, Egidija Rinkūnienė 1,2,3, Alma Čypienė 1,2,3, Vilma Dženkevičiūtė 1,2,3, Jolita Badarienė 1,2,31 Institute of Clinical Medicine, Clinic of Cardiac and Vascular Diseases, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
2 Clinic of Cardiac and Vascular Diseases, Vilnius University Hospital Santaros Klinikos, 08406 Vilnius, Lithuania
3 Center of Cardiology and Angiology, Vilnius University Hospital Santaros Klinikos, 08406 Vilnius, Lithuania
Abstract
Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis (M. tuberculosis) and is transmitted through airborne particles. Although TB usually damages the lungs, this disease can also cause complications in various organs, including the cardiovascular system. Indeed, pericarditis represents the most frequently reported cardiac manifestation of TB, and may present alongside fever, dyspnea, cough, or increased central venous pressure, hepatomegaly, and peripheral edema. Tuberculous-related pericarditis treatment is challenging due to the poor penetration of anti-tuberculous drugs into the pericardium. Myocarditis is another form of cardiac manifestation and is often associated with arrhythmias. Tuberculous aortitis typically causes dilatation leading to pseudoaneurysm formation and is usually asymptomatic; however, this manifestation can result in sepsis, aortic rupture, or even death, although rarely. Cardiac tuberculomas may present with general symptoms and can impair heart function by obstructing the outflow tracts, leading to ventricular dysfunction. Additionally, the primary treatment of TB carries cardiotoxicity risks, such as various arrhythmias. Moreover, TB significantly increases the risk of cardiovascular conditions, including myocardial infarction and coronary artery obstruction. Therefore, early recognition and a multidisciplinary approach are crucial to prevent severe outcomes such as sudden cardiac death, sepsis, or aortic rupture. Thus, this review highlights the spectrum of TB-related cardiac complications and underscores the importance of greater awareness and timely multidisciplinary care.
Keywords
- tuberculosis
- cardiovascular complications
- pericarditis
- myocarditis
- aortitis
Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium Tuberculosis (M. tuberculosis). It predominantly affects the lungs, but can disseminate throughout the body and damage other organ systems, such as the gastrointestinal, central nervous system, or cardiovascular [1]. According to the recent World Health Organization (WHO) Global Tuberculosis Report 2024, the global TB incidence rate (new cases per 100,000 population per year) increased by 4.6% between 2020 and 2023, with a slowdown in the last year; however, between 2010 and 2020, an annual 2% decrease was observed. Also, TB has potentially regained as the leading global cause of mortality from a single infectious agent, replacing COVID-19 [2]. Most TB cases were registered in South-East Asia (45%), Africa (24%) and the Western Pacific (17%) regions, which represent countries with low socioeconomic status (low income, limited education, crowdedness and lack of employment)—one of the main TB risk factors, as well as human immunodeficiency virus (HIV), immunosuppressive treatment, chronic illnesses (diabetes, rheumatoid arthritis and other), malnutrition, alcohol or tobacco use [2, 3].
Cardiovascular involvement in tuberculosis primarily affects the pericardium, less often the myocardium, and the aorta [4]. Even though the disease is completely curable, in 2023 there were 1.25 million deaths due to TB, with a global mortality rate was 2.4 per 100,000 population. For instance, tuberculous pericarditis carries a 40% risk of death at 6 months in patients with HIV infection and 25% in those without HIV [2, 5]. To prevent potentially serious cardiac complications in tuberculosis, attentive cardiological examination and tracking are recommended [4, 6].
The main aim of this literature review is to provide a comprehensive summary of recent scientific literature on cardiac involvement in tuberculosis, epidemiology, clinical presentation, and potential outcomes.
