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Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
The diagnosis of constrictive tuberculous pericarditis (TBP) remains challenging. This study aimed to evaluate 5 tests (acid-fast bacilli [AFB] smear, Mycobacterium tuberculosis [MTB] culture, Xpert MTB/RIF assay, CapitalBio Mycobacterium real-time PCR detection assay [CapitalBio assay], and pathology) for constrictive TBP using pericardial tissue.
Methods
We reviewed the case histories of patients with suspected constrictive TBP. We analyzed the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of these assays.
Results
A total of 69 patients were included. The sensitivity, specificity, PPV, NPV, and AUC of AFB smear were 7.3%, 100.0%, 100.0%, 21.5%, and 0.54, respectively; those of culture were 23.6%, 100.0%, 100.0%, 25.0%, and 0.62, respectively; those of Xpert MTB/RIF were 52.7%, 100.0%, 100.0%, 35.0%, and 0.76, respectively; those of CapitalBio assay were 50.9%, 100.0%, 100.0%, 34.2%, and 0.75, respectively; and those of pathology were 92.7%, 92.9%, 98.1%, 76.5%, and 0.93, respectively.
Conclusions
The validity of AFB smear and MTB culture remains low. Nucleic acid amplification tests can provide diagnostic efficacy for TBP but only moderately. The CapitalBio assay and Xpert MTB/RIF were considered similar for diagnosing TBP. Pathology showed the best diagnostic accuracy among the 5 tests.
). It results in decreased pericardial compliance and can severely affect the diastolic filling function of the heart, mainly as a symptom of right heart failure, such as multiple plasma chamber effusions and edema (
). It has several etiologies, including infection (eg, tuberculosis [TB], viral infection, and bacterial infection), malignancy, or radiation therapy (
). Pericardial fluid can rarely be obtained by pericardiocentesis from patients with constrictive TBP for relevant tests; even if it can be obtained, the diagnostic efficacy of acid-fast bacilli (AFB) smear and MTB culture using pericardial fluid is unsatisfactory (
Nucleic acid amplification tests (NAATs) are a significant advance in the diagnosis of TB and can detect MTB DNA or RNA, which can provide microbiological evidence (
). The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) is one of the most widely used NAATs for diagnosing TB and shows good diagnostic performance for both PTB and EPTB; its test results can be obtained within 2 hours to meet the need for rapid diagnosis (
The CapitalBio Mycobacterium real-time PCR (RT-PCR) detection assay (CapitalBio assay, CapitalBio Technology Inc., Beijing, China; http://www.capitalbiotech.com) is a new NAAT that can detect both MTB and nontuberculous mycobacteria (NTM) in a single test (
). The CapitalBio assay is becoming more widely used in clinical practice and has shown diagnostic efficacy for PTB and EPTB that is not inferior to that of the Xpert MTB/RIF assay (
'Comparison of the diagnostic efficacy of the CapitalBio Mycobacterium real-time polymerase chain reaction detection test and Xpert MTB/RIF in smear-negative pulmonary tuberculosis'.
A comparison of the accuracy of the CapitalBio Mycobacterium real-time polymerase chain reaction and the Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis.
). This study aimed to evaluate the efficacy of AFB smear, MTB culture, Xpert MTB/RIF, CapitalBio assay, and pathology using pericardial tissue for the diagnosis of constrictive TBP and to perform a head-to-head comparison of these methods.
2. Materials and methods
2.1 Study design
This retrospective study was conducted at the Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, which is the TB diagnosis and treatment center of Zhejiang Province. We reviewed the case histories of patients with suspected constrictive TBP hospitalized between June 1, 2019 and June 31, 2021, who underwent 5 tests—AFB smear, MTB culture, Xpert MTB/RIF, CapitalBio assay, and pathology—using pericardial tissue. We included patients with corresponding clinical symptoms of constrictive pericarditis (eg, chest tightness and shortness of breath, lower limb edema, and multiple plasma cavity effusions), computed tomography or ultrasound findings of pericardial thickening or calcification, increased central venous pressure, history of TB or contact with patients with TB, positive gamma interferon release test or purified protein derivative test, or suspected constrictive TBP in combination with other sites of TB. Patients who had liver cirrhosis, restrictive cardiomyopathy, or other related diseases that can cause symptoms similar to constrictive pericarditis were excluded. No patient improved after symptomatic treatment and thus, they underwent pericardiectomy. All patients signed a written informed consent document for pericardiectomy to provide permission for the collection of a pericardial tissue specimen for testing. Patients who did not undergo pericardiectomy, who had inconclusive test results, or in whom all 5 tests were not performed at the same time were excluded. Patients were classified as acute or subacute pericarditis and chronic pericarditis (> 3 months) on the basis of the duration of symptoms (
2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS).
