Cardiovascular pathology

Front Cover
Cardiovascular Pathology
Copyright Page
Contents
List of contributors
About the editors
Preface
Acknowledgments
1 Cardiovascular pathology: guide to practice and training
	Introduction
	Autopsy
		Heart weights and measurements
		Sudden cardiac death
		Assessment of coronary artery disease
	Genetics and molecular biology
	Surgical pathology
	Endomyocardial biopsy
	Heart transplant pathology
	Cardiovascular clinical diagnostic and imaging studies
	Training in cardiovascular pathology
	Cardiovascular pathologist roles as diagnostician, teacher, consultant, and care team member
	Summary
	References
2 Anatomic considerations and examination of cardiovascular specimens (excluding devices)
	Gross examination of the heart
		Position in the chest
		Determination of sidedness (situs)
		Pericardium and pericardial reflections
		Removal of the heart
		External anatomy and landmarks
			Great vessels
			Coronary vessels
		Opening the heart
			Right atrium
			Tricuspid valve
			Right ventricle
			Pulmonary valve
			Left atrium
			Mitral valve
			Left ventricle
			Aortic valve
			Conduction system
			Cardiac innervation
		Heart weight and measurements
	Examination of surgical cardiovascular specimens
		Practical considerations
			General
			Receipt/accession of specimens
			Gross examination
		Reporting
			Handling particular specimens
			Vascular specimens
			Native heart valves
			Prosthetic heart valves
			Myocardium
			Pericardium
			Tumor and tumor-like conditions
			Limbs excised for peripheral vascular disease
	Microscopic examination of the blood vessels and heart
		Blood vessels
			Organization
			Light microscopy
			Aorta and other elastic arteries
				General features
				Intima
				Media
				Adventitia
				Internal thoracic artery
			Muscular arteries
				General features
				Intima
				Media
				Adventitia
			Arterioles
			Capillaries
			Venules and small veins
			Medium veins
			Large veins
			Pulmonary vessels
				Adult circulation
			Fetal circulation
		Lymphatic vessels
		Ultrastructure of vessels
			Endothelium
				General features
				Endocytotic structures
				Filaments and microtubules
				Weibel-Palade bodies
				Cell membrane, surface coat, and basal lamina
				Cell junctions
			Smooth muscle
				General features
				Endocytotic structures
				Filaments
		Cell membrane and external lamina
			Cell junctions
			Matrix elements
				General features
				Collagen
				Elastic
		Heart
			Organization
			Endocardium
			Myocardium
			Light microscopy
			Ultrastructure
				Cell membrane
				Nucleus
				Sarcoplasmic reticulum
				Cell junctions
				Contractile elements
				Other cytoplasmic elements
				Atrial granules
		Interstitium
			Extracellular components
				Collagen and other fibers
				Proteoglycan particles
				Matrical lipidic debris, spherical microparticles, and matrix vesicles
			Cellular components
		Pericardium
		Valves
			Atrioventricular valves
			Semilunar valves
	Genetics
	Summary
	References
3 Age-related cardiovascular changes and diseases
	Introduction
	Nonspecific cardiovascular changes of aging
		Changes in the weight and appearance
		Size and shape of chambers
		Changes in the valves
			Aortic valve
			Mitral valve
			Pulmonic valve
			Tricuspid valve
			Jet lesion
	Changes in the conduction system
		Sinoatrial node
		Atrioventricular node
		Cardiac autonomic nervous system
	Changes in arteries
		Aorta
		Coronary artery
		Carotid artery
		Pulmonary artery
		Mönckeberg’s sclerosis (medial calcific sclerosis)
	Age-related diseases
		Coronary artery disease
		Myocardial infarction
		Tako-Tsubo (stress) cardiomyopathy
		Amyloidosis
			Isolated atrial amyloidosis
			Senile systemic amyloidosis
			Senile aortic amyloid
		Cardiomyopathies
			Dilated cardiomyopathy
			Hypertrophic cardiomyopathy
			Idiopathic restrictive cardiomyopathy
			Arrhythmogenic cardiomyopathy
		Valvular disease
			Degenerative (calcific) aortic stenosis
			Myxoid change and regurgitation
			Postinflammatory valvular disease
			Functional valvular disease
			Nonbacterial thrombotic endocarditis
		Arrhythmia
			Atrial fibrillation
			Atrioventricular block
			Sick sinus syndrome
		Heart failure accompanied by preserved ejection fraction
	Genetic and molecular aspects of cardiovascular aging
		Genetics and molecular biology
			Role of oxidative stress
			d-Galactose-induced aging
			Proteostasis
			Long noncoding RNA
			Telomere
		Disorders of premature aging
			Hutchinson–Gilford progeria syndrome
			Werner syndrome
	Summary
	References
4 Fundamental principles in cardiovascular genetics
	Central concept figure
