ESC Guidelines

Guidelines on the Diagnosis and Managementof Pericardial DiseasesFull Text

The Task Force on the Diagnosis and Management of PericardialDiseases of the European Society of Cardiology

Task Force members, Bernhard Maisch, Chairperson* (Germany), Petar M. Seferovic(Serbia and Montenegro), Arsen D. Ristic (Serbia and Montenegro), Raimund Erbel(Germany), Reiner Rienmuller (Austria), Yehuda Adler (Israel), Witold Z. Tomkowski(Poland), Gaetano Thiene (Italy), Magdi H. Yacoub (UK)

ESC Committee for Practice Guidelines (CPG), Silvia G. Priori (Chairperson) (Italy), Maria Angeles Alonso Garcia(Spain), Jean-Jacques Blanc (France), Andrzej Budaj (Poland), Martin Cowie (UK), Veronica Dean (France), JaapDeckers (The Netherlands), Enrique Fernandez Burgos (Spain), John Lekakis (Greece), Bertil Lindahl (Sweden),Gianfranco Mazzotta (Italy), Jo~ao Morais (Portugal), Ali Oto (Turkey), Otto A. Smiseth (Norway)

Document Reviewers, Gianfranco Mazzotta, CPG Review Coordinator (Italy), Jean Acar (France), Eloisa Arbustini(Italy), Anton E. Becker (The Netherlands), Giacomo Chiaranda (Italy), Yonathan Hasin (Israel), Rolf Jenni(Switzerland), Werner Klein (Austria), Irene Lang (Austria), Thomas F. Luscher (Switzerland), Fausto J. Pinto(Portugal), Ralph Shabetai (USA), Maarten L. Simoons (The Netherlands), Jordi Soler Soler (Spain),David H. Spodick (USA)

Table of contents

Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . 2Aetiology and classication of pericardial disease . . . 2Pericardial syndromes . . . . . . . . . . . . . . . . . . . . . . 2

Congenital defects of the pericardium . . . . . . . . 2Acute pericarditis . . . . . . . . . . . . . . . . . . . . . 2Chronic pericarditis . . . . . . . . . . . . . . . . . . . . 6Recurrent pericarditis . . . . . . . . . . . . . . . . . . 6Pericardial effusion and cardiac tamponade . . . . 7

Constrictive pericarditis . . . . . . . . . . . . . . . . . 9Pericardial cysts . . . . . . . . . . . . . . . . . . . . . 13

Specic forms of pericarditis . . . . . . . . . . . . . . . 13Viral pericarditis . . . . . . . . . . . . . . . . . . . . . 13Bacterial pericarditis . . . . . . . . . . . . . . . . . . 14

Tuberculous pericarditis . . . . . . . . . . . . . . 14Pericarditis in renal failure . . . . . . . . . . . . . . 16Autoreactive pericarditis and pericardial

involvement in systemic autoimmunediseases . . . . . . . . . . . . . . . . . . . . . . . . 16

The post-cardiac injury syndrome:postpericardiotomy syndrome . . . . . . . . . . 17

Postinfarction pericarditis . . . . . . . . . . . . . . . 17Traumatic pericardial effusion and

haemopericardium in aortic dissection . . . . . 17Neoplastic pericarditis . . . . . . . . . . . . . . . . . 19Rare forms of pericardial disease . . . . . . . . . . 20

Fungal pericarditis . . . . . . . . . . . . . . . . . . 20

* Corresponding author: Chairperson: Prof. Bernhard Maisch, MD, FESC,FACC, Dean of the Faculty of Medicine, Director of the Department ofInternal Medicine-Cardiology, Philipps University, Marburg, Baldingerst-rasse 1, D-35033 Marburg, Germany. Tel.: +49-6421-286-6462; Fax: +49-6421-286-8954.

E-mail address: BerMaisch@aol.com (B. Maisch).

0195-668X/$ - see front matter c 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.doi:10.1016/j.ehj.2004.02.001

European Heart Journal (2004) , 128

Preamble

Guidelines and Expert Consensus documents aim topresent all the relevant evidence on a particular issue inorder to help physicians to weigh the benets and risks ofa particular diagnostic or therapeutic procedure. Theyshould be helpful in everyday clinical decision-making.

A great number of Guidelines and Expert ConsensusDocuments have been issued in recent years by differentorganisations, the European Society of Cardiology (ESC)and by other related societies. By means of links to websites of National Societies several hundred guidelines areavailable. This profusion can put at stake the authorityand validity of guidelines, which can only be guaranteed ifthey have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC andothers have issued recommendations for formulating andissuing Guidelines and Expert Consensus Documents.

In spite of the fact that standards for issuing goodquality Guidelines and Expert Consensus Documents arewell dened, recent surveys of Guidelines and ExpertConsensus Documents published in peer-reviewed jour-nals between 1985 and 1998 have shown that methodo-logical standards were not complied within the vastmajority of cases. It is therefore of great importancethat guidelines and recommendations are presented informats that are easily interpreted. Subsequently, theirimplementation programmes must also be well con-ducted. Attempts have been made to determine whetherguidelines improve the quality of clinical practice andthe utilisation of health resources.

The ESC Committee for Practice Guidelines (CPG)supervises and coordinates the preparation of newGuidelines and Expert Consensus Documents producedby Task Forces, expert groups or consensus panels. TheCommittee is also responsible for the endorsement ofthese Guidelines and Expert Consensus Documents orstatements.

Introduction

The strength of evidence related to a particular diagnosticor treatment option depends on the available data: (1)level of evidence A. Multiple randomised clinical trials ormeta-analyses; (2) level of evidence B. A single rando-mised trial or non-randomised studies; (3) level of evi-dence C. Consensus opinion of the experts. Indications forvarious tests and procedures were ranked in three classes:Class I: Conditions for which there is evidence and/or

general agreement that a given procedure ortreatment is useful and effective.

Class II: Conditions for which there is conicting evidenceand/or a divergence of opinion about the useful-ness/efcacy of a procedure or treatment.Class IIa: Weight of evidence/opinion is in

favour of usefulness/efcacy.Class IIb: Usefulness/efcacy is less well estab-

lished by evidence/opinion.Class III: Conditions for which there is evidence and/or

general agreement that the procedure/treat-ment is not useful/effective and in some casesmay be harmful.

Aetiology and classication of pericardialdisease

The spectrum of pericardial diseases comprises congen-ital defects, pericarditis (dry, effusive, effusive-con-strictive, constrictive), neoplasm, and cysts. Theaetiological classication is shown in Table 1.13

Pericardial syndromes

Congenital defects of the pericardium

Congenital defects of the pericardium (1/10.000 autop-sies) comprise partial left (70%), right (17%) or total bi-lateral (extremely rare) pericardial absence. About 30%of patients have additional congenital abnormalities.4

Most patients with a total absence of pericardium areasymptomatic. However, homolateral cardiac displace-ment and augmented heart mobility impose an increasedrisk for traumatic aortic type A dissection.5 Partial leftside defects can be complicated by cardiac strangulationcaused by herniation of the left atrial appendage, atriumor left ventricle through the defect (chest pain, shortnessof breath, syncope or sudden death). The chest X-ray istypical but the diagnosis is conrmed by echocardiogra-phy and CT/MRI.6;7 Excision of the atrial appendage andsurgical pericardioplasty (Dacron, Gore-tex, or bovinepericardium) is indicated for imminent strangulation.8

Acute pericarditis

Acute pericarditis is either dry, brinous or effusive, in-dependent from its aetiology (Table 1).9 A prodrome offever (usually

Table 1 Review of aetiology, incidence and pathogenesis of pericarditis13

Aetiology Incidence (%) Pathogenesis

Infectious pericarditis Multiplication and spread of thecausative agent and release of toxic sub-stances in pericardial tissue cause serous,serobrinous or haemorrhagic (bacterial, vi-ral, tuberculous, fungal)or purulent inammation (bacterial)

Viral (Coxsackie A9, B1-4, Echo 8, Mumps, EBV, CMV,Varicella, Rubella, HIV, Parvo B19...)

