trombose coronária enfarte do miocárdio morte súbita perda de músculo remodelagem dilatação...
TRANSCRIPT
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Trombose
coronária
Enfarte do
miocárdio
Morte
súbita
Perda de
músculo
Remodelagem
Dilatação
ventricular
Insuficiência cardíaca
Morte
Isquemia
miocárdica
D.Coronária
Aterosclerose
HVE
Factores de risco:
• Hipertensão Arterial
• Hiperlipidemia
• Diabetes
• Obesidade
• Tabagismo
Adaptado de Dzau V e col., 1991
MORTALIDADE CARDIOVASCULARMORTALIDADE CARDIOVASCULARCadeia de eventosCadeia de eventos
MORTALIDADE CARDIOVASCULARMORTALIDADE CARDIOVASCULARCadeia de eventosCadeia de eventos
ActivaçãoActivação
neurohumoralneurohumoral
ActivaçãoActivação
neurohumoralneurohumoral
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INSUFICIÊNCIA CARDÍACA
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INSUFICIÊNCIA CARDÍACA
• SINDROME COMPLEXO, COM ETIOLOGIAS VÁRIAS
• ATINGE CERCA DE 20 MILHÕES DE PESSOAS EM TODO O MUNDO
• NÚMERO DE CASOS SOBE EXPONENCIAL- MENTE SOBRETUDO NO IDOSO
10% DOS IDOSOS COM IDADE > 75 ANOS
TÊM INSUFICIÊNCIA CARDÍACA
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INSUFICIÊNCIA CARDÍACA
O PROGNÓSTICO É MAU
• A MORBILIDADE É MUITO SIGNIFICATIVA
• AS ADMISSÕES HOSPITALARES SÃO MUITO FREQUENTES ( CAUSA MAIS HABITUAL DE INTERNAMENTO EM IDADE > 65 ANOS)
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INSUFICIÊNCIA CARDÍACA
PORQUE É QUE A INS. CARDÍACA AUMENTA?
• POPULAÇÃO MAIS ENVELHECIDA
• SUCESSO DA TERAPÊUTICA NA MELHORIA DA SOBREVIVÊNCIA PÓS-EAM (trombólise ou outras medidas)
• AUMENTO NA DURAÇÃO DA SOBREVIDA DOS DOENTES COM INSUFICIÊNCIA CARDÍACA
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DEFINITIONDEFINITION
“The situation when the heart is
incapable of maintaining a cardiac
output adequate to accommodate
metabolic requirements and the
venous return."
“The situation when the heart is
incapable of maintaining a cardiac
output adequate to accommodate
metabolic requirements and the
venous return."E. BraunwaldE. Braunwald
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New York Heart Association Functional Classification
Class I: No symptoms with ordinary activity
Class II: Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, dyspnea, or angina
Class III: Marked limitation of physical activity. Comfortable at rest, but less than ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain
Class IV: Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency may be present even at rest
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MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized intervention trial in MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). congestive heart failure (MERIT-HF). LANCET. LANCET. 1999;353:2001-07.1999;353:2001-07.
Severity of Heart FailureModes of Death
12%12%
24%24%
64%64%
CHFCHF
OtherOther
SuddenSuddenDeathDeath
n = 103n = 103
NYHA IINYHA II
26%26%
15%15%
59%59%
CHFCHF
OtherOther
SuddenSuddenDeathDeath
n = 103n = 103
NYHA IIINYHA III
56%56%
11%11%
33%33%
CHFCHF
OtherOther
SuddenSuddenDeathDeath
n = 27n = 27
NYHA IVNYHA IV
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Etiology of Heart FailureWhat causes heart failure?
• The loss of a critical quantity of functioning myocardial cells after injury to the heart due to:
– Ischemic Heart Disease
– Hypertension
– Idiopathic Cardiomyopathy
– Infections (e.g., viral myocarditis, Chagas’ disease)
– Toxins (e.g., alcohol or cytotoxic drugs)
– Valvular Disease
– Prolonged Arrhythmias
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30%30%
70%70%
Diastolic DysfunctionDiastolic DysfunctionSystolic DysfunctionSystolic Dysfunction
(EF < 40%)(EF < 40%)(EF > 40 %)(EF > 40 %)
Left Ventricular Dysfunction• Systolic: Impaired contractility/ejection
– Approximately two-thirds of heart failure patients have systolic dysfunction1
• Diastolic: Impaired filling/relaxation
1 Lilly, L. 1 Lilly, L. Pathophysiology of Heart DiseasePathophysiology of Heart Disease. Second Edition p 200. Second Edition p 200
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DETERMINANTS OF VENTRICULAR FUNCTION
DETERMINANTS OF VENTRICULAR FUNCTION
STROKE VOLUMESTROKE VOLUME
PRELOADPRELOAD
CONTRACTILITYCONTRACTILITY
CARDIAC OUTPUTCARDIAC OUTPUT
HEART RATE
HEART RATE
- Synergistic LV contraction - LV wall integrity - Valvular competence
- Synergistic LV contraction - LV wall integrity - Valvular competence
AFTERLOADAFTERLOAD
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Hemodynamic Basis for Heart Failure Symptoms
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Hemodynamic Basis forHeart Failure Symptoms
LVEDP
Left Atrial Pressure
Pulmonary Capillary Pressure
Pulmonary Congestion
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Left Ventricular DysfunctionSystolic and Diastolic
• Symptoms
– Dyspnea on Exertion
– Paroxysmal Nocturnal Dyspnea
– Tachycardia
– Cough
– Hemoptysis
• Physical Signs
– Basilar Rales
– Pulmonary Edema
– S3 Gallop
– Pleural Effusion
– Cheyne-Stokes Respiration
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Disfunção miocárdica
Retenção H2O e sal Vasoconstrição
Redistribuição fluxoInotropia +Taquicardia
Dilatação e hipertrofia
Activação neurohumoral
ICC - Fase de respostas compensatórias
Melhoria transitória Melhoria transitória
Frank-Starling< stress da parede
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Compensatory Mechanisms
• Frank-Starling Mechanism
• Neurohormonal Activation
• Ventricular Remodeling
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Compensatory Mechanisms
Frank-Starling Mechanism
a. At rest, no HF
b. HF due to LV systolic dysfunction
c. Advanced HF
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Compensatory Mechanisms
Neurohormonal Activation
Many different hormone systems are involved in maintaining normal cardiovascular homeostasis, including:
• Sympathetic nervous system (SNS)
• Renin-angiotensin-aldosterone system (RAAS)
• Vasopressin (a.k.a. antidiuretic hormone, ADH)
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VasodilatoresVasodilatoresNatriuréticosNatriuréticos
Anti-proliferativosAnti-proliferativosAnti-inflamatóriosAnti-inflamatórios
AntitrombogénicosAntitrombogénicos
Equilíbrio sistemas neuro-humorais reguladores perfusão
VasoconstritoresVasoconstritoresAnti-natriuréticosAnti-natriuréticosPró-proliferativosPró-proliferativosPró-inflamatóriosPró-inflamatóriosTrombogénicosTrombogénicos
DopaminaDopaminaANF, BNF, CNFANF, BNF, CNF
AdrenomedulinaAdrenomedulinaProstaciclinaProstaciclinaBradicininaBradicinina
NONO
Angiotensina 2Angiotensina 2AldosteronaAldosteronaAdrenalinaAdrenalina
NoradrenalinaNoradrenalinaEndotelinaEndotelina
VSPVSPTBX A2TBX A2UbaínaUbaína
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Initially AdaptiveInitially Adaptive
ResponseShort-Term Effects
Salt and Water Retention Augments Preload
Vasoconstriction Maintains BP for perfusion of vital organs
Sympathetic Stimulation Increases HR and ejection
Neurohormonal Responses to ImpairedCardiac Performance
Jaski, B, MD: Jaski, B, MD: Basics of Heart Failure: A Problem Solving ApproachBasics of Heart Failure: A Problem Solving Approach
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Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52.Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52.
