Angiotensin II Induces Cardiac Edema and Hypertrophic Remodeling through Lymphatic-Dependent Mechanisms.

Cardiac lymphatic vessel growth (lymphangiogenesis) and integrity play an essential role in maintaining tissue fluid balance. Inhibition of lymphatic lymphangiogenesis is involved in cardiac edema and cardiac remodeling after ischemic injury or pressure overload. However, whether lymphatic vessel integrity is disrupted during angiotensin II- (Ang II-) induced cardiac remodeling remains to be investigated. In this study, cardiac remodeling models were established by Ang II (1000 ng/kg/min) in VEGFR-3 knockdown (Lyve-1Cre VEGFR-3f/-) and wild-type (VEGFR-3f/f) littermates. Our results indicated that Ang II infusion not only induced cardiac lymphangiogenesis and upregulation of VEGF-C and VEGFR-3 expression in the time-dependent manner but also enhanced proteasome activity, MKP5 and VE-cadherin degradation, p38 MAPK activation, and lymphatic vessel hyperpermeability. Moreover, VEGFR-3 knockdown significantly inhibited cardiac lymphangiogenesis in mice, resulting in exacerbation of tissue edema, hypertrophy, fibrosis superoxide production, inflammation, and heart failure (HF). Conversely, administration of epoxomicin (a selective proteasome inhibitor) markedly mitigated Ang II-induced cardiac edema, remodeling, and dysfunction; upregulated MKP5 and VE-cadherin expression; inactivated p38 MAPK; and reduced lymphatic vessel hyperpermeability in WT mice, indicating that inhibition of proteasome activity is required to maintain lymphatic endothelial cell (LEC) integrity. Our results show that both cardiac lymphangiogenesis and lymphatic barrier hyperpermeability are implicated in Ang II-induced adaptive hypertrophic remodeling and dysfunction. Proteasome-mediated hyperpermeability of LEC junctions plays a predominant role in the development of cardiac remodeling. Selective stimulation of lymphangiogenesis or inhibition of proteasome activity may be a potential therapeutic option for treating hypertension-induced cardiac remodeling.

History of Atrial Fibrillation and Trajectory of Decongestion in Acute Heart Failure.

OBJECTIVES: This study sought to characterize the course of decongestion among patients hospitalized for acute heart failure (AHF) by history of atrial fibrillation (AF) and/or atrial flutter (AFL). BACKGROUND: AF/AFL and chronic heart failure (HF) commonly coexist. Little is known regarding the impact of AF/AFL on relief of congestion among patients who develop AHF. METHODS: We pooled patients from 3 randomized trials of AHF conducted within the Heart Failure Network, the DOSE (Diuretic Optimization Strategies) trial, the ROSE (Renal Optimization Strategies) trial, and the CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) trial. The association between history of AF/AFL and in-hospital changes in various metrics of congestion was assessed using covariate-adjusted linear and ordinal logistic regression models. RESULTS: Of 750 unique patients, 418 (56%) had a history of AF/AFL. Left ventricular ejection fraction was higher (35% vs. 27%, respectively; p < 0.001), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were nonsignificantly lower at baseline (4,210 pg/ml vs. 5,037 pg/ml, respectively; p = 0.27) in patients with AF/AFL. After adjustment of covariates, history of AF/AFL was associated with less substantial loss of weight (-5.7% vs. -6.5%, respectively; p = 0.02) and decrease in NT-proBNP levels (-18.7% vs. -31.3%, respectively; p = 0.003) by 72 or 96 h. History of AF/AFL was also associated with a blunted increase in global sense of well being at 72 or 96 h (p = 0.04). There was no association between history of AF/AFL and change in orthodema congestion score (p = 0.67) or 60-day composite clinical endpoint (all-cause mortality or any rehospitalization; hazard ratio: 1.21; 95% confidence interval: 0.92 to 1.59; p = 0.17). CONCLUSIONS: More than half of the patients admitted with AHF had a history of AF/AFL. History of AF/AFL was independently associated with a blunted course of in-hospital decongestion. Further research is required to understand the utility of specific therapies targeting AF/AFL during hospitalization for AHF.

Cardioprotective effect of Pycnogenol in ischemic-reperfusion injury (IRI) in rats.

