CHRONIC HEART FAILURE Faculty of Medicine University of Brawijaya

CHRONIC HEART CHRONIC HEART FAILUREFAILURE

Faculty of MedicineFaculty of Medicine

University of BrawijayaUniversity of Brawijaya

IntroductionIntroduction

Definition : Heart Failure

“The situation when the heart is incapable of maintaining a cardiac output adequate to accommodate metabolic requirements and the venous return.“ E. Braunwald

“Pathophysiological state in which an abnormality of cardiac function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues.” Euro Heart J; 2001. 22: 1527-1560

DEFINITION OF HEART FAILURE. Criteria 1 and 2 should be fulfilled in all cases

1. Symptoms of heart failure(at rest or during exercise)

And2. Objective evidence of cardiac dysfunction

(at rest)And

(in cases where the diagnosis is in doubt)3. Response to treatment directed towards

heart failure

Task Force Report. Guidelines for the diagnosis and treatment of chronic heart failure. European Society of Cardiology.2001

EPIDEMIOLOGYEPIDEMIOLOGY

Europe

The prevalence of symptomatic HF range from 0.4-2%.10 million HF pts in 900 million total population

USA

nearly 5 million HF pts. ± 500,000 pts are D/ HF for the 1st time each year. Last 10 years number of hospitalizations has increased.Nearly 300,000 patients die of HF each year.

Guidelines for the diagnosis and treatment of chronic heart failure

European Heart Journal (2001) 22, 1527-1560

ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult 2001

DESCRIPTIVE TERMS in HEART FAILUREDESCRIPTIVE TERMS in HEART FAILURE


European Heart Journal (2001) 22, 1528

Acute vs Chronic Heart Failure Systolic vs Diastolic Heart Failure Right vs Left Heart Failure Mild , Moderate, Severe Heart Failure

New York Heart Association (NYHA) New York Heart Association (NYHA) Classification of Heart FailureClassification of Heart Failure

Class – INo limitation : ordinary physical exercise does not cause undue fatigue, dyspnoea or palpita-tions.

Class – IISlight limitation of physical activity : comfor-table at rest but ordinary activity results in fatigue, dyspnoea, or palpitation.

Class - IIIMarked limitation of physical activity : comfor-table at rest but less than ordinary activity results in symptoms.

Class - IV

Unable to carry out any physical activity with-out discomfort : symptoms of heart failure are present even at rest with increased discomfort with any physical activity.


European Heart Journal (2001) 22, 1531

(Adapted from Williams JF et al., Circulation. 1995; 92 : 2764-2784)

ACC/AHA – A New Approach To The Classification of HF

Stage Descriptions Examples

A Patient who is at high risk for developing HF but has no structural disorder of the heart.

Hypertension; CAD; DM; rheumatic fever; cardiomyopathy.

B Patient with a structural disorder

of the heart but who has never developed symptoms of HF.

LV hypertrophy or fibrosis;

LV dilatation; asymptomatic VHD; MI.

C Patient with past or current symptoms of HF associated with underlying structural heart disease.

Dyspnea or fatigue ec LV systolic dysfunction; asymptomatic patients with HF.

D Patient with end-stage disease Frequently hospitalized pts ; pts awaiting heart transplantation etc


Stage A Stage B Stage C Stage D

Pts with :• Hypertension• CAD• DM• Cardiotoxins• FHx CM

THERAPY• Treat Hypertension• Stop smoking • Treat lipid disorders• Encourage regular

exercise• Stop alcohol

& drug use• ACE inhibition

Pts with :• Previous MI• LV systolic

dysfunction• Asymptomatic

Valvular disease

THERAPY• All measures under

stage A• ACE inhibitor • Beta-blockers


stage A• Drugs for routine use:

• diuretic• ACE inhibitor• Beta-blockers• digitalis


stage A,B and C• Mechanical assist

device• Heart transplantation• Continuous IV

inotrphic infusions for palliation

Pts who have marked symptoms at rest despite maximal medical therapy.

Pts with :

• Struct. HD

• Shortness of breath and fatigue, reduce exercise tolerance

Struct.Heart Disease

DevelopSymp.of

HF

Refract. Symp.of HF at rest

Stages in the evolution of HF and recommended therapy by stage


EVOLUTION OF CLINICAL STAGES

EVOLUTION OF CLINICAL STAGES

NORMALNORMAL

Asymptomatic LV DysfunctionAsymptomatic LV Dysfunction

CompensatedCHF

CompensatedCHF

DecompensatedCHF

DecompensatedCHF

No symptomsNormal exerciseNormal LV fxn

No symptomsNormal exerciseNormal LV fxn

No symptomsNormal exerciseAbnormal LV fxn

No symptomsNormal exerciseAbnormal LV fxn

No symptoms ExerciseAbnormal LV fxn

No symptoms ExerciseAbnormal LV fxn

Symptoms ExerciseAbnormal LV fxn

Symptoms ExerciseAbnormal LV fxn

RefractoryCHF

RefractoryCHF

Symptoms not controlled with treatmentSymptoms not controlled with treatment

Evolution of the Concept of Heart Evolution of the Concept of Heart Failure 1950 to 2000Failure 1950 to 2000

1950 2000

Aetiology Hypertension CHD Valvular heart dis Hypertension Dilated CMP

Natural Course Slowly progressive Slowly progressive (remodelling) or unpredictable and rapid ( coronary event )Understanding Hemodynamic model Neurohormonal model

Common cause Pulmonary infection Sudden deathof death Pump failure

Arrhythmia Atrial Ventricular

Treatment goal Control edema Improve quality of life Slowing Heart Rate + reduce mortality + reduce hospitalization

Patophysiology of C H F

Patophysiology of C H F

g a b c d e f g a

AO

AorticclosureAortic

pressureVentricularpressure

Cross-over Atrial

pressureMO

Heartsounds

S4

M1T1

A2P2 S3

Cardiologicsystole

a c

v

JVP

P T

ECGP

Q S

0 800 msec

The Wiggers cycle

Op

ie (

2001

)

g

a b

iso

c d

isoe

f

Input

Block diagram of left ventricular pump performance(Little, 2001)

Output

PULMONARY VENOUSPRESSURE

CARDIAC OUTPUT

Filling Emptying

ED volume x EFeffective =Strokevolume

Heartrate

x

Diastolic function Systolic function

LV DistensibilityRelaxationLeft atriumMitral valvePericardium

ContractilityAfterloadPreloadStructure

SYSTOLIC FAILURE

Normal

Normaldiastolicchamberdistensibility

Left Ventricular Volume

Lef

t V

entr

icu

lar

Pre

ssu

re

Left Ventricular Volume

Lef

t V

entr

icu

lar

Pre

ssu

re

DIASTOLIC FAILURE

Decreaseddiastolicchamberdistensibility

PRESSURE – VOLUME CURVE OF SYSTOLIC AND DIASTOLIC FAILUREPRESSURE – VOLUME CURVE OF SYSTOLIC AND DIASTOLIC FAILUREPRESSURE – VOLUME CURVE OF SYSTOLIC AND DIASTOLIC FAILUREPRESSURE – VOLUME CURVE OF SYSTOLIC AND DIASTOLIC FAILURE

(Zile & Brutsaert 2002)

Abnormalrelaxation

A B

Pericardialrestraint

D

Chamberdilation

C

Increasedchamber stiffness

Lef

t ve

ntr

icu

lar

pre

ssu

re

Left ventricular volume

Mechanisms that cause diastolic dysfunction. (Zile, 1990)

DETERMINANTS OF

VENTRICULAR FUNCTION

STROKE VOLUME

PRELOAD

CONTRACTILITY

CARDIAC OUTPUT

HEART RATE

- Synergistic LV contraction - LV wall integrity - Valvular competence

AFTERLOAD

Frank-Starling Law

NormalCompensated

CHF

Normal C.O.

