Pericarditis

Authors: Doctor Sabiha Gati BSc (Hons), MBBS and Doctor Sanjay Sharma BSc (Hons), MBChB, MRCP (UK), MD1 Creation Date: March 2005

Scientific Editor: Professor William McKenna

1 University Hospital Lewisham, Lewisham High Street, London SE13 6LH. [email protected]

Abstract Keywords Background Definition and Classification Frequency ACUTE Clinical manifestation Other investigations Management Complications Clinical Manifestations Investigations Management CONSTRICTIVE PERICARDITIS Clinical manifestations Investigations Management References

Abstract Pericarditis is an inflammatory disorder of the serous resulting from a primary insult to the or is secondary to a systemic disorder. Of the many causes, the most frequently encountered include acute idiopathic pericarditis and viral infections. The condition is classically diagnosed by the presence of , presence of a and characteristic changes on ECG. Extensive investigations to elicit a cause are not necessary as they are of low diagnostic yield. Because of its frequently self-limiting nature, non-steroidal anti-inflammatory drugs are normally used as the first line treatment with the aim of dampening the inflammatory process and expediting recovery. Specific therapy should be initiated for an underlying disorder perpetuating pericarditis. Complications of pericarditis include pericardial effusions and subsequent tamponade and long term constrictive pericarditis. Further laboratory evaluation, and should be considered for individuals likely to have these complications. Keywords Pericarditis, pericardial effusion, pericardial constriction

the two layers of the serous pericardium that normally Background contains 15 to 50 mls of plasma fluid (1). The heart is surrounded by a protective pericardium made up of two layers, a serous and a fibrous Definition and Classification component. The serous component is further divided Pericarditis is an inflammatory disorder of the serous into an inner, visceral and outer, parietal layer. A pericardium which may result from either a primary potential space, the pericardial cavity exists between insult directly to the heart or be secondary to a large number of systemic disorders (Table 1). In most

Gati S., Sharma S. Pericarditis. Orphanet Encyclopedia, March 2005. 1 http://www.orpha.net/data/patho/GB/uk-Pericarditis.pdf

