Chronic Heart Failure

Definition
Heart failure (HF) o Clinical syndrome in which the hearts inability to properly eject or fill with blood results in circulatory congestion and a constellation of clinical symptoms (dyspnea and fatigue) and signs (edema and rales) Chronic HF o HF that develops or progresses slowly Vascular congestion is common but arterial pressure is well maintained until very late in the course. Exacerbations are precipitated by infection, tachycardia, noncompliance with medications, emotional stress, and arrhythmias. Refractory HF o Inadequate response to usual treatment

Forms of HF

Systolic vs diastolic failure o Systolic failure: HF with depressed ejection fraction (EF)

Inability of the ventricle to contract normally, with symptoms resulting from inadequate cardiac output EF < 40% o Diastolic failure: HF with preserved EF Inability of the ventricle to relax and fill normally, with symptoms from elevated filling pressures EF > 4050% o Systolic and diastolic failure coexist in most patients with HF. Low-output vs high-output HF o Low-output HF: cardiac output at rest < 2.5 L/min per m2 (lower limit of normal) and fails to increase normally with exertion Seen after myocardial infarction (MI), and in hypertension, dilated cardiomyopathy, and valvular or pericardial disease Often accompanied by vasodilation and warm extremities

High-output HF: cardiac output > 3.5 L/min per m2 or upper limit of normal (before development of HF) Seen in hyperthyroidism, anemia, pregnancy, arteriovenous fistulas, beriberi, and Pagets disease, usually with underlying heart disease Left-sided vs right-sided HF
o

Left-sided HF: Left ventricle (LV) is hemodynamically overloaded and/or weakened, resulting in pulmonary congestion (dyspnea, orthopnea) and/or weakness due to an inadequate forward cardiac output. o Right-sided HF: abnormality primarily affecting right ventricle, resulting in peripheral edema, congestive hepatomegaly, and systemic venous distention
o

Epidemiology

All types of HF o Worldwide Affects > 20 million people o Developed countries Overall prevalence in the adult population: 2% Age o More common in elderly persons o Affects 610% of people over the age of 65 years Sex o Relative incidence of HF is lower in women than in men. o Women constitute at least half of the cases of HF because of their longer life expectancy. Lifetime risk of developing HF (North America and Europe) o Approximately 1 in 5 for a 40-year-old Increasing in prevalence and incidence in North America and Europe o In the U.S.

Affects 4.5 million people About 0.5 million new cases annually 1 million hospital admissions annually >50,000 deaths annually Diastolic HF More common in women than in men

Risk Factors

Seen especially in elderly women with hypertension

Advanced age Hypertension Coronary artery disease Diabetes mellitus Dilated or hypertrophic cardiomyopathy Valvular heart disease Cardiotoxins Obesity

Etiology
Etiology Any condition that leads to an alteration in LV structure or function can predispose a patient to developing HF (Table 227-1). In industrialized countries o Coronary artery disease (CAD) has become the predominant cause; responsible for 6075% of cases. o Hypertension contributes to the development of HF in 75% of patients, including most patients with CAD. o Both CAD and hypertension interact to augment the risk of HF, as does diabetes mellitus. Considerable overlap exists between the etiologies of HF in patients with preserved EF and those with depressed EF.

Depressed EF (< 40%)

CAD
o o

Myocardial infarction Myocardial ischemia Chronic pressure overload o Hypertension o Obstructive valvular disease Chronic volume overload o Regurgitant valvular disease o Intracardiac (left-to-right) shunting, e.g., ventricular septal defect o Extracardiac shunting, e.g., patent ductus arteriosus Nonischemic dilated cardiomyopathy o Familial/genetic disorders Secondary to specific genetic defects, encoding cytoskeletal proteins (desmin, cardiac myosin, vinculin), and nuclear membrane proteins (lamin)

Most are inherited in an autosomal dominant fashion. Dilated cardiomyopathy may also be associated with Duchennes, Beckers, and limb girdle muscular dystrophies. o Infiltrative disorders o Toxic/drug-induced damage o Metabolic disorder o Viral o Chagas disease Disorders of rate and rhythm o Chronic bradyarrhythmias o Chronic tachyarrhythmias Unknown o In 2030% of the cases of HF with a depressed EF, the exact etiologic basis is not known. These patients are referred to as having nonischemic, dilated, idiopathic cardiomyopathy.

Preserved EF (>4050%)

CAD
o o

Myocardial infarction Myocardial ischemia Chronic pressure overload o Hypertension o Obstructive valvular disease Nonischemic dilated cardiomyopathy o Infiltrative disorders o Metabolic disorder Pathologic hypertrophy o Primary (hypertrophic cardiomyopathies) o Secondary (hypertension) Aging Restrictive cardiomyopathy o Infiltrative disorders (amyloidosis, sarcoidosis) o Storage diseases (hemochromatosis) Fibrosis Endomyocardial disorders Pulmonary heart disease o Cor pulmonale o Pulmonary vascular disorders High-output states o Conditions that lead to a high cardiac output are seldom responsible for the development of HF in a normal heart.