	Notable abbreviations
	Genetic variation
		Aneuploidy
		Translocations and other variant chromosomes
		Insertions and deletions (indels)
		Copy number variations
		Single-nucleotide variants
	Modern molecular diagnostics
		Karyotyping
		In situ hybridization
		DNA microarray
		Polymerase chain reaction
		Multiplex ligation-dependent probe amplification
		Classical sequencing
		Next generation sequencing
		Expression studies
		Epigenetic studies
		Other “omics”
	Identifying the genetic basis of cardiovascular disease
		Linkage analysis
		Genome-wide association studies
		Sequencing-based linkage
		Odds ratios
	Molecular diagnostics in cardiovascular pathology practice
		Knowing when to test
		Choosing the right test
		Choosing the right specimen
		Variant interpretation
	Summary
	References
5 Pathophysiology of heart failure and an overview of therapies
	Overview of heart failure
		Definition of heart failure and general features of the condition
		Prevalence and socioeconomic burden of heart failure
		Long-term prognosis: morbidity and mortality
		Risk factors and underlying causes of heart failure
	Clinical presentation and diagnostic criteria
		Diagnosing heart failure
		Symptomatic presentation in patients
		Structural and functional
			Biomarkers
		Criteria for classifying heart failure severity
	Pathophysiology of heart failure
		Structure of the failing heart
		Hemodynamic alterations in heart failure
		Left and right heart failure
		Myocardial remodeling in heart failure: cell death and regeneration
		Heart failure with preserved ejection fraction
	Neurohormonal alterations in heart failure
		Neurohormonal paradigm
		Sympathetic nervous system in heart failure
		Renin–angiotensin–aldosterone system in the failing heart
		Other neurohormonal abnormalities in heart failure
		Therapeutic neurohormonal modulation
		Signaling responses to various stimuli during heart failure
		Physiological hypertrophy
		Insulin/IGF-1
		PI3K/Akt/GSK-3β
		Mammalian target of rapamycin
		Pathological hypertrophy
		Hypertension
		Calcineurin
		Small guanosine triphosphate-binding proteins Ras/Rho
		Protein kinase C
		Serum response factor/GATA4
		Beta-adrenergic/alpha-adrenergic/renin–angiotensin–aldosterone system
		Calpains
		Protein synthesis/protein degradation
		Ubiquitin proteasome system
		Mammalian target of rapamycin
		Micro-RNA
		Diabetic cardiomyopathy
		Nuclear factor-κB
		Peroxisome proliferator-activated receptor
		Heart failure-related alterations in cellular function and biochemical pathways
	Myocardial architecture
		Cardiomyocyte apoptosis/necrosis
		Fibroblast activity
		Extracellular matrix and fibrosis
		Cellular infiltration
		Angiogenesis
		Cardiomyocyte contraction/shortening
	Molecular responses and adaptation of cardiac cells
		Structural remodeling
		Activation of fetal gene expression and physiological adaptations of the heart during heart failure
		Calcium handling
		Contractile apparatus
		Inflammation
		Tumor necrosis factor α
		Interleukin-6 family
		Oxidative stress
		Autophagy
	Metabolic remodeling in heart failure
		Energy demand of the myocardium
		Coronary blood flow and myocardial oxygen uptake (MVO2)
		ATP and substrate utilization in energy metabolism
		The creatine kinase (CK) system
		Glucose metabolism
		Fatty acid metabolism
		Feedback regulation of metabolism
		Mitochondrial dysfunction
		Metabolic remodeling in the failing heart
		Metabolic intermediates: beyond ATP production
		Summary of heart failure
		Therapeutic management of heart failure
		Goals of heart failure therapies
		Management components
		Treating underlying cardiovascular disease
		Pharmacologic therapy of heart failure
		Exercise training
		Surgical interventions for heart failure
		Mechanical circulatory support devices
	Short- to intermediate-term circulatory support devices
		Intraaortic balloon pump
		Abiomed Impella
		Extracorporeal membrane oxygenation
		Ventricular assist devices
		Devices
		First generation
		Extracorporeal and paracorporeal ventricular assist devices
		Intracorporeal ventricular assist devices
		Second generation
		HeartMate II
		Jarvik 2000
		Third generation
		HeartMate III
		HeartWare HVAD and MVAD
		DuraHeart LVAS
		VentrAssist LVAD
		EvaHeart
		Incor Berlin Heart
		Clinical outcomes of ventricular assist devices
		Resuscitation procedures in ventricular assist device patients
		Complications related to mechanical cardiac support
		Hemorrhage
		Thrombotic and thromboembolic events
		Infection
		Device malfunction
		Cardiac arrythmias and fibrillations
		Right ventricular failure
		Tricuspid regurgitation
		Left atrium collapse
