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- Karlström, Patric
(författare)
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Heart failure : biomarker effect and influence on quality of life
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 2. |
- Ostrowska, Bozena
(författare)
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Risk factors for incident heart failure and atrial fibrillation in an elderly population : The role of cardiac conduction and heart rate variability
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Heart failure (HF) and atrial fibrillation (AF) are epidemic diseases, frequently coexisting, sharing risk factors and conferring poor prognosis. Identification of individuals at high risk of HF and AF may enable early treatment and improve the prognosis. Reliable prediction models for daily clinical practice are lacking. Early modification and treatment of risk factors may reduce the incidence of AF and HF. Because atrial structure and function abnormalities increase the risk of AF, ECG indices reflecting atrial pathology may prove useful in predicting AF and HF.The main objectives were to evaluate whether:P-wave duration (Pdur) and PR-interval in V1 predicted incident HF and incident AF (Paper I-II)low frequency/high frequency (L-F/H-F) ratio, a marker of autonomic balance, predicted incident HF (Paper IV)combining selected ECG variables or the L-F/H-F ratio with traditional risk factors improved the performance of the traditional HF prediction model (Paper III-IV).The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) with 15 years of follow-up was used for all four studies. After applying the exclusion criteria, 836 subjects were evaluated for incident HF (Paper I, III-IV) and 877 subjects for incident AF (Paper II). Cox proportional hazard analysis related ECG-derived variables to incident HF and incident AF. Study III used machine learning to determine which ECG variables correlated to incident HF. C-statistic was used to test whether adding selected ECG variables to traditional HF risk factors improved the performance of the HF prediction model.Short Pdur was significantly associated with incident HF (Paper I) and incident AF (Paper II). Of 134 ECG variables, high R-wave amplitude variation (SD Ramp) had the highest predictive value for HF (Paper III). A decreased L-F/H-F ratio significantly predicted HF (Paper IV). Adding eight selected ECG variables (Paper III) and the L-F/H-F ratio (Paper IV) to the traditional risk factors significantly improved HF predictive performance by 11.7% and 3.3%, respectively.In conclusion, the ECG may prove useful for predicting incident HF and AF beyond the traditional risk factors. An autonomic imbalance may precede the development of HF.
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