Pulmonary regurgitation

Highlights
Summary Overview

Basics
Definition Epidemiology Aetiology Pathophysiology

Prevention
Secondary

Diagnosis
History & examination Tests Differential Step-by-step Criteria Guidelines Case history

Treatment
Details Step-by-step Emerging Guidelines

Follow Up
Recommendations Complications Prognosis

Resources
References Images Patient leaflets Credits Email Print Feedback Share Add to Portfolio Bookmark Add notes

History & exam

Key factors

presence of risk factors

Other diagnostic factors

dyspnoea decreased exercise tolerance orthopnoea

paroxysmal nocturnal dyspnoea palpitations fatigue diaphoresis displaced point of maximal apical impulse diastolic murmur systolic murmur signs of right-sided heart failure History & exam details

Diagnostic tests
1st tests to order

ECG trans-thoracic Doppler echocardiogram (TTE) CXR

Tests to consider

trans-oesophageal Doppler echocardiogram (TEE) MRI chest CT scan chest Diagnostic tests details

Treatment details

Acute
o o o

acute pulmonary regurgitation non-severe medical management of heart failure severe medical management of heart failure inotropic support + surgical valve replacement

Ongoing
o o

chronic pulmonary regurgitation asymptomatic treatment of the underlying cause pulmonary valve replacement anticoagulation symptomatic with NYHA class I treatment of the underlying cause + medical management of heart failure pulmonary valve replacement anticoagulation symptomatic with NYHA class II or III treatment of the underlying cause + medical management of heart failure

pulmonary valve replacement anticoagulation symptomatic with NYHA class IV symptoms treatment of underlying cause + individualised medical and/or surgical treatment Treatment details

Summary
Any disease of the left side of the heart or the lungs that results in significant pulmonary HTN and dilated pulmonary arteries may lead to acquired pulmonary regurgitation. Pulmonary regurgitation may also be due to a congenital defect. Acquired pulmonary valve regurgitation also typically results from surgical repair of tetralogy of Fallot, pulmonary stenosis, or atresia. Isolated pulmonary regurgitation is rarely symptomatic; however, large regurgitant volume in the presence of dilated right ventricle may be associated with exertional dyspnoea, easy fatigability, and intermittent chest pain. Trans-thoracic echo, trans-oesophageal echo, and MRI are essential to determine the severity and mechanism of pulmonary regurgitation. In symptomatic patients with severe regurgitation, pulmonary valve replacement should be considered.

Definition
Pulmonary regurgitation is rare and is infrequently symptomatic. It gradually develops over many years and results in volume overload and right ventricular (RV) dysfunction. It can be congenital or acquired, caused by conditions that increase pulmonary artery pressure, such as left ventricular (LV) dysfunction or severe lung disease. The acquired form occurs from any secondary cause that leads to pulmonary regurgitation through increased pulmonary pressure secondary to left-sided failure, or after surgical intervention for tetralogy of Fallot, pulmonary stenosis, or pulmonary atresia. Isolated pulmonary regurgitation occurs as a result of any cause that impacts the valve directly: for example, endocarditis. The murmur of pulmonary regurgitation is diastolic and is associated with RV lift. [1]

Epidemiology
Non-severe pulmonary regurgitation is usually asymptomatic and is most commonly secondary to pulmonary HTN. Severe isolated pulmonary

regurgitation is usually a manifestation of surgical repair, so patients are usually in their third or fourth decade of life at presentation. However, even with severe isolated pulmonary regurgitation, only 40% of the patients present with symptoms, so the true incidence and prevalence is unknown. There is no specific sex or ethnicity predominance; however, it is commonly associated with younger age. [2]

Aetiology
Pulmonary regurgitation may be congenital or acquired. In the acquired form it may result from any left-sided cardiac condition, such as mitral stenosis, or severe pulmonary disease and pulmonary HTN. Other known causes are dilation of the pulmonary annulus secondary to pulmonary HTN or post balloon inflation for pulmonary valve stenosis. Endocarditis may destroy the integrity of the pulmonary valve leaflets, resulting in pulmonary regurgitation. [1] [2] Other conditions that may result in abnormal pulmonary valve leaflets are congenital anomalies, rheumatic heart disease, carcinoid heart disease, syphilis, and trauma (e.g., from a Swan-Ganz catheter). [3] Connective tissue disease, such as Marfan's syndrome, may also be an associated cause. [3] Very rarely, it may be caused by primary or metastatic malignancies that involve the main pulmonary artery. In addition, the acquired form commonly results decades after surgical repair of tetralogy of Fallot, pulmonary stenosis, or atresia. It has also been associated with the Ross procedure (pulmonary autograft used for aortic valve replacement). [4]

Pathophysiology
Severe isolated pulmonary valve regurgitation is rare. However, when present, it results in volume overload and dilation of the right ventricle with compensatory RVH. Eventually, this results in equalisation of the pulmonary artery pressure and the RV pressure in diastole. Furthermore, with severe progression and RV failure, right-sided stroke volume decreases, leading to peripheral oedema, dyspnoea, and easy fatigability. Pulmonary regurgitation associated with pulmonary HTN is usually nonsignificant and has few to no haemodynamic consequences. It is the pulmonary HTN that results in RV failure and dilation and low right-sided cardiac output. The regurgitant pulmonary volume depends on a number of factors: [2]

diastolic filling period the regurgitant orifice dimension pressure gradient across pulmonary valve pulmonary artery distensibility RV compliance and function.

Secondary prevention
The underlying cause, such as mitral stenosis, LV dysfunction, and pulmonary HTN, should be treated. All patients with prosthetic valves need antibiotics for prophylaxis against infective endocarditis when undergoing dental procedures that involve manipulation of either gingival tissue or the periapical region of teeth, or perforation of the oral mucosa. [16]

Monitoring
Pulmonary regurgitation may worsen over time. Periodic echocardiogram with Doppler colour flow studies will provide serial assessment of progression of pulmonary regurgitation and RV size and function. In cases of significant pulmonary regurgitation, exercise capacity should be assessed and documented, observing for a change or decrease in function. The aim is to assess and accurately decide on the need and timing for pulmonary valve replacement.

After pulmonary valve replacement, patients should be followed up at 30 days and then 6 months, followed by yearly visits. In general, all patients who receive a mechanical valve require lifelong anticoagulation. INR should be monitored and kept between 2.5 and 3.5. Frequency of monitoring should be individualised according to the patient's need and response.

Patient Instructions
If symptoms occur, patients should be reviewed by their physicians. Although there is little available on the risk of endocarditis postpulmonary valve surgery, the current recommendation is to provide antibiotic prophylaxis before dental or urological procedures.

Complications
Complicationhide all

right-heart heart failure see our comprehensive coverage of Chronic congestive heart failure In severe cases where right-sided heart failure has occurred, diuretics may be used. Decision to use a diuretic would depend on the clinical condition of the patient, and the choice of diuretic should be individualised by the treating specialist. When the condition is severe, patients may not tolerate any diuretics. Further information on treatment of heart failure is available in the monographs on CHF. congestive heart failure see our comprehensive coverage of Chronic congestive heart failure Long-standing pulmonary regurgitation can lead to severe RV dilation and diminished RV systolic performance, which can lead to an inadequate ability to augment cardiac output with exercise, and, in some cases, result in CHF. Further information on treatment of heart failure is available in the monographs on CHF. valve failure Patient needs to be re-evaluated and consideration given to repeat valve replacement. infectious endocarditis see our comprehensive coverage of Infective endocarditis All patients with prosthetic valves need antibiotics for prophylaxis against infective endocarditis when undergoing dental procedures that involve manipulation of either gingival tissue or the periapical region of teeth, or perforation of the oral mucosa. [16] thromboembolic events

In general, all patients who receive a mechanical valve require lifelong anticoagulation. INR should be monitored and kept between 2.5 and 3.5. complications of valve replacement Early mortality for isolated pulmonary valve replacement is 1% in children, and freedom from reoperation for bioprosthetic valve deterioration is approximately 90% at 10 years. [16] Patients with mechanical pulmonary valve should be monitored for bleeding complications with warfarin.

Prognosis
In general, patients do well after pulmonary valve replacement. [5] [12] [11] Early mortality for isolated pulmonary valve replacement is 1% in children, and freedom from reoperation for bioprosthetic valve deterioration is approximately 90% at 10 years. [16] Patients with mechanical pulmonary valve should be monitored for bleeding complications with warfarin. Prognosis in patients with severe pulmonary regurgitation who do not undergo surgery (although they may be candidates) depends on a number of factors that include the primary disease causing PR, involvement of other valves, associated CAD, and right ventricular dilation and dysfunction. In patients with repaired tetralogy of Fallot and chronic pulmonary regurgitation, right ventricular dilation has been shown to correlate with an increased incidence of sudden death. There are no large trials of prosthetic valves in patients with isolated pulmonary regurgitation to provide evidence for the prognosis in untreated patients.

