Heart Failure - Clinical Manifestations and Diagnosis in Adults - UpToDate

05/04/2022 06:12 Heart failure: Clinical manifestations and diagnosis in adults - UpToDate
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Heart failure: Clinical manifestations and diagnosis in

adults
Authors: Wilson S Colucci, MD, Barry A Borlaug, MD
Section Editor: Stephen S Gottlieb, MD
Deputy Editor: Todd F Dardas, MD, MS
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2022. | This topic last updated: Mar 04, 2021.
INTRODUCTION
Heart failure (HF) is a common clinical syndrome caused by a variety of cardiac diseases (
table 1) [1-5]. The initial evaluation of the patient with suspected HF will be reviewed here.
Evaluation of the etiology and management of HF and evaluation and treatment of acute
decompensated HF are discussed separately. (See "Determining the etiology and severity of
heart failure or cardiomyopathy" and "Heart failure with preserved ejection fraction: Clinical
manifestations and diagnosis" and "Approach to diagnosis and evaluation of acute
decompensated heart failure in adults" and "Treatment of acute decompensated heart
failure: General considerations" and "Overview of the management of heart failure with
reduced ejection fraction in adults".)
DEFINITION
HF is a complex clinical syndrome identified by presence of current or prior characteristic

symptoms, such as dyspnea and fatigue, and evidence of cardiac dysfunction as a cause of
these symptoms (eg, abnormal left ventricular [LV] and/or right ventricular [RV] filling and
elevated filling pressures) [1-5]. From a hemodynamic perspective, HF is a disorder in which
the heart cannot pump blood to the body at a rate commensurate with its needs, or can do
so only at the cost of high filling pressures [6]. Patients with HF may or may not have
associated physical signs, such as those related to fluid retention. HF can result from any
structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or
eject blood. (See 'Causes and classification' below and "Determining the etiology and severity
of heart failure or cardiomyopathy" and "Pathophysiology of heart failure with reduced
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ejection fraction: Hemodynamic alterations and remodeling" and "Pathophysiology of heart

failure: Neurohumoral adaptations".)
There is no single, noninvasive diagnostic test that serves as a gold standard for HF, since it
is largely a clinical diagnosis based upon a careful history, physical examination, laboratory
and imaging data. While most patients with suspected HF do not require invasive testing for
diagnosis, the clinical gold standard for diagnosis of HF is identification of an elevated
pulmonary capillary wedge pressure at rest or exercise on an invasive hemodynamic
exercise test in a patient with symptoms of HF. (See 'An approach to diagnosis' below and
'Hemodynamic exercise test' below.)
The clinical diagnosis of HF is limited to patients with current or prior symptoms of HF

(American College of Cardiology/American Heart Association [ACC/AHA] stages C and D HF)
and excludes patients with stage A (at high risk for HF but without structural heart disease or
symptoms of HF) or stage B HF (structural heart disease but no symptoms or signs of HF) (
table 2). Asymptomatic systolic or diastolic dysfunction are forms of ACC\AHA stage B HF
which are not encompassed by the clinical diagnosis of HF but are associated with risk of
developing HF. (See "Determining the etiology and severity of heart failure or
cardiomyopathy", section on 'Stages in the development of HF' and "Epidemiology and
causes of heart failure".)
CAUSES AND CLASSIFICATION
HF is caused by a number of conditions, including LV dysfunction, RV dysfunction, valvular

heart disease, pericardial disease, obstructive lesions in the heart or great vessels, or high-
output HF ( table 1).
HF caused by LV dysfunction is commonly categorized according to LV ejection fraction

(LVEF):
● HF with LVEF ≤40 percent is known as HF with reduced ejection fraction (HFrEF).
● HF with LVEF of 41 to 49 percent is HF with mid-range ejection fraction (HFmrEF).
● HF with LVEF ≥50 percent may be caused by HF with preserved ejection fraction (HFpEF)
or a cardiomyopathy (restrictive, hypertrophic, or noncompaction).
HF is often referred to as left-sided failure when caused primarily by left heart pathologies
(eg, LV, mitral valve, or aortic valve dysfunction). HF is called right-sided when caused by
right heart conditions (eg, pulmonary hypertension or RV, pulmonic valve, or tricuspid valve
dysfunction). Left HF and right HF may each occur separately or concurrently. Left HF is a
common cause of right HF, and most patients with right HF have some element of left HF.

The functional status of patients with HF is often described using the New York Heart
Association (NYHA) classification, with severity of disability ranging from I to IV ( table 3).
By definition, all patients with HF have current or prior symptoms of HF. Thus, an
asymptomatic patient (NYHA class I) can carry a diagnosis of HF only if symptoms of HF were
previously present. (See "Determining the etiology and severity of heart failure or
cardiomyopathy", section on 'Classification of HF severity'.)
CLINICAL PRESENTATION
Symptoms and associated conditions — Identification of symptoms of HF is a key step in

diagnosing HF. While a history alone is insufficient to make the diagnosis of HF, a detailed
history remains the single best discriminator to determine the acuity, etiology, and rate of
progression of HF, and the history often provides important clues to the cause of HF. (See
"Determining the etiology and severity of heart failure or cardiomyopathy".)
Symptoms of HF include those due to excess fluid accumulation (dyspnea, orthopnea,

edema, pain from hepatic congestion, and abdominal discomfort due to distention from
ascites) and those due to a reduction in cardiac output (fatigue, weakness) that is most
pronounced with exertion. Fluid retention in HF is initiated by the fall in cardiac output,
leading to alterations in renal function, due in part to activation of the sodium-retaining
renin-angiotensin-aldosterone and sympathetic nervous systems. While left-sided heart
failure is a major cause of right-sided failure, right-sided failure also has other causes,
including pulmonary hypertension and tricuspid valve and pulmonic valve dysfunction (
table 1).
In a systematic review that included data from 15 studies of patients with suspected HF,
dyspnea was the only symptom or sign with high sensitivity (89 percent), but its specificity
was low (51 percent) [7]. Other elements of the history had relatively high specificity but low
sensitivity: orthopnea (specificity and sensitivity of 89 and 44 percent) and history of
myocardial infarction (89 and 26 percent). However, the sensitivity and specificity of these
clinical features are likely to vary among different patient populations.
Important information concerning the acuity of HF is suggested by the presenting

symptoms:
● Acute and subacute presentations (days to weeks) are characterized primarily by

shortness of breath, at rest and/or with exertion. Also common are orthopnea,
paroxysmal nocturnal dyspnea, and, with right HF, right upper quadrant discomfort
due to acute hepatic congestion, which can be confused with acute cholecystitis.
Patients with atrial and/or ventricular tachyarrhythmias may complain of palpitations
with or without lightheadedness.
Patients with acute decompensated HF require prompt diagnosis and management.

