Treatment Of Acute Decompensation Research Articles

Acute and non-acute decompensation of liver cirrhosis (47/130).

In the traditional view, the occurrence of cirrhosis-related complications, such as hepatic encephalopathy, formation of ascites or variceal haemorrhage, marks the transition to the decompensated stage of cirrhosis. Although the dichotomous stratification into a compensated and decompensated state reflects a prognostic water-shed moment and remains to hold its prognostic validity, it represents an oversimplification of clinical realities. A broadening understanding of pathophysiological mechanisms underpinning decompensation have led to the identification of distinct prognostic subgroups, associated with different clinical courses following decompensation. Data provided by the PREDICT study uncovered three distinct sub-phenotypes of acute decompensation (AD). Moreover, acute-on-chronic liver failure (ACLF) has been established as a distinct clinical entity for many years, which is associated with a high short-term mortality. Recently, non-acute decompensation (NAD) has been proposed as a distinct pathway of decompensation, complementing current concepts of the spectrum of decompensation. In contrast to AD, NAD is characterized by a slow and progressive development of complications, which are often presented at first decompensation and/or in patients in an earlier stage of chronic liver disease. Successful treatment of AD or NAD may lead to a clinical stabilization or even the concept of recompensation. This review aims to provide an overview on current concepts of decompensation and to delineate recent advances in our clinical and pathophysiological understanding.

Comparison of the Use of Carvedilol Versus Nebivolol in the Treatment of Acute Decompensation in the Patient with Chronic Heart Failure: Evaluation of Clinical Variables

Previous trials demonstrated the safety of using beta-blockers in the acute decompensation of heart failure; it is unknown whether the use of nebivolol translates into an improvement in clinical parameters at 96 hours, compared to the use of carvedilol in a similar study group. Objectives: To compare the effect of 2 treatment strategies, where the difference is made by the type of beta-blocker, in patients with acutely decompensated chronic heart failure. Methods: A single-center, prospective, experimental, randomized, double-blind clinical trial was carried out, 22 patients with LVEF ≤ 40% were randomly assigned to receive carvedilol or nebivolol with daily dose increase, clinical variables were measured for 96 hours. Results: The carvedilol group reached a maximum dose of 33.3 ± 10 mg and nebivolol 9.37 ± 1.25 mg, with both treatment strategies compensation was achieved in more than 50% of the patients in both groups, without statistically significant differences for the majority of patients. clinical variables, except for greater weight loss in the carvedilol group, reaching an absolute reduction of 5.62 kg (95% CI 3.22-8.02 kg) versus nebivolol with 2.54 kg (95% CI 0. 14-4.94 kg) at 96 hours of follow-up (p 0.001) Conclusions: In patients with acutely decompensated chronic heart failure and reduced LVEF, the use of beta-blockers is safe and well tolerated, guarantees clinical improvement and rapid compensation, with doses diuretic drops. The group with carvedilol showed greater weight reduction, compared to the nebivolol group in the study population.

Comparison of The Use of Carvedilol Versus Nebivolol in The Treatment of Acute Decompensation in The Patient With Chronic Heart Failure: Evaluation of Clinical Variables

Previous trials demonstrated the safety of using beta-blockers in the acute decompensation of heart failure; it is unknown whether the use of nebivolol translates into an improvement in clinical parameters at 96 hours, compared to the use of carvedilol in a similar study group. Objectives: To compare the effect of 2 treatment strategies, where the difference is made by the type of beta-blocker, in patients with acutely decompensated chronic heart failure. Methods: A single-center, prospective, experimental, randomized, double-blind clinical trial was carried out, 22 patients with LVEF ≤ 40% were randomly assigned to receive carvedilol or nebivolol with daily dose increase, clinical variables were measured for 96 hours. Results: The carvedilol group reached a maximum dose of 33.3 ± 10 mg and nebivolol 9.37 ± 1.25 mg, with both treatment strategies compensation was achieved in more than 50% of the patients in both groups, without statistically significant differences for the majority of patients. clinical variables, except for greater weight loss in the carvedilol group, reaching an absolute reduction of 5.62 kg (95% CI 3.22-8.02 kg) versus nebivolol with 2.54 kg (95% CI 0. 14-4.94 kg) at 96 hours of follow-up (p 0.001). Conclusions: In patients with acutely decompensated chronic heart failure and reduced LVEF, the use of beta-blockers is safe and well tolerated, guarantees clinical improvement and rapid compensation, with doses diuretic drops. The group with carvedilol showed greater weight reduction, compared to the nebivolol group in the study population.