3050a

Bacterial (Pneumo-, Meningo-, Gonococcosis,Hemophilus, Treponema pallidum, Borreliosis,Chlamydia, Tuberculosis...)

510a

Fungal (Candida, Histoplasma...) RareParasitary (Entameba histolytica, Echinococcus,Toxoplasma...)

Rare

Pericarditis in systemic autoimmune dis. Cardiac manifestations of the basicdisease, often clinically mild or silentSystemic lupus erythematosus 30b

Rheumatoid arthritis 30b

Spondylitis ankylosans 1b

Systemic sclerosis >50b

Dermatomyositis RarePeriarteritis nodosa RareReiters syndrome 2bFamilial Mediterranean fever 0.7b

Type 2 (auto)immune process Secondary, after infection/surgeryRheumatic fever 2050b Mostly in acute phasePostcardiotomy syndrome 20b 1014 days after surgeryPostmyocardial infarction syndrome 15b DDg P. epistenocardicaAutoreactive (chronic) pericarditis 23.1a Common form

Pericarditis and pericardial effusion in diseasesof surrounding organsAcute MI (P. Epistenocardica) 520b 15 days after transmural MIMyocarditis 30b Accompanying epimyocarditisAortic aneurysm Rare Dissection: haemorrhagic PELung infarction RarePneumonia RareOesophageal diseases RareHydropericardium in CHF RareParaneoplastic pericarditis Frequent No direct neoplastic inltrate

Pericarditis in metabolic disordersRenal insufciency (uraemia) Frequent Viral/toxic/autoimmuneMyxedema 30b Serous, cholesterol rich PEAddisons disease Rare Membranous leak?Diabetic ketoacidosis RareCholesterol pericarditis Very rare Transudation of cholesterol

(sterile serobrinous PE)Pregnancy Rare

Traumatic pericarditisDirect injury (penetrating thoracic injury,oesophageal perforation, foreign bodies)

Rare

Indirect injury (Non-penetrating thoracic injury,mediastinal irradiation)

Rare Less frequent after introduction oftopical convergent irradiation

Neoplastic pericardial disease 35a

Primary tumours RareSecondary metastatic tumours Frequent Serous or brinous, frequently

haemorrhagic effusionLung carcinoma 40c

Breast carcinoma 22c Accompanying disease during theinltration of malignant cells

Gastric and colon 3c

Other carcinoma 6c

Leukemia and lymphoma 15c

Melanoma 3c

Sarcoma 4c

Other tumours 7c

ESC Guidelines 3

timyosin antibodies, and structural changes in MRI areindicative.9 However, only endomyocardial/epimyocar-dial biopsy ndings are diagnostic.

The diagnostic algorithm can be derived fromTable 2.1021 Heart rate is usually rapid and regular. Mi-crovoltage and electrical alternans are reversible aftereffusion drainage.22 Findings by chest X-ray, computertomography (CT), and magnetic resonance imaging (MRI)

are shown in Table 3.23;24 Echocardiography is essentialto detect pericardial effusion and to check for concom-itant heart disease or paracardial pathology.12;13

Hospitalisation is warranted for most patients to de-termine the aetiology, observe for tamponade, and startanti-inammatory and symptomatic treatment. Nonste-roidal anti-inammatory drugs (NSAID) are the mainstay(level of evidence B, class I). Ibuprofen is preferred for its

Table 2 Diagnostic pathway and sequence of performance in acute pericarditis (level of evidence B for all procedures)

Technique Characteristic ndings Reference

Obligatory (indication class I)Auscultation Pericardial rub (mono-, bi-, or triphasic) 11

ECGa Stage I: anterior and inferior concave ST segment elevation. PR segmentdeviations opposite to P polarity.

9

Early stage II: ST junctions return to the baseline, PR deviated.Late stage II: T waves progressively atten and invertStage III: generalised T wave inversionsStage IV: ECG returns to prepericarditis state.

Echocardiography Effusion types B-D (Horowitz) (Fig. 1) 12; 13Signs of tamponade (see Section 3.5)

Blood analyses (a) ESR, CRP, LDH, leukocytes (inammation markers) 14(b) Troponin I, CK-MB (markers of myocardial lesion)b

Chest X-ray Ranging from normal to water bottle heart shadow. 15Revealing additional pulmonary/mediastinal pathology.

Mandatory in tamponade (indication class I), optional in large/recurrent effusions or if previous tests inconclusive (indicationclass IIa) in small effusions (indication class IIb)Pericardiocentesis and drainage PCR and histochemistry for aetiopathogenetic classication of infection or

neoplasia2; 10; 16

Optional or if previous tests inconclusive (indication class IIa)CT Effusions, peri-, and epicardium 17MRI Effusions, peri-, and epicardium 17Pericardioscopy, pericardial biopsy Establishing the specic aetiology 2; 10; 18; 19

a Typical lead involvement: I, II, aVL, aVF, and V3-V6. The ST segment is always depressed in aVR, frequently in V1, and occasionally in V2. Oc-casionally, stage IV does not occur and there are permanent T wave inversions and attenings. If ECG is rst recorded in stage III, pericarditis cannotbe differentiated by ECG from diffuse myocardial injury, biventricular strain, or myocarditis. ECG in EARLY REPOLARIZATION is very similar tostage I. Unlike stage I, this ECG does not acutely evolve and J-point elevations are usually accompanied by a slur, oscillation, or notch at the end ofthe QRS just before and including the J point (best seen with tall R and T waves large in early repolarisation pattern). Pericarditis is likely if in leadV6 the J point is >25% of the height of the T wave apex (using the PR segment as a baseline).b Cardiac troponin I was detectable in 49% and >1.5 ng/ml in 22% of 69 patients with acute pericarditis (only in those with ST elevation in ECG)investigated by Bonnefoy et al.20 In another study21 troponin I was detected in 10/14 patients with a median peak concentration of 21.4 mg/ml(range 0.5 to >50 ng/ml). CK-MB was elevated in 8/14 patients with the median peak of 21 U/l (range 1343), corresponding to the relative index of10.2% of the total CK activity.

Table 1 (continued)

Aetiology Incidence (%) Pathogenesis

Idiopathic 3.5a,in otherseries >50a

Serous, brinous, sometimes haemorrhagicPE with suspect viral or autoimmune sec-ondary immunopathogenesis

CHF, congestive heart failure; DDg, differential diagnosis; MI, myocardial infarction; P., pericarditis; PE, pericardial effusion.a Percentage related to the population of 260 subsequent patients undergoing pericardiocentesis, pericardioscopy and epicardial biopsy (Marburgpericarditis registry 19882001).1b Percentage related to the incidence of pericarditis in the specic population of patients (e.g., with systemic lupus erythematosus).c Percentage related to the population of patients with neoplastic pericarditis.

