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ESC Guidelines
Guidelines on the Diagnosis and Managementof Pericardial DiseasesExecutive Summary
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 . . . . . . . . . . . . . . . . . . . . . . . . . . 587Introduction. . . . . . . . . . . . . . . . . . . . . . . . . 588Aetiology and classification of pericardial disease . 588Pericardial syndromes . . . . . . . . . . . . . . . . . . 588
Congenital defects of the pericardium . . . . . . 588Acute pericarditis . . . . . . . . . . . . . . . . . . . 588Chronic pericarditis . . . . . . . . . . . . . . . . . . 591Recurrent pericarditis . . . . . . . . . . . . . . . . 592Pericardial effusion and cardiac tamponade . . 592Constrictive pericarditis . . . . . . . . . . . . . . . 593Pericardial cysts . . . . . . . . . . . . . . . . . . . . 595
Specific forms of pericarditis . . . . . . . . . . . . . . 597Viral pericarditis . . . . . . . . . . . . . . . . . . . . 597Bacterial pericarditis . . . . . . . . . . . . . . . . . 598
Tuberculous pericarditis . . . . . . . . . . . . . 598Pericarditis in renal failure . . . . . . . . . . . . . 600Autoreactive pericarditis and pericardial
involvement in systemic autoimmunediseases . . . . . . . . . . . . . . . . . . . . . . . 600
The post-cardiac injury syndrome:postpericardiotomy syndrome . . . . . . . . . 600
Postinfarction pericarditis . . . . . . . . . . . . . . 601Traumatic pericardial effusion and
haemopericardium in aortic dissection . . . . 601Neoplastic pericarditis . . . . . . . . . . . . . . . . 603Rare forms of pericardial disease . . . . . . . . . 603
Fungal pericarditis . . . . . . . . . . . . . . . . . 603Radiation pericarditis . . . . . . . . . . . . . . . 604Chylopericardium . . . . . . . . . . . . . . . . . 604Drug- and toxin-related pericarditis . . . . . . 605
*Corresponding author: Chairperson: 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: [email protected] (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.2004.02.002
European Heart Journal (2004) 25, 587610
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Preamble
Guidelines and Expert Consensus documents aim to pres-ent all the relevant evidence on a particular issue in orderto help physicians to weigh the benefits and risks of aparticular 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 guaranteedif they have been developed by an unquestionable deci-sion-making process. This is one of the reasons why theESC and others have issued recommendations for for-mulating and issuing Guidelines and Expert ConsensusDocuments.
In spite of the fact that standards for issuing goodquality Guidelines and Expert Consensus Documents arewell defined, 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 diag-nostic or treatment option depends on the availabledata: (1) level of evidence A: multiple randomised clin-ical trials or meta-analyses; (2) level of evidence B: asingle randomised trial or non-randomised studies; and(3) level of evidence C: consensus opinion of the experts.Indications for various tests and procedures were rankedin three classes:
Class I: Conditions for which there is evidence and/orgeneral agreement that a given procedure ortreatment is useful and effective.
Class II: Conditions for which there is conflicting evi-dence and/or a divergence of opinion aboutthe usefulness/efficacy of a procedure or treat-ment.Class IIa: Weight of evidence/opinion is in
favour of usefulness/efficacy.Class IIb: Usefulness/efficacy 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 classification of pericardialdisease
The spectrum of pericardial diseases consists of con-genital defects, pericarditis (dry, effusive, effusive-constrictive, and constrictive), neoplasm, and cysts. Theaetiological classification comprises: infectious pericar-ditis, pericarditis in systemic autoimmune diseases, type2 (auto) immune process, postmyocardial infarctionsyndrome, and auto-reactive (chronic) pericarditis(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 (rare) pericardial absence. Additional congenitalabnormalities occur in 30% of patients.4 Most patientswith a total pericardial absence are asymptomatic. Ho-molateral cardiac displacement and augmented heartmobility impose an increased risk for traumatic aorticdissection.5 Partial left side defects can be complicatedby herniation and strangulation of the heart through thedefect (chest pain, shortness of breath, syncope or sud-den death). Surgical pericardioplasty (Dacron, Gore-tex,or bovine pericardium) is indicated for imminent stran-gulation.6
Acute pericarditis
Acute pericarditis is dry, fibrinous or effusive, indepen-dent from its aetiology. The diagnostic algorithm can bederived from Table 2.818 A prodrome of fever, malaise,and myalgia is common, but elderly patients may not befebrile. Major symptoms are retrosternal or left precor-dialchest pain (radiates to the trapezius ridge, can bepleuritic or simulate ischemia, and varies with posture)and shortness of breath. The pericardial friction rub canbe transient, mono-, bi- or triphasic. Pleural effusionmay be present. Heart rate is usually rapid and regular.
Pericardial effusion in thyroid disorders . . . 605Pericardial effusion in pregnancy . . . . . . . 605
Uncited references . . . . . . . . . . . . . . . . . . . . 605Acknowledgements . . . . . . . . . . . . . . . . . . . . 605References . . . . . . . . . . . . . . . . . . . . . . . . . 605
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Table 1 Review of aetiology, incidence and pathogenesis of pericarditis13
Aetiology Incidence (%) Pathogenesis
Infectious pericarditis Multiplication and spread of the causativeagent and release of toxic substances in peri-cardial tissue cause serous, serofibrinous orhaemorrhagic (bacterial, viral, tuberculous,fungal) or purulent inflammation (bacterial)
Viral (Coxsackie A9, B1-4, Echo 8, Mumps,EBV, CMV, Varicella, Rubella, HIV, Parvo B19,etc.)
3050a
Bacterial (Pneumo-, Meningo-, Gonococcosis,Hemophilus, Treponema pallidum, Borreliosis,Chlamydia, Tuberculosis, etc.)
510a
Fungal (Candida, Histoplasma, etc.) RareParasitary (Entameba histolytica, Echinococcus,Toxoplasma. . .)
