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Section 2: Conceptualization and WorkingDefinition of Heart Failure

Heart failure (HF) remains a major and growing societal

problem despite advances in detection and therapy.1-4 How-

ever, there is no widely accepted characterization and def-

inition of HF, probably because of the complexity of the

syndrome. The conceptualization and working definition

of HF presented here emerged as these guidelines were de-

veloped. They are critical to understanding HF and ap-

proaching its treatment appropriately.

Conceptual Background. HF is a syndrome rather than

a primary diagnosis. It has many potential etiologies, di-

verse clinical features, and numerous clinical subsets. Pa-

tients may have a variety of primary cardiovascular

diseases and never develop cardiac dysfunction, and those

in whom cardiac dysfunction is identified through testing

may never develop clinical HF. In addition to cardiac dys-

function, other factors, such as vascular stiffness, dyssyn-

chrony, and renal sodium handling, play major roles inthe manifestation of the syndrome of HF.

Patients at risk for many cardiovascular diseases are at

risk for HF. Early identification and treatment of risk fac-

tors is perhaps the most significant step in limiting the pub-

lic health impact of HF.5-7 Emphasis on primary and

secondary prevention is particularly critical because of

the difficulty of successfully treating left ventricular (LV)

dysfunction, especially when severe.5 Current therapeutic

advances in the treatment of HF do not make prevention

any less important.

Although HF is progressive, current therapy may provide

stability and even reversibility. The inexorable progressionof HF from LV remodeling and dysfunction is no longer in-

evitable. Prolonged survival with mild to moderate LV dys-

function is now possible. Therapy with angiotensin-

converting enzyme inhibitors (or angiotensin receptor

blockers), beta blockers, and cardiac resynchronization

therapy can lead to slowing or to partial reversal of remod-

eling.

Because of this prolonged survival, comorbid conditions,

such as coronary artery disease or renal failure, can prog-

ress, complicating treatment. Given this prolonged survival,

considerable attention is devoted in this guideline to disease

management, the use of multidrug therapy, and the manage-

ment of patients with HF at the end of life.

Working Definition. Although HF may be caused by

a variety of disorders, including valvular abnormalities

and dysrhythmias, the following comprehensive guideline

and this working definition focus on HF primarily

from the loss or dysfunction of myocardial muscle or inter-

stitium.

HF is a syndrome caused by cardiac dysfunction, gen-erally resulting from myocardial muscle dysfunction

or loss and characterized by either LV dilation or

hypertrophy or both. Whether the dysfunction is pri-

marily systolic or diastolic or mixed, it leads to neuro-

hormonal and circulatory abnormalities, usually

resulting in characteristic symptoms such as fluid

retention, shortness of breath, and fatigue, especially

on exertion. In the absence of appropriate therapeutic

intervention, HF is usually progressive at the level of

both cardiac function and clinical symptoms. The

severity of clinical symptoms may vary substantially

during the course of the disease process and may notcorrelate with changes in underlying cardiac func-

tion. Although HF is progressive and often fatal,

patients can be stabilized and myocardial dysfunction

and remodeling may improve, either spontaneously or

as a consequence of therapy. In physiologic terms, HF

is a syndrome characterized by either or both pulmo-

nary and systemic venous congestion and/or inade-

quate peripheral oxygen delivery, at rest or during

stress, caused by cardiac dysfunction.

Additional Definitions

HF is often classified as HF with reduced systolic func-

tion versus HF with preserved systolic function. Myocardial

remodeling often precedes the clinical syndrome of HF.

Additional definitions are provided in Table 2.1. A table

of acronyms and their meaning is provided in Appendix B.

Disclosures

See Appendix C.

Table 2.1. Additional HF Definitions

HF With Reduced LeftVentricular Ejection Fraction(LVEF) Sometimes:HF With a Dilated LeftVentricle

A clinical syndrome characterized bysigns and symptoms of HF andreduced LVEF. Most commonlyassociated with LV chamberdilation.

