Pearls and perils of acute pericarditis

Etiology of acute pericarditis

Pericarditis is a common disease but is usually subclinical. Causes of pericarditis include idiopathic, infectious, and systemic disease, trauma, neoplasm, and iatrogenic causes, both surgical and medical.[1]

Causes of acute pericarditis in immunologically competent patients are shown in Table 1.[2] Viral infection has been postulated as the most common cause of idiopathic pericarditis. Causes of acute pericarditis in HIV-positive patients are demonstrated in Table 2.[3]

Systemic diseases that cause pericarditis can be categorized as follows:[4]

• Vasculitis/connective tissue disease, such as rheumatoid arthritis, systemic lupis erythematosus (SLE), systemic sclerosis, CREST syndrome, and inflammatory bowel disease.

• Hypersensitivity and immunopathy, such as serum sickness, post-myocardial infarction, and drugs such as procainamide, hydralazine, reserpine, methyldopa, isoniazid, methysergide, and doxorubicin.

• Metabolic diseases such as renal failure and hypothyroidism.

In the pre-dialysis era, uremic pericarditis affected 35% to 50% of chronic renal failure patients, but occurred in a smaller percentage in the acute renal failure setting. With advances in diagnosis and treatment, the incidence of acute pericarditis prior to the onset of dialysis has fallen to less than 10%, but the incidence of pericarditis after dialysis has remained the same at 8% to 12%. A variety of factors have been suggested as the causes of this, such as calcium, uric acid, and blood urea nitrogen (BUN), but the ultimate cause remains unknown.[5]

In the pre-thrombolytic era, postmyocardial infarction pericarditis usually developed on day 2 or day 3 after a transmural infarction. The clinical course is benign and the prognosis is not altered by the development of this complication.[6]

Another type of myocardial infarction-related pericarditis, Dressler’s syndrome, usually develops within weeks to months after acute myocardial infarction.[7] The mechanism is thought to be an autoimmune reaction.

The GISSI trial found that thrombolytic treatment halved the incidence of postinfarction pericarditis. However, this complication was shown to be associated with a larger myocardial infarction and a significant increase in 6 and 12 months’ mortality.[8] Dressler’s syndrome has become a rare phenomenon in the patients who benefit from thrombolytic treatment.

Recurrent pericarditis is most commonly observed in the cases of acute nonspecific pericarditis. The recurrence rate appears to be in the range of 15% to 32% after an initial attack. The cause is still unknown, although some cases can be traced to viral infection or may be the consequence of coronary bypass grafting.[9]

Diagnosis

Symptoms

The typical pericardial pain is described as a retrosternal or precordial sharp pain. The character of the pain is almost always pleuritic, usually aggravated by inspiration, coughing, and sometimes by swallowing. The pain usually worsens with recumbence and is relieved by leaning forward.[1] On occasion the pain may imitate the pain of acute myocardial infarction, as well as pulmonary infarction. The symptoms of pericardial effusion include dyspnea, orthopnea, fatigue, weakness, and syncope.

Signs

Pericardial rub is the pathognomomic sign of pericarditis. It is nearly 100% specific, but not very sensitive. The pericardial rub is supposedly caused by friction between the two layers of the inflamed pericardium, but it may also persist in the presence of a significant pericardial effusion. The character of the rub is usually a scratchy or scraping superficial sound. More than 50% have a triphasic component. The monophasic rub is the least common.

ECG

Typically, the acute ECG change in acute pericarditis is a concave-upward ST-segment elevation in all leads except aVr and V1.[1] There are few ECG clues to help differentiate acute pericarditis from acute myocardial infarction. These are demonstrated in Table 3. Other differential diagnoses of this ECG pattern, other than acute myocardial infarction, include early repolarization and ventricular aneurysm.

The ST-segment elevation as a result of early repolarization is more commonly observed in young black males.[13] It is also usually J-point elevation as opposed to the true ST-segment elevation. Furthermore, it is persistent and occurs in the absence of chest pain.

The most helpful ECG criteria may be the ST-T ratio (as demonstrated in Figure 1) in V6 greater than or equal to 0.25, which indicated acute pericarditis in all 19 patients in one study.[14]

CPK

Cardiac isoenzyme is usually normal except for a modest elevation of the MB fraction, which may occur in the presence of myopericarditis.

