Background
The pericardium, a term originating from the Greek words ” περί” (around) and “κάρδιον” (heart), is a delicate, fibrous sac that encloses the heart and the roots of its major vessels. This sac is composed of two layers: the inner serous visceral layer and the outer fibrous parietal layer. Under normal physiological conditions, the pericardial space between these layers contains a small amount, typically 10 to 50 mL, of pericardial fluid, which is essentially plasma ultrafiltrate. Inflammation of this pericardial sac is termed pericarditis.
Pericardial syndromes encompass a range of conditions, including pericarditis (in its acute, subacute, chronic, and recurrent forms), pericardial effusion (fluid buildup), cardiac tamponade (pressure on the heart due to fluid), and pericardial masses. Among these, pericarditis stands out as the most prevalent pericardial disease globally, frequently affecting young and middle-aged individuals. It accounts for approximately 0.2% of all hospital admissions related to cardiovascular issues and about 5% of patients presenting with non-ischemic chest pain in emergency departments across North America and Western Europe. Acute pericarditis is the most frequently encountered pericardial syndrome in clinical practice.
This article provides an in-depth review of acute pericarditis, covering its underlying causes, clinical presentation, key inflammatory markers, electrocardiogram (ECG) findings, and the role of multimodality imaging in diagnosis. We will also briefly touch upon the differential diagnosis to distinguish pericarditis from other conditions.
Etiology of Pericarditis
Pericarditis can occur as an isolated condition or as an initial sign of a broader systemic disease. The causes of acute pericarditis are broadly categorized into infectious and non-infectious origins, as outlined in Table 1. The specific cause often depends on factors such as geographical location, patient demographics, and the clinical setting. Notably, viral infections are the leading cause in developed countries, whereas tuberculosis is more common in developing nations. In regions where tuberculosis is endemic, it frequently co-exists with human immunodeficiency virus (HIV) infection. Among non-infectious causes, autoimmune diseases, metastatic cancers, and post-cardiac injury syndromes are the most frequently observed.
Table 1. Main Causes of Acute Pericarditis
| Categories | Causes | Frequency |
|---|---|---|
| A. Idiopathic | Unknown | Most frequent cause |
| B. Infectious Causes | ||
| Viral | Epstein-Barr virus, influenza virus, hepatitis virus, human immunodeficiency virus, mumps virus, echovirus, adenovirus, cytomegalovirus, varicella-zoster virus, rubella virus, human herpesvirus, parvovirus, coxsackievirus | Most frequent cause in developed countries |
| Bacterial | Mycobacterium tuberculosis, Coxiella burnetii, Streptococcus spp., Staphylococcus spp., Pneumococcus spp., Legionella spp., Salmonella spp., Haemophilus spp. | Rare (except Mycobacterium tuberculosis) |
| Fungal | Candida spp., Aspergillus spp., Histoplasma spp., Blastomyces spp. | Very rare |
| Parasitic | Toxoplasma gondii, Echinococcus spp. | Very rare |
| C. Non-Infectious Causes | ||
| Neoplastic | Primary: Pericardial mesothelioma Secondary tumors: Leukemia, breast cancer, lung cancer, lymphoma, melanoma | Frequent as secondary metastasis |
| Metabolic | Hypothyroidism, renal failure, hypercholesterolemia, gout, anorexia nervosa | Frequent |
| Cardiovascular | Acute myocardial infarction, Dressler’s syndrome, aortic dissection | Frequent |
| Autoimmune | Rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, dermatomyositis, sarcoidosis, systemic vasculitides, Behçet’s syndrome, familial Mediterranean fever | Frequent |
| Traumatic and iatrogenic | Catheterization, surgery, chest trauma, radiation therapy | Frequent |
| Drug-related | Phenytoin, minoxidil, isoniazid, procainamide, hydralazine, methyldopa, doxorubicin, amiodarone, clozapine, streptomycin | Rare |
| Other | Congenital absence of pericardium | Rare |
Diagnostic Evaluation of Pericarditis
Diagnosing pericarditis involves a comprehensive approach, starting with a detailed medical history, particularly inquiring about recent viral infections. A thorough physical examination is crucial to detect pericardial friction rubs during auscultation and identify any signs of underlying systemic diseases. Blood tests, including white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), troponin levels, complete blood count (CBC), urea, and creatinine, are essential. An electrocardiogram (ECG), transthoracic echocardiography (TTE), and chest X-ray are also standard diagnostic tools.
Clinical Presentation of Acute Pericarditis
Acute pericarditis is defined as an “inflammatory pericardial syndrome, which may or may not involve pericardial effusion.” The diagnosis is primarily clinical and is established based on the presence of at least two of the following criteria:
- Pericardial chest pain: A characteristic symptom in the patient’s medical history.
- Pericardial friction rub: Heard during auscultation.
- ECG changes: New widespread ST-segment elevation or PR depression.
- Pericardial effusion: New or worsening effusion detected on imaging.
Supportive diagnostic findings include elevated inflammatory markers and evidence of pericardial inflammation from computed tomography (CT) or cardiac magnetic resonance (CMR) imaging. Certain clinical features at presentation are indicative of a poorer prognosis, such as a temperature above 38°C (100.4°F), subacute symptom onset, large pericardial effusion (>20 mm), tamponade, and lack of response to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs). Minor risk factors include concurrent myocarditis, immunocompromised status, trauma, and oral anticoagulant therapy.
Chest pain is the predominant symptom in acute pericarditis, reported in 85% to 90% of cases. This pain often radiates to the trapezius ridge of the left shoulder or arm and can mimic ischemic pain. However, pericarditic chest pain is typically sharp and pleuritic in nature, worsened by lying supine, coughing, and deep inspiration. Conversely, pain usually eases when sitting upright and leaning forward, due to reduced pressure on the parietal pericardium. Common accompanying symptoms include low-grade intermittent fever, shortness of breath (dyspnea), cough, general discomfort (malaise), muscle pain (myalgia), and sometimes hiccups. Patients’ medical history often reveals recent symptoms suggestive of a viral infection.
A pericardial friction rub, a pathognomonic sign of pericarditis, is audible in about one-third of patients during auscultation. This sound is described as a superficial, scratchy or squeaking noise, best heard with the stethoscope’s diaphragm over the left sternal border, with the patient leaning forward. The rub typically has three phases, corresponding to heart movements during atrial systole (absent in atrial fibrillation), ventricular systole, and the rapid filling phase of early ventricular diastole. In some instances, the rub may have only two or even one component. It’s important to note that a pericardial friction rub can disappear not only as pericarditis resolves but also with the accumulation of more pericardial fluid, indicating either improvement or worsening of the condition. The intensity of the friction rub in acute pericarditis can vary from moment to moment, a characteristic less common in other forms of pericarditis. The auscultation of a pericardial friction rub is highly specific for acute pericarditis, with a specificity of approximately 100%.
ECG Findings in Pericarditis
Characteristic ECG changes in acute pericarditis are observed in up to 60% of cases and typically progress through four stages (Figure 1). Initially (within hours to days), the ECG shows diffuse concave ST-segment elevation across most leads (except aVR and often V1) along with PR depression (stage 1). This is followed by a return of ST-segments and PR segments to baseline, and T-wave flattening (stage 2), usually within the first week. Subsequently, diffuse T-wave inversions appear after the ST-segments become isoelectric (stage 3), and finally, the ECG may normalize or T-wave inversions may persist (stage 4). Sustained atrial or ventricular arrhythmias are uncommon in acute pericarditis; their presence may suggest concomitant myocarditis or another underlying cardiac condition.
Figure 1. ECG of a 32-Year-Old Man with Acute Pericarditis, Presenting with Chest Pain. Note the characteristic concave ST elevation in leads I, II, aVL and V5-V6.
The ECG in acute pericarditis can resemble that of ST-elevation myocardial infarction (STEMI). ECG features that help distinguish acute pericarditis from STEMI include:
- ST-elevation typically less than 5 mm.
- Concave ST-segment morphology.
- More widespread lead involvement.
- Less pronounced reciprocal ST-segment depression.
- PR-segment elevation in lead aVR with reciprocal PR-segment depression in other leads.
- Absence of abnormal Q-waves.
- Variable timing of T-wave inversion following ST-segment elevation.
- Lack of QRS widening and QT interval shortening in leads with ST elevation.
Distinguishing acute pericarditis ECG from early repolarization patterns can also be challenging. In acute pericarditis, the ratio of ST elevation to T-wave amplitude in lead V6 is often greater than 0.24, a useful differentiating sign with high positive and negative predictive values. A study suggested using leads I and V4-V6 to differentiate acute pericarditis from early repolarization and left ventricular hypertrophy, finding that an ST/T amplitude ratio ≥0.25 in leads I, V4, V5, and V6 was predictive of acute pericarditis, particularly when ST elevation was present in lead I.
Laboratory Tests – Inflammatory Markers
Elevated inflammatory markers are frequently observed in patients with acute pericarditis. The most commonly used markers include white blood cells (WBCs), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). CRP levels are particularly useful not only for confirming the diagnosis but also for monitoring disease activity and guiding treatment adjustments based on individual patient characteristics.
In cases of myopericarditis (pericarditis with concurrent myocarditis), serum biomarkers of myocardial injury, such as creatine kinase (CK) and troponins (troponin I or T), are elevated. Troponin assessment is primarily used to rule out myopericarditis, as it does not appear to have prognostic value in acute pericarditis alone. Interestingly, pericarditis patients with elevated myocardial injury biomarkers almost invariably exhibit ECG changes characteristic of ST-segment elevation.
Emerging biomarkers such as carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), an immune inhibitory protein, and MHC class I chain related protein A (MICA), an immune-stimulating protein, show promise for prognostic value in acute and recurrent pericarditis. These serum proteins can be released from damaged or inflamed pericardial tissues. Studies have shown that patients with acute pericarditis often have elevated serum CEACAM1 levels, possibly due to unique splicing in injured pericardial cells or other mechanisms like proteolytic cleavage. While serum MICA levels may be elevated in some pericarditis patients, significant correlations were particularly noted in recurrent pericarditis cases, suggesting MICA as a potential prognostic marker for recurrence, independent of other confounding factors.
Routine laboratory evaluation should also include markers of renal function (urea, creatinine), electrolytes, lactate dehydrogenase (LDH), and liver transaminases (SGOT, SGPT). Depending on clinical suspicion, further specific tests may be warranted, such as blood cultures, thyroid function tests, antinuclear antibodies (ANA), anti-neutrophil cytoplasm antibodies (ANCA), anti-extractable nuclear antigens (ENA), HIV testing, and even pericardial biopsy.
Chest X-ray in Pericarditis
In patients with acute pericarditis, chest X-rays are often normal, as cardiomegaly becomes apparent only with pericardial effusions exceeding 300 mL. Chest X-rays may reveal signs of pleuropericardial involvement in the context of underlying pleuropulmonary disease. They can also help identify malignancies, sarcoidosis, or certain infections that may be the cause of pericarditis. Small pleural effusions may be present, especially in viral or mycoplasmal infections. Unexplained new-onset cardiomegaly, particularly with clear lung fields, should prompt evaluation for acute pericarditis.
Echocardiography for Pericarditis Diagnosis
Echocardiography is a cost-effective, widely accessible, and rapidly deployable imaging modality. It offers valuable insights into pericardial disease, including the thickness and echogenicity of the pericardial layers, the presence, volume, and hemodynamic impact (tamponade, restriction) of pericardial effusion. Pericardial effusion, if present, is typically mild and is detected in about 60% of acute pericarditis cases. M-mode echocardiography can demonstrate pericardial effusion as an echo-free space between the pericardial layers during both systole and diastole; a simple systolic separation might be considered physiological. Pericardial effusion is classified based on diastolic size: mild (<10 mm), moderate (10-20 mm), and large (>20 mm). However, transthoracic echocardiography (TTE) has limitations, such as poor image quality in obese patients or those with chronic obstructive pulmonary disease (COPD), limited tissue characterization, and operator dependence. These limitations have spurred the development of other imaging techniques to aid in diagnosing pericarditis.
Figure 2. Echocardiographic Examination (parasternal short-axis view) of a 60-Year-Old Woman with Acute Pericarditis Reveals Echo-Free Space.
CT and CMR in Pericarditis Diagnosis
Multimodality imaging, including CT and CMR, plays an integral role in the diagnostic workup of acute pericarditis, especially when echocardiography is inconclusive or needs further clarification. Cardiac CT offers advantages in assessing pericardial calcifications and thickening, as well as evaluating for associated diseases. ECG-gated CT techniques provide high-quality images with minimal motion artifacts. However, CT involves ionizing radiation and iodinated contrast agents, requires breath-holding, and may not be suitable for unstable patients or those with arrhythmias.
Cardiac magnetic resonance (CMR), on the other hand, excels in tissue characterization, assessment of pericardial thickening and constriction, and evaluation of myocardial involvement. CMR does not use radiation or nephrotoxic contrast. Late gadolinium enhancement (LGE) on CMR can correlate with inflammation severity. A typical CMR protocol for pericardial disease includes cine imaging, black-blood imaging, tagging, phase-contrast sequences, and delayed enhancement imaging to assess LGE. Limitations of CMR include its time-consuming nature, higher cost, limited availability, and requirement for stable patients with regular heart rhythms. Patients with severe renal impairment or pacemakers may not be eligible for CMR.
Differential Diagnosis of Pericarditis
The differential diagnosis of acute pericarditis is broad, encompassing various conditions that present with chest pain (Table 2). These include acute coronary syndromes, aortic dissection, pulmonary embolism, pneumonia, pneumonitis, gastric ulcer, gastroesophageal reflux disease, pneumothorax, and herpes zoster.
Table 2. Differential Diagnosis of Acute Pericarditis
| Condition Category | Specific Conditions |
|---|---|
| Cardiovascular | Angina, Acute coronary syndromes, Aortic dissection, Aortic stenosis, Pulmonary embolism, Pulmonary hypertension |
| Gastrointestinal | Oesophagitis, Oesophageal spasm, Oesophageal rupture, Gastric ulcer, Pancreatitis |
| Respiratory | Pneumonia, Pneumonitis, Pleuritis, Tuberculosis, Pneumothorax |
| Musculoskeletal | Musculoskeletal disorders, Trauma |
| Neurological | Herpes zoster |
| Psychiatric | Depression, Panic disorder |
Distinguishing acute pericarditis from myocardial ischemia or infarction is crucial. This differentiation is typically made based on clinical findings, ECG, myocardial necrosis markers, and imaging, particularly echocardiography. However, coronary angiography may sometimes be necessary to definitively rule out coronary artery disease. It’s also important to consider that acute pericarditis can sometimes be the presenting manifestation of a silent myocardial infarction.
Specific Forms of Pericarditis
According to the 2015 European Society of Cardiology (ESC) guidelines on pericardial diseases, a definitive diagnosis of viral pericarditis requires comprehensive histological, cytological, immunohistological, and molecular investigations of pericardial fluid and pericardial/epicardial biopsies. In the absence of such confirmation, the term “presumed viral pericarditis” should be used. For suspected purulent pericarditis, urgent pericardiocentesis is recommended, with pericardial fluid sent for bacterial, fungal, and tuberculous studies, along with blood cultures. In patients with a history of chest trauma and systemic arterial hypotension, urgent TTE or CT is advised. For suspected malignancy-related pericarditis, cytological analysis of pericardial fluid is recommended.
Conclusions
Acute pericarditis is the most commonly encountered pericardial syndrome, with diverse etiologies. Chest pain is the cardinal symptom, often requiring differentiation from ischemic pain. The diagnosis is primarily clinical, based on fulfilling at least two of four criteria: chest pain, pericardial rub, ECG changes, and pericardial effusion. Elevated inflammatory markers and imaging evidence of pericardial inflammation (CT/CMR) provide supportive evidence. Emerging inflammatory markers like CEACAM1 and MICA hold promise for future diagnostic and prognostic applications. Multimodality imaging is indispensable in the diagnostic workup of acute pericarditis.
