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Myopericarditis versus viral or idiopathic acute pericarditis
  1. M Imazio,
  2. E Cecchi,
  3. B Demichelis,
  4. A Chinaglia,
  5. S Ierna,
  6. D Demarie,
  7. A Ghisio,
  8. F Pomari,
  9. R Belli,
  10. R Trinchero
  1. Department of Cardiology, Maria Vittoria Hospital, Torino, Italy
  1. Dr M Imazio, Cardiology Department, Maria Vittoria Hospital, Via Cibrario 72, 10141 Torino, Italy; massimo_imazio{at}yahoo.it

Abstract

Objective: To investigate the relative incidence, clinical presentation and prognosis of myopericarditis among patients with idiopathic or viral acute pericarditis.

Design: Prospective observational clinical cohort study.

Setting: Two general hospitals from an urban area of 220 000 inhabitants.

Patients: 274 consecutive cases of idiopathic or viral acute pericarditis between January 2001 and June 2005.

Main outcome measures: Relative prevalence of myopericarditis. Clinical features at presentation including echocardiographic data (ejection fraction (EF), wall motion score index (WMSI)) and follow-up data at 12 months including complications, results of echocardiography, electrocardiography and treadmill testing.

Results: Myopericarditis was recorded in 40/274 (14.6%) consecutive patients. At presentation, the following clinical features were independently associated with myopericarditis: arrhythmias (odds ratio (OR) = 17.6, 95% confidence interval (CI) 5.7 to 54.1; p<0.001), male gender (OR = 6.4, 95% CI 2.3 to 18.4; p = 0.01), age <40 years (OR = 6.1, 95% CI 2.2 to 16.9; p = 0.01), ST elevation (OR = 5.4, 95% CI 1.4 to 20.5; p = 0.013) and a recent febrile syndrome (OR = 2.8, 95% CI 1.1 to 7.7; p = 0.044). After 12 months’ follow-up an increase of EF (basal EF 49.6 (5.1)% vs 12-month EF 59.1 (4.6)%; p<0.001) and decrease of WMSI (basal WMSI 1.19 (0.27) vs 12-month WMSI 1.02 (0.09); p<0.001) were recorded in patients with myopericarditis, with a normalisation of echocardiography, electrocardiography and treadmill testing in 98% of cases. Use of heparin or other anticoagulants (OR = 1.1, 95% CI 0.3 to 3.5; p = 0.918) and myopericarditis (OR = 2.3, 95% CI 0.7 to 7.6; p = 0.187) was not associated with an increased risk of cardiac tamponade or recurrences.

Conclusions: Myopericarditis is relatively common and shows a benign evolution also in spontaneous cases not related to vaccination.

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Myopericarditis and acute pericarditis share the same viral aetiological agents, and myocardial involvement may be not uncommon in acute pericarditis.13 In clinical practice both pericarditis and myocarditis may coexist. However, they are rarely of equivalent intensity, giving rise to clinical syndromes that are mainly “pericarditic” or “myocarditic”. The term “myopericarditis” indicates a primarily “pericarditic syndrome” and it is responsible for the majority of cases encountered in clinical practice.13 A large amount of data have been recently published on myopericarditis following smallpox vaccination as a consequence of the vaccination programme for US military forces.47 On the contrary, few data are available on sporadic cases, not related to vaccinations. Viral or idiopathic pericarditis is responsible for the majority of cases of acute pericarditis in Europe and the USA.814 In clinical practice, a common concern is the possible persistence or worsening of left ventricular dysfunction after acute myopericarditis.

The aim of this work was to study the relative incidence of myopericarditis among patients with idiopathic or viral pericarditis, and compare the clinical presentation and prognosis of myopericarditis with that of acute pericarditis.

METHODS

Participants

Between January 2001 and June 2005 all consecutive patients with acute pericarditis were enrolled in a prospective cohort study from an urban area of 220 000 inhabitants. Acute pericarditis diagnosis was performed with at least two of the following criteria: pericarditic chest pain, pericardial friction rub, widespread ST-segment elevation on the electrocardiogram (ECG), and new or worsening pericardial effusion. A clinical diagnosis of myopericarditis5 6 was performed in patients with a definite diagnosis of pericarditis, and one of the following features: evidence of raised cardiac enzymes (creatine kinase (CK)-MB fraction, or troponin I or T), or new onset of focal or diffuse depressed left ventricular function by an imaging study (generally echocardiography) in the absence of evidence of any other cause.

