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Proteomics Can Detect Response to Heart Failure Treatment

Key findings

  • This retrospective study investigated whether severity-specific proteomic signatures could be isolated at separate time points and, in turn, be used to gauge the response to treatment of heart failure with reduced ejection fraction (HFrEF)
  • Improvements in cardiac functioning after left ventricular assist device implantation or angiotensin receptor/neprilysin inhibitor therapy resulted in measurable changes in proteomic signatures
  • Core sets of proteins were identified for stage C HFrEF (nine proteins) and stage D HFrEF (18 proteins)
  • A core set of five proteins was specific to HFrEF regardless of disease severity or treatment; these "core five" proteins include some previously described in heart failure, but also newer, previously unrecognized proteins
  • It may be possible to create a multi-biomarker panel that would be more useful than measuring N-terminal pro-B type natriuretic peptide alone

Proteomics, the study of all proteins in the human genome, has led to a better understanding of the progression of heart failure with reduced ejection fraction (HFrEF). Sam Michelhaugh, BA, currently a medical student at Geogetown Medical School, James L. Januzzi Jr., MD, director of the Dennis and Marilyn Barry Fellowship in Cardiology Research in the Massachusetts General Hospital Corrigan Minehan Heart Center, and colleagues recently added to the insights by showing that proteomics can be used to gauge changes in cardiac function after HFrEF treatment.

Their findings, which might lead to better detection of the disease, evaluation of treatment response and identification of drug targets, appear in Circulation: Heart Failure.

Study Details

The team measured a targeted set of 625 proteins in blood samples from two patient cohorts. The primary analysis group was 29 patients with American College of Cardiology/American Heart Association stage D HFrEF who received a left ventricular assist device (LVAD) (any of three different models). The reference group, matched on age, sex and race, was 12 patients who had stage C HFrEF treated with sacubitril/valsartan.

In both cohorts considered together, 248 proteins were extracted at baseline and 275 proteins after the intervention.

Protein Signatures

Collections of related proteins are called protein signatures. Researchers found the following proteins uniquely associated with each HFrEF stage:

Stage D

  • 71 before left ventricular assist device implantation
  • 75 afterward
  • 18 at both time points

Stage C

  • 66 before initiation of drug therapy
  • 63 afterward
  • 9 at both time points

Shared Protein Signatures

Five proteins were independently associated with both stage D and stage C at both timepoints:

  • N-terminal pro-B type natriuretic peptide (NT-proBNP), a well-established biomarker of heart failure (HF)
  • Endothelial cell-specific molecule 1, a biomarker of inflammation and endothelial dysfunction
  • Cathepsin L1 and osteopontin, which promote cardiac remodeling
  • Macrophage colony-stimulating factor 1, which helps protect cardiomyocytes and improve left ventricular function

Toward Better Clinical Decision-making

If the core set of five proteins can be validated, it may be possible to create a multi-biomarker panel that would be more useful than measuring NT-proBNP alone. It could be used to determine HF status, evaluate treatment efficacy and guide clinicians in tailoring their management of patients with HF.

Of the 18 proteins that formed the core set for stage D, eight were associated with at least moderate improvement in cardiac function after LVAD implantation. These and other study findings could help reveal the specific pathways of reverse remodeling, which could lead to new drug targets.

Learn more about the Heart Failure and Cardiac Transplant Program

Refer a patient to the Corrigan Minehan Heart Center at Mass General

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