The Role of the Physician Assistant and Nurse Practitioner in the Management of Recurrent Pericarditis at a Model Center for Pericardial Diseases


Recurrent pericarditis (RP) is the most troublesome complication of acute pericarditis and can occur in 15-32 % of cases especially in those treated early with steroids.1,2 The rate of subsequent relapse increases by 50 % after the first recurrence and the management of recurrent pericarditis can be challenging.3 A center of excellence for management of pericardial diseases has been established at the Cleveland Clinic, where a multifaceted team of clinicians have improved patient outcomes by employing an evidence-based multimodality imaging-based therapeutic approach to patient care. This article focuses on the role physician assistants (PAs) and nurse practitioners (NP) play as part of the treatment team at the pericardial center.


The pericardium is a double-walled sac made of both a serous visceral layer (in contact with the epicardium) and a fibrous parietal layer adjacent to the lungs. There is a small amount of physiological pericardial fluid between the layers. The pericardium functions to anchor the heart to the mediastinum, to serve as a barrier against infection, and to provide lubrication for the heart. The phrenic nerves are enveloped by the parietal pericardium and supply afferent receptors to the pericardium and epicardium, which transmit pericardial pain.4 Prostaglandins are released by the pericardium, and play a role in modulating neural signals and coronary artery tone.4

Pericarditis may occur with or without pericardial effusion and can occur in the context of systemic disease or independently.5, 6, 7 In developed countries, the most common cause is viral or idiopathic, and in the developing world tuberculosis is the most common etiology, often with a high prevalence that is frequently associated with HIV infection8,9 Despite the fact that most idiopathic cases are presumed to be viral in cause, testing for specific viruses is not done routinely due to cost, low diagnostic yield, and little impact on overall management.4, 8 Noninfectious causes of pericarditis include post-cardiac injury syndromes such as post radiation, post myocardial infarction syndrome, post-pericardiotomy, or other post traumatic forms from iatrogenic trauma (e.g. .coronary percutaneous intervention, pacemaker lead insertion, and radiofrequency ablation).6-10 Other etiologies are metabolic (e.g. uremia, hypothyroidism), autoimmune (e.g. occurring in context of systemic lupus erythematous, rheumatoid arthritis, Sjögren syndrome, scleroderma), neoplastic (primary tumors or from secondary metastasis), drug-related, amyloidosis, and chronic heart failure.6-10


Recurrent pericarditis is defined as a relapse of pericarditis after an initial episode of acute pericarditis with a symptom-free interval of 4-6 weeks or longer. Chronic pericarditis is defined as disease process lasting >3 months. 6-8, 10-14 Recurrent pericarditis is presumed to be immune-mediated, but often occurs due to inadequate treatment.15, 16 Lower rates of relapse have been reported in patients who received colchicine in the first or subsequent episodes of pericarditis.3, 11, 13, 17

Role of the Physian Assistant and Nurse Practitioners:

The PA and NP play an essential role in the process of medication adjustment and periodic follow up at the pericardial clinic. These team members co-manage patients with physicians by monitoring inflammatory marker levels while titrating dosages of mediations accordingly. This is done primarily via telephone with lab values faxed in for geographically distant patients, and standard follow up visits with an NP/PA every 2-3 months and with the physician every 6 months. Patients with persistent symptoms or rebounding symptoms, may require more frequent office visits, and referral to appropriate subspecialty teams may become necessary (see Figure 1).

Figure 1: Elements of a Pericardial Disease Center

Figure 1

Diagnosis and Management:

A thorough history and physical exam is imperative in order to differentiate pericardial symptoms from other cardiac syndromes and in possibly isolate an underlying cause. The classic clinical syndrome of pericarditis is chest pain, which is typically sharp, pleuritic in nature, improved with sitting up and leaning forward. Patients may experience other types of pain such as neck, back, shoulder, or arm pain as well as fatigue, malaise, or fever. Diagnostic findings may include pericardial friction rub (albeit this occurs in less than 33% of cases) best heard over the left sternal border, ECG changes and evidence of pericardial effusion either on physical exam or by echocardiography.2, 4, 7, 17 In approximately 60% of cases, there may be classic widespread ST elevations or PR depressions; however ECG changes often vary between patients, the stage of the syndrome, and response to therapy. Other signs and symptoms such as fever or signs of autoimmune, metabolic, infectious, rheumatologic or immunologic disease may point to the etiology of pericarditis.18

Diagnosis of recurrence is similar to that of acute pericarditis with return of symptoms along with elevations in inflammatory markers. It is important to obtain markers of inflammation, including C-reactive protein (CRP) or ultra-sensitive CRP (USCRP) and Westergren erythrocyte sedimentation rate (WSR) at the onset of recurrent episodes. It is crucial to obtain baseline markers of inflammation during the acute and subsequent episodes to help monitor the progression of the disease and response to therapy later on.19

