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CHRONIC CONGESTIVE HEART FAILURE
A Comprehensive Overview on Diagnosis and A Comprehensive Overview on Diagnosis and TreatmentTreatment
Dr. Irwan, SpJP.Dr. Irwan, SpJP.
Faculty of Medicine of Riau UniversityArifin Achmad Hospital,Pekanbaru
Introduction
Definition : Heart Failure “The situation when the heart is incapable of maintaining a cardiac output adequate to accommodate metabolic requirements and the venous return.“ E. Braunwald
“Pathophysiological state in which an abnormality of cardiac function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues.” Euro Heart J; 2001. 22: 1527-1560
DEFINITION OF HEART FAILURE. Criteria 1 and 2 should be fulfilled in all cases
1. Symptoms of heart failure(at rest or during exercise)
And2. Objective evidence of cardiac dysfunction
(at rest)And
(in cases where the diagnosis is in doubt)3. Response to treatment directed towards
heart failureTask Force Report. Guidelines for the diagnosis and treatment of chronic heart failure. European Society of Cardiology.2001
EPIDEMIOLOGYEPIDEMIOLOGY
Europe
• The prevalence of symptomatic HF range from 0.4-2%.• 10 million HF pts in 900 million total population
USA
• nearly 5 million HF pts. • ± 500,000 pts are D/ HF for the 1st time each year. • Last 10 years number of hospitalizations has increased.• Nearly 300,000 patients die of HF each year.
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult 2001
DESCRIPTIVE TERMS in HEART FAILUREDESCRIPTIVE TERMS in HEART FAILURE
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1528
Acute vs Chronic Heart Failure Systolic vs Diastolic Heart Failure Right vs Left Heart Failure Mild , Moderate, Severe Heart Failure
New York Heart Association (NYHA) New York Heart Association (NYHA) Classification of Heart FailureClassification of Heart Failure
Class – INo limitation : ordinary physical exercise does not cause undue fatigue, dyspnoea or palpita-tions.
Class – IISlight limitation of physical activity : comfor-table at rest but ordinary activity results in fatigue, dyspnoea, or palpitation.
Class - IIIMarked limitation of physical activity : comfor-table at rest but less than ordinary activity results in symptoms.
Class - IVUnable to carry out any physical activity with-out discomfort : symptoms of heart failure are present even at rest with increased discomfort with any physical activity.
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1531
(Adapted from Williams JF et al., Circulation. 1995; 92 : 2764-2784)
ACC/AHA – A New Approach To The Classification of HF Stage Descriptions Examples
A Patient who is at high risk for developing HF but has no structural disorder of the heart.
Hypertension; CAD; DM; rheumatic fever; cardiomyopathy.
B Patient with a structural disorder of the heart but who has never developed symptoms of HF.
LV hypertrophy or fibrosis; LV dilatation; asymptomatic VHD; MI.
C Patient with past or current symptoms of HF associated with underlying structural heart disease.
Dyspnea or fatigue ec LV systolic dysfunction; asymptomatic patients with HF.
D Patient with end-stage disease Frequently hospitalized pts ; pts awaiting heart transplantation etc
ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult 2001
Stage A Stage B Stage C Stage D
Pts with :• Hypertension• CAD• DM• Cardiotoxins• FHx CM
THERAPY• Treat Hypertension• Stop smoking • Treat lipid disorders• Encourage regular
exercise• Stop alcohol
& drug use• ACE inhibition
Pts with :• Previous MI• LV systolic
dysfunction• Asymptomatic
Valvular disease
THERAPY• All measures under
stage A• ACE inhibitor • Beta-blockers
THERAPY• All measures under
stage A• Drugs for routine use:
• diuretic• ACE inhibitor• Beta-blockers• digitalis
THERAPY• All measures under
stage A,B and C• Mechanical assist
device• Heart transplantation• Continuous IV
inotrphic infusions for palliation
Pts who have marked symptoms at rest despite maximal medical therapy.
