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      Dyspnoea and worsening heart failure in patients with acute heart failure: results from the Pre-RELAX-AHF study

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          Abstract

          Aims

          Although dyspnoea is the most common cause of admission for acute heart failure (AHF), more needs to be known about its clinical course and prognostic significance.

          Methods and results

          The Pre-RELAX-AHF study randomized 232 subjects with AHF to placebo or four doses of relaxin and evaluated early (6–24 h Likert scale) and persistent [change in visual analogue scale area under the curve (VAS AUC) through Day 5] dyspnoea relief. Worsening heart failure (WHF) was defined as worsening AHF signs and symptoms requiring additional therapy. Patients were followed until Day 180. Early dyspnoea relief was observed in only 25% of all patients, and VAS AUC at 5 days was 45% over baseline values in all patients (32% placebo; 50% all relaxin-treated patients). Worsening heart failure to Day 5 was observed in 16% of all patients (21% placebo; 14% relaxin). Lack of persistent dyspnoea relief and WHF were associated with a longer length of initial hospital stay and worse 60-day outcomes.

          Conclusion

          Dyspnoea relief in patients admitted with AHF is often incomplete, and many may show WHF after the initial stabilization. Both lack of persistent dyspnoea relief and in-hospital WHF predict a longer length of stay and worse outcome.

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          Most cited references28

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          ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).

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            Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database.

            Approximately 50% of patients hospitalized for heart failure have preserved systolic function. These patients are more likely to be older, women, and hypertensive. Their duration of hospitalization is similar to that of heart failure patients with systolic dysfunction, but their in-hospital mortality risk is lower. This mortality risk is increased in the setting of renal insufficiency, and the two most important risk predictors are elevated blood urea nitrogen and systolic blood pressure 100,000 hospitalizations from the Acute Decompensated Heart Failure National Registry (ADHERE) database were analyzed. Heart failure with PSF was present in 50.4% of patients with in-hospital assessment of left ventricular function. When compared with patients with systolic dysfunction, patients with PSF were more likely to be older, women, and hypertensive and less likely to have had a prior myocardial infarction or be receiving an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. In-hospital mortality was lower in patients with PSF compared with patients with systolic dysfunction (2.8% vs. 3.9%; adjusted odds ratio [OR]: 0.86; p = 0.005), but duration of intensive care unit stay and total hospital length of stay were similar. Serum creatinine >2 mg/dl was associated with increased in-hospital mortality in both systolic function groups (PSF: 4.8%; systolic dysfunction: 8.4%; p 37 mg/dl (OR: 2.53; 95% confidence interval [CI]: 2.22 to 2.87) and systolic blood pressure < or =125 mm Hg (OR: 2.58; 95% CI: 2.33 to 2.86). Heart failure with PSF is common and is characterized by a unique patient profile. Event rates are worrisome and reflect a need for more effective management strategies.
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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.

              Heart 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. To evaluate short-term effects of tolvaptan when added to standard therapy in patients hospitalized with heart failure. Two 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. Patients were randomized to receive either tolvaptan (30 mg/d) or matching placebo, within 48 hours of admission. Primary 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). Rank 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. In 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. clinicaltrials.gov Identifier: NCT00071331
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                Author and article information

                Journal
                Eur J Heart Fail
                eurjhf
                eurjhf
                European Journal of Heart Failure
                Oxford University Press
                1388-9842
                1879-0844
                October 2010
                22 August 2010
                22 August 2010
                : 12
                : 10
                : 1130-1139
                Affiliations
                [1 ]Cardiology, Department of Experimental and Applied Medicine, simpleUniversity of Brescia , Brescia, Italy
                [2 ]Division of Cardiology, simpleUniversity of California , San Francisco, CA, USA
                [3 ]Duke Clinical Research Institute, Durham, NC, USA
                [4 ]simpleUniversity of California, San Diego Medical Center , San Diego, CA, USA
                [5 ]simpleAthens University Hospital , Athens, Greece
                [6 ]Department of Heart Diseases, simpleMedical University , Clinical Military Hospital, Wrocław, Poland
                [7 ]Corthera, Inc. (part of Novartis Pharmaceutical Corp.), San Carlos, CA, USA
                [8 ]simpleUniversity Medical Center Groningen , Groningen, Netherlands
                [9 ]Momentum Research Inc., Durham, NC, USA
                Author notes
                [* ]Corresponding author. Tel: +39 030 3995572, Fax: +39 030 3700359, Email: metramarco@ 123456libero.it
                Article
                hfq132
                10.1093/eurjhf/hfq132
                2944016
                20732868
                fff6ebb7-61e3-41be-a51c-a32f727c6884
                Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2010. For permissions please email: journals.permissions@oxfordjournals.org.

                The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

                History
                : 6 February 2010
                : 23 April 2010
                : 4 May 2010
                Categories
                Clinical Trial

                Cardiovascular Medicine
                prognosis,dyspnoea,relaxin,acute heart failure
                Cardiovascular Medicine
                prognosis, dyspnoea, relaxin, acute heart failure

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