HEART FAILURE Adapted From: American Heart Association HEART FAILURE Adapted From: American Heart...

HEART FAILURE

Adapted From:

American Heart Association

HEART FAILURE

Adapted From:

American Heart Association

Chronic Congestive Heart FailureChronic Congestive Heart Failure

Committee on Post Graduate Education,Council on Clinical Cardiology,American Heart Association

Developed in collaboration with the Sociedad Española de Cardiología

Prepared by:Ann F. Bolger, MDJosé López-Sendón, MD

The content of these slides is current as of March 2003Future revisions will be posted on the American Heart Association website (www.americanheart.org).

Committee on Post Graduate Education,Council on Clinical Cardiology,American Heart Association

Developed in collaboration with the Sociedad Española de Cardiología

Prepared by:Ann F. Bolger, MDJosé López-Sendón, MD

The content of these slides is current as of March 2003Future revisions will be posted on the American Heart Association website (www.americanheart.org).


Definition of Heart FailureDefinition of Heart Failure

Clinical syndrome that can result from any Clinical syndrome that can result from any structural or functional cardiac disorder thatstructural or functional cardiac disorder thatimpairs the ability of the ventricle to fill with impairs the ability of the ventricle to fill with or eject bloodor eject blood


EpidemiologyEpidemiology

•• 5,000,000 patients5,000,000 patients

•• 6,500,000 hospital 6,500,000 hospital daysdays / year / year

•• 300,000 deaths / year300,000 deaths / year

•• 10% of people > 65 years10% of people > 65 years

•• 5.4% of healthcare budget ($28 billion)5.4% of healthcare budget ($28 billion)

•• Incidence x 2 in last ten yearsIncidence x 2 in last ten years

Gottdiener J et al. JACC 2000;35:1628Gottdiener J et al. JACC 2000;35:1628Haldeman GA Haldeman GA et al.et al. Am Heart J 1999;137:352 Am Heart J 1999;137:352Kannel WB Kannel WB et al.et al. Am Heart J 1991;121:951 Am Heart J 1991;121:951O’Connell JB O’Connell JB et al.et al. J Heart Lung Transplant 1993;13:S107 J Heart Lung Transplant 1993;13:S107


Suspect Heart FailureSuspect Heart Failure

Assess presence of CARDIAC DISEASEAssess presence of CARDIAC DISEASEby PE, EKG, CXR, or by PE, EKG, CXR, or BNPBNP

ABNORMALABNORMAL

Assess LV FUNCTION Assess LV FUNCTION by by Echocardiogram, Echocardiogram, Nuclear Nuclear

angiography, or MRI if availableangiography, or MRI if available

ABNORMALABNORMAL

NORMALNORMALNo Heart FailureNo Heart Failure

NORMALNORMALNo Heart FailureNo Heart Failure

Heart FailureHeart Failure

Chronic Congestive Heart FailureChronic Congestive Heart FailureRisk FactorsRisk Factors

Gottdiener J et al. Gottdiener J et al. The Cardiovascular Health Study The Cardiovascular Health Study JACC 2000;35:1628JACC 2000;35:1628


Direct CausesDirect Causes

1- 1- Myocardial Abnormalities (Myocardial Abnormalities (CHDCHD))

2- 2- Hemodynamic OverloadHemodynamic Overload

3- 3- Ventricular Filling AbnormalitiesVentricular Filling Abnormalities

4- 4- Ventricular DyssynergyVentricular Dyssynergy

5- 5- Changes in Cardiac RhythmChanges in Cardiac Rhythm


Aggravating FactorsAggravating Factors

• Medications• New Heart Disease

• Myocardial Ischemia

• Medications• New Heart Disease

• Myocardial Ischemia

• Endocarditis

• Obesity

• Hypertension

• Physical Activity

• Dietary Excess

• Endocarditis

• Obesity

• Hypertension

• Physical Activity

• Dietary Excess

• Pregnancy

• Arrhythmias (AF)

• Infections

• Thromboembolism

• Hyper/hypothyroidism

• Pregnancy

• Arrhythmias (AF)

• Infections

• Thromboembolism

• Hyper/hypothyroidism


Clinical Manifestations• Dyspnea: First on exertion, then with

progressively less strenuous activity• Orthopnea: Increased venous return in the

recumbent position• PND: multiple factors• Nocturnal Angina: Increased cardiac workload, 2º

to increased venous return• Cheyne Stokes Respiration: Alternating phases of

apnea and hyperventilation• Fatigue: low cardiac output• Peripheral Edema


Physical Exam FindingsLeft Sided Failure

• Pulmonary Rales• Tachypnea• S3 Gallop• Cardiac Murmurs (AS,

AR, MR)• Paradoxical Splitting

of S2

Right Sided Failure• Jugular Venous

Distention• Peripheral Edema• Peripheral/ Perioral

cyanosis• Hepatomegaly• Ascites• Hepatojugular Reflux


Assessment of JVD

Shasham, Fadi, and Judith Mitchell, M.D. “Essentials of the Diagnosis of Heart Failure.” American Family Physician, March, 2001.


