January 26, 2017 — For the first time, researchers have developed tests that could improve treatment for heart failure patients by diagnosing the condition with greater accuracy and detecting the onset of congestive heart failure earlier. The findings were published in the Cardiovascular Disease issue of Clinical Chemistry, the journal of the American Association for Clinical Chemistry (AACC).
Heart failure occurs when the heart is weakened and can no longer pump blood adequately. There are numerous conditions that can damage the heart muscle and lead to heart failure, from coronary artery disease to diabetes to drug abuse, and in the United States, it is the leading cause of hospitalization for people older than age 65. At present, the main blood tests used to aid in the diagnosis of heart failure are those for B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide (NT-proBNP). However, natriuretic peptide tests have a high false-positive rate and a limited ability to detect the early and asymptomatic stages of the disease.
With the goal of overcoming the drawbacks of current heart failure tests, a group of researchers developed a diagnostic panel that provides a more comprehensive representation of the heart’s functioning by measuring multiple biological molecules. Led by Hugo A. Katus, M.D., Ph.D., of Heidelberg University Hospital in Heidelberg, Germany, the researchers began by identifying 92 metabolites — byproducts of the body’s metabolism — that changed significantly in heart failure patients compared with healthy individuals. They chose three of these metabolites that belong to the lipid classes of sphingomyelins, triglycerides and phosphatidylcholines for their cardiac lipid panel (CLP).1
In a second confirmation study, the researchers then tested the ability of CLP combined with NT-proBNP measurements to diagnose heart failure in 649 individuals who either had the condition, were healthy or had pulmonary diseases (which can often be confused with heart failure). CLP plus NT-proBNP diagnosed heart failure with much greater certainty than NT-proBNP alone, even in the early and asymptomatic stages, demonstrating a high specificity of 97.6 percent, while NT-proBNP by itself only has a specificity of 88.1 percent.
“A low false-positive rate is particularly important in the outpatient setting and may prevent patients from unnecessary diagnostic workup and treatment, which in turn will save resources and avoid potential side-effects,” said Katus. “A more accurate diagnosis of patients with early and intermediate […] and mild or asymptomatic systolic dysfunction as observed with the novel panel compared to NT-proBNP alone may accelerate adequate pharmacological or behavioral treatments for the reduction of mortality and morbidity in these patients.”
Heart failure can also progress to congestive heart failure, which occurs when fluid builds up in the limbs, lungs and/or other organs as an indirect result of the heart’s weakened pumping. Systemic congestion is a major determinant of organ dysfunction and death in chronic heart failure patients. Currently, there is no reliable test that can diagnose congestion in its pre-symptomatic stages, which is needed so that healthcare providers can start or adjust decongestive therapy for patients before the condition worsens.
In this paper2, a group of researchers led by Alexandre Mebazaa, M.D., of Université Paris Diderot, show that a test for the protein-soluble CD146 (sCD146) could potentially detect congestion early. One of the initial signs of congestion is a subclinical increase of venous pressures. To demonstrate that sCD146 is released as a response to this, the researchers compressed the dominant arm of 44 stable chronic heart failure patients and measured sCD146 levels in both arms at the start time and after 90 minutes. In the compressed arm, sCD146 levels increased significantly by 60 µg/L compared with a small 16 µg/L increase in the control arm. These results indicate that, if validated in larger studies, sCD146 could serve as a marker of the increased venous pressure that signals the onset of congestion.
For more information: www.clinchem.aaccjnls.org
1. Mueller-Hennessen, M., Dungen, H-D., Lutz, M., Trippel, T.D., et al. "A Novel Lipid Biomarker Panel for the Detection of Heart Failure with Reduced Ejection Fraction," Clinical Chemistry. Published online Dec. 30, 2016. DOI: 10.1373/clinchem.2016.257279
2. Arrigo, M., Truong, Q.A., Onat, D., Szymonifka, J., et al. "Soluble CD146 Is a Novel Marker of Systemic Congestion in Heart Failure Patients: An Experimental Mechanistic and Transcardiac Clinical Study," Clinical Chemistry. Published online Dec. 30, 2016. DOI: 10.1373/clinchem.2016.260471