LVEDP

Ca

rdia

c O

utpu

t

Ventricular Function Curve:Frank-Starlings

Congestion

SV

Normal

LVEDV

The Pathophysiology of Heart Failure

Hurst. The Heart. Diagnosis and Management of Heart Failure.10 th ed. 688

Pathophysiological Sequence of CHF

Heart Failure

Inadequate Cardiac Output

( ) O2 Delivery (rest and/or exercise)

Systemic Vasoconstriction

SAS (NE)) RAAS (A-II)

() Flow to Skin, Gut, and Renal Circulations

Activation ofRAS and ANS

Neurohormonal Activation

Hurst. The Heart. Diagnosis and Management of Heart Failure.10 th ed. 688

Frank-Starling Effect

Ventricular dilatation

Wall stress

O2 consumption Coronary perfusion

SNS

Renin release

Angiotensin II

Vasoconstriction

Growth factors

Hypertrophy Apoptosis

ALDO

Fluid accumulation

Collagen deposition

Myofibril necrosis

Preload Afterload

SNS: sympathetic nervous system

Sympathetic nervous system up-regulation

IncreasedNorepinephrine levels

DirectMyocardial toxicity

Myocyte dysfunction

Myocytenecrosis

IntracellularCa2+ overload/

Energy depletion

Apoptosis

DecreasedRenal blood

flow

Activation of theRAA system

Increased HR, PVR & arteriolar vasoconstriction

Increased myocardialoxygen demand

IncreasedAngiotensin II &

Aldosteron

Na+ & water retention

Vasoconstriction Cardiac remodeling

Cesario et.al; Reviews in cardiovascular medicine, vol 3, no.1, 2002

Causes of Heart Failure

Myocardial Damage or Disease Infarction (Acute) / Ischemia Myocarditis Hypertrophic Cardiomyopathy

Excess Load on Ventricle Volume/ Pressure Overload

Resistance to Flow into VentricleCardiac Arrhythmias

Primary Changes in CHF

Site ofFailure

BackwardFailure

ForwardFailure

Right HeartFailure

( ) SystemicVenousPressure

( ) ejectionintoPulmonaryArtery

Left HeartFailure

( ) PulmonaryVenousPressure

( ) ejectioninto aorta

MI-INDUCED HEART FAILURE

Myocardial Damage

Contractility

Pump Performance

SAS DriveVasoconstriction

Systolic Work Load

RAAS SYSTEMFLUID RETENTION

Diagnosis of C H FDiagnosis of C H FDiagnosis of C H FDiagnosis of C H F

IDENTIFICATIONS OF HF PATIENTSIDENTIFICATIONS OF HF PATIENTS

With a Syndrome of Decrease With a Syndrome of Decrease Exercise ToleranceExercise Tolerance

With a Syndrome of Fluid RetentionWith a Syndrome of Fluid Retention

With No Symptoms or Symptoms of With No Symptoms or Symptoms of Another Cardiac or Non Cardiac Another Cardiac or Non Cardiac DisorderDisorder

(MI, Arrythmias, Pulmonary or (MI, Arrythmias, Pulmonary or Systemic Thromboembolic Events)Systemic Thromboembolic Events)

SYMPTOMS AND SIGNSYMPTOMS AND SIGN

Breathlessness, Ankle Swelling, FatiqueBreathlessness, Ankle Swelling, Fatique

→ → Characteristic SymptomsCharacteristic Symptoms

Peripheral Oedema, JVP ↑, HepatomegalyPeripheral Oedema, JVP ↑, Hepatomegaly

→ → Signs of Congestion of Systemic Signs of Congestion of Systemic VeinsVeins

SS33 , Pulmonary Rales , Pulmonary Rales , Cardiac Murmur , Cardiac Murmur

E C GE C G

A low Predictive ValueA low Predictive Value LAH and LVH May Be Associated wit LV DysfunctionLAH and LVH May Be Associated wit LV Dysfunction Anterior Q-wave and LBBB a good predictors of EF Anterior Q-wave and LBBB a good predictors of EF ↓↓↓↓ Detecting Arrhytmias as Causative of HFDetecting Arrhytmias as Causative of HF

CHEST X-RAYCHEST X-RAY

A Part of Initial Diagnosis of HFA Part of Initial Diagnosis of HF

→ → Cardiomegaly, Pulmonary CongestionCardiomegaly, Pulmonary Congestion Relationship Between Radiological Signs andRelationship Between Radiological Signs and

Haemodynamic Findings may Depend on the Haemodynamic Findings may Depend on the DurationDuration

and Severity HFand Severity HF

HAEMATOLOGY & BIOCHEMISTRYHAEMATOLOGY & BIOCHEMISTRY

A Part of Routine DiagnosticA Part of Routine Diagnostic Hb, Leucocyte, PlateletsHb, Leucocyte, Platelets Electrolytes, Creatinine, Glucose, Hepatic Electrolytes, Creatinine, Glucose, Hepatic

Enzyme, UrinalysisEnzyme, Urinalysis TSH, C-RP, Uric AcidTSH, C-RP, Uric Acid

ECHOCARDIOGRAPHYECHOCARDIOGRAPHY

The Preferred MethodsThe Preferred Methods Helpful in Determining the AetiologyHelpful in Determining the Aetiology Follow Up of Patients Heart FailureFollow Up of Patients Heart Failure

PULMONARY FUNCTIONSPULMONARY FUNCTIONS

A Little Value in Diagnosis Heart FailureA Little Value in Diagnosis Heart Failure Usefull in Excluding Respiratory DiseasesUsefull in Excluding Respiratory Diseases

EXERCISE TESTINGEXERCISE TESTING

Focused on Functional, Treatment Assessment Focused on Functional, Treatment Assessment andand

PrognosticPrognostic

STRESS ECHOCARDIOGRAPHYSTRESS ECHOCARDIOGRAPHY

For Detecting IschaemiaFor Detecting Ischaemia Viability StudyViability Study

NUCLEAR CARDIOLOGYNUCLEAR CARDIOLOGY

Not Recommended as a Routine Use

CMR CMR ( CARDIAC MAGNETIC RESONANCE IMAGING)( CARDIAC MAGNETIC RESONANCE IMAGING)

Recommended if Other Imaging Techniques not Provided Diagnostic Answer

INVASIVE INVESTIGATIONINVASIVE INVESTIGATION

Elucidating the Cause and Prognostic Elucidating the Cause and Prognostic InformationsInformations

Coronary Angiography :Coronary Angiography :

in CAD’s Patientsin CAD’s Patients

Haemodynamic Monitoring : Haemodynamic Monitoring :

