A lecture on diagnosis and treatment of TB pericarditis tailored to practitioners in the Global South.

1. Tuberculous Pericarditis
Zhenya Krapivinsky, MD
By Yale Rosen from USA (Tuberculous pericarditis Uploaded by CFCF)
[CC BY-SA 2.0 (https://creativecommons.org/licenses/by-sa/2.0)], via
Wikimedia Commons

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INSERT
PICTURE
Zhenya Krapivinsky, MD
Assistant Clinical Professor, Division of Hospital Medicine
University of California, San Francisco

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No disclosures or conflicts of interest
FACULTY DISCLOSURE
Health4TheWorld is not responsible for, and to the extent not prohibited by law, disclaims all liability
relating to, the information, content and materials included by medical professionals in their lectures.

4. 01
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PATHOPHYSIOLOGY
SIGNS AND SYMPTOMS
DIAGNOSIS
PATIENT EVALUATION
TREATMENT
SUB-TOPICS

5. Learning Objectives
1. Be able to correctly identify a patient presenting with symptoms of TB pericarditis.
2. Be able to recognize physical exam findings of TB pericarditis, constrictive
pericarditis and tamponade.
3. Be able to order appropriate investigations for a patient with suspected TB
pericarditis
4. Be able to list the diagnostic criteria for definite and presumptive diagnoses of TB
pericarditis
5. Be able to order and interpret appropriate investigations of pericardial fluid in a
patient with suspected TB pericarditis.
6. Be able to appropriately treat TB pericarditis and determine when steroids and/or
pericardiectomy are indicated.

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BACKGROUND AND PATHOPHYSIOLOGY

7. Tuberculous Pericarditis
1. Important Complication of Tuberculosis
2. Diagnosis is difficult and often delayed
3. Pericardial effusion is the most common clinical
presentation
4. Delayed diagnosis can lead to constrictive pericarditis with
limited treatment options.

8. TB Pericarditis: epidemiology
• # 1 Cause of pericarditis on the African continent
• Mortality 50%
• Most common cause of pericardial effusion
• Constrictive pericarditis 40%,
• leading cause of death.

9. 3 Clinical Stages
1. Effusive Stage
2. Effusive-Constrictive Stage
3. Constrictive Stages

10. TB pericarditis : 4 Stages of pathogenesis
1. Serous effusion
• Exudative effusion, many neutrophils, lots of bacteria
2. Serosanguinous effusion (tamponade & heart failure)
• First clinically recognizable phase
• Lymphocyte predominant, high protein
3. Fibrosis (benefit from steroids)
• No effusion, calcified pericardium on CT
4. Constriction (need surgery)

11. Effusive Constrictive Pericarditis
1. Combination of tamponade ands constriction
• leg edema, ascites and hypotension, raised JVP
2. Diagnose: after pericardiocentesis
• elevated RA pressure or
• elevated JVP
• CT: effusion + calcified pericardium
Pericardial Effusion
Calcified pericardium:
enhanced with IV contrast
By K.Yamazak, General Thoracic and Cardiovascular Surgery, 2012, Volume 60, Number 5, Page 297

12. Risk Factors - Weakened Immune System
1. HIV infection
2. Diabetes mellitus
3. Severe kidney disease
4. Low body weight
5. Head and neck cancer
6. Medical treatments such as corticosteroids or organ transplant
7. Specialized treatment for rheumatoid arthritis or Crohn’s disease
8. Older Age

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SIGNS AND SYMPTOMS

14. Mr R. is a 45-year-old man, who presented to the hospital with shortness
of breath (SOB) and right upper quadrant abdominal pain.
● 2 months of increasing SOB and dyspnea on exertion.
● Decreased exercise tolerance, only able to walk a few steps before getting
SOB.
● Orthopnea , could only sleep sitting up in a chair.
● No cough, hemoptysis, or chest pain
● + Leg edema
● Dull, constant right upper abdominal pain without nausea, vomiting or
diarrhea.
● 7kg weight loss over the past 3 months with fevers and sweats.
● He had a history of unprotected sex with multiple female partners
● His family history was significant for 2 siblings who had died from AIDS

