A 35-year-old female marathon runner with a past medical history of acute pericarditis that resolved with treatment 3 months ago presents to the emergency department with sharp, pleuritc chest pain that is worse when supine and relieved by leaning forward. Her inflammatory markers are elevated and her ECG is displayed below:

Figure 1: Presenting ECG

She had a cardiac MRI which is shown below:

Figure 2: Cardiac MRI Showing Delayed Enhancement

She is diagnosed with recurrent pericarditis and started on colchicine and ibuprofen. The patient has been training for a marathon that is two months away and is interested in continuing her training. What is the most appropriate recommendation?

Of the various pericardial disease processes, acute pericarditis is by far the most common with a reported incidence of about 27.7 cases per 100,000 populations per year.¹ Acute pericarditis accounts for 0.1% of hospital admissions and 5% of emergency department visits for chest pain.^2,3,4 Unfortunately, recurrences of pericarditis can affect up to about 30% of patients within 18 months after the initial diagnosis.^5,6

There are various etiologies of pericarditis largely grouped into idiopathic, infectious, and non-infectious. In the developed world, the most common etiology is idiopathic or viral,⁷ whereas in the developing world tuberculosis is the leading cause.⁸ The diagnosis of pericarditis is based on a constellation of clinical symptoms, physical exam, ECG changes, laboratory abnormalities, and imaging findings. Typically, there is a history of characteristic precordial chest pain that is worse with inspiration and laying supine, diffuse concave ST segment elevation and PR deviation on ECG, and a pericardial friction rub with or without a pericardial effusion.^4,9

The various presentations of pericarditis include acute, incessant, chronic, and recurrent pericarditis. The incessant form occurs when symptoms last for about 4-6 weeks but less than 3 months without remission. The chronic form occurs once symptoms exceed three months. Finally, the recurrent form of pericarditis is a recurrence after the first episode of pericarditis and a symptom free interval of 4 to 6 weeks or longer,¹⁰ such as the patient in our clinical vignette. The primary aim of treatment is the resolution of pain and inflammation and consists of anti-inflammatory agents, usually starting with non-steroidal anti-inflammatory drugs (NSAIDS) and colchicine.^11,12,13 Treatment with steroids and immune modulators is usually reserved for incessant, chronic, or recurrent cases. However, there are also non-pharmacologic therapies, such as physical activity restriction, that are promulgated as aids in healing.^14,15 Here we discuss the reasoning and available literature behind these recommendations.

The literature is limited when it comes to evaluating the impact of exercise on cases of pericarditis. Most of the proposed data guiding recommendations is extrapolated from retrospective analyses or from basic science studies looking at regulation of inflammatory cascades from cases of myocarditis.^14-20 Yet, both the European Society of Cardiology and consensus groups within the United States agree that restriction of physical activity can serve a non-pharmacological treatment for pericarditis in the general population.^10,16 Current guidelines in the US recommend that athletes do not participate in competitive sports until there is evidence of complete absence of active disease.¹⁶ Therefore, in the case of our patient, it would be recommended not only to abstain from her marathon training but also to avoid other forms of intense physical activity. This is frequently quite distressing to athletes as it has a major impact on their lifestyle.

The rationale behind the avoidance of physical activity when diagnosed with pericarditis is to reduce the risk of complications such as progression to myocarditis, worsening pericardial effusion and cardiac tamponade, constrictive pericarditis, or recurrent/refractory symptoms. The predominant mechanism behind these complications seems to be immune mediated with some hypotheses being based on animal and autopsy studies that looked primarily at cases of myocarditis.^17-21 Though physical exercise is generally associated with improved health, there is a period after strenuous endurance activity that is associated with a functional immunodepression that can vary in length depending on the extent of the exercise.¹⁷ This period could predispose individuals with pericarditis to infectious agents that can infect metabolically active cells such as the myocardium leading to a myocarditis, a condition known to increase the risk of sudden cardiac death.^18,19

If an infection or other source of inflammation is detected following the immunodepression period, an acute phase reaction will occur. This results in a surge of inflammation that mobilizes the humoral and cell mediated immune response causing cytolysis and necrosis.^20-23 Mouse models in cases of myocarditis have shown that continued physical activity can further exaggerate this inflammatory response.^24,25,27 The inflammatory response not only can delay healing, but can progress symptoms or make them refractory. Perhaps the mechanism is the same in cases of pericarditis; however, there currently is no definitive evidence that this mechanism exists in cases of isolated pericarditis.

It also may be possible that exercise can further enhance the inflammatory response through increased friction between the two inflamed surfaces of the pericardium at high heart rates. While theoretically plausible, again there is unfortunately no robust data supporting this concept. However, anecdotally, in the authors' experience, patients often attribute recurrence or exacerbation of symptoms temporally to involvement in moderate or intense physical activity prior to complete resolution of pericardial inflammation.

Exercise is known to increase catabolic reactions within the body to break down protein, carbohydrates, and fatty acids as energy sources to maintain high performance. Unfortunately, inflammatory conditions like pericarditis also increase the body's demand for these energy sources.²⁰ Thus, continued exercise with pericarditis may accelerate muscle wasting and deconditioning. Therefore, in addition to a delay in healing, there may be a risk of worsening performance and predisposition to musculoskeletal injury.^20,26 Of note, there are no adequately controlled studies to further clarify the impact of pericarditis on decreased exercise performance or exercise related injury.

There are currently no randomized trials investigating the optimal time to return to sport or physical exercise post pericarditis. It also remains unclear if one should gradually increase the intensity of their physical activity (low to moderate to high) or resume high performance activity right away after a period of physical restriction. Current guidelines recommend that return to physical exercise or sport is permissible if there is no longer evidence of active disease.¹⁶ This includes the absence of fever, absence of pericardial effusion, and normalization of inflammatory markers (ESR and or C-reactive protein).¹⁶ However, these guidelines are limited to athletes who perform at high levels of intensity. It remains unclear whether or not the same amount of activity restriction would also benefit the general population who do not exercise as intensely. Our practice is to recommend restriction to low intensity physical activity until there is clinical and biological evidence of complete resolution of inflammation followed by a gradual return to full intensity exercise.

In conclusion, pericarditis is a common inflammatory condition of the pericardium with multiple etiologies. Current guidelines recommend restriction of intense physical activity and return to activity once there is no evidence of active inflammation. However, the evidence to support these recommendations is very limited. Further investigation is warranted to better understand the impact of exercise on the natural history of acute pericarditis. Until that evidence is available we follow the current recommendations based on our anecdotal experience of exercise induced exacerbation of the pericardial inflammatory process.

References

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Keywords: Acute-Phase Reaction, Anti-Inflammatory Agents, Anti-Inflammatory Agents, Non-Steroidal, Athletes, C-Reactive Protein, Cardiac Tamponade, Chest Pain, Electrocardiography, Heart Rate, Myocarditis, Myocardium, Pericardial Effusion, Pericarditis, Pericarditis, Constrictive, Pericardium, Sports

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