instances the disorder is self-limiting but may be complicated by pericardial effusion or constriction. Aetiology Table 1: Diseases affecting the pericardium. The cause of pericardial disease in many cases is Adapted from (1). unknown, particularly in young adults. Studies suggest Trauma a viral aetiology (coxsackie B) in most cases. Since Radiotherapy the disease is usually self-limiting the cause is not Aortic dissection investigated as there is a considerable time lag before Blunt or penetrating injury the results of the viral titre are available and the Infection Bacterial – Tuberculosis, initiation of treatment. The diagnosis can be made Streptococcus, Staphylococcus, from the clinical presentation and does not require Pneumococcus, Haemophilus, positive virology titres. Individuals may present with Legionella, Salmonella, Lyme disease, chest pain and flu-like symptoms. Although the Neisseria meningitides & Gonorrhoea, condition is self-limiting, recurrence over the following Chlamydia psittaci & Trachomotis 6 to 12 months may occur with an immunological Viral – HIV, Coxsackie virus A&B, basis. echovirus, EBV, mumps, hepatitis B, influenza, varicella Viral pericarditis Fungal – Histoplasmosis, aspergillosis, Coxsackie virus A & B, echovirus, adenovirus and HIV nocardia, candida, coccidiomycosis are the most commonly implicated viral causes of Parasitic – Echinococcus, amebiasis, acute pericarditis. Seasonal epidemics are known to toxoplasmosis occur with influenza and coxsackie B. Viral pericarditis Neoplasm Primary or secondary is typically self-limiting, lasting 1-3 weeks and is Drugs Hydralazine, Procainamide, Cytotoxics, treated symptomatically. HIV can facilitate infection of Phenytoin, Penicillin, Anticoagulants the pericardium by non-virulent organisms or can Endocrine Hypothyroidism directly infect the pericardium. HIV typically causes small asymptomatic pericardial effusions. Metabolic Uraemia, Inflammatory Dressler’s syndrome, Postcardiotomy Bacterial pericarditis Connective RA, SLE, SS, PAN, Churg-strass, The most common bacterial causes are Tissue GCA, sarcoidosis, IBD, wegener’s Staphylococcus aureus, Streptococcus pneumonie, disorders granulomatosis Haemophilus influenzae and Mycobacterium Acute tuberculosis. The spread is either haematogenous or Idiopathic directly from the lungs or pleura. Less common HIV= Human immunodeficiency virus, EBV= Ebstein bacterial infections may be seen in the bar virus, RA= Rheumatoid arthritis, SLE= Systemic immunocompromised and in those with altered erythematosus, SS= Systemic sclerosis, PAN= bacterial flora from extensive prolonged antibiotic Polyarteritis nodosa, GCA= giant cell arteritis, IBD= therapy. inflammatory bowel disease. Tuberculosis pericarditis Frequency is rare in the western world, Epidemiological data on the incidence of pericarditis however, it is still an important cause of pericardial are scarce, possibly because the condition can be disease in the third world. Both parietal and visceral difficult to identify, and of its self-limiting nature. The layers of pericardium are infected and the frequency of pericarditis can vary in numerous myocardium is involved in most cases. Tuberculous disorders (Table 2). Mortality may vary according to pericarditis can present in the form of acute the aetiology, being low with viral/idiopathic pericarditis, pericardial effusion or with constrictive pericarditis and very high with purulent pericarditis (2). pericarditis. Treatment is with antituberculous drugs. Steroids hasten recovery in the first 11 weeks but Table 2: Frequency of the disorder under should be avoided in tuberculous pericarditis different causes of pericarditis. Adapted from secondary to HIV syndrome. (14) Fungal infection Cause Accountable cases Fungal pericarditis is rare and is usually manifest in Infection immunocompromised patients. Histoplasma is the Bacterial 1-8% most common fungal organism in the immuno- Tuberculosis 4% sufficient individuals and is known to cause Viral 1-10% constriction and calcification. Infections with Autoimmune actinomycosis (Actinomyces), coccidiodomycosis Rheumatoid arthritis 11-50% (Coccidioides), Candida and Aspergillus have also Systemic lupus 25% (after autopsy 62%) been reported. erythematosus Systemic sclerosis 5-10%(after autopsy 70%) Malignancy Chronic Renal failure 12% Neoplastic disorders affecting the pericardium include Hypothyroidism 4% rare primary tumours such as mesotheliomas or Myocardial infarction 7-23% myosarcomas or, more commonly are secondary to Dressler’s syndrome 4% metastases from the lung, breast, gastro-intestinal Postcardiotomy 10-40% tract and haematological malignancies. Malignancy is frequently associated with moderate to large effusions Neoplasm 5-17% (2,3), and may lead to tamponade. Patients with

