Tuberculosis (TB) continues to be a major cause of death across sub-Saharan Africa (SSA). In parallel, non-communicable disease and especially cardiovascular disease (CVD) burden has increased substantially in the region. Cardiac manifestations of TB are well-recognised but the extent to which they co-exist with pulmonary TB (PTB) has not been systematically evaluated. The aim of this study is to improve understanding of the burden of cardiac pathology in PTB in those living with and without HIV in a high-burden setting.

This is a cross-sectional and natural history study to evaluate the burden and natural history of cardiac pathology in participants with PTB in Lusaka, Zambia, a high burden setting for TB and HIV. Participants with PTB, with and without HIV will be consecutively recruited alongside age- and sex-matched TB-uninfected comparators on a 2:1 basis. Participants will undergo baseline assessments to collect clinical, socio-demographic, functional, laboratory and TB disease impact data followed by point-of-care and standard echocardiography. Participants with PTB will undergo further repeat clinical and functional examination at two- and six months follow-up. Those with cardiac pathology at baseline will undergo repeat echocardiography at six months.

The outcomes of the study are to a) determine the burden of cardiac pathology at TB diagnosis, b) describe its association with patient-defining risk factors and biochemical markers of cardiac injury and stretch and c) describe the natural history of cardiac pathology during the course of TB treatment.

An infectious aortic aneurysm is a rare disease entity. We report a challenging case of a 29-year-old male presenting with chest pain and constitutional symptoms. The patient was found to have three pseudoaneurysms of the aorta on imaging, significant pathological findings of necrotizing granulomatous lymphadenitis from a supraclavicular lymph node biopsy, and a highly suggestive clinical picture of tuberculous aortitis. He was referred to vascular surgery for intervention and discharged on antituberculous therapy for 6 months. To the best of our knowledge, only five cases of tuberculous aortic aneurysms have been reported from the Middle East and North Africa (MENA) region, all with favorable outcomes. A high index of suspicion, early detection, and prompt intervention are essential in managing such cases.

Tuberculous pericarditis is an extrapulmonary manifestation of tuberculosis that is most commonly associated with pericardial thickening, effusion, and calcification. We present a case of tuberculous pericarditis mimicking a malignant pericardial tumor in a 77-year-old male. CT revealed an irregular and nodular pericardial thickening. MRI revealed high signal intensity on T1-weighted fat-suppressed images and peripheral rim enhancement after gadolinium administration. MRI can be helpful in determining the differential diagnoses in cases of tuberculous pericarditis with nonspecific imaging findings.

Tuberculosis (TB) remains the leading cause of death from a single infectious agent globally, despite being a potentially curable disease. This disease typically affects the lungs but may involve many extrapulmonary sites, especially in patients with risk factors such as HIV infection. The clinical features of extrapulmonary TB may mimic many different disease entities, particularly at less common thoracic sites such as the heart, chest wall, and breast. Imaging has an important role in the early diagnosis of TB, helping to detect disease, guide appropriate laboratory investigation, demonstrate complications, and monitor disease progress and response to treatment. Imaging supports the clinical objective of achieving effective treatment outcome and complication prevention. This review aims to highlight the imaging spectrum of TB affecting both pulmonary and extrapulmonary sites in the thorax. We also briefly provide key background information about TB, such as epidemiology, pathogenesis, and diagnosis.

This paper reports on the unlikely case of a 68-year-old man presenting with a non-resolving, mild lower respiratory tract infection, subsequently diagnosed with pericardial tuberculosis (TB) in the absence of TB risk factors and with negative TB serology. Pericardial and pleural effusions were found incidentally on CT pulmonary angiogram, with a small pericardial effusion without tamponade seen on the echocardiogram. During his three-month inpatient stay, the patient was rarely very unwell, though no treatment led to clinical and biochemical resolution of symptoms. Later deterioration prompted another echocardiogram, which found a moderate-sized pericardial effusion, septal bounce, and new regional wall motion abnormalities. To avert the impending cardiac tamponade, the patient underwent pericardiectomy, which provided a tissue diagnosis of TB. Pericardial TB is extremely uncommon, especially outside of TB endemic regions, though it is well described. This case is especially noteworthy, as serology, bronchial washings, and pleural aspirate had been negative for TB though a Quantiferon test was positive. The diagnosis was only confirmed after pericardiectomy. The patient was subsequently treated with anti-TB therapy, with a good clinical response. This case highlights diagnostic challenges and strategies for investigating and managing similar complex scenarios, particularly in non-endemic settings.

