Introduction of Introduction of Cardiac FunctionCardiac Function

Theoretical Considerations of Cardiac Function

The cardiovascular system supplies the The cardiovascular system supplies the tissues with oxygen and metabolic tissues with oxygen and metabolic substrates and removes carbon dioxide substrates and removes carbon dioxide and other waste products. and other waste products.

This requires the integration of all its This requires the integration of all its components (venous circulation, right side components (venous circulation, right side of the heart, lungs and pulmonary of the heart, lungs and pulmonary vascular system, left side of the heart, vascular system, left side of the heart, arterial circulation, and blood). arterial circulation, and blood).

Theoretical Considerations of Cardiac Function

Most circulatory dysfunction of cardiac Most circulatory dysfunction of cardiac origin in adults is due to abnormalities of origin in adults is due to abnormalities of the left ventricle. the left ventricle.

Thus, the clinical evaluation of cardiac Thus, the clinical evaluation of cardiac function predominately concerns the function predominately concerns the performance of the left ventricle. performance of the left ventricle.

Levels of IntegrationMyocardium, Pump, Cardiac OutputMyocardium, Pump, Cardiac Output

The performance of the left ventricle as a pumThe performance of the left ventricle as a pump depends on the contraction of the sarcomeres p depends on the contraction of the sarcomeres in the myocardium as well as on the organizatioin the myocardium as well as on the organization and configuration of the left ventricular chamn and configuration of the left ventricular chamber, valvular function, and loading conditions.ber, valvular function, and loading conditions.

Ultimately, the interaction of the left ventricle, tUltimately, the interaction of the left ventricle, the other cardiac chambers, and the arterial, puhe other cardiac chambers, and the arterial, pulmonary, and venous circulations results in the lmonary, and venous circulations results in the cardiac output.cardiac output.

Levels of IntegrationThus, cardiac function can be evaluated at Thus, cardiac function can be evaluated at

several levels of integration:several levels of integration:

(1) myocardial function(1) myocardial function (2) chamber (usually left ventricular) (2) chamber (usually left ventricular)

pump performancepump performance (3) integrated cardiac output(3) integrated cardiac output

It is important to recognize at which level It is important to recognize at which level of integration cardiac function is being of integration cardiac function is being

evaluated.evaluated.

Factors Controlling Myocardial Function

(1) preload(1) preload (2) afterload(2) afterload

(3) the myocardial contractile state (3) the myocardial contractile state (contractility)(contractility)

(4) heart rate and cardiac rhythm.(4) heart rate and cardiac rhythm.

Measurement of Key Variables

Pressures Pressures

The intracardiac, arterial, and venous preThe intracardiac, arterial, and venous pressures are important variables used in assessures are important variables used in assessing cardiac function. ssing cardiac function.

These pressures have been traditionally mThese pressures have been traditionally measured using fluid-filled catheters.easured using fluid-filled catheters.

Arterial pressure can be obtained noninvaArterial pressure can be obtained noninvasively by sphygmomanometrysively by sphygmomanometry

Measurement of Key Variables

Noninvasive Pressure MeasurementNoninvasive Pressure Measurement

Cuff sphygmomanometry Cuff sphygmomanometry

arterial systolic and diastolic pressuresarterial systolic and diastolic pressures

Doppler echocardiographyDoppler echocardiography

determine the velocity of the systolic regurgitant jdetermine the velocity of the systolic regurgitant jet across the tricuspid, mitral, or aortic valves.et across the tricuspid, mitral, or aortic valves.

Measurement of Key Variables

Pulmonary Capillary Wedge PressurePulmonary Capillary Wedge Pressure

Because the pulmonary venous pressure Because the pulmonary venous pressure approximates left atrial pressure in most approximates left atrial pressure in most circumstances.circumstances.

The mean pulmonary capillary wedge prThe mean pulmonary capillary wedge pressure provides a clinically useful estimatessure provides a clinically useful estimate of mean left atrial pressure and the left e of mean left atrial pressure and the left ventricular filling pressure.ventricular filling pressure.

