Heart Failure

Author: Ioana Dumitru, MD; Chief Editor: Henry H Ooi, MB, MRCPI more...

Updated: Apr 5, 2013

Practice EssentialsHeart failure is when the heart, via an abnormality of cardiac function (detectable or not), fails to pump blood at a ratecommensurate with the requirements of the metabolizing tissues or is able to do so only with an elevated diastolicfilling pressure.

Essential update: FDA approves imaging agent for cardiac risk evaluation in heart failure patients

In March 2013, the FDA approved the scintigraphic imaging agent iobenguane I 123 injection (AdreView) for theevaluation of myocardial sympathetic innervation in patients with NYHA class 23 heart failure with an LVEF 35%. Theradionuclide tracer, which functions molecularly as a norepinephrine analog, can show relative levels of norepinephrineuptake in the cardiac sympathetic nervous system and contribute to risk stratification in heart failure patients. Improvedreuptake of norepinephrine is associated with a better prognosis.[1]

Signs and symptoms

Signs and symptoms of heart failure include the following:

Exertional dyspnea and/or dyspnea at restOrthopneaAcute pulmonary edemaChest pain/pressure and palpitationsTachycardiaFatigue and weaknessNocturia and oliguriaAnorexia, weight loss, nauseaExophthalmos and/or visible pulsation of eyesDistention of neck veinsWeak, rapid, and thready pulseRales, wheezingS3 gallop and/or pulsus alternansIncreased intensity of P2 heart soundHepatojugular refluxAscites, hepatomegaly, and/or anasarcaCentral or peripheral cyanosis, pallor

See Clinical Presentation for more detail.

Diagnosis

Heart failure criteria, classification, and staging

Medscape ReferenceReference

NewsReferenceEducationMEDLINE

Heart Failure http://emedicine.medscape.com/article/163062-overview

1 of 27 14/04/2013 15:17

The Framingham criteria for the diagnosis of heart failure consists of the concurrent presence of either 2 major criteriaor 1 major and 2 minor criteria.[2]

Major criteria include the following:

Paroxysmal nocturnal dyspneaWeight loss of 4.5 kg in 5 days in response to treatmentNeck vein distentionRalesAcute pulmonary edemaHepatojugular refluxS3 gallopCentral venous pressure greater than 16 cm waterCirculation time of 25 secondsRadiographic cardiomegalyPulmonary edema, visceral congestion, or cardiomegaly at autopsy

Minor criteria are as follows:

Nocturnal coughDyspnea on ordinary exertionA decrease in vital capacity by one third the maximal value recordedPleural effusionTachycardia (rate of 120 bpm)Bilateral ankle edema

The New York Heart Association (NYHA) classification system categorizes heart failure on a scale of I to IV,[3] asfollows:

Class I: No limitation of physical activityClass II: Slight limitation of physical activityClass III: Marked limitation of physical activityClass IV: Symptoms occur even at rest; discomfort with any physical activity

The American College of Cardiology/American Heart Association (ACC/AHA) staging system is defined by thefollowing 4 stages[4, 5] :

Stage A: High risk of heart failure but no structural heart disease or symptoms of heart failureStage B: Structural heart disease but no symptoms of heart failureStage C: Structural heart disease and symptoms of heart failureStage D: Refractory heart failure requiring specialized interventions

Testing

The following basic tests may be useful in the initial evaluation for suspected heart failure[4, 6, 7] :

Complete blood count (CBC)UrinalysisElectrolyte levelsRenal and liver function studiesFasting blood glucose levelsLipid profileThyroid stimulating hormone (TSH) levelsB-type natriuretic peptide levelsN-terminal pro-B-type natriuretic peptideElectrocardiographyChest radiography2-dimensional (2-D) echocardiographyMaximal exercise testingPulse oximetry or arterial blood gas

See Workup for more detail.

Management

Treatment includes the following:

Nonpharmacologic therapy: Oxygen and noninvasive positive pressure ventilation, dietary sodium and fluid


2 of 27 14/04/2013 15:17

restriction, physical activity as appropriate, and attention to weight gainPharmacotherapy: Diuretics, vasodilators, inotropic agents, anticoagulants, beta blockers, and digoxin

Surgical options

Surgical treatment options include the following:

Electrophysiologic interventionRevascularization proceduresValve replacement/repairVentricular restorationExtracorporeal membrane oxygenationVentricular assist devicesHeart transplantationTotal artificial heart

See Treatment and Medication for more detail.

Image library

This chest radiograph shows an enlarged cardiac silhouette and edema at the lung bases, signs of acute heart failure.

BackgroundHeart failure is the pathophysiologic state in which the heart, via an abnormality of cardiac function (detectable or not),fails to pump blood at a rate commensurate with the requirements of the metabolizing tissues or is able to do so onlywith an elevated diastolic filling pressure.

Heart failure (see the images below) may be caused by myocardial failure but may also occur in the presence ofnear-normal cardiac function under conditions of high demand. Heart failure always causes circulatory failure, but theconverse is not necessarily the case, because various noncardiac conditions (eg, hypovolemic shock, septic shock)can produce circulatory failure in the presence of normal, modestly impaired, or even supranormal cardiac function. Tomaintain the pumping function of the heart, compensatory mechanisms increase blood volume, cardiac fillingpressure, heart rate, and cardiac muscle mass. However, despite these mechanisms, there is progressive decline inthe ability of the heart to contract and relax, resulting in worsening heart failure.

This chest radiograph shows an enlarged cardiac silhouette and edema at the lung bases, signs of acute heart failure.


3 of 27 14/04/2013 15:17

A 28-year-old woman presented with acute heart failure secondary to chronic hypertension. The enlarged cardiac silhouette on thisanteroposterior (AP) radiograph is caused by acute heart failure due to the effects of chronic high blood pressure on the left ventricle.The heart then becomes enlarged, and fluid accumulates in the lungs (ie, pulmonary congestion).

This magnetic resonance image shows a scar in the anterior cardiac wall, which may be indicative of a previous myocardial infarction(MI). MIs can precipitate heart failure.

Signs and symptoms of heart failure include tachycardia and manifestations of venous congestion (eg, edema) andlow cardiac output (eg, fatigue). Breathlessness is a cardinal symptom of left ventricular (LV) failure that may manifestwith progressively increasing severity.

Heart failure can be classified according to a variety of factors (see Heart Failure Criteria and Classification). The NewYork Heart Association (NYHA) classification for heart failure comprises 4 classes, based on the relationship betweensymptoms and the amount of effort required to provoke them, as follows[3] :

Class I patients have no limitation of physical activityClass II patients have slight limitation of physical activityClass III patients have marked limitation of physical activityClass IV patients have symptoms even at rest and are unable to carry on any physical activity withoutdiscomfort

The American College of Cardiology/American Heart Association (ACC/AHA) heart failure guidelines complement theNYHA classification to reflect the progression of disease and are divided into 4 stages, as follows[4, 5] :

Stage A patients are at high risk for heart failure but have no structural heart disease or symptoms of heartfailureStage B patients have structural heart disease but have no symptoms of heart failureStage C patients have structural heart disease and have symptoms of heart failureStage D patients have refractory heart failure requiring specialized interventions

Laboratory studies for heart failure should include a complete blood count (CBC), electrolytes, and renal functionstudies. Imaging studies such as chest radiography and 2-dimensional echocardiography are recommended in theinitial evaluation of patients with known or suspected heart failure. B-type natriuretic peptide (BNP) and N-terminalpro-B-type natriuretic peptide (NT-proBNP) levels can be useful in differentiating cardiac and noncardiac causes ofdyspnea. (See the Workup Section for more information.)

In acute heart failure, patient care consists of stabilizing the patient's clinical condition; establishing the diagnosis,etiology, and precipitating factors; and initiating therapies to provide rapid symptom relief and survival benefit. Surgicaloptions for heart failure include revascularization procedures, electrophysiologic intervention, cardiac resynchronizationtherapy (CRT), implantable cardioverter-defibrillators (ICDs), valve replacement or repair, ventricular restoration, hearttransplantation, and ventricular assist devices (VADs). (See the Treatment Section for more information.)

The goals of pharmacotherapy are to increase survival and to prevent complications. Along with oxygen, medicationsassisting with symptom relief include diuretics, digoxin, inotropes, and morphine. Drugs that can exacerbate heartfailure should be avoided (nonsteroidal anti-inflammatory drugs [NSAIDs], calcium channel blockers [CCBs], and mostantiarrhythmic drugs). (See the Medication Section for more information.)

For further information, see the Medscape Reference articles Pediatric Congestive Heart Failure, Congestive HeartFailure Imaging, Heart Transplantation, Coronary Artery Bypass Grafting, and Implantable Cardioverter-Defibrillators.

PathophysiologyThe common pathophysiologic state that perpetuates the progression of heart failure is extremely complex,regardless of the precipitating event. Compensatory mechanisms exist on every level of organization, from subcellularall the way through organ-to-organ interactions. Only when this network of adaptations becomes overwhelmed does


4 of 27 14/04/2013 15:17

heart failure ensue.[8, 9, 10, 11, 12]

Adaptations

Most important among the adaptations are the following[13] :

The Frank-Starling mechanism, in which an increased preload helps to sustain cardiac performanceAlterations in myocyte regeneration and deathMyocardial hypertrophy with or without cardiac chamber dilatation, in which the mass of contractile tissue isaugmentedActivation of neurohumoral systems

The release of norepinephrine by adrenergic cardiac nerves augments myocardial contractility and includes activationof the renin-angiotensin-aldosterone system [RAAS], the sympathetic nervous system [SNS], and other neurohumoraladjustments that act to maintain arterial pressure and perfusion of vital organs.

