Result card

  • CUR10: What are the symptoms and burden of disease for the patient at different stages of the disease?

What are the symptoms and burden of disease for the patient at different stages of the disease?

Authors: Ingrid Wilbacher, Nadine Berndt, Francesca Gillespie

Internal reviewers: Alessandra Lo Scalzo, Christian Vladescu, Christina Mototolea, Kristina Lampe, Maria Camerlingo

  • The basic search for the CUR domain did not provide any relevant information to answer this assessment element. Hence, a manual search was done to find relevant information about symptoms and burden of disease for the patient at different stages of the HF syndrome as published in evidence-based guidelines on the HF epidemiology. European and American guidelines for the diagnosis and treatment of acute and chronic HF were consulted by doing a manual search on the website of the ESC and the AHA resulting in the following guidelines and references:
  • Since the Killip classification describes the severity of a patient’s HF condition in the context of myocardial infarction in different stages and this was mentioned in the ESC guidelines from 2012, two additional studies were consulted on this classification system:
  • Furthermore, the website of the ESC was consulted which led to one additional position paper on advanced chronic HF relevant for this assessment element:
  • The searches for the additional guidelines were conducted the 06th of January 2015 by one of the investigators (NB).

Burden of disease for different stages of heart failure

According to the ESC guidelines published in 2012 {77}, “a patient who has never exhibited the typical signs or symptoms of HF is described as having asymptomatic left ventricular systolic dysfunction (or whatever the underlying cardiac abnormality is)”. HF generally is a chronic condition and patients who have had HF for some time are often said to have ‘chronic HF’. A treated patient with symptoms and signs that have unchanged for at least a month is said to be ‘stable’.


‘Acute HF’ is the term used to describe the rapid onset of, or change in, HF symptoms and signs. Acute HF is an event with severe symptoms and signs of considerable prognostic importance. Causes of acute HF include arrhythmias, myocardial ischemia, and acute preload or afterload changes. In most cases, acute HF arises as a result of deterioration in patients with chronic stable HF who had a previous diagnosis of HF. Hence, the patient may be described as ‘decompensated’. AHF usually requires admission to hospital and immediate intervention. Acute HF may also be the first presentation of HF (‘de novo’ acute HF). In that case, acute HF may be caused by an abnormality of a cardiac function such as acute myocardial infarction, for example in a patient who has had asymptomatic cardiac dysfunction, often for an indeterminate period, and may persist or resolve. In that case, patients may become ‘compensated’. Patients with pre-existing HF often have a clear trigger, such as an arrhythmia or discontinuation of diuretic therapy in a HF patient with a reduced ejection fraction, and volume overload or severe hypertension in HF patients with a preserved ejection fraction. The acuteness may vary. Patients may experience a period of days or even weeks of deterioration (e.g. increasing breathlessness or edema) whereas others develop HF within a few hours to minutes (e.g. in association with an acute myocardial infarction).


HF symptoms can range from life-threatening pulmonary edema or cardiogenic shock to worsening peripheral edema. Although symptoms and signs may resolve in patients with a new HF, the underlying cardiac dysfunction may not. These patients have an increased risk of recurrent ‘decompensation’. Sometimes, however, a patient may have HF due to a problem that resolves completely (e.g. acute viral myopericarditis). Particularly those patients with ‘idiopathic’ dilated cardiomyopathy may show considerable or complete recovery of left ventricular systolic function with modern treatment including an angiotensinconverting enzyme inhibitor, beta-blocker, and mineralocorticoid receptor antagonist.


‘Congestive HF’ is a term may describe acute or chronic HF with evidence of congestion (i.e. sodium and water retention). Congestion, though not other symptoms of HF (e.g. fatigue), may resolve with diuretic treatment {77}. Many patients may further progress to ‘advanced chronic HF’. The ESC developed a definition of advanced HF with objective criteria that is helpful. According to the ESC, these patients often have severe symptoms (NYHA class III or IV), episodes with clinical signs of fluid retention and/or peripheral hypofusion, objective evidence of severe cardiac dysfunction, severe impairment of physical exercise, history of at least 1 HF hospitalization the previous 6 months, and presence of all the named features besides optimal therapy. These patients generally have a poor prognosis and high risk of events {79}.


‘End-stage HF’ indicates a highly advanced and irreversible stage of HF where conventional HF treatment cannot lead to an improvement. In these patients, palliative care or heart transplantation are indicated. Many or all of these terms may be accurately applied to the same patient at different times, depending upon their stage of illness {77}.


A useful classification of HF based on the nature of clinical representation has been revealed by the ESC guidelines on the diagnosis and treatment of HF:


Table 2. Classification of heart failure

Classification of heart failure

New onset

First presentation (‘de novo’)

Acute or slow onset


Recurrent or episodic



Stable, worsening, or decompensated

Source: ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure (Dickstein et al., 2008) {19}


New-onset HF refers to the first presentation of HF. Transient HF refers to symptomatic HF over a particular time period, although long-term treatment may be indicated. Examples are patients with mild myocarditis from who almost recover completely, patients with a myocardial infarction who need diuretics in the coronary care unit but who don’t need long-term HF treatment, or transient HF caused by ischemia and resolved by revascularization. Worsening HF in chronic HF (decompensation) is a very common form of HF leading to hospital admission. Treatment should be based on the clinical presentation for which specific therapy is indicated (e.g. pulmonary edema, hypertension emergency, acute MI) {19}.