		Mitral valve
		Left ventricle
		Aortic valve
		Examination of ventricular assist device
		Surgically submitted tissue
		Cost-effectiveness of mechanical circulatory support devices
		Total artificial heart
		SynCardia
		AbioCor
		Wireless energy transfer
		Managing arrhythmia in heart failure
		Pacemakers and cardiac resynchronization therapy
		Implantable cardioverter defibrillators
		Cardiac resynchronization-defibrillation therapy
		Cardiac remodeling surgery in heart failure
		Dor procedure
		Batista procedure
		Dynamic cardiomyoplasty
		Passive restraint devices
		Elastic diastolic assist devices
	Conclusion
	Summary
	References
6 Congenital heart disease: pathology, natural history, and interventions
	Abbreviations
	Introduction
	Definition
	Epidemiology
		Prevalence
		Mortality
		Survival
	Etiology
		Genetic risk factors
		Environmental risk factors
	Embryology of the cardiovascular system
		Molecular biology of genes controlling development of the cardiovascular system
		Morphogenesis of the cardiovascular system
	Clinical features and consequences
	Specific forms of congenital heart disease
		Body habitus and position of the heart
		Right-to-left shunts
			Tetralogy of Fallot
			Dextro-transposition of the great arteries
			Levo-transposition of the great arteries
			Tricuspid atresia
			Persistent truncus arteriosus
			Total anomalous pulmonary venous connection
			Double outlet right ventricle
			Ebstein’s anomaly
			Hypoplastic left heart syndrome
		Left-to-right shunts
			Patent foramen ovale
			Atrial septal defects
			Patent ductus arteriosus
			Ventricular septal defects
			Atrioventricular septal defects
		Obstructions: valvular and vascular anomalies
			Pulmonary valve stenosis
			Coarctation of the aorta
			Aortic valve stenosis
			Other anomalies of the thoracic aorta
	Surgical and nonsurgical interventions
	Congenital heart disease in the adult
	Natural history without and with interventions
	Summary
	References
7 Vascular Pathobiology: Atherosclerosis and Large Vessel Disease
	Introduction to atherosclerosis
	Epidemiology and risk factors
	Gross and microscopic morphology of the fibroinflammatory lipid plaque
		Precursor lesions
			Fatty streaks
			Intimal thickening
			Gelatinous lesions
			Mural microthrombi
		Fibroinflammatory lipid plaque (atheroma)
		Complicated advanced plaque
	Steps in atherosclerotic plaque formation and complications
		Initiation/formation stage
			Precursor lesions, endothelial dysfunction, lipoprotein metabolism, macrophage activation
			ECM alterations
			Inflammation
			Early plaque growth
		Adaptation stage
			Vessel wall remodeling
			Continual plaque growth
		Clinical stage
			Plaque complications
			Advanced plaque growth
			Plaque rupture
			Atherosclerotic aneurysm
			Regression
	Cellular function and pathways in atherogenesis
		Endothelial functions
		Vascular SMCs, vasomotion, and phenotypic modulation
		Inflammatory cells and pathways
			Macrophages
			Dendritic cells
			Lymphocytes
			Mast cells
		Cell–cell adhesion
			Cadherins
		Cell–matrix interactions
			Collagen
			Elastin
			Fibronectin
			Other ECM proteins
		Matrix synthesis and degradation
		Vascular calcification
		Hemodynamic forces and mechanotransduction
		Epigenetic regulation
			DNA methylation
			Histone modifications
			MicroRNAs
			Long noncoding RNAs
		Stem/progenitor cells
	Nonatherosclerotic diseases of the aorta
		Annuloaortic ectasia
		Aneurysm of the sinus of Valsalva
		Aortic dissection
		Marfan syndrome
		Loeys–Dietz syndrome
		Ehlers–Danlos syndrome
		Aortitis
			Pyogenic aortitis and infectious aneurysm
			Takayasu aortitis
			Kawasaki disease
			Giant cell aortitis
			Rheumatoid aortitis
			Ankylosing spondylitis
			Syphilitic aortitis
			Tuberculous aortitis
		Reactive arthritis
		Behcet disease
		Inflammatory aneurysm of the abdominal aorta
		Trauma
	Summary
	References
8 Diseases of small and medium-sized blood vessels
	Introduction
	Vascular activation and common vascular pathologic changes
	Congenital vascular diseases
		Caliber-persistent artery (Dieulafoy’s disease)
		Congenital arteriovenous fistula
		Congenital pulmonary artery stenosis
		Unilateral absence of pulmonary artery
		Scimitar syndrome
		Anomalous pulmonary venous connection
	Genetic vascular disorders
		Alkaptonuria
		Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
		Cutis laxa
		Pseudoxanthoma elasticum
		Homocystinuria and hyperhomocysteinemia
		Neurofibromatosis type 1
		Myotonic dystrophy
		Sickle cell disease
		Fabry disease
		Menkes disease
		Mucopolysaccharidoses
		Mucolipidoses
		Osteogenesis imperfecta
