Pericarditis chronicI31.9

One form of chronic pericarditis, constitutional pericarditis, was probably the first to be described by Galen. As early as 190 AD, Galen observed a thickening of the pericardium in animals and considered it possible in humans as well (Gall 1992).

A pericarditis existing for at least 6 months is called chronic pericarditis. The chronic form often develops from acute pericarditis. However, there are also cases in which the disease has a primarily chronic course (Bob 2001).

The persistent inflammation leads to a scarring thickening of the pericardium and in 50% of cases extensive calcifications form in the area of the pericardium. These obstruct the heart, especially during diastolic ventricular filling. As a consequence, there is an influence congestion in the large circulation (Piper 2007).

Pathoanatomically we distinguish 3 groups of the chronic form of the disease:

• persistent or recurrent fibrinous pericarditis
• Pericarditis with chronic inflammatory effusion
• chronic constrictive pericarditis

The first two forms can change into a constitutional form of pericarditis (Bob 2001).

• Accretio pericardii: In this case adhesions of the pericardium to the neighbouring organs are found
• Concretio pericardii: Here the visceral and parietal pericardium become sticky
• Constrictio pericardii: Here a callous shrinking pericardium is found, which is also called an armoured heart and in which calcified deposits often appear (Herold 2018).

According to Maisch (Maisch 2008) uremic pericarditis is divided into 2 forms:

• Patients with renal insufficiency shortly before or shortly after the start of dialysis
• Patients who have already been dialyzed over a longer period of time

However, all pathogens that cause acute pericarditis (see d.) can also cause a chronic form of pericarditis.

Autopsies reveal pericarditis in 2% - 10% of cases (Maisch 2008).

Patients with acute pericarditis develop a recurrent form of pericarditis in 15% - 30% - regardless of the cause. According to Schölmerich (Schölmerich 2005), possible causes for such a development can be:

• there was no adequate initial therapy
• immunological causes
• too early treatment with corticosteroids

Primarily, the following pathogens can lead to a chronic or chronically recurrent form of pericarditis:

• Tuberculosis
• Autoimmune diseases
• Suction. Collagenoses
• Uremia
• X-ray irradiation
• Neoplasia
• Chylopericardium

Tuberculosis is the most common cause, followed by autoimmune diseases and uremia (Bob 2001). However, all pathogens that cause acute pericarditis (see d.) can also cause a chronic form of pericarditis.

The symptoms of the chronic form can be similar to those of the acute form, but are usually less severe:

• circumscribed left thoracic pain
• Occasionally, the pain radiates into the left shoulder, left arm and neck
• sometimes there is also isolated pain along the upper trapezius margin (pathognomonic for irritation of the pericardium)
• the pain is reduced when the posture is bent forward
• the pain increases when lying down, during deep inspiration, occasionally also when coughing or swallowing

(Cool 2004)

otherwise there are rather unspecific symptoms like:

• liver enlargement
• Ascites
• peripheral leg edemas
• Adynamics
• occasionally also unclear fever spikes
• Dyspnoea, especially under stress
• possibly also weight loss (but this may be absent due to the oedema that develops or weight gain may occur)

Chronic effusions develop only gradually. Symptomatically, they only become apparent from an effusion volume of approx. 300 ml. However, completely asymptomatic courses have also been described (Bob 2001).

X-ray thorax: Calcifications in the area of the pericardium can often be seen on the X-ray (Herold 2018).

The heart can be normal in size as in the case of fibrinous pericarditis and the chronic constrictive form (Piper 2007)..However, there can also be an enlargement of the heart shadow. This is visible on x-ray from an effusion of 250 ml (Piper 2007). The heart then takes on a so-called box-bag shape with a strongly protruding midsection. Echocardiography is recommended to rule out myogenic cardiac dilatation in a differential diagnosis (Herold 2018).

Echocardiography: Echocardiography is the simplest and also the most sensitive method to detect or even exclude chronic pericarditis. It is often found enhanced echoes at the calcified pericardial calluses. In addition, the detection of a so-called dip plateau phenomenon (decreased motion amplitude of the posterior wall in the area of the left ventricle with a sudden stop of the filling of the ventricle in mid-diastole [Herold 2018]). Likewise, the hemodynamic relevance of an effusion (echocardiographically detectable from 50ml) can be well assessed.

Cave: The anechoic space behind the heart and, in the case of large effusions, also in front of the heart cannot be visualized echocardiographically (Herold 2018). Computed tomography should be performed for concrete assessment of the mentioned spaces. The accompanying pericardial effusion may often be absent in viral genesis. In contrast, in bacterial and tuberculous genesis, a regular effusion of varying extent is found [Kühl 2004]).

According to Maisch (Maisch 2008), the extent of the effusion is echocardiographically divided into:

• small effusion (the anechoic diastolic separation of peri- and epicardium is < 10 mm)
• moderate effusion (diastolic separation is between 10mm - 20 mm)
• large effusion (diastolic separation is more than 20 mm)
• very large effusion (diastolic separation is more than 20 mm and there are additional signs of compression).

