Tuberculous Pericardial Disease: A Focused Update on Diagnosis, Therapy and Prevention of Complications

Tuberculous pericarditis (TBP) is the most important manifestation of tuberculous heart disease and is still associated with a significant morbidity and mortality in TB endemic areas. The high prevalence of the disorder over the last 3 decades has been fueled by the human immunodeficiency virus/AIDS (HIV/AIDS) pandemic in these areas. The objective of this review is to provide a focused update on developments in the diagnosis and therapy of this condition, prevention of its complications, as well as future novel therapies. The definitive diagnosis of a tuberculous etiology in patients with suspected TBP continues to pose a challenge for clinicians. Clinical prediction scores, although never formally validated have been used with some success. However, they may be prone to both over and underdiagnosis due to lack of pericardial fluid analysis. Recent studies evaluating Xpert MTB/RIF, suggest that this advanced polymerase chain reaction (PCR) based technology does not provide increased accuracy compared to earlier iterations. However a combined two test approach starting with Xpert MTB/RIF followed by either adenosine deaminase (ADA) or interferon gamma (IFN-γ) may provide for significantly enhanced specificity and sensitivity cost permitting. Pericardiocentesis remains the gold standard for managing the compressive pericardial fluid and its adverse hemodynamic sequelae. A four drug anti-TB drug regimen at standard doses and duration is recommended. However recent evidence suggests that these drugs penetrate the pericardium very poorly potentially explaining the high mortality observed particularly in those who are culture positive with a high bacillary load. Constrictive pericarditis is the main long-term complication of TBP and is still a significant cause of heart failure in Sub-Saharan Africa. This is important because access to definitive surgical therapy where TBP is prevalent continues to be low, highlighting the need to develop strategies or interventions to prevent fibrosis and constriction. Recent detailed advanced studies of pericardial fluid in TBP have revealed a strong profibrotic transcriptomic profile, with high amounts of pro-inflammatory cytokines and low levels of the anti-fibrotic tetrapeptide N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP). These new insights may explain in part the high propensity to fibrosis associated with the condition and offer hope for the future use of targeted therapy to interrupt pathways and mediators of tissue damage and subsequent maladaptive healing and fibrosis. The value of effective pericardiocentesis in reducing these pro-inflammatory and pro-fibrotic cytokines and peptides in an attempt to prevent pericardial constriction has yet to be established but has generated hypotheses for ongoing and future research.

Keywords: Tuberculous pericarditis (TBP); constrictive pericarditis; pericardial effusion; tamponade.