Gagal Jantung

Dr.Pramudjo Abdulgani,Sp.JP,FIHA

Pekanbaru

Pendahuluan
Gagal jantung : Sindroma klinis akibat jantung tidak mampu memompakan darah untuk mempertahankan kebutuhan metabo lisme jaringan atau mampu memenuhi rnetabolisme jaringan tetapi pada tekanan pengisian yang meningkat.

Definition of Heart Failure

HF is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.

Heart Failure vs. Congestive Heart Failure

Because not all patients have volume overload at the time of initial or subsequent evaluation, the term heart failure is preferred over the older term congestive heart failure.

HF Incidence and Prevalence

Prevalence
Worldwide, 22 million1 United States, 5 million2

Incidence
Worldwide, 2 million new cases annually1 United States, 500,000 new cases annually2

HF afflicts 10 out of every 1,000 over age 65 in the U.S.2

1 World Health Statistics, World Health Organization, 1995. 2 American Heart Association, 2002 Heart and Stroke Statistical Update.

Evolution of the Concept of Heart Failure 1950 to 2000

Aetiology Hypertension Valvular heart dis Slowly progressive

1950

CHD Hypertension Dilated CMP Slowly progressive or unpredictable and rapid ( coronary event )

2000

Natural Course (remodeling) Understanding Common cause of death Arrhythmia Treatment goal

Hemodynamic model Neurohormonal model Pulmonary infection Sudden death Pump failure Atrial Control edema Ventricular Improve quality of life + reduce mortality + reduce hospitalization

New York Heart Association Functional Classification

Class I: Class II: No symptoms with ordinary activity Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, dyspnea, or angina Marked limitation of physical activity. Comfortable at rest, but less than ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency may be present even at rest

Class III:

Class IV:

HF Classification: Evolution and Disease Progression

Four Stages of HF (ACC/AHA Guidelines):
Stage A: Patient at high risk for developing HF with no structural disorder of the heart Stage B: Patient with structural disorder without symptoms of HF Stage C: Patient with past or current symptoms of HF associated with underlying structural heart disease Stage D: Patient with end-stage disease who requires specialized treatment strategies

Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001

Stages of Heart Failure

At Risk for Heart Failure:

STAGE A High risk for developing HF STAGE B Asymptomatic LV dysfunction Heart Failure: STAGE C Past or current symptoms of HF STAGE D End-stage HF

Stages of Heart Failure

Designed to emphasize preventability of HF Designed to recognize the progressive nature of LV dysfunction

Stages of Heart Failure

COMPLEMENT, DO NOT REPLACE NYHA CLASSES
NYHA Classes - shift back/forth in individual patient (in response to Rx and/or progression of disease)

Stages - progress in one direction due to cardiac remodeling

Etiology of Heart Failure

What 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

Pathophysiology of Acute Heart Failure: Determinants of stroke volume:

Contractility Preload Afterload Note that the failing heart is more afterload sensitive than normal hearts

Pathomechanisms

CO = SV HR
1. 2. 3. Preload After load contractility

1. Systolic Dysfunction

3. Arrythmias
SA 4. Dyssynchrony
Atrio-ventricular
Inter-ventricular Intra-ventricular

2. Diastolic Dysfunction

5. High out put cardiac failure

The Cardiovascular Circulation: Right and Left Heart Failure:

SVC Pulmonary Artery Lungs Pulmonary Vein LV

RA

RV

LA

IV C
Aorta

Acute Left Heart Failure:

Relative Preservation of RV Function Compared to LV function, and Sympathetic Activation Increased Preload and Afterload
Due to systolic or diastolic dysfunction of LV, or mitral or aortic valve stenosis or regurgitation, malignant hypertension
LV EDP

Lungs
Pulmonary Venous Pressure

LA

LA

LV

Pulmonary Edema

Aorta

Afterload
(sympathetic activation)

CHF
Its a hemodynamic disease !
Afterload

Preload

Contractility

CHF
What is diastolic dysfunction?

