INTRODUCTION — Malignant involvement of the pericardium is seen in 1 to 20 percent of autopsies in patients with cancer. The most common metastatic tumor involving the pericardium is lung cancer; others include breast and esophageal cancer, melanoma, lymphoma, and leukemia. Although AIDS-related Kaposi's sarcoma (KS) has been an important cause of neoplastic pericardial disease, the incidence of KS has declined dramatically since the advent of potent antiretroviral therapy. (See 'Etiology and pathogenesis' below and "AIDS-related Kaposi sarcoma: Clinical manifestations and diagnosis", section on 'Epidemiology and risk factors' and "Cardiac and vascular disease in patients with HIV", section on 'Pericardial disease'.)
Here we will discuss the presentation and management of pericardial disease associated with malignancy. An overview of the etiology of pericardial disease, and the general presentation, diagnosis, and management of constrictive pericarditis and pericardial effusion are presented elsewhere. (See "Etiology of pericardial disease" and "Constrictive pericarditis: Diagnostic evaluation and management".)
EPIDEMIOLOGY — Malignant involvement of the pericardium is detected in 1 to 20 percent of cancer cases in autopsy studies [1,2]. Direct involvement of the myocardium is much less frequent, either by metastatic or primary tumors [3,4]. In two large autopsy series [2,5], the incidence of any cardiac involvement was 11 and 12 percent, respectively. Of these, 76 percent had pericardial involvement, and 34 percent had an associated effusion [2].
Malignancy is also a common cause of large symptomatic pericardial effusions [6]. In some cases, the effusion may be the initial clinical manifestation of the malignancy. This was suggested in a review of 173 consecutive patients undergoing pericardiocentesis for symptomatic pericardial effusion [7]. Symptomatic effusions were defined as those with cardiorespiratory symptoms (eg, dyspnea), signs (eg, tachycardia), echocardiographic features of right heart compromise, or if pericardiocentesis was deemed therapeutic by the clinician. A cause for the effusion was found in all but 13 patients. The most common cause was malignancy, which was found in 58 patients (33 percent), 45 of whom had known malignant disease. After exclusion of pericardial effusions in which the etiology was apparent from the history, physical examination, and simple laboratory tests (eg, trauma, uremia, post-pericardiotomy, rheumatic disease, known malignancy), newly found cancer was responsible for 18 percent of the remaining 74 cases.
Importantly, pericardial effusions in patients with cancer may also be triggered by a mechanism other than the cancer itself, including chemotherapy and radiation therapy. Traditional chemotherapy agents such as fludarabine, cytarabine, doxorubicin, docetaxel, and cyclophosphamide have been associated with acute pericarditis and pericardial effusion [8,9]. Dasatinib, a tyrosine kinase inhibitor targeting BCR-ABL, KIT, and platelet-derived growth factor receptor beta, has also been linked to an increased incidence of pericardial effusions [10]. More recently, immune checkpoint inhibitors are increasingly recognized as a cause of acute pericarditis, pericardial effusion, and tamponade [11,12]. (See "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Cardiovascular toxicity'.)
ETIOLOGY AND PATHOGENESIS — Most pericardial disease in patients with known malignancy is due to malignant involvement, although a substantial minority of cases are not caused by direct involvement by the cancer. In several single-center series of pericardiocentesis, a malignant etiology for pericardial disease was identified in up to 60 percent of patients [1,13-16]. In the remainder, idiopathic pericarditis was most common, while prior radiation therapy was thought to be contributory in 10 to 20 percent [17-19]. (See "Etiology of pericardial disease" and "Cardiotoxicity of radiation therapy for breast cancer and other malignancies".)
The most common primary tumor involving the pericardium is lung cancer, and the approximately 5 percent of non-small cell lung cancers that harbor an anaplastic lymphoma kinase (ALK) rearrangement are particularly likely to involve the pericardium or to present with a pericardial effusion [20]. (See "Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer", section on 'Clinicopathologic features'.)
Other common tumor types include breast and esophageal cancer, melanoma, lymphoma, and leukemia [2,5,13,14,21-23]. Although AIDS-related Kaposi's sarcoma (KS) has been an important cause of neoplastic pericardial disease [24,25], the incidence of KS has declined dramatically in the era of potent antiretroviral therapy. (See "AIDS-related Kaposi sarcoma: Clinical manifestations and diagnosis", section on 'Epidemiology and risk factors' and "Cardiac and vascular disease in patients with HIV", section on 'Pericardial disease'.)
