The Problem Of Heart Failure

The Problem of Heart The Problem of Heart FailureFailure

Fathi Fathi MakladyMaklady . .MD,FRCPMD,FRCP

Suez Canal UniversitySuez Canal University

Overview

• Epidemiology of heart failure

• Highlights of the ACC/AHA guidelines

• Overview of the clinical trials

A Public Health Crisis: Heart Failure A Public Health Crisis: Heart Failure Hospitalizations have Tripled in 25 Hospitalizations have Tripled in 25

YearsYears

NHLBI. Morbidity and Mortality: 2000 Chartbook on Cardiovascular, Lung, and Blood Diseases. Geneva: World Health Organization; 1996.

Ho

spit

aliz

atio

ns/

100,

000

Po

pu

lati

on

19700

50

100

150

200

250

1975 1980 1985 1990 1995

Year

65+ years

45-64 years

Prevalence of Heart FailurePrevalence of Heart FailureWorldwideWorldwide

19,00019,0002.42.4JapanJapan

18,00018,000North AmericaNorth America

14,00014,0005.35.3Western EuropeWestern Europe

RateRate((per million popper million pop).).

Absolute NumbersAbsolute Numbers((millions of patientsmillions of patients))

Murray CJL, Lopez AD. Global health statistics: a compendium of incidence, prevalence and mortality estimates for over 200 conditions. Geneva: World Health Organization;.

Hospitalization: The Major Factor in Heart Failure Costs in the US

60.6%Hospitalization

$23.1 billion

38.6%Outpatient care$14.7 billion)3.4 visits/year/patient(

0.7%Transplants$270 millionTotal = $38.1 billion

)5.4% of total health care costs(

O’Connell JB, Bristow MR. J Heart Lung Transplant. 1994;13:S107-S112.

Heart FailureHeart Failure

A A clinical syndrome in which the heart isclinical syndrome in which the heart is

unable to pump sufficient blood to meetunable to pump sufficient blood to meet

the metabolic demands of the bodythe metabolic demands of the body..

DEFINITIONDEFINITION

““HF is a complex clinical syndrome thatHF is a complex clinical syndrome that

can result from any functionalcan result from any functional

or structural Cardiac disorder that or structural Cardiac disorder that impairimpair

the ability of The ventricles to fill the ability of The ventricles to fill withwith

or eject blood”or eject blood” ACC/AHA 2005 ACC/AHA 2005

Stages of Heart Failure

At Risk for Heart Failure:

STAGE A High risk for developing HF

STAGE B Asymptomatic LV dysfunction

Heart Failure:

STAGE C Past or current symptoms of HF

STAGE D End-stage HF

New Approach to the New Approach to the Classification of Heart Classification of Heart

FailureFailure

Marked symptoms at rest despite Marked symptoms at rest despite maximal medical therapy (eg, those maximal medical therapy (eg, those who are recurrently hospitalized or who are recurrently hospitalized or cannot be safely discharged from the cannot be safely discharged from the hospital without specialized hospital without specialized interventions)interventions)

Refractory Refractory end-stage HFend-stage HFDD

Known structural heart diseaseKnown structural heart disease Shortness of breath and fatigueShortness of breath and fatigue Reduced exercise toleranceReduced exercise tolerance

Symptomatic Symptomatic HFHFCC

Previous MIPrevious MI LV systolic dysfunctionLV systolic dysfunction Asymptomatic valvular diseaseAsymptomatic valvular disease

Asymptomatic Asymptomatic HFHFBB

Hypertension obesityHypertension obesity CAD MTSCAD MTS Diabetes mellitusDiabetes mellitus Family history of cardiomyopathyFamily history of cardiomyopathy

High risk for High risk for developing heart developing heart failure (HF)failure (HF)

AAPatient DescriptionPatient DescriptionStageStage

Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113.

