Introduction
Current guidelines recommend intravenous (IV) albumin as a treatment of various complications of decompensated cirrhosis, but recent data point towards clinically relevant volume overload post-infusion in this population. A prospective cohort study assessing point-of-care ultrasound (POCUS) of the inferior vena cava (IVC) found potentially severe intravascular volume overload in almost 20% of patients after albumin. However, it is still unknown whether underlying cardiac function may predict post-infusion hypervolemia and short to mid-term clinical outcomes.
Aims & Methods
In this retrospective analysis of 54 individual adults with cirrhosis receiving IV albumin, we assessed associations between transthoracic echocardiography (TTE) parameters, IVC-derived potential volume overload using POCUS, and clinical outcomes during a period of 6 months. TTE parameters were extracted from examinations within 3 months of inclusion. Any volume overload was defined as maximum IVC diameter (IVC_max) >2.1cm and IVC collapsibility index (IVCCI) < 50%; severe overload as IVC_max > 2.1cm and IVCCI < 20%. Potential associations between TTE parameters and any or severe volume overload and clinical outcomes up to 6 months (p<0.10) in univariable regression analyses were consequently analyzed in multivariable regression models adjusting for age, sex, and model of end stage liver disease (MELD).
Results
Among 76 POCUS measurements from 54 patients (female 22.4%, median age 62 years, median MELD 15), any degree of volume overload occurred in 51.3% and severe overload in 22.4% after albumin infusion. The median right ventricular-right atrial gradient (RVRA) was 23 mmHg (interquartile range [IQR] 20-28), while cirrhotic cardiomyopathy (CCM) was present in 15.8% (12/76) and diastolic dysfunction (DD ≥ Grade 1) in 36.1% (26/76). In multivariable analyses, higher RVRA levels were independently associated with any volume overload (odds ratio [OR] 1.83 per 5 mmHg increase, 95% confidence interval [CI] 1.09–3.10; p=0.023). This was further supported by a threshold analysis, showing that RVRA ≥ 25 mmHg significantly increased the risk of any volume overload (OR 4.30, 95%CI 1.21-15.31; p=0.024). Sensitivity analyses restricted to individual patients (n=54) confirmed these findings. Regarding clinical outcomes, we only included the first examination. High rates of liver-related events such as acute kidney injury (55.6%), spontaneous bacterial peritonitis (SBP; 22.2%), hepatic encephalopathy (HE; 29.6%) and mortality (29.6%) were observed within 6 months from baseline. In multivariable models, DD was associated with SBP at 3 months (OR 20.78, 95%CI 1.76–245.30; p=0.016). Furthermore, CCM according to the 2019 CCM consortium definitions was significantly associated with HE at 3 months (OR 6.12, 95%CI 1.30–28.72; p=0.022), but this effect did not persist until 6 months from baseline.
Conclusion
This study provides initial evidence of an association between RVRA and volume overload following albumin therapy, potentially reflecting an increased susceptibility to fluid challenge in conditions associated with subclinically elevated pulmonary arterial pressure in patients with decompensated cirrhosis. Although transient associations were observed between TTE parameters and liver-related outcomes, these findings require confirmation. Furthermore, clinically inapparent DD and CCM are a common finding in this population, while their prognostic role deserves further exploration in larger prospective cohort studies.
Disclosure
FB and SdM have nothing to declare. DS reports travelling fees from GIlead and Falk. AB serves as consultant and/or speaker for Boehringer Ingelheim, GE HealthCare; Hologic; W. L. Gore & Associates. JB was a consultant for AstraZeneca, NovoNordisk, Boehringer Ingelheim and Resolution Therapeutics.
