Background and Aims Paracentesis‐induced circulatory dysfunction (PICD) is a serious complication of large‐volume (>5 L) paracentesis in cirrhosis and is reduced with albumin infusion. There is a lack of data on PICD in acute‐on‐chronic liver failure (ACLF). Because ACLF patients have greater hemodynamic derangements than patients with decompensated cirrhosis, we investigated whether PICD could develop with modest‐volume paracentesis (MVP) and the role of albumin infusion. Approach and Results A total of 80 ACLF patients undergoing <5 L paracentesis were randomized to receive albumin (8 g/dL of ascitic fluid; n = 40) or no albumin (n = 40) and serially followed to detect PICD. Baseline characteristics were comparable between groups, including volume of ascitic tap (4.16 ± 0.23 versus 4.14 ± 0.27 L; P = 0.72) and plasma renin activity (PRA; 20.5 ± 7.03 versus 23.2 ± 8.24 ng/mL/hour; P = 0.12). PICD was more frequent in the no‐albumin group than the albumin group (70% versus 30%; P = 0.001), with higher incidence of hepatic encephalopathy (50% versus 27.5%; P = 0.04), hyponatremia (67.5% versus 22.5%; P < 0.001), acute kidney injury (62.5% versus 30%; P = 0.001), and in‐house mortality (62.5% versus 27.5%; P = 0.003). PRA of 25.15 ng/mL at day 3 had sensitivity and specificity of 71% and 68%, respectively, for development of PICD at day 6. Albumin infusion decreased the incidence of PICD at day 6 (odds ratio, 0.068; 95% confidence interval, 0.011‐0.43; P = 0.005). Conclusions PICD is common and develops even with MVP in ACLF patients. Albumin infusion decreases the incidence of PICD and mortality in patients with ACLF. Clinical trial identifier: NCT02467348

ImportanceNo proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation.ObjectiveTo compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients.Design, setting and participantsA multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group.InterventionOne group received COPLA with SMT (n=200), and another group received SMT only (n=200).Main outcome measuresPrimary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O2 therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events.ResultsThe median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7–13) (p=0.328). The median duration of O2 therapy was 8 days (IQR=6–12) in COPLA and 10 days (IQR=6–12) in SMT group (p=0.64). The PaO2/FiO2 ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80–80)) were higher than SMT group (0 (IQR 0–80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group.Conclusion and relevanceConvalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes.Trial registration numberNCT04425915.

Background: The presence of left ventricular diastolic dysfunction (LVDD) in patients with cirrhosis leads to a restriction of activities and a poor health related quality of life (HRQoL), which should be taken into consideration when treating them for liver and cardiac complications. Aims: The prevalence, complications, predictors of HRQoL and survival in cirrhotic patients with LVDD were studied. Methods: We report a prospective cohort study of 145 consecutive cirrhotic patients with LVDD who were evaluated for cardiac functional status at enrollment and followed up for hepatic complications, cardiac events, outcome and HRQoL using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) over a period of 2 years. Results: In total, 145 (mean age 61 years, 59% male) patients were included. Seventeen patients died with 10.5%, 22.5% and 40% mortality rates in patients with Grades 1, 2 and 3 LVDD respectively over 24 months. The parameters that were significant for predicting mortality on bivariate analysis were MELD, MELDNa, hepatic venous pressure gradient, MLHFQ, and left ventricular (LV) diastolic function (e 0 and E/e 0 ratio), but only MELD, MELDNa and E/e 0 remained significant on multivariate analysis. The E/e 0 ratio (8.7 ± 3.3 in survivors vs. 9.1 ± 2.3 in non-survivors) predicted outcome.

Background: Left ventricular diastolic dysfunction (LVDD) refers to impaired cardiac diastolic relaxation and may be improved by targeted heart rate reduction (THR). The authors evaluated whether a combination of carvedilol and ivabradine, an If channel blocker that reduces heart rate without affecting blood pressure, could improve LVDD and outcomes in cirrhosis. Patients and Methods: THR was defined as heart rate reduction to 55 to 65 beats per minute. Of 260 patients with cirrhosis, 189 (72%) with LVDD were randomized to THR [group (Gr.)A; n=94; carvedilol±ivabradine)] or standard care (Gr.B; n=95; no β-blockers) and followed for 12 months. Results: In Gr.A, THR was achieved at 4 weeks in 88 (93%) patients (responders, R): 48 (61.5%) with carvedilol alone and 40 (86.9%) of 46 patients with additional ivabradine. In Gr.A, LVDD reversed in 16 (20.5%) and improved from grade 2 to 1 in 34 (35.4%)], whereas in Gr.B, it progressed from grade 1 to 2 in 10 (10.5%) patients. At 12 months, 21 (11.1%) patients died, 6 (14%) in Gr.A and 15 (18%) in Gr.B (P=0.240), but no mortality was seen in those who had persistent THR at 1 year (n=78; P=0.000). In multivariate analysis, model for end-stage liver disease [hazard ratio (HR), 1.52; 95% confidence interval (CI), 1.22-2.75; P=0.034] and E-wave transmitral/early diastolic mitral annular velocity (HR, 1.28; 95% CI, 1.23-2.42; P=0.048) predicted 1-year mortality. Nonresponders had an increased mortality risk (HR, 1.3; 95% CI, 1.2-1.8; P=0.046) independent of age, gender, and baseline model for end-stage liver disease. Levels of norepinephrine, N terminal brain natriuretic peptide, plasma renin activity, and aldosterone were reduced (P<0.01) in responders. More patients in Gr.B developed acute kidney injury (odds ratio, 4.2; 95% CI, 2.8-10.5; P=0.027) and encephalopathy (odds ratio, 6.6; 95% CI, 1.9-9.7; P=0.040). Conclusions: Ivabradine combined with carvedilol improves LVDD, achieves THR more often and reduces risk of encephalopathy, acute kidney injury with improved survival in patients with cirrhosis.

The burden of disease in patients with congestive heart failure is high. The future of BNP looks promising as it may be a better diagnostic tool for the diagnosis of CHF in developing countries in new millennium. Natriuretic peptide hormones, a family of vasoactive peptides with many favourable physiological properties, have emerged as important contenders for development of diagnostic tools and therapeutic agents in cardiovascular disease. Measurement of B-type natriuretic peptide has become as an easy-to-perform bedside test. The clinical and diagnostic significance of the measurement of plasma Nt-proBNP in the diseases of the cardiovascular system with particular emphasis on the assessment of patients with heart failure and their effects on predicting survival rate. The plasma levels of Nt-proBrain Natriuretic peptide responds more vigorously after myocardial infarction than those of other natriuretic peptides. This article is an attempt to give a short overview on the utility of BNP-blood levels for the diagnosis and treatment of heart failure.