Uremic pericarditis is a complication of chronic renal failure (CRF), more frequent in the end stages of the disease, particularly in patients undergoing hemodialysis. It is caused by the accumulation of uremic toxins that trigger a chronic inflammatory process with the formation of a fibrinous pericardial effusion. In dialysis patients, altered immune response and increased risk of infections may facilitate the onset of superimposed infectious pericarditis.
Two main forms of uremic pericarditis are distinguished:
Pre-dialysis: typical of patients with severe renal failure not yet on replacement therapy, due to accumulation of nitrogenous metabolites and pro-inflammatory cytokines.
Post-dialysis: observed in patients already on dialysis, often secondary to ineffective extracorporeal clearance, hypoalbuminemia or chronic inflammatory state.
Pathophysiology
Pericardial damage in uremic pericarditis is linked to the accumulation of nitrogenous metabolic products and the action of pro-inflammatory cytokines (IL-6, TNF-α), which induce a chronic inflammatory process with increased capillary permeability and progressive accumulation of fluid in the pericardial space. In uremic patients, there is also impaired platelet function and coagulation cascade deficiency, factors that favor the formation of serohemorrhagic effusions. In dialysis patients, the use of heparin as an anticoagulant may further increase the risk of intrapericardial bleeding.
Clinical Features
The clinical picture is similar to other forms of pericarditis, with pleuritic chest pain, dyspnea and signs of cardiac tamponade in advanced cases. However, in uremic pericarditis:
Chest pain may be less intense or absent in severely uremic patients.
Fever is generally absent, unless a superimposed infectious pericarditis is present.
Pericardial effusion may accumulate slowly, leading to subtle symptoms until hemodynamic compromise occurs.
Diagnosis
In addition to the standard investigations used to diagnose pericarditis (ECG, echocardiography, chest X-ray), in uremic pericarditis it is useful to assess:
Myxedema pericarditis is a typical complication of severe hypothyroidism and is characterized by a slowly evolving pericardial effusion, generally asymptomatic, which may become abundant and, in the most severe cases, cause cardiac tamponade. Unlike inflammatory pericarditis, the pericardial fluid in myxedema pericarditis is usually devoid of inflammatory signs and is characterized by a high concentration of mucopolysaccharides and proteins.
Pathophysiology
Hypothyroidism leads to a profound alteration in basal metabolism, with systemic effects involving the pericardium:
Reduced pericardial clearance: metabolic slowing causes fluid accumulation in the pericardial space.
Increased capillary permeability: promotes the passage of fluids into the pericardial space.
Accumulation of mucopolysaccharides: the pericardial fluid is dense and protein-rich, with gelatinous features.
Since progression is slow, the pericardium has time to adapt to the increased effusion volume, making the risk of tamponade lower than in acute pericarditis. However, in cases of severe and prolonged hypothyroidism, the effusion may become massive and impair cardiac function.
Clinical Features
Symptoms of myxedema pericarditis are often subtle and overlap with those of advanced hypothyroidism. They may include:
Dyspnea: progressive, due to reduced pericardial compliance.
Peripheral edema: reflecting hypothyroidism and impaired fluid clearance.
Bradycardia and hypotension: typical of thyroid dysfunction.
Absence of fever and chest pain: the effusion develops slowly, without a significant inflammatory response.
Signs of cardiac tamponade: in more advanced cases, with jugular vein distension, hypotension and pulsus paradoxus.
Diagnosis
In addition to the standard investigations for diagnosing pericarditis (ECG, echocardiography, chest X-ray), the diagnosis of myxedema pericarditis is based on:
Hormonal assays: abnormal thyroid hormone levels as per underlying pathology (elevated TSH and reduced FT3/FT4).
Pericardial fluid analysis: dense serous fluid, rich in mucopolysaccharides, with low cell content and absence of inflammatory markers.
Treatment
Treatment of myxedema pericarditis is based on correction of the hormonal deficit, with progressive resolution of the effusion.
Levothyroxine replacement therapy: leads to spontaneous reabsorption of the effusion over weeks or months.
Echocardiographic monitoring: to assess the evolution of the effusion and the appearance of any signs of tamponade.
Pericardiocentesis: rarely necessary, reserved for cases with hemodynamic compromise.
Complications
The main complications of myxedema pericarditis are:
Cardiac tamponade: if the effusion reaches critical volumes.
Recurrence of the effusion: in patients with inadequately treated hypothyroidism.
Collagen disease pericarditis is a common manifestation of systemic autoimmune diseases, especially connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis and polymyositis/dermatomyositis. It may present with pericardial effusion of variable severity, sometimes with hemorrhagic or recurrent characteristics, and in chronic cases may evolve into constrictive pericarditis with fibrosis and calcification.
Pathophysiology
Collagen disease pericarditis is caused by a direct autoimmune response against the pericardium, with production of autoantibodies and immune complex deposition that trigger chronic inflammation. This process leads to:
Increased capillary permeability with accumulation of fluid in the pericardial space.
Persistent inflammation which, in chronic cases, can evolve into pericardial fibrosis.
Possible hemorrhagic effusion, more frequent in SLE and RA.
Clinical Features
In addition to the typical symptoms of pericarditis (pleuritic chest pain, dyspnea, signs of cardiac tamponade in advanced cases), collagen disease pericarditis is distinguished by:
Systemic involvement: fever, arthralgia, skin rash, Raynaud's phenomenon, mucosal dryness (depending on the underlying autoimmune disease).
High tendency to chronicity: with possible recurrences.
Risk of constrictive evolution: in patients with chronic pericardial inflammation.
