10-50: Acute Inflammatory Pericarditis

Acute (less than 2 weeks) inflammation of the pericardium may be infectious in origin or may be due to systemic diseases (autoimmune syndromes, uremia), neoplasm, radiation, drug toxicity, hemopericardium, postcardiac surgery, or contiguous inflammatory processes in the myocardium or lung. In many of these conditions, the pathologic process involves both the pericardium and the myocardium. Overall pericarditis accounts for 0.2% of hospital admissions and about 5% of patients with nonischemic chest pain seen in the emergency department. The ESC in 2015 proposed four definitions for pericarditis and elucidated diagnostic criteria for each (Table 10–18). Viral infections (especially infections with coxsackieviruses and echoviruses but also influenza, Epstein-Barr, varicella, hepatitis, mumps, and HIV viruses) are the most common cause of acute pericarditis and probably are responsible for many cases classified as idiopathic. Males—usually under age 50 years—are most commonly affected. The differential diagnosis primarily requires exclusion of acute MI. Tuberculous pericarditis is rare in developed countries but remains common in certain areas of the world. It results from direct lymphatic or hematogenous spread; clinical pulmonary involvement may be absent or minor, although associated pleural effusions are common. Bacterial pericarditis is equally rare and usually results from direct extension from pulmonary infections. Pneumococci, though, can cause a primary pericardial infection. Borrelia burgdorferi, the organism responsible for Lyme disease, can also cause myopericarditis (and occasionally heart block). Uremic pericarditis is a common complication of chronic kidney disease. The pathogenesis is uncertain; it occurs both with untreated uremia and in otherwise stable dialysis patients. Spread of adjacent lung cancer as well as invasion by breast cancer, renal cell carcinoma, Hodgkin disease, and lymphomas are the most common neoplastic processes involving the pericardium and have become the most frequent causes of pericardial tamponade in many countries. Pericarditis may occur 2–5 days after infarction due to an inflammatory reaction to transmural myocardial necrosis (post-MI or postcardiotomy pericarditis [Dressler syndrome]). Radiation can initiate a fibrinous and fibrotic process in the pericardium, presenting as subacute pericarditis or constriction. Radiation pericarditis usually follows treatments of more than 4000 cGy delivered to ports including more than 30% of the heart.

Other causes of pericarditis include connective tissue diseases, such as lupus erythematosus and rheumatoid arthritis, drug-induced pericarditis (minoxidil, penicillins, clozapine), and myxedema. In addition, pericarditis may result from pericardial injury from invasive cardiac procedures (such as cardiac pacemaker and defibrillator perforation and intracardiac ablation, especially atrial fibrillation ablation), and the implantation of intracardiac devices (such as ASD occluder devices).

Pericarditis and myocarditis may coexist in 20–30% of patients. Myocarditis is often suspected when there is an elevation of serum troponins, although there are no data that suggest troponin elevations are associated with a poor prognosis.

A. Symptoms and Signs

The presentation and course of inflammatory pericarditis depend on its cause, but most syndromes have associated chest pain, which is usually pleuritic and postural (relieved by sitting). The pain is substernal but may radiate to the neck, shoulders, back, or epigastrium. Dyspnea may also be present and the patient is often febrile. A pericardial friction rub is characteristic, with or without evidence of fluid accumulation or constriction. The presentation of tuberculous pericarditis tends to be subacute, but nonspecific symptoms (fever, night sweats, fatigue) may be present for days to months. Pericardial involvement develops in 1–8% of patients with pulmonary tuberculosis. Symptoms and signs of bacterial pericarditis are similar to those of other types of inflammatory pericarditis, but patients appear toxic and are often critically ill. Uremic pericarditis can present with or without symptoms; fever is absent. Often neoplastic pericarditis is painless, and the presenting symptoms relate to hemodynamic compromise or the primary disease. At times the pericardial effusion is very large, consistent with its chronic nature. Post-MI or postcardiotomy pericarditis (Dressler syndrome) usually presents as a recurrence of pain with pleural-pericardial features. A rub is often audible, and repolarization changes on the ECG may be confused with ischemia. Large effusions are uncommon, and spontaneous resolution usually occurs in a few days. Dressler syndrome occurs days to weeks to several months after MI or open heart surgery, may be recurrent, and probably represents an autoimmune syndrome. Patients present with typical pain, fever, malaise, and leukocytosis. Rarely, other symptoms of an autoimmune disorder, such as joint pain and fever, may occur. Tamponade is rare with Dressler syndrome after MI but not when it occurs postoperatively. The clinical onset of radiation pericarditis is usually within the first year but may be delayed for many years; often a full decade or more may pass before constriction becomes evident.

B. Laboratory Findings and Diagnostic Studies

The diagnosis of viral pericarditis is usually clinical, and leukocytosis is often present. Rising viral titers in paired sera may be obtained for confirmation but are rarely done. Cardiac enzymes may be slightly elevated, reflecting an epicardial myocarditis component. The echocardiogram is often normal or reveals only a trivial amount of extra fluid during the acute inflammatory process. The diagnosis of tuberculous pericarditis can be inferred if acid-fast bacilli are found elsewhere. The tuberculous pericardial effusions are usually small or moderate but may be large when chronic. The yield of mycobacterial organisms by pericardiocentesis is low; pericardial biopsy has a higher yield but may also be negative, and pericardiectomy may be required. If bacterial pericarditis is suspected on clinical grounds, diagnostic pericardiocentesis can be confirmatory. In uremic patients not on dialysis, the incidence of pericarditis correlates roughly with the level of blood urea nitrogen (BUN) and creatinine. The pericardium is characteristically “shaggy” in uremic pericarditis, and the effusion is hemorrhagic and exudative. The diagnosis of neoplastic pericarditis can occasionally be made by cytologic examination of the effusion or by pericardial biopsy, but it may be difficult to establish clinically if the patient has received mediastinal radiation within the previous year. Neoplastic pericardial effusions develop over a long period of time and may become quite huge (more than 2 L). The sedimentation rate is high in post-MI or postcardiotomy pericarditis and can help confirm the diagnosis. Large pericardial effusions and accompanying pleural effusions are frequent. Myxedema pericardial effusions due to hypothyroidism usually are characterized by the presence of cholesterol crystals within the fluid.

