International Journal of Cardiology 167 (2013) 640645

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International Journal of Cardiology

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Review

Tuberculous Endocarditis
Alexander Liu a, Edward Nicol a, Yanmin Hu b, Anthony Coates b,
a
National Heart and Lung Institute, Imperial College London, United Kingdom
b
Division of Clinical Sciences, St George's University London, United Kingdom

a r t i c l e i n f o a b s t r a c t

Article history: Mycobacterium tuberculosis (TB) is a major cause of death globally. TB is capable of infecting every organ in
Received 31 May 2012 the body, and the heart is no exception. Tuberculous endocarditis (TBE) was rst reported in 1892 and sub-
Received in revised form 11 July 2012 sequently many other cases have been described, highlighting the signicant morbidity and mortality asso-
Accepted 21 August 2012
ciated with this manifestation of TB. TBE usually presents with miliary tuberculosis and most early cases
Available online 26 September 2012
were diagnosed on autopsy. With increasing application of prosthetic valve replacements in the treatment
Keywords:
of infective endocarditis (IE), TB infections have begun to affect these as well as native valves. With the intro-
Mycobacterium tuberculosis duction of TB culture methods and drug therapy, the prognosis has improved. HIV and drug resistance are
Tuberculosis likely to make the management of TBE more difcult in the future. Large scale studies, both prospective
Tuberculous and retrospective, are required to ascertain the true incidence of TBE whilst development of novel anti-TB
Endocarditis therapy is also required to combat resistance. We present the rst extensive literature review on TBE in over
75 years.
Crown Copyright 2012 Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction
Mycobacterium tuberculosis (TB) kills nearly 4700 people daily [1].
It is most lethal in the developing world but is re-emerging in Europe
and North America, in part due to the emergence of multiple drug re-
sistance and co-infection with human immunodeciency virus (HIV)
[1]. Many of the difculties in managing TB reside in its complex
pathogenesis, particularly its persistence despite treatment, which re-
mains incompletely understood.
TB is an acid-fast bacillus (AFB) transmitted by aerosol. In clinical
practice, rapid diagnosis, case-nding and directly observed treatment
short-course (DOTS) therapy are effective measures of disease control
[2]. Problems arise however when these measures are unavailable,
poorly delivered or patient compliance is low. Once inhaled, AFB are
engulfed by alveolar macrophages and dendritic cells [3]. Rather than
perishing, like most other bacteria, TB persists in these metabolically
hostile environments, leading to further phagocytic chemotaxis [3].
Meanwhile, antigen presentation by dendritic cells results in the inux
of lymphocytes to the site of infection. Macrophage activation by lym-
phocytes leads to the partial destruction of the AFB with granuloma for-
mation [3]. Over time, these foci of inammatory cells undergo central
caseation and a proportion of bacilli remains dormant only to reactivate
leading to miliary disease [3].
TB is known to affect the pericardium [4], myocardium [5] and val-
vular structures of the heart[6] as well as virtually every other organ
Corresponding author. Tel.: +44 2087255725; fax: +44 2087250137.
E-mail address: acoates@sgul.ac.uk (A. Coates).
in the body [7]. Tuberculous endocarditis (TBE) has not been reviewed
in the medical literature since 1935.
We performed a literature search of MEDLINE using criteria
containing tuberculous endocarditis, tuberculosis endocarditis,
TB endocarditis, valvular tuberculosis, endocardial tuberculosis,
endocardial tuberculous, endocardial TB. All relevant articles and
the references were reviewed with exclusion of animal studies. We
obtained permission and consent for the use of patient material. We
aim to summarise the evidence for TBE to reect the evolution of diag-
nostics, treatment and future challenges in this cardiovascular manifes-
tation of the most prevalent infectious disease in the world.
2. The golden age of pioneering discovery
Giant cells and caseating granulomas were the benchmark features
used to diagnose TBE at the turn of the 20th century [8]. However, with-
out positive culture conrmation, these histological ndings were high-
ly suggestive of TBE rather than diagnostic. The spread of tuberculosis in
endocarditis is likely to be haematological, and as early as 1903, Braillon
and Jousset described a patient in whom tubercle bacilli were isolated
both from venous samples during life and from valvular vegetations
on autopsy. They claimed to have reported a case of primary TBE, how-
ever failure to specify the presence or absence of hepatic and splenic TB
meant that such a conclusion was contentious [9,10].
In 1899, Marshall and Benda specied that TBE could only be diag-
nosed if tubercle bacilli were found deep within valvular vegetations
located above the elastica [1012]. Bacilli found supercially may occur
due to accidental contamination and lesions found below the elastica
are more indicative of myocarditis [10]. Clinically, the vast majority of