4 ESC Guidelines

rare side effects, favourable effect on the coronary ow,and the large dose range.9 Depending on severity andresponse, 300800 mg every 68 h may be initially re-quired and can be continued for days or weeks, best untilthe effusion has disappeared. Gastrointestinal protectionmust be provided in all patients. Colchicine (0.5 mg bid)added to an NSAID or as monotherapy also appears to beeffective for the initial attack and the prevention of re-currences (level of evidence B, class IIa indication).25 It iswell tolerated with fewer side effects than NSAIDs. Sys-temic corticosteroid therapy should be restricted toconnective tissue diseases, autoreactive or uremic peri-

carditis. Intrapericardial application avoids systemic sideeffects and is highly effective (level of evidence B, classIIa).2 For tapering of prednisone, ibuprofen or colchicineshould be introduced early (class IIa, level of evidenceB).25 Recovered patients should be observed for recur-rences or constriction. If patients require anticoagulants,heparin is recommended under strict observation. Peri-cardiocentesis is indicated for clinical tamponade, highsuspicion of purulent or neoplastic pericarditis (class Iindication, level of evidence B), or for large or symp-tomatic effusions despite the medical treatment for morethan one week 9;2637 (Focus box 1).

Focus box 1 PericardiocentesisPericardiocentesis is life saving in cardiac tamponade (level of evidence B, class I indication).27 Aortic dissection is amajor contraindication.28 Relative contraindications include uncorrected coagulopathy, anticoagulant therapy,thrombocytopenia 20 mm in echocardiography indiastole29 or for diagnostic purposes if additional procedures are available (e.g., pericardial uid and tissue anal-yses, pericardioscopy, and epicardial/pericardial biopsy) which could reveal the etiology of the disease and permitfurther causative therapy (level of evidence B, class IIa indication).2;10;18;19

Pericardiocentesis guided by uoroscopy is performed in the cardiac catheterisation laboratory with ECG mon-itoring. Direct ECG monitoring from the puncturing needle is not an adequate safeguard.30 Right-heart catheteri-sation can be performed simultaneously with pericardiocentesis, allowing monitoring the improvement as theeffusion is drained. The subxiphoid approach has been used most commonly, with a long needle with a mandrel(Tuohy or thin-walled 18-gauge) directed towards the left shoulder at a 30 angle to the skin. This route is extra-pleural and avoids the coronary, pericardial, and internal mammary arteries. The operator intermittently attemptsto aspirate uid and injects small amounts of contrast. If haemorrhagic uid is freely aspirated a few millilitres ofcontrast medium may be injected under uoroscopic observation. The appearance of sluggish layering of contrastmedium inferiorly indicates that the needle is correctly positioned. A soft J-tip guidewire is introduced and after

Table 3 Patterns of pericardial changes, their visualization and interpretation in chest X-ray, computer tomography (CT) andmagnetic resonance imaging (MRI)23;24

Pattern Patho-anatomicbasis

Chest X-ray CT MR Interpretation(Differentialdiagnosis)

Normal thickness Lateral viewbetweenmediastinaland subepicardialfat

Thin line in frontof the right atriumand rightventricle betweenmediastinumand subepicardialfat +++

Thin signal-freeline round the heartas long subepicardialand mediastinalfat present(for delineation) ++

No pathology

Thickened andsmooth

Acute inammatoryprocess, effusion

Thickenedpericardial line onlateral chest X-rayview +

CT-values forDD +++

MR-signals forDD ++

Acute, subacutepericarditis,pericardial effusion,DD liquid, semiliquid,haemorrhagic,purulent, solid

Thickenedirregular

Chronicinammatoryprocess

Irregular contoursof cardiacsilhouette +

+++ +++ Chronic pericarditis,pericardial brosis,tumour, metastasispost surgery

Thickenedirregular,calcied

End-stage ofinammatorytraumatic ofhaemorrhagic process

High density + High CT value+++

Poor signal++

Pericarditis calcarea,calcied tumours

+, visible; ++, good; +++, best visualization.

ESC Guidelines 5

Chronic pericarditis

Chronic pericardial inammation (>3 months) includeseffusive, adhesive, and constrictive forms.9 It is impor-tant to differentiate chronic inammatory effusions fromnon-inammatory hydropericardium (congestive heartfailure). Symptoms are usually mild (chest pain, palpi-tations, fatigue), related to the degree of chronic car-diac compression and residual pericardial inammation.

The diagnostic algorithm is similar as in acute peri-carditis (Table 2). The detection of the curable causes(e.g., tuberculosis, toxoplasmosis, myxedema, autoim-mune, and systemic diseases) allows specic therapywith high success rate. Symptomatic treatment is as inacute pericarditis. Intrapericardial instillation of crys-talloid nonabsorbable corticosteroids is highly efcient inautoreactive forms.2 Pericardiocentesis is indicated asdiagnostic and therapeutic procedure. If the recurrencesare frequent, pleuropericardial fenestration and percu-taneous balloon pericardiotomy may be appropriate (le-vel of evidence B, indication class IIb).38 For chronicpersistent/recurrent large effusions despite intraperi-cardial therapy or balloon pericardiotomy, pericardiec-tomy should be considered.29

Recurrent pericarditis

The term recurrent pericarditis encompasses (1) the in-termittent type (widely varying symptom-free interval

without therapy) and (2) the incessant type (discontinu-ation of anti-inammatory therapy always ensures a re-lapse). Mechanisms suggested to explain recurrenceinclude: (1) insufcient dose or/and insufcient treat-ment duration of antiphlogistics or corticoids in an au-toimmune pericardial disease, (2) early corticosteroidtreatment causing augmented viral DNA/RNA replicationin pericardial tissue leading to increased viral antigenexposure, (3) reinfection, and (4) exacerbation of theconnective tissue disease. Evidence for an immunopath-ological process includes: (1) the latent period lasting formonths; (2) the presence of anti-heart antibodies; (3) thequick response to steroid treatment and the similarityand co-existence of recurrent pericarditis with otherautoimmune conditions (lupus, serum sickness, polyser-ositis, postpericardiotomy/postmyocardial infarctionsyndrome, celiac disease, dermatitis herpetiformis, fre-quent arthralgias, eosinophilia, allergic drug reaction,and history of allergy). Evidence of a potential underlyinggenetic disorder in recurrent pericarditis is rare familialclustering with autosomal dominant inheritance with in-complete penetrance39 and sex-linked inheritance(chronic recurrent pericarditis associated with ocularhypertension) suggested in two families.40 Precordialpain, often with a pleuritic component, is characteristic.Fever, pericardial rub, dyspnoea, elevated erythrocytesedimentation rate, and electrocardiographic changesmay also occur. Massive pericardial effusion, cardiactamponade, and pericardial constriction are rare.

dilatation exchanged for a multi-holed pigtail catheter. It is prudent to drain the uid in steps of less than 1 l at atime to avoid the acute right-ventricular dilatation (sudden decompression syndrome).31 It is essential to checkthe position of the guidewire in at least two angiographic projections. If the guidewire was erroneously placedintracardially, this should be recognized before insertion of the dilator and drainage catheter. If, despite thecaution, the introducer set or the catheter have perforated the heart and are laying intracardially, the cathetershould be secured and the patient promptly transferred to the cardiac surgery. Alternatively, a second puncture canbe attempted. If successful, surgery may be avoided using autotransfusion of pericardial blood.

