Pericardial diseases

Article written and reviewed by Dr Luca Moretti

Pericardial diseases include inflammatory abnormalities, liquid or gaseous collections, fibrotic processes, neoplastic infiltrations, and congenital abnormalities of the sac surrounding the heart. This definition brings together very different conditions: some mainly cause chest pain, others hinder cardiac filling, and still others are detected incidentally during imaging. Their assessment requires distinguishing the cause, the anatomical change, and the hemodynamic consequence, because none of these three dimensions can be inferred automatically from the others. An effusion, for example, may accompany inflammation, but it may also result from altered venous pressures, hypothyroidism, or lymphatic obstruction.

Pericarditis is the most common inflammatory manifestation. Estimates of its incidence depend strongly on the population examined and on the ability to identify episodes managed without hospitalization; by contrast, there is no single incidence rate applicable to the entire spectrum of pericardial diseases. In high-income countries, idiopathic forms, presumably viral or immune-mediated, predominate, whereas tuberculosis remains far more important in endemic areas. Effusions associated with neoplasms, renal failure, and cardiac procedures are particularly represented in hospital settings, where the distribution of causes differs from that in outpatient populations.

The pericardium is not merely a covering. Its distensibility, its relationship with intrathoracic pressures, and the interaction between the two ventricles explain why a rapid accumulation of fluid can cause shock, whereas a collection that develops slowly may remain relatively well tolerated. Similarly, a modest increase in thickness may have little functional relevance, whereas a rigid envelope can severely limit filling even without marked calcification. Modern assessment therefore integrates anatomy, inflammatory activity, and circulatory physiology.

Etiology, pathogenesis, and pathophysiology

The pericardial sac consists of an outer fibrous component and a serous lining that reflects onto the surface of the heart to form the visceral layer. A small amount of fluid is present between the mesothelial surfaces, facilitating sliding during the cardiac cycle. The mesothelium, underlying connective tissue, vessels, and lymphatic drainage form a biologically active system: injury can alter permeability, recruit inflammatory cells, increase fluid production, or impair its reabsorption. Continuity with the epicardium also explains the possible association between pericardial disease and myocardial injury.

Etiologies of pericarditis include infections, immune-mediated diseases, tissue injury, metabolic conditions, drugs, and neoplasms. A bacterial infection may reach the pericardium through hematogenous spread, extension from a thoracic focus, or inoculation during a procedure. Tuberculosis often involves the pericardium in the setting of lymphatic or systemic dissemination. After cardiac injury, a delayed inflammatory response may instead develop, in which antigen exposure and immune activation contribute to a pleuropericardial syndrome. However, a simple temporal sequence between a respiratory infection and chest pain does not demonstrate viral invasion of pericardial tissue.

These causes must be distinguished from conditions that increase the likelihood of encountering them. Immunosuppression, neoplasia, dialysis, recent surgery, and intracardiac procedures modify risk and guide the etiologic workup; they do not all produce the same lesion through an identical mechanism. In a patient with cancer, for example, an effusion may result from tumor infiltration, radiotherapy, a drug, an opportunistic infection, or an unrelated cause. In rheumatic diseases, involvement may accompany systemic activity, whereas abnormalities of the innate response predominate in autoinflammatory syndromes. The label idiopathic means that an appropriate evaluation has not identified a cause; it does not constitute positive proof of a viral etiology.

Injury to the serosal surfaces causes mesothelial desquamation, increased vascular permeability, and passage of proteins and cells into the pericardial space. Deposition of fibrin makes the layers irregular; contact between inflamed surfaces contributes to pain and friction rub. The immune response can be amplified through the interleukin-1 axis, which is particularly relevant in some recurrent forms. Repair may restore a functional surface or produce granulation tissue, adhesions, and fibrosis. The pathological forms of pericarditis describe these different outcomes and the predominant composition of the exudate, without necessarily identifying the responsible microorganism or disease.

Pericardial effusion develops when fluid entry exceeds removal capacity. In inflammation, increased permeability predominates; in venous congestion, drainage may be impaired; in neoplasms, infiltration, lymphatic obstruction, and bleeding may coexist. The relationship between volume and pressure is nonlinear. Initially, the sac can accommodate an increase in volume with a modest pressure change, but once the reserve of distensibility is exhausted, small further increases cause a marked rise in pressure. Therefore, the rate of accumulation matters, in addition to the amount of fluid and pre-existing distensibility.

When external pressure impairs chamber filling and reduces cardiac output, cardiac tamponade develops. Transmural pressure, that is, the difference between intracavitary pressure and surrounding pressure, becomes insufficient to sustain adequate filling. Adrenergic compensation increases heart rate and peripheral resistance, but may fail to prevent hypoperfusion. Inspiration promotes right-sided venous return; within a constrained pericardial volume, expansion of the right ventricle takes space away from the left ventricle and accentuates the inspiratory reduction in left-sided output. This mechanism contributes to pulsus paradoxus, although it is not specific to tamponade.

In constrictive pericarditis the problem is instead rigidity of the envelope, with restricted filling and abnormal transmission of intrathoracic pressure changes to the cardiac chambers. Early filling may begin rapidly and then stop when the limit imposed by the pericardium is reached. Ventricular interdependence becomes more evident and systemic venous pressures rise. An inflammatory phase can produce reversible constriction; mature fibrosis is a much less reversible substrate. In effusive-constrictive disease, the constrictive component persists even after the pressure caused by the effusion is reduced.

Other conditions do not necessarily follow this inflammatory sequence. Pericardial cysts are generally benign fluid-containing lesions; diverticula communicate with the pericardial space, although this communication may not be evident on imaging. In congenital absence of the pericardium, the anatomy of the defect determines any mechanical risk, which is greater in some partial forms that allow herniation and strangulation of cardiac structures. Blood, chyle, and air can also occupy the sac because of specific traumatic, iatrogenic, or pathological causes, with consequences depending mainly on the pressure generated.

Clinical manifestations and patient assessment

The history begins with the reason for consultation and its temporal evolution. In a patient with chest pain, onset, location, radiation, duration, relationship with breathing, body position, and physical activity are characterized. Inflammatory pericardial pain is often worsened by inspiration and the supine position and improves when sitting up and leaning forward; radiation to the trapezius ridge may reflect involvement of phrenic afferents. These features increase the plausibility of the diagnosis but do not exclude a coronary syndrome or pulmonary embolism. Their significance must be integrated with age, comorbidities, and hemodynamic status.

Dyspnea may predominate in the presence of effusion, tamponade, constriction, or myocardial involvement. It is necessary to establish whether it occurs only with exertion, at rest, or when lying down, and whether it is accompanied by syncope, weakness, reduced urine output, or intolerance of usual activities. A slowly progressive collection may mainly cause a sense of chest pressure, cough, or compressive symptoms; in other cases it causes no symptoms and is detected incidentally. The absence of pain therefore does not make an effusion irrelevant, just as pain intensity does not measure the volume of the collection.

When the main problem is systemic congestion, the history should assess lower-limb edema, increased abdominal girth, early satiety, fatigue, and progressive reduction in exercise capacity. This presentation is important in constriction, which can be mistaken for liver disease or other causes of right-sided heart failure. A history of cardiac surgery, exposure to thoracic radiotherapy, or tuberculosis is relevant. The interval may be long, and the absence of a clearly remembered episode of pericarditis does not exclude the problem.

The clinical etiologic workup proceeds from the most discriminating information. High fever, chills, and concomitant infections raise concern for a bacterial form; night sweats, weight loss, and epidemiologic exposure also point toward tuberculosis or neoplasia, without being specific. Arthralgia, skin rashes, Raynaud phenomenon, oral ulcers, and other systemic signs suggest an immune-mediated disease. Renal function, oncologic treatments, recently introduced drugs, immunosuppression, trauma, and procedures should be reviewed. During flares, documentation of the first episode, remission intervals, doses actually taken, and the relationship between symptom recurrence and treatment tapering are essential.

The physical examination must first establish whether an emergency is present. Blood pressure, heart rate, respiratory rate, temperature, oxygen saturation, mental status, and peripheral perfusion help identify instability and sepsis. Hypotension, cold extremities, oliguria, and altered consciousness indicate compromise requiring immediate evaluation. In tamponade, however, blood pressure may initially be preserved or elevated, especially in patients with pre-existing hypertension; one should not wait for the classic triad of hypotension, jugular venous distension, and muffled heart sounds before suspecting it. Its absence likewise does not exclude tamponade.

Examination of the jugular venous pulse provides information about right-sided filling. Elevated venous pressure is compatible with both tamponade and constriction, but the pattern of waves and descents may differ. The Kussmaul sign, namely an increase or an inadequate fall in jugular venous pressure during inspiration, points to impaired right-sided filling and is common in constriction, although it is not specific. Pulsus paradoxus is instead assessed as an exaggerated inspiratory fall in systolic pressure, conventionally greater than 10 mmHg; severe respiratory conditions and other circumstances can produce it or alter its interpretation.

Auscultation should assess for a pericardial friction rub, a superficial sound that may vary over a few hours and is more readily heard with the patient leaning forward. It may be present even without a significant effusion, and its disappearance does not necessarily indicate recovery. In constriction, an early diastolic sound, the pericardial knock, may occur because of abrupt cessation of filling. Examination should include the lungs, abdomen, and limbs: pleural effusions, hepatomegaly, ascites, and edema help define the hemodynamic phenotype, whereas focal pulmonary findings may indicate an infectious focus or an alternative diagnosis.

Clinical assessment remains equally important for incidental findings. An apparently simple cyst requires verification of whether any compressive symptoms are truly attributable to the lesion; a congenital defect must be interpreted in relation to its morphology and the structures involved. Finding a mass in a patient with cancer is not sufficient to classify it as a metastasis, but it changes the pretest probability and urgency of investigation. At the end of the examination, a precise question should be formulated: is the predominant problem inflammation, a collection with hemodynamic risk, chronic limitation of filling, or a structural lesion?

Investigations, diagnosis, and definition of disease

There are no unified diagnostic criteria for all pericardial diseases: each syndrome requires appropriate demonstration. The initial sequence includes an electrocardiogram, blood tests, and transthoracic echocardiography, adjusted to clinical urgency. When tamponade is suspected, echocardiography must be immediately available and should not be replaced by a lengthy etiologic workup. In chest pain, coronary, aortic, and thromboembolic emergencies are assessed at the same time. A diagnosis of pericardial disease should not become a way to prematurely explain any pain associated with a small echo-free space.

The electrocardiogram may show diffuse ST-segment elevation and PR depression in inflammation, or low voltages and electrical alternans with large collections. None of these findings is mandatory. Cardiac troponin, C-reactive protein, complete blood count, renal function, and electrolytes answer different questions: associated myocardial injury, inflammatory response, infection or cytopenias, etiologic conditions, and treatment safety. A normal C-reactive protein level may depend on the timing of sampling, treatments already started, or the disease phenotype; it should not be interpreted in isolation. Thyroid tests are particularly relevant in effusions unexplained by the clinical picture.

Echocardiography identifies the distribution and size of fluid, any septations and localized compression, ventricular function, and concomitant disease. Assessment of the collection should report the site and measurement of the echo-free space, without automatically converting a distance into a precise estimate of volume. Right-sided chamber collapse, respiratory variation in flows, and inferior vena cava dilatation contribute to recognition of tamponade, but depend on pre-existing pressures, ventilation, and volume status. A single echocardiographic sign does not always equal clinically significant tamponade; conversely, after surgery a loculated collection may selectively compress one chamber without reproducing the classic picture.

When the question is constriction, Doppler and analysis of septal motion assess respiratory dependence of filling. Respiratory septal shift, preserved or increased early diastolic velocity of the medial mitral annulus, and expiratory diastolic flow reversal in the hepatic veins form a validated set of findings. The main differential diagnosis is restrictive cardiomyopathy, in which impaired filling originates in the myocardium. Severe tricuspid regurgitation, pulmonary hypertension, and abnormalities of volume status can complicate interpretation, making an integrated examination necessary rather than automatic application of a threshold.

Cardiac magnetic resonance imaging adds tissue characterization and assessment of functional consequences. Water-sensitive sequences can demonstrate edema; late gadolinium enhancement may indicate abnormal pericardial tissue and should be interpreted together with edema, symptoms, and clinical course. Persistent enhancement does not always correspond to clinically active inflammation and does not identify the cause. The same examination can demonstrate myocardial involvement, which is important for prognosis and guidance on physical activity. In constrictive forms, it can help identify a potentially treatable inflammatory component and describe ventricular interdependence.

Computed tomography clearly defines calcifications, the distribution of thickening, relationships with the mediastinum and lungs, masses, and preoperative anatomy. It can characterize a lesion as predominantly fluid, fatty, or solid and can suggest blood in a relatively hyperdense collection, but it does not replace cytologic or microbiologic analysis. A calcified pericardium may not be constrictive, and constriction may occur without calcification. Positron emission tomography is reserved for selected questions, especially oncologic or infectious ones: uptake indicates metabolic activity and does not by itself distinguish tumor from inflammation.

Etiologic investigations depend on clinical probability and the consequences of the result. Blood cultures and fluid sampling are important when bacterial infection is suspected; in tuberculous forms, microbiologic testing, molecular tests, and documentation of extracardiac sites are integrated. Fluid cytology can identify neoplasia, whereas biopsy is useful when tissue is needed to distinguish infectious, neoplastic, or infiltrative processes and the result may alter management. A negative test does not always have sufficient exclusionary power, especially with focal lesions or scant material. Broad viral serology is not a reliable method for systematically attributing a specific infection to the pericardium.

After the syndromic diagnosis, extent, activity, and risk are defined. The course of the effusion, myocardial involvement, hepatic and renal congestion, nutritional status in chronic forms, and need for intervention should be documented. Catheterization with simultaneous ventricular pressure measurements can clarify constriction when noninvasive methods remain discordant or when distinction from restrictive disease is critical. The final diagnosis should therefore specify what has actually been demonstrated: an effusion of still-undetermined origin, pericarditis with documented activity, physiologically confirmed constriction, or a mass characterized to the level allowed by the available evidence.

Treatment and prognosis

Therapy is determined by the predominant mechanism. Inflammation requires anti-inflammatory treatment and, when identified, treatment of the cause; tamponade requires removal of the mechanical obstruction; irreversible constriction may require surgery. These objectives may coexist in the same patient. It is not appropriate to treat all effusions indiscriminately with corticosteroids or to regard drainage as the definitive solution to every collection, because the procedure does not necessarily correct the process that caused the fluid. Likewise, a drug's effectiveness on pain does not by itself establish the nature of the disease.

In uncomplicated idiopathic or immune-mediated forms, first-line therapy generally includes aspirin or a nonsteroidal anti-inflammatory drug, together with colchicine, with gastroprotection when indicated and reduction of physical activity during the active phase. Drug choice and dose should take into account renal function, bleeding risk, gastrointestinal disease, and interactions. Colchicine reduces the likelihood of an incessant or recurrent course, but does not replace antibiotics in bacterial infection or remove a mechanical obstruction. Treatment tapering should be guided by clinical remission and relevant activity parameters, avoiding accelerated discontinuation while disease remains demonstrable.

Corticosteroids have selected indications, such as certain systemic diseases or inability to use first-line therapy, and require attention to the risk of treatment dependence and relapse during tapering. In inflammatory phenotypes with recurrences and an inadequate response to conventional treatments, interleukin-1 antagonists have changed management. Anakinra and rilonacept have shown efficacy in selected populations; their choice, monitoring, and duration require specific expertise, assessment of infectious risk, and verification of conditions of use. The response observed in trials should not be automatically extrapolated to noninflammatory effusions, active infections, or every form of persistent chest pain.

Etiologic therapy radically changes the pathway. Purulent forms require systemic antibiotics and adequate drainage; tuberculosis requires an appropriate antimycobacterial regimen. In advanced kidney disease, initiation or optimization of dialysis may be central, with surveillance for hemodynamic complications. Hypothyroidism-related effusion is managed by correcting thyroid dysfunction, whereas neoplastic forms require an oncologic strategy and local management of the collection tailored to symptoms, risk of recurrence, and goals of care. A drug suspected of causing a pericardial reaction is reassessed in the context of its indication and available alternatives.

In unstable tamponade, pericardiocentesis or surgical drainage should not be delayed by investigations that do not change the need for decompression. The procedure is guided by imaging and the location of the collection; clotted blood, pus, loculated collections, or the need to repair an injury may make surgery preferable. Sampling also provides a diagnostic opportunity. In stable chronic effusions without inflammatory signs and without a specific cause after appropriate evaluation, size alone does not always mandate preventive drainage: prospective data support selected observation, with clinical and echocardiographic follow-up and instructions to recognize deterioration.

In constriction with evidence of inflammation and clinical stability, a trial of anti-inflammatory therapy with reassessment of physiology may be indicated. Persistent symptomatic fibrotic constriction instead points toward pericardiectomy, performed in experienced centers after definition of anatomy and organ dysfunction. Diuretics can relieve congestion, but excessive reduction in preload may further impair output. Surgery should not be postponed until severe hepatic, renal, or nutritional compromise develops when the indication is clear; prognosis also depends on any associated myocardial injury, which is particularly important after radiotherapy.

Simple, asymptomatic cysts may be observed, whereas growth, compression, or diagnostic uncertainty may justify invasive treatment. In congenital anomalies, the decision is based on the specific anatomy and the presence of a risk of herniation, not merely on the absence of a pericardial layer. These conditions therefore require reasoning different from that applied to inflammatory disease. Solid masses, especially when infiltrative or associated with recurrent collections, should be discussed in a multidisciplinary setting integrating imaging, pathology, cardiology, and oncology.

Prognosis cannot be summarized by a single percentage. Idiopathic inflammatory forms generally carry a low risk of death and constriction, but may impose a substantial burden of recurrence and functional limitation. Bacterial infections, tuberculosis, neoplasms, and post-radiation forms have different courses, influenced by the cause and effectiveness of treatment. Follow-up should jointly assess symptoms, functional capacity, inflammatory activity, the volume and consequences of effusion, medication tolerance, and recovery of congested organs. Normalization of a single test does not complete the assessment, just as a residual imaging abnormality does not automatically require intensification of therapy.

Complications and long-term consequences

In idiopathic inflammatory forms, the most common clinical complication is recurrence, which may occur after documented remission or be confused with activity that was never fully suppressed. Repeated exposure to inflammatory stimuli, abnormal regulation of the immune response, and overly rapid treatment tapering may contribute to the course, but not all mechanisms are defined in an individual patient. Recurrent pain requires reassessment of disease activity: not every chest symptom after pericarditis represents a recurrence. This distinction avoids both undertreatment of inflammation and unjustified exposure to immunosuppression.

The effusion may increase, organize, or become loculated. Fibrinous septa and adhesions divide the space into compartments, making complete drainage more difficult and altering pressure distribution. After cardiac surgery, hematomas or posterior collections may selectively compress atria or ventricles. This anatomy explains why an unfavorable echocardiographic window or absence of classic signs should not be overly reassuring when the patient is deteriorating. Assessment should be adapted to the context, using methods capable of rapidly identifying the responsible site.

Tamponade is the most urgent hemodynamic complication. Progressive reduction in cardiac output compromises renal, cerebral, and coronary perfusion, leading to obstructive shock and cardiac arrest. Its likelihood is not linearly related to fluid volume: rapid hemorrhage may be far more dangerous than a larger but slowly developing effusion. Coexisting sepsis, hypovolemia, or ventricular dysfunction can accelerate deterioration and alter physical findings. Anticoagulation and recent procedures are particularly relevant when a hemorrhagic component is suspected, but must be interpreted within the actual etiologic context.

Organization of the exudate and collagen deposition can produce constriction, with persistent elevation of venous pressures and reduced cardiac output reserve. The risk is very low after many idiopathic forms and substantially higher in some bacterial etiologies; it should not be inferred from the number of recurrences alone. A reversible component must be distinguished from an established scar because treatment options differ. When effusion and constriction coexist, improvement after drainage may be incomplete: persistently elevated right-sided pressures require assessment for other causes as well, including right ventricular failure and pulmonary hypertension.

Chronic congestion can cause congestive hepatopathy, ascites, worsening renal function, malabsorption, and, in more advanced forms, protein-losing enteropathy and wasting. Prolonged elevation of venous pressure is not merely a peripheral sign but a mechanism of organ injury. The interaction between reduced perfusion and renal congestion can make diuretic use difficult; nutritional and hepatic impairment also increase the risk of subsequent surgery. For this reason, specialist assessment should, when possible, precede the development of advanced systemic injury.

Associated myocardial injury may add ventricular dysfunction, arrhythmias, or conduction disturbances. These events should not be attributed indiscriminately to inflammation of the pericardial sac alone: troponin, ventricular function, and tissue characterization help identify a myopericardial syndrome. In purulent forms, sepsis and spread of infection are additional threats; in neoplasms, recurrence of the collection may reflect disease progression or persistent lymphatic obstruction. Some partial congenital anomalies may instead become complicated through herniation and compression of cardiac structures, by an entirely different mechanism.

Treatments themselves also have consequences that require surveillance. Anti-inflammatory drugs can cause gastrointestinal bleeding and renal injury, colchicine can cause gastrointestinal toxicity and, in the presence of accumulation or interactions, systemic adverse effects, whereas corticosteroids and biologic agents require metabolic and infectious monitoring. Drainage can be complicated by cardiac or vascular injury, arrhythmias, pneumothorax, and infection. Rarely, after decompression of a large effusion, pericardial decompression syndrome develops with hemodynamic deterioration or pulmonary edema; the mechanism is multifactorial and justifies monitoring and controlled drainage when the situation permits.

Finally, the long-term burden includes recurrent pain, reduced physical activity, time away from work, and fear of recurrence. These consequences can be relevant even when the risk of death remains low. Effective management should link suppression of disease activity to a gradual return to daily life, avoiding indefinite restrictions without clinical justification. Outcome assessment therefore requires both objective indicators of function and inflammation and evaluation of the patient's ability to regain independence, exercise, and quality of life.

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