In acute heart failure, the finite adaptive mechanisms that may be adequate to maintain the overall contractileperformance of the heart at relatively normal levels become maladaptive when trying to sustain adequate cardiacperformance.[14]

The primary myocardial response to chronic increased wall stress is myocyte hypertrophy, death/apoptosis, andregeneration.[15] This process eventually leads to remodeling, usually the eccentric type. Eccentric remodeling furtherworsens the loading conditions on the remaining myocytes and perpetuates the deleterious cycle. The idea oflowering wall stress to slow the process of remodeling has long been exploited in treating heart failure patients.[16]

The reduction of cardiac output following myocardial injury sets into motion a cascade of hemodynamic andneurohormonal derangements that provoke activation of neuroendocrine systems, most notably the above-mentionedadrenergic systems and RAAS.[17]

The release of epinephrine and norepinephrine, along with the vasoactive substances endothelin-1 (ET-1) andvasopressin, causes vasoconstriction, which increases calcium afterload and, via an increase in cyclic adenosinemonophosphate (cAMP), causes an increase in cytosolic calcium entry. The increased calcium entry into the myocytesaugments myocardial contractility and impairs myocardial relaxation (lusitropy).

The calcium overload may induce arrhythmias and lead to sudden death. The increase in afterload and myocardialcontractility (known as inotropy) and the impairment in myocardial lusitropy lead to an increase in myocardial energyexpenditure and a further decrease in cardiac output. The increase in myocardial energy expenditure leads tomyocardial cell death/apoptosis, which results in heart failure and further reduction in cardiac output, perpetuating acycle of further increased neurohumoral stimulation and further adverse hemodynamic and myocardial responses.

In addition, the activation of the RAAS leads to salt and water retention, resulting in increased preload and furtherincreases in myocardial energy expenditure. Increases in renin, mediated by decreased stretch of the glomerularafferent arteriole, reduce delivery of chloride to the macula densa and increase beta1-adrenergic activity as aresponse to decreased cardiac output. This results in an increase in angiotensin II (Ang II) levels and, in turn,aldosterone levels, causing stimulation of the release of aldosterone. Ang II, along with ET-1, is crucial in maintainingeffective intravascular homeostasis mediated by vasoconstriction and aldosterone-induced salt and water retention.

The concept of the heart as a self-renewing organ is a relatively recent development.[18] This new paradigm formyocyte biology has created an entire field of research aimed directly at augmenting myocardial regeneration. Therate of myocyte turnover has been shown to increase during times of pathologic stress.[15] In heart failure, thismechanism for replacement becomes overwhelmed by an even faster increase in the rate of myocyte loss. Thisimbalance of hypertrophy and death over regeneration is the final common pathway at the cellular level for theprogression of remodeling and heart failure.

Ang II

Research indicates that local cardiac Ang II production (which decreases lusitropy, increases inotropy, and increasesafterload) leads to increased myocardial energy expenditure. Ang II has also been shown in vitro and in vivo toincrease the rate of myocyte apoptosis.[19] In this fashion, Ang II has similar actions to norepinephrine in heart failure.

Ang II also mediates myocardial cellular hypertrophy and may promote progressive loss of myocardial function. Theneurohumoral factors above lead to myocyte hypertrophy and interstitial fibrosis, resulting in increased myocardialvolume and increased myocardial mass, as well as myocyte loss. As a result, the cardiac architecture changes, which,in turn, leads to further increase in myocardial volume and mass.

Myocytes and myocardial remodeling


5 of 27 14/04/2013 15:17

In the failing heart, increased myocardial volume is characterized by larger myocytes approaching the end of their lifecycle.[20] As more myocytes drop out, an increased load is placed on the remaining myocardium, and this unfavorableenvironment is transmitted to the progenitor cells responsible for replacing lost myocytes.

Progenitor cells become progressively less effective as the underlying pathologic process worsens and myocardialfailure accelerates. These featuresnamely, the increased myocardial volume and mass, along with a net loss ofmyocytesare the hallmark of myocardial remodeling. This remodeling process leads to early adaptive mechanisms,such as augmentation of stroke volume (Frank-Starling mechanism) and decreased wall stress (Laplace's law), and,later, to maladaptive mechanisms such as increased myocardial oxygen demand, myocardial ischemia, impairedcontractility, and arrhythmogenesis.

As heart failure advances, there is a relative decline in the counterregulatory effects of endogenous vasodilators,including nitric oxide (NO), prostaglandins (PGs), bradykinin (BK), atrial natriuretic peptide (ANP), and B-type natriureticpeptide (BNP). This decline occurs simultaneously with the increase in vasoconstrictor substances from the RAASand the adrenergic system, which fosters further increases in vasoconstriction and thus preload and afterload. Thisresults in cellular proliferation, adverse myocardial remodeling, and antinatriuresis, with total body fluid excess andworsening of heart failure symptoms.

Systolic and diastolic failure

Systolic and diastolic heart failure each result in a decrease in stroke volume. This leads to activation of peripheral andcentral baroreflexes and chemoreflexes that are capable of eliciting marked increases in sympathetic nerve traffic.

While there are commonalities in the neurohormonal responses to decreased stroke volume, the neurohormone-mediated events that follow have been most clearly elucidated for individuals with systolic heart failure. The ensuingelevation in plasma norepinephrine directly correlates with the degree of cardiac dysfunction and has significantprognostic implications. Norepinephrine, while directly toxic to cardiac myocytes, is also responsible for a variety ofsignal-transduction abnormalities, such as down-regulation of beta1-adrenergic receptors, uncoupling of beta2-adrenergic receptors, and increased activity of inhibitory G-protein. Changes in beta1-adrenergic receptors result inoverexpression and promote myocardial hypertrophy.

ANP and BNP

ANP and BNP are endogenously generated peptides activated in response to atrial and ventricular volume/pressureexpansion. ANP and BNP are released from the atria and ventricles, respectively, and both promote vasodilation andnatriuresis. Their hemodynamic effects are mediated by decreases in ventricular filling pressures, owing to reductionsin cardiac preload and afterload. BNP, in particular, produces selective afferent arteriolar vasodilation and inhibitssodium reabsorption in the proximal convoluted tubule. It also inhibits renin and aldosterone release and, therefore,adrenergic activation. ANP and BNP are elevated in chronic heart failure. BNP, in particular, has potentially importantdiagnostic, therapeutic, and prognostic implications.

For more information, see the Medscape Reference article Natriuretic Peptides in Congestive Heart Failure.

Other vasoactive systems

Other vasoactive systems that play a role in the pathogenesis of heart failure include the ET receptor system, theadenosine receptor system, vasopressin, and tumor necrosis factor-alpha (TNF-alpha).[21] ET, a substance producedby the vascular endothelium, may contribute to the regulation of myocardial function, vascular tone, and peripheralresistance in heart failure. Elevated levels of ET-1 closely correlate with the severity of heart failure. ET-1 is a potentvasoconstrictor and has exaggerated vasoconstrictor effects in the renal vasculature, reducing renal plasma bloodflow, glomerular filtration rate (GFR), and sodium excretion.

TNF-alpha has been implicated in response to various infectious and inflammatory conditions. Elevations in TNF-alphalevels have been consistently observed in heart failure and seem to correlate with the degree of myocardialdysfunction. Some studies suggest that local production of TNF-alpha may have toxic effects on the myocardium, thusworsening myocardial systolic and diastolic function.

In individuals with systolic dysfunction, therefore, the neurohormonal responses to decreased stroke volume result intemporary improvement in systolic blood pressure and tissue perfusion. However, in all circumstances, the existingdata support the notion that these neurohormonal responses contribute to the progression of myocardial dysfunction inthe long term.

Heart failure with normal ejection fraction

In diastolic heart failure (heart failure with normal ejection fraction [HFNEF]), the same pathophysiologic processesoccur that lead to decreased cardiac output in systolic heart failure, but they do so in response to a different set ofhemodynamic and circulatory environmental factors that depress cardiac output.[22]


6 of 27 14/04/2013 15:17

In HFNEF, altered relaxation and increased stiffness of the ventricle (due to delayed calcium uptake by the myocytesarcoplasmic reticulum and delayed calcium efflux from the myocyte) occur in response to an increase in ventricularafterload (pressure overload). The impaired relaxation of the ventricle then leads to impaired diastolic filling of the leftventricle (LV).

Morris et al found that RV subendocardial systolic dysfunction and diastolic dysfunction, as detected byechocardiographic strain rate imaging, are common in patients with HFNEF. This dysfunction is potentially associatedwith the same fibrotic processes that affect the subendocardial layer of the LV and, to a lesser extent, with RVpressure overload. This may play a role in the symptomatology of patients with HFNEF.[23]

LV chamber stiffness

An increase in LV chamber stiffness occurs secondary to any one of, or any combination of, the following 3mechanisms:

Rise in filling pressureShift to a steeper ventricular pressure-volume curveDecrease in ventricular distensibility

A rise in filling pressure is the movement of the ventricle up along its pressure-volume curve to a steeper portion, asmay occur in conditions such as volume overload secondary to acute valvular regurgitation or acute LV failure due tomyocarditis.

A shift to a steeper ventricular pressure-volume curve results, most commonly, not only from increased ventricularmass and wall thickness (as observed in aortic stenosis and long-standing hypertension) but also from infiltrativedisorders (eg, amyloidosis), endomyocardial fibrosis, and myocardial ischemia.

Parallel upward displacement of the diastolic pressure-volume curve is generally referred to as a decrease inventricular distensibility. This is usually caused by extrinsic compression of the ventricles.

Concentric LV hypertrophy

Pressure overload that leads to concentric LV hypertrophy (LVH), as occurs in aortic stenosis, hypertension, andhypertrophic cardiomyopathy, shifts the diastolic pressure-volume curve to the left along its volume axis. As a result,ventricular diastolic pressure is abnormally elevated, although chamber stiffness may or may not be altered.