Echocardiographic guidance of pericardiocentesis is technically less demanding and can be performed in theintensive care unit at the bedside.16 Echocardiography should identify the shortest route where the pericardium canbe entered intercostally (usually in the sixth or seventh rib space in the anterior axillary line). Prolonged pericardialdrainage is performed until the volume of effusion obtained by intermittent pericardial aspiration (every 46 h) fallto

Symptomatic management relies on exercise restric-tion and the regimen used in acute pericarditis. Indo-methacin should be avoided in elderly patients due to itsow reduction in the coronaries.9 Colchicine inhibitsmitoses in the cell nucleus, binds to tubulin, inhibitsvarious polymorphonuclear functions, interferes withtranscellular movement of collagen. It was effective forrecurrent pericarditis when NSAIDs and corticosteroidsfailed to prevent relapses.25;4143 During 1004 months ofcolchicine treatment, only 13.7% new recurrences oc-curred.25 During the 2333 months of follow-up, 60.7% ofthe patients remained recurrence-free. The recom-mended dose is two mg/day for one or two days, followedby one mg/day (level of evidence B, indication class I).Corticosteroids should be used only in patients with poorgeneral condition or in frequent crises9(level of evidenceC, indication class IIa). A common mistake is to use a dosetoo low to be effective or to taper the dose too rapidly.The recommended regimen is: prednisone 11.5 mg/kg,for at least one month. If patients do not respond ade-quately, azathioprine (75100 mg/day) or cyclophos-phamide can be added.44 Tapering of corticoids shouldoccur over a three-month period. If symptoms recurduring the taper, return to the last dose that suppressedthe manifestations, maintain that dose for 23 weeks andthen recommence tapering. Towards the end of the ta-per, introduce anti-inammatory treatment with colchi-cine or NSAID. Renewed treatment should continue for atleast three months. Pericardiectomy is indicated only infrequent and highly symptomatic recurrences resistant tomedical treatment (level of evidence B, indication classIIa).45 Before pericardiectomy, the patient should be on asteroid-free regimen for several weeks.46 Post pericar-diectomy recurrences were also demonstrated, possiblydue to incomplete resection of the pericardium.

Pericardial effusion and cardiac tamponade

Pericardial effusion may appear as transudate (hydro-pericardium), exudate, pyopericardium or haemoperi-cardium. Large effusions are common with neoplastic,tuberculous, cholesterol, uremic pericarditis, myx-edema, and parasitoses.47 Effusions that develop slowlycan be remarkably asymptomatic, while rapidly accu-mulating smaller effusions can present with tamponade.Loculated effusions are more common when scarring hassupervened (e.g., postsurgical, posttrauma, postpuru-lent pericarditis). Massive chronic pericardial effusionsare rare (23.5% of all large effusions).48 Cardiac tam-ponade is the decompensated phase of cardiac com-pression caused by effusion accumulation and theincreased intrapericardial pressure. In surgical tam-ponade intrapericardial pressure is rising rapidly, in thematter of minutes to hours (i.e., haemorrhage), whereasa low-intensity inammatory process is developing indays to weeks before cardiac compression occurs(medical tamponade). The volume of uid causingtamponade varies inversely with both parietal pericardialstiffness and thickness (1502000 ml). In local com-pression, dyspnoea, dysphagia, hoarseness (recurrentlaryngeal nerve), hiccups (phrenic nerve), or nausea

(diaphragm) can occur. Heart sounds are distant. Com-pression of the base of the lung results in a dullnessunder the left scapula (BambergerPinsEwarts sign).9

In tamponade chest discomfort, tachypnea and dyspnoeaon exertion progress to orthopnoea, cough and dyspha-gia, occasionally also with episodes of unconsciousness.Insidiously developing tamponade may present with thesigns of its complications (renal failure, abdominalplethora, shock liver and mesenteric ischaemia). In 60%of the patients, the cause of pericardial effusion may bea known medical condition.49 Tamponade without two ormore inammatory signs (typical pain, pericardial fric-tion rub, fever, diffuse ST segment elevation) is usuallyassociated with a malignant effusion (likelihood ratio2.9). Electrocardiography may demonstrate diminishedQRS and T-wave voltages, PR-segment depression, ST-Tchanges, bundle branch block, and electrical alternans(rarely seen in the absence of tamponade).50 In chestradiography large effusions are depicted as globularcardiomegaly with sharp margins (water bottle sil-houette).15 On well-penetrated lateral radiographies, orbetter on cine lms, pericardial uid is suggested bylucent lines within the cardiopericardial shadow (epi-cardial halo sign, or various other terms for this phe-nomenon).15;51;52 Recently, it was suggested that this signmight be useful for uoroscopic guidance of pericardio-centesis.34 The separation of pericardial layers can bedetected in echocardiography, when the pericardial uidexceeds 1535 ml (Fig. 1).50 The size of effusions can be

Fig. 1 Horowitz classication of pericardial effusions. Type A, no ef-fusion; Type B, separation of epicardium and pericardium (316 ml 13mm); Type C 1, systolic and diastolic separation of epicardium andpericardium (small effusion >15 mlP 1 mm in Diastole); Type C 2, sys-tolic and diastolic separation of epicardium and pericardium with at-tenuated pericardial motion; Type D, pronounced separation ofepicardium and pericardium with large echo-free space; Type E, peri-cardial thickening (>4 mm). (Horowitz, Circulation 74). CopyrightsAmerican Heart Association.

ESC Guidelines 7

graded as: (1) small (echo-free space in diastole 100 beats/min, but may be lower in hypothyroidism and in uremic patients.c Pulsus paradoxus is absent in tamponade complicating atrial septal defect71 and in patients with signicant aortic regurgitation.d Occasional patients are hypertensive especially if they have pre-existing hypertension.72e Febrile tamponade may be misdiagnosed as septic shock.f Right ventricular collapse can be absent in elevated right ventricular pressure and right ventricular hypertrophy73 or in right ventricular infarction.g If after drainage of pericardial effusion intrapericardial pressure does not fall below atrial pressure, the effusive-constrictive disease should beconsidered.

8 ESC Guidelines

scending aorta. Diagnostic pitfalls are: small loculatedeffusions, haematoma, cysts, tumours, foramen of Mor-gagni hernia, hiatus hernia, lipodystrophia with para-cardial fat, inferior left pulmonary vein, left pleuraleffusion, mitral annulus calcication, giant left atrium,epicardial fat (best differentiated in CT), and left ven-tricular pseudoaneurysm.55 Metastatic inltration of thepericardium may masquerade pericardial tamponade inechocardiography in patients with no pericardial effu-sion.56 After open-heart surgery, localized effusion atthe posterior wall can be found with complete com-pression of the right atrium leading to cardiac tampon-ade. This may be misinterpreted as atrial myxoma orother cardiac tumour.57 When bleeding into the peri-cardium occurs and thrombosis develops the typicalecholucent areas may disappear, so that development ofcardiac tamponade may be overlooked. Transesophagealechocardiography is particularly useful in postoperativeloculated pericardial effusion or intrapericardial clot58 aswell as in identifying metastases and pericardialthickening.59 CT, spin-echo and cine MRI can also be usedto assess the size and extent of simple and complexpericardial effusions. The effusions measured by CT or byMRI may tend to be larger than by echocardiography.24;60

Up to one-third of patients with asymptomatic largepericardial chronic effusion developed unexpected car-diac tamponade.29 Triggers for tamponade include hyp-ovolemia, paroxysmal tachyarrhythmia and intercurrentacute pericarditis; often no trigger is identiable.61 Ma-jor diagnostic ndings in cardiac tamponade are noted inTable 46270 and Focus box 2.71;72

