The Signs That Keep Coming Back: Understanding Recurrent Pericarditis

Pericarditis gets far less attention, although two features make it easy to underestimate: a first episode is often mistaken for another condition, and in a significant share of patients the disease returns after it appears to have resolved. For those patients, the question shifts from diagnosis to preventing the next flare, which is where much of the current research, including Cardiol’s Phase III MAVERIC trial, is focused.

What Is Pericarditis

The pericardium is the thin, two-layered sac that surrounds the heart, and pericarditis is inflammation of that sac. According to the American College of Cardiology’s 2025 consensus statement on the condition, the typical symptom is sharp chest pain that worsens with breathing and eases when the patient sits up or leans forward. Shortness of breath, fatigue and fever can accompany it.

Because the pain comes on suddenly and sits in the centre of the chest, many patients are first seen in an emergency department. The European Society of Cardiology’s 2025 guidelines report that pericarditis accounts for about 5% of emergency room admissions for chest pain. Some cases follow a viral infection, and in many others no specific cause is identified. A first episode usually settles within a few weeks of anti-inflammatory treatment, although in a substantial minority of patients the symptoms come back.

When It Comes Back

Recurrent pericarditis is diagnosed when symptoms return after a symptom-free interval of at least four to six weeks. The ESC guidelines estimate that recurrence occurs in about 20% to 30% of patients within 18 months of a first episode. Once a patient has had one recurrence, the risk of another rises to as much as 50%.

Once recurrence sets in, pericarditis behaves more like a chronic illness than an acute one, with flares of severe chest pain, breathlessness and fatigue that can arrive with little warning. The condition can lead to physical limitations, reduced quality of life, repeated emergency department visits, hospitalizations, and anxiety, as many patients spend the time between episodes expecting the next one.

The ACC identifies several factors associated with a higher risk of recurrence, including a lack of response to first-line anti-inflammatory drugs, early use of corticosteroids, and elevated levels of C-reactive protein, a blood marker of inflammation. Recognizing these factors early helps clinicians identify the patients whose disease is most likely to return.

The Inflammation Behind Each Recurrence

Pericarditis is an auto-inflammatory disease, and each recurrence reflects inflammation that has not been fully brought under control. Much of the research into its biology has focused on the NLRP3 inflammasome, a protein complex inside cells that becomes activated after injury or viral infection and triggers the release of pro-inflammatory cytokines such as interleukin-1 and interleukin-6. In pericarditis, that cytokine release can become self-perpetuating, damaging pericardial tissue and sustaining the cycle of flares. Genetic and autoinflammatory factors are also suspected in patients with multiple recurrences.

Pericarditis is one of several heart conditions in which inflammation is treated as a driver of disease. The American College of Cardiology’s 2025 Scientific Statement on inflammation and cardiovascular disease named it alongside heart failure and atherosclerosis, a shift we examined in more detail in Inflammation and the Heart: Why the Field Is Asking a Different Question.

Treatment typically follows a stepped approach. Most patients start with anti-inflammatory medication and colchicine. If recurrences continue, clinicians may add corticosteroids, which carry side effects with prolonged use and, when started early, are associated with a higher risk of recurrence. For disease that persists, current ESC and ACC guidance recommends biologic therapies that block interleukin-1, usually after colchicine has failed to prevent further recurrences. Each step adds to the treatment burden patients carry, clearly showing the need for options that can be used earlier in that sequence, before patients are exposed to prolonged corticosteroid therapy.

Where Cardiol’s Work Fits

Cardiol Therapeutics is developing CardiolRx™, an oral small-molecule therapy that targets inflammasome pathway activation, for reducing the risk of pericarditis recurrence. The U.S. Food and Drug Administration has granted CardiolRx™ Orphan Drug Designation for the treatment of pericarditis, including recurrent pericarditis.

Results from the Phase II MAVERIC study were published in the Journal of the American Heart Association in July 2026. CardiolRx™ was associated with rapid and sustained reductions in pericarditis pain and inflammation in patients with a high baseline disease burden, along with substantial reductions in pericarditis episodes per year and a favourable safety and tolerability profile.

Those findings led to MAVERIC, a pivotal Phase III randomized, double-blind, placebo-controlled trial of CardiolRx™ in patients with recurrent pericarditis currently ongoing at leading cardiovascular research centres. Its primary endpoint is time to a new episode of recurrent pericarditis from the timepoint of stopping the IL-1 blocker to Week 24, and the secondary endpoints include freedom from pericarditis recurrence at 24 weeks, and percentage of days with no or minimal pain.

On September 23, 2026, Cardiol announced that MAVERIC had reached its original enrollment target of 110 patients ahead of schedule. Enrollment is expanding to up to 150 patients to further strengthen the assessment of efficacy, and topline data are expected in mid-2027.

Recognizing the Signs

Anyone who experiences sudden, sharp chest pain should seek medical attention promptly. Patients whose pericarditis has returned, or who are managing ongoing flares, should talk with their cardiologist about treatment options. Details on the MAVERIC trial, including participating sites, are available on ClinicalTrials.gov under the identifier NCT06708299.

The first episode is when chest pain needs prompt evaluation. After that, the concern for patients shifts to reducing the chance of the next flare, and the patients and investigators taking part in MAVERIC are building the evidence on whether CardiolRx™can do that.

Related Reading

Inflammation and the Heart: Why the Field Is Asking a Different Question

Why Inflammation Is Becoming One of the Most Important Targets in Cardiology