TB is considered the leading cause of pericardial diseases worldwide, particularly in low and middle-income countries [7, 8]. Among individuals with pulmonary TB, approximately 1–2% develop TB pericarditis, which is associated with a substantial 6-month mortality ranging from 17% to 40%. If left untreated, up to half of cases progress to cardiac tamponade, with mortality rates reaching 85% at 6 months [9, 10]. However, global data on the incidence and outcomes of TB pericarditis are limited, as most available studies originate from endemic regions. M. tuberculosis mostly reaches the pericardium by spreading through the lymphatic system, though in HIV patients, hematogenous spread is the most common route, and in rare cases, there is a direct contiguous spread from nearby structures such as the lungs, pleura, or spine [10, 11]. Although TB primarily affects the lungs, rarely, but there are some clinical cases that report TB pericarditis as the only manifestation [12, 13, 14].
The clinical presentation of TB pericarditis can manifest in four different stages: dry, effusive, adsorptive, and constrictive (Table 1). In the dry stage, the entire pathological process begins in the pericardium when M. tuberculosis antigens are presented by macrophages to CD4+ T lymphocytes, triggering the activation of lymphocytes, macrophages, and complement-fixing antibodies. It results in the inflammation of pericardial leaflets, granuloma formation, cytolysis, and a fibrous exudate with an abundance of inflammatory cytokines. Notably, HIV patients have low CD4+ T cell levels, which leads to low immune response, and this process is disrupted [9, 15]. The dry stage is the least common, but it presents with symptoms of acute pericarditis and ST-segment elevation in the electrocardiogram (ECG). It has been observed that the predominant acute TB pericarditis symptoms are fever (73%) and cough, dyspnea, chest pain (41–46%), while stabbing pain and pericardial rubbing, which are typical symptoms of acute pericarditis, are uncommon in TB pericarditis [10]. Another study in an intermediate-burden country noticed that the most frequently observed symptom was dyspnea (84.1%) and is associated with a higher risk of unfavourable outcomes such as cardiac tamponade, constrictive pericarditis, and death [16].
| Stage | 1. Dry | 2. Effusive | 3. Adsorptive | 4. Constrictive |
| Percentage | 1–2% | 79.5% | Rare | 5–25% |
| Pathophysiology | Fibrinous exudation, early granuloma formation with macrophages and T cells | Serosanguineous effusion | Effusion absorption, organized granulomatous caseation, pericardial fibrous thickening, fibrosis | Constrictive pericardial scarring and/or calcification |
| Pericardial fluid | Low polymorphonuclear, predominantly Mtb concentration | Predominantly lymphocytic exudate | Pericardial fibrous thickening -fibrin deposition and collagen accumulation | No residual fluid in the pericardium |
| Clinical signs and symptoms | Mostly asymptomatic | Fever, cough, dyspnea, chest pain | Increased central venous pressure, hepatomegaly, peripheral edema, ascites, muffled heart sounds, sinus tachycardia, palpable apical impulse | |
| Imaging findings | Widespread ST elevation, PR depression, non-specific T wave changes in the electrocardiogram (ECG) | Thick fibrinous fluid around the heart | Little or no pericardial effusion | |
| Chest x-ray | Enlargement of cardiac silhouette | Pericardial layer calcifications | ||
| Echocardiography | ||||
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| |
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TB, tuberculosis; ST, ST-segment; PR, PR interval; ECG, electrocardiogram.
In some patients, dry pericarditis may progress to a second stage—effusive pericarditis, which is the most common TB pericarditis presentation: a systematic review of 36 studies on pericardial cases in Africa, an endemic region of TB, revealed that 79.5% of tuberculous pericarditis cases presented as effusive pericarditis [5]. It is the large accumulation of fluid in the pericardium that compresses the heart chambers, affecting cardiac filling and contraction. At this stage, pericardial fluid contains a lymphocytic exudate with monocytes and foam cells, and patients may present with signs and symptoms of heart failure. If fluid accumulation in the pericardium occurs suddenly and rapidly, the patient may present with tachycardia, hypotension, and/or evolve into tamponade (20%). Moreover, in this stage, the combination of effusion and constriction may occur when the pericardium constricts and pericardial fluid simultaneously accumulates [4, 9, 10]. In this stage, changes in the pericardium may be detected using imaging techniques, with echocardiography recommended as the first-line investigation. Pericardial effusion may appear as an echo-free (anechoic or hypoechoic) space between the separated layers of the pericardium. Moreover, in cases of large or chronic effusion, fibrinous strands may be visible [4, 17].
