anesthesiology, Columbia University, New York, NY, USA
| | - Lucas Liaudet
- Department of Intensive Care Medicine and Burn Center, University Hospital Medical Center, Faculty of Biology and Medicine, Lausanne, Switzerland
| | - Eszter Trojnar
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health/NIAAA, Bethesda, MD, USA
| | - Pal Pacher
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health/NIAAA, Bethesda, MD, USA.
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11
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Cirrhotic Cardiomyopathy - A Veiled Threat. Cardiol Rev 2020; 30:80-89. [PMID: 33229904 DOI: 10.1097/crd.0000000000000377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction in patients with liver cirrhosis without pre-existing cardiac disease. According to the definition established by the World Congress of Gasteroenterology in 2005, the diagnosis of CCM includes criteria reflecting systolic dysfunction, impaired diastolic relaxation, and electrophysiological disturbances. Because of minimal or even absent clinical symptoms and/or echocardiographic signs at rest according to the 2005 criteria, CCM diagnosis is often missed or delayed in most clinically-stable cirrhotic patients. However, cardiac dysfunction progresses in time and contributes to the pathogenesis of hepatorenal syndrome and increased morbidity and mortality after liver transplantation, surgery or other invasive procedures in cirrhotic patients. Therefore, a comprehensive cardiovascular assessment using newer techniques for echocardiographic evaluation of systolic and diastolic function, allowing the diagnosis of CCM in the early stage of subclinical cardiovascular dysfunction, should be included in the screening process of liver transplant candidates and patients with cirrhosis in general. The present review aims to summarize the most important pathophysiological aspects of CCM, the usefulness of contemporary cardiovascular imaging techniques and parameters in the diagnosis of CCM, the current therapeutic options, and the importance of early diagnosis of cardiovascular impairment in cirrhotic patients.
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12
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Impact of cardiac function, refractory ascites and beta blockers on the outcome of patients with cirrhosis listed for liver transplantation. J Hepatol 2020; 72:463-471. [PMID: 31622697 DOI: 10.1016/j.jhep.2019.10.002] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 09/27/2019] [Accepted: 10/07/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Whether non-selective beta blockers (NSBBs) are deleterious in patients with end-stage cirrhosis and refractory ascites has been widely debated. We hypothesized that only the subset of patients on the liver transplant waiting list who had impaired cardiac performance would be at increased risk of mortality if receiving NSBBs. METHODS This study included 584 consecutive patients with cirrhosis evaluated for transplantation between 1999 and 2014. All patients had right heart catheterization with hemodynamic measurements at evaluation. Fifty percent received NSBBs. Refractory ascites was present in 33%. Cardiac performance was assessed by left ventricular stroke work index (LVSWI). Waiting list mortality without liver transplantation was explored using competing risk analysis. RESULTS LVSWI was significantly lower in patients with refractory ascites. In multivariate analysis using competing risk, refractory ascites, NSBBs and LVSWI were associated with waiting list mortality in the whole population, with a statistically significant interaction between NSBBs and LVSWI. The most discriminant value of LVSWI was 64.1 g-m/m2. In the final model, refractory ascites (subdistribution hazard ratio 1.52; 95% CI1.01-2.28; p = 0.0083) and treatment by NSBBs with LVSWI <64.1 g-m/m2 (subdistribution hazard ratio 1.96; 95% CI 1.32-2.90; p = 0.0009) were significantly associated with waiting list mortality, taking into account serum sodium and the model for end-stage liver disease score. CONCLUSIONS This study suggests that compromised cardiac performance is more common in patients with refractory ascites and that NSBBs are deleterious in cirrhotic patients with compromised cardiac performance. These results highlight the prognostic value of cardiac function in patients with end-stage cirrhosis. LAY SUMMARY There are still controversies concerning the impact of non-selective beta blockers on outcomes in patients with decompensated cirrhosis, especially in those with refractory ascites. In this study of 584 cirrhotic patients evaluated for liver transplantation, who underwent right heart catheterization, we have shown that global cardiac performance measured by left ventricular stroke work index is lower in patients with refractory ascites. Administration of non-selective beta blockers in patients with compromised cardiac performance may increase waiting list mortality. These results highlight the prognostic value of global cardiac performance in patients with end-stage cirrhosis.