CNS sympathetic outflowCNS sympathetic outflow
Disease progressionDisease progression
Cardiac sympatheticCardiac sympatheticactivityactivity
11--
receptorsreceptors22--
receptorsreceptors11--
receptorsreceptors
VasoconstrictionVasoconstrictionSodium retentionSodium retention
Myocardial toxicityMyocardial toxicityIncreased arrhythmiasIncreased arrhythmias
SympatheticSympatheticactivity to kidneysactivity to kidneys
+ peripheral vasculature+ peripheral vasculature
ActivationActivationof RASof RAS
11-- 11--
Sympathetic Activation in Heart Failure
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1 and 2 receptor densities in the failing and non-failing heart
Receptor density (ƒ mol/mg)Receptor density (ƒ mol/mg)
Non-failingNon-failing
FailingFailing
**pp<0.05<0.05
****pp=NS=NS
11 22
8080
6060
4040
2020
00
****
**
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VasoconstrictionVasoconstriction
Oxidative StressOxidative Stress
Cell GrowthCell Growth ProteinuriaProteinuria
LV remodelingLV remodeling
Vascular remodelingVascular remodeling
AngiotensinogenAngiotensinogen
Angiotensin IAngiotensin I
Angiotensin IIAngiotensin II
AT I receptorAT I receptor
ReninRenin
AngiotensinAngiotensinConvertingConverting
EnzymeEnzyme
Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS)
Na+ retentionNa+ retention
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Other Neurohormones
• Natriuretic Peptides: Three known types– Atrial Natriuretic Peptide (ANP)
• Predominantly found in the atria
• Diuretic and vasodilatory properties
– Brain Natriuretic Peptide (hBNP) • Predominantly found in the cardiac ventricles
• Diuretic and vasodilatory properties
– C-type Natriuretic Peptide (CNP)• Predominantly found in the central nervous system
• Limited natriuretic and vasodilatory properties
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Hemodynamic Hemodynamic (balanced vasodilation)(balanced vasodilation)
•• veinsveins
•• arteriesarteries
•• coronary arteriescoronary arteries
NeurohormonalNeurohormonal
aldosteronealdosterone
norepinephrinenorepinephrine
RenalRenal
diuresis & natriuresisdiuresis & natriuresis
DR I
M
K
RG
S SS
SG
L
GF
CC
S S
GSGQVM
K V LR
RH
KPS
Pharmacological Actions of hBNP
Abraham WT and Schrier RW, 1994Abraham WT and Schrier RW, 1994
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Produced by a thin lining of cells within the arteries and veins called the endothelium
Endothelium-derived relaxing factors (EDRF) – Vasodilators:• Nitric Oxide (NO)
• Bradykinin
• Prostacyclin
Endothelium-derived constricting factors (EDCF) – Vasoconstrictors:
• Endothelin I
Endothelium-Derived Vasoactive Substances
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Mediators of Heart FailureCytokines
• Small protein molecules produced by a variety of tissues and cells
• Negative inotropes
• Elevated levels associated with worse clinical outcomes
• Examples:– Tumor necrosis factor (TNF)-alpha– Interleukin 1-alpha– Interleukin-2– Interleukin-6– Interferon-alpha
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Initially Adaptive, Deleterious if SustainedInitially Adaptive, Deleterious if Sustained
ResponseShort-Term Effects
Long-Term Effects
Salt and Water Retention Augments Preload Pulmonary Congestion, Anasarca
Vasoconstriction Maintains BP for perfusion of vital organs
Exacerbates pump dysfunction (excessive afterload), increases cardiac energy expenditure
Sympathetic Stimulation Increases HR and ejection Increases energy expenditure
Neurohormonal Responses to ImpairedCardiac Performance
Jaski, B, MD: Jaski, B, MD: Basics of Heart Failure: A Problem Solving ApproachBasics of Heart Failure: A Problem Solving Approach
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Disfunção miocárdica
Dilatação ventricularRemodelagem
Stress oxidativoCitocinasApoptose
Activação neurohumoral
ICC - Fase de descompensação
agravamento
Mitogénese Proliferação celular
Dilatação e hipertrofia
Perda de miócitos, necrose e fibrose
Alterações estruturais, miocárdio, tecido conjuntivo, vasos
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General Measures
Lifestyle Modifications:
• Weight reduction
• Discontinue smoking
• Avoid alcohol and other cardiotoxic substances
• Exercise
Medical Considerations:
• Treat HTN, hyperlipidemia, diabetes, arrhythmias
• Coronary revascularization
• Anticoagulation
• Immunization
• Sodium restriction