In the presence of underlying structural heart disease, these conditions can lead to overt HF. o Metabolic disorders Thyrotoxicosis Nutritional disorders (beriberi) o Excessive blood flow requirements Systemic arteriovenous shunting Chronic anemia
o

Pathogenesis

HF with a depressed EF: index event

Damages the heart muscle, with a resultant loss of functioning cardiac myocytes, which disrupts the ability of the myocardium to generate force, thereby preventing the heart from contracting normally Results in a decline in the pumping capacity of the heart In most instances, patients remain asymptomatic or minimally symptomatic following the initial decline in pumping capacity, and develop symptoms only after the severe dysfunction has been present for some time. o Why many patients with LV dysfunction remain asymptomatic is not certain; probably due to compensatory mechanisms that become activated in the presence of cardiac injury and/or LV dysfunction. Activation of the renin-angiotensinaldosterone (RAA) and adrenergic nervous systems helps maintain cardiac output through increased retention of salt and water. Increased myocardial contractility o Heart responds to pressure overload with concentric hypertrophy, and wall tension is maintained. o Over time, or after a new acute insult (e.g., MI), myocardial function deteriorates and the ventricular wall dilates, leading to symptomatic HF. Activation of vasodilatory molecules, including the atrial and brain natriuretic peptides (ANP and BNP), prostaglandins (PGE2 and PGI2), and nitric oxide, offsets the excessive peripheral vasoconstriction. Genetic background, sex, age, or environment may influence these compensatory mechanisms. Transition to symptomatic HF

Accompanied by increasing activation of neurohormonal, adrenergic, and cytokine systems that lead to a series of adaptive changes within the myocardium, collectively referred to as LV remodeling. This term refers to the changes in LV mass, volume, shape, and composition that increase LV wall stress and increase the burden on the already compromised heart.
o

HF with a preserved EF
Understanding of pathogenesis is still evolving. Diastolic dysfunction describes any situation that impairs LV filling. o Reduced LV compliance o Slowed myocardial relaxation o Accelerated heart rate disproportionately shortens diastole. In all of these cases, elevated LV end-diastolic pressures lead to increased pressures in the pulmonary vascular system with resultant dyspnea, edema, etc. Diastolic dysfunction is not the only mechanism responsible for the development of HF with a preserved EF. o Community-based studies suggest that additional mechanisms, such as increased vascular and ventricular (ventricular-vascular) stiffness, may also be important.

Associated Conditions
Atrial fibrillation occurs in 1530% of patients with HF and is a frequent cause of further cardiac decompensation. LV remodeling often leads to mitral valve regurgitation.

Symptoms & Signs

Symptoms

Dyspnea with exertion (early) or at rest (late) Orthopnea o Dyspnea when recumbent; relief with sitting upright or use of several pillows o Nocturnal cough may be present. Paroxysmal nocturnal dyspnea o Attacks of severe shortness of breath and coughing at night; usually awaken patient o Coughing and wheezing often persist even with sitting upright. o Cardiac asthma: nocturnal dyspnea, wheezing, and cough due to bronchospasm

Cheyne-Stokes respiration o Periodic respiration or cyclic respiration o Common in advanced HF and is usually associated with low cardiac output o In the apneic phase, the arterial PO2 falls, and the arterial PCO2 rises. This stimulates the depressed respiratory center, leading to hyperventilation and hypocapnia. The respiratory center is again depressed, the apneic phase recurs, and the cycle repeats. o May be perceived by the patient or the patients family as severe dyspnea or as a transient cessation of breathing Fatigue and weakness GI symptoms o Anorexia o Nausea o Early satiety o Abdominal pain and fullness o Right upper quadrant pain (congestion of the liver and stretching of its capsule) Cerebral symptoms o Altered mental status due to reduced cerebral perfusion Confusion Disorientation Difficulty concentrating Impaired memory Headache Insomnia Anxiety Mood disturbances Nocturia

Physical findings General appearance and vital signs o Systolic blood pressure Normal or high in early HF Generally reduced in advanced HF o Pulse pressure may be diminished o Sinus tachycardia o Cool peripheral extremities o Cyanosis of the lips and nail beds Jugular veins o Jugular venous distention

Differential Diagnosis

Elevated right atrial pressure Positive abdominojugular reflux In the early stages of HF, the jugular venous pressure may appear to be normal at rest but may become abnormally elevated with sustained (~1 min) pressure on the abdomen. o Giant v waves (presence of tricuspid regurgitation) Pulmonary examination o Pulmonary crackles (rales or crepitations) with or without expiratory wheeze o Pleural effusions Often bilateral When unilateral, they occur more frequently in the right pleural space. Cardiac examination o Point of maximal impulse (PMI) may be displaced and sustained (as in hypertension) or weak, as in idiopathic dilated cardiomyopathy. o Third and fourth heart sounds: often present but not specific o Murmurs of mitral and tricuspid regurgitation are frequently present in patients with advanced HF. Abdomen and extremities o Hepatomegaly o Ascites (late sign) o Jaundice (late finding) o Peripheral edema Occurs predominantly in the ankles and pretibial region in ambulatory patients In bedridden patients, edema may be found in the sacral area (presacral edema) and the scrotum. Long-standing edema may be associated with indurated and pigmented skin. Cardiac cachexia o Marked weight loss and cachexia (with severe chronic HF) Depression Sexual dysfunction Pulsus alternans o Regular rhythm with alternation in strength of peripheral pulses o Most common in cardiomyopathy, hypertensive, and ischemic heart disease Decreased urine output
o o