The following indications were considered for endomyocardial biopsy: subacute or acute symptoms of heart failure refractory to standard management, substantial worsening of the ejection fraction (EF) despite optimised pharmacological treatment, development of haemodynamically significant arrhythmias, heart failure with concurrent rash, fever or peripheral eosinophilia, history of collagen vascular disease, suspicion of possible giant cell myocarditis (young age, new subacute heart failure or progressive arrhythmias without apparent aetiology). According to available published evidence,1 47 15 16 a clinical diagnosis of myopericarditis was performed even in the absence of endomyocardial biopsy in patients responsive to conventional medical treatment. Results from serological and cultural studies were considered for the viral aetiological diagnosis.

It has been shown that some cases of myopericarditis may mimic acute myocardial infarction. In such cases, an acute coronary syndrome was excluded by coronary angiography, or by a stress imaging test such as a stress echocardiogram or a nuclear stress perfusion scan, when coronary artery disease risk was considered low.6

Different aetiologies may have a substantial impact on the complication rate and the natural history of the disease. Therefore, we excluded patients with a specific aetiology and only patients with viral or idiopathic pericarditis were considered.

Treatment

Aspirin or a non-steroidal anti-inflammatory drug (NSAID) were considered the mainstay of treatment in patients with an established diagnosis of myopericarditis and acute pericarditis. Aspirin was the first-choice drug and was given at the dose of 800 mg orally every 6 or 8 hours for 7–10 days with gradual tapering over 2–3 weeks (the aspirin dose was reduced by 800 mg/day every week). In animal models of myocarditis, NSAIDs are not effective and may actually enhance the myocarditic process and increase mortality.1719

On this basis a possible reduction of the dosage of aspirin to 800 mg every 12 hours was considered for patients with myopericarditis according to the judgment of the treating doctor, when myocardial involvement was considered clinically more important. Corticosteroids were considered as the second choice for patients with contraindications or intolerance to aspirin and NSAIDs. In every case gastroprotection with a proton pump inhibitor was prescribed.

Data on the use of other treatments such as thrombolytic agents, heparin, low molecular weight heparins, glycoprotein IIb/IIIa inhibitors and oral anticoagulants were recorded, including data also for patients with a suspected acute coronary syndrome at presentation but with a final diagnosis of myopericarditis or acute pericarditis, in order to assess the possible negative influence of these treatments on the risk of cardiac tamponade, recurrences and other complications.

Clinical measures

The relative prevalence of myopericarditis was assessed among patients with viral or idiopathic acute pericarditis. Cases of acute pericarditis and myopericarditis were recorded, including the main clinical characteristics and treatments of all cases. During follow-up, echocardiography, electrocardiography and treadmill testing was performed at 6 and 12 months, and all adverse events were recorded, including recurrent pain, relapses, cardiac tamponade, constrictive pericarditis, residual left ventricular dysfunction.

Statistical analysis

Data were expressed as mean (SD). Comparison between patients groups was performed using an unpaired t-test for continuous variables and a χ2 analysis for categorical variables. A p value of <0.05 was considered to show significance. Logistic regression multivariate analysis was performed using SPSS 13.0 software (Chicago, Illinois, USA). Odd ratios were given with 95% confidence intervals (CIs).

RESULTS

In the study period 274 first episodes of viral or idiopathic acute pericarditis were recorded with an incidence of 27.7 cases per 100 000 population/year. Forty (14.6%) of them (mean (SD) age 36.0 (14.7) years, male/female ratio 3.0, peak CK 469 (325) IU/l (range 89–1222 IU/l), peak CK-MB 20 (18) ng/ml (range 6–93 ng/ml), peak cardiac troponin I 7.7 (6.7) ng/ml (range 1.5–22.5 ng/ml)) were cases of myopericarditis with an incidence of 4.0 cases per 100 000 population/year.

According to currently accepted criteria15 endomyocardial biopsy was indicated and performed in four cases, while a viral aetiological diagnosis was already available on the basis of serological or cultural studies in a further 24 cases. Table 1 gives a detailed summary of myopericarditis aetiologies.