Myocardial Dysfunction

Systolic Dysfunction

Diastolic

Left ventricle has reduced muscle contractility

Decreased left ventricular filling Caused by ventricular stiffness, decreased rate of relaxation, or rapid heart rate

CHF

Dilated

Normal

Hypertrophic

Types of Heart Failure

include left, right or both sides left ventricular heart failure

most common
systolic failure: unable to contract diastolic failure: unable to relax right ventricular heart failure usually occurs after left failure

less blood received causes right damage

less pumping by right side venous pooling of blood in legs

Kriteria Gagal Jantung menurut Framingham Heart Study (1) Kriteria Mayor

Paroxysmal Nocturnal Dyspnoe Dyspnoe On Effort Peningkatan Tekanan Vena Jugularis Ronkhi paru Kardiomegali Udema paru akut Gallop S3 Pemanjangan waktu sirkulasi (>25 detik) Refluks hepato jugular

Kriteria Gagal Jantung menurut Framingham Heart Study (2) Kriteria minor

Udema pergelangan kaki Batuk malam Hepatomegali Efusi Pleura Takikardia (> 120 x / menit) Penurunan kapasitas vital paru (1/3 dan maksimal) Penurunan berat badan lebih dari 4,5 kg selama 5 hari perawatan.

Kriteria mayor atau minor

Disebut gagal jantung kongestif bila memenuhi 2 kriteria mayor atau 1 mayor dengan 2 minor.

Kriteria Gagal Jantung menurut Framingham Heart Study (3)

Sensitivity (%)

Specificity (%)

Positive* predictive value (%)

23 2 26 22

Symptom
Dyspnoea Orthopnoea Paroxysmal nocturnal dyspnoea History of oedema 66 21 33 23 52 81 76 80

Sign
Heart rate>100/minute at rest Pulmonary crackles Oedema by examination Third heart sound Jugular venous distension 7 13 10 31 10 99 91 93 95 97 8 27 3 61 2

*proportion of patients in whom heart failure was correctly diagnosed

Sensitivity (%)

Specificity (%)

Positive* predictive value (%)

23 2 26 22

Symptom
Dyspnoea Orthopnoea Paroxysmal nocturnal dyspnoea History of oedema 66 21 33 23 52 81 76 80

Sign
Heart rate>100/minute at rest Pulmonary crackles Oedema by examination Third heart sound Jugular venous distension 7 13 10 31 10 99 91 93 95 97 8 27 3 61 2

*proportion of patients in whom heart failure was correctly diagnosed

Tujuan pengobatan
Jangka pendek :
menghilangkan keluhan dan gejala klinik

Jangka panjang :
memperbaiki kualitas hidup dan masa harapan hidup mengurangi kekerapan masuk rumah sakit mencegah kematian dengan mencegah perbu rukan fungsi ventrikel.

TREATMENT OBJECTIVES Survival Morbidity Exercise capacity Quality of life Neurohormonal changes Progression of CHF Symptoms

GAGAL JANTUNG AKUT

Secara klinis dibagi dalam 3 kelompok yaitu: 1. udema paru akut kardiogenik 2. syok kardiogenik 3. dekompensasi akut pada gagal jantung kronik

diagnostik dini
1.Riwayat penyakit dan pemeriksaan fisik 2.EKG 12 sandapan & monitoring EKG 3.Pemeriksaan darah: rutin, elektrolit, ureaN, kreatinin dan enzim jantung 4.Pulse oximetry/analisa gas darah 5.Rontgen dada 6.Ekokardiografi transtoraks

The Donkey Analogy

Ventricular dysfunction limits a patient's ability to perform the routine activities of daily living

Left Ventricular Dysfunction

Systolic: Impaired contractility/ejection
Approximately two-thirds of heart failure patients have systolic dysfunction1

Diastolic: Impaired filling/relaxation

30%
(EF > 40 %) (EF < 40%)