Case history #1
A 32-year-old woman with history of repaired tetralogy of Fallot in childhood presents with exertional dyspnoea, easy fatigability, and non-exertional chest pain. On physical examination her jugular venous pressure is around 10 cm with prominent RV anterior precordial lift. A short, low-pitched, grade 2/6 diastolic and a loud, grade 3/6 systolic murmur along the left sternal border are heard.

Case history #2
A 52-year-old woman with history of congenital pulmonic stenosis, for which she underwent open valvotomy at age 9, presents to the adult congenital heart disease clinic for a second opinion, after being followed by a general cardiologist for several years. She is asymptomatic and has excellent exercise capacity. Physical examination reveals no jugular venous distension. Auscultation reveals a short, low-pitched 2/6 diastolic and a loud 3/6 systolic murmur along the left sternal border.

Differential diagnosis
Condition Mitral stenosis

Differentiating signs/symptoms Differentiating tes

Malar flush, low volume pulse, a tapping and undisplaced apex beat, and loud S1 with an opening snap. The murmur is rumbling and mid-diastolic. In mild AR the murmur is early

CXR: pulmonar calcification.

ECG: can prese

Echocardiogram

Aortic regurgitation (AR)

CXR: may show chronic AR.

diastolic, and increases in duration to holodiastolic in severe AR.

ECG: may show or conduction a

Echocardiogram width; detection

A diastolic murmur may be absent in acute AR. The murmur is mid-late diastolic, and changes in character and intensity with alterations in position.

Atrial myxoma

Echocardiogram interatrial septu

History & examination

Key diagnostic factorshide all
presence of risk factors (common)

Key risk factors include hx of tetralogy of Fallot repair or Ross procedure, pulmonary stenosis or valvuloplasty, hx of endocarditis or left-sided heart disease (e.g., LV dysfunction, mitral valve stenosis). Other diagnostic factorshide all dyspnoea (common) Patients may experience dyspnoea on exertion. Worsening dyspnoea associated with leg swelling may signify right heart failure. decreased exercise tolerance (common) Important to determine if there is sensation of passing out with exertion. If tolerance is getting progressively worse this requires immediate attention. diastolic murmur (common) Low-pitched murmur along the left sternal border may be heard. orthopnoea (uncommon) If present, other valve pathologies that affect the left side of the heart should be sought. paroxysmal nocturnal dyspnoea (uncommon) If present, other valve pathologies that affect the left side of the heart should be sought. palpitations (uncommon) Atrial fibrillation, flutter, or SVT are most common and should be ruled out with proper history.

fatigue (uncommon) Is common when there is pulmonary HTN leading to decreased cardiac output. diaphoresis (uncommon) In severe cases, usually with acute mitral regurgitation. displaced point of maximal apical impulse (uncommon) Indicates severe and chronic mitral regurgitation. systolic murmur (uncommon) Low-pitched murmur along the left sternal border may be heard. signs of right-sided heart failure (uncommon) These are elevated jugular venous pressure, lower extremity oedema, hepatomegaly, and ascites. Risk factorshide all Strong pulmonary HTN Pulmonary HTN, both primary and secondary, results in RV failure and dilation and has been associated with pulmonary regurgitation. [1] [2] surgical repair of tetralogy of Fallot, pulmonary stenosis, or pulmonary atresia Repair of pulmonary atresia or stenosis is a known and significant risk factor for future

pulmonary regurgitation.[1] [2] Details such as balloon size used at pulmonary valvuloplasty and degree of regurgitation post valvuloplasty should be determined. endocarditis Any condition that may destroy the integrity of the valve leaflets may result in pulmonary regurgitation. [1] [2] left-sided heart disease Any left-sided condition, such as severe LV dysfunction, that results in pulmonary HTN may cause pulmonary regurgitation. [1] [2] previous Ross procedure (with prosthetic pulmonary valve, homograph valve replacement) Acquired pulmonary regurgitation has also been associated with the Ross procedure (pulmonary autograft used for aortic valve replacement). [4] Weak collagen vascular disease Conditions that result in pulmonary HTN, such as scleroderma or CREST syndrome (calcinosis, Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly, and telangiectasia), may be secondary causes of pulmonary HTN. [1] [2]

malignancies that involve the main pulmonary artery Very rarely, pulmonary regurgitation may be caused by primary or metastatic malignancies that involve the main pulmonary artery.

Diagnostic tests
1st tests to orderhide all
Test

ECG RV dilation produces incomplete right bundle branch blo

RV hypertrophy produces a tall R wave in V1 or qR in V1 R wave progression reversal in the precordial leads, and precordial leads. Right atrial enlargement produces right axis deviation.

Pulmonary regurgitation after repair of tetralogy of Fallot

Left ventricular size may also influence QRS duration. [1

trans-thoracic Doppler echocardiogram (TTE) Should be ordered in any patient where pulmonary regur

TTE is useful for determining severity, mechanism, aetio valvular abnormalities, and RV systolic pressure. View im imageView imageView image Additionally, it is useful in pulmonary valve. Evidence of tricuspid regurgitation sho

CXR Appearance of the lung fields depends on the chronicity severe LV dysfunction have normal lung fields because t compensated. View imageView image

Tests to considerhide all

Test

trans-oesophageal Doppler echocardiogram (TEE) In general, if TTE indicates severe PR, then a TEE would degree and cause of regurgitation. TEE is also indicated is suspected but availability of TTE is limited.

TEE is useful for determining severity, mechanism, aetio valvular abnormalities, and RV systolic pressure. Additio vegetations on the pulmonary valve. Evidence of tricuspi consideration.

MRI chest In patients where the decision to treat pulmonary regurgi

chest may be very helpful. View imageView image

CT scan chest In patients where the decision to treat pulmonary regurgi chest may be very helpful.

Step-by-step diagnostic approach

History and physical examination are non-specific, and the patient is often asymptomatic.

History
In a symptomatic patient, exertional dyspnoea, easy fatigability, and nonexertional chest pain are the most common symptoms. The patient may also complain of palpitations, diaphoresis, paroxysmal nocturnal dyspnoea, and orthopnoea. A history of left-sided heart failure and other valve pathologies such as mitral stenosis and endocarditis may be present. A thorough history regarding previous cardiac surgeries and pulmonary valvuloplasty should be obtained, including repair of tetralogy of Fallot and Ross procedure (with prosthetic pulmonary valve or homograph valve replacement).

Physical examination
Jugular venous pressure may be elevated and a prominent RV anterior precordial lift present. Most commonly, a short, low-pitched diastolic murmur and systolic murmur may be heard along the left sternal border. [5] Although the likelihood of isolated right-sided heart failure secondary to valve failure is low, it should be considered in patients with lower extremity oedema, hepatomegaly, and ascites.

Tests
ECG may show incomplete right bundle branch block and right axis deviation, findings consistent with right ventricular dilation that occurs either while in a compensated volume overload state or in a decompensated pressure

overload state. In a compensated state of pressure overload, RVH may be present by ECG criteria that include the following: tall R wave in V1 or qR in V1; R wave greater than S wave in V1; R wave progression reversal in the precordial leads; inverted T wave in the anterior precordial leads; right axis deviation and right atrial enlargement. In pulmonary regurgitation after repair of tetralogy of Fallot, QRS prolongation may be found. A trans-thoracic echocardiogram (TTE) can be used to assess severity, mechanism, aetiology, RV size and function, other valvular abnormalities, and RV systolic pressure, and should be ordered in all patients in whom pulmonary regurgitation is suspected. Colour flow imaging is most often used for detection of PR. Severity of PR is usually assessed by the diameter of the jet at its origin immediately below the valve, in the right ventricular outflow tract (RVOT), on the parasternal short axis view. A jet width that occupies >65% of the RVOT is suggestive of severe PR. [6] View imageView imageView imageView imageView imageView image Occasionally a transoesophageal echocardiogram (TEE) may be needed to better assess the severity and aetiology of pulmonary regurgitation. In general, if TTE indicates severe pulmonary regurgitation, then a TEE would be recommended to better assess the degree and cause of regurgitation. TEE is also indicated in cases where pulmonary regurgitation is suspected but availability of TTE is limited. Severe pulmonary regurgitation extends 1 to 2 cm into the right ventricle, and the duration of the jet usually occupies 75% or more of the entire duration of diastole. [7] Catheterisation and angiocardiography are less helpful in this setting because they may falsely elevate the quantity of pulmonary regurgitation as the catheter is crossing the pulmonary valve. Other imaging modalities, such as CXR, View imageView image MRI, View imageView image and CT, are also useful to identify pulmonary anatomy and the cause of pulmonary regurgitation and quantify the degree of regurgitation. Additionally, MRI can measure pulmonary regurgitant fraction, RV end-diastolic and end-systolic volumes, and RV ejection fraction. [8] [9] In patients where the decision to treat pulmonary regurgitation is being considered, an MRI and/or CT may be extremely helpful.