Malignant tumors can involve the pericardium by direct local invasion or through metastatic spread via the lymphatics or bloodstream. In addition, primary tumors can arise in the pericardium, although these are much less frequent than secondary involvement [3]. (See 'Miscellaneous pericardial lesions' below and "Cardiac tumors".)
Importantly, pericardial effusions in patients with cancer may also be triggered by a mechanism other than the cancer itself, including chemotherapy, radiation therapy, and, less commonly, an infectious disease:
●Traditional chemotherapy agents such as fludarabine, cytarabine, doxorubicin, docetaxel, and cyclophosphamide have been associated with acute pericarditis and pericardial effusion [8,9]. Dasatinib, a tyrosine kinase inhibitor targeting BCR-ABL, KIT, and platelet-derived growth factor receptor beta, has also been linked to an increased incidence of pericardial effusions [10]. More recently, immune checkpoint inhibitors are increasingly recognized as a cause of acute pericarditis, pericardial effusion, and tamponade [11,12]. (See "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Cardiovascular toxicity'.)
●Radiation therapy to the chest is also well known to be associated with acute pericarditis, pericardial effusion, and also the long-term side effect of constrictive pericarditis [26]. (See 'Constrictive pericarditis' below.)
●Infectious etiologies are not believed to be a common cause of pericardial diseases in cancer patients [16] but can be associated with high mortality in these immunocompromised patients, especially when etiology is related to fungal infection [27]. (See "Etiology of pericardial disease".)
CLINICAL SYNDROMES AND THEIR PRESENTATION — Malignant involvement of the pericardium can manifest as pericarditis, pericardial effusion, cardiac tamponade, or pericardial constriction (constrictive pericarditis). In some cases, pericardial disease is the first manifestation of malignancy, and an important clinical question is whether to pursue a search for an occult cancer as the etiology for the pericardial disease.
Presentations of patients with previously undiagnosed malignancy — A detailed evaluation to search for occult malignancy should generally be reserved for patients who have persistent acute or recurrent pericarditis that is unresponsive to anti-inflammatory therapy and in whom malignancy is a concern (eg, because of unexplained weight loss or a heavy smoking history) and those who present with a new large pericardial effusion or cardiac tamponade. (See "Cardiac tamponade" and "Diagnosis and treatment of pericardial effusion", section on 'Quantification of the pericardial effusion'.)
Among patients presenting with acute pericarditis or a small pericardial effusion without known malignancy, the likelihood of finding previously undiagnosed cancer has historically been reported as between 4 and 7 percent [28-31]. Subsequently, however, in a nationwide Danish cohort study of 13,759 patients with a first episode of acute pericarditis between 1994 and 2013, 1550 persons (11.3 percent) were subsequently diagnosed with a malignancy [32]. Similarly, utilizing the United Kingdom database of 6530 patients with a first episode of acute pericarditis between 1998 and 2015, 728 persons (11.1 percent) were diagnosed with a malignancy [33].
As an example, a prospective study evaluated 231 consecutive patients presenting with acute pericarditis or cardiac tamponade without apparent cause [29]. All received an empiric trial of anti-inflammatory therapy, and nonresponders went on to pericardiocentesis and/or pericardial biopsy. A specific diagnosis was established in 32 (14 percent), only 13 of whom had cancer (6 percent of the total).
Patients presenting with constrictive pericarditis also have a low likelihood of harboring an undiagnosed malignancy. In three large case series of patients with constriction, malignancy was identified in fewer than 3 percent [34-36]. However, radiation therapy, mostly for previously diagnosed Hodgkin's disease or breast cancer, was thought to be causative in 9 to 31 percent of patients. (See "Constrictive pericarditis: Diagnostic evaluation and management".)
By contrast, the likelihood of finding malignancy is higher in patients who present with a large pericardial effusion or cardiac tamponade or in those who are identified with effusive-constrictive pericarditis:
●In a series of 57 patients with a new large effusion, a specific diagnosis was established by pericardial biopsy and/or fluid cytology in 93 percent; 13 (23 percent) had a previously undiagnosed malignancy [37]. (See "Diagnosis and treatment of pericardial effusion".)
●In a report of 450 patients with acute pericardial disease, 33 (7.3 percent) had a neoplastic cause [28]. Other than a prior history of malignancy, the major clinical characteristics associated with a neoplastic cause were cardiac tamponade at presentation (odds ratio [OR] 7.0, 95% CI 1.3-38.2), lack of response to nonsteroidal anti-inflammatory drugs, and recurrent or persistent pericarditis (OR 10.0, 95% CI 3.6-27.1). (See "Cardiac tamponade".)
