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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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Almeida F, Sousa A. Cirrhotic cardiomyopathy: Pathogenesis, clinical features, diagnosis, treatment and prognosis. Rev Port Cardiol 2024; 43:203-212. [PMID: 38142819 DOI: 10.1016/j.repc.2023.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 06/09/2023] [Accepted: 07/30/2023] [Indexed: 12/26/2023] Open
Abstract
Cardiac dysfunction among cirrhotic patients has long been recognized in the medical community. While it was originally believed to be a direct result of alcohol toxicity, in the last 30 years cirrhotic cardiomyopathy (CCM) has been described as a syndrome characterized by chronic cardiac dysfunction in cirrhotic patients in the absence of known cardiac disease, regardless of the etiology of cirrhosis. CCM occurs in about 60% of patients with cirrhosis and plays a critical role in disease progression and treatment outcomes. Due to its predominantly asymptomatic course, diagnosing CCM is challenging and requires a high index of suspicion and a multiparametric approach. Patients with CCM usually present with the following triad: impaired myocardial contractile response to exercise, inadequate ventricular relaxation, and electrophysiological abnormalities (notably prolonged QT interval). In recent years, research in this area has grown expeditiously and a new set of diagnostic criteria has been developed by the Cirrhotic Cardiomyopathy Consortium, to properly identify patients with CCM. Nevertheless, CCM is still largely unknown among clinicians, and a major part of its pathophysiology and treatment is yet to be understood. In the present work, we aim to compile and summarize the available data on the pathogenesis, clinical features, diagnosis, treatment, and prognosis of CCM.
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Affiliation(s)
| | - Alexandra Sousa
- Cardiology Department, Unidade Local de Saúde de Entre o Douro e Vouga, Santa Maria da Feira, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal; CINTESIS - Centre for Health Technology and Services Research, Porto, Portugal; RISE - Health Research Network, Porto, Portugal
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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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Behera SK, Behera P, Behera JR, Behera G. Study of Cardiac Dysfunction in Portal Hypertension: A Single-Center Experience From Eastern India. Cureus 2023; 15:e51259. [PMID: 38283536 PMCID: PMC10822045 DOI: 10.7759/cureus.51259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/28/2023] [Indexed: 01/30/2024] Open
Abstract
INTRODUCTION Cardiac functional abnormalities are common in patients with cirrhosis of the liver. Nonetheless, the effect of portal hypertension and liver disorder on cardiac abnormalities is yet to be investigated. The current study evaluated the contribution of cirrhotic and non-cirrhotic portal hypertension as the potential cause of cardiac abnormalities. METHODS The present study was a cross-sectional observational study. After excluding known heart diseases, 128 patients with portal hypertension from different causes were enrolled in the study. Cardiac functional activity was assessed by electrocardiogram (ECG) and transthoracic echocardiography (TTE). Results: This study included a total of 128 patients, out of which 24 had extrahepatic portal vein obstruction (EHPVO), four patients had Budd-Chiari syndrome and 100 had liver cirrhosis. Normal ventricular function was observed in patients with EHPVO and Budd-Chiari syndrome. Sixty-eight percent of cases had liver cirrhosis diastolic abnormalities. The mean QTc interval in patients with cirrhotic cardiomyopathy (CCM) was 0.49 ± 0.05 sec which was significantly increased when compared to patients without CCM with 0.432 ± 0.07 at p=0.0016. The Child Turcotte Pugh (CTP) score and MELD (Model for End-Stage Liver Disease) score in patients with CCM were significantly higher as compared to patients without CCM. All alcoholic cirrhotic and non-alcoholic cirrhotic patients had equal prevalence of diastolic dysfunction (p-value >0.05). CONCLUSION Patients with Child class C or a high MELD score are associated with a higher prevalence rate of CCM while normal cardiac function was observed among patients having portal hypertension due to extrahepatic causes. We recommend cardiac evaluation by echocardiography in all cirrhotic patients. Institution of specific medical therapy and early referral for liver transplantation should be considered to improve survival in patients with decompensated cirrhosis.
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Affiliation(s)
- Sambit Kumar Behera
- Gastroenterology, Srirama Chandra Bhanja (SCB) Medical College, Cuttack, IND
| | - Prajyoti Behera
- Physiology, Institute of Medical Sciences (IMS) & SUM Hospital, Bhubaneswar, IND
| | | | - Gayatri Behera
- Pathology, Institute of Medical Sciences (IMS) & SUM Hospital, Bhubaneswar, IND
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Virk MK, Mian MUM, Bashir DA, Wilkes JK, Schlingman T, Flores S, Kennedy C, Lam F, Arikan AA, Nguyen T, Mysore K, Galvan NTN, Coss-Bu J, Karpen SJ, Harpavat S, Desai MS. Elevated bile acids are associated with left ventricular structural changes in biliary atresia. Hepatol Commun 2023; 7:e0109. [PMID: 37058680 PMCID: PMC10109457 DOI: 10.1097/hc9.0000000000000109] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 02/09/2023] [Indexed: 04/16/2023] Open
Abstract
BACKGROUND In children with biliary atresia (BA), pathologic structural changes within the heart, which define cirrhotic cardiomyopathy, are associated with adverse perioperative outcomes. Despite their clinical relevance, little is known about the pathogenesis and triggers of pathologic remodeling. Bile acid excess causes cardiomyopathy in experimental cirrhosis, but its role in BA is poorly understood. METHODS Echocardiographic parameters of left ventricular (LV) geometry [LV mass (LVM), LVM indexed to height, left atrial volume indexed to BSA (LAVI), and LV internal diameter (LVID)] were correlated with circulating serum bile acid concentrations in 40 children (52% female) with BA listed for transplantation. A receiver-operating characteristic curve was generated to determine optimal threshold values of bile acids to detect pathologic changes in LV geometry using Youden index. Paraffin-embedded human heart tissue was separately analyzed by immunohistochemistry for the presence of bile acid-sensing Takeda G-protein-coupled membrane receptor type 5. RESULTS In the cohort, 52% (21/40) of children had abnormal LV geometry; the optimal bile acid concentration to detect this abnormality with 70% sensitivity and 64% specificity was 152 µmol/L (C-statistics=0.68). Children with bile acid concentrations >152 µmol/L had ∼8-fold increased odds of detecting abnormalities in LVM, LVM index, left atrial volume index, and LV internal diameter. Serum bile acids positively correlated with LVM, LVM index, and LV internal diameter. Separately, Takeda G-protein-coupled membrane receptor type 5 protein was detected in myocardial vasculature and cardiomyocytes on immunohistochemistry. CONCLUSION This association highlights the unique role of bile acids as one of the targetable potential triggers for myocardial structural changes in BA.
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Affiliation(s)
- Manpreet K. Virk
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | | | - Dalia A. Bashir
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - John K. Wilkes
- Pediatric Cardiology, Cook Children’s Medical Centre, Fort Worth, Texas, USA
| | - Tobias Schlingman
- Department of Pediatrics, Section of Pediatric Cardiology, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Saul Flores
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Curtis Kennedy
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Fong Lam
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Ayse A. Arikan
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
- Department of Pediatrics, Section of Nephrology, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Trung Nguyen
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Krupa Mysore
- Department of Pediatrics, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas
| | - Nhu Thao Nguyen Galvan
- Division of Abdominal Transplantation and Hepatobiliary Surgery, Department of Surgery, Baylor College of Medicine, Houston, Texas
| | - Jorge Coss-Bu
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Saul J. Karpen
- Department of Pediatric Gastroenterology and Hepatology, Emory School of Medicine, Atlanta, Georgia, USA
| | - Sanjiv Harpavat
- Department of Pediatrics, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas
| | - Moreshwar S. Desai
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
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Cardiac Dysfunction in the Pathogenesis of Hepatorenal Syndrome. Am J Gastroenterol 2023; 118:179-180. [PMID: 36191281 DOI: 10.14309/ajg.0000000000002032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 09/27/2022] [Indexed: 11/06/2022]
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Téllez L, Albillos A. Non-selective beta-blockers in patients with ascites: The complex interplay among the liver, kidney and heart. Liver Int 2022; 42:749-761. [PMID: 35051310 DOI: 10.1111/liv.15166] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/31/2021] [Accepted: 01/09/2022] [Indexed: 12/12/2022]
Abstract
Non-selective beta-blockers (NSBBs) are the cornerstone of the primary and secondary prophylaxis of variceal bleeding in cirrhotic patients. They additionally prevent ascites development and death in compensated patients with clinically significant portal hypertension. After ascites onset, NSBBs remain beneficial for preventing further decompensations. However, as the cirrhosis progresses, the inflammation increases, systemic vasodilatation worsens, ascites turns refractory and cardiodynamic equilibrium becomes extremely fragile. In this scenario, NSBBs can critically impair the cardiac reserve and facilitate a haemodynamic breakdown, imperilling renal perfusion. Consequently, NSBB treatment should be carefully monitored or even avoided in such patients, and other options for portal hypertension management should be considered. In the present review, we explore the effects of NSBBs in patients with ascites and discuss the complex interplay among their hepatic, systemic and renal haemodynamic effects in this scenario.