• Daily weights
• Close outpatient monitoring
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sobrevidaMorbilidadeCapacidade de Exercicio Qualidade de vidaAlterações NeurohormonaisProgressão da CHFSintomas
sobrevidaMorbilidadeCapacidade de Exercicio Qualidade de vidaAlterações NeurohormonaisProgressão da CHFSintomas
Objectivos terapêuticosObjectivos terapêuticos
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Tratamento da Ins. cardiaca Diureticos e digitalicos
Vasodilatadores
Directos e nitratos
Inibidores da ECA
Antagonistas dos receptores AT1
Bloqueadores beta
Antiarrítmicos, anticoagulantes
Inibidores das fosfodiesterases redutores da produçãode FNT e outras citocinas)
Ressincronização cardíaca
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DRUGSHEMODYNAMIC EFFECTS
DRUGSHEMODYNAMIC EFFECTS
AAII
A + VA + V
VV
DD
Ventricular Filling PressureVentricular Filling Pressure
StrokeVolumeStrokeVolume
NormalNormal
CHFCHF
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Pharmacologic Management
Digoxin
• Enhances inotropy of cardiac muscle
• Reduces activation of SNS and RAAS
• Controlled trials have shown long-term digoxin therapy:– Reduces symptoms
– Increases exercise tolerance
– Improves hemodynamics
– Decreases risk of HF progression
– Reduces hospitalization rates for decompensated HF
– Does not improve survival
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oCH3
OH
OHCH3
= O
- o- - o-HO -
HO -
o o o
HO -HO -
CH 3CH 3CH 3
- O -
Genina
Esteroide
Lactona
Tri-digitoxose (açucares)
Figura 1. Estrutura da digoxina, protótipo dos digitálicos
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Na+Na+
K+K+
K+K+
Na+Na+
Na+Na+ Ca++Ca++
Ca++Ca++
Na-K ATPaseNa-K ATPase Na-Ca ExchangeNa-Ca Exchange
MyofilamentsMyofilaments
DIGOXINDIGOXIN
CONTRACTILITYCONTRACTILITY
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Figura 2. Efeitos inotrópicos e neurais dos digitálicos
Efeito simpático-inibidor
Adaptado de Opie, 1990
aferências
Estimulação simpática
Estimulação vagal
Taquiarritmias
Aumento Ca2+ intracelular
TrocadorNa+/Ca2+
> Ca 2+
intracelular
> saídade sódio2K + 3Na +
Digitálicos
> sódiointracelular
EFEITO INOTRÓPICO POSITIVO
Doses
tóxicas
dosesterapêuticas
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Normal Conduction Pathway in the Heart and the ECG
Sinoatrial (SA) Node Atrioventricular (AV) Node
Left Bundle Branches
Right Bundle Branch
Purkinje Fibers
P = Atrial DepolarizationQRS = Ventricular DepolarizationT = Ventricular Repolarization
P T
QRS
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DIGOXIN PHARMACOKINETIC PROPERTIES
DIGOXIN PHARMACOKINETIC PROPERTIES
Oral absorption (%)Protein binding (%)Volume of distribution (l/Kg)Half lifeEliminationOnset (min)
i.v.oral
Maximal effect (h)i.v.oral
DurationTherapeutic level (ng/ml)
Oral absorption (%)Protein binding (%)Volume of distribution (l/Kg)Half lifeEliminationOnset (min)
i.v.oral
Maximal effect (h)i.v.oral
DurationTherapeutic level (ng/ml)
60 - 7525
6 (3-9)36 (26-46) h
Renal
5 - 3030 - 90
2 - 43 - 6
2 - 6 days0.5 - 2
60 - 7525
6 (3-9)36 (26-46) h
Renal
5 - 3030 - 90
2 - 43 - 6
2 - 6 days0.5 - 2
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DIGOXIN
HEMODYNAMIC EFFECTSDIGOXIN
HEMODYNAMIC EFFECTS
Cardiac output
LVejection fraction
LVEDP
Exercisetolerance
Natriuresis
Neurohormonalactivation
Cardiac output
LVejection fraction
LVEDP
Exercisetolerance
Natriuresis
Neurohormonalactivation
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DIGOXIN NEUROHORMONAL EFFECTS
DIGOXIN NEUROHORMONAL EFFECTS
Plasma Noradrenaline
Peripheral nervous system activity
RAAS activity
Vagal tone
Normalizes arterial baroreceptors
Plasma Noradrenaline
Peripheral nervous system activity
RAAS activity
Vagal tone
Normalizes arterial baroreceptors
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DIGOXIN
LONG TERM EFFECTSDIGOXIN
LONG TERM EFFECTS
Survival similar to placebo
Fewer hospital admissions
More serious arrhythmias
More myocardial infarctions
Survival similar to placebo
Fewer hospital admissions
More serious arrhythmias
More myocardial infarctions
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DIGOXIN
CLINICAL USESDIGOXIN
CLINICAL USES
AF with rapid ventricular response
CHF refractory to other drugs
Other indications?
Can be combined with other drugs
AF with rapid ventricular response
CHF refractory to other drugs
Other indications?