Acute pericarditis — Acute pericarditis can present with a variety of nonspecific signs and symptoms, depending on the underlying etiology. The major clinical manifestations of acute pericarditis include pleuritic chest pain, pericardial friction rub, and widespread saddle-shaped or concave up ST-segment elevation on the electrocardiogram (ECG) (waveform 1), with or without pericardial effusion. The chest pain is characteristically pleuritic, radiates to the trapezius ridge, and is worse in the supine position. These factors help to differentiate it from pain due to myocardial ischemia.
At least two of the four clinical features (chest pain, pericardial friction rub, ECG changes, and pericardial effusion) should be present to make the diagnosis. Pericarditis should also be suspected in a patient with persistent fever and either a pericardial effusion or new unexplained cardiomegaly. (See "Acute pericarditis: Clinical presentation and diagnosis".)
Pericardial effusion with or without cardiac tamponade — Pericardial effusion is an accumulation of fluid in the pericardial space, with or without associated pericarditis. Cardiac tamponade refers to a situation in which the pressure from an accumulating pericardial effusion approaches and then equalizes with intracardiac pressures, leading to impaired filling of one or usually both ventricles and decreased cardiac output. (See "Diagnosis and treatment of pericardial effusion" and "Cardiac tamponade".)
Most patients without a hemodynamically significant pericardial effusion (ie, without cardiac tamponade) will have no symptoms specific to the effusion, but they may have symptoms related to the underlying cause (eg, fever in the setting of pericarditis, etc). The clinical features of cardiac tamponade usually depend upon whether the onset of fluid accumulation is acute or subacute; cardiac tamponade is usually subacute in the setting of malignancy:
●Acute cardiac tamponade is generally rapid in onset, may be associated with chest pain and dyspnea, and is life-threatening if not promptly treated. With rapid introduction of even a small amount of fluid into the pericardial space, the parietal pericardium cannot "stretch" to accommodate the increase in volume. This results in an acute rise in pericardial pressure, which is transmitted to all cardiac chambers and limits diastolic filling.
●Subacute cardiac tamponade is a less dramatic process. Patients may be asymptomatic or complain of dyspnea, chest discomfort or fullness, and/or easy fatigability. The physical examination may reveal hypotension with a narrow pulse pressure, reflecting the limited stroke volume.
While an effusion may present with recognizable clinical findings, the most common method of detection is by echocardiography. A pericardial effusion that arises in a patient with a known malignancy usually represents metastatic spread of the malignancy [1]. However, other etiologies for the pericardial effusion should be considered. Patients with a history of thoracic radiation treatment can develop a radiation-induced pericarditis with a pericardial effusion. In addition, patients who are immunocompromised due to treatment of an underlying malignancy can develop infectious or autoimmune pericardial effusions [1]. (See "Etiology of pericardial disease", section on 'Pericardial effusion' and "Diagnosis and treatment of pericardial effusion" and "Cardiotoxicity of radiation therapy for breast cancer and other malignancies", section on 'Esophageal cancer'.)
Constrictive pericarditis — Constrictive pericarditis, sometimes referred to as pericardial constriction, results from scarring and fibrosis of the visceral and/or parietal pericardium, which progressively restricts diastolic filling of the ventricles. Patients with constrictive pericarditis typically present with one or both of the following constellations of symptoms: symptoms related to fluid overload, ranging from peripheral edema to anasarca; and/or symptoms related to diminished cardiac output in response to exertion, such as fatigability and dyspnea on exertion. The clinical features of cardiac tamponade and constrictive pericarditis overlap somewhat, but there are important differences in terms of management and prognosis. (See "Constrictive pericarditis: Diagnostic evaluation and management".)
In effusive-constrictive pericarditis, there is both stiffening of the pericardium and a hemodynamically significant effusion. Drainage of pericardial fluid may unmask findings typical of constrictive physiology [38]. This subject is discussed in greater detail elsewhere. (See "Variants of constrictive pericarditis", section on 'Effusive-constrictive pericarditis'.)
Miscellaneous pericardial lesions — Although a number of primary tumors may arise in the pericardium, they are extremely rare. These include lesions such as mesotheliomas, teratomas, and paragangliomas. In addition, benign lesions such as pericardial cysts and lipomas should be included in the differential diagnosis. These issues are discussed in detail elsewhere. (See "Cardiac tumors".)
OVERVIEW OF THE APPROACH TO THE PATIENT — We pursue an algorithmic approach to the patient with a known or suspected malignancy who has suspected neoplastic pericardial disease, as shown in the figure (algorithm 1).
Our approach — For nearly all patients, the initial workup will entail an ECG, chest radiograph, and echocardiogram, with or without cross-sectional imaging of the chest as part of staging or restaging of malignancy.