To be able to assess the development of a pericardial effusion, according to Herold (Herold 2018):

• close-meshed blood pressure checks (blood pressure drops)
• regular CVD measurements (CVD increases)
• Echocardiography checks

If the pericarditis is infectious, CRP, BSG and leukocytes may be elevated. In this case, virus serology and cultures for bacteria and mycobacteria are recommended (Herold 2018).

Otherwise, according to Fritze (Fritze 2012), the following laboratory changes may exist:

• Troponin I/T increased
• CK-MB increased
• Myoglobin increased
• occasionally also TNF (tumour necrosis factor) increased

According to Erdmann (Erdmann 2009), inflammatory processes can be elevated if they affect the myocardium:

• Creatine kinase
• Isoenzymes

In systemic autoimmune diseases (Maisch 2008):

• Lymphocytes > 5.000/mm3
• Monocytes > 5,000/mm3
• in epicardial or endocardial biopsy, evidence of an inflammatory infiltrate with more than 14 cells/mm3)

Clinic, laboratory

Auscultation

• Pulse-synchronous systolic-diastolic, creaking noise close to the ear, most clearly above the lingula near the sternum (so-called pericardial rubbing)
• Pericardial drift may also be present only passagally
• intensifies with the inspiration
• no change in noise during a respiratory pause (in contrast to pleural rubbing)
• However, the absence of pericardial rubbing does not rule out pericarditis.

If the pericarditis is infectious, CRP, ESR and leucocytes may be elevated. In this case, virus serology and cultures for bacteria and mycobacteria are recommended (Herold 2018).

ECG: The ECG need not be fundamentally altered by the pericarditis. The damage to the outer layer, which usually occurs in all leads, is rather caused by inflammation of the adjacent myocardial layers (Herold 2018).

However, in the majority of patients (90%) ECG changes occur.

These are T-negativations over several leads, whereby the leads cannot be assigned to any coronary care area and the indirect signs of infarction are missing.

Sometimes there is also peripheral / central low voltage (Maisch 2008). Atrial fibrillation can also occur (Herold 2018).

In case of a large pericardial effusion, an electrical alternans can occur due to the rhythmic amplitude change (so-called swinging heart) (Maisch 2008).

Echocardiography: Echocardiography is the simplest and most sensitive method to detect or exclude chronic pericarditis.

Puncture of effusion: If the genesis of chronic exudative pericarditis is unclear, a diagnostic puncture of the effusion with subsequent microbiological examination is recommended. However, in case of suspected tuberculous etiology, this should only be carried out after initiation of antituberculostatic treatment (Bob 2001).

The treatment of chronic pericarditis is similar to the treatment of the acute form.

No anticoagulants: The use of anticoagulants is also contraindicated in the chronic form due to the risk of hematothorax (Maisch 2008).

Symptomatic treatment: If the patient complains of pain, NSAIDs (e.g. ibuprofen 3 x 200 - 600 mg /d) should be administered under gastric protection (e.g. cimetidine 200 mg - 400 mg / d).

Primary treatment of the underlying disease:

In case of bacterial genesis: antibiotics according to the determination of resistance. However, this alone is not sufficient. The infection itself can only be controlled by early surgical opening of the pericardium with a suction-irrigation drainage. Drainage alone, even with instillation of antibiotics, does not lead to the desired success. This is of particular importance considering the high mortality rate of up to 50 % (Paumgartner 2015).

• Tuberculosis: In the case of tuberculous genesis in particular, an attempt should be made to detect the pathogens in the pericardial point. However, this is rarely successful. In pericardial biopsy, however, the detection of granulomas with central cheese and/or mycobacteria is usually possible (Maisch 2008). However, the collection of pericardial fluid and the pericardial biopsy should only be performed after initiating an antituberculostatic treatment (Bob 2001). Since a negative result does not exclude chronic pericarditis caused by tuberculosis, the antituberculostatic therapy should be continued in case of clinical suspicion. If the proof of a tuberculous genesis is successful, a 4-fold antituberculostatic therapy is recommended.

For the 4-fold therapy, 4 main substances are available as first choice agents:

• Isoniazid
• Rifampicin
• Pyrazinamide
• Ethambutol.

According to the WHO, the second choice is now streptomycin. However, since it cannot be administered orally, it is no longer used for treatment in several countries.

According to Paumgartner (Paumgartner 2015) the following dosage is recommended for daily administration:

• Isoniazid (INH) 5 - 10 mg/kg KW, max. 400 mg
• Rifampicin (RMP) 10 mg/kg KW,
• Pyrazinamide (PZA) 25 mg/kg HC, max. 2000 mg/d
• Ethambutol (EMB) 25 mg/kg KW,

The medication should be administered orally 1 x / d as a single dose. In some countries, intermittent drug administration with 3 x weekly intake is practiced. This procedure is not recommended in Germany, as the maximum therapeutic safety is only given if the drugs are taken daily. If there is any doubt about the regular intake of the medication, it must be constantly monitored. The success of the therapy should be checked regularly once a month, including the organs that are at risk from taking the medication. These include:

• Liver function with INH, RMP, PZA (additive effect!)
• ophthalmological controls in case of EMB
• Renal function with aminoglycosides
• Check audiogram for aminoglycosides
• Blood glucose monitoring with additional administration of cortisone (see above)
• In addition, the patient's body weight should be monitored regularly.

