Congestive heart failure overview

# Overview
Heart failure is a complex syndrome whereby there is inadequate output of the heart to meet the metabolic demands of the body. Abnormal function of different anatomic parts of the heart cause heart failure including the pericardium, the myocardium, the endocardium, the heart valves and the great vessels. Symptoms of heart failure are due to a lack of both forward blood flow to the body, and backward flow into the lungs. Heart failure is a clinical syndrome characterized by symptoms of dyspnea, edema and fatigue and signs such as rales on physical examination. Heart failure may be classified based on ejection fraction into heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). LV remodeling is the basic concept for HFpEF pathophysiolgy. Two models are emerging in HFpEF pathophysiology, the traditional model discussed about ventricular diastolic dysfunction , LV hypertrophy, impaired relaxation, endothelial dysfunction, arterial and ventricular stiffness and their effect on cardiac function. The emerged model discussed role of systemic microvascular endothelial inflammation due to existing comorbidities such as, diabetes, hypertension, obesity, smoking and ischemia in cardiac remodeling and dysfunction. The pathogenesis of HFrEF is related largely to cellular proliferation and metabolism. Pathological processes that result in progression of HF and are common to both HFrEF and HFpEF are altered excitation-contraction coupling, epigenetic modifications, changes in sarcomeric coupling proteins, increased adrenergic drive, increased activity of renin-angiotensin aldosterone axis, nitric oxide insensitivity, adensoine triphosphate (ATP) depletion, reactive oxygen species production and an elevated cell death rate. The causes of heart failure can be broadly divided into cardiac and non-cardiac. Cardiac causes include aortic regurgitation, aortic stenosis, arrhythmias, arrhythmogenic right ventricular dysplasia, arteriovenous fistula, atrial fibrillation, atrial septal defect, cardiac amyloidosis, cardiac aneurysm, congenital heart disease, constrictive pericarditis, dilated cardiomyopathy, Eisenmenger syndrome, endocarditis, hypertension, hypertrophic cardiomyopathy, hypoplastic left heart syndrome, interferon gamma, ischemic heart disease, malignant hypertension, mitral regurgitation, mitral stenosis, myocardial infarction, oxaprozin, patent ductus arteriosus, pericardial effusion, pericardial tamponade, pericarditis, peripartum cardiomyopathy, pertuzumab, restrictive cardiomyopathy, rheumatic carditis, rupture of the papillary muscles, Takotsubo cardiomyopathy, tricuspid insufficiency, valvular heart disease, ventricular aneurysm, ventricular septal defect. Congestive heart failure should be distinguished from other conditions that cause dyspnea, fatigue and edema. Heart failure affects close to 5 million people in the the United States of America and each year close to 500,000 new cases are diagnosed. Congestive heart failure is responsible for a significant portion of the healthcare budget, and more than 50% of patients seek re-admission within 6 months after treatment and the average duration of hospital stay is 6 days.  In 2005 the prevalence among adults aged 20 and older in the United States was 5,300,000 (about 2,650,000 males, and 2,650,000 females). Heart failure is associated with significantly reduced physical and mental health, resulting in a markedly decreased quality of life. Congestive heart failure is also associated with a poor prognosis. If left untreated, heart failure may result in death due to complications associated with the condition. Heart failure resulting from atherosclerotic coronary artery disease has been shown to be associated with higher incidence of fatal events compared to heart failure that results from other cardiac diseases. Heart failure is a progressive disease with a major impact on the patient's quality of life. With the exception of heart failure caused by reversible conditions, the condition usually worsens with time. Although some people survive many years, progressive disease is associated with an overall annual mortality rate of 10%. In the Framingham experience, 80% of men and 70% of women with heart failure who were under 65 years of age had died within 8 years of the diagnosis. There are several diagnostic criteria / algorithms that are used to diagnose heart failure including an algorithm from the ESC, Framingham study, and Boston. The classic symptoms of heart failure include dyspnea, fatigue, and fluid retention. Patients with heart failure present in different ways. Some patients present with exercise intolerance but show little evidence of congestion or edema. Other patients present with mild symptoms of edema and pulmonary congestion. The ejection fraction is usually below 35% in patients who are symptomatic with systolic heart failure. BNP levels may be useful in the initial establishment of the diagnosis of heart failure in the patient with dyspnea of unclear etiology. Chest x-ray in a patient with heart failure shows cardiomegaly (cardiac enlargement and pulmonary congestion (Kerley B lines, and in some cases pleural effusion). CMR may be used for assessment of LV and RV size and morphology, systolic and diastolic function, and for characterizing myocardial tissue for the purpose of understanding the etiology of LV systolic or diastolic dysfunction. Echocardiography is commonly used to diagnose and monitor the progression of heart failure. This modality uses ultrasound to determine the stroke volume (SV, the amount of blood in the heart that exits the ventricles with each beat), the end-diastolic volume (EDV, the total amount of blood at the end of diastole), and the SV divided by the EDV, a value known as the ejection fraction (EF). In pediatrics, the shortening fraction is the preferred measure of systolic function. Coronary angiography is perfomred in patients with heart failure in whom there is a suspicion of underlying atherosclerosis as the basis for the heart failure. Patients who are troponin or CK-MB positive, who have dynamic EKG changes or other signs and symptoms of an acute coronary syndrome who are revascularization candidates should undergo coronary angiography. Acute heart failure can occur in the setting of a new onset heart failure or worsening of an existing chronic heart failure (also known as acute decompensated heart failure, flash pulmonary edema, ADHF). ADHF presents with acute shortness of breath due to the development of pulmonary edema (the rapid accumulation of fluid in the lung). Other signs and symptoms of ADHF include hypotension with impaired and organ perfusion manifested by worsening renal function, altered mentation and cold clammy extremities. ADHF associated with a poor prognosis if not treated aggressively. Like chronic heart failure therapy, the goal is to improve symptoms but unlike chronic therapy the other goals are to improve oxygenation and hemodynamic stability. The mainstays of the acute medical treatment in acute decompensated congestive heart failure include oxygen to improve hypoxia, diuresis to reduce both preload and intravascular volume and vasodilators to reduce afterload. Some of the mainstays of chronic heart failure therapy are not initiated acutely (ACE inhibtors,beta blockers and digoxin). End of life care in the patient with congestive heart failure is focused on making the patient comfortable. Invasive procedures should be minimized, and patients may elect to have their defibrillators inactivated. The growing number of patients with Stage IV heart failure (intractable symptoms of fatigue, shortness of breath or chest pain at rest despite optimal medical therapy) should be considered for palliative care or hospice.