●If a pericardial effusion is demonstrated, the next step is to determine if there are signs or symptoms suspicious for cardiac tamponade, which implies the need for urgent pericardial drainage. (See 'Pericardial effusion with or without cardiac tamponade' above.)
●If a pericardial effusion is demonstrated without evidence of cardiac tamponade, pericardial fluid sampling or a pericardial biopsy may still be needed, particularly if there has not been a preexisting diagnosis of malignancy, to document potential spread of the malignancy to the pericardial space. (See 'Cytology, flow cytometry, and pericardial biopsy' below.)
●If there are signs or symptoms of constrictive pericarditis rather than a pericardial effusion, cardiac magnetic resonance imaging or right heart catheterization may be needed. (See 'Diagnostic evaluation' below.)
Once evidence of neoplastic pericardial disease has been demonstrated, the choice of treatment depends on a number of factors including the symptom burden (ie, is there a need for acute management of an effusion versus prevention of reaccumulation), the specific malignancy and whether there are available antitumor therapy options to control the malignancy, the estimated life expectancy of the patient (which is based upon status of the malignancy, comorbidity, and performance status), and goals of care. An understanding of patients' care goals in the context of their illness permits clinicians to align the care provided with what is most important to the patient. (See "Discussing goals of care".)
Many patients will benefit from formal palliative care consultation and services. Early referral and initiation of palliative care services improve clinical and quality of care outcomes. (See "Benefits, services, and models of subspecialty palliative care".)
Importance of prognosis and the status of the underlying malignancy — The potential for prolonged survival is an important issue when choosing the therapeutic intervention for an individual patient with a suspected pericardial effusion. Most patients with a symptomatic malignant pericardial effusion have a short life expectancy (median two to four months) [39-50]. However, prognosis may be better in certain subsets of patients, such as those without malignant cells in the pericardium (at least in the setting of non-small cell lung cancer) [51,52], hematologic rather than solid tumors [41], breast cancer rather than lung cancer [16,41,53,54], and in patients who are candidates for systemic therapy versus not [55,56] or whose malignancy is otherwise well controlled [40].
With improved systemic chemotherapy and molecularly targeted therapy for non-small cell lung cancer (NSCLC) in recent years, the prognosis for such patients has improved [57]. In particular, the approximately 5 percent of patients with NSCLC who harbor an anaplastic lymphoma kinase (ALK) rearrangement as a driver mutation have a high propensity to present with pericardial metastases or a pericardial effusion [20] and may demonstrate a dramatic and prolonged response to targeted therapies against this molecular target for several years. (See "Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer".)
DIAGNOSTIC EVALUATION — All patients with suspected pericardial disease should have an ECG, chest radiograph, and echocardiogram, with cross-sectional imaging (ie, computed tomography [CT] or magnetic resonance imaging [MRI]) as needed as part of the staging or restaging of the malignancy (algorithm 1). Additional testing is guided by the results of the initial tests but may include pericardial biopsy or pericardiocentesis to obtain material for histologic/cytologic analysis and cardiac catheterization to assess hemodynamics.
Electrocardiography — All patients with suspected pericardial disease should have an ECG.
●In patients with acute pericarditis, characteristic ECG findings include diffuse ST elevation (typically concave up) with reciprocal ST depression in leads aVR and V1 (waveform 1). There is also frequently an atrial current of injury, reflected by elevation of the PR segment in lead aVR and depression of the PR segment in other limb leads and in the left chest leads, primarily V5 and V6. Thus, the PR and ST segments typically change in opposite directions. (See "Acute pericarditis: Clinical presentation and diagnosis", section on 'Electrocardiogram'.)
●In patients with a pericardial effusion, especially if cardiac tamponade is present, QRS voltage may be decreased, and occasionally electrical alternans is seen (waveform 2). This abnormality is characterized by a cyclic beat-to-beat shift in the QRS axis associated with mechanical swinging of the heart to-and-fro, usually in a large pericardial effusion. (See "Diagnosis and treatment of pericardial effusion", section on 'ECG findings'.)
Atrial fibrillation may be seen in patients with pericardial disease, especially constrictive pericarditis.
Chest radiography — All patients with suspected pericardial disease should have a chest radiograph.
●Chest radiography is insensitive for the detection of pericardial disease and is typically normal in acute pericarditis. (See "Acute pericarditis: Clinical presentation and diagnosis", section on 'Chest radiograph'.)
●In patients with subacute cardiac tamponade, typical findings can include an enlarged cardiac silhouette with clear lung fields. (See "Cardiac tamponade", section on 'Chest radiograph'.)
