Episodes Of Acute Decompensation Research Articles

Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias

BackgroundHyperammonaemia is a key sign of decompensation in organic acidurias (OAs) and can contribute to severe neurological complications, thus requiring rapid treatment.MethodsA post-hoc analysis of two retrospective studies analysed the efficacy of carglumic acid ± ammonia (NH3) scavengers compared with scavengers alone for reducing plasma NH3 levels in patients with OAs and hyperammonaemia (plasma NH3 > 60 μmol/L) during decompensation episodes. NH3 was analysed in 12-h periods at 0–48 h and 24-h periods at 48–120 h. Treatment-emergent adverse events (TEAEs) were recorded.ResultsOf 98 episodes, 38 were treated with carglumic acid (34 patients), 33 with NH3 scavengers (22 patients) and 27 with carglumic acid combined with NH3 scavengers (27 patients). Overall, 45% (carglumic acid group), 46% (NH3 scavengers group) and 74% (combination group) of episodes occurred in neonates. Median episode duration was 6 days for the carglumic acid and combination groups, and 9 days for the NH3 scavenger group. Median baseline NH3 level was: 199 μmol/L, carglumic acid; 122 μmol/L, NH3 scavengers; and 271 μmol/L, combination; 13, 30 and 11% of episodes required extracorporeal detoxification (ED), respectively. Data were censored at ED initiation. While baseline NH3 levels were higher in the combination and carglumic acid groups, mean reduction in NH3 levels to 72 h in both groups was greater than the NH3 scavengers’ group; reductions were greatest in the combination group.Mean change in plasma NH3 vs baseline in the carglumic acid, NH3 scavengers and combination groups, respectively, was − 13, + 12% and − 27% at 0–12 h (p < 0.05 NH3 scavengers vs combination); − 47, − 22% and − 52% at 12–24 h (not significant); − 44, − 5% and − 61% at 24–48 h; and − 66, − 16% and − 76% at 48–72 h (p < 0.05 carglumic acid/combination groups vs NH3 scavengers for both timepoints). The number of TEAEs was similar between groups and mainly related to the disease/condition.ConclusionsCarglumic acid is a well-tolerated and efficacious treatment for OA decompensation episodes. When given alone or combined with NH3 scavengers, the reduction in NH3 was greater than with NH3 scavengers alone in the first 72 h.

Long-term Prognosis of Acute-on-Chronic Liver Failure Survivors.

Goals:We aimed to investigate significant factors influencing the long-term prognosis of patients who survived acute-on-chronic liver failure (ACLF).Background:The mortality of ACLF is predominantly affected by the organ failure severity. However, long-term outcomes of patients who survive ACLF are not known.Study:A cohort of 1084 cirrhotic patients who survived for more than 3 months following acute deterioration of liver function was prospectively followed. ACLF was defined by the European Association for the Study of the Liver Chronic Liver Failure Consortium definition.Results:The mean follow-up duration was 19.4±9.9 months. In the subgroup of patients without previous acute decompensation (AD), ACLF occurrence did not affect long-term outcomes. However, in patients with previous AD, ACLF negatively affected long-term transplant-free survival even after overcoming ACLF (hazard ratio, 2.00, P=0.012). Previous AD was the significant predictive factor of long-term mortality and was independent of the Model for End-stage Liver Disease score in these ACLF-surviving patients. Organ failure severity did not affect transplant-free survival in patients who survived an ACLF episode.Conclusions:A prior history of AD is the most important factor affecting long-term outcomes following an ACLF episode regardless of Model for End-stage Liver Disease score. Prevention of a first AD episode may improve the long-term transplant-free survival of liver cirrhosis patients.

Plasma levels of microRNA-21, -126 and -423-5p alter during clinical improvement and are associated with the prognosis of acute heart failure.