Imaging 

An echocardiogram is very sensitive for the detection of pericardial effusion. It is therefore the investigation of choice for the diagnosis of pericardial diseases.[1,15]

Gadolinium-DTPA (diethylene triamine penta acetic acid) enhanced magnetic resonance imaging has also been reported to successfully identify the exact region of the inflamed pericardium.[16]

CT and MRI provide more diagnostic information in certain cases,[17] such as constrictive pericarditis. The use of CT and MRI in acute pericarditis is not routinely needed. The success of pericardioscopy in increasing the diagnostic yield has been reported.[18]

Pericardial biopsy 

If performed in selected patients, pericardial biopsy has a higher diagnostic yield, especially in patients with cardiac tamponade. However, it is not routinely performed for general diagnostic purposes.[2]

Complications

Pericardial effusion

Pericardial effusion may complicate acute pericarditis of any cause. Spontaneous hemorrhagic pericarditis has also been reported.

Pericardial tamponade

The classic quartet of tamponade consists of tachycardia, hypotension, increased pulsus paradoxus, and jugular venous distension. Significant pulsus paradoxus was present in more than 98% of patients with tamponade in one study of 56 cases, but it may be absent in cases of left ventricular hypertrophy, severe left ventricular failure, or severe aortic regurgitation, as well as in severe hypotension.[19]

Constrictive pericarditis

Constrictive pericarditis is a chronic complication of acute pericarditis. Tuberculosis was once the most common cause, but with the declining incidence of tuberculosis the most common cause of constrictive pericarditis currently is idiopathic. This process results in the elevation of the latter two-thirds of the ventricular filling pressure, leading to venous hypertension, and consequently leads to symptoms and signs of right-sided heart failure.

Arrhythmia

Pericarditis is also thought to be a possible cause of arrhythmia, but one study using Holter monitoring in 49 patients with acute pericarditis failed to demonstrate this relationship.[20]

Treatment

The treatment of acute pericarditis should be directed at treating the underlying cause, when possible. However, the most common cause is viral infection, which is usually self-limited.

In purulent pericarditis, antibiotics and surgical drainage are mandatory.[8]

Symptomatic therapy is aimed at the control of pain, which usually responds to amino salicylic acid (650 mg every 3 to 4 hours) or indomethacin (25 to 50 mg four times a day taken orally). The dose can be tapered off after the patient has been asymptomatic for 5 to 7 days.[1] Corticosteroids may be helpful if the pain is severe and doesn’t respond to the above treatments within 48 hours.

In the case of recurrent pericarditis or steroid-dependent pericarditis, several studies have shown that colchicine is an effective substitute, prescribed as a loading dose of 3 mg and maintenance at 1 mg daily for 1 to 27 months.[21] The mechanism of action is its anti-inflammatory effect on neutrophil function.

Incidence of misdiagnosis with acute myocardial infarction

A misdiagnosis may be made because of the similar clinical presentation of chest pain and/or localized ST elevation.[21] Therefore, these patients might erroneously receive thrombolytic treatment.

Prior to the use of standard ECG criteria for thrombolytic treatment in acute myocardial infarction, the rate of misdiagnosis ranged from 5.8% (in the GISSI trial [11 806 patients]) to 10.5% (in the ASSET trial [13 308 patients]).[22,23]

The TAMI trials 1-5, which imposed ECG criteria for thrombolytic treatment in acute myocardial infarction, demonstrated that the percentage of the misdiagnosis dropped significantly to 1.4%; furthermore, acute pericarditis accounted for only 0.27% of the misdiagnosed group (3/1387).[24]

The early administration of intravenous thrombolytic treatment to the patients with acute myocardial infarction reduces early mortality compared to the placebo treatment.[22,23] The risk of serious bleeding remains a concern, especially in patients who present with cardiovascular conditions mimicking acute myocardial infarction, including acute pericarditis. These patients are at risk for unnecessary bleeding complication from thrombolytic treatment.

There are several reported cases of acute pericarditis patients who were initially misdiagnosed as acute myocardial infarction and received thrombolysis, as demonstrated in Table 4. Most patients of pericarditis who mistakenly received thrombolytic treatment developed no complication. However, there was still a small chance that these patients could develop cardiac tamponade, but when it was detected in time to perform pericardiocentesis when indicated, most of these patients were shown to have saved outcomes.

Similar outcomes were reported in 1995 in France. Nine patients with myopericarditis were reported to have received thrombolytic treatment; only one patient developed small and no clinical pericardial effusion.[26]

In conclusion, most—but not all—of the patients with pericarditis who received thrombolytic treatment did not develop cardiac tamponade.