Increases in diastolic pressure lead to increased myocardial energy expenditure, remodeling of the ventricle,increased myocardial oxygen demand, myocardial ischemia, and eventual progression of the maladaptivemechanisms of the heart that lead to decompensated heart failure.

Arrhythmias

While life-threatening rhythms are more common in ischemic cardiomyopathy, arrhythmia imparts a significant burdenin all forms of heart failure. In fact, some arrhythmias even perpetuate heart failure. The most significant of all rhythmsassociated with heart failure are the life-threatening ventricular arrhythmias. Structural substrates for ventriculararrhythmias that are common in heart failure, regardless of the underlying cause, include ventricular dilatation,myocardial hypertrophy, and myocardial fibrosis.

At the cellular level, myocytes may be exposed to increased stretch, wall tension, catecholamines, ischemia, andelectrolyte imbalance. The combination of these factors contributes to an increased incidence of arrhythmogenicsudden cardiac death in patients with heart failure.

EtiologyMost patients who present with significant heart failure do so because of an inability to provide adequate cardiac outputin that setting. This is often a combination of the causes listed below in the setting of an abnormal myocardium. The listof causes responsible for presentation of a patient with heart failure exacerbation is very long, and searching for theproximate cause to optimize therapeutic interventions is important.

From a clinical standpoint, classifying the causes of heart failure into the following 4 broad categories is useful:

Underlying causes: Underlying causes of heart failure include structural abnormalities (congenital or acquired)that affect the peripheral and coronary arterial circulation, pericardium, myocardium, or cardiac valves, thusleading to increased hemodynamic burden or myocardial or coronary insufficiencyFundamental causes: Fundamental causes include the biochemical and physiologic mechanisms, throughwhich either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results inimpairment of myocardial contraction


7 of 27 14/04/2013 15:17

Precipitating causes: Overt heart failure may be precipitated by progression of the underlying heart disease(eg, further narrowing of a stenotic aortic valve or mitral valve) or various conditions (fever, anemia, infection) ormedications (chemotherapy, NSAIDs) that alter the homeostasis of heart failure patientsGenetics of cardiomyopathy: Dilated, arrhythmic right ventricular and restrictive cardiomyopathies are knowngenetic causes of heart failure.

Underlying causes

Specific underlying factors cause various forms of heart failure, such as systolic heart failure (most commonly, leftventricular systolic dysfunction), heart failure with preserved LVEF, acute heart failure, high-output heart failure, andright heart failure.

Underlying causes of systolic heart failure include the following:

Coronary artery diseaseDiabetes mellitusHypertensionValvular heart disease (stenosis or regurgitant lesions)Arrhythmia (supraventricular or ventricular)Infections and inflammation (myocarditis)Peripartum cardiomyopathyCongenital heart diseaseDrugs (either recreational, such as alcohol and cocaine, or therapeutic drugs with cardiac side effects, such asdoxorubicin)Idiopathic cardiomyopathyRare conditions (endocrine abnormalities, rheumatologic disease, neuromuscular conditions)

Underlying causes of diastolic heart failure include the following:

Coronary artery diseaseDiabetes mellitusHypertensionValvular heart disease (aortic stenosis)Hypertrophic cardiomyopathyRestrictive cardiomyopathy (amyloidosis, sarcoidosis)Constrictive pericarditis

Underlying causes of acute heart failure include the following:

Acute valvular (mitral or aortic) regurgitationMyocardial infarctionMyocarditisArrhythmiaDrugs (eg, cocaine, calcium channel blockers, or beta-blocker overdose)Sepsis

Underlying causes of high-output heart failure include the following:

AnemiaSystemic arteriovenous fistulasHyperthyroidismBeriberi heart diseasePaget disease of boneAlbright syndrome (fibrous dysplasia)Multiple myelomaPregnancyGlomerulonephritisPolycythemia veraCarcinoid syndrome

Underlying causes of right heart failure include the following:

Left ventricular failureCoronary artery disease (ischemia)Pulmonary hypertensionPulmonary valve stenosisPulmonary embolismChronic pulmonary disease


8 of 27 14/04/2013 15:17

Neuromuscular disease

Precipitating causes of heart failure

A previously stable, compensated patient may develop heart failure that is clinically apparent for the first time when theintrinsic process has advanced to a critical point, such as with further narrowing of a stenotic aortic valve or mitral valve.Alternatively, decompensation may occur as a result of failure or exhaustion of the compensatory mechanisms butwithout any change in the load on the heart in patients with persistent, severe pressure or volume overload. Inparticular, consider whether the patient has underlying coronary artery disease or valvular heart disease.

The most common cause of decompensation in a previously compensated patient with heart failure is inappropriatereduction in the intensity of treatment, such as dietary sodium restriction, physical activity reduction, or drug regimenreduction. Uncontrolled hypertension is the second most common cause of decompensation, followed closely bycardiac arrhythmias (most commonly, atrial fibrillation). Arrhythmias, particularly ventricular arrhythmias, can be lifethreatening. Also, patients with one form of underlying heart disease that may be well compensated can develop heartfailure when a second form of heart disease ensues. For example, a patient with chronic hypertension andasymptomatic LVH may be asymptomatic until a myocardial infarction (MI) develops and precipitates heart failure.

Systemic infection or the development of unrelated illness can also lead to heart failure. Systemic infectionprecipitates heart failure by increasing total metabolism as a consequence of fever, discomfort, and cough, increasingthe hemodynamic burden on the heart. Septic shock, in particular, can precipitate heart failure by the release ofendotoxin-induced factors that can depress myocardial contractility.

Cardiac infection and inflammation can also endanger the heart. Myocarditis or infective endocarditis may directlyimpair myocardial function and exacerbate existing heart disease. The anemia, fever, and tachycardia that frequentlyaccompany these processes are also deleterious. In the case of infective endocarditis, the additional valvular damagethat ensues may precipitate cardiac decompensation.

Patients with heart failure, particularly when confined to bed, are at high risk of developing pulmonary emboli, which canincrease the hemodynamic burden on the right ventricle by further elevating right ventricular (RV) systolic pressure,possibly causing fever, tachypnea, and tachycardia.

Intense, prolonged physical exertion or severe fatigue, such as may result from prolonged travel or emotional crisis, isa relatively common precipitant of cardiac decompensation. The same is true of exposure to severe climate change(ie, the individual comes in contact with a hot, humid environment or a bitterly cold one).

Excessive intake of water and/or sodium and the administration of cardiac depressants or drugs that cause saltretention are other factors that can lead to heart failure.

Because of increased myocardial oxygen consumption and demand beyond a critical level, the following high-outputstates can precipitate the clinical presentation of heart failure:

Profound anemiaThyrotoxicosisMyxedemaPaget disease of boneAlbright syndromeMultiple myelomaGlomerulonephritisCor pulmonalePolycythemia veraObesityCarcinoid syndromePregnancyNutritional deficiencies (eg, thiamine deficiency, beriberi)

Longitudinal data from the Framingham Heart Study suggests that antecedent subclinical left ventricular systolic ordiastolic dysfunction is associated with an increased incidence of heart failure, supporting the notion that heart failure isa progressive syndrome.[24, 25] Another analysis of over 36,000 patients undergoing outpatient echocardiographyreported that moderate or severe diastolic dysfunction, but not mild diastolic dysfunction, is an independent predictorof mortality.[26]

Genetics of cardiomyopathy

Autosomal dominant inheritance has been demonstrated in dilated cardiomyopathy and in arrhythmic right ventricularcardiomyopathy. Restrictive cardiomyopathies are usually sporadic and associated with the gene for cardiac troponin I.Genetic tests are available at major genetic centers for cardiomyopathies.[27]


9 of 27 14/04/2013 15:17

In families with a first-degree relative who has been diagnosed with a cardiomyopathy leading to heart failure, theat-risk patient should be screened and followed.[27] The recommended screening consists of an electrocardiogramand an echocardiogram. If the patient has an asymptomatic left ventricular dysfunction, it should be treated.[27]

Epidemiology

United States statistics

According to the American Heart Association, heart failure affects nearly 5.7 million Americans of all ages[28] and isresponsible for more hospitalizations than all forms of cancer combined. It is the number 1 cause of hospitalization forMedicare patients. With improved survival of patients with acute myocardial infarction and with a population thatcontinues to age, heart failure will continue to increase in prominence as a major health problem in the UnitedStates.[29, 30, 31, 32]

Analysis of national and regional trends in hospitalization and mortality among Medicare beneficiaries from 1998-2008showed a relative decline of 29.5% in heart failure hospitalizations[33] ; however, wide variations are noted betweenstates and races, with black men having the slowest rate of decline. A relative decline of 6.6% in mortality was alsoobserved, although the rate was uneven across states. The length of stay decreased from 6.8 days to 6.4 days,despite an overall increase in the comorbid conditions.[33]

Heart failure statistics for the United States are as follows:

Heart failure is the fastest-growing clinical cardiac disease entity in the United States, affecting 2% of thepopulationHeart failure accounts for 34% of cardiovascular-related deaths[28]

Approximately 670,000 new cases of heart failure are diagnosed each year[28]

About 277,000 deaths are caused by heart failure each year[28]

Heart failure is the most frequent cause of hospitalization in patients older than 65 years, with an annualincidence of 10 per 1,000[28]

Rehospitalization rates during the 6 months following discharge are as much as 50%[34]

Nearly 2% of all hospital admissions in the United States are for decompensated heart failure, and the averageduration of hospitalization is about 6 daysIn 2010, the estimated total cost of heart failure in the United States was $39.2 billion,[35] representing 1-2% ofall health care expenditures

The incidence and prevalence of heart failure are higher in blacks, Hispanics, Native Americans, and recent immigrantsfrom developing nations, Russia, and the former Soviet republics. The higher prevalence of heart failure in blacks,Hispanics, and Native Americans is directly related to the higher incidence and prevalence of hypertension anddiabetes. This problem is particularly exacerbated by a lack of access to health care and by substandard preventivehealth care available to the most indigent of individuals in these and other groups; in addition, many persons in thesegroups do not have adequate health insurance.