15. Symptoms
● Dyspnea
● Chest Pain
improves leaning forward
● Cough
● Fevers
● Sweats
● Weight Loss

16. Symptoms of Constrictive Pericarditis
• Right upper abdominal pain
• From liver congestion
• Ascites
• Leg edema
• Hypotension from tamponade

17. Back to Mr. R.
1. General: Cachectic man in respiratory distress, sitting upright in bed.
2. Vital signs: Temp 38.9ºC, HR 105 BP 98/60, RR 30, O2 Sat 98%
3. Head: bitemporal wasting, no icterus, conjunctival pallor, no thrush
4. Neck: no adenopathy. JVP seen with patient sitting upright without respiratory
variation
5. Lungs: clear to auscultation bilaterally.
6. Heart: regular tachycardia, no murmurs and no S3 heart sound and no
pericardial rub, but the heart sounds are distant.
7. Abdomen: tender hepatomegally with liver edge palpated at 4 cm below the
costal margin. Abdomen soft and without fluid wave or splenomegaly.
8. Extremities: No edema.

18. Physical Exam
• Vitals: Lower Blood Pressure, +/- weak pulse, +/- fever
• Gen: Thin, Dyspneic
• Neck: Raised JVP (Kussmaul’s sign)
• CV: Distant heart sounds, Pericardial Rub (ask patient to hold
breath), Pericardial nock (high pitch S3, diaphragm)
• Abd: Ascites & tender hepatomegaly
• Ext: Leg edema

19. Back to our case of Mr. R.:
Laboratory tests:
1. WBC 5,000 cells/mL with an absolute lymphocyte count 6500 cells/uL
(normal 1300 - 3500 cells/uL).
2. ESR: 75
3. An HIV test was ordered.
Chest X ray: A very enlarged cardiac silhouette, with a cardiothoracic ratio of
approximately 75%. No pulmonary infiltrates, effusions, or hilar
lymphadenopathy seen.

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PATIENT EVALUATION

21. Pericardial TB: My Diagnostic Approach
1. Chest x-ray
2. ECG
3. Echocardiogram
4. Consider CT of the chest to eval lymph nodes
5. Obtain sputum and urine for AFB and Gene-Xpert
6. Pericardiocentesis (smear, culture and PCR)
7. HIV testing

22. Pericardial TB: Chest X-ray
● Enlarged cardiac silhouette
● 30% pleural effusion
● Calcified pericardium
● No Hilar Adenopathy
Image courtesy of James Heilman, MD (Own work) [CC BY-SA 3.0
(https://creativecommons.org/licenses/by-sa/3.0) , via Wikimedia Commons

23. Pericardial TB
pleural effusion
calcified pericardium

24. ECG: concave ST elevation

25. ECG: Large pericardial effusion

26. ECG: Tamponade

27. Back to our case of Mr. R.:
Laboratory tests:
1. WBC 5,000 cells/mL with an absolute lymphocyte count 6500 cells/uL
(normal 1300 - 3500 cells/uL).
2. ESR: 75
3. An HIV test was ordered.
Chest X ray: A very enlarged cardiac silhouette, with a cardiothoracic ratio of
approximately 75%. No pulmonary infiltrates, effusions, or hilar
lymphadenopathy seen.

28. Diagnosis
1. Definitive Diagnosis: Gold Standard
1. Detection of TB bacilli in smear or culture of pericardial fluid
2. Detection of TB bacilli on or caseating granulomas on histological exam of excised
pericardium
2. Presumptive Diagnosis
1. TB is diagnosed in another body area in a patient with a pericardial effusion.
2. Lymphocyte predominant pericardial effusion (exudate) or an elevated level of Adenosine
Deaminases (ADA) in the pericardial fluid (ADA > 40U/L)
3. Mediastinal (non-hilar)lymph nodes on chest computed tomography with hypodense centre
and matting + positive tuberculin skin test (matting = coalescing of adjacent lymph nodes).
4. Appropriate response to anti-TB therapy

29. Pericardial TB: Echocardiogram
● Pericardial effusion
● Calcified pericardium
● Fibrin stranding
● RV collapse in tamponade PE = pericardial effusion
Image courtesy of Kalumet (Own work)
[GFDL(http://www.gnu.org/copyleft/fdl.html), via Wikimedia Commons