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Moludi J, Maleki V, Jafari‐Vayghyan H, Vaghef‐Mehrabany E, Alizadeh M. Metabolic endotoxemia and cardiovascular disease: A systematic review about potential roles of prebiotics and probiotics. Clin Exp Pharmacol Physiol 2020; 47:927-939. [DOI: 10.1111/1440-1681.13250] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 12/28/2019] [Accepted: 12/31/2019] [Indexed: 12/31/2022]
Affiliation(s)
- Jalal Moludi
- School of Nutrition Sciences and Food Technology Kermanshah University of Medical Sciences Kermanshah Iran
- Clinical Research Development Center Imam Reza Hospital Kermanshah University of Medical Sciences Kermanshah Iran
| | - Vahid Maleki
- Student Research Committee Tabriz University of Medical Sciences Tabriz Iran
| | | | - Elnaz Vaghef‐Mehrabany
- Nutrition Research Center Faculty of Nutrition Tabriz University of Medical Sciences Tabriz Iran
| | - Mohammad Alizadeh
- Nutrition Research Center Faculty of Nutrition Tabriz University of Medical Sciences Tabriz Iran
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14
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The diagnostic and prognostic value of serum endocan in patients with cirrhotic cardiomyopathy. ACTA ACUST UNITED AC 2019; 56:182-192. [PMID: 29453929 DOI: 10.2478/rjim-2018-0007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Indexed: 01/26/2023]
Abstract
BACKGROUND We aimed to determine the relationship between endocan and cirrhotic cardiomyopathy. MATERIALS AND METHODS Patients with liver cirrhosis and no heart disease were included in a prospective observational study with liver disease decompensation and death as primary outcomes. RESULTS 83 cirrhotic patients were included and 32 had cirrhotic cardiomyopathy. Endocan levels were significantly lower in patients with cirrhotic cardiomyopathy (5.6 vs. 7 ng/mL, p = 0.034). Endocan correlated with severity of cirrhosis, time to decompensation or death from liver disease (OR 4.5 95% CI 1.06-31.1). CONCLUSION Endocan is a promising biomarker of severity of cirrhosis and may help in the diagnosis of cardiac dysfunction in this population.
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15
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Abstract
Cirrhosis with portal hypertension and related complications are associated with a high mortality. Excess of circulating vasodilators and cardiodepressive substances lead to a hyperdynamic circulation with changed myocardial structure and function. The entity cirrhotic cardiomyopathy seems to be involved in different aspects of hepatic decompensation, which focuses on new targets of treatment. Areas covered: This review deals with contemporary aspects of cirrhotic cardiomyopathy, and the literature search was undertaken by PubMed with 'cirrhotic' and 'cardiomyopathies' as MeSH Terms. Cirrhotic cardiomyopathy is defined as the presence of systolic and diastolic dysfunction and electrophysiological abnormalities. The diagnosis is based on contemporary Doppler/Echocardiography measurements or quantitative magnetic resonance imaging. Cirrhotic cardiomyopathy is independent of the etiology of the liver disease but related to severity and survival. Expert commentary: The outcome of invasive procedures and liver transplantation is influenced by the presence of cardiac dysfunction. Therefore, a cautious cardiac evaluation should be included in the patient evaluation prior to liver transplantation. Liver transplantation ameliorates most of the abnormalities seen in cirrhotic cardiomyopathy, but no specific treatment can yet be recommended.
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Affiliation(s)
- Søren Møller
- a Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital , University of Copenhagen , Hvidovre , Denmark
| | - Karen V Danielsen
- a Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital , University of Copenhagen , Hvidovre , Denmark.,b Gastroenterology Unit, Medical Division, Hvidovre Hospital , University of Copenhagen , Hvidovre , Denmark
| | - Signe Wiese
- a Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital , University of Copenhagen , Hvidovre , Denmark.,b Gastroenterology Unit, Medical Division, Hvidovre Hospital , University of Copenhagen , Hvidovre , Denmark
| | - Jens D Hove
- c Department of Cardiology, Hvidovre Hospital , University of Copenhagen , Hvidovre , Denmark
| | - Flemming Bendtsen
- b Gastroenterology Unit, Medical Division, Hvidovre Hospital , University of Copenhagen , Hvidovre , Denmark
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16
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Huang CH, Wu LS, Jeng WJ, Cheng YF, Ko YS, Sheen IS, Lin CY. In HCV-related liver cirrhosis, local pulse wave velocity increases and in decompensated patients correlates with poorer survival. PLoS One 2019; 14:e0212770. [PMID: 30889181 PMCID: PMC6424395 DOI: 10.1371/journal.pone.0212770] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 02/08/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Cirrhotic cardiomyopathy (CCM) refers to cardiac dysfunction in patients with liver cirrhosis, in the absence of other known cardiac disease. METHODS Control group and patients diagnosed of liver cirrhosis without known cardiac disease or hepatocellular carcinoma were enrolled for this clinical observation study. Patients with diabetes mellitus, hypertension were excluded. Absolute global longitudinal strain, one-point carotid pulse wave velocity (one-point PWV) and various parameters were measured in resting status. RESULTS There were 29 participants in the control group and 80 patients in the liver cirrhosis group. 27.8% of cirrhotic patients presented with normal systolic but abnormal diastolic functions and QTc prolongation that were compatible with CCM. 34.2% of cirrhotic patients presented with diastolic dysfunction in resting state comparing to 24.1% in control group. Systolic functions did not show conspicuous difference between cirrhosis and control group nor between compensated and decompensated cirrhosis, neither. Furthermore, one-point PWV was significantly higher in liver cirrhosis than in control group and higher in CCM than in non-CCM patients. One-point PWV predicted CCM and diastolic dysfunction in cirrhosis. Most importantly, its value > 1370cm/s predicted overall mortalities in decompensated cirrhosis (multivariable Cox analysis OR = 6.941) in addition to CTP score specifically in HCV related cirrhotic patients (AUC = 0.817). CONCLUSIONS In patients with cirrhosis, 27.8% were diagnosed with CCM by resting cardiovascular parameters. One-point PWV increased in CCM, correlated with diastolic dysfunction. It also correlated with overall mortality in patients with hepatitis C virus (HCV) related decompensated cirrhosis. Further study may be needed to confirm its capability for assessing CV and mortality risks in HCV related decompensated cirrhotic patients.
