Mitja , Ilaria , and Andrew JS: Definition and Classification of Heart Failure.


Heart failure is defined by the European Society of Cardiology (ESC) as a clinical syndrome characterised by symptoms such as shortness of breath, persistent coughing or wheezing, ankle swelling and fatigue, that may be accompanied by the following signs: jugular venous pressure, pulmonary crackles, increased heart rate and peripheral oedema.[1] However, these signs may not be present in the early stages and in patients treated with diuretics. When apparent, they are due to a structural and/or functional cardiac abnormality, leading to systolic and/or diastolic ventricular dysfunction, resulting in a reduced cardiac output and/or elevated intra-cardiac pressures at rest or during stress [2,3]. According to the most recent ESC guidelines [1] the initial evaluation of patients with suspected heart failure should include a clinical history and physical examination, laboratory assessment, chest radiography, and electrocardiography. Echocardiography can confirm the diagnosis. Beyond detecting myocardial abnormality, other impairments such as abnormalities of the valves, pericardium, endocardium, heart rhythm, and conduction may be found [4,2] The identification of the underlying aetiology is pivotal for the diagnosis of heart failure and its treatment [5].

Clinical course of heart failure

According to the “progressive model” [4], heart failure may be considered as a progressive disorder that starts from a trigger, or “index event”, that damages the heart muscle and consequently impairs cardiac myocytes, therefore reducing the myocardium’s ability to fill with or eject blood, and finally precluding the heart from contracting normally. This inciting event may have a sudden onset (e.g. myocardial infarction) or a gradual or insidious onset (e.g. haemodynamic pressure or volume overloading), or it may be hereditary. Regardless of the aetiology, the consequence is a decline in pump function of the heart [4] Also, a progressive, albeit non-linear, decline in health-related quality of life is observed;[6] this course can be interrupted at any time either by sudden cardiac death usually caused by an arrhythmia or can end in a more gradual death caused by progressive pump failure. Patients may also experience progressive episodes of acute decompensation, further reducing the heart’s ability to fill with or eject blood appropriately.

Acute heart failure is defined as the rapid onset of symptoms and signs secondary to abnormal cardiac function, which may occur with or without previous cardiac disease [7]. The cardiac dysfunction can be related to systolic or diastolic dysfunction, to abnormalities in cardiac rhythm, or to preload and afterload mismatch [8]. Acute heart failure is often life threatening and requires urgent treatment. In addition, the patient with acute heart failure may present with one of several distinct clinical conditions [9].

Finally, subclinical forms of heart failure also exist, with asymptomatic cardiac abnormalities. These silent forms of heart failure are considered as its precursors, and should be identified as early intervention may improve outcomes and reduce mortality [10,11]. Unfortunately, subclinical forms of heart failure remain unnoticed and are frequently underdiagnosed [12]. For these reasons, given the heterogeneity of heart failure phenotypes [13], classification systems and diagnostic algorithms have been developed.

Classifications of heart failure

Heart failure with preserved (HFpEF), mid-range (HFmrEF) and reduced ejection fraction (HFrEF)

From the ‘90s clinical trials began to select patients based on left ventricular ejection fraction (LVEF), usually measured using echocardiography, a radionuclide technique, or cardiac magnetic resonance. Table 1 shows the diagnostic criteria to define heart failure with preserved (HFpEF), mid-range (HFmrEF) and reduced ejection fraction (HFrEF) according to ESC guidelines[1] Figure 1 shows typical echocardiographic pictures of HFrEF and HFpEF.

An old definition for HFpEF was “diastolic’ heart failure”, as opposed to “systolic” heart failure that corresponded to HFrEF. However, the term diastolic heart failure was replaced by HFpEF given that diastolic dysfunction of the left ventricle may also characterise HFrEF [14]. On the other hand, the term systolic heart failure was substituted by HFrEF given that subtle abnormalities of systolic function may be also found in patients with HFpEF [15].

The definition of the range of “normality’ of LVEF in heart failure has been long debated [16,17]. According to the European Study Group on Diastolic Heart Failure[18] diagnostic criteria for HFpEF were: a) clinical symptoms and signs; b) normal or mildly reduced LV systolic function (LVEF >50% and LVEDVI <97 mL/m2); c) diastolic dysfunction. In contrast, criteria from the Framingham study[19] were more pragmatic and less dependent on detailed testing and included: a) clinical symptoms and signs, and b) LVEF ≥50% within 72 h of heart failure; whereas assessment of diastolic function was not needed for diagnosis.

Recent and more stringent criteria for HFpEF and HFrEF have been proposed by the new ESC guidelines [1] (see Table 1).