To Assess Diagnostic and Treatment of HFTo Assess Diagnostic and Treatment of HF

Endomyocardial Biopsy :Endomyocardial Biopsy :

in Patients with Unexplained HFin Patients with Unexplained HF

NATRIURETIC PEPTIDESNATRIURETIC PEPTIDES

Cardiac Function Cardiac Function ↓↓ ↓↓ (LV Function ↓↓)(LV Function ↓↓) → →

↑↑ ↑↑ Plasma Natriuretic Peptide Plasma Natriuretic Peptide ConcentrationConcentration

(Diagnostic Blood Use for HF)(Diagnostic Blood Use for HF)

Natriuretic Peptide Natriuretic Peptide ↑↑ ↑↑ ::

Greatest Risk of CV EventsGreatest Risk of CV Events

Natriuretic Peptide Natriuretic Peptide ↓↓ ↓↓ ::

Improve Outcome in Patients withImprove Outcome in Patients with Treatment Treatment

Identify Pts. With Asymptomatic LVIdentify Pts. With Asymptomatic LV Dysfunction (MI, CAD) Dysfunction (MI, CAD)

Suspected Heart FailureSuspected Heart Failure Because of symptoms and Because of symptoms and

signssigns

Assess Presence of Cardiac Disease by ECG, Assess Presence of Cardiac Disease by ECG, X-Ray or NatriureticPeptides (Where X-Ray or NatriureticPeptides (Where

Available)Available)

Imaging by Echocardiography Imaging by Echocardiography (Nuclear Angiography or MRI Where (Nuclear Angiography or MRI Where

Available)Available)

Assess Etiology, Degree, Precipitating Assess Etiology, Degree, Precipitating Factors and Type of Cardiac Factors and Type of Cardiac

DysfunctionDysfunction

Tests AbnormalTests Abnormal

Tests AbnormalTests Abnormal

Choose TherapyChoose Therapy

ALGORITHM FOR THE DIAGNOSIS OF THE HFALGORITHM FOR THE DIAGNOSIS OF THE HF

If NormalIf NormalHeart FailureHeart Failure

UnlikelyUnlikely

Additional Diagnosis Tests Additional Diagnosis Tests Where Appropriate (e.g. Where Appropriate (e.g. Coronary Angiography)Coronary Angiography)

If NormalIf NormalHeart Failure Heart Failure

UnlikelyUnlikely

(ESC, 2001)(ESC, 2001)

Treatment of C H FTreatment of C H F

Aims of Treatment

1. Preventiona) Prevention and/or controlling of diseases leading

to cardiac dysfunction and heart failure

b) Prevention of progression to heart failure once cardiac dysfunction is established

2. Morbidity Maintenance or improvement in quality of life

3. Mortality Increased duration of life



ACC/AHA & EUROPE (ESC) 2001GUIDELINES FOR THE MANAGEMENT

OF HEART FAILURE

ACE-inhibitor

→ Use as first line therapy

→ Should be up titrated to the dosages shown in the large

clinical trial, and not titrated based on symptomatic

improvement

DIURETIC → to control fluid overload

Β-BLOCKER

→ For all patients with stable mild-severe HF on

standard treatment

ACC/AHA & EUROPE (ESC) 2001GUIDELINES FOR THE MANAGEMENT

OF HEART FAILURE

Aldosteron Receptor Antagonis

→ in advance HF ( NYHA III-IV )

DIGOXIN

→ in AF (atrial fibrillation)

→ May be added for symptom relief

ARB

→ Considered in patients not tolerate ACE-

inhibitors and not on β - blocker

Management Outline

Establish that the patient has HF.

Ascertain presenting features: pulmonary oedema, exertional

breathlessness, fatigue, peripheral oedema

Assess severity of symptoms

Determine aetiology of heart failure

Identify precipitating and exacerbating factors

Identify concomitant diseases

Estimate prognosis

Anticipate complications

Counsel patient and relatives

Choose appropriate management

Monitor progress and manage accordingly



TREATMENT

Correction of aggravating factors

TREATMENT

Correction of aggravating factors

MEDICATIONSMEDICATIONS

Endocarditis

Obesity

Hypertension

Physical activity

Dietary excess

Endocarditis

Obesity

Hypertension

Physical activity

Dietary excess

Pregnancy

Arrhythmias (AF)

Infections

Hyperthyroidism

Thromboembolism

Pregnancy

Arrhythmias (AF)

Infections

Hyperthyroidism

Thromboembolism

Treatment options

Non-pharmacological managementGeneral advice and measuresExercise and exercise training

Pharmacological therapyAngiotensin-converting enzyme (ACE) inhibitorsDiureticsBeta-adrenoceptor antagonistsAldosterone receptor antagonistsAngiotensin receptor antagonistsCardiac glycosidesVasodilator agents (nitrates/hydralazine)Positive inotropic agentsAnticoagulationAntiarrhythmic agentsOxygen

Devices and surgeryRevascularization (catheter interventions and surgery), other forms of surgeryPacemakersImplantable cardioverter defibrillators (ICD)Heart transplantation, ventricular assist devices, artificial heartUltrafiltration, haemodialysis



PHARMACOLOGIC THERAPYPHARMACOLOGIC THERAPY

DIURETICSDIURETICS

Improved symptomsImproved symptoms

Decreasedmortality

Decreasedmortality

Preventionof CHF

Preventionof CHF

yesyes ?? ??

Vasodil.(Nitrates)Vasodil.(Nitrates) yesyes yesyes ??

DIGOXINDIGOXIN yesyes == minimalminimal

INOTROPESINOTROPES yesyes mort. mort. ??

Other neurohormonal control drugsOther neurohormonal control drugs

yesyes + / -+ / - ??

ACEIACEI yesyes YESYES yesyes

NeurohumoralControl

NeurohumoralControl

NONO

yesyes

nono

nono

YESYES

YESYES

TREATMENTTREATMENT

NormalNormal

AsymptomaticLV dysfunctionEF <40%

AsymptomaticLV dysfunctionEF <40%

Symptomatic CHFNYHA II

Symptomatic CHFNYHA II

InotropesSpecialized therapyTransplant

InotropesSpecialized therapyTransplant

Symptomatic CHFNYHA - IV

Symptomatic CHFNYHA - IV

Symptomatic CHFNYHA - III

Symptomatic CHFNYHA - III

Secondary preventionModification of physical activitySecondary preventionModification of physical activity

ACEIACEI

Diuretics mild

Neurohormonal inhibitors Digoxin?

Diuretics mild

Neurohormonal inhibitors Digoxin?

Loop DiureticsLoop Diuretics

Pharmacological therapy

Pharmacological therapy

Stage A Stage B Stage C Stage D

Pts with :• Hypertension• CAD• DM• Cardiotoxins• FHx CM

THERAPY• Treat Hypertension• Stop smoking • Treat lipid disorders• Encourage regular

exercise• Stop alcohol

& drug use• ACE inhibition

Pts with :• Previous MI• LV systolic

dysfunction• Asymptomatic

Valvular disease


stage A• ACE inhibitor • Beta-blockers


stage A• Drugs for routine use:

• diuretic• ACE inhibitor• Beta-blockers• digitalis


stage A,B and C• Mechanical assist

device• Heart transplantation• Continuous IV

inotrphic infusions for palliation

Pts who have marked symptoms at rest despite maximal medical therapy.