0167-5273/$ see front matter. Crown Copyright 2012 Published by Elsevier Ireland Ltd. All rights reserved.
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 A. Liu et al. / International Journal of Cardiology 167 (2013) 640645
TBE cases were accompanied by miliary disease, with dismal prognosis
[1214]. Patients presented with non-specic symptoms of miliary TB
rather than characteristic features of infective endocarditis [10]. Meek
described two patients with symptoms of haemoptysis and abdominal
discomfort, however at autopsy, orid evidence of TB was observed
deep within the aortic and mitral vegetations of the rst patient,
while bacilli were sparsely distributed in the mitral lesions of the
second [10]. No other micro-organisms were isolated [10]. Only the
rst case was regarded as true TBE as the second failed to satisfy Marshall
and Benda's diagnostic criteria.
3. 1935 to 1950 A renaissance of ideas
In 1935, Baker reviewed 30 cases of TBE, of which only 5 satised
his upgraded diagnostic criteria: 1) microscopic evidence of tuberculous
reaction; 2) positive tubercle bacilli staining; 3) exclusion of other causes
of endocardial lesions. The presence of tubercle bacilli in the blood stream
or miliary TB, in isolation, is insufcient to diagnose TBE [10,12,14,15]. In
the same period, Beare described 16 patients with cardiac tuberculosis
from a cohort of 3,500 cadavers. Of these, only one case demonstrated
Ziehl-Neelsen (ZN) positive valvular involvement (0.03%) [16]. In a sim-
ilar autopsy study of 900 patients with TB, Baker found 6 cases of TBE
(0.67%) [15]. Notably, miliary tuberculosis co-existed with every case
described [17,18].
Extensive TBE has a predilection for the systemic circulation and may
affect multiple valves [10,19,20]. In 1936, Davie described a 24 years old
female with systemic TB in whom AFB were detected in aortic and mitral
valve vegetations. Similarly, Bevan and Wilkins reported a 17 year old
male with dyspnoea, arthralgia and heart block in whom inammatory
inltrates and AFB were found in aortic and mitral lesions [19,20].
Haematological deposition of bacilli leading to right sided TBE
usually affects the pulmonary valves [21,22]. Gilmore et al. isolated AFB
from vegetations on the right anterior cusp of the pulmonary valve in a
21 years old man with extensive systemic tuberculosis and proposed
that TB was seeded via a plexus of blood vessels at the base of the valvu-
lar cusp [22]. The true mechanism of the origins of tuberculous vegeta-
tions remains largely hypothetical.
4. Modern era of antibiotics, immunosuppression and valve surgery
The discovery and widespread use of anti-tuberculous antibiotics
caused a paradigm shift in the management of TB. Remission from
TBE was rst reported in 1981 by Soyer et al. in a 20 year old woman
with severe aortic insufciency secondary to aortic annulus erosion by
an endocardial tuberculoma [23]. She underwent aortic valve replace-
ment and anti-TB chemotherapy [23]. Pharmacological management
alone has produced mixed results in patients with TBE, notably, many
patients still succumbed to miliary tuberculosis [24,25].
Individuals with tuberculosis and HIV co-infections have worsened
prognoses since immunosuppression renders these patients vulnerable
to the development of miliary tuberculosis. In 2002, Fumagalli reported
TBE in a 35 years old intravenous drug user (IVDU) with poorly treated
HIV infection [26]. Blood cultures were positive for TB and trans-
thoracic echocardiography (TTE) demonstrated tricuspid valve vegeta-
tions, which resolved following chemotherapy with rifampicin, isoniazid,
pyrazinamide and ethambutol [26]. The authors encouraged the consid-
eration of TB as a differential diagnosis of valvular disease in HIV patients
[26]. This report showed that tricuspid valve endocarditis can result from
TB as well as conventional bacteria such as Staphylococcus aureus in IVDU.
Three cases of TBE without systemic involvement, in immune-
competent patients, have been described. In all cases, valve replace-
ment accompanied by anti-TB drugs formed the cornerstones in manage-
ment [6,27,28]. Klingler et al. describe a 64 years old man with severe