Pericardiocentesis may not be necessary when thediagnosis can be made based on other systemic featuresor the effusions are very small or resolving under anti-inammatory treatment. Where doubt remains, peri-cardiocentesis, pericardioscopy and epicardial and peri-cardial biopsy (including PCR, immunocytochemistry andimmunohistochemistry) may be valuable (level of evi-dence B, class IIa indication).2;10;18; 19 (Focus box 1, 3-5)Haemodynamic compromise and cardiac tamponade is anabsolute indication for drainage (class I indication). Pa-tients with dehydration and hypovolemia may tempo-rarily improve with intravenous uids enhancingventricular lling. Pericardiocentesis is not applicable inwounds, ruptured ventricular aneurysm, or dissectingaortic haematoma, when clotting makes needle evacu-

ation impossible so that surgical drainage with suppres-sion of bleeding sources is mandatory. Loculatedeffusions may require thoracoscopic drainage, subxy-phoid window or open surgery.45 All patients should bemonitored for postdrainage decompensation. Wheneverpossible, treatment should be aimed at the underlyingaetiology rather than the effusion itself. However, evenin idiopathic effusions extended pericardial catheterdrainage (3 2 days, range 113 days) was associatedwith a trend to lower recurrence rates (6% vs. 23%) thanin those without catheter drainage during the follow-upof 3.8 4.3 years.32 Resistant neoplastic processes re-quire intrapericardial treatment,89 percutaneous balloonpericardiotomy38 or rarely pericardiectomy. Surgicalapproach is recommended only in patients with verylarge chronic effusion (with or without symptoms) inwhom repeated pericardiocentesis and/or intrapericar-dial therapy were not successful.99

Constrictive pericarditis

Constrictive pericarditis is a rare but severely disablingconsequence of the chronic inammation of the peri-cardium, leading to an impaired lling of the ventriclesand reduced ventricular function. Tuberculosis, medias-tinal irradiation, and previous cardiac surgical proce-dures are frequent causes of the disease, which canpresent in several pathoanatomical forms23 (Fig. 2).Constrictive pericarditis may rarely develop only in theepicardial layer in patients with previously removed pa-rietal pericardium.100 Transient constrictive pericarditisis rare entity, distinguished by its self-limiting nature.101

Patients complain about fatigue, peripheral oedema,breathlessness, and abdominal swelling, which may beaggravated by a protein-loosing enteropathy. Typically,there is a long delay between the initial pericardial in-ammation and the onset of constriction. In decompen-sated patients venous congestion, hepatomegaly, pleuraleffusions, and ascites may occur. Haemodynamic im-pairment of the patient can be additionally aggravatedby a systolic dysfunction due to myocardial brosis oratrophy. Clinical, echocardiographic, and haemodynamicparameters can be derived from Table 5.23;59;103106 Dif-ferential diagnosis has to include acute dilatation of theheart, pulmonary embolism, right ventricular infarction,pleural effusion, chronic obstructive lung diseases102 and

Focus box 2 Determination of pulsus paradoxusPulsus paradoxus is dened as a drop in systolic blood pressure >10 mmHg during inspiration whereas diastolic bloodpressure remains unchanged. It is easily detected by feeling the pulse.71;72 During inspiration, the pulse may dis-appear or its volume diminishes signicantly. Clinically signicant pulsus paradoxus is apparent when the patient isbreathing normally. When present only in deep inspiration it should be interpreted with caution. The magnitude ofpulsus paradoxus is evaluated by sphygmomanometry. If the pulsus paradoxus is present, the rst Korotkoff sound isnot heard equally well throughout the respiratory cycle, but only during expiration at a given blood pressure. Theblood pressure cuff is therefore inated above the patients systolic pressure. Then it is slowly deated while theclinician observes the phase of respiration. During deation, the rst Korotkoff sound is intermittent. Correlationwith the patients respiratory cycle identies a point at which the sound is audible during expiration, but disappearsin inspiration. As the cuff pressure drops, another point is reached when the rst blood pressure sound is audiblethroughout the respiratory cycle. The difference in systolic pressure between these two points is the measure ofpulsus paradoxus.

ESC Guidelines 9

restrictive cardiomyopathy. The best way to distinguishconstrictive pericarditis from restrictive cardiomyopathyis the analysis of respiratory changes with or withoutchanges of preload by Doppler and/or tissue Dopplerechocardiography,107 but physical ndings, ECG, chestradiography, CT and MRI, haemodynamics, and endo-myocardial biopsy may be helpful as well (Table 6).9

Pericardiectomy is the only treatment for permanentconstriction. The indications are based upon clinicalsymptoms, echocardiography ndings, CT/MRI, and heartcatheterisation. There are two standard approaches,both aiming at resecting the diseased pericardium as faras possible:108111 (1) The antero-lateral thoracotomy(fth intercostal space) and (2) median sternotomy(faster access to the aorta and right atrium for extra-corporeal circulation). A primary installation of cardio-pulmonary bypass is not recommended, due to theenhanced diffuse bleeding during dissection of the peri-cardium, following systemic heparinisation. If severecalcied adhesions between peri- and epicardium or ageneral affection of the epicardium (outer porcelainheart) are present surgery carries a high risk of eitherincomplete success or severe myocardial damage. Analternative approach in such cases may be a lasershaving using an Excimer laser.109 Areas of strong cal-cication or dense scaring may be left as islands to avoidmajor bleeding. Pericardiectomy for constrictive peri-carditis has a mortality rate of 6%12% in the currentseries.109;111 The complete normalization of cardiachaemodynamics is reported in only 60% of the pa-tients.108;110 The deceleration time (DT) may remain

prolonged112 and postoperative respiratory variations ofmitral/tricuspid ow are found in 925%.110;113 Leftventricular ejection fraction increases due to a betterventricular lling110; 112 but consistent changes of the leftand right atrial sizes were not reported. Major compli-cations include acute perioperative cardiac insufciencyand ventricular wall rupture.114 Cardiac mortality andmorbidity at pericardiectomy is mainly caused by thepre-surgically unrecognised presence of myocardial at-rophy or myocardial brosis (Fig. 2).23 Myocardial atro-phy in CT is characterized by: (1) Thinning of theinterventricular septum and posterolateral wall (

Table

5Diagn

ostic

approachin

constrictivepericarditis

Clinical

presentation

Severe

chronic

systemic

venousco

ngestionassociatedwithlow

cardiacoutput,

includingjugu

larvenousdistension,hyp

otensionwithalow

pulse

pressure,ab

dominaldistension,oedemaan

dmuscle

wasting.

ECG

Can

benorm

al,orreveal

low

QRSvoltage,ge

neralizedT-w

aveinversion/

attening,

LAabnorm

alities,

atrialbrillation,atrioventricularblock,

intraventricularco

nductiondefects,

orrarely

pseudoinfarctionpattern

Chest

X-ray

Pericardialcalcications,

pleuraleffusions

Mmode/2

Dech

ocardiogram

Pericardialthickeningan

dcalcicationsa

aswellas

theindirect

sign

sofco

nstriction:

RA&

LAenlargementwithnorm

alap

pearan

ceoftheventricles,

andnorm

alsystolicfunction.

Early

pathologicaloutw

ardan

dinwardmovementoftheinterventricularseptum

(dip-plateauphenomenon)1

02

Flatteringwavesat

theLV

posteriorwall

LVdiameterisnotincreasingaftertheearly

rapid

llingphase.