Diagnostic criteria
There are no specific criteria to diagnose this condition. The extent and severity depend on echocardiographic evaluation (trans-thoracic echo and trans-oesophageal echo). However, severe pulmonary regurgitation extends

1 to 2 cm into the RV and the duration of the jet usually occupies 75% or more of the entire duration of diastole. [7] Occasionally other modalities such as MRI or CT may need to be used to assess the RV outflow tract and to identify the aetiology of pulmonary regurgitation.

NYHA functional classification for stages of heart failure

Class I: no limitation of activities; no symptoms from ordinary activities Class II: slight, mild limitation of activity; comfortable with rest or with mild exertion Class III: marked limitation of activity; comfortable only at rest Class IV: confined to bed or chair; any physical activity brings on discomfort, and symptoms occur at rest.

Treatment Options

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Patient group acute pulmonary regurgitatio n non-severe

Treatment Treatmenthide all line

1st

medical management of heart failure An almost unavoidable complication of balloon pulmonary valvuloplasty. The severity is more dependent on symptoms than on imaging in this setting. Severe symptoms and signs include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. However, in general, severe pulmonary

Treatment approach
Management of pulmonary regurgitation is different from that of aortic regurgitation and rarely requires surgery. Treatment should be directed at the underlying pathology (e.g., pulmonary HTN, mitral stenosis, LV dysfunction, and other underlying conditions). Longstanding pulmonary regurgitation can lead to severe RV dilation and diminished RV systolic performance, which can lead to an inadequate ability to augment cardiac output with exercise and, in some cases, right-sided heart failure or CHF. While the likelihood of isolated right-sided heart failure secondary to valve failure is low, it should be considered in patients with lower extremity oedema, elevated jugular venous pressure, hepatomegaly, or ascites. In severe cases where right-sided heart failure has occurred, diuretics may be used. Pulmonary valve replacement is required in patients post tetralogy of Fallot repair or Ross procedure who develop NYHA class II or III symptoms, but may be considered earlier. Although there are no specific criteria to diagnose this condition, severe pulmonary regurgitation can be diagnosed based on echo demonstrating pulmonary regurgitation that extends from 1 to 2 cm into the right ventricle, with the duration of the jet usually occupying 75% or more of the entire duration of diastole. [7] Symptoms and signs of severe pulmonary regurgitation include dyspnoea on exertion, syncope, orthopnoea, and lower extremity oedema. In many situations (e.g., acute pulmonary regurgitation post valvuloplasty, post-tetralogy of Fallot repair patients with NYHA class II symptoms or higher), the clinical judgement of severity is more dependent on symptoms than on imaging.

Acute pulmonary regurgitation

Acute severe pulmonary regurgitation is an almost unavoidable complication of balloon pulmonary valvuloplasty and can be managed conservatively in most cases. The clinical judgement of severity in these patients is more dependent on symptoms than on imaging. Severe pulmonary regurgitation post valvuloplasty is rare. Treatment of even the most severe cases is directed at treating heart failure. Rarely, surgical valve replacement may be required, especially in a neonate with critical pulmonary stenosis following balloon dilation and a large patent ductus arteriosus. Fluid resuscitation and intravenous pressors such as dopamine or dobutamine may be necessary, acutely, for severe disease.

Chronic pulmonary regurgitation in asymptomatic patients

In most cases, no specific treatment is required, and treatment is directed at the underlying cause. The indications for valve replacement based on regurgitant fraction, RV end-diastolic or end-systolic volume, and RV ejection fraction in asymptomatic patients remain unclear. [11]The typical situation in which pulmonary valve replacement may be considered is in patients who develop pulmonary regurgitation after repair of tetralogy of Fallot or a Ross procedure (a procedure in which the diseased aortic valve is replaced with the patient's own pulmonary valve, and the pulmonary valve is then replaced with a cryopreserved cadaveric pulmonary valve). Many would share the concern that it may be unwise to wait until RV function deteriorates in these patients, and that valve replacement should be considered before irreversible damage to ventricular performance occurs. [12]

Chronic pulmonary regurgitation in patients with NYHA class I symptoms

Patients are classed as NYHA class I if there is no limitation of physical activity and ordinary physical activity does not cause undue fatigue, palpitations, or dyspnoea, but symptoms appear with more than ordinary activity. In most cases, no specific treatment is required. Underlying conditions such as LV failure, mitral stenosis, and pulmonary HTN need to be treated. Heart failure should be managed using standard therapies. Patients who develop pulmonary regurgitation after repair of tetralogy of Fallot or a Ross procedure may be considered for pulmonary valve replacement, as it may be better to perform valve replacement early in these patients. [11] If pulmonary regurgitation is severe and associated with right-sided heart failure, then surgical valve replacement may be necessary. There are, however, no definitive guidelines and the best course of action is unclear.

Chronic pulmonary regurgitation in patients with NYHA class II or III symptoms

Clinical judgement of disease severity is more dependent on symptoms than on imaging in this situation. Most patients with NYHA class II or III symptoms have developed pulmonary regurgitation as a complication of tetralogy of Fallot repair or a Ross procedure. Underlying and associated conditions such as LV failure, mitral stenosis, and pulmonary HTN need to be treated. Pulmonary valve replacement, usually with a homograft or xenograft, has been performed with low risk of complications, [13] and most specialists would perform pulmonary valve replacement in patients with NYHA class II or III symptoms. [14]

Chronic pulmonary regurgitation in patients with NYHA class IV symptoms

Patients are defined as NYHA class IV if they are confined to their bed or chair, any physical activity brings on discomfort, and symptoms occur at rest. There are no guidelines or standard protocols on management of these patients. Specialist referral for individualised management is advised in all circumstances.

Choice of valve replacement

Traditionally bioprosthetic pulmonary valves have been implanted; however, they have the disadvantage of time-related structural valve failure. Mechanical pulmonary valves may be advantageous due to their structural stability, but they have been infrequently used due to concerns regarding thrombosis. Reports on long-term outcomes of mechanical pulmonary valve are emerging; however, there is a selection bias for patients with prior operations in such reports. [15] The appropriate valve used in pulmonary valve replacement needs to be tailored for the individual patient depending on age, multiple operations, and the need for long-term anticoagulation. All patients who receive a mechanical valve require lifelong anticoagulation. Anticoagulation may also be indicated due to the presence of other mechanical prostheses or as part of the treatment of comorbid conditions. [16]

Emerging treatments
Transcatheter pulmonary valve replacement (TPVR)

TPVR is emerging as a less invasive approach than surgery in patients with right ventricle-to-pulmonary artery conduit dysfunction (regurgitation or stenosis). Using a valve composed of a trileaflet bovine jugular vein sutured into a balloon expandable stent, several clinical trials in Europe and the US have demonstrated a high rate of procedural success with few procedural complications, and restoration of pulmonary valve competence. [17] [18] In 2010, the FDA approved the use of this valve in the US for placement in dysfunctional (stenotic or regurgitant) right ventricular outflow conduits. One of the concerns raised recently with this valve is stent fracture, with an incidence as high as 25%. [19] Another type of transcatheter heart valve was recently evaluated in a multicentre phase 1 clinical trial for the same indication and demonstrated safety and short-term durability. [20] Additional data with long-term follow-up is necessary to understand the timing and role of TPVR in this patient population.

