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Pericardial effusion: a continuing drain on our diagnostic acumen
Pericardial Effusion: A Continuing Drain on our Diagnostic Acumen Elyse Foster, MD
E
ffusive pericardial disease is a relatively rare cause of hospital admission. Its presenting clinical symptoms are frequently non-specific, and the treating physicians may not suspect the diagnosis. Although the clinical course may be benign, pericardial effusions can be associated with substantial morbidity and mortality. Even when the condition is recognized, clinicians are often frustrated in their attempts to determine its underlying etiology and to treat a persistent effusion. The indication for drainage of an effusion is clear if there is cardiac tamponade, but is less certain in the absence of hemodynamic instability. Pericardiocentesis is not without risk, and the diagnostic yield of pathological examination of the fluid is frequently low, even when pericardial tissue is obtained by surgical biopsy. Clinicians have benefitted from the work of a small group of clinical investigators who became ardent “students” of the pericardium. The authors of the article in this issue of The Green Journal, “Large pericardial effusion in a general hospital: clinical clues to etiologic diagnosis”, are members of that small circle (1). In 1977, Drs. Sagrista-Sauleda, Permanyer-Miralda and Soler-Soler from the Hospital General Universitari Vall d’Hebro´n in Barcelona established one of the first “clinical pathways” in cardiology for the diagnosis and treatment of pericardial disease. Their prospective application of this systematic and logical approach, and their careful data collection, are excellent examples of this special breed of clinical investigation. Not only have they written some of the seminal papers in the field, but they have also provided young clinician-investigators with an important model for ongoing “grassroots” hospital and patient-based research. In an era of advanced technology, innovative therapeutics, and the randomized trial, we often forget that there is still much to be learned about the natural history of a disease. The protocol developed by these investigators consists of three stages, which involve progressively more invasive diagnostic tests (1). Stage I consists of the basics: history, physical examination, electrocardiogram (EKG), and chest radiograph. Laboratory tests in this stage include sputum for acid-fast bacilli, anti-nuclear antibody assays,
Am J Med. 2000;109:169 –170. From the Associate Professor of Clinical Medicine, Director, Adult Echocardiography Laboratory, University of California, San Francisco, California. Correspondence should be addressed to Elyse Foster, MD, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0214. 䉷2000 by Excerpta Medica, Inc. All rights reserved.
and thyroid studies as well as others suggested by the history and physical examination. In Stage II, pericardiocentesis is performed for tamponade, suspicion of purulent pericarditis, or large effusions. Finally, in Stage III, the authors proceed to open pericardial biopsy if tamponade recurs following the pericardiocentesis or if there is a persistent effusion and no diagnosis after 3 weeks. In the paper in this issue (1), that protocol was used in 322 hospitalized patients with moderate and large effusions identified in the echocardiography laboratory during a 6-year period. Patients were divided into three groups: 124 with moderate effusions (10 to 20 mm in diastole); 79 with large effusions (⬎20 mm in diastole) and 119 with tamponade. The investigators hypothesized that clinical data, including the size of the effusion, the presence of tamponade, and the presence of inflammatory signs (chest pain, friction rub, fever, and EKG signs of diffuse ST elevation) would point to the etiology of the effusion. An underlying condition was identified on this basis after the first stage of their investigation in 60% of their patients. Of the remaining 130 patients, 76 had inflammatory signs; after a careful laboratory examination, the majority of these patients (n ⫽ 61) were classified as “acute idiopathic pericarditis.” Of the 54 without inflammatory signs, there were 19 with tamponade and 35 without. Nine of those with tamponade and without inflammation had neoplastic pericarditis. Moreover, tamponade was most common in those with neoplastic disease. Still, among the patients without an underlying diagnosis apparent on presentation, the majority in each clinical category had idiopathic pericarditis, confirming the diagnostic importance of noninvasive tests in the exclusion of underlying disease. The authors reported that the incidence of acute inflammatory signs varied among the final diagnostic categories in the 130 patients with no diagnosis after Stage I. Not surprisingly, they were most frequent (98%) among those with a final diagnosis of acute idiopathic pericarditis and uncommon among those with chronic idiopathic pericarditis or other etiologies. The importance of this finding is uncertain, since acute idiopathic pericarditis was diagnosed when “clinical symptoms subsided with bed rest and nonsteroidal anti-inflammatory drugs” in the absence of any other specific diagnosis. Thus, the observation that inflammatory signs were frequent in this group seems self-evident. However, inflammatory signs were not uncommon among patients with neoplastic effusions (33%) and, importantly, their presence did not exclude malignancy. 0002-9343/00/$–see front matter 169 PII S0002-9343(00)00505-2