MicroRNAs are associated with myocardial damage and heart failure (HF). The present study investigated whether the plasma levels of microRNA (miR)‑21, ‑126 and ‑423‑5p alter according to the (de)compensated state of patients with HF and are associated with all‑cause mortality. In 48patients with HF admitted to the emergency room for an episode of acute decompensation, blood samples were collected to measure miR and B‑type natriuretic peptide levels within 24h of hospital admission, at the time of hospital discharge, and a number of weeks post‑discharge (chronic stable compensated state). Levels of miR‑21, miR‑126 and miR‑423‑5p increased between admission and discharge, and decreased following clinical compensation. During follow‑up (up to 48months), 38patients (79%) were rehospitalized at least once and 21patients (44%) succumbed. Patients who had increased levels of miR‑21 and miR‑126 at the time of clinical compensation exhibited better 24‑month survival and remained rehospitalization‑free for a longer period compared with those with low levels. Additionally, patients whose levels of miR‑423‑5p increased between admission and clinical compensation experienced fewer hospital readmissions in the 24months following the time of clinical compensation compared with those who had decreased levels. It was concluded that the plasma levels of miR‑21, miR‑126 and miR‑423‑5p altered during clinical improvement and were associated with the prognosis of acute decompensated HF.

Опыт госпитальной инициации сакубитрил/валсартана у пациентки после эпизода декомпенсации сердечной недостаточности

The article discusses management of a female patient with chronic heart failure with reduced left ventricular ejection fraction after an episode of acute decompensation. Replacing an angiotensin-converting enzyme inhibitor with a representative of a new angiotensin receptor-neprilysin inhibitor class, sacubitril/valsartan, in the combination therapy allowed fast achievement and maintenance of the compensation state. The treatment was well tolerated and was not associated with clinically significant adverse effects.

Hospital mortality in cirrhotic patients at a tertiary care center.

Cirrhosis of the liver is known for its high risk of mortality associated with episodes of acute decompensation. There is an even greater risk in patients that present with acute-on-chronic liver failure. The identification of patients at higher risk for adverse outcomes can aid in making the clinical decisions that will improve the prognosis for these patients. To determine in-hospital mortality and evaluate the epidemiologic and clinical characteristics of patients with cirrhosis of the liver seen at a tertiary referral hospital. A descriptive, observational, cohort study was conducted on adult patients with cirrhosis of the liver, admitted to a tertiary care center in Bucaramanga, Colombia, within the time frame of March 1, 2015 and February 29, 2016. Eighty-one patients with a mean age of 62 years were included in the study. The main etiology of the cirrhosis was alcoholic (59.3%). In-hospital mortality was 23.5% and the most frequent cause of death was septic shock (68.4%), followed by hypovolemic shock (10.5%). A MELD score≥18, a leukocyte count>12,000/ul, and albumin levels below<2.5g/dl were independent factors related to hospital mortality. In-hospital mortality in cirrhotic patients is high. Sepsis and bleeding are the 2 events leading to acute-on-chronic liver failure and death. A high MELD score, elevated leukocyte count, and low level of albumin are related to poor outcome during hospitalization. Adjusted prevention-centered public health measures and early and opportune diagnosis of this disease are needed to prevent the development of complications and to improve outcome in cirrhotic patients.

Hospital mortality in cirrhotic patients at a tertiary care center

IntroductionCirrhosis of the liver is known for its high risk of mortality associated with episodes of acute decompensation. There is an even greater risk in patients that present with acute-on-chronic liver failure. The identification of patients at higher risk for adverse outcomes can aid in making the clinical decisions that will improve the prognosis for these patients. AimsTo determine in-hospital mortality and evaluate the epidemiologic and clinical characteristics of patients with cirrhosis of the liver seen at a tertiary referral hospital. MethodologyA descriptive, observational, cohort study was conducted on adult patients with cirrhosis of the liver, admitted to a tertiary care center in Bucaramanga, Colombia, within the time frame of March 1, 2015 and February 29, 2016. ResultsEighty-one patients with a mean age of 62 years were included in the study. The main etiology of the cirrhosis was alcoholic (59.3%). In-hospital mortality was 23.5% and the most frequent cause of death was septic shock (68.4%), followed by hypovolemic shock (10.5%). A MELD score≥18, a leukocyte count>12,000/ul, and albumin levels below<2.5g/dl were independent factors related to hospital mortality. ConclusionsIn-hospital mortality in cirrhotic patients is high. Sepsis and bleeding are the 2 events leading to acute-on-chronic liver failure and death. A high MELD score, elevated leukocyte count, and low level of albumin are related to poor outcome during hospitalization. Adjusted prevention-centered public health measures and early and opportune diagnosis of this disease are needed to prevent the development of complications and to improve outcome in cirrhotic patients.

