Valvular Heart Disease: A Companion to Braunwald's Heart Disease

Front Cover
Inside front cover
Front Matter
Valvular Heart Disease A Companion to Braunwald's Heart Disease FIFTH EDITION
Copyright
Contributors
Foreword
Preface
Acknowledgments
Braunwald's heart disease family of books
Table of Contents
1 Epidemiology of valvular heart disease
Key points
Incidence and prevalence of valve disease
Valve disease in industrially underdeveloped areas
Incidence of rheumatic fever and chronic rheumatic disease
Prevalence of rheumatic disease
Valve disease in industrially developed areas
Causes of valve disease
Rheumatic fever
Endomyocardial fibrosis
Calcific aortic stenosis
Mitral prolapse
Secondary mitral regurgitation
Secondary aortic regurgitation resulting from aortic dilation
Secondary tricuspid regurgitation
Infective endocarditis
Replacement heart valves
Congenital conditions
Systemic inflammatory conditions
Carcinoid, drugs, and radiation
Carcinoid
Drugs
Radiation
Disease by valve type
Aortic stenosis and regurgitation
Mitral stenosis
Mitral regurgitation
Right-sided valve disease
Tricuspid valve disease
Pulmonary valve disease
Multiple valve disease
Conclusions
References
2 Three-dimensional anatomy of the aortic and mitral valves
Key points
Mitral valve
Mitral valve anatomy
Mitral valve annulus
Mitral valve leaflets
Mitral valve commissures
Mitral valve chordae
Papillary muscles
3DE and mitral valve apparatus
3DE imaging
Image acquisition
Image display
3DE mechanisms of mitral valve dysfunction
Degenerative mitral valve disease
Ischemic mitral regurgitation
Mitral leaflet tethering in ischemic mitral regurgitation.
Mitral valve annulus in ischemic mitral regurgitation.
Leaflet growth in ischemic mitral regurgitation.
Treatment of ischemic mitral regurgitation.
3DE quantification of mitral regurgitation
3D vena contracta area
3D proximal isovelocity surface area
3D anatomic regurgitant orifice area
3D mitral inflow and left ventricular outflow tract stroke volume
Limitations of 3D-derived quantitative measurements for mitral regurgitation
Mitral stenosis
Aortic valve
Aortic valve anatomy
Aortic valve cusps
Aortic valve annulus
Aortic root complex
Aortic valve physiology
3DE imaging
Image acquisition
Image display
Roles for 3DE
Aortic valve anatomy
Native valves.
Prosthetic valves.
Endocarditis.
Aortic stenosis assessment
Left ventricular outflow tract.
Stroke volume quantification.
Aortic valve planimetry.
Transcatheter aortic valve replacement
Preprocedure: Aortic root assessment.
Periprocedure.
Postprocedure.
Aortic regurgitation assessment
Classification.
Vena contracta.
Stroke volume.
Aortic-mitral valve interactions
Conclusions
References
3 Molecular mechanisms of calcific aortic valve disease
Key points
Background
The normal aortic valve
General concepts
Experimental models
Initiation phase
Lipid deposition
Inflammation
Angiogenesis
Matrix remodeling and fibrosis
Angiotensin II
Valve interstitial cell and matrix interaction
Propagation phase
Bone morphogenetic protein signaling
WNT/β-catenin signaling
Transforming growth factor-β signaling
RANK, RANKL, and osteoprotegerin
Ectonucleotidases and matrix vesicles
Cell death as a contributor to non-osteogenic calcification
Additional modulators of osteogenic activity
Direct inhibitors of osteogenic signaling
SMAD6
Matrix GLA protein
Oxidative stress
Nitric oxide signaling
Peroxisome proliferator–activated receptor-γ signaling
NOTCH1/cadherin 11 signaling
Galectin 3
Dipeptidyl peptidase 4 inhibition
Fetuin-A
Epigenetic regulation of osteogenic signaling
Summary of molecular mechanisms in the valve
Myocardial response to pressure overload
Left ventricular hypertrophy
Diffuse interstitial fibrosis
Cell death and replacement fibrosis
Transition to heart failure
Translation to therapeutic interventions and future directions
Conclusions
Acknowledgments
References
4 Clinical and genetic risk factors for calcific valve disease
Key points
Calcific aortic valve disease
Clinical risk factors
Older age
Male sex
Race and ethnicity
Cigarette smoking
Blood pressure, hypertension, and vascular stiffness
Dyslipidemia and lipoprotein(a)
Diabetes, obesity, and the metabolic syndrome
Chronic kidney disease and mineral metabolism
Osteoporosis and bone metabolism
Aortic valve calcium
Multiple risk factors and risk scores
Genetic factors
Heritability
Mendelian disorders of calcific aortic stenosis
Candidate genes for calcific aortic stenosis
Genome-wide association studies and mendelian randomization
Mitral annular calcification
Risk factors
Genetic factors
Summary
References
5 Left ventricular and vascular changes in valvular heart disease