Table 1 Aetiologies of myopericarditis in 40 patients according to diagnostic tests

The presentation mimicked a myocardial infarction in 17 patients (6.2% of all, 42.5% of those with myopericarditis): six patients (2.6%) with a final diagnosis of acute pericarditis, and 11 (27.5%) with a final diagnosis of myopericarditis (p<0.001). Fifteen of 17 (88%) agreed to coronary angiography, one patient refused to have the invasive examination. One patient had a very low risk of coronary artery disease on the basis of age, clinical history and presentation: for this patient and for the patient who refused to undergo coronary angiography, we excluded an acute coronary syndrome by a nuclear stress perfusion scan. Overall, coronary angiography was performed in 15 patients, and was normal in all cases.

Aspirin or an NSAID was prescribed in 196 patients (83.8%) with acute pericarditis and 39 patients (97.5%) with myopericarditis. Corticosteroids were prescribed respectively in 38 patients (16.2%) with acute pericarditis and one patient (2.5%) with myopericarditis, because of aspirin contraindication or intolerance.

Comparison of patients with simple acute pericarditis and myopericarditis

Compared with simple acute pericarditis (table 2), patients with myopericarditis had more frequently the following features at presentation: younger age (36.0 (14.7) years vs 54.8 (18.3) years; p<0.001), male gender (75.0% vs 45.7%; p = 0.001), recent febrile syndrome with gastrointestinal symptoms and/or skeletal muscle myalgias (50.0% vs 21.8%; p<0.001), ST-segment elevation at presentation (90.0% vs 70.1%; p = 0.018), atypical ST changes or ECG evolution as compared with classical four stages of acute pericarditis811 (42.5% vs 20.9%; p = 0.006), and cardiac arrhythmias (65.0% vs 16.7%; p<0.001), but less frequently pericardial effusion (37.5% vs 60.3%; p = 0.012).

Table 2 Comparison of the clinical characteristics of patients with myopericarditis and patients with acute pericarditis

After logistic regression multivariate analysis the following clinical features were independently associated with myopericarditis: arrhythmias (odds ratio (OR) = 17.6, 95% CI 5.7 to 54.1; p<0.001), male gender (OR = 6.4, 95% CI 2.3 to 18.4; p = 0.01), age <40 years (OR = 6.1, 95% CI 2.2 to 16.9; p = 0.01), ST elevation (OR = 5.4, 95% CI 1.4 to 20.5; p = 0.013) and a recent febrile syndrome (OR = 2.8, 95% CI 1.1 to 7.7; p = 0.044).

Follow-up data

All patients were alive at the end of the follow-up. After 12-months’ follow-up an increase of the EF (basal EF 49.6 (5.1)% vs 12-month EF 59.1 (4.6)%; p<0.001) and decrease of the wall motion score index (WMSI) were recorded (basal WMSI 1.19 (0.27) vs 12-month WMSI 1.02 (0.09); p<0.001) in patients with myopericarditis with a normalisation of echocardiography, electrocardiography, and treadmill testing in 39/40 (97.5%) cases. Moreover no significant differences were detected in the 12-month follow-up complications rate either for recurrent pain without objective evidence of disease, recurrences, cardiac tamponade, pericardial constriction or new residual left ventricular dysfunction (table 3).

Table 3 Follow-up data at 12 months

About 15.0% of patients with myopericarditis reported persistence of atypical chest pain without objective evidence of recurrence. Similar baseline clinical features were recorded in patients with or without continued symptoms, but a higher recurrence rate was found in patients with continued symptoms (66.7% vs 11.8%; p = 0.011) during follow-up.

Risk factors for recurrences and cardiac tamponade

In multivariate analysis (table 4), use of heparin, other anticoagulants, and glycoprotein IIb/IIIa inhibitors (OR = 1.1, 95% CI 0.3 to 3.5; p = 0.918) as well as myopericarditis (OR = 2.3, 95% CI 0.7 to 7.6; p = 0.187) was not associated with an increased risk of cardiac tamponade or recurrences. On the contrary, lack of complete response to aspirin or an NSAID (OR = 14.6, 95% CI 6.1 to 35.1; p<0.001), or corticosteroid use (OR = 3.0, 95% CI 1.1 to 8.9; p = 0.048) were found to be possible risk factors for complications during follow-up.