		Hereditary hemorrhagic telangiectasia
		Klippel-Trenaunay syndrome
	Endocrine/metabolic vascular disorders
		Diabetic vasculopathy
		Hypothyroidism
	Vasculitis
		Introduction to vasculitis
		Small vessel vasculitis
		Granulomatosis with polyangiitis
		Eosinophilic granulomatosis with polyangiitis
		Microscopic polyangiitis
		Henoch–Schönlein purpura
		Cryoglobulinemic vasculitis
		Drug-induced vasculitis
		Polyarteritis nodosa
		Cutaneous polyarteritis nodosa
		Cutaneous lymphocytic thrombophilic (macular) arteritis
		Kawasaki disease
		Primary angiitis of the central nervous system
		Behçet’s disease
		Cogan syndrome
		Systemic lupus erythematosus
		Rheumatoid vasculitis
		Giant cell arteritis
		Takayasu arteritis
		IgG4-related disease
		Vasculitis mimics
	Infection
		Rocky mountain spotted fever
		Epidemic typhus
		Scrub typhus
		Queensland tick typhus
		Q fever
		Meningococcus
		Pseudomonas
		Syphilis
		Fungi
		Whipple disease
		Leptospirosis
		Schistosomiasis
		Lyme disease
		Filoviruses
		Betacoronaviruses
	Toxic vasculopathies
		Vascular toxicity of drugs
	Coagulopathic disorders
		Thrombotic thrombocytopenic purpura
		Heparin-induced thrombocytopenia
		Hemolytic uremic syndrome
		Disseminated intravascular coagulation
	Hypertension
		Systemic hypertension
		Pulmonary hypertension
	Vascular deposition disorders
		Amyloidosis
		Light-chain deposition disease
		Vascular calcification (Mönckeberg’s arteriosclerosis)
		Calciphylaxis
		Oxalosis
	Intimal proliferative diseases
		Idiopathic intimal hyperplasia of small arteries and arterioles
		Progressive arterial occlusive disease (Köhlmeier-Degos)
		Moyamoya disease
		The hypothenar hammer syndrome
		Arterial endofibrosis
	Arterial dissections
		Cervical artery dissections
		Spontaneous coronary artery dissection
		Segmental arterial mediolysis
		Pulmonary interstitial emphysema
	Miscellaneous conditions
		Fibromuscular dysplasia
		Thromboangiitis obliterans
		Cystic adventitial disease
		Radiation vasculopathy
		Dermal angiopathy of end-stage renal disease
		Pulmonary capillary hemangiomatosis
		Misalignment of lung vessels
		Angiodysplasia of the gastrointestinal tract
		Cerebral aneurysms
		Pulmonary vascular complications of chronic liver disease
	Disorders of veins
		Phlebosclerosis
		Varicose veins
		Venous thrombosis (phlebothrombosis) and pulmonary embolism
		Superficial thrombophlebitis
		Enterocolic lymphocytic phlebitis
		Hepatic venoocclusive disease (sinusoidal obstruction syndrome)
		Pulmonary venoocclusive disease
	Summary
	References
9 Aneurysms of the aorta: ascending, thoracic, and abdominal and their management
	Introduction
	Normal anatomy and histology of the aorta
	Aging changes of the aorta
	Thoracic aortic aneurysms
		Aneurysms of the ascending thoracic aorta
		Annuloaortic ectasia
		Aneurysm of the sinus of Valsalva
		Aneurysms of the transverse or descending thoracic aorta
	Etiology and pathologic findings
		Marfan syndrome
		Familial thoracic aortic aneurysm syndrome
		Loeys–Dietz syndrome
		Ehlers–Danlos syndrome
		Bicuspid aortic valve
		Turner syndrome
		Aortitis
		Takayasu’s arteritis
		Giant cell arteritis
		IgG4-related sclerosing disease-associated aortitis
		Syphilitic aortitis
		Rheumatoid aortitis
		Ankylosing spondylitis
		Reiter’s syndrome
		Behçet’s disease
		Granulomatosis with polyangiitis
		Infectious aortitis (aneurysm) (previously referred to as “mycotic”)
		Traumatic pseudoaneurysms
		Thoracic aortic aneurysms: pathologic findings
	Clinical presentation and natural history
		Natural history
	Abdominal aortic aneurysm
		Atherosclerotic aneurysms
		Aortic thrombosis
		Pathology and biologic mechanism
		Natural history
		Inflammatory aneurysms of the abdominal aorta
		Genetics of abdominal aortic aneurysm
	Aortic dissection
		Classification
		Associated conditions and etiologic factors
		Pathologic findings
		Ultrastructural findings
		Clinical presentation
		Complications and cause of death
		Imaging studies
		Abdominal aortic dissections
	Management
		Medical
		Surgical
		Endovascular aneurysm repair
		Thoracic endovascular repair
		Complications
	Summary
	References
10 Myocardial ischemia and its complications
	Definition and history
	Universal definition of myocardial infarction
	Clinical manifestations
	Epidemiology
	Biochemical changes with ischemia and biochemical markers
	Ultrastructural evolution of acute ischemic injury
	Cellular and subcellular mechanisms of myocardial injury
	Microscopic evolution of acute ischemic injury
	Morphology of coronary arteries and plaques
	Tako–Tsubo cardiomyopathy
	Gross evolution of acute ischemic injury