In the absorptive stage, the pericardial effusion begins to be absorbed, a granulomatous caseation starts to organise, and a pericardial fibrous thickening occurs because of fibrin deposition and collagen accumulation. Echocardiographically, it may appear as a thick fibrinous fluid surrounding the heart [9].
When no pericardial fluid remains, it is referred to as the constrictive stage,
which is associated with the poorest prognosis regarding associated dysfunction.
This stage is characterized by a loss of pericardial elasticity and
calcification, with little or no effusion, resulting in reduced cardiac diastolic
filling [4, 9]. It presents as heart failure symptoms with progressive fluid
retention: increased central venous pressure (100%), hepatomegaly (100%),
peripheral edema (94%), ascites (89%) and less common symptoms such as muffled
heart sounds (76%), sinus tachycardia (70%) and palpable apical impulse (58%)
[10]. The main echocardiographic signs of constrictive pericarditis are no
residual fluid in the pericardium, respirophasic ventricular septal shift (septal
bounce), increasing mitral E-wave velocity and E/A ratio
One Investigation of the Management of Pericarditis (IMPI) trial analyzed 1370
adult patients (median age for HIV-positive individuals is 34.0 years, for
HIV-negative individuals 47.7) with TB pericarditis, of whom 939 were co-infected
with HIV. The results showed that HIV-infected patients were approximately 13–14
years younger than those without HIV. They had a higher occurrence of
tachycardia, hypotension, anemia, and radiographic pulmonary infiltrates
indicating TB, but had a lower incidence of peripheral edema. Furthermore, it was
noted that HIV infection modifies the cardiovascular presentation and reduces the
incidence of constrictive pericarditis, without increasing the mortality rate
[20]. These changes can be explained by immunological mechanisms, as demonstrated
in a study that analyzed pericardial fluid contamination using the flow
cytometric method. It showed that in HIV-positive patients, CD4+ memory cells
exhibit a less differentiated phenotype with reduced expression of tumor necrosis
factor (TNF), interleukin-2 (IL-2), and interferon-gamma (IFN-
| HIV-negative | HIV-positive | |
| Age | About 34 years old | About 47–48 years old |
| Common mechanism of TB spread | Lymphatic system | Hematogenous dissemination |
| Common symptoms | Fever, cough, dyspnea, chest pain, night sweats, weight loss | |
| Peripheral edema | Tachycardia, hypotension, anemia | |
| Pericardial fluid (PF) | Dominates CD8+ T cells | Dominates CD4+ T cells |
| Less viral load than in plasma (Viral load: PF |
Higher viral load than in plasma (Viral load: PF | |
| Prognosis | Acute TB pericarditis – poor prognosis (17–40% die in 6 months) | Poor prognosis |
| Less chance of developing constrictive pericarditis | ||
| Treatment linked to increased risk of malignancy | ||
HIV, human immunodeficiency virus.