Rare
Pericarditis in systemic autoimmune diseases Cardiac manifestations of the basic disease,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 diseases of 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 infiltrate
Pericarditis in metabolic disordersRenal insufficiency (uraemia) Frequent Viral/toxic/autoimmuneMyxedema 30b Serous, cholesterol rich PEAddisons disease Rare Membranous leak?Diabetic ketoacidosis RareCholesterol pericarditis Very rare Transudation of cholesterol
(sterile serofibrinous 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 of topicalconvergent irradiation
Neoplastic pericardial disease 35a
Primary tumours RareSecondary metastatic tumours Frequent
Lung carcinoma 40c Serous or fibrinous, frequently haemorrhagiceffusion
Breast carcinoma 22c Accompanying disease during the infiltration ofmalignant cells
Gastric and colon 3c
Other carcinoma 6c
Leukemia and lymphoma 15c
Melanoma 3c
Sarcoma 4c
Other tumours 7c
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Microvoltage and electrical alternans are reversible aftereffusion drainage.19 Echocardiography is essential todetect effusion, concomitant heart or paracardial dis-ease.11;12
Perimyocarditis is evidenced by global or regionalmyocardial dysfunction, elevations of troponins I and T,MB creatine-kinase, myoglobin and tumour necrosis fac-tor. Auscultation of a new S3 heart sound, convexly el-evated J-ST segment in the ECG, fixation of Indium-111-
labelled antimyosin antibodies, and structural changes inMRI are indicative, but only endomyocardial/epimyo-cardial biopsy is diagnostic.7;8
Hospitalisation is warranted to determine the aeti-ology and observe for tamponade as well as the effectof treatment. Nonsteroidal anti-inflammatory drugs(NSAID) are the mainstay (level of evidence B, class I).Indomethacine should be avoided in elderly patientsdue to its flow reduction in the coronaries. Ibuprofen is
Table 2 Diagnostic pathway and sequence of performance in acute pericarditis (level of evidence B for all procedures)
Technique Characteristic findings Reference
Obligatory (indication class I)Auscultation Pericardial rub (mono-, bi-, or triphasic) 7
ECGa Stage I: anterior and inferior concave ST segment elevation. PR segmentdeviations opposite to P polarity.
7,19
Early stage II: ST junctions return to the baseline, PR deviated.Late stage II: T waves progressively flatten and invertStage III: generalised T wave inversionsStage IV: ECG returns to prepericarditis state.
Echocardiography Effusion types BD (Horowitz) (Fig. 1) 9,10Signs of tamponade (see Section Pericardial effusion and cardiac tamponde)
Blood analyses (a) ESR, CRP, LDH, leukocytes (inflammation markers) 11(b) Troponin I, CK-MB (markers of myocardial lesion)b
Chest X-ray Ranging from normal to water bottle heart shadow. Revealing additionalpulmonary/mediastinal pathology.
12
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 anddrainage
PCR and histochemistry for aetiopathogenetic classification of infection orneoplasia
2,8,13
Optional or if previous tests inconclusive (indication class IIa)CT Effusions, peri-, and epicardium 14MRI Effusions, peri-, and epicardium 14Pericardioscopy, pericardial biopsy Establishing the specific aetiology 2,8,15,16
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 flattenings. If ECG is first recorded in stage III, pericarditis cannotbe differentiated by ECG from diffuse myocardial injury, biventricular strain, or myocarditis. ECG in Early repolarization is very similar to stage 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 of the QRSjust before and including the J point (best seen with tall R and T waves large in early repolarisation pattern). Pericarditis is likely if in lead V6 the Jpoint 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.17 In another study18 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 other series >50a Serous, fibrinous, sometimes haemorrhagic PEwith suspect viral or autoimmune secondaryimmunopathogenesis
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 specific population of patients (e.g., with systemic lupus erythematosus).c Percentage related to the population of patients with neoplastic pericarditis.
590 ESC Guidelines
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preferred for its rare side-effects, favourable impact onthe coronary flow, and the large dose range.7 De-pending on severity and response, 300800 mg every68 hours may be initially required and can be con-tinued for days or weeks, best until the effusion hasdisappeared. Gastrointestinal protection must be pro-vided. Colchicine (0.5 mg bid) added to an NSAID or asmonotherapy also appears to be effective for the initialattack and the prevention of recurrences (level of ev-idence B, class IIa indication).20 It is well tolerated withfewer side effects than NSAIDs. Systemic corticosteroidtherapy should be restricted to connective tissue dis-eases, autoreactive or uremic pericarditis. Intraperi-cardial application avoids systemic side effects and ishighly effective (level of evidence B, class IIa indica-tion).2 For tapering of prednisone, ibuprofen or col-chicine should be introduced early.20 Indications forpericardiocentesis are listed in Focus box 1.7;2130 Re-
covered patients should be observed for recurrences orconstriction.
Chronic pericarditis
Chronic (>3 months) pericarditis includes effusive (in-flammatory or hydropericardium in heart failure), adhe-sive, and constrictive forms.7 Symptoms are usually mild(chest pain, palpitations, fatigue), related to the degreeof cardiac compression and pericardial inflammation.The diagnostic algorithm is similar as in acute pericar-ditis (Table 2). The detection of the curable causes (e.g.,tuberculosis, toxoplasmosis, myxedema, autoimmune,and systemic diseases) allows successful specific ther-apy. Symptomatic treatment and indications for peri-cardiocentesis are as in acute pericarditis. For frequentand symptomatic recurrences balloon pericardiotomy orpericardiectomy should be considered (level of evidenceB, indication IIb).23;31
Focus box 1 PericardiocentesisPericardiocentesis is life saving in cardiac tamponade (level of evidence B, class I indication) and indicated in ef-fusions >20 mm in echocardiography (diastole)23 but also in smaller effusions for diagnostic purposes (pericardialfluid and tissue analyses, pericardioscopy, and epicardial/pericardial biopsy)(level of evidence B, class IIa indica-tion).2;8;15;16 Aortic dissection is a major contraindication.22 Relative contraindications include uncorrected coag-ulopathy, anticoagulant therapy, thrombocytopenia
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Recurrent pericarditis
The term recurrent pericarditis encompasses (1) theintermittent type (symptom free intervals withouttherapy) and (2) the incessant type (discontinuation ofanti-inflammatory therapy ensures a relapse). Massivepericardial effusion, overt tamponade or constrictionare rare. Evidence for an immunopathological processinclude: (1) the latent period lasting for months; (2) thepresence of anti-heart antibodies; (3) the quick re-sponse to steroid treatment and the similarity and co-existence of recurrent pericarditis with other autoim-mune conditions (lupus, serum sickness, polyserositis,postpericardiotomy/postmyocardial infarction syn-drome, celiac disease, dermatitis herpetiformis, fre-quent arthralgias, eosinophilia, allergic drug reaction,and history of allergy). Potential underlying geneticdisorders were also reported: autosomal dominant in-heritance with incomplete penetrance32 and sex-linkedinheritance (recurrent pericarditis associated with ocu-lar hypertension).33
Symptomatic management relies on exercise restric-tion and the regimen used in acute pericarditis. Col-chicine was effective when NSAIDs and corticosteroidsfailed to prevent relapses.20;3435 During 1004 months ofcolchicine treatment, only 13.7% new recurrences oc-curred.20 During the 2333 months of follow-up, 60.7% ofthe patients remained recurrence-free. The recom-mended dose is 2 mg/day for one or two days, followedby 1 mg/day (level of evidence B, indication I). Corti-costeroids should be used only in patients with poorgeneral condition or in frequent crises7 (level of evi-dence C, indication IIa). A common mistake is to use adose too low to be effective or to taper the dose toorapidly. The recommended regimen is: prednisone11.5 mg/kg, for at least one month. If patients do notrespond adequately, azathioprine (75100 mg/day) orcyclophosphamide can be added.36 Corticoids should betapered over a three-month period. If symptoms stillrecur, return to the last dose that suppressed themanifestations, maintain that dose for 23 weeks andthen recommence tapering. Towards the end of thetaper, introduce anti-inflammatory treatment with col-chicine or NSAID. Renewed treatment should continuefor at least three months. Pericardiectomy is indicatedonly in frequent and highly symptomatic recurrencesresistant to medical treatment (level of evidence B,indication IIa).37 Before pericardiectomy, the patientshould be on a steroid-free regimen for several weeks.Post pericardiectomy recurrences were also demon-strated, possibly due to incomplete resection of thepericardium.