Pleural effusion
Highlights
Summary Overview

Basics
Definition Epidemiology Aetiology Pathophysiology Classification

Prevention
Primary Secondary

Diagnosis
History & examination

Tests Differential Step-by-step Guidelines Case history

Treatment
Details Step-by-step Emerging Guidelines Evidence

Follow Up
Recommendations Complications Prognosis

Resources
References Images Patient leaflets Credits Email Print Feedback Share Add to Portfolio Bookmark

Add notes

History & exam

Key factors

presence of risk factors dyspnoea dullness to percussion

Other diagnostic factors

pleuritic chest pain cough decreased breath sounds decreased or absent tactile fremitus History & exam details

Diagnostic tests
1st tests to order

posteroanterior (PA) and lateral CXR pleural ultrasound LDH and protein in pleural fluid and serum RBC count in pleural fluid WBC count and differential of pleural fluid cytology of pleural fluid culture of pleural fluid pH of pleural fluid

glucose in pleural fluid protein gradient FBC CRP blood culture sputum Gram stain and culture NT-proBNP in pleural fluid

Tests to consider

thoracic CT scan thoracic MRI helical CT scan amylase in pleural fluid adenosine deaminase (ADA) level in pleural fluid lipid analysis of pleural fluid thoracoscopy bronchoscopy pleural biopsy

Emerging tests

tumour markers in pleural fluid interferon-gamma in pleural fluid and real-time PCR of pleural fluid soluble triggering factor expressed on myeloid cells Diagnostic tests details

Treatment details
Acute
o o

CHF diuretic symptomatic large effusion therapeutic thoracocentesis oxygen infective empiric intravenous antibiotics therapeutic thoracocentesis symptomatic large effusion oxygen empyema tube thoracostomy malignant therapeutic thoracocentesis symptomatic large effusion oxygen

o o

Ongoing

persistent empyema despite chest tube direct visualisation and lysis of adhesions recurrent symptomatic malignant effusion life expectancy of weeks or less repeated therapeutic thoracocenteses life expectancy beyond several weeks indwelling catheter pleurodesis Treatment details

o o o

Summary

Presents with SOB, cough, and pleuritic chest pain. The aetiology of the pleural effusion determines other signs and symptoms. Postero-anterior CXR will show an effusion of >200 mL of fluid. An ultrasound, chest CT scan, or lateral decubitus study indicates whether the fluid is free-flowing or loculated. Aspiration and evaluation of the pleural fluid with biochemistry, cytology, and culture determines the nature of the effusion. Treatment is based on the nature of the effusion and underlying condition.

Therapeutic thoracocentesis with nearly complete removal of the fluid collection alleviates dyspnoea and cough in most circumstances.

Definition
A pleural effusion results when fluid collects between the parietal and visceral pleural surfaces of the thorax. A thin layer of fluid is always present in this space for lubrication and ease of movement of the lung during inspiration and expiration. If the normal flow of fluid is disrupted, with either too much fluid produced or not enough removed, then fluid accumulates, resulting in a pleural effusion. [1] [2]

Epidemiology
The leading cause of pleural effusion in the US is CHF, with an estimated annual incidence of 500,000. Pneumonia is second with an incidence of 300,000. [4] Approximately 40% of the hospitalised patients with pneumonia have an associated parapneumonic effusion. [5]Malignancy is the third leading cause overall, with an estimated incidence of 200,000; however, it is the second most common cause of effusion in patients >50 years of age. [4] Pulmonary embolus, viral disease, coronary artery bypass surgery, and cirrhosis are also common causes of effusion. Small pleural effusions are present in up to 40% of patients with pulmonary embolism. Of all patients with cirrhosis, 5% have an associated pleural effusion. [6] TB is an important cause of pleural effusion in the developing world and should also be considered in travellers returning from endemic areas and in immunocompromised people.

Aetiology
A pleural effusion can result from an incredibly diverse list of conditions, but the end result is that an effusion collects when the rate of fluid formation is greater than that of fluid removal. An effusion can be exudative or transudative. An exudative effusion occurs when local factors are altered, such as inflammation of the lung or the pleura leading to capillary leakage of fluid into the pleural space. A transudative effusion, by contrast, occurs when systemic factors come into play. This includes an elevated portal pressure from cirrhosis, elevated visceral pulmonary capillary pressure from left-sided heart failure, elevated parietal pleural capillary pressure from right-sided heart failure, or low oncotic pressure due to hypoalbuminaemia (with or without fluid overload).

The leading causes of pleural effusions in the US include CHF, pneumonia, malignancy, viral disease, coronary artery bypass surgery, and cirrhosis with ascites, while a small pleural effusion may be found in pulmonary embolus. [4] TB is an important cause in the developing world and should also be considered in travellers returning from endemic areas and in immunocompromised people. Large pleural effusions are unlikely to be due to pulmonary emboli, where local tissue hypoxia and the consequent release of inflammatory, vasoactive cytokines may result in pleuritis and increased pleural fluid production. [7] After thoracic surgery, pleural effusion is relatively common [8] with a number of factors implicated, including topical cardiac cooling, surgical interruption of mediastinal lymphatic drainage, pleuritis, and possible underlying pericarditis. Drugs are a rarer cause of pleural effusion and idiosyncratic reactions can occur with medications such as nitrofurantoin and dantrolene. The mechanisms are multiple and generally poorly understood

Pathophysiology
The primary cause of a pleural effusion is simply an imbalance between the fluid production and fluid removal in the pleural space. The pleural space must, under normal circumstances, have a small amount of lubricating fluid present to allow the lung surface to glide within the thorax during the respiratory cycle. Normally approximately 15 mL/day of fluid enters this potential space, primarily from the capillaries of the parietal pleura. This fluid is removed by the lymphatics in the parietal pleura. At any one time there is about 20 mL of fluid in each hemithorax and the layer of fluid is 2 to 10 mm thick. [3] This regulated fluid balance is disrupted when local or systemic derangements occur. When local factors are altered, the fluid is protein- and LDH-rich and is called an exudate. Local factors include leaky capillaries from inflammation due to infection, infarction, or tumour. When systemic factors are altered, producing a pleural effusion, the fluid has low protein and LDH levels and is called a transudate. This can be caused by an elevated pulmonary capillary pressure with heart failure, excess ascites with cirrhosis, or low oncotic pressure due to hypoalbuminaemia (e.g., with nephrotic syndrome). In clinical practice, transudates are often multifactorial, with renal failure plus cardiac failure plus poor nutritional status being a common trilogy. [3]

Classification
Light's criteria for transudate/exudate differentiation

[3]

Light's criteria are used to differentiate between a transudative and exudative effusion. An exudate is defined as the presence of any of the following:

Pleural protein to serum protein ratio >0.5 Pleural LDH to serum LDH ratio >0.6 Pleural LDH greater than two-thirds of upper limit of normal for serum.

Primary prevention
Prevention of primary causes of pleural effusion; for example, immunisation to prevent pneumococcal pneumonia, anticoagulation to prevent pulmonary embolus, or prevention of heart disease which will prevent pleural effusions due to these causes. Colchicine may help prevent early post-operative pleural and pericardial effusions after cardiac surgery. [9]

Secondary prevention
Recurrence of pleural effusion can be prevented by adequate treatment of primary cause (e.g., heart failure, malignancy, or cirrhosis).
Monitoring
Approximately 10% of patients with exudative pleural effusions who undergo complete investigation, including pleural biopsy, at thoracoscopy will have no definitive diagnosis made.[1] One study has shown that over a 2year follow-up period, 8.3% of such patients subsequently had diagnoses of malignant disease. [57] Routine monitoring is not required following treatment of most pleural effusions. If the patient again becomes symptomatic, then a CXR is indicated. In patients with complicated parapneumonic effusions, the pleura are markedly thickened after the infection is treated. These patients should be followed with serial CXRs, and if the pleural thickening persists for 6 months and the patient's quality of life is limited by dyspnoea, then decortication should be considered.

Patients with undiagnosed pleural effusions should be followed until the effusion resolves and should be followed up for 2 years in case of potential malignancy. If the effusion increases in size, more aggressive diagnostic procedures such as thoracoscopy should be performed.

Patient Instructions
Patients who have had a procedure that may insert air into the cavity surrounding their lung (thoracocentesis, thoracoscopy, or tube thoracostomy) should be advised to avoid high altitudes, scuba diving, or flying in unpressurised aircraft until they are cleared by their physician.

Complications
Complicationhide all

atelectasis/lobar collapse Large pleural fluid collections can cause compressive atelectasis of surrounding lung. Drainage of the pleural fluid will allow the lung to re-expand. However, re-expansion pulmonary oedema is a possibility when large pleural fluid collections are drained quickly. pneumothorax following thoracocentesis see our comprehensive coverage of Pneumothorax This occurs in approximately 10% of patients, following either diagnostic or therapeutic thoracocentesis. [29] If the pneumothoraces are symptomatic, they should first be treated with aspiration. If the aspiration is unsuccessful, then a small-bore chest tube should be inserted. Ultrasound guidance is sometimes used to facilitate localisation of the pleural fluid and has been shown to reduce the chance of iatrogenic pneumothoraces and organ puncture following thoracocentesis. [1] However, that benefit is lost once an effusion is marked and the patient moved, presumably due to differences in patient position. [56] . Small pneumothoraces should be monitored with serial CXR. Large pneumothoraces require insertion of a chest tube. re-expansion pulmonary oedema A rare complication that occurs when a chronically collapsed lung rapidly re-expands after removal of a large volume of pleural fluid or air by thoracentesis. The pathophysiological mechanisms are poorly understood but it manifests itself immediately, or within a few hours, of thoracentesis as unilateral pulmonary oedema with acute chest pain, dyspnoea, and hypoxia. It is commonly managed conservatively but if hypoxia persists, there may be recourse to continuous positive airway pressure (CPAP).

pleural fibrosis Six months after therapy is initiated, many patients with pleural TB have residual pleural thickening. This is usually asymptomatic and does not require therapy. Occasionally, a benign asbestos effusion will develop progressive pleural thickening. It is unclear whether any therapy is effective in this situation. pseudochylothorax A pseudochylothorax is characterised by high cholesterol levels and occurs 5 years after a pleural effusion has been present. Therapeutic thoracocentesis is indicated if the patient is symptomatic. trapped lung In very inflammatory states such as empyema, fibrous bands can start to form in <24 hours. If infected pleural effusions are not drained or are inadequately treated, fibroblasts grow into the pleural space forming a fibrous peel around the lung preventing the lung from expanding. Tumour encasement of the pleura can also cause trapped lung. Decortication (the surgical removal of all fibrous tissue from the pleura and the pus from the pleural space) may then be needed to allow the lung to re-expand. This procedure can be performed in the acute stages to control pleural sepsis, but if there is no ongoing infection and only residual thickened pleura with restrictive lung function, patients can be observed for 6 months. By this time, the pleural thickening usually improves or resolves. [5] If this does not occur, then decortication may be indicated.