CXR Findings• Cardiomegaly

(Cardiothoracic ratio >0.5)

• Large Hila with indistinct margins

• Prominence of superior pulmonary veins

• Fluid in intralobar fissures

• Kerley B lines• Alveolar edema• Blunting of Angles


Stage AStage AHF Risk FactorsHF Risk Factors

No Heart DiseaseNo Heart DiseaseNo SymptomsNo Symptoms

Stage BStage B AsymptomaticAsymptomaticHeart DiseaseHeart Disease

Stage DStage D RefractoryRefractory

HF HF symptomssymptoms

Stage CStage C Prior or Prior or CurrentCurrent

HF SymptomsHF Symptoms

Stages in the Stages in the EvolutionEvolution

of Heart Failureof Heart Failure

DefinitionsDefinitions


Stage AStage AHTN, DM, CAD, HTN, DM, CAD,

Obesity, Metabolic Obesity, Metabolic SyndromeSyndrome

Stage BStage B MI, LV Dysfunction, MI, LV Dysfunction,

Valvular DiseaseValvular Disease

Stage DStage D Symptoms at rest Symptoms at rest

despite max. therapydespite max. therapy

Stage CStage C Dyspnea, Fatigue, Dyspnea, Fatigue, Exercise ToleranceExercise Tolerance



Clinical Clinical CharacteristicsCharacteristics


Stage AStage ARisk Factor Reduction, Risk Factor Reduction, ACE-I / ARB in DM & ACE-I / ARB in DM &

Vascular DZVascular DZ

Stage BStage B ACE-I / ARB, B-ACE-I / ARB, B-

BlockersBlockers

Stage DStage D Mechanical Devices,Mechanical Devices,

Heart TransplantHeart Transplant

Stage CStage C Pharmacologic Pharmacologic

Therapy, DevicesTherapy, Devices



TreatmentTreatment


New York Heart Association Classification


Goals of Initial / Ongoing EvaluationGoals of Initial / Ongoing Evaluation• Identify Heart DiseaseIdentify Heart Disease

• Assess Functional Capacity (NYHA, 6 min walk)Assess Functional Capacity (NYHA, 6 min walk)

• Assess Volume Status (edema, crackles, JVD, Assess Volume Status (edema, crackles, JVD, hepatomegaly, body weight)hepatomegaly, body weight)

• Testing: Testing: Initial: CBC, U/A, CMP, HbA1C, FLP, CXR, EKG, TSH, Echo Initial: CBC, U/A, CMP, HbA1C, FLP, CXR, EKG, TSH, Echo Periodic: electrolytes, RFP, EchocardiogramPeriodic: electrolytes, RFP, Echocardiogram

• Assess PrognosisAssess Prognosis


8080707060605050404030302020

54-6054-60 >60>60

5050

4040

3030

2020

1010

00

Post MIPost MIn=196n=196

<30<30

31-3531-35

36-4536-45

46-5346-53

% C

ard

iac

Mo

rtal

ity

% C

ard

iac

Mo

rtal

ity

LVEFLVEFBrodie B. et al, Am J Cardiol 1992;69:1113Brodie B. et al, Am J Cardiol 1992;69:1113

PrognosisPrognosis


Treatment ObjectivesTreatment Objectives

SurvivalMorbidityExercise CapacityQuality of LifeNeurohormonal Changes Progression of CHFSymptoms

SurvivalMorbidityExercise CapacityQuality of LifeNeurohormonal Changes Progression of CHFSymptoms


Treatment ModalitiesTreatment Modalities• Prevention, Control of Risk FactorsPrevention, Control of Risk Factors• LifestyleLifestyle• Treat Cause / Aggravating FactorsTreat Cause / Aggravating Factors• Pharmacologic TherapyPharmacologic Therapy• Personal Care / Healthcare Team Personal Care / Healthcare Team • Revascularization for Ischemic Causes Revascularization for Ischemic Causes • ICDICD• Ventricular ResyncronizationVentricular Resyncronization• Ventricular Assist DevicesVentricular Assist Devices• Heart TransplantHeart Transplant• Artificial HeartArtificial Heart• Neoangiogenesis, Gene Therapy, Etc.Neoangiogenesis, Gene Therapy, Etc.

