The burden and natural history of cardiac pathology at TB diagnosis in a high-HIV prevalence district in Zambia: protocol for the TB-Heart study

Abstract

Background: 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.

Methods: 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.

Discussion: 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.

Keywords: Cardiac biomarkers; Cardiovascular disease; Echocardiography; Non-communicable diseases; Pulmonary tuberculosis.

Fig. 1

A Study Diagram: Cross-sectional Study to determine the prevalence of cardiac pathology in consecutively recruited participants with PTB in Lusaka, Zambia. 250 consecutively recruited participants with PTB will be matched to comparator participants without PTB on a 2:1 basis. Participants and comparators will undergo a comprehensive clinical assessment; functional assessments including Bandim TB score, WHO Performance status and six-minute walk test; point-of-care echocardiography; and 2D-echocardiography. B Study Diagram: Natural history study where participants with PTB will be followed up at 2- and 6-months to a) evaluate TB outcomes and b) determine change in functional status over time and c) biomarkers of inflammation and cardiac pathology in those with PTB with and without echocardiographic evidence of cardiac pathology at diagnosis. Legend: 6MWT = 6-min walk test

Fig. 2

Study Flow Diagram. Describes the study visits that participants will attend over the course of six months from enrolment. *Clinical assessment is history and examination, functional assessment (Bandim TB, WHO Performance Status, and six-minute walk test). Blood draws are cardiac biomarkers including high-sensitivity troponin I and non-terminal pro-B type natriuretic peptide, and inflammatory biomarkers including C-reactive protein. POC Echo = point-of-care echocardiography; TTE = transthoracic echocardiogram; PTB = pulmonary TB