Pericarditis and Cancer

Pericarditis Etiology

Most pericarditis cases are self-limiting with a relatively benign clinical course.1 The etiologic diagnosis of pericarditis is often elusive, and around two-thirds of cases are considered idiopathic or attributed to viral infections.2,3 Other risk factors are recent cardiothoracic surgery, myocardial infarction, and bacterial infection (e.g., tuberculosis), as well as autoimmune disease and cancer.3,4 In unselected cohorts of pericarditis patients, approximately 5% of cases were attributable to underlying cancer.3,5,6 Among patients with pericardial effusion, malignancy is more prevalent, ranging between 12% and 23% of pericarditis cases.7-10

Cancer Occurrence in Pericarditis Patients

Given the increased occurrence of cancer in subgroups of patients with pericarditis, the differential diagnosis between cancer and other underlying conditions is essential. Diagnosis of cancer as the cause of pericarditis requires imaging (e.g., a computed tomography [CT] scan or cardiac magnetic resonance [CMR] imaging), cytology of pericardial fluid, and ultimately biopsies, confirming malignant infiltration within the pericardial tissue.

Primary malignant tumors of the heart (mesotheliomas, fibrosarcomas, and angiosarcomas) are rare, and most cases of cancer-related pericarditis are caused by metastatic tumors of remote origin.11 Lung cancer is the most common cancer type that may be complicated by pericarditis. Other cancers often identified in pericarditis patients are lymphoma, leukemia, and malignant melanoma, in addition to breast, ovary, prostate, colon, gastric, kidney, and bladder cancer.12-19

Plausible mechanisms linking cancer to development of pericarditis include direct infiltration by malignant cancer cells from proximate structures, pericardial hemorrhage, or spread of cancer cells through the bloodstream.20 Among patients with known cancer disease, pericardial effusion may arise from cancer treatment, most frequently radiation therapy. Chemotherapy also can increase the risk of opportunistic viral or bacterial infections. As well, pericarditis may occur as part of the paraneoplastic syndrome.21

Case reports and descriptive studies first identified the potential link between pericarditis and cancer.12-18 Recently the link was documented in a large population-based cohort study.19 The study was based on several Danish national medical databases, with data cross-linked at the patient level. The study included patients admitted to hospital with pericarditis over a 20-year period (1994–2013) with no previous cancer diagnoses. Follow-up for cancer started upon admission for pericarditis and continued for up to 20 years.

The risk of receiving a cancer diagnosis subsequent to the hospital admission for pericarditis was compared with expected cancer risk in a population with a similar gender and age distribution. Overall, pericarditis patients had a 50% higher occurrence of subsequent cancer diagnoses than the comparison group. Within the first 3 months, the risk was 12-fold higher than expected.

The study's results indicate that pericarditis may be the first clinical manifestation of a hidden cancer, most frequently lung cancer, lymphoma, leukemia, and unspecified metastatic cancer. Prostate, kidney, bladder, ovary, and colon cancers also were detected shortly after pericarditis diagnosis. As noted above, the risk of a cancer diagnosis was highest within the first 3 months after the pericarditis diagnosis, and most pronounced among patients with pericardial effusion (wet pericarditis). Importantly, however, an increased risk also was observed among patients with dry pericarditis. Furthermore, the study indicated that elevated cancer risk may be associated with heart failure, chronic obstructive pulmonary disease, alcohol-related diagnoses, and recent pneumonia or empyema—in addition to pericardial effusion.19

Diagnostic Work-Up for Cancer in Patients Presenting with Pericarditis

The European Society of Cardiology's 2015 guidelines for pericarditis recommend assessment of inflammatory markers, renal and liver function, creatinine kinase, and troponin in all cases of suspected pericarditis. Imaging may be indicated in high-risk patients according to clinical indicators (e.g., large pericardial effusion).1

Clinical examination alone, including auscultation, ECG, and echocardiography, does not discriminate between malignant and non-malignant causes of pericarditis. Specific tumor markers, CT scans or CMR imaging can reveal the presence of cancer.7,22

Physicians treating pericarditis should be aware of the increased risk of cancer. In particular, patients with pericardial effusion or underlying conditions such as heart failure, chronic obstructive pulmonary disease, alcohol-related diagnoses, or recent pneumonia or empyema may need to be considered high-risk patients and referred for a work-up targeted at diagnosing or ruling out incident cancer.

Still, it is important to consider the pros and cons of an extended diagnostic work-up in patients presenting with pericarditis. The absolute cancer risk among these patients is low. Accordingly, the number of patients needed to examine to detect additional cancers is high. The clinical utility of extended screening should not outweigh the economic and patient-related costs, including radiation exposure and anxiety associated with the diagnostic work-up.

Prognosis of Pericarditis and Cancer

Overall, cancer patients with acute idiopathic or viral pericarditis have a good long-term prognosis.23 However, some characteristics are associated with a less favorable course. Factors identified as indicators of poor 6-12 month survival include fever above 38°C, subacute course, large pericardial effusion or cardiac tamponade, and lack of response within seven days to non-steroidal anti-inflammatory drugs (NSAIDs).3 In particular, purulent pericarditis and pericardial effusion have serious implications for cancer prognosis.4,24,25 In-hospital mortality is higher among patients with heart failure or severe infections such as pneumonia or sepsis.15

The cancer stage distribution among patients presenting with pericarditis is comparable to that in cancer patients without this condition. Among patients with lung cancer, complicating pericarditis is a prognostic factor for both short-term and long-term cancer survival. Among patients with bladder and breast cancer, pericarditis may have an impact on or be a clinical marker of reduced long-term survival.19


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Keywords: Pericardial Effusion, Cardiac Tamponade, Hemangiosarcoma, Risk Factors, Urinary Bladder Neoplasms, Troponin, Ovary, Pericarditis, Mesothelioma, Melanoma, Lymphoma, Biopsy, Tomography, X-Ray Computed, Echocardiography, Breast Neoplasms, Tuberculosis, Lung Neoplasms, Pneumonia, Pulmonary Disease, Chronic Obstructive, Heart Failure, Empyema, Leukemia, Anti-Inflammatory Agents, Non-Steroidal, Autoimmune Diseases, Paraneoplastic Syndromes, Auscultation, Colonic Neoplasms, Fibrosarcoma, Electrocardiography, Myocardial Infarction, Magnetic Resonance Spectroscopy, Tomography, Cardiotoxicity

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