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neoplastic pericardial effusions may also present with pericardium may also be involved in allergic supraventricular , or features of hypersensitivity reactions to penicillins. constrictive pericarditis. Generally, malignant pericardial effusions require drainage. The diagnosis Clinical manifestation of neoplastic pericardial effusion is based on Clinical presentation of acute pericarditis consists of a cytological examination of pericardial fluid or direct triad of chest pain, pericardial friction rub and histological tests on the pericardium (4,5). Recurrent generalised widespread ST segment and effusions are treated by surgical fashioning of a changes on the ECG. continuum window into the pleural cavity. Chest pain Hypothyroidism The onset of the pain is sudden. The pain is Hypothyroidism causes silent pericardial effusion that classically located in the retrosternal area and is rarely of haemodynamic significance. Low voltage characteristically sharp in nature with exacerbation complexes are seen on the ECG. Thyroxine during movement or deep inspiration. The intensity of replacement alone is sufficient to resolve the the pain decreases with sitting forward. Dyspnoea is pericardial effusion. the consequence of the pain aggravated by breathing. Myocardial infarction Pericardial friction rub Acute pericarditis and/or effusion, are manifested in Precordial examination of a patient with acute approximately 15% of patients following an myocardial pericarditis often reveals a scratchy superficial sound infarct (MI) (5,6,7,8). The overall incidence of MI audible over the precordium, in any position termed a induced pericardial disease is reduced by 50% with “pericardial rub”. The rub can be fleeting and may vary thrombolytic therapy (7). Infarct size and early with posture and is best heard with the diaphragm of initiation of thrombolytic therapy determines the the stethoscope at the left sternal border. A pericardial incidence and extent of pericardial involvement (7). rub can be distinguished from a pleural rub by halting The acute insult to the pericardium presents in the first respiration for a few seconds. The pericardial rub is an 24 to 72 hours, and gives rise to a friction rub, dull effect of maximal movement of the heart within the retrosternal chest pain varying with posture and pericardial sac. respiration and pericarditis, widespread ST elevation Electrocardiogram (ECG) is labile. Patients are also more prone to There are four stages to the ECG changes in acute supraventricular . An acute effusion may pericarditis: develop secondary to the inflammatory process Stage 1: Diffuse symmetrical concave ST segment related with the infarct but is usually silent. elevation by 1mm or more (Fig 1). This is associated Dressler’s syndrome with reciprocal ST segment depression in aVR and Dressler’s syndrome is seen in 3 to 4% of patients V1. There is also elevation of the PR segment in aVR and occurs 2 to 4 weeks following a myocardial and reciprocal depression in the left chest leads and infarction. Also known as postcardiac injury syndrome, remaining limb leads (1). it is immunologically mediated and presents with a Stage 2: ST and PR segment normalisation. self-limiting febrile illness, pleural or pericardial pain Stage 3: Diffuse T wave inversions occurring over 2 to and a pneumonitis. Patients with successful 3 weeks. This stage is not always seen in all patients. reperfusion after treatment with thrombolysis following Stage 4: Normalisation of the ECG. Persistence of T MI are less likely to develop Dressler’s syndrome (9). wave inversion is indicative of chronic pericarditis. Arrhythmias are generally uncommon in isolated Metabolic cause of pericarditis acute pericarditis (11) but their presence should raise Patients with untreated severe chronic renal failure the suspicion of concomitant myocardial disease. are prone to uraemic pericarditis. Uraemic pericarditis is often complicated by pericardial effusion (9,10). The Other investigations typical electrocardiogram (ECG) changes of Cardiac I and T pericarditis are not seen, however, patients do Troponin I and T elevation may be seen in viral or develop pericardial pain and friction rub. The acute idiopathic pericarditis and are related to the incidence of uraemic pericarditis is very rare in areas extent of myocardial inflammatory involvement. where dialysis is readily available. Raised cardiac are observed particularly in Autoimmune disorders the young, males, and patients with ST segment Patients with rheumatoid arthritis, systemic lupus elevation and pericardial effusion at presentation (12). erythematosus and other connective tissue disorders Chest X-ray (CXR) (Table 1) can develop extensive pericardial disease. The chest X-ray is rarely informative in acute Clinically signs of pericardial involvement are often pericarditis. The presence of cardiac enlargement absent and the ECG rarely demonstrates typical does not differentiate between pericardial effusion, changes of pericarditis. Treatment is recommended pericardial wall thickness or cardiac chamber on symptomatic grounds. enlargement. Patients with acute pericarditis typically Drug induced pericardial disease have a normal CXR. Up to 200mls of pericardial fluid Certain drugs such as procainamide and hydralazine would have to accumulate to manifest as an enlarged may precipitate a lupus like syndrome involving the cardiac shadow (13) (Fig 2). pericardium. Other drugs implicated in the aetiology of Echocardiogram pericarditis include isoniazid and phenytoin. Cytotoxic The echocardiogram is often normal in individuals with drugs such as doxarubicin and daunorubicin cause acute pericarditis. The presence of a pericardial pericardial and disease. The effusion (Fig 3) provides support for the diagnosis of