30. Pericardial Stranding
- Seen in up to 60%
of patients with TB
pericardial effusion

31. Normal
Echocardiogram
Apical 4 chamber view- Normal
"Echo Apical 4 Chamber View-
Normal." YouTube. N. p., 2019. Web.
24 Jan. 2019.
RV

32. Cardiac
Tamponade
RV collapse
Image courtesy of Kalumet (Own work)
[GFDL(http://www.gnu.org/copyleft/fdl.html), via Wikimedia Commons

34. Diagnosis
1. Definitive Diagnosis: Gold Standard
1. Detection of TB bacilli in smear or culture of pericardial fluid
2. Detection of TB bacilli on or caseating granulomas on histological exam of excised
pericardium
2. Presumptive Diagnosis
1. TB is diagnosed in another body area in a patient with a pericardial effusion.
2. Lymphocyte predominant pericardial effusion (exudate) or an elevated level of
Adenosine Deaminases (ADA) in the pericardial fluid (ADA > 40U/L)
3. Mediastinal (non-hilar)lymph nodes on chest computed tomography with
hypodense centre and matting + in a patient with pericardial effusion
4. Appropriate response to anti-TB therapy

35. Pericardial TB: CT Chest
● Mediastinal Lymph
Nodes
● No hilar nodes
● Lymph nodes >
10mm
● Hypodense center
(due to necrosis)

36. Diagnosis
1. Definitive Diagnosis: Gold Standard
1. Detection of TB bacilli in smear or culture of pericardial fluid
2. Detection of TB bacilli on or caseating granulomas on histological exam of excised
pericardium
2. Presumptive Diagnosis
1. TB is diagnosed in another body area in a patient with a pericardial effusion.
2. Lymphocyte predominant pericardial effusion (exudate) or an elevated level of
Adenosine Deaminases (ADA) in the pericardial fluid (ADA > 40U/L)
3. Mediastinal (non-hilar)lymph nodes on chest computed tomography with
hypodense centre and matting + in a patient with pericardial effusion
4. Appropriate response to anti-TB therapy

37. Why do a Pericardiocentesis?
1. Relieves symptoms
2. Prevents constriction
3. To prevents/treats tamponade
• Echocardiographic evidence of tamponade
• Hypotension
• Presence of pulsus paradoxus (>12 mmHg)
4. It is recommended in cases of suspected impending
tamponade (severe dyspnea & resting tachycardia)
Image courtesy of N. Patchett (Own
work) [CC BY-SA 4.0
(https://creativecommons.org/licens
es/by-sa/4.0)], via Wikimedia
Commons

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DIAGNOSIS

39. Decision Tree for Diagnosing TB pericarditis
Legend
Pc-ADA, - pericardial ADA
PB-WCC - peripheral WBC
count
Pc L/N ratio - pericardial
lymphocyte/neutrophil ratio
Sensitivity: 96%
Specificity: 97%
** Important Slide**

40. Back to our case: Mr. R
1. Echocardiogram with a portable ultrasound machine showed a massive pericardial
effusion with fibrin strands.
2. Pulsus paradoxus was 8 mmHg
3. Despite normal BP & absence of pulsus paradoxus, the severity of Mr.R’s dyspnea,
along with tachycardia at rest, was consistent with a high risk of impending
tamponade and a pericardiocentesis was done.
4. Pericardiocentesis: 1.2L of blood tinged pericardial fluid.
5. Pericardial Fluid:
a. ADA 72
b. AFB smear was negative
c. WBC count elevated at 12,000 cells/uL and 5600 lymphocytes & 1200
neutrophils.
d. Pericardial fluid was sent for culture (which can take up to 6 weeks to return
with results).
6. HIV serology was positive.