Abstract 13502: Statins Buffer the Vasoconstricting, Pro-Inflammatory and Pro-Oxidant Effects of Experimental Venous Congestion in Patients With Systolic Heart Failure on Stable Medical Regimen

Background: In heart failure (HF), statins decrease hospitalizations for acute decompensation, which are primarily due to venous congestion (VC). The reason is unknown. We tested whether statins buffer the vasoconstricting, pro-inflammatory and pro-oxidant effects of VC in an established human model of this condition. Methods: We studied 41 pts, NYHA class II-III, LVEF <40%, euvolemic and on stable medical therapy. To experimentally model VC, venous arm pressure was increased to 30 mmHg above baseline by inflating a pressure cuff around the dominant arm. Blood was sampled from test and control arm (lacking an inflated cuff) before and after 90 minutes of VC. Plasma endothelin-1 (ET-1), interleukin-6 (IL-6), and vascular cell adhesion molecule 1 (VCAM-1) were measured by ELISA; isoprostane by LC-MS. Results: Age was 53±2 years, 32% were female, 29% had an ischemic etiology, LVEF was 22±1%, 56% were treated with a statin. Experimental VC increased plasma isoprostane, ET-1, VCAM-1 and IL-6. However, the use of a statin greatly influenced the rate of this response: the increase in isoprostane (marker of oxidative stress) was four-fold higher among nonstatin vs statin users (62.3±11 vs 15.4±11.2 pg/ml, p=0.01); ET-1 (marker of vasoconstriction and inflammation) increased 50% more among nonstatin users (1.83±0.23 vs 1.21±0.21 pg/ml, p=0.05); VCAM-1 (marker of endothelial activation) increased 80% more among non-statin users (62.5±15.1 vs 33.6±13.3 pg/ml, p=0.16). Changes in IL-6 (marker of inflammation) did not differ in the two groups (1.2±.08 vs 1.1±0.08 pg/ml, p=0.78). Of note, the effects of statins on ET-1 was dose-dependent. Conclusions: We provide the first evidence that statins (particularly at high dose) partially buffer the vasoconstricting, pro-inflammatory and pro-oxidant effects of experimental VC. Future studies are warranted to address whether short-term high dose statins have an adjunctive role in the treatment of acute decompensation in HF pts.

A case of intractable pruritus in Turner’s syndrome successfully treated with molecular adsorbent recirculating system

