CLINICAL STUDY
clinical correlates of pr-segment depression in asymptomatic patients with pericardial effusion
Yoshihiro Kudo, MD*,*,
Fumiyasu Yamasaki, MD*,
Yoshinori Doi, MD and
Tetsuro Sugiura, MD*
* Clinical Laboratory MedicineKochi, Japan
Department ofGeriatric Medicine, Kochi Medical School, Kochi, Japan
Manuscript received November 6, 2001;
revised manuscript received March 5, 2002,
accepted March 27, 2002.
* Reprint requests and correspondence: Dr. Yoshihiro Kudo, Department of Clinical Laboratory Medicine, Kochi Medical School, Kohasu Oko-cho Nankoku City, Kochi, Japan 783-8505. kudohy{at}med.kochi-ms.ac.jp
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Abstract
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OBJECTIVES: The purpose of this study was to determine the clinical correlates of PR-segment depression among consecutive asymptomatic patients with pericardial effusion (PE) detected by routine echocardiography.
BACKGROUND: Pericardial effusion is a relatively common finding in clinical practice, but not many studies have evaluated electrocardiographic (ECG) changes associated with the occurrence of PE.
METHODS: Among 4,061 consecutive patients referred to our echocardiography laboratory, 176 asymptomatic patients had PE correlated with their clinical history and ECG findings.
RESULTS: PR-segment depression was detected in 40 patients (23%). There were no significant differences in age, gender distribution or heart rate between patients with and without PR-segment depression. Fifteen post-pericardiotomy patients (33%), 19 patients (40%) with malignant disease and 6 patients (46%) with connective tissue disease had PR-segment depression, whereas no patient with heart disease (dilated cardiomyopathy, hypertensive heart disease, old myocardial infarction, valvular heart disease), renal disease or hypothyroidism had PR-segment depression, nor widespread ST-segment elevation. Among 40 patients with PR-segment depression, 8 had ST-segment elevation in the leads of epicardial derivation, 8 had upright T waves, 20 had low to inverted T waves with an isoelectric ST-segment and 4 had ST-Twave changes due to bundle branch block.
CONCLUSIONS: PR-segment depression was a relatively common ECG sign associated with clinically silent PE, and it was an ECG indicator of inflammatory pericardial involvement.
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Abbreviations and Acronyms
| | ECG = electrocardiogram/electrocardiographic | | LV = left ventricular | | MI = myocardial infarction | | PE = pericardial effusion |
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Pericardial effusion (PE) is a relatively common finding in clinical practice; echocardiography is the procedure of choice for detecting PE. Although PE demonstrated by echocardiography may indicate fluid retention, this is not diagnostic of pericardial injury (1). Pericardial rub and stage I ST-segment elevation (ST-segment elevation in all leads except aVR and V1) are two specific signs of pericardial inflammation (1,2). PR-segment depression is almost as characteristic as the classic ST-segment deviation and is detected in most patients with pericarditis (3,4). Moreover, PR-segment depression is observed longer after acute pericardial injury, when the ST-segment has already returned to baseline (2). However, not many studies have evaluated electrocardiographic (ECG) changes associated with the occurrence of PE. Accordingly, we designed a study to evaluate the frequency and clinical correlates of PR-segment depression in patients with PE detected by routine echocardiography.
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Methods
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Patients.
Among 4,061 consecutive patients who were referred to our echocardiography laboratory between November 10, 1997 and May 9, 2001, we studied 176 clinically stable asymptomatic patients (age 19 to 89 years) with PE who were in sinus rhythm. Exclusion criteria were sinus tachycardia (>120/min) and P-wave abnormalities. The study procedure was approved by the institutional review board of Kochi Medical School.
Echocardiography
M-mode and two-dimensional echocardiography was performed with a Toshiba SSH 160A phased-array sector scanner (Toshiba Co. Ltd., Tokyo, Japan), with a 3.75- or 2.5-MHz transducer used by an experienced echocardiographer. Echocardiography was performed with the patients in the 45° left lateral decubitus position, and all classic views were recorded on videotape for subsequent analysis by observers who were unaware of the ECG data. Anterior and posterior PE were measured as the maximal diastolic epicardial-pericardial separation recorded at the level of the tip of the mitral valve. However, anterior separation was considered representative of effusion only in the presence of a posterior echo-free space. Pericardial effusion was classified as small (pattern C; <10 mm), moderate (pattern D; 10 to 20 mm) or large (pattern D; >20 mm), as described by Horowitz et al. (5) and Weitzman et al. (6). A detailed chart review was performed to assess the most likely causes of PE in each patient.