Prognosis
The prognosis of the patient with a pleural effusion depends on the underlying condition. If due to heart failure, cirrhosis, or malignancy, the effusion is likely to recur. However, most patients with a pleural effusion have no long-term sequelae. Complicated parapneumonic effusions and empyema can result in long-term complications such as pleural thickening or trapped lung, with consequent restrictive lung

defects. Malignant effusions may change the staging and subsequent prognosis of the underlying cancer.

Case history #1
A 70-year-old women presents with slowly increasing dyspnoea. She cannot lie flat without feeling more short of breath. She has a history of HTN and osteoarthritis, and she has been taking NSAIDs with increasing frequency over the previous few months. On physical examination, she appears dyspnoeic at rest, her BP is 140/90 mm Hg, and pulse is 90 bpm. Her jugular venous pressure is elevated to the angle of the jaw. The left lung field is dull to percussion with decreased air entry basally. Crackles are heard in the right lung field and above the line of dullness on the left. Lower extremities have pitting oedema to the knee.

Case history #2
A thin 56-year-old man has pain in his right chest with deep inspiration and is short of breath at rest and with exertion. He has felt feverish for a week and complains of a productive cough with foul-smelling and -tasting sputum. He regularly drinks alcohol and was inebriated and vomited 1 week or 2 before his symptoms began. Past medical history and family history are noncontributory. On physical examination, he is febrile to 38C (100.7F), BP is 130/78 mmHg, and pulse is 110 bpm. He looks unwell and has poor dental hygiene. Breath sounds are reduced over the right lower lobe with dullness to percussion and decreased tactile fremitus in the lower half of the lung field.

Other presentations
Pleural effusions can result from a wide range of causes, and the patient's presentation will reflect the underlying cause. A patient with a malignant effusion may present with weight loss and cachexia, malaise, and dyspnoea. Pleural effusions can result from rheumatoid pleuritis, and a patient may present with dyspnoea and an arthritis flare.

Differential diagnosis
Condition Pleural thickening Differentiating signs/symptoms

Differentiatin

Patient has a history of prior pleural disease such as TB or empyema, or exposure to environmental agents. History to support a possible underlying cause, such as haemoptysis and weight loss in lung cancer.

Thickened pleural inf asbestos, effusion o thickening

Pulmonary collapse and consolidation

Can occu compress CT scan o between l

Elevated hemidiaphragm

Can result from paralysis of the phrenic nerve. Paradoxical chest movement during the respiratory cycle can be a clue to diagnosis. Extrapleural fat is asymptomatic.

A fluorosc rapid brea diaphragm

Pleural tumours/extrapleural fat

The dens and shou

Pleural tu

The prese process. [

History & examination

Key diagnostic factorshide all
presence of risk factors (common)

Key risk factors include CHF, pneumonia, and malignancy. dyspnoea (common) The patient may complain of SOB as the effusion occupies space in the thoracic cavity and decreases the lung volume. With very large effusions, the fluid also compresses the surrounding lung, further reducing expansion. dullness to percussion (common) Percussion of the chest demonstrates a dull note over the effusion, compared with the resonant sound of air-filled spaces. Other diagnostic factorshide all pleuritic chest pain (common) Commonly presents with pain that is worse with inspiration and may be exacerbated by cough and movement. cough (common) A productive cough may be present if the effusion results from pneumonia. However, fluid collection and irritation of the pleural surfaces alone cause a non-productive cough. decreased breath sounds (common) Decreased or absent over the area of effusion. decreased or absent tactile fremitus (common)

Sound waves travel well though the aerated lung, and this sound is transmitted to the palm of the examiner's hand on the thoracic cage when a patient speaks. When the fluid barrier of the effusion is present, the sound waves do not travel and the vibrations are not felt over this area. [28] Risk factorshide all

Strong CHF Most common cause of pleural effusion and frequently recurs with heart failure decompensations. [4] pneumonia Effusions that form from pneumonia are called parapneumonic effusions. Second most common cause of pleural effusion and occurs in up to 40% of patients hospitalised with pneumonia. [4] malignancy Third most common cause of pleural effusion overall. Most common in patients >50 years of age. [4] recent CABG surgery Up to 10% of post-CABG patients will develop a pleural effusion occupying >25% of the hemithorax. [8]

Weak pulmonary embolism Fourth most common cause of pleural effusion in the US. [2] recent MI Patients with post-MI syndrome, also called Dressler syndrome, can develop fever, pleuropericarditis, and pulmonary infiltrates. occupational lung disease Beryllium exposure may occur from working with fluorescent lamps, ceramics, and metal machining. Asbestos exposure is common in those working in ship yards. Silica exposure is found in miners and sandblasters. rheumatoid arthritis Suspect rheumatoid pleuritis in patients with rheumatoid arthritis and an effusion. SLE Patients with SLE are at increased risk of pulmonary emboli and subsequent pleural effusion. Lupus pleuritis may also cause a pleural effusion. renal failure Uraemia can cause pleural effusion. drug induced

The most common drugs implicated include nitrofurantoin, dantrolene, ergot alkaloids, valproate, propylthiouracil, isotretinoin, and tyrosine kinase inhibitors. chylothorax Can occur following trauma or cardiothoracic surgery, or with carcinoma or lymphoma.

Diagnostic tests
1st tests to orderhide all
Test

posteroanterior (PA) and lateral CXR Indicated in any patient with dyspnoea. A postero-anterio commonly done) is the first test for this condition. It may incidentally reveal, a pleural effusion, but should usually An effusion as small as 50 mL can be seen on the latera millilitres will be visible on the PA film. [3] View image May show an effusion before any other symptoms arise.

pleural ultrasound Useful in locating an area of fluid collection for thoracoce loculated or small.

More sensitive and specific than CXR for pleural effusion

Can identify 5 to 10 mL of fluid. [29]

LDH and protein in pleural fluid and serum Indicates an exudate if the ratio of pleural fluid protein to pleural fluid LDH to serum LDH is >0.6, or if the pleural f the normal upper limit for serum LDH. [1] [2] One or more of these is required for the diagnosis of an findings, the effusion is likely to be a transudate. These criteria are highly sensitive to determine whether determines what subsequent tests are required.

RBC count in pleural fluid Seen in malignancy, trauma, parapneumonic effusions, a

There will be some RBC in most samples. Fluid for cell c anticoagulated container to prevent clots and inaccuracy

If fluid appears bloody, it is recommended to obtain Hct. peripheral value indicates haemothorax. [1][3]

WBC count and differential of pleural fluid The pleural fluid needs to be sent in an anticoagulated c

Lymphocyte-rich fluid (>50% lymphocytes) may suggest embolism. [2] However, most effusions, regardless of ae become predominantly monocytic. If the lymphocyte population is >90%, lymphoma and TB diagnoses. [1] [3] A high lymphocyte population may indicate a chylothorax Eosinophil count >10% is non-specific.

cytology of pleural fluid Cytology is positive in >60% of malignant pleural effusion Repeated thoracocenteses will help increase the diagno to 3 times before thoracoscopy is advised..

culture of pleural fluid Routine cultures are not useful or cost effective, but, if a or there is frank pus, then this is a valuable test. [31] Pleural fluid should be innoculated into aerobic and anae same time as standard culture as this increases microbia

pH of pleural fluid The results are not accurate if the pH is not measured w

Generally, pH is low in conjunction with high LDH and lo complicated parapneumonic effusion, rheumatoid arthriti

Pleural fluid for pH should be collected anaerobically with gas analyser (avoiding putting frank pus through analyse that manufacturers of blood gas analysers may void thei is processed through the machine.

glucose in pleural fluid Pleural glucose can be difficult to interpret in patients wit

