Hospitalized elderly patients for acute pericarditis deserve more clinical attention and a closer follow-up monitoring

This editorial refers to ‘Trends in acute pericarditis hospitalizations and outcomes among the elderly in the USA, 1999--2012’, by P Mody et al., on page 98. Acute pericarditis refers to inflammation of the pericardial sac and is the commonest form of pericardial disease. It can occur in isolation or may be a manifestation of an underlying systemic disease.1 The aetiologic spectrum of acute pericarditis is very wide, but in approximately 85–90% patients, it is thought to be idiopathic or presumably viral in origin in the developed world. The yield of diagnostic testing to confirm an aetiology has been relatively low. Among those patients with an established aetiology of acute pericarditis on diagnostic testing, about two-third cases have an infectious aetiology (most commonly viral infection followed by a bacterial infection), and one-third have a non-infectious aetiology (most common causes include systemic autoimmune diseases, pericardial injury syndromes, and neoplastic pericarditis).2,3 The diagnosis of pericarditis is suggested by the presence of at least two of the four clinical criteria: pericarditic chest pain, friction rub, characteristic electrocardiographic (ECG) changes, and new or worsening pericardial effusion. Electrocardiographic changes associated with pericarditis occur in four stages, though not all the stages are observed in all pericarditis patients.4 In Stage 1, diffuse concave ST-segment elevation and PR-segment depression is seen (TP-segment being the isoelectric reference) within the first few hours to days with corresponding ST-depression and/or PR-elevation in aVR and V1. ST-segment normalization is noted in Stage 2 followed by T-wave flattening and inversion in Stage 3. Stage 4 is characterized by the return of the ECG to either normal pre-pericarditis state or indefinitely persistent T-wave inversions (common in cases destined to constrict).4 Initial diagnostic work-up should include an ECG, chest radiograph, complete blood cell count, cardiac biomarkers (creatine kinase and troponin), inflammatory markers (sedimentation rate and C-reactive protein), and echocardiography for most patients3,5 (Figure 1). Serum cardiac biomarkers may be elevated in pericarditis and may suggest concomitant myocardial involvement and are important for patients’ risk stratification. In older patients with additional cardiac risk factors and especially conflicting features in the history or clinical findings, coronary angiography may sometimes be unavoidable to exclude myocardial infarction. Echocardiography is reasonable in all cases of pericarditis, while urgent echocardiography should be strongly considered in cases to facilitate an accurate diagnosis in the emergency settings and especially if there is haemodynamic compromise or suspicion for cardiac tamponade. For patients in whom an autoimmune aetiology is suspected, an antinuclear antibody titre, rheumatoid factor, or anti-neutrophil cytoplasmic antibody should be ordered. Tuberculin skin test or QuantiFERON-tuberculosis (TB) assay and human immunodeficiency virus serology should be ordered in patients from areas with endemic prevalence of TB and/or suspected immunosuppression. If the clinical suspicion for an underlying malignancy is present (relatively common in elderly patients), then appropriate additional testing should be performed. Pericardiocentesis is indicated in suspected purulent, tuberculous, or neoplastic pericarditis or in patients with persistent symptomatic pericardial effusions.3 Diagnostic and treatment algorithm for acute pericarditis. Most patients with acute pericarditis can be managed on outpatient basis. Patients with high-risk clinical features such as pyrexia (temperature > 38 °C), leucocytosis, large pericardial effusion (size >2 cm), subacute symptom onset, cardiac tamponade, acute trauma, immunosuppressed state, concurrent oral anticoagulation, suspected neoplastic pericarditis, failure of non-steroidal anti-inflammatory drug (NSAID) therapy, abnormal cardiac biomarkers, and incessant or recurrent symptoms should be considered for hospitalization.3,5,7 Therapy for acute pericarditis or myopericarditis should be aimed at the specific aetiology, when known. Non-steroidal anti-inflammatory drugs (usually for 2–4 weeks) in combination with Colchicine (for 3 months) are recommended as the first line of therapy for acute idiopathic or viral pericarditis3,5 (Figure 1). The goals of NSAID therapy are the relief of pain and resolution of the inflammation. Colchicine offers anti-inflammatory effect and decreases the recurrence rate of pericarditis. Corticosteroids should be avoided as first line therapy due to increased risk of disease recurrence. They may be considered as second-line agent in non-responders to NSAID and colchicine therapy. Systemic corticosteroids may sometimes be considered as an initial treatment in pericarditis related to autoimmune conditions, pericardial injury syndromes (such as post-ablation pericarditis), and as one of the treatment agents in tuberculous pericarditis.6 The long-term outcomes and mortality in patients with pericarditis have not been previously well evaluated, especially in the elderly patients.3 For majority of patients, acute idiopathic or viral pericarditis represents a benign aetiology without any serious clinical sequela.3,7 Other forms of pericarditis such as exudative/bacterial and neoplastic pericarditis carry a higher morbidity and mortality potential. Clinical presentation of cardiac tamponade is rare and usually occurs in the beginning of the disease. It often requires