●Pericardial calcifications in the presence of typical symptoms are strongly suggestive of constrictive pericarditis, although calcification is infrequently seen. (See "Constrictive pericarditis: Diagnostic evaluation and management", section on 'Chest radiograph'.)
A chest radiograph is useful for detecting a concomitant pleural effusion. In a surgical series of 47 patients treated for symptomatic pericardial effusion, 41 (87 percent) had a concomitant pleural effusion, and 20 (42 percent) of these were cytologically positive for malignancy (image 1) [39].
Echocardiography — All patients with suspected pericardial disease should have an echocardiogram. Echocardiography is the primary imaging tool used to establish the presence and quantity of a pericardial effusion and to evaluate its hemodynamic impact, particularly the presence of cardiac tamponade or constrictive physiology. For patients not requiring immediate therapeutic intervention, echocardiography is also the primary means to monitor changes in hemodynamic status or effusion size. (See "Diagnosis and treatment of pericardial effusion", section on 'Diagnostic approach' and "Constrictive pericarditis: Diagnostic evaluation and management" and "Cardiac tamponade".)
CT and MRI — We proceed with cross-sectional imaging, usually with CT but sometimes with MRI, when the suspicion of pericardial disease remains following nondiagnostic initial testing (ECG, chest radiograph, and echocardiogram) (image 2 and image 3 and image 4) [58]. Additionally, cross-sectional imaging is frequently a part of the staging/restaging process of the malignancy. Both abdominal and chest CT can provide information about the pericardial space (image 5).
Beyond the identification of pericardial effusion or pericardial thickening, large tumor masses within the pericardial sac (image 6) can be recognized by most imaging modalities, although CT and MRI are both superior to echocardiography for providing anatomic information. CT and MRI are also more specific for determining whether an effusion is hemorrhagic or loculated [59]. These modalities also have the advantage of providing information about the remainder of the chest as well (eg, detecting the presence of a primary tumor or metastatic foci within lung parenchyma). In some cases (particularly in the setting of trauma), a hematoma may be mistaken for a neoplasm. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Pericardial disease'.)
Cytology, flow cytometry, and pericardial biopsy — Pericardiocentesis with cytologic and/or flow cytometric examination of the pericardial fluid should be performed in patients with a pericardial effusion whenever there is a reason to suspect malignancy. Cytologic evaluation is especially important if the effusion is hemorrhagic and there is no history of antecedent trauma; such effusions are more likely to be malignant than nonhemorrhagic effusions [60]. (See "Diagnosis and treatment of pericardial effusion".)
The sensitivity of cytology for the diagnosis of a malignant effusion is between 67 and 92 percent and is lowest for mesothelioma and lymphoma [13,15,61-63]. Immunohistochemical staining may help in the distinction between malignant cells and atypical mesothelial cells, as well as provide information as to the likely tissue of origin if malignant cells are present [64-66].
Negative cytology should not be used to exclude the diagnosis of malignancy, particularly if the index of suspicion is high [67]. A pericardial biopsy may be required and can be performed via a subxiphoid or transthoracic pericardiostomy (window) or by pericardioscopy (where available). Pericardioscopy allows direct visualization of the pericardial space; the reported sensitivity for the diagnosis of malignancy is as high as 97 percent [15,68,69]. By contrast, the sensitivity for blind pericardial biopsy is lower (55 to 65 percent), presumably because of sampling error [13,15,61-63]. The therapeutic drainage "window" created by a subxiphoid or transthoracic approach yields a four square centimeter piece of tissue, which can be useful to confirm the diagnosis.
A positive cytology may be predictive of a poorer outcome in patients with neoplastic pericardial disease. In a multivariate analysis of patients with malignancy-related pericardial effusion, a positive cytology was an independent predictor of shortened survival (median survival 7 versus 30 weeks in the setting of normal cytology) [14]. Patients with positive cytology were also more likely to require repeat pericardiocentesis or surgical intervention. (See 'Prevention of effusion reaccumulation' below.)
Flow cytometry is an important adjunct to cytology, particularly for lymphomas [70,71]. In one report of 115 consecutive serous cavity effusions in patients with a variety of malignant diagnoses, the provisional cytopathologic diagnosis was altered by the results of flow cytometry in 18 cases (16 percent of the total), from atypical/suspicious to benign in 8 cases and from benign or atypical/suspicious to malignant in 10 cases [71]. (See "Clinical presentation and initial evaluation of non-Hodgkin lymphoma", section on 'Pleural/pericardial fluid'.)