	Patterns of myocardial infarction
	Phenomena associated with ischemic injury
		Stunned myocardium
		Conditioned myocardium
		Hibernating myocardium
		Infarct expansion
		Ventricular remodeling and compensatory hypertrophy
	Reperfusion of ischemic myocardium
	Complications of myocardial infarction
		Left ventricular dysfunction
		Left ventricular aneurysm
		Rupture of the free wall
		Ventricular septal defect
		Mitral regurgitation
		Endocardial mural thrombi
		Electrophysiologic abnormalities
		Sudden cardiac death
		Pericardial lesions
		Chronic ischemic heart disease
	Recognition and quantification of acute ischemic injury
	Pathology of interventions
	Pathophysiological and pharmacological interventions
	Genetics and molecular biology of ischemic heart disease
	Genetics of coronary artery disease
		CAD as a monogenic disease
		CAD as a complex disease
		The 9p21 locus
		Other CAD loci
	Molecular biology of coronary artery disease
		From genomic loci to mechanism
		From mechanism to therapy
	Cell-based therapies for ischemic heart disease
	Summary
	References
11 Pathology of sudden death, cardiac arrhythmias, and conduction system
	Sudden death
		Introduction
		Definition of terms
		Epidemiology
		Pathophysiologic mechanisms and prevalence of sudden death
			Cerebral
			Respiratory
			Cardiovascular
			Mechanical arrest
			Arrhythmic arrest
		Aortic rupture and sudden cardiac death
			Syphilitic aneurysm
			Mycotic aneurysm
			Aortic dissection
			Atherosclerotic aneurysm
		Arrhythmic sudden cardiac death
			Coronary artery disease
				Atherosclerotic coronary artery disease
					Acute myocardial infarction
					Healed myocardial infarction
					Transient ischemia
				Congenital coronary artery anomalies
					Origin of the coronary artery from pulmonary artery
					Origin from aorta
				Nonatherosclerotic, acquired coronary artery disease
					Coronary embolism
					Coronary artery dissection
					Coronary arteritis
			Cardiomyopathies
				Dilated cardiomyopathy
				Hypertrophic cardiomyopathy
				Restrictive cardiomyopathy
				Arrhythmogenic cardiomyopathy
				Myocarditis
				Idiopathic left ventricular hypertrophy
			Valve diseases
				Aortic stenosis
				Mitral valve prolapse
				Ebstein malformation
			Ion channel diseases
				Long QT syndrome
				Short QT syndrome
				Brugada syndrome (nonischemic ST segment elevation)
				Catecholaminergic polymorphic ventricular tachycardia
		Other rare conditions
			Sudden death after heart surgery
			Sudden death and congenital heart diseases
		Sudden death in the athlete
		How to detect diseases at risk of sudden death through cardiological screening
		In vivo diagnosis of concealed defects, treatment, and prevention
		Prevention of sudden death and the pathologist’s role
	Cardiac conduction system
		Normal anatomy
			Sinoatrial node
			Internodal and interatrial pathways
			Atrioventricular conduction system
			Innervation
		Pathology
			Sinoatrial block
			Atrioventricular block
			Iatrogenic
			Ventricular preexcitation
				Wolff–Parkinson–White syndrome
				Lown–Ganong–Levine syndrome
			The conduction system in congenital heart diseases
	Atrial fibrillation
	Appendix guidelines for postmortem study of sudden death
		Clinical information relevant to autopsy
		Final recommendation
	Acknowledgments
	Summary
	References
12 Toxins and the heart
	Introduction
	Endocardium
		Valve injury
		Endocardial fibrosis
	Myocardium
		Myocarditis
		Acute myocardial cell death
		Dilated cardiomyopathy and depressed cardiac function
		Cardiac hypertrophy
	Pericardium
	Coronary arteries and ischemia
	Conduction system
	Specific drug considerations
		Alcohol
		Chemotherapeutic agents
		Sympathomimetics
			Cocaine and recreational drugs
			Weight loss
			Attention deficit hyperactivity disorder
		Opiates/opioids
		Marijuana
		Psychotropic medications
		Nonsteroidal antiinflammatory drugs
		Other stimulants
	Environmental pollutants
	Myocardial toxins as a cause of death
	Genetics and molecular biology
	Summary
	References
13 Myocarditis
	Abbreviations
	Definition of myocarditis
	Diagnosis of myocarditis
	Histopathologic patterns of myocarditis
		Lymphocytic myocarditis
		Granulomatous myocarditis
		Giant cell myocarditis
		Myocarditis with well-formed granulomas (cardiac sarcoidosis and others)
		Eosinophilic myocarditis
		Neutrophilic myocarditis
		Healing and healed myocarditis
		Myocardial vasculitis
		Borderline and acellular myocarditis
		Distinguishing from ischemia
	Etiologies of myocarditis
		Viral myocarditis
		Bacterial, fungal, and parasitic myocarditis
		Hypersensitivity and toxic myocarditis