Low glucose is found in empyema, rheumatoid arthritis, T

Almost 100% of effusions due to empyema and rheumat This also applies to 30% of complicated parapneumonic <10% of effusions due to malignancy. [2]

protein gradient Protein gradient between serum and pleural fluid of 31 transudate. [3] This determines what subsequent tests a as helpful in the context of diuretic therapy, though it is n

FBC Suggests underlying infective process, such as pneumon

CRP CRP will usually be elevated in acute bacterial infection a the severity of infection.

blood culture Indicated if clinical presentation and CXR suggest pneum

sputum Gram stain and culture Indicated if clinical presentation and CXR suggest pneum

NT-proBNP in pleural fluid Indicated if CHF-related pleural effusion is suspected. [1 Data suggests that raised levels of pleural fluid N-termin proBNP) can accurately diagnose CHF-related pleural ef laboratory cut-off value of 1500 picograms/mL is commo

Tests to considerhide all

Test

thoracic CT scan Thoracic CT scans are useful to define the size and loca loculations, and indicate if there are suspicious changes thickening, which require further investigation. [2] [33] If there is suspicion of TB, thoracic CT is also indicated f changes, as well as mediastinal lymphadenopathy, whic transbronchial nodal aspiration via bronchoscopy.

thoracic MRI MRI provides better imaging of soft tissues than CT, so i wall or diaphragm, and using differences in signal intens malignant effusions. [21] MRI is, however, not routinely indicated in investigation o sectional imaging should be CT. [21]

helical CT scan May also offer alternative explanation for pleural effusion If no cause is established, pulmonary embolus should be imaging, such as helical CT scan. Pleural effusions due and unilateral exudates.[22]

amylase in pleural fluid Requested only if pancreatitis or oesophageal disease (i as a cause of pleural effusion though it can be elevated a

adenosine deaminase (ADA) level in pleural fluid Requested if TB effusion is suspected. [19] Factors such as a positive skin test for TB, a positive inte incarceration, travel to an endemic area, immuncomprom cavities on CXR increase suspicion.

Pleural fluid ADA >40 U/L has a sensitivity of 90% to 100 tuberculous pleurisy. [2]

lipid analysis of pleural fluid Indicated if a chylothorax is suspected. Chyle is sometim empyema, but if chylothorax is suspected, lipid analysis performed.

The presence of chylomicrons on microscopy confirms a level, usually >1.24 mmol/L (110 mg/dL) is diagnostic. C the triglyceride level is <0.56 mmol/L (50 mg/dL). [1] Lipo the definitive test, but this is rarely available and even m

Pleural fluid cholesterol levels higher than the simultaneo are very suggestive of pseudochylothorax, which occurs Cholesterol crystals are often present in pseudochylotho Pleural cholesterol has also been used to distinguislh ex regarded as fully validated and is not routinely used. [34

thoracoscopy Surgical or medical biopsy of abnormality is possible. Dia malignancy. [2] Thoracoscopy for diagnostic purposes is indicated if the the effusion is unknown, TB is suspected, or cytology is suspected. If malignancy is confirmed, then thoracoscop Thoracoscopy is traditionally carried out by surgeons but safe, simple, and accurate alternative.[23]

bronchoscopy Bronchoscopy is not routinely indicated in the investigati

However, if the cause of an exudative effusion cannot be used to exclude small malignant endobronchial lesions.

Bronchoscopy should be performed after pleural fluid dra conditions. pleural biopsy

Closed pleural biopsy is used after ultrasound and/or CT in undiagnosed exudative effusions for suspected TB or before thoracoscopy, or when it is not available.

Emerging testshide all

Test

tumour markers in pleural fluid Tumor markers in pleural fluid, such as carbohydrate ant 21-1, are highly specific but insufficiently sensitive for dia However, a combination of 2 or more of these is conside whether they should replace or complement conventiona endothelial growth factor (VEGF) is insufficiently sensitiv effusions. [35] Mesothelin is a glycoprotein tumor marker which is eleva mesothelioma patients, but also in bronchial adenocarcin carcinoma, and lymphoma. A sensitivity of 48-84% and a of mesothelioma has been demonstrated. A positive resu and might expedite invasive testing. Mesothelin also add lesser extent, to negative cytology. [1] The negative pred in sarcomatoid mesothelioma. Further study is required b routinely recommended in the investigation of an undiag

interferon-gamma in pleural fluid and real-time PCR of pleura Interferon-gamma measurement in pleural fluid is sensiti tuberculous pleurisy and may be clinically useful. [24] [25

on blood or pleural fluid are not sensitive or specific enou TB pleurisy. [26]

soluble triggering factor expressed on myeloid cells Soluble triggering factor expressed on myeloid cells (TR separating bacterial effusions (empyema and parapneum 78% and specificity of 84% is reported. Further studies a recommended routinely. [36]

Step-by-step diagnostic approach

The first step in diagnosis is confirmation of the pleural effusion (suspected clinically or on CXR) by ultrasound. Diagnostic aspiration (which may be included in therapeutic aspiration) establishes whether it is a transudate or an exudate, which then determines the potential aetiology. This subdivision, along with relevant history, dictates further specific tests. [1] [2][10]

History and examination

Symptoms of cough, pleuritic chest pain, and dyspnoea with typical examination findings of absent breath sounds, dullness to percussion, decreased or absent tactile fremitus, and decreased vocal

transmission over the base of the lung strongly suggest a fluid collection. Further history and examination may reveal the underlying cause. A past medical history of CHF, renal failure, cirrhosis, previous malignancy, SLE, or rheumatoid arthritis may be associated with pleural effusions. Full occupational history with particular relevance to asbestos exposure is essential. Full drug history is also important. The most common drugs implicated include nitrofurantoin, dantrolene, ergot alkaloids, valproate, propylthiouracil, isotretinoin, and tyrosine kinase inhibitors. The presence of risk factors for thromboembolism, such as family history, recent long-distance travel, leg trauma, SLE, or immobilisation may be present in cases of pulmonary embolism. Fever and cough productive of purulent sputum suggests pneumonia. Age >50 years, coupled with a history of cigarette smoking and unexplained weight loss may indicate an underlying malignancy.

Investigations
A postero-anterior CXR and lateral (now less commonly done) is the first test for this condition. It may confirm the clinical suspicion of, or incidentally

reveal, a pleural effusion, but should usually prompt pleural ultrasound. [1] [2] FBC, blood culture, and sputum Gram stain and culture are indicated if clinical presentation and CXR suggest pneumonia. CRP measurement may be useful. [11] Except for patients with clear evidence of heart failure (suspected in patients with a past history of ischaemic or other heart disease and suggestive clinical examination, including a raised jugular venous pressure and pitting oedema of the legs, or echocardiographic evidence or raised serum, BNP or NT-pro-BNP), thoracentesis is indicated in all patients to identify and diagnose the underlying cause. [2] The procedure can be done quickly and easily at the bedside, but should usually be preceded by ultrasound, as this improves yield and safety. An ultrasound may be required to guide the best position for thoracocentesis, especially if the effusion is loculated or small. CXR after thoracocentesis is not routinely indicated unless air is drawn during the procedure or the patient develops symptoms, such as increased dyspnoea, cough, or chest pain. [12] [13] The pleural LDH and protein levels, and serum LDH and protein should be measured to determine whether the effusion is a transudate or exudate using the Lights criteria, where one or more of the following suggest an exudate: pleural fluid protein divided by

serum protein >0.5; pleural fluid LDH divided by serum LDH >0.6; and pleural fluid LDH >two-thirds of the upper limit of laboratory normal range for serum LDH. [1] [2] Pleural cholesterol analysis has been used to distinguish exudates from transudates but is not used routinely. [14] A transudate is likely to be caused by CHF, cirrhosis, or nephrosis. An exudative effusion will require further studies. In congestive cardiac failure, diuretic therapy, which is the mainstay of treatment, can cause elevated levels of pleural fluid protein and LDH resulting in a misclassification of pleural effusions as exudative in up to 25% of cases. [15] Evidence is emerging that, in such settings, raised levels of pleural fluid N-terminal probrain natriuretic peptide (NT-proBNP) can accurately diagnose CHF-related pleural effusions. [16] A laboratory cut-off value of 1500 picogramsg/mL is commonly used. [1] Chyle is sometimes difficult to differentiate from empyema but if chylothorax is suspected, lipid analysis of the pleural fluid should be performed. The presence of chylomicrons on microscopy confirms a chylothorax and a high triglyceride level, usually >1.24 mmol/L (110 mg/dL) is diagnostic. Chylothorax can usually be excluded if the triglyceride levelis <0.56 mmol/L (50 mg/dL). [1] Total and differential cell count, glucose, pH, cytology, and cultures of the pleural fluid are