Diagnosing TB pericarditis is a difficult challenge for healthcare workers. It
is estimated that 15–20% of all pericardial diseases remain undiagnosed and
have an elevated risk of morbidity and mortality [9]. Imaging tests play a key
role in diagnosing TB pericarditis. Echocardiography is the most used imaging
modality, helping to identify pericardial fluid, which appears as an area of
increased echogenicity due to a large amount of fibrin or fibrous strands, and to
assess its volume. Moreover, in chest radiography, effusive TB pericarditis may
present as an enlarged cardiac silhouette, while in the constrictive stage,
pericardial layer calcifications may be observed. The most diagnostically
informative imaging test is a chest CT scan, which can provide detailed
information about pericardial fluid volume, localization, density, thickness,
and/or calcifications. Enlarged mediastinal and tracheobronchial lymph nodes
(
The key diagnostic markers of TB pericarditis in a sterile pericardial sample
include M. Tuberculosis cultures found with acid-fast bacilli staining,
polymerase chain reaction (PCR) for M. Tuberculosis DNA, along with
adenosine deaminase (ADA)
| Criteria | Points |
| Fever | 1 |
| Night sweats | 1 |
| Weight loss | 2 |
| Globulin level |
3 |
| Peripheral leukocyte count |
3 |
| A total score | |
Constrictive pericarditis must be differentiated from restrictive
cardiomyopathy, as the two conditions present with similar features. The key
factors supporting the diagnosis of constrictive pericarditis include
echocardiographic findings such as septal bounce, pericardial thickening and/or
calcifications, respiratory variations of the mitral inflow (peak E velocity
The prognosis of patients with acute TB pericarditis remains poor (17–40% of
patients diagnosed with TB pericarditis die in 6 months) despite adequate four
anti-TB drugs treatment (isoniazid, rifamycin, pyrazinamide, and ethambutol) due
to insufficient penetration from plasma to pericardial fluid. A pilot study
analyzed 16 patients treated for TB pericarditis, focusing on measurements of
anti-TB drugs, pH, and protein in pericardial TB fluid compared to plasma. The
results showed that free (non-protein-bound) rifampicin concentration in
pericardial fluid in no sample exceeded the minimum inhibitory concentration
(MIC) with a value of 0.208 mg/L, while the highest detected concentration was
0.125 mg/L (p = 0.001). The free peak concentration of ethambutol
(p
TB myocarditis is a very rare extrapulmonary TB manifestation and is most commonly diagnosed only postmortem during autopsy [27, 28]. As well as TB pericarditis, M. Tuberculosis can reach the myocardium through hematogenous or lymphatic spread, or even directly. However, some literature suggests that the most common is the hematogenous pathway [10, 29]. One study noted that TB myocarditis is usually diagnosed in patients with a normal immune system (not HIV-positive), and in most patients under 45 years old, it is the sole sign of TB [29].
Some literature suggests that there is a higher risk of TB myocarditis on the right side of the heart due to a tendency to primarily involve the right-sided mediastinal lymph nodes, while one systematic review found that 68% of all cases of TB mainly involved in left ventricle, less common myocarditis damaged the right ventricle and atrium, and at least – left atrium. It is important to acknowledge that conflicting results may be attributable to limited data and potential bias [10, 28, 29]. In autopsy, it may present as nodular tuberculomas with central caseation, miliary tubercles in the heart, or a diffuse infiltrative pattern linked to pericarditis [28].
Clinically, TB myocarditis may present as the only TB manifestation, together with pericarditis as myopericarditis, and in rare cases, can be asymptomatic or with different heart conduction system disorders [29, 30]. Myocarditis in the ECG may show up as long QT interval syndrome, p pulmonale, right bundle branch block, or other nonspecific ventricular arrhythmias, for example, ventricular tachycardia [27, 31, 32]. Moreover, it can cause chest pain, dyspnea, heart failure, lymphadenopathy, or even sudden cardiac death [31, 32, 33]. It is essential to note that these symptoms are non-specific and may mislead healthcare specialists, as acute TB myocarditis can be misinterpreted as acute myocardial infarction or chronic myocarditis may present with symptoms similar to chronic heart failure [33].
Severe laboratory findings may help in the diagnosis of TB myocarditis, including elevated troponin and C-reactive protein (CRP) levels. Echocardiographic abnormalities may include regional wall motion or biventricular (global) dysfunction. On cardiac magnetic resonance (CMR) imaging, TB myocarditis may present as myocardial edema, inflammation, or fibrosis [31, 33].
It should be emphasized that TB myocarditis usually responds to anti-TB therapy, but the risk of sudden cardiac death remains unchanged despite the treatment. Therefore, continuous patient monitoring and intensive management of symptoms are crucial [29].