mitral regurgitation who was cured with a mitral valve replacement
(MVR) and anti-TB drugs. Histology of the excised tissue valve demon-
strated calcied granulomas and culture of the vegetation conrmed
641
TBE [27]. Of note, the valvular vegetation was missed on transthoracic
echocardiography and supports the argument that endocarditis (of any
cause) remains a clinical diagnosis. Sogabe et al. present a 63 year old
man with acute aortic insufciency and a sub-aortic valve aneurysm
who underwent aortic valve replacement. Histology suggested TBE, how-
ever AFB were not detected in either blood cultures or surgical specimens
[28]. Recently, Sultan et al. described a 30 years old man with tuberculous
involvement of the mitral valve and right atrium who underwent MVR
[6]. TB was cultured from the excised valve 20 days post-operatively.
He received anti-TB chemotherapy for 10 months leading to resolution
of disease [6]. Of note, anti-TB chemotherapy is considered adjuvant to
surgery and facilitated disease eradication.
Having noted a case where echocardiography missed the vegeta-
tion, we illustrate two cases of suspected TBE in whom transthoracic
echocardiogram (TTE) images were diagnostic (Fig. 3). The rst patient
was a male intravenous drug user who presented in cardiogenic shock
(Fig. 3A). His TTE images demonstrated tricuspid valve endocarditis
and he subsequently underwent tricuspid valve replacement. Tissue
culture of the resected valve failed to demonstrate evidence of tubercu-
losis. The second patient had a history of prolonged prostration and
weight loss and also presented in cardiogenic shock. TTE images dem-
onstrate an aortic valve vegetation (Fig. 3B). Once again tissue culture
of the resected aortic valve did not show evidence of tuberculosis, how-
ever gram positive rods were found in blood cultures of both patients. In
both these cases, TTE provided early indications of endocarditis without
specically diagnosing TBE. Serial blood cultures remain key to provid-
ing the denitive diagnosis.
5. Prosthetic valve TBE
Surgical management of TBE involves replacement with either
metallic or porcine valves. allowing the treatment of the original valvu-
lar defect as well as extraction of the diseased tissue for TB culture [6].
Positive cultures enable commencement of appropriate anti-TB chemo-
therapy maximising the likelihood of TB eradication [6]. This is ex-
tremely important as empirical antibiotics have limited action against
TB.
Despite obvious benets of surgical management, TB may also affect
valvular prostheses, albeit in b 1% of cases.[29] Porcine valves and ho-
mografts are predominantly affected. Implantation of contaminated ho-
mografts has led to miliary tuberculosis in recipients. In 1979, Anyanwu
et al. analysed a pool of over 800 homograft recipients and demonstrat-
ed seven cases of miliary TB post operatively [29]. This alarming rate of
homograft infections was attributed to post-mortem contamination
and a lack of antibiotics treatment in the processing of extracted valves.
More recent studies demonstrate much lower rates of miliary TB in
Fig. 1. Summary of the available management of tuberculous endocarditis through
time. TB denotes Mycobacterium tuberculosis.
642 A. Liu et al. / International Journal of Cardiology 167 (2013) 640645
Fig. 2. Ziehl-Neelsen (ZN) staining of tubercle bacilli. This image from our laboratory
demonstrates dark purple stained tuberculous bacilli on a background of pink stained
macrophages.
recipients whilst the most recent analysis of 27,840 valves failed to
identify a single case of TB contamination [3032]. This is largely due
to the exclusion of at-risk donors which is a superior method compared
to graft screening with AFB stains.
In 1979, Wainwright described the rst cases of TBE on a mitral
valve prosthesis in a 28 year old lady with heart failure and pulmonary
hypertension [33]. She underwent an MVR of a calcied and stenosed
mitral valve. Five months later, she presented with non-specic symp-
toms of chest pain, backache, loss of appetite and diarrhoea [33]. At
autopsy, miliary TB was diagnosed with isolation of AFB from the mitral