Pericardial Effusion: A Drain on Diagnostic Acumen/Foster
These results are similar in several ways to an earlier report from these same investigators that was published in 1985 (2). When a pericardiocentesis was performed for therapeutic reasons (e.g., to relieve tamponade), the diagnostic yield in the article in this issue was 24%; in 1985, it was 29%. The yield for a “diagnostic” tap was 4% in the current series and 6% in the 1985 report. However, the yield of a biopsy was lower in the current study than in the previous report, even when it was performed because of recurrent effusion or tamponade. Seventeen of the 322 patients in the present study remained “non-categorized,” even after assigning patients to acute or chronic idiopathic groups. Thus, the additional yield of diagnostic pericardiocentesis or biopsy was low, which is especially pertinent in view of the high morbidity of the procedure. Compared with the earlier study in 1985 (2), the incidence of tuberculosis as a final diagnosis was similar, although it occurred more commonly in patients with human immunodeficiency virus (HIV) infection in the more recent series. A report from another group in Spain described one hundred patients with primary acute pericarditis, of whom sixty had effusions (3). A general diagnostic protocol similar to Stage I was employed, with a 15% yield. Additional diagnoses were made by pericardiocentesis in only 7 (7%) of patients. In comparison with other studies (4,5), idiopathic pericarditis was somewhat more common in the current series, even among those presenting with tamponade. As the authors acknowledge, the frequency of the specific etiologic class depends on the type of patients in the sample and must be considered in the context of the patients typical to the institution. In this study, mortality in patients with moderate and large effusions was high (26%) and was even greater (36%) in those with tamponade on presentation. Most patients died of the underlying disease. In a study of hospitalized patients with pericardial effusions at the University of California, San Francisco, the size of the effusion (i.e., large effusions) was the most powerful predictor of outcome, predicting the end-points of tamponade, surgi-
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August 1, 2000
THE AMERICAN JOURNAL OF MEDICINE威
cal drainage or pericardiocentesis. Death was not an endpoint in that study (6). The report in this issue of The Green Journal does not suggest a change in the approach to the diagnosis of effusive pericardial disease. It confirms the validity of the step-wise approach that the authors and their co-workers in pericardial disease have advocated for the past 20 years. Moreover, clinicians must keep in mind that pericardiocentesis and pericardiectomy are associated with substantial morbidity and mortality. In this series, there were four deaths associated with pericardial procedures. Thus, these invasive tests should not be undertaken lightly and should be performed by experienced operators, preferably in the cardiac catheterization laboratory with fluoroscopic imaging. Simultaneous echocardiograph guidance is indicated for pericardiocentesis except in the most dire circumstances. In the modern era, the diagnosis of pericardial disease remains a conundrum in many patients. Perhaps in the 21st century, we will make a breakthrough in discovering the true etiology of so-called “idiopathic” pericarditis and in preventing its late complications, such as constrictive disease.
REFERENCES 1. Sagrista-Sauleda J, Merce J, Permanyer-Miralda G, Soler-Soler J. Clinical clues to the etiology of large pericardial effusions. Am J Med. 2000;109:95–101. 2. Permanyer-Miralda G, Sagrista-Sauleda J, Soler-Soler J. Primary acute pericardial disease: a prospective series of 231 consecutive patients. Am J Cardiol. 1985;56:623–30. 3. Zayas R, Anguita M, Torres F, et al. Incidence of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis. Am J Cardiol. 1995;75:378 –382. 4. Corey GR, Campbell PT, Van Trigt P, et al. Etiology of large pericardial effusions. Am J Med. 1993;95:209 –13. 5. Guberman BA, Fowler NO, Engel PJ, Gueron M, Allen JM. Cardiac tamponade in medical patients. Circulation. 1981;64:633– 40. 6. Eisenberg M, Oken K, Guerrero S, Ali Saniei M, Schiller N. Prognostic value of echocardiography in hospitalized patients with pericardial effusion. Am J Cardiol. 1992;70:934 –939.