A rare case of ventricular tachycardia caused by extrapulmonary tuberculosis has been followed up. Automatic implantable cardioverter defibrillator implantation was done at the time of presentation. Following this, the patient is clinically well without any episodes of ventricular tachycardia and is considered for an implantable cardioverter defibrillator explantation.

Myocarditis is an infrequent extrapulmonary manifestation of tuberculosis that confers an unfavourable prognosis.

A 36-year-old man presented to the hospital with palpitations and dyspnoea. Tests revealed the presence of non-sustained ventricular tachycardia, with mild elevation of troponin and C-reactive protein levels. Coronary angiography showed normal results. A cardiac magnetic resonance (CMR) showed moderate hypertrophy, preserved ejection fraction, and an extensive multi-segmental pattern of fibrosis and oedema. An 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET-CT) scan revealed multiple hypermetabolic adenopathies and patchy cardiac uptake. A tuberculin skin test and interferon-gamma release assay were both positive. An endomyocardial biopsy (EMB) showed inflammation without granulomas; and microbiological stains were negative. Biopsy of an adenopathy revealed the presence of multiple necrotizing granulomas with Langhans cells. Based on the test results and clinical presentation, the suspected diagnosis was tuberculous myocarditis. Treatment with anti-tuberculosis drugs was started. One month later, the presence of mycobacterium tuberculosis (MT) was detected in the lymph node culture. At 7 months of follow-up, the patient remains asymptomatic, ventricular arrhythmias have ceased, and radiological signs of inflammation have resolved.

Ventricular arrhythmia is one of the clinical manifestations of tuberculous myocarditis. Cardiac magnetic resonance and 18F-FDG-PET-CT imaging are an essential component of the non-invasive evaluation of inflammatory cardiomyopathy. However, a confirmatory biopsy may be required to identify potentially treatable aetiologies. Although the diagnosis of tuberculous myocarditis requires an isolation of MT by staining or culture in EMB, the diagnostic yield is very low. For this reason, extra-cardiac findings may provide the definitive diagnostic clue.

The burden of cardiovascular diseases is sharply rising in low- and middle-income countries (LMICs). Along with the increasing rates of cardiovascular risk factors in these regions, there is a growing recognition of the contribution of neglected tropical diseases and other infections. Several cardiac implications of these infections have been reported but have not yet been validated by robust population data. This is in part due to limited access to health care and insufficient data collection infrastructure in many LMICs. Therefore, the true impact of these infections on the cardiovascular system may be underestimated, because of both underdiagnosis and underreporting bias. There is an urgent need to thoroughly delineate the cardiac impact of these conditions with elevated prevalence in LMICs and to propose strategies to reduce the negative consequences of these diseases in health systems with limited resources.

Although primarily a lung disease, extra-pulmonary tuberculosis (TB) can affect any organ or system. Of these, cardiovascular complications associated with disease or drug toxicity significantly worsen the prognosis. Approximately 60% of patients with TB have a cardiovascular disease, the most common associated pathological entities being pericarditis, myocarditis, and coronary artery disease. We searched the electronic databases PubMed, MEDLINE, and EMBASE for studies that evaluated the impact of TB on the cardiovascular system, from pathophysiological mechanisms to clinical and paraclinical diagnosis of cardiovascular involvement as well as the management of cardiotoxicity associated with antituberculosis medication. The occurrence of pericarditis in all its forms and the possibility of developing constrictive pericarditis, the association of concomitant myocarditis with severe systolic dysfunction and complication with acute heart failure phenomena, and the long-term development of aortic aneurysms with risk of complications, as well as drug-induced toxicity, pose complex additional problems in the management of patients with TB. In the era of multidisciplinarity and polymedication, evidence-based medicine provides various tools that facilitate an integrative management that allows early diagnosis and treatment of cardiac pathologies associated with TB.

Physiologically based pharmacokinetic (PBPK) models have gained in popularity in the last decade in both drug development and regulatory science. PBPK models differ from classical pharmacokinetic models in that they include specific compartments for tissues involved in exposure, toxicity, biotransformation, and clearance processes connected by blood flow. This study aimed to address the gaps between the mathematics and pharmacology framework observed in the literature. These gaps included nonconserved systems of equations and compartment concentration that were not biologically relatable to the tissues of interest. The resulting system of nonlinear differential equations is solved numerically with various methods for benchmarking and comparison. Furthermore, a sensitivity analysis of all parameters were conducted to elucidate the critical parameters of the model. The resulting model was fit to clinical data as a performance benchmark. The clinical data captured the second line of antiretroviral treatment, lopinavir and ritonavir. The model and clinical data correlate well for coadministration of lopinavir/ritonavir with rifampin. Drug-drug interaction was captured between lopinavir and rifampin. This article provides conclusions about the suitability of physiologically based pharmacokinetic models for the prediction of drug-drug interaction and antiretroviral and anti-TB pharmacokinetics.