Diagnostic Approach

HF resembles but should be distinguished from: o Conditions in which there is circulatory congestion secondary to abnormal salt and water retention (e.g., renal failure) without any disturbance of cardiac structure or function o Noncardiac causes of pulmonary edema (e.g., acute respiratory distress syndrome) Pulmonary disease with dyspnea o Obstructive airway disease o Diffuse parenchymal lung disease o Pulmonary vascular occlusive disease o Disease of chest wall and respiratory muscles o Cardiac asthma: wheezing secondary to bronchospasm occurring at night Other conditions leading to peripheral edema o Varicose veins, cyclic edema, or gravitational effects: no jugular venous hypertension o Renal disease: abnormal renal function tests, urinalysis o Obesity o Elevation of venous pressure is uncommon. Hepatic cirrhosis o Enlargement of liver o Ascites o Normal jugular venous pressure o Negative abdominojugular reflux

Approach to patient o Detailed history and clinical examination including: Assessment of risk factors for heart failure History regarding use of alcohol, illicit drugs, alternative therapies, chemotherapy Ability to perform activities of daily living o 2-dimensional echocardiography with Doppler flow studies o Electrocardiography (ECG) o Chest radiography o BNP measurement o Coronary angiography in patients with angina or ischemia who are eligible for revascularization Framingham criteria for diagnosis of congestive heart failure o To establish a clinical diagnosis of CHF by these criteria, at least 1 major and 2 minor criteria are required. o Major criteria

Paroxysmal nocturnal dyspnea Neck vein distention Rales Cardiomegaly Acute pulmonary edema S3 gallop Increased venous pressure Positive hepatojugular reflux Minor criteria Extremity edema Night cough Dyspnea on exertion Hepatomegaly Pleural effusion Vital capacity reduced by one-third from normal Tachycardia ( 120 beats/min) Major or minor criterion Weight loss 4.5 kg over 5 days of treatment

Laboratory Tests

Biomarkers o BNP and N-terminal pro-BNP Relatively sensitive markers for the presence of HF with depressed EF Elevated in patients with HF and a preserved EF, albeit to a lesser degree Levels increase with age and renal impairment, are more elevated in women, and can be elevated in right HF from any cause. Levels can be falsely low in obese patients. Levels may normalize in some patients following appropriate treatment. Normal concentration of natriuretic peptides in an untreated patient is extremely useful for excluding the diagnosis of HF. Cannot be used alone to confirm or exclude HF o BNP measurement > 200 pg/mL supports diagnosis. < 40 pg/mL is rarely seen in HF. Useful in diagnosis, prognosis, and monitoring therapy Helps in differentiating between cardiac and pulmonary causes of dyspnea

Troponin T and I, C-reactive protein, and uric acid may be elevated in HF and provide adverse prognostic information. Urinalysis o Albuminuria o High specific gravity o Low sodium level Complete blood count Renal function o Prerenal azotemia o Increased blood urea nitrogen o Increased serum creatinine and cystatin C Electrolytes o Hypokalemia from thiazide diuretics o Hyperkalemia from potassium-retaining diuretics o Dilutional hyponatremia in late HF Liver function testing o Hepatic enzymes; frequently elevated o Elevated direct and indirect bilirubin levels (late finding) Selected patients o Assessment for diabetes mellitus Fasting serum glucose or Oral glucose tolerance test o Dyslipidemia Fasting lipid panel o Thyroid abnormalities Thyroid-stimulating hormone level
o

Imaging
2-dimensional echocardiography with Doppler flow provides: o Noninvasive cardiac imaging: essential for the diagnosis, evaluation, and management of HF o Semiquantitative assessment of LV size and function (severity of ventricular systolic and/or diastolic dysfunction) as well as the presence or absence of valvular and/or regional wall motion abnormalities (indicative of a prior MI) o Presence of left atrial dilation and LV hypertrophy, together with abnormalities of LV diastolic filling provided by pulse-wave and tissue Doppler, are useful for the assessment of HF with a preserved EF. When the EF is normal (50%), systolic function is usually adequate. When the EF is significantly depressed (< 30%), contractility is usually also depressed.