The treatment itself should be carried out over at least 6 months (Paumgartner 2015). The additional administration of corticosteroids is controversially discussed. In a study of the Cochrane Database it could be shown that patients with additional corticosteroid therapy show lower mortality and the necessity of pericardiocentesis or pericardiocentesis is reduced (Mayosi 2002).

Autoimmunological chronic pericarditis: If chronic pericarditis is caused by an autoimmune process , the following treatment regimen should be used:

• z. e.g. acetylsalicylic acid 2-3 g/d
• Colchicine 2-3 g/d for 1-3 weeks, then reduction to 1-2 g/d; the maintenance dose should be maintained for 3-6 months. If no therapeutic success can be achieved, glucocorticoids are recommended: e.g. prednisone 100 mg for 3 days or a maximum of 3 weeks, followed by a reduction in dose under echocardiographic and clinical observation (Paumgartner 2015).

If large effusions have formed and a puncture is necessary, a single intrapericardial administration of triamcinolone acetate should be performed. This can be done in a high dose - without serious systemic side effects - (e.g. 500 - 1000 mg over 24 h). Subsequently, peroral therapy is continued (Paumgartner 2015). However, drug therapy of the underlying disease is always in the foreground in this form of pericarditis (Maisch 2008).

Pericarditis in uremia: In both forms of uremic pericarditis, intensive haemodialysis is required. Heparin should be administered carefully or - if justifiable - not at all (to avoid a hemopericardium). Corticosteroids and non-steroidal anti-inflammatory drugs are not able to eliminate the effusion or improve pain. For "dialysis-refractory" effusions, intrapericardial instillation of triamcinolone hexacetonide (e.g. 4 x 50 mg/d for 2-3 days) has proven to be useful (Maisch 2008).

Corticosteroids: see also above under the therapy of the individual causative pathogens: Schölmerich (2005) considers an initial therapy with corticosteroids to be often unavoidable because of the rapid improvement of the symptoms, but also points out that chronic forms of the disease can only be triggered by long-term treatment with corticosteroids or treatment that starts too early. He therefore recommends only short-term therapy with glucocorticoids (e.g. prednisolone approx. 10 - 20 mg/d). Further details on the start and duration of treatment are not given. Other dosage recommendations are: 1-1.5 mg/kg bw p.o. for one month, followed by a three-month dose reduction. An overlapping administration of NSAID and colchicine shortly before the end of corticoid therapy is recommended (Maisch 2008). However, corticosteroids do not lead to an improvement of symptoms in uremic pericarditis (see above) (Maisch 2008).

Colchicine: An attempt at therapy with colchicine should be made in any case. Its effectiveness has been proven in several studies. Colchicine keeps up to 60% of patients free of recurrence, it also reduces the symptoms in the event of recurrence and corticosteroids can be saved (Schölmerich 2005). The initial dose of colchicine should be 2-3 mg / d with subsequent reduction to 1 mg/d for a period of approx. 6 - 12 months (Schölmerich 2005). If the pericarditis does not heal in the patient under colchicine, the following therapy scheme is recommended:

In the first 3 weeks a combination treatment of:

• prednisone 1,25 mg/kg bw/day
• Azathioprine 2,00 mg kg bw/day

can be given. Afterwards the dose should be reduced to:

• prednisone 0.3 mg/kg bw/day
• Azathioprine 0,85 mg kg bw/day

The reduced dose must be maintained for 3 - 6 months. The total leukocyte count should not fall below 3,000 / mm³ during the duration of therapy (Paumgartner 2018). Colchicine is not indicated for uremic pericarditis (see above) (Maisch 2008). Gastric protection under corticosteroid or NSAID therapy (e.g. cimetidine 200 mg - 400 mg / d ) is mandatory.

Pericardiocentesis or pericardial windowing: In the case of recurrent pericardial effusions requiring puncture, which have proved to be refractory to therapy - even with colchicine - surgical treatment with pericardial windowing or pericardiocentesis should be performed (Kühl 2004).

Both the prognosis and the course of the disease can be very different, as both depend on the respective cause of the disease (Bob 2001).

Pericarditis caused by bacteria or mycoses has a very unfavourable prognosis. The mortality here is up to 50 % (Maisch 2008).

If it is a disease that is notifiable according to the IfSG § (e.g. Mycobacterium tuberculosis), there is a medical obligation to notify the public health department responsible for the patient both in the case of illness and death, even if no bacteriological evidence is already available.

In addition, persons who have fallen ill with tuberculosis requiring treatment and who discontinue or refuse treatment must notify the public health department.

According to § 7 of the IfSG, the investigating laboratory must report the direct detection of mycobacterium tuberculosis / africanum and mycobacterium bovis. The same applies to the detection of acid-resistant rods in sputum and the result of the resistance determination.

The notification to the public health department must be made by name and at the latest 24 hours after the knowledge has been obtained. In addition, information on the country of birth, year of entry into Germany and nationality must be provided.

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