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Affiliation(s)
- Luis Téllez
- Department of Gastroenterology and Hepatology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain
| | - Agustín Albillos
- Department of Gastroenterology and Hepatology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain
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Abid N, Mani AR. The mechanistic and prognostic implications of heart rate variability analysis in patients with cirrhosis. Physiol Rep 2022; 10:e15261. [PMID: 35439350 PMCID: PMC9017982 DOI: 10.14814/phy2.15261] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/19/2022] [Accepted: 03/23/2022] [Indexed: 06/14/2023] Open
Abstract
Chronic liver damage leads to scarring of the liver tissue and ultimately a systemic illness known as cirrhosis. Patients with cirrhosis exhibit multi-organ dysfunction and high mortality. Reduced heart rate variability (HRV) is a hallmark of cirrhosis, reflecting a state of defective cardiovascular control and physiological network disruption. Several lines of evidence have revealed that decreased HRV holds prognostic information and can predict survival of patients independent of the severity of liver disease. Thus, the aim of this review is to shed light on the mechanistic and prognostic implications of HRV analysis in patients with cirrhosis. Notably, several studies have extensively highlighted the critical role systemic inflammation elicits in conferring the reduction in patients' HRV. It appears that IL-6 is likely to play a central mechanistic role, whereby its levels also correlate with manifestations, such as autonomic neuropathy and hence the partial uncoupling of the cardiac pacemaker from autonomic control. Reduced HRV has also been reported to be highly correlated with the severity of hepatic encephalopathy, potentially through systemic inflammation affecting specific brain regions, involved in both cognitive function and autonomic regulation. In general, the prognostic ability of HRV analysis holds immense potential in improving survival rates for patients with cirrhosis, as it may indeed be added to current prognostic indicators, to ultimately increase the accuracy of selecting the recipient most in need of liver transplantation. However, a network physiology approach in the future is critical to delineate the exact mechanistic basis by which decreased HRV confers poor prognosis.
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Affiliation(s)
- Noor‐Ul‐Hoda Abid
- Network Physiology LabDivision of MedicineUCLLondonUK
- Lancaster Medical SchoolLancaster UniversityLancasterUK
| | - Ali R. Mani
- Network Physiology LabDivision of MedicineUCLLondonUK
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Diastolic Dysfunction Is a Predictor of Poor Survival in Patients with Decompensated Cirrhosis. Int J Hepatol 2021; 2021:5592376. [PMID: 34900353 PMCID: PMC8660240 DOI: 10.1155/2021/5592376] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 11/17/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Left ventricular diastolic dysfunction (LVDD) appears to be the earliest cardiac disturbance in cirrhosis patients. There are many previous reports reporting the significance of severity of LVDD on the outcome of liver transplantation or TIPS insertion, a few Indian studies have addressed the role of LVDD on survival in decompensated cirrhosis. The objective of this study is to assess the effect of LVDD on the survival of decompensated cirrhotic patients. METHODS We prospectively evaluated 92 decompensated cirrhotic patients from April 2015 to March 2017 at IMS and SUM Hospital, Bhubaneswar, India. 2D echocardiography with tissue Doppler imaging was used to evaluate cardiac function, as per the American society of echocardiography guidelines. The primary endpoint was to evaluate the effect of LVDD on overall mortality. RESULTS Ninety-two decompensated cirrhotic patients were evaluated in this prospective cohort study. Twenty-eight out of 92 patients (30%) died due to liver-related complications after a follow-up of 24 months. The decompensated cirrhotic patients with MELD score ≥ 15 had a significantly higher E/e' ratio (11.94 ± 4.24 vs. 8.74 ± 3.32, p < 0.001) suggesting severe LV dysfunction in advanced cirrhosis. Patients with E/e' ratio > 10 had significantly higher MELD score and Child-Pugh score (19.88 ± 7.72 vs. 14.31 ± 5.83; 10.25 ± 1.74 vs. 9.02 ± 1.74, p < 0.01, respectively) as compared to theE/e' ratio < 10 group. In Cox proportional hazard multivariate analysis, E/e' ≥ 10 (HR 2.72, 95% CI 1.07-6.9, p = 0.03) and serum albumin (HR 0.32, 95% CI 0.14-0.7, p < 0.01) were found to be independent predictors of mortality in decompensated cirrhotic patients. CONCLUSION : The presence of LVDD and low serum albumin were independent predictors of mortality in decompensated cirrhotic patients. Hence, LVDD is an indicator of advanced cirrhosis and mortality.
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10
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Abstract
BACKGROUND Hepatorenal syndrome (HRS) is a serious complication of liver cirrhosis with poor survival in the absence of liver transplantation (LT). HRS represents a state of profound circulatory and cardiac dysfunction. Whether it increases risk of perioperative major adverse cardiovascular events (MACE) following LT remains unclear. METHODS We performed a retrospective cohort study of 560 consecutive patients undergoing cardiac workup for LT of whom 319 proceeded to LT. All patients underwent standardized assessment including dobutamine stress echocardiography. HRS was defined according to International Club of Ascites criteria. RESULTS Primary outcome of 30-day MACE occurred in 74 (23.2%) patients. A significantly higher proportion of patients with HRS experienced MACE (31 [41.9%] versus 54 [22.0%]; P = 0.001). After adjusting for age, model for end-stage liver disease score, cardiovascular risk index, history of coronary artery disease, and a positive stress test, HRS remained an independent predictor for MACE (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.13-5.78). Other independent predictors included poor functional status (OR, 3.38; 95% CI, 1.41-8.13), pulmonary hypertension (OR, 3.26; 95% CI, 1.17-5.56), and beta-blocker use (OR, 2.56; 95% CI, 1.10-6.48). Occurrence of perioperative MACE was associated with a trend toward poor age-adjusted survival over 3.6-year follow-up (hazard ratio, 2.0; 95% CI, 0.98-4.10; P = 0.057). CONCLUSIONS HRS, beta-blocker use, pulmonary hypertension, and poor functional status were all associated with over a 2-fold higher risk of MACE following LT. Whether inclusion of these variables in routine preoperative assessment can facilitate cardiac risk stratification warrants further study.
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11
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Koshy AN, Gow PJ, Testro A, Teh AW, Ko J, Lim HS, Han HC, Weinberg L, VanWagner LB, Farouque O. Relationship between QT interval prolongation and structural abnormalities in cirrhotic cardiomyopathy: A change in the current paradigm. Am J Transplant 2021; 21:2240-2245. [PMID: 33453141 PMCID: PMC8819736 DOI: 10.1111/ajt.16500] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 01/04/2021] [Accepted: 01/07/2021] [Indexed: 01/25/2023]
Abstract
It is postulated that cardiac structural abnormalities observed in cirrhotic cardiomyopathy (CCM) contribute to the electrophysiologic abnormality of QT interval (QTc) prolongation. We sought to evaluate whether QTc prolongation is associated with intrinsic abnormalities in cardiac structure and function that characterize CCM. Consecutive patients undergoing liver transplant work-up between 2010 and 2018 were included. Measures of cardiac function on stress testing including cardiac reserve and chronotropic incompetence were collected prospectively and a corrected QTc ≥ 440 ms was considered prolonged. Overall, 439 patients were included and 65.1% had a prolonged QTc. There were no differences in markers of left ventricular and atrial remodeling, or resting systolic and diastolic function across QTc groups. The proportion of patients that met the criteria for a low cardiac reserve (39.2 vs 36.6%, p = .66) or chronotropic incompetence (18.1 vs 21.3%, p = .52) was not different in those with a QTc ≥ 440 vs <440 ms. Further, there was no association between QTc prolongation and CCM by either the 2005 World College of Gastroenterology or modified 2020 Cirrhotic Cardiomyopathy Consortium criteria. QT interval prolongation was not associated with structural or functional cardiac abnormalities that characterize CCM. These findings suggest that CCM and QT interval prolongation in cirrhosis may be two separate entities with distinct pathophysiological origins.
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Affiliation(s)
- Anoop N. Koshy
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia,The University of Melbourne, Parkville, Victoria, Australia
| | - Paul J. Gow
- The University of Melbourne, Parkville, Victoria, Australia,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Adam Testro
- The University of Melbourne, Parkville, Victoria, Australia,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Andrew W. Teh
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia,The University of Melbourne, Parkville, Victoria, Australia
| | - Jefferson Ko
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia
| | - Han S. Lim
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia,The University of Melbourne, Parkville, Victoria, Australia
| | - Hui-Chen Han
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia,The University of Melbourne, Parkville, Victoria, Australia
| | - Laurence Weinberg
- The University of Melbourne, Parkville, Victoria, Australia,Department of Anaesthesia, Austin Health, Melbourne, Victoria, Australia
| | - Lisa B. VanWagner
- Division of Gastroenterology & Hepatology and Preventive Medicine-Epidemiology Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Omar Farouque
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia,The University of Melbourne, Parkville, Victoria, Australia
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Koshy AN, Gow PJ, Farouque O. Cirrhotic Cardiomyopathy: An Evolving Diagnostic Entity With Long-Term Clinical Sequelae. Liver Transpl 2021; 27:794-796. [PMID: 33683815 DOI: 10.1002/lt.26046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 03/05/2021] [Indexed: 01/13/2023]
Affiliation(s)
- Anoop N Koshy
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Paul J Gow
- The University of Melbourne, Parkville, Victoria, Australia.,Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Omar Farouque
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
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Abstract
Cirrhotic cardiomyopathy (CCM) connotes systolic and/or diastolic dysfunction in patients with end-stage liver disease in the absence of prior heart disease. Its prevalence is variable across different studies but recent data suggest that CCM may affect up to one third of liver transplant candidates. The etiology of CCM is multifactorial. CCM defining features were recently revised to improve the diagnostic and prognostic yield of CCM criteria and inform candidate selection for liver transplantation. CCM appears to increase the risk for unfavorable outcomes pre- and post-transplant. Close clinical and echocardiographic follow-up of patients with CCM may mitigate adverse cardiac outcomes.