Can be combined with other drugs
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DIGOXIN
CONTRAINDICATIONSDIGOXIN
CONTRAINDICATIONSABSOLUTE:
- Digoxin toxicity
RELATIVE- Advanced A-V block without pacemaker- Bradycardia or sick sinus without PM- PVC’s and TV- Marked hypokalemia- W-P-W with atrial fibrillation
ABSOLUTE:- Digoxin toxicity
RELATIVE- Advanced A-V block without pacemaker- Bradycardia or sick sinus without PM- PVC’s and TV- Marked hypokalemia- W-P-W with atrial fibrillation
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DIGOXIN TOXICITY
CARDIAC MANIFESTATIONSDIGOXIN TOXICITY
CARDIAC MANIFESTATIONS
ARRHYTHMIAS :- Ventricular (PVCs, TV, VF)- Supraventricular (PACs, SVT)
BLOCKS:- S-A and A-V blocks
CHF EXACERBATION
ARRHYTHMIAS :- Ventricular (PVCs, TV, VF)- Supraventricular (PACs, SVT)
BLOCKS:- S-A and A-V blocks
CHF EXACERBATION
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DIGOXIN TOXICITYEXTRACARDIAC MANIFESTATIONSDIGOXIN TOXICITYEXTRACARDIAC MANIFESTATIONS
GASTROINTESTINAL:- Nausea, vomiting, diarrhea
NERVOUS:- Depression, disorientation, paresthesias
VISUAL:- Blurred vision, scotomas and yellow-green
vision HYPERESTROGENISM:
- Gynecomastia, galactorrhea
GASTROINTESTINAL:- Nausea, vomiting, diarrhea
NERVOUS:- Depression, disorientation, paresthesias
VISUAL:- Blurred vision, scotomas and yellow-green
vision HYPERESTROGENISM:
- Gynecomastia, galactorrhea
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CARDIAC GLYCOSIDES
SYMPATHOMIMETICSCatecholaminesß-adrenergic agonists
PHOSPHODIESTERASE INHIBITORS Amrinone Enoximone
Others
CARDIAC GLYCOSIDES
SYMPATHOMIMETICSCatecholaminesß-adrenergic agonists
PHOSPHODIESTERASE INHIBITORS Amrinone Enoximone
Others
MilrinonePiroximoneMilrinonePiroximone
POSITIVE INOTROPESPOSITIVE INOTROPES
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ß-ADRENERGIC STIMULANTS
CLASSIFICATION
ß-ADRENERGIC STIMULANTS
CLASSIFICATION
B1 StimulantsIncrease contractility
Dobutamine Doxaminol XamoterolButopamine Prenalterol Tazolol
B1 StimulantsIncrease contractility
Dobutamine Doxaminol XamoterolButopamine Prenalterol Tazolol
B2 StimulantsProduce arterial vasodilatation and reduce SVR
B2 StimulantsProduce arterial vasodilatation and reduce SVR
PirbuterolCarbuterolPirbuterolCarbuterol
RimiterolFenoterolRimiterolFenoterol
TretoquinolSalbutamolTretoquinolSalbutamol
TerbutalineSalmefamolTerbutalineSalmefamol
SoterenolQuinterenolSoterenolQuinterenol
MixedMixedDopamineDopamine
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DOPAMINE AND DOBUTAMINEEFFECTS
DOPAMINE AND DOBUTAMINEEFFECTS
ReceptorsReceptors
ContractilityContractility
Heart RateHeart Rate
Arterial Press.Arterial Press.
Renal perfusionRenal perfusion
ArrhythmiaArrhythmia
DA (µg / Kg / min)DA (µg / Kg / min) DobutamineDobutamine
< 2< 2DA1 / DA2DA1 / DA2
±±
±±
±±
++++
--
2 - 52 - 5ß1ß1
++++
++
++
++
±±
> 5> 5ß1 + ß1 +
++++
++++
++++
±±
++++
ß1ß1
++++
±±
++++
++
±±
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POSITIVE INOTROPES
CONCLUSIONSPOSITIVE INOTROPES
CONCLUSIONS
May increase mortality
Safer in lower doses
Use only in refractory CHF
NOT for use as chronic therapy
May increase mortality
Safer in lower doses
Use only in refractory CHF
NOT for use as chronic therapy
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CortexCortex
MedullaMedulla
ThiazidesInhibit active exchange of Cl-Na
in the cortical diluting segment of the ascending loop of Henle
ThiazidesInhibit active exchange of Cl-Na
in the cortical diluting segment of the ascending loop of Henle
K-sparingInhibit reabsorption of Na in the
distal convoluted and collecting tubule
K-sparingInhibit reabsorption of Na in the
distal convoluted and collecting tubule
Loop diuretics Inhibit exchange of Cl-Na-K in
the thick segment of the ascending loop of Henle
Loop diuretics Inhibit exchange of Cl-Na-K in
the thick segment of the ascending loop of Henle
Loop of HenleLoop of HenleCollecting tubuleCollecting tubule
DIURETICSDIURETICS
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THIAZIDESMECHANISM OF ACTION
THIAZIDESMECHANISM OF ACTION
Excrete 5 - 10% of filtered Na+
Elimination of K
Inhibit carbonic anhydrase: increase elimination of HCO3
No dose - effect relationship
Excrete 5 - 10% of filtered Na+
Elimination of K
Inhibit carbonic anhydrase: increase elimination of HCO3
No dose - effect relationship
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LOOP DIURETICSMECHANISM OF ACTION
LOOP DIURETICSMECHANISM OF ACTION
Excrete 15 - 20% of filtered Na+
Elimination of K+, Ca+ and Mg++
Resistance of afferent arterioles
-Cortical flow and GFR
- Release renal PGs
- NSAIDs may antagonize diuresis
Excrete 15 - 20% of filtered Na+
Elimination of K+, Ca+ and Mg++
Resistance of afferent arterioles
-Cortical flow and GFR
- Release renal PGs
- NSAIDs may antagonize diuresis
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K-SPARING DIURETICS MECHANISM OF ACTION
K-SPARING DIURETICS MECHANISM OF ACTION
Eliminate < 5% of filtered Na+
Inhibit exchange of Na+ for K+ or H+
Spironolactone = competitive antagonist for the aldosterone receptor
Amiloride and triamterene block Na+ channels controlled by aldosterone
Eliminate < 5% of filtered Na+
Inhibit exchange of Na+ for K+ or H+
Spironolactone = competitive antagonist for the aldosterone receptor
Amiloride and triamterene block Na+ channels controlled by aldosterone
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Volume and preloadImprove symptoms of congestion
No direct effect on CO, but
excessive preload reduction may
Improves arterial distensibility
Neurohormonal activation Levels of NA, Ang II and ARP Exception: with spironolactone
Volume and preloadImprove symptoms of congestion
No direct effect on CO, but
excessive preload reduction may
Improves arterial distensibility
Neurohormonal activation Levels of NA, Ang II and ARP Exception: with spironolactone
DIURETIC EFFECTSDIURETIC EFFECTS
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DIURETICS ADVERSE REACTIONS
Thiazide and Loop Diuretics
DIURETICS ADVERSE REACTIONS
Thiazide and Loop Diuretics Changes in electrolytes:
Volume Na+, K+, Ca++, Mg++ metabolic alkalosis
Metabolic changes: glycemia, uremia, gout LDL-C and TG