In patients with an identified cause of pericarditis other than viral infection, specific therapy targeted at the underlying disorder should be implemented.20, 21 Anti-inflammatory therapy with aspirin or NSAIDs is typically the mainstay of medical therapy. Colchicine is recommended in addition to standard anti-inflammatory therapy with a course of 3-6 months, and the dose is based on creatinine clearance.7, 11 In certain individuals, colchicine may be required for longer than 6 months. When used in the primary episode of pericarditis, colchicine has been shown to improve the response to therapy and decrease the likelihood of recurrence.11

Women and those who initially fail treatment with NSAIDs are at increased risk for recurrence.4 Individuals suboptimally treated after the initial episode, or those whose anti-inflammatory treatment was tapered too rapidly, have an increased risk of relapse. This includes patients treated with high-dose corticosteroids during the initial episode, individuals rapidly tapered from steroids (e.g., over a course of days to a couple of weeks), and those in whom colchicine was not used. In fact, pericarditis has been shown to recur in up to 50% of those not treated with colchicine after the first recurrence episode.3, 11-3, 17

A simple but effective treatment rule is to taper one class of drug at a time only when symptoms have resolved and CRP levels are normal. One has to bear in mind that recurrence is possible with discontinuation of even a single class of drug. Tapering of therapy may take several months, and colchicine should be gradually discontinued thereafter.7,8,19,22 NSAIDs or aspirin should be used with doses tapered gradually every 1-2 weeks (see table 1).7,8,22 Aspirin may be favored over other NSAIDs (e.g., ibuprofen) primarily in the setting of advanced coronary artery disease or concomitant congestive heart failure.22 Aspirin or NSAIDs may not be a treatment option for those with prior major bleeding events, particularly gastrointestinal bleeding. Corticosteroids should only be considered in patients who are refractory to the aforementioned therapy, or who have contraindications to aspirin/NSAIDs and fail mono therapy with colchicine alone.5 Steroids are reserved for patients refractory to therapy or who demonstrate evidence of significant pericardial inflammation, thickening, scarring, and constriction as evidenced by cardiac MRI. It is imperative to be conservative with steroid therapy as corticosteroids often necessitate a prolonged course, a propensity for developing chronic pericarditis, and increased likelihood of recurrences; this is especially evident when used at high doses.2, 23

Table 1

Corticosteroids should be tapered slowly with monitoring of inflammatory markers and symptoms to guide the process.23 During this process, a slow decrease in daily prednisone dose may prevent recurrence of symptoms (see table 2).23

Table 2

Symptoms are likely to return in the 10-15 mg per day dose range and slower decreases should be considered when approaching this dosage range.7, 8, 23 Should inflammatory markers elevate from baseline or symptoms recur, the patient should be advised to either stop reducing the dose of prednisone or to increase the dose to the previous dosage level. Similarly, among patients not on corticosteroid therapy, our clinical practice is to typically increase the dose of NSAID, aspirin, or colchicine back to the original dose which was associated with absence of symptoms and a normal CRP level. The patient's inflammatory markers are retested in two to four weeks before resumption of the tapering process. NP and PA at the clinic form an important bridge between the physicians and the patients during the process of titration of medications. All patient data including inflammatory marker levels are stored in the electronic medical record.

Another important facet of treatment is in relation to physical activity. Restriction of physical activity is imperative in patients with recurrent symptoms until CRP level is normal and patient is asymptomatic; this is particularly important if there is an association of recurrent symptoms with activity.22, 24 Activity limitations are generally tailored to the individual depending on his or her daily activity level at baseline. Each circumstance is different, but inflammatory markers can be used as a guide in making treatment decisions especially when there is suspicion of a recurrence.

Throughout this process mindfulness to deleterious effects of medications must be kept in mind. Proton pump inhibitor therapy is indicated in all patients on high-dose NSAID therapy.25 Renal function should be regularly monitored while on high-dose NSAIDs. Steroids must be used judiciously in patients with congestive heart failure as this may precipitate an exacerbation of symptoms from fluid retention. Furthermore, it is important to ensure patients on long-term steroid therapy receive adequate calcium and vitamin D supplementation to prevent osteopenia, and bisphosphonates may be indicated in post-menopausal women and men 50 year of age or greater.5, 23 Colchicine interacts with many cardiovascular medicines, particularly with amiodarone and statins, and caution must be used prior to initiating therapy.