). All patients were followed up for at least 9 months. The study received ethical approval from the Human Research Ethics Committee of the Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine.
MTB culture combined with the clinical diagnosis was used as the reference standard according to the 2015 European Society of Cardiology (ESC) guidelines for the diagnosis and management of pericardial diseases (
2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS).
). A ‘definite’ diagnosis of TBP on the basis of the presence of MTB in the pericardial fluid or on histological section of the pericardium, by MTB culture or by PCR testing; a ‘probable’ diagnosis was made when there was proof of TB elsewhere in the same patient with unexplained pericarditis, a lymphocytic pericardial exudate (if applicable) with elevated unstimulated interferon-gamma, adenosine deaminase or lysozyme levels, and/or an appropriate response to anti-TB therapy in endemic areas (
2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS).
). A “non-TBP” diagnosis was made when there was no evidence of MTB infection, other diagnoses of pericarditis were established, and the disease was cured without anti-TB treatment. In this study, the definite and probable TBP were considered as clinical diagnosis of TBP. Once the clinical data were collected, we discussed with a TB specialist to determine the final diagnosis.
2.2 Diagnostic specimen collection and handling
Fresh, diseased pericardial tissue collected during pericardial dissection was used to perform the 5 tests. Half of the diseased pericardial tissue was sent to the Pathology Department for pathological examination, and the other half was mixed by grinding and divided into 4 equal portions for AFB smear, MTB culture, Xpert MTB/RIF, and CapitalBio assay.
2.3 AFB smear microscopy
Digestion and decontamination of the specimens was performed using the N-acetyl-l-cysteine–NaOH method. The ground pericardial tissue specimens were centrifuged at 3000 g for approximately 15 minutes. The treated deposits were examined by smear microscopy using auramine O fluorescent dye and stained with Ziehl–Neelsen for confirmation, according to the US Centers for Disease Control and Prevention guidelines.
2.4 MTB culture
Lowenstein–Jensen solid medium and liquid culture medium (BACTEC MGIT 960 Mycobacteria Culture System, BD Diagnostic Systems, Sparks, MD, USA) were used for MTB culture; culturing was performed according to the manufacturer's instructions.
This test was performed according to the manufacturer's instructions. Briefly, at least 3 ml of pericardial fluid was centrifuged at 3000 g for approximately 15 minutes. After discarding the supernatant, the pellet was obtained. The pellet and nucleic acid extraction solution were then added to the nucleic acid extraction tube. After subjecting the samples to vibration and incubation in a water bath at 95°C for 10 minutes, the centrifuged samples were used for the extraction of MTB DNA. The extracted MTB DNA was used to perform the CapitalBio assay according to the manufacturer's instructions. An RT-fluorescence quantification PCR instrument (SLAN-96S Real-Time PCR System ZEESAN Xiamen CN) was used for nucleic acid amplification to detect IS6110 and HSP65 multicopy elements for MTB and NTM, respectively. The test results were obtained within 3 hours.
2.6 Xpert MTB/RIF
As with the CapitalBio assay, we used at least 3 ml of pericardial fluid for the Xpert MTB/RIF. The pericardial fluid was first centrifuged at 3000 g for 15 minutes. After discarding the supernatant, we added 2 ml of sample treatment solution, mixed it thoroughly by shaking, and finally added 2 ml of the treated sample to the first-generation Xpert MTB/RIF reaction cassette. The system performed automatic testing and reported the results within 2 hours.