Question diagnosis if all cardiac chambers are normal in volume, shortening, and wall thickness. Chest radiography o Provides useful information about cardiac size and shape o State of the pulmonary vasculature o May identify noncardiac causes of the patients symptoms o Evidence of pulmonary hypertension, interstitial edema, and/or pulmonary edema Cardiac MRI o Provides a comprehensive analysis of cardiac anatomy and function o "Gold standard" for assessing LV mass and volumes
o

Diagnostic Procedures

ECG
o o

Assess cardiac rhythm. Determine the presence of LV hypertrophy or prior MI (presence or absence of Q waves). If old ECGs are available, evolution of LV hypertrophy, particularly with repolarization abnormalities (ST-segment depression and T wave inversion) may suggest comparable evolution in HF. o Determine QRS width to ascertain whether the patient may benefit from resynchronization therapy. o Normal ECG virtually excludes LV systolic dysfunction. Exercise testing o Treadmill or bicycle exercise testing Not routinely advocated for patients with HF Useful for assessing the need for cardiac transplantation in patients with advanced HF Peak oxygen uptake (VO2) < 14 mL/kg per min is associated with a relatively poor prognosis. Patients with a maximum VO2< 14 mL/kg per min have been shown, in general, to have better survival with transplantation than when treated medically.

Classification
HF should be viewed as a continuum that is composed of 4 interrelated stages. o Stage A At high risk for HF, but no evident structural heart disease or symptoms of HF Examples

o o o o

Hypertension CAD Diabetes mellitus

Stage B Structural heart disease without symptoms of HF Examples o Previous MI o Left ventricular systolic dysfunction, as in longstanding hypertension o Asymptomatic valvular disease o Dilated, hypertrophic, or restrictive cardiomyopathy Stage C Structural heart disease with prior or current symptoms of HF o Shortness of breath o Fatigue o Reduced exercise tolerance Stage D Refractory HF requiring specialized interventions o Marked symptoms at rest despite maximal medical therapy (e.g., recurrent hospitalizations or unable to be safely discharged from hospital without specialized interventions) New York Heart Association (NYHA) classification Class I Patients with cardiac disease but without resulting limitation of physical activity Ordinary physical activity does not cause undue fatigue, palpitations, dyspnea, or anginal pain. Class II Patients with cardiac disease resulting in slight limitation of physical activity They are comfortable at rest. Ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain. Class III Patients with cardiac disease resulting in marked limitation of physical activity They are comfortable at rest. Less than ordinary activity causes fatigue, palpitations, dyspnea, or anginal pain.

Class IV Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

Treatment Approach

Recommended therapy, by disease stage[1] o Stage A: at risk, but without structural heart disease or symptomatic heart failure Treat hypertension (if present). Prescribe angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), especially in hypertension. Strongly encourage smoking cessation. Treat lipid disorders. Encourage regular exercise. Strongly discourage alcohol intake and illicit drug use. o Stage B: structural heart disease but without signs or symptoms of heart failure All measures listed under stage A Add beta blocker. Implantable defibrillators with biventricular pacing in selected patients o Stage C: structural heart disease with prior or current symptoms All measures listed under stages A and B Add diuretic. Add digoxin in systolic HF. Add spironolactone. Hydralazine and nitrates in selected patients Restrict dietary salt to < 2 g/d (eliminate salt-rich foods and added salt in cooking or at table). Biventricular pacing and implantable cardioverter defibrillators(ICDs) in selected patients o Stage D: refractory heart failure requiring specialized interventions All measures listed under stages A, B, and C Dietary salt restriction to < 1 g/d Mechanical assist devices Heart transplantation

Specific Treatments

Continuous intravenous inotropic infusions for palliation (does not prolong life) Experimental surgery or drugs Hospice care Drugs that exacerbate HF should be avoided. o Antiarrhythmic agents (exceptions amiodarone and dofetilide) o Calcium-channel blockers o NSAIDs

Management of HF with depressed EF (< 40%)

General measures
Treat comorbid conditions o Hypertension o Lipid disorders o CAD o Diabetes mellitus o Anemia o Sleep-disordered breathing Encourage smoking cessation. Discourage alcohol intake and illicit drug use. o Limit alcohol consumption to 2 standard drinks per day in men or 1 per day in women. o Patients suspected of having alcohol-induced cardiomyopathy should be urged to abstain from alcohol consumption indefinitely. Recommend influenza and pneumococcal vaccines. Achieve optimal weight. Activity o Heavy physical labor is not recommended in HF. o Routine modest exercise has been shown to be beneficial in patients with NYHA classes IIII HF. Regular isotonic exercise such as walking or riding a stationary bicycle ergometer, as tolerated, should be encouraged in compensated HF. o In moderately severe chronic HF: additional rest on weekends, scheduled naps or rest periods, avoidance of strenuous exertion o Avoid temperature extremes and tiring trips. Avoid drugs known to make HF worse. o Calcium antagonists (verapamil, diltiazem) o NSAIDs o Antiarrhythmic agents (all class I agents, sotalol [class III])

Anti-TNF antibodies

Diet
Reduce sodium intake (normal diet contains 610 g of sodium daily). o Dietary restriction of sodium (23 g daily) is recommended in all patients with HF and preserved or depressed EF. o Further restriction (< 2 g daily) may be considered in moderate to severe HF. Fluid restriction o Generally unnecessary unless the patient develops hyponatremia (< 130 meq/L) o Fluid restriction (< 2 L/day) should be considered in hyponatremic patients or for those whose fluid retention is difficult to control despite high doses of diuretics and sodium restriction. Caloric supplementation o Recommended for patients with advanced HF and unintentional weight loss or muscle wasting (cardiac cachexia) o Anabolic steroids are not recommended. o Dietary supplements (nutriceuticals) should be avoided.

