Congestive Heart Failure

Dr. T. Tamilselvan. M.Pharm.,Ph.D.,

Professor & Head
Department of Pharmacy Practice
Nehru College of Pharmacy.
 Definition

• Heart failure is defined as the pathophysiologic state in

which impaired cardiac function is unable to maintain
an adequate circulation for the metabolic needs of the
tissues of the body. It may be acute or chronic.
 Etiology
1. INTRINSIC PUMP FAILURE. The most common
and most important cause of heart failure is
weakening of the ventricular muscle due to disease
so that the heart fails to act as an efficient pump. The
various diseases which may culminate in pump
failure by this mechanisms are as under:
i) Ischaemic heart disease
ii) Myocarditis
iii) Cardiomyopathies
iv) Metabolic disorders e.g. beriberi
v) Disorders of the rhythm e.g. atrial fibrillation and
flutter.
 Etiology
2. INCREASED WORKLOAD ON THE HEART
Increased mechanical load on the heart results in
increased myocardial demand resulting in
myocardial failure. Increased load on the heart may
be in the form of pressure load or volume load.
i) Increased pressure load may occur in the following
states:
a) Systemic and pulmonary arterial hypertension.
b) Valvular disease e.g. mitral stenosis, aortic stenosis,
pulmonary stenosis.
c) Chronic lung diseases.
 Etiology
ii) Increased volume load occurs when a ventricle is
required to eject more than normal volume of the
blood resulting in cardiac failure. This is seen in the
following conditions:
a) Valvular insufficiency
b) Severe anaemia
c) Thyrotoxicosis
d) Arteriovenous shunts
e) Hypoxia due to lung diseases.
 Etiology
3. IMPAIRED FILLING OF CARDIAC CHAMBERS.
Decreased cardiac output and cardiac failure may result from
extra-cardiac causes or defect in filling of the heart:
a) Cardiac tamponade e.g. haemopericardium, hydroperi-
cardium
b) Constrictive pericarditis.
 Types of Heart Failure
Acute heart failure. Sudden and rapid development of heart
failure occurs in the following conditions:
i) Larger myocardial infarction
ii) Valve rupture
iii) Cardiac tamponade
iv) Massive pulmonary embolism
v) Acute viral myocarditis
vi) Acute bacterial toxaemia.
In acute heart failure, there is sudden reduction in cardiac
output resulting in systemic hypotension but oedema
does not occur. Instead, a state of cardiogenic shock and
cerebral hypoxia develops.
 Types of Heart Failure
Chronic heart failure. More often, heart failure
develops slowly as observed in the following states:
i) Myocardial ischaemia from atherosclerotic coronary
artery disease
ii) Multivalvular heart disease
iii) Systemic arterial hypertension
iv) Chronic lung diseases resulting in hypoxia and
pulmo- nary arterial hypertension
v) Progression of acute into chronic failure.
 Types of Heart Failure
In chronic heart failure, compensatory mechanisms like
tachycardia, cardiac dilatation and cardiac
hypertrophy try to make adjustments so as to
maintain adequate cardiac output.

This often results in well-maintained arterial pressure

and there is accumulation of oedema.
 Pathophysiology
The clinical manifestations of heart failure result from
accumulation of excess fluid upstream to the left or right
cardiac chamber whichever is initially affected

Left-sided heart failure. It is initiated by stress to the left

heart.
The major causes are as follows:
i) Systemic hypertension
ii) Mitral or aortic valve disease (stenosis)
iii) Ischaemic heart disease
iv) Myocardial diseases e.g. cardiomyopathies, myocarditis.
v) Restrictive pericarditis.
 Pathophysiology
The clinical manifestations of left-sided heart failure result
from decreased left ventricular output and hence there is
accumulation of fluid upstream in the lungs. Accordingly,
the major pathologic changes are as under:
i) Pulmonary congestion and oedema causes dyspnoea and
orthopnoea
ii) Decreased left ventricular output causing hypoperfusion
and diminished oxygenation of tissues e.g. in kidneys
causing ischaemic acute tubular necrosis , in brain
causing hypoxic encephalopathy and in skeletal muscles
causing muscular weakness and fatigue.
 Pathophysiology
Right-sided heart failure. Right-sided heart failure
occurs more often as a consequence of left-sided heart
failure.
i) As a consequence of left ventricular failure.
ii) Cor pulmonale in which right heart failure occurs due
to intrinsic lung diseases.
iii) Pulmonary or tricuspid valvular disease.
iv) Pulmonary hypertension secondary to pulmonary
thromboembolism.
v) Myocardial disease affecting right heart.
vi) Congenital heart disease with left-to-right shunt.
 Pathophysiology