Measurement of Key Variables

Ventricular VolumeVentricular Volume Angiographic techniques provide the most Angiographic techniques provide the most

widely accepted means for measuring widely accepted means for measuring ventricular chamber volumes and ventricular chamber volumes and segmental wall motion. segmental wall motion.

They allow calculation of the extent and They allow calculation of the extent and velocity of wall shortening and the velocity of wall shortening and the assessment of regional wall motion.assessment of regional wall motion.

Although noninvasive techniques are now Although noninvasive techniques are now widely used in the assessment of widely used in the assessment of ventricular dimensions and volumes, ventricular dimensions and volumes, their application to the assessment of their application to the assessment of cardiac function is based on the earlier cardiac function is based on the earlier work using ventricular angiography, work using ventricular angiography, which remains a benchmark for these which remains a benchmark for these measurements.measurements.

Measurement of Key Variables

Quantitative AngiocardiolographyQuantitative Angiocardiolography

The left ventricle is outlined most clearly by direcThe left ventricle is outlined most clearly by direct injection of contrast medium into the ventricut injection of contrast medium into the ventricu

lar cavity.lar cavity.

In patients with severe aortic regurgitation the contrast mIn patients with severe aortic regurgitation the contrast material may be injected into the aorta, with the resultanaterial may be injected into the aorta, with the resultant reflux outlining the left ventricular cavity. Digital subt reflux outlining the left ventricular cavity. Digital subtraction angiography utilizing injections into a periphetraction angiography utilizing injections into a peripheral vein, pulmonary artery, or left ventricle also may be ral vein, pulmonary artery, or left ventricle also may be used to define the left ventricle.used to define the left ventricle.

Measurement of Key VariablesConclution (P177-179)

PressuresPressures

arterial systolic and diastolic pressuresarterial systolic and diastolic pressures

Pulmonary Capillary Wedge PressurePulmonary Capillary Wedge Pressure Left Ventricular VolumeLeft Ventricular Volume Left Ventricular MassLeft Ventricular Mass Left Ventricular ForceLeft Ventricular Force Ejection Fraction (EF) Ejection Fraction (EF) Regional Ventricular Wall Motion Regional Ventricular Wall Motion Right Ventricular and Atrial Volume Right Ventricular and Atrial Volume

Assessment of Left Ventricular Function

Preload,Preload, Afterload,Afterload,

Contractility,Contractility, Heart rate,Heart rate,

and Rhythmand Rhythm

(P179 in textbook)(P179 in textbook)

Heart Failure

Introduction

￭￭ Heart failureHeart failure (HF) is a principal comp (HF) is a principal complication of virtually all forms of heart diselication of virtually all forms of heart dise

asease

￭￭ It is a pathophysiological state in which tIt is a pathophysiological state in which the heart is unable to pump enough blood he heart is unable to pump enough blood to supply the metabolic needs of the bodyto supply the metabolic needs of the body

Introduction HF can be preventedHF can be prevented

HF has established risk factorsHF has established risk factors

HF is a progressive condition with asymptomatic HF is a progressive condition with asymptomatic and symptomatic stagesand symptomatic stages

HF morbidity and mortality can be reduced by HF morbidity and mortality can be reduced by stage specific treatmentsstage specific treatments

Definition

Heart failure occurs when an abnormality Heart failure occurs when an abnormality of cardiac function causes the heart to of cardiac function causes the heart to fail to pump blood at a rate required by fail to pump blood at a rate required by the metabolizing tissues or when the the metabolizing tissues or when the heart can do so only with an elevated heart can do so only with an elevated

filling pressurefilling pressure

Definition

Heart's inability to pump a sufficient Heart's inability to pump a sufficient amount of blood to meet the needs of the amount of blood to meet the needs of the body tissues may be due to insufficient or body tissues may be due to insufficient or defective cardiac filling and/or impaired defective cardiac filling and/or impaired

contraction and emptying.contraction and emptying.

