Cardio-hepatology : connections between hepatic and cardiovascular disease

We are pleased to introduce the first book devoted to the relationship between the heart and liver. This field,called “cardio-hepatology” has been the subject of study over the past century. However, interest in the heart/liver relationship actually dates back several thousand years. This history is detailed in Chapter 1.The book is then divided into three major sections. Part I has five chapters devoted to various aspects of theheart
liver interaction. Part II comprises six chapters on the theme of the hepatobiliary system in heart failure.Finally, the theme of Part III is the converse: the cardiovascular system in liver failure, with nine chapters.Befitting the theme of this book, the editors are a cardiologist (TT) and hepatologist (SSL).This is a truly international project with authors from several countries spanning the globe. They are all wellpublished authorities in their fields and were encouraged to write exhaustive and definitive monographs withextensive figures and illustrations.Producing any book, especially a large complex one such as this with several specialized subtopics, in the ageof Covid-19 was a daunting and difficult challenge. However, thanks to the hard work and efficiency of theauthors and the Elsevier Production staff, including the project managers Megan Ashdown and FranchezcaCabural, the project finally came to fruition.We hope that clinicians and researchers in cardiology, hepatology, surgery, anesthesiology, pediatrics, intensivecare medicine, histopathology, and translational medicine will find this book useful and informative. Front Cover Cardio-Hepatology Copyright Page Dedication Contents List of contributors Preface I. Liver and heart 1 The liver–heart relationship: a history Introduction The ancient world: east and west The medieval era The modern era The liver in heart failure The heart in liver failure Hyperdynamic circulation of cirrhosis Cirrhotic cardiomyopathy References 2 Nonalcoholic fatty liver disease and cardiovascular disease Introduction The definition of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis Association between nonalcoholic fatty liver disease/nonalcoholic steatohepatitis and cardiovascular disease Dyslipidemia as causative factors for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis and cardiovascular disease Possible underlining molecular mechanisms between nonalcoholic steatohepatitis and atherosclerosis Association between NAFLD/hepatic fibrosis and cardiac dysfunction Conclusion References 3 Pathophysiologic changes in chronic heart failure affecting drug pharmacokinetics Introduction Fundamental clinical pharmacokinetic principles Clearance concepts Hepatic clearance and oral bioavailability Renal clearance Volume of distribution Half-life Pathophysiological changes affecting pharmacokinetics in patients with chronic heart failure Intestinal permeability Hepatic clearance Hepatic blood flow, hepatic intrinsic clearance Plasma protein binding Intravenous administration of high hepatic extraction ratio drugs Oral administration Renal clearance Volume of distribution Pharmacotherapeutic implications: general recommendations Conclusion References 4 Drugs at the crossroads of heart and liver Introduction Part 1: amiodarone Historical perspective Why amiodarone has not been replaced Pharmacokinetics: the secret to understanding amiodarone Pharmacokinetics: the determinant of drug exposure Pharmacokinetics: the untenable concept of total cumulative dose of amiodarone Amiodarone: separating direct and indirect toxicity Amiodarone: lessons from pulmonary toxicity when considering hepatotoxicity Timelines for amiodarone hepatotoxicity Amiodarone: a drug outside the comfort zone of mainstream therapeutics Amiodarone hepatotoxicity: plausible pathogenesis Amiodarone hepatotoxicity: clinical picture and histological findings Amiodarone hepatotoxicity: diagnosis How toxic is amiodarone to the liver? Amiodarone: effects on hepatic metabolism and other drugs Amiodarone hepatotoxicity: the challenge of attribution Monitoring hepatic function in patients receiving amiodarone Therapy for hepatotoxicity Amiodarone: principles of clinical pharmacology Conclusions Part 2: beta-blockers Introduction Pathophysiology of portal hypertension and cirrhosis stages Clinical pharmacology of nonselective beta-blockers in portal hypertension related to cirrhosis Clinical contexts for the use of nonselective beta-blockers Prevention of the development of varices Prevention of decompensation Prevention of first esophageal variceal bleeding Preventing esophageal variceal rebleeding Beta-blockers in acute on chronic liver failure Bleeding from gastric varices Beta-blockers for portal hypertensive gastropathy The concept of a therapeutic window of nonselective beta-blockers in decompensated cirrhosis Summary and current recommendations References 5 Obstruction of the liver circulation Introduction Budd–Chiari syndrome Risk factors Natural history Staging and prognosis Treatment and management of complications Stepwise treatment strategy Anticoagulation Thrombolysis Recanalization Transjugular intrahepatic portosystemic shunt Liver transplantation