Table 4 summarizes and compares the diagnostic findings in TB pericarditis and TB myocarditis based on [5, 7, 23, 27, 31, 32, 33]. In summary, TB pericarditis may clinically present with fever and/or cough, as well as peripheral edema. Echocardiographically, the space between the two pericardial layers may be observed, and most importantly, pericardial fluid laboratory analysis may be useful, revealing the presence of M. tuberculosis bacilli along with elevated adenosine deaminase and interferon-gamma levels. In contrast, TB myocarditis may present with new-onset chest pain, dyspnea, and heart failure, accompanied by distinct ECG abnormalities, and echocardiography may reveal new myocardial dysfunctions, while no pericardial effusion may be present.
| TB pericarditis | TB myocarditis | |
| Most common reach | By the lymphatic system | By hematogenous spread |
| Symptoms | ||
| ECG | PR depression, ST elevation | Long QT syndrome, p pulmonale, right bundle branch block, unspecific ventricular arrhythmias |
| Echocardiography | Echo-free (anechoic or hypoechoic) space between the separated two layers of the pericardium (increased pericardial fluid volume), fibrin or fibrous strands, septal bounce, and pericardial thickening | Newly developed regional wall motion abnormalities or global ventricular dysfunction |
| MRI/CMR | Ventricular interdependence on real-time cine MRI | Myocardial edema, inflammation, or fibrosis |
| CT | Pericardial thickness |
Similar to MRI/CMR |
| Pericardial fluid | Without changes, except if the pericardium is involved (myopericarditis) | |
Bold font indicates the most important findings. MRI, magnetic resonance
imaging; CMR, cardiac magnetic resonance; CT, computed tomography; M.
tuberculosis, Mycobacterium tuberculosis;
Tuberculous endocarditis as a complication of TB is extremely rare, and just a few case reports are described in the literature, and there is a notable absence of large-scale studies [10, 34, 35]. M. tuberculosis reaches the endocardium through hematogenous spread, directly attaching and colonizing the valve tissue. This process activates specific molecules such as fibrinogen and other surface proteins (clumping factors, coagulase), leading to prolonged bacterial adhesion, the formation of new fibrin and platelets, resulting in vegetations and the formation of granulomas. These vegetations produce toxins that damage the valves, starting a pathological cycle—a broken valve further promotes the fibrin-platelet aggregation and activation of the extrinsic clotting pathway, which may contribute to cytokine storm. As the vegetations continue to grow, they stimulate a pro-inflammatory chemokine response and even more active TB endocarditis development, which may cause the formation of circulating immune complexes and potentially damage other organs such as the kidneys, eyes, and skin. This severe and disseminated TB form is called miliary TB [36, 37]. Moreover, due to bacteriemia, there is an increased risk of abscess formation [38].
TB endocarditis manifests with non-specific systemic symptoms such as fever, weight loss, and heart failure if there is significant valve damage. Cough and hemoptysis, which are the main symptoms of pulmonary TB, are not common [38]. Most commonly, vegetations form in the aortic or mitral valve, destroying the heart’s leaflets and causing significant cardiac damage, leading to myocardial infarction or acute coronary syndrome. Less frequently, the tricuspid valve is affected, leading to an embolization to the lungs [36]. Clinically, valve damage may present as a new-onset cardiac murmur [36, 39].
The 2023 European Society of Cardiology (ESC) Guidelines for endocarditis recommend transthoracic echocardiography (TTE) and transesophageal echocardiography (TOE) as the first-line imaging tests. TTE is always performed due to its good availability and specificity, despite its low sensitivity (IB class recommendation). TOE is recommended for all patients with clinical suspicion of endocarditis, even if TTE is positive, because it more precisely evaluates valve damage, small vegetations, perivalvular complications, and endocarditis associated with a prosthetic valve or cardiac implantable electronic device [39].