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Affiliation(s)
- MANHAL J IZZY
- Assistant Professor, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, TN
| | - LISA B VANWAGNER
- Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology,Department of Preventive Medicine, Division of Epidemiology, Northwestern University Feinberg School of Medicine, Chicago, IL
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Abstract
Cirrhotic cardiomyopathy (CCM), cardiac dysfunction in end-stage liver disease in the absence of prior heart disease, is an important clinical entity that contributes significantly to morbidity and mortality. The original definition for CCM, established in 2005 at the World Congress of Gastroenterology (WCG), was based upon known echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Subsequent advances in cardiovascular imaging and in particular myocardial deformation imaging have rendered the WCG criteria outdated. A number of investigations have explored other factors relevant to CCM, including serum markers, electrocardiography, and magnetic resonance imaging. CCM characteristics include a hyperdynamic circulatory state, impaired contractility, altered diastolic relaxation, and electrophysiological abnormalities, particularly QT interval prolongation. It is now known that cardiac dysfunction worsens with the progression of cirrhosis. Treatment for CCM has traditionally been limited to supportive efforts, but new pharmacological studies appear promising. Left ventricular diastolic dysfunction in CCM can be improved by targeted heart rate reduction. Ivabradine combined with carvedilol improves left ventricular diastolic dysfunction through targeted heart rate reduction, and this regimen can improve survival in patients with cirrhosis. Orthotopic liver transplantation also appears to improve CCM. Here, we canvass diagnostic challenges associated with CCM, introduce cardiac physiology principles and the application of echocardiographic techniques, and discuss the evidence behind therapeutic interventions in CCM.
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15
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Koshy AN, Ko J, Farouque O, Cooray SD, Han HC, Cailes B, Gow PJ, Weinberg L, Testro A, Lim HS, Teh AW. Effect of QT interval prolongation on cardiac arrest following liver transplantation and derivation of a risk index. Am J Transplant 2021; 21:593-603. [PMID: 32530547 DOI: 10.1111/ajt.16145] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 06/01/2020] [Accepted: 06/06/2020] [Indexed: 01/25/2023]
Abstract
Liver transplantation (LT) has a 4-fold higher risk of periprocedural cardiac arrest and ventricular arrhythmias (CA/VAs) compared with other noncardiac surgeries. Prolongation of the corrected QT interval (QTc) is common in patients with liver cirrhosis. Whether it is associated with an increased risk of CA/VAs following LT is unclear. Rates of 30-day CA/VAs post-LT were assessed in consecutive adults undergoing LT between 2010 and 2017. Pretransplant QTc was measured by a cardiologist blinded to clinical outcomes. Among 408 patients included, CA/VAs occurred in 26 patients (6.4%). QTc was significantly longer in CA/VA patients (475 ± 34 vs 450 ± 34 ms, P < .001). Optimal QTc cut-off for prediction of CA/VAs was ≥480 ms. After adjustment, QTc ≥480 ms remained the strongest predictor for the occurrence of CA/VAs (odds ratio [OR] 5.2, 95% confidence interval [CI] 2.2-12.6). A point-based cardiac arrest risk index (CARI) was derived with the bootstrap method for yielding optimism-corrected coefficients (2 points: QTc ≥480, 1 point: Model for End-Stage Liver Disease [MELD] ≥30, 1 point: age ≥65, and 1 point: male). CARI score ≥3 demonstrated moderate discrimination (c-statistic 0.79, optimism-corrected c-statistic 0.77) with appropriate calibration. QTc ≥480 ms was associated with a 5-fold increase in the risk of CA/VAs. The CARI score may identify patients at higher risk of these events. Whether heightened perioperative cardiac surveillance, avoidance of QT prolonging medications, or beta blockers could mitigate the risk of CA/VAs in this population merits further study.
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Affiliation(s)
- Anoop N Koshy
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Jefferson Ko
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia
| | - Omar Farouque
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Shamil D Cooray
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Hui-Chen Han
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Benjamin Cailes
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia
| | - Paul J Gow
- The University of Melbourne, Parkville, Victoria, Australia.,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Laurence Weinberg
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia.,Department of Anaesthesia, Austin Health, Melbourne, Victoria, Australia
| | - Adam Testro
- The University of Melbourne, Parkville, Victoria, Australia.,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Han S Lim
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Andrew W Teh
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia.,Cardiology Department, Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
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16
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Chelakkat M, Jacob M, Sebastian S, Paul G, NM A, Joy B, Afsal M. Echocardiographic abnormalities in patients with chronic liver disease: Observations from Thrissur, Kerala, India. MGM JOURNAL OF MEDICAL SCIENCES 2021. [DOI: 10.4103/mgmj.mgmj_84_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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17
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Honar H, Liu H, Zhang ML, Glenn TK, Ter Keurs HEDJ, Lee SS. Impaired myosin isoform shift and calcium transients contribute to cellular pathogenesis of rat cirrhotic cardiomyopathy. Liver Int 2020; 40:2808-2819. [PMID: 32654385 DOI: 10.1111/liv.14599] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 06/28/2020] [Accepted: 07/04/2020] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Cirrhotic cardiomyopathy is a recently recognized entity, but detailed cellular and molecular mechanisms remain unclarified. We aimed to elucidate the role of myosin heavy chain isoform shifts and their relation to calcium transients in the contractile kinetics of cirrhotic rats. METHODS Cirrhosis was induced in male Lewis Brown-Norway rats by bile duct ligation (BDL). Myosin heavy chain (MHC) isoform distribution was evaluated by gel electrophoresis. Contractile force, Ca2+ transients and cell shortening were studied at varied frequency and extracellular [Ca2+ ]. T-tubular integrity was analysed by power spectrum analysis of images of myocytes stained with di-8-ANEPPS. RESULTS Compared with sham controls, the phenotypes of cirrhotic rats were as follows: (a) alpha-myosin heavy chain shifted to beta-MHC isoform; (b) mild loss of T-tubular integrity in myocytes; (c) a reduced maximum and rate of rise of the Ca2+ transient (max F/Fo ); (d) a reduction in both the rate of rise and fall of contraction; (e) decreased maximal force-generating capacity; (f) loss of the inotropic effect of increased stimulus frequency; (g) unchanged sensitivity of force development to varied extracellular [Ca2+ ] and (h) increased spontaneous diastolic sarcomere length fluctuations. CONCLUSION Cardiomyocytes and ventricular trabeculae in a cirrhotic rat model showed features of typical heart failure including systolic and diastolic prolongation, impaired force-frequency relation and decreased force-generating capacity. Impaired myosin isoform shift and calcium transients are important contributory mechanisms underlying the pathogenesis of the heart failure phenotype seen in cirrhosis.
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Affiliation(s)
- Hooman Honar
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
| | - Hongqun Liu
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
| | - Mei L Zhang
- Department of Cardiac Sciences of the Libin Institute, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
| | - Tamara K Glenn
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
| | - Henk E D J Ter Keurs
- Department of Cardiac Sciences of the Libin Institute, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
| | - Samuel S Lee
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
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18
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Mousavi K, Niknahad H, Ghalamfarsa A, Mohammadi H, Azarpira N, Ommati MM, Heidari R. Taurine mitigates cirrhosis-associated heart injury through mitochondrial-dependent and antioxidative mechanisms. Clin Exp Hepatol 2020; 6:207-219. [PMID: 33145427 PMCID: PMC7592093 DOI: 10.5114/ceh.2020.99513] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 04/09/2020] [Indexed: 12/15/2022] Open
Abstract
Cirrhosis-induced heart injury and cardiomyopathy is a serious consequence of this disease. It has been shown that bile duct ligated (BDL) animals could serve as an appropriate experimental model to investigate heart tissue injury in cirrhosis. The accumulation of cytotoxic chemicals (e.g., bile acids) could also adversely affect the heart tissue. Oxidative stress and mitochondrial impairment are the most prominent mechanisms of bile acid cytotoxicity. Taurine (Tau) is the most abundant non-protein amino acid in the human body. The cardioprotective effects of this amino acid have repeatedly been investigated. In the current study, it was examined whether mitochondrial dysfunction and oxidative stress are involved in the pathogenesis of cirrhosis-induced heart injury. Rats underwent BDL surgery. BDL animals received Tau (50, 100, and 500 mg/kg, i.p.) for 42 consecutive days. A significant increase in oxidative stress biomarkers was detected in the heart tissue of BDL animals. Moreover, it was found that heart tissue mitochondrial indices of functionality were deteriorated in the BDL group. Tau treatment significantly decreased oxidative stress and improved mitochondrial function in the heart tissue of cirrhotic animals. These data provide clues for the involvement of mitochondrial impairment and oxidative stress in the pathogenesis of heart injury in BDL rats. On the other hand, Tau supplementation could serve as an effective ancillary treatment against BDL-associated heart injury. Mitochondrial regulating and antioxidative properties of Tau might play a fundamental role in its mechanism of protective effects in the heart tissue of BDL animals.