Pts with :

• Struct. HD

• Shortness of breath and fatigue, reduce exercise tolerance

Struct.Heart Disease

DevelopSymp.of

HF

Refract. Symp.of HF at rest

Stages in the evolution of HF and recommended therapy by stage


1. ACE INHIBITOR

Angiotensin-converting enzyme inhibitors

Recommended as first-line therapy.

Should be uptitrated to the dosages shown to be effective in the large, controlled trials, and not titrated based on symptomatic improvement.

Moderate renal insufficiency and a relatively low blood pressure (serum creatinine 250 µmol.l-1 and systolic BP 90 mmHg) are not contraindications.

Absolute contraindications: bilateral renal artery stenosis and angioedema.



Venous Vasodilatation

Venous Vasodilatation

MIXEDCalcium antagonists -adrenergic Blockers

ACEIAngiotensin II inhibitors

K+ channel activatorsNitroprusside

MIXEDCalcium antagonists -adrenergic Blockers

ACEIAngiotensin II inhibitors

K+ channel activatorsNitroprusside

VENOUSNitrates

Molsidomine

VENOUSNitrates

Molsidomine

ARTERIALMinoxidil

Hydralazine

ARTERIALMinoxidil

Hydralazine

VASODILATORS

CLASSIFICATION

VASODILATORS

CLASSIFICATION

Arterial Vasodilatation

Arterial Vasodilatation

VASOCONSTRICTIONVASOCONSTRICTION VASODILATATION VASODILATATION

KininogenKininogen

KallikreinKallikrein

Inactive FragmentsInactive Fragments

AngiotensinogenAngiotensinogen

Angiotensin IAngiotensin I

RENINRENIN

Kininase IIKininase IIInhibitorInhibitor

ALDOSTERONEALDOSTERONE

SYMPATHETICSYMPATHETICVASOPRESSINVASOPRESSIN

PROSTAGLANDINSPROSTAGLANDINS

tPAtPA

ANGIOTENSIN IIANGIOTENSIN II

BRADYKININBRADYKININ

ACEI

MECHANISM OF ACTION

ACEI

MECHANISM OF ACTION

A.C.E.A.C.E.

ACEI

HEMODYNAMIC EFFECTS

ACEI

HEMODYNAMIC EFFECTS

Arteriovenous Vasodilatation- PAD, PCWP and LVEDP- SVR and BP- CO and exercise tolerance

No change in HR / contractilityMVO2

Renal, coronary and cerebral flowDiuresis and natriuresis

Arteriovenous Vasodilatation- PAD, PCWP and LVEDP- SVR and BP- CO and exercise tolerance

No change in HR / contractilityMVO2

Renal, coronary and cerebral flowDiuresis and natriuresis

ACEI

ADVANTAGES

ACEI

ADVANTAGESInhibit LV remodeling post-MI

Modify the progression of chronic CHF

- Survival

- Hospitalizations

- Improve the quality of life

In contrast to others vasodilators, do not produce neurohormonal activationor reflex tachycardia

Tolerance to its effects does not develop

Inhibit LV remodeling post-MI

Modify the progression of chronic CHF

- Survival

- Hospitalizations

- Improve the quality of life

In contrast to others vasodilators, do not produce neurohormonal activationor reflex tachycardia

Tolerance to its effects does not develop

ACEI

UNDESIRABLE EFFECTS

ACEI

UNDESIRABLE EFFECTS

Inherent in their mechanism of action- Hypotension- Hyperkalemia- Angioneurotic edema

Due to their chemical structure- Cutaneous eruptions- Neutropenia,

thrombocytopenia- Digestive upset

Inherent in their mechanism of action- Hypotension- Hyperkalemia- Angioneurotic edema

Due to their chemical structure- Cutaneous eruptions- Neutropenia,

thrombocytopenia- Digestive upset

- Dry cough- Renal Insuff.- Dry cough- Renal Insuff.

- Dysgeusia- Proteinuria- Dysgeusia- Proteinuria

ACEI

CONTRAINDICATIONS

ACEI

CONTRAINDICATIONS

Renal artery stenosis

Renal insufficiency

Hyperkalemia

Arterial hypotension

Intolerance (due to side effects)

Renal artery stenosis

Renal insufficiency

Hyperkalemia

Arterial hypotension

Intolerance (due to side effects)

ACE-Inhibitors in Asymptomatic Heart Failure

Development of symptomatic HF

Hospitalization of HF



SAVE & TRACE StudySAVE & TRACE Study

ACE-Inhibitors in Symptomatic Heart Failure

All patients symptomatic Heart Failure should receive

ACE-I.

A) No fluid retention, ACE-I should be given first.

B) With fluid retention, ACE-I + Diuretic

ACE-I : A) improves survival and symptoms.

B) reduces hospitalization.



ACE INHIBITORS USED TO TREAT HEART FAILURE

DOSE RANGE TARGET DOSE FORDRUG (mg) FREQUENCY SURVIVAL BENEFIT*

Captopril 6.25 – 150 Three times daily 50 mg three times dailyEnalapril 2.5 – 20 Twice daily 10 mg twice dailyLisinopril 2.5 – 40 Daily -Ramipril 2.5 – 10 Once or twice daily 5 mg twice dailyQuinapril 5 – 20 Twice daily -Zofenopril† - - 30 mg twice dailyTrandolapril† - - 4 mg dailyImidapril HCl 5 – 10 Once daily 10 mg daily

* Target doses are those associated with increased survival in clinical trials† This drug is not approved in the United States

2. DIURETICS

Diuretics

Essential for symptomatic treatment when

fluid overload is present and manifest.

Always be administered in combination

with ACE inhibitors if possible.



CortexCortex

MedullaMedulla

ThiazidesInhibit active exchange of Cl-Na

in the cortical diluting segment of the ascending loop of Henle

ThiazidesInhibit active exchange of Cl-Na

in the cortical diluting segment of the ascending loop of Henle

K-sparingInhibit reabsorption of Na in the

distal convoluted and collecting tubule

K-sparingInhibit reabsorption of Na in the

distal convoluted and collecting tubule

Loop diuretics Inhibit exchange of Cl-Na-K in

the thick segment of the ascending loop of Henle

Loop diuretics Inhibit exchange of Cl-Na-K in

the thick segment of the ascending loop of Henle

Loop of HenleLoop of HenleCollecting tubuleCollecting tubule

DIURETICSDIURETICS

LOOP DIURETICS

MECHANISM OF ACTION

LOOP DIURETICS

MECHANISM OF ACTION

Excrete 15 - 20% of filtered Na+

Elimination of K+, Ca+ and Mg++

Resistance of afferent arterioles

-Cortical flow and GFR

- Release renal PGs

- NSAIDs may antagonize diuresis

Excrete 15 - 20% of filtered Na+

Elimination of K+, Ca+ and Mg++

Resistance of afferent arterioles

-Cortical flow and GFR

- Release renal PGs

- NSAIDs may antagonize diuresis

K-SPARING DIURETICS

MECHANISM OF ACTION

K-SPARING DIURETICS

MECHANISM OF ACTION

Eliminate < 5% of filtered Na+

Inhibit exchange of Na+ for K+ or H+

Spironolactone = competitive antagonist for the aldosterone receptor

Amiloride and triamterene block Na+ channels controlled by aldosterone

Eliminate < 5% of filtered Na+

Inhibit exchange of Na+ for K+ or H+

Spironolactone = competitive antagonist for the aldosterone receptor

Amiloride and triamterene block Na+ channels controlled by aldosterone

Volume and preloadImprove symptoms of congestion

No direct effect on CO, but

excessive preload reduction may

Improves arterial distensibility

Neurohormonal activation Levels of NA, Ang II and ARP Exception: with spironolactone

