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OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Dr. Riccardo Asteggiano,
Pericarditis in its common acute viral form is frequent in clinical practice and generally a benign illness. Sometimes it complicates with myocardial involvement, recurrent and incessant forms, pericardial effusion sometimes leading to tamponade and the management of these situations may be challenging. Pericarditis due to less common aetiology may be also more difficult to diagnose and to treat. Pericardial disease may be an isolated disease or part of a systemic disease. The new clinical Guidelines of the ESC for the Diagnosis and management of Pericardial Disease were presented at the ESC Congress 2015 in London and published in November 2015 in the European Heart Journal (1). The novelty of this edition in comparison with the previous edition of 2004 may be summarized in: 1) New triage strategies for detection of high risk cases and to determine when and how additional investigations are indicated, 2) Multimodality Imaging, 3) Aetiology and Pathophysiology, 4) Age and Gender specific issues, 5) Therapy advances, 6) Early detection of constrictive pericarditis.These new Guidelines have been organized in seven main chapters about the epidemiology, aetiology and classification, the pericardial syndromes, the multimodality imaging and the diagnostic work-up, specific aetiology of pericardial syndromes, specific issues related to age and gender and advances in interventional techniques and surgery.
Despite the incontrovertible high diffusion of pericarditis, especially in some subsets like during influenza epidemics, precise epidemiological data are still lacking, and mainly related to hospital admissions, with a consequent selection bias. Pericarditis is responsible for 0.1% of hospital admissions and 5% of emergency room admissions for chest pain. Men with ages 16-65 years seem at higher risk (relative risk 2.02). One data about in-hospital mortality (1.1%) is confusing due to the high age and comorbidities of the population. About 30% of acute pericarditis may recur in 18 months.A simple classification from the aetiological point of view distinguishes between infectious and non-infectious causes. In the first group are the viral (the most common), the bacterial and the rare fungal and parasitic pericarditis. The non-infective pericarditis are the common autoimmune, the neoplastic, the metabolic, the traumatic and iatrogenic, the rare drug related and a miscellanea of different clinical situations frequent in aortic dissection, heart failure, pulmonary arterial hypertension and amyloidosis.
Acute pericarditis occurs with or without effusion. Two of the following 4 criteria are required to diagnose it: 1) typical pericardial chest pain, 2) pericardial rubs, 3) ST elevation or PR depression on the electrocardiogram, 4) pericardial effusion. Additional useful findings are the elevation of inflammation markers (CRP, ESR, WB cells count) or evidence of pericardial inflammation by CT or MRI. May be present also signs of systemic infection (fever, malaise, muscular pain) or of systemic illnesses. All patients with acute pericarditis should have an ECG, an Echocardiography, a Chest X-ray for the search of pleuro-pericardial involvement and the markers of inflammation and of myocardial involvement. Hospital admission is reserved to high risk cases (fever > 38°, subacute onset, large effusions or tamponade, or lack of response to aspirin or NSAIDs for at least one week of therapy, and also in case of myopericarditis, immunosuppression, trauma, and anticoagulation) or in highly suspected specific aetiologies. All the other patients may be managed on an out-patient basis with anti-inflammatory drugs programming a control in a week to assess the response to therapy. The non-responders should be indicated as moderate risk cases and admitted for aetiology search. Aspirin (750-1000 mg every 8 hours for 1-2 weeks, then progressive tapering doses) or Ibuprofen (600 mg every 8 hours for 1-2 weeks, then tapering doses) associated to Colchicine (0.5 mg once a day if < 70 Kg or twice a day of > 70 Kg for 3 months) is the recommended anti-inflammatory therapy. It should be guided by CRP normalization. Also a restriction of physical activity is recommended until symptoms disappear and CRP, Echocardiogram and ECG normalize. Corticosteroids are not recommended as first line therapy, but only at low doses if there are contraindications to the common drugs or in cases of autoimmune pericarditis. The prognosis is generally good with rare case of constriction (only with bacterial or tuberculosis could it be a concern – 20-30% of cases). 15-30% of patients may develop recurrent or incessant pericarditis if not treated with colchicine which halves its occurrence.
