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Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study

Applicant Mueller Christian
Number 127005
Funding scheme Project funding (Div. I-III)
Research institution Abteilung für Allgemeine Innere Medizin Medizinische Universitätsklinik A Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Internal Medicine
Start/End 01.01.2010 - 31.12.2011
Approved amount 220'666.00
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All Disciplines (2)

Discipline
Internal Medicine
Clinical Cardiovascular Research

Keywords (2)

Acute heart failure treatment;

Lay Summary (English)

Lead
Lay summary
Heart failure is a common and unfortunately very severe disease. The main symptom of heart failure is dyspnea. When heart failure deteriorates and the severity of dyspnea increases to an extent that it is present not only during regular daily exercise but also at rest, patients are admitted to the hospital. This episode is then called acute heart failure.In contrast to the treatment of stable chronic heart failure, the treatment of patients with acute heart failure has not improved over the last decades. Therefore, for patients with acute heart failure the risk of dying or being readmitted for another episode of acute heart failure within the next months is still extremely high. Previous studies have focused on the evaluation of novel drugs. Unfortunately, none of these new drugs provided a clinical relevant benefit, some in fact resulted in worse outcome. In our study we pursue a fundamentally different approach. We investigate the potential of a novel strategy, not a novel drug. This strategy aims for a maximal unloading of the heart during the in-hospital period. For this unloading we use the same drugs (e.g. nitrates) as used since decades, but apply them in much higher concentrations. Our international randomized controlled multicenter study examines whether this novel strategy is safe and whether this strategy reduces the risk of dying or being readmitted for acute heart failure. If in fact our results are positive, this study and thereby our strategy of maximal unloading of the heart would be the first in the world to show how to improve outcome in acute heart failure patients.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Association Between Elevated Blood Glucose and Outcome in Acute Heart Failure: Results From an International Observational Cohort
Mebazaa A Gayat E Lassus J Meas T Mueller C Maggioni A Peacock F Spinar J Harjola VP van Ki (2013), Association Between Elevated Blood Glucose and Outcome in Acute Heart Failure: Results From an International Observational Cohort, in J Am Coll Cardiol, 61(8), 820-829.
Incremental value of biomarkers to clinical variables for mortality
Lassus J Gayat E Mueller C Peacock F Harjola VP van Kimmenade R Mueller T Disomma S Pascual- (2013), Incremental value of biomarkers to clinical variables for mortality, in Int J Cardiol, 168, 2186-2194.
Pathophysiology of lower extremity edema in acute heart failure revisited
Breidthardt T Irfan A Klima T Drexler B Balmelli C Arenja N Socrates T Ringger R Heinisch C (2012), Pathophysiology of lower extremity edema in acute heart failure revisited, in Am J Med, 125(11), 1124.e1-1124.e8.
Plasma Neutrophil Gelatinase-Associated Lipocalin for the Prediction of Acute Kidney Injury in Acute Heart Failure
Breidthardt T et al (2012), Plasma Neutrophil Gelatinase-Associated Lipocalin for the Prediction of Acute Kidney Injury in Acute Heart Failure, in Critical Care, 2012 Jan 7;16(1):R2, 1-10.
Quantifying cardiac hemodynamic stress and cardiomyocyte damage in ischemic and nonischemic acute heart failure
Drexler B et al. (2012), Quantifying cardiac hemodynamic stress and cardiomyocyte damage in ischemic and nonischemic acute heart failure, in Circulation Heart Failure, 2012 Jan 1;5(1):17-24. Epub 2011 Oct 5, 17-24.
The novel marker LTBP2 powerfully predicts all-cause and pulmonary death in patients with acute dyspnea
Breidthardt T Vanpoucke G Mosimann T Potocki M Ziller R Thomas G Laroy W Moerman P Verleysen (2012), The novel marker LTBP2 powerfully predicts all-cause and pulmonary death in patients with acute dyspnea, in Clin Science , 123(9), 557-566.
Unbiased plasma proteomics for novel diagnostic biomarkers in cardiovascular disease: identification of QSOX1 as a candidate biomarker of acutely decompensated heart failure
Mebazaa A Vanpoucke G Thomas G Verleysen K Cohen Solal A Vanderheyden M Bartunek J Mueller C (2012), Unbiased plasma proteomics for novel diagnostic biomarkers in cardiovascular disease: identification of QSOX1 as a candidate biomarker of acutely decompensated heart failure, in Eur Heart J, 33(18), 2317-2324.
Risk Stratification for 1-Year Mortality in Acute Heart Failure: Classification and Regression Tree Analysis.
Arenja N et al. (2011), Risk Stratification for 1-Year Mortality in Acute Heart Failure: Classification and Regression Tree Analysis., in Swiss Medical Weekly, 2011 Oct 9;141, 1-10.
Sensitive Cardiac Troponin in the Diagnosis and Risk Stratification of Acute Heart Failure
Arenja N et al. (2011), Sensitive Cardiac Troponin in the Diagnosis and Risk Stratification of Acute Heart Failure, in Journal of Internal Medicine, 2011; Oct 11. doi: 10.1111/j.1365-2796.2011.02469., 1-10.
Natriuretic peptide-guided therapy by the GP: how to interpret the signal
Drexler B et al. (2010), Natriuretic peptide-guided therapy by the GP: how to interpret the signal, in European Journal of Heart FAilure, 2010;12:1265-7., 1265-1267.
Novelties in the early management of acute heart failure syndromes
Salem R et al. (2010), Novelties in the early management of acute heart failure syndromes, in Swiss Medical Weekly, Jul 22;140:w13031. doi: 10.4414/smw.2010.13031., 1-7.