Cutaneous allergic reactions
Changes in electrolytes: Volume Na+, K+, Ca++, Mg++ metabolic alkalosis
Metabolic changes: glycemia, uremia, gout LDL-C and TG
Cutaneous allergic reactions
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DIURETICSADVERSE REACTIONS
Thiazide and Loop Diuretics
DIURETICSADVERSE REACTIONS
Thiazide and Loop Diuretics
Idiosyncratic effects:Blood dyscrasia, cholestatic jaundice and acute pancreatitis
Gastrointestinal effectsGenitourinary effects:
Impotence and menstrual cramps
Deafness, nephrotoxicity (Loop diuretics)
Idiosyncratic effects:Blood dyscrasia, cholestatic jaundice and acute pancreatitis
Gastrointestinal effectsGenitourinary effects:
Impotence and menstrual cramps
Deafness, nephrotoxicity (Loop diuretics)
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Pharmacologic Management
Diuretics
• Used to relieve fluid retention
• Improve exercise tolerance
• Facilitate the use of other drugs indicated for heart failure
• Patients can be taught to adjust their diuretic dose based on changes in body weight
• Electrolyte depletion a frequent complication
• Should never be used alone to treat heart failure
• Higher doses of diuretics are associated with increased mortality
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DIURETICSADVERSE REACTIONSK-SPARING DIURETICS
DIURETICSADVERSE REACTIONSK-SPARING DIURETICS
Changes in electrolytes:
Na+, K+, acidosis
Musculoskeletal:
Cramps, weakness
Cutaneous allergic reactions :
Rash, pruritis
Changes in electrolytes:
Na+, K+, acidosis
Musculoskeletal:
Cramps, weakness
Cutaneous allergic reactions :
Rash, pruritis
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COCO
PRELOADPRELOAD AFTERLOADAFTERLOAD
Normal ContractilityNormal Contractility
Diminished Contractility Diminished Contractility
Normal ContractilityNormal Contractility
DiminishedContractility DiminishedContractility
VVVV AVAV
VASODILATOR DRUGSPRINCIPLES
VASODILATOR DRUGSPRINCIPLES
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Venous Vasodilatation
Venous Vasodilatation
MIXEDCalcium antagonists -adrenergic Blockers
ACEIAngiotensin II inhibitors
K+ channel activatorsNitroprusside
MIXEDCalcium antagonists -adrenergic Blockers
ACEIAngiotensin II inhibitors
K+ channel activatorsNitroprusside
VENOUSNitrates
Molsidomine
VENOUSNitrates
Molsidomine
ARTERIALMinoxidil
Hydralazine
ARTERIALMinoxidil
Hydralazine
VASODILATORSCLASSIFICATIONVASODILATORSCLASSIFICATION
Arterial Vasodilatation
Arterial Vasodilatation
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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
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0.60.6
PROBABILITYOFDEATH
PROBABILITYOFDEATH
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
VHefT-1N Engl J Med 1986;314:1547VHefT-1N Engl J Med 1986;314:1547
NITRATESSURVIVALNITRATESSURVIVAL
00 66 1212 1818 2424 3030 3636 4242
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" Decrease in the effect of a drugwhen administered in a long-acting form"
" Decrease in the effect of a drugwhen administered in a long-acting form"
NITRATESTOLERANCE
NITRATESTOLERANCE
Develops with all nitrates
Is dose-dependent
Disappears in 24 h. after stopping the drug
Tolerance can be avoided- Using the least effective dose- Creating discontinuous plasma levels
Develops with all nitrates
Is dose-dependent
Disappears in 24 h. after stopping the drug
Tolerance can be avoided- Using the least effective dose- Creating discontinuous plasma levels
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NITRATES
TOLERANCENITRATES
TOLERANCECan be avoided or minimized
- Intermittent administration- Use the lowest possible dose- Intersperse a nitrate-free interval
Allow peaks and valleys in plasma levels- Vascular smooth muscle recovers its nitrate sensitivity during the nadirs- Patches: remove after 8-10 h
Can be avoided or minimized- Intermittent administration- Use the lowest possible dose- Intersperse a nitrate-free interval
Allow peaks and valleys in plasma levels- Vascular smooth muscle recovers its nitrate sensitivity during the nadirs- Patches: remove after 8-10 h
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s.l. NTG
ISDN
I 5-MN
Percutaneous NTG
s.l. NTG
ISDN
I 5-MN
Percutaneous NTG
TOLERANCE
TOLERANCE
HALF
LIFE
HALF
LIFE
NITRATESTOLERANCE
NITRATESTOLERANCE
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NITRATES
CONTRAINDICATIONSNITRATES
CONTRAINDICATIONS
Previous hypersensitivity
Hypotension ( < 80 mmHg)
AMI with low ventricular filling pressure
1st trimester of pregnancy
Previous hypersensitivity
Hypotension ( < 80 mmHg)
AMI with low ventricular filling pressure
1st trimester of pregnancy
WITH CAUTION:WITH CAUTION:� Constrictive pericarditis� Intracranial hypertension� Hypertrophic cardiomyopathy
� Constrictive pericarditis� Intracranial hypertension� Hypertrophic cardiomyopathy
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NITRATES
CLINICAL USESNITRATES
CLINICAL USES
Pulmonary congestion
Orthopnea and paroxysmal nocturnal
dyspnea
CHF with myocardial ischemia
In acute CHF and pulmonary edema:
NTG s.l. or i.v.
Pulmonary congestion
Orthopnea and paroxysmal nocturnal
dyspnea
CHF with myocardial ischemia
In acute CHF and pulmonary edema:
NTG s.l. or i.v.
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Pharmacologic Management
ACE Inhibitors
• Blocks the conversion of angiotensin I to angiotensin II; prevents functional deterioration
• Recommended for all heart failure patients
• Relieves symptoms and improves exercise tolerance
• Reduces risk of death and decreases disease progression
• Benefits may not be apparent for 1-2 months after initiation
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VASOCONSTRICTIONVASOCONSTRICTION VASODILATATION VASODILATATION
KininogenKininogen
KallikreinKallikrein
Inactive FragmentsInactive Fragments
AngiotensinogenAngiotensinogen
Angiotensin IAngiotensin I
RENINRENIN
Kininase IIKininase IIInhibitorInhibitor
ALDOSTERONEALDOSTERONE
SYMPATHETICSYMPATHETICVASOPRESSINVASOPRESSIN
PROSTAGLANDINSPROSTAGLANDINS
tPAtPA
ANGIOTENSIN IIANGIOTENSIN II
BRADYKININBRADYKININ
ACEIMECHANISM OF ACTION
ACEIMECHANISM OF ACTION
A.C.E.A.C.E.