Noncirrhotic nontumoral portal vein thrombosis Risk factors Systemic risk factors Local factors Diagnosis and staging Natural history Treatment of recent nontumoral portal vein thrombosis Anticoagulation Interventional treatment Surgery Treatment of underlying causes Treatment of chronic nontumoral portal vein thrombosis Management of complications of portal hypertension Anticoagulation Transjugular intrahepatic portosystemic shunt Management of portal biliopathy Sinusoidal obstruction syndrome Incidence Pathology Risk factors Diagnosis Imaging studies Biopsy Hepatic venous pressure gradient Baltimore and Seattle criteria Nanjing criteria European society for blood and marrow transplantation Assessing severity Preventive measures Nonpharmacologic prevention Pharmacologic prevention Treatment Supportive therapy General Defibrotide Transjugular intrahepatic portosystemic shunt Hepatic artery thrombosis Etiology and risk factors Surgical cause Portal vein thrombosis Infections Intra-arterial liver-directed therapy Coagulation abnormalities Splenic artery steal syndrome Pediatric liver transplant Clinical presentation Treatment Acknowledgment Conflict of interest statement Financial support References II. Hepatobiliary system in heart failure 6 Epidemiology of liver diseases in heart failure Introduction The liver diseases in patients with heart failure Etiological factors of heart failure associated with hepatic disorders Hepatic consequences in cardiac patients Liver function tests abnormalities Congestive hepatopathy Hypoxic hepatitis Drug induced liver injury Liver diseases causing heart failure Cirrhosis Hepatocellular carcinoma Nonalcoholic fatty liver disease Liver transplantation Diseases leading to heart failure and affecting the liver Infections Congenital causes References 7 Cardio-hepatology: liver function tests in heart failure Liver function tests Blood supply of the liver and its anatomy Pathophysiology of abnormal liver function tests in heart failure Bilirubin metabolism in the liver Association between abnormal liver function tests and impaired hemodynamics Liver function tests and prognosis in heart failure Total and direct bilirubin Transaminases (aspartate aminotransferase and alanine aminotransferase) Gamma-glutamyltranspeptidase and alkaline phosphatase Prothrombin time international normalized ratio Albumin, cholinesterase, and total protein Hepatic fibrotic markers in heart failure References 8 Prognostic value of liver assessment (including liver stiffness measurement) in cardiovascular diseases Introduction Heart failure and liver impairment Liver disease is associated with poor outcome of heart failure Liver disease is associated with poor outcomes of cardiovascular diseases Liver function tests and prognosis of HF Liver function tests in HF Prevalence and prognostic value of abnormal liver function in chronic heart failure Prevalence and prognostic relevance of abnormal liver chemistry in acute decompensated heart failure Abnormal liver synthetic function and heart failure Prognostic relevance of markers of hepatic and renal dysfunction in heart failure Markers of hepatic fibrosis and prognosis of HF Serologic markers of hepatic fibrosis in HF Liver specific micro-RNAs in heart failure Imaging markers of hepatic fibrosis in HF Summary References 9 Passive liver congestion and hypoxic hepatitis Introduction Passive liver congestion Hepatic circulation Mechanism of injury Clinical manifestations Imaging findings Pathologic findings Management Prognosis Summary Hypoxic hepatitis Mechanism of injury Clinical manifestations Imaging findings Pathologic findings Management Prognosis Summary Conclusion References 10 Histopathology of the liver in heart failure Introduction Natural history Pathological analysis Pathogenesis Conclusion References 11 The Fontan procedure and liver disease Introduction Fontan procedure Physiology and prevalence of Fontan-associated liver disease Examination to detect Fontan-associated liver disease Recommendation References III. Cardiovascular system in liver failure 12 Sepsis and the liver Introduction Sepsis in the general population Pathophysiology of organ dysfunction during the early phase of sepsis The liver as a victim of deregulated host response to infection Liver failure Shock liver Sepsis-induced alterations in hepatic biotransformation, including hepatocellular cholestasis Sepsis-induced ductular cholestasis Secondary sclerosing cholangitis Infection-induced protective responses originating in the liver Acute-phase protein synthesis during infection Urea cycle during infection Hepatic catabolic metabolism during infection Hepatic triglyceride release during infection Sepsis in patients with cirrhosis Inflammatory phenotype of sepsis in acute-on-chronic liver failure What is acute-on-chronic liver failure? Infection-related acute-on-chronic liver failure versus acute-on-chronic liver failure unrelated to infection Pathophysiology of infection-related acute-on-chronic liver failure Immunosuppression in cirrhosis and acute-on-chronic liver failure Clinical features and management of sepsis syndromes in patients with cirrhosis Spontaneous bacterial peritonitis Diagnosis Differential diagnosis Treatment