Compensatory mechanisms increase blood Compensatory mechanisms increase blood volume and raise cardiac filling pressures, volume and raise cardiac filling pressures,

heart rate, and cardiac muscle mass to heart rate, and cardiac muscle mass to maintain the heart's pumping function and maintain the heart's pumping function and

cause redistribution of blood flow.cause redistribution of blood flow.

Definition

Eventually, however, despite these Eventually, however, despite these compensatory mechanisms, the ability of the compensatory mechanisms, the ability of the

heart to contract and relax declines heart to contract and relax declines progressively, and the heart failure worsensprogressively, and the heart failure worsens

Definition Congestive heart failure (CHF)Congestive heart failure (CHF) represent represent

s a complex clinical syndrome characteris a complex clinical syndrome characterized by abnormalities of left ventricular fuzed by abnormalities of left ventricular function and neurohormonal regulation, wnction and neurohormonal regulation, which are accompanied by effort intoleranhich are accompanied by effort intolerance, fluid retention, and reduced longevityce, fluid retention, and reduced longevity

Epidemiology 4.6 million 4.6 million HF HF patientspatients in the United States in the United States

10 million HF 10 million HF patients patients in Europe in Europe

550,000 new cases diagnosed each year550,000 new cases diagnosed each year

Approximately 80 percent of all heart failure admApproximately 80 percent of all heart failure admissions occur in patients older than 65issions occur in patients older than 65

Half of HF Half of HF patients will die within 4 yearspatients will die within 4 years

Patients with severe Patients with severe HF HF willwill die within 1 year die within 1 year

In the United States, the estimated costs for the mIn the United States, the estimated costs for the management of patients with heart failure exceed $anagement of patients with heart failure exceed $

10 billion annually. 10 billion annually.

Prevalence rates of congestive heart failure (CHF) by gender and age

Descriptive terms of Heart Failure

Acute vs. Chronic HFAcute vs. Chronic HF

Systolic vs. Diastolic HFSystolic vs. Diastolic HF

Left vs. Right HFLeft vs. Right HF

Chronic Heart Failure

Heart Functional Classification

NYHA ClassificationNYHA Classification

Forrester ClassificationForrester Classification

Killip Classification

Proposed Stage of HFProposed Stage of HF

NYHA Classification

Class I—Class I—NoNo limitation:limitation: Ordinary physical activity does Ordinary physical activity does not cause undue fatigue, dyspnea, or palpitation. not cause undue fatigue, dyspnea, or palpitation.

Class II—Class II—SlightSlight limitation of physical activity:limitation of physical activity: Such patients are comfortable at rest. Ordinary physicSuch patients are comfortable at rest. Ordinary physic

al activity results in fatigue, palpitation, dyspnea, or anal activity results in fatigue, palpitation, dyspnea, or angina. gina.

Class III—Class III—MarkedMarked limitation of physical activity:limitation of physical activity: Altho Although patients are comfortable at rest, less than ordinary ugh patients are comfortable at rest, less than ordinary activity will lead to symptoms.activity will lead to symptoms.

Class IV—Class IV—Inability to carry on any physical activity withInability to carry on any physical activity without discomfort:out discomfort: Symptoms of congestive failure are pres Symptoms of congestive failure are present even at rest. With any physical activity, increased dent even at rest. With any physical activity, increased discomfort is experienced.iscomfort is experienced.

A clinical estimate of the severity of

LV dysfunction in the treatment of AMI

Class I – No heart failure.

No clinical signs of cardiac decompensation.

Class II – Heart failure.

Diagnostic criteria include rales, S3 gallop

and pulmonary venous hypertension.

Pulmonary congestion with wet rales up to half of the lung fields.

Killip Classification

Class III – Severe heart failure.

Pulmonary edema with rales inall lung fields.

Class IV – Cardiogenic shock.

Signs include hypotension

(systolic BP< 90 mmHg), and evidence of peripheral vasoconstriction such as oliguria, cyanosis

and diaphoresis.