# Historical Perspective
Heart failure (HF) is known to be recognized as a disease since ancient times. Italian Egyptologist Ernesto Schiaparelli reported the first case of decompensated heart failure (HF) in the remains of a tomb in the Valley of the Queens over 3500 years ago the remains are now housed in the Egyptian museum in Turin, Italy. They belonged to an Egyptian dignitary named Nebiri who lived under the reign of the 18th dynasty Pharaoh Thutmose III (147924 BC). Various other features of HF such as cardiac hypertrophy and coronary atherosclerosis were also known to Egyptians. In China, the Yellow Emperors Classic of Internal Medicine described edema as early as 2600 B.C. The medieval Arab scholar Ibn Sina, known to the West as Avicenna (9801037), had a reputation as an authority on heart disease. His treatise entitled Kitab al-Adviyt-al-Qalbiye or The book on drugs for cardiac diseases discusses therapies for difficulty in breathing, palpitation, and syncope. Widely used in the West in a Latin translation in the 14th century, the treatise remains in the Galenic tradition of humours. In 1628 when William Harvey clearly described circulation and elucidated hemodynamic abnormalities occurring in HF. Rontgen discovered x-rays in 1895 and allowed a more thorough understanding of maladaptive changes occurring in HF patients.In the 1940s and 1960s the advent of cardiac catheterization and cardiac surgery furthered our understanding of HF. The 1960s was also the decade that saw the emergence of LV assist devices (LVADs), beginning in 1961 when Dennis and co-workers uses a roller pump to assist the left ventricle. From the mid-1970s, the availability of vasodilators provided a means to reduce afterload in order to increase cardiac efficiency and cardiac output in HF

# Classification
Several classification schemes are used to characterize heart failure based on:
- The pathophysiology of heart failure (systolic vs diastolic; left vs right; low output vs high output)
- The chronicity of heart failure (acute vs chronic)
- The severity of heart failure (the NY Heart Association Class)
- The stage of congestive heart failure (AHA Class A,B,C,D)
- The most recent classification according to the left ventricular ejection fraction; heart failure with reduced ejection fraction(HFrEF) vs heart failure with preserved ejection fraction (HFpEF)