Thiazides
Indications o Use thiazides alone in mild stage C HF and in combination with other diuretics in late, severe stage C or D HF. Side effects o Hypokalemia o Hyponatremia o Metabolic alkalosis o Fatigue o Lethargy o Reduced excretion of uric acid or hyperuricemia o Impaired glucose tolerance o Rashes o Thrombocytopenia o Granulocytopenia Specific agents o Hydrochlorothiazide Dosage: 25 mg/d to 25 mg qid o Chlorthalidone Convenient Most widely used long-acting thiazide o Dosage: 25100 mg/d

Loop diuretics

Indications for loop diuretics

o

All forms of HF, with edema or other evidence of fluid accumulation despite treatment with a thiazide, in patients with severe or refractory HF and pulmonary edema Side effects o Metabolic alkalosis o Hypokalemia o Hyperuricemia o Hyperglycemia o Weakness o Nausea o Dizziness Specific agents o Furosemide IV: initial dose, 20 mg (maximum, 80 mg) PO: initial dosage, 2040 mg 12 times daily (maximum, 400 mg/d) o Bumetanide IV: initial dose, 0.5 mg (maximum, 2 mg) PO: initial dosage, 0.51.0 mg 12 times daily (maximum, 10 mg/d) o Torsemide IV: initial dose, 5 mg (maximum, 20 mg) PO: initial dosage, 10-20 mg 12 times daily (maximum, 200 mg/d)

Other diuretics
Metolazone o Dosage: 2.5-5.0 mg 12 times daily (maximum, 20 mg/d) o Actions and indications similar to thiazides Aldosterone antagonists: potassium-sparing diuretics o Shown to have mortality benefit in patients with NYHA class III or IV heart failure Indications o Patients with NYHA class IV or III (previously class IV) HF who have a depressed EF (< 35%) and who are receiving standard therapy, including diuretics, ACE inhibitors, and beta blockers Specific agents o Spironolactone Dose: 12.525 mg/d; max: 2550 mg/d o Eplerenone Dose: 25 mg/d; max: 50 mg/d

Side effects o Hyperkalemia: Monitor potassium and renal function closely. o Nausea o Epigastric distress o Mental confusion o Drowsiness o Gynecomastia (with spironolactone, may substitute eplerenone) o Erythematous eruptions Contraindications to potassium-sparing diuretics o Potassium level > 5 mmol/L Monitor potassium level. o Renal failure Not recommended when the serum creatinine is >2.5 mg/dL (or creatinine clearance is < 30 mL/min) o Hyponatremia

ACE inhibitors
ACE inhibitors have a central role in prevention and treatment of HF at all stages. o Overwhelming evidence that ACE inhibitors should be used in symptomatic and asymptomatic patients with a depressed EF (< 40%). Contraindications o Do not use in hypotensive, pregnant, or possibly pregnant patients. Side effects o Cough o Angioneurotic edema o Leukopenia o Teratogenic effects in first trimester o Hypotension o Hyperkalemia o Renal insufficiency Patients intolerant of ACE inhibitors because of hyperkalemia or renal insufficiency are likely to experience the same side effects with ARBs. o In these cases, the combination of hydralazine and an oral nitrate should be considered. Specific agents o Enalapril maleate Initial dosage: 2.5 mg bid (maximum, 10 mg bid) o Fosinopril sodium

o o

Initial dosage: 510 mg/d (maximum, 40 mg/d) Lisinopril Initial dosage: 2.55.0 mg/d (maximum, 20 35 mg/d) Quinapril hydrochloride Initial dosage: 10 mg bid (maximum, 40 mg bid) Ramipril Initial dosage: 1.252.5 bid (maximum, 2.5 5.0 mg bid) Trandolapril Initial dose: 0.5 mg/d (maximum, 4 mg/d) Captopril Initial dose: 6.25 mg tid (maximum, 50 mg tid)

ARBs
Indications for ARBs o Symptomatic and asymptomatic patients with an EF < 40% who are ACE-intolerant for reasons other than hyperkalemia or renal insufficiency o Should be used instead of, not with ACE inhibitors Worse outcomes and greater adverse events seen in non-hypertensive patients who had ARB added to ACE and beta-blocker therapy[2] Side effects o Hypotension o Azotemia o Hyperkalemia Specific agents o Losartan Initial dosage, 12.5 mg qd; target dosage, 50 mg bid o Valsartan Initial dosage, 40 mg bid; target dose, 160 mg bid o Candesartan Initial dosage, 4 mg qd; target dose, 32 mg qd o Irbesartan Initial dosage, 75 mg qd; target dose, 300 mg qd

Beta blockers

Indications for beta blockers: o Patients with symptomatic or asymptomatic HF and a depressed EF < 40%