When to perform pericardiocentesis

There is no consensus in the available literature with respect to the timing of pericardiocentesis in cases of misdiagnosed pericarditis patients who receive thrombolytic treatment.

In the setting of acute myocardial infarction developing cardiac tamponade after thrombolytic treatment, there was a report of four patients who had pericardiocentesis performed at 20 +/- 6 hours after thrombolytic treatment with favorable outcomes.[31]

Case 1

A 58-year-old woman presented to a community hospital complaining of a 4-hour history of retrosternal chest pain radiating to her neck and back. She had no previous coronary artery disease but had history of type II diabetes mellitus, hypertension, past smoking, and hypercholesterolemia. There was no antecedent history of viral illness.

The initial physical examination did not reveal a pericardial rub. The ECG was normal. The diagnosis of unstable angina was entertained and the patient was treated with ASA, a beta-blocker, intravenous heparin, and intravenous nitroglycerine.

Six hours later she developed recurrent chest pain. The repeated ECG was interpreted as an acute inferolateral wall myocardial infarction (Figure 2 [Figure not available online]). Streptokinase (1.5 million IU) was administered intravenously over 60 minutes. She continued to have chest pain, so she was transferred to a tertiary centre for possible urgent coronary angiography.

There, physical examination revealed a biphasic pericardial rub. Serial cardiac enzyme measurements remained normal and the subsequent ECG showed no evolution of the ST-segment (Figure 3). The diagnosis of acute pericarditis was made and the patient was treated with oral ASA (650 mg) every 6 hours. An echocardiogram showed a small pericardial effusion without any signs of cardiac tamponade.

Eight days later, the patient became hypotensive and had a pulsus paradoxus of 15 mm.Hg. Repeat echocardiogram revealed moderate- to large-sized pericardial effusion with evidence of a pericardial tamponade. An urgent echocardiogram-guided pericardiocentesis was performed with the aspiration of 1000 mL of bloody fluid.

The patient subsequently improved and was discharged home 3 days later with ASA for symptomatic treatment for 10 days. Persantine MIBI (a heart perfusion scan) prior to discharge revealed no evidence of ischemia. Pericardial fluid was negative for malignancy and culture.

Case 2 

An 81-year-old woman presented to the hospital emergency room with a 6-hour history of retrosternal pressure-type chest pain. She has no previous history of coronary artery disease or cardiac risk factors other than history of uncontrolled hypertension. There was also no previous history of renal disease. Physical examination did not reveal a pericardial rub.

The ECG showed ST-segment elevation consistent with an acute anteroseptal myocardial infarction (Figure 4). The initial creatine kinase (CK) was 378 with an MB fraction of 6 (1.5%). Laboratory investigations showed pH of 7.18 with an anion gap metabolic acidosis, BUN of 32.1 (normal 2.5 to 8), and creatinine of 717 (normal 40 to 120).

The presumptive diagnosis of acute myocardial infarction was made. An urgent cardiac catheterization showed no evidence of significant coronary artery disease. She was referred to nephrology, and urgent hemodialysis was initiated.

Her chest pain resolved after the first run of hemodialysis. CK enzyme peaked at 693 with an MB fraction of 9 (1.2%). Serial ECG revealed ST-segment evolution compatible with acute pericarditis.

The patient improved but required regular hemodialysis. Her kidney biopsy subsequently showed chronic glomerulonephritis. An echocardiogram 10 days later showed no evidence of pericardial fluid or evidence of constrictive pericarditis.

Competing interests

None declared.

Table 1. Causes of acute pericarditis in immunologically competent patients.[2]

Table 2. Causes of acute pericarditis in HIV-positive patients.[3]

Note: These percentages do not total 100%, but are reproduced as reported in the original paper.

Table 3. ECG criteria that help differentiate acute pericarditis from acute myocardial infarction.

Table 4. Reported cases of acute pericarditis patients who were initially misdiagnosed as acute myocardial infarction and received thrombolytic treatment.

Mann Chandavimol, MD, FRCPC, Stephen Cheung, MD, FRCPC, and Andrew Ignaszewski, MD, FRCPC, FACC

Dr Chandavimol is a cardiology resident at the University of British Columbia, Vancouver. Dr Cheung is a cardiology resident at the University of Massachusetts Medical Center, Worcester, Massachusetts. Dr Ignaszewski is the medical director of Healthy Heart and Heart Function Clinic, St. Paul’s Hospital, Vancouver.