(See "Approach to diagnosis and evaluation of acute decompensated heart failure in
adults" and "Treatment of acute decompensated heart failure: General
considerations".)
● Chronic presentations (months) differ in that fatigue, anorexia, abdominal distension,

and peripheral edema may be more pronounced than dyspnea, as dyspnea may be
more subtle and exertional in nature. Because patients developing HF tend to gradually
withdraw from physical activity, they are less likely to perceive symptoms. It is therefore
important to identify patient activity levels and symptoms during those activities. Over
time, pulmonary venous capacitance and lymphatic drainage accommodates to the
chronic state of volume overload, leading to less or no fluid accumulation in the alveoli,
despite the increase in total lung water and high filling pressures. Patients in this
setting present with excessive fatigue and low-output symptoms, and some report
dyspnea predominantly with exertion rather than at rest or in the supine position (as
with acute HF). Anorexia is secondary to several factors including poor perfusion of the
splanchnic circulation, bowel edema, and nausea induced by hepatic congestion.
Patients with chronic HF often develop secondary pulmonary hypertension, which can
contribute to dyspnea as pulmonary pressures rise with exertion. These patients may
also complain of substernal chest pressure, typical of angina. In this setting, elevated
RV end-diastolic pressure may cause secondary RV subendocardial ischemia. (See
"Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension)
in adults".)
Clinical features such as older age, hypertension, history of coronary artery disease or
myocardial infarction, history of atrial fibrillation (AF), obesity, and use of a loop diuretic are
associated with increased likelihood of HF [7-9].
Physical examination — The physical examination can provide evidence of the presence

and extent of cardiac filling pressure elevation, right-sided failure, ventricular enlargement,
pulmonary hypertension, and reduction in cardiac output. Some of the physical examination
findings of HF, while not very specific on their own, can be very specific in the setting of
typical symptoms of HF, but sensitivity is low, so the absence of physical findings does not
exclude HF.
In a study of primary care patients, a physical finding of a displaced apical impulse had the
best combination of sensitivity, specificity, and positive and negative predictive value of any
physical sign of HF with reduced ejection fraction [10]. However, patients with HF and
preserved ejection fraction (HFpEF) typically have a nondilated heart, so displacement of the
apical impulse is not a helpful finding for diagnosis of HFpEF. Other strong predictors of HF
included a gallop rhythm and elevated jugular venous pressure.
The accuracy of physical signs for the diagnosis of HF was evaluated in the above cited
systematic review that included data from 15 studies of patients with suspected HF [7]. Extra
heart sounds were highly specific (99 percent) but had low sensitivity (11 percent). In this
population, hepatomegaly was also highly specific (97 percent) but had low sensitivity (17
percent). Greater specificity than sensitivity was also seen for cardiomegaly (85 and 27
percent), lung crepitation (81 and 51 percent), edema (72 and 53 percent), and elevated
jugular venous pressure (70 and 52 percent).
Vital signs and appearance — A patient’s general appearance and vital signs may suggest
presence of HF, particularly if HF is advanced. An irregularly irregular pulse is suggestive of
AF, which frequently accompanies HF. (See "The management of atrial fibrillation in patients
with heart failure".)
Patients with mild or moderate HF may appear completely normal on physical examination,
with normal vital signs. However, many patients with normal cardiac output at rest have an
inability to augment cardiac output during exercise without excessive increase in filling
pressures, resulting in exertional fatigue and intolerance. Right-sided signs with fluid
overload are often the presenting sign.
In contrast, patients with advanced HF may show evidence of decreased tissue perfusion
caused by a major decline in cardiac output. Four key findings suggest greater severity of
cardiac dysfunction even at steady state: resting sinus tachycardia, narrow pulse pressure,
diaphoresis, and peripheral vasoconstriction. The last abnormality is manifested as cool,
pale, and sometimes cyanotic extremities (due to the combination of decreased perfusion
and increased oxygen extraction). Peripheral vasoconstriction may be absent in patients
treated with vasodilators. A decrease in cardiac output should be suspected when the pulse
pressure is reduced below 25 mmHg or if the proportional pulse pressure (pulse pressure
divided by systolic pressure) is less than 20 to 25 percent. Both the cardiac disease itself and
the secondary neurohumoral adaptation contribute to the low-output state. Patients
compensate for a fall in cardiac output by increasing sympathetic outflow with resultant
shunting of the cardiac output to vital organs.
Pulsus alternans, if present, is virtually pathognomonic of severe LV systolic dysfunction. This

phenomenon is characterized by evenly spaced alternating strong and weak peripheral
pulses. It is best appreciated by applying light pressure on the peripheral arterial pulse and
can be confirmed by measuring the blood pressure. When the cuff pressure is slowly
released, phase I Korotkoff sounds are initially heard only during the alternate strong beats;
with further release of cuff pressure, the softer sounds of the weak beat also appear. Pulsus
alternans can also be appreciated based upon variation in the intensity of the first Korotkoff
sound during auscultatory blood pressure assessment. (See "Examination of the arterial
pulse", section on 'Pulsus alternans'.)

Volume assessment — There are three major manifestations of volume overload in

patients with HF: pulmonary congestion, peripheral edema, and elevated jugular venous
pressure. Volume overload with right-sided failure can be secondary to left-sided failure,
pulmonary hypertension, or valvular disease.
● Pulmonary congestion that may manifest as rales is more prominent in acute or

subacute disease. As noted above, chronic HF is associated with increases in venous
capacitance and lymphatic drainage of the lungs, and alterations in the alveolar
capillary interface that reduce permeability and fluid transit; as a result, rales (crackles)
are often absent even though the pulmonary capillary pressure is elevated. This also
explains why evidence of pulmonary edema is often absent on chest radiographs.
Continued sodium retention in this setting preferentially accumulates in the periphery,
although a chronic elevation in pulmonary venous pressure can lead to pleural
effusions. (See 'Chest radiograph' below.)
● Right-sided failure may be manifested as peripheral edema with swelling of the legs
(which is more prominent when the patient has been upright), and ascites, scrotal
edema, hepatomegaly, and splenomegaly [11]. In this setting, manual compression of
the right upper quadrant to increase venous return may elevate jugular venous
pressure above the transient 1 to 3 cm elevations seen in normal individuals. This sign
is known as the hepatojugular reflux (also known as the abdominojugular test). (See
"Examination of the jugular venous pulse", section on 'Abdominojugular test'.)
● Elevated jugular venous pressure is usually present if peripheral edema is due to HF,
since it is the high intracapillary pressure that is responsible for fluid movement into
the interstitium. With the patient sitting at 45 degrees, jugular venous pressure can be
estimated from the height above the right atrium of venous pulsations in the internal
jugular vein. The height of external jugular vein pulsations may also be helpful, but
care must be taken to avoid spurious interpretation. In some patients, it is necessary to
seat the patient completely upright or at a lower angle to see the meniscus of the
jugular venous pressure ( movie 1). (See "Examination of the jugular venous pulse".)
The accuracy of clinical evaluation of cardiac filling pressures varies among observers, as
illustrated by a study of 116 patients undergoing cardiac catheterization [12]. Signs of
elevated right heart filling pressure included increased jugular venous pressure, peripheral
edema, and ascites. Signs of elevated left heart filling pressure included findings of elevated
right heart filling pressure as well as gallops or rales.
● Right and left heart filling pressures were accurately estimated by physical examination
in 71 and 60 percent of 215 observations. Examination by staff cardiologists was more
accurate than by trainees for right heart pressures (82 versus 67 percent) and left heart
pressures (71 versus 55 percent).
● The use of echocardiography and plasma N-terminal pro-B-type natriuretic peptide (NT-
proBNP) values did not provide better accuracy than the clinical examination. The
accuracy of estimation of right filling pressure by echocardiographic examination of the
inferior vena cava (75 percent) was similar to the accuracy of physical examination. The
accuracy of estimates of left heart filling pressures by NT-proBNP (67 percent) and by
echocardiography E/e’ ratio (60 percent) were also similar to physical examination. (See
'NT-proBNP' below and 'Echocardiography' below.)
Cardiac examination — Ventricular chamber size can be estimated by precordial