2.7 Pathology
The Pathology Department received the specimens fixed in 10% formalin solution. The specimens were first rinsed and then gradually dehydrated with 80%–100% alcohol. After dehydration, the specimens were soaked in paraffin wax and embedded to obtain wax blocks. The wax blocks were trimmed and sliced to a thickness of 4–6 μm. The sections were placed on slides and subsequently baked at 60°C for 15–30 minutes to remove the paraffin wax. The obtained sections were subjected to pathological examination and anti-acid staining by an experienced pathology professional. TB was considered when granulomatous inflammation along with coagulative necrosis were observed. Histological results were available within 1 week.
2.8 Data processing and statistical analysis
We used Microsoft Excel 2019 (Albuquerque, New Mexico, USA) to manage the data obtained. SPSS 24.0 (IBM Corp., Armonk, NY, USA) was used to calculate mean values, standard deviations, and proportions and to determine true positive (TP), false positive (FP), false negative (FN), and true negative (TN) values in the cross-tabulations. Using TP, FP, FN, and TN values, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) with 95% confidence interval of the 5 tests were calculated using MedCalc v15.2.2 (MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org) to evaluate their diagnostic accuracy for constrictive TBP. McNemar test was used to compare paired data, and chi-square test or Fisher exact test was used to compare proportions. Z-test was used to compare AUCs. A Venn diagram was generated using jvenn, an interactive Venn diagram viewer. Differences with P-value of <0.05 were considered statistically significant.
3. Results
We screened the clinical data of patients with suspected constrictive TBP and ultimately included 69 patients who met the inclusion criteria. A single pericardial tissue specimen was obtained from each included patient, leading to a total of 69 specimens. The median age of the included patients was 58 years, of whom 53 were men. All patients tested negative for HIV. A total of 19 patients had coexisting PTB. No patient received a diagnosis of NTM infection. Table 1 shows the clinical characteristics of the included patients.
Table 1Clinical features of the included patients.
Figure 1 illustrates the classification of the included patients. A total of 55 patients were diagnosed with constrictive TBP, and the remaining 14 had no TBP. Among the 69 cases, there were 34 cases of acute or subacute pericarditis (31 TBP and 3 non-TBP) and 35 cases of chronic pericarditis (24 TBP and 11 non-TBP). Among all patients, 4, 13, 29, 28, and 52 patients showed positive AFB smear, MTB culture, Xpert MTB/RIF, CapitalBio assay, and pathology, respectively. Figure 2 shows the distribution and overlap of the positive AFB smear, MTB culture, Xpert MTB/RIF, CapitalBio assay, and pathology.
Figure 1Flowchart showing the classification of patients included in the study.
Among those with constrictive TBP, 4, 13, 29, 28, and 51 patients showed positive AFB smear, MTB culture, Xpert MTB/RIF, CapitalBio assay, and pathology, respectively; conversely, among those without TBP, only 1 patient showed positive pathology. Among those with acute or subacute TBP, 2, 8, 17, 18, and 30 patients showed positive AFB smear, MTB culture, Xpert MTB/RIF, CapitalBio assay, and pathology, respectively, and among those with chronic TBP, 2, 5, 12, 10, and 21 patients showed positive AFB smear, MTB culture, Xpert MTB/RIF, CapitalBio assay, and pathology, respectively.
3.1 Diagnostic accuracies of the 5 tests
The sensitivity, specificity, PPV, NPV, and AUC of AFB smear for constrictive TBP were 7.3% (2.0%–17.6%), 100.0% (76.8%–100.0%), 100.0% (39.8%–100.0%), 21.5% (12.3%–33.5%), and 0.54 (0.41–0.66), respectively; those of culture were 23.6% (13.2%–37.0%), 100.0% (76.8%–100.0%), 100.0% (75.3%–100.0%), 25.0% (14.4%–38.4%), and 0.62 (0.49–0.73), respectively; those of the Xpert MTB/RIF were 52.7% (38.8%–66.4%), 100.0% (76.8%–100.0%), 100.0% (88.1%–100.0%), 35.0% (20.6%–51.7%), and 0.76 (0.65–0.86), respectively; those of the CapitalBio assay were 50.9% (37.1%–64.7%), 100.0% (76.8%–100.0%), 100.0% (87.6%–100.0%), 34.2% (20.1%–50.6%), and 0.75 (0.64–0.85), respectively; and those of pathology were 92.7% (82.4%–98.0%), 92.9% (66.1%–99.8%), 98.1% (89.7%–100.0%), 76.5% (50.1%–93.2%), and 0.93 (0.84–0.98), respectively. These results are presented in Table 2. The diagnostic accuracy of each of the 5 tests in acute or subacute and chronic TBP is shown in Table 3.
