Introduction

Acute pericarditis and acute myocarditis are often difficult to distinguish; they constitute a continuum, with frontier forms named “myopericarditis”. Acute pericarditis is diagnosed in case of two of the following elements: typical chest pain or pericardial rub; typical electrocardiogram; pericardial effusion (often on echocardiography); and biological inflammatory syndrome. On the other hand, acute myocarditis involves myocardium with biomarker elevation (mainly troponin) and left ventricular (LV) dysfunction.

Acute pericarditis is rather frequent with an annual incidence estimated at 27.7 new cases per 100,000 inhabitants in Europe . About 5% of all patients with non-ischaemic chest pain who are admitted to emergency departments could have pericarditis . The causes of pericarditis vary, with most common causes including viral or bacterial infections of the pericardium . Most patients are young, with a heavy cost to society, especially due to hospitalizations.

Myocarditis is less common than pericarditis. The main difficulty in the assessment of this condition is the wide spectrum of possible clinical presentations, ranging from acute fulminant forms to late dilated cardiomyopathies. A broad range of pathological processes are involved and many classifications have been proposed . Epidemiological studies are lacking and real incidences and prevalences are not well established . Prospective post-mortem data suggested that myocarditis could be implicated in the sudden death of young adults at rates of 8.6–12% . Up to 15% of pericarditis could be considered as myopericarditis, including cardiac enzyme elevation, wall motion abnormalities, arrhythmias and conduction disturbance . The introduction of hypersensitive dosages of cardiac enzymes, such as high-sensitivity troponin, should increase the prevalence of this diagnosis; the value of these sorts of biomarkers in these clinical settings has to be investigated.

Main guidelines for acute pericarditis were published by the European Society of Cardiology (ESC), in 2004 . Diagnosis is consensually defined. Hospitalizations are recommended in the worst cases and treatments include non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, other anti-inflammatory drugs and colchicine. Although rest is highly recommended, this is difficult to obtain in this young population and the means of achieving it are lacking. Importantly, there are many problems associated with the management of this disease, including different procedures in different centres (despite guidelines), hospitalization, choice of drugs and duration of treatment. Relief of symptoms is the immediate goal for the physician, but the high risk of recurrences and even the aim of controlling the inflammatory process deserve to be considered. Guidelines for the management of myocarditis are patchier, especially for heart rate (HR)-controlling treatments.

However, HR-controlling treatments may exert several beneficial effects. HR is a well-established risk-marker for various cardiovascular diseases , including coronary artery disease and heart failure (HF) . Sinus tachycardia is almost invariably observed in myopericarditis , even in the absence of other contributing factors, such as fever or haemodynamic compromise . Nevertheless, data are scarce and sinus tachycardia is often considered as linked to pain or associated with complications of pericarditis or myocarditis, such as tamponade or acute HF, respectively. In the case of HF, suitable beta-blockers are indicated as HR-controlling treatments; however, these drugs have to be introduced after the initial phase. In other cases, the place of beta-blockers and other HR-reducing therapies has to be clarified. In this article, we review the literature, including recent results from our group suggesting a possible link between HR and pericardial inflammation, paving the way for more studies on this topic. Controlling HR could then be a new endpoint to treat pericardial inflammation and improve the symptoms (pain). Rest and a few pharmacological strategies are available to achieve this goal.

To simplify the discussion, pericarditis and myocarditis are schematically distinguished in the manuscript, even if a continuum binds the diseases. Only diseases without LV dysfunction will be extensively discussed here, as the question seems solved in that case, with strong evidence for beta-blockers. In this article, we aim to summarize the available data on HR control and the management of patients with acute pericarditis or myocarditis. Rest, beta-blockers and new HR-reducers are reviewed, and further directions are discussed.

Methods

An exhaustive review of the literature was performed, using the PubMed platform, with the following keywords: “bradycardia”; “beta-blockers”; “calcium channel inhibitors”; “pericarditis”; “myocarditis”; “myopericarditis”; “rest”; and “guidelines”. Combining two keywords, as appropriate, a total of 786 articles were initially screened and 103 were further analysed. Original data were considered as a higher level of pertinent information, including experimental data. Review articles were considered as secondary level information and are rarely cited in this manuscript. The available guidelines on the topic were screened with particular attention.

Prognostic factors: is heart rate a prognostic factor in myopericardial diseases?

Many prognostic factors have been proposed for acute pericarditis. According to a literature review , several clinical features are usually considered to be more frequently associated with an increased risk of short-term complications or a specific diagnosis: fever > 38 °C ; subacute onset (symptoms developed over a period of several days or weeks) ; immunodepression ; trauma ; oral anticoagulant therapy ; myopericarditis (pericarditis with clinical or serological evidence of myocardial involvement) ; large pericardial effusion (effusion with a diastolic echo-free space > 20 mm wide) or cardiac tamponade ; lack of initial response to aspirin or NSAIDs within 1 week ; and corticosteroid use . Some clinical features (fever > 38 °C, subacute course, large effusion or tamponade and aspirin or NSAID failure) have also been proposed as prognostic factors for higher risk of specific causal conditions and complications , and help with risk stratification when deciding about hospitalization. More recently, biological markers were proposed to stratify the risk, especially troponin, even if mildly elevated , and C-reactive protein (CRP) . Some clinical conditions may favour a higher probability of autoimmune disease, especially female sex . Although sinus tachycardia is frequently observed in patients with pericarditis , tachycardia was not clearly identified as a prognostic marker. Recently, our group identified a link between HR and CRP ( Fig. 1 ). In this retrospective study of 73 patients (median age, 38 years; interquartiles 28–51), median HR was 88.0 beats per minute on admission (interquartiles 76.0–100.0) and 72.0 beats per minute on discharge (65.0–80.0). HR on admission was significantly correlated with CRP peak ( p < 0.001), independent of temperature on admission, hospitalization duration and age. HR on hospital discharge was correlated with recurrence, independent of age. In acute pericarditis, HR on admission seemed to be independently correlated with CRP concentrations and HR on discharge seemed to be independently correlated with recurrence. This may suggest a link between HR and pericardial inflammation.

Heart rate on admission is correlated with C-reactive protein (CRP) peak in a retrospective study in patients with acute pericarditis. Reproduced from Khoueiry et al. , with permission. bpm: beats per minute.

For acute myocarditis, clinical markers, advanced New York Heart Association functional class and lack of beta-blocker therapy have been associated with poor outcome . Immunohistological signs of inflammation, but not histology (positive Dallas criteria) or viral genome detection, were also related to poor outcome . Although troponin elevation was proposed as a marker to distinguish pericarditis from myopericarditis , troponin elevation did not seem to predict outcome in myocarditis . Electrocardiography might provide additional information, especially in the presence of prolonged QRS duration . More recently, magnetic resonance imaging was proposed as the best predictor, showing that late gadolinium enhancement could be better than clinical or echocardiographical markers for predicting outcome .