The higher incidence and prevalence of heart failure in recent immigrants from developing nations are largely due to alack of prior preventive health care, a lack of treatment, or substandard treatment for common conditions, such ashypertension, diabetes, rheumatic fever, and ischemic heart disease.

Men and women have the same incidence and the same prevalence of heart failure. However, there are still manydifferences between men and women with heart failure, such as the following:

Women tend to develop heart failure later in life than men doWomen are more likely than men to have preserved systolic functionWomen develop depression more commonly than men doWomen have signs and symptoms of heart failure similar to those of men, but they are more pronounced inwomenWomen survive longer with heart failure than men do

The prevalence of heart failure increases with age. The prevalence is 1-2% of the population younger than 55 yearsand increases to a rate of 10% for persons older than 75 years. Nonetheless, heart failure can occur at any age,depending on the cause.

International statistics

Heart failure is a worldwide problem. The most common cause of heart failure in industrialized countries is ischemiccardiomyopathy, with other causes, including Chagas disease and valvular cardiomyopathy, assuming a moreimportant role in developing countries. However, in developing nations that have become more urbanized and more


10 of 27 14/04/2013 15:17

affluent, eating a more processed diet and leading a more sedentary lifestyle have resulted in an increased rate ofheart failure, along with increased rates of diabetes and hypertension. This change was illustrated in a population studyin Soweto, South Africa, where the community transformed into a more urban and westernized city, followed by anincrease in diabetes, hypertension, and heart failure.[36]

In terms of treatment, one study showed few important differences in uptake of key therapies in European countrieswith widely differing cultures and varying economic status for patients with heart failure. In contrast, studies ofsub-Saharan Africa, where health care resources are more limited, have shown poor outcomes in specificpopulations.[37, 38] For example, in some countries, hypertensive heart failure carries a 25% 1-year mortality rate, andhuman immunodeficiency virus (HIV)associated cardiomyopathy generally progresses to death within 100 days ofdiagnosis in patients who are not treated with antiretroviral drugs.

While data regarding developing nations are not as robust as studies of Western society, the following trends indeveloping nations are apparent:

Causes tend to be largely nonischemicPatients tend to present at a younger ageOutcomes are largely worse where health care resources are limitedIsolated right heart failure tends to be more prominent, with a variety of causes having been postulated, rangingfrom tuberculous pericardial disease to lung disease and pollution

PrognosisIn general, the mortality following hospitalization for patients with heart failure is 10.4% at 30 days, 22% at 1 year, and42.3% at 5 years, despite marked improvement in medical and device therapy.[28, 39, 40, 41, 42, 43] Each rehospitalizationincreases mortality by about 20-22%.[28]

Mortality is greater than 50% for patients with NYHA class IV, ACC/AHA stage D heart failure. Heart failure associatedwith acute MI has an inpatient mortality of 20-40%; mortality approaches 80% in patients who are also hypotensive (eg,cardiogenic shock). (See Heart Failure Criteria and Classification).

Numerous demographic, clinical and biochemical variables have been reported to provide important prognostic valuein patients with heart failure, and several predictive models have been developed.[44]

A study by van Diepen et al suggests that patients with heart failure or atrial fibrillation have a significantly higher risk ofnoncardiac postoperative mortality than patients with coronary artery disease; this risk should be considered even if aminor procedure is planned.[45]

A study by Bursi et al found that among community patients with heart failure, pulmonary artery systolic pressure(PASP), assessed by Doppler echocardiography, can strongly predict death and can provide incremental and clinicallysignificant prognostic information independent of known outcome predictors.[46]

Higher concentrations of galectin-3, a marker of cardiac fibrosis, were associated with an increased risk for incidentheart failure (hazard ratio: 1.28 per 1 SD increase in log galectin-3) in the Framingham Offspring Cohort. Galectin-3was also associated with an increased risk for all-cause mortality (multivariable-adjusted hazard ratio: 1.15).[47]

Patient EducationTo help prevent recurrence of heart failure in patients in whom heart failure was caused by dietary factors ormedication noncompliance, counsel and educate such patients about the importance of proper diet and the necessityof medication compliance. Dunlay et al examined medication use and adherence among community-dwelling patientswith heart failure and found that medication adherence was suboptimal in many patients, often because of cost.[48] Arandomized controlled trial of 605 patients with heart failure reported that the incidence of all-cause hospitalization ordeath was not reduced in patients receiving multi-session self-care training compared to those receiving a singlesession intervention. The optimum method for patient education remains to be established. It appears that moreintensive interventions are not necessarily better.[49]

For patient education information, see the Heart Health Center, Cholesterol Center, and Diabetes Center, as well asCongestive Heart Failure, High Cholesterol, Chest Pain, Heart Rhythm Disorders, Coronary Heart Disease, and HeartAttack.

Contributor Information and DisclosuresAuthorIoana Dumitru, MD Associate Professor of Medicine, Division of Cardiology, Founder and Medical Director, HeartFailure and Cardiac Transplant Program, University of Nebraska Medical Center; Associate Professor of Medicine,


11 of 27 14/04/2013 15:17

Division of Cardiology, Veterans Affairs Medical Center

Ioana Dumitru, MD is a member of the following medical societies: American College of Cardiology, Heart FailureSociety of America, and International Society for Heart and Lung Transplantation

Disclosure: Nothing to disclose.

Coauthor(s)Mathue M Baker, MD Cardiologist, BryanLGH Heart Institute and Saint Elizabeth Regional Medical Center

Mathue M Baker, MD is a member of the following medical societies: American College of Cardiology


Chief EditorHenry H Ooi, MB, MRCPI Director, Advanced Heart Failure and Cardiac Transplant Program, Nashville VeteransAffairs Medical Center; Assistant Professor of Medicine, Vanderbilt University School of Medicine


Additional ContributorsBarry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, ProgramDirector, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve UniversitySchool of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, AmericanAcademy of Emergency Medicine, American College of Chest Physicians, American College of EmergencyPhysicians, American College of Physicians, American Heart Association, American Thoracic Society, ArkansasMedical Society, New York Academy of Medicine, New York AcademyofSciences,and Society for AcademicEmergency Medicine


David FM Brown, MD Associate Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair,Department of Emergency Medicine, Massachusetts General Hospital

David FM Brown, MD is a member of the following medical societies: American College of Emergency Physiciansand Society for Academic Emergency Medicine


William K Chiang, MD Associate Professor, Department of Emergency Medicine, New York University School ofMedicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center

William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology,American College of Medical Toxicology, and Society for Academic Emergency Medicine


Joseph Cornelius Cleveland Jr, MD Associate Professor, Division of Cardiothoracic Surgery, University ofColorado Health Sciences Center

Joseph Cornelius Cleveland Jr, MD is a member of the following medical societies: Alpha Omega Alpha, AmericanAssociation for the Advancement of Science, American College of Cardiology, American College of ChestPhysicians, American College of Surgeons, American Geriatrics Society, American Physiological Society, AmericanSociety of Transplant Surgeons, Association for Academic Surgery, Heart Failure Society of America, InternationalSociety for Heart and Lung Transplantation, Phi Beta Kappa, Society of Critical Care Medicine, Society of ThoracicSurgeons, and Western Thoracic Surgical Association

Disclosure: Thoratec Heartmate II Pivotal Tria; Grant/research funds Principal Investigator - Colorado; AbbottVascular E-Valve E-clip Honoraria Consulting; Baxter Healthcare Corp Consulting fee Board membership;Heartware Advance BTT Trial Grant/research funds Principal Investigator- Colorado; Heartware Endurance DT trialGrant/research funds Principal Investigator-Colorado

Shamai Grossman, MD, MS Assistant Professor, Department of Emergency Medicine, Harvard Medical School;Director, The Clinical Decision Unit and Cardiac Emergency Center, Beth Israel Deaconess Medical Center

Shamai Grossman, MD, MS is a member of the following medical societies: American College of EmergencyPhysicians


12 of 27 14/04/2013 15:17


John D Newell Jr, MD Professor of Radiology, Head, Division of Radiology, National Jewish Health; Professor,Department of Radiology, University of Colorado School of Medicine

John D Newell Jr, MD is a member of the following medical societies: American College of Chest Physicians,American College of Radiology, American Roentgen Ray Society, American Thoracic Society, Association ofUniversity Radiologists, Radiological Society of North America, and Society of Thoracic Radiology

Disclosure: Siemens Medical Grant/research funds Consulting; Vida Corporation Ownership interest Boardmembership; TeraRecon Grant/research funds Consulting; Medscape Reference Honoraria Consulting; HumanaPress Honoraria Other

Craig H Selzman, MD, FACS Associate Professor of Surgery, Surgical Director, Cardiac Mechanical Support andHeart Transplant, Division of Cardiothoracic Surgery, University of Utah School of Medicine

Craig H Selzman, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, AmericanAssociation for Thoracic Surgery, American College of Surgeons, American Physiological Society, Association forAcademic Surgery, International Society for Heart and Lung Transplantation, Society of Thoracic Surgeons,Southern Thoracic Surgical Association, and Western Thoracic Surgical Association


Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Divisionof Emergency Medicine, Harvard Medical School

Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians,National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Managementposition; ProceduresConsult.com Royalty Other