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.38 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, purulentpericarditis). Massive chronic pericardial effusions arerare (23.5% of all large effusions).39 Cardiac tamponadeis the decompensated phase of cardiac compressioncaused by effusion accumulation and the increased in-trapericardial pressure. In surgical tamponade intra-pericardial pressure is rising rapidly, in the matter ofminutes to hours (i.e. haemorrhage), whereas a low-in-tensity inflammatory process is developing days to weeksbefore cardiac compression occurs (medical tampon-ade). Heart sounds are distant. Orthopnoea, cough anddysphagia, occasionally with episodes of unconsciousnesscan be observed. Insidiously developing tamponade maypresent with the signs of its complications (renal failure,abdominal plethora, shock liver and mesenteric ische-mia). In 60% of the patients, the cause of pericardialeffusion may be a known medical condition.40 Tampon-ade without two or more inflammatory signs (typicalpain, pericardial friction rub, fever, diffuse ST segmentelevation) is usually associated with a malignant effusion(likelihood ratio 2.9). Electrocardiography may demon-strate diminished QRS and T-wave voltages, PR-segmentdepression, ST-T changes, bundle branch block, andelectrical alternans (rarely seen in the absence of tam-ponade).7 In chest radiography large effusions are de-picted as globular cardiomegaly with sharp margins(water bottle silhouette).12 On well-penetrated lateralradiographies, or cine films, pericardial fluid is suggestedby lucent lines within the cardiopericardial shadow(epicardial halo).12;41;42 This sign is useful for the fluo-roscopic guidance of pericardiocentesis.27 The separa-tion of pericardial layers can be detected inechocardiography, when the pericardial fluid exceeds1535 ml (Fig. 1).43 The size of effusions can be gradedas: (1) small (echo-free space in diastole
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typical echolucent areas may disappear, so that cardiactamponade may be overlooked. Transesophageal echo-cardiography is here particularly useful58 as well as inidentifying metastases and pericardial thickening.59 CT,spin-echo and cine MRI can also be used to assess the sizeand extent of simple and complex pericardial effusions.51
Effusions measured by CT/MRI tend to be larger than inechocardiography.24;60 Up to one-third of patients withasymptomatic large pericardial chronic effusion developunexpected cardiac tamponade.23 Triggers for tampon-ade include hypovolemia, paroxysmal tachyarrhythmiaand intercurrent acute pericarditis. Diagnostic criteriafor cardiac tamponade are listed in Table 35260 andFocus box 2.61;62
Pericardiocentesis is not necessary when the diagnosiscan be made otherwise or the effusions are small or re-
solving under anti-inflammatory treatment. Haemody-namic compromise and cardiac tamponade is an absoluteindication for drainage (Focus box 1). Patients with de-hydration and hypovolemia may temporarily improvewith intravenous fluids. Whenever possible, treatmentshould be aimed at the underlying aetiology. Even inidiopathic effusions extended pericardial catheterdrainage (3 2 days, range 113 days) was associatedwith a lower recurrence rates (6% vs. 23%) than in thosewithout catheter drainage during the follow-up of3.8 4.3 years.25 Resistant neoplastic processes requireintrapericardial treatment,63 percutaneous balloon per-icardiotomy31 or rarely pericardiectomy. Surgical ap-proach is recommended only in patients with very largechronic effusion in whom repeated pericardiocentesisand/or intrapericardial therapy were not successful.64
Constrictive pericarditis
Constrictive pericarditis is a rare but severely disablingconsequence of the chronic inflammation of the peri-cardium, leading to an impaired filling of the ventriclesand reduced ventricular function. Until recently, in-creased pericardial thickness has been considered anessential diagnostic feature of constrictive pericarditis.However, in the large surgical series from the Mayo clinicconstriction was present in 18% of the patients withnormal pericardial thickness.65 Tuberculosis, mediastinalirradiation, and previous cardiac surgical procedures arefrequent causes of the disease, which can present inseveral pathoanatomical forms66 (Fig. 2). Constrictivepericarditis may rarely develop only in the epicardiallayer in patients with previously removed parietal peri-cardium.67 Transient constrictive pericarditis is uncom-mon but important entity, since these patients are notindicated for pericardiectomy.68 Patients complainabout fatigue, peripheral oedema, breathlessness, andabdominal swelling, which may be aggravated by a pro-tein-loosing enteropathy. Typically, there is a long delaybetween the initial pericardial inflammation and theonset of constriction. In decompensated patients venouscongestion, hepatomegaly, pleural effusions, and ascitesmay occur. Haemodynamic impairment of the patientcan be additionally aggravated by a systolic dysfunctiondue to myocardial fibrosis or atrophy. Clinical, echocar-diographic, and haemodynamic parameters can be de-rived from Table 4.50;65;66;6971 Differential diagnosis hasto include acute dilatation of the heart, pulmonary em-
Focus box 2 Determination of pulsus paradoxusPulsus paradoxus is defined as a drop in systolic blood pressure >10 mmHg during inspiration whereas diastolic bloodpressure remains unchanged. It is easily detected by feeling the pulse.61;62 During inspiration, the pulse may dis-appear or its volume diminishes significantly. Clinically significant 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 first Korotkoff sound isheard only during expiration. The blood pressure cuff is therefore inflated above the patients systolic pressure.During deflation, the first Korotkoff sound is intermittent. Correlation with the patients respiratory cycle identifiesa point at which the sound is audible during expiration, but disappears in inspiration. As the cuff pressure drops,another point is reached when the first blood pressure sound is audible throughout the respiratory cycle. The dif-ference is the measure of pulsus paradoxus.
Fig. 1 Horowitz classification of pericardial effusions.43 Type A: Noeffusion; Type B: Separation of epicardium and pericardium (316 ml);Type C 1: Systolic and diastolic separation of epicardium and pericardium(small effusion >16 ml); Type C 2: Systolic and diastolic separation ofepicardium and pericardium with attenuated pericardial motion; Type D:Pronounced separation of epicardium and pericardium with large echo-free space; Type E: Pericardial thickening (>4 mm). Copyrights AmericanHeart Association.