ACC/AHA Staging SystemACC/AHA Staging Systemfor HFfor HF

StageStage Patient Patient descriptiondescription

A:A: High risk High risk for for developing developing HFHF

-HTN -CAD-HTN -CAD

-DM -Dyslipidaemia -FH of -DM -Dyslipidaemia -FH of CMCM

B:B: AsymptomatiAsymptomaticc

HFHF

-Previous MI -LVH -LVSD-Previous MI -LVH -LVSD

-Asymptomatic valvular Ht -Asymptomatic valvular Ht diseasedisease

C:C: Symptomatic Symptomatic

HFHF

-Known structural Ht disease -Known structural Ht disease

-SOB& Fatigue –reduced -SOB& Fatigue –reduced exercise toleranceexercise tolerance

D:D: Refractory Refractory

HFHF-Marked symptoms at rest-Marked symptoms at rest

-Maximal medical therapy-Maximal medical therapy

Stages of Heart Failure

COMPLEMENT, DO NOT REPLACE NYHA CLASSES

• NYHA Classes - shift back/forth in individual patient )in response to Rx and/or progression of disease(

• Stages - progress in one direction due to cardiac remodeling

Systolic Heart Failure

Diastolic Heart Failure

Neurohormonal System and Neurohormonal System and HFHF

There is substantial evidence that There is substantial evidence that activation of neurohormonal system activation of neurohormonal system plays an important part in cardiac plays an important part in cardiac remodeling and thereby in the remodeling and thereby in the progression of HF :progression of HF :

--Nor epinephrine -Nor epinephrine -Angiotensin11Angiotensin11

-Aldosteron --Aldosteron -EndothelineEndotheline

-vasopressin -Cytokines-vasopressin -Cytokines

The Progressive The Progressive Development of Development of

Cardiovascular DiseaseCardiovascular Disease

Endstage Heart DiseaseEndstage Heart Disease

Congestive Heart FailureCongestive Heart Failure

Ventricular DilationVentricular Dilation

RemodelingRemodeling

Arrhythmia & Loss of MuscleArrhythmia & Loss of Muscle

Myocardial InfarctionMyocardial Infarction

Myocardial IschemiaMyocardial Ischemia

CADCAD

AtherosclerosisAtherosclerosis

Endothelial DysfunctionEndothelial Dysfunction

Risk FactorsRisk Factors

Coronary ThrombosisCoronary Thrombosis

Assessment of patient with Assessment of patient with HFHF

HistoryHistory --HTN DiabetesHTN Diabetes -Dyslipidemia-Dyslipidemia Valvular heart Valvular heart

diseasedisease -CAD -PVD-CAD -PVD -Myopathy RH -Myopathy RH

feverfever -Smoking -Obesity-Smoking -Obesity -Alcohol -Pheo-Alcohol -Pheo -Thyroid disorder-Thyroid disorder Sexually transmitted Sexually transmitted

DD

Family History:Family History: -MI -Stroke --MI -Stroke -

PVDPVD -Sudden cardiac -Sudden cardiac

deathdeath -Myopathy-Myopathy -Cardiomyopathy-Cardiomyopathy -Conduction -Conduction

defectdefect -Tachyarrhythmia-Tachyarrhythmia

CHF Patient Population by NYHA CHF Patient Population by NYHA ClassClass

Class INo limitations of physical activityClass IISlight limitations of physical activityClass IIIMarked limitations of physical activityClass IVInability to carry out physical activities without discomfort and/or symptoms at rest

Class II1.68 M(35%)

Class IV240 K(5%)

Class III1.20 M(25%)

Class I1.68 M(35%)

AHA Heart and Stroke Statistical Update 2001

Assessment of patient with Assessment of patient with HFHF

Physical ExaminationPhysical Examination --Assessment of PT volume status, Assessment of PT volume status,