Key points
Left ventricular hemodynamics: Pressure-volume loops
Left ventricular hypertrophic remodeling
Changes to the left ventricle with left-sided valve disease
Aortic stenosis
Pressure overload
Effects on left ventricular remodeling and function
Mitral regurgitation
Volume overload
Effects on left ventricular remodeling and function
Aortic regurgitation: Mixed pressure and volume overload
Vascular properties and load
Pulmonary vascular changes
Systemic vascular changes
References
6 Principles of medical therapy for patients with valvular heart disease
Key points
The heart valve clinic
Diagnosis of valve disease
Preventive measures
Diagnosis and prevention of rheumatic fever
Prevention of infective endocarditis
Prevention of embolic events
Native valve disease with atrial fibrillation
Other indications for anticoagulation
Anticoagulation clinics
General health maintenance
Monitoring disease progression
Medical therapy
Prevention of progressive valve disease
Prevention of left ventricular contractile dysfunction
Prevention of left atrial enlargement and atrial fibrillation
Prevention of pulmonary hypertension
Symptoms caused by valve disease
Management of concurrent cardiovascular conditions
Hypertension
Coronary artery disease
Aortic disease
Arrhythmias
Heart failure
Noncardiac surgery in patients with valve disease
Patient education
References
7 Surgical and procedural risk assessment of patients with valvular heart disease
Key points
Risk algorithms
Goals
Construction of risk models
Limitations
Clinical utility
Predicted outcomes
Risk algorithms for surgical aortic valve replacement
Logistic EuroSCORE
STS-PROM risk model
Risk algorithms for transcatheter aortic valve implantation
German Aortic Valve Score
FRANCE 2 risk model
TAVI2-SCORe
OBSERVANT risk model
CoreValve U.S. risk score
STS/ACC TVT risk model
Frailty and procedural assessment
Integrative approach
References
8 Imaging the aortic valve
Key points
Imaging aortic valve anatomy
Normal anatomy of the aortic valve and aortic root
Echocardiography of normal aortic valve anatomy
Cross-sectional imaging of normal aortic valves
Congenitally abnormal anatomy of the aortic valve
Aortic stenosis severity
Echocardiography
Direct visualization and planimetry
Velocity and pressure gradients
Valve area by the continuity equation
Other echocardiographic measures of stenosis severity
Cardiac catheterization
Gated computed tomography angiography
Cardiac magnetic resonance imaging
Aortic regurgitation severity
Echocardiography
Color doppler parameters
Pulsed-wave doppler
Continuous-wave doppler
Quantitative assessment
Regurgitation quantitation by 3D echocardiography
Cardiac catheterization
Computed tomography
Cardiac magnetic resonance imaging
Assessment of pathophysiology
Aortic stenosis
Aortic regurgitation
Left ventricular volumes and size
Linear measurements
Volumetric measurements
Measures of ventricular function
Global left ventricular systolic function
Left ventricular mass
Cardiac magnetic resonance for evaluating left ventricular response to aortic valve disease
References
9 Aortic stenosis: Clinical presentation, disease stages, and timing of intervention
Key points
Stages of disease
Etiology
Clinical presentation
Clinical history
Physical examination
Evaluation
Echocardiography
Cardiac catheterization
Stress testing
Exercise treadmill stress testing
Low-dose dobutamine stress echocardiography
Computed tomography
Biomarkers
Clinical course
At risk for aortic stenosis (stage A)
Progressive mild to moderate aortic stenosis (stage B)
Asymptomatic severe aortic stenosis (stage C)
Symptomatic severe aortic stenosis (stage D)
Sudden death
Heart failure
Atrial fibrillation
Other
Medical therapy
Prevention of disease progression
Comorbid conditions
Periodic monitoring
Exercise limitations
Noncardiac surgery
Aortic valve replacement
Timing of intervention
Symptomatic severe aortic stenosis (stage D1)
Asymptomatic severe aortic stenosis (stage C)
Low-flow, low-gradient aortic stenosis with reduced ejection fraction (stage D2)
Low-flow, low-gradient aortic stenosis with preserved ejection fraction (stage D3)
Undergoing cardiac surgery
Choice of valve
Outcomes after aortic valve replacement
Clinical outcomes
Hemodynamic outcomes
Palliative care
References
10 Aortic regurgitation: Clinical Presentation, Disease Stages, and Management
Key points
Etiology
Acute aortic regurgitation
Diagnosis
Pathophysiology
Management
Chronic aortic regurgitation
Clinical presentation
Clinical history
Physical examination
Electrocardiography and chest radiography
Echocardiography
Other imaging modalities
Cardiac magnetic resonance.