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Affiliation(s)
- Chien-Hao Huang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang-Gung University, Taoyuan, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan
| | - Lung-Sheng Wu
- Department of Cardiology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | - Wen-Juei Jeng
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang-Gung University, Taoyuan, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang-Gung University, Taoyuan, Taiwan
| | - Yu-Fu Cheng
- Department of Internal medicine, Chang-Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan
| | - Yu-Shien Ko
- College of Medicine, Chang-Gung University, Taoyuan, Taiwan
- Department of Cardiology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | - I-Shyan Sheen
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang-Gung University, Taoyuan, Taiwan
| | - Chun-Yen Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang-Gung University, Taoyuan, Taiwan
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17
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Left Ventricular Diastolic Dysfunction is Associated with Renal Dysfunction, Poor Survival and Low Health Related Quality of Life in Cirrhosis. J Clin Exp Hepatol 2019; 9:324-333. [PMID: 31360025 PMCID: PMC6637070 DOI: 10.1016/j.jceh.2018.08.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 08/22/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The presence of left ventricular diastolic dysfunction (LVDD) in patients with cirrhosis leads to a restriction of activities and a poor health related quality of life (HRQoL), which should be taken into consideration when treating them for liver and cardiac complications. AIMS The prevalence, complications, predictors of HRQoL and survival in cirrhotic patients with LVDD were studied. METHODS We report a prospective cohort study of 145 consecutive cirrhotic patients with LVDD who were evaluated for cardiac functional status at enrollment and followed up for hepatic complications, cardiac events, outcome and HRQoL using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) over a period of 2 years. RESULTS In total, 145 (mean age 61 years, 59% male) patients were included. Seventeen patients died with 10.5%, 22.5% and 40% mortality rates in patients with Grades 1, 2 and 3 LVDD respectively over 24 months. The parameters that were significant for predicting mortality on bivariate analysis were MELD, MELDNa, hepatic venous pressure gradient, MLHFQ, and left ventricular (LV) diastolic function (e' and E/e' ratio), but only MELD, MELDNa and E/e' remained significant on multivariate analysis. The E/e' ratio (8.7 ± 3.3 in survivors vs. 9.1 ± 2.3 in non-survivors) predicted outcome. On univariate analysis, the predictors of poor HRQoL were the Child-Pugh score ≥9.8 (OR 2.6; 95% confidence intervals (CI) 2.3-9.1, P = 0.041), MELD score ≥ 15.7 (OR 2.48; 95% CI 1.4-3.9, P = 0.029), refractory ascites (OR 1.9; 95% CI 1.1-6.1, P = 0.050), and E/e' ratio ≥7.6 (OR 1.9; 95% CI 1.8-7.1, P = 0.036) The presence of Class II/III (P = 0.046) symptoms of heart failure and MLHFQ≥ 45 (P = 0.042) were predictors of mortality at 24 months. CONCLUSION The grade of LVDD correlates with liver function, clinical events, risk of renal dysfunction and HRQoL. Evaluation of novel therapies which target symptomatic improvement in LVDD, should be done with suitable outcome measures, including HRQoL assessment.
