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Metabolite panel shows strong prognostic value for patients with HF
Results from a mass spectrometry-based profiling of plasma metabolites indicated strong prognostic value for estimating metabolic disturbances in patients with HF, according to new research.
Although the pathophysiology and hemodynamics of HF are much better understood than they once were, rates of HF-related hospitalization and mortality remain high, and new interventional measures are needed “to curb maladaptive molecular processes and avoid the progression of HF to advanced stages,” the researchers wrote.
They tested the applicability and significance of plasma metabolic analysis in the diagnosis and prognosis of HF.
The researchers profiled a panel of plasma metabolites, including histidine, phenylalanine, phosphatidylcholine C34:4 and spermidine, in 515 participants. The analysis was conducted in two phases: The discovery phase included 183 patients with HF and 51 healthy controls, and the validation phase included 218 patients with stage C HF and 63 healthy controls.
An independent group of 32 patients with stage C HF who recovered to NYHA class I at 6 months and 12 months was profiled as the recovery group. The values of the panel improved significantly at 6 months and 12 months in this group, Mei-Ling Cheng, PhD, and colleagues found.
Strong prognostic value
To evaluate the prognostic values of the metabolites, Cheng, from the Healthy Aging Research Center, Chang Gung University, Tao-Yuan, Taiwan, and colleagues analyzed the combined endpoints of death or HF-related rehospitalization. Eighteen deaths and 29 HF-related rehospitalizations occurred during a mean follow-up of 1.3 years.
A metabolite panel consisting of the asymmetric methylarginine/arginine ratio, butyrylcarnitine, spermidine and the total amount of essential amino acids yielded significant prognostic values independent of B-type natriuretic peptide (BNP) and traditional risk factors (P < .0001), the researchers wrote.
They also found that the prognostic value of this panel was better than that of BNP, with an area under the curve of 0.85 for the panel compared with 0.74 for BNP, and of Kaplan-Meier curves categorized by BNP (log rank: 17.5 vs. 9.95). A panel value of at least 2.9 before discharge was associated with a higher rate of HF-related rehospitalization or death (P < .0001).
The validation study confirmed the findings of the discovery study, according to the researchers.
More research needed
“In the context of existing literature, this supports the concept that HF is associated with metabolic dysfunction,” Thomas J. Wang, MD, and Deepak K. Gupta, MD, wrote in a related editorial. “However, the clinical utility of metabolite profiling in HF remains uncertain, largely because discriminating symptomatic HF patients from healthy control subjects is not representative of clinical practice. Studies comparing the circulating metabolic profile of symptomatic patients with and without HF would be more informative.”
They added that because HF is a heterogeneous syndrome, “we need to parse out unique phenotypes that may respond differently to therapies or have different natural histories.”
“There is hope that metabolomic profiling, in combination with other ‘-omic’ techniques, such as genomics and proteomics, will eventually facilitate identification of these phenotypic signatures,” wrote Wang and Gupta, both from the Vanderbilt Translational and Clinical Cardiovascular Research Center and the division of cardiovascular medicine at Vanderbilt University Medical Center in Nashville, Tennessee. – by Erik Swain
Disclosures: The researchers and Gupta report no relevant financial disclosures. Wang reports being named as a co-inventor on patent applications on metabolomic and neurohormonal biomarkers of cardiometabolic disease; receiving grant or assay support from Brahms, Critical Diagnostics, Diasorin, LabCorp, Siemens and Singulex; and serving on advisory committees for Critical Diagnostics and Diasorin.