Cervical myelopathy involving os odontoideum and retro-odontoid cyst treated with Harms C1–C2 arthrodesis

An episode of acute decompensation of cervical myelopathy occurred after an injury without fracture of an os odontoideum associated with a compressive retro-odontoid cyst. The 51-year-old female patient presented Fränkel C, Nurick grade 4 neurological status and pyramid syndrome. The initial MRI demonstrated an intramedullary T2 hyperintense signal in the context of spinal cord narrowing. The retro-odontoid cyst demonstrates atlantoaxial instability related to the os odontoideum. Harms C1–C2 arthrodesis without laminectomy was performed and the cyst disappeared completely. Spinal cord decompression was thus obtained on the MRI taken 3 months later. Neurological recovery was complete and continued at 1 year.

Evaluation of Pulmonary Hypertension with CMR: Pulmonary Hypertension Patients and Healthy Volunteers Control Study

背景与目的肺高血压（pulmonary hypertension, PH）临床病程表现为进行性恶化和间断急性失代偿发作，死亡可突然或缓慢发生，而临床医生往往对病情的进展评估不足。本研究旨在应用心脏核磁共振（cardiac magnetic resonance, CMR）评估PH患者右心室（right ventricle, RV）形态、功能及主肺动脉（main pulmonary artery, MPA）血液动力学，并与健康人对照，探讨CMR在检出PH中的临床应用价值。方法对56例PH患者及22例健康志愿者进行CMR扫描并获得RV舒张末期容积（end-diastolic volume, EDV）、收缩末期容积（end-systolic volume, ESV）、射血分数（ejection fraction, EF）、心肌质量（myocardial mass, MM）、RV面积变化分数（RV fractional area change, RVFAC）、室间隔与左室游离壁曲率比，MPA正向峰值流速、最大截面积、最小截面积及顺应性。PH组与对照组测量结果采用两独立样本t检验进行比较。受试者工作特征曲线（receiver operating characteristic curve，ROC曲线）用于比较MPA正向峰值流速、顺应性、曲率比、RVFAC单项指标及综合评估检出PH的效能。P < 0.05为差异有统计学意义。结果与对照组相比，PH组RV形态改变、功能明显下降，血液动力学指标恶化。顺应性对检出PH的效能较高（AUC为0.950）；综合应用正向峰值流速、顺应性、曲率比和RVFAC时，检出PH的效能最高（AUC为0.988）。结论CMR综合评估指标有利于准确反映PH患者RV-肺循环整体状态。

Macrophage activation marker, soluble CD163, is an independent predictor of short-term mortality in patients with cirrhosis and bacterial infection.

Innate immune system dysfunction is common in advanced cirrhosis, with a central role of the monocyte/macrophage system. Monocytes and macrophages express the scavenger receptor CD163, which is regulated by inflammatory mediators. Cleavage of the receptor leads to the formation of soluble (s)CD163 that represents an anti-inflammatory response. We aimed to study the clinical importance of sCD163 in cirrhosis. Sera of 378 patients were assayed for sCD163 by ELISA [193 outpatients and 185 patients with acute decompensation (AD)]. A 5-year follow-up observational study was conducted to assess the possible association between sCD163 level and poor disease outcomes. sCD163 level was associated with disease severity, but not with the presence of varices or prior variceal bleeding. In outpatients, sCD163 level did not predict the development of disease-specific complications or the long-term mortality. In patients with AD episode, sCD163 level was significantly higher compared to outpatients but only in the presence of bacterial infection (INF) (AD-INF:4586, AD-NON-INF:3792 and outpatients: 3538 ng/ml, P < 0.015 and P = 0.001, respectively). sCD163 level gradually increased according to severity of infection. During bacterial infections, high sCD163 level (>7000 ng/ml) was associated with increased mortality rate (42% vs. 17%, P < 0.001) and was identified as an independent predictor of 28-day mortality (hazard ratio:2.96, 95% confidence intervals:1.27-6.95) in multivariate Cox-regression model comprising aetiology, co-morbidity, model for end-stage liver disease score and leucocyte count as covariates. High sCD163 level is useful to identify patients with high-risk of death during an AD episode complicated by bacterial infection. This finding serves as an additional hint towards the significance of anti-inflammatory response during bacterial infection.

