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Responder to BNP-guided treatment in heart failure. The process of defining a responder.
Department of Medicine , Division of Cardiology, County Hospital Ryhov , Jönköping , Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.ORCID iD: 0000-0001-6353-8041
Research unit Skellefteå Department of Medicine , Institution of Public Health and Clinical Medicine, Umeå University Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
2015 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 49, no 6, 316-324 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: B-type natriuretic peptide (BNP) levels predict prognosis and outcome in heart failure (HF) patients. To evaluate the optimal cut-off level of BNP to predict death, need for hospitalization, and worsening HF, and also to determine the optimal time to apply the chosen cut-off value.

DESIGN: In a sub-study from the Use of PeptideS in Tailoring hEart failure Project or UPSTEP study where tailoring treatment of HF by BNP level was evaluated, we assessed the change in percentage between levels of BNP at study start versus a specific week (2, 6, 10, 16, 24, 36, or 48) during the follow-up period.

RESULTS: The optimum cut-off percentage levels were obtained using a Cox proportional regression analysis of death, hospitalization, and worsening HF. A decrease in BNP by less than 40% in week 16 compared with study start and/or a BNP > 300 ng/L presented the highest hazard ratio (HR) for a non-responder to reach a combined endpoint (HR: 2.43; 95% confidence interval or CI: 1.61-3.65; p < 0.00003). This definition gave a 78% risk reduction of cardiovascular (CV) mortality (p > 0.0005) and an 89% risk reduction of HF mortality (p > 0.004), and reduced risk of CV and HF hospitalization for the responders.

CONCLUSIONS: Patients with a decrease in BNP of more than 40% compared with that at study start and/or a BNP level below 300 ng/L at week 16 had a significantly reduced risk of CV and HF mortality and hospitalization.

Place, publisher, year, edition, pages
2015. Vol. 49, no 6, 316-324 p.
Keyword [en]
BNP; heart failure; natriuretic peptides; responder; treatment
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:liu:diva-123450DOI: 10.3109/14017431.2015.1070961ISI: 000369893500003PubMedID: 26153427OAI: oai:DiVA.org:liu-123450DiVA: diva2:884880
Note

Funding agencies: Linnaeus University, Sweden

Available from: 2015-12-17 Created: 2015-12-17 Last updated: 2016-04-24Bibliographically approved
In thesis
1. Heart failure: biomarker effect and influence on quality of life
Open this publication in new window or tab >>Heart failure: biomarker effect and influence on quality of life
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background and aims: Heart failure (HF) is a life threatening condition and optimal handling is necessary to reduce risk of therapy failure. The aims of this thesis were: (Paper I) to examine whether BNP (B-type natriuretic peptide)-guided HF treatment improves morbidity and mortality when compared with HF therapy implemented by a treating physician at sites experienced in managing patients with HF according to guidelines; (Paper II) to investigate how to define a responder regarding optimal cut-off level of BNP to predict death, need for hospitalisation, and worsening HF and to determine the optimal time to apply the chosen cut-off value; (Paper III) to evaluate how Health-Related Quality of Life (HR-QoL) is influenced by natriuretic peptide guiding and to study how HR-QoL is affected in responders compared to non-responders; (Paper IV) to evaluate the impact of patient age on clinical outcomes, and to evaluate the impact of duration of the HF disease on outcomes and the impact of age and HF duration on BNP concentration.

Methods: A randomized, parallel group, multi-centre study was undertaken on 279 patients with HF and who had experienced an episode of worsening HF with increased BNP concentration. The control group (n=132) was treated according to HF guidelines and in the BNP-guided group (n=147) the HF treatment algorithm goal was to reduce BNP concentration to < 150 ng/L in patients < 75 years and <300 ng/L in patients > 75 years (Paper I), and to define the optimal percentage decrease in BNP and at what point during the follow-up to apply the definition (Paper II). To compare the BNP-guided group with the conventional HF treated group (Paper I), and responders and non-responders (Paper II) regarding HR-QoL measured with Short Form 36 (SF-36) at study start and at study end (Paper III) and to evaluate if age or HF duration influenced the HF outcomes and the influence of BNP on age and HF duration (Paper IV).

Results: The primary outcome (mortality, hospitalisation and worsening HF) was not improved by BNP-guided HF treatment compared to conventional HF treatment or in any of the secondary outcome variables (Paper I). Applying a BNP decrease of at least 40 percent in week 16 (compared to study start) and/or a BNP<300 ng/L demonstrated the best risk reduction for cardiovascular mortality, by 78 percent and 89 percent respectively for HF mortality (Paper II). The HR-QoL improved in four domains in the BNP-guided group and in the control group in six of eight domains; however there were no significant differences between the groups (Paper III). For responders the within group analysis showed improvement in four domains compared to the non-responders that improved in one domain; however there were no significant differences between the two groups. There were improvements in HR-QoL in all four groups (Paper III). Age did not influence outcome but HF duration did. HF duration was divided into three groups: HF duration less than 1 year (group 1), 1-5 years (group 2) and >5 years (group 3). A 1.65-fold increased risk could be demonstrated in those with HF duration of more than five years compared to patients with short HF duration. The BNP concentration was increased with increased age, and there was a better response regarding BNP decrease in NP-guiding in patients with short HF duration, independent of age (Paper IV).

Conclusions: There were no significant differences between BNP-guided HF treatment group and the group with conventional HF treatment as regards mortality, hospitalisation or HR-QoL. The responders to HF treatment showed a significantly better outcome in mortality and hospitalisation compared to non-responders but no significant differences in HR-QoL. The duration of HF might be an important factor to consider in HF treatment by BNP-guiding in the future.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 123 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1499
Keyword
Heart failure, Biomarker, B-type natriuretic peptide, Heart failure treatment, B-type Natriuretic Peptide guided heart failure treatment, Responders, Health-related quality of life, Heart failure duration, Outcomes
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-124560 (URN)10.3384/diss.diva-124560 (DOI)978-91-7685-869-1 (Print) (ISBN)
Public defence
2016-03-04, Belladonna, Campus US, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Funder
Swedish Heart Lung Foundation
Available from: 2016-02-03 Created: 2016-02-03 Last updated: 2016-02-09Bibliographically approved

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Dahlström, UlfAlehagen, Urban
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Division of Cardiovascular MedicineFaculty of Medicine and Health SciencesDepartment of Cardiology in LinköpingDepartment of Cardiology in Linköping
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