Volume and preloadImprove symptoms of congestion

No direct effect on CO, but

excessive preload reduction may

Improves arterial distensibility

Neurohormonal activation Levels of NA, Ang II and ARP Exception: with spironolactone

DIURETIC EFFECTSDIURETIC EFFECTS

DIURETICS

ADVERSE REACTIONS Thiazide and Loop Diuretics

DIURETICS

ADVERSE REACTIONS Thiazide and Loop Diuretics

Changes in electrolytes: Volume Na+, K+, Ca++, Mg++ metabolic alkalosis

Metabolic changes: glycemia, uremia, gout LDL-C and TG

Cutaneous allergic reactions

Changes in electrolytes: Volume Na+, K+, Ca++, Mg++ metabolic alkalosis

Metabolic changes: glycemia, uremia, gout LDL-C and TG

Cutaneous allergic reactions

DIURETICS

ADVERSE REACTIONSThiazide and Loop Diuretics

DIURETICS

ADVERSE REACTIONSThiazide and Loop Diuretics

Idiosyncratic effects:Blood dyscrasia, cholestatic jaundice and acute pancreatitis

Gastrointestinal effectsGenitourinary effects:

Impotence and menstrual cramps

Deafness, nephrotoxicity (Loop diuretics)

Idiosyncratic effects:Blood dyscrasia, cholestatic jaundice and acute pancreatitis

Gastrointestinal effectsGenitourinary effects:

Impotence and menstrual cramps

Deafness, nephrotoxicity (Loop diuretics)

DIURETICS

ADVERSE REACTIONSK-SPARING DIURETICS

DIURETICS

ADVERSE REACTIONSK-SPARING DIURETICS

Changes in electrolytes:

Na+, K+, acidosis

Musculoskeletal:

Cramps, weakness

Cutaneous allergic reactions :

Rash, pruritis

Changes in electrolytes:

Na+, K+, acidosis

Musculoskeletal:

Cramps, weakness

Cutaneous allergic reactions :

Rash, pruritis

3. ALDOSTERONE INHIBITORS

ALDOSTERONEALDOSTERONE

Retention Na+

Retention H2O

Excretion K+

Excretion Mg2+

Retention Na+

Retention H2O

Excretion K+

Excretion Mg2+

Collagen

deposition

Fibrosis - myocardium

- vessels

SpironolactoneSpironolactone

Edema Edema

Arrhythmias Arrhythmias

Competitive antagonist of thealdosterone receptor(myocardium, arterial walls, kidney)

Competitive antagonist of thealdosterone receptor(myocardium, arterial walls, kidney)

ALDOSTERONE INHIBITORSALDOSTERONE INHIBITORS

ALDOSTERONE INHIBITORS

INDICATIONS

ALDOSTERONE INHIBITORS

INDICATIONS

FOR DIURETIC EFFECT• Pulmonary congestion (dyspnea)• Systemic congestion (edema)

FOR ELECTROLYTE EFFECTS• Hypo K+, Hypo Mg+

• Arrhythmias• Better than K+ supplementsFOR NEUROHORMONAL EFFECTS• Please see RALES results,

N Engl J Med 1999:341:709-717

FOR DIURETIC EFFECT• Pulmonary congestion (dyspnea)• Systemic congestion (edema)

FOR ELECTROLYTE EFFECTS• Hypo K+, Hypo Mg+

• Arrhythmias• Better than K+ supplementsFOR NEUROHORMONAL EFFECTS• Please see RALES results,

N Engl J Med 1999:341:709-717

Recommended in advanced HF (NYHA III-IV),

in addition to ACE inhibition and diuretics to

improve survival and morbidity

Aldosterone receptor antagonists - spironolactone



The RALES mortality trial

Low dose spironolactone (12.5–50 mg) on top of an ACE inhibitor and a loop diuretic improved survival of patients in advanced heart failure (NYHA class III or IV).

Aldosterone receptor antagonists - spironolactone

4. ß-Blockers 4. ß-Blockers Start Low Go SlowStart Low Go Slow

Activation and Blockade of Neurohumoral System in CHF

RAA System SNS System

Angiotensin II Noradrenalin

Hypertrophy, apoptosis, ischaemia, arrhytmia, remodeling, fibrosis

β-BlockerACE-I

ADRENERGIC ACTIVATION

↑ CNS Sympathetic Outflow

↑ Sympathetic activity to kidneys & blood vessels

↑ Cardiac Sympathetic activity

β1-receptors β2-receptors 1-receptors

Mycocyte hypertrophy & death, dilatation, ischaemia & arrhytmia’s

Vasoconstriction Sodium Retention

Packer, AHA 2000

Why add-on Why add-on ββ-blocker-blocker,,

if HF patient is already stableif HF patient is already stable

on standard therapy withon standard therapy with

ACE-I, diuretics ± digoxinACE-I, diuretics ± digoxin

??

Benefits of “Add-on” β-Blocker

Short-term :

1. Improvement of symptoms (LVEF ↑)

2. Improvement of NYHA class

3. Improvement of daily activities

4. Reduction of hospitalization rate & length of hospital stay (financial & psychological burden)

Long-term :

1. Slowing the progression of CHF

2. Increase of survival rate

Recommended for the treatment of all pts with stable, mild, moderate and severe heart failure on standard treatment, unless there is a contraindication.

Patients with LV systolic dysfunction, with or without symptomatic HF, following an AMI long-term betablockade is recommended in addition to ACE inhibitor.