		Autoimmune myocarditis
		Immune checkpoint inhibitor-related myocarditis
	Treatment of myocarditis
	Molecular and genetic technologies and considerations in myocarditis
		Polymerase chain reaction
		In situ hybridization
		Next generation sequencing
		Genetic risk factors
	Summary
	References
14 Cardiomyopathies
	Definition and classification of cardiomyopathies
	Dilated cardiomyopathy
		Etiology and pathophysiology
			Genetic
			Inflammatory
			Toxic
		Gross morphology
		Microscopic features and role of endomyocardial biopsy in the diagnostic flowchart
		Peripartum cardiomyopathy
		Diabetic cardiomyopathy
		Primary endocardial fibroelastosis
	Hypertrophic cardiomyopathy
		Definition
		Etiology
		Sarcomeric hypertrophic cardiomyopathy
			Gross morphology
			Microscopic features
			Pathophysiology and clinical pathologic correlations
		Mitochondrial cardiomyopathies
			Mitochondrial genetics
			Gross morphology and histologic clues for the diagnosis of etiology
			Pathophysiology and clinical pathologic correlations
		Cardiomyopathy associated with Friedreich ataxia
		Cardiomyopathy associated with disorders of fatty acid beta oxidation
		Storage disease
			Anderson–Fabry disease
			Danon disease
			Glycogenosis
		Noonan syndrome
		Role of pathology in the diagnostic flowchart of unexplained left ventricular hypertrophy
	Arrhythmogenic cardiomyopathy
		Definition
		Etiology and pathophysiology
		Gross morphology
		Microscopic features and role of endomyocardial biopsy
		Natural history and clinical pathologic correlations
	Restrictive cardiomyopathy
		Definition
		Etiology
		Sarcomeric restrictive cardiomyopathy
		Amyloidosis
			Etiology
				Light-chain amyloidosis (AL)
				Transthyretin-related amyloidosis (ATTR)
			Morphologic features
			Diagnosis and typing of amyloidosis
			Clinical pathologic correlations
		Myofibrillar myopathies
		Iron-overload cardiomyopathy
			Etiology and pathophysiology
			Morphologic features and role of ancillary techniques
		Endomyocardial fibrosis
	Others
		Left ventricular noncompaction
		Stress cardiomyopathy (Takotsubo disease)
		Histiocytoid cardiomyopathy
	Genetics and molecular biology
	Summary
		Overview
		Dilated cardiomyopathy (DCM)
		Hypertrophic cardiomyopathy (HCM)
		Arrhythmogenic (right ventricular) cardiomyopathy (AC)
		Restrictive cardiomyopathy (RCM)
	References
15 The pericardium and its diseases
	Normal pericardium
		Structure
			Anatomy
			Embryology
			Histology
		Physiology
	Patterns of pathology
		Reaction of pericardium to injury
		Fibrinous (“acute”) pericarditis
		Constrictive pericarditis
		Effusions and expansion of potential space
			Pericardial effusion, general
			Postsurgical
			Hemopericardium
			Chylopericardium
			Pneumopericardium
			Cardiac tamponade
	Diagnostic techniques
		Radiology
			Echocardiography
			Computed tomography
			Magnetic resonance imaging
			Positron emission tomography
		Tissue sampling
			Pericardiocentesis
			Biopsy
	Major diagnoses
		Physiologic derangements
			Myocardial infarction and Dressler syndrome
			Pregnancy
			Uremic pericarditis
		Infections
			Bacterial
				Tuberculosis
				Lyme disease
			Viral
			Fungal
				Histoplasmosis
				Candidiasis
				Others
			Parasitic
				Ameba
				Toxoplasma
				Echinococcus
				Chagas disease
				Filariasis
				Schistosomiasis
		Systemic disease
			Rheumatoid arthritis
			Rheumatic fever
			Systemic lupus erythematosus
			Systemic sclerosis
			IgG4 disease
			Vasculitides
			Endocrine and metabolic disorders
			Acquired immune deficiency syndrome-associated pericarditis
			Other
		Neoplasms and mass lesions
			Cysts
			Mesothelioma
			Malignant neoplasms and effusions
			Metastases
			Solitary fibrous tumor
			Angiosarcoma
			Germ cell tumors
				Teratomas
		Iatrogenic and extrinsic injury
			Postpericardiotomy syndrome
			Cardiovascular surgery
			Drug related
			Radiation
		Congenital
			Pericardial defect
			Diverticulum
		Idiopathic
	Molecular considerations
		Viral sequencing
			Tumors
	Summary
	References
16 Valvular heart disease
	Introduction
	Normal valvular function
	Valvular dysfunction
	Aortic stenosis
		Etiology
			Calcific aortic stenosis
		Congenital valvular stenosis
			Bicuspid aortic valvular stenosis
			Unicuspid aortic valvular stenosis
		Postinflammatory aortic stenosis
		Other causes of aortic stenosis
		Pathogenesis of aortic valve calcification
		Sequelae and complications
		Treatment of aortic stenosis
	Mitral stenosis
		Rheumatic mitral stenosis
			Incidence of acute rheumatic fever
			Etiopathogenesis of acute rheumatic fever
			Basic pathology of acute rheumatic fever