Pts with :
• Struct. HD
• Shortness of breath and fatigue, reduce exercise tolerance
Struct.Heart Disease
DevelopSymp.of
HF
Refract. Symp.of HF at rest
Stages in the evolution of HF and recommended therapy by stage
ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult 2001
EVOLUTION OF CLINICAL STAGES
NORMAL
Asymptomatic LV Dysfunction
CompensatedCHF
DecompensatedCHF
No symptomsNormal exerciseNormal LV fxn
No symptomsNormal exerciseAbnormal LV fxn
No symptoms ExerciseAbnormal LV fxn
Symptoms ExerciseAbnormal LV fxn
RefractoryCHF
Symptoms not controlled with treatment
Patophysiology of C H F
Input
Block diagram of left ventricular pump performance(Little, 2001)
Output
PULMONARY VENOUSPRESSURE
CARDIAC OUTPUT
Filling EmptyingED volume x EFeffective = Stroke
volume
Heartrate
x
Diastolic function Systolic function
LV DistensibilityRelaxationLeft atriumMitral valvePericardium
ContractilityAfterloadPreloadStructure
DETERMINANTS OF
VENTRICULAR FUNCTION
STROKE VOLUME
PRELOAD
CONTRACTILITY
CARDIAC OUTPUT
HEART RATE
- Synergistic LV contraction - LV wall integrity - Valvular competence
AFTERLOAD
Frank-Starling Law
NormalCompensated
CHF
Normal C.O.
LVEDP
Cardi
ac O
utput
The Pathophysiology of Heart Failure
Hurst. The Heart. Diagnosis and Management of Heart Failure.10th ed. 688
Pathophysiological Sequence of CHF
Heart Failure
Inadequate Cardiac Output
( ) O2 Delivery (rest and/or exercise)
Systemic Vasoconstriction
SAS (NE)) RAAS (A-II)() Flow to Skin, Gut, and Renal Circulations
Activation ofRAS and ANS
Neurohormonal Activation
Hurst. The Heart. Diagnosis and Management of Heart Failure.10 th ed. 688
SNS
Renin release
Angiotensin II
VasoconstrictionGrowth factors
Hypertrophy Apoptosis
ALDO
Fluid accumulationCollagen depositionMyofibril necrosis
Preload Afterload
RBF
Renin release
Angiotensin II
Vasoconstriction
Growth factors
Hypertrophy Apoptosis
ALDO
Collagen depositionMyofibril necrosis
Perfusion of Vital Organs
Na filtered
Afterload
Fluid accumulation
Sympathetic nervous system up-regulation
IncreasedNorepinephrine levels
DirectMyocardial toxicity
Myocyte dysfunction
Myocytenecrosis
IntracellularCa2+ overload/
Energy depletion
Apoptosis
DecreasedRenal blood
flow
Activation of theRAA system
Increased HR, PVR & arteriolar vasoconstriction
Increased myocardialoxygen demand
IncreasedAngiotensin II &
Aldosteron
Na+ & water retention
Vasoconstriction Cardiac remodeling
Cesario et.al; Reviews in cardiovascular medicine, vol 3, no.1, 2002
Causes of Heart Failure
• Myocardial Damage or Disease– Infarction (Acute) / Ischemia– Myocarditis– Hypertrophic Cardiomyopathy
• Excess Load on Ventricle– Volume/ Pressure Overload
• Resistance to Flow into Ventricle• Cardiac Arrhythmias
MI-INDUCED HEART FAILUREMyocardial Damage
Contractility
Pump Performance
SAS DriveVasoconstriction
Systolic Work Load
RAAS SYSTEMFLUID RETENTION
Diagnosis of C H F
IDENTIFICATIONS OF HF PATIENTS
With a Syndrome of Decrease Exercise Tolerance
With a Syndrome of Fluid Retention With No Symptoms or Symptoms of
Another Cardiac or Non Cardiac Disorder
(MI, Arrythmias, Pulmonary or Systemic Thromboembolic Events)
SYMPTOMS AND SIGN
Breathlessness, Ankle Swelling, Fatique→ Characteristic Symptoms
Peripheral Oedema, JVP ↑, Hepatomegaly→ Signs of Congestion of Systemic Veins
S3 , Pulmonary Rales , Cardiac Murmur
E C G A low Predictive Value LAH and LVH May Be Associated wit LV Dysfunction Anterior Q-wave and LBBB a good predictors of EF ↓↓ Detecting Arrhytmias as Causative of HF
CHEST X-RAY
A Part of Initial Diagnosis of HFA Part of Initial Diagnosis of HF→ → Cardiomegaly, Pulmonary CongestionCardiomegaly, Pulmonary Congestion
Relationship Between Radiological Signs andRelationship Between Radiological Signs and Haemodynamic Findings may Depend on the Haemodynamic Findings may Depend on the DurationDuration and Severity HFand Severity HF
HAEMATOLOGY & BIOCHEMISTRY• A Part of Routine Diagnostic
Hb, Leucocyte, Platelets Electrolytes, Creatinine, Glucose, Hepatic
Enzyme, Urinalysis TSH, C-RP, Uric Acid
ECHOCARDIOGRAPHY The Preferred MethodsThe Preferred Methods Helpful in Determining the AetiologyHelpful in Determining the Aetiology Follow Up of Patients Heart FailureFollow Up of Patients Heart Failure
INVASIVE INVESTIGATION
• Elucidating the Cause and Prognostic Informations