0110: Predictive factors of tolerance to carvedilol in systolic heart failure

Heart failure experiencing exponential growth in Algeria. Among the recommended therapeutic, the b blockers are largely under prescribed. The objective of this study was to determine predicting factors of tolerance to carvedilol in systolic heart failure. Carvedilol has been introduced in 100 consecutive patients hospitalized with systolic heart failure. Clinical parameters, the BNP levels and echocardiographic indices were measured blind to admission to the first and second week. The average age of patients was 66±1 year. The FE: 31±1%, the NYHA 2.8±0.1, BNP 620±48pg/mL, E/A: 1 8±0.3, TDE 160±7, E/E’,9.1±0.3, PAPS: 36±0.4, VCI: 15+1mm. An acute decompensation episode occurred in 21patients and b blocker was arrested at 9 of them without the possibility of reintroduction. In univariate analysis, the values on admission NYHA stage, the plasma level of BNP, the TDE and reports E/A and E/E’ predicted the occurrence of acute decompensation. The combination of NYHA class 4 to a BNP level greater than 410pg/mL or at elevated filling pressures predicted the occurrence of decompensation in 100% of cases. Despite the directives of learned societies, b blockers remain largely under prescribed in systolic heart failure. The combined use of BNP or echocardiographic indices to NYHA stage allows to accurately predict the occurrence of acute decompensation.

Loop Diuretics Strategies in Acute Heart Failure: From Clinical Trials to Practical Application.

Although loop diuretics are the most commonly used drugs for the treatment of acute heart failure (AHF), their short and long-term effects are relatively unknown. The use of loop diuretics is essential in the management of HF, particularly during episodes of acute decompensation, therefore more than 90% of patients admitted with HF receive this drug. The administration of intravenous loop diuretics to patients with heart failure and congestion typically results in the improvement of dyspnea, pulmonary congestion and in the reduction of Left Ventricular (LV) filling pressures. However, little is known about its appropriate dose, timing and modality administration in patients with AHF: several side effects may result from the administration of high diuretics dose, including worsening kidney function, diuretic resistance and sympathetic overdrive. Furthermore, there is no specific strategy that shows a clear benefit in HF outcome in relation to continuous versus intermittent administration modalities. Current data based on small and heterogeneous studies did not demonstrate a clear risk benefit ratio and larger prospective trials need to be completed in order to be able to provide definitive recommendations in the future. Since every patient represents a single entity and may have different responses to the same treatment, the best clinical approach should take into account physical examination, neuro-hormonal overdrive and kidney functional status. Due to these reasons, treatment with loop diuretics should be specifically customized for each patient, until multicenter blinded trials will provide satisfactory answers regarding optimal dosing, modality administration and precise targets.

Early Warning of Acute Decompensation in Heart Failure Patients Using a Noncontact Measure of Stability Index.

Hospitalization due to heart failure (HF) continues to be a major clinical and economic challenge. To reduce hospitalization, this paper proposes a novel home telemonitoring system for an early warning of acute decompensation in patients with chronic stable New York Heart Association class II-IV HF. It is based on deriving nocturnal respiratory related time series using a noncontact radio-wave bio-motion sensor. The system generates an alert when there is a change in the underlying probability distribution of the time series which can be regarded as a surrogate marker of patient stability. The system's performance is evaluated using dual-site longitudinal data collected from 104 HF patients over 12-24 months. The system reported an average sensitivity of 0.62 to detect a change during an episode of acute decompensation and an average specificity of 0.67 on the blind validation set, when the frequency of alert was four weeks. The system also performed well to predict acute decompensation with an average sensitivity of 0.55 and specificity of 0.73 on the validation set, where an event window was defined as three weeks preceding an event. These results demonstrate that the design and implementation of such a system is a positive step toward developing noncontact systems capable of preventing acute decompensation, reducing readmissions to hospital and ensuring better quality of life for HF patients.

