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Cesare Orlandi - One of the best experts on this subject based on the ideXlab platform.
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continental differences in clinical characteristics management and outcomes in patients hospitalized with worsening heart failure results from the everest efficacy of Vasopressin antagonism in heart failure outcome study with tolvaptan program
Journal of the American College of Cardiology, 2008Co-Authors: John E A Blair, Marvin A Konstam, John C Burnett, Liliana Grinfeld, Aldo P Maggioni, Faiez Zannad, Thomas D Cook, Brian Traver, Holly B Krasa, Cesare OrlandiAbstract:Objectives Our aim was to examine continental and regional differences in baseline characteristics and post-discharge clinical outcomes in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) trial. Background Continental and regional differences in clinical trials of acute heart failure syndromes (AHFS) have not been well studied. Methods We analyzed data from the EVEREST trial, which randomized 4,133 patients hospitalized for worsening (HF) and left ventricular ejection fraction ≤40% to oral tolvaptan, a Vasopressin Antagonist, or placebo and followed for a median of 9.9 months. Baseline characteristics, mortality, and outcomes were analyzed across North America (n = 1,251), South America (n = 688), Western Europe (564 patients), and Eastern Europe (n = 1,619). Results There were major differences between the 4 groups in the severity, etiology, and management of HF. Unadjusted 1-year mortality and cardiovascular mortality/HF hospitalization were 30.4% and 52.5% in North America, 27.2% and 41.6% in South America, 27.1% and 47.3% in Western Europe, and 20.5% and 35.3% in Eastern Europe. After adjustment, South American patients had the highest overall mortality (hazard ratio: 1.42, 95% confidence interval: 1.15 to 1.76), while Eastern European patients had the lowest cardiovascular death and HF hospitalization rate (hazard ratio: 0.84, 95% confidence interval: 0.73 to 0.97), compared with patients in North America. Conclusions Major continental and regional differences in HF severity, etiology, and management exist among AHFS patients, resulting in varied post-discharge outcomes, despite pre-defined selection criteria. These differences should be taken into account when planning global trials in AHFS. (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan [EVEREST]; NCT00071331 )
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prognostic value of blood urea nitrogen in patients hospitalized with worsening heart failure insights from the acute and chronic therapeutic impact of a Vasopressin Antagonist in chronic heart failure activ in chf study
Journal of Cardiac Failure, 2007Co-Authors: Gerasimos Filippatos, Wendy Gattis Stough, John Ouyang, David D Shin, Kirkwood F. Adams, Joseph S. Rossi, Donald M Lloydjones, Christopher M Oconnor, Cesare OrlandiAbstract:Abstract Background Hospitalization for acute decompensated heart failure (ADHF) is associated with a high postdischarge mortality and readmission rate. The association between baseline blood urea nitrogen (BUN) and clinical outcomes in patients admitted for ADHF was evaluated in a post-hoc analysis of the ACTIV in CHF trial. Methods and Results Patients were categorized into quartiles according to baseline BUN. Cox proportional hazards regression was used to test the association between BUN, mortality, and death or readmission within 60 days. Patients in the highest quartile (>40 mg/dL) had the highest 60-day mortality (14.3%, 9.3%, 4.0%, 0%, respectively; P P Conclusions Higher baseline BUN is a powerful predictor of increased postdischarge mortality in patients hospitalized for heart failure, even in the absence of severe renal failure. Even mild to moderate elevations in baseline BUN were predictive. BUN remains an easily accessible risk stratification tool that physicians should closely monitor in the hospital setting.
Claude Barberis - One of the best experts on this subject based on the ideXlab platform.
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characterization of a novel linear radioiodinated Vasopressin Antagonist an excellent radioligand for Vasopressin v1a receptors
Neuroendocrinology, 1995Co-Authors: Claude Barberis, Jean Jacques Dreifuss, Maurice Manning, Marienoelle Balestre, S Jard, Eliane Tribollet, Yvan Arsenijevic, Krysztof Bankowski, Walter Y Chan, Stephan S SchlosserAbstract:We report on the pharmacological properties of a potent and selective linear Vasopressin (AVP) V1a receptor Antagonist HO-Phenylacetyl1-D-Tyr(Me)2-Phe3-Gln4-Asn5-Arg6-Pro7-Arg8-NH2 (HO-LVA). Iodinated on the phenolic substituent at position 1, [125I]-HO-LVA displayed the highest affinity for rat liver V1a receptors (8 pM) ever reported. Furthermore, affinities of HO-LVA and I-HO-LVA for V1b, V2 and oxytocin (OT) receptors was 400- to 1,000-fold lower than for V1a receptors, rendering it a highly selective ligand. Both HO-LVA and its iodinated derivative are V1 Antagonists, they potently inhibited AVP-induced inositol-phosphate accumulation in WRK1 cells, and also, although with a much lower potency, the AVP-induced ACTH release from freshly prepared pituitary cells. Using autoradiography [125I]-HO-LVA appeared to be the first radioligand to successfully identify and localize the presence of V1a receptors in rat liver and blood vessel walls. Moreover, several new brain regions expressing V1a receptors could be identified, in addition to those brain regions that were previously identified with other radiolabelled AVP analogues.