Oxidative stress plays a critical task in the biochemical and pathological alteration linked with myocardial ischemic-reperfusion injury (IRI). This warrants identifying agents with a potential for preventing such damage in an effective way. A novel plant based product, Pycnogenol, obtained from the French maritime pine (Pinus pinaster ssp. atlantica) bark extract was known for its tremendous antioxidant potential (both in vivo, in vitro). It was able to attenuate the symptoms of immune dysfunction through restoring a cellular antioxidant status in low micronutrient-induced immune deficient mice. Consequently, the present study was deals with the determination of protective effect of Pycnogenol in ischemic-reperfusion injury (IRI) in rats via Non-recirculating Langendorff's technique. The effect of Pycnogenol  on the level of various key biomarkers in the rat heart homogenate was determined, such as, myocardial thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation), lactic dehydrogenase (LDH) (a marker of tissue injury) and effect on endogenous antioxidants, e.g., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx). The activity of these biomarkers appreciably improved in Pycnogenol-treated group than IRI group (P < 0.05). The effect of Pycnogenol was further confirmed via histopathological examination of cardiac tissues, which suggests that, it considerably improved the injury related to tissue damage through suppression of edema and infiltration of neutrophil compared to IRI group. It also showed modulation of the expression of apoptotic factors, e.g. Bcl-2, bax and caspase-9 as confirmed by western blot analysis.

Evaluation of therapy management and outcome in Takotsubo syndrome.

BACKGROUND: To date there is no validated evidence for standardized treatment of patients with Takotsubo syndrome (TTS). Medication therapy after final TTS diagnosis remains unclear. Previous data on patient outcome is ambivalent. Aim of this study was to evaluate medication therapy in TTS and to analyze patient outcome. METHODS: Within an observational retrospective cohort study we analyzed our medical records and included 72 patients with TTS that underwent cardiovascular magnetic resonance imaging (CMR) after a median of 2 days interquartile range (IQR 1-3.5). We investigated medication therapy at discharge. Medication implementation and major adverse clinical events (MACE) were prospectively evaluated after a median follow-up of 24 months (IQR 6-43). Left ventricular function, myocardial oedema and late gadolinium enhancement were analyzed in a CMR follow-up if available. RESULTS: Antithrombotic therapy was recommended in 69 (96%) patients including different combinations. Antiplatelet monotherapy was prescribed in 28 (39%) patients. Dual antiplatelet therapy was recommended in 29 (40%) patients. Length of therapy duration varied from one to twelve months. Only in one case oral anticoagulation was prescribed due to apical ballooning with a left ventricular ejection fraction <30%. In all other cases oral anticoagulation was recommended due to other indications. ß-adrenoceptor antagonists and ACE inhibitors were recommended in 63 (88%), mineralocorticoid receptor antagonists were prescribed in 31 (43%) patients. After a median of 2 months (IQR 1.3-2.9) left ventricular function significantly recovered (49.1% ± 10.1 vs. 64.1% ± 5.7, P < 0.001) and myocardial oedema significantly decreased (13.5 ± 11.3 vs. 0.6% ± 2.4, P = <0.001) in the CMR follow-up. The 30-day mortality was 1%. MACE rate after 24 months was 12%. CONCLUSION: Although therapy guidelines for TTS currently do not exist, we found that the majority of patients were treated with antithrombotic and heart failure therapy for up to twelve months. Left ventricular function and myocardial oedema recovered rapidly within the first two months. Outcome analysis showed a low bleeding rate and a high short-term survival. Therefore, TTS patients might benefit from antithrombotic and heart failure therapy at least for the first two months.

Global myocardial oedema in advanced decompensated heart failure.