Cardiac computed tomography.
Radionuclide angiography.
Exercise testing
Disease stages
Pathophysiology
Aortic regurgitation progression
Normal left ventricular systolic function.
Left ventricular systolic dysfunction.
Medical management
Vasodilator therapy
Endocarditis prevention
Serial evaluations
Indications for surgery
Aortic valve replacement or repair
Concomitant disease of the ascending aorta and aortic root
References
11 The bicuspid aortic valve and associated aortic disease
Key points
Prevalence
Etiology
Embryology
Genetics
Clinical phenotype
Valve anatomy
Associated cardiovascular lesions
Coarctation of the aorta
Turner syndrome
Coronary artery anomalies
Other congenital heart malformations
Aortopathy
Pathophysiology
Histopathology
Ascending aortic dilation
Clinical presentation and diagnosis
Physical examination
Transthoracic echocardiography
Transesophageal echocardiography
Other tomographic imaging
Overall disease course
Valvular complications
Aortic stenosis
Aortic regurgitation
Infective endocarditis
Aortic complications
Progressive aortic dilation
Risk of aortic dissection
Late aortic complications after aortic valve replacement
Recommendations for treating bicuspid aortic valve patients
Surgical treatment of the bicuspid aortic valve and ascending aorta
Pregnancy in patients with a bicuspid aortic valve
References
12 Transcatheter aortic valve replacement: Indications, procedure, and outcomes
Key points
Percutaneous aortic valve designs
Balloon-expandable valves
Self-expanding valves
Other valve systems
Randomized TAVR trials
Partner
Corevalve U.S. pivotal trial
Partner 2
Sapien 3 intermediate-risk registry
Surtavi
Reprise III
Portico
TAVR in patients at low surgical risk
Findings from TAVR registries
U.K. TAVI registry
U.S. TVT registry
TAVR guidelines
Patient selection
Complications and management
Postprocedural care
State-of-the-art TAVR
Ancillary devices used in TAVR
Cerebral embolic protection
Vascular closure devices
Expanding clinical indications
Valve-in-valve procedures
Bicuspid aortic valve disease
Low-flow aortic stenosis
Moderate aortic stenosis with left ventricular dysfunction
Asymptomatic severe aortic stenosis
Alternatives to TAVR
Surgical aortic valve replacement
Balloon aortic valvuloplasty
Conclusions
References
13 Imaging assessment for transcatheter aortic valve replacement
Key points
Preprocedural cardiac imaging
General principles
Echocardiography
Computed tomography
Magnetic resonance imaging
Annular and aortic root assessment
Computed tomography
Echocardiography
Magnetic resonance imaging
Novel techniques
Peripheral and central vascular access
Computed tomography
Magnetic resonance imaging
Novel techniques
Additional case planning
Prediction of delivery angles
Embolic protection planning
Coronary artery and bypass graft analysis
Emergency surgical planning
Left atrial appendage thrombus
Technical considerations
Computed tomography
Magnetic resonance imaging
Preprocedural noncardiovascular imaging
Periprocedural evaluation
Immediate preprocedural evaluation
Periprocedural guidance considerations
Immediate postprocedural evaluation
Postprocedural monitoring
Postprocedural valve assessment
Replacement valve durability
Postprocedural evaluation for cerebrovascular events
Future directions
References