Figure 1

Echocardiographic differences between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The figure shows echocardiographic images from a patient with HFrEF (above, images 1 and 2) and a patient with HFpEF (below, images 3 and 4). In the images above, ejection fraction (EF) is depressed and the end-systolic volume is increased (image 2). In the right heart chambers electrocatheter is also observable (both images 1 and 2). Conversely, it is noticeable that volumes of the left ventricles as well as EF are preserved in HFpEF (images 3 and 4).


Table 1

Advanced heart failure definitions/classifications

HFA position statement 2007 criteria ESC definition of advanced heart failure in ACCF/AHA 2013 guidelines INTERMACS classification system
1. Severe symptoms of HF (NYHA class III or IV) 1. Severe symptoms of HF with dyspnoea and/or fatigue at rest or with minima exertion (NYHA class III or IV) 1. Critical cardiogenic shock despite escalating support (“Crash and burn”)
2. Episodes of fluid retention and/or peripheral hypoperfusion 2. Episodes of fluid retention (pulmonary and/or systemic congestion, peripheral edema) and/or reduced cardiac output at rest (peripheral hypoperfusion) 2. Progressive decline with inotrope dependence (“Sliding on inotropes”)
3. Objective evidence of severe cardiac dysfunction 3. Objective evidence of severe cardiac dysfunction shown by at least 1 of the following:
  1. LVEF <30%

  2. Pseudonormal or restrictive mitral inflow pattern

  3. Mean PCWP >16 mm HG and/or RAP >12 mm HG by PA catheterisation

  4. High BNP or NT-proBNP plasma levels in the absence of non-cardiac causes

3. Clinically stable with mild to moderate inotrope dependence (“Dependent stability”)
4. Severe impairment of functional capacity 4. Severe impairment of functional capacity shown by one of the following:
  1. Inability to exercise

  2. 6-minute walk distance ≤300 m

  3. Peak VO2 <12 to 14 lM/kg/min

4. Recurrent, not refractory, advanced HF that can be stabilised (“Frequent flyer”)
5. History of ≥1 HF hospitalisation in the past 6 months 5. History of ≥1 HF hospitalisation in past 6 months 5. Exertion intolerant but is comfortable at rest and able to perform activities of daily living with slight difficulty (“Housebound”)
6. Presence of all the previous features despite “attempts to optimise” therapy 6. Presence of all the previous features despite “attempts to optimise” therapy, including diuretics and GDMT, unless these are poorly tolerated or contraindicated, and CRT when indicated 6. Exertion limited; is able to perform mild activity, but fatigue results within a few minutes of any meaningful physical exertion (“Walking wounded”)
7. Advanced NYHA functional class III (“Placeholder”)

BNP = B-type natriuretic peptide; CRT = cardiac resynchronization therapy; GDMT = guideline-directed medical therapy; HF = heart failure; INTERMACS = Interagency Registry for Mechanically Assisted Circulatory Support; LVEF = left ventricular ejection fraction; NT-proBNP = N-terminal pro-B type natriuretic peptide; NYHA = New York Heart Association; PA = pulmonary artery; PCWP = pulmonary capillary wedge pressure; RAP = right atrial pressure; VO2 = oxygen consumption.

Selecting patients according to LVEF is relevant as these heart failure syndromes have distinct patterns of underlying aetiologies, demographics, comorbidities and response to therapies [2,20]. Typically, patients with HFpEF are older, more likely female, and present the following co-morbidities more commonly: arterial hypertension, atrial fibrillation, kidney dysfunction, metabolic syndrome, obesity, physical deconditioning, pulmonary disease, pulmonary hypertension and sleep apnoea [1]. Due to polymorbidity, the diagnosis may be more difficult, especially in older adults [21].

In HFrEF, LVEF is considered as 40% or below. The heart muscle does not contract effectively and less oxygen-rich blood is pumped out to the body. In HFrEF only, therapies have been shown to reduce both morbidity and mortality [1].

The recent ESC guidelines [1] have finally provided diagnostic criteria for a newly defined group HFmrEF standing for Heart Failure with mid-range Ejection Fraction. Such an ‘intermediate group’ or ‘grey area’ presents as mild systolic dysfunction, with a LVEF in the range of 40–49%. Further studies are warranted to clarify its risk factors, demographics, co-morbidities and pathophysiological processes and, consequently, whether its treatments should be similar to those used for HFrEF [23].

Classifications of heart failure according to the severity of symptoms

The ACC/AHA guidelines have proposed a staging of severity of heart failure based on the structure and damage of the heart muscle [3]. According to this classification, patients may be classified as follows: Stage A patients are at high risk for developing heart failure but do not present any structural or functional abnormality or symptoms of heart failure; Stage B comprises patients with structural heart disease that is associated with the development of heart failure but signs or symptoms of heart failure are not apparent; Stage C includes patients with symptomatic heart failure associated with underlying structural heart disease; Stage D patients have advanced structural heart disease and marked symptoms of heart failure at rest despite maximal medical therapy.