AIMS: To use cardiac magnetic resonance (CMR) imaging with quantitative T2 mapping as surrogate for myocardial water content in patients with advanced decompensated heart failure (ADHF), compare these values with T2-values observed in chronic heart failure, and evaluate the change with decongestive therapy. METHODS AND RESULTS: Volumetric CMR measurements and quantitative T2 mapping were performed in 18 consecutive ADHF patients with clinical signs of volume overload. Eleven patients with stable heart failure were used as controls. Vasodilator therapy and diuretics were administered to achieve a pulmonary arterial wedge pressure (PAWP) of <18 mmHg and central venous pressure (CVP) of <12 mmHg, after which CMR was repeated. ADHF patients (62 ± 12 years; 89% male; left ventricular ejection fraction 23 ± 8%) presented with low cardiac index (2.08 ± 0.59 L/min/m2), high PAWP (25 ± 7 mmHg), and high CVP (14 ± 5 mmHg). After decongestion, the patients had a significant increase in cardiac index (+0.41 ± 0.53 L/min/m2; P = 0.005) and decreases in both PAWP (-9 ± 6 mmHg; P < 0.001) and CVP (-6 ± 5 mmHg; P < 0.001). At baseline, global left ventricular T2-values were higher in ADHF patients compared with controls (59.5 ± 4.6 vs. 54.7 ± 2.2 ms, respectively; P = 0.001). After decongestion, T2-values fell significantly to 55.9 ± 5.1 ms (P = 0.001), comparable with controls (P = 0.580). In contrast, psoas muscle T2-values were similar at baseline (38.6 ± 4.4 ms) vs. after decongestion (37.8 ± 4.8 ms; P = 0.397). Each 1 ms decrease in global left ventricular T2-value during decongestion was associated with a 1.14 ± 0.40 mmHg decrease in PAWP (P = 0.013), after correction for age and gender. CONCLUSION: Patients presenting with ADHF and volume overload have increased global left ventricular-but not psoas muscle-T2-values, which decrease with successful decongestion. Relief of myocardial oedema correlates with haemodynamic unloading.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Fluid Management.

OBJECTIVE: In this Consensus Statement, we review the etiology and pathophysiology of fluid disturbances in critically ill children with cardiac disease. Clinical tools used to recognize pathologic fluid states are summarized, as are the mechanisms of action of many drugs aimed at optimal fluid management. DATA SOURCES: The expertise of the authors and a review of the medical literature were used as data sources. DATA SYNTHESIS: The authors synthesized the data in the literature in order to present clinical tools used to recognize pathologic fluid states. For each drug, the physiologic rationale, mechanism of action, and pharmacokinetics are synthesized, and the evidence in the literature to support the therapy is discussed. CONCLUSIONS: Fluid management is challenging in critically ill pediatric cardiac patients. A myriad of causes may be contributory, including intrinsic myocardial dysfunction with its associated neuroendocrine response, renal dysfunction with oliguria, and systemic inflammation with resulting endothelial dysfunction. The development of fluid overload has been associated with adverse outcomes, including acute kidney injury, prolonged mechanical ventilation, increased vasoactive support, prolonged hospital length of stay, and mortality. An in-depth understanding of the many factors that influence volume status is necessary to guide optimal management.

[Position of diuretics in the treatment of heart failure in light of current guidelines].

Diuretics are the longest-used drugs in heart failure after digoxin. This is due to their effect on the retention of sodium and an increase in the volume of fluid in the extracellular space secondary to neurohormonal and hemodynamic disorders occurs in heart failure, and their effectiveness in the treatment of symptomatic heart failure. Discontinuation of treatment with diuretics or use them in too small doses is one of the causes of exacerbation or acute heart failure.The effectiveness of most of diuretics does not confirm in the clinical trials, and the indications for their use are often based only on expert opinion. The effect of these drugs on morbidity and mortality in patients with HF was not examined. Diuretics reduce shortness of breath and swelling. For this reasons it is recom-mended to use them in patients with signs and symptoms of fluid retention regardless of the left ventricular ejection fraction.

Effects of tolvaptan in the early postoperative stage after heart valve surgery: results of the STAR (Study of Tolvaptan for fluid retention AfteR valve surgery) trial.

