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Chronic Heart Failure
Harriette F. Verwey, MD,PhDDept of cardiology
LUMCJune 2010
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Heart Failure
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Content
• Chronic Heart Failure
References.
ESC guidelines: Eur J Heart Fail 2008;10:933-989
ACC/AHA guidelines : J Am Coll Card 2009;53(15)
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Definition
• Heart Failure is a clinical syndrome including circulatory congestion or inadequate tissue perfusion, due to abnormal heart function and associated neurohormonal abnormalities
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Definition of Heart Failure (HF)
• HF is a clinical syndrome in which the patient have the following features
– Symptoms typical of HF • Breathlessness at rest or on exercise, fatigue,
tiredness, ankle swelling
– Signs typical of HF• Tachycardia , tachypnoea, rales, pleural effusion,
raised venous pressure etc
– Objective evidence of structural or functionalabnormality of the heart at rest• Cardiomegaly, S3,cardiac murmurs, abnormality on
echo, raised natriuretic peptides
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Epidemiology of CHF
• ESC population: > 900 million in 51 countries• Prevalence of HF : 15 million• Prevalence of asymptomatic LV dysfunction: 15 million• Estimated prevalence ~ 4 % of the population and increases with
age– Ageing of the population– Success of treatment of heart disease– Hypertension– Diabetes– Success of treatment in pts with malignancies– Obesitas
• Prognosis is poor: overall survival at 4 years is 50 %• HF : 5 % of acute hospital admissions/ 10 % of pts in hospital
beds and ~ 2% of national expenditure on health
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Prevalence of HF by Age and Gender
0
2
4
6
8
10
20-24 25-34 35-44 45-54 55-64 65-74 75+
Males
Females
Source: NHANES III (1988-94), CDC/NCHS and the American Heart Association
Perc
en
t of
Po
pu
lati
on
•• HF afflicts 10 out of every 1,000 over age 65 in the U.S.
United States 1988United States 1988--9494
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Annual absolute mortality in the E.U. for different pathologies
0 100000 200000 300000 400000 500000 600000 700000 800000
heart failure
sudden cardiac death
all cancers combined
lung cancer
colon/rectum cancer
breast cancer
prostate cancer
bowel cancer
ovary cancer
myocardial infarction
•( Murdoch RD et al. Importance of heart failure as a cause of death. Eur H J 1998;19 )
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The mortality from heart failure is as bad as , or even worse than, that of many common cancers
J. McMurray, H. Dargie, Chronic Heart Failure
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Netherlands
• Prevalence: 250.000 pts
• Incidence : 20.000 pts annually
• 10 % of the population > 75 years
• Poor prognosis due to progression of HF and sudden cardiac death
• 14 % of total hospital admissions for heart disease ( 8% of all types of heart and vessel)
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Prevalence of HF in relation to ageThe Rotterdam Study
• 55-64 year: 0.9%• 65-74 year: 4.0%• 75-84 year: 9.7%• >84 year: 17.4%
Bleumink GS et al. Quantifying the heart failure epidemic. The Rotterdam Study. Eur. Heart J 2004:25:1614-19.
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Life-time risk for HFThe Rotterdam Study
• 55 year: 30.2%• 65 year: 30.3%• 75 year: 28.7%• 85 year: 23.1%
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Class I
Asymptomatic heart failure
ejection fraction (EF) <40%
Class II
Mild symptomaticheart failure
with ordinaryexertion
Class IV
Symptomaticheart failure
at rest
Class III
Moderatesymptomatic heart failure
with less thanordinary exertion
Advisory Council to Improve Outcomes Nationwide in Heart Failure. Consensus recommendations for the management of chronic heart failure. Am J Cardiol. 1999;83(2A).
NYHA Class
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100100
75
50
25
0I II III IV
1
10
NYHA CLASS
An
nu
al s
urv
ival
(%
)
Ho
spit
aliz
atio
ns
/ ye
ar
Survival
Hospitalization
.1
•With the progress of the disease hospitalizations become frequent
Ondanks maximale medicatie
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NYHA II
12%
24%
64%
CHF
Other
SCD
NYHA III
26%
15%
59% CHF
Other
SCD
NYHA IV
56%
11%
33%
CHF
Other
SCD
MERIT-HF studie. Lancet 1999;353: 2001-07
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Gemiddelde HF populatie 1,2
15%
85%
IVCD
NCD
Severe Heart Failure class III/ IV 3-5
30%
70%
IVCD
NCD
Incidence of intraventricular conduction disturbances
1,2: Am H J 2002:; 143: 412-7/ Circ 2000; 102 ( 18 suppl II)
3-5: Am J Card 1993; 71: 720-6; Circ 1997; 95: 2660-7; Eur H J 2000;21:1246-50
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Heart Failure Definition
in which the heart is incapable of maintaining
a cardiac output adequate to accommodate the metabolic requirements
A Complex Clinical Syndrome
( E . Braunwald 1997)
in which the heart is incapable of maintaining
an adequate an adequate venous return.venous return.
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Classification of HF
• To the onset:– acute/ transient/ chronic
• Based on LV function:– HF with low ejection fraction: Systolic Heart Failure– HF with preserved ejection fraction: Diastolic Heart
Failure
• Clinical syndrome: – Forward vs backward failure
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Etiology of Heart Failure
Ischemic Heart DiseaseHypertension,
Idiopathic Cardiomyopathy,Infections
(viral myocarditis,Chagas’ disease),Toxins
(alcohol,cytotoxic drugs),Valvular Disease,
Prolonged Arrhythmias
InjuryInjury to the heart to the heart
What causes Heart Failure ?
Loss of a criticalLoss of a critical quantity of quantity of functioningfunctioning myocardialmyocardial cellscells
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The progression of Heart Failure
Ho et al., Epidemiology of Congestive Heart Failure
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The HF SyndromeThe HF Syndrome( Different Profiles) ( Different Profiles)
Systolic and Diastolic Dysfunction
70%
Diastolic Dysfunction and systolic function preserved
30%
(EF < 40%)(EF < 40%)(EF > 40 %)(EF > 40 %)
1 Lilly, L. Pathophysiology of Heart Disease. Second Edition p 200
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Ischemic Heart Disease
• Myocardial infarction: scar tissue• Chronic ischaemia : diffuse regional wall abnormalities.
» Hybernation» Stunning
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Hypertension
• Related to Diastolic Heart Failure: cardiac hypertrophy and cardiac fibrosis
• Diagnosis: echocardiography• Left ventricular hypertrophy
» Measurements of the IVS and LVPW thickness• Left ventricular mass: risk for CVD
» Male: ≥ 125 g/ m 2
» Female: ≥ 110 g/ m 2
• Concentric versus eccentric hypertrophy• Cardiac fibrosis• LV ejection fraction: > 45 %• Diastolic function
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Cardiomyopathies
• Primarily in the Heart– Genetic– Infectious disease– Metabolic disorders– Toxic– Endocrine– Infiltrative disease: Amyloid; rheumatoid disease
(MCTD); LE– Ageing– Idiopathic
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Valvular heart disease
• Valve stenosis: Aortic valve stenosis
• Valve incompetence: Mitral valve regurgitation» Aortic valve regurgitation
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Rhythm and conduction abnormalities
• Tachycardia and bradycardia
• Heart block
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Distribution of LVEF among women and men enrolled in the Euro Heart Survey
Hogg K et al. JACC 2004;43:317-27
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Kaplan-Meier Survival curves for Pts with Heart Failure and Preserved orreduced Ejection Fraction
N Engl J Med 2006;355:260-9
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Type hartfalen• HF + low EF: systolic HF• Younger• Males• Ischemic heart disease• Less comorbidity• Cardiologist• Evidence based medicine
(RCT)
• HF + normal EF: diastolicHF
• Older• Females• Hypertension• More comorbidities• GP/ internal med• Treatment: ?
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Definition
• Heart Failure is a clinical syndrome including circulatory congestion or inadequate tissue perfusion, due to abnormal heart function and associated neurohormonal abnormalities
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Cardiac Output
• Cardiac output is the amount of blood that the ventricle ejects per minute
Cardiac Output = HR x SV
44--8 liters / min8 liters / min 6060--100 ml100 ml
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StrokeStrokeVolumeVolume
PreloadPreload Afterload
Contractility
Determinants of Ventricular Function
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Preload Afterload
Contractility
Determinants of Ventricular Function
Cardiac OutputCardiac Output
Heart RateHeart Rate• Synergistic LV Contraction• Wall Integrity• Valvular Competence
StrokeStrokeVolumeVolume
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2) Frank Starling curve
Pressure-volume curves for the intact ventricle
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Relation pressure vs ECG
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Neuro HormonalNeuro Hormonal ActivationActivation MechanismMechanism
NormalNormal CardiovascularCardiovascular HomeostasisHomeostasis
HormonalHormonal SystemsSystems
SNSSNS RAASRAAS
VasopressinVasopressin
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Pathophysiology of HF
CompensatoryCompensatory mechanisms and mechanisms and secondary damagedamage
EjectionFraction
Asymptomatic SymptomaticTime
60%
20%
Secondary damage
Compensatorymechanisms
Trigger injury
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↑↑Sympathetic Nervous SystemSympathetic Nervous System
Compensatory Mechanisms: Sympathetic Nervous System
Decreased MAP
↑↑ContractilityContractility TachycardiaTachycardia VasoconstrictionVasoconstriction
↑↑SV x SV x ↑↑HR HR ↑↑TPR TPR
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Downloaded from: Heart Disease (on 4 April 2006 11:06 AM)
© 2005 Elsevier
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Compensatory Mechanisms
Neurohormonal Activation
Many different hormone systems are involved in maintaining normal cardiovascular homeostasis, including:
• Sympathetic nervous system (SNS)
• Renin-angiotensin-aldosterone system (RAAS)
• Vasopressin (a.k.a. antidiuretic hormone, ADH)
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Neurohormonal stimulation
• Actication of the Sympathetic nervous system:• Tachycardia• Increased Oxygen demand: ischaemia• Fibrosis• Increased cell death: apoptosis• Vasoconstriction• Activation of RAAS
• Activation of the Renin Angiotensin Aldosteron System• Retention of Sodium and H2O• Increased Aldosteron secretion• Vasoconstriction
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Volume Overload
Pressure Overload
Loss of Myocardium
Impaired Contractility
LV DysfunctionLV DysfunctionEF < 40%EF < 40%
Left Ventricular Dysfunction
CardiacCardiacOutputOutput
Hypoperfusion Hypoperfusion
End Systolic End Systolic Volume Volume
End Diastolic End Diastolic Volume Volume
Pulmonary CongestionPulmonary Congestion
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Hemodynamic Basis for HF Symptoms
LVEDP LVEDP
Left Atrial Pressure Left Atrial Pressure
Pulmonary Capillary Pressure Pulmonary Capillary Pressure
Pulmonary CongestionPulmonary Congestion
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Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52.
↑↑ CNS sympathetic outflow
Disease progressionDisease progression
CardiacCardiac sympatheticsympatheticactivityactivity
11--receptorsreceptors
22--receptorsreceptors
1-receptors
VasoconstrictionSodium retention
Myocardial toxicityMyocardial toxicityIncreased arrhythmiasIncreased arrhythmias
SympatheticSympatheticactivity to activity to kidneyskidneys
+ peripheral vasculature+ peripheral vasculature
ActivationActivationof RASof RAS
11-- 11--
Sympathetic Activation in Heart Failure
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Vasoconstriction
Oxidative StressStress
Cell GrowthGrowth Proteinuria
LV remodelingLV remodeling
Vascular remodelingremodeling
Angiotensinogen
Angiotensin II
Angiotensin IIII
AT I receptorI receptor
ReninRenin
AngiotensinAngiotensinConverting
EnzymeEnzyme
Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS)
!!
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Renin-Angiotensin-Aldosterone(↓ renal perfusion)
Salt-water retentionThirst
Sympathetic Augmentation Vasoconstriction
↑↑SV x SV x ↑↑HR HR ↑↑TPR TPR
Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS)
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VasodilatingVasodilating ActionsActions
NatriureticNatriuretic PepetidesPepetides
ANPANP BNPBNP
CNPCNP
Other Neurohormones
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Short- and Longterm results of activation of the neurohormonal
system• Retention of sodium and water: Increase of preload:
Congestion
• Vasoconstriction: increase of afterload
• SNS stimulation: increased oxygen expenditure
• Hypertrophy: cell death
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Packer (1998)
CNS: sympatheticactivation
1-receptoren
2-receptoren 1-receptoren
Hypertrophy and myocyte death,dilatation, ischaemia and
arrhythmia
Vasoconstriction &Na+-retention
Cardiac sympathetic activitation Renal and peripheralvascular& sympathetic
activitation
- Combined 1-, 1- en 2-blockade at heart failure (1) -
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Siragy, Am J Cardiol 1999:84;3S-8S; FogariFogari, Blood Pressure, 2001:10;6, Blood Pressure, 2001:10;6--1515Pfeffer, data gepresenteerd tijdens Scientific Sessions AHA, Orlando 2003FogariFogari, Blood Pressure, 2001:10;6, Blood Pressure, 2001:10;6--1515
RRenine AAngiotensin AAldosteron SSysteem
Angiotensinogen
Non-ACE Pathways(bijv. chymase)
Vasoconstriction Oxidative stress Cellgrowth Na+ /H2O retention Sympathic activation
renin Angiotensin I
Angiotensin IIACE
Cough, Angio-edema
Benefits?Bradykinin
Inactivemetabolites
Vasodilatation Antiproliferative
effects (kinines) NO release
Aldosteron AT2
AT1
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GFRGFRProteinurieProteinurieAldosteron releaseAldosteron releaseGlomerulaireGlomerulaire sclerosissclerosis
Angiotensine II and end organ damage
Rouleau J., data gepresenteerd tijdens WCC, Sydney 2002
ATAT11
receptorreceptor
AtherosclerosisAtherosclerosis**VasoconstrictionVasoconstrictionVasculaireVasculaire hypertrophyhypertrophyEndothelial dysfunctionEndothelial dysfunction
LV hypertrophyLV hypertrophyFibrosisFibrosisRemodelingRemodeling
CVACVA
DeathDeath
**
HypertensionHypertensionMI
Heart failHeart fail
Renal failRenal fail
AIIAII
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Siragy, Am J Cardiol 1999:84;3S-8S; FogariFogari, Blood Pressure, 2001:10;6, Blood Pressure, 2001:10;6--1515Pfeffer, data gepresenteerd tijdens Scientific Sessions AHA, Orlando 2003FogariFogari, Blood Pressure, 2001:10;6, Blood Pressure, 2001:10;6--1515
RRenine AAngiotensin AAldosteron SSysteem
Angiotensinogen
Non-ACE Pathways(bijv. chymase)
Vasoconstriction Oxidative stress Cellgrowth Na+ /H2O retention Sympathic activation
renin Angiotensin I
Angiotensin IIACE
Cough, Angio-edema
Benefits? Bradykinin
Inactivemetabolites
Vasodilatation Antiproliferative
effects (kinines) NO release
Aldosteron AT2
AT1
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Downloaded from: Heart Disease (on 4 April 2006 11:06 AM)
© 2005 Elsevier
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Symptoms of Heart Failure
• Reduced cardiac output• Decreased circulation: fatigue; dyspnea; mental
disturbancy. Loss of apetite. Sleep disorders• Vasoconstriction: pale, clammy skin• Decrease in urine output
• Retention of Sodium and fluid• Increased JVP• Pulmonary congestion• Ankle edema• Hepatomegaly
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Diagnosis of HF
• Careful assessement of symptoms• Pitfalls: elderly and obese patients• Poor relation between symptoms and severity of
cardiac dysfunction• Alertness, nutritional status, weight
• Careful physical examination• Bloodpressure/ pulse pressure• Fluid overload• Heart: murmurs• Lungs: respiratory rate; rales, pleural effusion
• Severity of HF: NYHA classification/ Killip classification and Forestor classification
• Diagnostic tests
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Additional diagnostic tests
• Electrocardiogram• Laboratory tests• X Ray• Echocardiography• Exercise tests ( 6 minute walk tests)• Nuclear imaging• Coronary and ventriculography• MRA• MSCT• Holter monitoring• Myocardial biopsy: suspected infiltrative diseases e.g.