Coronary Angiography : in CAD’s Patients
Haemodynamic Monitoring : To Assess Diagnostic and Treatment of HF
Endomyocardial Biopsy : in Patients with Unexplained HF
NATRIURETIC PEPTIDES
• Cardiac Function ↓↓ (LV Function ↓↓) → ↑↑ Plasma Natriuretic Peptide
Concentration (Diagnostic Blood Use for HF)
• Natriuretic Peptide ↑↑ : Greatest Risk of CV EventsNatriuretic Peptide ↓↓ : Improve Outcome in Patients with
Treatment
• Identify Pts. With Asymptomatic LV Dysfunction (MI, CAD)
Suspected Heart Failure Suspected Heart Failure Because of symptoms and Because of symptoms and
signssigns
Assess Presence of Cardiac Disease by ECG, Assess Presence of Cardiac Disease by ECG, X-Ray or NatriureticPeptides (Where X-Ray or NatriureticPeptides (Where
Available)Available)
Imaging by Echocardiography Imaging by Echocardiography (Nuclear Angiography or MRI Where (Nuclear Angiography or MRI Where
Available)Available)
Assess Etiology, Degree, Precipitating Assess Etiology, Degree, Precipitating Factors and Type of Cardiac Factors and Type of Cardiac
DysfunctionDysfunction
Tests AbnormalTests Abnormal
Tests AbnormalTests Abnormal
Choose TherapyChoose Therapy
ALGORITHM FOR THE DIAGNOSIS OF THE HFALGORITHM FOR THE DIAGNOSIS OF THE HF
If NormalIf NormalHeart FailureHeart Failure
UnlikelyUnlikely
Additional Diagnosis Tests Additional Diagnosis Tests Where Appropriate (e.g. Where Appropriate (e.g. Coronary Angiography)Coronary Angiography)
If NormalIf NormalHeart Failure Heart Failure
UnlikelyUnlikely
(ESC, 2001)(ESC, 2001)
Treatment of C H F
Aims of Treatment
1. Preventiona) Prevention and/or controlling of diseases leading
to cardiac dysfunction and heart failure b) Prevention of progression to heart failure once
cardiac dysfunction is established
2. Morbidity Maintenance or improvement in quality of life
3. Mortality Increased duration of life
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
Management Outline
• Establish that the patient has HF.• Ascertain presenting features: pulmonary oedema, exertional
breathlessness, fatigue, peripheral oedema• Assess severity of symptoms• Determine aetiology of heart failure• Identify precipitating and exacerbating factors• Identify concomitant diseases• Estimate prognosis• Anticipate complications• Counsel patient and relatives• Choose appropriate management• Monitor progress and manage accordingly
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
TREATMENT
Correction of aggravating factors
MEDICATIONS
EndocarditisObesityHypertensionPhysical activityDietary excess
PregnancyArrhythmias (AF)InfectionsHyperthyroidismThromboembolism
Treatment options • Non-pharmacological management
– General advice and measures– Exercise and exercise training
• Pharmacological therapy– Angiotensin-converting enzyme (ACE) inhibitors– Diuretics– Beta-adrenoceptor antagonists– Aldosterone receptor antagonists– Angiotensin receptor antagonists– Cardiac glycosides– Vasodilator agents (nitrates/hydralazine)– Positive inotropic agents– Anticoagulation– Antiarrhythmic agents– Oxygen
• Devices and surgery– Revascularization (catheter interventions and surgery), other forms of
surgery– Pacemakers– Implantable cardioverter defibrillators (ICD)– Heart transplantation, ventricular assist devices, artificial heart– Ultrafiltration, haemodialysis
Guidelines for the diagnosis and treatment of chronic heart failureEuropean Heart Journal (2001) 22, 1527-1560
ACC/AHA & EUROPE (ESC) 2001GUIDELINES FOR THE MANAGEMENT
OF HEART FAILURE
ACE-inhibitor
→ Use as first line therapy
→ Should be up titrated to the dosages shown in the large
clinical trial, and not titrated based on symptomatic
improvement DIURETIC → to control fluid overload Β-BLOCKER
→ For all patients with stable mild-severe HF on standard treatment
ACC/AHA & EUROPE (ESC) 2001GUIDELINES FOR THE MANAGEMENT
OF HEART FAILURE
Aldosteron Receptor Antagonis
→ in advance HF ( NYHA III-IV ) DIGOXIN
→ in AF
→ May be added for symptom relief ARB
→ Considered in patients not tolerate ACE inhibitors and not on β - blocker
TREATMENT
NormalAsymptomaticLV dysfunctionEF <40%
Symptomatic CHFNYHA II
InotropesSpecialized therapyTransplant
Symptomatic CHFNYHA - IV
Symptomatic CHFNYHA - III
Secondary preventionModification of physical activity
ACEI Diuretics mildNeurohormonal inhibitors Digoxin?