VCIan

dthehepatic

veinsaredilatedwithrestrictedrespiratory

uctuations.

b

Doppler

Restrictedllingofboth

ventricleswithrespiratory

variation>25

%overtheAV-valves).1

03c

TEE

Measurementofthepericardialthickness

59

CT/M

RI

Thickenedan

d/o

rcalciedpericardium,tube-likeco

ngu

rationofoneorboth

ventricles,

enlargementofoneorboth

atria,narrowingofoneor

both

atrio-ventriculargrooves,

congestionofthecavalveins2

3

Cardiaccatheterisation

Dip

andplateau

orsquareroutesign

inthepressure

curveoftherigh

tan

d/o

rleft

ventricle

EqualisationofLV

/RVend-diastolicpressuresin

therange

of5mmHgorless.1

02d

RV/LVan

giograp

hy

ThereductionofRV&

LVsize

andincreaseofRA&

LAsize

Duringdiastole

arapid

early

llingwithstopoffurtherenlargement(dip-plateau

)

Coronaryan

giograp

hy

Inallpatients

over35

yearsan

din

patients

withahistory

ofmediastinal

irradiation,regardless

oftheage

LA,left

atrium;LV

,left

ventricle;RA,righ

tatrium;RV,righ

tventricle;VCI,inferiorvenacava;TEE,tran

soesophageal

ech

ocardiograp

hy.

aThicke

ningofthepericardium

isnotalwaysequal

toco

nstriction(absentin

18%of14

3surgically

provencases).Whenclinical,ech

ocardiographic,orinvasive

haemodynamic

featuresindicate

constriction,

pericardiectomyshould

notbedeniedonthebasisofnorm

alpericardialthickn

ess.1

04

bDiagn

osisisdifcu

ltin

atrial

brillation.Hepatic

diastolicvein

ow

reversal

inexp

irium

isobservedevenwhentheow

velocity

pattern

isinco

nclusive.1

03

cPatients

withincreasedatrialpressuresormixedco

nstrictionan

drestrictiondemonstrate

3.0 g/dl;uid/serum ratio >0.5), LDH (>200 mg/dL; serum/uid >0.6), and glucose (exudates vs. transudates 77.9 41.9vs. 96.1 50.7 mg/dl) can separate exudates from transudates but are not directly diagnostic (class IIb).14 However,purulent effusions with positive cultures have signicantly lower uid glucose levels (47.3 25.3 vs. 102.5 35.6mg/dl) and uid to serum ratios (0.28 0.14 vs. 0.84 0.23 mg/dl), than non-infectious effusions.14 White cellcount (WBC) is highest in inammatory diseases, particularly of bacterial and rheumatologic origin. A very low WBCcount is found in myxedema. Monocyte count is highest in malignant and effusions in hypothyroidisms (79 27% and74 26%), while rheumatoid and bacterial effusions have the highest proportions of neutrophils (78 20% and69 23%). Compared with controls, both bacterial and malignant pericardial uids have higher cholesterol levels(49 18 vs. 121 20 and 117 33 mg/dl).14

ESC Guidelines 13

Pericardial manifestation of human immunodeciencyvirus (HIV) infection can be due to infective, non-infec-tive and neoplastic diseases (Kaposi sarcoma and/orlymphoma). Infective (myo)pericarditis results from thelocal HIV infection and/or from the other viral (cyto-megalovirus, herpes simplex), bacterial (S. aureus, K.pneumoniae, M. avium, and tuberculosis) and fungalcoinfections (cryptococcus neoformans).127130 In pro-gressive disease the incidence of echocardiographicallydetected pericardial effusion is up to 40%.131; 132 Cardiactamponade is rare.133 During the treatment with retro-viral compounds, lipodystrophy can develop (best dem-onstrated by MRI) with intense paracardial fat depositionleading to heart failure. Treatment is symptomatic,while in large effusions and cardiac tamponade pericar-diocentesis is necessary. The use of corticoid therapy iscontraindicated except in patients with secondary tu-berculous pericarditis, as an adjunct to tuberculostatictreatment (level of evidence A, indication class I).134

Bacterial pericarditis

Purulent pericarditis in adults is rare (Table 7),135147 butalways fatal if untreated. Mortality rate in treated pa-tients is 40%, mostly due to cardiac tamponade, toxicity,and constriction. It is usually a complication of an in-fection originating elsewhere in the body, arising bycontiguous spread or haematogenous dissemination.148

Predisposing conditions are: pre-existing pericardial ef-fusion, immunosuppression, chronic diseases (alcoholabuse, rheumatoid arthritis, etc), cardiac surgery andchest trauma. Rarely, left ventricular pseudoaneurysmmay complicate bacterial pericarditis.149

The disease appears as an acute, fulminant infectiousillness with short duration. Percutaneous pericardiocen-tesis must be promptly performed. Obtained pericardialuid should undergo urgent Gram, acid-fast and fungalstaining, followed by cultures of the pericardial and bodyuids (level of evidence B, indication class I).

Rinsing of the pericardial cavity, combined with ef-fective systemic antibiotic therapy is mandatory (com-bination of antistaphylococcal antibiotic andaminoglycoside, followed by tailored antibiotic therapyaccording to the results of pericardial uid and bloodcultures).136 Intrapericardial instillation of antibiotics(e.g., gentamycin) is useful but not sufcient. Frequentirrigation of the pericardial cavity with urokinase orstreptokinase, using large catheters, may liquefy the

purulent exudate,137;138 but open surgical drainagethrough subxiphoid pericardiotomy is preferable.135

Pericardiectomy is required in patients with dense ad-hesions, loculated and thick purulent effusion, recur-rence of tamponade, persistent infection, andprogression to constriction.136 Surgical mortality up to 8%was reported for pericardiectomy combined with anti-biotic treatment but the total mortality is higher.

Tuberculous pericarditisIn the last decade TBC pericarditis in the developedcountries has been primarily seen in immunocompromisedpatients (AIDS).140 The mortality rate in untreated acuteeffusive TBC pericarditis approaches 85%. Pericardialconstriction occurs in 3050%.139;142 The clinical presen-tation is variable: acute pericarditis with or without ef-fusion; cardiac tamponade, silent, often large pericardialeffusion with a relapsing course, toxic symptoms withpersistent fever, acute constrictive pericarditis, subacuteconstriction, effusive-constrictive, or chronic constric-tive pericarditis, and pericardial calcications.3; 73 Thediagnosis made by the identication of Mycobacteriumtuberculosis in the pericardial uid or tissue, and/or thepresence of caseous granulomas in the pericardium.3;140

Pericarditis in a patient with proven extracardiac tuber-culosis is strongly suggestive of TBC aetiology (severalsputum cultures should be taken).3;143 The tuberculin skintest may be false negative in 2533% of patients139 andfalse positive in 3040% (elderly patients).140 A moreaccurate enzyme-linked immunospot (ELISPOT) test wasrecently developed,150, detecting T-cells specic for My-cobacterium tuberculosis antigen. Perimyocardial TBCinvolvement is also associated with high titres of anti-myolemmal and antimyosin antibodies in the sera.151 Thediagnostic yield of pericardiocentesis in TBC pericarditisranges from 3076% according to the methods applied forthe analyses of pericardial effusion.139;144 Pericardial uiddemonstrates high specic gravity, high protein levels,and high white-cell count (from 0.754 109/l).140 Im-portantly, PCR can identify DNA of Mycobacterium tu-berculosis rapidly from only 1 lL of pericardial uid.144;145

High adenosine deaminase activity and interferon c con-centration in pericardial effusion are also diagnostic, witha high sensitivity and specicity (Focus box 4): Bothpericardioscopy and pericardial biopsy have also im-proved the diagnostic accuracy for TBC pericarditis.18

Pericardial biopsy enables rapid diagnosis with bettersensitivity than pericardiocentesis (100 vs. 33%).