Role of Multimodality Imaging in Guiding Therapy in Patients with RP

Under physician guidance, PAs and NPs determine which imaging technique is needed for the patient. Echocardiography is the first line imaging technique that is cost-effective in guiding management of the condition, particularly in the setting of pericardial effusion, to characterize the fluid, assess for hemodynamic compromise and monitor for progression serially.14, 26 Echocardiography also allows detection of ventricular dysfunction, valvular pathology, and other concomitant conditions. Computed tomography is useful in identifying pericardial calcification and for further characterization of the pericardium.22, 23

Cardiac MRI (CMR) can be used to support or confirm the diagnosis of RP in atypical or doubtful cases by detecting pericardial inflammation evidenced by increased pericardial enhancement and edema4, 27, 28 CMR is an important imaging modality at our center since it is comprehensive, not dependent on acoustic windows and allows for comprehensive tissue characterization. It is also useful in deciding intensification of therapy, such as initiation of triple therapy (i.e. NSAID, colchicine, and corticosteroids), by objectively identifying inflammation in spite of previous trials of NSAIDs and colchicine therapy. CMR can also provide assessment of response to medical therapy with serial monitoring of pericardial enhancement (see Figure 2). Furthermore, CMR-guided therapy has been shown to reduce recurrence rate of pericarditis, and incidence of premature steroid exposure of pericarditis patients.14 It has been recently used to identify constriction patients who have potential of reversibility by anti-inflammatory treatment.29, 30 This potentially improves treatment outcomes and eliminates the deleterious effects of long-term steroid use.

Figure 2: Cardiac MRI imaging of 40 year old man with recurrent pericarditis. Delayed gadolinium enhancement demonstrating improvement of pericardial inflammation with triple anti-inflammatory therapy (right).

Figure 2

Recurrent Pericarditis: Scope and Prognosis

The center for management of pericarditis at the Cleveland Clinic receives patients from all over the country. There is a general lack of awareness about the management of RP among the general medical community. Recurrent bouts of pain can be very debilitating for patients with RP. This can affect patients both physically and psychologically and can adversely impact quality of life. Reassuringly, many with recurrent pericarditis will eventually have full remission.4 Much like the chronic heart failure, patients require frequent monitoring of symptoms and progress and benefit from close follow-up. Patients often experience frustration over the waxing and waning course of the disease, the duration of treatment, and limitations on activity. Fear and anxiety over having a reoccurrence is also common. Therefore, it is important to provide reassurance and empathy to patients during this process, while remaining objective with the use of laboratory and imaging evidence as a guide. Our clinic typically keeps a log of inflammatory markers for patients with chronic pericarditis to trend response to therapy and correlate symptoms with elevations in the lab values. Referral to psychiatry or pain management may be needed in certain cases of refractory recurrent pericarditis.

Prognosis is generally good for those with recurrent pericarditis.15, 16, 31 Death or progression to heart failure or symptomatic left ventricular dysfunction are very rare.32 Progression to constrictive pericarditis and tamponade is low (<1%) but needs to be monitored.16, 31, 33 Immunosuppressant medications including IV immunoglobulin, DMARD drugs like Azathioprine, as well as immunomodulating agents such as anakinra are being used as adjuvant therapy, particularly as steroid-sparing agents in patients with steroid-dependent pericarditis who can no longer tolerate the side effects of long-term corticosteroid use.34, 35, 36 Referral to colleagues in rheumatology may be appropriate for this subset of patients and it is important to identify those refractory to traditional therapy. There is a shift at our facility moving towards a cardio-rheumatology subspecialty clinic and it is foreseeable that the physician assistant and nurse practitioner can play a vital role in the coordination of management of these patients. In 2015, our pericardial clinic had 2027 visits for pericardial disease alone; comprising both new and established patients and the number is expected to rise.37 It has become evident that there is a need for these providers to play a pivotal role in the management of pericardial disease by providing continuity of care, enabling access to care, and coordinating care with these often complicated patients amongst other medical specialties. We have met this demand by encouraging the active participation of NPs and PAs in managing these patients in the outpatient clinic along with our staff physicians.


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Keywords: Adrenal Cortex Hormones, Ambulatory Care Facilities, Amiodarone, Amyloidosis, Anti-Inflammatory Agents, Non-Steroidal, Antirheumatic Agents, Azathioprine, Blood Sedimentation, Bone Diseases, Metabolic, C-Reactive Protein, Chest Pain, Cicatrix, Colchicine, Constriction, Continuity of Patient Care, Coronary Artery Disease, Creatinine, Diphosphonates, Echocardiography, Edema, Electrocardiography, Friction, Gadolinium, HIV Infections, Heart Failure, Hemodynamics, Hypothyroidism, Iatrogenic Disease, Immunoglobulins, Intravenous, Immunosuppressive Agents, Inflammation, Interleukin 1 Receptor Antagonist Protein, Mediastinum, Motor Activity, Myocardial Infarction, Neoplasms, Nurse Practitioners, Pain Management, Patient Care, Pericardial Effusion, Pericardiectomy, Pericarditis, Pericarditis, Constrictive, Pericardium, Phrenic Nerve, Physician Assistants, Prednisone, Prognosis, Prostaglandins, Proton Pump Inhibitors, Psychiatry, Quality of Life, Sjogren's Syndrome, Tomography, Treatment Outcome, Tuberculosis, Uremia, Ursidae, Ventricular Dysfunction, Left, Viruses, Vitamin D

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