New Diagnostic Tests Improve Care for Heart Failure Patients

For the first time, researchers have developed tests that could improve treatment for heart failure patients by diagnosing the condition with greater accuracy, as well as by detecting the onset of congestive heart failure earlier.

Heart failure is a leading cause of hospitalization for people older than age 65 in developed “Western” countries. At present, the main blood tests used to aid in the diagnosis of heart failure are those for B-type natriuretic peptide (BNP) 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, MD, PhD, of Heidelberg University Hospital, the researchers began by identifying 92 metabolites (metabolic byproducts) that changed significantly in heart failure patients compared with healthy individuals. They chose 3 of these metabolites, which belong to the lipid classes of sphingomyelins, triglycerides, and phosphatidylcholines, for their cardiac lipid panel (CLP).

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 misidentified as 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% while NT-proBNP by itself has a specificity of only 88.1%.

“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 Dr. Katus, “A more accurate diagnosis of patients […] may accelerate adequate pharmacological or behavioral treatments for the reduction of mortality and morbidity.”

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 a second paper, a group of researchers led by Alexandre Mebazaa, MD, of Université Paris Diderot showed 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 determine if 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 increased venous pressure that signals the onset of congestion.

Both studies, by Mueller-Hennessen M et al and by Arrigo M et al, were published January 6, 2017, in the Cardiovascular Disease special issue of the journal Clinical Chemistry.