Pruritus is the most disabling symptom in patients with cholestatic liver diseases, such as primary biliary cirrhosis, primary sclerosing cholangitis and drug induced cholestasis. Many drug therapies have been used for treating pruritus in these patients, such as histamine antagonists, ursodeoxycholic acid, cholestyramine, enzyme inducing agents as rifampicin or phenobarbital, for inactivation of putative peripheral pruritogens, and finally opioid antagonists as naloxone or naltrexone, which modulate altered central neurotransmission. Other methods have been tried in patients who do not respond to medical therapies. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system (MARS) is used for the treatment of acute decompensation of chronic liver disease, acute liver failure, liver failure after surgery or liver transplantation [1, 2]. It has also been claimed that it may be useful in intractable pruritus in cholestatic syndromes [1, 3, 4]. We report the effect of this treatment in a patient with Turner’s syndrome and drug induced cholestasis refractory to medical therapy. A 54-year-old woman came to our attention because of intractable pruritus. She was affected by Turner’s syndrome (karyotype 45, X0),and hypothyroidism. Since the age of 23 years she had suffered of amenorrea and she had been treated with estro-progestinic therapy for many years. One year before hospitalisation, her therapy was changed into tibolone at a dose of 2.5 mg once daily. Approximately 6 months later, the patient presented itching and mild jaundice, she was admitted to the hospital and a percutaneous liver biopsy was performed; it revealed a pattern of drug induced cholestatic hepatitis. She was treated with ursodeoxycholic acid, cholestiramine and histamine antagonist, and a resolution of jaundice occurred. After an initial improvement of pruritus, later on she suffered from a severe relapse, in spite of continuing medical therapy. Six months later she was admitted to our hospital; the patient presented scratching skin lesions on arms and legs and sleep deprivation that made worse her quality of life. Our laboratory data demonstrated a normal liver function (Child-Pugh-Turcotte: A5), a moderate elevation of transaminases (GOT: 55 U/L, GPT: 51 U/L) and elevated AP: 863 U/L and gGT: 53 U/L. Bilirubin level was within normal values. Autoimmune liver disease was excluded because of negative antimytochondrian antibodies, antinuclear antibodies, antineutrophilic cytoplasm antibodies, smooth muscle antibodies, C-reactive protein, rheumatoid factor. Hepatic ultrasonography was normal. Taking into account the unsuccessful previous medical treatment we decided to treat the patient with the extracorporeal albumin dialysis (MARS). The MARS system (MARS module: Teraklin AG, Rostock, Germany) was used in combination with a standard dialysis machine. The blood flow was set to 185 ml/min, the flow in the closed albumin dialysate E. Silvagni B. Stagni L. Bolondi (&) Division of Internal Medicine, Department of Internal Medicine and Gastroenterology, University of Bologna, S.Orsola-Malpighi Hospital, Via Albertoni, 15, 40138 Bologna, Italy e-mail: bolondi@med.unibo.it

41 Circulating indices of collagen turnover during treatment of acute decompensation in chronic heart failure patients

41 Circulating indices of collagen turnover during treatment of acute decompensation in chronic heart failure patients

Tumor Necrosis Factor-a Serum Activity During Treatment of Acute Decompensation of Cachectic and Non-Cachectic Patients with Advanced Congestive Heart Failure

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that produces left ventricular dysfunction and a negative inotropic effect in cardiac tissue when overexpressed in human subjects. Previous studies have shown that levels of circulating TNF-alpha are elevated in patients with advanced congestive heart failure (CHF) and especially in those with cardiac cachexia. To clarify the potential role of TNF-alpha in the unstable state of decompensated advanced CHF, we investigated the TNF-alpha serum activity in 25 cachectic and 22 non-cachectic CHF patients (New York Heart Association, NYHA functional classes III or IV), who were treated with intravenous diuretics and positive inotropic agents for acute decompensation of the disease, during a 5-day hospitalization period, as well as in 15 age-matched healthy control subjects. Cachectic CHF patients needed higher dosages of inotropic agents than non-cachectic patients and the determination of TNF-alpha serum concentrations in this patient group showed high levels of TNF-alpha at hospital admission (18.3 +/- 3.2 pg/ml) and a transient increase in circulating TNF-alpha during the treatment period with the highest levels on the 2nd day of hospitalization (32.5 +/- 7.1 pg/ml). The TNF-alpha serum levels were low in non-cachectic CHF patients and healthy controls on the 1st day (4.0 +/- 0.9 and 3.7 +/- 0.6 pg/ml, respectively) and did not change substantially during the course of the study. The present results show that TNF-alpha serum activity is transiently increased during the treatment of decompensated cachectic CHF patients only and may be related to the clinical instability and the consequent therapeutic interventions in this category of CHF patients.