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).
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Assessment of JVD
Shasham, Fadi, and Judith Mitchell, M.D. “Essentials of the Diagnosis of Heart Failure.” American Family Physician, March, 2001.
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Stages in the Stages in the EvolutionEvolution
of Heart Failureof Heart Failure
Clinical Clinical CharacteristicsCharacteristics
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Stages in the Stages in the EvolutionEvolution
of Heart Failureof Heart Failure
TreatmentTreatment
Chronic Congestive Heart FailureChronic Congestive Heart Failure
New York Heart Association Classification
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Treatment ObjectivesTreatment Objectives
SurvivalMorbidityExercise CapacityQuality of LifeNeurohormonal Changes Progression of CHFSymptoms
SurvivalMorbidityExercise CapacityQuality of LifeNeurohormonal Changes Progression of CHFSymptoms
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Pharmacologic TherapyPharmacologic Therapy
•Diuretics•ACE Inhibitors•Beta Blockers• Digitalis• Spironolactone• Others
•Diuretics•ACE Inhibitors•Beta Blockers• Digitalis• Spironolactone• Others
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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%
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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)
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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.
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ACE-I: Clinical EffectsACE-I: Clinical Effects
• Improve Symptoms
• Reduce Remodeling / Progression
• Reduce Hospitalization
• Improve Survival
• Improve Symptoms
• Reduce Remodeling / Progression
• Reduce Hospitalization
• Improve Survival
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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)
Chronic Congestive Heart FailureChronic Congestive Heart Failure
% 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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• Symptomatic Heart Failure• Asymptomatic Ventricular Dysfunction
- LVEF < 40%• Selected High Risk Subgroups
• Symptomatic Heart Failure• Asymptomatic Ventricular Dysfunction
- LVEF < 40%• Selected High Risk Subgroups
ACE-I: IndicationsACE-I: Indications
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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”
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ACE-I: Adverse EffectsACE-I: Adverse Effects
• Hypotension (1st dose effect)Hypotension (1st dose effect)
• Worsening Renal FunctionWorsening Renal Function
• HyperkalemiaHyperkalemia
• CoughCough
• AngioedemaAngioedema
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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)
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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???
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ARB: Indications
Stage A B C
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ARB: Dose (mg)
Initial Target
Candesartan 4 – 8 / d 32 / d
Losartan 25 – 50 / d 50 – 100 / d
Valsartan 20 – 40 BID 160 BID
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ß-Blockers: Clinical Effectsß-Blockers: Clinical Effects
• Improve Symptoms (only long term)
• Reduce Remodelling / Progression
• Reduce Hospitalization
• Reduce Sudden Death
• Improve Survival
• Improve Symptoms (only long term)
• Reduce Remodelling / Progression
• Reduce Hospitalization
• Reduce Sudden Death
• Improve Survival
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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%
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• Symptomatic Heart Failure• Asymptomatic Ventricular Dysfunction
- LVEF < 35%• After AMI
• Symptomatic Heart Failure• Asymptomatic Ventricular Dysfunction
- LVEF < 35%• After AMI
ß-Blockers: Indicationsß-Blockers: Indications
Stage A B C
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• 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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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)
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• 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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
-
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Digitalis: Clinical EffectsDigitalis: Clinical Effects• Improve Symptoms
• Modest Reduction in Hospitalization
• Does Not Improve Survival
• Improve Symptoms
• Modest Reduction in Hospitalization
• Does Not Improve Survival
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• 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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
-
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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)
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
•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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• 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)
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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.
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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
Chronic Congestive Heart FailureChronic Congestive Heart Failure
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)
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Top Related