Brett C Sheridan, MD, FACS Associate Professor of Surgery, University of North Carolina at Chapel Hill School ofMedicine


George A Stouffer III, MD Henry A Foscue Distinguished Professor of Medicine and Cardiology, Director ofInterventional Cardiology, Cardiac Catheterization Laboratory, Chief of Clinical Cardiology, Division of Cardiology,University of North Carolina Medical Center

George A Stouffer III, MD is a member of the following medical societies: Alpha Omega Alpha, American Collegeof Cardiology, American College of Physicians, American Heart Association, Phi Beta Kappa, and Society forCardiac Angiography and Interventions


Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center Collegeof Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Additional ContributorsBarry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, ProgramDirector, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve UniversitySchool of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, AmericanAcademy of Emergency Medicine, American College of Chest Physicians, American College of EmergencyPhysicians, American College of Physicians, American Heart Association, American Thoracic Society, ArkansasMedical Society, New York Academy of Medicine, New York AcademyofSciences,and Society for AcademicEmergency Medicine


David FM Brown, MD Associate Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair,Department of Emergency Medicine, Massachusetts General Hospital

David FM Brown, MD is a member of the following medical societies: American College of Emergency Physiciansand Society for Academic Emergency Medicine


13 of 27 14/04/2013 15:17


William K Chiang, MD Associate Professor, Department of Emergency Medicine, New York University School ofMedicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center

William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology,American College of Medical Toxicology, and Society for Academic Emergency Medicine


Joseph Cornelius Cleveland Jr, MD Associate Professor, Division of Cardiothoracic Surgery, University ofColorado Health Sciences Center

Joseph Cornelius Cleveland Jr, MD is a member of the following medical societies: Alpha Omega Alpha, AmericanAssociation for the Advancement of Science, American College of Cardiology, American College of ChestPhysicians, American College of Surgeons, American Geriatrics Society, American Physiological Society, AmericanSociety of Transplant Surgeons, Association for Academic Surgery, Heart Failure Society of America, InternationalSociety for Heart and Lung Transplantation, Phi Beta Kappa, Society of Critical Care Medicine, Society of ThoracicSurgeons, and Western Thoracic Surgical Association

Disclosure: Thoratec Heartmate II Pivotal Tria; Grant/research funds Principal Investigator - Colorado; AbbottVascular E-Valve E-clip Honoraria Consulting; Baxter Healthcare Corp Consulting fee Board membership;Heartware Advance BTT Trial Grant/research funds Principal Investigator- Colorado; Heartware Endurance DT trialGrant/research funds Principal Investigator-Colorado

Shamai Grossman, MD, MS Assistant Professor, Department of Emergency Medicine, Harvard Medical School;Director, The Clinical Decision Unit and Cardiac Emergency Center, Beth Israel Deaconess Medical Center

Shamai Grossman, MD, MS is a member of the following medical societies: American College of EmergencyPhysicians


John D Newell Jr, MD Professor of Radiology, Head, Division of Radiology, National Jewish Health; Professor,Department of Radiology, University of Colorado School of Medicine

John D Newell Jr, MD is a member of the following medical societies: American College of Chest Physicians,American College of Radiology, American Roentgen Ray Society, American Thoracic Society, Association ofUniversity Radiologists, Radiological Society of North America, and Society of Thoracic Radiology

Disclosure: Siemens Medical Grant/research funds Consulting; Vida Corporation Ownership interest Boardmembership; TeraRecon Grant/research funds Consulting; Medscape Reference Honoraria Consulting; HumanaPress Honoraria Other

Craig H Selzman, MD, FACS Associate Professor of Surgery, Surgical Director, Cardiac Mechanical Support andHeart Transplant, Division of Cardiothoracic Surgery, University of Utah School of Medicine

Craig H Selzman, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, AmericanAssociation for Thoracic Surgery, American College of Surgeons, American Physiological Society, Association forAcademic Surgery, International Society for Heart and Lung Transplantation, Society of Thoracic Surgeons,Southern Thoracic Surgical Association, and Western Thoracic Surgical Association


Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Divisionof Emergency Medicine, Harvard Medical School

Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians,National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Managementposition; ProceduresConsult.com Royalty Other

Brett C Sheridan, MD, FACS Associate Professor of Surgery, University of North Carolina at Chapel Hill School ofMedicine


George A Stouffer III, MD Henry A Foscue Distinguished Professor of Medicine and Cardiology, Director ofInterventional Cardiology, Cardiac Catheterization Laboratory, Chief of Clinical Cardiology, Division of Cardiology,University of North Carolina Medical Center


14 of 27 14/04/2013 15:17

George A Stouffer III, MD is a member of the following medical societies: Alpha Omega Alpha, American Collegeof Cardiology, American College of Physicians, American Heart Association, Phi Beta Kappa, and Society forCardiac Angiography and Interventions


Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center Collegeof Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References

Stiles S. FDA Approves Heart Sympathetic Activity Imaging Agent for HF Evaluation. Available athttp://www.medscape.com/viewarticle/781309. Accessed April 5, 2013.

1.

Framingham Classification: Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: theFramingham Study. J Am Coll Cardiol. Oct 1993;22(4 Suppl A):6A-13A. [Medline].

2.

American Heart Association. Classes of heart failure. Available at http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/Classes-of-Heart-Failure_UCM_306328_Article.jsp. AccessedSeptember 6, 2011.

3.

[Guideline] Hunt SA, Abraham WT, Chin MH, et al, and the American College of Cardiology Foundation;American Heart Association. 2009 Focused update incorporated into the ACC/AHA 2005 guidelines for thediagnosis and management of heart failure in adults: a report of the American College of CardiologyFoundation/American Heart Association Task Force on practice guidelines developed in collaboration with theInternational Society for Heart and Lung Transplantation. J Am Coll Cardiol. Apr 14 2009;53(15):e1-e90.[Medline].

4.

[Guideline] Hunt SA, for the Task Force on Practice Guidelines (Writing Committee to Update the 2001Guidelines for the Evaluation and Management of Heart Failure). ACC/AHA 2005 guideline update for thediagnosis and management of chronic heart failure in the adult: a report of the American College ofCardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. Sep 202005;46(6):e1-82. [Medline].

5.

[Guideline] Dickstein K, Cohen-Solal A, Filippatos G, et al. for the Task Force for the Diagnosis andTreatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. ESC Guidelinesfor the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis andTreatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed incollaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society ofIntensive Care Medicine (ESICM). Eur Heart J. Oct 2008;29(19):2388-442. [Medline].

6.

[Guideline] Lindenfeld J, Albert NM, Boehmer JP, et al, for the Heart Failure Society of America. Executivesummary: HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. Jun 2010;16(6):e1-194.[Medline].

7.

Braunwald E. The pathogenesis of heart failure: Then and now. Medicine. 1991;70:68.8.

Braunwald E, Ross J Jr, Sonnenblick EH. 2 ed. Mechanisms of Contraction of the Normal and FailingHeart. Boston: Little Brown & Co; 1976:417.

9.

Clifford R Greyson, MD. Pathophysiology of right ventricular failure. Crit Care Med. 2008;36(suppl):S57-65.10.

Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in cardiovascular disease, part II:pathophysiology, clinical importance, and management of right ventricular failure. Circulation. Apr 12008;117(13):1717-31. [Medline].

11.

Onwuanyi A, Taylor M. Acute decompensated heart failure: pathophysiology and treatment. Am J Cardiol. Mar26 2007;99(6B):25D-30D. [Medline].

12.

Ross J Jr, Braunwald E. Studies on Starling's law of the heart. The effects of impeding venous return onperformance of the normal and failing human left ventricle. Circulation. 1954;30:719.

13.

Gheorghiade M, Pang PS. Acute heart failure syndromes. J Am Coll Cardiol. Feb 17 2009;53(7):557-73.[Medline].

14.

Kajstura J, Leri A, Finato N, Di Loreto C, Beltrami CA, Anversa P. Myocyte proliferation in end-stage cardiacfailure in humans. Proc Natl Acad Sci U S A. Jul 21 1998;95(15):8801-5. [Medline]. [Full Text].

15.


15 of 27 14/04/2013 15:17

Cohn JN. Structural basis for heart failure. Ventricular remodeling and its pharmacological inhibition.Circulation. May 15 1995;91(10):2504-7. [Medline].

16.

Cody RJ. Hormonal alterations in heart failure. In: Hosenpud JB, Greenberg BH, eds. Congestive HeartFailure: Pathophysiology, Diagnosis and Comprehensive Approach to Management. Philadelphia:Lippincott Williams & Wilkins; 2000:199-212.

17.

Anversa P, Nadal-Ginard B. Myocyte renewal and ventricular remodelling. Nature. Jan 102002;415(6868):240-3. [Medline].

18.

Leri A, Claudio PP, Li Q, Wang X, Reiss K, Wang S, et al. Stretch-mediated release of angiotensin II inducesmyocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases theBcl-2-to-Bax protein ratio in the cell. J Clin Invest. Apr 1 1998;101(7):1326-42. [Medline]. [Full Text].

19.

Kajstura J, Leri A, Castaldo C, Nadal-Ginard B, Anversa P. Myocyte growth in the failing heart. Surg Clin NorthAm. Feb 2004;84(1):161-77. [Medline].

20.

Feldman AM, Combes A, Wagner D, Kadakomi T, Kubota T, Li YY, et al. The role of tumor necrosis factor inthe pathophysiology of heart failure. J Am Coll Cardiol. Mar 1 2000;35(3):537-44. [Medline].

21.

Rebecca Gary, RN, PhD, Leslie Davis, MSN, RN, et al. Diastolic heart failure. Heart & Lung.2007;37(6):405-16.

22.

