Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy
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 dete...
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MDPI AG
2021
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oai:doaj.org-article:a9ba77202bd64ddd8d0b7f6a3dbc9ef42021-11-25T17:09:41ZDistinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy10.3390/cells101129502073-4409https://doaj.org/article/a9ba77202bd64ddd8d0b7f6a3dbc9ef42021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2950https://doaj.org/toc/2073-4409Hypertrophic 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 (<i>n</i> = 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.Maike SchuldtBeau van DrielSila AlgülRahana Y. ParbhudayalDaniela Q. C. M. Barge-SchaapveldAhmet GüçlüMark JansenMichelle MichelsAnnette F. BaasMark A. van de WielMax NieuwdorpEvgeni LevinTjeerd GermansJudith J. M. JansJolanda van der VeldenMDPI AGarticlemetabolomicshypertrophic cardiomyopathydisease signaturedisease stageserumbiomarkerBiology (General)QH301-705.5ENCells, Vol 10, Iss 2950, p 2950 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
metabolomics hypertrophic cardiomyopathy disease signature disease stage serum biomarker Biology (General) QH301-705.5 |
| spellingShingle |
metabolomics hypertrophic cardiomyopathy disease signature disease stage serum biomarker Biology (General) QH301-705.5 Maike Schuldt Beau van Driel Sila Algül Rahana Y. Parbhudayal Daniela Q. C. M. Barge-Schaapveld Ahmet Güçlü Mark Jansen Michelle Michels Annette F. Baas Mark A. van de Wiel Max Nieuwdorp Evgeni Levin Tjeerd Germans Judith J. M. Jans Jolanda van der Velden Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
| description |
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 (<i>n</i> = 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. |
| format |
article |
| author |
Maike Schuldt Beau van Driel Sila Algül Rahana Y. Parbhudayal Daniela Q. C. M. Barge-Schaapveld Ahmet Güçlü Mark Jansen Michelle Michels Annette F. Baas Mark A. van de Wiel Max Nieuwdorp Evgeni Levin Tjeerd Germans Judith J. M. Jans Jolanda van der Velden |
| author_facet |
Maike Schuldt Beau van Driel Sila Algül Rahana Y. Parbhudayal Daniela Q. C. M. Barge-Schaapveld Ahmet Güçlü Mark Jansen Michelle Michels Annette F. Baas Mark A. van de Wiel Max Nieuwdorp Evgeni Levin Tjeerd Germans Judith J. M. Jans Jolanda van der Velden |
| author_sort |
Maike Schuldt |
| title |
Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
| title_short |
Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
| title_full |
Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
| title_fullStr |
Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
| title_full_unstemmed |
Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
| title_sort |
distinct metabolomic signatures in preclinical and obstructive hypertrophic cardiomyopathy |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/a9ba77202bd64ddd8d0b7f6a3dbc9ef4 |
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