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acute pericarditis and identifies individuals who may CARDIAC TAMPONADE be at risk of developing tamponade or constrictive Cardiac tamponade is an acute medical emergency, pericarditis. However, the absence of an effusion does that results from increased pressure within the not exclude the diagnosis of acute pericarditis. pericardial cavity from fluid accumulation in the space surrounding the heart. Consequently, there is Pericardiocentesis interference with ventricular filling, reduced cardiac Diagnostic pericardiocentesis is not routinely output and fall in blood pressure. warranted (2). Pericardiocentesis can be considered for therapeutic purpose if malignancy, tuberculosis or Clinical Manifestations purulent pericarditis are suspected. Pericardiocentesis Symptoms include dyspnoea, fatigue, dull central is performed on therapeutic grounds in patients with chest pain, facial engorgement, abdominal and ankle moderate to severe tamponade, and recurrent swelling, or altered mental state may present. symptomatic effusions. Physical signs include raised with prominent ‘x’ descent (Fig 4), , a Specific aetiological tests rapid low volume , muffled (Becks In patients without a classical history for viral triad), and (fall in the arterial pericarditis, further investigations are recommended pressure by more than 10mmHg on inspiration). to elucidate the aetiology of acute pericarditis which Paradoxical filling of the neck on inspiration include blood cultures, antistreptolysin-O (ASO) titre, (Kussumaul’s sign) is less specific. Oliguria or anuria rheumatoid factor and screens for various due to a profound drop in cardiac output are well autoimmune conditions and tuberculin skin testing. recognised but resolve rapidly after percardiocentesis. Management Investigations The majority of cases of acute pericarditis are either ECG may show low voltage QRS complex viral or idiopathic, and usually self-limiting. Therefore, and depending on the quantity of the effusion, non-steroidal anti-inflammatory drugs (NSAIDs) (alternating QRS complex remain the first line treatment for uncomplicated morphology). CXR may demonstrate a large globular cases. Pain relief with simple analgesics and bed rest heart depending on the quantity and time duration of if is a possibility should also be fluid accumulation. Emergency echocardiography will considered. The use of NSAIDs for example confirm the presence and quantity of fluid, and identify and aims to dampen the inflammatory diastolic right ventricular collapse (an process and expedite recovery. Empirical treatment echocardiographic hallmark of tamponade) from the with steroids may be considered if patients are not rising pericardial pressure. responding to NSAIDs, if symptoms are prolonged, severe, or recurrent and if a specific cause cannot be Management identified (13). Specific therapy should be initiated for Short-term benefit is provided from pericardial needle patients with an underlying disorder. aspiration with a maximum of 500mls of fluid removal. Larger volumes should be drained more slowly by Complications insertion of a pericardial drain to prevent Pericarditis can be complicated by pericardial cardiovascular collapse. Recurrent effusions (usually effusions that may be large enough to compromise due to malignancy) are treated by fashioning a cardiac function and lead to collapse. Both acute and pericardial window into the pleural cavity. chronic pericarditis and small effusion can culminate in constrictive pericarditis. These complications are discussed below. CONSTRICTIVE PERICARDITIS PERICARDIAL EFFUSION Constrictive pericarditis is caused by pathological The pericardial space contains approximately 15 – activation of fibrocystic deposition of collagen building 50mls fluid of electrolyte and protein composition a thickened fibrotic pericardium that eventually similar to plasma and serves to lubricate the layers of restricts cardiac filling. Clinical features of constrictive the pericardium. The abnormal accumulation of fluid in pericarditis occur as a result of restricted ventricular the potential pericardial space defines pericardial filling. There is elevation and equalisation of right and effusion (Fig 3). Pericardial effusion may complicate left atrial pressure with subsequent venous pericarditis from any cause but is more common in engorgement and reduced cardiac output. inflammatory, infectious, malignant, and autoimmune Constrictive pericarditis may be difficult to distinguish processes. Effusion may be acute or chronic, and from restrictive since the patient’s symptoms depend upon the time course of physiological, clinical and radiographic imaging effusion development. Rapid accumulation of studies may be similar. The differentiation between pericardial fluid as little as 80mls can raise the the two entities is set out below (Table 3). In the vast intrapericardial pressures extensively with significant majority of cases of constrictive pericarditis, the adverse hemodynamic effects, whilst slowly aetiology is not ascertained. In the developed world accumulating fluid can measure more than 2 litres and idiopathic or viral aetiology is commonly implicated. the patient may not have any symptoms. Treatment is Infectious diseases such as tuberculosis are directed at removal of the underlying cause and profoundly a dominant cause in the developing world. aspiration of pericardial fluid if the patient is symptomatic. Pericardial effusion can lead to tamponade if not treated and in the long term can result in pericardial constriction.