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Key Words
- 2D, two-dimensional
- A, atrial wave-filling peak
- ASE, the American Society of Echocardiography
- AUC, area under the curve
- BNP, brain natriuretic peptide
- CI, confidence interval
- CO, cardiac output
- DT, deceleration time
- E, E-wave transmitral peak early filling
- E/A, early diastolic mitral inflow velocity/late diastolic
- E/e′ ratio, E-wave transmitral/early diastolic mitral annular velocity
- FHVP, free hepatic venous pressure
- GI, gastrointestinal
- HE, hepatic encephalopathy
- HR, heart rate
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- Health related Quality of Life
- Heart Failure
- IVRT, isovolumetric relaxation time
- LT, liver transplantation
- LV, left ventricular
- LVDD, left ventricular diastolic dysfunction
- LVEF, left ventricular ejection fraction
- MAP, mean arterial pressure
- MELD, Model for End-Stage Liver Disease
- MLHFQ, Minnesota Living with Heart Failure questionnaire
- OR, Odds Ratio
- PAP, pulmonary artery pressure
- PCWP, pulmonary capillary wedged pressure
- PH, portal hypertension
- RAP, right atrial pressure
- RR, relative risk
- SBP, spontaneous bacterial peritonitis
- SD, standard deviation
- TDI, tissue Doppler imaging
- TIPS, transjugular intrahepatic portosystemic shunt
- TTE, transthoracic echocardiography
- USG, ultrasonography
- WHVP, wedged hepatic venous pressures
- cirrhosis
- cirrhotic cardiomyopathy
- e′, early diastolic mitral annular velocity
- left ventricular diastolic dysfunction
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18
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Kazory A, Ronco C. Hepatorenal Syndrome or Hepatocardiorenal Syndrome: Revisiting Basic Concepts in View of Emerging Data. Cardiorenal Med 2018; 9:1-7. [PMID: 30223273 DOI: 10.1159/000492791] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 08/08/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Accumulating evidence on the pathophysiology of hepatorenal syndrome has challenged the conventional model of liver-kidney connection. While liver cirrhosis is traditionally considered the origin of a cascade of pathophysiologic mechanisms directly affecting other organs such as the kidney, emerging data point to the heart as the potential mediator of the untoward renal effects. SUMMARY Herein, we briefly review the often-overlooked contribution of the heart to circulatory dysfunction in hepatorenal syndrome and put forward evidence arguing for the involvement of systemic inflammation and endothelial dysfunction in this setting. The temporality of cardiorenal interactions in hepatorenal syndrome and the observed beneficial effects of portosystemic shunting on these pathways lend further support to the notion that cardiac involvement plays a key role in the development of renal dysfunction in severe cirrhosis. Key Messages: The disturbances traditionally bundled within hepatorenal syndrome could represent a hepatic form of cardiorenal syndrome whereby the liver affects the kidney in part through cardiorenal pathways. This new model has practical implications and calls for a shift in the focus of diagnostic and therapeutic approaches to renal dysfunction in advanced cirrhosis.
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Affiliation(s)
- Amir Kazory
- Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, Florida,
| | - Claudio Ronco
- Department of Nephrology, San Bortolo Hospital, Vicenza, Italy.,International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Vicenza, Italy
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19
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Zhao RH, Shi Y, Zhao H, Wu W, Sheng JF. Acute-on-chronic liver failure in chronic hepatitis B: an update. Expert Rev Gastroenterol Hepatol 2018; 12:341-350. [PMID: 29334786 DOI: 10.1080/17474124.2018.1426459] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Acute-on-chronic liver failure is a common pattern of end-stage liver disease in clinical practice and occurs frequently in patients with chronic hepatitis B or HBV-related cirrhosis. New progress in recent years leads to a better understanding of this disease. Areas covered: This review updates the current comprehensive knowledge about HBV-ACLF from epidemiological studies, experimental studies, and clinical studies and provide new insights into the definition, diagnostic criteria, epidemiology, nature history, pathogenesis, treatment and prognostication of HBV-ACLF. Expert commentary: Patients with chronic hepatitis B or HBV-related cirrhosis are at risk of developing acute-on-chronic liver failure, with multi-organ failure and high short-term mortality. The precipitating events can be intra-hepatic or extra-hepatic and the underlying chronic liver injury can be cirrhotic or non-cirrhotic. Host and viral factors contribute to the susceptibility of developing HBV-ACLF. Systemic inflammation is the driver of HBV-ACLF, which can be attributed to non-sterile and sterile factors. Liver transplantation is the definitive treatment for HBV-ACLF. Cell therapy is a promising alternative to LT, but requires validation and still has concern of long-term safety. Other medical therapies, such as nucleoside analogue, artificial liver supporting and glucocorticoid may improve survival in a specific subgroup. New scoring systems improve the accuracy of prognostication in HBV-ACLF, which is critical for early identification of candidates for LT.
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Affiliation(s)
- Rui-Hong Zhao
- a Department of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , China
| | - Yu Shi
- a Department of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , China
| | - Hong Zhao
- a Department of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , China
| | - Wei Wu
- a Department of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , China
| | - Ji-Fang Sheng
- a Department of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , China
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20
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Rimbaş RC, Baldea SM, Guerra RDGA, Visoiu SI, Rimbaş M, Pop CS, Vinereanu D. New Definition Criteria of Myocardial Dysfunction in Patients with Liver Cirrhosis: A Speckle Tracking and Tissue Doppler Imaging Study. ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:562-574. [PMID: 29306590 DOI: 10.1016/j.ultrasmedbio.2017.11.013] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 10/25/2017] [Accepted: 11/20/2017] [Indexed: 06/07/2023]
Abstract
There are no clear recommendations regarding cirrhotic cardiomyopathy (CC) evaluation in patients with pre-transplant liver cirrhosis. The roles of new methods, tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) in the diagnosis and prognosis of cirrhotic cardiomyopathy remain controversial. We investigated the utility of TDI/STE parameters in cirrhotic cardiomyopathy diagnosis and also in predicting mortality in patients with liver cirrhosis. Left/right ventricular function was studied using conventional TDI (velocities) and STE (strain/strain rate). We assessed left ventricular diastolic dysfunction, graded into four new classes (I/Ia/II/III). Serum NTproBNP (N-terminal prohormone of brain natriuretic peptide), troponin I, β-crosslaps, QTc interval, arterial compliance and endothelial function were measured. Liver-specific scores (Child-Pugh, MELD, MELDNa) were computed. There was a 1-y follow-up visit to determine mortality. We observed resting biventricular diastolic myocardial dysfunction, not presently included in the definition of cirrhotic cardiomyopathy. We provided an improved characterization of cardiac dysfunction in patients with liver cirrhosis. This might change the current definition. However, the utility of STE/TDI parameters in predicting long-term mortality in patients with liver cirrhosis remains controversial.