The real nature of the cells found in the pericardial effusion can be difcult to recognize. Grams stains inpericardial uid have a specicity of 99%, but a sensitivity of only 38% for exclusion of the infection in comparison tobacterial cultures.14 Combination of epithelial membrane antigen, CEA and vimentin immunocytochemical stainingcan be useful to distinguish reactive mesothelial and adenocarcinoma cells.85 Antimyolemmal and antisarcolemmalantibodies, as well as complement xation, were seen predominantly in viral and autoreactive effusions.10 In vitrocardiocytolysis of isolated rat heart cells by the pericardial effusion uid, with or without addition of a freshcomplement source, was seen primarily in autoreactive effusions. Mediators of inammation such as Il-6, Il-8 andIFN-c in pericardial uids may be also helpful in the discrimination of autoreactive effusions.75;86 A cut-off value of200 pg/L for pericardial IFN-c resulted in a sensitivity and specicity of 100% for the diagnosis of tuberculouspericarditis.84

14 ESC Guidelines

Table

7Differential

diagn

osisofthespecicform

sofpericarditis13

514

7

Viral

Bacterial

Tuberculous

Autoreactive

Cardiotropic

microbial

agents

Entero-,

ech

o-,

adeno-,

cytomegalo,

Ebstein

Barr,

herpessimplex,

inuenza,parvo

B19

,hepatitis

A,B,C

virus,

HIV

Stap

hyloco

cci,pneumoco

cci,

streptoco

cci,Neisseria,

proteus,

gram

negative

rods,

Legionella

Mycobacterium

tuberculosis

Autoim

muneproce

ssin

theabsence

ofviralandbacterialage

nts

Etiologicalevidence

by

PCRorin

situ

hyb

ridisation

(evidence

levelB,indicationIIa)

Gram-stain,bacterial

culture,

PCRforBorrelia&

chlamyd

iapneumoniae(evidence

levelB,

indicationI)

Ziehl-Neelsen,auramin

0stain,

culture,PCR(evidence

levelB,

indicationI)

Ig-bindingto

peri-andepicardium,

negative

PCRforcardiotropic

age

nts,

epicarditis(evidence

levelB,indica-

tionIIa)

Incidence

(%)Western

countries

305

1025%

Aspect

ofPE

Serous/serosanginous

Purulent

Serosanginous

Serous

Protein

content

>3g/dl

High

High/interm

ediate

Interm

ediate

Leuko

cyte

count(PE)

>50

00/m

l10

,000

/ml

Interm

ediate

>8000

Interm

ediate

40

U/m

l)ADA-negative

Peri-&epicardialbiopsy

Lymphocyticperi-/epicarditis,

PCRpositive

forcardiotropic

virus

Leuko

cyticepicarditis

Caseousgran

uloma,PCR

Lymphocyticperi-/epicarditis,PCR

negative

Mortalityifuntreated

Dependingonagentan

dtamponad

e10

0%85

%In

untreatedtamponade

Intrap

ericardialtreatment

Drainage,ifneeded,no

intrap

ercardialco

rticoids

Drainagean

drinsing(saline)

gentamycin

80mgi.p.,

Drainage,ifneeded

Drainage

,i.p.triamcinolon

(evidence

B,indicationIIa)

Pericardiotomy/

Pericardiectomy

Rarely

needed

Promptlyneeded

(evidence

levelB,indicationI)

Rarely

needed

Rarely

needed

Systemic

treatment

I.V.im

munoglobulins,

IFN

(inenteroviralP)s.c.

I.V.an

tibiotics

Tuberculostatic

+prednisone

NSA

IDs,

Colchicine,

prednisolone/A

zathioprin

Constriction

Rare

Frequent

Frequent(30

50%)

Rare

ESC Guidelines 15

Various antituberculous drug combinations of differ-ent lengths (6, 9, 12 months) have been ap-plied.78;139;140;143 However, only patients with proven orvery likely TBC pericarditis should be treated. Preventionof constriction in chronic pericardial effusion of unde-termined aetiology by ex iuvantibus antituberculartreatment was not successful.152 The use of steroids re-mains controversial.143; 147;153 A meta analysis of patientswith effusive and constrictive TBC pericarditis154 sug-gested that tuberculostatic treatment combined withsteroids might be associated with fewer deaths, lessfrequent need for pericardiocentesis or pericardiectomy(level of evidence A, indication class IIa).143;146 If given,prednisone should be administered in relatively highdoses (12 mg/kg per day) since rifampicin induces itsliver metabolism.9 This dose is maintained for 57 daysand is progressively reduced to discontinuation in 68weeks. If, in spite of combination therapy, constrictiondevelops pericardiectomy is indicated (level of evidenceB, class I indication).

Pericarditis in renal failure

Renal failure is a common cause of pericardial disease,producing large pericardial effusions in up to 20% of pa-tients.155 Two forms have been described: (1) Uremicpericarditis in 610% of patients with advanced renalfailure (acute or chronic) before dialysis has been insti-tuted or shortly thereafter.156 It results from inammationof the visceral and parietal pericardium and correlateswith the degree of azotemia (the BUN is usually >60 mg/dl). (2) Dialysis-associated pericarditis in up to 13% ofpatients on maintenance haemodialysis,157 and occasion-ally with chronic peritoneal dialysis due to inadequatedialysis and/or uid overload.158 Pathologic examinationof the pericardium shows adhesions between the thick-ened pericardial membranes (bread and butter ap-pearance). The clinical features may include fever andpleuritic chest pain but many patients are asymptomatic.Pericardial rubs may persist even in large effusions or maybe transient. Due to autonomic impairment in uremic pa-tients, heart rate may remain slow (6080 beats/min)during tamponade, despite fever and hypotension. Anae-mia, due to induced resistance to erythropoetin159 mayworsen the clinical picture. The ECG does not show thetypical diffuse ST/T wave elevations observed with othercauses of acute pericarditis due to the lack of the myo-cardial inammation.160 If the ECG is typical of acutepericarditis, intercurrent infection must be suspected.

Most patients with uremic pericarditis respond rapidlyto haemo- or peritoneal dialysis with resolution of chest

pain and pericardial effusion. To avoid haemopericar-dium heparin-free haemodialysis should be used. Careshould be taken since acute uid removal with hae-modialysis can lead to cardiovascular collapse in patientswith tamponade or pretamponade. Hypokalemia andhypophosphatemia should be prevented by supplement-ing the dialysis solution when appropriate.161 Intensieddialysis usually leads to resolution of the pericarditiswithin 12 weeks.162 Peritoneal dialysis, which does notrequire heparinisation, may be therapeutic in pericardi-tis resistant to haemodialysis, or if heparin-free hae-modialysis cannot be performed. NSAIDs and systemiccorticosteroids have limited success when intensive di-alysis is ineffective.163165 Cardiac tamponade and largechronic effusions resistant to dialysis must be treatedwith pericardiocentesis (level of evidence B, class IIaindication). Large, non-resolving symptomatic effusionsshould be treated with instillation of intrapericardialcorticosteroids after pericardiocentesis or subxiphoidpericardiotomy (triamcinolone hexacetonide 50 mg ev-ery 6 h for 23 days).157; 166 Pericardiectomy is indicatedonly in refractory, severely symptomatic patients due toits potential morbidity and mortality. Within two monthsafter renal transplantation pericarditis has been re-ported in 2.4% of patients.167 Uraemia or infection (CMV)may be the causes.