ESC Guidelines 593
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Table
3Diagn
osisofca
rdiactamponad
e
Clinical
presentation
Eleva
tedsystemic
venouspressure
a,hyp
otensionb,pulsusparad
oxu
sc,tach
ycardia
d,dyspnoeaortach
ypnoeawith
clear
lungs
Precipitatingfactors
Drugs
(cyclosporine,an
tico
agulants,thrombolytics,etc.),rece
ntca
rdiacsurgery,indwellinginstrumentation,
bluntch
est
trau
ma,
malignan
cies,
connectivetissuedisease,renalfailure,septica
emia
e
ECG
Can
benorm
alornon-specifica
llych
ange
d(ST-T
wav
e),
electrica
lalternans(Q
RS,
rarely
T),
bradycardi(end-stage
),Electromech
anical
dissociation(ago
nal
phase)
Chest
X-ray
Enlargedca
rdiacsilhouettewithclear
lungs.
Mmode/2
Dech
oca
rdiogram
Diastolicco
llap
seofthe(1)an
teriorRVfreewall52f ,
RAco
llap
se53,LA
54andve
ryrarely
LV55
collapse,increasedLV
diastolicwallthickn
ess
pseudohyp
ertrophy
56,VCIdilatation(noco
llapse
ininspirium),
sw
ingingheart5
7
Doppler
Tricu
spid
flow
increasesan
dmitralflow
decreasesduringinspiration(reve
rsein
exp
iration)
Systolican
ddiastolicflowsarereduce
din
systemic
veinsin
exp
irium
andreve
rseflow
withatrialco
ntractionis
increased58
M-m
odeco
lourDoppler
Largerespiratory
fluctuationsin
mitral/tricuspid
flows5
9
Cardiacca
theterisation
(1)Confirm
ationofthediagn
osisan
dquan
tifica
tionofthehae
modyn
amic
compromise60
RApressure
iseleva
ted(preservedsystolicxdescentan
dabsentordim
inisheddiastolicydescent)
Intrap
erica
rdialpressure
isalso
eleva
tedan
dvirtually
identica
lto
RApressure
(both
pressuresfallin
inspiration)
RVmid-diastolicpressure
eleva
tedan
dequal
totheRAan
dperica
rdialpressures(nodip-and-plateau
configu
ration)
Pulm
onaryartery
diastolicpressure
isslightlyeleva
tedan
dmayco
rrespondto
theRVpressure.
Pulm
onaryca
pillary
wedge
pressure
isalso
eleva
tedan
dnearlyequalto
intraperica
rdialandrigh
tatrialpressure.
LVsystolican
dao
rtic
pressuresmay
benorm
alorreduce
d.
(2)Docu
mentingthat
perica
rdialaspirationis
followedbyhae
modyn
amic
improve
mentg
(3)Detectionoftheco
existinghae
modyn
amic
abnorm
alities(LVfailure,co
nstriction,pulm
onary
hyp
ertension)
(4)Detectionofassociatedca
rdiova
sculardiseases(cardiomyo
pathy,
coronaryartery
disease)
RV/L
Van
giograp
hy
Atrialco
llap
sean
dsm
allhyp
eractiveve
ntricularch
ambers.
Coronaryan
giograp
hy
Coronaryco
mpressionin
diastole.
Computertomograp
hy
Novisualisationofsubepicardialfatalongboth
ventricles,
whichshow
tube-likeco
nfigu
rationan
dan
teriorlydrawn
atrias
LA,left
atrium,LV
,left
ventricle,RA,righ
tatrium,RV,righ
tve
ntricle,VCI,inferiorve
naca
va.
aJu
gularve
nousdistensionis
less
notable
inhyp
ovo
lemic
patients
orin
surgical
tamponad
e.
Aninspiratory
increaseorlack
offallofthepressure
intheneck
veins(Kussmaulsign
),whenve
rifiedwith
tamponad
e,orafterperica
rdialdrainag
e,indicateseffusive
-constrictivedisease.
bHeartrate
isusually
>100
beats/min,butmay
belowerin
hyp
othyroidism
andin
uremic
patients.
cPulsusparad
oxu
sis
absentin
tamponad
eco
mplica
tingatrial
septaldefect
61an
din
patients
withsign
ifica
ntao
rtic
regu
rgitation.
dOccasional
patients
arehyp
ertensive
especially
iftheyhav
epre-existinghyp
ertension.6
2
eFe
brile
tamponad
emay
bemisdiagn
osedas
septicshock.
fRightve
ntricularco
llap
seca
nbeab
sentin
eleva
tedrigh
tve
ntricularpressure
andrigh
tve
ntricularhyp
ertrophy6
3orin
righ
tve
ntricularinfarction.
gIfafterdrainag
eofperica
rdialeffusionintrap
erica
rdialpressure
doesnotfallbelow
atrial
pressure,theeffusive
-constrictivediseaseshould
beco
nsidered.
594 ESC Guidelines
-
bolism, right ventricular infarction, pleural effusion,chronic obstructive lung diseases72 and restrictive car-diomyopathy. The best way to distinguish constrictivepericarditis from restrictive cardiomyopathy is theanalysis of respiratory changes with or without changesof preload by Doppler and/or tissue Doppler echocardi-ography,73 but physical findings, ECG, chest radiography,CT and MRI, haemodynamics, and endomyocardial biopsymay be helpful as well.7
Pericardiectomy is the only treatment for permanentconstriction. The indications are based upon clinicalsymptoms, echocardiography findings, CT/MRI, and heartcatheterisation. There are two standard approaches,both aiming at resecting the diseased pericardium as faras possible:7477 (1) The antero-lateral thoracotomy (fifthintercostal space) and (2) median sternotomy (fasteraccess to the aorta and right atrium for extracorporealcirculation). A primary installation of cardiopulmonarybypass is not recommended (diffuse bleeding followingsystemic heparinisation). If severe calcified adhesionsbetween peri- and epicardium or a general affection ofthe epicardium (outer porcelain heart) are presentsurgery carries a high risk of either incomplete success orsevere myocardial damage. An alternative approach insuch cases may be a laser shaving using an Excimerlaser.75 Areas of strong calcification or dense scaring maybe left as islands to avoid major bleeding. Pericardiec-tomy for constrictive pericarditis has a mortality rate of612%.75;77 The complete normalization of cardiac hae-modynamics is reported in only 60% of the patients.74;76
The deceleration time (DT) may remain prolonged78 andpostoperative respiratory variations of mitral/tricuspid
flow are found in 925%.76;79 Left ventricular ejectionfraction can increase due to a better ventricular fill-ing.76;78 Major complications include acute perioperativecardiac insufficiency and ventricular wall rupture.80 Car-diac mortality and morbidity at pericardiectomy is mainlycaused by the pre-surgically unrecognised presence ofmyocardial atrophy or myocardial fibrosis (Fig. 2).66 Ex-clusion of patients with extensive myocardial fibrosisand/or atrophy reduced the mortality rate for pericardi-ectomy to 5%. Postoperative low cardiac output80 shouldbe treated by fluid substitution and catecholamines, highdoses of digitalis, and intraaortic balloon pump in mostsevere cases. If indication for surgery was establishedearly, long-term survival after pericardiectomy corre-sponds to that of the general population.75;76 However, ifsevere clinical symptoms were present for a longer periodbefore surgery, even a complete pericardiectomy maynot achieve a total restitution.
