Dataset Information

Non-targeted metabolomics identify polyamine metabolite acisoga as novel biomarker for reduced left ventricular function.

ABSTRACT:

Aims

Chronic heart failure with reduced ejection fraction remains a major health issue. To date, no reliable biomarker is available to predict reduced left ventricular ejection fraction (LV-EF). We aimed to identify novel circulating biomarkers for reduced left ventricular function using untargeted serum metabolomics in two independent patient cohorts.

Methods and results

Echocardiography and non-targeted serum metabolomics were conducted in two patient cohorts with varying left ventricular function: (1) 25 patients with type 2 diabetes with established cardiovascular disease or high cardiovascular risk (LV-EF range 20-66%) (discovery cohort) and (2) 37 patients hospitalized for myocardial infarction (LV-EF range 25-60%) (validation cohort). In the discovery cohort, untargeted metabolomics revealed seven metabolites performing better than N-terminal pro-B-type natriuretic peptide in the prediction of impaired left ventricular function shown by LV-EF. For only one of the metabolites, acisoga, the predictive value for LV-EF could be confirmed in the validation cohort (r = -0.37, P = 0.02). In the discovery cohort, acisoga did not only correlate with LV-EF (r = -60, P = 0.0016), but also with global circumferential strain (r = 0.67, P = 0.0003) and global longitudinal strain (r = 0.68, P = 0.0002). Similar results could be detected in the discovery cohort in a 6 month follow-up proofing stability of these results over time. With an area under the curve of 0.86 in the receiver operating characteristic analysis, acisoga discriminated between patients with normal EF and LV-EF < 40%. Multivariate analysis exposed acisoga as independent marker for impairment of LV-EF (Beta = -0.71, P = 0.004).

Conclusions

We found the polyamine metabolite acisoga to be elevated in patients with impaired LV-EF in two independent cohorts. Our analyses suggest that acisoga may be a valuable biomarker to detect patients with heart failure with reduced ejection fraction.

SUBMITTER: Puetz A

PROVIDER: S-EPMC8788009 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Non-targeted metabolomics identify polyamine metabolite acisoga as novel biomarker for reduced left ventricular function.

Puetz Andreas A Artati Anna A Adamski Jerzy J Schuett Katharina K Romeo Francesco F Stoehr Robert R Marx Nikolaus N Federici Massimo M Lehrke Michael M Kappel Ben A BA

ESC heart failure 20211122 1

<h4>Aims</h4>Chronic heart failure with reduced ejection fraction remains a major health issue. To date, no reliable biomarker is available to predict reduced left ventricular ejection fraction (LV-EF). We aimed to identify novel circulating biomarkers for reduced left ventricular function using untargeted serum metabolomics in two independent patient cohorts.<h4>Methods and results</h4>Echocardiography and non-targeted serum metabolomics were conducted in two patient cohorts with varying left v ...[more]

PMID: 34811951

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Project description:Background Diastolic dysfunction is one important causal factor for heart failure with preserved ejection fraction, yet the metabolic signature associated with this subclinical phenotype remains unknown. Methods and Results Ultra-high-performance liquid chromatography-tandem mass spectroscopy was used to conduct untargeted metabolomic analysis of fasting serum samples in 1050 white and black participants of the BHS (Bogalusa Heart Study). After quality control, 1202 metabolites were individually tested for association with 5 echocardiographic measures of left ventricular diastolic function using multivariable-adjusted linear regression. Measures of left ventricular diastolic function included the ratio of peak early filling velocity to peak late filling velocity, ratio of peak early filling velocity to mitral annular velocity, deceleration time, isovolumic relaxation time, and left atrial maximum volume index (LAVI). Analyses adjusted for multiple cardiovascular disease risk factors and used Bonferroni-corrected alpha thresholds. Eight metabolites robustly associated with left ventricular diastolic function in the overall population and demonstrated consistent associations in white and black study participants. N-formylmethionine (B=0.05; P=1.50×10-7); 1-methylhistidine (B=0.05; P=1.60×10-7); formiminoglutamate (B=0.07; P=5.60×10-7); N2, N5-diacetylornithine (B=0.05; P=1.30×10-7); N-trimethyl 5-aminovalerate (B=0.04; P=5.10×10-6); 5-methylthioadenosine (B=0.04; P=1.40×10-5); and methionine sulfoxide (B=0.04; P=3.80×10-6) were significantly associated with the natural log of the ratio of peak early filling velocity to mitral annular velocity. Butyrylcarnitine (B=3.18; P=2.10×10-6) was significantly associated with isovolumic relaxation time. Conclusions The current study identified novel findings of metabolite associations with left ventricular diastolic function, suggesting that the serum metabolome, and its underlying biological pathways, may be implicated in heart failure with preserved ejection fraction pathogenesis.

Project description:ObjectivesThe aim of this study was to investigate the prognostic value of stress cardiac magnetic resonance imaging (CMR) in patients with reduced left ventricular (LV) systolic function.BackgroundPatients with ischemic cardiomyopathy are at risk from both myocardial ischemia and heart failure. Invasive testing is often used as the first-line investigation, and there is limited evidence as to whether stress testing can effectively provide risk stratification.MethodsIn this substudy of a multicenter registry from 13 U.S. centers, patients with reduced LV ejection fraction (<50%), referred for stress CMR for suspected myocardial ischemia, were included. The primary outcome was cardiovascular death or nonfatal myocardial infarction. The secondary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, hospitalization for unstable angina or congestive heart failure, and unplanned late coronary artery bypass graft surgery.ResultsAmong 582 patients (mean age 62 ± 12 years, 34% women), 40% had a history of congestive heart failure, and the median LV ejection fraction was 39% (interquartile range: 28% to 45%). At median follow-up of 5.0 years, 97 patients had experienced the primary outcome, and 182 patients had experienced the secondary outcome. Patients with no CMR evidence of ischemia or late gadolinium enhancement (LGE) experienced an annual primary outcome event rate of 1.1%. The presence of ischemia, LGE, or both was associated with higher event rates. In a multivariate model adjusted for clinical covariates, ischemia and LGE were independent predictors of the primary (hazard ratio [HR]: 2.63; 95% confidence interval [CI]: 1.68 to 4.14; p < 0.001; and HR: 1.86; 95% CI: 1.05 to 3.29; p = 0.03) and secondary (HR: 2.14; 95% CI: 1.55 to 2.95; p < 0.001; and HR 1.70; 95% CI: 1.16 to 2.49; p = 0.007) outcomes. The addition of ischemia and LGE led to improved model discrimination for the primary outcome (change in C statistic from 0.715 to 0.765; p = 0.02). The presence and extent of ischemia were associated with higher rates of use of downstream coronary angiography, revascularization, and cost of care spent on ischemia testing.ConclusionsStress CMR was effective in risk-stratifying patients with reduced LV ejection fractions. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891).

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Dataset Information

Non-targeted metabolomics identify polyamine metabolite acisoga as novel biomarker for reduced left ventricular function.

Aims

Methods and results

Conclusions

Publications

Non-targeted metabolomics identify polyamine metabolite acisoga as novel biomarker for reduced left ventricular function.

Similar Datasets

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