ACE inhibitors in the treatment of heart failure with reduced ejection fraction

Heart failure with reduced ejection fraction is associated with increased mortality and reduced quality of life. In episodes of acute decompensation, compensatory mechanisms such as the sympathetic nervous system and the renin-angiotensin-aldosterone system attempt to maintain peripheral perfusion but also increase the workload of a failing left ventricle. Treatment with angiotensin converting enzyme (ACE) inhibitors has reduced mortality, reduced frequency of hospital admissions and improved quality of life. Despite benefits in mortality reduction and improved quality of life, several contraindications exist, such as bilateral renal artery stenosis. In addition, there is potential for drug to drug interactions potentiating the risk for symptomatic hypotension.

Milrinone therapy in adults with heart failure

Heart failure is a chronic progressive condition where the myocardial pump fails to maintain peripheral perfusion. Treatment aims to alleviate signs and symptoms, reduce hospitalizations and mortality. Heart failure patients may experience episodes of acute decompensation where cardiac output fails to maintain adequate peripheral perfusion. Inotropes such as dobutamine and milrinone have a role in augmenting contractility as a means of increasing cardiac output. Milrinone is a phosphodiesterase III inhibitor with inotropic and vasodilatory properties. The added benefit of its vasodilatory action is reduction in afterload and pulmonary pressures, therefore reducing the myocardial workload. Two main adverse effects associated with this therapy are arrhythmias and hypotension.

Milrinone therapy in adults with heart failure

Heart failure is a chronic progressive condition where the myocardial pump fails to maintain peripheral perfusion. Treatment aims to alleviate signs and symptoms, reduce hospitalizations and mortality. Heart failure patients may experience episodes of acute decompensation where cardiac output fails to maintain adequate peripheral perfusion. Inotropes such as dobutamine and milrinone have a role in augmenting contractility as a means of increasing cardiac output. Milrinone is a phosphodiesterase III inhibitor with inotropic and vasodilatory properties. The added benefit of its vasodilatory action is reduction in afterload and pulmonary pressures, therefore reducing the myocardial workload. Two main adverse effects associated with this therapy are arrhythmias and hypotension.

Rationale and Design of a Randomized, Double-Blind, Placebo Controlled Multicenter Trial to Study Efficacy, Security, and Long Term Effects of Intermittent Repeated Levosimendan Administration in Patients with Advanced Heart Failure: LAICA study

BackgroundAdvanced heart failure (HF) is associated with high morbidity and mortality; it represents a major burden for the health system. Episodes of acute decompensation requiring frequent and prolonged hospitalizations account for most HF-related expenditure. Inotropic drugs are frequently used during hospitalization, but rarely in out-patients. The LAICA clinical trial aims to evaluate the effectiveness and safety of monthly levosimendan infusion in patients with advanced HF to reduce the incidence of hospital admissions for acute HF decompensation.MethodsThe LAICA study is a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel group trial. It aims to recruit 213 out-patients, randomized to receive either a 24-h infusion of levosimendan at 0.1 μg/kg/min dose, without a loading dose, every 30 days, or placebo.ResultsThe main objective is to assess the incidence of admission for acute HF worsening during 12 months. Secondarily, the trial will assess the effect of intermittent levosimendan on other variables, including the time in days from randomization to first admission for acute HF worsening, mortality and serious adverse events.ConclusionsThe LAICA trial results could allow confirmation of the usefulness of intermittent levosimendan infusion in reducing the rate of hospitalization for HF worsening in advanced HF outpatients.

Human Hepatocyte Transplantation in Patients with Hepatic Failure Awaiting a Graft

Background: Hepatocyte transplantation (HT) has the potential to become a promising treatment to temporarily support liver function in patients with liver failure. Methods: Two patients, who had already received a liver transplant (LT) in the past, with an end-stage liver disease due to recurrent hepatitis C virus cirrhosis, suffering acute-on-chronic liver failure while on the waiting list for an LT, received HT as a bridge to whole-organ retransplantation. After HT and during intensive care unit admission, blood tests and ammonia levels were determined every 12 and 24 h, respectively, before and after each hepatocyte infusion. Results: The present study describes monitoring of analytical and clinical parameters and improvement of liver function following HT. In both patients, we managed to lower the blood ammonia levels and clinically improve the degree of hepatic encephalopathy, thus serving as a bridge to liver retransplantation in 1 patient. Conclusions: We believe that this therapy may be an alternative treatment in patients with chronic liver disease who suffer episodes of acute decompensation as a bridge to conventional LT.

