Heart rate variability in patients with cirrhosis: a systematic review and meta-analysis

Background. Cirrhosis is associated with abnormal autonomic function and regulation of cardiac rhythm. Measurement of heart rate variability (HRV) provides an accurate and non-invasive measurement of autonomic function as well as liver disease severity currently calculated using the MELD, UKELD, or Child-Pugh scores. This review assesses the methods employed for the measurement of HRV, and evaluates the alteration of HRV indices in cirrhosis, as well as their value in prognosis. Method. We undertook a systematic review using Medline, Embase and Pubmed databases in July 2020. Data were extracted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The risk of bias of the included studies was assessed by a modified version of the Newcastle-Ottawa Scale. The descriptive studies were analysed and the standardized mean differences of HRV indices were pooled. Results. Of the 247 studies generated from our search, 14 studies were included. One of the 14 studies was excluded from meta-analysis because it reported only the median of HRV indices. The studies included have a low risk of bias and include 583 patients with cirrhosis and 349 healthy controls. The HRV time and frequency domains were significantly lower in cirrhotic patients. Between-studies heterogeneity was high in most of the pooled studies (P < 0.05). Further, HRV indices predict survival independent of the severity of liver disease as assessed by MELD. Conclusion. HRV is decreased in patients with cirrhosis compared with healthy matched controls. HRV correlated with severity of liver disease and independently predicted survival. There was considerable variation in the methods used for HRV analysis, and this impedes interpretation and clinical applicability. Based on the data analysed, the standard deviation of inter-beat intervals (SDNN) and SDNN corrected for basal heart rate (cSDNN) are the most suitable indices for prognosis in patients with cirrhosis.