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Blunted cardiac reserve strongly predicts incident hepatorenal syndrome

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Study raises questions about role of CV dysfunction, risk of hepatorenal syndrome

Cardiovascular abnormalities develop in patients with advanced chronic liver disease to produce a hyperdynamic systemic circulation with splanchnic vasodilation, decreased systemic vascular resistance, and increased cardiac output (J Hepatol. 2018;69[4]:958-60). The term cirrhotic cardiomyopathy has also been used for the changes of systolic dysfunction with impaired cardiac contractile response to stress and altered diastolic relaxation that develops in patients with cirrhosis (J Hepatol. 2010;53[1]:179-90).

Dr. Rowen K. Zetterman

In this study by Dr. Koshy and colleagues, the inability to increase cardiac output during dobutamine stress echo (DSE) was associated with a greater subsequent risk for hepatorenal syndrome (J Hepatol. 2019;70:e56).

All patients in the study were undergoing pretransplant liver evaluation. Those who developed hepatorenal syndrome (HRS) in follow-up had a higher mean cardiac output with a reduction of the increase in cardiac output that follows dobutamine administration when compared with those who did not develop HRS. A multivariate analysis that adjusted for age, gender, MELD score, and Child-Pugh score found that “impaired contractile response was the strongest predictor of hepatorenal syndrome” as defined by a less than 22% increase in cardiac output following dobutamine. Overall, 40% of those with impaired contractile reserve developed hepatorenal syndrome, compared with 25% of those with normal contractile reserve following dobutamine (P = .006). It is of interest that cirrhotic patients with HRS at the time of initial dobutamine stress echo had a 25% higher average cardiac output than those without HRS. Patients who subsequently developed hepatorenal syndrome also had higher average cardiac output at initial evaluation than those who did not.

This study continues to raise important questions about the role of cardiovascular dysfunction and the risk of hepatorenal syndrome. Additional studies seem warranted to evaluate progression of cardiac changes and dobutamine response throughout follow-up of end-stage liver disease patients, including at the development of hepatorenal syndrome. Studies of HRS patients with specific associations such as sepsis, spontaneous bacterial peritonitis, and gastrointestinal bleeding may also provide information on the role of systolic and diastolic dysfunction during such events.

This article also draws attention to “concerns about using nonselective beta-blocker drugs in patients with cirrhosis.” Current data indicate that nonselective beta-blockers reduce all-cause mortality and the risk of first variceal hemorrhage in patients with advanced liver disease (Hepatology. 2019;69[4]:1657-75). Until we have studies that reveal a clear association between beta-blockers and development of hepatorenal syndrome, I will continue to recommend the use of beta-blockers in cirrhotic patients at risk for first variceal hemorrhage.

Rowen K. Zetterman, MD, is dean emeritus of the Creighton University School of Medicine in Omaha, Neb. He serves as the Associate Vice Chancellor for Academic Affairs and the Associate Vice Chancellor for Planning at the University of Nebraska Medical Center in Omaha. Dr. Zetterman, a gastroenterologist and hepatologist, is also a member of the editorial advisory board of Internal Medicine News.



– Patients with cirrhosis and undergoing work-up for a possible liver transplant who had low cardiac reserve had a nearly fourfold increased rate of developing hepatorenal syndrome (HRS) during an average 17 months of follow-up, compared with patients with normal cardiac reserve, in a review of 560 Australian patients assessed for a possible liver transplant.

Dr. Anoop N. Koshy, cardiologist, Austin Health, Melbourne Mitchel L. Zoler/MDedge News

Dr. Anoop N. Koshy

The findings suggest that patients with advanced liver disease should routinely undergo assessment for low cardiac reserve, Anoop N. Koshy, MBBS, said at the meeting sponsored by the European Association for the Study of the Liver.

“Low cardiac reserve may improve clinical risk prediction algorithms for hepatorenal syndrome, and identify patients who may benefit from intensified surveillance and treatment,” said Dr. Koshy, a cardiologist with Austin Health in Melbourne. “We propose that it’s not low cardiac output that leads to HRS, but an inability of patients to increase their cardiac output” in response to usual stimuli.

The findings also add to the concerns about using nonselective beta-blocker drugs in patients with cirrhosis because of the potential of these drugs to further blunt increases in cardiac output; they also suggest that noninvasive measurement of cardiac reserve could identify patients with low cardiac reserve who could benefit from closer monitoring and new approaches to treatment, he suggested. About 10%-30% of patients with cirrhosis develop HRS, and the new finding suggests a noninvasive way to identify patients with the highest risk for this complication.

The study included 560 consecutive patients with cirrhosis and end-stage liver disease who were awaiting a liver transplant at the Victoria Liver Transplant Unit in Melbourne and underwent assessment by stress echocardiography using low-dose dobutamine (10 mcg/kg per min) during 2010-2017 as part of their standard pretransplant work-up. Exclusion of patients with known cardiac disease prior to their stress echo examination or incomplete measurement left 488 patients, of whom 424 were free from HRS at baseline. Patients with HRS at the time of their stress echo assessment had on average a cardiac output that was about 25% higher than patients without HRS, a statistically significant difference driven by both a significantly increased heart rate and stroke volume.

Among the 424 patients free from HRS at baseline, 85 developed HRS during an average 17-month follow-up. Patients with low cardiac reserve after dobutamine challenge, defined as an increase in cardiac output of less than 25%, had a 3.9-fold increased rate of incident HRS during follow-up, compared with patients who had a larger rise in their cardiac output after adjustment for several clinical and echocardiographic baseline variables, Dr. Koshy reported. In this analysis low cardiac reserve was the strongest predictor of subsequent HRS, he said.

Dr. Koshy had no disclosures.

SOURCE: Koshy AN et al. J Hepatol. 2019 April;70(1):e56.

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