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Affiliation(s)
- Khadijeh Mousavi
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Niknahad
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amin Ghalamfarsa
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamidreza Mohammadi
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Reza Heidari
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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19
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Arya S, Deshpande H, Belwal S, Sharma P, Sadana P, Chandrakant, Rahman F, Gupta M, Uniyal B. Association between cardiac dysfunction, arrhythmias and chronic liver diseases: A narrative review. TRENDS IN ANAESTHESIA AND CRITICAL CARE 2020. [DOI: 10.1016/j.tacc.2020.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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20
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Arora H, Kumar PA. Time to Simplify Transesophageal Echocardiography for Liver Transplantation? J Cardiothorac Vasc Anesth 2020; 34:1833-1835. [PMID: 32402700 DOI: 10.1053/j.jvca.2020.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 03/05/2020] [Indexed: 11/11/2022]
Affiliation(s)
- Harendra Arora
- Department of Anesthesiology, University of North Carolina School of Medicine, Chapel hill, NC and Outcomes Research Consortium, Cleveland, OH
| | - Priya A Kumar
- Department of Anesthesiology, University of North Carolina School of Medicine, Chapel hill, NC and Outcomes Research Consortium, Cleveland, OH
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21
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Koshy AN, Farouque O, Calafiore P, Gow PJ. Letter to the Editor: Diagnosis of Cirrhotic Cardiomyopathy: The Role of an Impaired Cardiac Reserve. Hepatology 2020; 71:1883. [PMID: 31709570 DOI: 10.1002/hep.31034] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Anoop N Koshy
- Department of Cardiology, Austin Health, Melbourne, Vic, Australia.,The University of Melbourne, Parkville, Vic, Australia
| | - Omar Farouque
- Department of Cardiology, Austin Health, Melbourne, Vic, Australia.,The University of Melbourne, Parkville, Vic, Australia
| | - Paul Calafiore
- Department of Cardiology, Austin Health, Melbourne, Vic, Australia
| | - Paul J Gow
- The University of Melbourne, Parkville, Vic, Australia.,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Vic, Australia
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22
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Impaired Cardiac Reserve on Dobutamine Stress Echocardiography Predicts the Development of Hepatorenal Syndrome. Am J Gastroenterol 2020; 115:388-397. [PMID: 31738284 DOI: 10.14309/ajg.0000000000000462] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Cardiac dysfunction has been implicated in the genesis of hepatorenal syndrome (HRS). It is unclear whether a low cardiac output (CO) or attenuated contractile response to hemodynamic stress can predict its occurrence. We studied cardiovascular hemodynamics in cirrhosis and assessed whether a diminished cardiac reserve with stress testing predicted the development of HRS on follow-up. METHODS Consecutive patients undergoing liver transplant workup with dobutamine stress echocardiography (DSE) were included. CO was measured at baseline and during low-dose dobutamine infusion at 10 μg/kg/min. HRS was diagnosed using guideline-based criteria. RESULTS A total of 560 patients underwent DSE, of whom 488 were included after preliminary assessment. There were 64 (13.1%) patients with established HRS. The HRS cohort had a higher baseline CO (8.0 ± 2 vs 6.9 ± 2 L/min; P < 0.001) and demonstrated a blunted response to low-dose dobutamine (ΔCO 29 ± 22% vs 44 ± 32%, P < 0.001) driven primarily by inotropic incompetence. Optimal cutpoint for ΔCO in patients with HRS was determined to be <25% and was used to define a low cardiac reserve. Among the 424 patients without HRS initially, 94 (22.1%) developed HRS over a mean follow-up of 1.5 years. Higher proportion with a low cardiac reserve developed HRS (52 [55.0%] vs 56 [16.9%]; hazard ratio 4.5; 95% confidence interval 3.0-6.7; P < 0.001). In a Cox multivariable model, low cardiac reserve remained the strongest predictor for the development of HRS (hazard ratio 3.9; 95% confidence interval 2.2-7.0; P < 0.001). DISCUSSION Patients with HRS demonstrated a higher resting CO and an attenuated cardiac reserve on stress testing. On longitudinal follow-up, low cardiac reserve was an independent predictor for the development of HRS. Assessment of cardiac reserve with DSE may provide a novel noninvasive risk marker for developing HRS in patients with advanced liver disease.HRS is a life-threatening complication of liver disease. We studied whether an inability to increase cardiac contraction in response to stress can assist in the prediction of HRS. We demonstrate that patients with liver disease who exhibit cardiac dysfunction during stress testing had a 4-fold increased risk of developing HRS. This may improve our ability for early diagnosis and treatment of patients at a higher risk of developing HRS.
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23
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Carvalho MVH, Kroll PC, Kroll RTM, Carvalho VN. Cirrhotic cardiomyopathy: the liver affects the heart. ACTA ACUST UNITED AC 2019; 52:e7809. [PMID: 30785477 PMCID: PMC6376321 DOI: 10.1590/1414-431x20187809] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 12/04/2018] [Indexed: 12/14/2022]
Abstract
Cirrhotic cardiomyopathy historically has been confused as alcoholic cardiomyopathy. The key points for diagnosis of cirrhotic cardiomyopathy have been well explained, however this entity was neglected for a long time. Nowadays the diagnosis of this entity has become important because it is a factor that contributes significantly to morbidity-mortality in cirrhotic patients. Characteristics of cirrhotic cardiomyopathy are a hyperdynamic circulatory state, altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, particularity QT interval prolongation. The pathogenesis includes impaired function of beta-receptors, altered transmembrane currents and overproduction of cardiodepressant factors, such as nitric oxide, cytokines and endogenous cannabinoids. In addition to physical signs of hyperdynamic state and heart failure under stress conditions, the diagnosis can be done with dosage of serum markers, electrocardiography, echocardiography and magnetic resonance. The treatment is mainly supportive, but orthotopic liver transplantation appears to improve this condition although the prognosis of liver transplantation in patients with cirrhotic cardiomyopathy is uncertain.
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Affiliation(s)
- M V H Carvalho
- Departamento de Cirurgia, Faculdade de Medicina de Jundiaí, Jundiaí, SP, Brasil
| | - P C Kroll
- Hospital de Transplante E.J. Zerbini, São Paulo, SP, Brasil
| | - R T M Kroll
- Instituto Dante Pazzanese de Cardiologia, São Paulo, SP, Brasil
| | - V N Carvalho
- Hospital Municipal Dr. Mario Gatti, Campinas, SP, Brasil
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24
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Jansen C, Schröder A, Schueler R, Lehmann J, Praktiknjo M, Uschner FE, Schierwagen R, Thomas D, Monteiro S, Nickenig G, Strassburg CP, Meyer C, Arroyo V, Hammerstingl C, Trebicka J. Left Ventricular Longitudinal Contractility Predicts Acute-on-Chronic Liver Failure Development and Mortality After Transjugular Intrahepatic Portosystemic Shunt. Hepatol Commun 2019; 3:340-347. [PMID: 30984902 PMCID: PMC6444053 DOI: 10.1002/hep4.1308] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 12/20/2018] [Indexed: 12/14/2022] Open
Abstract
Acute deterioration of liver cirrhosis (e.g., infections, acute-on-chronic liver failure [ACLF]) requires an increase in cardiac contractility. The insufficiency to respond to these situations could be deleterious. Left ventricular global longitudinal strain (LV-GLS) has been shown to reflect left cardiac contractility in cirrhosis better than other parameters and might bear prognostic value. Therefore, this retrospective study investigated the role of LV-GLS in the outcome after transjugular intrahepatic portosystemic shunt (TIPS) and the development of ACLF. We included 114 patients (48 female patients) from the Noninvasive Evaluation Program for TIPS and Their Follow-Up Network (NEPTUN) cohort. This number provided sufficient quality and structured follow-up with the possibility of calculating major scores (Child, Model for End-Stage Liver Disease [MELD], Chronic Liver Failure Consortium acute decompensation [CLIF-C AD] scores) and recording of the events (development of decompensation episode and ACLF). We analyzed the association of LV-GLS with overall mortality and development of ACLF in patients with TIPS. LV-GLS was independently associated with overall mortality (hazard ratio [HR], 1.123; 95% confidence interval [CI],1.010-1.250) together with aspartate aminotransferase (HR, 1.009; 95% CI, 1.004-1.014) and CLIF-C AD score (HR, 1.080; 95% CI, 1.018-1.137). Area under the receiver operating characteristic curve (AUROC) analysis for LV-GLS for overall survival showed higher area under the curve (AUC) than MELD and CLIF-C AD scores (AUC, 0.688 versus 0.646 and 0.573, respectively). The best AUROC-determined LV-GLS cutoff was -16.6% to identify patients with a significantly worse outcome after TIPS at 3 months, 6 months, and overall. LV-GLS was independently associated with development of ACLF (HR, 1.613; 95% CI, 1.025-2.540) together with a MELD score above 15 (HR, 2.222; 95% CI, 1.400-3.528). Conclusion: LV-GLS is useful for identifying patients at risk of developing ACLF and a worse outcome after TIPS. Although validation is required, this tool might help to stratify risk in patients receiving TIPS.
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Affiliation(s)
- Christian Jansen
- Department of Internal Medicine I University Clinic Bonn Bonn Germany
| | - Anna Schröder
- Department of Internal Medicine I University Clinic Bonn Bonn Germany
| | - Robert Schueler
- Department of Internal Medicine II University Clinic Bonn Bonn Germany
| | - Jennifer Lehmann
- Department of Internal Medicine I University Clinic Bonn Bonn Germany
| | | | - Frank E Uschner
- Department of Internal Medicine I University Clinic Bonn Bonn Germany.,Department of Internal Medicine I University Clinic Frankfurt Frankfurt Germany
| | | | - Daniel Thomas
- Department of Radiology University Clinic Bonn Bonn Germany
| | - Sofia Monteiro
- Department of Internal Medicine I University Clinic Bonn Bonn Germany.,Department of Internal Medicine Hospital Pedro Hispano, Matosinhos Local Health Unit Matosinhos Portugal
| | - Georg Nickenig
- Department of Internal Medicine II University Clinic Bonn Bonn Germany
| | | | - Carsten Meyer
- Department of Radiology University Clinic Bonn Bonn Germany
| | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure Barcelona Spain
| | | | - Jonel Trebicka
- Department of Internal Medicine I University Clinic Bonn Bonn Germany.,Department of Internal Medicine I University Clinic Frankfurt Frankfurt Germany.,European Foundation for the Study of Chronic Liver Failure Barcelona Spain.,Faculty of Health Sciences University of Southern Denmark Odense Denmark.,Institute of Bioengineering Catalunya Barcelona Spain
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25
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Closed-Loop Lumped Parameter Modeling of Hemodynamics During Cirrhogenesis in Rats. IEEE Trans Biomed Eng 2018; 65:2311-2322. [DOI: 10.1109/tbme.2018.2793948] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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26
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Scarpati G, De Robertis E, Esposito C, Piazza O. Hepatic encephalopathy and cirrhotic cardiomyopathy in Intensive Care Unit. Minerva Anestesiol 2018; 84:970-979. [PMID: 29624025 DOI: 10.23736/s0375-9393.18.12343-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Acute and chronic liver diseases may escalate to hepatic encephalopathy (HE) and multiple organ failure, requiring admission and organ support in Intensive Care Unit (ICU). Hepatic dysfunction in ICU is a broad and complex topic; unfortunately, up to now, the understanding of its underlying pathophysiology is far from complete. HE and cirrhotic cardiomyopathy (CCM) need timely diagnostic and therapeutic measures aiming at the identification and elimination of causative factors, to improve patients' prognosis. Through this short review, we tried to answer the most asked questions about clinical features of HE and CCM at the ICU stage.
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Affiliation(s)
- Giuliana Scarpati
- Anesthesia and Intensive Care, University of Salerno, Salerno, Italy
| | - Edoardo De Robertis
- Department of Neurosciences, Reproductive and Odonto-Stomatological Sciences, University Hospital Federico II, Naples, Italy -
| | - Ciro Esposito
- Anesthesia and Intensive Care, Cardarelli Hospital, Naples, Italy
| | - Ornella Piazza
- Anesthesia and Intensive Care, University of Salerno, Salerno, Italy
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27
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Q-T Interval Prolongation in Patients with Liver Cirrhosis. CURRENT HEALTH SCIENCES JOURNAL 2018; 44:274-279. [PMID: 30647948 PMCID: PMC6311219 DOI: 10.12865/chsj.44.03.11] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Accepted: 09/13/2018] [Indexed: 02/07/2023]
Abstract
Liver cirrhosis (LC) is the end stage of chronic liver disease characterized by the appearance of extensive fibrosis and regeneration nodes associated with hepatocyte necrosis in liver but also by the reshuffling of hepatic architecture. The triad consisting of hepatic parenchymal necrosis, regeneration and scarring is always present regardless of the type of clinical manifestation. The Child-Pugh-Turcotte classification dates back more than 30 years and has been widely used in diagnosing and assessing the severity of liver cirrhosis. This is preferred due to a low degree of complexity and a good predictive value. Prolongation of the QT interval on the electrocardiogram is common, with a prevalence exceeding 60% in patients with advanced stage of cirrhosis. In these cases, beta blockers and antiarrhythmics should be avoided or used with caution and with close QT interval monitoring. Changes in heart rate and Q-T interval are new entities in cirrhosis complications. A prolonged Q-T interval in chronic liver disease could lead to ventricular arrhythmias and sudden death. There is no report on heart rate and Q-T interval disorders in our area.
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28
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Møller S, Bendtsen F. The pathophysiology of arterial vasodilatation and hyperdynamic circulation in cirrhosis. Liver Int 2018; 38:570-580. [PMID: 28921803 DOI: 10.1111/liv.13589] [Citation(s) in RCA: 121] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Accepted: 09/11/2017] [Indexed: 12/11/2022]
Abstract
Patients with cirrhosis and portal hypertension often develop complications from a variety of organ systems leading to a multiple organ failure. The combination of liver failure and portal hypertension results in a hyperdynamic circulatory state partly owing to simultaneous splanchnic and peripheral arterial vasodilatation. Increases in circulatory vasodilators are believed to be due to portosystemic shunting and bacterial translocation leading to redistribution of the blood volume with central hypovolemia. Portal hypertension per se and increased splanchnic blood flow are mainly responsible for the development and perpetuation of the hyperdynamic circulation and the associated changes in cardiovascular function with development of cirrhotic cardiomyopathy, autonomic dysfunction and renal dysfunction as part of a cardiorenal syndrome. Several of the cardiovascular changes are reversible after liver transplantation and point to the pathophysiological significance of portal hypertension. In this paper, we aimed to review current knowledge on the pathophysiology of arterial vasodilatation and the hyperdynamic circulation in cirrhosis.
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Affiliation(s)
- Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, University of Copenhagen, Copenhagen, Denmark
| | - Flemming Bendtsen
- Gastro Unit, Medical Division, Faculty of Health Sciences, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
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29
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VanWagner LB, Harinstein ME, Runo JR, Darling C, Serper M, Hall S, Kobashigawa JA, Hammel LL. Multidisciplinary approach to cardiac and pulmonary vascular disease risk assessment in liver transplantation: An evaluation of the evidence and consensus recommendations. Am J Transplant 2018; 18:30-42. [PMID: 28985025 PMCID: PMC5840800 DOI: 10.1111/ajt.14531] [Citation(s) in RCA: 104] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Revised: 09/12/2017] [Accepted: 09/28/2017] [Indexed: 01/25/2023]
Abstract
Liver transplant (LT) candidates today are older, have greater medical severity of illness, and have more cardiovascular comorbidities than ever before. In addition, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Cirrhotic cardiomyopathy, a condition characterized by increased cardiac output and a reduced ventricular response to stress, is present in up to 30% of patients with cirrhosis, thus challenging perioperative management. Current noninvasive tests that assess for subclinical coronary and myocardial disease have low sensitivity, and altered hemodynamics during the LT surgery can unmask latent cardiovascular disease either intraoperatively or in the immediate postoperative period. Therefore, this review, assembled by a group of multidisciplinary experts in the field and endorsed by the American Society of Transplantation Liver and Intestine and Thoracic and Critical Care Communities of Practice, provides a critical assessment of the diagnosis of cardiac and pulmonary vascular disease and interventions aimed at managing these conditions in LT candidates. Key points and practice-based recommendations for the diagnosis and management of cardiac and pulmonary vascular disease in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.
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Affiliation(s)
- Lisa B. VanWagner
- Division of Gastroenterology and Hepatology, Department of Medicine and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL USA
| | - Matthew E. Harinstein
- Heart and Vascular Institute, Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA USA
| | - James R. Runo
- Division of Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI USA
| | - Christopher Darling
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI USA
| | - Marina Serper
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA USA
| | - Shelley Hall
- Division of Transplant Cardiology, Baylor University Medical Center, Dallas, TX USA
| | - Jon A. Kobashigawa
- Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA USA
| | - Laura L. Hammel
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI USA
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Farouk H, Al-Maimoony T, Nasr A, El-Serafy M, Ghany MA. Echocardiographic assessment of the left ventricular diastolic function in patients with non-alcoholic liver cirrhosis. COR ET VASA 2017. [DOI: 10.1016/j.crvasa.2016.12.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Isaak RS, Kumar PA, Arora H. PRO: Transesophageal Echocardiography Should Be Routinely Used for All Liver Transplant Surgeries. J Cardiothorac Vasc Anesth 2017; 31:2282-2286. [DOI: 10.1053/j.jvca.2016.11.026] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Indexed: 11/11/2022]
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Pesce M, D'Alessandro A, Borrelli O, Gigli S, Seguella L, Cuomo R, Esposito G, Sarnelli G. Endocannabinoid-related compounds in gastrointestinal diseases. J Cell Mol Med 2017; 22:706-715. [PMID: 28990365 PMCID: PMC5783846 DOI: 10.1111/jcmm.13359] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 07/23/2017] [Indexed: 12/14/2022] Open
Abstract
The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More recently, the identification of several EC-like compounds able to modulate ECS function without the typical central side effects of cannabino-mimetics has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases.
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Affiliation(s)
- Marcella Pesce
- Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, Naples, Italy.,Division of Neurogastroenterology & Motility, Great Ormond Street Hospital and University of College (UCL), London, UK
| | - Alessandra D'Alessandro
- Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, Naples, Italy
| | - Osvaldo Borrelli
- Division of Neurogastroenterology & Motility, Great Ormond Street Hospital and University of College (UCL), London, UK
| | - Stefano Gigli
- Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza University of Rome, Rome, Italy
| | - Luisa Seguella
- Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza University of Rome, Rome, Italy
| | - Rosario Cuomo
- Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, Naples, Italy
| | - Giuseppe Esposito
- Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza University of Rome, Rome, Italy
| | - Giovanni Sarnelli
- Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, Naples, Italy
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Zhao J, Li S, Ren L, Guo X, Qi X. Pro-Brain Natriuretic Peptide and Troponin T-Hypersensitivity Levels Correlate With the Severity of Liver Dysfunction in Liver Cirrhosis. Am J Med Sci 2017; 354:131-139. [PMID: 28864370 DOI: 10.1016/j.amjms.2017.04.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 03/20/2017] [Accepted: 04/05/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Increased pro-brain natriuretic peptide (pro-BNP) or troponin T-hypersensitivity (TnT-HSST) levels are common in liver cirrhosis. We conducted a retrospective observational study aimed to evaluate the correlation of pro-BNP and TnT-HSST levels with the clinical characteristics, laboratory data and in-hospital outcomes of patients with liver cirrhosis. MATERIALS AND METHODS We selected cirrhotic patients admitted to our hospital between January 2011 and June 2014. All eligible patients had pro-BNP or TnT-HSST data, or both. The pro-BNP and TnT-HSST data were further divided according to the presence of cardiac diseases. RESULTS The prevalence of pro-BNP level >900pg/mL was 41.72% (63 of 151 patients). The prevalence of TnT-HSST level >0.05ng/mL was 11.22% (45 of 401 patients). In the overall analysis, pro-BNP level significantly correlated with red blood cell (RBC), platelet, ascites, blood urea nitrogen (BUN), creatinine (Cr), Child-Pugh score, model for end-stage liver disease (MELD) score and in-hospital death; TnT-HSST level significantly correlated with white blood cell, ascites, albumin (ALB), BUN, Cr, Child-Pugh score, MELD score and in-hospital death. In patients with cardiac diseases, pro-BNP level significantly correlated with RBC, ascites, BUN, Cr, Child-Pugh score and MELD score; TnT-HSST level significantly correlated with sex, ascites, white blood cell, ALB, BUN, Cr, Child-Pugh score, MELD score and in-hospital death. In patients without cardiac diseases, pro-BNP level significantly correlated with ascites, RBC, platelet, BUN, Cr, MELD score and in-hospital death; TnT-HSST level significantly correlated with age, ascites, RBC, ALB, BUN, Cr, Child-Pugh score, MELD score and in-hospital death. CONCLUSIONS Pro-BNP and TnT-HSST levels significantly correlated with the severity of liver dysfunction and in-hospital mortality in cirrhosis.