Orthostatic BP changes, Orthostatic BP changes, WT,hight and BMIWT,hight and BMI

-Exercise tolerance-Exercise tolerance

Assessment of Patient Assessment of Patient with HFwith HF

Laboratory EvaluationLaboratory Evaluation -Complete BL picture -urine -Complete BL picture -urine

analysisanalysis

-Serum electrolytes:Ca ,,Mg,BUN,SC,LFTs, TSH-Serum electrolytes:Ca ,,Mg,BUN,SC,LFTs, TSH

Glycohemoglobin,Lipid profileGlycohemoglobin,Lipid profile 12 lead ECG12 lead ECG 2Dechocadiography2Dechocadiography Coronary angio in PTs presenting with Coronary angio in PTs presenting with

anginaangina

Assessment of Patient with Assessment of Patient with HFHF

Value of Echocardiography: Value of Echocardiography:

The single most useful diagnostic The single most useful diagnostic test in evaluation of a PT with HFtest in evaluation of a PT with HF

THE Value of Echocardiography

The most useful diagnostic test in the

evaluation of HF

Value of EchocardiographyValue of Echocardiography

Three fundamental questions must be Three fundamental questions must be addressed:addressed:

1- Is the LVEF preserved or reduced ?1- Is the LVEF preserved or reduced ?

2-Is the structure of LV normal or 2-Is the structure of LV normal or abnormal ?abnormal ?

3-Are there other structural abnormality 3-Are there other structural abnormality

such as valvular,pericardial or RV that such as valvular,pericardial or RV that could account for the clinical could account for the clinical presentation ?presentation ?

Pathogenesis andPathogenesis andTherapeutic ApproachesTherapeutic Approaches

LV Function

Cardiac Output

NeurohormoneActivation

ProgressiveProgressiveHeart FailureHeart Failure

DiureticsDiuretics

VasodilatorsVasodilatorsACE InhibitorsACE Inhibitors

Imepdance

Salt and WaterRetention

RAA SystemANFCatecholamines

ACE InhibitorACE Inhibitor

DigoxinDigoxin

{

B-blockers

Targets for drug Targets for drug therapytherapy

* To improve symptoms* To improve symptoms DiureticsDiuretics DigoxinDigoxin ACE-inhibitorsACE-inhibitors

* To improve survival* To improve survival ACE-inhibitorsACE-inhibitors blockersblockers ARBsARBs SpironolactoneSpironolactone

Davies et al. BMJ 2000; 320: 428-431

Stage A Therapy

Recommended Therapies to Reduce Risk Include:• Treating known risk factors )hypertension, diabetes, etc.(

with therapy consistent with contemporary guidelines• Avoiding behaviors increasing risk )i.e., smoking

excessive consumption of alcohol, illicit drug use(• Periodic evaluation for signs and symptoms of HF• Ventricular rate control or sinus rhythm restoration• Noninvasive evaluation of LV function• Drug therapy –

•Angiotensin Converting Enzyme Inhibitors )ACEI(•Angiotensin Receptor Blockers )ARBs(

Stage A Therapy

Routine use of nutritional supplements solelyto prevent the development of structural heart disease should not be recommended for patients at high risk for developing HF.

Therapies NOT Recommended

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Stage BStage B

Patients with Asymptomatic LV Dysfunction

Stage B Therapy

Recommended Therapies:General Measures as advised for Stage A

•Drug therapy for all patients•ACEI or ARBs•Beta-Blockers

•ICDs in appropriate patients•Coronary revascularization in appropriate patients•Valve replacement or repair in appropriate patients

Stage CStage C

Patients with Past or CurrentSymptoms of Heart Failure

Recommended Therapies:•General measures as advised for Stages A and B•Drug therapy for all patients

•Diuretics for fluid retention•ACEI•Beta-blockers

•Drug therapy for selected patients•Aldosterone Antagonists•ARBs•Digitalis•Hydralazine/nitrates

•ICDs in appropriate patients•Cardiac resynchronization in appropriate patients•Exercise Testing and Training