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Regional differences in testosterone effects on Vasopressin receptors and on Vasopressin immunoreactivity in intact and castrated Siberian hamsters
Brain Research, 1994Co-Authors: Michel Dubois-dauphin, Jean-marc Theler, Ali Ouarour, Paul Pévet, Claude Barberis, Jean Jacques DreifussAbstract:Abstract Vasopressin binding sites were detected in the brain of the Siberian hamster, using [ 3 H]Vasopressin and a 125 I-labelled linear Vasopressin Antagonist specific for V 1 Vasopressin receptors. In the ventromedial and remammillary nuclei, the density of the binding was lower in the females than in the males. The effect of castration and of testosterone replacement was assessed in males. Two distinct effects were observed. Orchidectomy diminished significantly the Vasopressin binding in the ventromedial nucleus, an effect which was prevented by implantation of a mini-pump releasing testosterone. On the contrary, in the premammillary nucleus no significant differences were noticed following castration and testosterone treatment. In addition, Vasopressin immunoreactivity was examined in males, in females and in castrated males. No sex differences were evident. However, in the bed nucleus of the stria terminalis and the lateral septal nucleus, castration decreased Vasopressin immunoreactivity in either sex. This effect of castration was prevented by testosterone. Vasopressin immunoreactivity was detected neither in the ventromedial nor in the premammillary hypothalamic nuclei. Our observations suggest that, in adult Siberian hamster premammillary nucleus, the expression of Vasopressin receptors is not controlled by gonadal steroids but is sex related and could be induced during fetal or early postnatal life.
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A radioiodinated linear Vasopressin Antagonist: a ligand with high affinity and specificity for V1a receptors.
FEBS letters, 1991Co-Authors: Anne Schmidt, Claude Barberis, Maurice Manning, Sylvie Audigier, Serge Jard, A. S. Kolodziejczyk, Wilbur H. SawyerAbstract:A linear Vasopressin Antagonist, Phaa-D-Tyr(Me)-Phe-Gin-Asn-Arg-Pro-Arg-Tyr-NH2 (Linear AVP Antag) (Phaa = Phenylacetyl), was monoiodinated at the phenyl moiety of the tyrosylamide residue at position 9. This Antagonist appeared to be a highly potent anti-vasopressor peptide with a pA2 value in vivo of 8.94. It was demonstrated to bind to rat liver membrane preparations with a very high affinity (Kd = 0.06 nM). The affinity for the rat uterus oxytocin receptor was lower (Ki = 2.1 nM), and affinities for the rat kidney- and adenohypophysis-Vasopressin receptors were much lower (Ki 47 nM and 92 nM, respectively), resulting in a highly specific Vasopressin V18 receptor ligand. Autoradiographical studies using rat brain slices showed that this ligand is a good tool for studies on Vasopressin receptor localization and characterization.
Rebecca Ireland - One of the best experts on this subject based on the ideXlab platform.
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Hyponatremia: Prolonged use of the Vasopressin Antagonist tolvaptan is a safe and effective treatment for hyponatremia.
Nature Reviews Nephrology, 2010Co-Authors: Rebecca IrelandAbstract:Hyponatremia: Prolonged use of the Vasopressin Antagonist tolvaptan is a safe and effective treatment for hyponatremia
Wendy Gattis Stough - One of the best experts on this subject based on the ideXlab platform.