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Affiliation(s)
- Jiancheng Zhao
- Department of Gastroenterology (JZ, LR, XG, XQ), General Hospital of Shenyang Military Area, Shenyang, China; Department of Rehabilitation (JZ), Jia He Hospital of the Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Sai Li
- Department of Cardiology (SL), No. 4 People's Hospital of Shenyang City, Shenyang, China
| | - Linan Ren
- Department of Rehabilitation (JZ), Jia He Hospital of the Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Xiaozhong Guo
- Department of Rehabilitation (JZ), Jia He Hospital of the Liaoning University of Traditional Chinese Medicine, Shenyang, China.
| | - Xingshun Qi
- Department of Rehabilitation (JZ), Jia He Hospital of the Liaoning University of Traditional Chinese Medicine, Shenyang, China.
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Kumbasar A, Navdar M, Ataoglu E, Uzunhasan I, Ergen K, Poturoglu S, Basinoglu F, Yilmaz F, Yenigun M, Sar F, Tanriverdi O. N-Terminal pro-B-Type Natriuretic Peptide Levels are Linked with Modified Child-Pugh Classification in Patients with Nonalcoholic Cirrhosis [NT-ProBNP and Liver Cirrhosis]. Cell Biochem Biophys 2016; 75:111-117. [PMID: 27914003 DOI: 10.1007/s12013-016-0773-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 11/25/2016] [Indexed: 01/21/2023]
Abstract
Excess N-terminal pro-brain natriuretic peptide secretion has been linked to cirrhosis in previously studies. The relationship of plasma N-terminal pro-brain natriuretic peptide levels and cardiac dysfunction determined by echocardiography were investigated in patients with nonalcoholic cirrhosis and a control group of chronic hepatitis. This study was designed as a cross-sectional study. Thirty-two men and thirty-three women who gave informed consent who were followed-up for chronic liver failure were enrolled. All patients gave clinical history, physical examination was carried out and information about ongoing medication has been obtained. Serum N-terminal pro-brain natriuretic peptide level was measured in all patients. The same cardiologist determined ejection fraction, end-diastolic left ventricular diameter, interventricular septum, and posterior wall on transthoracic echocardiography. Patients with extensive liver disease according to Child-Pugh classification from A to C had increasing N-terminal pro-brain natriuretic peptide levels in association (P < .001). According to the Child-Pugh classification there were no significant difference between groups for echocardiographic measurements (P > .05). N-terminal pro-brain natriuretic peptide may be an important marker for cardiac dysfunction in patients with chronic liver failure in accordance with Child-Pugh stage.
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Affiliation(s)
- Abdulbaki Kumbasar
- Clinic of Internal Medicine, Haseki Education and Research Hospital, Istanbul, Turkey
| | - Mehtap Navdar
- Clinic of Internal Medicine, Haseki Education and Research Hospital, Istanbul, Turkey
| | - Esra Ataoglu
- Clinic of Internal Medicine, Haseki Education and Research Hospital, Istanbul, Turkey
| | - Isil Uzunhasan
- Department of Cardiology, Istanbul University Institute of Cardiology, Istanbul, Turkey
| | - Kadir Ergen
- Clinic of Internal Medicine, Haseki Education and Research Hospital, Istanbul, Turkey
| | - Sule Poturoglu
- Department of Gastroenterohepatology, Haseki Education and Research Hospital, Istanbul, Turkey
| | - Filiz Basinoglu
- Clinic of Biochemistry, Haseki Education and Research Hospital, Istanbul, Turkey
| | - Fatih Yilmaz
- Clinic of Internal Medicine, Haseki Education and Research Hospital, Istanbul, Turkey
| | - Mustafa Yenigun
- Clinic of Internal Medicine, Haseki Education and Research Hospital, Istanbul, Turkey
| | - Fuat Sar
- Clinic of Internal Medicine, Haseki Education and Research Hospital, Istanbul, Turkey
| | - Ozgur Tanriverdi
- Department of Internal Medicine, Trakya University Faculty of Medicine, Edirne, Turkey.
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Licata A, Novo G, Colomba D, Tuttolomondo A, Galia M, Camma' C. Cardiac involvement in patients with cirrhosis: a focus on clinical features and diagnosis. J Cardiovasc Med (Hagerstown) 2016; 17:26-36. [PMID: 26065511 DOI: 10.2459/jcm.0000000000000288] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cirrhotic heart has been traditionally considered protected from cardiovascular disease, even if a large amount of literature has recently shown that patients affected by chronic liver disease are exposed to cardiovascular events, as well. Since the first recognition of cardiac involvement in cirrhosis, all published studies explain that decompensated cirrhotic patients suffer from haemodynamic changes, currently known as hyperdynamic syndrome, which finally lead to cirrhotic cardiomyopathy. This is defined by the presence of a subclinical systolic dysfunction unmasked under stress conditions, impaired diastolic function and electrophysiological abnormalities, in the absence of any known cardiac disease. In this review, we will discuss the clinical and diagnostic features of this condition, the prevalence of associated comorbidities, echocardiographic, electrocardiographic and cardiac magnetic resonance hallmarks and the possible diagnostic role of serum biomarkers.
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Affiliation(s)
- Anna Licata
- aSezione di Gastroenterologia ed Epatologia bSezione di Medicina Clinico-Sperimentale, Dipartimento di Medicina Interna e Specialistica, DIBIMIS, Università di Palermo, Italy cDivisione di Cardiologia dSezione di Radiologia, Dipartimento di Biopatologia e Biotecnologie Mediche, DiBiMEF, Università di Palermo, Palermo, Italy
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Zhao J, Qi X, Hou F, Ning Z, Zhang X, Deng H, Peng Y, Li J, Wang X, Li H, Guo X. Prevalence, Risk Factors and In-hospital Outcomes of QTc Interval Prolongation in Liver Cirrhosis. Am J Med Sci 2016; 352:285-95. [PMID: 27650234 DOI: 10.1016/j.amjms.2016.06.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2015] [Revised: 06/05/2016] [Accepted: 06/21/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND QTc interval prolongation is an electrocardiographic abnormality in liver cirrhosis. The objective of this study was to evaluate the prevalence, risk factors and in-hospital outcomes of QTc interval prolongation in Chinese patients with liver cirrhosis. METHODS This was a retrospective analysis of a total of 1,268 patients with liver cirrhosis who were consecutively admitted to our hospital between January 2011 and June 2014. QTc interval data were collected from the medical records. QTc interval prolongation was defined as QTc interval > 440 milliseconds. RESULTS The prevalence of QTc interval prolongation was 38.2% (485 of 1268). In the entire cohort, the risk factors for QTc interval prolongation included an older age, a higher proportion of alcohol abuse and ascites, higher bilirubin, blood urea nitrogen, creatinine, prothrombin time, international normalized ratio, Child-Pugh score and model for end-stage liver diseases score, and lower red blood cell (RBC), hemoglobin (Hb), albumin (ALB), alanine aminotransferase and calcium. The in-hospital mortality was not significantly different between patients with and without QTc interval prolongation (2.1% versus 1.3%, P = 0.276). In the subgroup analyses of patients with hepatitis B virus or alcohol alone-related liver cirrhosis, the risk factors included higher bilirubin, creatinine, prothrombin time, international normalized ratio, Child-Pugh score and model for end-stage liver diseases score, and lower RBC, Hb and ALB. In the subgroups analyses of patients with acute upper gastrointestinal bleeding or ascites, the risk factors included lower RBC, Hb and ALB. CONCLUSIONS QTc interval prolongation was frequent in liver cirrhosis. Although QTc interval prolongation was positively associated with alcohol-related liver cirrhosis and more severe liver dysfunction, it did not significantly influence the in-hospital mortality.
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Affiliation(s)
- Jiancheng Zhao
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, China; Postgraduate College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, China.
| | - Feifei Hou
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, China; Postgraduate College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Zheng Ning
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, China; Postgraduate College, Dalian Medical University, Dalian, Liaoning, China
| | - Xintong Zhang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, China; Postgraduate College, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Han Deng
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, China; Postgraduate College, Dalian Medical University, Dalian, Liaoning, China
| | - Ying Peng
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, China; Postgraduate College, Dalian Medical University, Dalian, Liaoning, China
| | - Jing Li
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, China; Postgraduate College, Dalian Medical University, Dalian, Liaoning, China
| | - Xiaoxi Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, China; Postgraduate College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Hongyu Li
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, China
| | - Xiaozhong Guo
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, China.
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Comparison of Intraoperative Changes in Blood Glucose According to Model for End-stage Liver Disease Score During Living Donor Liver Transplantation. Transplant Proc 2016; 47:1877-82. [PMID: 26293066 DOI: 10.1016/j.transproceed.2015.03.052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Revised: 02/11/2015] [Accepted: 03/04/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Recipients of liver transplantation (LT) may experience disturbance of blood glucose balance, which is aggravated by various exogenous factors. The Model for End-stage Liver Disease (MELD) score is an indicator of the severity of pretransplantation liver disease. In this study, we investigated the role of the MELD score in intraoperative changes in blood glucose in patients undergoing living donor LT (LDLT). METHODS Perioperative data from 280 patients undergoing LDLT were reviewed, including glucose-related data. Intraoperatively, blood glucose levels were checked every hour, and the mean values at each phase of LDLT were calculated. Patients were divided into high and low MELD groups. An unpaired t-test and repeated measures analysis of variance (RMANOVA) were used in intergroup and intragroup comparisons of perioperative blood glucose. RESULTS The high MELD group consisted of 79 patients. Both the time sequential change during LDLT and the interaction between perioperative blood glucose and MELD score were significant (RMANOVA with multivariate adjustment; P < .05). Pretransplant blood glucose levels did not differ between the 2 groups, but the mean levels of blood glucose were lower and the incidence of hypoglycemia was higher in the high compared with the low MELD group during all phases of LDLT (P < .05). CONCLUSIONS Blood glucose levels progressively increased during LDLT with an interaction with the MELD score. Patients with a high MELD score had low blood glucose levels and a greater incidence of intraoperative hypoglycemia. MELD score is a useful determinant of intraoperative blood glucose levels in LDLT patients.