Cardiac catheterization — Hemodynamic assessment with simultaneous right and left heart catheterization is useful diagnostically and can also characterize the impact of pericardial disease upon cardiac filling and performance, particularly if echocardiographic findings are inconclusive or equivocal. Constrictive pericarditis is often indistinguishable from restrictive cardiomyopathy based upon clinical and echocardiographic criteria alone, and invasive hemodynamic assessment, particularly the examination of respirophasic changes in pressures, can be vital in the diagnostic algorithm [72]. Indeed, both entities may coexist, particularly in the setting of radiation-induced pericardial disease. (See "Constrictive pericarditis: Diagnostic evaluation and management" and "Differentiating constrictive pericarditis and restrictive cardiomyopathy", section on 'Cardiac catheterization'.)
TREATMENT — Treatment of pericardial disease in malignancy is indicated to improve symptoms (eg, pain, dyspnea, edema) and to reverse and prevent hemodynamic compromise (algorithm 1).
Management of painful acute pericarditis — In the treatment of acute symptomatic pericarditis, the goals of therapy are the relief of pain, resolution of inflammation (and, if present, pericardial effusion), and the prevention of recurrence. Because of limited available data to guide management of acute pericarditis specifically in cancer patients, most treatment recommendations are empirical and based on small cohort studies and experts opinions.
For nearly all patients with acute pericarditis, we recommend combination therapy with colchicine plus nonsteroidal anti-inflammatory drugs (NSAIDs), although there are no data to support benefit in the specific setting of malignant pericardial disease. For patients with an identified cause of the pericarditis (eg, malignancy, specific infection in the setting of being immunocompromised, etc), specific therapy appropriate to the underlying disorder is indicated. Our general approach to treatment of painful acute pericarditis from a variety of etiologies is discussed in detail separately. (See "Acute pericarditis: Treatment and prognosis".)
Management of pericardial effusion — The management of pericardial effusion has two components:
●Acute management, with the intent of alleviating any hemodynamic compromise in patients with cardiac tamponade and/or obtaining fluid for diagnostic evaluation
●Chronic management, aimed at preventing fluid reaccumulation that could result in symptoms or recurrent cardiac tamponade
Acute management of the effusion — For highly symptomatic patients or those with evidence of hemodynamic compromise, urgent fluid removal is needed to alleviate symptoms and prevent hemodynamic collapse [6]. Fluid is typically removed either by percutaneous pericardiocentesis under echocardiographic guidance or at the time of surgical creation of a pericardial window. This generally results in rapid and dramatic improvement in symptoms and hemodynamics, even if clinical or echocardiographic signs of cardiac tamponade persist. (See 'Surgical decompression of the pericardium' below and "Diagnosis and treatment of pericardial effusion", section on 'Percutaneous pericardiocentesis versus surgical drainage'.)
The development of symptoms such as fatigue, dyspnea, or chest heaviness should prompt repeat echocardiography and consideration of therapeutic intervention. Asymptomatic or minimally symptomatic pericardial effusions can be managed conservatively with careful monitoring, avoidance of volume depletion, and appropriate antineoplastic therapy, if possible (see below). Some patients will never develop symptoms or require treatment. As an example, in one series of 20 women with breast cancer and an incidentally found pericardial effusion, only one subsequently became symptomatic [18].
Prevention of effusion reaccumulation — Among the approaches to prevent reaccumulation are prolonged catheter drainage and the creation of a permanent pericardial "window" allowing drainage of fluid into the pleural or peritoneal cavity. There is no single approach that is applicable to all patients, and the therapeutic choice should be guided by the patient's overall medical status, prognosis of the underlying malignancy, goals of care, and the availability of medical and surgical resources.
Although pericardiocentesis effectively relieves symptoms and improves hemodynamics, fluid reaccumulates in as many as 60 percent of cases [42,73]. In a systematic review of percutaneous interventions for malignant pericardial effusion, which included data from 31 nonrandomized studies, any intervention other than isolated pericardiocentesis was associated with significantly lower rates of recurrence [74]:
●Isolated pericardiocentesis (305 patients) – 38.3 percent recurrence rate
●Pericardiocentesis with extended catheter drainage (486 patients) – 12.1 percent recurrence rate
●Balloon pericardiotomy (157 patients) – 10.3 percent recurrence rate
Thus, initial management of a proven malignant pericardial effusion should usually be combined with measures to prevent recurrence.
