Significant reduction in heart rate variability is a feature of acute decompensation of cirrhosis and predicts 90-day mortality

Background: 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. // Aims: 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. // Methods: 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. // Results: 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. // Conclusions: 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

Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects.

BACKGROUND: The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. METHODS: We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). RESULTS: The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. CONCLUSIONS: Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.