HF With Preserved LVEFSometimes: HF WithNondilated LV

A clinical syndrome characterized bysigns and symptoms of HF withpreserved LVEF. Most commonlyassociated with a nondilated LVchamber. May be the result ofvalvular disease or other causes(Section 11).

Myocardial Remodeling Pathologic myocardial hypertrophyor dilation in response to increasedmyocardial stress. These changesare generally accompanied bypathologic changes in the cardiacinterstitium. Myocardialremodeling is generally aprogressive disorder.

1071-9164/$ - see front matter 2010 Elsevier Inc. All rights reserved.doi:10.1016/j.cardfail.2010.05.011

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References

1. Fang J, Mensah GA, Croft JB, Keenan NL. Heart failure-related hospi-

talization in the U.S., 1979 to 2004. J Am Coll Cardiol 2008;52:

428e34.

2. Koelling TM, Chen RS, Lubwama RN, LItalien GJ, Eagle KA.

The expanding national burden of heart failure in the United States:

the influence of heart failure in women. Am Heart J 2004;147:

74e

8.3. Loehr LR, Rosamond WD, Chang PP, Folsom AR, Chambless LE.

Heart failure incidence and survival (from the Atherosclerosis Risk in

Communities study). Am J Cardiol 2008;101:1016e22.

4. McCullough PA, Philbin EF, Spertus JA, Kaatz S, Sandberg KR,

Weaver WD. Confirmation of a heart failure epidemic: findings from

the Resource Utilization Among Congestive Heart Failure (REACH)

study. J Am Coll Cardiol 2002;39:60e9.

5. Baker DW. Prevention of heart failure. J Card Fail 2002;8:333e46.

6. DunlaySM, Weston SA,JacobsenSJ, Roger VL.Riskfactorsfor heart fail-

ure: a population-based case-control study. Am J Med 2009;122:1023e8.

7. Lee DS, Gona P, Vasan RS, Larson MG, Benjamin EJ, Wang TJ, et al.

Relation of disease pathogenesis and risk factors to heart failure with

preserved or reduced ejection fraction: insights from the framingham

heart study of the national heart, lung, and blood institute. Circulation

2009;119:3070e7.

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Appendix B. Acronyms

Acronym MeaningACE angiotensin converting enzymeADA American Diabetes AssociationADHF acute decompensated heart failureAF atrial fibrillationAHA/ACC American Heart Association/American College of

CardiologyALVD asymptomatic left ventricular dysfunctionARB angiotensin receptor blockerARVD/C arrhythmogenic right ventricular dysplasia/

cardiomyopathyAV arteriovenousBMI body mass indexBNP B-type natriuretic peptideBUN blood urea nitrogenCABG coronary artery bypass graftCAD coronary artery diseaseCHD congenital heart diseaseCI confidence intervalCK-MM creatinine kinase MM isoenzymeCOPD chronic obstructive pulmonary diseaseCOX-2 cyclooxygenase-2CPAP continuous positive airway pressureCPR cardiopulmonary resuscitation

CR/XL controlled release/extended releaseCREST a limited cutaneous form of scleroderma defined by

calsinosis, Raynauds syndrome, esophagealdysmotility, sclerodactyly, and telangiectasia

CRT cardiac resynchronization therapyCRT-D cardiac resynchronization therapy device and

defibrillatorCTR cardiothoracic ratioDASH Dietary Approaches to Stop HypertensionDBP diastolic blood pressureDCM dilated cardiomyopathyDNR do not resuscitateDVT deep venous thrombosisECG electrocardiogramED emergency departmentEP, EPS electrophysiology, electrophysiology studyEVCPP endoventricular circular patch plastyFDC familial dilated cardiomyopathyGFR, eGFR glomerular filtration rate, estimated glomerular filtration

rateHCM hypertrophic cardiomyopathyHF heart failureHFSA Heart Failure Society of AmericaHR hazard ratioICD implantable cardioverter defibrillatorINR international normalized ratioJVP jugular venous pressureLA left atrialLMWH low molecular weight heparinLV left ventricularLVAD left ventricular assist deviceLVEF left ventricular ejection fractionLVH left ventricular hypertrophy