Awards

Title Year
Wissenschaftliche Aufsteigerin des Jahres 2011, KLinik für Innere Medizin, Universitätsspital Basel 2012

Associated projects

Number Title Start Funding scheme
135434 Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE) Study 01.04.2011 Project funding (Div. I-III)

Abstract

Background: In contrast to treatment for chronic HF, which is based on several large prospective randomized controlled trials, treatment for acute HF is largely based on uncontrolled studies, clinical experience and expert opinion. Perhaps at least in part related to the uncertainties in the treatment of acute HF, outcome of patients with acute HF is extremely poor. Mortality is 50% at 3 years. More than 85% of patients with acute HF are treated in the non-ICU/CCU setting -the ED and the regular medical ward. Unfortunately, appropriate treatment is particularly ill-defined in this setting. Aim: To test the hypothesis that a comprehensive approach using an early goal-directed decrement of preload and afterload with a target systolic blood pressure of 90-110 mmHg by aggressive vasodilatation in patients with acute HF in the non-ICU setting is safe, and leads to a better clinical and economical outcome.Methodology: This is a prospective, randomised controlled multicenter study designed to enrol 770 patients presenting with acute HF to the emergency department. Patients are enrolled at the University Hospital Basel, the Kantonsspital Luzern, the Kantonsspital Aarau, the University Hospital Zürich, the Kantonsspital Olten, and the Hôpital cantonal de Fribourg the University Hospital Zürich, the University Hospital Geneve, and the University Hospital Lausanne. Patients will be randomly assigned 1:1 after stratification for site and BNP levels to an early goal-directed therapy or standard care according to current ESC guidelines. Early goal-directed therapy applies aggressive vasodilatation using sublingual and transdermal nitrates, hydralazine to avoid tolerance to nitrates, and rapid up-titration of ACE-inhibitors and angiotensin receptor blockers with a target systolic blood pressure of 90-110 mmHg. Timing and dosing of diuretics and all other treatments are left to the discretion of the physician in both groups. The primary end point is death or HF readmission within 180 days. Secondary end points include the quantitative assessment of dyspnea, need for admission to the intensive care unit, surrogate markers like BNP, the digitally recorded third heart sound, renal function, time to discharge, functional status and quality of life, falls, total treatment cost, and cost-effectiveness. Patients will receive extensive clinical and economic follow-up of at least 360 days. End points will be adjudicated by a clinical end point committee blinded to group assignment.Potential significance: It is our hypothesis that a comprehensive approach using an early goal-directed therapy has the potential to more rapidly improve dyspnea, to more rapidly and more extensively reduce HF disease severity as quantified by BNP levels, and most importantly to reduce the occurrence of death and HF readmission. Due to the high cost associated with hospitalisations for HF, our study has the potential to define a novel treatment strategy that might also significantly reduce the treatment cost associated with acute HF.
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