41. Decision Tree for Diagnosing TB pericarditis : Mr. R
Sensitivity: 96%
Specificity: 97%
ADA=72U/L
5 x 109/L

42. Differential Diagnosis for TB Pericarditis
• Infectious
• Bacterial (none-typhoid salmonella)
• Noninfectious
• Kaposi’s Sarcoma
• Lymphoma
• Trauma

43. Review Diagnostic Criteria: Pericardial TB
1. Definitive Diagnosis: Gold Standard
1. Detection of TB bacilli in smear or culture of pericardial fluid
2. Detection of TB bacilli on or caseating granulomas on histological exam of excised
pericardium
2. Presumptive Diagnosis
1. TB is diagnosed in another body area in a patient with a pericardial effusion.
2. Lymphocyte predominant pericardial effusion (exudate) or an elevated level of Adenosine
Deaminases (ADA) in the pericardial fluid (ADA > 40U/L)
3. Mediastinal (non-hilar)lymph nodes on chest computed tomography with hypodense centre
and matting + positive tuberculin skin test (matting = coalescing of adjacent lymph nodes).
4. Appropriate response to anti-TB therapy

44. ***Review: Approach to Pericardial TB diagnosis****
1. Obtain samples from other sources: sputum, urine, lymph nodes etc.
i. AFB stain, PCR, culture all other fluids
2. Get a CXR, Echo, CT – supporting findings
3. Check HIV status
4. Most patients should undergo a pericardiocentesis - check ADA, follow
decision tree.
5. Empiric Therapy should be started before diagnosis is confirmed in most
cases with high suspicion (in TB endemic areas and in HIV+ patients)
6. Pericardial biopsy should be the last option and reserved for difficult cases
where other etiologies (such as cancer) are high on the differential diagnosis.

45. Complications of Pericardial TB
1. Congestive heart failure
2. Constrictive pericarditis
a. #1 complications that clinicians should try to prevent (with appropriate steroid use and
drainage of effusion)
3. Cardiac tamponade
4. Congestive hepatopathy and cardiac cirrhosis

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TREATMENT

47. Pericardial TB: Treatment
1. Six month regimen is used to treat pericardial TB
- two months Isoniazid + Rifampicin + Pyrazinamide +/- Ethambutol
- four months Isoniazid + Rifampicin
+/- prednisolone (based on risk of constrictive pericarditis)
For patients in areas where TB is endemic, when clinical suspicion of tuberculous
pericarditis is high & in the case of presumptive diagnosis, initiation of empiric anti-TB
therapy is appropriate prior to establishing a definitive diagnosis (culture results).

48. Pericardial TB Treatment: corticosteroids? Cochrane Review
1. 7 RCTs, all from sub-Saharan Africa, 1959 participants, 54% HIV-positive
2. Trials looked at adjuvant steroids vs. placebo in the treatment of TB pericarditis.
3. Conclusions:
a. In HIV-, corticosteroids may reduce deaths from all causes (RR 0.80, low certainty evidence)
and the need for repeat pericardiocentesis (RR 0.85, low certainty evidence).
b. In HIV+, corticosteroids may reduce constriction (RR 0.55, low certainty evidence), uncertain
if there is an effect on all-cause mortality (low certainty evidence), there may be a slight
increase in Kaposi’s Sarcoma with the use of steroids (low certainty evidence); no effect on
repeat pericardiocentesis (RR 1.02, low certainty evidence).

49. Recommendations: steroids to prevent constrictive pericarditis
1. Corticosteroids may prevent constrictive pericarditis, and should be used in all HIV-
patients.
2. Recommend using steroids in HIV+ patients at highest risk for constrictive pericarditis
a. In those with large effusion
b. In those with high WBC in the pericardial fluid
c. In those with early signs of constriction on echocardiogram
3. Corticosteroid Regimen
a. Prednisolone 60 mg/day for 4 weeks.
b. Prednisolone 30 mg/day for 4 weeks
c. Prednisolone 15 mg/day for 2 weeks
d. Prednisolone 5 mg/day for 1 week
e. A shorter course of 60 mg of prednisone daily, tapering by 10/mg day each week for 6 weeks
has been shown to be effective in HIV+ patients.