Killip Classification

Forrester Classification

Normal

Hypovolemic

Diuretics

vasodilators

Pulmonary oedema

Normal blood pressure :

VasodilatorsReduced blood pressure :Inotropics or vasopressors

Pulmonary congestion

PCWP: 18 mmHg

Cardiac index :2,2 l/min/m²

Tissue perfusion

Proposed Stage of HF

STAGE ASTAGE A High risk for developing HF High risk for developing HF

STAGE BSTAGE B Asymptomatic LV dysfunction Asymptomatic LV dysfunction

STAGE CSTAGE C Past or current symptoms of HF Past or current symptoms of HF

STAGE DSTAGE D End-stage HF End-stage HF

the causes of heart failure into the causes of heart failure into threethree b broad categories: road categories:

(1) (1) underlying causesunderlying causes

(2) (2) fundamental causesfundamental causes

(3) (3) precipitating causesprecipitating causes

Causes of Heart Failure

Underlying Causes

comprising the structural abnormalitiescomprising the structural abnormalities

congenital or acquiredcongenital or acquired

affect the peripheral and coronary vessels, pericaaffect the peripheral and coronary vessels, pericardium, myocardium, or cardiac valves rdium, myocardium, or cardiac valves

lead to the increased hemodynamic burden or mlead to the increased hemodynamic burden or myocardial or coronary insufficiency yocardial or coronary insufficiency

responsible for heart failureresponsible for heart failure

Fundamental Causes

comprising the biochemical and physiological comprising the biochemical and physiological mechanismsmechanisms

either an increased hemodynamic burden or either an increased hemodynamic burden or a reduction in oxygen delivery to the myocaa reduction in oxygen delivery to the myoca

rdium rdium

results in impairment of myocardial contractiresults in impairment of myocardial contraction on

Precipitating Causes

including the specific causes or incidents thincluding the specific causes or incidents that precipitate heart failure in 50 to 90 perat precipitate heart failure in 50 to 90 per

cent of episodes of cent of episodes of

clinical heart failure.clinical heart failure.

Precipitating Causes

SSystemic Infectionystemic Infection

IInappropriate nappropriate RReductioneduction of of TTherapyherapy

AArrhythmiasrrhythmiasTachyarrhythmias Tachyarrhythmias ((atrial fibrillationatrial fibrillation))

Marked bradycardia Marked bradycardia Dissociation between atrial and ventricular contraction Dissociation between atrial and ventricular contraction

Abnormal intraventricular conductionAbnormal intraventricular conduction

MMyocardial yocardial I Ischemia or schemia or I Infarctionnfarction

PPulmonaryulmonary E Embolismmbolism

PPhysical, hysical, EEmotionalmotional, , andand E Environmental nvironmental SStresstress

HHigh-outputigh-output S Statestates

CCardiac Toxinsardiac Toxins

Pathophysiology

SShort-term adaptive mechanismshort-term adaptive mechanisms(1)(1) the Frank-Starling mechanismthe Frank-Starling mechanism

an increased preload helps to sustain cardiac an increased preload helps to sustain cardiac performance;performance;

(2) activation of neurohumoral systems, (2) activation of neurohumoral systems,

especially the release of the neurotransmitter especially the release of the neurotransmitter norepinephrine (NE) norepinephrine (NE)

(3) myocardial remodeling with or without cardia(3) myocardial remodeling with or without cardiac chamber dilatation, c chamber dilatation,

in which the mass of contractile tissue is augmin which the mass of contractile tissue is augmented.ented.

Pathophysiology

ChronicChronic 　　 myocardial remodelingmyocardial remodeling

ApoptosisApoptosis

NecrosisNecrosis

FibrosisFibrosis

HypertrophyHypertrophy

Cardiac ContractilityCardiac Contractility↓↓

Peripheral PerfusionPeripheral Perfusion↓↓

The relationship between left ventricular wall thickness and

chamber radius

Myocardial injury

Activation ofANS, RAASendothelin, AVPinflammatory cytokinesoxidative stress

Cardiac function↓

Blockers of ACEaldo, adren, AT1, ETA,

TNF-, receptors

Hypertrophy,remodeling,apoptosis

＊

＊Acute(adaptive)

Relationship between remodeling and dysfunction

Activation of compensatory mechanisms leads to a decrease in intrinsic and modulata

ble myocardial function

Neurohormonal Activation in Heart Failure

Hypertrophy, apoptosis, ischemia,arrhythmias, remodeling, fibrosis

Angiotensin II Norepinephrine

Morbidity and Mortality

CNS sympathetic outflow

Cardiac sympathetic activity Renal sympathetic activity

Sodium retentionMyocyte hypertrophy

Myocyte injuryIncreased arrhythmias

Disease progression

111 2 1

Vascular sympathetic activity

Vasoconstriction

1

Activationof RAS

Adrenergic Pathway in Heart Failure Progression

Harmful effects of neurohormonal, cytokin

e, and wall stress

Clinical Symptoms

FACESFACES......• FFatigueatigue

• AActivities limitedctivities limited• CChest congestionhest congestion

• EEdema or ankle swellingdema or ankle swelling• SShortness of breathhortness of breath

Left-Side Heart Failure

Symptoms SignsSymptoms Signs

Apical SMApical SM Diastolic Gallop (SDiastolic Gallop (S33, S, S44))

HR↑HR↑ SS11↓↓

PP22↑↑

Rales HydrothoraxHydrothorax

Shortness of breathShortness of breathDyspnea

FatigueFatigue

Exertional dyspnes

Paroxysmal nocturnal

dyspnea Orthopnea

Cardiac asthma

Right-Side Heart Failure

Symptoms SignsSymptoms Signs

Edema Edema AscitesAscites

Ankle swelling Ankle swellingAnkle swelling Ankle swelling

FatigueFatigue Jugular venous distention

Systolic VS. Diastolic Heart Failure

Parameters Systolic Diastolic

History    

Coronary artery disease

+++ ++

Hypertension ++ ++++

Diabetes ++ ++

Valvular heart disease ++++ –

Paroxysmal dyspnea ++ +++

Physical Examination      

Cardiomegaly +++ +

Soft heart sounds ++++ +

S3 gallop +++ +

S4 gallop + +++

Hypertension ++ ++++

Mitral regurgitation +++ +

Rales ++ ++

Edema +++ +

Jugular venous distention +++ +

X-Ray     

Cardiomegaly +++ +

Pulmonary congestion +++ +++

Electrocardiogram      

Left ventricular hypertrophy ++ ++++

Q waves ++ +

Low voltage +++ –

Echocardiogram      

Left ventricular hypertrophy ++ ++++

Left ventricular dilation ++ –

Left atrial enlargement ++ ++

Reduced ejection fraction ++++ –

EchocardiogramEchocardiogramEjection FractionEjection Fraction

Healthy heart = 60% or moreHealthy heart = 60% or more

Heart failure = 40 % or lessHeart failure = 40 % or less

ElectrocardiogramElectrocardiogram ( (ECGECG))

Chest X-rayChest X-ray

Laboratory Test

Rule for establishing the diagnosis of heart failure

and determining etiology and prognosis

Assess symptoms & signs

Heart Diseases?ECG/BNP/X-Ray ?

Abnormal

Evaluate cardiac function

by echocardiography

Heart failure

Characterize type and severity

Selected tests,

(angio, Haemodynamic monitoring)

Consider other

diagnosis

Abnormal

Normal

Normal

Suspected Chronic Heart Failure

Differential Diagnosis

Left-side HF Right-side HFLeft-side HF Right-side HF

Respiratory System Disease Liver DiseaseRespiratory System Disease Liver Disease

Lung Disease Pericardium DiseaseLung Disease Pericardium Disease

Treatment Objectives

Decrease symptoms Decrease symptoms

Improve exercise capacityImprove exercise capacity

Enhance quality of lifeEnhance quality of life

Decrease morbidityDecrease morbidity

Retard the progression of heart failureRetard the progression of heart failure

Improve survivalImprove survival

A, B, C, D, Es of Heart Failure Therapy

AA angiotensin converting enzyme inhibitorsangiotensin converting enzyme inhibitors aaldosterone ldosterone aantagonistsntagonists