Table 4 Risk factors for complications* during follow-up in multivariate analysis

DISCUSSION

An increasing interest in myopericarditis has arisen after the identification of cases after smallpox vaccination in US military forces.47 The overall rate of symptomatic myopericarditis approached approximately 1 in 10 000, a rate similar to that reported in previous European studies in the 1960s. All evaluated patients had objective normalisation of cardiac function at follow-up, although about 20% reported persistent symptoms despite normal testing.7 Interestingly, normalisation of echocardiography, ECG and functional status was recorded even in those with a reduced EF at presentation.

Acute pericarditis may often be accompanied by some degree of myocardial involvement. In clinical practice both pericarditis and myocarditis coexist because they share common aetiological agents, mainly cardiotropic viruses. Preliminary studies have reported a possible increase of cardiac troponin in 32–50% of cases of viral and idiopathic acute pericarditis as biochemical evidence of inflammatory myocardial damage and possible evidence of myopericarditis.2 20 21 However, few data are available on spontaneous cases of myopericarditis, not related to vaccinations. Remes et al reported a good clinical outcome in a long-term follow-up of 18 patients with Coxsackievirus myopericarditis.22 Karjalainen and Heikkilä reported 19 cases of myopericarditis with a good outcome within a study primarily devoted to evaluation of the incidence and clinical presentation of myocarditis among military men in Finland.23 On the contrary, the prognosis has been reported to be less good in cases with predominant myocardial involvement.24

This study shows that recognisable myopericarditis is not uncommon in patients with acute viral or idiopathic pericarditis, and a clinical diagnosis is possible in about 10–15% of unselected cases. Myocardial involvement is particularly common in younger male patients with acute pericarditis. The following can be considered as clues to myocardial involvement in acute pericarditis: presence of cardiac arrhythmias, ST-segment elevation at presentation, atypical ECG changes and evolution, a recent febrile syndrome with gastrointestinal symptoms and/or skeletal muscle myalgias, raised serum cardiac enzymes and evidence of myocardial dysfunction on echocardiography.

There is a great concern about the possible complications after acute myopericarditis, especially the possible persistence or worsening of left ventricular dysfunction. A preliminary study has shown that, unlike acute coronary syndromes, the rise of cardiac troponin does not seem to carry an adverse prognosis.3

Our study confirms a benign clinical evolution of myopericarditis, that is, when pericarditis is predominant on myocardial involvement. At 12 months the frequency of complications was similar both in acute pericarditis and myopericarditis, with normalisation of echocardiography, electrocardiography and treadmill testing in the majority of cases.

Another common concern is the possible risk of complications related to the use of heparin, oral anticoagulants or glycoprotein IIb/IIIa inhibitors in patients with acute pericarditis or myopericarditis. The use of these drugs is common when acute pericarditis or myopericarditis mimics an acute coronary syndrome. This study shows that myopericarditis may simulate an acute coronary syndrome in about one-third of cases in unselected patients. However, either myopericarditis or the use of heparin, anticoagulants and glycoprotein IIb/IIIa inhibitors is not associated with an increased risk of cardiac tamponade or recurrences during follow-up (table 4). The main risk factors for complications are the lack of response to medical treatment within 1 week and the use of corticosteroids, as already reported in other studies.14 2528

Communication with the patient is very important. The nature of the disease, the likely course, the need for follow-up, the treatment options should be clearly explained, and the patient must be reassured about the natural history of the disease. Up to 10–15% of cases may present atypical, non-limiting chest discomfort without objective evidence of disease, as previously reported either for acute pericarditis25 or myopericarditis following smallpox vaccination.7 The clinical meaning of this observation is unclear. In patients with acute pericarditis this feature may be a marker of more chronic disease and may precede attacks of recurrent pericarditis.25 This may be true also in patients with myopericarditis. Further investigation is required in these patients with a larger study population and long-term follow-up.

Further research should also evaluate the clinical usefulness of other diagnostic techniques for myopericarditis. Contrast-enhanced magnetic resonance imaging appears to be the most promising non-invasive technique for diagnosing myocardial inflammation and myocyte injury, as reported in observational studies on myocarditis.15

Acknowledgments

We are grateful to the staff of Maria Vittoria Hospital, and Amedeo di Savoia Hospital, Torino for participation in data collection.

REFERENCES

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Footnotes

  • Funding: This research was supported by institutional funding.

  • Competing interests: None.

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