Loop Diuretics
Pharmacological therapy
Stage A Stage B Stage C Stage D
Pts with :• Hypertension• CAD• DM• Cardiotoxins• FHx CM
THERAPY• Treat Hypertension• Stop smoking • Treat lipid disorders• Encourage regular
exercise• Stop alcohol
& drug use• ACE inhibition
Pts with :• Previous MI• LV systolic
dysfunction• Asymptomatic
Valvular disease
THERAPY• All measures under
stage A• ACE inhibitor • Beta-blockers
THERAPY• All measures under
stage A• Drugs for routine use:
• diuretic• ACE inhibitor• Beta-blockers• digitalis
THERAPY• All measures under
stage A,B and C• Mechanical assist
device• Heart transplantation• Continuous IV
inotrphic infusions for palliation
Pts who have marked symptoms at rest despite maximal medical therapy.
Pts with :
• Struct. HD
• Shortness of breath and fatigue, reduce exercise tolerance
Struct.Heart Disease
DevelopSymp.of
HF
Refract. Symp.of HF at rest
Stages in the evolution of HF and recommended therapy by stage
ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult 2001
1. ACE INHIBITOR
Angiotensin-converting enzyme inhibitors
• Recommended as first-line therapy.
• Should be uptitrated to the dosages shown to be effective in the large, controlled trials, and not titrated based on symptomatic improvement.
• Moderate renal insufficiency and a relatively low blood pressure (serum creatinine 250 µmol.l-1 and systolic BP 90 mmHg) are not contraindications.
• Absolute contraindications: bilateral renal artery stenosis and angioedema.
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
VASOCONSTRICTION VASODILATATION
Kininogen
Kallikrein
Inactive Fragments
Angiotensinogen
Angiotensin IRENIN
Kininase IIInhibitor
ALDOSTERONE
SYMPATHETICVASOPRESSIN
PROSTAGLANDINStPA
ANGIOTENSIN II
BRADYKININ
ACEI
MECHANISM OF ACTION
A.C.E.
ACEI
UNDESIRABLE EFFECTSInherent in their mechanism of action
- Hypotension- Hyperkalemia- Angioneurotic edema
Due to their chemical structure- Cutaneous eruptions- Neutropenia,
thrombocytopenia- Digestive upset
- Dry cough- Renal Insuff.
- Dysgeusia- Proteinuria
ACEI
CONTRAINDICATIONS
Renal artery stenosisRenal insufficiencyHyperkalemiaArterial hypotensionIntolerance (due to side effects)
ACE-Inhibitors in Asymptomatic Heart Failure
Development of symptomatic HF Hospitalization of HF
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560SAVE & TRACE StudySAVE & TRACE Study
ACE-Inhibitors in Symptomatic Heart Failure
• All patients symptomatic Heart Failure should receive ACE-I.
A) No fluid retention, ACE-I should be given first.
B) With fluid retention, ACE-I + Diuretic
• ACE-I : A) improves survival and symptoms.
B) reduces hospitalization.Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
2. DIURETICS
Diuretics
• Essential for symptomatic treatment when
fluid overload is present and manifest.
• Always be administered in combination
with ACE inhibitors if possible.