A widely-used classification is the New York Heart Association (NYHA) functional classification (1994), which describes heart failure according to severity of its symptoms and impairment of physical activity. Class I patients present no limitation in physical activity; therefore symptoms such as breathlessness, fatigue or palpitations are absent during ordinary physical activity. Class II includes patients characterised by slight limitation of physical activity. Undue breathlessness, fatigue or palpitations are present during ordinary physical activity, whereas the patient is comfortable at rest. Class III comprises patients with a marked limitation of physical activity. The patient is still comfortable at rest, but less than ordinary physical activity results in undue breathlessness, fatigue or palpitations. Class IV patients are unable to carry on any physical activity without discomfort and symptoms at rest can also appear [24]. Other classifications developed in the ‘70s describe the severity of heart failure in the context of acute myocardial infarction, the Killip (1967) [25] and Forrester (1977) [26] classifications.

Advanced heart failure

Advanced heart failure was first defined in 1998 as a syndrome requiring a resting left ventricular ejection fraction <30% and NYHA class III to IV or a peak oxygen uptake (VO2) below 14 mL/kg/min [27]. In 2004, a U.S. consensus statement defined advanced heart failure as a “state in which patients have significant cardiac dysfunction with marked symptoms of dyspnoea, fatigue, or symptoms relating to end-organ hypoperfusion at rest or with minimal exertion despite maximal medical therapy” [28]. This definition did not include the criterion of a previous hospitalisation and did not try objectively to assess the impairment of cardiac dysfunction and functional capacity. In 2007, the Heart Failure Association (HFA) of the ESC [9] published a position statement in which the definition and clinical characteristics of advanced chronic heart failure were outlined. According to this definition, both symptoms of severe heart failure and objective evidence of severe cardiac dysfunction, impaired exercise capacity and an unstable clinical course must be present, despite optimal medical treatment. Clinical characteristics and classifications of advanced heart failure are shown in Table 1.

The HFA criteria of the ESC were inserted into the AHA/ACC Foundation criteria for destination therapy with cardiac devices[29]. The AHA/ACC guidelines also described heart failure as a progressive disease into four stages from A to D, with stage D being defined as end-stage or advanced heart failure.

The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), a prospective registry that collects data on all patients who receive a durable, FDA approved mechanical circulatory support device in the United States, developed seven profiles that can be used further to stratify patients with advanced heart failure [30] INTERMACS patient profiles were defined based on clinical descriptors at the time of mechanical circulatory support implant (1=critical cardiogenic shock to 7=advanced NYHA Class III symptoms) (Table 1.2). Such a system classification may be useful to predict outcomes after mechanical assist device implantation [31].

Despite these classification systems, mostly descriptive, it is vital to realise that a consensus definition for advanced heart failure still needs to be developed. Indeed, there is still considerable variation in the definition of advanced heart failure utilised for clinical trial purposes [32]. Clinicians must recognise the transition to advanced heart failure in order to provide timely and appropriate therapeutic options [33].

Other definitions of heart failure
End-stage heart failure

Advanced heart failure should be kept distinct from end-stage heart failure. This term indicates an extremely advanced condition where no improvement with conventional heart failure treatment is possible and where palliative care, ventricular assist devices or heart transplantation are indicated. Indeed, there are remarkable differences between advanced and end-stage heart failure in terms of quality of life and outcomes. End-stage heart failure should be also distinguished from acute heart failure in which a certain degree of reversibility can be achieved [6].

Refractory heart failure

Refractory heart failure is similar to end-stage heart failure and is observed in clinical practice when patients continue to be symptomatic at rest or develop recurrence of heart failure despite optimal contemporary pharmacotherapy proven to be of benefit in clinical trials. Physical examination, laboratory testing, multi-modality imaging, and cardiopulmonary exercise testing are pivotal for the definition of refractory heart failure. These patients commonly have rapid clinical deterioration and may require inotropic agents to augment cardiac performance [34,35].

Declarations of Interest

The authors declare no conflicts of interest.


The authors state that they abide by the requirements for ethical publishing in biomedical journals.[36]



Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016; May20pii:ehw12827206819


McMurray JJ, Adamopoulos S, Anker SD et al ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012; 33: 1787–1847


Hunt SA, Abraham WT, Chin MH et al 2009; focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009; 11914e391–e479


Mann DL, Bristow MR Mechanisms and models in heart failure: the biomechanical model and beyond. Circulation. 2005; May31111212837–2849


King M, Kingery J, Casey B Diagnosis and Evaluation of Heart Failure. Am Fam Physician. 2012; Jun1585121161–1168


Metra M, Ponikowski P, Dickstein K et al Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2007; 9: 684–94


Gheorghiade M, Zannad F, Sopko G et al Acute heart failure syndromes: current state and framework for future research. Circulation. 2005; Dec20112253958–68


