Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy

Cells

Tjeerd Germans¹  Ahmet Güçlü¹  Michelle Michels²  Daniela Q. C. M. Barge-Schaapveld³  Mark A. van de Wiel⁴  Annette F. Baas⁵  Judith J. M. Jans⁵  Mark Jansen⁵  Evgeni Levin⁶  Max Nieuwdorp⁶  Rahana Y. Parbhudayal⁷  Beau van Driel⁷  Sila Algül⁷  Maike Schuldt⁷  Jolanda van der Velden⁷ 

[1] Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands;Department of Cardiology, Thorax Center, Erasmus Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands;Department of Clinical Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands;Department of Epidemiology and Data Science, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands;Department of Genetics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands;Department of Internal and Vascular Medicine, Amsterdam UMC, Universiteit van Amsterdam, 1105 AZ Amsterdam, The Netherlands;Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands;

关键词: metabolomics;    hypertrophic cardiomyopathy;    disease signature;    disease stage;    serum;    biomarker;   

DOI  :  10.3390/cells10112950

来源: DOAJ

【 摘 要 】

Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype–phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To determine whether disturbed myocardial energetics with the potential to serve as biomarkers are also reflected in the serum metabolome, we analyzed the serum metabolome of asymptomatic carriers in comparison to healthy controls and obstructive HCM patients (HOCM). We performed non-quantitative direct-infusion high-resolution mass spectrometry-based untargeted metabolomics on serum from fasted asymptomatic gene variant carriers, symptomatic HOCM patients and healthy controls (n = 31, 14 and 9, respectively). Biomarker panels that discriminated the groups were identified by performing multivariate modeling with gradient-boosting classifiers. For all three group-wise comparisons we identified a panel of 30 serum metabolites that best discriminated the groups. These metabolite panels performed equally well as advanced cardiac imaging modalities in distinguishing the groups. Seven metabolites were found to be predictive in two different comparisons and may play an important role in defining the disease stage. This study reveals unique metabolic signatures in serum of preclinical carriers and HOCM patients that may potentially be used for HCM risk stratification and precision therapeutics.

【 授权许可】

Unknown