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Table 3 Difference between constrictive does not exclude the diagnosis of constrictive pericarditis and restrictive cardiomyopathy pericarditis. Constrictive pericarditis Restrictive Cardiac catheterisation helps differentiate from cardiomyopathy restrictive cardiomyopathy. It may demonstrate high Right Right heart failure atrial pressure with prominent X and Y descents and Pericardial calcification on equalisation of left ventricular end diastolic pressure CXR (LVEDP) and right ventricular end diastolic pressure Normal size atria Enlarged atria (RVEDP) in all phases of respiration (Fig 7). Rapid early filling of both ventricles followed by diastasis is Myocardial texture normal Myocardial texture also evident. infiltrated e.g. amyloid No mitral or tricuspid Mitral and tricuspid Management regurgitation regurgitation common Treatment of constrictive pericarditis is primarily Systolic function normal Systolic function impaired surgical. Pericardiectomy is the definitive treatment LVEDP =RVEDP LVEDP >RVEDP with rapid improvement of symptoms and haemodynamic status. Clinical manifestations Patients with constrictive pericarditis may present with References gradual onset of symptoms and signs of 1. Shabetai R. Evaluation and management of acute predominantly right-sided heart failure. The most pericarditis. www.uptodate.com common presenting complaints include dyspnoea, 2. Sagrista-Sauleda, J, Merce, J, Permanyer-Miralda, abdominal swelling and ankle oedema although G, Soler-Soler, J. Clinical clues to the causes of large patients may also present with fatigue and pericardial effusions. Am J Med 2000; 109:95 orthopnoea. 3. Wilkes, JD, Fidias, P, Vaickus, L, Perez, RP. Characteristically, the jugular pressure (JVP) Malignancy-related pericardial effusion. 127 cases exhibits prominent X and Y decents (Fig 4) (that are from the Rosewell park institute. Cancer 1995; persistent even in patients with atrial ) and 76:1377 may rise during inspiration (Kussumaul’s sign). Other 4. Porte. HL. Janecki-Delebeca. TJ. Finzi. L. et al. clinical features including pleural effusion, Pericardoscopy for primary management of pericardial hepatosplenomegaly, ascites and ankle oedema. The effusion in cancer patients. Eur J Cardiothracic Surg is often impalpable and the heart sounds 1999; 16:287 are soft. The sudden cessation of ventricular filling in 5. Galve, E, Garcia-del-Castillo, H, Evangelista, A, et early corresponds with a pericardial knock al. Pericardial effusion in the course of myocardial which is often mistaken for the third heart sound, infarction: Incidence, natural history, and clinical however, it is of a higher frequency and occurs slightly relevance. Circulation 1986; 73:294 earlier than third heart sound. In advanced case, 6. Correale, E, Maggioni, AP, Romano, S, et al. cardiac cachexia with marked muscle wasting is Comparison of frequency, diagnostic and prognostic noted. significance of pericardial involvement in acute myocardial infarction treated with and without Investigations thrombolytics. Am J Cardiol 1993; 71:1377 Chest radiograph is rarely helpful in the diagnosis of 7. Belkin, RN, Mark, DB, Aronson, L. Pericardial constrictive pericarditis, however the presence of effusion after intravenous recombinant tissue-type pericardial calcification in a patient with right heart plasminogen activator for acute myocardial infarction. failure may be indicative of previous tuberculous Am J Cardiol 1991; 67:496 pericarditis (Fig 5). Generally, the cardiac silhouette 8. Shahar, A, Hod, H, Barabash, GM, et al. appears normal. Disappearance of a syndrome: Dressler’s syndrome in Two-dimensional echocardiography is not regarded to the era of thrombolysis. 1994; 85:255 be a very sensitive tool in the diagnosis of constrictive 9. Rostand, SG, Rutsky, EA. Pericarditis in end-stage pericarditis since the pericardium is not echodense in renal disease. Cardiol Clin 1990; 8:701 most cases. However, doppler echocardiography 10. Gunukula SR, Spodick, DH. Pericardial disease in across mitral and tricuspid valves show filling patterns renal patients. Semin Nephrol 2001; 21:52 that vary with respiration (Fig 6). The early (E) and 11. Spodick, DH. Arrhymias during acute pericarditis. late (A) filling ratio (E/A) across the is A prospective study of 100 consecutive cases. J Am reduced during inspiration and increased with Med Assoc 1976; 235:39 expiration. The pattern is reversed at the tricuspid 12. Imazio M, Demichelis B, Cecchi E, et al. Cardiac valve with increased velocity with inspiration and Troponin I in acute pericarditis. J Am Coll Cardiol reduction during expiration. These doppler findings 2003; 42:2144 are consistent with the diagnosis of constrictive 13. Spodick, DH. Acute cardiac tamponade. N Engl J pericarditis but their absence does not exclude the Med 2003; 349:684 condition. 14. John S. Constrictive pericarditis. High resolution CT scan may demonstrate pericardial www.emedicine.com 2003 . thickening up to 4 mm. A normal pericardial thickness