Autoreactive pericarditis and pericardialinvolvement in systemic autoimmune diseases

The diagnosis of autoreactive pericarditis is establishedusing the following criteria:2 (1) increased number oflymphocytes and mononuclear cells >5000/mm3 (auto-reactive lymphocytic), or the presence of antibodiesagainst heart muscle tissue (antisarcolemmal) in thepericardial uid (autoreactive antibody-mediated); (2)signs of myocarditis on epicardial/endomyocardial biop-sies by P 14 cells/mm2; (3) exclusion of active viral in-fection both in pericardial effusion and endomyocardial/epimyocardial biopsies (no virus isolation, no IgM-titeragainst cardiotropic viruses in pericardial effusion, andnegative PCR for major cardiotropic viruses); (4) tuber-culosis, Borrelia burgdorferi, Chlamydia pneumoniae,and other bacterial infection excluded by PCR and/orcultures; (5) neoplastic inltration absent in pericardialeffusion and biopsy samples; (6) exclusion of systemic,metabolic disorders, and uraemia. Intrapericardialtreatment with triamcinolone is highly efcient with lowincidence of side effects.2

Pericarditis, with or without effusion, is also a com-ponent of a multiserositis in systemic autoimmune dis-

Focus box 4 Pericardioscopy and epicardial/pericardial biopsyTechnical advances in instrumentation, introduction of pericardioscopy and contemporary pathology, virology, andmolecular biology techniques have improved the diagnostic value of epicardial/pericardial biopsy.2;10;18;19;8762;9093

Pericardioscopy performed through air instead of uid, made it possible to inspect large areas of pericardial sur-face, select the biopsy site, and take numerous samples safely.19 Targeted pericardial/epicardial biopsy duringpericardioscopy was particularly useful in the diagnosis of neoplastic pericarditis.18;19; 87;88;89 No major complicationsoccurred in any of the exible pericardioscopy studies. Mortality reported in the studies with rigid endoscopes was2.1%,18 and 3.5%88 due to induction of anaesthesia in patients with very large pericardial effusions.

16 ESC Guidelines

eases: rheumatoid arthritis, systemic lupus erythemato-sus (SLE), progressive systemic sclerosis, polymyositis/dermatomyositis, mixed connective tissue disease, se-ronegative spondyloarthropathies, systemic and hyper-sensitivity vasculitides, Behcet syndrome, Wegenergranulomatosis and sarcoidosis.9 Intensied treatment ofthe underlying disease and symptomatic managementare indicated (level of evidence B, indication class I).Treatment should focus on pericardial symptoms, man-agement of the pericardial effusion, and the underlyingsystemic disease.

The post-cardiac injury syndrome:postpericardiotomy syndrome

Post-cardiac injury syndrome develops within days tomonths after cardiac, pericardial injury or both.9;168 Itresembles the post-myocardial infarction syndrome,both appearing to be variants of a common immuno-pathic process. Unlike post-myocardial infarction syn-drome, post-cardiac injury syndrome acutely provokes agreater antiheart antibody response (antisarcolemmaland antibrillary), probably related to more extensiverelease of antigenic material.168;169 Pericardial effusionalso occurs after orthotopic heart transplantation (21%).It is more frequent in patients receiving aminocaproicacid during the operation.170 Cardiac tamponade afteropen heart surgery is more common following valvesurgery (73%) than coronary artery bypass grafting(CABG) alone (24%) and may be related to the preoper-ative use of anticoagulants.171 Constrictive pericarditismay also occur after cardiac surgery. Warfarin adminis-tration in patients with early postoperative pericardialeffusion imposes the greatest risk, particularly in thosewho did not undergo pericardiocentesis and drainage ofthe effusion.172 Symptomatic treatment is as in acutepericarditis (NSAIDs or colchicine for several weeks ormonths, even after disappearance of effusion).173 Longterm (36 months) oral corticoids or preferably peri-cardiocentesis and intrapericardial instillation of triam-cinolone (300 mg/m2) are therapeutic options inrefractory forms. Redo surgery and pericardiectomy arevery rarely needed. Primary prevention of postperiocar-diotomy syndrome using short-term perioperative steroidtreatment or colchicine is under investigation.174

Postinfarction pericarditis

Two forms of postinfarction pericarditis can be distin-guished: an early form (pericarditis epistenocardica)and a delayed form (Dresslers syndrome).175 Epi-stenocardiac pericarditis, caused by direct exudation,occurs in 520% of transmural myocardial infarctions butis clinically discovered rarely. Dresslers syndrome oc-curs from one week to several months after clinical onsetof myocardial infarction with symptoms and manifesta-tions similar to the post-cardiac injury syndrome. It doesnot require transmural infarction176 and can also appearas an extension of epistenocardiac pericarditis. Its inci-dence is 0.55%177 and is still lower in patients treated

with thrombolytics (10 mm is most frequentlyassociated with haemopericardium, and two thirds ofthese patients may develop tamponade/free wall rup-ture.182 Urgent surgical treatment is life saving. How-ever, if the immediate surgery is not available orcontraindicated pericardiocentesis and intrapericardialbrin-glue instillation could be an alternative in subacutetamponade.182;183

Hospitalisation to observe for tamponade, differ-ential diagnosis, and adjustments of treatment isneeded. Ibuprofen, which increases coronary ow, isthe agent of choice.184 Aspirin, up to 650 mg every 4h for 25 days has also been successfully applied.Other nonsteroidal agents risk thinning the infarctionzone.185 Corticosteroid therapy can be used for re-fractory symptoms only but could delay myocardialinfarction healing (level of evidence B, class IIa indi-cation).

Traumatic pericardial effusion andhaemopericardium in aortic dissection

Direct pericardial injury can be induced by accidents oriatrogenic wounds.9;186189 Blood loss, vasoconstriction,and haematothorax leading to severe hypotension andshock may mask pulses paradoxus.189 Thoracotomy andsurgical repair should be performed to stabilize thehaemodynamics.

Iatrogenic tamponade occurs most frequently in per-cutaneous mitral valvuloplasty, during or after trans-septal puncture, particularly, if no biplanecatheterisation laboratory is available and a small leftatrium is present. Whereas the puncture of the intera-trial septum is asymptomatic, the passage of the freewall induces chest-pain immediately. If high-pressurecontaining structures are punctured, rapid deteriorationoccurs. However, if only the atrial wall is passed, theonset of symptoms and the tamponade may be delayedfor 46 h. Rescue pericardiocentesis is successful in95100% with a mortality of less than 1%36(Table 8).

Transsection of the coronary artery and acute orsubacute cardiac tamponade may occur during percuta-neous coronary interventions.191;192 A breakthrough inthe treatment of coronary perforation are membrane-covered graft stents.196;197 Perforation of the coronaryartery by a guidewire is not infrequent and causes veryrarely a relevant pericardial haemorrhage.

During right ventricular endomyocardial biopsy, dueto the low stiffness of the myocardium, the catheter maypass the myocardium, particularly, when the bioptomehas not been opened before reaching the endocardialborder. The rate of perforation is reported to be in therange of 0.35%, leading to tamponade and circulatory

ESC Guidelines 17

Table

8Traumatic

pericardialeffusion

18621

3

Effusiondueto

Incidence

(%)

Mortality(%)

Man

agement

Comment/reference

Iatroge

nic

Transseptalpuncture

13

30

%ofmyocardium

atstake

orbleedingcannotbestopped191;192

Rotablation

0.1

3Notavailable

Seeab

ove

Seeabove

191;19

2

Transluminal

extraction

atherectomy(atherocath)

02%

Notavailable

Seeab

ove

Seeabove

Excim

erlaseran

gioplasty

1.7

3%Notavailable

Seeab

ove

Seeabove

192

Highpressure

stenting