Recurrent pericarditis is a new episode of pericarditis after a symptom free interval of 4-6 weeks from a first episode. A common cause is inadequate treatment of the first episode. The basic therapy consists of aspirin or ibuprofen or indometacine at similar dosages as for acute pericarditis but for a longer time, up to many months, in association with colchicine for at least 6 months. Corticosteroids should be restricted to systemic diseases, post-pericardiectomy and pregnancy with a very slow tapering because they favour chronicisation. In cases resistant to the standard therapy, after careful assessment of the clinic situation, may be proposed azathioprine, IVIG, and anakinra. Specific treatment is required for recurrent pericarditis of specific aetiologies.
Myopericarditis is a form of pericarditis with associated myocardial involvement. In association with the clinic and instrumental findings of a pericarditis in this case occurs a significant elevation of troponins or CKMB. The differential diagnosis of predominant pericarditis with myocardial involvement versus true myocarditis requires the absence in echocardiography or CMR of new focal or diffuse myocardial lesions and a coronary angiography versus an acute coronary syndrome. Hospitalization is recommended.
Pericardial effusions are classified based on onset (acute, subacute and chronic), size (mild, moderate and large), distribution (circumferential or loculated) and composition (transudate or exudate). Echocardiography allows the diagnosis and the assessment of the size and haemodynamic effects. Sometimes CT and CMR may be useful in the detection of loculated effusions and recognition of thickening or masses. A chest X-ray is useful to evaluate concomitant pleuro-pulmonary involvement. Up to 60% of pericardial effusions are associated with a known or unknown medical condition that has to be ruled out (hypothyroidism, kidney disease, neoplasms, and so on). If there are inflammatory signs (CRP, ESR) the management is similar to that of an acute pericarditis. Small effusions generally have a good prognosis and outcome, not requiring monitoring. Moderate and large effusions may evolve in one third of cases in cardiac tamponade, and require a careful monitoring based on stability and evolution.
Cardiac tamponade is a life-threatening condition requiring prompt echocardiographic or fluoroscopic guided drainage. A surgical approach is required in special conditions like purulent pericarditis or bleeding situations. Vasodilators and mainly diuretics are contraindicated in cardiac tamponade.
Constrictive pericarditis may occur after any pericardial disease. It is rare after recurrent pericarditis, frequent in bacterial or purulent pericarditis. The differential diagnosis is with a restrictive cardiomyopathy. Kussmaul sign, pericardial knock, low QRS voltage, pericardial calcification (1/3 cases) on chest X-Ray, typical echocardiographic findings, the typical “dip-plateau” curve in right catheterization, and the pericardial increased thickness on CT or CMR are the main signs. Three forms of specific constrictive pericarditis may be identified: the transient constriction (reversible with recovery), the effusive-constrictive (with a lack of reduction in right atrial pressure of 50% or < 10 mmHg, generally resolved by pericardiocentesis associated to medical therapy) and the chronic constriction after 3-6 months). Surgery is the main therapeutic option. Medical therapy is restricted to specific forms to avoid the progression of constriction and to anti-inflammatory drugs in concomitant inflammation evidence.
The rapid development of multimodality imaging has made available also for pericardial disease the use of CT and CMR, in adjunct to echocardiography. The choice of one or the association of more methods follows the needs of every clinical specific situation to improve the diagnostic power and ameliorate the patient's management. In the text of the guidelines tables 12 and 13 are useful to recognize pros and contras of echo, CT and CMR modalities.
For the diagnostic work-up some issues have been underlined. The essential controversy is the opportunity of a complete aetiological research in all patients with pericarditis. A rational cost-effective management should be based on an epidemiological background, reserving specific path and hospital admission to cases with a specific aetiology requiring particular diagnostic and therapeutic tools. The common diagnostic tests in association with the clinical signs are generally sufficient for the diagnosis of pericarditis (and myopericarditis). In specific situations a bacterial (mainly TB), neoplastic or associated with a systemic disease pericarditis has to be ruled out. High fever (> 38°), subacute onset, large pericardial effusions, cardiac tamponade, lack of response to therapy and also myopericarditis, immunodepression, trauma and OAC, are considered markers of high-risk situations having a non-viral and a non-idiopathic origin and require hospitalisation and complete work-out. Over the basal assessment every patient should have a renal, liver and thyroid assessment. Second level investigations are CT and CMR and the complete analysis of the pericardial fluid, while additional tests for specific aetiologies are reserved according to the clinic features.