Classification of heart failure by its symptoms and functional capacity

The severity of the symptoms and limitations of physical activity of HF are usually assessed according to the New York Heart Association (NYHA) functional classification. This classification system has been proven to be clinically useful. Patients in NYHA class I are essentially asymptomatic and have no symptoms attributable to heart disease or are well treated and their symptoms may have relieved. Patients in NYHA class II have mild symptoms of HF and a slight limitation in physical activity; those in class III have moderate symptoms and symptoms while walking on the flat; and those in class IV are said to have severe symptoms while being breathless at rest and essentially housebound  {77},{115}.

It is important to note that symptom severity correlates poorly with underlying cardiac dysfunction. Although there is a clear relationship between severity of symptoms and survival, patients with mild symptoms may still have a relatively high absolute risk of hospital admission and death (McMurray, 2010; Chen et al., 2011; Dunlay et al., 2009) {76},{9},{22}. HF symptoms can also change promptly. As such, a stable patient with mild symptoms can become abruptly breathless at rest with the onset of an arrhythmia, and an acutely unwell patient with pulmonary edema and NYHA class IV symptoms may recover quickly with diuretic treatment. Deterioration in symptoms increase the likelihood of hospital admission and death {77}.

Table 3. New York Heart Association functional classification based on functional capacity


Severity of symptoms and physical activity

Class I (Asymptomatic)

No limitation of physical activity. Ordinary physical activity does not cause symptoms (undue breathlessness, fatigue, or palpitations).

Class II (Mild)

Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in undue breathlessness, fatigue, or palpitations.

Class III (Moderate)

Marked limitation of physical activity. Comfortable at rest, but less than ordinary physical activity results in undue breathlessness, fatigue, or palpitations.

Class IV (Severe)

Unable to carry on any physical activity without discomfort. Symptoms at rest can be present. If any physical activity is undertaken, discomfort is increased.

Source: Hunt et al., Circulation 2005;112:e154–e235. {46}

Another classification by the American Heart Association (AHA) and the American College of Cardiology (ACC) describes HF in stages based on structural changes and symptoms as follows:

Table 4. ACC/AHA stages of heart failure


Stage of heart failure based on structure and damage to heart muscle

Stage I

At high risk for developing heart failure. No identified structural or functional abnormality; no signs or symptoms.

Stage II

Developed structural heart disease that is strongly associated with the development of heart failure, but without signs or symptoms.

Stage III

Symptomatic heart failure associated with underlying structural heart disease.

Stage IV

Advanced structural heart disease and marked symptoms of heart failure at rest despite maximal medical therapy. Stage IV HF is sometimes called refractory HF to indicate a lack of response specifically to diuretic treatment.

Source: Yancy et al., JACC 2013;16:e148-e231. {115}

The ACCF/AHA stages recognize that risk factors and abnormalities of the heart are associated with HF. The stages are progressive and violate, meaning that once a patient moves to a higher stage, regression to a former HF stage is not possible. The NYHA functional classification rates the severity of symptoms in those with structural heart disease and the stage in which a patient resides can change short time periods. Whereas the ACCF/AHA classification system of HF emphasizes the development and progression of disease and can be used to describe patient, the NYHA classification focuses on exercise capacity and the symptomatic status of the disease {115}.

The Killip classification may be used to describe the severity of a patient’s HF condition in the context of myocardial infarction. In fact, patients are categorized according to the presence or absence of simple physical examination findings that suggest ventricular dysfunction in order to provide a clinical estimate of the severity of acute myocardial infarction {59}. According to this classification system, patients are classified into four levels during physical examination. Patients in Class I demonstrate no evidence of congestive HF due to the absence of clinical signs of cardiac decompensation. Patients in Class II have findings and clinical signs consistent with mild to moderate HF (i.e. lung rales, pulmonary venous hypertension, pulmonary congestion). Patients in Class III demonstrate severe HF by overt pulmonary edema with rales throughout the lung fields. Patients in Class IV are in cardiogenic shock with clinical signs of hypotension and evidence of peripheral vasoconstriction {23}.


Table 5. The Killip classification for the severity of a patient’s HF condition in the context of myocardial infarction

Class I

no evidence of congestive HF

absence of clinical signs of cardiac decompensation

Class II

mild to moderate HF

i.e. lung rales, pulmonary venous hypertension, pulmonary congestion

Class III

severe heart failure

overt pulmonary edema with rales throughout the lung fields

Class IV

cardiogenic shock

clinical signs of hypotension and evidence of peripheral vasoconstriction

Sources: De Gaere et al., 2001 {17 }; El-Menyar et al., 2010 {23}

Wilbacher I et al. Result Card CUR10 In: Wilbacher I et al. Health Problem and Current Use of the Technology In: Jefferson T, Cerbo M, Vicari N [eds.]. Structured telephone support (STS) for adult patients with chronic heart failure [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali ; 2015. [cited 16 June 2021]. Available from: