- Natriuretic peptides are important biomarkers for the diagnosis, prognosis and management of heart failure (HF), but they have limitations
- Promising, alternate-pathway novel biomarkers are emerging that should be tested further
- By exploiting new pathophysiologic pathways, future HF care may use multibiomarker panels
- Personalized care and improved HF management are likely outcomes of integrating use of novel biomarkers with traditional clinical HF variables
Natriuretic peptides (NP) are highly valued biomarkers that have helped advance understanding and improve care of heart failure (HF) patients. But these markers have limits. For example, obesity and renal disease alter NP levels, reducing NP’s clinical utility for diagnosing HF.
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Beyond Natriuretic Peptides
A team from Massachusetts General Hospital is working to change this. In a biomarker review article published in Clinical Chemistry, researchers look to expanded research and validation trials of novel biomarkers to improve HF care and outcomes.
“Several novel HF biomarkers have shown promise but have substantial expectations to meet before being used clinically,” says Nasrien E. Ibrahim, MD, cardiologist in the Advanced Heart Failure and Transplant Section within the Division of Cardiology at the Massachusetts General Hospital. “Nonetheless, it is reasonable to expect the future lies in the application of multibiomarker panels for the improvement in management of HF and the personalization of care.”
Evaluating Candidate Biomarker Usefulness
The researchers propose a five-criteria test to guide biomarker development:
- Methods of judging biomarkers must be thorough
- Assays used must be uniformly robust, broadly available, easy to interpret and affordable
- Pathophysiologic pathway and therapeutic target should be identified in the research rationale
- Knowledge generated by a new agent should extend beyond what is already achievable
- Clinical judgment for improving HF management must be enhanced
They stratify candidates by seven major pathophysiologic pathways proposed by Braunwald et al.:
- Myocardial stretch/stress
- Cardiac extracellular matrix remodeling
- Cardiomyocyte injury/death
- Oxidative stress
- Neurohumoral activation
- Renal dysfunction
Novel Biomarker Highlights
Several of the most promising new HF biomarkers are sST2 protein in the myocardial stretch/stress pathway and galectin-3 protein in the extracellular matrix remodeling pathway. Importantly, unlike NPs, sST2 concentrations are not affected by age, obesity, atrial fibrillation or renal function.
In the myocyte injury pathway, the highly-sensitivity biomarker troponin is becoming more widely used. It is especially useful for prognosis of adverse outcomes in HF patients, to predict left ventricular remodeling and to enhance NP prognostication.
In the renal dysfunction pathway, the biomarker cystatin-C has proven to be valuable in prognostication in HF with data indicating it may be a biomarker for inflammation and underlying heart disease.
The researchers argue testing these and other promising emerging biomarkers should be prioritized so their role in clinical practice can be determined.