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Affiliation(s)
- Roxana Cristina Rimbaş
- Cardiology Department, University and Emergency Hospital, Bucharest, Romania; Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
| | - Sorina Mihăilă Baldea
- Cardiology Department, University and Emergency Hospital, Bucharest, Romania; Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | | | | | - Mihai Rimbaş
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; Gastroenterology Department, Colentina Clinical Hospital, Bucharest, Romania
| | - Corina Silvia Pop
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; Gastroenterology Department, University and Emergency Hospital, Bucharest, Romania
| | - Dragoş Vinereanu
- Cardiology Department, University and Emergency Hospital, Bucharest, Romania; Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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21
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Voiosu A, Wiese S, Voiosu T, Bendtsen F, Møller S. Bile acids and cardiovascular function in cirrhosis. Liver Int 2017; 37:1420-1430. [PMID: 28222247 DOI: 10.1111/liv.13394] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 02/12/2017] [Indexed: 02/13/2023]
Abstract
Cirrhotic cardiomyopathy and the hyperdynamic syndrome are clinically important complications of cirrhosis, but their exact pathogenesis is still partly unknown. Experimental models have proven the cardiotoxic effects of bile acids and recent studies of their varied receptor-mediated functions offer new insight into their involvement in cardiovascular dysfunction in cirrhosis. Bile acid receptors such as farnesoid X-activated receptor and TGR5 are currently under investigation as potential therapeutic targets in a variety of pathological conditions. These receptors have also recently been identified in cardiomyocytes, vascular endothelial cells and smooth muscle cells where they seem to play an important role in cellular metabolism. Chronic cholestasis leading to abnormal levels of circulating bile acids alters the normal signalling pathways and contributes to the development of profound cardiovascular disturbances. This review summarizes the evidence regarding the role of bile acids and their receptors in the generation of cardiovascular dysfunction in cirrhosis.
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Affiliation(s)
- Andrei Voiosu
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Hvidovre, Denmark.,Gastroenterology and Hepatology Department, Colentina Clinical Hospital, Bucharest, Romania.,"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Signe Wiese
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Hvidovre, Denmark.,Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Theodor Voiosu
- Gastroenterology and Hepatology Department, Colentina Clinical Hospital, Bucharest, Romania.,"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Flemming Bendtsen
- Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.,Gastro Unit, Medical Division, Hvidovre Hospital, Hvidovre, Denmark
| | - Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Hvidovre, Denmark.,Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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22
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23
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Barbosa M, Guardado J, Marinho C, Rosa B, Quelhas I, Lourenço A, Cotter J. Cirrhotic cardiomyopathy: Isn't stress evaluation always required for the diagnosis? World J Hepatol 2016; 8:200-206. [PMID: 26839643 PMCID: PMC4724582 DOI: 10.4254/wjh.v8.i3.200] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Revised: 12/02/2015] [Accepted: 12/17/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To describe the proportion of patients with cirrhotic cardiomyopathy (CCM) evaluated by stress echocardiography and investigating its association with the severity of liver disease. METHODS A cross-sectional study was conducted. Cirrhotic patients without risk factors for cardiovascular disease were included. Data regarding etiology and severity of liver disease (Child-Pugh score and model for end-stage liver disease), presence of ascites and gastroesophageal varices, pro-brain natriuretic peptide (pro-BNP) and corrected QT (QTc) interval were collected. Dobutamine stress echocardiography (conventional and tissue Doppler imaging) was performed. CCM was considered present when diastolic and/or systolic dysfunction was diagnosed at rest or after pharmacological stress. Therapy interfering with cardiovascular system was suspended 24 h before the examination. RESULTS Twenty-six patients were analyzed, 17 (65.4%) Child-Pugh A, mean model for end-stage liver disease (MELD) score of 8.7. The global proportion of patients with CCM was 61.5%. At rest, only 2 (7.7%) patients had diastolic dysfunction and none of the patients had systolic dysfunction. Dobutamine stress echocardiography revealed the presence of diastolic dysfunction in more 6 (23.1%) patients and of systolic dysfunction in 10 (38.5%) patients. QTc interval prolongation was observed in 68.8% of the patients and increased pro-BNP levels in 31.2% of them. There was no association between the presence of CCM and liver impairment assessed by Child-Pugh score or MELD (P = 0.775, P = 0.532, respectively). Patients with QTc interval prolongation had a significant higher rate of gastroesophageal varices comparing with those without QTc interval prolongation (95.0% vs 50.0%, P = 0.028). CONCLUSION CCM is a frequent complication of cirrhosis that is independent of liver impairment. Stress evaluation should always be performed, otherwise it will remain an underdiagnosed condition.