valve prosthesis. Her rapid clinical deterioration meant that the diagnosis
was not suspected prior to death. A decade later, Yamane et al. reported
two fatal cases of miliary TB after aortic xenograft endocarditis. Neither
patients survived beyond one year [34].
Although post-operative survival following TBE is considered to be
excellent, there is a lack of data on long term follow-up, due to the
relatively infrequent occurrence of valvular tuberculosis. TB may be-
come dormant and reactivate later causing endocarditis and miliary
disease [33]. Since TBE commonly occurs with systemic involvement,
it is important to know the rate of valvular infection upon reactivation.
Table 1 summarises the signicant cases of TBE.
6. The evolution TBE diagnosis
TBE diagnostics evolved greatly since the 1900s with a shift from
histological observations made on autopsy to post-operative tissue
cultures from the living (summarised in Fig. 1). An early reliance on
histological diagnosis led to the development of stringent criteria which
A B
Fig. 3. Trans-thoracic Echocardiograms (TTE) images of suspected tuberculous endocarditis. A) apical four chamber view demonstrating a tricuspid valve vegetation in a male
intravenous drug user (arrow). B) parasternal long axis view demonstrating an aortic valve vegetation in a man with a history of prostration and weight loss (arrow).
partly improved specicity at the cost of potentially overlooking impor-
tant cases [15].
Obtaining reliable diagnosis from clinical features alone was dif-
cult due to the concurrence with miliary TB, which presented with
non-specic symptoms [10]. Interestingly, early reports rarely de-
scribed clinical features characteristic of valvular disease. Instead,
most patients presented with constitutional symptoms indicative of
systemic tuberculosis [22]. Fever was the most frequently reported
complaint [6]. Unexplained weight-loss and lethargy were also com-
mon [22]. Symptoms of pulmonary TB such as cough and haemoptysis,
although commonly described one hundred years ago, did not feature
in recent cases [6,10,27].
TBE rarely presents with signs and symptoms of other cardiovascu-
lar diseases, such as pericarditis or myocarditis, unless there was con-
current involvement [6,19,27]. The case of TBE described by Bevans
and Wilkins demonstrated myocardial and interventricular septal bro-
sis. Such extensive cardiac damage would have accounted for the con-
duction defect (heart block) and exercised induced palpitations, which
the patient experienced [19]. Currently, substantial association data be-
tween TBE and pericarditis or aortic mycotic aneurysms are lacking.
When related to valvular dysfunction, patients presented with symp-
toms indicative of cardio-pulmonary failure, e.g. dyspnoea and reduced
exercise tolerance [6,19].
In 2008, the WHO estimated the case detection rate of sputum-
positive TB to be 61% [1]. However, TBE does not always manifest
with pulmonary involvement meaning sputum analysis alone is un-
likely to yield a high specicity for TBE [9]. No study to date has investi-
gated valvular manifestations in patients with pulmonary tuberculosis.
Indeed, miliary TB, rather than pulmonary, is more intimately associated
with endocarditis. This adds weight to the hypothesis that TB is deposited
onto valves haematologically [9].
Advances in TB treatment have led to improved prognosis with the
clinical goal now being curative, upon early diagnosis. Two major de-
velopments have transformed TBE diagnosis; rstly the ability to de-
tect TB from diseased valves after surgery and secondly the use of
echocardiography.
7. Tissue detection of TB
The widespread use of AFB staining (Fig. 2) and TB cultures has
undoubtedly increased diagnostic accuracy. However, there is cur-
rently no single assay, which offers 100% predictive value for the diag-
nosis of TB [35]. The cases reported have relied on best evidence
obtained from diagnostic methods employed for pulmonary TB [35].
Ziehl-Neelsen (ZN) staining has a sensitivity of 50%-80% whilst that
 A. Liu et al. / International Journal of Cardiology 167 (2013) 640645 643