PURPOSE: The purpose of this study was to assess the efficacy of tolvaptan, a vasopressin V2 receptor antagonist, for the management of postoperative surgical fluid retention after heart valve surgery. METHODS: This was a prospective observational study of 64 patients with heart valve disease who underwent valve surgery between 2013 and 2014. Those in the tolvaptan group received tolvaptan in addition to conventional diuretic therapy. The results were compared to the results of 55 patients who underwent heart valve surgery between 2007 and 2010 and received conventional postoperative diuretics alone. RESULTS: The time to return to the preoperative BW was significantly shorter in the patients who received tolvaptan (6.1 ± 3.8 vs. 8.7 ± 6.7 days, p < 0.05), while the level of sodium was significantly decreased in the patients who received conventional diuretics. The degree of increase in the creatinine level tended to be smaller in the tolvaptan group. The response to tolvaptan was related to the postoperative degree of BW increase and the preoperative creatinine level. CONCLUSIONS: Tolvaptan was effective in treating fluid retention during the early postoperative stage in cardiac surgery patients, without increased renal failure or abnormal electrolyte levels. This new type of diuretic therapy may be a suitable option for postoperative fluid management in patients undergoing cardiac surgery.

Diagnosis of viral myocarditis by cardiac magnetic resonance and viral genome detection in peripheral blood.

In patients with acute myocarditis, viral genome can be detected in plasma and peripheral leukocytes. Its relationship with active myocardial inflammation, however, is not well understood. Myocardial edema as a feature of inflammation and myocardial necrosis or fibrosis can be frequently observed in patients with acute myocarditis by cardiovascular magnetic resonance (CMR). We assessed the association of viral genome presence in peripheral blood samples with myocardial edema and irreversible injury. We examined consecutive patients with clinically suspected myocarditis after an episode of viral illness. State-of-the-art methods were used for detecting myocardial edema and irreversible injury using CMR and viral genome applying reverse transcribed, nested polymerase chain reaction in peripheral blood samples. The specificity of viral amplification products was confirmed by automatic DNA sequencing. Of a total of 55 patients (53.5 ± 15.6 years), 21 were positive for viral genome in peripheral leukocytes. Interestingly, 18 (86%) of these patients also showed global myocardial edema, as compared to only 7/34 (21%) without PCR evidence for viral genome. The overall agreement between CMR criteria for edema and viral PCR was 84%. In contrast, there was no significant relationship of viral genome presence with myocardial necrosis or scars. In patients with clinically suspected myocarditis, myocardial edema but not irreversible myocardial injury is associated with the presence of viral genome in peripheral blood.

Effects of glutamine treatment on myocardial damage and cardiac function in rats after severe burn injury.

Treatment with glutamine has been shown to reduce myocardial damage associated with ischemia/reperfusion injury. However, the cardioprotective effect of glutamine specifically after burn injury remains unclear. The present study explores the ability of glutamine to protect against myocardial damage in rats that have been severely burned. Seventy-two Wistar rats were randomly divided into three groups: normal controls (C), burned controls (B) and a glutamine-treated group (G). Groups B and G were subjected to full thickness burns comprising 30% of total body surface area. Group G was administered 1.5 g/ (kg•d) glutamine and group B was given the same dose of alanine via intragastric administration for 3 days. Levels of serum creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and blood lactic acid were measured, as well as myocardial ATP and glutathione (GSH) contents. Cardiac function indices and histopathological changes were analyzed at 12, 24, 48 and 72 post-burn hours. In both burned groups, levels of serum CK, LDH, AST and blood lactic acid increased significantly, while myocardial ATP and GSH contents decreased. Compared with group B, CK, LDH, and AST levels were lower and blood lactic acid, myocardial ATP and GSH levels were higher in group G. Moreover, cardiac contractile function inhibition and myocardial histopathological damage were significantly reduced in group G compared to B. Taken together, these results show that glutamine supplementation protects myocardial structure and function after burn injury by improving energy metabolism and by promoted the synthesis of ATP and GSH in cardiac myocytes.

Effects of tolvaptan on volume overload in Japanese patients with heart failure: results of a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

