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Complex congenital heart disease associated with disordered myocardial architecture in a midtrimester human fetus

DOI: 10.1161/CIRCIMAGING.118.007753 DOI Help

Authors: Patricia Garcia-canadilla (University College London Institute of Child Health; Universitat Pompeu Fabra) , Hector Dejea (Swiss Light Source) , Anne Bonnin (Swiss Light Source) , Vedrana Balicevic (University of Zagreb) , Sven Loncaric (University of Zagreb) , Chong Zhang (Universitat Pompeu Fabra) , Constantine Butakoff (Universitat Pompeu Fabra) , Jazmin Aguado-sierra (Campus Nord Universitat Politecnica de Catalunya) , Mariano Vázquez (Campus Nord Universitat Politecnica de Catalunya) , Laurence H. Jackson (University College London) , Daniel J. Stuckey (University College London) , Christoph Rau (Diamond Light Source) , Marco Stampanoni (Swiss Light Source; ETH Zurich) , Bart Bijnens (Universitat Pompeu Fabra; Institución Catalana de Investigación y Estudios Avanzados) , Andrew C. Cook (University College London (UCL))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Circulation: Cardiovascular Imaging , VOL 11

State: Published (Approved)
Published: October 2018
Diamond Proposal Number(s): 11716

Abstract: Background: In the era of increasingly successful corrective interventions in patients with congenital heart disease (CHD), global and regional myocardial remodeling are emerging as important sources of long-term morbidity/mortality. Changes in organization of the myocardium in CHD, and in its mechanical properties, conduction, and blood supply, result in altered myocardial function both before and after surgery. To gain a better understanding and develop appropriate and individualized treatment strategies, the microscopic organization of cardiomyocytes, and their integration at a macroscopic level, needs to be completely understood. The aim of this study is to describe, for the first time, in 3 dimensions and nondestructively the detailed remodeling of cardiac microstructure present in a human fetal heart with complex CHD. Methods and Results: Synchrotron X-ray phase-contrast imaging was used to image an archival midgestation formalin-fixed fetal heart with right isomerism and complex CHD and compare with a control fetal heart. Analysis of myocyte aggregates, at detail not accessible with other techniques, was performed. Macroanatomic and conduction system changes specific to the disease were clearly observable, together with disordered myocyte organization in the morphologically right ventricle myocardium. Electrical activation simulations suggested altered synchronicity of the morphologically right ventricle. Conclusions: We have shown the potential of X-ray phase-contrast imaging for studying cardiac microstructure in the developing human fetal heart at high resolution providing novel insight while preserving valuable archival material for future study. This is the first study to show myocardial alterations occur in complex CHD as early as midgestation.

Journal Keywords: fetal heart; humans; isomerism; myocardium; synchrotrons; X-ray microtomography

Subject Areas: Biology and Bio-materials

Instruments: I13-2-Diamond Manchester Imaging

Other Facilities: Swiss Light Source