# Pathophysiology
Heart failure is a complex syndrome whereby there is inadequate output of the heart to meet the metabolic demands of the body. Heart failure is caused by abnormal function of different anatomic parts of the heart including the pericardium, the myocardium, the endocardium, the heart valves and the great vessels. Heart failure is characterized by decreased cardiac output but not necessarily decreased ejection fraction. Symptoms of heart failure are due to a lack of both forward blood flow to the body, and backward flow into the lungs. The body tries to compensate for the low cardiac output by mechanisms that increase the preload and afterload. These mechanisms lead to exacerbation of the cardiac malfunction and symptoms associated with heart failure. LV remodeling is the basic concept for HFpEF pathophysiolgy. Two models are emerging in HFpEF pathophysiology, the traditional model discussed about ventricular diastolic dysfunction , LV hypertrophy, impaired relaxation, endothelial dysfunction, arterial and ventricular stiffness and their effect on cardiac function. The emerged model discussed role of systemic microvascular endothelial inflammation due to existing comorbidities such as, diabetes, hypertension, obesity, smoking and ischemia in cardiac remodeling and dysfunction. The pathogenesis of HFrEF is related largely to cellular proliferation and metabolism. Pathological processes that result in progression of HF and are common to both HFrEF and HFpEF are altered excitation-contraction coupling, epigenetic modifications, changes in sarcomeric coupling proteins, increased adrenergic drive, increased activity of renin-angiotensin aldosterone axis, nitric oxide insensitivity, adensoine triphosphate (ATP) depletion, reactive oxygen species production and an elevated cell death rate.

# Causes
The causes of heart failure can be broadly divided into cardiac and non-cardiac. Cardiac causes include aortic regurgitation, aortic stenosis, arrhythmias, arrhythmogenic right ventricular dysplasia, arteriovenous fistula, atrial fibrillation, atrial septal defect, cardiac amyloidosis, cardiac aneurysm, congenital heart disease, constrictive pericarditis, dilated cardiomyopathy, Eisenmenger syndrome, endocarditis, hypertension, hypertrophic cardiomyopathy, hypoplastic left heart syndrome, interferon gamma, ischemic heart disease, malignant hypertension, mitral regurgitation, mitral stenosis, myocardial infarction, oxaprozin, patent ductus arteriosus, pericardial effusion, pericardial tamponade, pericarditis, peripartum cardiomyopathy, pertuzumab, restrictive cardiomyopathy, rheumatic carditis, rupture of the papillary muscles, Takotsubo cardiomyopathy, tricuspid insufficiency, valvular heart disease, ventricular aneurysm, ventricular septal defect.

# Differentiating Heart Failure From Other Diseases
Congestive heart failure should be distinguished from other conditions that cause dyspnea, fatigue and edema.

# Epidemiology and Demographics
Heart failure affects close to 5 million people in the the United States of America and each year close to 500,000 new cases are diagnosed. Congestive heart failure is responsible for a significant portion of the healthcare budget, and more than 50% of patients seek re-admission within 6 months after treatment and the average duration of hospital stay is 6 days.  In 2005 the prevalence among adults aged 20 and older in the United States was 5,300,000 (about 2,650,000 males, and 2,650,000 females).

# Risk Factors
Several risk factors may predispose to heart failure. These risk factors can be demographic, genetic, associated with lifestyle or medications.

# Screening
There is insufficient evidence to recommend routine screening for heart failure.

# Natural History, Complications And Prognosis
Heart failure is associated with significantly reduced physical and mental health, resulting in a markedly decreased quality of life. Congestive heart failure is also associated with a poor prognosis. If left untreated, heart failure may result in death due to complications associated with the condition. Heart failure resulting from atherosclerotic coronary artery disease has been shown to be associated with higher incidence of fatal events compared to heart failure that results from other cardiac diseases. Heart failure is a progressive disease with a major impact on the patient's quality of life. With the exception of heart failure caused by reversible conditions, the condition usually worsens with time. Although some people survive many years, progressive disease is associated with an overall annual mortality rate of 10%. In the Framingham experience, 80% of men and 70% of women with heart failure who were under 65 years of age had died within 8 years of the diagnosis.