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Affiliation(s)
- Mara Barbosa
- Mara Barbosa, Joana Guardado, Carla Marinho, Bruno Rosa, Isabel Quelhas, António Lourenço, José Cotter, Gastroenterology Department, Centro Hospitalar do Alto Ave, 4835 Guimarães, Portugal
| | - Joana Guardado
- Mara Barbosa, Joana Guardado, Carla Marinho, Bruno Rosa, Isabel Quelhas, António Lourenço, José Cotter, Gastroenterology Department, Centro Hospitalar do Alto Ave, 4835 Guimarães, Portugal
| | - Carla Marinho
- Mara Barbosa, Joana Guardado, Carla Marinho, Bruno Rosa, Isabel Quelhas, António Lourenço, José Cotter, Gastroenterology Department, Centro Hospitalar do Alto Ave, 4835 Guimarães, Portugal
| | - Bruno Rosa
- Mara Barbosa, Joana Guardado, Carla Marinho, Bruno Rosa, Isabel Quelhas, António Lourenço, José Cotter, Gastroenterology Department, Centro Hospitalar do Alto Ave, 4835 Guimarães, Portugal
| | - Isabel Quelhas
- Mara Barbosa, Joana Guardado, Carla Marinho, Bruno Rosa, Isabel Quelhas, António Lourenço, José Cotter, Gastroenterology Department, Centro Hospitalar do Alto Ave, 4835 Guimarães, Portugal
| | - António Lourenço
- Mara Barbosa, Joana Guardado, Carla Marinho, Bruno Rosa, Isabel Quelhas, António Lourenço, José Cotter, Gastroenterology Department, Centro Hospitalar do Alto Ave, 4835 Guimarães, Portugal
| | - José Cotter
- Mara Barbosa, Joana Guardado, Carla Marinho, Bruno Rosa, Isabel Quelhas, António Lourenço, José Cotter, Gastroenterology Department, Centro Hospitalar do Alto Ave, 4835 Guimarães, Portugal
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24
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Sampaio F, Pimenta J. Left ventricular function assessment in cirrhosis: Current methods and future directions. World J Gastroenterol 2016; 22:112-125. [PMID: 26755864 PMCID: PMC4698479 DOI: 10.3748/wjg.v22.i1.112] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 07/29/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
Cirrhotic cardiomyopathy has been defined as a chronic cardiac dysfunction in patients with cirrhosis characterized by impaired contractile responsiveness to stress and/or altered diastolic relaxation with electrophysiological abnormalities in the absence of other known cardiac disease. Non-invasive cardiovascular imaging modalities play a major role in unmasking systolic and diastolic dysfunction in patients with cirrhosis. Echocardiography has been the most commonly used modality for assessing myocardial function in these patients. Conventional echocardiographic indices rely on several assumptions that may limit their applicability in patients with a hyperdynamic circulation. Newer imaging modalities may contribute to a more accurate diagnosis of cardiovascular abnormalities in cirrhotic patients, thereby influencing clinical management. We aimed to review the different non-invasive imaging technologies currently used for assessing left ventricular systolic and diastolic function in cirrhosis, as well as to describe new imaging modalities with potential clinical applicability in the near future.
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25
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Voiosu AM, Daha IC, Voiosu TA, Mateescu BR, Dan GA, Băicuş CR, Voiosu MR, Diculescu MM. Prevalence and impact on survival of hepatopulmonary syndrome and cirrhotic cardiomyopathy in a cohort of cirrhotic patients. Liver Int 2015; 35:2547-55. [PMID: 25974637 DOI: 10.1111/liv.12866] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Accepted: 05/04/2015] [Indexed: 12/29/2022]
Abstract
BACKGROUND & AIMS Extrahepatic complications of cirrhosis increase the risk for decompensation of the liver disease and death. Previous studies show common pathogenetic mechanisms involved in the development of hepatopulmonary syndrome and cirrhotic cardiomyopathy. We aimed to assess the link between these entities and their effect on disease-related patient morbidity and mortality. METHODS Seventy-four consecutive cirrhotic patients without prior history of cardiovascular and pulmonary disease were included in a prospective observational study. Routine blood work, arterial blood gas analysis, pulse oximetry measurements, N-terminal pro-brain natriuretic peptide levels and contrast enhanced echocardiography examination with tissue Doppler imaging were performed in all patients. Patients were followed up for a median of 6 months and disease-related adverse events and death were the main outcomes tested. Statistical analysis was conducted according to the presence of hepatopulmonary syndrome or cirrhotic cardiomyopathy. RESULTS Hepatopulmonary syndrome was diagnosed in 17 patients (23%) and cirrhotic cardiomyopathy in 30 patients (40.5%). There was no association between the presence of cirrhotic cardiomyopathy and the existence of mild or moderate hepatopulmonary syndrome. No echocardiographic parameters were useful in predicting the presence of hepatopulmonary syndrome. N-terminal pro-brain natriuretic peptide levels and length of QT interval did not aid in diagnosis of cirrhotic cardiomyopathy. Neither entity had significant influence on disease-related outcomes in the follow-up period. CONCLUSIONS Hepatopulmonary syndrome and cirrhotic cardiomyopathy are independent complications arising in cirrhosis and have a limited influence on morbidity and mortality on a pre-liver transplantation population.
