Ehs 372
Ehs 372
Ehs 372
doi:10.1093/eurheartj/ehs372
Clinical update
Pericardial effusion is a common finding in clinical practice either as incidental finding or manifestation of a systemic or cardiac disease. The
spectrum of pericardial effusions ranges from mild asymptomatic effusions to cardiac tamponade. The aetiology is varied (infectious, neo-
plastic, autoimmune, metabolic, and drug-related), being tuberculosis the leading cause of pericardial effusions in developing countries
and all over the world, while concurrent HIV infection may have an important promoting role in this setting. Management is guided by
the haemodynamic impact, size, presence of inflammation (i.e. pericarditis), associated medical conditions, and the aetiology whenever pos-
sible. Pericardiocentesis is mandatory for cardiac tamponade and when a bacterial or neoplastic aetiology is suspected. Pericardial biopsy is
generally reserved for cases with recurrent cardiac tamponade or persistence without a defined aetiology, especially when a bacterial or
neoplastic aetiology is suspected and cannot be assessed by other conventional and less invasive means. A true isolated effusion may not
require a specific treatment if the patient is asymptomatic, but large ones are at risk of progression to cardiac tamponade (up to one
third). Pericardiocentesis alone may be curative for large effusions, but recurrences are also common and pericardiectomy or less invasive
options (i.e. pericardial window) should be considered with recurrent cardiac tamponade or symptomatic pericardial effusion (either circum-
ferential or loculated). The aim of this paper was to summarize and critically evaluate current knowledge on the management of pericardial
effusion.
-----------------------------------------------------------------------------------------------------------------------------------------------------------
Keywords Pericardial effusion † Aetiology † Diagnosis † Management † Pericarditis
* Corresponding author. Tel: +39 011 4393391, Fax: +39 011 4393334, Email: massimo_imazio@yahoo.it
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2012. For permissions please email: journals.permissions@oup.com
Management of pericardial effusion 1187
Initial evaluation and but, in any case, terminate to mediastinal, tracheobronchial, or iux-
taesophageal lymph nodes. On the ventral surface, the lymphatics
pathophysiological issues of the parietal pericardium connect to lymphatics in the pericardial
When a pericardial effusion is detected, the first step is to evaluate fat and areolar tissue. On the lateral and posterior surfaces, the
its size and haemodynamic importance, as well as the possible as- lymphatics of the parietal pericardium anastomose with lymphatics
sociation with concomitant diseases. Echocardiography is the first of the reflected mediastinal pleura (Supplementary material online,
diagnostic tool for this assessment as also acknowledged by the Reference C). Lymphatic drainage of the pericardium to the medi-
AHA/ACC guidelines on the use of echocardiography, that gave astinal and tracheobronchial lymph nodes and interactions with
a class I indication for the use of echocardiography in any case pleural lymphatics (Supplementary material online, Reference D)
of suspected pericardial disease.10 provide the anatomical basis for pathological involvement of the
Pericardial effusion may be classified based on its onset (acute, pericardium in specific diseases (i.e. pleuro-pulmonary diseases
subacute vs. chronic when dating .3 months), distribution (cir- such as pulmonary tuberculosis and lung cancer).
cumferential or loculated), haemodynamic impact (none, cardiac Any pathological process usually causes an inflammatory
Figure 2 Presentation of a mild (A) vs. moderate to large pericardial effusions (B) on echocardiography. Mild pericardial effusion is evident
adjacent to the right atrium in four-chambers view and only posterior in parasternal long-axis view (A). As fluid accumulates, the effusion
becomes circumferential (B). Pe, pericardial effusion; RA, right atrium; Ao, aorta.
be causative agents (Table 2). The more common causes of renal failure), myopericardial diseases (especially pericarditis, but
pericardial effusions include infections (viral, bacterial, especially also myocarditis, heart failure), aortic diseases, especially aortic dis-
tuberculosis), cancer, connective tissue diseases, pericardial in- section extending into the pericardium, and selected drugs (i.e.
jury syndromes (post-myocardial infarction effusions, post- minoxidil). Hydropericardium, a non-inflammatory transudative
pericardiotomy syndromes, post-traumatic pericarditis either pericardial effusion, may occur not only in heart failure, but also
iatrogenic or not), metabolic causes (especially hypothyroidism, advanced hypoalbuminaemia, such as in cirrhosis and nephrotic
Management of pericardial effusion 1189
Figure 4 Pressure/volume curve of the pericardium with fast accumulating pericardial fluid leading to cardiac tamponade with a smaller
volume (A) compared with the slowly accumulating pericardial fluid reaching cardiac tamponade only after larger volumes (B).