Table 2The diagnostic efficiency of the 5 tests for the diagnosis of tuberculous pericarditis using pericardial tissue compared with MTB culture combined with clinical diagnosis.
TBP
Test
Positive
Negative
Sensitivity (%)
Specificity (%)
PPV (%)
NPV (%)
AUC
AFB smear
Positive
4
0
7.3 (2.0-17.6)
100.0 (76.8-100.0)
100.0 (39.8-100.0)
21.5 (12.3-33.5)
0.54 (0.41-0.66)
Negative
51
14
MTB Culture
Positive
13
0
23.6 (13.2-37.0)
100.0 (76.8-100.0)
100.0 (75.3-100.0)
25.0 (14.4-38.4)
0.62 (0.49-0.73)
Negative
42
14
Xpert MTB/RIF
Positive
29
0
52.7 (38.8-66.4)
100.0 (76.8-100.0)
100.0 (88.1-100.0)
35.0 (20.6-51.7)
0.76 (0.65-0.86)
Negative
26
14
CapitalBio assay
Positive
28
0
50.9 (37.1-64.7)
100.0 (76.8-100.0)
100.0 (87.6-100.0)
34.2 (20.1-50.6)
0.75 (0.64-0.85)
Negative
27
14
Pathology
Positive
51
1
92.7 (82.4-98.0)
92.9 (66.1-99.8)
98.1 (89.7-100.0)
76.5 (50.1-93.2)
0.93 (0.84-0.98)
Negative
4
13
AFB, acid-fast bacilli; AUC, area under the curve; MTB, Mycobacterium tuberculosis; NPV, negative predictive value; PPV, positive predictive value; TBP, tuberculous pericarditis.
Table 3The diagnostic efficiency of the 5 tests for different stages of tuberculous pericarditis using pericardial tissue compared with MTB culture combined with clinical diagnosis.
Test
TBP stage
Sensitivity (%)
Specificity (%)
PPV (%)
NPV (%)
AUC
AFB smear
Acute or subacute
6.5 (0.8-21.4)
100.0 (29.2-100.0)
100.0 (15.8-100.0)
9.4 (2.0-25.0)
0.53 (0.35-0.70)
Chronic
8.3 (1.0-27.0)
100.0 (71.5-100.0)
100.0 (15.8-100.0)
33.3 (19.0-51.8)
0.54 (0.37-0.71)*
MTB Culture
Acute or subacute
25.8 (11.9-44.6)
100.0 (29.2-100.0)
100.0 (63.1-100.0)
11.5 (2.5-30.2)
0.63 (0.45-0.79)
Chronic
20.8 (7.1-42.2)
100.0 (71.5-100.0)
100.0 (47.8-100.0)
36.7 (19.9-56.1)
0.60 (0.43-0.76)*
Xpert MTB/RIF
Acute or subacute
54.8 (36.0-72.7)
100.0 (29.2-100.0)
100.0 (80.5-100.0)
17.7 (3.8-43.4)
0.77 (0.60-0.90)
Chronic
50.0 (29.1-70.9)
100.0 (71.5-100.0)
100.0 (73.5-100.0)
47.8 (26.8-69.4)
0.75 (0.58-0.88)*
CapitalBio assay
Acute or subacute
58.1 (39.1-75.5)
100.0 (29.2-100.0)
100.0 (81.5-100.0)
18.8 (4.1-45.7)
0.79 (0.62-0.91)
Chronic
47.6 (25.7-70.2)
100.0 (76.8-100.0)
100.0 (69.2-100.0)
56.0 (34.9-75.6)
0.74 (0.56-0.87)*
Pathology
Acute or subacute
96.8 (83.3-99.9)
100.0 (29.2-100.0)
100.0 (88.4-100.0)
75.0 (19.4-99.4)
0.98 (0.87-1.00)
Chronic
87.5 (67.6-97.3)
90.9 (58.7-100.0)
95.5 (77.2-100.0)
76.9 (46.2-95.0)
0.89 (0.74-0.97)*
* Comparison of acute or subacute tuberculosis pericarditis and chronic tuberculosis pericarditis using the same test, P > 0.05.
