Constrictive Pericarditis Secondary to
Tuberculosis Infection: Literature Review
Maria Isabel Gomez Coral1*, Astrid Carolina Barco Guillén2, Jessica Mariela Amaya Alvarez3, Nancy Carolina Amaya Gomez4, Cristina Mariuxi Kuon Yeng Escalante5, Catherine Nathaly Espinal Amaya6, Carolina Michelle Mejia Alaniz7, Ericka Alexandra Saldana8, Stephany Paola Valko9, Daisy Marielos Torres Treminio10, Laura Sofia Trivino Cuellar11, Ana Belen Brito Galvez12, Emilio Israel Wong Valenzuela13 and Angel Gustavo Barrera Ventura14
1Universidad del Valle de México, México
2Universidad de Especialidades Espíritu Santo, Ecuador
3Universidad Salvadoreña Alberto Masferrer, El Salvador
4Universidad Nacional De El Salvador, El Salvador
5Universidad de Especialidades Espíritu Santo, Ecuador
6Universidad de El Salvador, El Salvador
7Universidad Americana, Nicaragua
8Universidad Salvadoreña Alberto Masferrer, El Salvador
9Pontificia Universidad Católica del Ecuador, Ecuador
10Universidad Dr. Jose Matias Delgado, El Salvador
11Fundacion Universitaria Juan N. Corpas, Colombia
12Universidad de Especialidades Espíritu Santo, Ecuador
13Universidad Autónoma de Baja California, México
14Universidad de El Salvador, El Salvador
Submission: December 05, 2022; Published: December 12, 2022
*Corresponding author: Maria Isabel Gomez Coral, Universidad del Valle de México, 154 Samson Rd, Frisco, TX, 76081, Texas, USA
How to cite this article: Maria I G C, Astrid C B G, Jessica M A A, Nancy C A G, Cristina M K Yeng E, et al . Constrictive Pericarditis Secondary to Tuberculosis
Infection: Literature Review. J Cardiol & Cardiovasc Ther. 2022; 18(1): 555976. DOI: 10.19080/JOCCT.2022.18.555976
Tuberculous pericarditis is produced by Mycobacterium tuberculosis, accounting for 1% of all forms of tuberculosis. Its prevalence varies according to coinfection with HIV. Mortality varies between 17 and 40%. In the US, the prevalence is low compared to developing countries. This article aims to review the literature on pericarditis caused by tuberculosis (TBP), its prevalence in the US, clinical manifestations, diagnosis, and treatment. Among the most frequent clinical manifestations are dyspnea, fever, chest pain, and cough. TBP should be suspected in patients at high risk of exposure to tuberculosis. There are multiple lab tests for diagnosis, and its primary treatment is triple therapy with isoniazid, rifampin, and streptomycin or ethambutol. In case of persistent elevation of systemic venous pressure, surgical intervention is indicated. The clinical presentation was found to be variable.
Tuberculosis (TB) is a potentially dangerous infectious disease caused by Mycobacterium tuberculosis (Mtb) which primarily affects the lungs but can also attack other tissues and form caseating granulomas. According to the CDC, in 2021, 7,860 TB cases were provisionally reported in the US . People contract tuberculosis from one another by coughing and sneezing, which release microscopic droplets of germs into the air. One of the organs that can be affected is the heart, mostly the pericardium,
causing pericarditis (inflammation of the pericardial sac), and the
scarring and the subsequent loss of the pericardial sac’s typical
flexibility can lead to constrictive pericarditis. The pericardium
can become infected with Mtb bacilli through retrograde lymphatic
spread, hematogenous dissemination, or, less frequently, direct
contiguous spread from nearby infected tissues such as the lungs,
pleura, and spine . Heart failure is the most common clinical
presentation of tuberculosis pericarditis (TBP). However, some
patients with tamponade may also experience hemodynamic
compromise with hypotension, tachycardia, and shock .
The most common diagnostic test for TBP is pericardial fluid
culture, which has a sensitivity of between 53 and 75% . The
treatment of TBP consists in eradicating the Mtb with rifampicin,
isoniazid, ethambutol, and pyrazinamide, in combination, for
a minimum of six months. The preferred procedure to drain
compressive pericardial fluid from the pericardium is needle
pericardiocentesis guided by fluoroscopic or echocardiographic
imaging. Also, oral or intrapericardial corticosteroids can prevent
constriction progression. Finally, the goal of the treatment is to
avoid pericardial fibrosis . The purpose of this review article
is to provide a general understanding of TBP to enable the
correct diagnosis and treatment of the condition to prevent the
development of complications, such as pericardial fibrosis.