70%

Diastolic Dysfunction Systolic Dysfunction

1 Lilly, L. Pathophysiology of Heart Disease. Second Edition p 200

Cardiac Output
Cardiac output is the amount of blood that the ventricle ejects per minute

Cardiac Output = HR x SV

Determinants of Ventricular Function

Contractility Preload Afterload

Stroke Volume
Synergistic LV Contraction Wall Integrity Valvular Competence

Heart Rate Cardiac Output

Hemodynamic Basis for Heart Failure Symptoms

Left Ventricular Dysfunction Systolic and Diastolic

Symptoms
Dyspnea on Exertion

Physical Signs
Basilar Rales

Paroxysmal Nocturnal Dyspnea

Tachycardia

Pulmonary Edema
S3 Gallop Pleural Effusion

Cough
Hemoptysis

Cheyne-Stokes Respiration

Right Ventricular Failure Systolic and Diastolic

Symptoms
Abdominal Pain

Physical Signs
Peripheral Edema

Anorexia
Nausea Bloating

Jugular Venous Distention

Abdominal-Jugular Reflux Hepatomegaly

Swelling

Compensatory Mechanisms
Frank-Starling Mechanism Neurohormonal Activation Ventricular Remodeling

Compensatory Mechanisms
Frank-Starling Mechanism
a. At rest, no HF

b. HF due to LV systolic dysfunction

c. Advanced HF

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)

Compensatory Mechanisms: Sympathetic Nervous System

Decreased MAP

Sympathetic Nervous System

Contractility Tachycardia Vasoconstriction

MAP = (SV x HR) x TPR

Sympathetic Activation in Heart Failure

CNS sympathetic outflow
Cardiac sympathetic activity
1receptors 2receptors 1receptors

Sympathetic activity to kidneys + peripheral vasculature

11Activation of RAS

Myocardial toxicity Increased arrhythmias

Vasoconstriction Sodium retention

Disease progression
Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52.

Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS)

Angiotensinogen Renin Angiotensin I Angiotensin Converting Enzyme

Angiotensin II

AT I receptor Vasoconstriction Oxidative Stress Vascular remodeling LV remodeling

Cell Growth

Proteinuria

Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS)

Renin-Angiotensin-Aldosterone ( renal perfusion)

Salt-water retention Thirst
Sympathetic augmentation

Vasoconstriction

MAP = (SV x HR) x TPR

Compensatory Mechanisms: Neurohormonal Activation Vasopressin

Decreased systemic blood pressure

Central baroreceptors Stimulation of hypothalamus, which produces vasopressin for release by pituitary gland

Increased systemic blood pressure

Vasoconstriction

Release of vasopressin by pituitary gland

Compensatory Neurohormonal Stimulation: Summary

Decreased Cardiac Output Sympathetic nervous system Renin-angiotensin system Antidiuretic hormone (vasopressin)

Contractility

Heart rate

Vasoconstriction

Circulating volume

Anteriolar
Maintain blood pressure

Venous

Venous return to heart ( preload)

Cardiac output

+
Stroke volume

Peripheral edema and pulmonary congestion

Compensatory Mechanisms
Ventricular Remodeling Alterations in the hearts size, shape, structure, and function brought about by the chronic hemodynamic stresses experienced by the failing heart.

Curry CW, et al. Mechanical dyssynchrony in dilated cardiomyopathy with intraventricular conduction delay as depicted by 3D tagged magnetic resonance imaging. Circulation 2000 Jan 4;101(1):E2.