The pathologic changes are as under:

i) Systemic venous congestion in different tissues and
organs e.g. subcutaneous oedema on dependent parts,
passive congestion of the liver, spleen, and kidneys,
ascites, hydrothorax, congestion of leg veins and neck
veins.
ii) Reduced cardiac output resulting in circulatory
stagnation causing anoxia, cyanosis and coldness of
extremities.
Pathophysiology
 Pathophysiology
• Backward heart failure. According to this concept, either
of the ventricles fails to eject blood normally, resulting in
rise of end-diastolic volume in the ventricle and increase in
volume and pressure in the atrium which is transmitted
backward producing elevated pressure in the veins.
• Forward heart failure. According to this hypothesis,
clinical manifestations result directly from failure of the
heart to pump blood causing diminished flow of blood to
the tissues, especially diminished renal perfusion and
activation of renin- angiotensin-aldosterone system.
COMPENSATORY MECHANISMS
 CLINICAL PRESENTATION

• The primary symptoms are dyspnea (particularly on exertion)

and fatigue, which lead to exercise intolerance.
• Other pulmonary symptoms include orthopnea, paroxysmal
nocturnal dyspnea, tachypnea, and cough.
• Fluid overload can result in pulmonary congestion and peripheral
edema.
• Nonspecific symptoms may include fatigue, nocturia, hemoptysis,
abdominal pain, anorexia, nausea, bloating, ascites, poor
appetite, mental status changes, and weight gain.
 DIAGNOSIS

• Exhibiting characteristic signs and symptoms.

• Complete history and physical examination

• Laboratory tests for identifying disorders that may cause or worsen HF

include compete blood count; serum electrolytes (including calcium

and magnesium); renal, hepatic, and thyroid function tests;

urinalysis; lipid profile; and hemoglobin A1C

• Ventricular hypertrophy can be demonstrated on chest x-ray or ECG.

• Echocardiogram -left ventricular ejection fraction (LVEF) to

determine if systolic or diastolic dysfunction

 TREATMENT OF CHF

• The first step in managing chronic HF is to determine

the etiology or precipitating factors. Treatment of
underlying disorders (e.g., anemia, hyperthyroidism).
• Nonpharmacologic interventions include cardiac
rehabilitation and restriction of fluid intake
(maximum 2 L/day from all sources) and dietary
sodium (approximately 2 to 3 g of sodium per day).
 TREATMENT OF CHF

Stage A:

Identifying and modifying risk factors to prevent development of structural

heart disease and subsequent HF.

• Strategies include smoking cessation and control of hypertension, diabetes.

The primary symptoms are dyspnea (particularly on exertion) and

mellitus, and dyslipidemia according to current treatment guidelines.

• Angiotensin-converting enzyme (ACE) inhibitors (or ARBs) should be

strongly considered for antihypertensive therapy in patients with multiple

vascular risk factors

 TREATMENT OF CHF
Stage B:

In these patients with structural heart disease but no symptoms,

treatment is targeted at minimizing additional injury and preventing or

slowing the remodeling process.

In addition to treatment measures out- lined for stage A, patients with a

previous MI should receive both ACE inhibitors (or ARBs) and β-

blockers regardless of the ejection fraction.

Patients with reduced ejection fractions (less than 40%) should also

receive both agents, regardless of whether they have had an MI.

 TREATMENT OF CHF
Stage C:

Most patients with structural heart disease and previous or current HF symptoms

should receive the treatments for Stages A and B as well as initiation and titration of a

diuretic (if clinical evidence of fluid retention), ACE inhibitor, and β-blocker (if not

already receiving a β- blocker for previous MI, left ventricular [LV] dysfunction, or

other indication).

If diuresis is initiated and symptoms improve once the patient is euvolemic, long-term

monitoring can begin.