# Differential Diagnosis of Causes of Heart Failure Segregated by Left and Right Sided Heart Failure

## Left Ventricular Failure

### Most Common Causes:
- Aortic regurgitation
- Aortic stenosis
- Hypertension
- Mitral regurgitation
- Myocardial ischemia

### Expanded List of Causes:
- Atrial fibrillation
- Alcoholism
- Anemia
- Angina
- Aortic regurgitation
- Aortic Stenosis
- Arteriovenous fistula
- Beriberi
- Cardiac aneurysm
- Cardiomyopathy
- Constrictive pericarditis
- Drugs, toxins
- Hypertension
- Hyperthyroidism
- Hypovolemia
- Hypoxia
- Mediastinal tumors
- Mitral Regurgitation
- Myocardial Infarction
- Paget's Disease
- Pancoast's Tumor
- Pericardial effusion
- Pericardial tamponade
- Perimyocarditis
- Protein deficiency
- Restrictive cardiomyopathy
- Rupture of the papillary muscles
- Sepsis
- Superior vena cava syndrome

## Right Ventricular Failure

### Most Common Causes:
- Cardiomyopathy
- Cor pulmonale
- Diffuse myocarditis
- Left heart failure

### Other Causes:
- After left ventricular failure
- After pulmonary resection
- Allergic alveolitis
- Bronchial asthma
- Chronic bronchitis
- Honeycomb lung
- Hyperglobulia
- Emphysema
- Mitral Stenosis
- Right ventricular myocardial infarction
- Pickwickian Syndrome
- Pleural fibrosis
- Pneumoconiosis
- Pulmonary fibrosis
- Pulmonic regurgitation
- Pulmonic stenosis
- Sarcoidosis
- Severe relapsing pulmonary emboli
- Silicosis
- Tachycardia
- Tricuspid insufficiency

## Others
- Ascorbic acid deficiency
- Cardiac amyloidosis
- Carnitine deficiency
- Cervical vein stasis of non-cardiac genesis
- Congenital heart disease
- Cyanosis of non-cardiac genesis
- Diabetes Mellitus
- Dyspnea of non-cardiac genesis
- Edema of non-cardiac genesis
- Hemochromatosis
- Pleural effusion of non-cardiac genesis
- Pulmonary edema of non-cardiac genesis
- Thiamine deficiency
- Thyroid disease

# Diagnosis

## Clinical assessment
There are several diagnostic criteria / algorithms that are used to diagnose heart failure including an algorithm from the ESC, Framingham study, and Boston.

## History and symptoms
The classic symptoms of heart failure include dyspnea, fatigue, and fluid retention. Patients with heart failure present in different ways. Some patients present with exercise intolerance but show little evidence of congestion or edema. Other patients present with mild symptoms of edema and pulmonary congestion. The ejection fraction is usually below 35% in patients who are symptomatic with systolic heart failure.

## Physical examination
Physical examination is of utmost important in the suspicion, diagnosis and follow up of heart failure. Focus should be targeted mainly on the evaluation of the fluid status, blood pressure and weight changes.

## Laboratory findings
Once the diagnosis of heart failure is made, subsequent laboratory studies should be directed toward the identification of an underlying cause of heart failure. Laboratory tests used for diagnosis and monitor disease activity include renal function tests, thyroid function tests, serum BNP levels and serum CA-125 levels. BNP levels may be useful in the initial establishment of the diagnosis of heart failure in the patient with dyspnea of unclear etiology. In a meta-analysis, BNP was superior N-terminal pro-BNP (NTproBNP) and was associated with a sensitivity of 85% and specificity of 84% in the diagnosis of heart failure in the primary care setting. Once the diagnosis of heart failure is made, subsequent laboratory studies should be directed toward the identification of an underlying cause of heart failure. Renal function should be assessed as a rough guide to the patient's intravascular volume status and renal perfusion. A urinalysis is helpful in the assessment of the patient's volume status. Electrolyte assessment and the correction of electrolyte disturbances such as hypokalemia, hyperkalemia and hypomagnesemia is critical in those patients treated with diuretics. Hyponatremia (due to poor stimulation of the baroreceptors and appropriate ADH release and free water retention) is associated with a poor prognosis.