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Reply to Letter: "When the Patient Is Sicker Than His Liver". Ann Surg 2015; 262:e93-4. [PMID: 26559781 DOI: 10.1097/sla.0000000000000725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Abstract
Patients with cirrhosis and portal hypertension are at an increased risk of the development of circulatory dysfunction that may potentially result in multiple organ failure. Apart from the liver, this may involve the heart, lungs, kidneys, the immune system, the adrenal glands, and other organ systems. As the disease progresses, the circulation becomes hyperdynamic, and signs of cardiac, pulmonary, and renal dysfunction are observed, in addition to reduced survival. Infections and an altered cardiac function known as cirrhotic cardiomyopathy may be precipitators for the development of other complications such as hepatorenal syndrome. In patients with chronic organ dysfunction, various precipitating events may induce an acute-on-chronic renal failure and acute-on-chronic liver failure that negatively affect the prognosis. Future research on the pathophysiologic mechanisms of the complications and the precipitating factors is essential to understand the basics of the treatment of these challenging conditions. The aim of the present review is to focus on the development and precipitating factors of various organ failures in patients with decompensated cirrhosis.
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High Rate of Cardiac Abnormalities in a Postmortem Analysis of Patients Suffering From Liver Cirrhosis. J Clin Gastroenterol 2015; 49:866-72. [PMID: 25856382 DOI: 10.1097/mcg.0000000000000323] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Cirrhotic cardiomyopathy is a recently defined cardiac disorder in patients with end-stage liver disease. The frequency and exact manifestations of cardiac changes in liver cirrhosis is unknown. GOALS We aim to describe cardiac changes in a large autopsy study of patients with liver cirrhosis. STUDY Postmortem data from 895 individuals with liver cirrhosis of different origin autopsied from 1995 to 2010 were analyzed. A total of 236 patients were excluded, mostly due to an advanced age above 70 years. The remaining 659 patients were assigned to 4 subgroups according to the etiology of cirrhosis: alcoholic cirrhosis (57.4%), nonalcoholic steatohepatitis (4.2%), viral hepatitis (9.3%), and cryptogenic cirrhosis (29.1%). Predefined clinical and cardiac parameters were assessed in these groups and compared by univariate and multivariate analyses to an age-matched and sex-matched control group including 40 deceased patients without evidence of chronic liver disease. RESULTS A critical heart weight (24%, P=0.024), hypertrophy of the right ventricle (24%, P<0.001), and dilatation of the right ventricle (36%, P=0.040) were significantly more frequent in the cirrhosis group compared with noncirrhotic controls. Cirrhosis patients had a greater risk for high-grade coronary sclerosis (30%, P=0.019). The etiology of cirrhosis was independently associated with hypertrophy and dilatation of the right ventricle, with nonalcoholic steatohepatitis patients being at the highest risk. CONCLUSION Our results demonstrate a high rate of right-ventricular abnormalities and coronary sclerosis in individuals suffering from liver cirrhosis regardless of the etiology of cirrhosis.
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Barakat AAEK, Metwaly AA, Nasr FM, El-Ghannam M, El-Talkawy MD, Taleb HA. Impact of hyponatremia on frequency of complications in patients with decompensated liver cirrhosis. Electron Physician 2015; 7:1349-58. [PMID: 26516441 PMCID: PMC4623794 DOI: 10.14661/1349] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Accepted: 09/20/2015] [Indexed: 02/06/2023] Open
Abstract
Introduction Hyponatremia is common in cirrhosis. The relationship between hyponatremia and severity of cirrhosis is evidenced by its close association with the occurrence of complications, the prevalence of hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, refectory ascites, and hepatic hydrothorax. The aim of this study was assess the impact of hyponatremia on the occurrence of both liver-related complications and the hemodynamic cardiovascular dysfunction. Methods This prospective study was conducted in 2015 on 74 patients with liver cirrhosis. The patients were from the Gastroenterology and Hepatology Department of Theodor Bilharz Research Institute in Giza, Egypt. The patients were divided into three groups according to their serum level of sodium. Group 1 included 30 patients with serum sodium >135 meq/L, group 2 included 24 patients with serum sodium between135 and 125 meq/L, and group 3 included 20 patients with serum sodium <125 meq/L. For each of the patients, we conducted aclinical examination, laboratory investigations, chest X-ray, ECG, abdominal sonar, and echocardiography. Results Hyponatremia was found in 59.46% of our cirrhotic patients, and they showed significantly increased Model for End-Stage Liver Disease (MELD) score, MELD-Na score, QTc interval, Pulmonary vascular resistance (PVR) and inferior vena cava (IVC) collapsibility, and decreased SVR and IVC diameter. Also hepatic encephalopathy, ascites, renal failure, infectious complications, and pleural effusion were significantly more common in hyponatremic cirrhotic patients. Conclusion In cirrhosis, hyponatremia is more common in severe cardiovascular dysfunction and associated with increased risk of hepatic encephalopathy, ascites, illness severity scores, renal failure, infectious complications, and pleural effusion. We recommend selective oral administration of vasopressin V2-receptor antagonist, tolvaptan, which acts to increase the excretion of free water, thereby resolving hypervolemic hyponatremia and may have the potential to improve outcomes in these patients.
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Affiliation(s)
| | - Amna Ahmed Metwaly
- Intensive Care Department, Theodor Bilharz Research Institute, Giza, Egypt
| | | | - Maged El-Ghannam
- Gastroenterology and Hepatology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | | | - Hoda Abu Taleb
- Biostatistics and Demography, Medical Statistician, Environment research Department, Theodor Bilharz Research Institute, Giza, Egypt
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De Pietri L, Mocchegiani F, Leuzzi C, Montalti R, Vivarelli M, Agnoletti V. Transoesophageal echocardiography during liver transplantation. World J Hepatol 2015; 7:2432-2448. [PMID: 26483865 PMCID: PMC4606199 DOI: 10.4254/wjh.v7.i23.2432] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 06/22/2015] [Accepted: 09/09/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) has become the standard of care for patients with end stage liver disease. The allocation of organs, which prioritizes the sickest patients, has made the management of liver transplant candidates more complex both as regards their comorbidities and their higher risk of perioperative complications. Patients undergoing LT frequently display considerable physiological changes during the procedures as a result of both the disease process and the surgery. Transoesophageal echocardiography (TEE), which visualizes dynamic cardiac function and overall contractility, has become essential for perioperative LT management and can optimize the anaesthetic management of these highly complex patients. Moreover, TEE can provide useful information on volume status and the adequacy of therapeutic interventions and can diagnose early intraoperative complications, such as the embolization of large vessels or development of pulmonary hypertension. In this review, directed at clinicians who manage TEE during LT, we show why the procedure merits a place in challenging anaesthetic environment and how it can provide essential information in the perioperative management of compromised patients undergoing this very complex surgical procedure.
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Khemakanok K, Khositseth A, Treepongkaruna S, Teeraratkul S, Pansrimangkorn W, Leelaudomlipi S, Bunmee U, Sriphojanart S. Cardiac abnormalities in cirrhotic children: pre- and post-liver transplantation. Hepatol Int 2015; 10:518-24. [DOI: 10.1007/s12072-015-9674-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2015] [Accepted: 09/14/2015] [Indexed: 12/23/2022]
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Prediction of gross post-transplant outcomes based on the intra-operative decline in C-reactive protein in living donor liver transplantation. Transplant Proc 2015; 47:431-7. [PMID: 25769586 DOI: 10.1016/j.transproceed.2015.01.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Accepted: 01/14/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND C-reactive protein (CRP), a marker of infection and inflammation, is produced mainly in the liver. Its slow onset and various influencing factors have limited studies on the intra-operative changes in CRP in living donor liver transplantation (LDLT). In this study, we asked whether the intra-operative changes in CRP predicts post-transplant outcome. METHODS The peri-transplant data of 263 LDLT patients were reviewed. "Intra-operative CRP decline" was calculated by subtracting the pretransplant CRP from the 1-day post-transplant CRP. A negative value defined an intra-operative decline. Peri-transplant variables were compared between patients with and without gross post-transplant outcomes (GPOs), including death, allograft dysfunction, infection, and kidney injury. Multivariate logistic regression was used to develop a model to predict GPO, and area receiver operating characteristic curve (AUC) analysis was used to evaluate the prognostic accuracies for GPO. RESULTS GPOs were determined in 95 LDLT patients (36.1%). GPO-positive patients had a lesser change in CRP levels (0.51 versus 1.16 mg/dL) and a higher incidence of a decline in CRP (34.7% versus 13.7%) during LDLT (P < .05) than did GPO-negative patients. The AUC of the intra-operative CRP change (0.585; P = .018) did not significantly differ from that of the pretransplant CRP. After multivariate adjustment, a patient with an intra-operative decline in CRP had a 3.21-fold higher risk for GPO occurrence (P = .001). CONCLUSIONS GPO occurrence was related to the intra-operative decline of CRP in LDLT patients. However, multivariate compensation might be required for the clinical utilization of intra-operative decline in CRP as a prognostic indicator.