BB beta blocking drugsbeta blocking drugs

CC calcium channel blocking drugs,calcium channel blocking drugs, coronarycoronary revascularization, revascularization, cardiac transplantcardiac transplant

DD diet, diuretics, digitalisdiet, diuretics, digitalis

EE exerciseexercise

Cornerstones of Medicine Therapy

Angiotensin converting enzyme (ACE) Angiotensin converting enzyme (ACE) inhibitorsinhibitors

Beta-BlockerBeta-Blocker diureticsdiuretics digitalisdigitalis guidelines for the severity-based therapguidelines for the severity-based therap

y of heart failure. y of heart failure.

Diet

Traditional approach non-pharmacologic Traditional approach non-pharmacologic management is sodium and water restrictmanagement is sodium and water restrictionion

Sodium excess is the main reason for heaSodium excess is the main reason for heart failure exacerbationrt failure exacerbation

Restrict sodium to 2 to 3 grams / dayRestrict sodium to 2 to 3 grams / day

Diuretics

sodium and water retentionsodium and water retention

symptoms of volume overloadsymptoms of volume overload

in resistant edema, loop diuretics, Kin resistant edema, loop diuretics, K++--sparing diuretics, and metolazone are sparing diuretics, and metolazone are indicatedindicated

Digitalis Beneficial hemodynamic effectsBeneficial hemodynamic effects

cardiac outputcardiac output left ventricular ejection fractionleft ventricular ejection fraction left ventricular diastolic pressureleft ventricular diastolic pressure exercise toleranceexercise tolerance natriuresisnatriuresis neurohormonal activationneurohormonal activation

Angiotensin Converting Enzyme Inhibitors Physiologic Benefits

Arteriovenous VasodilatationArteriovenous Vasodilatation

pulmonary arterial diastolic pressurepulmonary arterial diastolic pressure pulmonary capillary wedge pressurepulmonary capillary wedge pressure left ventricular end-diastolic pressureleft ventricular end-diastolic pressure systemic vascular resistancesystemic vascular resistance systemic blood pressure systemic blood pressure maximal oxygen uptake (MVOmaximal oxygen uptake (MVO22))

Angiotensin Converting Enzyme Inhibitors Physiologic Benefits

LV function and cardiac outputLV function and cardiac output renal, coronary, cerebral blood flowrenal, coronary, cerebral blood flow No change in heart rate or myocardial cNo change in heart rate or myocardial c

ontractilityontractility no neurohormonal activationno neurohormonal activation resultant diuresis and natriuresisresultant diuresis and natriuresis

Angiotensin Converting Enzyme Inhibitors Physiologic Benefit

s Increases exercise capacityIncreases exercise capacity improves functional classimproves functional class attenuation of LV remodeling post MIattenuation of LV remodeling post MI decrease in the progression of chronic HFdecrease in the progression of chronic HF decreased hospitalizationdecreased hospitalization enhanced quality of lifeenhanced quality of life improved survivalimproved survival

Guidelines to ACE Inhibitor Therapy

It is important to titrate to the dosage regimen It is important to titrate to the dosage regimen used in the clinical trials … in the absence of syused in the clinical trials … in the absence of symptoms or adverse effects on end-organ perfusimptoms or adverse effects on end-organ perfusionon

in very severe heart failure, hydralazine and nitin very severe heart failure, hydralazine and nitrates added to ACE inhibitor therapy can furthrates added to ACE inhibitor therapy can further improve cardiac outputer improve cardiac output

-Blocker Physiologic Benefits

increase the density of increase the density of -1 receptors-1 receptors inhibit catecholamine toxicityinhibit catecholamine toxicity decrease neurohormonal activationdecrease neurohormonal activation decrease heart ratedecrease heart rate provide antihypertensive, antianginal, aprovide antihypertensive, antianginal, a

nd antiarrhythmic effectsnd antiarrhythmic effects antioxidant and antiproliferative effectsantioxidant and antiproliferative effects