emergent intervention because of its life-threatening potential and is more common in patients with a specific underlying aetiology such as malignancy, TB, or purulent pericarditis. Constrictive pericarditis is a rare complication in idiopathic pericarditis and occurs in <1% cases of idiopathic pericarditis, although it may occur in about 2–5% cases of autoimmune, immune-mediated, and neoplastic aetiologies; and more commonly (about 20–30% patients) in tuberculous and purulent pericarditis.7,8 The current study by Mody et al.9 reported a surprisingly high mortality rate in acute pericarditis patients. The adjusted all-cause 30 days of mortality rates decreased from 7.6% in 1999 to 5.7% in 2012 and all-cause 1 year of mortality rates decreased from 19.7% in 1999 to 17.3% in 2011, respectively. One may potentially attribute to this slight absolute decline in mortality rates (despite the increase in the trend of patients’ underlying medical comorbidities) in recent years to possibly the utilization of more effective medical therapies such as standard use of colchicine in acute pericarditis and possibly improved inpatient/hospital care. Some of the major possible reasons for a very high mortality rate reported in patients with pericarditis in the this study are sole inclusion of hospitalized geriatric (Medicare) patient population who often have significant associated medical comorbidities and the mortality may be due to alternate unrelated reasons to pericarditis.3 Moreover, it is well known that majority of the acute pericarditis patients may be treated in outpatient setting and only a small proportion of the patients with high-risk clinical features are hospitalized which attributes to a selection bias while accounting mortality in acute pericarditis patients.3 The study incorporated all types of acute pericarditis, not just idiopathic or viral pericarditis. Patients with neoplastic pericarditis are often higher in elderly patients, and mortality in these patients is often dictated by the underlying malignancy. Of note, in almost two-thirds of patients with documented malignancy, pericardial effusion is caused by non-malignant diseases, e.g. radiation pericarditis, other therapies, or opportunistic infections [which would fit the inclusive International Classification of disease-9 diagnosis code of 423.9 (pericardial disease not otherwise specified)]. Study also included patients with post-infarction pericarditis and post-pericardiotomy syndrome which represents a very sick cohort of patients. The specific data on the pericardial diseases in the elderly are scarce since there are no major specific studies conducted on geriatric population, so only expert opinion exists.3 Regardless of the above mentioned considerations, the current study highlights the fact that many elderly hospitalized patients presenting with an acute pericarditis carry a high all-cause morbidity and mortality rate. This may be especially true for elderly patients who have a secondary or non-idiopathic cause of pericarditis and have other significant pre-existing medical comorbidities. One prior large study utilizing Finnish Hospital Registry data reported an in-hospital mortality rate of 1.1% in acute pericarditis patients, but that study excluded post-infarction and post-pericardiotomy patients, and patients were significantly younger compared to the current study [mean age 45.9 years (men) and 56.2 years (women) in prior study vs. overall mean age 76 years respectively in current study].10 Similarly, other two prior randomized studies enrolling patients with acute pericarditis and myopericarditis demonstrated 0% mortality rate on a median follow-up of 24 and 36 months, respectively.11,12 Again, both these prior studies enrolled younger patients (mean age 59 years and median age 39 years, respectively), and most of the patients had idiopathic pericarditis. In contrast, in a recent large population-based Danish Cohort study, pericarditis was found to be a marker for occult cancer and related mortality.13 The study was however significantly limited by the lack of details on the clinical data of the patients and also lack of adjustment or standardization for lifestyle risk factors for malignancy. Median age in this study was 49 years at the time of pericarditis diagnosis, and nearly 71% had unclassified acute pericarditis. Among 13 759 patients with acute pericarditis, 1550 subsequently were diagnosed with cancer during follow-up. Within the first <3 months following an incident pericarditis diagnosis, the absolute cancer development risk was 2.7% with a standardized incidence ratio of 12.4 and overall, 1 year of absolute cancer risk was 3.7% with a standardized incidence ratio of 1.5. The predominant cancer rate was driven by lung cancer followed by kidney, and bladder cancer, lymphoma, leukaemia, and unspecified metastatic cancer. Three months of survival post-cancer diagnosis was 80% and 86% among those with and without pericarditis, respectively (hazard ratio ∼ 1.5), while 1 year of survival rate was 65% and 70%, respectively, corresponding to a 3 to <12 months of hazard ratio of 1.3.13 In the light of current available data which demonstrates a high mortality rate in elderly hospitalized patients with acute pericarditis, it warrants an aggressive medical management with closer clinical attention and follow-up monitoring in those patients. Future long-term prospective studies and registry data specifically focusing on the elderly population would be further helpful to understand the cause-specific mortality and interplay of the various clinical variables and comorbidities in patients of acute pericarditis. Conflict of interest: none declared.