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Retenção de Na+Retenção de Na+
Inflamação/procoagulabilidadeInflamação/procoagulabilidadeStress oxidativoStress oxidativo
Efeitos centraisEfeitos centrais
EstimulaçãoEstimulaçãosimpáticasimpática
Estimulação deEstimulação deprotooncogenesprotooncogenes
Libertação deLibertação deAldosteronaAldosteronae ET-1e ET-1
Hipertrofia cardíacaHipertrofia cardíacaFibrose intersticialFibrose intersticialPro-ateromatosePro-ateromatose
Hipertrofia/HiperplasiaHipertrofia/HiperplasiaRemodelagem vascularRemodelagem vascular
Angiotensina IIAngiotensina II
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ACEI
HEMODYNAMIC EFFECTSACEI
HEMODYNAMIC EFFECTS
Arteriovenous Vasodilatation- PAD, PCWP and LVEDP- SVR and BP- CO and exercise tolerance
No change in HR / contractilityMVO2
Renal, coronary and cerebral flowDiuresis and natriuresis
Arteriovenous Vasodilatation- PAD, PCWP and LVEDP- SVR and BP- CO and exercise tolerance
No change in HR / contractilityMVO2
Renal, coronary and cerebral flowDiuresis and natriuresis
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ACEI
ADVANTAGESACEI
ADVANTAGESInhibit LV remodeling post-MI
Modify the progression of chronic CHF
- Survival
- Hospitalizations
- Improve the quality of life
In contrast to others vasodilators, do not produce neurohormonal activationor reflex tachycardia
Tolerance to its effects does not develop
Inhibit LV remodeling post-MI
Modify the progression of chronic CHF
- Survival
- Hospitalizations
- Improve the quality of life
In contrast to others vasodilators, do not produce neurohormonal activationor reflex tachycardia
Tolerance to its effects does not develop
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PlaceboPlacebo
EnalaprilEnalapril
1212111110109988776655
PROBABILITYOFDEATH
PROBABILITYOFDEATH
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
p< 0.002p< 0.002
CONSENSUSN Engl J Med 1987;316:1429CONSENSUSN Engl J Med 1987;316:1429
ACEI SURVIVALACEI SURVIVAL
4433221100
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ACEIINDICATIONS
ACEIINDICATIONS
Clinical cardiac insufficiency- All patients
Asymptomatic ventricular dysfunction
- LVEF < 35 %
Clinical cardiac insufficiency- All patients
Asymptomatic ventricular dysfunction
- LVEF < 35 %
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ACEI
UNDESIRABLE EFFECTSACEI
UNDESIRABLE EFFECTS
Inherent in their mechanism of action- Hypotension- Hyperkalemia- Angioneurotic edema
Due to their chemical structure- Cutaneous eruptions- Neutropenia,
thrombocytopenia- Digestive upset
Inherent in their mechanism of action- Hypotension- Hyperkalemia- Angioneurotic edema
Due to their chemical structure- Cutaneous eruptions- Neutropenia,
thrombocytopenia- Digestive upset
- Dry cough- Renal Insuff.- Dry cough- Renal Insuff.
- Dysgeusia- Proteinuria- Dysgeusia- Proteinuria
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ACEI
CONTRAINDICATIONSACEI
CONTRAINDICATIONS
Renal artery stenosis
Renal insufficiency
Hyperkalemia
Arterial hypotension
Intolerance (due to side effects)
Renal artery stenosis
Renal insufficiency
Hyperkalemia
Arterial hypotension
Intolerance (due to side effects)
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IECAS VANTAGENS DESVANTAGENS
- reduzem mortalidade - efeitos acessórios
e morbilidade (tosse /angioedema)
- melhoram sintomas
- aumentam tolerância
ao esforço
- reduzem hospitalizações
- eficazes na I C assintomáticaNEJM 1987: 316;1429 JAMA 1988:259; 539 NEJM 1991:325;293
NEJM 1991: 325; 303 ANN INTERN MED 1992:117 ; 234
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Mortality trials with ACE inhibitors in heart failure
Trial
CONSENSUS-1
V-HeFT-II
SOLVD
(treatment)
Treatments
Enalapril
Placebo
Enalapril
ISDN/Hydral
Enalapril
Placebo
n
253
804
2569
Treatment
duration
6 months
2 years
41 months
Mortality
(%)
26
44
18
25
35
40
p value
0.002
0.016
0.004
ISDN=isosorbide dinitrate; Hydral=hydralazine
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ACE inhibitor trials in heart failure following AMI
Trial
AIRE
SAVE
TRACE
n
2006
2231
1749
Treatment
duration
15 months
42 months
4 years
Mortalit
y
(%)
17
23
20
25
35
42
p value
0.002
0.019
0.001
Treatments
Ramipril
Placebo
Captopril
Placebo
Trandolapril
Placebo
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Estudos de mortalidade com In ECA na insuficiência cardíaca e E. miocárdio
• 32 estudos randomizados em 7105 doentes
• Redução significativa da mortalidade global
– odds ratio 0.77 (95% C.I. 0.67-0.88); p<0.001
• Redução significativa da mortalidade + hospitali-
zações por insuficiência cardíaca de 25%
– odds ratio 0.65 (95% C.I. 0.57-0.74); p<0.001
• Maiores benefícios em doentes com maior
deterioração da função cardíaca
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AngiotensinogénioAngiotensinogénioAngiotensinogénioAngiotensinogénio
Angiotensina IAngiotensina IAngiotensina IAngiotensina I
Angiotensina IIAngiotensina IIAngiotensina IIAngiotensina II
BradicininaBradicininaBradicininaBradicinina
PeptídeosPeptídeosinactivosinactivosPeptídeosPeptídeosinactivosinactivos
Receptores ATReceptores AT11Receptores ATReceptores AT11 Receptores ATReceptores AT22Receptores ATReceptores AT22
Receptores BK 2Receptores BK 2Receptores BK 2Receptores BK 2
Óxido nítricoÓxido nítricoÓxido nítricoÓxido nítrico
ReninaRenina
ChymaseChymaseCAGE,CAGE,Calicreína, ...Calicreína, ...
