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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 6, November/December 2016



The importance of perseverance, pilot studies and

the search for effective adjuvant therapies in the

management of tuberculous pericarditis

Arthur Mutyaba, Mpiko Ntsekhe

Tuberculous pericarditis remains one of the most feared

manifestations of extra-pulmonary tuberculosis (TB). The

relatively high morbidity and mortality rates associated with the

condition arise via two distinct mechanisms. The first is related

to the combined impact of the virulence of



(MTb) itself and TB-induced dysregulated immune

responses in both HIV-positive and -negative individuals,

resulting in disseminated infection, multi-organ involvement,

and prolonged acute infection.


The second mechanism is related

to compressive pericardial disease (cardiac tamponade, effusive

constrictive pericarditis and constrictive pericarditis), which can

cause significant compromise of cardiovascular function.

Prior to the advent of modern four-drug anti-tuberculous

regimens, tuberculosis-related mortality was almost universal in

patients with pericarditis. With the use of modern combination

anti-tuberculous therapy, which is able to achieve pericardial

sterilisation, prevent dissemination and cure tuberculous

infection, the mortality rate had fallen to below 10% by the


Given that anti-tuberculous therapy is now widely available

and used almost empirically, the residual morbidity and mortality

rate is driven predominantly by the second dreaded mechanism

discussed above. Heart failure, haemodynamic collapse and

death from reaccumulation of compressive effusion, constrictive

pericarditis and effusive constrictive pericarditis occur in up to

30%of cases.


Factors such as the size of effusion at presentation,

whether or not patients underwent pericardiocentesis at onset,

the degree of immunocompromise from HIV, and use of

adjuvant therapies such as corticosteroids have all been shown,

albeit inconsistently, to influence this composite complication

rate in various studies.


To date, corticosteroids remain the most studied adjuvant

therapy to reduce the rates of post-tuberculous constriction

and other compressive pericardial syndromes. In the largest

of these studies, the IMPI trial, a six-week tapered course

of prednisolone added to four-drug anti-tuberculous therapy

reduced the incidence of pericardial constriction in both

HIV-positive and -negative patients, compared to placebo, by

approximately 50%.


There has been much discussion and debate

about the role of corticosteroids in this condition since the

completion of the IMPI trial, particularly given the finding that

HIV-infected patients had an increased risk of malignancy with

the use of prednisolone.

With this background in mind, the study by Liebenberg

et al


published in this issue of the journal (page 350), is a welcome

attempt by colleagues who work in an environment where they

are still confronted with the scourge of tuberculous pericarditis,

to test whether an adjuvant medical intervention other than

steroids may be effective. Drawing from the effectiveness

of colchicine in preventing recurrences of acute idiopathic

pericarditis, as demonstrated in the COPE trial,


they sought to

test whether the same agent added to standard anti-tuberculous

therapy would significantly reduce the occurrence of pericardial

constriction in patients with definite or probable tuberculous

pericarditis, compared to placebo.

Thirty-three HIV-positive patients with definite or probable

tuberculous pericarditis were randomly assigned to receive 1 mg

per day of colchicine over six weeks (versus placebo) in addition

to standard four-drug anti-tuberculous therapy for six months

and oral steroids over eight weeks. Anti-retroviral therapy was

available to all participants. Pericardial constriction was assessed

by echocardiography after a follow-up period of 16 weeks in

21 participants. Five participants developed echocardiographic

features of constriction with no demonstrable difference between

the intervention and placebo arms of the study (relative risk 1.07,

95% CI: 0.46–2.46,




While the focus of the authors’ conclusions and discussion

centres around the absence of a significant efficacy outcome

with colchicine, rather than despair about yet another negative

study in TB pericarditis, it is important to keep in mind what

this study actually tested and teaches us. The first lesson is

about the importance of perseverance for clinician researchers.

Just because steroids have been shown not to work, Liebenberg

and colleagues have not folded their arms and given up trying

to find an effective intervention to help their patients with this


Their perseverance and that of others reminds us that there are

in fact various other medical interventions that have the potential

to be efficacious adjunctive therapies in tuberculous pericarditis

but are as yet untested in large-scale clinical trials. The use of

Division of Cardiology, University of Cape Town Medical

School, Cape Town, South Africa

Arthur Mutyaba, MB ChB, MMed, FCP (SA)

Mpiko Ntsekhe, BA, MD, PhD, FCP (SA), Cert Cardio (SA), FACC,