Acquired tuberculosis continues to be a challenge worldwide. Although tuberculosis has been considered a global public health emergency, it remains poorly controlled in many countries. Despite being primarily a pulmonary disease, tuberculosis could involve the heart. This systematic review is part of the "Neglected Tropical Diseases and Other Infectious Diseases Involving the Heart" (the NET-Heart Project) initiative from the Interamerican Society of Cardiology. This project aims to review the cardiovascular involvement of these heterogeneous diseases, advancing original algorithms to help healthcare providers diagnose and manage cardiovascular complications. In tuberculosis, pericardium involvement is relatively common, especially in AIDS, and tuberculosis is the most common cause of constrictive pericarditis in endemic countries. Myocarditis and aortitis by tuberculosis are rare. Clinical manifestations of cardiovascular involvement by tuberculosis differ from those typically found for bacteria or viruses. Prevailing systemic symptoms and the pericarditis diagnostic index should be taken into account. An echocardiogram is the first step for diagnosing cardiovascular involvement; however, several image modalities can be used, depending on the suspected site of infection. Adenosine deaminase levels, gamma interferon, or polymerase chain reaction testing could be used to confirm tuberculosis infection; each has a high diagnostic performance. Antituberculosis chemotherapy and corticosteroids are treatment mainstays that significantly reduce mortality, constriction, and hospitalizations, especially in patients with HIV. In conclusion, tuberculosis cardiac involvement is frequent and could lead to heart failure, constrictive pericarditis, or death. Early detection of complications should be a cornerstone of overall management.

Due to increasing global migration, the spectrum of cardiovascular disease (CVD) is changing in developed countries. Up to 3% of migrants arriving in Europe have underlying CVD. Despite their high global prevalence, conditions such as rheumatic heart disease, Chagas disease, endomyocardial fibrosis, tuberculous pericarditis, peripartum cardiomyopathy, and pulmonary hypertension are often under-recognized, and, as a result, neglected in industrialized countries. Many of these conditions, and their causes, are often unfamiliar to the health-care providers in host countries. In this review, we summarize the epidemiology, etiology, clinical presentation, diagnostic work-up, and management of neglected CVDs that have an increasing prevalence in the Global North.

Tuberculous pericarditis (TBP) is the most important manifestation of tuberculous heart disease and is still associated with a significant morbidity and mortality in TB endemic areas. The high prevalence of the disorder over the last 3 decades has been fueled by the human immunodeficiency virus/AIDS (HIV/AIDS) pandemic in these areas. The objective of this review is to provide a focused update on developments in the diagnosis and therapy of this condition, prevention of its complications, as well as future novel therapies. The definitive diagnosis of a tuberculous etiology in patients with suspected TBP continues to pose a challenge for clinicians. Clinical prediction scores, although never formally validated have been used with some success. However, they may be prone to both over and underdiagnosis due to lack of pericardial fluid analysis. Recent studies evaluating Xpert MTB/RIF, suggest that this advanced polymerase chain reaction (PCR) based technology does not provide increased accuracy compared to earlier iterations. However a combined two test approach starting with Xpert MTB/RIF followed by either adenosine deaminase (ADA) or interferon gamma (IFN-γ) may provide for significantly enhanced specificity and sensitivity cost permitting. Pericardiocentesis remains the gold standard for managing the compressive pericardial fluid and its adverse hemodynamic sequelae. A four drug anti-TB drug regimen at standard doses and duration is recommended. However recent evidence suggests that these drugs penetrate the pericardium very poorly potentially explaining the high mortality observed particularly in those who are culture positive with a high bacillary load. Constrictive pericarditis is the main long-term complication of TBP and is still a significant cause of heart failure in Sub-Saharan Africa. This is important because access to definitive surgical therapy where TBP is prevalent continues to be low, highlighting the need to develop strategies or interventions to prevent fibrosis and constriction. Recent detailed advanced studies of pericardial fluid in TBP have revealed a strong profibrotic transcriptomic profile, with high amounts of pro-inflammatory cytokines and low levels of the anti-fibrotic tetrapeptide N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP). These new insights may explain in part the high propensity to fibrosis associated with the condition and offer hope for the future use of targeted therapy to interrupt pathways and mediators of tissue damage and subsequent maladaptive healing and fibrosis. The value of effective pericardiocentesis in reducing these pro-inflammatory and pro-fibrotic cytokines and peptides in an attempt to prevent pericardial constriction has yet to be established but has generated hypotheses for ongoing and future research.