			Cardiac pathology in acute rheumatic fever
			Clinical features of acute rheumatic fever
			Sequelae of acute rheumatic fever
		Pathology
		Sequelae and complications
		Treatment [37]
	Nonrheumatic mitral stenosis
		Mitral regurgitation
			Mitral valve prolapse
		Pathology and pathogenesis
	Rheumatic mitral regurgitation
	Other causes of mitral regurgitation
		Sequelae
		Aortic regurgitation
	Tricuspid valvular dysfunction
	Pulmonary valvular dysfunction
	Verrucous endocarditis
		Infective endocarditis
			Etiology
			Pathogenesis [65,70]
			Pathology
			Sequelae and complications
			Clinical features
		Nonbacterial thrombotic endocarditis
			Etiopathogenesis
			Pathology
		Libman–Sacks endocarditis
	Summary
	References
17 Cardiac valve replacement and related interventions
	General considerations
		Clinical outcomes
		Sources of morbidity and mortality
			Pathologic considerations in operative mortality
			Late pathology
		Heart valve substitutes: mechanical and tissue valves
			Mechanical valves
			Tissue valves
		Structure–function correlations in tissue valve substitutes
			Aortic valve and pericardium
			Tissue changes induced by manufacture of a bioprosthesis
			Tissue changes following implantation
	Valve-related complications: clinical importance, morphology, secondary effects, and pathogenesis
		Obstruction and prosthesis-patient mismatch
		Thromboembolic complications
		Prosthetic valve endocarditis
		Structural valve deterioration
			Mechanical valves
			Bioprosthetic valves
		Nonstructural dysfunction
			Paravalvular leak
			Tissue overgrowth and extrinsic interference/occluder entrapment
			Hemolysis
	Other tissue valve substitutes
		Stentless porcine aortic valve bioprostheses
		Valvular allografts/homografts
		Pulmonary autograft aortic valve replacement (Ross procedure)
	Transcatheter valve implantation
		Clinical experience
		Devices
		Pathology
	Valve repair and valve sparing procedures
	New developments and future considerations
	Pathologic considerations in analysis of heart valve substitutes
		General considerations
		Prosthesis evaluation
	Disclosure
	Appendix. Some Heart valve prostheses approved by the FDA
	Summary
	References
18 The pathology of cardiovascular interventions and devices for coronary artery disease, vascular disease, heart failure, ...
	Introduction
	Endovascular therapies and myocardial revascularization
		Thrombolysis
		Balloon angioplasty
			Mechanisms of luminal expansion
			Comparison of percutaneous transluminal coronary angioplasty with thrombolytic therapy
			Complications
				Abrupt closure
				Late restenosis
		Atherectomy
		Endoluminal stents
			Bare-metal stents, drug-eluting stents, and new-generation stents
			Complications
			Pathologic findings in humans
		Coronary artery bypass graft surgery
			Mechanism of efficacy
			Complications
			Pathologic considerations
				Myocardial damage
			Bypass grafts
				Saphenous vein grafts
				Internal mammary artery
				Late symptom recurrence
		Transmyocardial revascularization
			Pathologic considerations
			Mechanisms
	Aortic and peripheral vascular replacement and reconstruction
		Vascular graft
			Dependence of patency on implant location, graft type, and other factors
			Graft healing
			Complications
		Endovascular prosthetic grafts
	Cardiac assist and replacement
		Pathologic considerations
			Complications
			Myocardial changes during cardiac assist
			Pathologic analysis of a removed ventricular assist device
	Arrhythmia control
		Cardiac pacemakers
			Complications
			Considerations at autopsy
		Implanted cardioverter-defibrillator
		Ablation or excision of arrhythmogenic foci
			Surgical treatment of arrhythmias
	Summary
	References
19 Tumors of the cardiovascular system: heart and blood vessels
	Incidence and classification
	Clinical symptoms
	Reactive cardiac masses and pseudotumors
		Mural thrombi
		Calcifying amorphous pseudotumor
		Inflammatory masses
		Mesothelial pseudotumors
	Ectopias
		Cystic tumor of the atrioventricular node
		Germ cell tumors of the heart
		Thyroid heterotopia
	Hamartomas and benign neoplasms
		Papillary fibroelastoma
	Hamartomas of the cardiac muscle
		Rhabdomyoma
		Adult cellular rhabdomyoma
		Histiocytoid/oncocytic cardiomyopathy, or purkinje cell hamartoma
	Benign fatty tumors
		Lipomatous hypertrophy of the atrial septum
		Cardiac lipoma
	Benign tumors of the myofibroblastic tissue
		Cardiac fibroma
	Miscellaneous benign fibrous tumors
		Cardiac hemangioma
	Cardiac myxoma
		Clinical findings
		Gross pathologic features
		Histologic features
		Immunohistochemical features
		Myxoma syndrome
		Molecular genetics of cardiac myxomas
