Researchers have found that left ventricular assist devices and heart transplantation might reduce endotoxemia, inflammation and oxidative stress and improve gut dysbiosis often seen in patients with advanced heart failure. Additionally, intestinal overgrowth of pathogenic bacteria and reduced microbial diversity may promote translocation of pro-inflammatory bacterial products into the systemic circulation, triggering or further exacerbating the heart failure syndrome itself.
Melana Yuzefpolskaya, MD, assistant professor of medicine and associate director of the Mechanical Circulatory Support Program at New York Presbyterian Hospital and Columbia University, presented these findings during an abstract poster session on Sunday.
“Our data demonstrated that patients with advanced heart failure present with an inflammatory phenotype concurrent with elevated markers of congestion, oxidative stress and gut dysbiosis,” Yuzefpolskaya said. “Our current treatment options — LVAD and heart transplantation — appear to favorably influence the inflammatory and microbial milieu.”
The study was part of a collaboration with Paolo C. Colombo, MD, Sudhir Choudhrie Associate Professor of Cardiology and director of the Center for Advanced Cardiac Care at New York Presbyterian Hospital/Columbia University, and Ryan Demmer, PhD, MPH, FAHA, associate professor of epidemiology and community health at the University of Minnesota School of Public Health in Minneapolis.
The study included 169 patients — 65 patients had NYHA class I-III heart failure, 28 had Class IV heart failure, 28 had an LVAD for a mean duration of 1.7 years and 48 were heart transplant recipients for a mean of 6.9 years prior to study entry.
The investigators assessed serum markers of endotoxemia (lipopolysaccharide), inflammation (adiponectin, CRP and endothelin-1), interleukin-6 (IL-6), sCD14, tumor necrosis factor-alpha (TNF-alpha) and oxidative stress (isoprostane) in venous blood. Stool samples were collected from hospitalized patients and home sample kits were given to ambulatory patients. Stool samples were analyzed for bacterial DNA to assess the number of taxa between patients and the microbial community similarities between patients.
“When heart failure becomes advanced, decreased blood flow and venous congestion contribute to a shift in the microbial community, releasing endotoxins into the systemic circulation triggering an inflammatory response,” Yuzefpolskaya said. “What we did not know was the effect of LVAD and heart transplantation on the degree of potential gut dysbiosis and associated levels of endotoxemia, inflammation and oxidative stress among these patients.”
Advanced heart failure patients (NYHA Class IV) showed the highest levels of endotoxemia, inflammation and oxidative stress, she said. Individuals with LVADs and heart transplantation showed significantly lower levels of serum biomarkers that were similar to the levels seen in patients with more stable disease (NYHA Class I-III). Gut dysbiosis also improved after cardiac replacement therapy (LVAD and heart transplantation).
Yuzefpolskaya noted that the severe heart failure group, who were the sickest in the study, had a unique set of organisms that were not present in the other patients and a trend toward less diversity in the taxa found in the gut microbiota.
“These findings open the door to further studies that might include dietary modulation, pre/probiotics, antibiotic therapy and possibly fecal transplantation as ways to favorably alter the gut microbiome and affect heart failure outcomes,” Yuzefpolskaya said.