palpation. An apical impulse that is laterally displaced past the midclavicular line is usually
indicative of LV enlargement. LV dysfunction can also lead to sustained apical impulse, which
may be accompanied by a parasternal lift in the setting of RV hypertrophy or enlargement.
The S3 may be palpable in severe ventricular failure. (See "Examination of the precordial
pulsation".)
An S3 (third heart sound) is associated with left atrial pressures exceeding 20 mmHg and
increased LV end-diastolic pressures (>15 mmHg). However, there is appreciable
interobserver variability in the ability to detect an S3 that cannot be solely explained by the
experience of the observer [13,14]. In addition, in a phonocardiographic study of patients
who were undergoing cardiac catheterization, an S3 was not very sensitive (40 to 50 percent)
for the detection of an elevated LV end-diastolic pressure or a reduced LV ejection fraction
(LVEF); however, an S3 was highly specific (90 percent) for these parameters and for an
elevated serum BNP concentration [15]. Similarly, an S3 has a low sensitivity (eg, 4 to 11
percent) but high specificity (eg, 99 percent) for clinical diagnosis of HF [7,8]. (See
"Auscultation of heart sounds", section on 'LV gallops'.)
Physical signs of pulmonary hypertension can include increased intensity of P2, a murmur of
pulmonary or tricuspid insufficiency, a parasternal lift, and a palpable pulmonic tap (felt in
the left second intercostal space). Elevation in central venous pressure accompanying
pulmonary hypertension and RV failure often leads to pulsatile hepatomegaly and ascites.
(See "Auscultation of heart sounds" and "Auscultation of cardiac murmurs in adults" and
"Examination of the precordial pulsation" and "Congestive hepatopathy".)
INITIAL TESTING
Electrocardiogram — Most patients with HF with reduced ejection fraction (HFrEF) have a

significant abnormality on an electrocardiogram (ECG). A normal ECG makes LV systolic
dysfunction unlikely (98 percent negative predictive value) [16]. An ECG has relatively high
sensitivity for identifying patients with HFrEF (eg, 89 percent) but more limited specificity (eg,
56 percent) [7]. In contrast, patients with HF with preserved ejection fraction (HFpEF)
commonly display a normal 12-lead ECG, though the presence of atrial fibrillation (AF) or
paced rhythm greatly increase the probability that HFpEF is present [9]. (See "Heart failure
with preserved ejection fraction: Clinical manifestations and diagnosis", section on
'Diagnosis'.)
Although the ECG is less predictive of HF than the B-type natriuretic peptide (BNP; or N-
terminal pro-BNP [NT-proBNP]) level [7], the ECG may show findings that favor the presence
of a specific cause of HF (eg, low voltage in amyloid heart disease) and can also detect
arrhythmias (eg, AF) that suggest heart disease and may cause or exacerbate HF. (See
"Arrhythmia-induced cardiomyopathy" and "Determining the etiology and severity of heart
failure or cardiomyopathy".)
The ECG is particularly important for identifying evidence of acute or prior myocardial
infarction or acute ischemia. Ischemia may cause symptoms of dyspnea similar to HF and
may also cause or exacerbate HF. (See "Electrocardiogram in the diagnosis of myocardial
ischemia and infarction" and "Treatment of acute decompensated heart failure in acute
coronary syndromes".)
Initial blood tests — Recommended initial blood tests for patients with symptoms and
signs of HF include:
● Natriuretic peptide (NP [BNP or NT-proBNP]) levels provide evidence as to whether HF

is present. In patients with dyspnea at rest, the negative predictive value of a normal
plasma NP level is high. NP levels are often (but not exclusively) elevated in patients
with HFrEF, but may be normal in a substantial number of patients with HFpEF. Thus,
the presence of an elevated NP level increases the likelihood that HF is present, but a
normal level does not exclude it, particularly in patients with a normal LVEF or obesity.
Conversely, elevations can be caused by elevated right heart pressures, renal
dysfunction, or many systemic diseases. (See "Natriuretic peptide measurement in
heart failure" and "Heart failure with preserved ejection fraction: Clinical manifestations
and diagnosis", section on 'Natriuretic peptide level'.)
● Cardiac troponin T or I in patients with acute decompensated HF and/or suspected

acute coronary syndrome. (See "Troponin testing: Clinical use" and "Diagnosis of acute
myocardial infarction" and "Initial evaluation and management of suspected acute
coronary syndrome (myocardial infarction, unstable angina) in the emergency
department".)
● A complete blood count, which may suggest concurrent or alternate conditions.

Anemia or infection can exacerbate preexisting HF. (See "Evaluation and management
of anemia and iron deficiency in adults with heart failure".)

● Serum electrolytes, blood urea nitrogen, and creatinine may indicate associated
conditions. Hyponatremia generally indicates severe HF, though other causes should
be considered [17]. Renal impairment may be caused by and/or contribute to HF
exacerbation. Baseline evaluation of electrolytes and creatine is also necessary when
initiating therapy with diuretics and/or angiotensin converting enzyme inhibitors.
● Liver function tests, which may be affected by hepatic congestion. In one study,
gamma-glutamyltransferase level >2 times the upper limit of normal was the only
standard initial blood test that added diagnostic value to the history and physical
examination [8]. However, NT-proBNP was the most powerful supplementary test. (See
"Congestive hepatopathy".)
● Fasting blood glucose to detect underlying diabetes mellitus. (See "Heart failure in
patients with diabetes mellitus: Epidemiology, pathophysiology and management".)
Chest radiograph — The chest radiograph is a useful initial diagnostic test, particularly in

the evaluation of patients who present with dyspnea, to differentiate HF from primary
pulmonary disease [18-20].
Findings suggestive of HF include cardiomegaly (cardiac to thoracic width ratio above 50

percent), cephalization of the pulmonary vessels, Kerley B-lines, and pleural effusions (
image 1A-E). The cardiac size and silhouette may also reveal signs of congenital
anomalies (ventricular or atrial septal defect) or valvular disease (mitral stenosis or aortic
stenosis). As noted above, due to chronic adaptive changes in the lungs, patients with very
high filling pressures and chronic HF will often display clear lung fields on plain chest film.
(See 'Volume assessment' above.)
A systematic review of the utility of the chest radiograph to diagnose LV dysfunction

concluded that redistribution and cardiomegaly were the best predictors of increased
preload and reduced ejection fraction, respectively [19]. Neither finding, however, was
sufficient to make a definitive diagnosis of HF. In a multicenter study of 880 patients,
alveolar edema, interstitial edema, and cephalization all had a specificity of >90 percent for
HFrEF, but only cardiomegaly had a sensitivity >50 percent [20]. A systematic review that
included 15 studies also found that chest radiograph evidence of HFrEF was helpful in
confirming the diagnosis since it had relatively high specificity (83 percent) though more
limited sensitivity (68 percent) [7].
The limitations of a chest radiograph are even more dramatic in patients with HFpEF, where
the sensitivity of cardiomegaly is 24 percent and pleural effusion is only 9 percent. In
contrast, the same study found that specificity for these findings is excellent (96 and 98
percent, respectively) [9]. (See "Heart failure with preserved ejection fraction: Clinical
manifestations and diagnosis", section on 'Clinical manifestations'.)

DIAGNOSIS
The approach to the patient with suspected HF includes the history and physical
examination as well as diagnostic tests to help establish the diagnosis, assess acuity and
severity, and initiate assessment of etiology. Recommendations for the evaluation of
patients with HF were included in the 2013 American College of Cardiology guidelines
[17,21], the 2010 Heart Failure Society of America guidelines [22], the 2016 European Society
of Cardiology guidelines [23], and the 2017 Canadian Cardiovascular Society consensus
conference [24].
The discussion below focuses on diagnosis of HF. Evaluation of the patient with suspected HF
should also include assessment of risk factors and potential etiologies of HF as discussed
separately. (See "Determining the etiology and severity of heart failure or cardiomyopathy"
and "Approach to diagnosis and evaluation of acute decompensated heart failure in adults".)
Diagnosis of HF with preserved ejection fraction (HFpEF) may be more challenging given the
presence of normal EF and is discussed in a separate topic. (See "Heart failure with
preserved ejection fraction: Clinical manifestations and diagnosis".)
When to suspect heart failure — HF should be suspected in individuals with both of the
following features based upon clinical evaluation including history, physical examination,
and initial testing.
● One or more symptoms of HF, such as dyspnea or fatigue; physical signs of HF may or
may not be present. (See 'Symptoms and associated conditions' above and "Heart
failure with preserved ejection fraction: Clinical manifestations and diagnosis", section
on 'Clinical manifestations'.)
● The symptoms are not clearly and completely caused by a noncardiac condition. Of
note, the presence of a noncardiac condition does not exclude HF, as some patients
with HF have concurrent conditions such as lung disease.
Evaluation to distinguish cardiac from other causes may include pulmonary function
studies and a cardiopulmonary exercise test, as discussed below. (See 'Differential
diagnosis' below and "Cardiopulmonary exercise testing in the evaluation of dyspnea".)
An approach to diagnosis — We suggest the following approach to diagnosis of HF based