-Blocker Clinical Benefits

decrease symptoms of HFdecrease symptoms of HF improve left ventricular functionimprove left ventricular function improve exercise toleranceimprove exercise tolerance

Beta-blocker Therapy in Heart Failure

Potential Beneficial EffectsPotential Beneficial Effects

Protection fromProtection fromCatecholamineCatecholamine

ToxicityToxicity

Renin Renin Angiotensin Angiotensin

SystemSystem

Reversal of Reversal of RemodelingRemodeling

Up-regulationUp-regulationof of --adrenergicadrenergic

ReceptorsReceptors

AncillaryAncillaryFactorsFactors

Major Placebo Controlled Trials of -Blockade in Heart Failure

34%

Cu

mu

lati

ve

Mo

rta

lity

(%

)

Days

20

15

5

0

10

P=.0062 (adjusted)

Metoprolol CR/XL(n=1990)

Placebo (n=2001)

US Carvedilol Trials1

Pro

ba

bil

ity

of

Ev

en

t-fr

ee

Su

rviv

al

Carvedilol (n=696)

Placebo (n=398)

Days

P<.001

0.00 100 200 300 400

65%

1.0

0.8

0.7

0.9

MERIT-HF2

Su

rviv

al

(% o

f P

ati

en

ts) 100

90

80

60

70

06000 400300200100

Days

Carvedilol (n=1156)

Placebo (n=1133)

500

6000 400300200100 500

35%

P=.00013

COPERNICUS4

Days

0.0200 400 800

1.0

0.8

0.6

P<.000134%

Bisoprolol (n=1327)

Placebo (n=1320)

CIBIS-II3

0 600

Su

rviv

al

0

5

10

15

20

25

30All Patients

(n=2289)Higher-Risk Patients

(n=624)

Nu

mb

er o

f E

ven

ts

0

60

180All Patients

(n=2289)Higher-Risk Patients

(n=624)

Nu

mb

er o

f E

ven

ts

8 Weeks 8 Weeks

DeathsDeath or Hospitalization

for Any Reason

Placebo Carvedilol

COPERNICUS: Early Clinical Outcomes

120

25

19

15

3

153

134

63

44

Calcium Channel Blocker

Potential benefit: Potential benefit: anti-ischemic and vasodilatory effectsanti-ischemic and vasodilatory effects

Adverse effect:Adverse effect: negative inotropic propertiesnegative inotropic properties

Anticoagulant Therapy

Recommended forRecommended for patients with NYHA III-IV and EF <30patients with NYHA III-IV and EF <30

% or ventricular aneurysm or very dil% or ventricular aneurysm or very dilated LVated LV

Indicated forIndicated for patients with heart failure who have atpatients with heart failure who have at

rial fibrillation, a prior embolic episodrial fibrillation, a prior embolic episode, identified intracardiac thrombuse, identified intracardiac thrombus, etc, etc

Arrhythmias

Sudden death occurs in about 50% Sudden death occurs in about 50% of patients with heart failureof patients with heart failure

Coronary Revascularization

80% of patients with heart failure have coronar80% of patients with heart failure have coronary diseasey disease

Patients should be evaluated for the presence of Patients should be evaluated for the presence of myocardial ischemia and the potential benefit myocardial ischemia and the potential benefit of revacularizationof revacularization

Survival was improved by revascularization coSurvival was improved by revascularization compared with medical therapy, even in the absempared with medical therapy, even in the absence of angina pectorisnce of angina pectoris

Ventricular Assist Devices

Biventricular Pacemaker

Cardiac Transplantation

Survival of 60%-90% at 1-yr, 70% at 5-yrSurvival of 60%-90% at 1-yr, 70% at 5-yr Inclusion Criteria:Inclusion Criteria:

must first exclude remediable myocardial ischemiamust first exclude remediable myocardial ischemia heart failure refractory to optimal medical Rxheart failure refractory to optimal medical Rx left ventricular ejection fraction <20%left ventricular ejection fraction <20% VOVO22 max max 14 mL/kg/min 14 mL/kg/min