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Affiliation(s)
- Andrei M Voiosu
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest, Romania.,"Carol Davila" University of Medicine, Bucharest, Romania
| | - Ioana C Daha
- "Carol Davila" University of Medicine, Bucharest, Romania.,Department of Cardiology, Colentina Clinical Hospital, Bucharest, Romania
| | - Theodor A Voiosu
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest, Romania.,"Carol Davila" University of Medicine, Bucharest, Romania
| | - Bogdan R Mateescu
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest, Romania.,"Carol Davila" University of Medicine, Bucharest, Romania
| | - Gheorghe A Dan
- "Carol Davila" University of Medicine, Bucharest, Romania.,Department of Cardiology, Colentina Clinical Hospital, Bucharest, Romania
| | - Cristian R Băicuş
- "Carol Davila" University of Medicine, Bucharest, Romania.,Department of Internal Medicine, Colentina Clinical Hospital, Bucharest, Romania
| | - Mihail R Voiosu
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest, Romania.,"Carol Davila" University of Medicine, Bucharest, Romania
| | - Mircea M Diculescu
- "Carol Davila" University of Medicine, Bucharest, Romania.,Department of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania
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Ruiz-del-Árbol L, Serradilla R. Cirrhotic cardiomyopathy. World J Gastroenterol 2015; 21:11502-11521. [PMID: 26556983 PMCID: PMC4631957 DOI: 10.3748/wjg.v21.i41.11502] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Revised: 06/17/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a failure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the follow-up progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function.
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27
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Dirchwolf M, Ruf AE. Role of systemic inflammation in cirrhosis: From pathogenesis to prognosis. World J Hepatol 2015; 7:1974-1981. [PMID: 26261687 PMCID: PMC4528271 DOI: 10.4254/wjh.v7.i16.1974] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 06/15/2015] [Accepted: 07/02/2015] [Indexed: 02/06/2023] Open
Abstract
The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure (ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts (evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted.
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Li Y, Han T. Mechanisms of susceptibility to bacterial infections in cirrhotic patients. Shijie Huaren Xiaohua Zazhi 2015; 23:3560-3566. [DOI: 10.11569/wcjd.v23.i22.3560] [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] [Indexed: 02/06/2023] Open
Abstract
Bacterial infections are very common in cirrhotic patients, and the incidence is 4-5 times higher than that in the general population. The mechanisms of susceptibility to bacterial infections in cirrhotic patients include intestinal bacterial overgrowth, bacterial translocation, increased number of potentially pathogenic bacteria accompanied by reduced number of beneficial bacteria; small bowel motility disturbances and delayed gut transit, increased intestinal permeability; genetic predisposition to bacterial infections; immunodeficiency accompanied by persistent activation of the immune cells with production of pro-inflammatory cytokines. In this paper, we will discuss the mechanisms of susceptibility to bacterial infections in cirrhotic patients.
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29
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Abstract
Cirrhotic cardiomyopathy is a cardiac condition observed in patients with cirrhotic regardless of the etiologies. It is characterized by the impaired systolic response to physical stress, diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. Its pathophysiology and clinical significance has been a focus of various researchers for the past decades. The impairment of β-adrenergic receptor, the increase in endogenous cannabinoids, the presence of cardiosuppressants such as nitric oxide and inflammatory cytokines are the proposed mechanisms of systolic dysfunction. The activation of cardiac renin-angiotensin system and salt retention play the role in the development of cardiac hypertrophy and impaired diastolic function. QT interval prolongation, which is observed in 40-50 % of cirrhotic patients, occurs as a result of the derangement in membrane fluidity and ion channel defect. The increased recognition of this disease will prevent the complications of overt heart failure after procedures such as transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation. Better understandings of the pathogenesis and pathology of cirrhotic cardiomyopathy is crucial in developing more accurate diagnostic tools and specific treatments of this condition.