AllAll

Sel

ecte

d P

atie

nts

Sel

ecte

d P

atie

nts


Pharmacologic TherapyPharmacologic Therapy

•Diuretics•ACE Inhibitors•Beta Blockers• Digitalis• Spironolactone• Others

•Diuretics•ACE Inhibitors•Beta Blockers• Digitalis• Spironolactone• Others


DiureticsDiuretics

•• Essential to Control SymptomsEssential to Control SymptomsSecondary to Fluid RetentionSecondary to Fluid Retention

•• Prevent DecompensationPrevent Decompensation

• • Loops Increase Sodium Excretion up Loops Increase Sodium Excretion up to 20 - 25%to 20 - 25%

• Thiazides Increase Sodium Excretion Thiazides Increase Sodium Excretion by 5 – 10%by 5 – 10%


Co

rtex

Co

rtex

Med

ulla

Med

ulla

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

Henle

Loop

of

Henle

Collecting

Tubule

Collecting

Tubule

DiureticsDiuretics


Diuretics: IndicationsDiuretics: Indications1.1. Symptomatic HF, with Fluid RetentionSymptomatic HF, with Fluid Retention

• EdemaEdema• DyspneaDyspnea• Lung CracklesLung Crackles• Jugular DistensionJugular Distension• HepatomegalyHepatomegaly• Pulmonary edema (Xray)Pulmonary edema (Xray)


Loop Diuretics / Thiazides: Practical Use Loop Diuretics / Thiazides: Practical Use

• Start with variable dose. Titrate to achieve Start with variable dose. Titrate to achieve dry weight.dry weight.

• Monitor serum KMonitor serum K++ at “frequent intervals.” at “frequent intervals.”

• Reduce dose when fluid retention is controlled.Reduce dose when fluid retention is controlled.

• Teach the patient when, how to adjust dose.Teach the patient when, how to adjust dose.

• Combine with ACE-I and B-BlockerCombine with ACE-I and B-Blocker


Loop diuretics: Dose (mg)Loop diuretics: Dose (mg)

InitialInitial MaximumMaximum

BumetanideBumetanide 0.5 to 1.0 / 12-24h 0.5 to 1.0 / 12-24h 10 / 10 /

dayday

FurosemideFurosemide 20 to 40 / 12-24h 20 to 40 / 12-24h 400 / day400 / day

TorsemideTorsemide 10 to 20 / 12-24h 10 to 20 / 12-24h 200 / day200 / day


Loop Diuretics / Thiazides: Adverse EffectsLoop Diuretics / Thiazides: Adverse Effects

•• KK++, Mg, Mg++ (15 - 60%) (15 - 60%)

•• NaNa++

• • Stimulation of Neurohormonal ActivityStimulation of Neurohormonal Activity

•• Hyperuricemia (15 - 40%)Hyperuricemia (15 - 40%)

•• Hypotension, Ototoxicity, Gastrointestinal Sx, Hypotension, Ototoxicity, Gastrointestinal Sx,

Metabolic AlkalosisMetabolic AlkalosisSharpe N. Heart failure. Martin Dunitz 2000;43Sharpe N. Heart failure. Martin Dunitz 2000;43

Kubo SH , et al. Am J Cardiol 1987;60:1322Kubo SH , et al. Am J Cardiol 1987;60:1322

MRFIT, JAMA 1982;248:1465MRFIT, JAMA 1982;248:1465

Pool Wilson. Heart failure. Churchill Livinston 1997;635Pool Wilson. Heart failure. Churchill Livinston 1997;635


Diuretics: ResistanceDiuretics: Resistance• Neurohormonal ActivationNeurohormonal Activation

• Rebound NaRebound Na++ uptake after Volume Loss uptake after Volume Loss

• Hypertrophy of Distal NephronHypertrophy of Distal Nephron

• Reduced Tubular Secretion Reduced Tubular Secretion (renal failure, (renal failure,

NSAIDs)NSAIDs)

• Decreased Renal Perfusion (low output)Decreased Renal Perfusion (low output)

• Altered Absortion Altered Absortion

• NoncomplianceNoncomplianceBrater NEJM 1998;339:387 Brater NEJM 1998;339:387 Kramer et al. Am J Med 1999;106:90Kramer et al. Am J Med 1999;106:90


Managing Resistance to DiureticsManaging Resistance to Diuretics

•• Restrict NaRestrict Na++/H/H22O intakeO intake

•• Increase DoseIncrease Dose

• • Combine: Combine: furosemide + thiazide / spiro / metolazonefurosemide + thiazide / spiro / metolazone

•• Dopamine (increase cardiac output)Dopamine (increase cardiac output)