PURPOSE: Tolvaptan may reduce the signs of volume overload in heart failure (HF) patients who experience volume overload despite using conventional diuretics. In this study, we evaluated the dose-response effects of tolvaptan on weight loss, urine volume and electrolyte excretion in furosemide-treated Japanese HF patients exhibiting volume overload. METHODS: In the study, 117 HF patients with volume overload on stable doses of furosemide (≥ 40 mg/day) were treated with tolvaptan (15, 30 or 45 mg) or placebo once-daily for 7 days. RESULTS: The decrease in body weight from baseline to the day after the final dose with 15, 30 or 45 mg tolvaptan (-1.62 ± 1.55, -1.35 ± 1.54 and -1.85 ± 1.10 kg, respectively), was significantly greater compared with that in the placebo group (-0.53 ± 0.96 kg) (p < 0.05). However, the decrease in body weight with tolvaptan was not significantly dose-dependent. Signs of volume overload improved at all doses of tolvaptan. Tolvaptan elicited a dose-dependent increase in urine volume and a decrease in urine osmolality, but did not affect urinary sodium or potassium excretion. Adverse reactions associated with diuresis were most frequently observed at the higher doses of tolvaptan. CONCLUSIONS: Once-daily tolvaptan (15, 30 or 45 mg) was effective and tolerable as an add-on treatment to furosemide therapy in Japanese HF patients with volume overload.

Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

PURPOSE: Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. METHODS: A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. RESULTS: Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. CONCLUSION: Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

Efficacy and safety of tolvaptan in heart failure patients with sustained volume overload despite the use of conventional diuretics: a phase III open-label study.

PURPOSE: Volume overload is a common complication associated with heart failure (HF) and is recommended to be treated with loop or thiazide diuretics. However, use of diuretics can cause serum electrolyte imbalances and diuretic resistance. Tolvaptan, a selective, oral, non-peptide vasopressin V2-receptor antagonist, offers a new option for treating volume overload in HF patients. The aim of this study was to investigate the efficacy and safety of tolvaptan in Japanese HF patients with volume overload. METHODS: Fifty-one HF patients with volume overload, despite using conventional diuretics, were treated with 15 mg/day tolvaptan for 7 days. If the response was insufficient at Day 7, tolvaptan was continued for a further 7 days at either 15 mg/day or 30 mg/day. Outcomes included changes in body weight, symptoms and safety parameters. RESULTS: Thirty-six patients discontinued treatment within 7 days, therefore 15 patients entered the second phase of treatment. In two patients, tolvaptan was increased to 30 mg/day after 7 days. Body weight was reduced on Day 7 (-1.95 ± 1.98 kg; n = 41) and Day 14 (-2.35 ± 1.44 kg; n = 11, 15 mg/day). Symptoms of volume overload, including lower limb edema, pulmonary congestion, jugular venous distention and hepatomegaly, were improved by tolvaptan treatment for 7 or 14 days. Neither tolvaptan increased the incidence of severe or serious adverse events when administered for 7-14 days. CONCLUSIONS: This study confirms the efficacy and safety of 15 mg/day tolvaptan for 7-14 days in Japanese HF patients with volume overload despite conventional diuretics.

Phase III clinical pharmacology study of tolvaptan.

PURPOSE: This study aimed to investigate the pharmacokinetics, pharmacodynamics, efficacy and safety of tolvaptan, an orally effective vasopressin V2-receptor antagonist. METHODS: This was a multicenter, randomized, double-blind, parallel group study. Tolvaptan was administered at 7.5 or 15 mg, in combination with furosemide, for 7 days in Japanese heart failure (HF) patients with volume overload that had not resolved despite receiving furosemide. RESULTS: The blood concentration of tolvaptan was maintained at a higher concentration for a longer time in patients who received 15 mg/day when compared with patients who received 7.5 mg/day. Tolvaptan increased urine volume and increased weight loss dose-dependently when used in combination with furosemide. Importantly, tolvaptan enhanced water diuresis without affecting blood electrolyte levels. CONCLUSION: Tolvaptan exerts diuretic effects and causes body weight loss at the low dose of 7.5 mg; however, these effects were less than those elicited by 15 mg tolvaptan.

Cardiac sarcoidosis complicated with atrioventricular block and wall thinning, edema and fibrosis in left ventricle: confirmed recovery to normal sinus rhythm and visualization of edema improvement by administration of predonisolone.