Morris DA, Gailani M, Vaz Perez A, et al. Right ventricular myocardial systolic and diastolic dysfunction in heartfailure with normal left ventricular ejection fraction. J Am Soc Echocardiogr. Aug 2011;24(8):886-97.[Medline].

23.

Lam CS, Lyass A, Kraigher-Krainer E, et al. Cardiac dysfunction and noncardiac dysfunction as precursors ofheart failure with reduced and preserved ejection fraction in the community. Circulation. Jul 52011;124(1):24-30. [Medline].

24.

Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failurein Framingham Heart Study subjects. Circulation. Jul 1993;88(1):107-15. [Medline].

25.

Halley CM, Houghtaling PL, Khalil MK, Thomas JD, Jaber WA. Mortality rate in patients with diastolicdysfunction and normal systolic function. Arch Intern Med. Jun 27 2011;171(12):1082-7. [Medline].

26.

Murphy RT, Starling RC. Genetics and cardiomyopathy: where are we now?. Cleve Clin J Med. Jun2005;72(6):465-6, 469-70, 472-3 passim. [Medline].

27.

Roger VL, Go AS, Lloyd-Jones DM, et al, for the American Heart Association Statistics Committee andStroke Statistics Subcommittee. Heart disease and stroke statistics--2011 update: a report from the AmericanHeart Association. Circulation. Feb 1 2011;123(4):e18-e209. [Medline].

28.

Fonarow GC. Epidemiology and risk stratification in acute heart failure. Am Heart J. Feb 2008;155(2):200-7.[Medline].

29.

Gottlieb SS, Khatta M, Friedmann E, Einbinder L, Katzen S, Baker B, et al. The influence of age, gender, andrace on the prevalence of depression in heart failure patients. J Am Coll Cardiol. May 5 2004;43(9):1542-9.[Medline].

30.

He J, Ogden LG, Bazzano LA, Vupputuri S, Loria C, Whelton PK. Risk factors for congestive heart failure inUS men and women: NHANES I epidemiologic follow-up study. Arch Intern Med. Apr 92001;161(7):996-1002. [Medline].

31.

Masoudi FA, Havranek EP, Smith G, Fish RH, Steiner JF, Ordin DL, et al. Gender, age, and heart failure withpreserved left ventricular systolic function. J Am Coll Cardiol. Jan 15 2003;41(2):217-23. [Medline].

32.

Chen J, Normand SL, Wang Y, Krumholz HM. National and regional trends in heart failure hospitalization andmortality rates for Medicare beneficiaries, 1998-2008. JAMA. Oct 19 2011;306(15):1669-78. [Medline].

33.

Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-serviceprogram. N Engl J Med. Apr 2 2009;360(14):1418-28. [Medline].

34.

Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al. Executive summary: heartdisease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. Feb23 2010;121(7):948-54. [Medline].

35.

Stewart S, Wilkinson D, Hansen C, Vaghela V, Mvungi R, McMurray J, et al. Predominance of heart failure inthe Heart of Soweto Study cohort: emerging challenges for urban African communities. Circulation. Dec 2

36.


16 of 27 14/04/2013 15:17

2008;118(23):2360-7. [Medline].

Damasceno A, Cotter G, Dzudie A, Sliwa K, Mayosi BM. Heart failure in sub-saharan Africa: time for action. JAm Coll Cardiol. Oct 23 2007;50(17):1688-93. [Medline].

37.

Cardiovascular Diseases. Dean T. Jamison, Richard G. Feachem, Eduard R. Bos, Malegapuru W. Makgoba,Florence K. Baingana, Karen J. Hofman, Kahma O. Rogo. Disease and mortality in Sub-Saharan Africa. 2.Washington D.C: World Bank Publications; 2006:21.

38.

Dries DL, Exner DV, Domanski MJ, Greenberg B, Stevenson LW. The prognostic implications of renalinsufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am CollCardiol. Mar 1 2000;35(3):681-9. [Medline].

39.

Fonarow GC, Adams KF Jr, Abraham WT, Yancy CW, Boscardin WJ. Risk stratification for in-hospitalmortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA. Feb 22005;293(5):572-80. [Medline].

40.

Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KK, et al. Long-term trends in the incidence ofand survival with heart failure. N Engl J Med. Oct 31 2002;347(18):1397-402. [Medline].

41.

Lucas C, Johnson W, Hamilton MA, Fonarow GC, Woo MA, Flavell CM, et al. Freedom from congestionpredicts good survival despite previous class IV symptoms of heart failure. Am Heart J. Dec2000;140(6):840-7. [Medline].

42.

MacIntyre K, Capewell S, Stewart S, Chalmers JW, Boyd J, Finlayson A, et al. Evidence of improvingprognosis in heart failure: trends in case fatality in 66 547 patients hospitalized between 1986 and 1995.Circulation. Sep 5 2000;102(10):1126-31. [Medline].

43.

Ketchum ES, Levy WC. Establishing prognosis in heart failure: a multimarker approach. Prog CardiovascDis. Sep-Oct 2011;54(2):86-96. [Medline].

44.

van Diepen S, Bakal JA, McAlister FA, Ezekowitz JA. Mortality and readmission of patients with heart failure,atrial fibrillation, or coronary artery disease undergoing noncardiac surgery: an analysis of 38 047 patients.Circulation. Jul 19 2011;124(3):289-96. [Medline].

45.

Bursi F, McNallan SM, Redfield MM, et al. Pulmonary pressures and death in heart failure a community study.J Am Coll Cardiol. Jan 17 2012;59(3):222-31. [Medline]. [Full Text].

46.

Ho JE, Liu C, Lyass A, Courchesne P, Pencina MJ, Vasan RS, et al. Galectin-3, a marker of cardiac fibrosis,predicts incident heart failure in the community. J Am Coll Cardiol. Oct 2 2012;60(14):1249-56. [Medline].

47.

Dunlay SM, Eveleth JM, Shah ND, McNallan SM, Roger VL. Medication adherence among community-dwelling patients with heart failure. Mayo Clin Proc. Apr 2011;86(4):273-81. [Medline]. [Full Text].

48.

Dewalt DA, Schillinger D, Ruo B, Bibbins-Domingo K, Baker DW, Holmes GM, et al. A Multisite RandomizedTrial of a Single- versus Multi-Session Literacy Sensitive Self-Care Intervention for Patients with Heart Failure.Circulation. May 9 2012;[Medline].

49.

Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM, et al. HFSA 2010Comprehensive Heart Failure Practice Guideline. J Card Fail. Jun 2010;16(6):e1-194. [Medline].

50.

Lainscak M, Cleland JG, Lenzen MJ, Follath F, Komajda M, Swedberg K. International variations in thetreatment and co-morbidity of left ventricular systolic dysfunction: data from the EuroHeart Failure Survey. EurJ Heart Fail. Mar 2007;9(3):292-9. [Medline].

51.

[Guideline] Peacock WF, Fonarow GC, Ander DS, Maisel A, Hollander JE, Januzzi JL Jr, et al. Society ofChest Pain Centers Recommendations for the evaluation and management of the observation stay acuteheart failure patient: a report from the Society of Chest Pain Centers Acute Heart Failure Committee. CritPathw Cardiol. Jun 2008;7(2):83-6. [Medline].

52.

[Best Evidence] Steinhart B, Thorpe KE, Bayoumi AM, Moe G, Januzzi JL Jr, Mazer CD. Improving thediagnosis of acute heart failure using a validated prediction model. J Am Coll Cardiol. Oct 132009;54(16):1515-21. [Medline].

53.

Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused update:ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the AmericanCollege of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developedin collaboration with the International Society for Heart and Lung Transplantation. Circulation. Apr 142009;119(14):1977-2016. [Medline].

54.


17 of 27 14/04/2013 15:17

Rich MW, McSherry F, Williford WO, Yusuf S. Effect of age on mortality, hospitalizations and response todigoxin in patients with heart failure: the DIG study. J Am Coll Cardiol. Sep 2001;38(3):806-13. [Medline].

55.

Badve SV, Roberts MA, Hawley CM, et al. Effects of Beta-adrenergic antagonists in patients with chronickidney disease a systematic review and meta-analysis. J Am Coll Cardiol. Sep 6 2011;58(11):1152-61.[Medline].

56.

Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in theemergency diagnosis of heart failure. N Engl J Med. Jul 18 2002;347(3):161-7. [Medline].

57.

Januzzi JL Jr, Camargo CA, Anwaruddin S, et al. The N-terminal Pro-BNP investigation of dyspnea in theemergency department (PRIDE) study. Am J Cardiol. Apr 15 2005;95(8):948-54. [Medline].

58.

Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT. Does this dyspneic patient in the emergencydepartment have congestive heart failure?. JAMA. Oct 19 2005;294(15):1944-56. [Medline].

59.

Stevenson LW, Perloff JK. The limited reliability of physical signs for estimating hemodynamics in chronicheart failure. JAMA. Feb 10 1989;261(6):884-8. [Medline].

60.

Pinamonti B, Di Lenarda A, Sinagra G, Camerini F. Restrictive left ventricular filling pattern in dilatedcardiomyopathy assessed by Doppler echocardiography: clinical, echocardiographic and hemodynamiccorrelations and prognostic implications. Heart Muscle Disease Study Group. J Am Coll Cardiol. Sep1993;22(3):808-15. [Medline].

61.

Temporelli PL, Scapellato F, Eleuteri E, Imparato A, Giannuzzi P. Doppler echocardiography in advancedsystolic heart failure: a noninvasive alternative to Swan-Ganz catheter. Circ Heart Fail. May 2010;3(3):387-94.[Medline].

62.

Maisel AS, McCord J, Nowak RM, et al. Bedside B-Type natriuretic peptide in the emergency diagnosis ofheart failure with reduced or preserved ejection fraction. Results from the Breathing Not Properly MultinationalStudy. J Am Coll Cardiol. Jun 4 2003;41(11):2010-7. [Medline].