recommended. Pleural fluid should be innoculated into aerobic and anaerobic blood culture bottles at the same time as standard culture as this increases microbial yield. [17] Pleural fluid pH <7.20 is highly suggestive of empyema and pleural fluid for pH should be collected anaerobically with heparin and measured in a blood gas analyser (avoiding putting frank pus through the analyser). [18] However, it is worth noting that manufacturers of blood gas analysers may void their warranty if any fluid other than blood is processed through the machine. If the cell count is predominantly lymphocyte dominant, then a test for markers of TB such as adenosine deaminase in the pleural fluid should be ordered. [19] Eosinophilic pleural effusions (defined as >10% of pleural white cells) account for 10% of exudates and are non-specific. Causes include malignancy (26%), idiopathic (25%), related to pleural air or blood (13%), parapneumonic (13%), and TB (7%), along with other less common miscellaneous causes. Likelihood of malignancy is inversely correlated with eosinophil count. [20] Thoracic CT scans are useful to define the size and location of the effusion and show loculations, and indicate if there are suspicious changes on CXR, such as lung mass or pleural thickening, which require further investigation. If there is suspicion of TB, thoracic CT is also indicated for detecting subtle

parenchymal changes, as well as mediastinal lymphadenopathy, which may represent a target for transbronchial nodal aspiration via bronchoscopy. MRI provides better imaging of soft tissues than CT, so it can reveal tumour invasion of the chest wall or diaphragm, and using differences in signal intensity it can distinguish between benign and malignant effusions. MRI is, however, not routinely indicated in investigation of pleural effusion and first-line cross sectional imaging should be CT. [21] If no cause is established, pulmonary embolus should be ruled out by further pulmonary imaging, such as a helical CT scan. Pleural effusions due to pulmonary emboli are usually small and unilateral exudates. [22] Bronchoscopy is not routinely indicated in the investigation of pleural effusion. However, if the cause of an exudative effusion cannot be established, bronchoscopy can be used to exclude small malignant endobronchial lesions. Bronchoscopy should be performed after pleural fluid drainage to ensure optimum diagnostic conditions. Thoracoscopy for diagnostic purposes is indicated if the patient is not improving, the cause of the effusion is unknown, TB is suspected, or cytology is negative when pleural malignancy is suspected. If malignancy is confirmed, then thoracoscopy can also be

therapeutic. [2]Thoracoscopy is traditionally carried out by surgeons but medical semi-rigid thoracoscopy is a safe, simple, and accurate alternative. [23] Closed pleural biopsy is used after ultrasound examination in undiagnosed exudative effusions for suspected TB or malignancy when thoracoscopy is not available. Interferon-gamma measurement in pleural fluid is sensitive and specific for the diagnosis of tuberculous pleurisy and may be clinically useful. [24] [25] T-cell gamma interferon assays (IGRA) on blood or pleural fluid are not sensitive or specific enough to be clinically useful for diagnosis of TB pleurisy. [26] Tumour markers in pleural fluid, such as carbohydrate antigen (CA) 15-3, CA 19-9, CYFRA 21-1, and mesothelin are highly specific but insufficiently sensitive for diagnosis of metastatic pleural disease. However, a combination of 2 or more of these is considered more sensitive. It is not clear yet whether they should replace or complement conventional cytological examination. [27] Measuring tumour markers and interferon-gamma may prove useful in the future.
Click to view diagnostic guideline references.

Treatment Options

Patient group CHF

Treatmen Treatmenthide all t line 1st diuretic Pleural effusions from heart failure are managed with diuretic therapy. Initial treatment is with loop diuretics. Oral or intravenous furosemide or bumetanide may be given, titrated in response to clinical signs, daily weight and renal function to avoid excessive volume depletion. In patients with refractory volume overload, nonloop diuretics such as hydrochlorothiazide or metolazone may be used in combination with loop diuretics to

Patient group CHF

Treatmen Treatmenthide all t line 1st diuretic Pleural effusions from heart failure are managed with diuretic therapy. Initial treatment is with loop diuretics. Oral or intravenous furosemide or bumetanide may be given, titrated in response to clinical signs, daily weight and renal function to avoid excessive volume depletion. In patients with refractory volume overload, nonloop diuretics such as hydrochlorothiazide or metolazone may be used in combination with loop diuretics to

Patient group CHF

Treatmen Treatmenthide all t line 1st diuretic Pleural effusions from heart failure are managed with diuretic therapy. Initial treatment is with loop diuretics. Oral or intravenous furosemide or bumetanide may be given, titrated in response to clinical signs, daily weight and renal function to avoid excessive volume depletion. In patients with refractory volume overload, nonloop diuretics such as hydrochlorothiazide or metolazone may be used in combination with loop diuretics to

Patient group CHF

Treatmen Treatmenthide all t line 1st diuretic Pleural effusions from heart failure are managed with diuretic therapy. Initial treatment is with loop diuretics. Oral or intravenous furosemide or bumetanide may be given, titrated in response to clinical signs, daily weight and renal function to avoid excessive volume depletion. In patients with refractory volume overload, nonloop diuretics such as hydrochlorothiazide or metolazone may be used in combination with loop diuretics to

Patient group CHF

Treatmen Treatmenthide all t line 1st diuretic Pleural effusions from heart failure are managed with diuretic therapy. Initial treatment is with loop diuretics. Oral or intravenous furosemide or bumetanide may be given, titrated in response to clinical signs, daily weight and renal function to avoid excessive volume depletion. In patients with refractory volume overload, nonloop diuretics such as hydrochlorothiazide or metolazone may be used in combination with loop diuretics to

Patient group CHF

Treatmen Treatmenthide all t line 1st diuretic Pleural effusions from heart failure are managed with diuretic therapy. Initial treatment is with loop diuretics. Oral or intravenous furosemide or bumetanide may be given, titrated in response to clinical signs, daily weight and renal function to avoid excessive volume depletion. In patients with refractory volume overload, nonloop diuretics such as hydrochlorothiazide or metolazone may be used in combination with loop diuretics to

Patient group CHF

Treatmen Treatmenthide all t line 1st diuretic Pleural effusions from heart failure are managed with diuretic therapy. Initial treatment is with loop diuretics. Oral or intravenous furosemide or bumetanide may be given, titrated in response to clinical signs, daily weight and renal function to avoid excessive volume depletion. In patients with refractory volume overload, nonloop diuretics such as hydrochlorothiazide or metolazone may be used in combination with loop diuretics to

Patient group CHF

Treatmen Treatmenthide all t line 1st diuretic Pleural effusions from heart failure are managed with diuretic therapy. Initial treatment is with loop diuretics. Oral or intravenous furosemide or bumetanide may be given, titrated in response to clinical signs, daily weight and renal function to avoid excessive volume depletion. In patients with refractory volume overload, nonloop diuretics such as hydrochlorothiazide or metolazone may be used in combination with loop diuretics to

Patient group CHF

Treatmen Treatmenthide all t line 1st diuretic Pleural effusions from heart failure are managed with diuretic therapy. Initial treatment is with loop diuretics. Oral or intravenous furosemide or bumetanide may be given, titrated in response to clinical signs, daily weight and renal function to avoid excessive volume depletion. In patients with refractory volume overload, nonloop diuretics such as hydrochlorothiazide or metolazone may be used in combination with loop diuretics to

Patient group persistent empyema despite chest tube

Treatment Treatmenthide all line 1st direct visualisation and lysis of adhesions Thoracoscopy allows close inspection of the pleural surfaces and the opportunity to break down fibrin membranes that produce loculations. By using videoassisted thoracoscopy surgery, the fibrous coating over the visceral pleural can be removed (decortication), which will allow the underlying lung to expand. The risks include infection, bleeding, and anaesthetic risks.

Patient group persistent empyema despite chest tube

Treatment Treatmenthide all line 1st direct visualisation and lysis of adhesions Thoracoscopy allows close inspection of the pleural surfaces and the opportunity to break down fibrin membranes that produce loculations. By using videoassisted thoracoscopy surgery, the fibrous coating over the visceral pleural can be removed (decortication), which will allow the underlying lung to expand. The risks include infection, bleeding, and anaesthetic risks.

Patient group persistent empyema despite chest tube

Treatment Treatmenthide all line 1st direct visualisation and lysis of adhesions Thoracoscopy allows close inspection of the pleural surfaces and the opportunity to break down fibrin membranes that produce loculations. By using videoassisted thoracoscopy surgery, the fibrous coating over the visceral pleural can be removed (decortication), which will allow the underlying lung to expand. The risks include infection, bleeding, and anaesthetic risks.

Patient group persistent empyema despite chest tube

Treatment Treatmenthide all line 1st direct visualisation and lysis of adhesions Thoracoscopy allows close inspection of the pleural surfaces and the opportunity to break down fibrin membranes that produce loculations. By using videoassisted thoracoscopy surgery, the fibrous coating over the visceral pleural can be removed (decortication), which will allow the underlying lung to expand. The risks include infection, bleeding, and anaesthetic risks.