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
Cortex
Medulla
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
Loop diuretics Inhibit exchange of Cl-Na-K in
the thick segment of the ascending loop of Henle
Loop of HenleCollecting tubule
DIURETICS
THIAZIDES
MECHANISM OF ACTIONExcrete 5 - 10% of filtered Na+
Elimination of KInhibit carbonic anhydrase: increase elimination of HCO3
Excretion of uric acid, Ca and MgNo dose - effect relationship
LOOP DIURETICS
MECHANISM OF ACTIONExcrete 15 - 20% of filtered Na+
Elimination of K+, Ca+ and Mg++
Resistance of afferent arterioles-Cortical flow and GFR- Release renal PGs- NSAIDs may antagonize diuresis
K-SPARING DIURETICS
MECHANISM OF ACTION
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
3. ALDOSTERONE INHIBITORS
ALDOSTERONE
Retention Na+
Retention H2O
Excretion K+
Excretion Mg2+
Collagen deposition
Fibrosis - myocardium
- vessels
Spironolactone
Edema
Arrhythmias
Competitive antagonist of thealdosterone receptor(myocardium, arterial walls, kidney)
ALDOSTERONE INHIBITORS
ALDOSTERONE INHIBITORS
INDICATIONSFOR DIURETIC EFFECT• Pulmonary congestion (dyspnea)• Systemic congestion (edema)
FOR ELECTROLYTE EFFECTS• Hypo K+, Hypo Mg+
• Arrhythmias• Better than K+ supplementsFOR NEUROHORMONAL EFFECTS• Please see RALES results,
N Engl J Med 1999:341:709-717
• Recommended in advanced HF (NYHA III-IV),
in addition to ACE inhibition and diuretics to
improve survival and morbidity
Aldosterone receptor antagonists - spironolactone
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
4. ß-Blockers Start Low Go Slow
Activation and Blockade of Neurohumoral System in CHF
RAA System SNS System
Angiotensin II Noradrenalin
Hypertrophy, apoptosis, ischaemia, arrhytmia, remodeling, fibrosis
β-BlockerACE-I
ADRENERGIC ACTIVATION↑ CNS Sympathetic
Outflow
↑ Sympathetic activity to kidneys & blood vessels
↑ Cardiac Sympathetic activity
β1-receptors β2-receptors 1-receptors
Mycocyte hypertrophy & death, dilatation, ischaemia & arrhytmia’s
Vasoconstriction Sodium Retention
Packer, AHA 2000
Benefits of “Add-on” β-BlockerShort-term :
1. Improvement of symptoms (LVEF ↑)
2. Improvement of NYHA class
3. Improvement of daily activities
4.Reduction of hospitalization rate & length of hospital stay (financial & psychological burden)
Long-term :
1.Slowing the progression of CHF
2. Increase of survival rate
• Recommended for the treatment of all pts with stable, mild, moderate and severe heart failure on standard treatment, unless there is a contraindication.
• Patients with LV systolic dysfunction, with or without symptomatic HF, following an AMI long-term betablockade is recommended in addition to ACE inhibitor.
Beta-adrenoceptor antagonists
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
THE RECOMMENDED PROCEDURE FOR STARTING β-BLOCKER
1. Patient should be on standard therapy
(ACE inhibitor +/- diuretic)
2. Patient in stable conditions No iv inotropic therapy Without signs of marked fluid retention
3. Start initial low doses and titrate to maintenance dose
(the dose may be doubled every 1 – 2 weeks)
(ESC.Guidelines for HF, 2001)
DOSES OF β-BLOCKER
β BLOCKER FIRST DOSE TARGET DOSE TITRATION PERIOD
Bisoprolol 1.25 mg 10 mg Weeks – Month
Metoprolol Tartrate
5 mg 150 mg Weeks – Month
Metoprolol Succinate
12.5 mg 200 mg Weeks – Month
Carvedilol 2 x 3.125 mg 2 x 25 mg Weeks – Month
(European Heart Journal, vol. 22, Sept. 2001)
CONTRAINDICATIONS OF
β-BLOCKER IN PATIENT H F
Asthma Bronchial Severe Bronchial Desease Symptomatic Bradycardia and
Hypotension
INTOLERANCE OF β-BLOCKER
Symptomatic Bradycardia
Worsening HF Hypotension
5. Angiotensin II receptor antagonists
ANGIOTENSIN II INHIBITORS
MECHANISM OF ACTIONRENIN
Angiotensinogen Angiotensin I
ANGIOTENSIN II
ACEOther paths
Vasoconstriction Proliferative Action
Vasodilatation Antiproliferative Action
AT1 AT2
AT1 RECEPTOR BLOCKERS
RECEPTORS
AT1 RECEPTOR BLOCKERS
DRUGS
LosartanValsartanIrbersartanCandesartan
Competitive and selective blocking of AT1 receptors
• ARBs could be considered in patients who do not tolerate ACE inhibitors for symptomatic treatment.
• It is unclear whether ARBs are as effective as ACE inhibitors for mortality reduction.
• In combination with ACE inhibition, ARBs may improve heart failure symptoms and reduce hospitalizations for worsening heart failure.
Angiotensin II receptor antagonists
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
6. Cardiac glycosides
Na+
K+
K+
Na+
Na+ Ca++
Ca++
Na-K ATPase Na-Ca Exchange
Myofilaments
DIGOXIN
CONTRACTILITY
DIGOXIN
DIGITALIZATION STRATEGIES
(mg)
0.125-0.5 / d
0.25 / d
i.v
0.5 + 0.25 / 4 h
ILD: 0.75-1
oral 12-24 h
0.75 + 0.25 / 6 h
1.25-1.5
oral 2-5 d
0.25 / 6-12 h
1.5-1.75
Loading dose (mg) Maintenance Dose
ILD = average INITIAL dose required for digoxin loading
DIGOXIN
HEMODYNAMIC EFFECTSCardiac outputLVejection fractionLVEDPExercisetolerance
NatriuresisNeurohormonalactivation
DIGOXIN
NEUROHORMONAL EFFECTS
Plasma Noradrenaline Peripheral nervous system activity RAAS activity Vagal tone
Normalizes arterial baroreceptors
DIGOXIN
CLINICAL USES
AF with rapid ventricular response
CHF refractory to other drugs
Other indications?
