Researchers at Vanderbilt University Medical Center have received a four-year, $6.2-million grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health to develop a novel panel of biomarkers to improve the diagnosis of acute heart failure (AHF).
Accurate diagnosis of AHF can be difficult because symptoms such as shortness of breath (dyspnea) and congestion (edema) are non-specific and may be caused by other conditions. The challenges to diagnosis may delay appropriate therapies, resulting in longer hospitalizations and worse outcomes.
Each year in the United States approximately 1 million people are hospitalized for AHF at a cost exceeding $40 billion. Roughly 50% of patients die within five years of diagnosis.
The current approach to diagnosing AHF relies on a combination of symptoms, signs, chest X-ray findings, and levels of natriuretic peptides, hormones made by the heart in response to cardiovascular stress. Incorporation of additional biomarkers, such as proteins circulating in blood, may help improve diagnostic accuracy for AHF.
“Accurate diagnosis is fundamental to not only inform delivery of appropriate therapies but also withdrawal of potential deleterious or unnecessary therapies,” said Deepak Gupta, MD, MSCI, assistant professor of Medicine and the study’s co-principal investigator with Sean Collins, MD, MSci, professor of Emergency Medicine.
“In this study, our collaborative team will discover, derive, and validate a novel multi-biomarker approach to diagnosing acute heart failure,” Gupta said.
Gupta directs the Vanderbilt Translational and Clinical Cardiovascular Research Center. Collins is co-director of the Vanderbilt Coordinating Center and director of the VUMC Center for Emergency Care Research and Innovation.
As a proof of concept, VUMC investigators previously utilized techniques known as plasma proteomics to identify a panel of 21 biomarkers that potentially will improve the accuracy of diagnosing AHF beyond current practice.
The newly funded research will build on a prior emergency department-based study, and will assay 925 proteins from the plasma samples of 989 patients to refine the multi-marker panel of 21 biomarkers.
This multi-marker panel will then be tested in 1,000 emergency department patients with acute dyspnea who participated in the Emergency Medicine Research and Outcomes Consortium (EMROC) multicenter study.
In the third step, results from the EMROC cohort will be independently validated in a new sample of 1,000 patients with acute dyspnea who will be recruited from four emergency departments in the EMROC network, including VUMC, the Nashville VA Medical Center and two others in Detroit, Michigan.
“Given the frequency of inaccurate diagnosis and its adverse consequences, we will address a significant unmet need by improving diagnostic accuracy for acute heart failure,” said Collins, co-director of the national EMROC network.
The multidisciplinary team includes VUMC faculty Lynne Stevenson, MD, the Lisa M. Jacobson Professor of Cardiovascular Medicine and professor of Medicine; Jin Ho Han, MD, MS, associate professor of Emergency Medicine; and Frank Harrell, PhD, professor of Biostatistics.
Others include Phillip Levy, MD, MPH, assistant vice president for Translational Sciences and Clinical Research Innovation at Wayne State University in Detroit; and Thomas Wang, MD, professor and chair of Internal Medicine at UT Southwestern Medical Center in Dallas.