Table 1
Signicant reports of tuberculous endocarditis.

Authors Year Method of TB diagnosis Precise Valvular Involvement Extra-cardiac involvement Management

Burkhardt [8] 1892 Histology Mitral Miliary disease Supportive

Benda [12] 1899 Histology Mitral Miliary disease Supportive
Braillon and Jousset [9] 1903 Histology Mitral Miliary disease Supportive
Witte [14] 1904 Histology Mitral Miliary disease Supportive
Sorgo and Suez [47] 1906 Histology Unspecied Miliary disease Supportive
Meek [10] 1908 Histology Aortic and Mitral Miliary disease Supportive
Reinhard [13] 1912 Histology Unspecied Miliary disease Supportive
Baker [15] 1935 Histology Aortic and Mitral Miliary disease Supportive
Marchiafava [15] 1935 Histology Unspecied Miliary disease Supportive
Davie [20] 1936 AF staining Aortic and Mitral Miliary disease Supportive
Mark [21] 1938 Histology Pulmonary Miliary disease Supportive
Ward [17] 1938 Histology Mitral Miliary disease Supportive
Gilmore [22] 1940 AF staining Pulmonary Miliary disease Supportive
Bevan and Wilkins [19] 1942 AF staining Aortic and Mitral Miliary disaese Supportive
Egidio [18] 1944 AF staining Aortic Miliary disease Supportive
Beare [16] 1947 AF staining Mitral Miliary disease Supportive
Anyanwu [29] 1976 AF staining / TB cultures Aortic and Mitral Miliary disease Anti-TB drugs (unspecied length)
Wainwright [33] 1979 AF staining Mitral Miliary disease Supportive
Yamane [34] 1989 TB cultures Mitral Miliary disease Supportive
Klingler [27] 1998 AF staining / TB cultures Mitral Unspecied VR / Anti-TB drugs (12 months)
Soyer[23] 1981 AF Staining Aortic Unspecied VR / Anti-TB drugs (12 months)
Kannangara[25] 1984 AF Staining Mitral Unspecied Supportive
Cope[24] 1990 AF Staining Aortic Miliary disease VR / Anti-TB drugs (12 months)
Fumagalli [26] 2002 TB cultures Tricuspid Miliary disease with HIV VR / Anti-TB drugs (6 months)
Sogabe [28] 2007 Histology Aortic Unspecied VR / Anti-TB drugs (9 months)
Sultan [6] 2010 TB cultures Mitral Unspecied VR / Anti-TB drugs (12 months)

Keys: TB denotes Mycobacterium tuberculosis; AF, Acid-fast; HIV, Human Immunodeciency Virus; VR, surgical valve replacement of the diseased valve.