AFB, acid-fast bacilli; AUC, area under the curve; MTB, Mycobacterium tuberculosis; NPV, negative predictive value; PPV, positive predictive value; TBP, tuberculous pericarditis.
3.2 Comparison of the diagnostic accuracies of the 5 tests
AFB smear showed the lowest diagnostic accuracy for constrictive TBP, followed by MTB culture, CapitalBio assay, and Xpert MTB/RIF. Conversely, the highest diagnostic accuracy was observed for pathology. The results of the 2-by-2 comparison are shown in Table 4. The diagnostic accuracy of AFB smear was significantly lower than that of all other tests (P < 0.05), except for MTB culture. The diagnostic accuracies of the 2 molecular tests (CapitalBio assay and Xpert MTB/RIF) were similar (P > 0.05). The diagnostic accuracy of MTB culture was lower than that of the molecular tests, but the difference was not statistically significant (P > 0.05). The diagnostic accuracy of pathology was significantly greater than that of all other tests (P < 0.05). For different stages of TBP, there was no significant difference in the diagnostic accuracy of the same test in acute or subacute TBP and chronic TBP (Table 3, P > 0.05).
Table 4Comparison of the diagnostic efficiency between the 5 tests for the diagnosis of tuberculous pericarditis using pericardial tissue.
Test
Sensitivity (P-value)
Specificity (P-value)
PPV (P-value)
NPV (P-value)
AUC (P-value)
AFB smear vs. Culture
0.018
1.000
1.000
0.653
0.464
AFB smear vs. Xpert
< 0.001
1.000
1.000
0.130
0.024
AFB smear vs. CapitalBio assay
< 0.001
1.000
1.000
0.152
0.031
AFB smear vs. Pathology
< 0.001
0.309
0.780
< 0.001
< 0.001
Culture vs. Xpert
0.002
1.000
1.000
0.288
0.121
Culture vs. CapitalBio assay
0.003
1.000
1.000
0.326
0.149
Culture vs. Pathology
< 0.001
0.309
0.614
< 0.001
< 0.001
Xpert vs. CapitalBio assay
0.849
1.000
1.0000
0.936
0.912
Xpert vs. Pathology
< 0.001
0.309
0.452
0.004
0.024
CapitalBio assay vs. Pathology
< 0.001
0.309
0.460
0.003
0.018
AFB, acid-fast bacilli; AUC, area under the curve; MTB, Mycobacterium tuberculosis; NPV, negative predictive value; PPV, positive predictive value; TBP, tuberculous pericarditis.
Although TBP accounts for a relatively small proportion of EPTB overall, it can account for >60% of all causes of pericarditis in areas with a high burden of TB (
). In this study, 79.7% (55/69) of patients had TBP, which could be related to the fact that our center is the TB diagnosis and treatment center for Zhejiang Province, where TB is clustered and where there are relatively few patients without TB. TBP itself is a serious disease with a poor prognosis, and when it is complicated by constrictive pericarditis, the condition becomes even more serious and can be life-threatening (
Predictive factors for unfavorable outcomes of tuberculous pericarditis in human immunodeficiency virus-uninfected patients in an intermediate tuberculosis burden country.
). However, in cases of constrictive TBP, there is little opportunity to obtain pericardial effusion for diagnosis. There is usually a thickened pericardium with no or minimal pericardial effusion, which makes the diagnosis of constrictive TBP more difficult (
Predictors of postoperative complication and prolonged intensive care unit stay after complete pericardiectomy in tuberculous constrictive pericarditis.
Pericardiectomy for Constrictive Tuberculous Pericarditis: A Systematic Review and Meta-analysis on the Etiology, Patients' Characteristics, and the Outcomes'.