Dickstein K Cohen-Solal A, Filippatos G, et al ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail. 2008; Oct1010933–89 10.1016/j.ejheart.2008.08.005Epub2008; Sep16Review. Erratum in: Eur J Heart Fail. 2009; Jan111110Eur J Heart Fail. 2010; Apr124416Dosage error in article text.18826876


Nieminen MS, Bohm M, Cowie MR et al Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology. Eur Heart J. 2005; 26: 384–416


Wang TJ Natural history of asymptomatic left ventricular systolic dysfunction in the 3746 community. Circulation. 2003; 108: 977–9823747


The SOLVD Investigators. Effect of enalapril on mortality and the development of heart 3748 failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J 3749 Med. 1992; 327: 685–691


Schocken DD, Benjamin EJ, Fonarow GC et al Prevention of heart failure: a scientific statement from the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group. Circulation. 2008; 117: 2544–2565


Senni M, Paulus WJ, Gavazzi A et al New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes. Eur Heart J. 2014; Oct2135402797–815 10.1093/eurheartj/ehu204


Borlaug B, Paulus W Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J. 2011; Mar326670–679


Shah AM, Claggett B, Sweitzer NK et al Prognostic Importance of Impaired Systolic Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone. Circulation. 2015; Aug41325402–1410.1161/CIRCULATIONAHA.115.015884


Davies M, Hobbs F, Davis R et al Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study. Lancet. 2001; Aug113589280439–44


Petrie M, McMurray J Changes in notions about heart failure. Lancet. 2001; Aug11589280432–4


Paulus WJ, Tschope C, Sanderson JE et al How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007; 28: 2539–2550


Vasan RS, Levy D Defining diastolic heart failure: a call for standardized diagnostic criteria. Circulation. 2000; 101: 2118–2121


Butler J, Fonarow GC, Zile MR et al Developing therapies for heart failure with preserved ejection fraction: current state and future directions. JACC Heart Fail. 2014; 2: 97–3756112


Bhuiyan T, Maurer MS Heart Failure with Preserved Ejection Fraction: Persistent Diagnosis, Therapeutic Enigma. Curr Cardiovasc Risk Rep. 2011; Oct55440–449


Iwano, William C, Little Shah SJ, Katz DH, Deo RC Phenotypic Spectrum of Heart Failure with Preserved Ejection Fraction. Heart Fail Clin. 2014; July103407–418


Lam CSP, Solomon SD The middle child in heart failure: heart failure with mid-range ejection fraction (40–50%). Eur J Heart Fail. 2014; 16: 1049–1055


The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th edLittle Brown & Co1994; pp253–256


Killip T 3rd, Kimball JT Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol. 1967; 20: 457–464


Forrester JS, Diamond GA, Swan HJ Correlative classification of clinical and hemodynamic function after acute myocardial infarction. Am J Cardiol. 1977; 39: 137–145


Adams KF Jr., Zannad F Clinical definition and epidemiology of advanced heart failure. Am Heart J. 1998; 135: S204–15


Goodlin SJ, Hauptman PJ, Arnold R et al Consensus statement: palliative and supportive care in advanced heart failure. J Card Fail. 2004; 10: 200–9


Yancy CW, Jessup M, Bozkurt B et al 2013; ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013; 62: e147–239


Stevenson LW, Pagani FD, Young JB, Jessup M, Miller L, Kormos RL, Naftel DC, Ulisney K, Desvigne-Nickens P, Kirklin JK INTERMACS profiles of advanced heart failure: the current picture. J Heart Lung Transplant. 2009; Jun286535–41


Alba AC, Rao V, Ivanov J, Ross HJ, Delgado DH Usefulness of the INTERMACS scale to predict outcomes after mechanical assist device implantation. J Heart Lung Transplant. 2009; 827–33


Bjork JB, Alton KK, Georgiopoulou VV, Butler J, Kalogeropoulos AP Defining Advanced Heart Failure: A Systematic Review of Criteria Used in Clinical Trials. Journal of Cardiac Failure (2016); 10.1016/j.cardfail.2016.03.003


Allen LA, Stevenson LW, Grady KL et al Decision making in advanced heart failure: a scientific statement from the American Heart Association. Circulation. 2012; 125: 1928–1952


Hunt SA, Abraham WT, Chin MH et al ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult-summary article. A report of the American College of Cardiology/American Heart Association. Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. 2005; 46: 11161143


Ahmad T, Patel CB, Milano CA, Rogers JG When the heart runs out of heartbeats: treatment options for refractory end-stage heart failure. Circulation. 2012; 125: 2948–2955


Shewan L.G., Coats A.J.S., Henein M Requirements for Ethical Publishing in Biomedical Journals. International Cardiovascular Forum Journal. 2015; 2: 2 10.17987/icfj.v2i1.4

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