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improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes insights from the acute and chronic therapeutic impact of a Vasopressin Antagonist in chronic heart failure activ in chf trial
Acute Cardiac Care, 2007Co-Authors: Joseph S. Rossi, Wendy Gattis Stough, John Ouyang, Kirkwood F. Adams, Melike Bayram, James E Udelson, Donald M Lloydjones, Christopher M Oconnor, David D ShinAbstract:Background: Hyponatremia predicts poor outcome in patients with acute heart failure syndromes. This study evaluated the relationship between baseline serum sodium, change in serum sodium, and 60‐day mortality in hospitalized heart failure patients. Methods: A post‐hoc analysis of the ACTIV in CHF trial was performed. ACTIV in CHF randomized 319 patients hospitalized for worsening heart failure to placebo or one of three tolvaptan doses. Cox proportional hazards regression‐analysis was used to explore the relationship between baseline hyponatremia, sodium change during the hospitalization, and 60‐day mortality. Results: Hyponatremia was observed in 69 patients (21.6%). After covariate adjustment, baseline hyponatremia was a statistically significant predictor of 60‐day mortality (P = 0.0016). Follow‐up serum sodium data were available in 68 patients. At hospital discharge, 45 of 68 (66.2%) hyponatremic patients had improvements in serum sodium levels (⩾2 mmol/l). Hyponatremic patients with a serum sodium i...
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prognostic value of blood urea nitrogen in patients hospitalized with worsening heart failure insights from the acute and chronic therapeutic impact of a Vasopressin Antagonist in chronic heart failure activ in chf study
Journal of Cardiac Failure, 2007Co-Authors: Gerasimos Filippatos, Wendy Gattis Stough, John Ouyang, David D Shin, Kirkwood F. Adams, Joseph S. Rossi, Donald M Lloydjones, Christopher M Oconnor, Cesare OrlandiAbstract:Abstract Background Hospitalization for acute decompensated heart failure (ADHF) is associated with a high postdischarge mortality and readmission rate. The association between baseline blood urea nitrogen (BUN) and clinical outcomes in patients admitted for ADHF was evaluated in a post-hoc analysis of the ACTIV in CHF trial. Methods and Results Patients were categorized into quartiles according to baseline BUN. Cox proportional hazards regression was used to test the association between BUN, mortality, and death or readmission within 60 days. Patients in the highest quartile (>40 mg/dL) had the highest 60-day mortality (14.3%, 9.3%, 4.0%, 0%, respectively; P P Conclusions Higher baseline BUN is a powerful predictor of increased postdischarge mortality in patients hospitalized for heart failure, even in the absence of severe renal failure. Even mild to moderate elevations in baseline BUN were predictive. BUN remains an easily accessible risk stratification tool that physicians should closely monitor in the hospital setting.
Marvin A Konstam - One of the best experts on this subject based on the ideXlab platform.
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weight changes after hospitalization for worsening heart failure and subsequent re hospitalization and mortality in the everest trial
European Heart Journal, 2009Co-Authors: John E A Blair, James E Udelson, Marvin A Konstam, John C Burnett, Liliana Grinfeld, Aldo P Maggioni, Karl Swedberg, Faiez Zannad, Sadiya S Khan, Christopher ZimmerAbstract:Aims Increases in body weight (BW) are important determinants for hospitalization in ambulatory patients with heart failure (HF), but have not yet been explored in patients hospitalized for worsening HF. We explore the relationship between change in BW after hospitalization for worsening HF and risk for repeat hospitalization and mortality in the EVEREST trial. Methods and results The EVEREST trial randomized 4133 patients hospitalized for worsening HF and low ejection fraction (≤40%) to tolvaptan, a Vasopressin Antagonist, or placebo. Following discharge, BW was assessed at 1, 4, and 8 weeks, and every 8 weeks thereafter. A time-dependent Cox proportional Hazard model explored the relationship between change in BW at 60, 120, and 180 days from discharge and the risks of HF hospitalization, cardiovascular (CV) hospitalization, and all-cause mortality. For subjects re-hospitalized for heart failure at 60, 120, and 180 days after discharge, mean BW increase prior to the event was 1.96, 2.07, and 1.97 kg, respectively, compared with 0.74, 0.90, and 1.04 kg in patients without re-hospitalization ( P < 0.001 all groups). A similar pattern was observed with CV hospitalization. However, increases in BW were not predictive of all-cause mortality. Conclusion Increases in BW after hospitalization for worsening HF was predictive of repeat hospitalization events, but not mortality in the post-discharge period.