TB endocarditis may be diagnosed based on modified Duke criteria for infective endocarditis, which include major criteria, such as positive blood culture and specific imaging findings of infective endocarditis (IE), as well as minor criteria, including various clinical symptoms (Table 5) [39]. M. tuberculosis grows slowly in blood culture, or even the test may often be negative; therefore, imaging tests and various minor criteria are commonly used to confirm the diagnosis of TB endocarditis [36, 37].
| Major criteria | |||
| 1. Blood cultures positive for IE | |||
| Microorganisms consistent with IE from continuously positive blood cultures: | |||
| a. | |||
| b. All of 3 or a majority of | |||
| 2. Imaging positive for IE | |||
| Valvular, perivalvular/periprosthetic, and foreign material anatomic and metabolic lesions characteristic of IE detected by any of the following imaging techniques: | |||
| a. Echocardiography (TTE and TOE). | |||
| b. Cardiac CT. | |||
| c. [18F]-FDG-PET/CT(A). | |||
| d. WBC SPECT/CT. | |||
| Minor criteria | |||
| 1. Predisposing conditions (i.e., predisposing heart condition at high or intermediate risk of IE or PWIDs) | |||
| 2. Fever is defined as a temperature | |||
| 3. Embolic vascular dissemination (including those asymptomatic, detected by imaging only): | |||
| a. Major systemic and pulmonary emboli/infarcts and abscesses. | |||
| b. Hematogenous osteoarticular septic complications (i.e., spondylodiscitis). | |||
| c. Mycotic aneurysms. | |||
| d. Intracranial ischemic/hemorrhagic lesions. | |||
| e. Conjunctival hemorrhages. | |||
| f. Janeway’s lessons. | |||
| 4. Immunological phenomena: | |||
| a. Glomerulonephritis. | |||
| b. Osler nodes and Roth spots. | |||
| c. Rheumatoid factor. | |||
| 5. Microbiological evidence: | |||
| a. Positive blood culture, but does not meet a major criterion as noted above. | |||
| IE Classification (at admission and during follow-up) | |||
| Definite: | Possible: | Rejected: | |
[18F]-FDG-PET/CT, 18F-fluorodeoxyglucose positron emission tomography; CT(A), computed tomography (angiography); IE, infective endocarditis; Ig, immunoglobulin; PWID, people who inject drugs; TOE, transesophageal echocardiography; TTE, transthoracic echocardiography; WBC SPECT/CT, white blood cell single photon emission tomography/computed tomography; ESC, European Society of Cardiology.
If the diagnosis of IE is unclear, the gold standard is histopathological examination, which can be performed by collecting damaged tissue or embolic fragments during valve surgery. During this examination, the most characteristic features of TB endocarditis are nodules on the valves, caseating granulomas, polypoidal tubercles, and thrombi containing M. tuberculosis bacilli [36, 39].
Treatment of TB endocarditis is similar to TB pericarditis and other TB-related cases, involving a combination of anti-TB drugs for six months. However, if the valves are completely damaged, surgical replacement may be necessary [10, 36]. Importantly, all Mycobacterium species can exhibit resistance to antibacterial therapy, which is associated with a higher relapse rate of IE. Therefore, appropriate treatment, active multidisciplinary (cardiologists, infectious disease specialists, cardiac surgeons, general practitioners) follow-up, and post-treatment prophylaxis are essential [39].
TB aortitis is a rare type of cardiac involvement in tuberculosis, but it has potentially good outcomes if diagnosed in time. A single-center study in Paris investigated 108 cases of tuberculosis and estimated that 3 patients (2.8%) were complicated by aortitis. Notably, all of them showed clinical improvement after treatment [40, 41].
M. tuberculosis can infect the aorta through lymphogenic or paravertebral abscess, hematogenous spread, and additionally, it can directly contaminate atherosclerotic plaques in the aorta [28, 42]. The TB infection in the aorta often leads to dilatation, which causes a pseudoaneurysm (mycotic aneurysm), mostly in the thoracic or abdominal part of the aorta, and less frequently it presents as aortic stenosis [40, 42]. Predominantly, pseudoaneurysms are asymptomatic and are often detected accidentally. In addition, it may present with chest pain, compression, weight loss, fever, pain in various parts of the body, or other nonspecific symptoms, which complicate the diagnostic process [40, 43, 44]. Moreover, if the aorta is stenotic, it may cause claudication, dyspnea, or syncope and may lead to heart failure [40, 45].