## Electrocardiogram
Although there is no diagnostic criteria of congestive heart failure on the EKG, there may be signs of the underlying cardiac cause(s) of congestive heart failure. The EKG often shows low QRS voltage. Other changes associated with HF include ventricular hypertrophy, atrial enlargement, poor R wave progression, left bundle branch block.

## Chest X-ray
Chest x-ray in a patient with heart failure shows cardiomegaly (cardiac enlargement and pulmonary congestion (Kerley B lines, and in some cases pleural effusion)

## MRI
CMR may be used for assessment of LV and RV size and morphology, systolic and diastolic function, and for characterizing myocardial tissue for the purpose of understanding the etiology of LV systolic or diastolic dysfunction. The writing committee recognizes the potential capabilities of spectroscopic techniques for acquiring metabolic information of the heart when evaluating individuals with heart failure.

## Echocardiography
Echocardiography is commonly used to diagnose and monitor the progression of heart failure. This modality uses ultrasound to determine the stroke volume (SV, the amount of blood in the heart that exits the ventricles with each beat), the end-diastolic volume (EDV, the total amount of blood at the end of diastole), and the SV divided by the EDV, a value known as the ejection fraction (EF). In pediatrics, the shortening fraction is the preferred measure of systolic function.

## Exercise stress test
Exercise stress testing with an assessment of oxygen consumption is useful in assessing the functional capacity of the heart failure patient. Angiography can exclude the presence of an ischemic basis for the disease, and cardiac catheterization can evaluate the hemodynamic basis of heart failure and the response to drug. Myocardial viability studies can determine whether hypocontractile myocardium is viable but just hibernating, and could therefore benefit from revascularization.

## Myocardial viability studies
Myocardial viability studies can determine whether hypocontractile myocardium is viable but just hibernating, and could therefore benefit from revascularization.

## Cardiac catheterization
Coronary angiography is perfomred in patients with heart failure in whom there is a suspicion of underlying atherosclerosis as the basis for the heart failure. Patients who are troponin or CK-MB positive, who have dynamic EKG changes or other signs and symptoms of an acute coronary syndrome who are revascularization candidates should undergo coronary angiography.

## Invasive hemodynamic monitoring
Based upon the results of the ESCAPE trial, there is no benefit in clinical outcomes associated with the routine use of a pulmonary artery line in patients with decompensated CHF.

# Treatment

## Acute Treatment
Acute heart failure can occur in the setting of a new onset heart failure or worsening of an existing chronic heart failure (also known as acute decompensated heart failure, flash pulmonary edema, ADHF). ADHF presents with acute shortness of breath due to the development of pulmonary edema (the rapid accumulation of fluid in the lung). Other signs and symptoms of ADHF include hypotension with impaired and organ perfusion manifested by worsening renal function, altered mentation and cold clammy extremities. ADHF associated with a poor prognosis if not treated aggressively. Like chronic heart failure therapy, the goal is to improve symptoms but unlike chronic therapy the other goals are to improve oxygenation and hemodynamic stability. The mainstays of the acute medical treatment in acute decompensated congestive heart failure include oxygen to improve hypoxia, diuresis to reduce both preload and intravascular volume and vasodilators to reduce afterload. Some of the mainstays of chronic heart failure therapy are not initiated acutely (ACE inhibtors,beta blockers and digoxin).

## General Measures in the Management of Heart Failure
- Treat the underlying cause of heart failure such as ischemic heart disease, hypertension, and valvular heart disease.
- Treat other non cardiac diseases that might contribute to the symptoms of heart failure such as diabetes and hyperthyroidism.
- Treat with a low salt diet
- Follow the patient's weight to check for fluid overload
- Treat with vaccines for influenza and pneumococcus 

## Diuresis: First Step in the Management of Heart Failure
The treatment of chronic heart failure often begins with the administration of diuretics, particularly if the patient has signs or symptoms of volume overload.  While increased left ventricular volume increases contractility to a point, if the heart is filled beyond that point, its contractility diminishes (the patient "falls of the Staring curve").  Diuretics can reduce volume overload and reduce shortness of breath and edema.  There are three kinds of diuretics, loop diuretics, thiazides and potassium-sparing diuretics.  Diuretics rapidly improve the symptoms of heart failure (within hours to days).  Diuretics reduce excess volume that accumulates with heart failure and decrease pulmonary edema that causes symptoms of dyspnea and orthopnea.  Lasix 20 to 40 mg PO daily is a conventional starting dose, but in some patients, torsemide may be a better choice due to its more predictable absorption.  Once a day dosing of a given diuretic is preferred to twice a day dosing at a lower dose.  A rise in BUN and Cr may reflect a reduction in renal perfusion, and further diuresis should only be undertaken with careful monitoring of renal function.  The patient should weigh themselves each morning at the same time on the same scale, and the diuretic dosing should be adjusted to maintain a constant weight.  Given the risk of hypokalemia or hyperkalemia, the blood level of electrolyes should be checked regularly.

## ACE Inhibition and Angiotensin Receptor Blockade: Second Step in the Management of Heart Failure
After diuretics are started or at the same time they are started, an ACE inhibitor can be initiated . This includes a large group of drugs, such as Enalapril (Vasotec/Renitec), Ramipril (Altace/Tritace/Ramace/Ramiwin), Quinapril (Accupril), Perindopril (Coversyl/Aceon), Lisinopril (Lisodur/Lopril/Novatec/Prinivil/Zestril) and Benazepril (Lotensin). They can improve symptoms and prognosis of heart failure in several ways including afterload reduction and favorable ventricular remodeling. Usual side effects include dry cough and angioedema.  Patients with bilateral renal artery stenosis or severe renal impairment are not appropriate for angiotensin converting enzyme inhibitor (ACEI).
During or after the initiation of diuresis, one could start, for example, lisinopril 5 mg Q day.  Every 1 - 2 weeks, the dose would be escalated to achieve a target dose of 15 to 20 mg Q day.  An ACE inhibitor is initiated before a beta blocker because an ACE inhibitor achieves its hemodynamic effect more rapidly, and is less likely to cause a decline in hemodynamics.  Although there is some data to suggest that aspirin blunts the hemodynamic effect of ACE inhibitors, there is no data to suggest that aspirin reduces the clinical efficacy of ACE inhibitors in heart failure patients.  Aspirin should be administered to patients with ischemic heart disease, but not to patients without it.
If a patient cannot tolerate a an ACE inhibitor (develops a cough), then an Angiotensin II receptor blocker can be administered in its place.  Angiotensin II receptor antagonists block the activation of angiotensin II AT1 receptors. Blockade of AT1 receptors directly causes vasodilation, reduces secretion of vasopressin, reduces production and secretion of aldosterone. Because angiotensin II receptor antagonists do not inhibit the breakdown of bradykinin or other kinins, and are thus only rarely associated with the persistent dry cough and/or angioedema that limit ACE inhibitor therapy. Commonly administered agents in the management of heart failure include Candesartan, Valsartan, Telmisartan, Losartan, Irbesartan, and Olmesartan.  The effectiveness of switching to an ARB from and ACE inhibitor was demonstrated for candesartan in the CHARM Alternative trial .
In general, ARBs are as effective or slightly less effective than ACE inhibitors in the treatment of congestive heart failure.  It is a class 2a recommendation to substitute an ARB as an alternative to ACE inhibitors if the patient is already taking an ARB for another indication.
The efficacy of adding an ARB to an ACE inhibitor was assessed in the CHARM Added trial. While there was a reduction in the composite primary endpoint in the study, there was no reduction in mortality.  Furthermore, the VALIANT trial demonstrated that an ARB should not be added to an ACE inhibitor in the post MI setting.   These results for ARBs are in contrast to the results of the EMPHASIS HF trial showed that the addition of eplerenone (an aldosterone antagonist) to ACE inhibition improved clinical outcomes including mortality among patients with class II or III heart failure with a reduced LVEF.  Thus, based upon the mortality benefit observed in the EMPHASIS HF trial, an aldosterone antagonist rather than and ARB should be added to an ACE inhibitor in patients with NYHA class II heart failure and an LVEF < 30%, in the post-MI patient who has an LVEF < 40% who has heart failure symptoms or diabetes, and the patient with class III or IV heart failure who has an LVEF < 35%.
"Triple therapy", the combined use of an ACE inhibitor, an ARB and an aldosterone antagonist is a relative contraindication.