Stabilize first with diuretics, ACE inhibitor (or ARBs) Begin with low doses. Up-titrate dose slowly. Observe closely for hypotension, bradycardia, and worsening HF. Contraindications o Unstable HF o Hypotension o Severe fluid overload o Recent receipt of intravenous inotropic agents o Sinus bradycardia o Atrioventricular block o Bronchospastic disorders 15% of patients cannot tolerate beta blockade. 15% cannot tolerate target doses. o Low-dose beta blockade is preferable to no therapy. Specific agents o Bisoprolol Initial dosage, 1.25 mg/d (maximum, 10 mg/d) o Carvedilol Initial dosage, 3.125 mg bid (maximum, 25 50 mg bid) o Metoprolol CR/XL Initial dosage, 12.525 mg/d (maximum, 200 mg/d) o Survival benefit has not been shown for other agents in this class such as xamoterol and bucindolol. [2]
o o

Special populations

Combination of hydralazine and isosorbide dinitrate o Recommended as part of standard therapy in addition to beta blockers and ACE inhibitors for African Americans with NYHA classes IIIV HF o Specific agents Combination hydralazine/isosorbide dinitrate o Initial dose: 1025 mg/10 mg tid (maximum: 75 mg/40 mg tid) Fixed-dose hydralazine/isosorbide dinitrate o Initial dose: 37.5 mg/20 mg (1 tablet) tid (maximum: 75 mg/40 mg [2 tablets] tid)

Patients who remain symptomatic

Additional pharmacologic therapy should be considered in patients who have persistent symptoms or progressive

worsening despite optimized therapy with an ACE inhibitor and beta blocker. o Agents that may be considered as part of additional therapy include: ARB (See above.) Spironolactone (See above.) Combination of hydralazine and isosorbide dinitrate (See above.) Digoxin (See below.) o The optimal choice of additional drug therapy to further improve outcome has not been firmly established.

Digoxin
Indications for digoxin o Patients with symptomatic LV systolic dysfunction who have concomitant atrial fibrillation/flutter with rapid ventricular response Especially useful in this setting o Consider for patients who have signs or symptoms of HF with reduced EF and sinus rhythm while receiving standard therapy, including ACE inhibitors and beta blockers. Reduces symptoms of HF and need for hospitalization Does not improve survival No value in HF with sinus rhythm and the following conditions: o Any form of diastolic HF o Hypertrophic cardiomyopathy (contraindicated) o Myocarditis o Mitral stenosis o Chronic constrictive pericarditis Oral dosage o Initiated and maintained at a dose of 0.1250.25 mg daily o Great majority of patients, the dose should be 0.125 mg daily o No indication for using loading doses of digoxin to initiate therapy in patients with chronic HF Serum digoxin level should be < 1.0 ng/mL, especially in: o Elderly patients o Patients with impaired renal function o Patients with low lean body mass Complications: digitalis intoxication o Serious and potentially fatal

Risk factors for adverse responses to digoxin Advanced age Hypokalemia Hypomagnesemia Hypoxemia Renal insufficiency Hypercalcemia Acute MI Quinidine, verapamil, amiodarone, and propafenone therapy o Reduce digoxin dose by half when patient is receiving these drugs. o Signs and symptoms Anorexia Nausea and vomiting Exacerbations of HF Weight loss Cachexia Neuralgias Yellow vision Delirium Gynecomastia Most frequent disturbances of cardiac rhythm o Nonparoxysmal atrial tachycardia and/or variable atrioventricular block o Ventricular premature beats, bigeminy o Ventricular tachycardia or rarely ventricular fibrillation Treatment o Discontinue digoxin therapy. o Beta blocker or lidocaine o Oral potassium replacement (if hypokalemic) o Fab fragments of purified, intact digoxin antibodies (if life threatening)
o

Anticoagulation and antiplatelet therapy

Routine anticoagulation is not indicated. Warfarin

o

Indications Patients with HF and chronic or paroxysmal atrial fibrillation, or with a history of systemic or pulmonary emboli, including stroke or transient ischemic attack o Duration: indefinite, unless there are contraindications

Patients with symptomatic or asymptomatic ischemic cardiomyopathy and documented recent large anterior MI or recent MI with documented LV thrombus o Duration: initial 3 months after MI, unless there are contraindications o Goal international normalized ratio (INR) 2.03.0 Aspirin o Recommended in HF patients with ischemic heart disease for the prevention of MI and death o Lower doses of aspirin (75 or 81 mg) preferable

Management of cardiac arrhythmias

Atrial fibrillation occurs in 1530% of patients with HF and is a frequent cause of cardiac decompensation. Premature ventricular contractions and asymptomatic ventricular tachycardia (VT) are common in advanced HF. Sudden death due to ventricular fibrillation causes half of all deaths in advanced HF. Treatment of arrhythmias o Correction of electrolyte and acidbase disturbances (especially hypokalemia and digoxin intoxication) o Amiodarone (class III antiarrhythmic) Effective against most supraventricular arrhythmias Preferred drug for restoring and maintaining sinus rhythm, and it may improve the success of electrical cardioversion in patients with HF. Caution: increases the level of phenytoin and digoxin and prolongs the INR in patients taking warfarin Rate of adverse events, such as hyperthyroidism, hypothyroidism, pulmonary fibrosis, and hepatitis, is relatively low, particularly when lower doses of amiodarone are used (100 200 mg/d). o Class I antiarrhythmics (quinidine, procainamide, flecainide) are contraindicated in HF. o Automatic ICD has been shown to prolong life. After resuscitation from sudden death Syncope or presyncope due to ventricular arrhythmia Asymptomatic VT VT can be induced during electrophysiologic testing.