). Pericardial tissue specimens can be obtained through pericardiectomy to further clarify the etiologic diagnosis of pericarditis. Studies on the assessment of the diagnostic efficacy of using pericardial tissue for the diagnosis of constrictive TBP are limited (
), and comparative studies on multiple assays using pericardial tissue are even fewer. Considering these research gaps, we performed this study.
Our results showed that the sensitivity, specificity, and AUC of AFB smear using pericardial tissue were 7.3%, 100.0%, and 0.54, respectively, and those of MTB culture using pericardial tissue were 23.6%, 100.0%, and 0.62, respectively, suggesting that the sensitivity of AFB smear and culture using pericardial tissue for the diagnosis of TBP is very low. These results are similar to the vast majority of those reporting the use of tissue specimens for the diagnosis of EPTB. The reason for this could be that the levels of Mycobacterium in tissue specimens are relatively low. The diagnostic accuracy of MTB culture was better than that of AFB smear; however, the difference between them was not statistically significant, which may be related to the limited number of specimens included. MTB culture is indisputably the gold standard for TB diagnosis, but in EPTB with low bacterial load (such as TB meningitis, TB pleurisy, TBP), the MTB culture positivity rate is low and does not effectively detect TB. In this study, only 13 patients had positive MTB culture, which also reflected that the MTB content in pericardial tissue was low. Using MTB culture as a single reference standard may miss many patients with TBP; therefore, according to ESC guidelines (
2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS).
), we chose to use MTB culture combined with clinical diagnosis as the reference standard, which can better distinguish between TBP and non-TBP. This reference standard has been maturely applied in previous studies (
A comparison of the accuracy of the CapitalBio Mycobacterium real-time polymerase chain reaction and the Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis.
Diagnostic values of Xpert MTB/RIF, T-SPOT.TB and adenosine deaminase for HIV-negative tuberculous pericarditis in a high burden setting: a prospective observational study'. 10. Sci Rep,
2020: 16325
). However, although most studies report using pericardial effusion for the test with good diagnostic efficacy, tests using pericardial tissues are less frequently reported. The results of previous studies using pericardial tissues for the Xpert MTB/RIF to diagnose TBP were similar to the current study (
). However, previous studies had a small sample size and did not perform a head-to-head comparison with AFB smears, MTB cultures, and other NAATs. The CapitalBio assay is a novel fluorescent RT-PCR-TaqMan-based NAAT that, like the Xpert MTB/RIF, is a commercially available assay. The difference between the Xpert MTB/RIF and the CapitalBio assay is that the latter is a semiautomatic test that requires manual extraction of MTB nucleic acid, which could increase the potential for contamination in the assay, whereas the former is fully automated and does not require manual nucleic acid extraction. The CapitalBio assay has a limit of detection (LOD) of 5000 colony forming units (CFUs)/ml, whereas the Xpert MTB/RIF has LOD of 131 CFUs/ml. The CapitalBio assay can detect both MTB and NTM infections, whereas the Xpert MTB/RIF can only detect MTB infections (
). In this study, NTM infection was not detected in any patients using the pericardial fluid; thus, the advantage of the simultaneous detection of 2 types of mycobacteria by the CapitalBio assay was not reflected in this study. The CapitalBio assay has an advantage over the Xpert MTB/RIF in the diagnosis and differential diagnosis of pulmonary mycobacterial infections. Although the LOD of the CapitalBio assay is higher than that of the Xpert MTB/RIF, in practical clinical application, the CapitalBio assay showed a diagnostic efficacy not weaker than that of the Xpert MTB/RIF for TB (
). For the diagnosis of TBP, the diagnostic accuracy of the CapitalBio assay was not previously evaluated for testing with pericardial tissue, and its head-to-head comparison with the Xpert MTB/RIF was not performed in previous studies. The results of this study showed that the sensitivity of the CapitalBio assay using pericardial tissue for diagnosing TBP was 50.9%, which was not very satisfactory and was lower than the sensitivity of the Xpert MTB/RIF (52.7%). However, considering that the difference between them was not statistically significant, their sensitivities could be considered similar. This might be related to the limited mycobacterial content in the included specimens. The specificities of both were 100.0%. The diagnostic accuracies of the 2 NAATs were significantly better than those of AFB smear and MTB culture.