Mycotic aneurysms are most accurately diagnosed through imaging techniques, as there are no specific laboratory tests, and blood culture may not always be positive in cases of TB. The CT angiography (CTA) is considered the gold standard for early diagnosis, planning surgical or endovascular treatment, and assessing the risk of complications. Other imaging tests, such as CT and magnetic resonance angiography (MRA), may also be used, but are not as fast and accurate as CTA [43].
The treatment of TB aortitis/pseudoaneurysm is variable and includes anti-TB therapy for small and asymptomatic aneurysms, as well as open or endovascular procedures for advanced aneurysms, or a combination of medical and surgical treatments [43].
Although usually there are good outcomes, early diagnosis and a multidisciplinary approach are essential to prevent patients from sepsis, aortic rupture, or dissection resulting in death [40, 43].
The link between infection and cardiovascular disease (CVD), which are two distinct health conditions, has been studied for many years, and it was found that both acute and chronic TB infections have a significant influence on coronary arteries and increase overall cardiovascular events. Literature suggests that coronary arteries may be strongly associated with chronic endothelial inflammation caused by TB infection, when increased levels of adenosine deaminase in the plasma stimulate neutrophils to secrete free oxygen radicals, contributing to vascular damage [46]. Moreover, a systematic review and meta-analysis found that statin therapy may help to reduce active TB infection through various mechanisms [47, 48]. The primary mechanism is the inhibition of cholesterol synthesis, as cholesterol is essential for M. tuberculosis entry into host cells, such as macrophages [47]. Additionally, some in vitro studies suggest that fluvastatin may enhance the immune response in cases of TB infection by increasing cytokine release from Th1 cells and activating caspase 1 [48].
Acute TB infection considerably doubles the risk of subsequent acute MI for 1 year, and latent TB infection increases all types of CVD risk by 8% [49, 50, 51]. Additionally, individuals with TB have a 51% increased risk of major adverse cardiovascular events, such as cardiovascular mortality, acute MI, unstable angina, and nonfatal stroke, compared to non-TB individuals. This elevated risk is attributable to increased inflammation, heat shock protein-mediated autoimmunity, and M. tuberculosis contamination, which all lead to increased morbidity and mortality [6, 52]. Latent TB infection is strongly associated with and independently contributes to an increased risk of chronic obstructive coronary artery disease [46]. This link is highlighted in one study, which showed that 9% of all patients with latent TB had obstructed coronary arteries, compared to 3% in TB-negative people [53].
Moreover, arterial hypertension, the primary determinant of CVD, is also associated with latent TB. TB-positive patients have a higher risk of developing hypertension, which is less controllable than in TB-negative individuals, particularly in those without other CVD risk factors, such as a high body mass index, hyperglycemia, or smoking [54, 55].
Although TB can be treated with generally good outcomes, TB survivors exhibited a 21% higher risk of developing ischemic heart disease and a 48% greater risk of myocardial infarction compared to matched controls, and the reason is unclear [56].
Tuberculomas are encapsulated granulomatous lesions caused by M. tuberculosis. They most commonly develop in the lungs, but may occur in other organs. Cardiac tuberculomas are extremely rare and typically are located in the right heart, particularly on the free right atrial wall, and this tendency is explained by the fact that mediastinal lymph nodes and lymphatic vessels on the right side are drained directly into the right subclavian vein and right atrium [4, 57]. However, there are some case reports in the literature describing tuberculomas in the left heart [58, 59].
Moreover, depending on their localization, tuberculomas can be classified as intracardiac and intracavitary. Intracardiac tuberculomas are less common and are located in the heart tissue, most commonly in the myocardium, whereas intracavitary tuberculomas are found in the heart chambers, usually in the right heart, as previously mentioned [4]. Clinically, tuberculomas may present with general symptoms (fever, night sweats, weight loss, weakness), can be asymptomatic or even present as sudden cardiac death [60, 61, 62]. Intracavitary tuberculomas may obstruct the right ventricular outflow tract, the superior vena cava, or even the coronary artery ejection tracts. This may have an impact on cardiac function and may lead to ventricular dysfunction, ventricular rupture, or different arrhythmias [62].
