Longitudinal Observational Study of Cardiac Outcome Risk Factor Prediction in Children, Adolescents, and Adults with Barth Syndrome.

Journal Article (Journal Article)

Barth Syndrome (BTHS) is an X-linked mitochondrial cardioskeletal myopathy caused by defects in TAFAZZIN, a gene responsible for cardiolipin remodeling. Altered mitochondrial levels of cardiolipin lead to cardiomyopathy (CM), muscle weakness, exercise intolerance, and mortality. Cardiac risk factors predicting outcome are unknown. Therefore, we conducted a longitudinal observational study to determine risk factors for outcome in BTHS. Subjects with minimum two evaluations (or one followed by death or transplant) were included. Cardiac size, function, and QTc data were measured by echocardiography and electrocardiography at 7 time points from 2002 to 2018. Analysis included baseline, continuous, and categorical variables. Categorical risk factors included prolonged QTc, abnormal right ventricle fractional area change (RV FAC), left ventricle (LV) or RV non-compaction, and restrictive CM phenotype. The association between variables and cardiac death or transplant (CD/TX) was assessed. Median enrollment age was 7 years (range 0.5-22; n = 44). Transplant-free survival (TFS) was 74.4% at 15 years from first evaluation. The cohort demonstrated longitudinal declines in LV size and stroke volume z-scores (end-diastolic volume, p = 0.0002; stroke volume p < 0.0001), worsening RV FAC (p = 0.0405), and global longitudinal strain (GLS) (p = 0.0001) with stable ejection (EF) and shortening (FS) fraction. CD/TX subjects (n = 9) displayed worsening LV dilation (p = 0.0066), EF (p ≤ 0.0001), FS (p = 0.0028), and RV FAC (p = .0032) versus stability in TFS. Having ≥ 2 categorical risk factors predicted CD/TX (p = 0.0073). Over 15 years, 25% of BTHS subjects progressed to CD/TX. Those with progressive LV enlargement, dysfunction, and multiple cardiac risk factors warrant increased surveillance and intense therapy.

Full Text

Duke Authors

Cited Authors

  • Chowdhury, S; Jackson, L; Byrne, BJ; Bryant, RM; Cade, WT; Churchill, TL; Buchanan, J; Taylor, C

Published Date

  • August 2022

Published In

Volume / Issue

  • 43 / 6

Start / End Page

  • 1251 - 1263

PubMed ID

  • 35238957

Pubmed Central ID

  • PMC9462389

Electronic International Standard Serial Number (EISSN)

  • 1432-1971

Digital Object Identifier (DOI)

  • 10.1007/s00246-022-02846-8


  • eng

Conference Location

  • United States