Pericardial cysts
Congenital pericardial cysts are uncommon; they may beunilocular or multilocular, with the diameter from 15cm.81 Inflammatory cysts comprise pseudocysts as wellas encapsulated and loculated pericardial effusions,caused by rheumatic pericarditis, bacterial infection,particularly tuberculosis, trauma and cardiac surgery.Echinococcal cysts usually originate from ruptured hy-datid cysts in the liver and lungs. Most patients areasymptomatic and cysts are detected incidentally onchest roentgenograms as an oval, homogeneous radio-dense lesion, usually at the right cardiophrenic angle.82
Fig. 2 Pathoanatomical forms of constrictive pericarditis vs. restrictive cardiomyopathy. (a) Annular form of pericardial constriction with bilateralthickening of the pericardium along the atrial ventricular grooves with normal configuration of both ventricles and enlargement of both atria. (b) Leftsided form of pericardial constriction with thickened pericardium along the left ventricle and right sided bending of the interventricular septum withtube-like configuration of mainly left ventricle and enlargement of both atria. (lateral sternotomy and partial pericardiectomy is indicated). (c) Rightsided form of pericardial constriction with thickened pericardium along the right ventricle and left sided bending of the interventricular septum withtube-like configuration of mainly right ventricle and enlargement of both atria (median sternotomy and partial pericardiectomy is indicated). (d) My-ocardial atrophy and global form of pericardial constriction with bilateral thickening of the pericardium along both ventricles separated from the rightmyocardial wall by a thin layer of subepicardial fat. Tube-like configuration of both ventricles and enlargement of both atria, however, thinning of theinterventricular septum and posterolateral wall of the left ventricle below 1 cm is suggesting myocardial atrophy (pericardiectomy is contraindicated).(e) Perimyocardial fibrosis and global form of pericardial constriction with bilateral thickening of the pericardium along both ventricles, however, theright sided thickened pericardium cannot be separated from the wave-like thin form of right sided ventricular wall suggesting perimyocardial fibrosis(pericardiectomy is contraindicated). (f) Global form of pericardial constriction with bilateral thickening of the pericardium along both ventriclesseparated from the right myocardial wall by a thin layer of subepicardial fat. Tube-like configuration of both ventricles and enlargement of both atria(median sternotomy and pericardiectomy is indicated). (g) Restrictive cardiomyopathy with normal thin pericardium along both ventricles that shownormal configuration and with enlargement of both atria.
ESC Guidelines 595
-
Table
4Diagn
ostic
approac
hin
constrictiveperica
rditis
Clinical
presentation
Seve
rech
ronic
systemic
venousco
nge
stionassociatedwithlow
cardiacoutput,
includingjugu
larve
nousdistension,
hyp
otensionwithalow
pulsepressure,ab
dominal
distension,oedemaandmuscle
wasting
ECG
Can
benorm
al,orreve
allow
QRSvo
ltag
e,ge
neralize
dT-w
aveinve
rsion/fl
attening,
LAab
norm
alities,
atrial
fibrillation,
atriove
ntricularblock,intrav
entricularco
nductiondefects,
orrarely
pseudoinfarctionpattern
Chest
X-ray
Perica
rdialca
lcifica
tions,
pleuraleffusions
Mmode/2
Dech
oca
rdiogram
Perica
rdialthicke
ningan
dca
lcifica
tionsa
aswellas
theindirect
sign
sofco
nstriction:
RA&LA
enlargementwithnorm
alap
pearan
ceoftheve
ntricles,
andnorm
alsystolicfunction
Early
pathologica
loutw
ardan
dinwardmove
mentoftheinterventricularseptum
(dip-plateau
phenomenon)
72
Flatteringwav
esat
theLV
posteriorwall
LVdiameteris
notincreasingaftertheearly
rapid
fillingphase
VCIan
dthehepatic
veinsaredilatedwithrestrictedrespiratory
fluctuationsb
Doppler
Restrictedfillingofboth
ventricleswithrespiratory
variation>25%ove
rtheAV-valves)
69c
TEE
Measurementoftheperica
rdialthickn
ess
50
CT/M
RI
Thicke
nedan
d/o
rca
lcifiedperica
rdium,tube-likeco
nfigu
rationofoneorboth
ventricles,
narrowingofoneorboth
atrio-
ventriculargroove
s,co
nge
stionoftheca
valve
ins6
6enlargementofoneorboth
atria
Cardiacca
theterisation
Dip
andplateau
orsquareroutesign
inthepressure
curveoftherigh
tan
d/o
rleft
ventricle
EqualisationofLV
/RVend-diastolicpressuresin
therange
of5mmHgorless
72d
RV/L
Van
giograp
hy
ThereductionofRV&LV
size
andincreaseofRA&LA
size
Duringdiastole
arapid
early
fillingwithstopoffurtherenlargement(dip-plateau
)
Coronaryan
giograp
hy
Inallpatients
ove
r35
yearsan
din
patients
withahistory
ofmediastinal
irradiation,rega
rdless
oftheag
e
LA,left
atrium,LV
,left
ventricle,RA,righ
tatrium,RV,righ
tve
ntricle,VCI,inferiorve
naca
va,TEE
tran
soesophag
eal
ech
oca
rdiograp
hy
aThicke
ningoftheperica
rdium
isnotalway
sequal
toco
nstriction(absentin
18%of14
3surgically
prove
nca
ses).Whenclinical,ech
oca
rdiographic,orinva
sive
haemodyn
amic
featuresindicate
constriction,
perica
rdiectomyshould
notbedeniedonthebasis
ofnorm
alperica
rdialthickn
ess.6
5
bDiagn
osisis
difficu
ltin
atrial
fibrillation.Hepatic
diastolicve
inflow
reve
rsal
inexp
irium
isobservedeve
nwhentheflow
velocity
pattern
isinco
nclusive
.69
cPatients
withincreasedatrial
pressuresormixedco
nstrictionan
drestrictiondemonstrate
-
However, the patients can also present with chest dis-comfort, dyspnoea, cough or palpitations, due to thecompression of the heart. Echocardiography is useful,but additional imaging by computed tomography (densityreadings) or magnetic resonance is often needed.83 Thetreatment for congenital and inflammatory cysts is per-cutaneous aspiration and ethanol sclerosis.84;85 If this isnot feasible, video assisted thoracotomy or surgical re-section may be necessary. The surgical excision of ec-chinococcal cysts is not recommended. Percutanousaspiration and instillation of ethanol or silver nitrateafter pre-treatment with Albendazole (800 mg/day 4weeks) is safe and effective.85
Specific forms of pericarditis
Viral pericarditis
Viral pericarditis is the most common infection of thepericardium. Inflammatory abnormalities are due to di-rect viral attack, the immune response (antiviral or an-ticardiac), or both.3;86 Early viral replication inpericardial and epimyocardial tissue elicits cellular andhumoral immune responses against the virus and/or car-diac tissue. Viral genomic fragments in pericardial tissuemay not necessarily replicate, yet they serve as a sourceof antigen to stimulate immune responses. Deposits ofIgM, IgG, and occasionally IgA, can be found in the peri-cardium and myocardium for years.86 Various virusescause pericarditis (entero-, echo-, adeno-, cytomegalo-,Ebstein Barr-, herpes simplex-, influenza, parvo B19,
hepatitis C, HIV, etc). Attacks of enteroviral pericarditisfollow the seasonal epidemics of Coxsackie virus A+B andEchovirus infections.87 Cytomegalovirus pericarditis hasan increased incidence in immunocompromised and HIVinfected hosts.88 Infectious mononucleosis may alsopresent with pericarditis. The diagnosis of viral pericar-ditis is not possible without the evaluation of pericardialeffusion and/or pericardial/epicardial tissue, preferablyby PCR or in-situ hybridisation (level of evidence B, classIIa indication) (Focus boxes 34). A four-fold rise in serumantibody levels is suggestive but not diagnostic for viralpericarditis (level of evidence B, class IIb indication).