		Differential diagnosis
	Benign neural neoplasms
		Paraganglioma
		Neurofibromas and schwannomas
		Granular cell tumor
		Malignant tumors
		Primary cardiac sarcomas
			Classification and prognosis
		Angiosarcoma
			Angiosarcoma: clinical and gross features
			Angiosarcoma: histologic features and differential diagnosis
		Undifferentiated pleomorphic sarcomas
			Undifferentiated pleomorphic sarcomas: histologic findings and differential diagnosis
		Leiomyosarcoma
		Rhabdomyosarcoma
		Miscellaneous sarcomas
		Cardiac lymphoma
			Incidence and clinical associations
			Pathologic findings
	Primary neoplasms and genetics
	Metastatic tumors
		Incidence and pathways of spread
		Clinical manifestations
		Metastases from epithelial tumors
		Metastases from nonepithelial tumors
		Pathologic features and surgical biopsy
	Sarcomas of the great vessels
		Sarcomas of the aorta
		Clinical findings
		Pathologic findings
		Treatment
		Sarcomas of the pulmonary artery
		Sarcomas of the inferior vena cava
	Summary
	References
20 Pathology of cardiac transplantation
	General clinicopathologic considerations
		Recipient and donor selection
		Heart transplantation surgery
		The role of pathology in heart transplantation
	Pathology of the explanted recipient heart
		Eosinophilic myocarditis
		Diseases which may recur in the allograft or affect recipient prognosis
		Discordance between pretransplant diagnosis and pathology of the explanted heart
		Pathology related to ventricular assist device
	Pathology of the donor heart
		Congenital or acquired heart disease
		Donor-transmitted infections
		Malignancy
		Ischemic injury acquired in the donor prior to procurement
	Pathology of the allograft
		Early graft failure
		Hyperacute rejection
		Ventricular failure or dysfunction
		Perioperative ischemic injury
		The pathology of rejection
		Acute cellular rejection
			Pathogenesis
			Histomorphology
			Grading systems for acute rejection
			Indications for therapeutic intervention
			Fatal acute rejection
		Antibody-mediated rejection
			Pathogenesis
			Histomorphology
			Immunohistochemistry and immunofluorescence studies
			Grading system for antibody-mediated rejection
			Relationship of antibody-mediated rejection to donor-specific antibodies
			Clinical considerations on treatment and outcome
		Endocardial inflammatory infiltrates (Quilty effect)
		Infection
		Malignancy
	Posttransplant lymphoproliferative disorders
		Cardiac allograft vasculopathy
			Morphology
			Pathogenesis
		Other long-term considerations
			Myocyte hypertrophy and interstitial fibrosis
			Denervation/reinnervation
			Systemic pathology secondary to immunosuppressive therapy
	Causes of death in heart transplant recipients
	Heart transplantation in combination with other organs
	Pathological review of an endomyocardial biopsy
		Specimen adequacy
		Specimen processing
			Use of frozen sections and rapid processing
		Specimen artifacts and caveats
		Reporting of endomyocardial biopsy results
	Approach to the examination of a failed allograft
	Noninvasive molecular testing for cardiac allograft rejection
	Future considerations
	Summary
	References
21 Basic pathobiology of cell-based therapies and cardiac regenerative medicine
	Introduction
	The rise (and fall) of the myocardial regeneration hypothesis
	Classic descriptions of growth, hypertrophy and failure of the heart
	Contemporary overview of cardiomyocytes biology
	Contemporary perspectives on myocardial pathobiology
	Experimental studies of stem cell therapy
	Clinical studies and trials of stem cell therapy
	Challenges to the rationale for cardiac stem cell therapy
	Regulatory considerations
	Alternatives to exogenous stem cell therapy
	Perspectives
	Summary
	References
22 Forensic aspects of cardiovascular pathology
	Investigative information
	General changes
	Cardiovascular pathology consultation
	Injuries of the heart and major vessels
		Penetrating injuries
		Blunt force injuries
	Primary diseases of the heart
		Congenital disorders
		Cardiomyopathies
		Channelopathies
	Infectious and inflammatory conditions affecting the heart
		Endocarditis
		Myocarditis
		Pericarditis
	Diseases of the cardiac valves
	Anomalies and diseases of the aorta and coronary arteries
	Systemic diseases affecting the heart and major vessels
		Metastatic tumors
		Immunological disorders
		Pulmonary disease
		Venous thromboembolic disease
	Ancillary studies
		Histology
		Toxicology
		Cultures and other studies
		Molecular genetics
	Sudden death following surgical and medical procedures
	Organ and tissue procurement
	Summary
	References
Index
Back Cover