Electrocardiography
A 12-lead ECG was obtained on the day of echocardiography. Atrial repolarization was assessed by studying the PR-segment with a magnifying glass. At least 0.5 mm of PR-segment depression from the TP segment in both the limb (more than two leads in leads I, II, aVL and aVF) and precordial leads (more than two leads in leads V3 through V6) was considered diagnostic of PR-segment depression. ST-segment elevation was defined as 0.5 mm or more from the TP segment in both the limb and precordial leads. PR-segment and ST-segment deviations were considered present only after diagnosed by two cardiologists who had no knowledge of the clinical findings. A P-wave abnormality in the standard leads was diagnosed when one or more of the following findings were made: 1) P-wave configuration other than the rounded form normally seen (notched, peaked or other abnormal configurations); 2) amplitude of 0.2 mm in lead II; and 3) duration of >100 ms in any lead.
Statistical analysis
Results are presented as the mean value ± SD. A statistical analysis between the two groups was performed by the Student t test for continuous variables and the Fisher exact probability test for discrete variables. A p value <0.05 was considered significant.
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Results
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Clinical characteristics.
Table 1 summarizes the causes of PE in 176 patients. One hundred fifty patients had minor PE, 20 patients had moderate PE and 6 patients had major PE. No patient had clinical or echocardiographic evidence of cardiac tamponade.
PR-segment depression
Among 176 patients with PE, PR-segment depression was detected in 40 patients (23%). There were no significant differences in age, gender distribution, heart rate or the amount of PE between patients with and without PR-segment depression (Table 2). Fifteen post-pericardiotomy patients (33%), 19 patients (40%) with malignant disease and 6 patients (46%) with connective tissue disease had PR-segment depression. The time from pericardiotomy to echocardiography was three to six weeks in patients with PR-segment depression, and it was one week to six months in patients with no PR-segment depression. No patient with primary heart disease (e.g., dilated cardiomyopathy, hypertensive heart disease, old myocardial infarction (MI), valvular heart disease), chronic renal failure, nephrotic syndrome or hypothyroidism had PR-segment depression.
ST-Twave changes
Among 105 patients with PE associated with pericardiotomy, malignant disease or connective tissue disease, 8 had ST-segment elevation and PR-segment depression in the leads of epicardial derivation, consistent with the stage I ECG change of pericarditis, 8 had upright T waves with PR-segment depression (early stage II ECG change) and 20 had low to inverted T waves with PR-segment depression (late stage II ECG change) (Figs. 1 and 2, Table 3). In contrast, 12 patients had low to inverted T waves with an isoelectric PR segment (late stage II ECG change), 4 had inverted T waves with an isoelectric PR segment (stage III ECG change) and 26 had normal ST-T waves with an isoelectric PR segment (stage IV ECG change). Primary widespread ST-Twave changes were not determined in 27 patients, because of bundle branch block, old MI or left ventricular (LV) hypertrophy. Interestingly, four patients with ST-T waves due to bundle branch block had PR-segment depression. No patient with primary heart disease, chronic renal failure, nephrotic syndrome or hypothyroidism had ST-Twaves changes suggestive of acute pericarditis.

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Figure 1 Electrocardiogram of a patient judged to have PR-segment depression with ST-segment elevation. Note the downward displacement of the PR segment in both the limb and precordial leads.
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Figure 2 Electrocardiogram of a patient judged to have PR-segment depression with low to inverted T waves. Note the downward displacement of the PR segment in both the limb and precordial leads.
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Discussion
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Echocardiography is the most accurate noninvasive tool to detect PE; however, to date, echocardiographic reports have concentrated on describing the sensitivity of quantification of PE, and surprisingly few studies have considered the prevalence of diagnostic ECG changes in patients with PE. Among clinically stable patients referred to our echocardiography laboratory for cardiac assessment, we found that 23% of patients with silent PE had PR-segment depression, in contrast to the low incidence of widespread ST-segment elevation (5%). These data indicate that the incidence of PR-segment depression is not rare in patients with clinically silent PE.
Pericardial fluid.