Tuberculous pericarditis is caused when infection of
Mycobacterium Tuberculosis reaches the pericardium. It is the
leading cause of pericarditis in countries where the prevalence
of tuberculosis is still high, and it is found in 1% of autopsies
performed in patients with the infection . Pericardial
involvement develops through three mechanisms dependent
on the immune competency of the host. The first mechanism
involves retrograde spread from mediastinal, peritracheal, and
parabronchial lymph nodes; the second is the hematogenous route
during primary tuberculosis infection; the third is by direct spread
from the lung parenchyma or pleura. Immune-competent hosts
favor lymphatic spread, whereas hosts with HIV-related immune
suppression will favor the hematogenous route . Among the
first, TB pericarditis is frequently a paucibacillary condition in
which the morbidity is related to the immune response and not
the pathogen’s virulence. In contrast, immune-deficient hosts
suffer from disseminated disease associated with TB bacteremia,
which may significantly impact morbidity and mortality. This has
been supported by histopathological and immunologic analyses
demonstrating diminished granuloma formation and aberrant
CD4+ function in patients with HIV.
Four pathological stages have been described in TB pericarditis.
In the first stage, protein antigens induce a hypersensitivity
reaction where CD4+ lymphocytes trigger the release of cytokines
that activate macrophages to induce granuloma formation and
induce the production of complement-fixing anti-myolemmal
and anti-myosin antibodies. These are responsible for the
cytolysis that characterizes the fibrinous exudate of this phase.
The second stage is the formation of a serosanguineous effusion
with abundant foam cells. Finally, the third stage constitutes the
absorption of the effusion and organization of granulomas with
pericardial thickening that will eventually lead to constrictive
scarring and calcification of the pericardium .
In a 2019 report of annual trends of patients admitted to
US hospitals with constrictive pericarditis from 2005 to 2014,
investigators found a stable prevalence of 9-10 cases per million
. Tuberculous pericarditis accounts for 1% of all forms of
tuberculosis and 1-2% of extrapulmonary tuberculosis . Most
data regarding TBP come from developing countries with a high
tuberculosis burden and frequent coinfection with M. tuberculosis
and HIV. In these geographic regions, TBP accounts for 50-70%
of effusive pericarditis in HIV-negative patients and more than
90% in HIV-positive patients . In industrialized countries,
tuberculosis accounts for only 4% of cases of pericardial effusion
and an even smaller proportion of constrictive pericarditis.
Tuberculous pericarditis is a dangerous disease with a mortality
of 17% to 40%. Constriction occurs in a similar proportion of
cases after tuberculous pericardial effusion .
Tuberculous pericarditis has a low prevalence in the USA.
Less than 1% of the patients with a diagnosis of TB had an
associated pericarditis diagnosis. While only 1% of TB patients
have pericarditis in the US, in developing countries with a high
prevalence of TB, 70% of cases of significant pericardial effusion
are attributable to TB, and it is an essential etiology of constrictive
The clinical manifestations of tuberculosis are pretty
variable and depend on several factors. Host and microberelated
characteristics, as well as their interactions, influence the
disease’s clinical features. Before the beginning of the epidemic of
infection with HIV, approximately 85% of reported tuberculosis
cases were limited to the lungs, with the remaining 15% involving
only non-pulmonary or both pulmonary and non-pulmonary sites.
This proportional distribution is substantially different among
persons with HIV infection. Although there are no national data
that describe the locations of involvement in HIV-infected persons
with tuberculosis, one large retrospective study of tuberculosis
in patients with advanced HIV infection reported that 38% had
only pulmonary involvement, 30% had only extrapulmonary sites,
and 32% had both pulmonary and non-pulmonary involvement.
Moreover, extrapulmonary involvement tends to increase in
frequency with worsening immune compromise .
Two broad mechanisms drive the clinical presentation of
pericarditis: fluid accumulation within the pericardium, which
compresses the heart chambers throughout the cardiac cycle impeding both cardiac filling and cardiac contraction (tamponade) or thickening of the pericardium with minimum or absent effusion
resulting in impairment of cardiac filling in diastole (constriction).
The predominant clinical manifestation of TBP is heart failure
syndrome, regardless of the mechanism. However, a relatively
small proportion of patients with tamponade may also have
hemodynamic compromise with hypotension, tachycardia, and
shock . However, the frequency of tuberculous pericarditis is
very different depending on the overall prevalence of tuberculosis
in the region and in particular categories of patients (for example,
HIV-infected). For example, among patients with constrictive
pericarditis in a South African Hospital, tuberculosis was
diagnosed in 29.8% of patients .
The diagnosis of tuberculous pericarditis should be
considered in patients with pericarditis that does not have a
self-limited course with a high-risk factor of exposure to TB .
The initial evaluation of a patient with tuberculous pericarditis
includes tuberculin skin test (TST) and interferon-gamma
release assay (IGRA) that supports the diagnosis of TB, and more
specific test as chest radiography, echocardiography showing
pericardial effusion, electrocardiography with non-specific ST-T
wave changes and micro voltages, sputum, and pericardial fluid
evaluation for acid-fast bacilli (AFB) smear and culture .
The pericardial fluid should also be evaluated for cell count,
protein concentration, lactate dehydrogenase concentration,
adenosine deaminase (ADA) concentration, and cytology .
