Heart failure : biomarker effect and influence on quality of life

Abstract: 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.