Empirical antibiotic schedules Antibiotic strategies for extensively drug-resistant bacteria Intravenous albumin Liver transplantation Bacterial infections unrelated to SBP Diagnosis Treatment Antibiotic treatment Intravenous albumin Management of septic shock Prevention of bacterial infections Fungal infections Conclusions Acknowledgments References 13 Bleeding and thrombosis in cirrhosis Introduction to hemostasis Platelets Coagulation Fibrinolysis Hemostatic changes in liver diseases Pitfalls of routine diagnostic tests of hemostasis The concept of rebalanced hemostasis Are liver patients really bleeders? Laboratory changes in hemostasis Platelets Coagulation and fibrinolysis Development of the concept of rebalanced hemostasis Hemostatic balance in different types and severities of liver diseases Compensated cirrhosis Decompensated cirrhosis and acute-on-chronic liver failure Fatty liver disease Acute liver failure Liver transplantation Bleeding in liver diseases Incidence and pathogenesis Prevention Treatment Thrombosis in liver diseases Incidence and pathogenesis Portal vein thrombosis Venous thrombosis Arterial thrombosis Prevention Portal vein thrombosis Venous thrombosis Arterial thrombosis Treatment Portal vein thrombosis Venous thrombosis Arterial thrombosis Which drugs? Intrahepatic thrombosis and disease progression Hemostasis and liver regeneration Delivery of growth factors Delivery of platelet-derived RNA Platelets as initiators of the inflammatory response Fibrin and liver regeneration Conclusion References 14 Peripheral vasculature in portal hypertension Introduction Hyperdynamic circulation Clinical features of hyperdynamic circulation Pathogenesis of hyperdynamic circulation Nitric oxide Endocannabinoids Heme oxygenase and carbon monoxide Role of other humoral agents Bile acids Central neural mechanisms Increased blood and plasma volume/decreased effective circulating volume Peripheral venous “sump” effect due to venous pooling Abnormalities of arterial vascular tone Vasoactive molecules Inflammation Nervous system and peripheral vascular changes Autonomic dysfunction Cerebral circulation Management of hyperdynamic circulation Conclusions References 15 Cirrhotic cardiomyopathy Introduction Definition and diagnostic criteria Distinction from other cardiomyopathies Clinical significance Prevalence Morbidity/mortality after cardiovascular challenges Transjugular intrahepatic portal systemic shunts Liver transplantation Hepatorenal syndrome Adrenal insufficiency Cirrhotic cardiomyopathy and prognosis Pathogenic mechanisms TNFα β-Adrenergic signaling Membrane fluidity Bile acids Nitric oxide Carbon monoxide Myosin heavy chain isoform shift The role of ion channels in cirrhotic cardiomyopathy Titin and collagen isoforms Endocannabinoids Summary of mechanisms Management β-Adrenergic receptor blockers (β-blockers) Combination vasoconstrictors and albumin Albumin Antioxidant and antiinflammatory treatments Liver transplantation CCM reversibility: QTc prolongation CCM reversibility: Systolic and diastolic function Conclusion References 16 Cardiovascular dysfunction in liver diseases: pediatric perspectives Introduction Cardiovascular consequences of structural congenital heart diseases coexisting with diseases of the liver Alagille syndrome Congenital cardiovascular defects associated with ALGS Peripheral vascular defects in ALGS Biliary atresia splenic malformation syndrome Heart defects associated with Abernathy malformation of portal vein Implications of coexisting congenital heart diseases for liver transplantation Cardiovascular complications of pediatric cirrhosis Bile acid-myocardial interaction as a potential mechanism of cardiomyopathy Heart as a target for bile acids Clinical evidence of pathologic bile acid-myocardial interaction Historic evidences of pathologic bile acid-myocardial interaction in animal models Mechanistic insights into bile acid-myocardial interaction Bile acids induce metabolic disturbance in the heart—the concept of cholecardia Implications for intensive care management and liver transplantation Cardiovascular consequences of inherited metabolic liver failure and failure of energy metabolism Hereditary hemochromatosis Neonatal hemochromatosis Glycogen storage diseases Wilson disease Tyrosinemia type 1 Primary hyperoxaluria type 1 Propionic acidemia Homozygous familial hypercholesterolemia Disorders of inborn error in energy metabolism Cardiovascular consequences of acute liver failure Implications for intensive care management and liver transplantation Cardiovascular consequences of chronic cirrhosis, portal hypertension, and portosystemic shunts Hepatopulmonary syndrome Implications of HPS for intensive care management and liver transplantation Portopulmonary hypertension Implications of PoPH for intensive care management and liver transplantation Cardiovascular consequences of immunotherapy used in liver transplants Implications of tacrolimus-induced cardiotoxicty for intensive care management and liver transplantation Evaluation of the cardiovascular status before liver transplantation Cardiac biomarkers in plasma/sera Electrocardiography Echocardiography Assessment of LV geometry in a cirrhotic child on echocardiography