upon symptoms, signs, and test results ( algorithm 1). This approach has not been
validated and its sensitivity and specificity have not been determined.
● After clinical evaluation (history and physical examination) and initial testing, obtain an
echocardiogram to assess LVEF and evaluate causes of HF, including diastolic and
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systolic dysfunction and valve dysfunction. (See 'Clinical presentation' above and 'Initial
testing' above and 'Echocardiography' below.)
If the LVEF cannot be adequately assessed by echocardiogram despite use of

microbubble contrast agent, alternative methods for assessment include nuclear
methods (radionuclide ventriculography or single-photon emission computed
tomography myocardial perfusion imaging, cardiovascular magnetic resonance
imaging, and cardiac computed tomography. (See "Tests to evaluate left ventricular
systolic function".)
• If the LVEF is ≥50 percent, we suggest an approach to evaluation of suspected

HFpEF as described separately. (See "Heart failure with preserved ejection fraction:
Clinical manifestations and diagnosis" and "Heart failure with preserved ejection
fraction: Clinical manifestations and diagnosis", section on 'Diagnosis'.)
● If the LVEF is <50 percent, the next step is to determine which of the following clinical
findings are present. E is peak velocity of early LV filling, A is peak velocity of late LV
filling, and e' is peak early diastolic velocity of LV myocardium adjacent to the mitral
annulus.
• Low-specificity/high-sensitivity findings:
- Symptoms: Dyspnea on exertion, fatigue, weight gain

- Signs: Peripheral edema
- Clinical feature: Age >60 years
• Intermediate-specificity/intermediate-sensitivity findings:
- Signs: Rales (crackles)

- Chest radiograph: Findings consistent with cardiomegaly or pleural effusion
- ECG: Atrial fibrillation (AF), left atrial enlargement, LV hypertrophy, or pathologic
Q waves
- Serum natriuretic peptide:
Age <50: N-terminal pro-B-type natriuretic peptide (NT-proBNP) 125 to 450
pg/mL or BNP 35 to 100 pg/mL
Age 50 to 75: NT-proBNP 450 to 900 pg/mL or BNP 35 to 100 pg/mL
Age >75: NT-proBNP 900 to 1800 pg/mL or BNP 35 to 100 pg/mL
- Clinical feature: Coronary artery disease (including prior myocardial infarction),
or moderate valvular regurgitation or stenosis
- Echocardiogram: Left atrial volume index >34 mL/m2, E/A ≥0.9 and <2.1, or E/A
≤0.8 and E >50 cm/s
• High-specificity/low-sensitivity findings
- Symptoms: Orthopnea, paroxysmal nocturnal dyspnea

- Signs: Elevated jugular venous pressure, a third heart sound (S3), pulsus
alternans, or laterally displaced point of maximal impulse (PMI)
- Chest radiograph: Findings consistent with pulmonary edema (cephalization of
pulmonary vessels and Kerley B lines, with or without peribronchial cuffing)
- Serum natriuretic peptide:
Age <50: NT-proBNP >450 pg/mL or BNP >100 pg/mL
Age 50 to 75: NT-proBNP >900 pg/mL or BNP >100 pg/mL
Age >75: NT-proBNP >1800 pg/mL or BNP >100 pg/mL
- Clinical feature: Severe valvular regurgitation or stenosis
- Echocardiogram: LVEF <30 percent, LV end-diastolic dimension >5.8 cm (men)
or >5.2 (women); E/e’ ≥15, E/A ≥2.1, or inferior vena cava >2.1 cm with collapse
during sniff <50 percent
● The number of categories (eg, “Symptoms,” “Signs,” “Clinical feature”) of low-specificity,

intermediate-specificity, and high-specificity findings are counted:
• If there are only low-specificity findings or only one or two categories of

intermediate-specificity findings, we recommend referral to a cardiologist or HF
specialist for further evaluation which may include a hemodynamic exercise test.
Evaluation in this setting varies depending upon clinical findings and suspected
concurrent conditions such as ischemic heart disease. If a diagnosis of HF remains
uncertain after noninvasive evaluation, a hemodynamic exercise test is the clinical
gold standard for diagnosis of HF. If a hemodynamic exercise test is performed,
pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg during
exercise is diagnostic for HF.
Many patients with LVEF <50 percent without HF require guideline-directed therapy
to reduce cardiovascular risk (particularly those with LVEF ≤40 percent, prior
myocardial infarction, and/or hypertension). However, a diagnosis of HF has
important therapeutic implications since some pharmacologic agents are indicated
for HF and not for asymptomatic LV systolic dysfunction. (See "Overview of the
management of heart failure with reduced ejection fraction in adults" and "Initial
pharmacologic therapy of heart failure with reduced ejection fraction in adults" and
"Secondary pharmacologic therapy in heart failure with reduced ejection fraction
(HFrEF) in adults" and "Treatment and prognosis of heart failure with mid-range
ejection fraction".)
• If there is at least one high-specificity finding or 3 or more intermediate-specificity

findings, HF is diagnosed.

Further evaluation of patients diagnosed with HF is discussed separately. (See "Determining

the etiology and severity of heart failure or cardiomyopathy".)
Key tests
Echocardiography — An echocardiogram alone does not establish or exclude the

diagnosis of HF but is helpful to identify findings consistent with HF and to identify potential
causes of HF (eg, LV systolic dysfunction, LV diastolic dysfunction, valve dysfunction).
Some studies have used depressed LVEF as a means of identifying patients with HF, but this
approach is inaccurate since approximately half of patients with HF have a preserved LVEF,
and some patients with depressed LVEF do not have the clinical syndrome of HF. While no
single echocardiographic parameter is diagnostic of HF, most patients with HF have one or
more echocardiographic abnormality (eg, reduced LVEF, diastolic dysfunction, LV
hypertrophy, valve stenosis, valve regurgitation, left atrial enlargement, or elevated
estimated pulmonary artery systolic pressure).
Important echocardiographic findings include the following:
● Atrial and ventricular sizes, which may be helpful in identifying the cause and chronicity
of disease. For example, patients with idiopathic dilated cardiomyopathy typically have
both left and right atrial and ventricular enlargement (four chamber dilatation) with
decreased left systolic ventricular function ( image 2 and movie 2 and movie 3
and movie 4). (See "Echocardiographic recognition of cardiomyopathies".)
● Global left and right ventricular systolic function (left and right ventricular ejection
fraction). (See "Tests to evaluate left ventricular systolic function".)
● Evidence of diastolic LV function. (See "Echocardiographic evaluation of left ventricular

diastolic function in adults".)
● Regional wall motion abnormalities in a coronary distribution are suggestive of

coronary heart disease, but segmental abnormalities also occur commonly in patients
with dilated cardiomyopathy and other conditions.
● Pericardial disease includes thickening suggestive of constrictive pericarditis or

effusion, which may or may not be associated with tamponade. (See "Constrictive
pericarditis" and "Cardiac tamponade".)
● Valvular heart disease, as described further in individual valve disease reviews.
Echocardiography also provides a noninvasive assessment of hemodynamic status:

● PCWP can be estimated via the ratio (E/Ea or E/e') of tissue Doppler of early mitral
inflow velocity (E) to early diastolic velocity of the mitral annulus (Ea or e'). An E/e' ratio
>15 suggests a PCWP >15 mmHg. Use and limitations of this method are discussed
separately. (See "Echocardiographic evaluation of left ventricular diastolic function in
adults", section on 'Tissue Doppler imaging'.)
● RV and pulmonary artery pressures can be estimated by the peak velocity of tricuspid
regurgitation on Doppler echocardiography. Right atrial pressure may be estimated
from evaluating the size of the inferior vena cava and its respiratory variation.
● The cardiac output can be estimated by pulsed-wave Doppler from the LV outflow tract
[25].
Natriuretic peptide — Measurement of plasma BNP or NT-proBNP is suggested in the

evaluation of patients with suspected HF when the diagnosis is uncertain, as recommended
in major society guidelines [17,22,23,26]. Natriuretic peptide levels should be interpreted in
the context of other clinical information; they may lend weight to the diagnosis of HF or
trigger consideration of HF but should NOT be used in isolation to diagnose or exclude HF
[17].
In the above cited systematic review that included 15 studies, BNP or NT-proBNP levels had
relatively high sensitivity (both 93 percent) and more limited specificity for diagnosis of HF
(74 and 65 percent) [7]. BNP or NT-proBNP levels are useful in distinguishing HF from other
causes of dyspnea. As noted below, studies developing and validating diagnostic rules for HF
have found that the BNP or NT-proBNP levels add greater diagnostic value to the history and
physical examination than other initial tests (ECG, chest radiograph, and initial blood tests)
[7,8]. Evidence of efficacy and limitations of BNP and NT-proBNP levels in the diagnosis of HF
are discussed in detail separately. (See "Natriuretic peptide measurement in heart failure".)
BNP — Most dyspneic patients with HF have values above 400 pg/mL, while values
below 100 pg/mL have a very high negative predictive value for HF as a cause of dyspnea
[27]. In the range between 100 and 400 pg/mL, plasma BNP concentrations are not very
sensitive or specific for detecting or excluding HF. Other diagnoses, such as pulmonary
embolism, LV dysfunction without exacerbation, LV hypertrophy, and cor pulmonale, should
also be considered in patients with plasma BNP concentrations in this range. AF is associated
with higher levels of BNP in the absence of HF. In one analysis, a BNP cutoff of ≥100 pg/mL
was associated with a specificity of only 40 percent compared with 79 percent in patients
without AF [28]. Using a cutoff of ≥200 pg/mL in patients with AF increased specificity from
40 to 73 percent with a smaller reduction in sensitivity from 95 to 85 percent.
Normal plasma BNP values increase with age and are higher in women than men [29]. Thus,
somewhat higher cutoff values may be needed in these settings, although the optimal

discriminatory values that should be used have not been determined.
NT-proBNP — In normal subjects, the plasma concentrations of BNP and NT-proBNP

are similar (approximately 10 pmol/L). However, in patients with LV dysfunction, plasma NT-
proBNP concentrations are approximately fourfold higher than BNP concentrations [30].
(See "Natriuretic peptide measurement in heart failure", section on 'Plasma N-terminal pro-
BNP'.)
The optimal values for distinguishing HF from other causes of dyspnea vary with patient age.
In a large multicenter study, for patients <50, 50 to 75, and >75 years of age, the optimal
plasma NT-proBNP cutoffs for diagnosing HF were 450 pg/mL, 900 pg/mL, and 1800 pg/mL,
respectively [31]. Overall, these cutoffs yielded a sensitivity and specificity of 90 and 84
percent, respectively. Across the entire population, NT-proBNP levels below 300 pg/mL were
optimal for excluding a diagnosis of HF, with a negative predictive value of 98 percent.
Limitations of BNP and NT-proBNP — There are several important limitations to the

use of plasma BNP and NT-proBNP for diagnosis of HF [32]:
● Patients may present with more than one cause of dyspnea (such as pneumonia and an
exacerbation of HF). Thus, a high plasma BNP or NT-proBNP concentration does not
exclude the presence of other diseases.
● In some patients with acute decompensated HF, plasma BNP or NT-proBNP levels are
not diagnostic.
● Right HF and pulmonary hypertension are associated with elevations in plasma BNP
and NT-proBNP. However, when right HF is due solely to lung disease and not due to
secondary pulmonary hypertension from left-sided heart disease or as part of a global
cardiomyopathy, elevated plasma BNP may be misinterpreted since dyspnea in these
patients is due to lung disease not left HF.
● Plasma BNP and NT-proBNP levels tend to be lower in obese patients and are elevated
in patients with renal failure and some acute noncardiac illnesses such as sepsis.
Greater increases in NT-proBNP than BNP levels are observed in renal failure.
● In patients receiving sacubitril-valsartan, which contains an angiotensin receptor

blocker (valsartan) and a neprilysin inhibitor (sacubitril), plasma BNP levels will be
elevated due to the inhibition of BNP degradation by the neprilysin inhibitor. NT-
proBNP retains its utility as an HF marker since its levels are not affected by the
neprilysin inhibitor.
● As noted above, BNP and NT-proBNP levels are frequently normal in patients with
HFpEF [33-35].

Measurement and interpretation of BNP and NT-proBNP levels is discussed in detail

separately. (See "Natriuretic peptide measurement in heart failure".)
Hemodynamic exercise test — A hemodynamic exercise test (right heart catheterization

with the PCWP assessed at rest and with exercise) is not required for diagnostic evaluation of
most patients with suspected HF. However, in selected patients with suspected HF with
uncertain diagnosis despite evaluation as described above (including history and physical
examination, laboratory tests, chest radiograph, ECG, and echocardiography), cardiology
consultation and right heart catheterization for assessment of cardiac filling pressures at
rest and exercise is useful as the clinical gold standard to make or exclude the diagnosis of
HF.
If a patient has symptoms consistent with HF and PCWP ≥15 mmHg at rest or ≥25 mmHg
during exercise, a diagnosis of HF is confirmed, regardless of LVEF. If these criteria are not
met, a diagnosis of HF is not supported, and further evaluation for other causes of dyspnea
is required. Pressures are measured at end-expiration. Exercise is performed during right
heart catheterization with cycle ergometry (in patients with internal jugular venous access)
or arm abduction with weights (in those with femoral venous access), though the latter
provides a less robust exercise stress [36].
The role of coronary angiography in patients with HF is discussed separately. (See

"Determining the etiology and severity of heart failure or cardiomyopathy", section on
'Detection of coronary artery disease'.)
Additional tests
Exercise testing — In selected patients, exercise testing is helpful in grading the severity of
functional impairment and may also detect underlying ischemic heart disease that warrants
further evaluation. (See "Stress testing for the diagnosis of obstructive coronary heart
disease".)
Cardiopulmonary exercise testing — Cardiopulmonary exercise testing can be useful

both in determining the contribution of HF versus other conditions to the patient’s
symptoms and in assessing the severity of functional impairment. The signs and symptoms
of HF are mimicked by many other conditions (eg, pulmonary disease, anemia). HF is also
frequently accompanied by other diseases, which affect the patients’ functional status.
Cardiopulmonary exercise testing, which combines standard exercise testing with
measurement of ventilatory gas exchange, can be very helpful in clarifying these situations
by defining the presence and extent of the cardiovascular component. (See
"Cardiopulmonary exercise testing in cardiovascular disease".)