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continental differences in clinical characteristics management and outcomes in patients hospitalized with worsening heart failure results from the everest efficacy of Vasopressin antagonism in heart failure outcome study with tolvaptan program
Journal of the American College of Cardiology, 2008Co-Authors: John E A Blair, Marvin A Konstam, John C Burnett, Liliana Grinfeld, Aldo P Maggioni, Faiez Zannad, Thomas D Cook, Brian Traver, Holly B Krasa, Cesare OrlandiAbstract:Objectives Our aim was to examine continental and regional differences in baseline characteristics and post-discharge clinical outcomes in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) trial. Background Continental and regional differences in clinical trials of acute heart failure syndromes (AHFS) have not been well studied. Methods We analyzed data from the EVEREST trial, which randomized 4,133 patients hospitalized for worsening (HF) and left ventricular ejection fraction ≤40% to oral tolvaptan, a Vasopressin Antagonist, or placebo and followed for a median of 9.9 months. Baseline characteristics, mortality, and outcomes were analyzed across North America (n = 1,251), South America (n = 688), Western Europe (564 patients), and Eastern Europe (n = 1,619). Results There were major differences between the 4 groups in the severity, etiology, and management of HF. Unadjusted 1-year mortality and cardiovascular mortality/HF hospitalization were 30.4% and 52.5% in North America, 27.2% and 41.6% in South America, 27.1% and 47.3% in Western Europe, and 20.5% and 35.3% in Eastern Europe. After adjustment, South American patients had the highest overall mortality (hazard ratio: 1.42, 95% confidence interval: 1.15 to 1.76), while Eastern European patients had the lowest cardiovascular death and HF hospitalization rate (hazard ratio: 0.84, 95% confidence interval: 0.73 to 0.97), compared with patients in North America. Conclusions Major continental and regional differences in HF severity, etiology, and management exist among AHFS patients, resulting in varied post-discharge outcomes, despite pre-defined selection criteria. These differences should be taken into account when planning global trials in AHFS. (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan [EVEREST]; NCT00071331 )
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short term clinical effects of tolvaptan an oral Vasopressin Antagonist in patients hospitalized for heart failure the everest clinical status trials
JAMA, 2007Co-Authors: Mihai Gheorghiade, James E Udelson, Marvin A Konstam, John C Burnett, Liliana Grinfeld, Aldo P Maggioni, Karl Swedberg, Faiez Zannad, Thomas D Cook, John OuyangAbstract:ContextHeart failure causes more than 1 million US hospitalizations yearly, mostly related to congestion. Tolvaptan, an oral, nonpeptide, selective Vasopressin V2-receptor Antagonist, shows promise in this condition.ObjectiveTo evaluate short-term effects of tolvaptan when added to standard therapy in patients hospitalized with heart failure.Design, Setting, and PatientsTwo identical prospective, randomized, double-blind, placebo-controlled trials at 359 sites in North America, South America, and Europe were conducted during the inpatient period of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) between October 7, 2003, and February 3, 2006. A total of 2048 (trial A) and 2085 (trial B) patients hospitalized with heart failure and congestion were studied.InterventionPatients were randomized to receive either tolvaptan (30 mg/d) or matching placebo, within 48 hours of admission.Main Outcome MeasuresPrimary end point was a composite of changes in global clinical status based on a visual analog scale and body weight at day 7 or discharge if earlier. Secondary end points included dyspnea (day 1), global clinical status (day 7 or discharge), body weight (days 1 and 7 or discharge), and peripheral edema (day 7 or discharge).ResultsRank sum analysis of the composite primary end point showed greater improvement with tolvaptan vs placebo (trial A, mean [SD], 1.06 [0.43] vs 0.99 [0.44]; and trial B, 1.07 [0.42] vs 0.97 [0.43]; both trials P<.001). Mean (SD) body weight reduction was greater with tolvaptan on day 1 (trial A, 1.71 [1.80] vs 0.99 [1.83] kg; P<.001; and trial B, 1.82 [2.01] vs 0.95 [1.85] kg; P<.001) and day 7 or discharge (trial A, 3.35 [3.27] vs 2.73 [3.34] kg; P<.001; and trial B, 3.77 [3.59] vs 2.79 [3.46] kg; P<.001), whereas improvements in global clinical status were not different between groups. More patients receiving tolvaptan (684 [76.7%] and 678 [72.1%] for trial A and trial B, respectively) vs patients receiving placebo (646 [70.6%] and 597 [65.3%], respectively) reported improvement in dyspnea at day 1 (both trials P<.001). Edema at day 7 or discharge improved significantly with tolvaptan in trial B (P = .02) but did not reach significance in trial A (P = .07). Serious adverse event frequencies were similar between groups, without excess renal failure or hypotension.ConclusionIn patients hospitalized with heart failure, oral tolvaptan in addition to standard therapy including diuretics improved many, though not all, heart failure signs and symptoms, without serious adverse events.Trial Registrationclinicaltrials.gov Identifier: NCT00071331Published online March 25, 2007 (doi:10.1001/jama.297.12.1332).