syndrome, when Starling forces promote the accumulation of a At present, the largest cohort of patients with moderate (echo-
plasma ultrafiltrate across the pericardium as well as other mem- free space of 10–20 mm during diastole) and large pericardial effu-
branes (e.g. pleura and peritoneum). sions (echo-free space .20 mm) comes from Spain and includes
In the last 20 years, five major surveys have been published on 322 cases (mean age 56 years, 52% males). Cases were collected
the characteristics of moderate to large pericardial effusions retrospectively from 1990 to 93 and then prospectively from
(Table 3).17 – 21 Obviously, the relative frequency of different 1994 to 96 in a 637-bed university general hospital in Barcelona.
causes depends on the local epidemiology (especially the preva- The authors adopted a three-stage protocol including a basic
lence of tuberculosis), the hospital setting, and the diagnostic evaluation for all (stage I including clinical history, physical examin-
protocol that has been adopted. Many cases still remain idiopathic ation, electrocardiography, chest X-ray, echocardiography, evalu-
in developed countries (up to 50%), while other common causes ation for tuberculosis, measurement of serum antinuclear
include especially cancer (10– 25%), pericarditis and infectious antibodies and thyroid hormones, and other targeted studies
causes (15–30%), iatrogenic causes (15 –20%), and connective according to specific presentation), followed by stage II with peri-
tissue disease (5–15%), whereas tuberculosis is the dominant cardiocentesis and pericardial fluid analysis for those with cardiac
cause in developing countries (.60%), where tuberculosis is tamponade, suspicion of purulent pericarditis, or chronic large
endemic.22 In the setting of pericarditis with pericardial effusion, pericardial effusions. Stage III (surgical biopsy of the pericardium)
the prevalence of malignant or infectious aetiologies ranges from was limited to those with persistent or recurring tamponade
15 to 50% depending on published series.12,17 – 21 after pericardiocentesis, and when the effusion lasted for .3
1190 M. Imazio and Y. Adler
Table 3 Aetiologic diagnosis of moderate to large pericardial effusions according to major published series
Feature Corey et al.17 Sagrista-Sauleda et al.18 Levy et al.19 Reuter et al.20 Ma et al.21
...............................................................................................................................................................................
Patients 57 322 204 233 140
Study years 1993 1990– 96 1998–2002 1995– 2001 2007– 09
Country USA Spain France South Africa China
Effusion size .5 mm .10 mm NR NR Moderate to largea
Cardiac NR 37 NR NR NR
tamponade
Evaluation Subxiphoid TB, ANA, TSH, BCx, TSH, ANA, Q HIV, sputum, TB, BCx, Pericardiocen-tesis
pericardiotomy pericardiocen-tesis, and fever, viral rectal, and blood chemistry,
biopsy throat swabs and serology
A selection of the most frequent aetiological diagnoses is reported (thus overall sum in columns may be ,100%).
NR, not reported; TB, aetiology search for tuberculosis; BCx, blood cultures.
a
All effusions requiring pericardiocentesis.