amyloid; sarcoid; haemochromatosis; restrictive cardiomyopathy and eosinophylic myocarditis
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ECG at the first visit
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Downloaded from: Heart Disease (on 12 September 2005 09:10 PM)
© 2005 Elsevier
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Echocardiography
• Distinction between systolic versus diastolic dysfunction– HFPEF: diastolic dysfunction
– Presence of signs & symptoms of HF– Presence of normal or only mildly abnormal
LVEF≥45-50 %– Evidence of abnormal LV relaxation or diastolic
stiffness• Ejection fraction; RWM; valvular disease; filling status of
the ventricle• TOE: inadequate TTE; complicated valvular pts;
endocarditis; CHD; suspection of thrombus in LAA in pts with AF
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Echocardiography
Ultrasound
Fast, available
Function:Structural abnormalitiesIschaemia / infarctionValve diseaseHaemodynamic implications
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2D-echo
4 chamber view
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2D-echo
2 chamber view
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2D-echo
Short axis view
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3D-echo
Automatic border (TomtTec®) detection on 4D volume contrast acquisitions
LV functie
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10,23
7,88
4,192,99
02468
1012
level 1 level 2 level 3 level 4
Mo
rta
lity
%
n=201n=176 n=241 n=215
p<0.02
Distance Walked, m, byPerformance Level
Prediction of mortality and morbidity with a 6-minute
walk test in patients with LVD
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40,91
33,6127,44
19,9
11,2
22,16
3,72 1,99
0
10
20
30
40
50
level 1 level 2 level 3 level 4
Pa
tie
nts
ho
spit
ali
ze
d %
Distance Walked, m, byPerformance Level
Total hospitalized
P<0.001
Hospitalized for CongestiveHeart Failure
P<0.01
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Six-minute walk performance in patients with
moderate-to-severe heart failure
Opasich, et al. Eur Heart J 2001;22:488-196
3/4
1/2
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Nucleaire imaging techniek
SPECT scan “Mibi of Myoview” / PET scanRadioactiviteitMeestal beschikbaar, complexe techniekIschemie / infarct, hartfunctie, innervatie
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Nuclear ischaemia / infarction
Myoview scan: normal
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myoview scan: ischaemia
Nuclear scan: ischaemia / infarction
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myoview scan: myocardial infarction
Nuclear scan: ischaemia / infarction
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Techniques, FDG
• FDG: marker of glucose utilization
Hypoperfused myocardium with FDG uptake = viable
Maddahi et al. J Nucl Med 1994
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Techniques,Thallium-201
• Early uptake is perfusion
• Late uptake is cellmembrane integrity
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(Reverse) remodelingn=50 pts, Tl-201 imaging
40
60
80
100
DalleMule J et al. EJCTS 2002
viable nonviable
EDVI (ml/m2)
Pre-CABG
Post-CABG
<0.01
<0.01
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Ischemic CMPΔLVEF post-revascularization
30%
EF
58%
EF
12%
EF
N=355 pts with LVEF <35%
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3745
36 36
0
10
20
30
40
50
LVEF pre LVEF post LVEF pre LVEF post
perc
enta
ge
Viable + Viable -
Improvement of LVEF
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MRI scanMagneet golven
Matig-redelijk beschikbaarComplexe techniekGeen metaal (pm, ICD)
FunctieStructurele afwijkingenIschemie / infarctBeoordeling myocard
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FUTURE MRI: ONE-STOP SHOP!
graftsLV function: rest - dobu
viability
valve lesionscoronaries
Lamb, de Roos, Bax
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D
BA
F
C
E
RCA LAD
LCX
LCX
LADRCA
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A C
D
B
E F
RCA LAD
LCX
LCX
LADRCA
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Coronair angiografieAcuut myocard infarct
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