Patient group persistent empyema despite chest tube

Treatment Treatmenthide all line 1st direct visualisation and lysis of adhesions Thoracoscopy allows close inspection of the pleural surfaces and the opportunity to break down fibrin membranes that produce loculations. By using videoassisted thoracoscopy surgery, the fibrous coating over the visceral pleural can be removed (decortication), which will allow the underlying lung to expand. The risks include infection, bleeding, and anaesthetic risks.

Treatment approach
The treatment of a pleural effusion is dictated by the precipitating cause. Patients with large symptomatic effusions may benefit from oxygen therapy. [37] CXR is not required after aspiration of an effusion, unless there is clinical suspicion of pneumothorax such as free air aspiration. CXR after chest tube drainage is recommended. [38]

CHF
Pleural effusions from heart failure are managed with diuretic therapy. Initial treatment is with loop diuretics. Oral or intravenous furosemide or bumetanide may be given, titrated in response to clinical signs, daily weight and renal function to avoid excessive volume depletion. In patients with refractory volume overload, nonloop diuretics such as hydrochlorothiazide or metolazone may be used in combination with loop diuretics to improve diuresis. A therapeutic thoracocentesis should be considered if the pleural effusion is large and is causing significant symptoms. It is generally safe to remove 1.5 litres of fluid from a hemithorax without the risk of re-expansion of the pulmonary oedema.

Infective
A considerable proportion of patients with pneumonia develop parapneumonic effusions, [39]but in the majority of cases, if appropriate antibiotic therapy is instigated early, the fluid resolves.[40] Treatment of underlying pneumonia with appropriate antibiotics is indicated in parapneumonic effusions. All patients should initially receive empirical intravenous antibiotics based on local microbiology guidelines to cover the likely causative organisms, both aerobic and anaerobic. The results of pleural fluid culture will further guide antibiotic use. Gram positive bacteria are the most common pathogens in community acquired parapneumonic effusion; Streptococcus pneumoniae , Streptococal milleri, Streptococcus intermedius (50% of all), and Staphylococcus aureus comprise 11% of cases. Gram negatives account for 9% and

anaerobes for 20%. [41] Anaerobic pathogens are also important and present in a more insidious fashion. In hospital-acquired pleural infection, S aureus (total 35%, mostly MRSA 25%) are relevant as well as Gram negative organisms (17%), including E coli,Enterobacter and Pseudomonas species, and anaerobes 8%. [41] These organisms should be covered with broad spectrum antibiotics by the intravenous route if the clinical scenario dictates. Penicillin-based antibiotics, including those combined with beta-lactamase inhibitors, metronidazole, and cephalosporins, penetrate the pleural space well, but aminoglycosides should be avoided. MRSA should be covered if a hospital-acquired infection is suspected. [40] If the patients' clinical state worsens and the effusion progresses to a complicated/loculated effusion or empyema, timely removal of the fluid is indicated. Loculations can develop in a matter of 12 to 24 hours. Therapeutic thoracocentesis is likely to be definitive in most patients. However, if the fluid obtained is frank pus, the bacterial smear or culture is positive, glucose is <3.3 mmol/L (60 mg/dL), pH is <7.20, LDH >1000 U/L, or the fluid is loculated, a more aggressive approach should be undertaken with a tube thoracostomy. Large-bore tubes are traditionally used (28 to 36 French) and can be inserted at the bedside by a trained physician. However, with the use of CT guidance, an interventional radiologist can usually get equally effective drainage with the use of well-placed smaller-bore tubes that are less painful for the patient. When chest tubes fail, thoracoscopy with lysis of adhesions, decortication, and open drainage are surgical options. The use of intrapleural fibrinolytics for loculated effusions is controversial. There is no additional benefit in instilling intra-pleural fibrinolytic therapy in the treatment of parapneumonic effusions or empyema. [42] [43] [B Evidence] Trials are currently ongoing to investigate the benefits of new approaches that combine the intrapleural administration of fibrinolytic drugs (egtPA) with viscosity-disrupting agents such as deoxyribonuclease (DNase). There are insufficient data to support the use of adjunctive corticosteroids in patients with tuberculous pleurisy. [44] [A Evidence]

Malignant

Malignant effusions are difficult to manage, as they usually re-accumulate after drainage. Therapeutic thoracocentesis is recommended first-line. [45] Repeated therapeutic thoracocenteses are recommended for the treatment of symptomatic recurrent malignant pleural effusion if the life expectancy of the patient is very short (i.e., days to weeks). In patients with a longer life expectancy, the 2 primary options are insertion of an indwelling catheter and the intrapleural injection of a sclerosing agent in an attempt to produce a pleurodesis. Patients who wish to be treated as outpatients and who have a home situation, such that it is feasible to drain the fluid at home can be treated with an indwelling catheter. There is no difference in relief of dyspnoea, and no significant difference in quality of life between indwelling catheter drainage and talc pleurodesis. However, indwelling catheter drainage is associated with less time in hospital, but more adverse effects. [46] Patients who do not meet these criteria should be treated with sclerosing agents to create an inflammatory reaction that will essentially attempt to stick the parietal and visceral pleura together. Talc, bleomycin, and tetracycline are commonly used agents. Talc, by poudrage under thorascopic guidance or slurry instilled by chest tube, is the most effective agent for pleurodesis, but the risk of respiratory failure is debated. [47] [45] [B Evidence] Pleurodesis may be a painful procedure and effective analgesia, including the use of intrapleural lidocaine, is mandatory. [48] Safe administration of agents inducing conscious sedation such as benzodiazepines should also be considered, ensuring appropriate monitoring with pulse oximetry. Intrapleural administration of fibrinolytic drugs is recommended for symptomatic management of dyspnoea related to loculated malignant effusions not amenable to simple drainage. [48]

Emerging treatments
Iodopovidone Has been trialled as a chemical pleurodesis agent. It appears to be safe, inexpensive, and effective in pleurodesing both pneumothoraces and pleural effusions. [53]

Varidase This drug is a combination of the fibrinolytics DNase and streptodornase. It is used to dissolve fibrous adhesions in loculated effusions. It is not available in the US and is not FDA approved. The use of Varidase was successful in a rabbit model, completely liquefying the empyema fluid in 4 hours. [54] A multi-centre randomised controlled trial (MIST-2) compared intra-pleural tissue plasminogen activator (t-PA) alone, t-PA in combination with DNAse, DNAse alone, and double placebo, used twice daily for 3 days. The combination of t-PA and DNAse together produced significantly greater fluid drainage (measured by reduction of pleural opacity on chest x-ray) compared with placebo; whereas, each monocomponent produced a non-significant reduction in pleural opacity. Surgical referral at 3 months and hospital inpatient stay were also significantly reduced in the combination group, but not the other groups. Adverse effects were not increased by any of the treatments. Combination treatment with t-PA and DNAse may therefore be useful in patients in whom standard medical therapy has failed and who are not suitable for surgery, but further controlled trials are needed to accurately define treatment effects. [50]

Intrapleural chemo- and hyperthermotherapies Intra-pleural cisplatin and picibanil weekly with hyperthermotherapy was superior to cisplatin and picibanil (OK-432) weekly (without hyperthermotherapy) in control of malignant effusions.[55]

Patent foramen ovale

Highlights
Summary Overview

Basics
Definition Epidemiology Aetiology Pathophysiology Classification

Prevention
Secondary

Diagnosis
History & examination Tests Differential Step-by-step Guidelines Case history

Treatment
Details Step-by-step Guidelines

Follow Up
Recommendations Complications Prognosis

Resources
References Images Patient leaflets Credits Email Print Feedback Share Add to Portfolio Bookmark Add notes

History & exam

Key factors

atrial septal aneurysm congenital heart conditions

CVA or TIA at age <50 years DVT abnormal cardiac examination

Other diagnostic factors

decompression symptoms related to diving cold sensation in limb limb pain SOB while upright in platypnoea-orthodeoxia syndrome History & exam details

Diagnostic tests
1st tests to order

transthoracic echo with colour Doppler and contrast injection trans-oesophageal echo with colour Doppler and contrast injection

Tests to consider

intracardiac echo ultrasound lower extremity MRI lower extremity tilt-table trans-oesophageal echo

Emerging tests

transcranial Doppler Diagnostic tests details

Treatment details
Ongoing
asymptomatic with low risk of thrombotic event (not in high-risk occupation) education and observation asymptomatic with 1 prior embolic event or high embolism risk (not in high-risk occupation) observation antiplatelet or anticoagulation therapy >1 thrombotic event or high-risk occupation antiplatelet or anticoagulation therapy percutaneous closure with postoperative antiplatelet therapy Treatment details
1