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Affiliation(s)
| | - Suthat Liangpunsakul
- Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University Hospital, 550 University Boulevard, UH 4100, Indianapolis, IN 46202-5149, USA; Roudebush Veterans Administration Medical Center, Indiana University, Indianapolis, IN, USA
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30
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Abstract
Cirrhotic cardiomyopathy is a cardiac condition observed in patients with cirrhotic regardless of the etiologies. It is characterized by the impaired systolic response to physical stress, diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. Its pathophysiology and clinical significance has been a focus of various researchers for the past decades. The impairment of β-adrenergic receptor, the increase in endogenous cannabinoids, the presence of cardiosuppressants such as nitric oxide and inflammatory cytokines are the proposed mechanisms of systolic dysfunction. The activation of cardiac renin-angiotensin system and salt retention play the role in the development of cardiac hypertrophy and impaired diastolic function. QT interval prolongation, which is observed in 40-50 % of cirrhotic patients, occurs as a result of the derangement in membrane fluidity and ion channel defect. The increased recognition of this disease will prevent the complications of overt heart failure after procedures such as transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation. Better understandings of the pathogenesis and pathology of cirrhotic cardiomyopathy is crucial in developing more accurate diagnostic tools and specific treatments of this condition.
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Affiliation(s)
| | - Suthat Liangpunsakul
- Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University Hospital, 550 University Boulevard, UH 4100, Indianapolis, IN 46202-5149, USA; Roudebush Veterans Administration Medical Center, Indiana University, Indianapolis, IN, USA
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Karagiannakis DS, Papatheodoridis G, Vlachogiannakos J. Recent advances in cirrhotic cardiomyopathy. Dig Dis Sci 2015; 60:1141-1151. [PMID: 25404411 DOI: 10.1007/s10620-014-3432-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Accepted: 11/08/2014] [Indexed: 12/15/2022]
Abstract
Cirrhotic cardiomyopathy, a cardiac dysfunction presented in patients with cirrhosis, represents a recently recognized clinical entity. It is characterized by altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, in particular prolongation of the QT interval. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, including impaired function of beta-receptors, altered transmembrane currents, and overproduction of cardiodepressant factors, like nitric oxide, tumor necrosis factor α, and endogenous cannabinoids. Diastolic dysfunction is the first manifestation of cirrhotic cardiomyopathy and reflects the increased stiffness of the cardiac mass, which leads to delayed left ventricular filling. On the other hand, systolic incompetence is presented later, is usually unmasked during pharmacological or physical stress, and predisposes to the development of hepatorenal syndrome. The prolongation of QT is found in about 50 % of cirrhotic patients, but rarely leads to fatal arrhythmias. Cirrhotics with blunted cardiac function seem to have poorer survival rates compared to those without, and the risk is particularly increased during the insertion of transjugular intrahepatic portosystemic shunt or liver transplantation. Till now, there is no specific treatment for the management of cirrhotic cardiomyopathy. New agents, targeting to its pathogenetical mechanisms, may play some role as future therapeutic options.
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Affiliation(s)
- Dimitrios S Karagiannakis
- Department of Gastroenterology, Medical School of Athens University, Laiko General Hospital, 17 Agiou Thoma Street, 11527, Athens, Greece,
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Fukui H. Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia. World J Hepatol 2015; 7:425-442. [PMID: 25848468 PMCID: PMC4381167 DOI: 10.4254/wjh.v7.i3.425] [Citation(s) in RCA: 136] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2014] [Revised: 12/14/2014] [Accepted: 12/31/2014] [Indexed: 02/06/2023] Open
Abstract
A “leaky gut” may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin, activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.
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Kalaitzakis E. Gastrointestinal dysfunction in liver cirrhosis. World J Gastroenterol 2014; 20:14686-14695. [PMID: 25356031 PMCID: PMC4209534 DOI: 10.3748/wjg.v20.i40.14686] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 04/27/2014] [Accepted: 06/05/2014] [Indexed: 02/06/2023] Open
Abstract
Patients with liver cirrhosis exhibit several features of gut dysfunction which may contribute to the development of cirrhosis complications as well as have an impact on nutritional status and health-related quality of life. Gastrointestinal symptoms are common in cirrhosis and their pathophysiology probably involves factors related to liver disease severity, psychological distress, and gut dysfunction (e.g., increased gastric sensitivity to distension and delayed gut transit). They may lead to reduced food intake and, thus, may contribute to the nutritional status deterioration in cirrhotic patients. Although tense ascites appears to have a negative impact on meal-induced accommodation of the stomach, published data on gastric accommodation in cirrhotics without significant ascites are not unanimous. Gastric emptying and small bowel transit have generally been shown to be prolonged. This may be related to disturbances in postprandial glucose, insulin, and ghrelin levels, which, in turn, appear to be associated to insulin resistance, a common finding in cirrhosis. Furthermore, small bowel manometry disturbances and delayed gut transit may be associated with the development of small bowel bacterial overgrowth. Finally, several studies have reported intestinal barrier dysfunction in patients with cirrhosis (especially those with portal hypertension), which is related to bacterial translocation and permeation of intestinal bacterial products, e.g., endotoxin and bacterial DNA, thus potentially being involved in the pathogenesis of complications of liver cirrhosis.
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