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Figure 1. ECG in pericarditis showing diffuse symmetrical concave ST segment elevation in most/all leads

Figure 2. Chest radiograph in pericardial effusion showing enlarged cardiac shadow

Gati S., Sharma S. Pericarditis. Orphanet Encyclopedia, March 2005. 6 http://www.orpha.net/data/patho/GB/uk-Pericarditis.pdf

Figure 3. Echo showing presence of pericardial effusion

Pericardial effusion

Figure 4. JVP waveform in cardiac tamponade and constrictive pericarditis

a v Normal y x a v y Cardiac Tamponade x Deep x decent

a v Constrictive Pericarditis y Deep x & y decent x :

Gati S., Sharma S. Pericarditis. Orphanet Encyclopedia, March 2005. 7 http://www.orpha.net/data/patho/GB/uk-Pericarditis.pdf

Figure 5. Chest radiograph in constrictive pericarditis showing pericardial calcification of tuberculous aetiology

Gati S., Sharma S. Pericarditis. Orphanet Encyclopedia, March 2005. 8 http://www.orpha.net/data/patho/GB/uk-Pericarditis.pdf

Figure 6. Early (E) and late (A) filling across mitral and tricuspid valves during respiration. E/A ratio across mitral valve decreases during inspiration and increases with expiration. E/A ratio across increases during inspiration and decreases with expiration.

Inspiration Expiration

Mitral 25% increase in E wave

Tricuspid 25% decrease of E wave

Figure 7. Dip and Plateau waveforms differentiating restrictive cardiomyopathy from constrictive pericarditis

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