ABSTRACT
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 ß-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.
Subject(s)
End Stage Liver Disease , Carvedilol , Humans , Ivabradine , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Severity of Illness IndexABSTRACT
BACKGROUND AND AIM: Echocardiographic assessment of the inferior vena cava diameter (IVCD) and collapsibility index (IVCCI) is a noninvasive estimate of intravascular volume status (IVS) but requires validation for cirrhosis. We evaluated IVC dynamics in cirrhosis and correlated it with conventional tools such as central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and right atrial pressure (RAP). METHODS: A total of 673 consecutive cirrhotic patients were screened by echocardiography, and 125 patients underwent right heart catheterization with recording of hepatic venous pressure gradient (HVPG), RAP, pulmonary artery (PA) pressure, and PCWP. CVP data were available for 80 (64%) patients, and finally, 76 patients (84% male, 50% ethanol related, mean age 52.1 years, 57.8% with ascites) with complete data were enrolled. RESULTS: The mean CVP measured was 12.8 ± 4.8 mmHg, and IVCCI was 29.5 ± 10.9%. The IVCD ranged from 0.97 to 2.26 cm and from 0.76 to 1.84 cm during expiration and inspiration, respectively, with a mean of 1.8 ± 0.9 cm. The mean IVCD correlated with RAP (r = 0.633, P = 0.043) but not with HVPG (r = 0.344, P = 0.755), PCWP (r = 0.562, P = 0.072), or PA pressure (r = 0.563, P = 0.588). A negative linear correlation was observed between the CVP and the IVCCI (r = -0.827, P = 0.023) in all patients and substratified for those with (r = -0.748, P = 0.039) and without ascites (r = -0.761, P = 0.047). A positive correlation was observed between CVP and IVCDmax (r = 0.671, P = 0.037) and IVCDmin (r = 0.612, P = 0.040). CONCLUSIONS: IVCD and collapsibility index provides noninvasive IVS assessment, independent of HVPG or ascites, with the potential for calculating fluid requirements in cirrhosis.
ABSTRACT
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' and E/e' ratio), but only MELD, MELDNa and E/e' remained significant on multivariate analysis. The E/e' ratio (8.7 ± 3.3 in survivors vs. 9.1 ± 2.3 in non-survivors) predicted outcome. On univariate analysis, the predictors of poor HRQoL were the Child-Pugh score ≥9.8 (OR 2.6; 95% confidence intervals (CI) 2.3-9.1, P = 0.041), MELD score ≥ 15.7 (OR 2.48; 95% CI 1.4-3.9, P = 0.029), refractory ascites (OR 1.9; 95% CI 1.1-6.1, P = 0.050), and E/e' ratio ≥7.6 (OR 1.9; 95% CI 1.8-7.1, P = 0.036) The presence of Class II/III (P = 0.046) symptoms of heart failure and MLHFQ≥ 45 (P = 0.042) were predictors of mortality at 24 months. CONCLUSION: The grade of LVDD correlates with liver function, clinical events, risk of renal dysfunction and HRQoL. Evaluation of novel therapies which target symptomatic improvement in LVDD, should be done with suitable outcome measures, including HRQoL assessment.
ABSTRACT
BACKGROUND & AIMS: Patients with cirrhosis are prone to develop volume over load, have increased capillary permeability and latent or overt cardiomyopathy. Whether albumin infusion causes volume overload in cirrhotics has not been adequately studied. METHODS: Ninety nine consecutive cirrhotic patients receiving 1gm per kg albumin infusion were evaluated for development of volume overload. Clinical, echocardiographic and haemodynamic changes were closely monitored during and after albumin infusion. RESULTS: Thirty (30.30%) patients developed volume overload. Patients with higher BMI (P=.003), lower CTP (P=.01) and MELD (P=.034) were more often associated with the development of volume overload. Though baseline diastolic dysfunction was present in 82.8% of the patients, it did not influence the development of volume overload or changes in the cardiac output. The cardiac output increased significantly after albumin infusion (4.9±1.554 L/min to 5.86±1.85 L/min, P<.001) irrespective of the development of volume overload, or the presence of diastolic dysfunction or the Child's status. CONCLUSION: Nearly, one-third of cirrhotics receiving standard albumin infusion develop volume overload, specially, those with higher BMI and lower severity of liver disease. Cardiac output increases after albumin infusion, and, baseline diastolic dysfunction has little effect on the development of volume overload or changes in cardiac output.
