Heart Failure

Final common pathway for many cardiovascular diseases whose natural history results in symptomatic or asymptomatic left ventricular dysfunction 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 3040% annually in patients with advanced disease

Main causes

Coronary artery disease

Hypertension
Valvular heart disease

Cardiomyopathy
Cor pulmonale

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

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

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

ACC/AHA guidelines, 2001

Types of heart failure

Diastolic dysfunction or diastolic heart failure

Systolic dysfunction or systolic heart failure

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 or fluid retaining properties (e. NSAIDs, corticosteroids) Alcohol

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

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 Diuretic (titrate to euvolemic state) No signs and symptoms of fluid retention ACE Inhibitor

b-blocker

Digoxin

Relation between plasma noradrenaline and mortality in patients with heart failure
Cumulative mortality (%) 100 80 60 40 Noradrenaline < 600 pg/ml 20 0 0 12 24 36 48 60 Months
NEJM 1984; 311: 819-823
Overall p<0.0001

Noradrenaline > 900 pg/ml

Noradrenaline > 600 pg/ml and < 900 pg/ml

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 a1 receptors
Am J Hypertens 1998; 11: 23S-37S

Receptor densities in human left ventricular myocardium

70
Normal myocardium

60
Receptor density (fmol/mg)

Idiopathic dilated cardiomyopathy

50 40 30 20 10 0 b 1 b

*p < 0.05

Scand Cardiovasc J 1998; Suppl 47:45-55

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 secretion

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

US Multicenter Program
Placebo (n=398) All-cause 31 mortality (7.8%) Death due to progressive 13 heart failure (3.3%) Sudden death 15 (3.8%) Risk of hospitalization for cardiovascular reasons Combined risk of mortality & hospitalization
NEJM 1996; 334:1349-1355

Carvedilol (n=696) 22 (3.2%) 5 (0.7%) 12 (1.7%) 78 (14.1%) 110 (16%)

% Risk Reduction 65%

78 (19.6%) 98 (25%)

27% 38%

ANZ Multicentre Heart Failure Trial

Placebo (n=208) All-cause mortality Risk of hospitalization for cardiovascular reasons Combined risk of mortality & hospitalization
Lancet 1997; 349: 375-380.

Carvedilol (n=207) 20 (10%) 64 (31%) 74 (36%)

% Risk Reduction 24% 28% 29%

26 (12.5%) 84 (40%) 97 (47%)

Effect of carvedilol on progression of congestive heart failure

All randomized patients Endpoint Primary endpoint Death due to CHF Placebo (n=134) 28 (21%) 4 (3%) Carvedilol (n=232) 25 (11%)* 0 (0%)

Hospitalization due to worsening CHF

Increase in CHF medication
* Placebo vs. carvedilol, p = 0.008
Drugs of Today 1998; 34 (Suppl B): 1-23.

8 (6%)
16 (12%)

9 (4%)
16 (7%)