The National Institutes of Health (NIH) has awarded a $3.8 million grant to Vanderbilt University Medical Center to study cirrhotic cardiomyopathy (CCM) in patients with decompensated cirrhosis (severe liver disease) and liver transplant recipients. VUMC will share the five-year grant with UT Southwestern Medical Center in Dallas.
CCM is a condition in which the cardiac structure and function become altered due to the effects of cirrhosis, said Manhal Izzy, MBChB, professor of Medicine, a transplant hepatologist and principal investigator for the study. Based on preliminary data, CCM can impact up to 45% of patients with advanced cirrhosis and liver transplant recipients, he said.
But scientists don’t yet understand how cirrhosis causes cirrhotic cardiomyopathy, which doubles the risk for cardiac events, according to preliminary data, Izzy said. Understanding the risk factors for heart disease in these patients is critically important, especially with heart disease being a leading cause of morbidity and mortality after liver transplant, he added.
The NIH-funded study will be the first U.S.-based prospective investigation of CCM in humans with decompensated cirrhosis, enrolling adult patients from VUMC and UT Southwestern. The study will define the natural history of the disease by serially evaluating patients throughout their pretransplant and posttransplant course, Izzy said, utilizing clinical, echocardiographic and serological assessments.
During the study, scientists will define clinical risk factors associated with CCM and its potential for reversal post-liver transplant, and they will test hypotheses to better understand the mechanism that causes it, including whether bile acids are a driver of CCM.
“By providing foundational prospective data needed to advance the field of CCM, our study will exert a powerful and enduring scientific and clinical impact,” Izzy said. “We will refine clinical risk stratification for adverse outcomes in patients with end-stage liver disease and inform clinical screening and surveillance for CCM.”
By better understanding the disease burdens and its mechanisms, scientists could develop therapies, perhaps in a future grant, Izzy said.
Co-investigators on the research at VUMC are Deepak Gupta, MD, MSCI (cardiology); Loren Lipworth, ScD (epidemiology); Robb Flynn, PhD (surgery); and Shi Huang, PhD (biostatistics).
“This grant exemplifies the collaborative environment at VUMC,” Izzy said, “which was essential for this multidisciplinary initiative where scientists in cardiology and hepatology worked closely together along with colleagues in epidemiology, surgery and biostatistics to develop this exciting study.”
The NIH grant number is R01HL181174.