Cardiopulmonary exercise testing is also used to evaluate potential candidates for cardiac
transplantation or mechanical circulatory support. (See "Heart transplantation in adults:
Indications and contraindications", section on 'Indications for transplantation' and
"Intermediate- and long-term mechanical circulatory support".)
Other diagnostic approaches — A number of other diagnostic approaches have been

proposed for HF [7,8,37], but none are universally accepted.
The modified Framingham criteria for HF are commonly used to identify patients with HF (
table 4). These criteria generally have excellent specificity but are less sensitive because
they largely rely on evidence of congestion that is present at rest. Well-compensated
patients who are adequately diuresed will not display many of these signs and symptoms,
regardless of LVEF.
Diagnostic rules have been developed that performed well when applied to validation
datasets, although their generalizability to various clinical settings is uncertain [7,8].
DIFFERENTIAL DIAGNOSIS
Many of the symptoms and signs of HF are nonspecific, so other potential causes should be
considered. Patients with HF may present with a syndrome of decreased exercise tolerance,
fluid retention, or both [17]. Various other causes for such symptoms and signs should also
be considered.
● Patients with decreased exercise tolerance have symptoms of dyspnea or fatigue with
exertion and may also have symptoms at rest.
• HF should be distinguished from other causes of dyspnea, including myocardial

ischemia, pulmonary disease, and other disorders [38]. Pulmonary function tests
may be helpful in evaluating respiratory symptoms. The presence of pulmonary
disease does not exclude HF, as some patients have concurrent lung disease and HF.
If the cause of dyspnea on exertion is uncertain, a cardiopulmonary exercise test
may be helpful. (See "Cardiopulmonary exercise testing in the evaluation of
dyspnea".)
As an example, chronic obstructive pulmonary disease and HF may be difficult to

distinguish in some patients. Because of the high prevalence of these disorders,
their similar presentations, and their frequent coexistence, it is reasonable to
consider both diagnoses, not only in patients presenting with dyspnea for the first
time, but also in any patient with one of these diagnoses who presents with a
deterioration in respiratory status [39]. This issue is discussed in detail separately.
(See "Chronic obstructive pulmonary disease: Definition, clinical manifestations,
diagnosis, and staging", section on 'Diagnosis' and "Chronic obstructive pulmonary

disease: Definition, clinical manifestations, diagnosis, and staging".)
• Causes of fatigue include deconditioning, sleep apnea, and depression. (See

"Approach to the patient with dyspnea" and "Approach to the adult patient with
fatigue".)
● Patients presenting with fluid retention may complain of leg or abdominal swelling. HF
should be distinguished from other causes of edema, including venous thrombosis or
insufficiency, renal sodium retention, drug side effect (eg, calcium channel blocker),
and cirrhosis. Right-sided failure may be present without left-sided failure. (See "Clinical
manifestations and evaluation of edema in adults" and "Pathophysiology and etiology
of edema in adults".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Heart failure in
adults".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topic (see "Patient education: Heart failure (The Basics)")
● Beyond the Basics topic (see "Patient education: Heart failure (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS

● Heart failure (HF) is a complex clinical syndrome characterized by current or prior

characteristic symptoms, such as dyspnea and fatigue, and evidence of cardiac
dysfunction as a cause of these symptoms ( table 1). From a hemodynamic
perspective, HF is a disorder in which the heart cannot pump blood to the body at a
rate commensurate with its needs, or can do so only at the cost of high filling
pressures. (See 'Definition' above.)
● HF should be suspected in individuals with one or more symptoms of HF not caused by

a noncardiac condition. Evaluation to distinguish cardiac from other causes may
include a cardiopulmonary exercise test. (See 'When to suspect heart failure' above and
'Differential diagnosis' above and 'Cardiopulmonary exercise testing' above.)
● An approach to diagnosis of HF is based upon clinical findings from history, physical

examination, electrocardiography, natriuretic peptide (NP; B-type NP [BNP] or N-
terminal pro-BNP [NT-proBNP]) levels, chest radiography, and echocardiography (
algorithm 1). This approach has not been validated and its sensitivity and specificity
have not been determined. (See 'An approach to diagnosis' above.)
● An echocardiogram alone does not establish or exclude the diagnosis of HF but is

helpful to identify findings consistent with HF and to identify potential causes of HF (eg,
left ventricular [LV] systolic dysfunction, LV diastolic dysfunction, valve dysfunction).
(See 'Echocardiography' above.)
● Natriuretic peptide levels should be interpreted in the context of other clinical

information; they may lend weight to the diagnosis of HF or trigger consideration of HF
but should NOT be used in isolation to diagnose or exclude HF. (See 'Natriuretic
peptide' above.)
● A hemodynamic exercise test is not required for diagnostic evaluation of most patients
with suspected HF. However, in selected patients with suspected HF with uncertain
diagnosis despite noninvasive evaluation, cardiology consultation and right heart
catheterization for assessment of cardiac filling pressures at rest and exercise is useful
as the clinical gold standard to make or exclude the diagnosis of HF. (See
'Hemodynamic exercise test' above.)
Use of UpToDate is subject to the Terms of Use.
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6. Braunwald E. Heart Disease: A Textbook of Cardiovascular Medicine, 4th ed, Saunders 1

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7. Mant J, Doust J, Roalfe A, et al. Systematic review and individual patient data meta-
analysis of diagnosis of heart failure, with modelling of implications of different
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8. Kelder JC, Cramer MJ, van Wijngaarden J, et al. The diagnostic value of physical
examination and additional testing in primary care patients with suspected heart
failure. Circulation 2011; 124:2865.
9. Reddy YNV, Carter RE, Obokata M, et al. A Simple, Evidence-Based Approach to Help
Guide Diagnosis of Heart Failure With Preserved Ejection Fraction. Circulation 2018;
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10. Davie AP, Francis CM, Caruana L, et al. Assessing diagnosis in heart failure: which
features are any use? QJM 1997; 90:335.
11. O'Reilly RA. Splenomegaly in 2,505 patients at a large university medical center from
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12. From AM, Lam CS, Pitta SR, et al. Bedside assessment of cardiac hemodynamics: the
impact of noninvasive testing and examiner experience. Am J Med 2011; 124:1051.
13. Ishmail AA, Wing S, Ferguson J, et al. Interobserver agreement by auscultation in the
presence of a third heart sound in patients with congestive heart failure. Chest 1987;
91:870.
14. Lok CE, Morgan CD, Ranganathan N. The accuracy and interobserver agreement in
detecting the 'gallop sounds' by cardiac auscultation. Chest 1998; 114:1283.
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third and fourth heart sounds and objective measures of left ventricular function. JAMA
2005; 293:2238.

16. Davie AP, Francis CM, Love MP, et al. Value of the electrocardiogram in identifying heart
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17. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M, 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. Circulation
2013; 128:e240.
18. Gillespie ND, McNeill G, Pringle T, et al. Cross sectional study of contribution of clinical
assessment and simple cardiac investigations to diagnosis of left ventricular systolic
dysfunction in patients admitted with acute dyspnoea. BMJ 1997; 314:936.
19. Badgett RG, Mulrow CD, Otto PM, Ramírez G. How well can the chest radiograph
diagnose left ventricular dysfunction? J Gen Intern Med 1996; 11:625.
20. Knudsen CW, Omland T, Clopton P, et al. Diagnostic value of B-Type natriuretic peptide
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the ESC. Eur Heart J 2016; 37:2129.
24. Ezekowitz JA, O'Meara E, McDonald MA, et al. 2017 Comprehensive Update of the
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25. Gola A, Pozzoli M, Capomolla S, et al. Comparison of Doppler echocardiography with

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28. Mehra MR, Uber PA, Park MH, et al. Obesity and suppressed B-type natriuretic peptide
levels in heart failure. J Am Coll Cardiol 2004; 43:1590.
29. Redfield MM, Rodeheffer RJ, Jacobsen SJ, et al. Plasma brain natriuretic peptide
concentration: impact of age and gender. J Am Coll Cardiol 2002; 40:976.
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natriuretic peptide (NT-PROBNP): a new marker of cardiac impairment. Clin Endocrinol
(Oxf) 1997; 47:287.
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34. Obokata M, Reddy YN, Pislaru SV, et al. Evidence Supporting the Existence of a Distinct
Obese Phenotype of Heart Failure with Preserved Ejection Fraction. Circulation 2017.
35. Anjan VY, Loftus TM, Burke MA, et al. Prevalence, clinical phenotype, and outcomes
associated with normal B-type natriuretic peptide levels in heart failure with preserved
ejection fraction. Am J Cardiol 2012; 110:870.
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early heart failure with preserved ejection fraction. Circ Heart Fail 2010; 3:588.
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39. Le Jemtel TH, Padeletti M, Jelic S. Diagnostic and therapeutic challenges in patients with
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Cardiol 2007; 49:171.
Topic 3510 Version 34.0

