Key result
Untargeted metabolomics identifies 30 serum metabolites discriminating asymptomatic HCM carriers, symptomatic HOCM patients, and controls.
Why the study?
HCM risk prediction is poor due to incomplete penetrance and unclear genotype-phenotype correlations, prompting evaluation of whether disturbed myocardial energetics are reflected in the serum metabolome.
Does serum metabolomic profiling identify distinct signatures that discriminate between asymptomatic HCM gene carriers, symptomatic HOCM patients, and healthy controls?
Observational (n=54)
Does serum metabolomic profiling identify distinct signatures that discriminate between asymptomatic HCM gene carriers, symptomatic HOCM patients, and healthy controls?
Serum metabolomic profiling identifies distinct metabolic signatures that can discriminate between preclinical HCM carriers, symptomatic HOCM patients, and healthy controls, potentially aiding in risk stratification.
Metabolomic signatures may aid preclinical HCM detection; hypothesis-generating and require prospective validation before clinical adoption.
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.
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Schuldt et al. (2021) conducted an observational in Hypertrophic Cardiomyopathy (HCM) (n=54). Untargeted metabolomics vs. Healthy controls was evaluated on Identification of biomarker panels discriminating the groups. Untargeted metabolomics identified panels of 30 serum metabolites that successfully discriminated asymptomatic HCM gene variant carriers, symptomatic HOCM patients, and healthy controls.
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