•• Reduce Dose of ACE-IReduce Dose of ACE-I

•• UltrafiltrationUltrafiltration

Motwani et al Circulation 1992;86:439Motwani et al Circulation 1992;86:439


VASOCONSTRICTIONVASOCONSTRICTION VASODILATATION VASODILATATION

KininogenKininogen

KallikreinKallikrein

Inactive FragmentsInactive Fragments

AngiotensinogenAngiotensinogen

Angiotensin IAngiotensin I

RENINRENIN

Kininase IIKininase IIInhibitorInhibitor

ALDOSTERONEALDOSTERONE

SYMPATHETICSYMPATHETICVASOPRESSINVASOPRESSIN

PROSTAGLANDINSPROSTAGLANDINS

tPAtPA

ANGIOTENSIN IIANGIOTENSIN II

BRADYKININBRADYKININ

ACE-I: Mechanism of ActionACE-I: Mechanism of Action

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


ACE-I: Clinical EffectsACE-I: Clinical Effects

• Improve Symptoms

• Reduce Remodeling / Progression

• Reduce Hospitalization

• Improve Survival


• Reduce Remodeling / Progression




Mortality Reduction with ACE-IMortality Reduction with ACE-I

StudyStudy ACE-IACE-I Clinical SetingClinical Seting

CONSENSUSCONSENSUS EnalaprilEnalapril CHFCHF

SOLVD treatment SOLVD treatment EnalaprilEnalapril CHFCHF

AIREAIRE RamiprilRamipril CHFCHF

Vheft-IIVheft-II EnalaprilEnalapril CHFCHF

TRACETRACE TrandolaprilTrandolapril CHF / LVDCHF / LVD

SAVESAVE CaptoprilCaptopril LVDLVD

SMILESMILE ZofenoprilZofenopril High Risk High Risk

HOPEHOPE RamiprilRamipril High Risk High Risk


PlaceboPlacebo

EnalaprilEnalapril

1212111110109988776655

Pro

bab

ility

of

Dea

thP

rob

abili

ty o

f D

eath

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


5050

4040

3030

2020

1010

00

MonthsMonths00 66 1212

p = 0.0036p = 0.0036

% M

ort

alit

y%

Mo

rtal

ity

24241818 3030 3636 4242 4848

Enalapriln=1285Enalapriln=1285

Placebon=1284Placebon=1284

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

NYHA II-IIIEF < 35%NYHA II-IIIEF < 35%

SOLVD (Treatment)SOLVD (Treatment)


% M

ort

alit

y%

Mo

rtal

ity

44

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

3030

2020

1010

0011 22 33

PlaceboPlacebo

CaptoprilCaptopril

00

n=1115n=1115

n=1116n=1116

p=0.019p=0.019² -19%² -19%

3 - 16 days post AMI

EF < 40%

Captopril12.5 - 150 mg/day

3 - 16 days post AMI

EF < 40%

Captopril12.5 - 150 mg/day

Asymptomatic VentricularDysfunction

Post MI

Asymptomatic VentricularDysfunction

Post MI

SAVESAVE


MonthsMonths

303024241212 181800 66

1010

3030

2020

00

PlaceboPlacebo

RamiprilRamipril

HFHFS/PS/PAMIAMI

p = 0.002p = 0.002% M

ort

alit

y%

Mo

rtal

ity

Lancet 1993;342:821Lancet 1993;342:821Lancet 1993;342:821Lancet 1993;342:821

AIREAIRE


• Symptomatic Heart Failure• Asymptomatic Ventricular Dysfunction

- LVEF < 40%• Selected High Risk Subgroups


- LVEF < 40%• Selected High Risk Subgroups

ACE-I: IndicationsACE-I: Indications


ACE-I: Practical UseACE-I: Practical Use

• Start with very low doseStart with very low dose

• Increase dose if well toleratedIncrease dose if well tolerated

• Renal function & serum KRenal function & serum K++ after 1-2 wks after 1-2 wks

• Avoid fluid retention / hypovolemia Avoid fluid retention / hypovolemia (diuretic use)(diuretic use)

• Dose NOT determined by symptomsDose NOT determined by symptoms

• Combine to overcome “resistance”Combine to overcome “resistance”


ACE-I: Dose (mg)ACE-I: Dose (mg) InitialInitial MaximumMaximum

CaptoprilCaptopril 6.25 / 8h 6.25 / 8h 50 / 8h50 / 8h

EnalaprilEnalapril 2.5 / 12 h 2.5 / 12 h 10 to 20 / 12h10 to 20 / 12h

FosinoprilFosinopril 5 to 10 / day 5 to 10 / day 40 / day40 / day

LisinoprilLisinopril 2.5 to 5.0 / day 2.5 to 5.0 / day 20 to 40 / day20 to 40 / day

QuinaprilQuinapril 10 / 12 h10 / 12 h 40 / 12 h40 / 12 h

RamiprilRamipril 1.25 to 2.5 / day 1.25 to 2.5 / day 10 / day10 / day


ACE-I: Adverse EffectsACE-I: Adverse Effects

• Hypotension (1st dose effect)Hypotension (1st dose effect)

• Worsening Renal FunctionWorsening Renal Function

• HyperkalemiaHyperkalemia

• CoughCough

• AngioedemaAngioedema


ACE-I: ContraindicationsACE-I: Contraindications

• Intolerance (angioedema, anuric renal failure)

• Bilateral Renal Artery Stenosis

• Pregnancy

• Renal Insufficiency (creatinine > 2 mg/dL)