LVNC left ventricular noncompactionMI myocardial infarctionMRI magnetic resonance imagingNCEP National Cholesterol Education ProgramNIV non-invasive ventilationNSAID non-steroidal anti-inflammatory drugNT-proBNP N-terminal pro-B-type natriuretic peptideNYHA New York Heart AssociationOMIM Online Mendelian Inheritance in Man (online resource)OU observation unitPCI percutaneous coronary interventionPCWP pulmonary capillary wedge pressurePE pulmonary embolismPET-CT positron emission tomographye computed tomographyPMI point of maximal impulsePND paroxysmal nocturnal dyspnea

(continued)

Appendix B. (continued)

PPAR-a peroxisome proliferator-activated receptor-alphaPUFA polyunsaturated fatty acidsPVC premature ventricular contractionQTc QT interval corrected for heart rateRAAS renin-angiotensin-aldosterone systemRCM restrictive cardiomyopathyRV right ventricularSAECG signal-averaged electrocardiogram

SAVER surgical anterior ventricular endocardial restorationSBP systolic blood pressureSCD sudden cardiac deathSDC serum digoxin concentrationSPECT single-photon emission computed tomographySSRI selective serotonin reuptake inhibitorsSTEMI ST-elevation myocardial infarctionTNF-a tumor necrosis factor-alphaUFH unfractionated heparinUSDA United States Department of AgricultureVE/VCO2 ventilation equivalent of carbon dioxide (production

slope)VF ventricular fibrillationVT ventricular tachycardiaClinical TrialsAcronym Full Trial Name

ACCOMPLISH Avoiding Cardiovascular Events Through Combination

Therapy in Patients Living with SystolicHypertension

ADHERE Acute Decompensated Heart Failure National Registry(Registry)

AFFIRM Atrial Fibrillation Follow-Up Investigation of RhythmManagement

A-HeFT African-American Heart Failure TrialALLHAT Antihypertensive and Lipid-Lowering Treatment to

Prevent Heart Attack TrialALOFT Aliskiren Observation of Heart Failure TreatmentB-CONVINCED Beta Blocker Continuation Versus Interruption on

Patients with Congestive Heart Failure Hospitalizedfor a Decompensation Episode

CANPAP Canadian Continuous Positive Airway Pressure forPatients with Central Sleep Apnea and Heart Failure

CAPRICORN Carvedilol Post-Infarct Survival Control in Left

Ventricular DysfunctionCARE-HF Cardiac Resynchronization-Heart FailureCHARM Candesartan in Heart Failure Assessment of Reduction

in Mortality and Morbidity (Also CHARM-Added,CHARM-Alternative, CHARM-Preserved)

CIBIS Cardiac Insufficiency Bisoprolol StudyCOACH Coordinating Study Evaluating Outcomes of Advising

and Counseling in Heart FailureCOMET Carvedilol or Metoprolol European TrialCOMPANION Comparison of Medical Therapy, Pacing, and

Defibrillation in Chronic Heart FailureCONSENSUS

IICooperative New Scandinavian Enalapril Survival

Study IICOPERNICUS Carvedilol Prospective Randomized Cumulative

Survival StudyDIG Digitalis Investigation GroupEFFECT Enhanced Feedback for Effective Cardiac Treatment

(Evaluation Tool)EPHESUS Epleronone Post-Acute Myocardial Infarction Heart

Failure Efficacy and Survival StudyESCAPE Evaluation Study of Congestive Heart Failure and

Pulmonary Artery Catheterization EffectivenessEUROPA European Trial on Reduction of Cardiac Events with