C. Other Studies

The ECG usually shows generalized ST and T wave changes and may manifest a characteristic progression beginning with diffuse ST elevation, followed by a return to baseline and then to T-wave inversion. Atrial injury is often present and manifested by PR depression, especially in the limb leads. The chest radiograph is frequently normal but may show cardiac enlargement (if pericardial fluid is present), as well as signs of related pulmonary disease (eFigure 10–79). Mass lesions and enlarged lymph nodes may suggest a neoplastic process. About 60% of patients have a pericardial effusion (usually mild) detectable by echocardiography. MRI and CT scan can visualize neighboring tumor in neoplastic pericarditis. A screening chest CT or MRI is often recommended to ensure there are no extracardiac diseases contiguous to the pericardium. A consensus statement from the American Society of Echocardiography proposes adding an elevated CRP and late gadolinium enhancement of the pericardium to confirmatory criteria for the diagnosis of pericarditis. There are data that the degree of quantitative delayed enhancement of the pericardium is associated with a higher rate of recurrent pericarditis. PET scanning can also be used to help define pericardial inflammation.

For acute pericarditis, experts suggest a restriction in activity until symptom resolution. For athletes, the duration of exercise restriction should be until resolution of symptoms and normalization of all laboratory tests (generally 3 months). The 2015 ESC guidelines recommend aspirin 750–1000 mg every 8 hours for 1–2 weeks with a taper by decreasing the dose 250–500 mg every 1–2 weeks or ibuprofen 600 mg every 8 hours for 1–2 weeks with a taper by decreasing the dose by 200–400 mg every 1–2 weeks. Gastroprotection should be included. Studies support initial treatment of the acute episode with colchicine to prevent recurrences. Colchicine should be added to the nonsteroidal anti-inflammatory medication at 0.5–0.6 mg once (for patients less than 70 kg) or twice (for patients more than 70 kg) daily and continued for at least 3 months. Tapering of colchicine is not mandatory; however, in the last week of treatment, the dosage can be reduced every other day for patients less than 70 kg or once a day for those more than 70 kg. Aspirin and colchicine should be used instead of nonsteroidal anti-inflammatory medications in post-MI pericarditis (Dressler syndrome), since nonsteroidal anti-inflammatory medications and corticosteroids may have an adverse effect on myocardial healing. Aspirin in doses of 750–1000 mg three times daily for 1–2 weeks plus 3 months of colchicine is the recommended treatment for Dressler syndrome. Despite initial treatment, recurrence has been reported in about 30%.

Colchicine should be used for at least 6 months as therapy in all refractory cases and in recurrent pericarditis. At times a longer duration of therapy is required. The CRP is used to assess the effectiveness of treatment, and once it is normalized, tapering is initiated. Indomethacin in doses of 25–50 mg every 8 hours can also be considered in recurrent pericarditis in place of ibuprofen. Systemic corticosteroids can be added in patients with severe symptoms, in refractory cases, or in patients with immune-mediated etiologies, but such therapy may entail a higher risk of recurrence and may actually prolong the illness. Colchicine is recommended in addition to corticosteroids, again for at least 3 months, to help prevent recurrences. Prednisone in doses of 0.25–0.5 mg/kg/day orally is generally suggested with tapering over a 4- to 6-week period.

As a rule, symptoms subside in several days to weeks. The major early complication is tamponade, which occurs in less than 5% of patients. There may be recurrences in the first few weeks or months. Rarely, when colchicine therapy alone fails or cannot be tolerated (usually due to gastrointestinal symptoms), the pericarditis may require more significant immunosuppression, such as cyclophosphamide, azathioprine, intravenous human immunoglobulins, interleukin-1 receptor antagonists (anakinra), or methotrexate. If colchicine plus more significant immunosuppression fails, surgical pericardial stripping may be considered in recurrent cases even without clinical evidence for constrictive pericarditis.

Standard antituberculous medication therapy is usually successful for tuberculous pericarditis (see Chapter 9), but constrictive pericarditis can occur. Uremic pericarditis usually resolves with the institution of—or with more aggressive—dialysis. Tamponade is fairly common, and partial pericardiectomy (pericardial window) may be necessary. Whereas anti-inflammatory agents may relieve the pain and fever associated with uremic pericarditis, indomethacin and systemic corticosteroids do not affect its natural history. The prognosis with neoplastic effusion is poor, with only a small minority surviving 1 year. If it is compromising the clinical comfort of the patient, the effusion is initially drained percutaneously. Attempts at balloon pericardiotomy have been abandoned because outcomes were not more effective than simple drainage. A pericardial window, either by a subxiphoid approach or via video-assisted thoracic surgery, allows for partial pericardiectomy. Instillation of chemotherapeutic agents or tetracycline may be used to reduce the recurrence rate. Symptomatic therapy is the initial approach to radiation pericarditis, but recurrent effusions and constriction often require surgery.

Patients who do not respond initially to conservative management, who have recurrences, or who appear to be developing constrictive pericarditis should be referred to a cardiologist for further assessment.