Volume 109
E
ffusive pericardial disease is a relatively rare cause of hospital admission. Its presenting clinical symptoms are frequently non-specific, and the treating physicians may not suspect the diagnosis. Although the clinical course may be benign, pericardial effusions can be associated with substantial morbidity and mortality. Even when the condition is recognized, clinicians are often frustrated in their attempts to determine its underlying etiology and to treat a persistent effusion. The indication for drainage of an effusion is clear if there is cardiac tamponade, but is less certain in the absence of hemodynamic instability. Pericardiocentesis is not without risk, and the diagnostic yield of pathological examination of the fluid is frequently low, even when pericardial tissue is obtained by surgical biopsy. Clinicians have benefitted from the work of a small group of clinical investigators who became ardent “students” of the pericardium. The authors of the article in this issue of The Green Journal, “Large pericardial effusion in a general hospital: clinical clues to etiologic diagnosis”, are members of that small circle (1). In 1977, Drs. Sagrista-Sauleda, Permanyer-Miralda and Soler-Soler from the Hospital General Universitari Vall d’Hebro´n in Barcelona established one of the first “clinical pathways” in cardiology for the diagnosis and treatment of pericardial disease. Their prospective application of this systematic and logical approach, and their careful data collection, are excellent examples of this special breed of clinical investigation. Not only have they written some of the seminal papers in the field, but they have also provided young clinician-investigators with an important model for ongoing “grassroots” hospital and patient-based research. In an era of advanced technology, innovative therapeutics, and the randomized trial, we often forget that there is still much to be learned about the natural history of a disease. The protocol developed by these investigators consists of three stages, which involve progressively more invasive diagnostic tests (1). Stage I consists of the basics: history, physical examination, electrocardiogram (EKG), and chest radiograph. Laboratory tests in this stage include sputum for acid-fast bacilli, anti-nuclear antibody assays,
Am J Med. 2000;109:169 –170. From the Associate Professor of Clinical Medicine, Director, Adult Echocardiography Laboratory, University of California, San Francisco, California. Correspondence should be addressed to Elyse Foster, MD, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0214. 䉷2000 by Excerpta Medica, Inc. All rights reserved.
and thyroid studies as well as others suggested by the history and physical examination. In Stage II, pericardiocentesis is performed for tamponade, suspicion of purulent pericarditis, or large effusions. Finally, in Stage III, the authors proceed to open pericardial biopsy if tamponade recurs following the pericardiocentesis or if there is a persistent effusion and no diagnosis after 3 weeks. In the paper in this issue (1), that protocol was used in 322 hospitalized patients with moderate and large effusions identified in the echocardiography laboratory during a 6-year period. Patients were divided into three groups: 124 with moderate effusions (10 to 20 mm in diastole); 79 with large effusions (⬎20 mm in diastole) and 119 with tamponade. The investigators hypothesized that clinical data, including the size of the effusion, the presence of tamponade, and the presence of inflammatory signs (chest pain, friction rub, fever, and EKG signs of diffuse ST elevation) would point to the etiology of the effusion. An underlying condition was identified on this basis after the first stage of their investigation in 60% of their patients. Of the remaining 130 patients, 76 had inflammatory signs; after a careful laboratory examination, the majority of these patients (n ⫽ 61) were classified as “acute idiopathic pericarditis.” Of the 54 without inflammatory signs, there were 19 with tamponade and 35 without. Nine of those with tamponade and without inflammation had neoplastic pericarditis. Moreover, tamponade was most common in those with neoplastic disease. Still, among the patients without an underlying diagnosis apparent on presentation, the majority in each clinical category had idiopathic pericarditis, confirming the diagnostic importance of noninvasive tests in the exclusion of underlying disease. The authors reported that the incidence of acute inflammatory signs varied among the final diagnostic categories in the 130 patients with no diagnosis after Stage I. Not surprisingly, they were most frequent (98%) among those with a final diagnosis of acute idiopathic pericarditis and uncommon among those with chronic idiopathic pericarditis or other etiologies. The importance of this finding is uncertain, since acute idiopathic pericarditis was diagnosed when “clinical symptoms subsided with bed rest and nonsteroidal anti-inflammatory drugs” in the absence of any other specific diagnosis. Thus, the observation that inflammatory signs were frequent in this group seems self-evident. However, inflammatory signs were not uncommon among patients with neoplastic effusions (33%) and, importantly, their presence did not exclude malignancy. 0002-9343/00/$–see front matter 169 PII S0002-9343(00)00505-2