Beta-adrenoceptor antagonists



PHARMACOLOGICAL PROPERTIES OF

β-BLOCKING AGENT FOR HF

AGENT

β1-BLOKADE

β2-BLOKADE

-BLOKADE ISA

ANCILLARY EFFECTS

Carvedilol + + + + + + + + + - + + +

Metoprolol + + + - - - -

Bisoprolol + + + - - - -

ISA: intrinsic sympathetic activity

THE RECOMMENDED PROCEDURE FOR STARTING β-BLOCKER

1. Patient should be on standard therapy

(ACE inhibitor +/- diuretic)

2. Patient in stable conditions

No iv inotropic therapy

Without signs of marked fluid retention

3. Start initial low doses and titrate to maintenance dose

(the dose may be doubled every 1 – 2 weeks)

(ESC.Guidelines for HF, 2001)

DOSES OF β-BLOCKER

β BLOCKER FIRST DOSE TARGET DOSE TITRATION PERIOD

Bisoprolol 1.25 mg 10 mg Weeks – Month

Metoprolol

Tartrate

5 mg 150 mg Weeks – Month

Metoprolol Succinate

12.5 mg 200 mg Weeks – Month

Carvedilol 2 x 3.125 mg 2 x 25 mg Weeks – Month

(European Heart Journal, vol. 22, Sept. 2001)

CONTRAINDICATIONS OF

β-BLOCKER IN PATIENT H F

Asthma Bronchial

Severe Bronchial Desease

Symptomatic Bradycardia and

Hypotension

INTOLERANCE OF β-BLOCKER

Symptomatic Bradycardia

Worsening HF Hypotension

How to Handle Intolerance

SYMPTOMATIC BRADYCARDIA

Check Blood Digoxin and/or reduce other AV nodus inhibiting drugs

Reduces β-Blocker dose or if necessary stop it

Consider implantation of pacemaker


WORSENING HF

Increase dose of Diuretics

Reduces β-Blocker dose or if necessary stop it

If indicated, give inotropic drugs or nitroprusside or nitroglycerin


HYPOTENSION

Reduces ACE-I or vasodilator

Take β-Blocker :

After meal

At different time than ACE-I

Reduces dose or if necessary stop it

5. Angiotensin II receptor antagonists

ANGIOTENSIN II INHIBITORS

MECHANISM OF ACTION

ANGIOTENSIN II INHIBITORS

MECHANISM OF ACTION

RENINRENIN

AngiotensinogenAngiotensinogen Angiotensin I

ANGIOTENSIN II

Angiotensin I

ANGIOTENSIN II

ACEACEOther pathsOther paths

VasoconstrictionVasoconstriction Proliferative Action

Proliferative Action

VasodilatationVasodilatation Antiproliferative Action

Antiproliferative Action

AT1 AT1 AT2AT2

AT1 RECEPTOR BLOCKERS


RECEPTORSRECEPTORS


DRUGS


DRUGS

Losartan

Valsartan

Irbersartan

Candesartan

Losartan

Valsartan

Irbersartan

Candesartan

Competitive and selective

blocking of AT1 receptors

Competitive and selective

blocking of AT1 receptors

ARBs could be considered in patients who do not tolerate ACE inhibitors for symptomatic treatment.

It is unclear whether ARBs are as effective as ACE inhibitors for mortality reduction.

In combination with ACE inhibition, ARBs may improve heart failure symptoms and reduce hospitalizations for worsening heart failure.

Angiotensin II receptor antagonists



6. Cardiac glycosides

Na+Na+

K+K+

K+K+

Na+Na+

Na+Na+ Ca++Ca++

Ca++Ca++

Na-K ATPaseNa-K ATPase Na-Ca ExchangeNa-Ca Exchange

MyofilamentsMyofilaments

DIGOXINDIGOXIN

CONTRACTILITYCONTRACTILITY

DIGOXIN

PHARMACOKINETIC PROPERTIES

DIGOXIN

PHARMACOKINETIC PROPERTIESOral absorption (%)Protein binding (%)Volume of distribution (l/Kg)Half lifeEliminationOnset (min)

i.v.oral

Maximal effect (h)i.v.oral

DurationTherapeutic level (ng/ml)

Oral absorption (%)Protein binding (%)Volume of distribution (l/Kg)Half lifeEliminationOnset (min)

i.v.oral

Maximal effect (h)i.v.oral

DurationTherapeutic level (ng/ml)

60 - 7525

6 (3-9)36 (26-46) h

Renal

5 - 3030 - 90

2 - 43 - 6

2 - 6 days0.5 - 2

60 - 7525

6 (3-9)36 (26-46) h

Renal

5 - 3030 - 90

2 - 43 - 6

2 - 6 days0.5 - 2

DIGOXIN

DIGITALIZATION STRATEGIES

DIGOXIN

DIGITALIZATION STRATEGIES

(mg)

0.125-0.5 / d

0.25 / d

(mg)

0.125-0.5 / d

0.25 / d

i.v

0.5 + 0.25 / 4 h

ILD: 0.75-1

i.v

0.5 + 0.25 / 4 h

ILD: 0.75-1

oral 12-24 h

0.75 + 0.25 / 6 h

1.25-1.5

oral 12-24 h

0.75 + 0.25 / 6 h

1.25-1.5

oral 2-5 d

0.25 / 6-12 h

1.5-1.75

oral 2-5 d

0.25 / 6-12 h

1.5-1.75

Loading dose (mg)Loading dose (mg) Maintenance Dose

Maintenance Dose

ILD = average INITIAL dose required for digoxin loading

ILD = average INITIAL dose required for digoxin loading

DIGOXIN

HEMODYNAMIC EFFECTS

DIGOXIN

HEMODYNAMIC EFFECTS

Cardiac output

LVejection fraction

LVEDP

Exercisetolerance

Natriuresis

Neurohormonalactivation

Cardiac output

LVejection fraction

LVEDP

Exercisetolerance

Natriuresis

Neurohormonalactivation

DIGOXIN

NEUROHORMONAL EFFECTS

DIGOXIN

NEUROHORMONAL EFFECTS

Plasma Noradrenaline

Peripheral nervous system activity

RAAS activity

Vagal tone

Normalizes arterial baroreceptors

Plasma Noradrenaline

Peripheral nervous system activity

RAAS activity

Vagal tone

Normalizes arterial baroreceptors

%WORSENING

OF CHF

%WORSENING

OF CHFp = 0.001p = 0.001DIGOXIN: 0.125 - 0.5 mg /d

(0.7 - 2.0 ng/ml)EF < 35%Class I-III (digoxin+diuretic+ACEI)Also significantly decreased exercisetime and LVEF.

DIGOXIN: 0.125 - 0.5 mg /d (0.7 - 2.0 ng/ml)EF < 35%Class I-III (digoxin+diuretic+ACEI)Also significantly decreased exercisetime and LVEF.

DIGOXIN

EFFECT ON CHF PROGRESSION

DIGOXIN

EFFECT ON CHF PROGRESSION

RADIANCEN Engl J Med 1993;329:1RADIANCEN Engl J Med 1993;329:1

Placebo n=93DIGOXIN Withdrawal

Placebo n=93DIGOXIN Withdrawal

DIGOXIN n=85DIGOXIN n=85

3030

1010

00

2020

1001008080202000 4040 6060DaysDays

DIGOXIN

LONG TERM EFFECTS

DIGOXIN

LONG TERM EFFECTS

Survival similar to placebo

Fewer hospital admissions

More serious arrhythmias

More myocardial infarctions

Survival similar to placebo

Fewer hospital admissions

More serious arrhythmias

More myocardial infarctions

DIGOXIN

CLINICAL USES

DIGOXIN

CLINICAL USES

AF with rapid ventricular response

CHF refractory to other drugs

Other indications?

Can be combined with other drugs

AF with rapid ventricular response

CHF refractory to other drugs

Other indications?

