Metabolic pathways associated with right ventricular adaptation to pulmonary hypertension: 3D analysis of cardiac magnetic resonance imaging. (7th December 2018)

• Record Type: Journal Article
• Authors: Attard, Mark I; Dawes, Timothy J W; de Marvao, Antonio; Biffi, Carlo; Shi, Wenzhe; Wharton, John; Rhodes, Christopher J; Ghataorhe, Pavandeep; Gibbs, J Simon R; Howard, Luke S G E; Rueckert, Daniel; Wilkins, Martin R; O'Regan, Declan P
• Is Part Of: European heart journal. Volume 20:Number 6(2019)
• Page Start: 668
• Page End: 676
• Publication Date: 2018-12-07
• Subjects: pulmonary hypertension -- metabolomics -- wall stress -- cardiac magnetic resonance imaging -- image segmentation -- machine learning; Cardiovascular system -- Imaging -- Periodicals; Heart -- Imaging -- Periodicals; 616.10754
• DOI: 10.1093/ehjci/jey175
• Languages: English
• ISSNs: 2047-2404

Abstract

Abstract: Aims: We sought to identify metabolic pathways associated with right ventricular (RV) adaptation to pulmonary hypertension (PH). We evaluated candidate metabolites, previously associated with survival in pulmonary arterial hypertension, and used automated image segmentation and parametric mapping to model their relationship to adverse patterns of remodelling and wall stress. Methods and results: In 312 PH subjects (47.1% female, mean age 60.8 ± 15.9 years), of which 182 (50.5% female, mean age 58.6 ± 16.8 years) had metabolomics, we modelled the relationship between the RV phenotype, haemodynamic state, and metabolite levels. Atlas-based segmentation and co-registration of cardiac magnetic resonance imaging was used to create a quantitative 3D model of RV geometry and function—including maps of regional wall stress. Increasing mean pulmonary artery pressure was associated with hypertrophy of the basal free wall ( β = 0.29) and reduced relative wall thickness ( β = −0.38), indicative of eccentric remodelling. Wall stress was an independent predictor of all-cause mortality (hazard ratio = 1.27, P = 0.04). Six metabolites were significantly associated with elevated wall stress ( β = 0.28–0.34) including increased levels of tRNA-specific modified nucleosides and fatty acid acylcarnitines, and decreased levels ( β = −0.40) of sulfated androgen. Conclusion: Using computational image phenotyping, we identify metabolic profiles, reporting on energy metabolism and cellular stress-response, which are associated with adaptive RV mechanisms to PH.