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Heart Failure

Final common pathway for many cardiovascular

diseases whose natural history results insymptomatic or asymptomatic left ventriculardysfunction

Cardinal manifestations of heart failure include

dyspnea, fatigue and fluid retention Risk of death is 5-10% annually in patients with

mild symptoms and increases to as high as 30-40% annually in patients with advanced disease

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Main causes

Coronary artery disease

Hypertension

Valvular heart disease

Cardiomyopathy Cor pulmonale

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Compensatory changes in heart

failure

 Activation of SNS

 Activation of RAS

Increased heart rate

Release of ADH

Release of atrial natriuretic peptide

Chamber enlargement

Myocardial hypertrophy

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NYHA Classification of heart failure

Class I: No limitation of physical activity

Class II: Slight limitation of physical activity

Class III: Marked limitation of physical

activity

Class IV: Unable to carry out physical

activity without discomfort

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New classification of heart failure

Stage A: Asymptomatic with no heart

damage but have risk factors for heart failure

Stage B: Asymptomatic but have signs ofstructural heart damage

Stage C: Have symptoms and heart damage Stage D: Endstage disease

 ACC/AHA guidelines, 2001

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Types of heart failure

Diastolic dysfunction or diastolic heart

failure

Systolic dysfunction or systolic heart failure

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Factors aggravating heart failure

Myocardial ischemia or infarct

Dietary sodium excess Excess fluid intake

Medication noncompliance

 Arrhythmias

Intercurrent illness (eg infection) Conditions associated with increased metabolic demand

(eg pregnancy, thyrotoxicosis, excessive physical activity)

 Administration of drug with negative inotropic properties orfluid retaining properties (e. NSAIDs, corticosteroids)

 Alcohol

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Goals of treatment

To improve symptoms and quality of life

To decrease likelihood of disease

progression

To reduce the risk of death and need for

hospitalisation

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Approach to the Patient with Heart Failure

Assessment of LV function (echocardiogram,radionuclide ventriculogram)

EF < 40%

Assessment of

volume status

Signs and symptoms

of fluid retention

No signs and symptoms of

fluid retention

Diuretic

(titrate to euvolemic state)

ACE Inhibitor

-blockerDigoxin

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NEJM 1984; 311: 819-823

Cumulative mortality (%)

100

80

60

40

20

0

0 12 24 36 48 60

Months

Overall

p<0.0001

Noradrenaline > 600 pg/mland 900 pg/ml<

Noradrenaline 600 pg/ml<

Noradrenaline > 900 pg/ml

Relation between plasma noradrenaline andmortality in patients with heart failure

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Effects of SNS Activation in Heart Failure

Dysfunction/death of cardiac myocytes

Provokes myocardial ischemia

Provokes arrhythmias

Impairs cardiac performance

These effects are mediated via stimulation

of  b  and a 1 receptors  Am J Hypertens 1998; 11: 23S-37S 

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*

*

*p < 0.05

Idiopathic dilated cardiomyopathy

Normal myocardium

70

60

50

40

30

20

10

0

b1

  a1

b

   R  e  c  e  p   t  o  r   d  e  n  s   i   t  y   (   f  m  o   l   /  m  g   )

Receptor densities in human left ventricular myocardium

Scand Cardiovasc J 1998; Suppl 47:45-55 

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Carvedilol in Heart Failure

Effective receptor-blockade approach to heart

failure

Negative inotropic effect counteracted by

vasodilation Provides anti-proliferative, anti-arrhythmic

activity and inhibition of apoptosis

Prevents renin secretionDrugs of Today 1998; 34 (Suppl B): 1-23.

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US Multicenter Program

Placebo Carvedilol % Risk

(n=398) (n=696) Reduction  All-cause 31 22 65%

mortality (7.8%) (3.2%)

Death due to progressive  13 5

heart failure (3.3%) (0.7%)Sudden death 15 12

(3.8%) (1.7%)

Risk of hospitalization for 78 78 27%

cardiovascular reasons (19.6%) (14.1%)

Combined risk of 98 110 38%

mortality & hospitalization (25%) (16%)

NEJM 1996; 334:1349-1355

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ANZ Multicentre Heart Failure Trial

Placebo Carvedilol % Risk

(n=208) (n=207) Reduction 

 All-cause 26 20 24%

mortality (12.5%) (10%)

Risk of hospitalization for 84 64 28%

cardiovascular reasons (40%) (31%)

Combined risk of 97 74 29%

mortality & hospitalization (47%) (36%)

Lancet 1997; 349: 375-380.

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Effect of carvedilol on progression

of congestive heart failure

All randomized patients

Endpoint Placebo Carvedilol

(n=134) (n=232) 

Primary endpoint 28 (21%) 25 (11%)*

Death due to CHF   4 (3%) 0 (0%)

Hospitalization due to worsening CHF   8 (6%) 9 (4%)

Increase in CHF medication  16 (12%) 16 (7%)

* Placebo vs. carvedilol, p = 0.008

Drugs of Today 1998; 34 (Suppl B): 1-23.