Myocardial interstitial fluid is reported to be the source of pericardial fluid that drains to the subepicardium, and pericardial fluid, regardless of the cause, arises primarily from the epicardial surface of the heart (7). Two major pathophysiologic bases for the accumulation of excessive pericardial fluid have been reported: pericardial inflammation and fluid retention due to hemodynamic factors (hydropericardium) (1). In this study, 54 patients had PE primarily associated with the diagnosis of heart disease; 45 patients had PE associated with pericardiotomy; and the primary disease was noncardiac in 77 patients. The patients with PE associated with chronic heart disease, hypothyroidism or renal disease had neither widespread PR-segment depression nor ST-segment elevation suggestive of pericarditis. Fluid flux at the level of the microvascular membrane into the interstitium is governed by hydrostatic and osmotic pressures generated in the microvessels and interstitium. Therefore, the factors related to the occurrence of noninflammatory PE are hemodynamic, as well as a combination of increased capillary permeability, lymphatic obstruction, lower colloid osmotic pressure and/or sodium and water retention. Most of the PE in hypothyroidism is caused by transudates, whereas uremic pericardial inflammation is caused by uremic exudates; however, uremic pericarditis is unique in that inflammatory cells do not penetrate the myocardium (8). Thus, it is not surprising to find an absence of customary widespread ST-Twave changes or PR-segment depression of subepicardial myocarditis in patients with chronic renal failure and hypothyroidism.
PR-segment deviations
The diagnosis of acute pericarditis requires typical widespread J-STsegment elevation (stage I ECG changes), but stage I ECG changes are frequently not recorded, and nearly half of the patients with acute pericarditis of mixed causes have a variation in the typical ECG evolution of acute pericarditis (8,9). PR-segment depression is also known to be one of the typical ECG changes associated with acute pericarditis (3,4). Pericarditis, sympathetic stimulation and left atrial overloading due to LV failure are some of the geneses of PR-segment depression (10,11). The ECG changes produced by hypersympathetic activity are characterized by concordant PR- and ST-segment depressions (the PR and ST-segments are in the arcs of circumference with the same radius) (10). However, none of our patients had concordant PR- and ST-segment deviations, and there was no significant difference in the heart rate between patients with and without PR-segment depression. Considering the fact that all of the patients with widespread PR-segment depression were at three to six weeks post-pericardiotomy or had malignant disease or connective tissue disease indicates that PR-segment depression in our patients reflects abnormal atrial repolarization due to atrial inflammation.
Diagnostic considerations
The diagnostic significance of PR-segment depression in patients with pericardial involvement is that PR-segment depression is detected longer after the ST-segments return to baseline and could be diagnosed in patients with ST-segment changes due to bundle branch block, MI or LV hypertrophy. Post-pericardiotomy syndrome develops within days to a month after the operation. The effect of anti-heart antibody in producing pericardial inflammation is proportional to the extent of surgical repair, but the anti-heart antibody appears to be pathogenetic in the presence of a viral infection (2,8). Although a small to moderate amount of PE is often observed in post-pericardiotomy syndrome, widespread ST-segment elevation suggestive of pericarditis is rarely seen (8). Our study is consistent with the observation that widespread ST-segment elevation was detected in only one patient (2%). However, pericardial inflammation could be diagnosed more frequently by PR-segment depression in post-pericardiotomy patients.
Pericarditis is a common cardiac manifestation of autoimmune disease. The inflammatory process associated with epicardial microvasculitis may increase the production of pericardial fluid by a loss of interstitial fluid from the myocardium to the pericardial space. Metastatic and multicentric malignancy can also affect the pericardium and pericardium is reported to be involved in 5% to 15% of patients with malignant neoplasm at autopsy (12,13). Asymptomatic pericardial effusions in patients with malignant neoplasm could be due to malignant pericardial involvement, impaired lymphatic drainage or nonmalignant causes, such as previous radiation, chemotherapy and infection. In contrast to the 12% incidence of widespread ST-segment elevation in patients with PE due to connective tissue disease or malignant disease, 42% had PR-segment depression. Moreover, 20 of 32 patients with an isoelectric ST-segment and low to inverted T-waves (late stage II ECG change of acute pericarditis) had PR-segment depression, indicating that patients whose ECG was recorded first in late stage II may only show widespread PR-segment depression due to subepicardial atrial inflammation associated with inflammatory pericardial fluid retention.
Conclusions
PR-segment depression was a relatively common ECG sign associated with clinically silent PE, and it was an ECG indicator of inflammatory pericardial involvement.
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References
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