Perindopril in Stable Coronary Artery DiseaseFAIR-HF Ferinject Assessment in Patients with Iron Deficiency

and Chronic Heart FailureGISSI Gruppo Italiano Per Lo Studio Della Sopravvivenza

Nellinfarto Miocardico (GISSI-Prevenzione, GISSI-HF)

GUSTO-1 Global Utilization of Streptokinase and TissuePlasminogen Activator for Occluded CoronaryArteries

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Appendix B. (continued)

HEART Heart Failure Revascularization TrialHELP Hospitalized Elderly Longitudinal ProjectHERS Heart and Estrogen/Progestin Replacement StudyHF-ACTION A Controlled Trial Investigating Outcomes of Exercise

TrainingHOBIPACE Homburg Biventricular Pacing EvaluationHOPE Heart Outcomes Prevention EvaluationHOT Hypertension Optimal Treatment

INTERMACS Interagency Registry for Mechanically AssistedCirculatory Support (Registry)

I-PRESERVE Irbesartan in Heart Failure with Preserved EjectionFraction

IRON-HF Iron Supplementation in Heart Failure Patients withAnemia

ISIS-4 Fourth International Study of Infarct SurvivalMADIT-CRT Multi-Center Automatic Defibrillator Implantation Trial

with Cardiac Resynchronization TherapyMERIT-HF Metoprolol CR?XL Randomized Intervention Trial in

Congestive Heart FailureMIRACLE Multicenter Insync Clinical StudyMTT Myocarditis Treatment TrialMUSTT Multicenter Unsustained Tachycardia TrialNHANES National Health and Nutrition Examination Survey

Epidemiologic Follow-Up StudyOAT Occluded Artery Trial

OPTIMAAL Optimal Trial in Myocardial Infarction with theAngiotensin II Antagonist Losartan

OPTIME-HF Outcomes of a Prospective Trial of IntravenousMilrinone for Exacerbations of Chronic Heart Failure

OPTIMIZE-HF Organized Program to Initiate Lifesaving Treatment inHospitalized Patients with Heart Failure (Registry)

PRIDE N-Terminal Pro-BNP Investigation of Dyspnea in theEmergency Department

PRIMA Can Pro-Brain-Natriuretic-Peptide Guided Therapy ofChronic Heart Failure Improve Heart FailureMorbidity and Mortality?

PROVED Prospective Randomized Study of Ventricular Functionand Efficacy of Digoxin

RADIANCE Randomized Assessment of Digoxin on Inhibitors of theAngiotensin Converting System

RALES Randomized Aldactone Evaluation Study

RED-HF Reduction of Events with Darbepoetin Alfa in HeartFailureREMATCH Randomized Evaluation of Mechanical Assistance for

the Treatment of Congestive Heart FailureREVERSE Resynchronization Reverses Remodeling in Systolic

Left Ventricular DysfunctionREVERT Reversal of Ventricular Remodeling with Toprol-XLSCD-HeFT Sudden Cardiac Death in Heart Failure TrialSENIORS Study of the Effects of Nebivolol Intervention on

Outcomes and Rehospitalization in Seniors withHeart Failure

SOLVD Studies of Left Ventricular DysfunctionSTARS-BNP Systolic Heart Failure Treatment Supported By BNPSTICH Surgical Treatment for Ischemic Heart FailureSUPPORT Study to Understand Prognoses and Preferences for

Outcomes and Risks of TreatmentTIME-CHF Trial of Intensified Vs Standard Medical Therapy in

Elderly Patients with Congestive Heart FailureUKPDS United Kingdom Prospective Diabetes StudyVal-HeFT Valsartan Heart Failure TrialVALIANT The Valsartan in Acute Myocardial Infarction TrialV-HeFT Vasodilator Heart Failure TrialVMAC Vasodilator in the Management of Acute Heart FailureWASH Warfarin/Aspirin Study in Heart FailureWATCH Warfarin and Antiplatelet Therapy in Chronic Heart

Failure

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