Can be combined with other drugs
DIGOXIN
CONTRAINDICATIONSABSOLUTE:
- Digoxin toxicity
RELATIVE- Advanced A-V block without pacemaker- Bradycardia or sick sinus without PM- PVC’s and TV- Marked hypokalemia- W-P-W with atrial fibrillation
DIGOXIN TOXICITY
CARDIAC MANIFESTATIONS
ARRHYTHMIAS :- Ventricular (PVCs, TV, VF)- Supraventricular (PACs, SVT)
BLOCKS:- S-A and A-V blocks
CHF EXACERBATION
DIGOXIN TOXICITY
EXTRACARDIAC MANIFESTATIONSGASTROINTESTINAL:
- Nausea, vomiting, diarrhea
NERVOUS:- Depression, disorientation, paresthesias
VISUAL:- Blurred vision, scotomas and yellow-green vision
HYPERESTROGENISM:- Gynecomastia, galactorrhea
• indicated in atrial fibrillation and any degree of symptomatic heart failure.
• A combination of digoxin and beta-blockade appears superior than either agent alone.
• In sinus rhythm, digoxin is recommended to improve the clinical status of patients with persisting heart failure despite ACE inhibitor and diuretic treatment.
Cardiac glycosides
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
7. Vasodilator agents
• No specific role for vasodilators in the treatment of HF• Used as adjunctive therapy for angina or concomitant
hypertension.
• In case of intolerance to ACE inhibitors ARBs are preferred to the combination hydralazine–nitrates.
• HYDRALAZINE-ISOSORBIDE DINITRATE
– Hydralazine (up to 300 mg) in combination with ISDN (up to 160 mg) without ACE inhibition may have some beneficial effect on mortality, but not on hospitalization for HF.
– Nitrates may be used for the treatment of concomitant angina or relief of acute dyspnoea.
Vasodilator agents in chronic heart failure
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
8. Positive inotropic therapy
CARDIAC GLYCOSIDES
SYMPATHOMIMETICSCatecholaminesß-adrenergic agonists
PHOSPHODIESTERASE INHIBITORS Amrinone Enoximone
Others
MilrinonePiroximone
POSITIVE INOTROPES
DOPAMINE AND DOBUTAMINE
EFFECTS
ReceptorsContractilityHeart RateArterial Press.Renal perfusionArrhythmia
DA (µg / Kg / min) Dobutamine< 2
DA1 / DA2
±±±
++-
2 - 5ß1
+++++±
> 5ß1 +
++++++±
++
ß1
++±
+++±
POSITIVE INOTROPES
CONCLUSIONS
May increase mortality
Safer in lower doses
Use only in refractory CHF
NOT for use as chronic therapy
10. Anticoagulation 11. Antiplatelet Drugs
ANTICOAGULANTS
PREVIOUS EMBOLIC EPISODEATRIAL FIBRILLATIONIdentified thrombusLV Aneurysm (3-6 mo post MI)Class III-IV in the presence of:
- EF < 30- Aneurysm or very dilated LV
PhlebitisProlonged bed rest
Recommendation
1. All pts with HF and AF should be treated with warfarin unless contraindicated.
2. Patients with LVEF 35% or less.
Anticoagulation
HFSA Guidelines for Management of Patients With Heart Failure Caused by Left
Ventricular Systolic Dysfunction - Pharmacological Approaches 2000
Chronic heart failure — choice of pharmacological therapy
LV systolic dysfunction ACE inhibitor Diuretic Beta-blockerAldosteroneAntagonist
Asymptomatic LV dysfunction Indicated Not indicated Post MI Not indicated
Symptomatic HF (NYHA II) IndicatedIndicated if
Fluid retentionIndicated Not indicated
Worsening HF (NYHA III-IV) IndicatedIndicated
comb. diureticIndicated
Indicated
End-stage HF (NYHA IV) IndicatedIndicated
comb. diureticIndicated
Indicated
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
A
Chronic heart failure — choice of pharmacological therapy
LV systolic dysfunctionAngiotensinII receptor
antagonistsCardiac glycosides
Vasodilator (hydralazine/ isosorbide dinitrate)
Potassium -sparing diuretic
Asymptomatic LV dysfunction Not indicated With AF Not indicated Not indicated
Symptomatic HF (NYHA II)
If ACE inhibitors are not tolerated and not on beta-
blockade
(a) when AF (b) when improved
from more severe HF in sinus rhythm
If ACE inhibitors and angiotensin II
antagonists are not tolerated
If persisting hypokalaemia
Worsening HF (NYHA III-IV)
If ACE inhibitors are not tolerated and not on beta-
blockade
indicated
If ACE inhibitors and angiotensin II
antagonists are not tolerated
If persisting hypokalaemia
End-stage HF (NYHA IV)If ACE inhibitors are not tolerated and not on beta-
blockade
indicated
If ACE inhibitors and angiotensin II
antagonists are not tolerated
If persisting hypokalaemia
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
B
Intervention
• Pts with heart failure of ischaemic origin revascularization symtomatic improvement.
• A strong negative correlation of operative mortality and LVEF, a low LVEF (<25%) was associated with increased operative mortality. Advance HF symptoms (NYHA IV) resulted in a greater mortality rate.
• Off pump coronary revascularization may lower the surgical risk for HF.
• Heart Transplantation is an accepted mode of treatment for end-stage HF.
RevascularizationSurgical
Non Surgical
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
Care and Follow-upRecommended components of programs
• use a team approach• vigilant follow-up, first follow-up within 10 days of
discharge • discharge planning • increased access to health care • optimizing medical therapy with guidelines • intense education and counselling inpatient and outpatient • strategies address barriers to compliance • early attention to signs and symptoms• flexible diuretic regimen
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
Future treatmentFuture treatment
1.1. Sympathetic nervous systemSympathetic nervous system2.2. The RAA systemThe RAA system3.3. Atrial and brain natriuretic peptidesAtrial and brain natriuretic peptides4.4. Arginin vasopressinArginin vasopressin5.5. EndothelinEndothelin6.6. Growth hormoneGrowth hormone7.7. Calcitonin gene related peptide Calcitonin gene related peptide
Neurohormonal modulationNeurohormonal modulation
Cardiac reparation: fixing the heart Cardiac reparation: fixing the heart with cells, new vessels and genes (1)with cells, new vessels and genes (1)
1.1. Multiplication of residual myocytes Multiplication of residual myocytes (forcing the cells to enter mytotic cycle)(forcing the cells to enter mytotic cycle)
2.2. Transforming fibrablasts in the scarTransforming fibrablasts in the scar3.3. Implanting exogenous contractiles cells Implanting exogenous contractiles cells
(foetal cardiomyocites, skeletal (foetal cardiomyocites, skeletal myoblasts, stem cells)myoblasts, stem cells)
Aims: to repopulate fibrous scars with new Aims: to repopulate fibrous scars with new contractile cellscontractile cells
Cell based Cell based interventionsinterventions
Eur Heart JEur Heart J 2002;4: D73-81 2002;4: D73-81
CON’T (2)CON’T (2)
1. Administration of angiogenic growth factors VEGF, basic FGF
2. Problems: nature of compound , dose, route, and adverse events (abnormal blood vessels, proliferative retinopathy, etc)
AngiogenesisAngiogenesisAimsAims:: to provides new blood supply to to provides new blood supply to
the diseased heartthe diseased heart
Eur Heart JEur Heart J 2002;4: D73-81 2002;4: D73-81
CON’T(3)CON’T(3)
1.1. Gene manipulation of 3 majors areas: Ca Gene manipulation of 3 majors areas: Ca handling, beta-adenergic signalling and handling, beta-adenergic signalling and apoptosisapoptosis
2.2. Inducing expression of silent genesInducing expression of silent genes
Gene therapyGene therapyAims: to improve the function of the failing Aims: to improve the function of the failing
heartheart
Safety problemsSafety problems:: control of targeted protein control of targeted protein expression, inflammation, autoimmunity expression, inflammation, autoimmunity and oncogenesis (basically irreversible)and oncogenesis (basically irreversible)
Eur Heart JEur Heart J 2002;4: D73-81 2002;4: D73-81
Dual-chamber pacemakers are Dual-chamber pacemakers are beneficial beneficial
• Drug-resistant CHFDrug-resistant CHF• Intact sinus rhythmIntact sinus rhythm• Absence of chronic atrial dysrhythmiasAbsence of chronic atrial dysrhythmias• EF <20%EF <20%• Viable myocardiumViable myocardium• No or stable anginaNo or stable angina• DMC and PR >, MR and TR, QRS >, QRS PR + DMC and PR >, MR and TR, QRS >, QRS PR +
QRS > 350 ms.QRS > 350 ms.• QRS >140 ms, MR > 450 ms, and LV filling time QRS >140 ms, MR > 450 ms, and LV filling time
<200 ms<200 ms• HOCMHOCM
ResumePharmacological Treatment :
I. Asymptomatic Systolic LV dysfunction :• ACE Inhibitor -Blocker (in CAD)
II. Symptomatic Systolic LV dysfunctionA. No fluid retention
ACE Inhibitor-BlockerIf ischaemia (+) nitrate / revascularization
B. Fluid retentionDiureticACE Inhibitor (ARBs if not tolerated)-Blocker± Digitalis
ResumeIII. Worsening HF
– Standard treatment : ACE Inhibitor, -Blocker – Diuretic : doses + loop diuretic– Low dose spironolactone– Digitalis– Consider :
» Revascularization» Valve surgery» Heart transplant
IV. End-stage HF– Intermittent inotrophic support– Circulatory support (IABP, Ventr.Assist Devices)– Haemofiltration on dialysis
briddging to heart transplantation
Conclusion
• Management of HF must be starting from the earlier stage (AHA/ACC stage A). Treatment at each stage can reduce morbidity and mortality.