Stage C Therapy)Reduced LVEF with Symptoms(

Recommended Therapies for Routine Use:•Treating known risk factor )hypertension( with therapy

consistent with contemporary guidelines•Ventricular rate control for all patients•Drugs for all patients -

•Diuretics•Drugs for appropriate patients –

•ACEI•ARBs•Beta-Blockers•Digitalis

•Coronary revascularization in selected patients•Restoration/maintenance of sinus rhythm in

appropriate patients

Stage C Therapy)Normal LVEF with Symptoms(

Calcium channel blocking drugs are not indicated as

routine treatment for HF in patients with current or prior symptoms of HF and reduced LVEF.

Hormonal therapies other than to replete deficiencies are not recommended and may be harmful to patients with current or prior symptoms of HF and reduced LVEF.

Routine combined use of an ACEI, ARB, and aldosterone antagonist is not recommended for patientswith current or prior symptoms of HF and reduced LVEF.

Unproven/Not Recommended Drugs and Interventions





Long-term use of an infusion of a positive inotropic drug may be harmful and is not recommended for patients with current or prior symptoms of HF and reduced LVEF, except as palliation for patients with end-stage disease who cannot be stabilized with standard medical treatment )see recommendations for Stage D(.

Use of nutritional supplements as treatment for HF is not indicated in patients with current or prior symptoms of HF and reduced LVEF.

Unproven/Not Recommended Drugs and Interventions




Unproven/Not RecommendedDrugs and Interventions for HF

• Nutritional Supplements

• Hormonal Therapies

• Intermittent Intravenous

Positive Inotropic Therapy


Patients with LVEF less than or equal to 35%, sinusrhythm, and NYHA functional class III or ambulatoryclass IV symptoms despite recommended, optimalmedical therapy and who have cardiac dyssynchrony, which is currently defined as a QRS duration greater than 120 ms, should receive

cardiac resynchronization therapy unless contraindicated.

Cardiac Resynchronization



An ICD is recommended as secondary prevention to prolong survival in patients with current or prior symptoms of HF and reduced LVEF who have a history of cardiac arrest, ventricular fibrillation, or hemodynamically destabilizing ventricular tachycardia.

ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with ischemic heart disease who are at least 40 days post-MI, have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year.

Implantable Cardioverter-Defibrillators )ICDs(




ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with nonischemic cardiomyopathy who have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year.

Placement of an ICD is reasonable in patients with LVEF of 30% to 35% of any origin with NYHA functional class II or III symptoms who are taking chronic optimal medical therapy and who have reasonable expectation of survival with good functional status of more than 1 year.

ICDs )cont’d(III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII



Stage DStage D

Patients with Refractory End-Stage HF

Stage D Therapy

Recommended Therapies Include:•Control of fluid retention •Referral to a HF program for appropriate pts•Discussion of options for end-of-life care•Informing re: option to inactivate defibrillator•Device use in appropriate patients•Surgical therapy –

•Cardiac transplantation•Mitral valve repair or replacement•Other

•Drug Therapy –•Positive inotrope infusion as palliation in appropriate patients

Stage D Therapy

Continuous intravenous infusion of a positive inotropic agent may be considered for palliation of symptoms in patients with refractory end-stage HF.

Routine intermittent infusions of positive inotropic agents are not recommended for patients with refractory end-stage HF.

Medical TherapyIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII


Stage D Therapy

Referral for cardiac transplantation in potentially eligible patients is recommended for patients with refractory end-stage HF.

The effectiveness of mitral valve repair or replacement is not established for severe secondary mitral regurgitation in refractory end-stage HF.

Surgical Therapy




Stage D Therapy

Consideration of an LV assist device as permanentor “destination” therapy is reasonable in highly selected patients with refractory end-stage HF and an estimated 1-year mortality over 50% with medical therapy.

Pulmonary artery catheter placement may be reasonable to guide therapy in patients with refractory end-stage HF and persistently severe symptoms.