Can be combined with other drugs

DIGOXIN

CONTRAINDICATIONS

DIGOXIN

CONTRAINDICATIONSABSOLUTE:

- Digoxin toxicity

RELATIVE- Advanced A-V block without pacemaker- Bradycardia or sick sinus without PM- PVC’s and TV- Marked hypokalemia- W-P-W with atrial fibrillation

ABSOLUTE:- Digoxin toxicity

RELATIVE- Advanced A-V block without pacemaker- Bradycardia or sick sinus without PM- PVC’s and TV- Marked hypokalemia- W-P-W with atrial fibrillation

DIGOXIN TOXICITY

CARDIAC MANIFESTATIONS

DIGOXIN TOXICITY

CARDIAC MANIFESTATIONS

ARRHYTHMIAS :- Ventricular (PVCs, TV, VF)- Supraventricular (PACs, SVT)

BLOCKS:- S-A and A-V blocks

CHF EXACERBATION

ARRHYTHMIAS :- Ventricular (PVCs, TV, VF)- Supraventricular (PACs, SVT)

BLOCKS:- S-A and A-V blocks

CHF EXACERBATION

DIGOXIN TOXICITY

EXTRACARDIAC MANIFESTATIONS

DIGOXIN TOXICITY

EXTRACARDIAC MANIFESTATIONS

GASTROINTESTINAL:- Nausea, vomiting, diarrhea

NERVOUS:- Depression, disorientation, paresthesias

VISUAL:- Blurred vision, scotomas and yellow-green

vision HYPERESTROGENISM:

- Gynecomastia, galactorrhea

GASTROINTESTINAL:- Nausea, vomiting, diarrhea

NERVOUS:- Depression, disorientation, paresthesias

VISUAL:- Blurred vision, scotomas and yellow-green

vision HYPERESTROGENISM:

- Gynecomastia, galactorrhea

indicated in atrial fibrillation and any degree of symptomatic heart failure.

A combination of digoxin and beta-blockade appears superior than either agent alone.

In sinus rhythm, digoxin is recommended to improve the clinical status of patients with persisting heart failure despite ACE inhibitor and diuretic treatment.

Cardiac glycosides



DIG trial

Long-term digoxin did not improve survival.

The primary benefit and indication for digoxin in heart failure is to reduce symptoms and improve clinical status decrease the risk of hospitalization for heart failure without an impact on survival.

Cardiac glycosides

7. Vasodilator agents

No specific role for vasodilators in the treatment of HF

Used as adjunctive therapy for angina or concomitant hypertension.

In case of intolerance to ACE inhibitors ARBs are preferred to the combination hydralazine–nitrates.

HYDRALAZINE-ISOSORBIDE DINITRATE

Hydralazine (up to 300 mg) in combination with ISDN (up to 160 mg) without ACE inhibition may have some beneficial effect on mortality, but not on hospitalization for HF.

Nitrates may be used for the treatment of concomitant angina or relief of acute dyspnoea.

Vasodilator agents in chronic heart failure



8. Positive inotropic therapy

CARDIAC GLYCOSIDES

SYMPATHOMIMETICSCatecholaminesß-adrenergic agonists

PHOSPHODIESTERASE INHIBITORS Amrinone Enoximone

Others

CARDIAC GLYCOSIDES

SYMPATHOMIMETICSCatecholaminesß-adrenergic agonists

PHOSPHODIESTERASE INHIBITORS Amrinone Enoximone

Others

MilrinonePiroximoneMilrinonePiroximone

POSITIVE INOTROPESPOSITIVE INOTROPES

ß-ADRENERGIC STIMULANTS

CLASSIFICATION

ß-ADRENERGIC STIMULANTS

CLASSIFICATION

B1 StimulantsIncrease contractility

Dobutamine Doxaminol XamoterolButopamine Prenalterol Tazolol

B1 StimulantsIncrease contractility

Dobutamine Doxaminol XamoterolButopamine Prenalterol Tazolol

B2 StimulantsProduce arterial vasodilatation and reduce SVR

B2 StimulantsProduce arterial vasodilatation and reduce SVR

PirbuterolCarbuterolPirbuterolCarbuterol

RimiterolFenoterolRimiterolFenoterol

TretoquinolSalbutamolTretoquinolSalbutamol

TerbutalineSalmefamolTerbutalineSalmefamol

SoterenolQuinterenolSoterenolQuinterenol

MixedMixedDopamineDopamine

DOPAMINE AND DOBUTAMINE

EFFECTS

DOPAMINE AND DOBUTAMINE

EFFECTS

ReceptorsReceptors

ContractilityContractility

Heart RateHeart Rate

Arterial Press.Arterial Press.

Renal perfusionRenal perfusion

ArrhythmiaArrhythmia

DA (µg / Kg / min)DA (µg / Kg / min) DobutamineDobutamine

< 2< 2DA1 / DA2DA1 / DA2

±±

±±

±±

++++

--

2 - 52 - 5ß1ß1

++++

++

++

++

±±

> 5> 5ß1 + ß1 +

++++

++++

++++

±±

++++

ß1ß1

++++

±±

++++

++

±±

POSITIVE INOTROPES

CONCLUSIONS

POSITIVE INOTROPES

CONCLUSIONS

May increase mortality

Safer in lower doses

Use only in refractory CHF

NOT for use as chronic therapy

May increase mortality

Safer in lower doses

Use only in refractory CHF

NOT for use as chronic therapy

Commonly used to limit severe episodes of HF or as a bridge to heart transplantation in end-stage HF.

Repeated or prolonged treatment with oral inotropic agents increases mortality.

Currently, insuffcient data are available to recommend dopaminergic agents for heart failure treatment.

Positive inotropic therapy



POSITIVE INOTROPHIC AGENTS

Dobutamin

Milrinone

Levosimendan

DOPAMINERGIC AGENTS

Ibopamine is not recommended for the treatment of chronic HF due to systolic LV dysfunction.

Intravenous dopamine is used for the sort-term correction of haemodynamic disturbances of severe episodes of worsening HF.

Positive inotropic therapy



9. Antiarrhythmics

ANTIARRHYTHMICSANTIARRHYTHMICS

Sustained VT, with/without symptoms- ß Blockers- Amiodarone

Sudden death from VF- Consider implantable defibrillator

Sustained VT, with/without symptoms- ß Blockers- Amiodarone

Sudden death from VF- Consider implantable defibrillator

ANTIARRHYTHMICS

MORTALITY

ANTIARRHYTHMICS

MORTALITY

EMIATAm Coll Cardiol 1996EMIATAm Coll Cardiol 1996

13.613.6 13.713.7

PlaceboPlacebo AmiodaroneAmiodarone00

55

1010

1515

101 / 743 102 / 743

MORTALITYAT 2 YEARS

%

MORTALITYAT 2 YEARS

%n=14865-21d post MIAmiodarone 200 mg/dFollow up 1 - 4 years

n=14865-21d post MIAmiodarone 200 mg/dFollow up 1 - 4 years

nsns

No indication for the use of antiarrhythmic agents in HF

Indications for antiarrhythmic drug therapy include AF (rarely flutter), non-sustained or sustained VT.

CLASS I ANTIARRHYTHMICS

should be avoidedCLASS II ANTIARRHYTHMICS

Beta-blockers reduce sudden death in heart failure

CLASS III ANTIARRHYTHMICS

Amiodarone is the only antiarrhythmic drug without clinically relevant negative inotropic effects.