Cathepsin G,Cathepsin G,Calicreína,Calicreína,Tonina,Tonina,TripsinaTripsina
ECAECA
--??
??
SISTEMA RENINA - ANGIOTENSINASISTEMA RENINA - ANGIOTENSINASISTEMA RENINA - ANGIOTENSINASISTEMA RENINA - ANGIOTENSINA
PGPGPGPG
VasoconstriçãoAntinatriureseProliferação celularInflamação, aterogeneseHipercoagulação
ALDO
VasodilataçãoEfeito antiproliferativoantiaterogenico
Antagonistas Antagonistas (AT(AT11))
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ANGIOTENSIN II INHIBITORS
MECHANISM OF ACTIONANGIOTENSIN II INHIBITORS
MECHANISM OF ACTION
RENINRENIN
AngiotensinogenAngiotensinogen Angiotensin I
ANGIOTENSIN II
Angiotensin I
ANGIOTENSIN II
ACEACEOther pathsOther paths
VasoconstrictionVasoconstriction Proliferative Action
Proliferative Action
VasodilatationVasodilatation Antiproliferative Action
Antiproliferative Action
AT1 AT1 AT2AT2
AT1 RECEPTOR BLOCKERS
AT1 RECEPTOR BLOCKERS
RECEPTORSRECEPTORS
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Pharmacologic Management
Angiotensin Receptor Blockers (ARBs)
• Block AT1 receptors, which bind circulating angiotensin II
• Examples: irbesartan, valsartan, candesartan, losartan
• Should not be considered equivalent or superior to ACE inhibitors
• In clinical practice, ARBs should be used to treat patients who are ACE intolerant due to intractable cough or who develop angioedema
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ATAT11 receptor receptor ATAT22 receptor receptor
• VasoconstrictionVasoconstriction
• Growth PromotionGrowth Promotion
• Anti-apoptoticAnti-apoptotic
• Pro-fibroticPro-fibrotic
• Pro-thromboticPro-thrombotic
• Pro-oxidantPro-oxidant
• VasodilationVasodilation
• Growth inhibitionGrowth inhibition
• Pro-apoptoticPro-apoptotic
• ? Fibrosis? Fibrosis
• ? Thrombosis? Thrombosis
• ? redox? redox
Angiotensin II Receptors
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AT1 RECEPTOR BLOCKERSDRUGS
AT1 RECEPTOR BLOCKERSDRUGS
Losartan
Valsartan
Irbersartan
Candesartan
Losartan
Valsartan
Irbersartan
Candesartan
Competitive and selective
blocking of AT1 receptors
Competitive and selective
blocking of AT1 receptors
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The ELITE-study
0
50
100
150
200
250
300
350
400
Number ofpatients
Adverseevents
Death andhospitalization
Death
Losartan
Captopril
Pitt et al. Lancet 1997: 349: 747-52
p = 0.035p = 0.075
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Losartan Heart Failure Survival StudyELITE II
Study Design
60 years; NYHA II-IV; EF 40%ACEI/AIIA naive or <7 days in 3 months prior to entryStandard Rx (± Dig/Diuretics),-blocker stratification
Captopril50 mg 3 times daily
(n=1574)
Losartan50 mg daily(n=1578)
Event-driven(Target 510 Deaths)
~2 years
Primary Endpoint: All-Cause MortalitySecondary Endpoint: Sudden Cardiac Death and/or Resuscitated ArrestOther Endpoints: All-Cause Mortality/Hospitalizations
Safety and Tolerability
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Losartan Heart Failure Survival Study – ELITE IIMortality by Cause (Adjudicated)
15
10
5
0Suddendeath
Heartfailure
MI Stroke OtherCV
Non-CV
Losartan (n=1578)
Captopril (n=1574)
% of Patients
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INSUFICIÊNCIA CARDÍACAVALOR DOS ANTAGONISTAS DA AII
• MELHORAM OS SINTOMAS, AUMENTAM A QUALIDADE DE VIDA E AUMENTAM A TOLERÂNCIA AO EXERCÍCIO
• REDUZEM A MORBILIDADE E O NÚMERO DE HOSPITALIZAÇÕES.
• AUMENTAM A ADERÊNCIA AO TRATA- MENTO (poucos efeitos secundários).
ÓPTIMA ALTERNATIVA AOS IECAS
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CONCEITO DOS INIBIDORES DAS VASOPEPTIDASES
- DUPLO BLOQUEIO DA NEP e da ECANEP e da ECA
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Inibição dasvasopeptidases ECANEP
ANP e peptideos Análogos
Adrenomedulina
BK Angiotensina II
Vasodilatação Excreção sódio Efeitos antihipertróficos
Vasoconstrição Retenção sódio Efeitos hipertróficos
Pressão arterial Melhoria da performance cardíaca Protecção dos orgãos-alvo
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Cardiomyopathic hamstersCardiomyopathic hamsters
OmapatrilatOmapatrilat
Su
rviv
al (
%)
Su
rviv
al (
%)
440440
146 d146 d 221 d221 d 290 d290 d
00
2020
4040
6060
8080
100100
36036032032028028024024020020016016012012080804040
Days of treatmentDays of treatment400400
Start treatmentStart treatment
CaptoprilCaptoprilPlaceboPlacebo
Omapatrilat: Survival BenefitOmapatrilat: Survival Benefit
Trippodo et al. J Cardiovasc Pharmacol 1999;34:782Trippodo et al. J Cardiovasc Pharmacol 1999;34:782
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Pharmacologic Management
Aldosterone Antagonists
• Generally well-tolerated
• Shown to reduce heart failure-related morbidity and mortality
• Generally reserved for patients with NYHA Class III-IV HF
• Side effects include hyperkalemia and gynecomastia. Potassium and creatinine levels should be closely monitored
• REDUÇÂO MORTALIDADE ASSOCIADOS AOS InECA
• (estudo RALES)
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ALDOSTERONEALDOSTERONE
Retention Na+
Retention H2O
Excretion K+
Excretion Mg2+
Retention Na+
Retention H2O
Excretion K+
Excretion Mg2+
Collagen
deposition
Fibrosis - myocardium
- vessels
SpironolactoneSpironolactone
Edema Edema
Arrhythmias Arrhythmias
Competitive antagonist of thealdosterone receptor(myocardium, arterial walls, kidney)
Competitive antagonist of thealdosterone receptor(myocardium, arterial walls, kidney)
ALDOSTERONE INHIBITORSALDOSTERONE INHIBITORS
