Charlie Hotel Foxtrot: New Maps For Complex Diseases
On a course from Seattle to San Diego, an airline pilot at 32,000 feet mean sea level essentially considers California to exist only in two parts – Oakland Center and Los Angeles Center - as split up by the Federal Aviation Administration (FAA) into northern and southern sectors respectively (see map). At that altitude the grape vines of Napa Valley and The Grapevine along the I5 south of San Joaquin Valley need not be distinguished. However, for those of us hanging out only a few feet above ground level who have traveled through the many separate and uniquely scenic regions of the third largest state by land area in the USA, it is clear that this simple division doesn’t come close to characterizing California. Unfortunately, our maps and categorizations of human disease aren’t much different the FAA’s sector chart – remarkably simplified.
Recently on hospital rounds as an intern presented her H&P for a newly admitted patient I was reminded of our limitations especially as our conversation pivoted from antibiotic choice in community acquired pneumonia to fully optimizing this patient’s congestive heart failure. Right now we primarily base our discussions of heart failure around the overall function of the left ventricle as defined by left ventricular ejection fraction (LVEF). As such, patients are designated as having heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF). While this either-or dichotomy, after accounting for the acute or chronic nature of the disease, facilitates billing, it does little to facilitate our better understanding of the actual disease process or specifically tailoring our therapeutic regimens for each patient. I recalled hearing Dr. Susan Desmond-Hellmann, then Chancellor of the University of California, San Francisco, in 2013 at the Future of Genomic Medicine meeting lament about our poor classifications of diabetes mellitus into just a handful of categories (type 1, type 2, MODY etc.) when the “types” are likely to be in the hundreds if not greater. As co-chairperson for a committee organized by The National Academies her challenge was formalized in Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease.
This rings particularly true for heart failure where the taxonomy of disease remains as limited as the success of our treatments. Efforts to move beyond definitions solely determined by LVEF that may include genetics, circulating biomarkers, and physiologic biometrics are poised to improve patient outcomes and identify novel treatments.
Through efforts like the All of Us Research Program the individual layers of complex data from our patients in their epigenome, microbiome, metabolome, transcriptome and beyond are to be incorporated into “Knowledge Networks” to drive the discoveries necessary in creating this enhanced taxonomy. Truly a more detailed map would allow us to “pilot alternate routes” in this area of frequent turbulence and instability and fully realize a precision-guided approach to heart failure treatment.
Evan Muse, MD, PhD, MCTI
Assistant Professor, Scripps Translational Science Institute, La Jolla, Calif.
Evan Muse is an Assistant Professor at the Scripps Translational Science Institute and Cardiologist at The Scripps Clinic in La Jolla, California. His research mines the transition zone of digital medicine, genomics and atherosclerosis. Join him on Twitter @EvanMuse