CardioMorph Atlas: a statistical approach to evaluate association between pulmonary tuberculosis and cardiac morphology from chest X-rays

Background: Patients with tuberculosis (TB) face an elevated risk of certain cardiovascular diseases. The inflammatory response associated with TB is linked to cardiac complications, though the spatial impact on cardiac structure remains understudied. In this study, we assess population-level differences in cardiac morphology in TB using an atlas-based approach applied to routine chest X-rays. Methods: A total of 8651 patients (with 2626 patients with TB) were selected from four cohorts: Shenzhen, TBX11K, TB Portals, and MIMIC, covering seven countries. We developed a representative cardiac template, CardioMorph Atlas, and compared population-level morphological differences between patients with TB and controls. Cardiac borders and areas were quantified into CardioMorph features and analysed for their association with all-cause mortality using Cox regression. Findings: CardioMorph Atlas revealed significant lateral elongation of the heart in patients with TB, in both left and right ventricles, with patterns distinct from those in pneumonia and cardiomegaly. Vector field analysis showed lateral extension of cardiac structures in patients with TB. Upper area (hazard ratio: 2.18, 95% CI: 1.1–4.30, p = 0.022) and right perimeter (HR = 2.07, 95% CI:1.06–4.02) were significantly associated with increased all-cause mortality in patients with TB. CardioMorph features showed strong associations with all-cause mortality in patients with TB, supporting their potential utility for risk stratification, and which demonstrates feasibility of quantitatively assessing impact of TB on cardiac morphology using routine chest X-rays. Interpretation: These findings suggest that tuberculosis is linked to distinct, prognostically relevant cardiac morphological alterations detectable on routine chest X-rays using the CardioMorph Atlas. Further prospective validation is warranted. Funding: National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases.