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Item Plasma soluble fms-like tyrosine kinase-1, placental growth factor, and vascular endothelial growth factor system gene variants as predictors of survival in heart failure.(John Wiley and Sons Ltd on behalf of European Society of Cardiology, 2024-07-09) Paterson MA; Pilbrow AP; Frampton CM; Cameron VA; Troughton RW; Pemberton CJ; Lund M; Devlin GP; Richards AM; Doughty RN; Palmer BRAims Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), components of the vascular endothelial growth factor (VEGF) system, play key roles in angiogenesis. Reports of elevated plasma levels of sFlt-1 and PlGF in coronary heart disease and heart failure (HF) led us to investigate their utility, and VEGF system gene single nucleotide polymorphisms (SNPs), as prognostic biomarkers in HF. Methods and results ELISA assays for sFlt-1, PlGF and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed on baseline plasma samples from the PEOPLE cohort (n = 890), a study of outcomes among patients after an episode of acute decompensated HF. Eight SNPs potentially associated with sFlt-1 or PlGF levels were genotyped. sFlt-1 and PlGF were assayed in 201 subjects from the Canterbury Healthy Volunteers Study (CHVS) matched to PEOPLE participants. All-cause death was the major endpoint for clinical outcome considered. In PEOPLE participants, mean plasma levels for both sFlt-1 (125 ± 2.01 pg/ml) and PlGF (17.5 ± 0.21 pg/ml) were higher (both p < 0.044) than in the CHVS cohort (81.2 ± 1.31 pg/ml and 15.5 ± 0.32 pg/ml, respectively). sFlt-1 was higher in HF with reduced ejection fraction compared to HF with preserved ejection fraction (p = 0.005). The PGF gene SNP rs2268616 was univariately associated with death (p = 0.016), and was also associated with PlGF levels, as was rs2268614 genotype. Cox proportional hazards modelling (n = 695, 246 deaths) showed plasma sFlt-1, but not PlGF, predicted survival (hazard ratio 6.44, 95% confidence interval 2.57–16.1; p < 0.001) in PEOPLE, independent of age, NT-proBNP, ischaemic aetiology, diabetic status and beta-blocker therapy. Conclusions Plasma sFlt-1 concentrations have potential as an independent predictor of survival and may be complementary to established prognostic biomarkers in HF.Item Heart failure is independently associated with white matter lesions: insights from the population-based LIFE-Adult Study(John Wiley and Sons Ltd on behalf of European Society of Cardiology, 2021-02) Stegmann T; Chu ML; Witte VA; Villringer A; Kumral D; Riedel-Heller SG; Roehr S; Hagendorff A; Laufs U; Loeffler M; Wachter R; Zeynalova SAims White matter lesions (WML) are common structural alterations in the white matter of the brain and their prevalence increases with age. They are associated with cerebral ischaemia and cognitive dysfunction. Patients with heart failure (HF) are at risk for cognitive decline. We hypothesized that the presence and duration of HF are associated with WML. Methods and results The LIFE-Adult Study is a population-based study of 10 000 residents of Leipzig, Germany. WML were quantitated in 2490 participants who additionally underwent cerebral MRI using the Fazekas score. Mean age was 64 years, and 46% were female; 2156 (86.6%) subjects had Fazekas score of 0–1, and 334 (13.4%) had Fazekas score of 2–3. Thirty participants had a medical history of HF, 1019 had hypertension, and 51 had a history of stroke. Median left ventricular ejection fraction of the participants with HF was 57% (interquartile ranges 54–62). Age, troponin T, NT-proBNP, body mass index, history of acute myocardial infarction, stroke, HF, and diabetes were positively associated with WML in univariate analysis. On multivariate analysis, age, hypertension, stroke, and HF were independently associated with WML. The odd's ratio for the association of WML (Fazekas 2–3) with HF was 2.8 (95% CI 1.2–6.5; P = 0.019). WML increased with longer duration of HF (P = 0.036 for trend). Conclusions In addition to age, hypertension, and stroke, the prevalence and duration of HF are independently associated with WML. This observation sets the stage to investigate the prognostic value of WML in HF and the impact of HF therapies on WML.Item Mathematical modelling of the cardiovascular system to study the effects of respiratory sinus arrhythmia and heart failure : this dissertation is submitted for the degree of Doctor of Philosophy, School of Natural and Computational Science, Massey University(Massey University, 2021) Noreen, ShumailaThis thesis presents the development of lumped parameter models of the cardiovascular system with a specific aim of simulating the system dynamics over a range of heart rates. The models contain several new modelling features that have been introduced progressively throughout the thesis starting with isolated models and continuing with closed loop models of the circulation. Specifically, the contraction of the cardiac chambers is modelled using a time-dependent muscle force with constant elasticity instead of time dependent elasticity. A new hypothesis about the mechanical contraction of the atria generates realistic pressure volume loops. The inter-ventricular interaction is modelled as well. Additionally, hysteresis is incorporated in the aortic valve to produce an end-systolic reverse (negative) flow. Most of the model parameters were taken from the literature and experimental data. Sensitivity analysis was performed on one of the models outputs by changing one parameter at a time; this analysis indicated that the total blood volume is the most influential parameter in the model. The developed models were used to study the effects of Respiratory Sinus Arrhythmia (RSA), variability in heart rate at the frequency of breathing. RSA is an indicator of good health but the mechanism that gives rise to RSA and its function are still debatable. Two potential sources of RSA were incorporated: periodic heart rate that mimics the central regulation of heart rate which originates in the brainstem, and periodic systemic veins resistance that mimics one possible effect of the pleural pressure which drives breathing. The effects of RSA on cardiac output were then studied. The simulations suggest that the mean cardiac output does not change significantly due to RSA at either low or high heart rates. Two types of heart failure were simulated using the new models by changing certain model parameters: systolic and diastolic. Both the systolic and diastolic heart failures caused an accumulation of blood in the lungs. The ejection fraction for diastolic heart failure remained within the normal physiological range while in the case of systolic heart failure the ejection fraction reduced rapidly. These results are consistent with physiological observations.Item Information gaps : a group perspective on the management of heart failure : a thesis presented in partial requirements [sic] for the degree of Master of Philosophy, Massey University(Massey University, 2000) Reed, SusanHeart failure is a complex condition that incurs considerable socio-economic burden, and poor prognosis. Careful management of the syndrome is required if a patient is to have a reasonable quality of life. Health professionals generally acknowledge that there is a need to improve care of patients with heart failure and that there are treatment gaps between the recommended therapies, and the care patients are actually receiving. This pilot study used the grounded theory approach to discover the main concerns, and how they are continually resolved, of a group that manage heart failure. It is argued that information gaps are present in the management of heart failure. It was demonstrated that when there is an absence of a cohesive group, occurring under conditions of changing funding structures within the context of boundaries merging, it is often necessary to alert others. The alerting of others is how the group continually resolve the information gaps. However, when people are not alerted, are left out of the loop, poor symptom management is more likely to occur, and information gaps are perpetuated. The loop in this study is comprised of information relating to heart failure and the members who both send and receive it. Indeed, if the loop is able to be activated so that people are in the loop information is shared and the chances for better heart failure management are more likely. The impact of effective heart failure management for the patients means that although heart failure as a chronic disease is limiting, it is still possible in many cases, to improve quality of life and longevity. The findings of this study also suggest that there is a need for nurses as health professionals to move towards ways to reduce information gaps and improve access to information, and it is suggested that case management and information systems are the ways to do so.