## Beta blockers: Third Step in the Management of Heart Failure
Beta blockers reduce the heart rate which lowers the myocardial energy expenditure. They also prolong diastolic filling and lengthen the period of coronary perfusion.  Beta blockers can also decrease the toxicity of catecholamines on the myocardium.
Once you have achieved a stable dose of a diuretic and an ACE inhibitor, then one of the three beta blockers that have been associated with improved survival (carvedilol, metoprolol succinate or bisoprolol) can be added and the dose titrated based upon the patient's tolerance.  You should avoid beta-blockers with intrinsic sympathomimetic activity (pindolol or acebutolol).  It should be noted that the 35% reduction in one year mortality  observed in meta-analyses of beta-blockers in heart failure was when these drugs were added to ACE inhibitors.  There are no direct comparisons of the various beta-blockers, but some data does suggest that carvedilol may improve LVEF more than the others, but it may not be as well tolerated due to its vasodilatory properties. If the patient has been over diuresed, they may not tolerate the addition of a beta blocker.
- Asthma or bronchospasm
- Hypotension resulting in poor end organ perfusion or symptoms
- Bradycardia or heart block (first degree heart block with a PR interval > 0.24, second degree heart block, third degree heart block
- Peripheral arterial disease with limb ischemia at rest
- Moderate or greater peripheral edema
- Recent intravenous inotropic therapy
Given the potential for hemodynamic decompensation, the initiation of beta-blockers is best undertaken by an individual or center specializing in heart failure management.  The patient should be aware of potential side effects, and should be aware that it may take one to three months for the beta-blockers to improve heart failure symptoms.  Therapy is initiated with very low doses, and the dose of the beta-blocker should be doubled every two weeks until the target dose is achieved or symptoms prevent further dose escalation.
- Carvedilol: Initial dose 3.125 mg twice daily, target dose 25 to 50 mg twice daily
- Metoprolol succinate: Initial dose 12.5 mg daily, target dose 200 mg daily
- Bisoprolol: Initial dose 1.25 mg daily, target dose 5 to 10 mg daily
Weight gain or peripheral edema that is not responsive to diuresis may require a reduction in the dose of beta-blockers.

## Aldosterone Antagonism: Fourth Step in the Management of Heart Failure
An aldosterone antagonist can be added to the regimen of 'select' patients.  These selected patients include:
- Class II heart failure and a left ventricular ejection fraction (LVEF) < 30%
- Class III/IV heart failure and a LVEF <35%
- Post ST segment elevation MI and a LVEF < 40% who have either symptomatic heart failure or diabetes.
- The serum potassium must be under 5.0 meq/li and the glomerular filtration rate (GFR) should be > 30 cc per minute
A requirement for aldosterone antagonist is that the patient's renal function and potassium can be carefully monitored. Eplerenone has fewer endocrine side effects (1%) than spironolactone (10%), but is more costly.  A reasonable strategy is to initiate therapy with spironolactone at a dose of 25 to 50 mg daily, and then switch to eplerenone at a dose of 25 to 50 mg daily if endocrine side effects develop.
Risk Factors for the Development of Hyperkalemia on an Aldosterone Antagonist
- Triple therapy with an ACE inhibitor and angiotensin II receptor blocker makes this combination a contraindication
- Higher doses of either an ACE inhibitor or an angiotensin receptor blocker (ARB)
- Hyperkalemia prior to initiation of spironolactone
- Comorbidities such as diabetes and chronic renal insufficiency
- Higher NYHA heart failure class
- Concomitant administration of beta blockers, nonsteroidal anti-inflammatory drugs (NSAIDs) or potassium supplements
- A daily dose of Spironolactone greater than 50 mg

## The Combination of Hydralazine and a Nitrate: Fifth step in the Management of Heart Failure
The combination of hydralazine and a nitrate (particularly among black patients) can be added if the patient continues to have symptoms on a diuretic, ACE inhibitor (or ARB in the intolerant patient) and a beta blocker.  The initial dose is isosorbide dinitrate 20 mg three times a day along with hydralazine 25 mg three times a day.  The dose(s) can be increased every 2 to 4 weeks to a target dose of isosorbide dinitrate 40 mg three times a day and hydralazine 75 mg three times a day.