Diagnosis
The diagnosis of pericardial effusion is generally performed by
echocardiography, that also allows the semiquantitative assessment
of the pericardial effusion size and its haemodynamic effects as out-
lined in the paragraph on the initial approach to pericardial effu-
Figure 5 The femoral artery pressure curve showing pulsus sion. The diagnosis of cardiac tamponade is essentially a clinical
paradoxus during cardiac tamponade. A systolic blood pressure diagnosis requiring echocardiographic confirmation of the initial
decline is .10 mmHg during inspiration. diagnostic suspicion. In most patients, cardiac tamponade should
be diagnosed by a clinical examination that shows elevated system-
ic venous pressure, tachycardia, dyspnoea, and paradoxical arterial
pulse. Systemic blood pressure may be normal, decreased, or even
easily detected recording the systolic pressure at which Korotkoff elevated. The diagnosis is confirmed by an echocardiographic dem-
sounds are first audible and the systolic pressure at which they are onstration of moderately large or large circumferential pericardial
audible through the whole respiratory cycle. Pulsus paradoxus is effusion and in most instances, of right atrial compression, abnor-
due to exaggerated ventricular interdependence occurring in mal respiratory variation in right and left ventricular dimensions,
cardiac tamponade when overall volume of cardiac chambers and in tricuspid and mitral valve flow velocities usually associated
becomes fixed and any change in the volume of one side of the with inferior vena cava plethora (Table 4 and Figure 6) (Supplemen-
heart causes the opposite changes in the other side (i.e. inspiratory tary material online, Reference H).27
increase of venous return and right chambers with decreased left However, a more complex task is the evaluation of the aeti-
chambers volume and reduced systemic blood pressure). ology. Different diagnostic protocols have been proposed.4,8,17 – 21
1192 M. Imazio and Y. Adler
Nevertheless, the diagnostic work-up should be guided by the glucose can separate exudates from transudates, but are not dir-
epidemiology and the clinical presentation to avoid performing ectly diagnostic (class IIb). Nevertheless, purulent effusions with
an extensive and blinded testing. As already remarked, developing positive cultures have significantly lower fluid glucose levels than
countries have a high rate of pericardial effusions correlated to tu- non-infectious effusions. White cell count is highest in inflamma-
berculosis (.60, and .80% with HIV infection)28,29 that should be tory and infectious diseases, and lowest in myxedema. Technical
ruled out in such context, as well as in immigrants and HIV-infected advances in instrumentation, introduction of pericardioscopy and
patients. Non-idiopathic and non-viral aetiologies (especially bac- contemporary pathology, virology, and molecular biology techni-
terial and neoplastic) are associated with an increased risk of ques have improved the diagnostic value of epicardial/pericardial
cardiac tamponade and large effusion, and pericardiocentesis is biopsy. Pericardioscopy performed through air instead of fluid,
mandatory when cardiac tamponade or such aetiologies are made it possible to inspect large areas of pericardial surface,
suspected.4,6,7 select the biopsy site, and take numerous samples. Targeted peri-
Analyses of pericardial effusion can establish the diagnosis of in- cardial/epicardial biopsy during pericardioscopy was particularly
fectious and neoplastic pericardial effusions. Cytology and tumour useful in the diagnosis of neoplastic pericarditis. No major compli-
(Supplementary material online, Reference K). Systemic corticos- weeks (e.g. 6–8 weeks), especially when there are signs of right-
teroids offer an effective treatment option for autoreactive peri- sided collapse, in order to prevent the possible progression of
carditis; however, their use is limited by adverse effects and they the effusion towards tamponade following additional events (e.g.
are an independent risk factor for pericarditis recurrence. In a re- pericarditis, bleeding following chest trauma).47
cently published systematic review (Supplementary material online, Unfortunately, there are no proven effective medical therapies
Reference L), one case series and three open-label trials evaluating to reduce an isolated effusion; in the absence of inflammation,
intrapericardial triamcinolone for the management of autoreactive NSAID as well as colchicine and corticosteroids are generally
pericarditis were reviewed. Included studies were limited by small not efficacious.42 Pericardiocentesis alone may be necessary for
sample sizes (n ¼ 2 –84), lack of control groups, short durations of the resolution of large effusions but recurrences are also
follow-up (24 h–12 months), use of adjuvant agents, lack of patient common and pericardiectomy or less invasive options (i.e. pericar-
demographic data, subjective report of symptom relief, and lack dial window) should be considered whenever fluid reaccumulates,
of consistent dose of intrapericardial triamcinolone. Despite becomes loculated, or biopsy material is required.37 The feasibility
these limitations, available data suggest symptom resolution and of pericardiocentesis is high (.90%) in patients with anterior effu-
success. The use of ‘pure’ sclerosing agents has been replaced by complications either early or intermediate (cardiac tamponade,
agents with both sclerosing and antineoplastic activity (bleomycin recurrences) or late (constrictive pericarditis).49 Idiopathic pericar-
or thiotepa), which seems to be quite effective in breast cancer, dial effusion and pericarditis have an overall good prognosis with a
at least when associated with systemic chemotherapy. Local chemo- very low risk of complications especially if the effusion is mild to
therapy with platinum, mitoxantrone, and other agents may lead to moderate. In contrast with these observations, a recently published
good local control of the disease, but the addition of systemic prospective study has shown that even with mild pericardial effu-
chemotherapy is probably relevant to improve survival. The ration- sion the overall prognosis may be worse than in age- and sex-
ale of local instillation of antineoplastic agents is to cure the metas- matched controls.50
tases, rather than simply prevent effusion by mechanical means. Large idiopathic chronic effusion (.3 months) have a 30 –35%
Intrapericardial treatment tailored to the type of cancer indicates risk of progression to cardiac tamponade.46 Also subacute (4–6
that cisplatin is more effective in secondary lung cancer, whereas weeks) large effusions not responsive to conventional therapy
thiotepa seems to be effective in breast cancer.7 Surgical or percu- and with echocardiographic signs of right chambers collapse may
taneous pericardiostomy and radiation therapy may be useful in re- have an increased risk of progression according to some authors
Figure 8 A simplified algorithm for pericardial effusion triage and management. CRP, C-reactive protein.