Anti-TB drugs typically consists of quadruple chemotherapy (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol) for 2 months, followed by duel therapy (Rifampicin and Isoniazid) for
the rest of the duration.

of blood culture is approximately 98% [36,37]. However, positively
stained bacilli are not always isolated and TB cultures take a
long time to complete [6,28]. Three main types of culture media are
available; egg-based Lowenstein-Jensen; agar-based Middlebrook
7 H10 or 7 H11; and liquid-based Middlebrook 7 H12. Among these,
liquid-based media facilitate the fastest growth of TB, with detection
within 13 weeks [38]. Of the solid media, AFB grows faster on
agar-based variants.[39] Newer automated liquid-based culture sys-
tems, such as BACTEC 460 TB, offer the fastest rate of TB growth and
are more sensitive than other currently available solid media [39]. Un-
fortunately, reports of TBE in the literature have not specied the
types of culture media used.
Polymerase chain reaction (PCR) can be used to amplify TB DNA
fragments [35]. It delivers a high detection rate, and requires only a
few base pairs of TB genome for diagnosis [5]. Real-Time-PCR (rtPCR),
which detects RNA fragments reecting tuberculous gene expression,
have a sensitivity and specicity of 98% and 99%, respectively.[40] TB
PCR has been successfully employed in the diagnosis of tuberculous
myocarditis, however its use has not been reported in TBE [5,41].
8. Cardiovascular imaging
Echocardiography is the rst line imaging tool performed for all
cases of suspected infective endocarditis and has provided pivotal infor-
mation in every case of TBE since 1980 [6,42]. However, trans-thoracic
echocardiography (TTE) is less invasive than trans-esophageal echocar-
diography (TEE) but is inferior in terms of spatial resolution and perfor-
mance in obese patients or those with respiratory pathology [42]. TTE is
performed if the quality of imaging is likely to be good [42] and the
majority of recent patients presented in this paper underwent TTE
without TEE. In patients with culture positive valves post replacement,
pre-operative TTE often fails to detect endocardial vegetations, despite
adequate assessment of valvular function [27,28]. It is likely that these
lesions were too small to be detectable trans-thoracically. There is no
published data on the use of TEE in the assessment of tuberculous endo-
carditis and there are no studies comparing the diagnostic accuracy of
the two modalities of echocardiography.
It is important to note that whilst the demonstration of vegetations or
valvular dysfunction is suggestive of TBE, the nding is neither sensitive
nor specic. Denitive diagnosis, as with all forms of infective endocardi-
tis, relies on a constellation of clinical assessment, blood tests, imaging
and tissue cultures [6]. When the diagnosis of TBE is in doubt, more com-
mon causes of infective endocarditis need to be excluded [43]. The Duke
Criteria necessitates the drawing of blood, which should be tested for
bacterial microscopy, culture and sensitivity including TB [43]. Positive
echocardiographic ndings of valvular vegetation and positive TB cul-
tures in a patient presenting with clinical signs of endocarditis would
sufce as diagnosis of TBE [6,27,28].
9. 21st Century management of TBE
Historically, TBE was diagnosed at autopsy and tissue conrmation
yielded little more than research data, conveying no treatment benets
[19]. The management of TBE was purely supportive and the develop-
ment of miliary disease with rapid clinical deterioration was almost in-
evitable in the pre-antibiotics era [10]. TBE remains a relatively rare
phenomenon despite its early discovery, therefore large randomised
controlled trials on management, follow up and pharmacology are lack-
ing. Treatment still relies on evidence derived from pulmonary or mili-
ary TB, with the assumption that the same chemotherapy is effective
against TBE. Fig. 1 summarises the management of TBE over time.
The modern management of TBE involves surgical replacement of
damaged valves and aggressive disease eradication with anti-TB chemo-
therapy [6]. Diagnosis relies on a high index of suspicion, especially in pa-
tients who are prone to miliary disease, namely the immunosuppressed
and patients presenting with orid constitutional symptoms.[39] TBE is
not infectious unless complicated with symptomatic pulmonary disease
and isolation may be stopped once respiratory symptoms cease [39]. Pos-
itive blood or tissue cultures necessitate the commencement of anti-TB