Device Use


Stage D Therapy

Partial left ventriculectomy is not recommended inpatients with nonischemic cardiomyopathy and refractory end-stage HF.

Routine intermittent infusions of positive inotropic agents are not recommended for patients with refractory end-stage HF.

Therapies NOT Recommended



DIURETICS

CHF THERAPYACE-InhibitorsB-blockers

Beta Blockers

B-Blockers in CHFB-Blockers in CHFHistorical PerspectiveHistorical Perspective

1975- 1980 First 1975- 1980 First reports of clinical reports of clinical benefit*benefit*

High NE associated High NE associated with high mortalitywith high mortality

B receptor down-B receptor down-regulationregulation

?Are B-Adrenergic-?Are B-Adrenergic-blocking agents usefulblocking agents useful in the treatment of in the treatment of DCM**DCM**

* Waagstein Br Heart Journal 1975, Swedberg Br Heart Journal 1980

**Alderman Grossman Circulation 1985

What is the evidence

*Disease progression was defined as HF death or hospitalization or the need for sustained increase in medications for HF.Patients were on a background of diuretics, ACE inhibitors, ± digoxin.

Colucci WS et al. Circulation. 1996;94:2800–2806.

Pro

bab

ilit

y of

eve

nt-

free

su

rviv

al

1.0

0.8

0.6

0 50 100 150 200 250 300 350 400

Carvedilol(n=232)

Placebo(n=134)

P=.008

Risk reduction

48%

Days

0

Effect of Carvedilol on Effect of Carvedilol on Disease Progression in Mild Disease Progression in Mild or Moderate Heart Failureor Moderate Heart Failure

Total MortalityTotal MortalityTotal MortalityTotal Mortality

P=0.0062

Risk reduction: 34%P

erce

nt o

f pat

ient

s

Months of follow-up0 3 6 9 12 15 18 21

20

15

5

0

10

Placebon=2001

Metoprolol XL n=1990

Key Findings from CIBIS11Key Findings from CIBIS11

All cause mortality reduced by All cause mortality reduced by 34%34%

Sudden Death reduced by 44%Sudden Death reduced by 44% Fewer hospitalization with Fewer hospitalization with

bisoprololbisoprolol Significant fewer CVdeathSignificant fewer CVdeath % of permanent treatment % of permanent treatment

withdrawal was identical in both withdrawal was identical in both groupsgroups

ß-Blockers: Use in Heart ß-Blockers: Use in Heart Failure is Now Supported Failure is Now Supported

by Overwhelming by Overwhelming EvidenceEvidence

>>15,000 patients evaluated in long-term 15,000 patients evaluated in long-term placebo-controlled clinical trialsplacebo-controlled clinical trials

Improvement in cardiac function and Improvement in cardiac function and symptoms; equivocal effects on exercise symptoms; equivocal effects on exercise tolerancetolerance

Decrease in all-cause mortality by 30%–Decrease in all-cause mortality by 30%–65% (65% (PP<.0001)<.0001)

Decrease in combined risk of death and Decrease in combined risk of death and hospitalization by 35%hospitalization by 35%––40% (40% (PP<.001) <.001)

Effect shown in patients already Effect shown in patients already receiving ACE inhibitorsreceiving ACE inhibitors

B-Blockers in CHFB-Blockers in CHF

Are B-Blockers Effective in CHF?Are B-Blockers Effective in CHF?

Is it a class effect?Is it a class effect?

Is it safe to use in advanced CHF (FTC Is it safe to use in advanced CHF (FTC IV)?IV)?

When should you initiate B-blockers?When should you initiate B-blockers?

Are B-blockers safe to use post MI & Are B-blockers safe to use post MI & CHF?CHF?