Management of pericardial effusion 1197
already mentioned. We usually recommend to tailor the follow-up 1997 Guidelines for the Clinical Application of Echocardiography). Circulation
2003;108:1146 – 1162.
to the aetiology, adopted therapies (usually a control after 1– 2
11. Weitzman LB, Tinker WP, Kronzon I, Cohen ML, Glassman E, Spencer FC. The
weeks and then after 1 month and 6 months), and monitoring incidence and natural history of pericardial effusion after cardiac surgery—an
the possible evolution towards worsening pericardial effusion, echocardiographic study. Circulation 1984;69:506 –511.
cardiac tamponade, and constrictive pericarditis. For idiopathic 12. Imazio M, Cecchi E, Demichelis B, Ierna S, Demarie D, Ghisio A, Pomari F,
Coda L, Belli R, Trinchero R. Indicators of poor prognosis of acute pericarditis.
moderate effusions, an appropriate timing for echocardiographic Circulation 2007;115:2739 –2744.
follow-up may be an echocardiogram every 6 months. For a 13. Najib MQ, Ganji JL, Raizada A, Panse PM, Chaliki HP. Epicardial fat can mimic peri-
severe effusion, an echocardiographic follow-up may be every cardial effusion on transoesophageal echocardiogram. Eur J Echocardiogr 2011;
12:804.
3–6 months. A tailored follow-up is warranted also considering 14. Alter P, Figiel JH, Rupp TP, Bachmann GF, Maisch B, Rominger MB. MR, CT, and
the relative stability or evolution of the size (i.e. a worsening effu- PET imaging in pericardial disease. Heart Fail Rev. Advance Access published
sion may require a closer timing also guided by symptoms).4 March 25, 2012, doi:10.1007/s10741-012-9309-z.
15. Elavunkal J, Bright L, Stone MB. Emergency ultrasound identification of loculated
pericardial effusion: the importance of multiple cardiac views. Acad Emerg Med
2011;18:e29.
41. Imazio M. Pericardial involvement in systemic inflammatory diseases. Heart 2011; 45. Hota SS, Chow CM, Bonneau D. Surgical treatment for incessant pericarditis. Can
97:1882 –1892. J Cardiol 2009;25:161 –162.
42. Imazio M, Brucato A, Trinchero R, Spodick DH, Adler Y. Colchicine for pericar- 46. Sagrista-Sauleda J, Angel J, Permanyer-Miralda G, Soler-Soler J. Long-term follow-
ditis: hype or hope? Eur Heart J 2009;30:532 – 539. up of idiopathic chronic pericardial effusion. N Engl J Med 1999;341:2054 – 2059.
43. Imazio M, Brucato A, Cumetti D, Trinchero R. Corticosteroids for recurrent peri- 47. Little WC, Freeman GL. Pericardial disease. Circulation 2006;113:1622 –1632.
carditis: high versus low doses: a nonrandomized observation. Circulation 2008;118: 48. Lange RA, Hillis DH. Acute pericarditis. N Engl J Med 2004;351:2195 –2202.
667–671. 49. Imazio M, Brucato A, Maestroni S, Trinchero R. Risk of constrictive pericarditis
44. Vianello F, Cinetto F, Cavraro M, Battisti A, Castelli M, Imbergamo S, after acute pericarditis. Circulation 2011;124:1270 –1275.
Marcolongo R. Azathioprine in isolated recurrent pericarditis: a single centre 50. Mitiku TY, Heidenreich PA. A small pericardial effusion is a marker of increased
experience. Int J Cardiol 2011;147:477 –478. mortality. Am Heart J 2011;161:152 –157.