Novel Pathophysiological, Diagnostic and Therapeutic Concepts in Acute and Recurrent Pericarditis

Abstract

Acute pericarditis is the most frequent pericardial disease characterized by inflammation of the pericardial layers resulting in pain, dyspnea and fatigue. Often limited to an isolated event, up to 30% of patients experience one or more recurrences. There is limited knowledge about the pathophysiology of this disease, possibly due to the limited availability of animal models. More recently, following seminal clinical trials with colchicine and interleukin-1 (IL-1) blockers and a novel murine model of acute pericarditis using zymosan A, it has become clear that the NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome/IL-1β axis plays a central role in driving acute pericardial inflammation and in sustaining this process during recurrences. Diagnostic management of pericarditis has been implemented with multimodality imaging including echocardiography, cardiac computed tomography, and cardiac magnetic resonance. These imaging modalities provide essential diagnostic and pathogenetic information, and are able to characterize pericardial inflammation, allowing to refine risk stratification and personalize treatment. Recent acquisitions yield relevant implications with regard to the therapeutic management of acute and recurrent pericarditis. Non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are cornerstone therapies either for acute and recurrent pericarditis. However, the benefits of targeted agents, such as anakinra -a recombinant human IL-1 receptor antagonist -and rilonacept -an IL-1α/IL-1β trap, are being increasingly recognized. To this end, phenotyping patients with pericarditis and addressing such therapies to those presenting with auto-inflammatory features (elevated C-reactive protein, sustained pericardial and systemic inflammation, multiple recurrences) is of utmost importance to identify patients who might be more likely to benefit from NLRP3 inflammasome/IL-1β pathway blockade.

Novel Therapeutic Insights Into the Treatment of Pericarditis: Targeting the Innate Immune System

“…It is now clear that recurrent pericarditis is more likely to depend on an autoinflammatory mechanism rather than on recurrent viral infections. 23,62,63 Accordingly, after the inflammation of the pericardium, IL-1a-that acts as an alarmin 26 -triggers an inflammatory reaction in the pericardium through the recruitment of neutrophils and macrophages as well as a large release of pro-IL-1b, then processed to IL-1b by the NLRP3 inflammasome. Because IL-1 is able to stimulate its own transcription and translation, 27 the increased production of IL-1b may release additional IL-1a and IL-1b, thus fueling a local inflammatory reaction of the pericardium.…”