Pericardial Effusion: A Drain on Diagnostic Acumen/Foster
These results are similar in several ways to an earlier report from these same investigators that was published in 1985 (2). When a pericardiocentesis was performed for therapeutic reasons (e.g., to relieve tamponade), the diagnostic yield in the article in this issue was 24%; in 1985, it was 29%. The yield for a “diagnostic” tap was 4% in the current series and 6% in the 1985 report. However, the yield of a biopsy was lower in the current study than in the previous report, even when it was performed because of recurrent effusion or tamponade. Seventeen of the 322 patients in the present study remained “non-categorized,” even after assigning patients to acute or chronic idiopathic groups. Thus, the additional yield of diagnostic pericardiocentesis or biopsy was low, which is especially pertinent in view of the high morbidity of the procedure. Compared with the earlier study in 1985 (2), the incidence of tuberculosis as a final diagnosis was similar, although it occurred more commonly in patients with human immunodeficiency virus (HIV) infection in the more recent series. A report from another group in Spain described one hundred patients with primary acute pericarditis, of whom sixty had effusions (3). A general diagnostic protocol similar to Stage I was employed, with a 15% yield. Additional diagnoses were made by pericardiocentesis in only 7 (7%) of patients. In comparison with other studies (4,5), idiopathic pericarditis was somewhat more common in the current series, even among those presenting with tamponade. As the authors acknowledge, the frequency of the specific etiologic class depends on the type of patients in the sample and must be considered in the context of the patients typical to the institution. In this study, mortality in patients with moderate and large effusions was high (26%) and was even greater (36%) in those with tamponade on presentation. Most patients died of the underlying disease. In a study of hospitalized patients with pericardial effusions at the University of California, San Francisco, the size of the effusion (i.e., large effusions) was the most powerful predictor of outcome, predicting the end-points of tamponade, surgi-
170
August 1, 2000
THE AMERICAN JOURNAL OF MEDICINE威
cal drainage or pericardiocentesis. Death was not an endpoint in that study (6). The report in this issue of The Green Journal does not suggest a change in the approach to the diagnosis of effusive pericardial disease. It confirms the validity of the step-wise approach that the authors and their co-workers in pericardial disease have advocated for the past 20 years. Moreover, clinicians must keep in mind that pericardiocentesis and pericardiectomy are associated with substantial morbidity and mortality. In this series, there were four deaths associated with pericardial procedures. Thus, these invasive tests should not be undertaken lightly and should be performed by experienced operators, preferably in the cardiac catheterization laboratory with fluoroscopic imaging. Simultaneous echocardiograph guidance is indicated for pericardiocentesis except in the most dire circumstances. In the modern era, the diagnosis of pericardial disease remains a conundrum in many patients. Perhaps in the 21st century, we will make a breakthrough in discovering the true etiology of so-called “idiopathic” pericarditis and in preventing its late complications, such as constrictive disease.
REFERENCES 1. Sagrista-Sauleda J, Merce J, Permanyer-Miralda G, Soler-Soler J. Clinical clues to the etiology of large pericardial effusions. Am J Med. 2000;109:95–101. 2. Permanyer-Miralda G, Sagrista-Sauleda J, Soler-Soler J. Primary acute pericardial disease: a prospective series of 231 consecutive patients. Am J Cardiol. 1985;56:623–30. 3. Zayas R, Anguita M, Torres F, et al. Incidence of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis. Am J Cardiol. 1995;75:378 –382. 4. Corey GR, Campbell PT, Van Trigt P, et al. Etiology of large pericardial effusions. Am J Med. 1993;95:209 –13. 5. Guberman BA, Fowler NO, Engel PJ, Gueron M, Allen JM. Cardiac tamponade in medical patients. Circulation. 1981;64:633– 40. 6. Eisenberg M, Oken K, Guerrero S, Ali Saniei M, Schiller N. Prognostic value of echocardiography in hospitalized patients with pericardial effusion. Am J Cardiol. 1992;70:934 –939.
Volume 109