63.

[Best Evidence] Januzzi JL, van Kimmenade R, Lainchbury J, et al. NT-proBNP testing for diagnosis andshort-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: theInternational Collaborative of NT-proBNP Study. Eur Heart J. Feb 2006;27(3):330-7. [Medline].

64.

Maeda K, Tsutamoto T, Wada A, Hisanaga T, Kinoshita M. Plasma brain natriuretic peptide as a biochemicalmarker of high left ventricular end-diastolic pressure in patients with symptomatic left ventricular dysfunction.Am Heart J. May 1998;135(5 Pt 1):825-32. [Medline].

65.

Fisher C, Berry C, Blue L, Morton JJ, McMurray J. N-terminal pro B type natriuretic peptide, but not the newputative cardiac hormone relaxin, predicts prognosis in patients with chronic heart failure. Heart. Aug2003;89(8):879-81. [Medline]. [Full Text].

66.

Hall C, Rouleau JL, Moye L, et al. N-terminal proatrial natriuretic factor. An independent predictor of long-termprognosis after myocardial infarction. Circulation. May 1994;89(5):1934-42. [Medline].

67.

Andersson B, Hall C. N-terminal proatrial natriuretic peptide and prognosis in patients with heart failure andpreserved systolic function. J Card Fail. Sep 2000;6(3):208-13. [Medline].

68.

Chen HH, Burnett JC. Natriuretic peptides in the pathophysiology of congestive heart failure. Curr CardiolRep. May 2000;2(3):198-205. [Medline].

69.

Cheng V, Kazanagra R, Garcia A, Lenert L, Krishnaswamy P, Gardetto N, et al. A rapid bedside test for B-typepeptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study. JAm Coll Cardiol. Feb 2001;37(2):386-91. [Medline].

70.

Cowie MR, Struthers AD, Wood DA, Coats AJ, Thompson SG, Poole-Wilson PA, et al. Value of natriureticpeptides in assessment of patients with possible new heart failure in primary care. Lancet. Nov 81997;350(9088):1349-53. [Medline].

71.

Dao Q, Krishnaswamy P, Kazanegra R, Harrison A, Amirnovin R, Lenert L, et al. Utility of B-type natriureticpeptide in the diagnosis of congestive heart failure in an urgent-care setting. J Am Coll Cardiol. Feb2001;37(2):379-85. [Medline].

72.

Maeda K, Tsutamoto T, Wada A, Hisanaga T, Kinoshita M. Plasma brain natriuretic peptide as a biochemicalmarker of high left ventricular end-diastolic pressure in patients with symptomatic left ventricular dysfunction.Am Heart J. May 1998;135(5 Pt 1):825-32. [Medline].

73.

Maisel AS, Koon J, Hope J, et al. A rapid bedside test for brain natriuretic peptide accurately predicts cardiac74.


18 of 27 14/04/2013 15:17

function in patients referred for echocardiography. Am Heart J. 2001;141:374-9.

Masson S, Vago T, Baldi G, et al. Comparative measurement of N-terminal pro-brain natriuretic peptide andbrain natriuretic peptide in ambulatory patients with heart failure. Clin Chem Lab Med. Aug 2002;40(8):761-3.[Medline].

75.

Song BG, Jeon ES, Kim YH, et al. Correlation between levels of N-terminal pro-B-type natriuretic peptide anddegrees of heart failure. Korean J Intern Med. Mar 2005;20(1):26-32. [Medline].

76.

Hobbs FD, Davis RC, Roalfe AK, et al. Reliability of N-terminal pro-brain natriuretic peptide assay in diagnosisof heart failure: cohort study in representative and high risk community populations. [abstract]. BMJ. Jun 222002;324(7352):1498.

77.

Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC Jr. Plasma brain natriureticpeptide concentration: impact of age and gender. J Am Coll Cardiol. Sep 4 2002;40(5):976-82. [Medline].

78.

St Peter JV, Hartley GG, Murakami MM, Apple FS. B-type natriuretic peptide (BNP) and N-terminal pro-BNP inobese patients without heart failure: relationship to body mass index and gastric bypass surgery. Clin Chem.Apr 2006;52(4):680-5. [Medline].

79.

Rivera M, Cortes R, Salvador A, ET AL. Obese subjects with heart failure have lower N-terminal pro-brainnatriuretic peptide plasma levels irrespective of aetiology. Eur J Heart Fail. Dec 2005;7(7):1168-70.[Medline].

80.

Hermann-Arnhof KM, Hanusch-Enserer U, Kaestenbauer T, et al. N-terminal pro-B-type natriuretic peptide asan indicator of possible cardiovascular disease in severely obese individuals: comparison with patients indifferent stages of heart failure. Clin Chem. Jan 2005;51(1):138-43. [Medline].

81.

Seino Y, Ogawa A, Yamashita T, et al. Application of NT-proBNP and BNP measurements in cardiac care: amore discerning marker for the detection and evaluation of heart failure. Eur J Heart Fail. Mar 152004;6(3):295-300. [Medline].

82.

Colucci WS, Elkayam U, Horton DP, Abraham WT, Bourge RC, Johnson AD, et al. Intravenous nesiritide, anatriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group. NEngl J Med. Jul 27 2000;343(4):246-53. [Medline].

83.

Ezekowitz JA, Hernandez AF, Starling RC, Yancy CW, Massie B, Hill JA, et al. Standardizing care for acutedecompensated heart failure in a large megatrial: the approach for the Acute Studies of Clinical Effectivenessof Nesiritide in Subjects with Decompensated Heart Failure (ASCEND-HF). Am Heart J. Feb2009;157(2):219-28. [Medline].

84.

Mills RM, LeJemtel TH, Horton DP, Liang C, Lang R, Silver MA, et al. Sustained hemodynamic effects of aninfusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. Natrecor Study Group. J Am Coll Cardiol. Jul 1999;34(1):155-62. [Medline].

85.

Silver MA, Horton DP, Ghali JK, Elkayam U. Effect of nesiritide versus dobutamine on short-term outcomes inthe treatment of patients with acutely decompensated heart failure. J Am Coll Cardiol. Mar 62002;39(5):798-803. [Medline].

86.

Miller WL, Hartman KA, Burritt MF, Borgeson DD, Burnett JC Jr, Jaffe AS. Biomarker responses during andafter treatment with nesiritide infusion in patients with decompensated chronic heart failure. Clin Chem. Mar2005;51(3):569-77. [Medline].

87.

Fitzgerald RL, Cremo R, Gardetto N, et al. Effect of nesiritide in combination with standard therapy on serumconcentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure. AmHeart J. Sep 2005;150(3):471-7. [Medline].

88.

Michels VV, Moll PP, Miller FA, et al. The frequency of familial dilated cardiomyopathy in a series of patientswith idiopathic dilated cardiomyopathy. N Engl J Med. Jan 9 1992;326(2):77-82. [Medline].

89.

Baig MK, Goldman JH, Caforio AL, Coonar AS, Keeling PJ, McKenna WJ. Familial dilated cardiomyopathy:cardiac abnormalities are common in asymptomatic relatives and may represent early disease. J Am CollCardiol. Jan 1998;31(1):195-201. [Medline].

90.

Grunig E, Tasman JA, Kucherer H, Franz W, Kubler W, Katus HA. Frequency and phenotypes of familialdilated cardiomyopathy. J Am Coll Cardiol. Jan 1998;31(1):186-94. [Medline].

91.

McNally E, MacLeod H, Dellefave L. Arrhythmogenic right ventricular dysplasia/cardiomyopathy, autosomaldominant. 2005;[Medline].

92.


19 of 27 14/04/2013 15:17

Cheitlin MD, Alpert JS, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ, et al. ACC/AHA Guidelinesfor the Clinical Application of Echocardiography. A report of the American College of Cardiology/AmericanHeart Association Task Force on Practice Guidelines (Committee on Clinical Application ofEchocardiography). Developed in collaboration with the American Society of Echocardiography. Circulation.Mar 18 1997;95(6):1686-744. [Medline].

93.

Patel AR, Alsheikh-Ali AA, Mukherjee J, Evangelista A, Quraini D, Ordway LJ, et al. 3D Echocardiography toEvaluate Right Atrial Pressure in Acutely Decompensated Heart Failure Correlation With InvasiveHemodynamics. JACC Cardiovasc Imaging. Sep 2011;4(9):938-45. [Medline].

94.

Prior D, Coller J. Echocardiography in heart failure - a guide for general practice. Aust Fam Physician. Dec2010;39(12):904-9. [Medline].

95.

Kirkpatrick JN, Wiegers SE, Lang RM. Left ventricular assist devices and other devices for end-stage heartfailure: utility of echocardiography. Curr Cardiol Rep. May 2010;12(3):257-64. [Medline].

96.

Abraham J, Abraham TP. The role of echocardiography in hemodynamic assessment in heart failure. HeartFail Clin. Apr 2009;5(2):191-208. [Medline].

97.

Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, et al. The use of contrast-enhanced magneticresonance imaging to identify reversible myocardial dysfunction. N Engl J Med. Nov 162000;343(20):1445-53. [Medline].

98.

Ritchie JL, Bateman TM, Bonow RO, Crawford MH, Gibbons RJ, Hall RJ, et al. Guidelines for clinical use ofcardiac radionuclide imaging. Report of the American College of Cardiology/American Heart AssociationTask Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee onRadionuclide Imaging), developed in collaboration with the American Society of Nuclear Cardiology. J AmColl Cardiol. Feb 1995;25(2):521-47. [Medline].

99.

