Department of Internal Medicine I, University of Bonn, Bonn, Germany.
Institiute of Liver and Digestive Health, University College London Medical School Royal Free Hospital Campus, London, UK.
Aliment Pharmacol Ther. 2019 Sep;50(5):568-579. doi: 10.1111/apt.15365. Epub 2019 Jul 8.
Heart rate variability (HRV) is reduced in cirrhosis and in conditions of systemic inflammation. Whether HRV is associated with cirrhosis decompensation and development of acute-on-chronic liver failure (ACLF) is unknown.
To (a) validate wireless remote HRV monitoring in cirrhosis decompensation; (b) determine if severely reduced HRV is a surrogate for inflammation and progression of cirrhosis decompensation; (c) assess if measuring HRV determines prognosis in cirrhosis decompensation.
One hundred and eleven patients at risk of cirrhosis decompensation at two clinical sites were monitored for HRV. Standard deviation of all normal beat-beat intervals (SDNN) reflecting HRV was assessed using remote monitoring (Isansys Lifetouch) and/or Holter ECG recording. Clinical outcomes and major prognostic scores were recorded during 90-day follow-up.
Reduced HRV denoted by lower baseline SDNN, correlated with severity of decompensation (median 14 (IQR 11-23) vs 33 (25-42); P < 0.001, decompensated patients vs stable outpatient cirrhosis). Furthermore, SDNN was significantly lower in patients developing ACLF compared to those with only decompensation (median 10 (IQR9-12) vs 16 (11-24); P = 0.02), and correlated inversely with MELD and Child-Pugh scores, and C-reactive protein (all P < 0.0001) and white cell count (P < 0.001). SDNN predicted disease progression on repeat measures and appeared an independent predictor of 90-day mortality (12 patients). An SDNN cut-off of 13.25 ms had a 98% negative predictive value.
This study demonstrates that remote wireless HRV monitoring identifies cirrhosis patients at high risk of developing ACLF and death, and suggests such monitoring might guide the need for early intervention in such patients. Clinical Trial number: NIHR clinical research network CPMS ID 4949.
心率变异性（HRV）在肝硬化和全身性炎症中降低。HRV 是否与肝硬化失代偿和慢加急性肝衰竭（ACLF）的发展有关尚不清楚。
（a）验证无线远程 HRV 监测在肝硬化失代偿中的应用；（b）确定严重降低的 HRV 是否是炎症和肝硬化失代偿进展的替代指标；（c）评估测量 HRV 是否可以确定肝硬化失代偿患者的预后。
在两个临床中心，对有发生肝硬化失代偿风险的 111 名患者进行 HRV 监测。使用远程监测（Isansys Lifetouch）和/或动态心电图记录评估反映 HRV 的所有正常心跳间隔的标准差（SDNN）。在 90 天随访期间记录临床结局和主要预后评分。
较低的基线 SDNN 表示 HRV 降低，与失代偿的严重程度相关（中位数 14（IQR 11-23）与 33（25-42）；P<0.001，失代偿患者与稳定的门诊肝硬化患者）。此外，与仅发生失代偿的患者相比，发生 ACLF 的患者 SDNN 显著降低（中位数 10（IQR9-12）与 16（11-24）；P=0.02），并且与 MELD 和 Child-Pugh 评分以及 C 反应蛋白（均 P<0.0001）和白细胞计数呈负相关（P<0.001）。SDNN 在重复测量中预测疾病进展，并且是 90 天死亡率的独立预测因子（12 例患者）。SDNN 截断值为 13.25ms 时具有 98%的阴性预测值。
本研究表明，远程无线 HRV 监测可识别出发生 ACLF 和死亡风险较高的肝硬化患者，并表明这种监测可能指导此类患者早期干预的必要性。临床试验编号：NIHR 临床研究网络 CPMS ID 4949。