• Before initiating therapy :– Established the correct diagnose.– Consider management outline.
Conclusion• Non pharmacolgical intervention are helpfull in :
– improving quality of life– reducing readmission– lowering cost.
• Organize multi-disciplinary care :– HF clinic, HF nurse specialist, pts telemonitoring.– Health care system.
• To optimize HF management – Treatment should be according to the Guidelines,
intensive education, and behavioral change efforts.
Thank YoU
DIASTOLIC HEART FAILURE
SCOPE OF THE PROBLEM• Epidemiological studies of HF have
suggested that 30-50% of cases of HF have preserved LV systolic function.
• DHF has mortality rate equal as systolic heart failure
• No guideline yet regarding the treatment of DHF
Greenberg & Hermann 2004
Defining Diastolic Heart FailureDefining Diastolic Heart Failure
• Diastolic dysfunction refers to a condition in which abnormalities in mechanical function are presenting during diastole.• Diastolic dysfunction is a condition in which higher than normal LV filling pressure are needed to maintain a normal cardiac output.• Diastolic heart failure is a clinical syndrome characterized by the symptoms and signs of heart failure, a preserved EF and abnormal diastolic function.
(Vasan & Levy 2000)
(Mandinov,Eberli,Seiler,Hess.Cardiosvasc Res 2000)
Other Methods in diagnosing DHF
• Plasma Brain Natriuretic Peptide• Doppler tissue imaging • Magnetic resonance imaging • Radionuclide angiography • Cardiac catheterization
Greenberg & Hermann 2004
Treatment of Diastolic Heart Failure
• Clinical investigations in relatively small groups of patients
• Clinical experience• Concepts based on pathophysiology
mechanisms
The guidelines are based on :
Treatment of Diastolic Heart failureTreatment of Diastolic Heart failure
• symptom targeted treatment
• disease / pathological targeted treatment
• the underlying mechanism targeted
treatment
( Zile & Brutsaert, 2002 )
Diastolic Heart Failure: TreatmentDiastolic Heart Failure: Treatment
Symptom targeted treatment
Decrease pulmonary venous pressure
Reduce LV volume
Maintain atrial contraction
Prevent tachycardia
Improve exercise tolerance
Use positive inotropic agents with caution
( Zile & Brutsaert, 2002 )
Diastolic Heart Failure: Treatment
Nonpharmacological treatmentRestrict sodium to prevent volume overloadRestrict fluid to prevent volume overloadPerform moderate aerobic exercise to improve cardiovascular conditioning, decrease heart rate and maintain skeletal muscle functionPharmacological treatmentDiuretics including loop diuretics thiazides, spironolactoneLong-acting nitrates, -Adrenergic blockersCalcium channel blockersRenin angiotensin-aldosterone antagonists including ACE inhibitors, angiotensin II receptor blockers and aldosterone antagonists
Symptom targeted treatment
( Zile & Brutsaert, 2002 )
Disease-targeted treatment
Prevent/treat myocardial ischemia
Prevent/regress ventricular hypertrophy
Mechanisms targeted treatment
Modify myocardial and extramyocardial mechanisms
Modify intracellular and extracellular mechanisms
An ideal therapeutic agent.
- Should target the underlying mechanisms
- Improve calcium homeostasis and energetics
- Blunt neurohumoral activation
- Prevent and regress fibrosis
Diastolic Heart FailureDiastolic Heart Failure
( Zile & Brutsaert, 2002 )