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Abstract
Background The right ventricle (RV) is not designed to sustain high pressure leading to failure. There are no current medications to help RV contraction, so further information is required on adaption of the RV to such hypertension.
Methods The Right Ventricle in Children (RVENCH) study assessed infants with congenital heart disease undergoing cardiac surgery with hypertensive RV. Clinical and echocardiographic data were recorded, and samples of RV were taken from matched infants, analysed for proteomics and compared between pathologies and with clinical and echocardiographic outcome data.
Results Those with tetralogy of Fallot (TOF) were significantly more cyanosed than those with ventricular septal defect (median oxygen saturation 83% vs 98%, P=0.0038), had significantly stiffer RV (tricuspid E wave/A wave ratio 1.95 vs 0.84, P=0.009) and had most had restrictive physiology. Gene ontology in TOF, with enrichment analysis, demonstrated significant increase in proteins of contractile mechanisms and those of calmodulin, actin binding and others associated with contractility than inventricular septal defect. Structural proteins were also found to be higher in association with sarcomeric function: Z-disc, M-Band and thin-filament proteins. Remaining proteins associated with actin binding, calcium signalling and myocyte cytoskeletal development. Phosphopeptide enrichment led to higher levels of calcium signalling proteins in TOF.
Conclusion This is the first demonstration that those with an RV, which is stiff and hypertensive in TOF, have a range of altered proteins, often in calcium signalling pathways. Information about these alterations might guide treatment options both in terms of individualised therapy or inotropic support for the Right ventricle when hypertensive due to pulmoanry hypertension or congenital heart disease.
- congenital heart disease
- right ventricle
- ventricular hypertrophy
- proteomics
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Footnotes
Contributors RMT, M-SG, SJG and MG designed the study and protocol. MC collected RV samples. CG performed and analysed the clinical and echocardiographic data. ARB, DI, SA-G and KH performed the laboratory analysis. RMT and AJB wrote the first draft, and all authors provided input to and approved the final version of the manuscript.
Funding Sparks, the Childrens charity * 13BTL01. This study was supported by the NIHR Biomedical Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. University Hospitals Bristol NHS Foundation Trust department of research and innovation number CH/2014/4571 provided sponsorship.
Disclaimer The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
Competing interests None declared.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval Ethical approval was granted by the National Research Ethics Service number 14/NW/1256, IRAS 143683.
Provenance and peer review Not commissioned; internally peer reviewed.