A new blood test identifies the sickest heart failure patients better than tests now used in emergency departments, researchers reported at the American Heart Association's Scientific Sessions 2008. Results of the Mid-Regional pro-Adrenomedullin (proADM) versus BNP and NTproBNP as Prognosticator in Heart Failure Patients: Results of the BACH Multinational Trial were presented as a late-breaking clinical trial.
"The ability to predict the sickest patients is of paramount importance to emergency physicians and critical care cardiologists," said Stefan D. Anker, M.D., Ph.D., co-principal investigator of the study and professor of cardiology and cachexia (malnutrition and wasting in the context of disease) research at Campus Virchow-Klinkum (Virchow Hospital) of the Charite Medical School, Berlin, Germany.
"These patients deserve the most aggressive interventions and warrant close surveillance. Biomarkers that can help the physician identify these patients can improve the patients' quality of life and help direct resources and hospital therapies where they are needed the most," he said.
In the trial, researchers followed 1,641 patients from 15 investigational centers around the globe, including eight from the United States, who experienced difficulty breathing upon arrival at the emergency department.
BACH is the first randomized comparison of two tests considered the gold standard for evaluating possible heart failure patients in the emergency setting versus the new test, approved for use in the European Union as of Oct. 1. Anker says the appropriate U.S. Food & Drug Administration (FDA) applications will be submitted early in 2009.
The researchers found that the MR-proADM test was prognostically accurate 73.1 percent of the time, making it superior to both the B-Natriuretic peptide (BNP) test (60.6 percent) and the NTproBNP test (63 percent), which measures a biological fragment associated with BNP.
Shortness of breath is a common symptom of patients arriving at the emergency room, but it can have many causes including asthma or other lung problems, respiratory infections, heart failure and many other conditions, he explained. Heart failure is the cluster of symptoms - including shortness of breath - that reflects the heart's inability to pump enough blood to oxygenate all the body's tissues adequately.
"A significant percentage of emergency room patients have heart failure and the BNP and NTproBNP tests have long been used to identify heart failure patients in the emergency setting," said Alan Maisel, M.D., the study's principal investigator and a long-standing BNP researcher at the University of California, San Diego Medical Center. "Both tests measure elevations in proteins released by the distressed heart as it tries to keep the blood's salt and water balance stable."
MR-proADM indirectly measures a hormone called adrenomedullin, which affects blood vessel dilation and is implicated in many cardiac and infectious diseases. Because the hormone, ADM, is very unstable, it was necessary to develop an indirect test for it, Anker said.
Previous retrospective studies by the same research group suggested that the MR-proADM test is useful in assessing disease severity and predicting prognosis in patients with heart failure. The BACH study validated these results and found the MR-proADM to be superior to anything previously available at correctly identifying the sickest heart failure patients, Anker said.
"Better prognostic markers help patients in multiple ways," he said. "First, they identify those patients who should 'move to the front of the line' with respect to immediate therapeutic interventions. In the emergency setting, untreated acute heart failure worsens rapidly and can lead to respiratory compromise, intubation with mechanical ventilation and even death. Second, these markers can help determine which patient might need longer courses of in-patient therapy to stabilize. Finally, the astute clinician will follow patients with poor prognostic markers more closely after discharge to prevent relapse and readmission. All in all, a superior risk stratification is a safer risk stratification and leads to better patient management."
Coauthors are: W. Frank Peacock, M.D.; Christian Mueller, M.D.; Richard Nowak, M.D.; Inder Anand, M.D.; Robert Christenson, Ph.D.; Lori B. Daniels, M.D.; Salvatore Di Somma, M.D.; Gerasimos Filippatos, M.D.; Christopher Hogan, M.D.; Martin Moeckel, M.D.; Sean-Xavier Neath, M.D., Ph.D.; Leong Ng, M.D.; Piotr Ponikowski, M.D., Ph.D.; A. Mark Richards, M.D., Ph.D.; Alan H.B. Wu, Ph.D.; Judd Landsberg, Ph.D.; and Paul Clopton, M.S. Individual author disclosures can be found on the abstract.
The study was funded by BRAHMS AG.