Intracardiac tuberculomas can be detected using imaging tests, such as echocardiography, FDG-PET/CT, and cardiovascular magnetic resonance imaging, which reveals isointense central caseation, a hypointense fibrous capsule, and a hyperintense line of inflammatory cellular infiltration. However, only histopathological examination and mycobacterial culture can confirm the diagnosis of TB, as it carries a substantial risk of being misdiagnosed as a cardiac tumor, particularly in immunosuppressed individuals [59, 62].
Cases of tuberculomas require special attention and a multidisciplinary approach by healthcare professionals to find the most appropriate individual treatment. There are no specific guidelines for the duration of anti-TB therapy and when surgery should be indicated. However, surgery is recommended in cases of uncertain diagnosis, hemodynamically unstable patients with significant obstruction, or when there is an inadequate response to medical treatment [4, 59].
Although M. tuberculosis affects the heart function differently, anti-TB treatment carries its own cardiotoxic risks, especially, speaking about treatment used for multi-drug resistant TB (MDR-TB) [4, 63, 64]. MDR-TB is a form of TB that is resistant to rifampicin and isoniazid, the most commonly used drugs for TB treatment. Drugs for MDR-TB treatment according to the WHO 2022 update are described in Table 6 [64]. Bedaquiline is strongly associated with prolonging the QTc interval due to inhibition of the potassium channel hERG (human Ether-à-go-Related Gene, which is encoded by the KCNH2). This leads to delayed ventricular repolarization and the left ventricle becomes more sensitive to premature electrical impulses, which increases the risk of polymorphic ventricular tachycardia, also known as Torsades de pointes [63, 65, 66].
| Group and steps | Medicine |
| Group A: | Levofloxacin or moxifloxacin |
| Include all three medicines | Bedaquiline |
| Linezolid | |
| Group B: | Clofazimine |
| Add one or both medicines | Cycloserine or terizidone |
| Group C: | Ethambutol |
| Add to complete the regimen, and when medicines from Groups A and B cannot be used | Delamanid |
| Pyrazinamide | |
| Imipenem-cilastatin or meropenem | |
| Amikacin or streptomycin | |
| Ethionamide or prothionamide | |
| P-aminosalicylic acid |
Other anti-TB drugs, such as fluoroquinolones (levofloxacin, moxifloxacin) and clofazimine, have similar effects and should not be combined [63, 65, 66]. Furthermore, the literature reports several cases of drug-induced cardiomyopathy from anti-TB treatment, including two patients who developed dilated cardiomyopathy [67]. Another report describes isoniazid-induced drug rash accompanied by eosinophilic myocarditis and fever [68]. Although drug-induced cardiac lesions are extremely rare, these cases highlight the importance of careful monitoring in patients receiving anti-TB therapy.
Cardiac complications in tuberculosis are infrequent, and the most common cardiovascular involvement in tuberculosis is pericarditis. Moreover, it has a significant effect on increasing the risk of cardiovascular diseases, such as myocardial infarction or coronary artery obstruction. All in all, it is essential to make an accurate diagnosis as early as possible and initiate adequate treatment to prevent patients from life-threatening outcomes, such as sudden cardiac death, sepsis, or aortic rupture. A multidisciplinary healthcare approach is essential for optimizing patient management and improving prognosis.
GM and ER designed the research study, performed the literature search, and wrote the initial draft of the manuscript. ER, AČ, VD, and JB contributed meaningfully to developing the study concept and design, participated in reviewing manuscript drafts, and approved the final version of the manuscript. All authors contributed to the critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
Not applicable.
Not applicable.
This research received no external funding.
The authors declare no conflict of interest.
References
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