Routine viral serology for viral pericarditis is not recommended except in suspected HIV or HCV infections; corticosteroids are contraindicated. Bacterial pericarditis is uncommon in developed countries, and the most common is the tuberculous pericarditis; in this case a chest X-Ray which may show pulmonary TB in 1/3 of cases, the large pericardial effusion thick with a “porridge like appearance”, the CT and CMR revealing pericardial thickening and lymphadenopathy, and the cultural exams for the search of MB tuberculosis may help in the diagnosis. Additionally a diagnostic pericardiocentesis may offer more information. Limited cases may be submitted to a biopsy. In endemic TB populations a trial with common chemotherapy for TB is recommended, while in non-endemic situations after the failure of the diagnostic for TB there are no indications for an empiric treatment. Purulent pericarditis is a rare condition generally part of a septic systemic process, requiring when suspected a prompt pericardiocentesis and an aggressive treatment to reduce the high mortality rate.
Three different forms of pericarditis in renal failure may develop: the uremic pericarditis in end stage kidney disease before or 8 weeks after kidney replacement, dialysis pericarditis during stabilisation and unfrequently a constrictive form.
Pericardial involvement in systemic autoimmune and auto-inflammatory disease may be common or less common in relation to the specific disease and may occur also totally asymptomatic.
The post-cardiac injury syndromes (PCIS) is a group of inflammatory pathologies including the post-myocardial infarction pericarditis, the post-pericardiectomy syndrome (PPS), and post-traumatic (iatrogenic or not) pericarditis. Aspirin is recommended in post infarction pericarditis and colchicine should be added in all PCIS; colchicine is recommended for 1 month in prevention of PPS. PCIS may evolve to constrictive pericarditis and should be closely followed-up.
Traumatic pericardial effusion and haemopericardium may occur during every cardiac intervention. After a major thoracic trauma symptoms and signs of more or less severe pericarditis may develop and urgent imaging technique (usual echocardiography) is necessary to evaluate the patient and to indicate an immediate thoracotomy in case of tamponade due to a penetrating trauma or cardiac lesion. A pericardiocentesis may be needed as bridge to the intervention to stabilize hemodynamic conditions.
Pericardial involvement in neoplastic disease is generally secondary to invasion or metastasis of malignant neoplasms, while mesothelioma or other primary tumours are rare. Pericardiocentesis may relieve symptoms and lead to the diagnosis by cytological analysis of the fluid, while extended pericardial drainage may prevent effusion recurrence and provide a tool for intrapericardial chemotherapy. Systemic cancer therapy should be warranted in defined neoplastic pericarditis.
Other forms of pericardial disease are radiation pericarditis, now less frequent with the new radiotherapy tools, chylopericardium, drug related pericarditis and pericardial effusion, pericardial effusion in metabolic and endocrine disorders as in hypothyroidism, pericardial involvement in pulmonary arterial hypertension present in 25% of cases, and pericardial cysts.
In the paediatric setting a marked inflammatory response with pleuro-pulmonary involvement is often present; aspirin is avoided in children and NSAIDs at high dosages in association with colchicine are the cornerstone of the treatment, while corticosteroids are proscribed. During pregnancy the most common form is the hydropericardium benign mild effusion during the third trimester; NSAIDs should be avoided after the 20th week because of their ability to constrict the ductus arteriosus of the foetus, small doses of prednisone being the only possibility. There is no specific evidence for elderly patients, in which indometacine is contraindicated and colchicine requires halving the dosages with careful attention to renal function.
No procedures except for emergency situations should be done without fluoroscopy or echocardiography, for the risk of complications (4-10%). A surgical pericardial window allowing the communication of pericardial cavity with pleura and thoracic cavity may be effective in draining pericardial effusion for example in neoplastic disease to avoid large frequent effusions. Pericardiectomy is the treatment of choice for constrictive pericarditis but due to its difficulty and high complication rate it should be performed only in very specialized centres.