Treatment of viral pericarditis is directed to resolvesymptoms (see acute pericarditis), prevent complica-tions, and eradicate the virus. In patients with chronic orrecurrent symptomatic pericardial effusion and con-firmed viral infection the following specific treatment isunder investigation: (1) CMV pericarditis: hyperimmu-noglobulin - 1 time per day 4 ml/kg on day 0, 4, and 8; 2ml/kg on day 12 and 16; (2) Coxsackie B pericarditis:Interferon alpha or beta 2,5 Mio. IU/m2 surface area s.c.3 per week; (3) adenovirus and parvovirus B19 peri-myocarditis: immunoglobulin treatment: 10 g intrave-nously at day 1 and 3 for 68 hours.113
Pericardial manifestation of human immunodeficiencyvirus (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 M. tuberculosis) and fungalcoinfections (Cryptococcus neoformans).114 In progres-
Focus box 3 Analyses of pericardial effusionAnalyses of pericardial effusion can establish the diagnosis of viral, bacterial, tuberculous, fungal, cholesterol, andmalignant pericarditis.7 It should be ordered according to the clinical presentation. Cytology and tumour markers(carcinoembryonic antigen (CEA), alpha-feto protein (AFP), carbohydrate antigens CA 125, CA 72-4, CA 15-3, CA 19-9, CD-30, CD-25, etc.) should be performed in suspected malignant disease. In suspected tuberculosis acid-fastbacilli staining, mycobacterium culture or radiometric growth detection (e.g., BACTEC-460), adenosine deaminase(ADA), interferon (IFN)-gamma, pericardial lysozyme, and as well as PCR analyses for tuberculosis should be per-formed (indication I, level of evidence B).11;89100 Differentiation of tuberculous and neoplastic effusion is virtuallyabsolute with low levels of ADA and high levels of CEA.94 In addition, very high ADA levels have prognostic value forpericardial constriction.95 However, it should be noted that PCR is as sensitive (75% vs. 83%), but more specific (100%vs. 78%) than ADA estimation for tuberculous pericarditis.99 In suspected bacterial infection at least three culturesof pericardial fluid for aerobes and anaerobes as well as the blood cultures are mandatory (level of evidence B,indication I). PCR analyses for cardiotropic viruses discriminate viral from autoreactive pericarditis (indication IIa,level of evidence B).2 Analyses of the pericardial fluid specific gravity (>1015), protein level (>3.0 g/dl; fluid/serumratio >0.5), LDH (>200 mg/dL; serum/fluid >0.6), and glucose (exudates vs. transudates 77.9 41.9 vs.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 significantly lower fluid glucose levels (47.3 25.3 vs. 102.5 35.6mg/dl) and fluid to serum ratios (0.28 0.14 vs. 0.84 0.23 mg/dl), than non-infectious effusions.11 White cellcount (WBC) is highest in inflammatory diseases, particularly of bacterial and rheumatologic origin. A very low WBCcount is found in myxedema. Monocyte count is highest in malignant effusions and 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 fluids have higher cholesterol levels(49 18 vs. 121 20 and 117 33 mg/dl).11
Grams stains in pericardial fluid have a specificity of 99%, but a sensitivity of only 38% for exclusion of the in-fection in comparison to bacterial cultures.14 Combination of epithelial membrane antigen, CEA and vimentin im-munocytochemical staining can be useful to distinguish reactive mesothelial and adenocarcinoma cells.101
ESC Guidelines 597
-
sive disease the incidence of echocardiographically de-tected pericardial effusion is up to 40%.115 Cardiactamponade is rare.116 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 I).117
Bacterial pericarditis
Purulent pericarditis in adults is rare (Table 5), but alwaysfatal if untreated.118121 Mortality rate in treated patientsis 40%, mostly due to cardiac tamponade, toxicity, andconstriction. It is usually a complication of an infectionoriginating elsewhere in the body, arising by contiguousspread or haematogenous dissemination.131 Predisposingconditions are pericardial effusion, immunosuppression,chronic diseases (alcohol abuse, rheumatoid arthritis,etc), cardiac surgery and chest trauma. The disease ap-pears as an acute, fulminant infectious illness with shortduration. Percutaneous pericardiocentesis must bepromptly performed. Obtained pericardial fluid shouldundergo urgent Gram, acid-fast and fungal staining, fol-lowed by cultures of the pericardial and body fluids (levelof evidence B, indication I). Rinsing of the pericardialcavity, combined with effective systemic antibiotictherapy is mandatory (antistaphylococcal antibiotic plusaminoglycoside, followed by tailored antibiotic therapyaccording to pericardial fluid and blood cultures).119 In-trapericardial instillation of antibiotics (e.g., gentamy-cin) is useful but not sufficient. Frequent irrigation of thepericardial cavity with urokinase or streptokinase, usinglarge catheters, may liquefy the purulent exudate,120;121
but open surgical drainage through subxiphoid pericardi-otomy is preferable.118 Pericardiectomy is required inpatients with dense adhesions, loculated and thick pu-rulent effusion, recurrence of tamponade, persistent in-
fection, and progression to constriction.119 Surgicalmortality is up to 8%.