• Hyperkalemia (> 5.5 mmol/l)

• Severe Hypotension

ACE-I: ContraindicationsACE-I: Contraindications

• Intolerance (angioedema, anuric renal failure)

• Bilateral Renal Artery Stenosis

• Pregnancy

• Renal Insufficiency (creatinine > 2 mg/dL)

• Hyperkalemia (> 5.5 mmol/l)

• Severe Hypotension


RENINRENIN

AngiotensinogenAngiotensinogen Angiotensin I

ANGIOTENSIN II

Angiotensin I

ANGIOTENSIN II

ACEACEOther pathwaysOther pathways

VasoconstrictionVasoconstriction Proliferative Action

Proliferative Action

VasodilatationVasodilatation Antiproliferative Action

Antiproliferative Action

AT1 AT1 AT2AT2

AT1 Receptor Blockers

AT1 Receptor Blockers

RECEPTORSRECEPTORS

Angiotensin II Receptor Blockers (ARB)Angiotensin II Receptor Blockers (ARB)


Angiotensin II Receptor Blockers (ARB)Angiotensin II Receptor Blockers (ARB)

• For Patients who can not take ACE-I

• “Reasonable Alternative” to ACE-I

• Similar in Benefit to ACE-I– CHARM

• Less Studied than ACE-I

• Combined with ACE-I may Decrease Morbidity and Mortality???


ARB: Indications

Stage A B C


ARB: Dose (mg)

Initial Target

Candesartan 4 – 8 / d 32 / d

Losartan 25 – 50 / d 50 – 100 / d

Valsartan 20 – 40 BID 160 BID


ß-Blockers: Mechanism of actionß-Blockers: Mechanism of action• Density of ß1 Receptors

• Inhibit Cardiotoxicity of Catecholamines

• Neurohormonal Activation

• HR

• Antiischemic

• Antihypertensive

• Antiarrhythmic

• Antioxidant, Antiproliferative

• Density of ß1 Receptors

• Inhibit Cardiotoxicity of Catecholamines

• Neurohormonal Activation

• HR

• Antiischemic

• Antihypertensive

• Antiarrhythmic

• Antioxidant, Antiproliferative


ß-Blockers: Clinical Effectsß-Blockers: Clinical Effects

• Improve Symptoms (only long term)

• Reduce Remodelling / Progression


• Reduce Sudden Death


• Improve Symptoms (only long term)

• Reduce Remodelling / Progression


• Reduce Sudden Death



NEJM 1996; 334: 1349-55NEJM 1996; 334: 1349-55

CarvedilolCarvedilol(n=696)(n=696)

PlaceboPlacebo(n=398)(n=398)

Risk Reduction = 65%Risk Reduction = 65%

pp<0.001<0.001

00 5050 100100 150150 200200 250250 300300 350350 400400

1.0

0.9

0.8

0.7

0.60.6

US Carvedilol HFUS Carvedilol HF

0.70.7

0.80.8

0.90.9

1.01.0

% S

urv

ival

% S

urv

ival

DaysDays

NYHANYHAI-III-II


P< 0.00005P< 0.00005

DaysDays

BisoprololBisoprolol11.8%11.8%

PlaceboPlacebo17.3%17.3%

11

0.90.9

0.80.8

0.70.7

0.60.6

0.50.5

Su

rviv

alS

urv

ival

NYHA NYHA III-IVIII-IV

00 800800400400 600600200200

Lancet 1999;353:9Lancet 1999;353:9

CIBIS-IICIBIS-II


1515

1010

55

Lancet 1999; 353: 2001Lancet 1999; 353: 2001

MonthsMonths

% M

ort

alit

y %

Mo

rtal

ity

00 33 66 99 1212 1515 1818 212100

PlaceboPlacebo

MetoprololMetoprolol

pp=0.0062=0.0062

Risk Reduction 34%Risk Reduction 34%

MERIT-HFMERIT-HF

NYHA NYHA II-IVII-IV


100100

9090

8080

6060

7070

5050242400 2020161612128844 2828

PlaceboPlacebo

CarvedilolCarvedilol

MonthsMonths

NYHANYHAIII-IVIII-IV

NEJM 2001;344:1651NEJM 2001;344:1651

% S

urv

ival

% S

urv

ival

COPERNICUSCOPERNICUS

pp=0.00014=0.00014

Risk Reduction 34%


11

Su

rviv

alS

urv

ival

YearsYears

0.90.9

0.850.85

0.70.7

0.750.75

0.80.8

0.950.95

00 0.50.5 11 1.51.5 22 2.52.5

CarvedilolCarvedilol116 / 975 (12%)116 / 975 (12%)

PlaceboPlacebo151 / 984 (15%)151 / 984 (15%)