-Efficacy seen with Bisoprolol, Metoprolol XL, Carvedilol

-Efficacy and safety established with Carvedilol

-May be started in the hospital when euvolemic )IMPACT-HF)

-May be initiated post MI with CHF/LV dysfunction )CAPRICORN)

-Yes

ACE-I

ACE-I

Aldosterone

Sympathetic activation

Growthfactor

stimulation

NA+ retentionH2O retentionK+ excretionMg+ excretion

Vascular smooth muscle

constriction

Angiotensinconverting

enzyme)ACE(

Angiotensin II

Liver secretes angiotensinogen

Kidneys secreterenin

The Renin-Angiotensin-Aldosterone (RAA) The Renin-Angiotensin-Aldosterone (RAA) SystemSystem

Angiotensinogen Angiotensin I

Adrenal cortex secretes

aldosterone

Blood Renin

Pro-Inflammtory

Apoptosis

Angiotensin I

Angiotensinogen(Liver)

AT1 AT2

Angiotensin II

ACE-inhibitor

ARBsAT1 receptor blocker

Bradykinin

Peptides

Chymase

Pathways of Ang II Pathways of Ang II generationgeneration

de Gasparo et al. Pharmacol Rev. 2000; 52: 415

Bad Good

X

X

X

Trial ACEI Controls RR (95% CI)

CONSENSUS I

SOLVD (Treatment)

SOLVD (Prevention)

Chronic CHF

Post MI

SAVE

TRACE

AIRE

39% 54% 0.56 (0.34–0.91)

40%35% 0.82 (0.70–0.97)

15% 16% 0.92 (0.79–1.08)

25%20% 0.81 (0.68–0.97)

17% 23% 0.73 (0.60–0.89)

SMILE 6.5% 8.3% 0.78 (0.52–1.12)

Average

0.78 (0.67–0.91)35% 42%

21% 25%

Effect of ACE Inhibitors on Effect of ACE Inhibitors on Mortality Reduction in Mortality Reduction in

Patients With CHFPatients With CHFMortality

Garg R et al. JAMA. 1995;273:1450–1456.Data shown from individual trials–not direct comparison data.

PlaceboPlacebo

EnalaprilEnalapril

1212111110109988776655

PROBABILITYOF DEATH

PROBABILITYOF DEATH

MONTHSMONTHS

0.10.1

0.80.8

00

0.20.2

0.30.3

0.70.7

0.40.4

0.50.5

0.60.6p< 0.001p< 0.001

CONSENSUSCONSENSUS

4433221100

N Engl J Med 1987;316:1429

30% risk reduction

Mortality%

Mortality%

N Engl J Med 1992;327:669N Engl J Med 1992;327:669

44YearsYears

3030

2020

1010

0011 22 33

PlaceboPlacebo

CaptoprilCaptopril

00

n=1115n=1115

n=1116n=1116Asymptomatic ventriculardysfunction post MI

Asymptomatic ventriculardysfunction post MI

SAVE

20% risk reduction

P<0.019

5050

4040

3030

2020

1010

00

MonthsMonths00 66 1212

p = 0.0036p = 0.0036%MORTALITY

%MORTALITY

24241818 3030 3636 4242 4848

Enalapriln=1285Enalapriln=1285

Placebon=1284Placebon=1284

N Engl J M 1991;325:293N Engl J M 1991;325:293

SOLVD )Treatment(

16% risk reduction

ACE Inhibition in Heart ACE Inhibition in Heart FailureFailure

All patients with heart failure due to All patients with heart failure due to left ventricular systolic dysfunction left ventricular systolic dysfunction should receive an ACE inhibitor unless should receive an ACE inhibitor unless they have a contraindication to its use they have a contraindication to its use or cannot tolerate treatment with the or cannot tolerate treatment with the drug. drug.

Treatment with an ACE inhibitor should Treatment with an ACE inhibitor should not be delayed until the patient is not be delayed until the patient is found to be resistant to treatment with found to be resistant to treatment with other drugs.other drugs.