drug treatments [6].
Despite signicant advances in tissue based diagnostics and cardiac
imaging techniques, the major difculty in TBE management lies in
making timely diagnosis. Due to the differences in antibiotic manage-
ment between TBE (prolonged quadruple therapy) and conventional
644 A. Liu et al. / International Journal of Cardiology 167 (2013) 640645
infective endocarditis (e.g. penicillin /aminoglycosides), there is a justi-
ed clinical reluctance in commencing anti-tuberculous chemotherapy
until a diagnosis of TBE is conrmed, or at least highly suspected [6]. In
the clinical setting, patients would not have been taking anti-TB drugs
upon presentation and further delays in establishing the diagnosis
would allow the disease to progress to an advanced stage. Therefore, re-
ducing the door-to-treatment time, which can take weeks in some
cases, is likely to lead to improved TBE management.
The delay in diagnosis is compounded by a failure of TTE to detect
certain TBE vegetations. Much like conventional infective endocardi-
tis, valvular vegetations in TBE occur in variable sizes. According to
autopsy studies these vegetations range from a few millimetres to a
few centimetres [10,20,27]. The physiological factors which govern
this are unclear. Clinically, the majority of the vegetations were large
enough to cause haemodynamic compromise [6,10,27]. There appears
to be little correlation between the sizes of TBE vegetations in immuno-
compromised patients compared to their immunocompetent counter-
parts. A wider application of TEE in future work will lead to improved
size classication of TBE vegetations.
10. Future challenges
Several reports have described successful treatment of TBE with
the standard anti-tuberculous chemotherapy; rifampicin, isoniazid,
pyrazinamide and ethambutol for 2 months, followed by rifampicin
and isoniazid for 4 months [6,27]. However, data on disease recurrence
and long term prognosis are lacking.
More recently, TB management has become more challenging in
the presence of drug resistance, which is estimated to approach
one-fth of all newly diagnosed active tuberculosis [1] . Up to 2.9%
of all new cases are multiple drug resistant (MDR-TB) and 1% are ex-
tensively drug resistant (XDR-TB) [1]. XDR-TB is dened as MDR-TB
resistant to a second-line injectable drug and a uoroquinolone [44].
Unsurprisingly, clinical outcomes in patients with drug resistant tuber-
culosis are signicantly worse than those with drug-sensitive infections
[45]. As yet there are no published reports of TBE involving MDR-TB or
XDR-TB.
A further, relatively common modern risk factor for TB is co-infection
with HIV, again worsening the prognosis of patients with XDR-TB [44].
New antibiotics and new drug regimens are urgently needed to deal
with MDR-TB and XDR-TB, and to shorten the duration of chemothera-
py in order to improve compliance to therapy. Poor compliance and in-
appropriate anti-tuberculous regimens continue to contribute to the
emergence of drug resistance [46]. It remains to be seen how MDR-TB
and XDR-TB will manifest in TBE.
11. Conclusion
TB remains a major health problem and TBE, although thought to
be rare, has been known to clinicians for over 120 years. Case reports
over time have reected the advances in the investigation and man-
agement of both systemic TB as well as TBE. Diagnostics have evolved
from simple histology to specic cultures and acid-fast staining. Manage-
ment of TBE has also improved with the advent of antibiotics and cardio-
thoracic surgical interventions. However, TBE may once again become
more difcult to manage with the emergence of MDR and XDR-TB. Post
treatment follow-up studies, either with or without valve replacement,
are required and novel anti-TB drugs advances are vital in the continuing
battle against tuberculosis.
Sources of Funding
AL was supported by a project from the Wellcome trust (VS/07/
IMP/A13). This work was also supported by a project from the European
Community's seventh Framework Programme (200999). The nancial
support of the Burton Medical Trust is gratefully acknowledged. AC
and YH are also grateful for nancial support from Helperby Therapeu-
tics Group Ltd. AC and YH are shareholders in Helperby, and AC is a
director.
Disclosures
None.
Acknowledgement
The authors of this manuscript have certied that they comply
with the Principles of Ethical Publishing in the International Journal
of Cardiology.
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