HR 0.77 (0.60 - 0.98) p<0.031HR 0.77 (0.60 - 0.98) p<0.031

Lancet 2001;357:1385Lancet 2001;357:1385

CAPRICORNCAPRICORN

HFHFPostPostAMIAMI



- LVEF < 35%• After AMI


- LVEF < 35%• After AMI

ß-Blockers: Indicationsß-Blockers: Indications

Stage A B C


• Patient StablePatient Stable• No physical evidence of fluid retentionNo physical evidence of fluid retention• No need for IV inotropic drugsNo need for IV inotropic drugs

• Start ACE-I / Diuretic FirstStart ACE-I / Diuretic First

• No ContraindicationsNo Contraindications

• In Hospital or notIn Hospital or not

ß-Blockers: When to Startß-Blockers: When to Start


InitialInitial TargetTarget

BisoprololBisoprolol 1.25 / 24h1.25 / 24h 10 / 24h 10 / 24h

CarvedilolCarvedilol 3.125 / 12h3.125 / 12h 25 / 12h25 / 12h

Metoprolol tartrateMetoprolol tartrate 6.25 / 12h6.25 / 12h 75 / 12h 75 / 12h

• Start Low, Increase SlowlyStart Low, Increase Slowly• Increase the dose every 2 - 4 weeksIncrease the dose every 2 - 4 weeks

ß-Blockers: Dose (mg)ß-Blockers: Dose (mg)


• HypotensionHypotension• Fluid Retention / Worsening Heart FailureFluid Retention / Worsening Heart Failure• FatigueFatigue• Bradycardia / Heart BlockBradycardia / Heart Block

ß-Blockers: Adverse Effectsß-Blockers: Adverse Effects

• Review Treatment (+/-diuretics, other drugs)Review Treatment (+/-diuretics, other drugs)• Reduce DoseReduce Dose• Consider Cardiac PacingConsider Cardiac Pacing• Discontinue Beta Blocker only in Severe CasesDiscontinue Beta Blocker only in Severe Cases


ß-Blockers: Contraindicationsß-Blockers: Contraindications

• Asthma (reactive airway disease)Asthma (reactive airway disease)

• AV block (unless pacemaker)AV block (unless pacemaker)

• Symptomatic Hypotension / BradycardiaSymptomatic Hypotension / Bradycardia

• Diabetes is NOT a contraindicationDiabetes is NOT a contraindication


Digitalis: Mechanism of ActionDigitalis: Mechanism of Action

Blocks NaBlocks Na++ / K / K++ ATPase => Ca ATPase => Ca+ ++ +

•• Inotropic effectInotropic effect

•• NatriuresisNatriuresis

•• Neurohormonal controlNeurohormonal control-- PlasmaPlasma NoradrenalineNoradrenaline

- - Peripheral Nervous System ActivityPeripheral Nervous System Activity

-- RAAS Activity RAAS Activity

-- VagalVagal ToneTone

-- Normalizes Arterial Baroreceptors Normalizes Arterial BaroreceptorsNEJM 1988;318:358NEJM 1988;318:358


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

DigitalisDigitalis

CONTRACTILITYCONTRACTILITY

-


Digitalis: Clinical EffectsDigitalis: Clinical Effects• Improve Symptoms

• Modest Reduction in Hospitalization

• Does Not Improve Survival


• Modest Reduction in Hospitalization

• Does Not Improve Survival


5050

4040

3030

2020

1010

00

Placebon=3403

Placebon=3403

Digoxinn=3397

Digoxinn=3397

484800 1212 2424 3636

% M

ort

alit

y%

Mo

rtal

ity

N Engl J Med 1997;336:525N Engl J Med 1997;336:525MonthsMonths

p = 0.8p = 0.8

DIGDIG

NYHA

II-III

NYHA

II-III


Digitalis: IndicationsDigitalis: Indications

• • When no adequate response toWhen no adequate response to ACE-I + diuretics + beta-blockersACE-I + diuretics + beta-blockers