Systolic HF with EF < 35% ICD is often combined in a single device with ventricular resynchronization. May be used as stand-alone therapy or in combination with amiodarone and/or a beta blocker. There is no role for treating ventricular arrhythmias with an antiarrhythmic agent without an ICD.

Device therapy
Cardiac resynchronization o Biventricular pacing, also termed cardiac resynchronization therapy (CRT) Indications o Patients in sinus rhythm with an EF < 35% and a QRS >120 msec; no benefit seen in patients who do not have a wide QRS complex o Patients who remain symptomatic (NYHA classes IIIV) despite optimal medical therapy Efficacy (CRT added to optimal medical therapy in patients in sinus rhythm): o Significant decrease in patient mortality and morbidity (hospitalization) o Reversal of LV remodeling o Improved quality of life and exercise capacity ICDs o Indications[1] To prolong survival in patients with reduced LV EF and history of cardiac arrest, ventricular fibrillation, or hemodynamically unstable ventricular tachycardia To prevent sudden cardiac death and reduce mortality in patients with: o Nonischemic dilated cardiomyopathy or ischemic heart disease >40 days post-MI o LV EF 35% o NYHA functional class II or III symptoms on optimal medical therapy o Expected survival with good functional status for > 1 year o Prophylactic implantation of ICDs in patients with mild to moderate HF (NYHA classes IIIII) has been shown to reduce the incidence of sudden cardiac death

in patients with ischemic or nonischemic cardiomyopathy. o ICD may be combined with a biventricular pacemaker in appropriate patients.

Refractory HF
Therapeutic options o Combination diuretics o LV or biventricular pacing o Additional vasodilators o Intravenous nitroglycerin o Mechanical circulatory support o Cardiac transplantation o Novel cardiac surgery, often accompanies multivessel coronary artery bypass grafting Ventricular remodeling surgery Mitral valve repair o Mechanical removal of extracellular fluid Thoracentesis Paracentesis Exhaustion of all therapeutic options o Comfort care; possible hospice o Continuous infusions of inotropic agents Relieve symptoms, may stabilize patient awaiting transplantation but may shorten life (See Acute Heart Failure for dosing.) Dopamine if hypotension is present Dobutamine in normotensive patients o Consider continued infusions of inotropic agents, diuretics, anxiolytics, and analgesics.

Management of HF with a preserved EF (>4050%) There are no proven and/or approved pharmacologic or device therapies for the management of patients with HF and a preserved EF. Recommendations o Initial treatment efforts should be focused on the underlying disease process (e.g., myocardial ischemia, hypertension) associated with HF with preserved EF. o Precipitating factors, such as tachycardia or atrial fibrillation, should be treated as quickly as possible through rate control and restoration of sinus rhythm when appropriate. o Dyspnea may be treated by reducing total blood volume (dietary sodium restriction and diuretics), decreasing central blood volume (nitrates), or blunting

neurohormonal activation with ACE inhibitors, ARBs, and/or beta blockers. o Treatment with diuretics and nitrates should be initiated at low doses to avoid hypotension and fatigue.

Monitoring
Daily measurement of weight to aid in adjustment of diuretic dosage Laboratory monitoring o Electrolytes and renal function should be routinely measured. Potassium levels are particularly important. o Serial BNP measurements BNP has a short half-life and can be used to monitor effect of therapy. Yearly ECG to evaluate rhythm and QRS duration to identify candidates for cardiac resynchronization therapy[3] Education of patient and family about condition and critical importance of close attention to compliance Supervision of outpatient care by specially trained nurse or physician assistant Planning for hospital discharge o Patient education with a specific focus on: Salt and fluid status and obtaining daily weights Medication schedules o Criteria for discharge should include: At least 24 hours of stable fluid status, blood pressure, and renal function on the oral regimen planned for home Patient should be free of dyspnea or symptomatic hypotension while at rest, washing, and walking on the ward

Complications
Arrhythmias Sudden death, most due to ventricular fibrillation o Responsible for ~50% of all deaths in heart failure o Can be prevented by ICD Pulmonary emboli secondary to venous thrombosis and systemic emboli secondary to intracardiac thrombi o Patients with HF and atrial fibrillation, previous venous thrombosis, and pulmonary or systemic emboli are at especially high risk and requireanticoagulation. Increased risk for arterial or venous thromboembolic events