Consensus Recommendations

Steering Committee and Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure.Am J Cardiol. 1999;83(suppl 2A):1A–39A.

Patients Not Receiving Patients Not Receiving ACE-IsACE-Is

ACE-Is No ACE-Is

Possible underusePossible underuse

ContraindicationContraindication

Other AEsOther AEs CoughCough

73% 27%22%

20%

33%25%

167 Cardiology and 250 Internal Medicine Clinics, Feb 14-25, 2000.Data from TEMISTOCLE Registry, ANMCO.

N = 2127

Utilization of Evidence Based Utilization of Evidence Based Therapies in Heart FailureTherapies in Heart Failure

ACE Inhibitors Beta Blockers0

20

40

60

80

100

Per

cen

t o

f P

atie

nts

29

19

69

University Hospital Consortium HF Registry: 33 Centers, 1239 patients, Year 2000Discharge Medications

Spironolactone

Under treatment of HF Under treatment of HF in Europein Europe

DiureticsDiuretics

ACE-inhibitorACE-inhibitor

blocker blocker

Digitalis glycosideDigitalis glycoside

NitrateNitrate

SpironolactoneSpironolactone

ARBARB

0 20 40 60 80 100Percent of patients receiving agent

Cardiovascular drug use

Cleland et al. Eur Heart J. 2001; 22: 494

ARBs

What is the Potential Role of What is the Potential Role of ARBs in Patients With ARBs in Patients With Congestive Heart Failure Congestive Heart Failure (CHF)(CHF)??

Are ARBs more efficacious than angiotensin-Are ARBs more efficacious than angiotensin-converting enzyme inhibitors (ACE-Is)?converting enzyme inhibitors (ACE-Is)?

Are ARBs as efficacious as ACE-Is?Are ARBs as efficacious as ACE-Is? Is the combination of an ARB and an ACE-I Is the combination of an ARB and an ACE-I

more efficacious than ACE-I monotherapy?more efficacious than ACE-I monotherapy? Are ARBs Are ARBs efficaciousefficacious in patients who cannot in patients who cannot

tolerate ACE-Is?tolerate ACE-Is? Are ARBs Are ARBs efficaciousefficacious in patients with heart in patients with heart

failure and preserved left ventricular function?failure and preserved left ventricular function?

Additional Benefits of Additional Benefits of ARB and ACE-I ARB and ACE-I

Combination TherapyCombination Therapy Neurohormonal profileNeurohormonal profile11

Prevention of left ventricular Prevention of left ventricular remodelingremodeling11

HemodynamicsHemodynamics22

Exercise capacityExercise capacity33However, only large-scale randomized controlled trials can prove reduction of morbidity and mortality in heart failure

1RESOLVD. Circulation. 1999;100:1056-1064.2Baruch L et al. Circulation. 1999;99:2658-2664. 3Hamroff G et al. Circulation. 1999;99:990-992.

New TherapiesNew Therapies

Biventricular pacing-LV pacing Biventricular pacing-LV pacing via the coronary sinusvia the coronary sinus

TNF-alpha blockers- for Class III-TNF-alpha blockers- for Class III-IV CHFIV CHF

Endothelin blockersEndothelin blockers Neutral endopeptidase blockersNeutral endopeptidase blockers Vasopressin Vasopressin

99Overview of Device Therapy

Biventricular PacingBiventricular PacingVentricular DysynchronyVentricular Dysynchrony

Abnormal ventricular conduction Abnormal ventricular conduction resulting in a mechanical delayresulting in a mechanical delay Wide QRS (IVCD); typically Wide QRS (IVCD); typically

LBBB morphologyLBBB morphology Poor systolic functionPoor systolic function Impaired diastolic functionImpaired diastolic function

ECG depicting interventricular conduction delayECG depicting interventricular conduction delay

THANK YOUTHANK YOU

The Problem Of Heart Failure

Health & Medicine