The tuberculous pericarditis effusion is usually exudative with
lymphocytes, monocytes, and high protein concentration. ADA
levels above 30 units/L in the pericardial fluid also indicate
tuberculous pericarditis. In cases when the pericardial fluid
and smear are not conclusive is recommended to obtain a right
scalene lymph node and/or pericardial biopsy for AFB stain and
examination for granulomatous disease [11,12]. It is to remark
that the sensitivity of the biopsy is 10-64%, so a negative biopsy
does not exclude the diagnosis . The diagnosis of tuberculous
pericarditis is made when there is evidence of tubercle bacilli in
the pericardial fluid either by smear or culture or by the presence
of caseating granulomas or bacilli in the histological examination
of the pericardium [9,11].
After the bacteriological diagnosis is established, the
treatment is based on triple-drug therapy for at least nine months
with isoniazid, rifampin, streptomycin, or ethambutol. For the first
two months, pyrazinamide can be used, and the total therapeutic
period can then be shortened to 6 months after culture conversion.
Also, it is reasonable to add treatment with three months of
corticosteroid therapy in patients with pericardial effusion that
persists or recurs despite the use of anti-tuberculous drugs .
In patients with extrapulmonary TB, the following treatment has been shown to be highly effective: at least two months of rifampicin, isoniazid, pyrazinamide, and ethambutol, then a regimen followed
by isoniazid and rifampicin, for a full six months of therapy. If the
treatment is for nine months or longer, it does not provide better
results and has disadvantages such as increasing cost and poor
compliance. For recurrent or life-threatening tamponade or
in cases when there is persistent elevation of systemic venous
pressure unrelieved by pericardiocentesis, surgical resection of
the pericardium is indicated [12,14].
It has been demonstrated that those patients with
tuberculosis pericarditis receiving antituberculosis medications
increase their survival dramatically. Because the management
of pericardial diseases is mainly empiric (because of the relative
lack of randomized trials), to prevent recurrences, the mainstay
of empiric anti-inflammatory therapy (NSAIDs) and some cases
adding colchicine can be the best course of action .
Patients with a compromised immune system uncommonly
develop constrictive pericarditis. However, they do have
higher mortality . In contrast, a study published in 2020,
consisting of 50 patients with different types of TB pericarditis
in immunocompetent patients, showed that only five patients
exhibited constrictive pericarditis after six months, one out of 28
patients with effusion developed constrictive pericarditis .
Constriction leads to impaired diastolic filling, which in time,
causes differences in intrathoracic and intracardiac pressures,
diminishing the left-sided diastolic filling and transmitral flow.
This can also cause an increase in interventricular dependence; the
right heart ventricular filling rises, hepatic vein diastolic forward
velocity, and cardiac filling pressure. Other findings in constrictive
pericarditis include fibrosis, inflammation edema, and pericardial
thickening. However, these are not seen in 100% of cases.
Late gadolinium enhancement (LGE) can discover pericardial
inflammation, chronic inflammation, neovascularization, and
fibroblastic proliferation in tuberculous constrictive pericarditis.
This finding stands out because it denotes the possible benefit of
NSAIDs and that constrictive pericarditis can be reverted . In
addition, echocardiography, CT, cardiac MRI, and 18F-FDG PET/
CT are used to assert a prognosis and estimate if patients will
improve with anti-inflammatory treatment . Constrictive
pericarditis is the most severe sequel of tuberculous pericarditis,
which makes it imperative that the anti-tuberculous therapy
begins quickly. A pericardiectomy could be performed if the
patient has failed conservative treatment [16,18].
Tuberculosis pericarditis is the leading cause of pericarditis in
the world. It is caused by Mycobacterium tuberculosis and can be
found in up to 1% of the autopsied cases of patients with TB and up
to 2% of the cases of pulmonary TB. Tuberculous pericarditis has a variable clinic presentation and should be considered in evaluating all cases of pericarditis without a rapidly self-limited course. The
most common manifestations are dyspnea, fever, chest pain, and
cough. Without treatment, mortality exceeds 90%, whereas antituberculous
therapy, usually rifampicin, isoniazid, pyrazinamide,
and ethambutol for at least two months, followed by isoniazid
and rifampicin for another four months. Therefore, reaching
the correct diagnosis is crucial in initiating appropriate therapy.
The diagnosis of TBP is made when there is evidence of tubercle
bacilli in the pericardial fluid by smear or culture. Tuberculous
pericarditis with constrictive physiology at initial diagnosis can
be reversible in 80% of cases if the appropriate steroid treatment
is given. Assessment of echocardiographic features in tuberculous
pericarditis can provide prognostic information and help predict
treatment response. Constrictive pericarditis is the most severe
sequel of tuberculous pericarditis. Management involves prompt
initiation of anti-tuberculous therapy and appropriate timing of
pericardiectomy for selected patients who have failed to respond
to medical treatment. Despite the advances in medical therapy
for TBP, further research is still needed in order to gain a deeper
understanding of this complex condition.