microRNAs Shown as Biomarkers for Heart Failure Prognosis

Rosetta Genomics, Ltd., developer and provider of microRNA-based molecular diagnostics, announced the results which came from a joint study by researchers at Rosetta Genomics and the Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center in Haifa, Israel.

The study, titled "Serum Levels of microRNAs in Patients with Heart Failure," was published online on November 25, 2011, and is set to appear in the December 2011 print edition of the European Journal of Heart Failure.

In this study, researchers characterized the levels of microRNAs in the sera of chronic systolic HF patients versus controls, and assessed the possible correlation between elevation in the levels of specific microRNAs and clinical prognostic parameters in HF patients.

The levels of 186 microRNAs were measured in the sera of 30 stable chronic systolic HF patients and 30 controls using qRT-PCR. The differences in microRNA levels between the two groups were characterized and a score, based on the levels of four specific microRNAs with the most significant increase in the HF group (miR-423-5p, miR-320a, miR-22, and miR-92b), was defined.

Key Findings
• The score, based on serum levels of miR-423-5p, miR-320a, miR-22 and miR-92b identified systolic HF patients and showed correlation with important clinical prognostic parameters.
• The score was able to discriminate HF patients from controls with sensitivity and specificity of 90%.
• In the HF group, there was a significant association between the score and important clinical prognostic parameters; high microRNA scores were correlated with elevated serum brain natriuretic peptide (BNP) levels (p=0.002), wide QRS (p=0.009), increased end diastolic diameter (p=0.03) and increased left atrial diameter (p=0.01).

Commenting on the clinical utility for such a potential microRNA as prognostic markers, Offer Amir, M.D., Lady Davis Carmel Medical Center & Heart Failure Clinic and the lead author of the study, said, "Diagnosis and risk stratification of patients with HF remain a challenge. The results of this study demonstrated that these four specific microRNAs may indeed serve as biomarkers for the diagnosis and risk stratification of HF patients. Early identification of patients at higher risk for severe HF could lead to earlier intervention that would potentially improve outcomes.

"Previous studies that demonstrated altered levels of microRNAs in the circulation of cardiac patients, combined with an increasing understanding of their role in myocardial injury and remodeling, have led to an appreciation for the potential use of microRNAs as biomarkers of myocardial injury and HF. The results of our current study are consistent with this notion, showing that increased levels of specific microRNAs in the circulation of HF patients may be used as markers for HF diagnosis. With regard to HF severity, our understanding of the clinical impact of microRNAs in HF patients is still in its infancy. However, studies showing correlations between circulating microRNAs and clinical parameters, similar to those reported in our work, are beginning to emerge," added Dr. Amir.

"We are especially pleased with these positive data demonstrating the clinical utility of our serum-based microRNA diagnostic to identify HF patients," said Kenneth A. Berlin, President and Chief Executive Officer of Rosetta Genomics. "With nearly 4.4 million patients diagnosed with HF in the US, there is a very large market opportunity for a simple, blood-based, prognostic test for HF especially given the complexity, prevalence and expense of treating this disease. We have an excellent patent position on this initial microRNA signature and look forward to continuing to advance the development of this potentially powerful, blood-based microRNA diagnostic test for stratification of patients with HF and hope to have it ready to launch by the end of 2013."
About Heart Failure

Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorders that impair the ability of the ventricles to fill with or eject blood. It is the most prevalent disease in the Western world and is the only cardiovascular disease whose prevalence continues to rise. It is estimated that 5 million Americans have HF and approximately 500,000 new cases are diagnosed each year. In addition to its high prevalence, heart failure is also the most expensive disease to treat in Western countries. American Heart Association estimates from 2004 showed that more than $26 billion per year was spent on treating patients with heart failure.