If symptoms do not improve, an aldosterone receptor antagonist, ARB (in ACE

inhibitor- intolerant patients), digoxin, and/or hydralazine /isosorbide dinitrate (ISDN)

may be useful in carefully selected patients.

Other general measures include moderate sodium restriction, daily weight measurement,

immunization against influenza and pneumococcus, modest physical activity, and avoidance
 TREATMENT OF CHF
Stage D:

Patients with symptoms at rest despite maximal medical therapy

should be considered for specialized therapies, including
mechanical circulatory support, continuous intravenous positive
inotropic therapy, cardiac transplantation, or hospice care.
TREATMENT OF CHF
 TREATMENT OF CHF

Diuretics
• Compensatory mechanisms in HF stimulate excessive
sodium and water retention
 TREATMENT OF CHF
Angiotensin-Converting Enzyme Inhibitors
• Decrease angiotensin II and aldosterone.
• reducing ventricular remodeling, myocardial fibrosis, myocyte
apoptosis, cardiac hypertrophy, norepinephrine release,
vasoconstriction, and sodium and water retention
 TREATMENT OF CHF
β-Blockers
• slow disease progression, decrease hospitalizations, and reduce mortality in

patients with HF

• Antiarrhythmic effects, slowing or reversing ventricular remodeling, decreasing

myocyte death from catecholamine-induced necrosis or apoptosis, preventing fetal

gene expression, improving LV systolic function, decreasing heart rate and

ventricular wall stress and thereby reducing myocardial oxygen demand, and

inhibiting plasma renin release.

• Carvedilol, 3.125 mg twice daily initially; target dose, 25 mg twice daily

• Metoprolol succinate CR/XL, 12.5 to 25 mg once daily initially; target dose, 200

mg once daily.

• Bisoprolol, 1.25 mg once daily initially; target dose, 10 mg once daily.

 TREATMENT OF CHF
Angiotensin II Receptor Blockers
• Candesartan, 4 to 8 mg once daily initially; target dose, 32 mg once
daily.
• Valsartan, 20 to 40 mg twice daily initially; target dose, 160 mg twice
daily.
• Blood pressure, renal function, and serum potassium should be evaluated
within 1 to 2 weeks after therapy initiation and dose increases, with these
endpoints used to guide subsequent dose changes.
• It is not necessary to reach target ARB doses before adding a β-blocker.

(Cough and angioedema are the most common causes of ACE inhibitor
intolerance)
 TREATMENT OF CHF
Aldosterone Antagonists
• Spironolactone and eplerenone block the mineralocorticoid receptor, the
target site for aldosterone. In the kidney, aldosterone antagonists inhibit
sodium reabsorption and potassium excretion.
• low-dose aldosterone antagonists may be appropriate for:

(1) patients with moderately severe to severe HF who are receiving

standard therapy
(2) those with LV dysfunction early after MI.
• Initial doses should be low (spironolactone 12.5 mg/day; eplerenone 25
mg/day), especially in the elderly and those with diabetes or creatinine
clearance <50 mL/min.
 TREATMENT OF CHF
Digoxin
• Digoxin has positive inotropic effects, its benefits in HF are related to its
neurohormonal effects. Digoxin attenuates the excessive sympathetic
nervous system activation present in HF patients, perhaps by reducing
central sympathetic outflow and improving impaired baroreceptor func-
tion. It also increases parasympathetic activity in HF patients and decreases
heart rate, thus enhancing diastolic filling.
• In patients with HF and supraventricular tachyarrhythmias such as atrial
fibrillation, digoxin should be considered early in therapy to help control
ventricular response rate.
• Doses should be adjusted to achieve plasma digoxin concentration of 0.5 to
1 ng/mL. (Normal renal function can achieve this level with a dose of
0.125 mg/day) ( with amiodarone) should receive 0.125 mg every other
 TREATMENT OF CHF
Nitrates and Hydralazine

• Nitrates (e.g., ISDN) and hydralazine were combined originally in the

treatment of HF because of their complementary hemodynamic actions.
• Nitrates (20 mg) are primarily venodilators, producing reductions in
preload.
• Hydralazine (37.5 mg) is a direct vasodilator that acts predominantly on
arterial smooth muscle to reduce systemic vascular resistance (SVR) and
increase stroke volume and cardiac output.
• Adverse effects (headache, dizziness, GI distress)
TREATMENT OF ACHF