Tuberculous pericarditisIn the last decade TBC pericarditis in the developedcountries has been primarily seen in immunocompro-mised patients (AIDS).123 The mortality rate in untreatedacute effusive TBC pericarditis approaches 85%. Peri-cardial constriction occurs in 3050%.122;125 The clinicalpresentation is variable: acute pericarditis with orwithout effusion; cardiac tamponade, silent, often largepericardial effusion with a relapsing course, toxicsymptoms with persistent fever, acute constrictivepericarditis, subacute constriction, effusive-constric-tive, or chronic constrictive pericarditis, and pericardialcalcifications.3;89 The diagnosis is made by the identifi-cation of Mycobacterium tuberculosis in the pericardialfluid or tissue, and/or the presence of caseous granulo-mas in the pericardium.3;123 Importantly, PCR can iden-tify DNA of Mycobacterium tuberculosis rapidly from only1 lL of pericardial fluid.127;128 High adenosine deaminaseactivity and interferon gamma concentration in pericar-dial effusion are also diagnostic, with a high sensitivityand specificity (Focus box 3): Both pericardioscopy andpericardial biopsy have also improved the diagnosticaccuracy for TBC pericarditis.15 Pericardial biopsy en-ables rapid diagnosis with better sensitivity than peri-cardiocentesis (100 vs. 33%).
Pericarditis in a patient with proven extracardiac tu-berculosis is strongly suggestive of TBC aetiology (severalsputum cultures should be taken).3;126 The tuberculinskin test may be false negative in 2533% of tests122 andfalse positive in 3040% of patients.123 More accurateenzyme-linked immunospot (ELISPOT) test detects T-cells specific for Mycobacterium tuberculosis antigen.132
Perimyocardial TBC involvement is also associated withhigh serum titres of antimyolemmal and antimyosin an-tibodies.133 The diagnostic yield of pericardiocentesis inTBC pericarditis ranges from 3076% according to themethods applied for the analyses of pericardial effu-sion.122;127 Pericardial fluid demonstrates high specific
Focus box 4 Pericardioscopy and epicardial/pericardial biopsyIntroduction of pericardioscopy and contemporary pathology, virology, and molecular biology techniques haveimproved the diagnostic value of epicardial/pericardial biopsy.2;8;15;16;102108 Pericardioscopy makes possible to in-spect pericardial surface, select the biopsy site, and take numerous samples safely.16 Targeted pericardial/epi-cardial biopsy during pericardioscopy was particularly useful in the diagnosis of neoplastic pericarditis.15;16;102104 Nomajor complications occurred in any of the flexible pericardioscopy studies. Mortality reported in the studies withrigid endoscopes was 2.1%,15 and 3.5%103 due to induction of anaesthesia in patients with very large pericardialeffusions.
Histology of epicardial/pericardial biopsies can establish the diagnosis in patients with neoplastic pericarditis andtuberculosis.16;63;102;103 Diagnosis of viral pericarditis can be established by PCR techniques with much higher sen-sitivity and specificity in comparison to viral isolation from fluid and tissue.107111 Immunohistochemistry, especiallyIgG-, IgM- and IgA- and complement fixation contribute significantly to the diagnostic value of epicardial biopsy.2
Specificity of immunoglobulin fixation in autoreactive pericarditis is 100%. Complement fixation was found primarilyin patients with the autoreactive form and rarely in patients with neoplastic pericarditis.8 Malignant mesotheliomascan be distinguished from pulmonary adenocarcinomas by immunohistochemical staining for CEA, surfactant apo-protein, Lewis a, and Tn antigen.112
598 ESC Guidelines
-
Table
5Differential
diagn
osisofthespecificform
sofperica
rditis11
813
0
Viral
Bac
terial
Tuberculous
Autoreac
tive
Cardiotropic
microbial
agents
Entero-,
ech
o-,
adeno-,
cytomega
lo,
Ebstein
Barr,
herpessimplex,
influenza,parvo
B19
,hepatitis
A,B,C
virus,
HIV
Stap
hyloco
cci,pneumoco
cci,
streptoco
cci,Neisseria,
proteus,
gram
nega
tive
rods,
Legionella
Mycobac
terium
tuberculosis
Autoim
muneproce
ssin
theab
sence
of
viralandbacterialage
nts
Etiologica
levidence
by
PCRorin
situ
hyb
ridisation
(evidence
leve
lB,indicationIIa)
Gram-stain,bac
terial
culture,
PCRforBorreliaan
dch
lamyd
iapneumoniae(evidence
leve
lB,
indicationI)
Ziehl-Neelsen,au
ramin
0stain,
culture,PCR(evidence
leve
lB,
indicationI)
Ig-bindingto
peri-andepicardium,
nega
tive
PCRforca
rdiotropic
agents,
epicarditis
(evidence
leve
lB,
indicationIIa)
Incidence
(%)Western
countries
305
105per10
0,00
0patients
25%
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)
Activatedlymphocytesan
dmac
rophag
es(sparse)ADA-nega
tive
Peri-an
depicardialbiopsy
Lymphocyticperi-/epicarditis,
PCRpositive
forca
rdiotropic
virus
Leuko
cyticepicarditis
Caseousgran
uloma,
PCR
Lymphocyticperi-/epicarditis,PCR
nega
tive
Mortalityifuntreated
Dependingonag
entan
dtamponad
e10
0%85
%In
untreatedtamponad
eIntrap
erica
rdialtreatment
Drainag
e,ifneeded,no
intrap
ercardialco
rticoids
Drainag
ean
drinsing(saline)
gentamycin
80mgi.p.,
Drainag
e,ifneeded
Drainag
e,i.p.triamcinolon(evidence
B,indicationIIa)
Perica
rdiotomy/
perica
rdiectomy
Rarely
needed
Promptlyneeded(evidence
leve
lB,indicationI)
Rarely
needed
Rarely
needed
Systemic
treatment
I.V.im
munoglobulins,
IFN
(inenteroviralperica
rditis)s.c.