• • In combination with ACE-I + diureticsIn combination with ACE-I + diuretics

if persisting symptomsif persisting symptoms

• • AFib, to slow AV conductionAFib, to slow AV conduction

Dose 0.125 to 0.250 mg / dayDose 0.125 to 0.250 mg / day


• Digoxin toxicity

• Advanced A-V block without pacemaker

• Bradycardia or sick sinus without PM

• PVC’s and VT

• Marked hypokalemia

• WPW with atrial fibrillation

• Digoxin toxicity

• Advanced A-V block without pacemaker

• Bradycardia or sick sinus without PM

• PVC’s and VT

• Marked hypokalemia

• WPW with atrial fibrillation

Digitalis: ContraindicationsDigitalis: Contraindications


ALDOSTERONEALDOSTERONE

• Retention Na+

• Retention H2O

• Excretion K+

• Excretion Mg2+

• Retention Na+

• Retention H2O

• Excretion K+

• Excretion Mg2+

• Collagen Collagen depositiondeposition

FibrosisFibrosis - - myocardiummyocardium

- - vesselsvessels

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

-


Aldactone

Placebo

Su

rviv

alS

urv

ival

1.0

0.9

0.8

0.7

0.6

0.5

0 6 12 18 24 30 36

months

p < 0.0001

Annual MortalityAldactone 18%; Placebo 23%

NYHANYHAIII-IVIII-IV

NEJM 1999;341:709NEJM 1999;341:709

RALESRALES


Spironolactone:Spironolactone: IndicationsIndications

• LV Dysfunction Early After MILV Dysfunction Early After MI

• Moderately Severe or Severe HF with Moderately Severe or Severe HF with Recent DecompensationRecent Decompensation

• HypokalemiaHypokalemia


Spironolactone:Spironolactone: Practical Use Practical Use

• Do not use if hyperkalemia, renal insuf.Do not use if hyperkalemia, renal insuf.

• Monitor serum KMonitor serum K++ at “frequent intervals” at “frequent intervals”

• Start ACE-I firstStart ACE-I first

• Start with 12.5 - 25 mg / 24hStart with 12.5 - 25 mg / 24h

• If KIf K++ >5.5 mmol/L, reduce to 25 mg / 48h >5.5 mmol/L, reduce to 25 mg / 48h

• If KIf K++ is low or stable consider 50 mg / day is low or stable consider 50 mg / day


1- VENOUS VASODILATATION Preload

2- Coronary vasodilatation Myocardial perfusion

3- Arterial vasodilatation Afterload

4- Others

1- VENOUS VASODILATATION Preload

2- Coronary vasodilatation Myocardial perfusion

3- Arterial vasodilatation Afterload

4- Others

Pulmonary congestionVentricular sizeVent. Wall stressMVO2

Pulmonary congestionVentricular sizeVent. Wall stressMVO2

NITRATESHEMODYNAMIC EFFECTS

NITRATESHEMODYNAMIC EFFECTS

• Cardiac output

• Blood pressure

• Cardiac output

• Blood pressure


0.60.6

Probabilityof

Death

Probabilityof

Death

00

Placebo (273)Prazosin (183)Hz + ISDN (186)

Placebo (273)Prazosin (183)Hz + ISDN (186)

MonthsMonths

0.70.7

0.50.5

0.30.3

0.40.4

0.20.2

0.10.1

N Engl J Med 1986;314:1547N Engl J Med 1986;314:1547

VHefT-1 (Nitrates)VHefT-1 (Nitrates)

00 66 1212 1818 2424 3030 3636 4242


0,540,54

0,480,48

00 1212 2424 4848 6060

0.750.75

0.500.50

0.250.25

00

0.470.47

0.360.36

0.250.25

0.130.13

0.090.09

0.310.31

0.180.18

0.420.42

3636

MonthsMonths

p = 0.08p = 0.08

EnalaprilEnalapril

HZ + ISDNHZ + ISDN

n = 804n = 804

p = 0.016p = 0.016ProbabilityProbability

ofofDeathDeath

V-HeFT IIV-HeFT II (Nitrate + Hydralazine)Nitrate + Hydralazine)

N Engl J Med 1991; 325:303N Engl J Med 1991; 325:303


Nitrates: Clinical UseNitrates: Clinical Use

• CHF with myocardial ischemia

• Orthopnea and paroxysmal nocturnal dyspnea

• In acute CHF and pulmonary edema: NTG sl / iv

• Nitrates + Hydralazine in intoleranceto ACE-I (hypotension, renal insufficiency)

• CHF with myocardial ischemia

• Orthopnea and paroxysmal nocturnal dyspnea

• In acute CHF and pulmonary edema: NTG sl / iv

• Nitrates + Hydralazine in intoleranceto ACE-I (hypotension, renal insufficiency)


Positive InotropesPositive Inotropes

• DigitalisDigitalis

• SympathomimeticsSympathomimetics• CatecholaminesCatecholamines• B-adrenergic agonistsB-adrenergic agonists

• Phosphodiesterase inhibitorsPhosphodiesterase inhibitors• Amrinone, Milrinone, EnoximoneAmrinone, Milrinone, Enoximone

• Calcium sensitizersCalcium sensitizers• Levosimendan, PimobendanLevosimendan, Pimobendan


•May increase mortality Exception: Digoxin, Levosimendan

•Use only in refractory CHF

•NOT for use as chronic therapy

•May increase mortality Exception: Digoxin, Levosimendan

•Use only in refractory CHF

•NOT for use as chronic therapy

Positive Inotropic TherapyPositive Inotropic Therapy


• Inotropes, long term / intermittentInotropes, long term / intermittent

• Antiarrhythmics (except amiodarone)Antiarrhythmics (except amiodarone)

• Calcium Channel BlockersCalcium Channel Blockers

• Non-steroidal antiinflammatory drugs (NSAIDS)Non-steroidal antiinflammatory drugs (NSAIDS)

• Tricyclic antidepressantsTricyclic antidepressants

• CorticosteroidsCorticosteroids

• LithiumLithium

Drugs to Avoid Drugs to Avoid (may increase symptoms, mortality)(may increase symptoms, mortality)


Refractory End-Stage HFRefractory End-Stage HF• Review etiology, treatment & aggrav. factorsReview etiology, treatment & aggrav. factors

• Control fluid retentionControl fluid retention• Resistance to diureticsResistance to diuretics• Ultrafiltration ?Ultrafiltration ?