50. Constrictive Pericardial TB Treatment: Pericardiectomy
• Surgical resection of the pericardium is indicated for those with echo findings
of pericardial constriction after 6-8 weeks of treatment and in those who
remain symptomatic after 6-8 weeks of treatment with steroids and ATB.
• Important: all patients should have a repeat echocardiogram after 6-8 weeks
of initiating treatment.
Fibrous Pericardium
Photo curtesy of Anatomist90 (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)],
via Wikimedia Commons

51. Back to Mr. R.
1. A presumptive diagnosis of TB pericarditis due to a lymphocyte predominant,
exudative pericardial fluid was made.
2. Mr. R’s symptoms improved dramatically following pericardiocentesis.
a. His exercise tolerance returned to baseline and he was immediately able
to lay flat on the bed.
b. His tachycardia immediately resolved
c. His Abdominal Pain improved over the course of 1 week.
3. A repeat echocardiogram done 5 days later revealed no reaccumulation of
pericardial fluid.
4. Mr.R was started on empiric 4-drug anti-TB therapy (rifampicin, isoniazid,
pyrazinamide, and ethambutol) and adjunctive prednisolone as his large
pericardial effusion put him at high risk for developing constrictive pericarditis.
5. He was discharged from the hospital on these medications & a repeat echo at
6 weeks after discharge. .

52. Take Home Summary
1. Symptoms: fever, weight loss, cough, dyspnea, chest pain,
2. Echocardiogram: do urgently if TB pericarditis suspected.
3. Pericardiocentesis should always be pursued if possible.
a. Send pericardial fluid for ADA, AFB, culture & PCR
4. “Presumptive diagnosis”: use the S. Africa decision tree.

53. Take Home Points
5. Empiric treatment
6. Steroids: can decrease mortality and prevent constriction in:”
a. All HIV - patients with pericardial TB should receive adjuvant steroids
b. Only HIV+ patients with established constrictive pericarditis or those at a high risk
of developing it (high WBCs in pericardial fluid, large effusion) should receive
adjuvant steroids.
7. Follow-up echocardiogram at 6 weeks to evaluate for constriction.

54. References
1. Diagnostic Value of Adenosine Deaminase Activity in TB serositis. P.C. Mathur et. al. Indian J Tuberc 2006; 53:92-95
2. Tuberculous pericarditis and myocarditis in adults and children, Bongani M Mayosi et. al. Tuberculosis, 2009
3. Pericardial Diseases, William C. Little, Jae K. Oh, in Goldman's Cecil Medicine (Twenty Fourth Edition), 2012
4. Clinical and Microbiologic Criteria for Diagnosis of Lung Disease Due to Nontuberculous Mycobacteria. Nicholas Walter, Charles L. Daley;
Clinical Respiratory Medicine (Fourth Edition), 2012
5. H. Reuter, L. Burgess, W. van Vuuren, A. Doubell; Diagnosing tuberculous pericarditis, QJM: An International Journal of Medicine, Volume
99, Issue 12, 1 December 2006, Pages 827–839
6. Advanced effusive-constrictive pericarditis rescued by the aggressive waffle procedure. Akira Marui, MD, PhD; Gen Thorac Cardiovasc Surg
(2012) 60:297–301
7. Wiysonge CS, Ntsekhe M, Thabane L, Volmink J, Majombozi D, Gumedze F, Pandie S, Mayosi BM. Interventions for treating tuberculous
pericarditis. Cochrane Database of Systematic Reviews 2017, Issue 9.
8. Tuberculous Pericarditis. Bongani M. Mayosi, Lesley J. Burgess and Anton F. Doubell. Circulation. 2005;112:3608-3616, originally published
December 5, 2005
9. Management of Effusive and Constrictive Pericardial Heart Disease. Circulation Journal of American Heart Association 2002;105;2939-2942
Brian D. Hoit
10. Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous pericarditis compared to adenosine deaminase and
unstimulated interferon-γ in a high burden setting: a prospective study. Pandie et al. BMC Medicine 2014, 12:101
11. Etiological Profile, Clinical Features and Medical Management of Acute, Pericarditis in Burkina Faso. Yameogo et al., J Trop Dis 2013, 1:3
12. Tuberculosis. Thomas R Frieden, Timothy R Sterling, Sonal S Munsiff, Catherine J Watt, Christopher Dye. Lancet 2003; 362: 887–99

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