Taillefer R, DePuey EG, Udelson JE, Beller GA, Latour Y, Reeves F. Comparative diagnostic accuracy ofTl-201 and Tc-99m sestamibi SPECT imaging (perfusion and ECG-gated SPECT) in detecting coronaryartery disease in women. J Am Coll Cardiol. Jan 1997;29(1):69-77. [Medline].

100.

Bonow RO, Maurer G, Lee KL, et al. Myocardial Viability and Survival in Ischemic Left Ventricular Dysfunction.N Engl J Med. Apr 4 2011;[Medline].

101.

Binanay C, Califf RM, Hasselblad V, et al. Evaluation study of congestive heart failure and pulmonary arterycatheterization effectiveness: the ESCAPE trial. JAMA. Oct 5 2005;294(13):1625-33. [Medline].

102.

Bitter T, Westerheide N, Prinz C, Hossain MS, Vogt J, Langer C, et al. Cheyne-Stokes respiration andobstructive sleep apnoea are independent risk factors for malignant ventricular arrhythmias requiringappropriate cardioverter-defibrillator therapies in patients with congestive heart failure. Eur Heart J. Jan2011;32(1):61-74. [Medline].

103.

Groenveld HF, Januzzi JL, Damman K, et al. Anemia and mortality in heart failure patients a systematic reviewand meta-analysis. J Am Coll Cardiol. Sep 2 2008;52(10):818-27. [Medline].

104.

Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. Nov 42008;52(19):1527-39. [Medline].

105.

House AA, Haapio M, Lassus J, Bellomo R, Ronco C. Therapeutic strategies for heart failure in cardiorenalsyndromes. Am J Kidney Dis. Oct 2010;56(4):759-73. [Medline].

106.

Giamouzis G, Butler J, Starling RC, Karayannis G, Nastas J, Parisis C, et al. Impact of dopamine infusion onrenal function in hospitalized heart failure patients: results of the Dopamine in Acute Decompensated HeartFailure (DAD-HF) Trial. J Card Fail. Dec 2010;16(12):922-30. [Medline].

107.

Pleister AP, Baliga RR, Haas GJ. Acute study of clinical effectiveness of nesiritide in decompensated heartfailure: nesiritide redux. Curr Heart Fail Rep. Sep 2011;8(3):226-32. [Medline].

108.

Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Effects of oraltolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. Mar 282007;297(12):1319-31. [Medline].

109.

Massie BM, O'Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, et al. Rolofylline, an adenosineA1-receptor antagonist, in acute heart failure. N Engl J Med. Oct 7 2010;363(15):1419-28. [Medline].

110.

Badve SV, Roberts MA, Hawley CM, et al. Effects of Beta-adrenergic antagonists in patients with chronickidney disease a systematic review and meta-analysis. J Am Coll Cardiol. Sep 6 2011;58(11):1152-61.

111.


20 of 27 14/04/2013 15:17

[Medline].

Roy D, Talajic M, Nattel S, et al, for the Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythmcontrol versus rate control for atrial fibrillation and heart failure. N Engl J Med. Jun 19 2008;358(25):2667-77.[Medline].

112.

Hsu LF, Jas P, Sanders P, Garrigue S, Hocini M, Sacher F, et al. Catheter ablation for atrial fibrillation incongestive heart failure. N Engl J Med. Dec 2 2004;351(23):2373-83. [Medline].

113.

Wilton SB, Fundytus A, Ghali WA, Veenhuyzen GD, Quinn FR, Mitchell LB, et al. Meta-analysis of theeffectiveness and safety of catheter ablation of atrial fibrillation in patients with versus without left ventricularsystolic dysfunction. Am J Cardiol. Nov 1 2010;106(9):1284-91. [Medline].

114.

MacDonald MR, Connelly DT, Hawkins NM, Steedman T, Payne J, Shaw M, et al. Radiofrequency ablation forpersistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolicdysfunction: a randomised controlled trial. Heart. May 2011;97(9):740-7. [Medline].

115.

Chen YM, Li ZB, Zhu M, Cao YM. Effects of exercise training on left ventricular remodelling in heart failurepatients: an updated meta-analysis of randomised controlled trials. Int J Clin Pract. Aug 2012;66(8):782-791.[Medline].

116.

Mozaffarian D, Lemaitre RN, King IB, et al. Circulating Long-Chain {omega}-3 Fatty Acids and Incidence ofCongestive Heart Failure in Older Adults: The Cardiovascular Health Study: A Cohort Study. Ann Intern Med.Aug 2 2011;155(3):160-70. [Medline].

117.

Marchioli R, Levantesi G, Silletta MG, et al, for the GISSI-HF investigators. Effect of n-3 polyunsaturated fattyacids and rosuvastatin in patients with heart failure: results of the GISSI-HF trial. Expert Rev CardiovascTher. Jul 2009;7(7):735-48. [Medline].

118.

Massie BM, Collins JF, Ammon SE, Armstrong PW, Cleland JG, Ezekowitz M, et al. Randomized trial ofwarfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy inChronic Heart Failure (WATCH) trial. Circulation. Mar 31 2009;119(12):1616-24. [Medline].

119.

Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence andoutcome of heart failure with preserved ejection fraction. N Engl J Med. Jul 20 2006;355(3):251-9. [Medline].

120.

Hogg K, Swedberg K, McMurray J. Heart failure with preserved left ventricular systolic function; epidemiology,clinical characteristics, and prognosis. J Am Coll Cardiol. Feb 4 2004;43(3):317-27. [Medline].

121.

Gheorghiade M, Abraham WT, Albert NM, et al, for the OPTIMIZE-HF Investigators and Coordinators.Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acuteheart failure. JAMA. Nov 8 2006;296(18):2217-26. [Medline].

122.

Masip J, Roque M, Sanchez B, Fernandez R, Subirana M, Exposito JA. Noninvasive ventilation in acutecardiogenic pulmonary edema: systematic review and meta-analysis. JAMA. Dec 28 2005;294(24):3124-30.[Medline].

123.

Peter JV, Moran JL, Phillips-Hughes J, Graham P, Bersten AD. Effect of non-invasive positive pressureventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis.Lancet. Apr 8 2006;367(9517):1155-63. [Medline].

124.

Winck JC, Azevedo LF, Costa-Pereira A, Antonelli M, Wyatt JC. Efficacy and safety of non-invasive ventilationin the treatment of acute cardiogenic pulmonary edema--a systematic review and meta-analysis. Crit Care.2006;10(2):R69. [Medline]. [Full Text].

125.

Vital FM, Saconato H, Ladeira MT, et al. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) forcardiogenic pulmonary edema. Cochrane Database Syst Rev. Jul 16 2008;CD005351. [Medline].

126.

Maeder MT, Kaye DM. Heart failure with normal left ventricular ejection fraction. J Am Coll Cardiol. Mar 172009;53(11):905-18. [Medline].

127.

Gray A, Goodacre S, Newby DE, Masson M, Sampson F, Nicholl J, et al. Noninvasive ventilation in acutecardiogenic pulmonary edema. N Engl J Med. Jul 10 2008;359(2):142-51. [Medline].

128.

The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure.Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUSTrial Study Group. N Engl J Med. Jun 4 1987;316(23):1429-35. [Medline].

129.

The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejectionfractions and congestive heart failure. N Engl J Med. Aug 1 1991;325(5):293-302. [Medline].

130.


21 of 27 14/04/2013 15:17

Zannad F, Alla F, Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover maycontribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights fromthe randomized aldactone evaluation study (RALES). Rales Investigators. Circulation. Nov 282000;102(22):2700-6. [Medline].

131.

Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, et al. Diuretic strategies in patientswith acute decompensated heart failure. N Engl J Med. Mar 3 2011;364(9):797-805. [Medline].

132.

Liu PP. Cardiorenal syndrome in heart failure: a cardiologist's perspective. Can J Cardiol. Jul 2008;24 supplB:25B-9B. [Medline]. [Full Text].

133.

Kramer BK, Schweda F, Riegger GA. Diuretic treatment and diuretic resistance in heart failure. Am J Med.Jan 1999;106(1):90-6. [Medline].

134.

Nieminen MS, Bohm M, Cowie MR, et al for the ESC Committe for Practice Guideline (CPG). Executivesummary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on AcuteHeart Failure of the European Society of Cardiology. Eur Heart J. Feb 2005;26(4):384-416. [Medline].

135.

Neuberg GW, Miller AB, O'Connor CM, et al. Diuretic resistance predicts mortality in patients with advancedheart failure. Am Heart J. Jul 2002;144(1):31-8. [Medline].

136.

Costanzo MR, Saltzberg M, O'Sullivan J, Sobotka P. Early ultrafiltration in patients with decompensated heartfailure and diuretic resistance. J Am Coll Cardiol. Dec 6 2005;46(11):2047-51. [Medline].

137.

Young JB, Abraham WT, Stevenson LW, et al. Results of the VMAC Trial: vasodilation in the management ofacute congestive heart failure. N Engl J Med. 2000;102:a2794.

138.

Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF).Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomizedcontrolled trial. JAMA. Mar 27 2002;287(12):1531-40. [Medline].

139.

Costanzo MR, Jessup M. Treatment of congestion in heart failure with diuretics and extracorporeal therapies:effects on symptoms, renal function, and prognosis. Heart Fail Rev. May 11 2011;[Medline].

140.

Costanzo MR, Guglin ME, Saltzberg MT, Jessup ML, Bart BA, Teerlink JR, et al. Ultrafiltration versusintravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol. Feb13 2007;49(6):675-83. [Medline].

141.

CIBIS Investigators and Committees. A randomized trial of beta-blockade in heart failure. The CardiacInsufficiency Bisoprolol Study (CIBIS). Circulation. Oct 1994;90(4):1765-73. [Medline].

142.

Chaudhry SI, Mattera JA, Curtis JP, Spertus JA,

Documents

Heart Failure