14 Surgical approach to diseases of the aortic valve and aortic root
Key points
Approaches to the aortic valve and root
Median sternotomy
Minimally invasive approaches
Upper hemisternotomy
Right anterior thoracotomy
Aortic valve replacement
Bioprosthetic valves: Stented
Sutureless valves
Bioprosthetic valves: Stentless
Mechanical valves
Aortic homografts
Ross procedure
Guidelines for valve choice
Aortic valve repair
Risks of aortic valve surgery
Aortic root surgery
Indications
Aortic root replacement with composite valve-graft: Modified bentall procedure
Valve-sparing aortic root replacement: David and Yacoub procedures
Yacoub procedure
David procedure
Aortic root enlargement
Special challenges
Aortic dissection
Aortic valve replacement after previous coronary artery bypass graft
Aortic valve replacement after previous aortic valve replacement
Failed aortic root replacement
Porcelain aorta
Future perspectives
New bioprosthetic leaflet technology
Non-warfarin therapy for mechanical valves
Conclusions
References
15 Diagnostic evaluation of mitral regurgitation
Key points
Imaging mitral valve anatomy
Valve leaflets
Mitral annulus
Dilation
Calcification
Chordae tendineae
Papillary muscles
Left ventricular dysfunction
Echocardiographic evaluation of mitral regurgitation
Jet origin and direction
Regurgitant volume
Vena contracta
Proximal isovelocity surface area method
Supportive evidence for mitral regurgitant severity
Challenging issues in evaluation of mitral regurgitation
Dynamic changes in mitral regurgitation severity
Role of exercise echocardiography
Quantitation of secondary mitral regurgitation
Imaging the left ventricle
Pathophysiology
Assessment of myocardial contractility
End-systolic volume
Left atrial compliance
Evaluation of mitral regurgitation in patients undergoing transcatheter interventions
Preprocedural evaluation
Postprocedural evaluation
Other imaging approaches
Cardiac magnetic resonance
Cardiac computed tomography
Left ventricular angiography
References
16 Rheumatic and calcific mitral stenosis and mitral commissurotomy
Key points
Epidemiology
Pathophysiology
Mechanisms of valve obstruction
Hemodynamic consequences of mitral stenosis
Mitral gradient
Left atrium
Pulmonary circulation
Right heart
Left ventricle
Exercise physiology
Clinical presentation
History
Physical examination
Chest radiography and electrocardiography
Echocardiography
Assessment of severity
Assessment of valve morphology
Consequences of mitral stenosis
Mitral regurgitation
Associated lesions
Thromboembolic risk
Stress testing
Cardiac computed tomography
Cardiac catheterization
Natural history
Onset and progression of valvular lesions
Clinical outcome without intervention
Complications
Medical therapy
Prevention of rheumatic fever and infective endocarditis
Treatment of symptoms
Prevention of thromboembolism
Modalities of follow-up
Interventions for mitral stenosis
Surgical commissurotomy
Balloon mitral commissurotomy
Patient selection
Technique
Monitoring the procedure and assessing immediate results
Immediate results
Efficacy.
Failures.
Risks.
Predictors of immediate results.
Long-term results
Predictors of long-term results.
Applications of balloon mitral commissurotomy in special patient groups
After surgical commissurotomy.
Patients for whom surgery poses a high risk.