GRAPHICS
Mechanisms of the clinical syndrome of heart failure
Left ventricular dysfunction
LVEF ≤40%: Heart failure with reduced ejection fraction (HFrEF)

Causes include ischemic cardiomyopathy and dilated cardiomyopathy
LVEF 41 to 49%: Heart failure with mid-range ejection fraction (HFmrEF)

Causes include ischemic cardiomyopathy and dilated cardiomyopathy
LVEF ≥50%:
Heart failure with preserved ejection fraction (HFpEF)
Cardiomyopathies with preserved ejection fraction
Restrictive cardiomyopathy (familial or nonfamilial causes)
Hypertrophic cardiomyopathy (familial or nonfamilial causes)
Noncompaction cardiomyopathy
Valvular heart disease
Valvular stenosis
Valvular regurgitation
Right ventricular dysfunction
Pulmonary hypertension
Right ventricular infarction
Cardiomyopathy affecting the right ventricle (including arrhythmogenic right ventricular

cardiomyopathy)
Pericardial disease
Cardiac tamponade
Constrictive pericarditis
Effusive-constrictive pericardial disease
Obstructive lesion in heart or great vessel
Atrial myxoma
Pulmonary vein stenosis
High-output heart failure
LVEF: left ventricular ejection fraction.
Graphic 130160 Version 3.0

Comparison of ACCF/AHA Stages of HF and NYHA Functional Classifications
ACCF/AHA stages of HF NYHA functional classification
A At high risk for HF but without structural None

heart disease or symptoms of HF
B Structural heart disease but without signs I No limitation of physical activity. Ordinary
or symptoms of HF physical activity does not cause symptoms
of HF.
C Structural heart disease with prior or I No limitation of physical activity. Ordinary

current symptoms of HF physical activity does not cause symptoms
of HF.
II Slight limitation of physical activity.

Comfortable at rest, but ordinary physical
activity results in symptoms of HF.
III Marked limitation of physical activity.

Comfortable at rest, but less than ordinary
activity causes symptoms of HF.
IV Unable to carry on any physical activity

without symptoms of HF, or symptoms of
HF at rest.
D Refractory HF requiring specialized IV Unable to carry on any physical activity

interventions without symptoms of HF, or symptoms of
HF at rest.
ACCF: American College of Cardiology Foundation;

AHA: American Heart Association;
HF: heart
failure;
NYHA: New York Heart Association.
Reproduced from: 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. Table used with the permission of Elsevier Inc. All rights reserved.

NYHA and other classifications of cardiovascular disability
Canadian
NYHA functional Cardiovascular Specific activity
Class
classification[1] Society functional scale[3]
classification[2]
I Patients with cardiac Ordinary physical Patients can perform to

disease but without activity, such as completion any activity
resulting limitations of walking and climbing requiring ≥7 metabolic
physical activity. stairs, does not cause equivalents (ie, can
Ordinary physical angina. Angina with carry 24 lb up 8 steps;
activity does not cause strenuous or rapid do outdoor work
undue fatigue, prolonged exertion at [shovel snow, spade
palpitation, dyspnea, or work or recreation. soil]; do recreational
anginal pain. activities [skiing,
basketball, squash,
handball, jog/walk 5
mph]).
II Patients with cardiac Slight limitation of Patients can perform to

disease resulting in ordinary activity. completion any activity
slight limitation of Walking or climbing requiring ≥5 metabolic
physical activity. They stairs rapidly, walking equivalents (eg, have
are comfortable at rest. uphill, walking or stair- sexual intercourse
Ordinary physical climbing after meals, in without stopping,
activity results in cold, in wind, or when garden, rake, weed,
fatigue, palpitation, under emotional stress, roller skate, dance
dyspnea, or anginal or only during the few foxtrot, walk at 4 mph
pain. hours after awakening. on level ground) but
Walking more than 2 cannot and do not
blocks on the level and perform to completion
climbing more than 1 activities requiring ≥7
flight of ordinary stairs metabolic equivalents.
at a normal pace and in
normal conditions.
III Patients with cardiac Marked limitation of Patients can perform to

disease resulting in ordinary physical completion any activity
marked limitation of activity. Walking 1 to 2 requiring ≥2 metabolic
physical activity. They blocks on the level and equivalents (eg, shower
are comfortable at rest. climbing 1 flight in without stopping, strip
Less-than-ordinary normal conditions. and make bed, clean
physical activity causes windows, walk 2.5
fatigue, palpitation, mph, bowl, play golf,
dyspnea, or anginal dress without stopping)
pain. but cannot and do not
perform to completion
any activities requiring

>5 metabolic
equivalents.
IV Patients with cardiac Inability to carry on any Patients cannot or do

disease resulting in physical activity not perform to
inability to carry on any without discomfort. completion activities
physical activity Anginal syndrome may requiring >2 metabolic
without discomfort. be present at rest. equivalents. Cannot
Symptoms of cardiac carry out activities
insufficiency or of the listed above (specific
anginal syndrome may activity scale III).
be present even at rest.
If any physical activity
is undertaken,
discomfort is increased.
NYHA: New York Heart Association.
References:
1. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the
Heart and Great Vessels, 9th ed, Little, Brown & Co, Boston 1994. p.253.
2. Campeau L. Grading of angina pectoris. Circulation 1976; 54:522.
3. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing
cardiovascular functional class: Advantages of a new specific activity scale. Circulation 1981; 64:1227.

Dilated cardiomyopathy chest radiograph
This plain frontal radiograph of the chest in a 51-year-old male

demonstrates marked enlargement of the cardiac silhouette
compatible with a dilated cardiomyopathy. Cardiomegaly is
nonspecific and can be seen with any etiology of cardiomyopathy.
Courtesy of Jonathan Kruskal, MD, PhD.
Normal chest radiograph
Posteroanterior view of a normal chest radiograph.
Courtesy of Carol M Black, MD.


Heart failure
This chest radiograph of a 65-year-old male with dyspnea and

orthopnea demonstrates mild pulmonary vascular congestion,
septal lymphatic distention (arrow), interstitial veiling, and enlarged
hilar shadows (arrowhead), indicative of left ventricular
decompensation.
Courtesy of Jonathan Kruskal, MD.


Pulmonary edema
This plain frontal chest radiograph of a 55-year-old male with known

coronary artery disease demonstrates characteristic radiographic
features of heart failure with interstitial pulmonary edema, bilateral
perihilar alveolar edema producing a characteristic butterfly pattern,
and bilateral pleural effusions.
Photo courtesy of Jonathan Kruskal, MD.


Hydrostatic pulmonary edema
Pulmonary edema in a "butterfly distribution" due to left ventricular

failure. Chest radiograph shows large perihilar opacities in patient
with enlarged cardiac silhouette.
Courtesy of Paul Stark, MD.

Radiograph and CT of acute pulmonary edema
(A) An anteroposterior radiograph shows perihilar consolidations and air bronchograms (arrows) of acute
alveolar edema.
(B) A coronal reconstruction of a CT scan of the same patient shows acute alveolar edema with diffuse
perihilar infiltrates and air bronchograms (arrows).
CT: computed tomography.

