In this study, we compared the clinical and laboratory characteristics between the first presentation of AP and the first documented recurrence. Our main finding is that ECG signs and pericardial effusion are less present or attenuated during recurrent events when compared to the first presentation. Also, serum markers of inflammation are increased to a lesser extent during recurrence. The presence of these findings was mostly not associated with initial disease management. In addition, we describe up to 20% of cases that had positive findings during their recurrence were negative for these findings during their index event. We suggest that the discrepancies in these cases are mainly caused by the timing of evaluation, but this is more speculative and the nature of this phenomenon, as well as its clinical and prognostic significance, warrant further evaluation. On the other hand, the majority of cases do show less pronounced findings that cannot be explained by timing alone, such as maximal CRP levels.

The diagnosis of AP recurrence is a challenge for clinicians. The significance of correct diagnosis is earlier initiation of management, and more rapid symptom relief. Our findings suggest that the sensitivity of the clinical parameters included in the diagnostic criteria supported by current guidelines for RP is low. It seems that in practice, much more emphasis is given to the recurrence of symptoms and the use of serum markers of inflammation. Many patients are diagnosed without meeting the rigid formal guideline-based criteria, most commonly based either on the recurrence of typical pain or pericardial effusion, accompanied by elevated inflammatory markers. They are treated with anti-inflammatory medications and mostly respond well to therapy. Though many contemporary cases go on to get ambulatory cardiac CMR studies that are much more available, we were unable to collect advanced imaging data in this historical cohort. In our experience as a tertiary referral center with a dedicated outpatient clinic for pericardial disease, this approach is useful when deciding on patient management, although some patients do present with persistent chest pain with no other objective evidence of active inflammation.

The low rates of significant pericardial effusion for example, suggest that evaluation with means beyond a bedside echo in the clinic or ED is not necessary in most cases. This understanding can potentially increase confidence in managing such cases in the outpatient setting, thereby reducing the burden of unnecessary hospitalizations and the associated costs of outpatient echo studies. This seems to be a valid strategy at least for patients with a RP, who are otherwise stable and are not at risk of rapid effusion accumulation (e.g., anticoagulant therapy) (Table 2).

Furthermore, our findings, that the manifestation of RP tend to be more subtle, should encourage clinicians to be more proactive in pursuing the diagnosis when it’s unclear, and the patient presents with persistent pain despite a lack of further objective evidence of active inflammation. In these instances, the use of advanced imaging techniques such as CMR can aid in decision making [10]. This could be critical, especially since ongoing pain may lead to up-titration of anti-inflammatory, corticosteroid, or immunomodulatory therapy.

This study has several limitations. First, this single-center retrospective observational study used ICD9 diagnosis coding to identify potential patients. Due to software issues, we were unable to detect PPS patients who did not have symptoms or recurrence beyond the initial hospitalization in the cardiothoracic surgery department. Data on recurrent events treated in other facilities were not available for inclusion in our analysis. Although all cases were reviewed manually to assure that the adjudicated diagnosis was adequate, we did allow for some amount flexibility with the definition in recurrent cases, which could also be defined according to concurrence of symptoms along with deranged laboratory biomarkers, as well as advanced imaging findings. We do believe that this was a more realistic approach to diagnosis, and we also believe that future guidelines will be in line with some form of similar definition, as expert opinion and novel clinical trials in the field have done so as well. We were also unable to obtain exact documentation of time from symptom onset to presentation, or proper documentation of the physical examination detailing the presence or absence of a pericardial friction rub, in either event.