Hc 01 intro heart failure verwey

transcript

Chronic Heart Failure

Harriette F. Verwey, MD,PhDDept of cardiology

LUMCJune 2010

Heart Failure

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)

Definition

• Heart Failure is a clinical syndrome including circulatory congestion or inadequate tissue perfusion, due to abnormal heart function and associated neurohormonal abnormalities

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

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

Prevalence of HF by Age and Gender

20-24 25-34 35-44 45-54 55-64 65-74 75+

Females

Source: NHANES III (1988-94), CDC/NCHS and the American Heart Association

•• HF afflicts 10 out of every 1,000 over age 65 in the U.S.

United States 1988United States 1988--9494

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 )

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

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)

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.

Life-time risk for HFThe Rotterdam Study

• 55 year: 30.2%• 65 year: 30.3%• 75 year: 28.7%• 85 year: 23.1%

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

100100

0I II III IV

NYHA CLASS

Survival

Hospitalization

•With the progress of the disease hospitalizations become frequent

Ondanks maximale medicatie

NYHA II

NYHA III

59% CHF

NYHA IV

MERIT-HF studie. Lancet 1999;353: 2001-07

Gemiddelde HF populatie 1,2

Severe Heart Failure class III/ IV 3-5

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

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.

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

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

The progression of Heart Failure

Ho et al., Epidemiology of Congestive Heart Failure

The HF SyndromeThe HF Syndrome( Different Profiles) ( Different Profiles)

Systolic and Diastolic Dysfunction

Diastolic Dysfunction and systolic function preserved

(EF < 40%)(EF < 40%)(EF > 40 %)(EF > 40 %)

1 Lilly, L. Pathophysiology of Heart Disease. Second Edition p 200

Ischemic Heart Disease

• Myocardial infarction: scar tissue• Chronic ischaemia : diffuse regional wall abnormalities.

» Hybernation» Stunning

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

Cardiomyopathies

• Primarily in the Heart– Genetic– Infectious disease– Metabolic disorders– Toxic– Endocrine– Infiltrative disease: Amyloid; rheumatoid disease

(MCTD); LE– Ageing– Idiopathic

Valvular heart disease

• Valve stenosis: Aortic valve stenosis

• Valve incompetence: Mitral valve regurgitation» Aortic valve regurgitation

Rhythm and conduction abnormalities

• Tachycardia and bradycardia

• Heart block

Distribution of LVEF among women and men enrolled in the Euro Heart Survey

Hogg K et al. JACC 2004;43:317-27

Kaplan-Meier Survival curves for Pts with Heart Failure and Preserved orreduced Ejection Fraction

N Engl J Med 2006;355:260-9

Type hartfalen• HF + low EF: systolic HF• Younger• Males• Ischemic heart disease• Less comorbidity• Cardiologist• Evidence based medicine

• HF + normal EF: diastolicHF

• Older• Females• Hypertension• More comorbidities• GP/ internal med• Treatment: ?

Definition

• Heart Failure is a clinical syndrome including circulatory congestion or inadequate tissue perfusion, due to abnormal heart function and associated neurohormonal abnormalities

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

StrokeStrokeVolumeVolume

PreloadPreload Afterload

Contractility

Determinants of Ventricular Function

Preload Afterload

Contractility

Determinants of Ventricular Function

Cardiac OutputCardiac Output

Heart RateHeart Rate• Synergistic LV Contraction• Wall Integrity• Valvular Competence

StrokeStrokeVolumeVolume

2) Frank Starling curve

Pressure-volume curves for the intact ventricle

Relation pressure vs ECG

Neuro HormonalNeuro Hormonal ActivationActivation MechanismMechanism

NormalNormal CardiovascularCardiovascular HomeostasisHomeostasis

HormonalHormonal SystemsSystems

SNSSNS RAASRAAS

VasopressinVasopressin

Pathophysiology of HF

CompensatoryCompensatory mechanisms and mechanisms and secondary damagedamage

EjectionFraction

Asymptomatic SymptomaticTime

Secondary damage

Compensatorymechanisms

Trigger injury

↑↑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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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)

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

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

Hemodynamic Basis for HF Symptoms

LVEDP LVEDP

Left Atrial Pressure Left Atrial Pressure

Pulmonary Capillary Pressure Pulmonary Capillary Pressure

Pulmonary CongestionPulmonary Congestion

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

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)

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)

VasodilatingVasodilating ActionsActions

NatriureticNatriuretic PepetidesPepetides

ANPANP BNPBNP

CNPCNP

Other Neurohormones

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

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) -

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

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

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

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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

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

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

ECG at the first visit

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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

Echocardiography

Ultrasound

Fast, available

Function:Structural abnormalitiesIschaemia / infarctionValve diseaseHaemodynamic implications

2D-echo

4 chamber view

2D-echo

2 chamber view

2D-echo

Short axis view

3D-echo

Automatic border (TomtTec®) detection on 4D volume contrast acquisitions

LV functie

4,192,99

level 1 level 2 level 3 level 4

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

33,6127,44

3,72 1,99

level 1 level 2 level 3 level 4

Distance Walked, m, byPerformance Level

Total hospitalized

P<0.001

Hospitalized for CongestiveHeart Failure

P<0.01

Six-minute walk performance in patients with

moderate-to-severe heart failure

Opasich, et al. Eur Heart J 2001;22:488-196

Nucleaire imaging techniek

SPECT scan “Mibi of Myoview” / PET scanRadioactiviteitMeestal beschikbaar, complexe techniekIschemie / infarct, hartfunctie, innervatie

Nuclear ischaemia / infarction

Myoview scan: normal

myoview scan: ischaemia

Nuclear scan: ischaemia / infarction

myoview scan: myocardial infarction

Nuclear scan: ischaemia / infarction

Techniques, FDG

• FDG: marker of glucose utilization

Hypoperfused myocardium with FDG uptake = viable

Maddahi et al. J Nucl Med 1994

Techniques,Thallium-201

• Early uptake is perfusion

• Late uptake is cellmembrane integrity

(Reverse) remodelingn=50 pts, Tl-201 imaging

DalleMule J et al. EJCTS 2002

viable nonviable

EDVI (ml/m2)

Pre-CABG

Post-CABG

Ischemic CMPΔLVEF post-revascularization

N=355 pts with LVEF <35%

LVEF pre LVEF post LVEF pre LVEF post

Viable + Viable -

Improvement of LVEF

MRI scanMagneet golven

Matig-redelijk beschikbaarComplexe techniekGeen metaal (pm, ICD)

FunctieStructurele afwijkingenIschemie / infarctBeoordeling myocard

FUTURE MRI: ONE-STOP SHOP!

graftsLV function: rest - dobu

viability

valve lesionscoronaries

Lamb, de Roos, Bax

RCA LAD

LADRCA

RCA LAD

LADRCA

Coronair angiografieAcuut myocard infarct

Hc 01 intro heart failure verwey

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