Vicious Cycle of Heart Failure

LV Dysfunction

Increased cardiac workload (increased preload and afterload)

Decreased cardiac output and Decreased blood pressure

Increased cardiac output (via increased contractility and heart rate) Increased blood pressure (via vasoconstriction and increased blood volume)

Frank-Starling Mechanism Remodeling Neurohormonal activation

Neurohormonal Responses to Impaired Cardiac Performance

Initially Adaptive, Deleterious if Sustained

Short-Term Effects Long-Term Effects Response

Salt and Water Retention Augments Preload Pulmonary Congestion, Anasarca

Vasoconstriction

Maintains BP for perfusion Exacerbates pump of vital organs dysfunction (excessive afterload), increases cardiac energy expenditure Increases HR and ejection Increases energy expenditure

Sympathetic Stimulation

Jaski, B, MD: Basics of Heart Failure: A Problem Solving Approach

Part II: Assessing Heart Failure

Assessing Heart Failure

Patient History Physical Examination Laboratory and Diagnostic Tests

Diagnostic Evaluation of New Onset Heart Failure

Determine the type of cardiac dysfunction (systolic vs. diastolic) Determine Etiology

Define prognosis
Guide therapy

Diagnostic Evaluation of New Onset Heart Failure

Initial Work-up: ECG Chest x-ray Blood work Echocardiography

diagnostik dini
1.Riwayat penyakit dan pemeriksaan fisik
2.EKG 12 sandapan & monitoring EKG 3.Pemeriksaan darah: rutin, elektrolit, ureaN, kreatinin dan enzim jantung 4.Pulse oximetry/analisa gas darah 5.Rontgen dada 6.Ekokardiografi transtoraks

CHF

Normal Heart

Enlarged Heart

Diagnostic Evaluation of New Onset Heart Failure

RV

LV

Septum LV cavity LV Wall LA RA

M-Mode Echo

2D Echo

Part III: Current Treatment of Heart Failure

The Vicious Cycle of Heart Failure Management

Chronic HF
Diurese & Home SOB Weight

Hospitalization
IV Lasix or Admit

MDs Office
PO Lasix

Emergency Room

General Measures
Lifestyle Modifications: Weight reduction Medical Considerations: Treat HTN, hyperlipidemia, diabetes, arrhythmias

Discontinue smoking
Avoid alcohol and other cardiotoxic substances

Coronary revascularization
Anticoagulation Immunization Sodium restriction Daily weights Close outpatient monitoring

Exercise

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

Digitalis Compounds
Like the carrot placed in front of the donkey

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

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

Diuretics, ACE Inhibitors

Reduce the number of sacks on the wagon

Pharmacologic Management
Beta-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, betablockers 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 Heart Failure in the Adult, 2001 p. 20.

-Blockers
Limit the donkeys speed, thus saving energy

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

Pharmacologic Management
Angiotensin Receptor Blockers (ARBs) Block AT1 receptors, which bind circulating angiotensin II Examples: 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

Angiotensin II Receptors

AT1 receptor
Vasoconstriction

AT2 receptor
Vasodilation

Growth Promotion
Anti-apoptotic Pro-fibrotic

Growth inhibition
Pro-apoptotic ? Fibrosis

Pro-thrombotic
Pro-oxidant

? Thrombosis
? redox

Treatment Approach for the Patient with Heart Failure

Stage A Stage B Stage C Stage D

At high risk, no structural disease

Structural heart disease, asymptomatic

Structural heart disease with prior/current symptoms of HF

Therapy All measures under stage A Drugs: Diuretics ACE inhibitors Beta-blockers Digitalis Dietary salt restriction

Refractory HF requiring specialized interventions

Therapy All measures under stages A,B, and C Mechanical assist devices Heart transplantation Continuous (not intermittent) IV inotropic infusions for palliation Hospice care

Therapy Treat Hypertension Treat lipid disorders Encourage regular exercise Discourage alcohol intake ACE inhibition

Therapy All measures under stage A ACE inhibitors in appropriate patients Beta-blockers in appropriate patients

Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001

Tujuan pengobatan
Jangka pendek :
menghilangkan keluhan dan gejala klinik

Jangka panjang :
memperbaiki kualitas hidup dan masa harapan hidup mengurangi kekerapan masuk rumah sakit mencegah kematian dengan mencegah perbu rukan fungsi ventrikel.

TREATMENT OBJECTIVES Survival Morbidity Exercise capacity Quality of life Neurohormonal changes Progression of CHF Symptoms

GAGAL JANTUNG AKUT

Secara klinis dibagi dalam 3 kelompok yaitu: 1. udema paru akut kardiogenik 2. syok kardiogenik 3. dekompensasi akut pada gagal jantung kronik

diagnostik dini
1.Riwayat penyakit dan pemeriksaan fisik 2.EKG 12 sandapan & monitoring EKG 3.Pemeriksaan darah: rutin, elektrolit, ureaN, kreatinin dan enzim jantung 4.Pulse oximetry/analisa gas darah 5.Rontgen dada 6.Ekokardiografi transtoraks

Penatalaksanaan Gagal Jantung Akut (1)

1. 2. 3.

Tindakan umum Obat-obatan : Diuretik, paling baik furosemid (lasix) dosis 4080 mg secara intravena Morfin sulfat (3 - 5 mg/iv) Nitroglisenin sublingual (0,4-0,6 mg, dapat diulang 4 kali setiap 5-10 menit), I.V. mulai dengan dosis 0,3-0,5 mikrogram/kg/BB/ menit, atau dengan ISDN I.V. 2-4 mg per jam

Penatalaksanaan Gagal Jantung Akut (2)

4.Penghambat ACE : kaptopril 2 kali 6,25-12.5 mg 5.Pada kasus-kasus berat dimana curah jantung tetap rendah perlu inotropik, seperti dobutamin, dopamin 6.Aminophilin jarang digunakan pada terapi gagal jantung akut

Penatalaksanaan Gagal Jantung Akut (3)

7.Terapi trombolitik dan revaskularisasi segera (angioplasti atau bedah pintas) untuk infark miokard akut/injury 8.Intubasi dan pemasangan ventilator 9 Koreksi penyebab/penyakit dasar

Chronic Congestive Heart Failure

EVOLUTION OF CLINICAL STAGES

NORMAL
No symptoms Normal exercise Normal LV fxn

Asymptomatic LV Dysfunction No symptoms Compensated Normal exercise CHF Abnormal LV fxn No symptoms Decompensated Exercise CHF Abnormal LV fxn Symptoms Refractory Exercise CHF Abnormal LV fxn
Symptoms not controlled with treatment

Normal Asymptomatic LV dysfunction EF <40% Symptomatic CHF ACEI NYHA II Symptomatic CHF NYHA - III Diuretics mild Neurohormonal Symptomatic CHF Loop inhibitors NYHA - IV Diuretics Digoxin? Inotropes Specialized therapy Transplant Secondary prevention Modification of physical activity

TREATMENT

TREATMENT Correction of aggravating factors

Pregnancy Arrhythmias (AF) Infections Hyperthyroidism Thromboembolism Endocarditis Obesity Hypertension Physical activity Dietary excess

MEDICATIONS

TREATMENT PHARMACOLOGIC THERAPY

DIURETICS INOTROPES VASODILATORS NEUROHORMONAL ANTAGONISTS

OTHERS (Anticoagulants, antiarrhythmics, etc)

Gagal Jantung Kronik

1.Anjuran Umum 2.Tindakan Umum 3.Obat-obatan
1.Diuretik: 2.penghambat enzim konversi angiotensin (EKA) 3.penyekat beta . 4.Digitalis 5.antagonis reseptor angiotensin II

3.Obat-obatan (lanjutan)
6.Antagonis aldosteron 7.Vasodilator hidralazin sampai 300 mg + ISDN 160 mg 8.Antikoagulan: 9.Antiaritmia pada fibrilasi atrial dan VT

Pathophysiology of Heart Failure

Initial Event
Myocardial Infarct with Excessive load

LV Remodeling
Ang II
Mitral regurgitation Loss of Chamber Cardiac enlargement & Myocytes Hypertrophy Direct WaII Stress Energy Supply