In clinical HF trials, the rate of stroke ranges from 1.32.4% per year.
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Prognosis
Poor prognostic factors include: o Severely depressed EF (< 20%) o Reduced maximal oxygen uptake (< 14 mL/kg per min) o Inability to walk on a level and at a normal pace for > 3 minutes o Reduced serum sodium concentration (< 133 mEq/L) o Reduced serum potassium concentration (< 3 mEq/L) o Markedly elevated BNP level (>500 pg/mL) o Frequent ventricular extrasystoles o Decreasing hematocrit o Worsening NYHA functional status o Widened QRS on ECG o Chronic hypotension o Resting tachycardia o Renal insufficiency o Intolerance to conventional therapy o Refractory volume overload Natural history of HF: progressive but not predictable o Annual mortality rate Asymptomatic patients: < 5% Mild disease: 10% Moderate disease: 2030% Severe disease: 3080% o Mechanism of death Sudden death: 50% Worsening HF (pump failure): 40% Other: 10% o Survival rate of up to 80% at 2 years for patients rendered free of congestion o Survival rate may be as low as 50% at 6 months in patients with refractory symptoms. Development of symptomatic HF still carries a poor prognosis. o 3040% of patients die within 1 year of diagnosis. o 6070% die within 5 years. Functional status is an important predictor of patient outcome. o Patients with symptoms at rest (NYHA class IV): 3070% annual mortality rate

Patients with symptoms with moderate activity (NYHA class II): 510% annual mortality rate
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Prevention
For persons at risk for HF o Treat hypertension. o Prescribe ACE inhibitors or ARBs. o Encourage smoking cessation. o Treat lipid disorders. o Encourage regular exercise. o Discourage alcohol intake and illicit drug use. Patients with established HF o All of the above measures o Dietary salt restriction o Immunization with influenza and pneumococcal vaccines to prevent respiratory infection o Should avoid temperature extremes and tiring trips

ICD-9-CM See Also

428.9 Heart failure, unspecified Acute Heart Failure Weight Loss, Unintentional Cor Pulmonale Dilated Cardiomyopathy Dyspnea Edema Heart Transplantation Myocarditis Pulmonary Arterial Hypertension, Secondary Pulmonary Edema

Internet Sites
Professionals o Homepage American Heart Association Patients o Heart Failure American Heart Association o Heart failure MedlinePlus

References
1. Hunt SA et al: 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung

Transplantation.Circulation 119:e391, 2009 [PMID:19324966] 2. Ramani GV, Uber PA, Mehra MR: Chronic heart failure: contemporary diagnosis and management. Mayo Clin Proc 85:180, 2010 [PMID:20118395] 3. Cubbon RM, Witte KK: Cardiac resynchronisation therapy for chronic heart failure and conduction delay. BMJ 338:, 2009 [PMID:19401320]

General Bibliography
ACC/AHA: Guidelines for the Evaluation and Management of Chronic Heart Failure in the AdultExecutive Summary. J Am Coll Cardiol 46: 1116, 2005. Full report found at American Heart Association Bardy GH et al: Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 352:225, 2005 [PMID:15659722] Colucci WS, Braunwald E (eds): Heart Failure: Cardiac Function and Dysfunction, in Atlas of Heart Diseases, 3d ed. Philadelphia, Current Medicine, 2002 Doust J, Lehman R, Glasziou P: The role of BNP testing in heart failure. Am Fam Physician 74:1893, 2006 [PMID:17168346] Kitzman DW et al: Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA 288:2144, 2002 [PMID:12413374] Kociol RD et al: Troponin elevation in heart failure prevalence, mechanisms, and clinical implications. J Am Coll Cardiol 56:1071, 2010 [PMID:20863950] Maisel AS et al: Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 347:161, 2002 [PMID:12124404]

Mann DL: Management of heart failure patients with reduced ejection fraction, in Braunwalds Heart Disease, 8th ed, P Libby et al (eds). Philadelphia, Elsevier, 2008. McAlister FA et al: Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review. JAMA 297:2502, 2007 [PMID:17565085] Moss AJ et al: Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med346:877, 2002 [PMID:11907286] Mosterd A, Hoes AW: Clinical epidemiology of heart failure. Heart93:1137, 2007 [PMID:17699180]

Sanderson JE: Heart failure with a normal ejection fraction. Heart93:155, 2007 [PMID:16387829] Stevenson LW: Heart Failure, in Cardiology for the Primary Care Physician, 2d ed, E Braunwald, L Goldman (eds). Philadelphia, Saunders, 2003 Van Bommel RJ et al: Critical appraisal of the use of cardiac resynchronization therapy beyond current guidelines. J Am Coll Cardiol56:754, 2010 [PMID:20797487] This topic is based on Harrisons Principles of Internal Medicine, 17th edition, chapter 227 Heart Failure and Cor Pulmonale by DL Mann.

PEARLS

HF is the price paid for success.

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As new treatments have reduced the mortality of acute MI, patients become candidates for later development of HF. Suspect HF in middle-aged or elderly patients who develop "asthma" for the first time.