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ALDOSTERONE INHIBITORSINDICATIONSALDOSTERONE INHIBITORSINDICATIONS
FOR DIURETIC EFFECT• Pulmonary congestion (dyspnea)• Systemic congestion (edema)
FOR ELECTROLYTE EFFECTS• Hypo K+, Hypo Mg+
• Arrhythmias• Better than K+ supplementsFOR NEUROHORMONAL EFFECTS• Please see RALES results, N Engl J Med 1999:341:709-717
FOR DIURETIC EFFECT• Pulmonary congestion (dyspnea)• Systemic congestion (edema)
FOR ELECTROLYTE EFFECTS• Hypo K+, Hypo Mg+
• Arrhythmias• Better than K+ supplementsFOR NEUROHORMONAL EFFECTS• Please see RALES results, N Engl J Med 1999:341:709-717
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• Hyperkalemia
• Severe renal insufficiency
• Metabolic acidosis
• Hyperkalemia
• Severe renal insufficiency
• Metabolic acidosis
ALDOSTERONE INHIBITORSCONTRAINDICATIONSALDOSTERONE INHIBITORSCONTRAINDICATIONS
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Pharmacologic ManagementBeta-Blockers
• Cardioprotective effects due to blockade of excessive SNS stimulation
• In the short-term, beta blocker decreases myocardial contractility; increase in EF after 1-3 months of use
• Long-term, placebo-controlled trials have shown symptomatic improvement in patients treated with certain beta-blockers1
• When combined with conventional HF therapy, beta-blockers reduce the combined risk of morbidity and mortality, or disease progression1
1 Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic 1 Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001 p. 20.Heart Failure in the Adult, 2001 p. 20.
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ß-ADRENERGIC BLOCKERS POSSIBLE BENEFICIAL EFFECTS
ß-ADRENERGIC BLOCKERS POSSIBLE BENEFICIAL EFFECTS
Density of ß1 receptors
Inhibit cardiotoxicity of catecholamines
Neurohormonalactivation
HR
Antihypertensive and antianginal
Antiarrhythmic
Antioxidant
Antiproliferative
Density of ß1 receptors
Inhibit cardiotoxicity of catecholamines
Neurohormonalactivation
HR
Antihypertensive and antianginal
Antiarrhythmic
Antioxidant
Antiproliferative
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5050
4040
3030
2020
1010
00
LV EJECTION FRACTIONLV EJECTION FRACTION< 30%< 30% 30-40%30-40% > 40%> 40%
%%
ß Blockerß Blocker Placebo Placebo
BHATJACC 1990;16:1327BHATJACC 1990;16:1327
ß BLOCKERSSURVIVAL
ß BLOCKERSSURVIVAL
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ß-ADRENERGIC BLOCKERSIDEAL CANDIDATE?
ß-ADRENERGIC BLOCKERSIDEAL CANDIDATE?
Suspected adrenergic activation
Arrhythmias
Hypertension
Angina
Suspected adrenergic activation
Arrhythmias
Hypertension
Angina
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Carvedilol(n=696)
Placebo(n=398)
Survival
Days
0 50 100 150 200 250 300 350 400
1.0
0.9
0.8
0.7
0.6
0.5
Risk reduction = 65%Risk reduction = 65%p<0.001
Packer et al (1996)
Lancet (1999)0 200 400 600 800
1.0
0.8
0.6
0
Bisoprolol
Placebo
Time after inclusion (days)
p<0.0001
Survival
Risk reduction = 34%Risk reduction = 34%
The MERIT-HF Study Group (1999)
Months of follow-up
Mortality %
0 3 6 9 12 15 18 21
20
15
10
5
0
Placebo
Metoprolol CR/XL
p=0.0062
Risk reduction = 34%Risk reduction = 34%
US Carvedilol StudyUS Carvedilol Study
blockers in blockers in heart failure -heart failure -
all-cause mortalityall-cause mortality
CIBIS-IICIBIS-II MERIT-HFMERIT-HF
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• Antioxidant effects – reduction in myocyte apoptosis– decreased lipid peroxidation
• Antiproliferative effects– inhibition of vascular smooth muscle
cell proliferation
• Reduction in circulating endothelin-1
Additional benefits of carvedilol in CHF
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Treatment Approach for the Patient with Heart FailureStage AStage A
At high risk, no At high risk, no structural diseasestructural disease
Stage BStage B
Structural heart Structural heart disease, disease,
asymptomaticasymptomatic
Stage DStage D
Refractory HF Refractory HF requiring specialized requiring specialized
interventionsinterventions
TherapyTherapy
• Treat HypertensionTreat Hypertension
• Treat lipid disordersTreat lipid disorders
• Encourage regular Encourage regular exerciseexercise
• Discourage alcohol Discourage alcohol intakeintake
• ACE inhibitionACE inhibition
TherapyTherapy
• All measures under All measures under stage Astage A
• ACE inhibitors in ACE inhibitors in appropriate patientsappropriate patients
• Beta-blockers in Beta-blockers in appropriate patientsappropriate patients
TherapyTherapy
• All measures under All measures under stage Astage A
Drugs:Drugs:
• DiureticsDiuretics
• ACE inhibitorsACE inhibitors
• Beta-blockersBeta-blockers
• DigitalisDigitalis
• Dietary salt restrictionDietary salt restriction
TherapyTherapy
• All measures under All measures under stages A,B, and Cstages A,B, and C
• Mechanical assist Mechanical assist devicesdevices
• Heart transplantationHeart transplantation
• Continuous (not Continuous (not intermittent) IV intermittent) IV inotropic infusions for inotropic infusions for palliationpalliation
• Hospice careHospice care
Stage CStage C
Structural heart Structural heart disease with disease with prior/current prior/current
symptoms of HFsymptoms of HF
Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001Heart Failure in the Adult, 2001
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Tratamento da Ins. cardiaca Inibidores das fosfodiesterases redutores da
produçãode FNT e outras citocinas
Pimobendam, vesnarinona,
pentoxifilina
Ressincronização cardíaca