Prolonged catheter drainage — Prolonged catheter drainage effectively prevents fluid reaccumulation, although the mechanism by which this occurs is unclear. In multiple series, this approach was successful in 70 to 90 percent of cases, although the duration of effusion control was not always reported [16,74-76]. As an example, one series reported recurrence in 30 percent of cases at a median average time of 39 days, whereas another series reported a 13 percent rate of recurrent effusion with one year of follow-up [43,77].
Catheter drainage may be required for several days [76,77]. The catheter should not be removed until drainage is minimal (<25 to 50 mL in a 24-hour period) to none. In one series of 171 patients with malignancy and pericardial effusion who underwent echocardiography-guided pericardiocentesis followed by extended catheter drainage, the average time to minimal catheter output (<50 mL in 24 hours) was three days [76]. If rates of fluid drainage are still high after three to five days, a pericardial window should be considered.
The reported incidence of complications from prolonged catheter drainage ranges from 7 to 17 percent and includes pericarditic chest pain, catheter occlusion, infection, fever, pneumothorax, ventricular puncture, and cardiac arrest [42,43,78]. Intermittent rather than continuous drainage may help to maintain catheter patency.
Surgical decompression of the pericardium — Surgical decompression of the pericardium is also known as pericardiotomy, pericardiostomy, and "window" pericardiectomy. Surgical creation of a pericardial "window" can be accomplished using various surgical techniques (eg, open surgery, video assisted thoracoscopy [VATS]). While no randomized trials have been done comparing surgical and percutaneous drainage of pericardial effusions, retrospective studies demonstrated immediate hemodynamic benefit in almost all patients with minimal post-procedural morbidity and mortality [43,45-48,75,79,80]. A systematic review including data from 59 nonrandomized studies suggested a higher likelihood of successful control of the effusion with surgical intervention as compared with a percutaneous approach [81]. However, the lack of randomized trials for this problem along with likely selection bias in these reports limit the power of any recommendation.
While recurrence rates vary slightly according to surgical technique, recurrence of a large or symptomatic pericardial effusion following transthoracic (thoracotomy or VATS) pericardiostomy was seen in only 5 to 10 percent of patients, compared with approximately a 20 percent rate following pericardiocentesis alone. Recurrence rates are slightly higher when a subxiphoid approach is used because these "windows" do not drain to an absorptive mesothelial surface [80]. Moreover, approximately one-third of patients with malignant pericardial disease have coexisting pleural pathology which may need to be addressed concurrently.
A hemodynamically significant pericardial effusion is often best treated with pericardiocentesis prior to surgery in order to avoid further instability or cardiovascular collapse during induction of general anesthesia for a surgical approach [80]. (See "Cardiac tamponade".)
Balloon pericardiotomy — Balloon pericardiotomy is an alternative to surgical creation of a pericardial window [49,74,82-85]. This procedure may be performed either immediately following initial pericardiocentesis or after pericardial effusion recurrence. (See "Diagnosis and treatment of pericardial effusion", section on 'Treatment'.)
Pericardial sclerosis — Intrapericardial instillation of sclerosing agents is thought to produce inflammation and scarring of the pericardial surfaces, thereby eliminating the potential space for fluid reaccumulation. A number of agents have been used, generally in conjunction with prolonged catheter drainage, including tetracycline and related agents [44,86-88], bleomycin [86,89-92], cisplatin [93], thiotepa [94,95], and talc [96]. However, no intrapericardial treatment has shown a clear advantage over prolonged catheter drainage alone [74], there are almost no high-quality data to support its use, and instillation of most of these agents is accompanied by severe pain, and the potential for constrictive pericarditis [97]. Although European guidelines still include this as an option, at least for non-small cell lung and breast cancers [98,99], we do not recommend its use in any setting.
Management of constrictive pericarditis — In cancer patients, "classic" constrictive pericarditis due to malignant involvement is unusual. Most cases fall into the effusive-constrictive category for which it is often the effusion and not the constriction that is causing symptoms and requires management.
Nevertheless, some patients with constrictive pericarditis may require surgical removal of the pericardium, provided that the prognosis from the malignancy justifies surgery. Pericardiectomy is the only definitive treatment option for patients with chronic constrictive pericarditis. Medical therapy (ie, diuretics) may be used as a temporizing measure and for patients who are not candidates for surgery. (See 'Importance of prognosis and the status of the underlying malignancy' above and "Constrictive pericarditis: Diagnostic evaluation and management", section on 'Treatment'.)