Clinical Syndrome

Sodium Retention

CHF
Oedema

Cohn et al,N Engl J Med,1996 ; LeJemtel et al,Circulation,1993;87

Ventricular Remodeling and Ventricular Dysfunction

Coronary artery disease Hypertension Cardiomyopathy Valvular disease
catecholamine RAAS endothelin natriuretic peptide cytokine growth factor
Cohn, N Engl J Med, 1996;335

Arrhythmia

Left ventricular dysfunction

Remodeling

Low ejection fraction

Death
Pump failure

Noncardiac factors

Symptoms

Chronic Heart failure

Changes in the Renin-Angiotensin System in CHF

Increased release of renin by the kidneys Increased production of angiotensin II - Stimulates smooth muscle cells - Increases extracellular matrix production by smooth muscle cells and cardiac fibroblasts - Causes hypertrophy of cardiac myocytes

Angiotensin II Formation

Alternate Pathways*
Angiotensinogen Renin t-PA Cathepsin G Tonin

Angiotensin I
ACE CAGE Cathepsin G Chymase

Angiotensin II

Angiotensin II receptors
* The clinical significance of the alternate pathway is unknown Adapted from Dzau VJ et al. J Hypertens. 1993: 11(suppl 3).

ARB site of action

Renin Angiotensin System SELECTIVE MECHANISM OF ACTION

ANGIOTENSINOGEN
(LIVER)

RENIN INHIBITOR BRADYKININ PEPTIDES ACE INHIBITOR

Other enzymes e.g.CHYMASE

ANGIOTENSIN I

ANGIOTENSIN II

AT1 RECEPTOR BLOCKER

AT1

AT2

Summary of Key Heart Failure Studies (1)

Trial
V-Heft (1986)

Scope
- n = 642 - Impaired cardiac function

Mission
CCHF Vasodilator therapy: - placebo, prazosin - ISDN + Hydralazine
- Enalapril

Result
Improvement

CONSENSUS (1988)

- n = 253 - Several CHF - n = 2569 - HF w/ conventional Th/ - n = 3164 - HF

- Mortality reduced - Improved symptoms Reduced hospt. and mortality

SOLVD (1991)

- Enalapril - Hospt. & Mortality - EF< 0.35 Low, medium, high dose lisinopril on mortality

ATLAS (1991)

High dose more effective in reducing mortality

Summary of Key Heart Failure Studies (2)

Trial
RESOLVD (1999)

Scope
- 769 HF patient

Mission
- Candesartan alone - Enalapril alone - Combination-QOL Losartan vs Captopril

Result
Combination therapy more effective Increased mortality w/ candesartan alone Losartan failed to show superiority

ELITE II (1999)

- 3,152 CHF - > 60 years

CIBIS II (1999)

- 2647 NYHA III/IV - EF < 35%

Efficacy of 1,25 mg bisoprolol in HF receiving ACE + D

Significant mortality benefit - trial stopped

MERIT-HF (1999)

- 3,991 HF patients Metoprolol CR/XL NYHA II-IV; EF < 40% - 1,094 patients CHF Mortality & morbidity effects carvedilol to standard therapy

All cause mortality was lower - trial stopped Trial stopped early, reduced risk or death

CARVEDILOL HF STUDY (1999)

TREATMENT Correction of aggravating factors

Pregnancy Arrhythmias (AF) Infections Hyperthyroidism Thromboembolism Endocarditis Obesity Hypertension Physical activity Dietary excess

MEDICATIONS

TREATMENT PHARMACOLOGIC THERAPY

DIURETICS INOTROPES VASODILATORS NEUROHORMONAL ANTAGONISTS

OTHERS (Anticoagulants, antiarrhythmics, etc)

CAUSES OF HEART FAILURE:

Final common pathway of many kinds of heart diseases
Ischemic, alcoholic, restrictive, hypertrophic Optimal treatment requires identification of primary & secondary factors leading to CHF HELPFUL RESULT of dilatation: increases cardiac output HARMFUL RESULT of dilation: more wall tension, more oxygen is needed to produce any given stroke volume

Effect on Cardiac Output

Overall decrease in FrankStarling curve with CHF