Surgical mitral valve replacement
Transcatheter prosthesis implantation
Treatment strategy
Rheumatic mitral stenosis
Calcific mitral stenosis
References
17 Mitral valve prolapse
Key points
Definition and anatomy
Pathogenesis
Natural history
Prevalence
Prognosis for mitral valve prolapse
Mortality, atrial fibrillation, and heart failure risks
Arrhythmias and risk of sudden death
Infective endocarditis
Echocardiographic evaluation
Assessment of regurgitant severity
Assessment of mitral regurgitation effects
Morphologic assessment of the valve
Management and timing of intervention
Class I or iia indications for intervention
Evaluation of asymptomatic patients and identification of high-risk subsets
Management of asymptomatic patients
Follow-up of conservatively managed patients
Summary
References
18 Secondary (functional) mitral regurgitation in ischemic and dilated cardiomyopathy
Key points
Definition
Epidemiology
Mechanism
Ischemic mitral regurgitation
Functional mitral regurgitation in the absence of coronary artery disease
Diagnosis
Echocardiography
Grading mitral regurgitation severity by echocardiography
Quantitative parameters
Integration of multiple parameters
Dynamic nature of mitral regurgitation
Value of exercise testing
Prognosis
Treatment
Medical therapy
Cardiac resynchronization therapy
Coronary revascularization
Surgical treatment of functional mitral regurgitation
Surgical mitral valve repair versus replacement
Transcatheter mitral valve therapies
Spectrum of functional mitral regurgitation
Conclusions
References
19 Surgical mitral valve repair and replacement
Key points
Surgical anatomy of the mitral valve
Mitral annulus
Mitral leaflets and commissures
Chordae tendineae
Papillary muscles and the left ventricle
Pathophysiologic triad of mitral valve regurgitation
Dysfunction
Etiology and lesions
Mitral valve surgery
Surgical approach
Mitral valve repair
Mitral valve replacement
Outcomes of mitral valve repair
Degenerative mitral valve disease
Ischemic mitral regurgitation
Rheumatic valve disease
Outcomes of mitral valve replacement
References
20 Transcatheter mitral valve repair and replacement
Key points
Rationale for transcatheter therapy
Classification of percutaneous repair techniques
Leaflet and chordal technology
Mitraclip
Other devices
Indirect annuloplasty
Direct annuloplasty and hybrid techniques
Left ventricular remodeling techniques
Transcatheter mitral valve replacement
Conclusions
References
21 Imaging guidance of transcatheter mitral valve procedures
Key points
Basic principles
Types of transcatheter mitral valve intervention
Goals of imaging guidance
Education and training for procedural imaging
Key steps for imaging guidance
Standard imaging tools
X-ray imaging
Two- and three-dimensional echocardiography
Intracardiac echocardiography
Cardiac magnetic resonance imaging
Multislice computed tomography
Advanced imaging tools
Echocardiographic-fluoroscopic fusion imaging
Overlay of computed tomography and fluoroscopy
Mitral valve 3d modeling
Rapid prototyping
General approach
Assessment of mitral valve morphology and function
Interatrial septum puncture
Catheters and devices
Imaging guidance of specific transcatheter mitral valve interventions
Balloon mitral commissurotomy
Mitral valve edge-to-edge repair
Preprocedural imaging planning
Intraprocedural guidance
Postprocedural assessment
Paravalvular mitral prosthesis leak repair
Preprocedural imaging planning
Intraprocedural guidance
Postprocedural assessment
Transcatheter mitral valve implantation and valve-in-valve percutaneous therapy
Conclusions and future directions
References
22 Intraoperative echocardiography for mitral valve surgery
Key points
Nomenclature
The intraoperative milieu
Pre-bypass assessment
Preoperative preparation
Systematic examination
Two-dimensional imaging
Epicardial echocardiography
Three-dimensional echocardiography
Mitral regurgitant severity
Loading conditions
Color doppler imaging
Vena contracta
Spectral doppler imaging
Reparability
Carpentier type I: Normal leaflet motion.
Carpentier type II: Excessive leaflet motion.
Carpentier type IIIB: Restricted systolic leaflet motion.
Carpentier type IIIA: Restricted systolic and diastolic leaflet motion.
