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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 6, November/December 2016
336
AFRICA
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
Mycobacterium
tuberculosis
(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.
1
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
1980s.
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.
2,3
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.
3–6
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%.
3
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,
7
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,
p
=
0.88).
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
condition.
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,
mpiko.ntsekhe@uct.ac.zaEditorial