• IV inotropics / vasodilators during IV inotropics / vasodilators during decompensationdecompensation

• Consider resynchronizationConsider resynchronization

• Consider mechanical assist devicesConsider mechanical assist devices

• Consider heart transplantationConsider heart transplantation


Heart Transplant: IndicationsHeart Transplant: Indications• Refractory cardiogenic shockRefractory cardiogenic shock

• Documented dependence on IV inotropic support Documented dependence on IV inotropic support to maintain adequate organ perfusionto maintain adequate organ perfusion

• Peak VO2 < 10 ml / kg / min Peak VO2 < 10 ml / kg / min

• Severe symptoms of ischemia not amenable to Severe symptoms of ischemia not amenable to revascularizationrevascularization

• Recurrent symptomatic ventricular arrhythmias Recurrent symptomatic ventricular arrhythmias refractory to all therapeutic modalitiesrefractory to all therapeutic modalities

Contraindications: age, severe comorbidityContraindications: age, severe comorbidity


Supraventricular ArrhythmiasSupraventricular Arrhythmias

• Risk of embolization (AF)Risk of embolization (AF)

• Anticoagulation in AFAnticoagulation in AF

• Systolic & diastolic dysfunctionSystolic & diastolic dysfunction

• Digoxin, beta blockersDigoxin, beta blockers

• Amiodarone if b-blocker ineffective/ contraind.Amiodarone if b-blocker ineffective/ contraind.


Ventricular Arrhythmias / Sudden DeathVentricular Arrhythmias / Sudden Death• Antiarrhythmics ineffective Antiarrhythmics ineffective (may increase mortality)(may increase mortality)

Amiodarone does not improve survivalAmiodarone does not improve survival

• -blockers reduce all cause mortality and SD-blockers reduce all cause mortality and SD

• Control ischemiaControl ischemia

• Control electrolyte disturbancesControl electrolyte disturbances

• ICD (Implantable Cardiac Defibrillator)ICD (Implantable Cardiac Defibrillator)• In secondary prevention of sudden deathIn secondary prevention of sudden death• In sustained, hemodynamic destabilizing VTIn sustained, hemodynamic destabilizing VT• In LVEF < 30% and mild - moderate HF symptomsIn LVEF < 30% and mild - moderate HF symptoms


Diastolic Heart FailureDiastolic Heart Failure• Incorrect diagnosis of HFIncorrect diagnosis of HF• Inaccurate measurement of LVEFInaccurate measurement of LVEF• Primary valvular diseasePrimary valvular disease• Restrictive (infiltrative) cardiomyopathies (Amyloidosis…)Restrictive (infiltrative) cardiomyopathies (Amyloidosis…)• Pericardial constrictionPericardial constriction• Episodic or reversible LV systolic dysfunctionEpisodic or reversible LV systolic dysfunction• Severe hypertension, ischemiaSevere hypertension, ischemia• High output states: Anemia, thyrotoxicosis, etcHigh output states: Anemia, thyrotoxicosis, etc• Chronic pulmonary disease with right HFChronic pulmonary disease with right HF• Pulmonary hypertension Pulmonary hypertension • Atrial myxomaAtrial myxoma• LV HypertrophyLV Hypertrophy• Diastolic dysfunction of uncertain originDiastolic dysfunction of uncertain origin


Diastolic Heart FailureDiastolic Heart Failure

• Treat as HF with low LVEFTreat as HF with low LVEF

• Control: Control: • HypertensionHypertension• TachycardiaTachycardia• Fluid RetentionFluid Retention• Myocardial IschemiaMyocardial Ischemia

• Ongoing ResearchOngoing Research


Treatment SummarySymptoms Morbidity Mortality

Increase Dose of ACEI

No effect ↓ 10-15% No effect

Add ARB ↓ ↓ 10-15% No effect

Add ß-blocker

↓ ↓ 20-35% ↓ 35%+

Add Aldactone

↓ ↓ 20% ↓ 16-25%

Add ISDN+ Hydralazine

↓ ↓ 30% ↓ 40%

AHA Scientific Sessions, 2004 (Lachel et al)

HEART FAILURE Adapted From: American Heart Association HEART FAILURE Adapted From: American Heart...

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