Echocardiographic assessment of systolic function in a cirrhotic child Echocardiographic assessment of diastolic function in a cirrhotic child Echocardiographic assessment of global (systolic and diastolic) function in a cirrhotic child Assessment of portopulmonary hypertension on echocardiography Assessments of hepatopulmonary syndrome on echocardiography Cardiac catheterization Cardiac MRI Future directions and opportunities for research References 17 Hepatorenal syndrome and acute kidney injury in cirrhosis Introduction The evolving concept of renal dysfunction in cirrhosis Definition and diagnostic criteria of acute kidney injury in cirrhosis Epidemiology Pathophysiology Hemodynamic changes in cirrhosis Cardiac dysfunction in cirrhosis The role of inflammation Predictive factors for the development of hepatorenal syndrome-acute kidney injury Diagnosis Biomarkers Management General measures Albumin Vasoconstrictors Terlipressin Norepinephrine Midodrine and octreotide Predictors of response to vasoconstrictors Renal replacement therapy Liver transplantation Combined liver kidney transplant Prognosis Prevention Conclusion References 18 Cardiopulmonary considerations for the anesthetic management of liver transplantation Perioperative cardiovascular management in the liver transplant patient Immediate preoperative evaluation, optimization, and planning Intraoperative management Early postoperative cardiac evaluation and management Perioperative pulmonary management in the liver transplant recipient Preoperative pulmonary assessment and optimization Intraoperative pulmonary considerations Postoperative pulmonary considerations References 19 Cardiovascular assessment before liver transplantation Introduction Assessment of coronary artery disease Prevalence of coronary artery disease in liver transplant candidates Risk factors Screening tests for coronary artery disease in liver transplantation candidates Dobutamine stress echocardiogram Myocardial perfusion imaging with real-time myocardial contrast echocardiography Single-photon emission computed tomography–Myocardial perfusion imaging Coronary artery calcium score and coronary computed tomography angiography Invasive coronary angiography Management of coronary artery disease in liver transplantation candidates Assessment of cardiac dysrhythmias Atrial dysrhythmia Prevalence and risk factors of atrial fibrillation in liver transplantation candidates Diagnosis and treatment of atrial fibrillation in liver transplantation candidates Ventricular arrhythmias Assessment of heart failure Prevalence and risk factors Diagnosis and management of cardiac muscle dysfunction in liver transplantation candidates References 20 Predicting cardiovascular complications after liver transplantation Introduction Epidemiology and established risk factors for cardiovascular complications in liver transplantation Natural history and timing of cardiovascular events in liver transplantation Perioperative complications Preload and cardiac output Electrolyte derangements Postreperfusion syndrome Cardiac arrest and arrhythmia Air embolism and thromboembolism Donor factors related to perioperative cardiovascular events Postoperative complications Early (90-day period) Cardiac function Pulmonary Edema Dilated cardiomyopathy Cardiac arrest and arrhythmia Myocardial infarction Stroke Pulmonary embolism Late (>90-day period) Metabolic syndrome General overview Hypertension Dyslipidemia Diabetes mellitus Abdominal obesity Renal disease/chronic kidney disease Identified future areas of study in liver transplantation complications Peripheral vascular disease Valvular heart disease Algorithms and risk calculators for prediction of cardiovascular risk after liver transplantation Liver specific risk predictors Nonsurgical general cardiac risk assessment tools Serum biomarkers Surgical cardiac risk calculators Individual predictors of perioperative cardiovascular disease mortality after liver transplantation Risk models for prediction of perioperative cardiovascular disease mortality after liver transplantation Conclusions References Index Back Cover Cardio-Hepatology: Connections Between Hepatic and Cardiovascular Disease provides a direct relationship between the cardiac and hepatic pathologies providing the link between the heart and liver and showing how liver diseases predispose to impairment in heart functioning and vice versa. Considering the growing number of patients living (and living longer) with heart failure and/or congenital heart disease, it is important to know when and how to test for liver disease in this population, how to interpret abnormal test results, and what management is appropriate. Coverage includes what should be done for patients to limit, avoid, or postpone the impairment in the liver functioning induced by heart diseases and the impairment in the heart functioning induced by liver diseases, on the basis of scientific-exposed evidence and pathophysiology knowledge. This comprehensive, extended review of the medical literature is perfect for researchers interested in the connection between cardiology and hepatology as well as clinicians making therapeutic decisions for patients suffering from heart or liver chronic diseases.