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Pagourelias ED, Sotiriou P, Papadopoulos CE, Cholongitas E, Giouleme O, Vassilikos V. Left Ventricular Myocardial Mechanics in Cirrhosis: A Speckle Tracking Echocardiographic Study. Echocardiography 2015; 33:223-32. [DOI: 10.1111/echo.13010] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Affiliation(s)
- Efstathios D. Pagourelias
- Third Cardiology Department; Hippokration University Hospital; Medical School; Aristotle University of Thessaloniki; Thessaloniki Greece
| | - Panagiota Sotiriou
- Third Cardiology Department; Hippokration University Hospital; Medical School; Aristotle University of Thessaloniki; Thessaloniki Greece
| | - Christodoulos E. Papadopoulos
- Third Cardiology Department; Hippokration University Hospital; Medical School; Aristotle University of Thessaloniki; Thessaloniki Greece
| | - Evaggelos Cholongitas
- Fourth Department of Internal Medicine, Liver and Transplantation Unit; Hippokration University Hospital; Medical School; Aristotle University of Thessaloniki; Thessaloniki Greece
| | - Olga Giouleme
- Second Propedeutic Department of Internal Medicine, Gastroenterology Unit; Hippokration University Hospital; Medical School; Aristotle University of Thessaloniki; Thessaloniki Greece
| | - Vassilios Vassilikos
- Third Cardiology Department; Hippokration University Hospital; Medical School; Aristotle University of Thessaloniki; Thessaloniki Greece
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Gaskari SA, Liu H, D'Mello C, Kunos G, Lee SS. Blunted cardiac response to hemorrhage in cirrhotic rats is mediated by local macrophage-released endocannabinoids. J Hepatol 2015; 62:1272-7. [PMID: 25640062 PMCID: PMC5045259 DOI: 10.1016/j.jhep.2015.01.021] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Revised: 12/05/2014] [Accepted: 01/21/2015] [Indexed: 01/17/2023]
Abstract
BACKGROUND & AIMS Cirrhosis is associated with blunted cardiovascular response to stimuli such as hemorrhage, but the mechanism remains unclear. We aimed to clarify the role of endocannabinoids in blunted hemorrhage response in cirrhotic rats. METHODS Cirrhosis was induced by bile duct ligation (BDL). Hemodynamics were measured. Cannabinoid receptor-1 (CB1) antagonist, AM251, and macrophage inhibitor gadolinium chloride (GdCl3) were administered. Myocardial levels of anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were measured and resident monocytes and macrophages quantified by immunohistochemistry. Isolated cardiomyocyte contractility was measured before and after incubation with monocytes from BDL and sham controls. RESULTS Hemorrhage significantly decreased arterial pressure and left ventricular dP/dT. After hemorrhage, these changes quickly reversed in controls, but were severely prolonged in BDL rats. Chronic AM251 treatment restored this impaired response. AEA and 2-AG levels were increased in BDL hearts and further increased after hemorrhage. Sham hearts showed virtually no monocytes or macrophages before or after hemorrhage, whereas BDL hearts had significantly more white blood cells which further increased after hemorrhage. GdCl3 treatment significantly reduced cardiac endocannabinoid levels both at baseline and after hemorrhage. This treatment also restored cardiovascular response to hemorrhage in BDL rats but did not affect sham controls. Monocytes isolated from BDL rats more potently inhibited cardiomyocyte contractility than sham control monocytes. CONCLUSIONS The cirrhotic heart showed increased monocyte recruitment and endocannabinoid levels. CB1 blockade or GdCl3 treatment restored blunted cardiovascular response to hemorrhage. Endocannabinoids released by monocytes blunt cardiac response to hemorrhage. Preventing monocyte recruitment or blocking endocannabinoid signaling may improve cardiovascular homeostasis in cirrhosis.
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Affiliation(s)
| | - Hongqun Liu
- Liver Unit, University of Calgary, Calgary, Canada
| | | | - George Kunos
- Laboratory of Physiologic Studies, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Samuel S Lee
- Liver Unit, University of Calgary, Calgary, Canada.
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Investigation of cardiomyopathy in children with cirrhotic and noncirrhotic portal hypertension. J Pediatr Gastroenterol Nutr 2015; 60:177-81. [PMID: 25250684 DOI: 10.1097/mpg.0000000000000580] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Cirrhotic cardiomyopathy (CCMP) is a functional disorder characterized by electrophysiological disturbances, and diastolic and/or systolic dysfunction in patients with liver disease. This disorder is a well-defined entity in adults, but pediatric data are limited. The aim of the study was to determine the incidence, features, and risk factors of CCMP in children with portal hypertension (PHT). METHODS This study included 50 children with cirrhotic PHT (40/50) and noncirrhotic PHT (10/50). Fifty healthy children were also selected for the control group. Electrocardiography and echocardiography were used to evaluate cardiac functions. Corrected QT (QTc) ≥ 0.45 was accepted as prolonged on electrocardiography. The study group was divided into 3 groups: cirrhotic, noncirrhotic, and control. Then, the CCMP group was created according to the diagnostic criteria. Latent CCMP was diagnosed in the presence of prolonged-QTc along with a minor criterion (tachycardia). Manifest CCMP was diagnosed in the presence of at least 2 major criteria (prolonged-QTc along with abnormal echocardiographic findings). Moreover, in this study, the risk factors for CCMP were investigated. RESULTS The CCMP group included 10 cases (20%). Nine of these cases had latent CCMP (18%), and the remaining one (2%) had manifest CCMP. All of the cases with CCMP had cirrhosis and ascites. None of the patients with CCMP had severe cardiac symptoms, but they were already using some cardioprotective drugs such as propanolol and spironolactone. As risk factors for CCMP, pediatric end-stage liver disease scores, Child-Pugh scores, and ascites grades were found to be significant for the determination of CCMP. The most important risk factor was ascites severity (P = 0.001, odds ratio 9.4). CONCLUSIONS Approximately 20% of children with PHT have CCMP. A detailed cardiac examination should be carried out periodically in children with cirrhotic PHT, especially in the presence of ascites and high Child-Pugh score.
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Escobar B, Taurá P, Martínez-Palli G, Fondevila C, Balust J, Beltrán J, Fernández J, García-Pagán JC, García-Valdecasas JC. Stroke volume response to liver graft reperfusion stress in cirrhotic patients. World J Surg 2014; 38:927-35. [PMID: 24132825 DOI: 10.1007/s00268-013-2289-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION In patients with advanced cirrhosis, stressful stimuli may reveal a silent reduced cardiac performance. During liver transplantation (LT), graft reperfusion strongly stresses the heart and may unmask latent myocardial dysfunction. AIM The objective of this study was to assess heart response to acutely increased preload after liver graft reperfusion and correlate this response with preoperative data and outcome. METHODS Preoperative clinical, echocardiographic, and hemodynamic data, and patient outcome were retrospectively recorded for 235 liver recipients who had no known cardiac disease. Myocardial dysfunction was defined as less than 10 % increase of stroke volume after graft reperfusion (non-responder). RESULTS We found 84 (35.7 %) non-responder patients. The non-responders showed higher Model for end-stage liver disease scores (p = 0.046), left atrial diameter (LAD) (p = 0.040), hepatic vein pressure gradient (p = 0.055), and hyperdynamic state than responders. The percentages of patients with hyponatremia (p = 0.048) and alcohol etiology (p = 0.025) were also higher among non-responders. Independent predictors of inadequate cardiac response in the multivariate analysis were low preoperative systemic vascular resistance (SVRI) [odds ratio (OR) 3.09, 95 % CI 1.15-4.82; p = 0.027] and enlargement of LAD (OR 2.08, 95 % CI 1.49-2.74; p = 0.044). Non-response was associated with higher rates of early cardiovascular events [hazard ratio (HR) 2.84, 95 % CI 1.09-4.22; p = 0.039] and higher length of intensive care unit stay (p = 0.038). No differences were found in 1-year survival rates. CONCLUSIONS Latent cardiac dysfunction among LT recipients, considered to be abnormal stroke volume response to unclamping of portal vein, is very prevalent. SVRI and LAD were independent predictors of inadequate responses. This condition deserves special attention since it may aggravate the early postoperative course of LT.
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Affiliation(s)
- Bibiana Escobar
- Department of Anesthesiology, Hospital Clinic, Barcelona, Spain,
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Raval Z, Harinstein ME, Flaherty JD. Role of cardiovascular intervention as a bridge to liver transplantation. World J Gastroenterol 2014; 20:10651-10657. [PMID: 25152569 PMCID: PMC4138446 DOI: 10.3748/wjg.v20.i31.10651] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Revised: 01/11/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
End stage liver disease (ESLD) is associated with many specific derangements in cardiovascular physiology, which influence perioperative outcomes and may profoundly influence diagnostic and management strategies in the preoperative period. This review focuses on evidence-based diagnosis and management of coronary, hemodynamic and pulmonary vascular disease in this population with an emphasis on specific strategies that may provide a bridge to transplantation. Specifically, we address the underlying prevalence of cardiovascular disease states in the ESLD population, and relevant diagnostic criteria thereof. We highlight traditional and non-traditional predictors of cardiovascular outcomes following liver transplant, as well as data to guide risk-factor based diagnostic strategies. We go on to discuss the alterations in cardiovascular physiology which influence positive- and negative-predictive values of standard noninvasive testing modalities in the ESLD population, and review the data regarding the safety and efficacy of invasive testing in the face of ESLD and its co-morbidities. Finally, based upon the totality of available data, we outline an evidence-based approach for the management of ischemia, heart failure and pulmonary vascular disease in this population. It is our hope that such evidence-driven strategies can be employed to more safely bridge appropriate candidates to liver transplant, and to improve their cardiovascular health and outcomes in the peri-operative period.
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