Comparative study of quality of life after hospital-at-home or in-patient admission for acute decompensation of chronic heart failure

AIMS: Hospitalisation at home (HaH) achieves comparable health outcomes to conventional in-patient care, in terms of cost-effectiveness and quality of life. Our objective was to assess the impact of episodes of acute decompensation of heart failure (ADCHF) on functional status and quality of life, in patients under HaH care compared with a matched group receiving conventional in-patient care at a Cardiology ward (CW). Methods: Randomised clinical trial in 71 patients with ADCHF attending the Emergency Department. Patients were either admitted to the hospital’s CW or to the HaH service. The functional status and health related quality of life (HRQOL) were assessed using the Barthel Index (BI) and the EQ-5D, Short Form-36 (SF-36) and Minnessota Living with Heart Failure (MLHFQ) questionnaires, administered at admission and, depending on the test, at discharge and 1, 3, 6 and 12 months after discharge. Results: MLHFQ and SF-36 experienced significant improvement in most domains with respect to the initial values at discharge and 6 months after only in the HaH group; though by 12-months there were no significant differences. Barthel Index and EQ-5D value scores showed improvement with respect to initial values in both arms. The improvement could be appreciated in more components and for longer among the HaH patients. Conclusions: Functional independence and quality of life improve at discharge compared to admission, after both home-based and in-patient hospitalisation, outcomes being better in various respects over the first year of follow-up after hospital-at-home care.

Ultrafiltration in acute decompensated heart failure: friend or foe for the kidney?

Congestion represents the common pathogenetic mechanism of both the acute decompensation episodes of heart failure and progression of the syndrome; it also increases the risk of rehospitalization, and is associated with renal function worsening. Diuretic therapy still represent the mainstay of therapy of congestion; however, ultrafiltration (i.e., fluid removal from blood by hemoconcentration obtained with dedicated machines) has been recently suggested as a more rapid and effective alternative to the conventional therapeutic approach. On the basis of the proposed mechanisms of action and rationale of ultrafiltration in heart failure, this review is aimed at discussing efficacy and safety issues of this mechanical modality of fluid removal, with special regard to renal function. The available evidence, also including recent data from a randomized clinical trial comparing ultrafiltration with adequately managed diuretic therapy (the CARRESS study), does not support its extensive employment as an alternative to well protocolized conventional diuretic therapy, especially in patients with acute decompensated heart failure. As a matter of fact, in this latter case highly negative effects on renal function are also to be expected. Ultrafiltration should be reserved to very selected patients with advanced heart failure and true diuretic resistance, as part of a more complex strategy aiming at an adequate control of fluid retention.

Lung ultrasound in diagnosing and monitoring pulmonary interstitial fluid

Chronic heart failure is a complex clinical syndrome often characterised by recurrent episodes of acute decompensation. This is acknowledged as a major public health problem, leading to a steadily increasing number of hospitalisations in developed countries. In decompensated heart failure, the redistribution of fluids into the pulmonary vascular bed leads to respiratory failure, a common cause of presentation to the emergency department. The ability to diagnose, quantify and monitor pulmonary congestion is particularly important in managing the disease. Lung ultrasound (US) is a relatively new method that has gained a growing acceptance as a bedside diagnostic tool to assess pulmonary interstitial fluid and alveolar oedema. The latest developments in lung US are not because of technological advance but are based on new applications and discovering the meanings of specific sonographic artefacts designated as B-lines. Real-time sonography of the lung targeted to detection of B-lines allows bedside diagnosis of respiratory failure due to impairment of cardiac function, as well as quantification and monitoring of pulmonary interstitial fluid. Lung US saves time and cost, provides immediate information to the clinician and relies on very easy-to-acquire and highly reproducible data.