The reported operative mortality for pericardiectomy for pericardial constriction is 6 to 12 percent [29,35,36,100]. Although the majority of patients have relief of symptoms after pericardiectomy, some do not. Pericardiectomy may not benefit patients with mild constriction or those patients with very advanced disease. Constriction in patients whose only abnormality is a mild to moderate increase in central venous pressure with little or no edema can be followed clinically. Patients with "end-stage" constrictive pericarditis manifest by cachexia, atrial fibrillation, low cardiac output at rest, and depressed serum albumin level due to protein losing enteropathy show little or no benefit, and the operative risk is inordinately high. (See "Constrictive pericarditis: Diagnostic evaluation and management".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pericardial disease".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient education: Pericarditis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Malignant involvement of the pericardium is detected in 1 to 20 percent of autopsy studies of cancer patients. While the most common primary tumor involving the pericardium is lung, tumors of the breast and esophagus, melanoma, lymphoma, and leukemia also frequently spread to the pericardium. (See 'Etiology and pathogenesis' above.)
●Malignant involvement of the pericardium can manifest as painful pericarditis, pericardial effusion, cardiac tamponade, or constrictive pericarditis. Among patients known to have an underlying malignancy who present with pericardial effusion requiring drainage, between 50 and 60 percent will have a malignant effusion. (See 'Clinical syndromes and their presentation' above and 'Etiology and pathogenesis' above.)
●In some cases, pericardial disease is the first manifestation of malignancy, and an important clinical question is whether to pursue a search for an occult cancer as the etiology for the pericardial disease. A detailed evaluation to search for occult malignancy should generally be reserved for patients who have persistent pericarditis that is unresponsive to anti-inflammatory therapy, and in whom malignancy is a concern (eg, because of unexplained weight loss or a heavy smoking history), and those who present with a new large pericardial effusion or cardiac tamponade. (See 'Presentations of patients with previously undiagnosed malignancy' above.)
●All patients with suspected malignant pericardial disease should have an ECG, chest radiograph, and echocardiogram, with cross-sectional imaging (ie, computed tomography [CT] or magnetic resonance imaging [MRI]) as needed as part of the staging or restaging of the malignancy (algorithm 1). Additional testing is guided by the results of the initial tests but may include pericardial biopsy or pericardiocentesis to obtain material for histologic/cytologic analysis, and cardiac catheterization to assess hemodynamics. (See 'Diagnostic evaluation' above.)
●An algorithmic approach to the patient with a known or suspected malignancy who has suspected pericardial disease is shown in the figure (algorithm 1). (See 'Overview of the approach to the patient' above.)
●Cytologic examination of the pericardial fluid with or without flow cytometric evaluation should be performed in patients with a pericardial effusion whenever there is a reason to suspect malignancy. At least in the setting of non-small cell lung cancer, positive cytology may be predictive of shorter survival in patients with neoplastic pericardial disease. Negative cytology does not exclude the diagnosis of malignancy, particularly if there is a high index of suspicion. In this situation, a pericardial biopsy should be considered to confirm or exclude pericardial malignancy. (See 'Cytology, flow cytometry, and pericardial biopsy' above.)
Management of neoplastic pericardial disease depends on a number of factors including the symptom burden (ie, is there a need for acute management of an effusion versus prevention of reaccumulation), the specific malignancy and whether there are available antitumor therapy options, the estimated life expectancy of the patient (which is based upon status of the malignancy, comorbidity, and performance status), and goals of care. (See 'Importance of prognosis and the status of the underlying malignancy' above.)
●Many patients will benefit from formal palliative care consultation and services. Early referral and initiation of palliative care services improve clinical and quality of care outcomes. (See "Benefits, services, and models of subspecialty palliative care".)
●For highly symptomatic patients or those with evidence of hemodynamic compromise, urgent fluid removal is needed to alleviate symptoms and prevent hemodynamic collapse. (See 'Acute management of the effusion' above.)
●Among the approaches to prevent reaccumulation are prolonged catheter drainage and the creation of a permanent pericardial "window" allowing drainage of fluid into the pleural or peritoneal cavity. There is no single approach that is applicable to all patients, and the therapeutic choice should be guided by the patient's overall medical status, prognosis of the underlying malignancy, goals of care, and the availability of medical and surgical resources. We specifically recommend against intrapericardial instillation of sclerosants to prevent effusion reaccumulation (Grade 1C). (See 'Management of pericardial effusion' above.)
●In cancer patients, "classic" constrictive pericarditis due to malignant involvement is unusual. Most cases fall into the effusive-constrictive category for which it is often the effusion and not the constriction that is causing symptoms and requires management. Nevertheless, some patients with constrictive pericarditis may require surgical removal of the pericardium, provided that the prognosis from the malignancy justifies surgery and that surgical management is consistent with the patient’s goals of care. (See 'Management of constrictive pericarditis' above.)