Tuberculous pericarditis is a severe form of extrapulmonary tuberculosis and is the commonest cause of pericardial effusion in high incidence settings. Mortality ranges between 8 and 34%, and it is the leading cause of pericardial constriction in Africa and Asia. Current understanding of the disease is based on models derived from studies performed in the 1940-50s. This review summarises recent advances in the histology, microbiology and immunology of tuberculous pericarditis, with special focus on the effect of Human Immunodeficiency Virus (HIV) and the determinants of constriction.

Extra pulmonary manifestations of tuberculosis (TB) are rare in developed countries. TB is the main etiology of chronic pericarditis in developing countries, but it's epidemiology is not unknown in the United States.

This retrospective study used the Healthcare Utilization Projects/Nationwide Inpatient Sample (HCUPS/NIS) database from 2002-2014 to evaluate the characteristics, risk factors, trends over time and region of tuberculous pericarditis in the United States.

The data during the study period consists of 100,790,900 discharges accounting for 482,872,274 weighted discharges. The data showed 744 weighted discharges with indication of both tuberculosis and pericarditis. A co-ocurrence of TB pericarditis and malignancy or chronic kidney disease was more common than in patients without TB pericarditis. The frequency of co-ocurrence of TB pericarditis and HIV infection, obesity, alcohol abuse and organ transplant was not elevated.

TB pericarditis is rare disease in the USA and the classical risk factors for lung tuberculosis may not be associated with TB pericarditis. CKD and malignancy appear to be associated with TB pericarditis, further studies are required to determine causality.

This scoping review sought to summarise available data on the prevalence, aetiology, diagnosis, treatment and outcome of pericardial disease in Africa.

We searched PubMed, Scopus and African Journals Online from 1 January 1967 to 30 July 2017 to identify all studies published on the prevalence, aetiologies, diagnosis, treatment and outcomes of pericardial diseases in adults residing in Africa.

36 studies were included. The prevalence of pericardial diseases varies widely according to the population of interest: about 1.1% among people with cardiac complaints, between 3.3% and 6.8% among two large cohorts of patients with heart failure and up to 46.5% in an HIV-infected population with cardiac symptoms. Tuberculosis is the most frequent cause of pericardial diseases in both HIV-uninfected and HIV-infected populations. Patients with tuberculous pericarditis present mostly with effusive pericarditis (79.5%), effusive constrictive pericarditis (15.1%) and myopericarditis (13%); a large proportion of them (up to 20%) present in cardiac tamponade. The aetiological diagnosis of pericardial diseases is challenging in African resource-limited settings, especially for tuberculous pericarditis for which the diagnosis is not definite in many cases. The outcome of these diseases remains poor, with mortality rates between 18% and 25% despite seemingly appropriate treatment approaches. Mortality is highest among patients with tuberculous pericarditis especially those coinfected with HIV.

Pericardial diseases are a significant cause of morbidity and mortality in Africa, especially in HIV-infected individuals. Tuberculosis is the most frequent cause of pericardial diseases, and it is associated with poor outcomes.

Several studies have investigated the diagnostic accuracy of tests of pericardial effusion interferon-gamma for tuberculous pericarditis in patients with pericardial effusion, but the results have varied. The aim of this study was to investigate the diagnostic accuracy of interferon-gamma for tuberculous pericarditis using meta-analysis.

The PubMed and EMBASE databases were searched to identify studies investigating the diagnostic accuracy of tests for interferon-gamma in pericardial effusion for tuberculous pericarditis. The quality of eligible studies was assessed by the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2), and the sensitivities and specificities of interferon-gamma across eligible studies were pooled by a bivariate model.

A total of four studies encompassing 488 subjects were included. The pooled sensitivity, specificity, positive and negative likelihood ratios (NLRs) were 0.97 [95% confidence interval (CI): 0.87-0.99], 0.99 (95% CI: 0.74-1.00), 187 (95% CI: 3-12,542) and 0.03 (95% CI: 0.01-0.14), respectively.

Testing for interferon-gamma in cases of pericardial effusion is adequate for identifying or ruling out tuberculous pericarditis.