A 65 year-old female had a node of some kind in her right leg five years ago and was diagnosed with sarcoidosis by gallium scintigraphy. Serum angiotension-converting enzyme levels had gradually increased, and three months ago she felt palpitations and dizziness when standing. On electrocardiogram, 2:1 atrioventricular (AV) block was observed. On transthoracic echocardiogram, the basal portion of the interventricular septum (IVS) revealed wall thinning with dyskinetic motion and lack of systolic thickening, and low attenuation. The basal portion of the left ventricular (LV) posterior inferior wall revealed mild wall thickening with low attenuation. Enhanced multislice-CT revealed a thickened LV posterior wall and thinned basal portion of IVS with interstitial change suggesting presence of fibrosis or edema. Late enhancement was also observed in the basal portion of the LV posterior inferior wall and basal IVS in T1 weighted magnetic resonance imaging (MRI); in addition, an area, the center of which indicated low attenuation surrounded by high attenuation, was observed in the basal portion of the LV posterior inferior wall in T2 weighted MRI. Positron emission tomography (PET) imaging using F-18 fluoro-deoxyglucose with the subject fasted for 6 h beforehand, revealed strong uptake in the basal portion of IVS and a thickened LV posterior wall, suggesting the presence of inflammation. Administration of predonisolone was started before pacemaker implantation and clinical symptoms immediately disappeared; in addition AV block recovered to normal sinus rhythm. On a repeat MRI performed four months later, the late enhancement in T1 weighted MRI and the high attenuation surrounding low attenuation in the basal portion of the LV posterior inferior wall in T2 weighted MRI both disappeared, and we confirmed that temporary edema had also disappeared.

Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity.

Endothelial cell-cell junctions regulate vascular permeability, vasculogenesis, and angiogenesis. Familial cerebral cavernous malformations (CCMs) in humans result from mutations of CCM2 (malcavernin, OSM, MGC4607), PDCD10 (CCM3), or KRIT1 (CCM1), a Rap1 effector which stabilizes endothelial cell-cell junctions. Homozygous loss of KRIT1 or CCM2 produces lethal vascular phenotypes in mice and zebrafish. We report that the physical interaction of KRIT1 and CCM2 proteins is required for endothelial cell-cell junctional localization, and lack of either protein destabilizes barrier function by sustaining activity of RhoA and its effector Rho kinase (ROCK). Protein haploinsufficient Krit1(+/-) or Ccm2(+/-) mouse endothelial cells manifested increased monolayer permeability in vitro, and both Krit1(+/-) and Ccm2(+/-) mice exhibited increased vascular leak in vivo, reversible by fasudil, a ROCK inhibitor. Furthermore, we show that ROCK hyperactivity occurs in sporadic and familial human CCM endothelium as judged by increased phosphorylation of myosin light chain. These data establish that KRIT1-CCM2 interaction regulates vascular barrier function by suppressing Rho/ROCK signaling and that this pathway is dysregulated in human CCM endothelium, and they suggest that fasudil could ameliorate both CCM disease and vascular leak.

[Application of methods of renal replacement therapy for abolishment of hyperhydration in patients with decompensated chronic heart failure].

UNLABELLED: Slow continuous ultrafiltration (SCUF), continuous veno venous haemofiltration (CVVHF) are alternative to diuretics methods of treatment of patients with chronic heart failure (CHF), edematous syndrome. METHODS: Patients of both sexes aged 30-82 years with functional class II-IV CHF were included because of decompensation of CHF. Randomization: experiment - 19 patients, 3-4 component therapy plus SCUF or CVVHF; control - 3-4 component therapy plus intravenous furosemide. EXAMINATION: I ñ at baseline, II ñ after compensation of CHF. RESULTS: Delta weight (kg) - experiment -10.1+/-1.08, control -1.92+/-0.83, p=0.00001; Delta left ventricular ejection fraction - experiment +10.09+/-2.26, control +0.52+/-1.14, p=0.0007; pulmonary artery systolic pressure (mm Hg) - experiment -12.32+/-3,43, control -4.05 +/-2.07, p=0.029; Delta 6 min walk test: experiment +304.22+/-39.4, control +91.91+/-23.4, p=0.00003; Delta glomerular filtration rate - experiment -1.16+/-3.23, control +4.44+/-3.68, p=0.85; duration of hospitalization (days) - experiment 17.26+/-1.43, control 17.52+/-1.02, p=0.59. We did not observe complications related to renal replacement therapy. CONCLUSION: SCUF and CVVHF are safe for patients. In decompensated CHF SCUF and CVVHF provide greater weight reduction and fluid removal than intravenous diuretics, abolish hypervolemia what cause improvement of myocardial contractility.