Pathology is a very important factor in the diagnosis of TB, and the typical pathological changes of TB are granulomatous inflammation with coagulative necrosis. Although the pathogenic diagnosis cannot be made solely on the basis of pathology, it is still a useful guide for the diagnosis of TB. Our study showed that of the 5 tests, pathology showed the highest diagnostic accuracy, possibly because pathological changes can be observed in the tissue despite the low levels of Mycobacterium. The differences in pathology compared with the other 4 tests were all statistically significant, suggesting that the role of pathology in the diagnosis of TB remains evident. Granulomatous inflammation with necrosis was suggested in the pathology of 1 patient, and tuberculosis was considered. However, the pericardial tissue culture showed bacterial infection, the immunological test for tuberculosis was negative, no antituberculosis treatment was administered, and the final prognosis was good, suggesting that granulomatous inflammation with necrosis can also occur in lesions with bacterial infection and requires careful differentiation.
The diagnostic accuracy of MTB-related assays may be reduced in chronic constrictive TBP of long duration, where MTB is no longer active in the tissue after pericardial scarring. We compared the difference in diagnostic accuracy of the same test in different stages of TBP, and basically all tests were slightly more accurate in acute or subacute TBP than in chronic TBP, except for AFB smears, but the difference between the 2 was not statistically significant. This may be related to the limited number of TBP at each stage, and relevant results need to be confirmed by studies with larger sample sizes.
This study had some limitations. First, patient selection was subject to bias, which is an unavoidable drawback of retrospective studies. Second, this study was conducted in an area with high TB burden and the findings might not be generalizable to areas with low TB burden. Third, the number of specimens included in this study was limited owing to the low incidence of TBP. Finally, the CapitalBio assay does not detect drug resistance; therefore, relevant drug resistance analyses were not performed in this study.
5. Conclusions
The diagnosis of constrictive TBP remains challenging. The validity of AFB smear and MTB culture using pericardial tissues remains low. NAATs can provide diagnostic efficacy for TBP, but the efficacy is moderate. The CapitalBio assay and Xpert MTB/RIF could be considered similar for diagnosing TBP. The role of pathology in the diagnosis of constrictive TBP cannot be ignored, considering that pathology showed the best diagnostic accuracy among the 5 tests. The diagnostic accuracy of the same test is similar in acute or subacute TBP and chronic TBP.
Ethics approval and consent to participate
All patients gave written informed consent and the study was approved by the Human Research Ethics Committee of Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine.
The funders do not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Availability of data and material
Data will be made available on reasonable request.
Declaration of Competing Interest
The authors declare that they have no conflict of interest.
Acknowledgements
We would like to express our gratitude to the patients and colleagues in our department.
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Imazio M.
Badano L.
Baron-Esquivias G.
Bogaert J.
Brucato A.
Gueret P.
Klingel K.
Lionis C.
Maisch B.
Mayosi B.
Pavie A.
Ristic A.D.
Sabate Tenas M.
Seferovic P.
Swedberg K.
Tomkowski W.
2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS).
Predictors of postoperative complication and prolonged intensive care unit stay after complete pericardiectomy in tuberculous constrictive pericarditis.
Diagnostic values of Xpert MTB/RIF, T-SPOT.TB and adenosine deaminase for HIV-negative tuberculous pericarditis in a high burden setting: a prospective observational study'. 10. Sci Rep,
2020: 16325
Predictive factors for unfavorable outcomes of tuberculous pericarditis in human immunodeficiency virus-uninfected patients in an intermediate tuberculosis burden country.
A comparison of the accuracy of the CapitalBio Mycobacterium real-time polymerase chain reaction and the Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis.
Pericardiectomy for Constrictive Tuberculous Pericarditis: A Systematic Review and Meta-analysis on the Etiology, Patients' Characteristics, and the Outcomes'.
'Comparison of the diagnostic efficacy of the CapitalBio Mycobacterium real-time polymerase chain reaction detection test and Xpert MTB/RIF in smear-negative pulmonary tuberculosis'.
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