## Digoxin: Sixth step in the Management of Heart Failure
Digitalis can strengthen the contractility of the heart and can also be useful to achieve rate control in patients with heart failure who also have atrial fibrillation. In the DIG trial, digoxin reduced the rate of re-hospitalization but did not improve mortality among all patients enrolled in the trial. However, in a retrospective analysis, mortality was reduced in male patients who had digoxin levels between 0.5 and 0.8 ng/mL and was increased in male patients with digoxin levels > 1.2 ng/ml.  A similar trend was observed among women patients: there was a trend towards lower mortality at digoxin concentrations between 0.5 to 0.9 ng/ml, but significantly higher mortality at digoxin concentrations > 1.2 ng/ml.
Digoxin should not be used as primary therapy for congestive heart failure.  The administration of digoxin is reasonable in patients with NYHA class II-IV heart failure symptoms who have an LVEF of < 40% despite treatment with diuretics, angiotensin-converting enzyme inhibitors, beta blockers, and an aldosterone antagonist.  Small doses of 0.125 mg per day of digoxin are often effective in maintaining a serum digoxin level between 0.5 and 0.8 ng/ml.

## Cardiac Resynchronization Therapy
Cardiac Resynchronization Therapy (CRT) is recommended in congestive heart failure patients with:
- Symptoms: NYHA Class II-IV
- QRS: A prolonged QRS interval > 0.12
- LVEF: A LVEF < 30% to 35%

## Percutaneous Coronary Intervention (PCI):
Coronary artery disease (CAD) and impaired blood flow to the heart is one of the main causes of heart failure. Relieving the blockages in the coronary arteries can improve overall heart function, which may improve or resolve heart failure symptoms. The procedure is usually performed in a cardiac catherization laboratory. A catheter, a very small tube with a tiny deflated balloon on the end, is inserted through an incision in the groin area and then guided over a floppy wire to the section of the diseased artery. The balloon is then inflated to prop open the artery. The balloon is deflated and withdrawn once the artery has been fully opened. A stent may be placed during the procedure to keep the blood vessel open. Clinical trials have demonstrated that percutaneous coronary intervention (PCI) is a very effective and safe procedure to dilate blocked vessels and can improve a patient's symptoms if ischemia or lack of blood flow is the problem.

## Left Ventricular Assist Device (LVAD):
A left ventricular assist device (LVAD) is a mechanical pump-type device that can help maintain the pumping ability of a failing heart.  One type of LVAD has tubing that pulls blood from the left ventricle into a pump. The pump then ejects blood into the aorta.  LVADs are typically used for weeks to months as a "bridge" to more definitive therapy such as a heart transplant rather than as a final or "destination" therapy.

## Intracardiac defibrillator
Fifty percent of patients with heart failure die of sudden cardiac death. ICDs are indicated for patients with previous myocardial infarction and an LVEF <30%, sustained ventricular tachycardia, inducible ventricular tachycardia. The morbidity and mortality benefit of ICD placement compared with anti-arrhythmic drug therapy is controversial.

## Ultrafiltration
In the setting of congestive heart failure, ultrafiltration has been associated with a reduced incidence of hospitalization compared with diuretics in the UNLOAD trial, but no difference in mortality.

## Heart Transplantation
A Heart transplant may be the only effective treatment option for patients with severe, progressive heart failure that can not be helped by medications, dietary and lifestyle changes. During a heart transplant procedure, the surgeons connect the patient to a heart-lung machine, which takes over the functions of the heart and lungs. Then the surgeons remove the diseased heart and replace it with the donor heart. Finally, the major blood vessels are reconnected and the new heart is ready to work. The outlook for people with heart transplants is good during the first few years after the transplant. Over 85 percent of patients are alive more than a year after their heart transplant.

## End-of-life considerations
End of life care in the patient with congestive heart failure is focused on making the patient comfortable. Invasive procedures should be minimized, and patients may elect to have their defibrillators inactivated. The growing number of patients with Stage IV heart failure (intractable symptoms of fatigue, shortness of breath or chest pain at rest despite optimal medical therapy) should be considered for palliative care or hospice, according to American College of Cardiology/American Heart Association guidelines listed below. Some have argued that any patient with NYHA class III CHF should have a palliative care referral. Palliative care can not only provide symptom management, but also assist with advanced care planning, goals of care in the case of a significant decline, and making sure the patient has a medical power of attorney and discussed his or her wishes with this individual.

## Treatment of special populations
There is unfortunately insufficient data in subgroups of patients to mandate a change to guidelines recommendations regarding the management of heart failure. Dosages should be altered as needed in the elderly or in those with altered metabolism. African american patients may respond to the addition of hydralazineand nitrates to the standard of care in the treatment of heart failure.