Problems:Problems: rejection, graft atherosclerosis, neoplasia, cost/availarejection, graft atherosclerosis, neoplasia, cost/availa

bilitybility

Cardiomyoplasty Cardiac Reduction Surgery

currently considered experimentalcurrently considered experimental

Exercise Training

Exercise training in patients with HFExercise training in patients with HF

decrease symptomsdecrease symptoms improves exercise toleranceimproves exercise tolerance benefit additive to that attained with benefit additive to that attained with

ACEIACEI no worsening of left ventricular funcno worsening of left ventricular func

tiontion

Asymptomatic Patients

For asymptomatic patients with left For asymptomatic patients with left ventricular dysfunction (ventricular dysfunction (NYHA class INYHA class I), ), typically those with an ejection fraction typically those with an ejection fraction below 40%,below 40%,

ACE inhibitors are recommended ACE inhibitors are recommended

Asymptomatic Patients

Enalopril Enalopril SOLVD Prevention Trial SOLVD Prevention Trial

EF<35%EF<35% HF progression, HF progression, hospitalization hospitalization

CaptoprilCaptoprilSAVE, GISSI-3, ISIS-4SAVE, GISSI-3, ISIS-4 Post MI, EF <40%Post MI, EF <40%

overall mortality, overall mortality, re-infarction re-infarction hospitalization, hospitalization, HF progression HF progression

Symptomatic Patients

NYHA class IINYHA class II

ACE inhibitors, mild diuretics, and digoxin, ACE inhibitors, mild diuretics, and digoxin, with or without the use of B-blocker therapywith or without the use of B-blocker therapy

NYHA class IIINYHA class III

add loop diuretics add loop diuretics NYHA class IV NYHA class IV

consider positive inotropic agentsconsider positive inotropic agents surgical therapies may also be appliedsurgical therapies may also be applied

Symptomatic Patients

Enalopril Enalopril + digoxin + diuretics+ digoxin + diuretics

SOLVD Treatment TrialSOLVD Treatment Trial

EF<35%, FC III-IV EF<35%, FC III-IV mortality, mortality, hospitalization hospitalization

CONSENSUS-IICONSENSUS-IIFC IVFC IV mortality (40%), mortality (40%), symptoms, symptoms, hospitalization hospitalization improved functional classimproved functional class

Conclusion of HF Treatment

• DiureticsDiuretics- - helps control symptoms helps control symptoms • DigitalisDigitalis - - helps control symptomshelps control symptoms• ACE InhibitorsACE Inhibitors - - can slow down diseasecan slow down disease progressionprogression • Beta BlockersBeta Blockers - - can slow down disease progression can slow down disease progression

This combination of medications has been proven toThis combination of medications has been proven to save lives and keep people out of the hospital.save lives and keep people out of the hospital.

Conclusion of HF Treatment

Improve in survivalImprove in survival ACE inhibitorsACE inhibitors ß-blockß-blocker er (selective)(selective)

Increased mortalityIncreased mortality positive inotropic agentspositive inotropic agents calcium channel blocking drugs (?)calcium channel blocking drugs (?)

Neutral on survivalNeutral on survival digitalisdigitalis

Effects of Heart Failure Therapies

Prevention of ischemiaPrevention of ischemia ß-blockß-blocker er (selective)(selective) ACEIACEI coronary revascularizationcoronary revascularization anticoagulant therapyanticoagulant therapy

Hemodynamic improvementHemodynamic improvement ACEI, digitalis, diureticsACEI, digitalis, diuretics

Conclusion of HF Treatment

Effects of Heart Failure Therapies

Assessment of LV function (echocardiogram,Assessment of LV function (echocardiogram,radionuclide ventriculogram)radionuclide ventriculogram)

-blocker-blocker

EFEF40%40%

Assessment of Assessment of Volume statusVolume status

ACE inhibitorACE inhibitor

Signs and symptoms ofSigns and symptoms of fluid retentionfluid retention

No signs and symptoms of No signs and symptoms of fluid retentionfluid retention

DigoxinDigoxin

DiureticDiuretic(titrate to euvolemic state)(titrate to euvolemic state)