Cardio-Hepatology: Connections Between Hepatic and Cardiovascular Disease

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
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