Prosthetic valves
Tricuspid regurgitation
Post-bypass evaluation
Native valve assessment
Mitral valve systolic anterior motion
Prosthetic valve assessment
Assessment of proximate structures
Guidelines and outcomes
Conclusions
References
23 Diseases of the tricuspid valve
Key points
Pathophysiology of tricuspid valve disease
Primary versus secondary tricuspid valve disease
Response of the right heart to pressure and volume overload
Principles of diagnosis
Tricuspid valve stenosis and regurgitation
Stages of tricuspid valve disease
Assessment of right ventricular size and function
Pulmonary artery pressures
Tricuspid valve anatomy
Normal anatomy and variants
Changes in anatomy with disease states
Imaging of tricuspid valve leaflets
Tricuspid regurgitation
Etiology
Diagnosis
Natural history
Medical and surgical treatment
Overview
Indications for surgery
Tricuspid regurgitation with left-sided valve disease
Isolated tricuspid valve surgery
Tricuspid valve repair versus replacement
Specific considerations based on etiology
Flail tricuspid valve leaflets
Ebstein anomaly
Carcinoid heart disease
Secondary tricuspid regurgitation due to pulmonary thromboembolic disease or pulmonary arterial hypertension
Pacemaker- or defibrillator-induced tricuspid regurgitation
Tricuspid regurgitation in patients undergoing left ventricular assist device implantation
Atrial septal defect
Tricuspid stenosis
Etiology
Diagnosis
Natural history
Medical and surgical treatment
Summary
References
24 Pulmonic valve disease in adults
Key points
Overview of pulmonic valve disease
Etiology
Pathophysiology
Pulmonic, subpulmonic, and supravalvular pulmonary stenosis
Pulmonic valve stenosis
Background
Clinical presentation and assessment
Management and outcomes
Subpulmonic stenosis
Background
Clinical presentation and assessment
Management and outcomes
Supravalvular and peripheral pulmonary artery stenosis
Background
Clinical presentation and assessment
Management and outcomes
Tetralogy of fallot
Background
Surgical repair and residuae
Clinical presentation and assessment
Pulmonic regurgitation and timing of pulmonic valve replacement
Pulmonic valve replacement surgery and outcomes
Transcatheter pulmonic valve replacement
Background
Outcomes
Impact on management of pulmonic valve disease
References
25 Infective endocarditis
Key points
Epidemiology
Pathogenesis
Prevention
Diagnosis
Clinical manifestations
Diagnostic criteria
Blood cultures
Biomarkers and polymerase chain reaction
Transthoracic and transesophageal echocardiography
Indications
Echocardiographic findings
Other imaging modalities
Management
Medical therapy
Antibiotic therapy
Anticoagulant and antiplatelet therapies
Complications
Valve regurgitation and heart failure
Embolic events
Neurologic complications
Surgical intervention
Indications
Optimal timing
Surgical approach
Cardiac implantable electronic device removal
Long-term prognosis and follow-up
References
26 Prosthetic heart valves
Key points
Types of prosthetic heart valves
Mechanical valves
Durability and long-term outcomes
Tissue valves
Stented bioprostheses
Stentless bioprostheses
Homografts
Autografts
Transcatheter bioprostheses
Comparison of mechanical and tissue valves
Choice of valve procedure and prosthesis type
Valve procedure
Prosthetic valve type
Medical management and surveillance after valve replacement
Anti-thrombotic therapy
General principles
Interruption of anti-thrombotic therapy
Pregnancy
Infective endocarditis prophylaxis
Clinical assessment
Doppler echocardiography
Evaluation and treatment of prosthetic valve dysfunction and complications
Prosthesis–patient mismatch
Structural valve deterioration
Paravalvular leak
Thromboembolism and bleeding
Prosthetic valve thrombosis
Infective endocarditis
Hemolytic anemia
References
27 Management of bioprosthetic valve degeneration
Key points
History of prosthetic heart valves
Characteristics of bioprosthetic heart valves
Mechanisms of failure of bioprosthetic heart valves
Open heart surgery for bioprosthetic heart valve failure
Transcatheter aortic valve-in-valve implantation
Preclinical and early clinical studies
Clinical outcomes after transcatheter aortic valve-in-valve implantation
Valve-in-valve procedure for severe prosthesis–patient mismatch
Persistent stenosis after aortic valve-in-valve procedures
Clinical thrombosis of aortic valve-in-valve prostheses
Coronary obstruction after aortic valve implantation
Aortic valve-in-valve implantation in uncommon bioprostheses
Future perspectives
References
28 Valvular heart disease in pregnancy
Key points
Physiologic changes of pregnancy
Normal hemodynamic changes
Pregnancy
Positional changes
Peripartum and postpartum changes
Evaluation by echocardiography
Normal anatomic changes
Doppler changes
Epidemiology
Risk factors for adverse outcomes
Basic clinical approach
Evaluation of disease severity
Management during pregnancy
Clinical monitoring
Medical therapy
Effects of intercurrent illness
Heritability
Management in the peripartum period
Peripartum hemodynamic monitoring
Type of delivery
Timing of surgical intervention
Specific valvular lesions and outcomes
Aortic stenosis
Mitral stenosis
Aortic regurgitation
Mitral regurgitation
Right-sided valve disease
Prosthetic valves
Outcomes
Anticoagulation
References
Index
A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
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