An approach to diagnosis of heart failure
This algorithm describes an approach to diagnosis of HF based upon a combination of clinical findings. Thi
HF: heart failure; LVEF: left ventricular ejection fraction; HFpEF: heart failure with preserved ejection fractio
fibrillation; LAE: left atrial enlargement; LVH: left ventricular hypertrophy; BNP: B-type natriuretic peptide; N
diastolic dimension; e': peak early diastolic velocity of left ventricular myocardium adjacent to the mitral an
computed tomography; PCWP: pulmonary capillary wedge pressure.
* HF symptoms include dyspnea, fatigue, and edema. Refer to the discussion of symptoms in UpToDate co
¶ In evaluating noncardiac causes, it is important to consider pulmonary causes. Pulmonary function tests
the cause of dyspnea on exertion is uncertain, a cardiopulmonary exercise test may be helpful. For further
Δ If the LVEF cannot be adequately assessed by echocardiogram despite use of microbubble contrast agen
to UpToDate content on tests to evaluate LV function.
◊ Evaluation in this setting varies depending upon clinical findings and suspected concurrent conditions su
diagnosis of HF. If a hemodynamic exercise test is performed, PCWP ≥15 mmHg at rest or ≥25 mmHg duri
LVEF ≤40%, prior myocardial infarction, and/or hypertension). However, a diagnosis of HF has important th
§ Refer to UpToDate content on determining the etiology and severity of HF or cardiomyopathy.

Dilated cardiomyopathy
M-mode scan of the heart is obtained by moving the transducer

from a cephalad to caudal direction, recording the aortic root, mitral
valve and mitral valve annulus, and the left ventricular chamber. In
this patient with a severe dilated cardiomyopathy, there is significant
enlargement of the left atrium and left ventricle. In addition, the
septum and posterior left ventricular wall are thinned and
hypokinetic.

Modified Framingham clinical criteria for the diagnosis of heart failure
Major
Paroxysmal nocturnal dyspnea
Orthopnea
Elevated jugular venous pressure
Pulmonary rales
3rd heart sound
Cardiomegaly on chest radiograph
Pulmonary edema on chest radiograph
Weight loss ≥4.5 kg in 5 days in response to treatment of presumed heart failure*
Minor
Bilateral leg edema
Nocturnal cough
Dyspnea on ordinary exertion
Hepatomegaly
Pleural effusion
Tachycardia (heart rate ≥120 beats/min)
Weight loss ≥4.5 kg in 5 days
Diagnosis
The diagnosis of heart failure requires that 2 major or 1 major and 2 minor criteria cannot be
attributed to another medical condition.
* This criterion was noted in the text of the source paper.
From Senni M, Tribouilloy CM, Rodeheffer RJ, et al, Circulation 1998; 98:2282; adapted from McKee, PA, Castelli, WP,
McNamara, PM, Kannel, WB. N Engl J Med 1971; 85:1441.

Contributor Disclosures
Wilson S Colucci, MD Grant/Research/Clinical Trial Support: Merck [Heart failure]. All of the relevant
financial relationships listed have been mitigated. Barry A Borlaug, MD Patent Holder: Heart Failure
Solutions[Percutaneous pericardiotomy device].
Grant/Research/Clinical Trial Support: AstraZeneca
[Heart failure with preserved ejection fraction];Corvia [Heart failure with preserved ejection
fraction];Medtronic [Heart failure with preserved ejection fraction];NIH/NHLBI [Heart failure with
preserved ejection fraction];Novo Nordisk [Heart failure with preserved ejection fraction];TENAX [Heart
failure with preserved ejection fraction and pulmonary hypertension];United States Department of
Defense [Heart failure with preserved ejection fraction].
Consultant/Advisory Boards: Amgen[Heart
failure with preserved ejection fraction];Aria [Heart failure with preserved ejection fraction];Boehringer
Ingelheim[Heart failure with preserved ejection fraction];Johnson & Johnson [Heart failure with
preserved ejection fraction];Lilly [Heart failure with preserved ejection fraction];Merck [Heart failure
with preserved ejection fraction];Novartis [Heart failure with preserved ejection fraction];Novo Nordisk
[Heart failure with preserved ejection fraction].
All of the relevant financial relationships listed have
been mitigated. Stephen S Gottlieb, MD Grant/Research/Clinical Trial Support: Pfizer [Amyloidosis,
heart failure]; Cytokinetics [Heart failure]; Ionis [Amyloidosis]; BTG International [Renal].
Consultant/Advisory Boards: Cytokinetics [Heart failure]; Pfizer [COVID treatment]. All of the relevant
financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial
relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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05/04/2022 06:12 Heart failure: Clinical manifestations and diagnosis in adults - UpToDate

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Heart failure: Clinical manifestations and diagnosis in

HF is a complex clinical syndrome identified by presence of current or prior characteristic

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ejection fraction: Hemodynamic alterations and remodeling" and "Pathophysiology of heart

The clinical diagnosis of HF is limited to patients with current or prior symptoms of HF

CAUSES AND CLASSIFICATION

HF is caused by a number of conditions, including LV dysfunction, RV dysfunction, valvular

HF caused by LV dysfunction is commonly categorized according to LV ejection fraction

● HF with LVEF of 41 to 49 percent is HF with mid-range ejection fraction (HFmrEF).

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Symptoms and associated conditions — Identification of symptoms of HF is a key step in

Symptoms of HF include those due to excess fluid accumulation (dyspnea, orthopnea,

Important information concerning the acuity of HF is suggested by the presenting

● Acute and subacute presentations (days to weeks) are characterized primarily by

Patients with acute decompensated HF require prompt diagnosis and management.

● Chronic presentations (months) differ in that fatigue, anorexia, abdominal distension,

Physical examination — The physical examination can provide evidence of the presence

Pulsus alternans, if present, is virtually pathognomonic of severe LV systolic dysfunction. This

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Volume assessment — There are three major manifestations of volume overload in

● Pulmonary congestion that may manifest as rales is more prominent in acute or

Cardiac examination — Ventricular chamber size can be estimated by precordial

Electrocardiogram — Most patients with HF with reduced ejection fraction (HFrEF) have a

● Natriuretic peptide (NP [BNP or NT-proBNP]) levels provide evidence as to whether HF

● Cardiac troponin T or I in patients with acute decompensated HF and/or suspected

● A complete blood count, which may suggest concurrent or alternate conditions.

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Chest radiograph — The chest radiograph is a useful initial diagnostic test, particularly in

Findings suggestive of HF include cardiomegaly (cardiac to thoracic width ratio above 50

A systematic review of the utility of the chest radiograph to diagnose LV dysfunction

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An approach to diagnosis — We suggest the following approach to diagnosis of HF based

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If the LVEF cannot be adequately assessed by echocardiogram despite use of

• If the LVEF is ≥50 percent, we suggest an approach to evaluation of suspected

- Symptoms: Dyspnea on exertion, fatigue, weight gain

- Signs: Rales (crackles)

- Symptoms: Orthopnea, paroxysmal nocturnal dyspnea

● The number of categories (eg, “Symptoms,” “Signs,” “Clinical feature”) of low-specificity,

• If there are only low-specificity findings or only one or two categories of

• If there is at least one high-specificity finding or 3 or more intermediate-specificity

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Further evaluation of patients diagnosed with HF is discussed separately. (See "Determining

Echocardiography — An echocardiogram alone does not establish or exclude the

Important echocardiographic findings include the following:

● Evidence of diastolic LV function. (See "Echocardiographic evaluation of left ventricular

● Regional wall motion abnormalities in a coronary distribution are suggestive of

● Pericardial disease includes thickening suggestive of constrictive pericarditis or

● Valvular heart disease, as described further in individual valve disease reviews.

Echocardiography also provides a noninvasive assessment of hemodynamic status:

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Natriuretic peptide — Measurement of plasma BNP or NT-proBNP is suggested in the

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discriminatory values that should be used have not been determined.

NT-proBNP — In normal subjects, the plasma concentrations of BNP and NT-proBNP

Limitations of BNP and NT-proBNP — There are several important limitations to the

● In patients receiving sacubitril-valsartan, which contains an angiotensin receptor

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Measurement and interpretation of BNP and NT-proBNP levels is discussed in detail

Hemodynamic exercise test — A hemodynamic exercise test (right heart catheterization

The role of coronary angiography in patients with HF is discussed separately. (See