Diagnosis
In addition to the standard investigations for pericarditis (ECG, echocardiography, chest X-ray), in collagen disease pericarditis it is essential to perform:
Autoimmune tests: detection of antibodies (ANA, anti-DNA, ENA, RF, anti-CCP, etc.) to confirm the underlying connective tissue disease.
Pericardial fluid analysis: in SLE patients, may reveal a serous or hemorrhagic effusion with high protein content.
Treatment
Treatment of collagen disease pericarditis is based on control of inflammation and the underlying disease.
Corticosteroids: first-line drugs in severe autoimmune forms.
NSAIDs: in mild-moderate forms.
Immunosuppressive drugs: methotrexate, azathioprine or mycophenolate in refractory cases.
Pericardiocentesis: indicated in cases of cardiac tamponade.
Complications
The main complications of collagen disease pericarditis include:
Recurrent pericarditis: particularly frequent in SLE.
Constrictive pericarditis: in cases with chronic fibrotic evolution.
NEOPLASTIC PERICARDITIS
Neoplastic pericarditis is a secondary form of pericarditis caused by infiltration of tumor cells into the pericardium. It may derive from direct extension of primary pericardial tumors or, more frequently, from metastatic spread of extrapericardial neoplasms, including:
Lung cancer (the most common cause).
Breast cancer.
Lymphomas and leukemias.
Melanoma (a tumor with marked tendency to pericardial spread).
Neoplastic pericardial effusion can be significant and, in most cases, has a characteristic hemorrhagic appearance. Its progression is often insidious, but in advanced cases it may cause cardiac tamponade, representing a potentially fatal condition.
Pathophysiology
Neoplastic pericarditis is caused by dissemination of tumor cells into the pericardium, which can occur through:
Direct extension: in primary tumors of the heart or pericardium.
Lymphatic or hematogenous dissemination: typical of lung, breast neoplasms and lymphomas.
Paraneoplastic mechanisms: some neoplasms can induce pericardial inflammation without direct cellular infiltration.
Tumor cells alter the vascular permeability of the pericardium, resulting in an effusion that may be serous, serohemorrhagic or markedly hemorrhagic. In advanced cases, pericardial fibrosis may develop, evolving into constrictive pericarditis.
Clinical Features
Symptoms of neoplastic pericarditis may be nonspecific or completely absent until significant accumulation of effusion occurs. Distinctive signs include:
Dyspnea: the most frequent symptom, due to progressive cardiac compression by the effusion.
Dull chest pain: less intense than in inflammatory pericarditis.
Signs of cardiac tamponade: hypotension, jugular vein distension, and pulsus paradoxus in advanced cases.
Peripheral edema and ascites: due to cardiac dysfunction secondary to tamponade.
In cancer patients, the appearance of worsening dyspnea or signs of heart failure should raise suspicion of a neoplastic pericardial effusion.
Diagnosis
In addition to the standard investigations used for pericarditis (ECG, echocardiography, chest X-ray), in neoplastic pericarditis it is essential to assess:
Echocardiography: reveals a large effusion, often with signs of tamponade. It may show the presence of pericardial masses.
Chest CT and cardiac MRI: useful for identifying the primary neoplasm or possible tumor infiltrations in the pericardium.
Pericardial fluid analysis: obtained by pericardiocentesis, may reveal neoplastic cells or tumor markers.
Treatment
The management of neoplastic pericarditis aims to control the pericardial effusion and treat the underlying neoplasm.
Pericardiocentesis: first-line treatment in cases of cardiac tamponade.
Pericardiodesis: instillation of sclerosing agents (e.g., bleomycin, tetracycline) to prevent recurrence of the effusion.
Oncological treatment: chemotherapy, radiotherapy or targeted therapy according to the type of primary tumor.
Pericardiectomy: indicated in cases of refractory neoplastic constrictive pericarditis.
Complications
The main complications of neoplastic pericarditis include:
Cardiac tamponade: a medical emergency requiring immediate drainage.
Recurrence of the effusion: common in patients with advanced metastatic neoplasms.
Constrictive pericarditis: possible in chronic cases with pericardial fibrosis.
References
Alpert MA, Ravenscraft MD et al. Pericardial involvement in end-stage renal disease. American Journal of Medicine. 1987;82(4):639-646.
Gunukula SR, Spodick DH et al. Pericardial disease in renal patients. Seminars in Nephrology. 2001;21(1):52-56.
Rutsky EA, Rostand SG et al. Treatment of uremic pericarditis and pericardial effusion. American Journal of Kidney Diseases. 1987;10(1):2-8.
Rubini Gimenez M, Keller DI et al. Uremic pericarditis: pathophysiology, diagnosis and management. Nephrology Dialysis Transplantation. 2018;33(1):16-23.
Mallick NP, Gokal R et al. Complications of peritoneal dialysis. Kidney International. 1987;32(Suppl 23):S119-S127.
Colucci WS et al. Uremic pericarditis: clinical presentation, diagnosis, and management. Circulation. 2009;120(14):1445-1452.
Chung J, Goldfarb DS et al. Pericardial disease in patients with chronic kidney disease. Current Opinion in Nephrology and Hypertension. 2011;20(6):611-618.
Rubin J, Rao K et al. Management of large pericardial effusions and cardiac tamponade. Journal of the American College of Cardiology. 2013;61(8):797-806.
Patel MR, Dehmer GJ et al. ACCF/SCAI/STS/AATS/AHA/ASNC 2012 appropriate use criteria for diagnostic catheterization. Journal of the American College of Cardiology. 2012;59(22):1995-2027.
Hoit BD et al. Pathophysiology and management of pericardial effusions in dialysis patients. Clinical Journal of the American Society of Nephrology. 2010;5(4):787-793.