Antiarrhythmics



10. Anticoagulation 11. Antiplatelet Drugs

ANTICOAGULANTSANTICOAGULANTS

PREVIOUS EMBOLIC EPISODEATRIAL FIBRILLATIONIdentified thrombusLV Aneurysm (3-6 mo post MI)Class III-IV in the presence of:

- EF < 30- Aneurysm or very dilated LV

PhlebitisProlonged bed rest

PREVIOUS EMBOLIC EPISODEATRIAL FIBRILLATIONIdentified thrombusLV Aneurysm (3-6 mo post MI)Class III-IV in the presence of:

- EF < 30- Aneurysm or very dilated LV

PhlebitisProlonged bed rest

Recommendation

1. All pts with HF and AF should be treated with warfarin unless contraindicated.

2. Patients with LVEF 35% or less.

Anticoagulation

HFSA Guidelines for Management of Patients With Heart Failure Caused by Left

Ventricular Systolic Dysfunction - Pharmacological Approaches 2000

Antiplatelet Drugs

Recommendation

There is insufficient evidence concerning the potential negative therapeutic interaction between ASA and ACE inhibitors.

Antiplatelet agent for pts with HF who have underlying CAD.

HFSA Guidelines for Management of Patients With Heart Failure Caused by Left

Ventricular Systolic Dysfunction - Pharmacological Approaches 2000

Chronic heart failure — choice of pharmacological therapy

LV systolic dysfunction ACE inhibitor Diuretic Beta-blockerAldosterone

Antagonist

Asymptomatic LV dysfunction

Indicated Not indicated Post MI Not indicated

Symptomatic HF (NYHA II) IndicatedIndicated if

Fluid retentionIndicated Not indicated

Worsening HF (NYHA III-IV) IndicatedIndicated

comb. diuretic

IndicatedIndicated

End-stage HF (NYHA IV) IndicatedIndicated

comb. diuretic

IndicatedIndicated



A

Chronic heart failure — choice of pharmacological therapy

LV systolic dysfunctionAngiotensin

II receptor antagonists

Cardiac glycosides

Vasodilator (hydralazine/ isosorbide dinitrate)

Potassium -sparing diuretic

Asymptomatic LV dysfunction

Not indicated With AF Not indicated Not indicated

Symptomatic HF (NYHA II)

If ACE inhibitors are not tolerated and not on beta-

blockade

(a) when AF

(b) when improved from more severe HF in sinus rhythm

If ACE inhibitors and angiotensin II

antagonists are not tolerated

If persisting hypokalaemia

Worsening HF (NYHA III-IV)

If ACE inhibitors are not tolerated and not on beta-

blockade

indicated




End-stage HF (NYHA IV)If ACE inhibitors are not tolerated and not on beta-

blockade

indicated






B

InterventionIntervention

Pts with heart failure of ischaemic origin revascularization

symtomatic improvement.

A strong negative correlation of operative mortality and LVEF,

a low LVEF (<25%) was associated with increased

operative mortality. Advance HF symptoms (NYHA IV)

resulted in a greater mortality rate.

Off pump coronary revascularization may lower the surgical

risk for HF.

Heart Transplantation is an accepted mode of treatment for

end-stage HF.

RevascularizationSurgical

Non Surgical



Care and Follow-up

Recommended components of programs

use a team approachvigilant follow-up, first follow-up within 10 days of discharge discharge planning increased access to health care optimizing medical therapy with guidelines intense education and counselling inpatient and outpatient strategies address barriers to compliance early attention to signs and symptomsflexible diuretic regimen



Future treatmentFuture treatment

1.1. Sympathetic nervous systemSympathetic nervous system2.2. The RAA systemThe RAA system3.3. Atrial and brain natriuretic peptidesAtrial and brain natriuretic peptides4.4. Arginin vasopressinArginin vasopressin5.5. EndothelinEndothelin6.6. Growth hormoneGrowth hormone7.7. Calcitonin gene related peptide Calcitonin gene related peptide

Neurohormonal modulationNeurohormonal modulation

Cardiac reparation: fixing the Cardiac reparation: fixing the heart with cells, new vessels heart with cells, new vessels

and genes (1)and genes (1)

1.1. Multiplication of residual myocytes Multiplication of residual myocytes (forcing the cells to enter mytotic cycle)(forcing the cells to enter mytotic cycle)

2.2. Transforming fibrablasts in the scarTransforming fibrablasts in the scar3.3. Implanting exogenous contractiles cells Implanting exogenous contractiles cells

(foetal cardiomyocites, skeletal (foetal cardiomyocites, skeletal myoblasts, stem cells)myoblasts, stem cells)

Aims:Aims: to repopulate fibrous scars with new to repopulate fibrous scars with new contractile cellscontractile cells

Cell based Cell based interventionsinterventions

Eur Heart JEur Heart J 2002;4: D73-81 2002;4: D73-81

CON’T (2)CON’T (2)

1. Administration of angiogenic growth factors VEGF, basic FGF

2. Problems: nature of compound , dose, route, and adverse events (abnormal blood vessels, proliferative retinopathy, etc)

AngiogenesisAngiogenesis

AimsAims:: to provides new blood supply to to provides new blood supply to the diseased heartthe diseased heart


CON’T(3)CON’T(3)

1.1. Gene manipulation of 3 majors areas: Ca Gene manipulation of 3 majors areas: Ca handling, beta-adenergic signalling and handling, beta-adenergic signalling and apoptosisapoptosis

2.2. Inducing expression of silent genesInducing expression of silent genes

Gene therapyGene therapy

Aims:Aims: to improve the function of the failing to improve the function of the failing heartheart

Safety problemsSafety problems:: control of targeted protein control of targeted protein expression, inflammation, autoimmunity expression, inflammation, autoimmunity and oncogenesis (basically irreversible)and oncogenesis (basically irreversible)


Resume

Pharmacological Treatment :

I. Asymptomatic Systolic LV dysfunction :• ACE Inhibitor -Blocker (in CAD)

II. Symptomatic Systolic LV dysfunctionA. No fluid retention

ACE Inhibitor-BlockerIf ischaemia (+) nitrate / revascularization

B. Fluid retentionDiureticACE Inhibitor (ARBs if not tolerated)-Blocker± Digitalis

Resume

III. Worsening HFStandard treatment : ACE Inhibitor, -Blocker Diuretic : doses + loop diureticLow dose spironolactoneDigitalisConsider :

» Revascularization» Valve surgery» Heart transplant

IV. End-stage HFIntermittent inotrophic supportCirculatory support (IABP, Ventr.Assist Devices)Haemofiltration on dialysis briddging to heart transplantation

Conclusion

Management of HF must be starting from the earlier stage (AHA/ACC stage A). Treatment at each stage can reduce morbidity and mortality.

Before initiating therapy :Established the correct diagnose.

Consider management outline.

Conclusion

Non pharmacolgical intervention are helpfull in :improving quality of life

reducing readmission

lowering cost.

Organize multi-disciplinary care :HF clinic, HF nurse specialist, pts telemonitoring.

Health care system.

To optimize HF management Treatment should be according to the Guidelines, intensive education, and behavioral change efforts.

THANK YOUHave a nice study !!!

Documents

CHRONIC HEART FAILURE Faculty of Medicine University of Brawijaya