I.V.an
tibiotics
Tuberculostatic+prednisone
NSA
IDs,
Colchicine,prednisolone/
azathioprin
Constriction
Rare
Frequent
Frequent(30
50%)
Rare
ESC Guidelines 599
-
gravity, high protein levels, and high white-cell count(from 0.754 109/l).123
Various antituberculous drug combinations of differ-ent lengths (6, 9, 12 months) have been ap-plied.94;122;123;126 However, only patients with proven orvery likely TBC pericarditis should be treated. Preventionof constriction in chronic pericardial effusion ofundetermined aetiology by ex iuvantibus antitubercu-lar treatment was not successful.134 The use of steroidsremains controversial.126;130;135137 A meta analysis ofpatients with effusive and constrictive TBC pericardi-tis136;137 suggested that tuberculostatic treatment com-bined with steroids might be associated with fewerdeaths, less frequent need for pericardiocentesis orpericardiectomy (level of evidence A, indicationIIb).126;129 If given, prednisone should be administered inrelatively high doses (12 mg/kg per day) since rifam-picin induces its liver metabolism.7 This dose is main-tained for 57 days and is progressively reduced todiscontinuation in 68 weeks. If, in spite of combinationtherapy, constriction develops pericardiectomy is indi-cated (level of evidence B, 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.138 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.139 It results from inflamma-tion of the visceral and parietal pericardium andcorrelates with the degree of azotemia (BUN >60 mg/dl). (2) Dialysis-associated pericarditis in up to 13% ofpatients on maintenance haemodialysis,140 and occa-sionally with chronic peritoneal dialysis due to inade-quate dialysis and/or fluid overload.141 Pathologicexamination of the pericardium shows adhesions be-tween the thickened pericardial membranes (bread andbutter appearance). The clinical features may includefever and pleuritic chest pain but many patients areasymptomatic. Pericardial rubs may persist even in largeeffusions or may be transient. Due to autonomic im-pairment in uremic patients, heart rate may remain slow(6080 beats/min) during tamponade, despite fever andhypotension. Anaemia, due to induced resistance toerythropoetin142 may worsen the clinical picture. TheECG does not show the typical diffuse ST/T wave ele-vations observed with other causes of acute pericarditisdue to the lack of the myocardial inflammation.143 If theECG is typical of acute pericarditis, intercurrent infec-tion must be suspected.
Most patients with uremic pericarditis respond rapidlyto haemo- or peritoneal dialysis with resolution of chestpain and pericardial effusion. To avoid haemopericar-dium heparin-free haemodialysis should be used. Hypo-kalemia and hypophosphatemia should be prevented bysupplementing the dialysis solution when appropriate.144
Intensified dialysis usually leads to resolution of thepericarditis within 12 weeks.145 Peritoneal dialysis,which does not require heparinisation, may be thera-
peutic in pericarditis resistant to haemodialysis, or ifheparin-free haemodialysis cannot be performed. NSAIDsand systemic corticosteroids have limited success whenintensive dialysis is ineffective.146 Cardiac tamponadeand large chronic effusions resistant to dialysis must betreated with pericardiocentesis. (level of evidence B,class IIa indication). Large, non-resolving symptomaticeffusions should be treated with intrapericardial instil-lation of corticosteroids after pericardiocentesis or sub-xiphoid pericardiotomy (triamcinolone hexacetonide 50mg every 6 h for 23 days).140;147 Pericardiectomy is in-dicated only in refractory, severely symptomatic pa-tients due to its potential morbidity and mortality. Afterrenal transplantation, pericarditis has also been reportedin 2.4% of patients, within two months.148 Uraemia orinfection (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 fluid (autoreactive antibody-mediated); (2)inflammation in epicardial/endomyocardial biopsies byP 14 cells/mm2; (3) exclusion of active viral infectionboth in pericardial effusion and endomyocardial/epi-myocardial 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 infiltration absent in pericardialeffusion and biopsy samples; (6) exclusion of systemic,metabolic disorders, and uraemia. Intrapericardialtreatment with triamcinolone is highly efficient with rareside effects.2
Pericarditis occurs in systemic autoimmune diseases:rheumatoid arthritis, systemic lupus erythematosus,progressive systemic sclerosis, polymyositis/ dermato-myositis, mixed connective tissue disease, seronegativespondyloarthropathies, systemic and hypersensitivityvasculitides, Behcet syndrome, Wegener granulomatosis,and sarcoidosis.7 Intensified treatment of the underlyingdisease and symptomatic management are indicated(evidence level B, indication I).
The post-cardiac injury syndrome:postpericardiotomy syndrome
Post-cardiac injury syndrome develops within days tomonths after cardiac, pericardial injury or both.7;149 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 antifibrillary), probably related to more extensiverelease of antigenic material.149;150 Pericardial effusion
600 ESC Guidelines
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also occurs after orthotopic heart transplantation (21%).It is more frequent in patients receiving aminocaproicacid during the operation.151 Cardiac tamponade afteropen heart surgery is more common following valvesurgery than coronary artery bypass grafting (CABG)alone and may be related to the preoperative use ofanticoagulants.152 Constrictive pericarditis may also oc-cur after cardiac surgery. Warfarin administration inpatients with early postoperative pericardial effusionimposes the greatest risk, particularly in those who didnot undergo pericardiocentesis and drainage of the ef-fusion.153 Symptomatic treatment is as in acute peri-carditis (NSAIDs or colchicine for several weeks ormonths, even after disappearance of effusion).154 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.155
Postinfarction pericarditis
Two forms of postinfarction pericarditis can be distin-guished: an early form (pericarditis epistenocardica)and a delayed form (Dresslers syndrome).156 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 infarction157 and can also appearas an extension of epistenocardiac pericarditis. Its inci-dence is 0.55%158 and is still lower in patients treatedwith thrombolytics (10 mm is most frequentlyassociated with haemopericardium, and two thirds ofthese patients may develop tamponade/free wall rup-ture.163 Urgent surgical treatment is life saving. How-ever, if the immediate surgery is not available orcontraindicated pericardiocentesis an intrapericardialfibrin-glue instillation could be an alternative in subacutetamponade.163;164
Hospitalisation to observe for tamponade, differentialdiagnosis, and adjustments of treatment is needed.Ibuprofen, which increases coronary flow, is the agent ofchoice.165 Aspirin, up to 650 mg every 4 hours for 2 to 5days has also been successfully applied. Other nonste-roidal agents risk thinning the infarction zone.164;166
Corticosteroid therapy can be used for refractory symp-toms only but could delay myocardial infarction healing(level of evidence B, class IIa indication).7
Traumatic pericardial effusion andhaemopericardium in aortic dissection
Direct pericardial injury can be induced by accidents oriatrogenic wounds.7;167170 Blood loss, vasoconstriction,and haematothorax leading to severe hypotension andshock may mask pulses paradoxus.170 Thoracotomy andsurgical repair should be performed.
Iatrogenic tamponade occurs most frequently inpercutaneous mitral valvuloplasty, during or aftertransseptal puncture, particularly, if no biplane cathe-terisation laboratory is available and a small left atriumis present. Whereas the puncture of the interatrial sep-tum is asymptomatic, the passage of the free wall in-duces 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 4 to 6 hours. Rescue pericardiocentesis is successfulin 95100% with a
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Table
6Traumatic
perica
rdialeffusion167
194
Effusiondueto
Incidence
(%)
Mortality(%)
Man
agement
Comment/Reference
Iatroge
nic
Transseptalpuncture
13
30
%ofmyo
cardium
atstak
eorbleedingca
nnotbestopped17
2;17
3
Rotablation
0.1
3Notav
ailable
Seeab
ove
Seeab
ove
172;173
Transluminal
extractionatherectomy
(atheroca
th)
02%
Notav
ailable
Seeab
ove
Seeab
ove
Excim
erlaseran
gioplasty
1.7
3%Notav
ailable
Seeab
ove
Seeab
ove
173
Highpressure
stenting