BackgroundSeveral studies suggest that circulating biomarkers of myocardial fibrosis are associated with worse prognosis in subjects with atrial fibrillation (AF). Here, we aimed to explore associations between fibrosis biomarkers, prevalent AF, and left atrial volume (LAV) enlargement in subjects with heart failure (HF). Additionally, we evaluated the prognostic impact of fibrotic biomarkers in HF with co-existing AF.Materials and methodsPatients hospitalized for HF (n = 316, mean age 75 years; 30% women) were screened for AF. Seven proteins previously associated with myocardial fibrosis [metalloproteinase inhibitor 4 (TIMP-4), suppression of tumorigenicity 2 (ST-2), galectin-3 (GAL-3), growth/differentiation factor-15 (GDF-15), and matrix metalloproteinase 2, 3, and 9 (MMP-3, MMP-3, and MMP-9, respectively)] were analyzed using a proximity extension assay. Proteins with significant Bonferroni-corrected associations with mortality and re-hospitalization risk were taken forward to multivariable Cox regression analyses. Further, Bonferroni-corrected multivariable logistic regression models were used to study associations between protein plasma levels, prevalent AF, and severely enlarged left atrial volume index (LAVI ≥ 48 ml/m2).ResultsPrevalent AF was observed in 194 patients at the hospitalization of whom 178 (92%) were re-hospitalized and 111 (57%) died during the follow-up period. In multivariable logistic regression models, increased plasma levels of TIMP-4, GDF-15, and ST-2 were associated with the prevalence of AF, whereas none of the seven proteins showed any significant association with severely enlarged LAVI. Increased plasma levels of five proteins yielded significant associations with all-cause mortality in patients with co-existing AF; TIMP-4 (HR 1.33; CI95% 1.07–1.66; p = 0.010), GDF-15 (HR 1.30; CI95% 1.05–1.62; p = 0.017), GAL-3 (HR 1.29; CI95% 1.03–1.61; p = 0.029), ST-2 (HR 1.48; CI95% 1.18–1.85; p < 0.001), and MMP-3 (HR 1.33; CI95% 1.09–1.63; p = 0.006). None of the proteins showed any significant association with re-hospitalization risk.ConclusionIn this study, we were able to demonstrate that elevated levels of three plasma proteins previously linked to myocardial fibrosis are associated with prevalent AF in a HF population. Additionally, higher levels of five plasma proteins yielded an increased risk of mortality in the HF population with or without co-existing AF.

Background The cross-sectional relationship between heart failure (HF) and cerebral oxygenation has been studied in the past but the prognostic significance of this relationship has been limited. Here, we aimed to assess the role of cerebral tissue oxygen saturation (SctO2) as a risk factor for HF mortality and rehospitalization as well as evaluate the association between SctO2 with physical activity in a Swedish prospective HF cohort. Methods Ninety-five patients hospitalized for HF (mean age 70 years; 21% women) were examined with near-infrared spectroscopy (NIRS) and screened for physical activity derived from questionnaires in the Swedish national public health survey. The median follow-up time to death and re-hospitalization was 1377 (interquartile range, 245–2392) and 293 (14–2363) days, respectively. Associations between SctO2 at rest, post-discharge mortality and re-hospitalization were analyzed using multivariable Cox regression analysis adjusted for age, sex, body-mass index, smoking, prevalence of atrial fibrillation, prevalence of diabetes and systolic blood pressure. The associations between SctO2 and self-reported physical activity were explored by using logistic regression analysis adjusted for the aforementioned risk factors. Results A total of 25 patients (26%) reported to be engaged in physical activity less than one hour throughout the week. In the fully adjusted Cox regression model, low SctO2 at rest was associated with post-discharge mortality (HR, 0.77; CI, 0.66–0.91; p=0.002). However, low SctO2 was not associated with post-discharge rehospitalization risk (HR, 0.94; CI, 0.88–1.01; p=0.092). In the fully adjusted logistic regression models, low SctO2 at rest was associated with decreased physical activity (<1h per week), (OR 1.22; CI, 1.05–1.42; p=0.01). Conclusion We have demonstrated that low cerebral tissue oxygen saturation at rest is associated with post-discharge mortality in patients hospitalized for HF, independently of traditional risk factors. In addition, low cerebral tissue oxygen saturation at rest is associated with low physical activity. These findings highlight the role of cerebral saturation as a risk factor for cardiovascular prognosis, as well as underline the potential importance of taking cerebral perfusion into account when treating for heart failure. Funding Acknowledgement Type of funding sources: None.

Introduction: Several studies suggest that cardiac rehabilitation through physical exercise could reduce heart failure (HF) morbidity and mortality. Hypothesis: Here, we aimed to evaluate the association of physical activity with plasma levels of 92 proteins associated with cardiovascular disease (CVD) as well as risk of re-hospitalization and mortality in patients hospitalized for HF. Methods: Four-hundred-and-thirty-three patients hospitalized for HF (mean age 75 years; 32% women) were screened for physical activity derived from questionnaires in the Swedish national public health survey. The median follow-up time to death and re-hospitalization was 842 (IQR, 390-1433) and 155 (IQR, 42-583) days, respectively. Associations between baseline reported physical activity scores, mortality and re-hospitalization risk were analyzed using multivariable Cox regression analysis. Plasma samples from 295 study participants were analyzed with a proximity extension assay consisting of 92 proteins. Associations between proteins and physical activity were explored using a false discovery rate of 5%, and significant associations were taken forward to multivariate analyses. Results: A total of 206 patients (48%) reported moderate and regular physical activity throughout the week. In the fully adjusted Cox regression model, absence of moderate to regular physical activity was associated with increased mortality (HR 1.50; CI95% 1.11-2.03; p=0.008), but not with re-hospitalization risk (HR 1.05; CI95% 0.84-1.32; p=0.684). Physical active time below 1 h throughout the week was associated with increased risk of mortality (HR 1.82; CI95% 1.36-2.43; p<0.001)as well as re-hospitalization irrespective of cause (HR 1.26; CI95% 1.01-1.58; p=0.049). Sedentary lifestyle was associated with elevated plasma levels of 24 proteins, whereof several implicated in myocardial fibrosis, migration and apoptosis. Conclusions: Low weekly physical activity is associated with increased risk of mortality and re-hospitalization in hospitalized HF patients, independently of traditional risk factors. Further sedentary lifestyle was associated with elevated levels of several proteins earlier linked to myocardial fibrosis, migration and apoptosis.

BackgroundSeveral studies have examined the role of physical activity as a predictor of heart failure (HF) mortality and morbidity. Here, we aimed to evaluate the role of self-reported physical activity as an independent risk factor of post-discharge mortality and re-hospitalization in patients hospitalized for HF, as well as study the association between physical activity and 92 plasma proteins associated with cardiovascular disease (CVD).MethodsFour-hundred-and-thirty-four patients hospitalized for HF (mean age 75 years; 32% women) were screened for physical activity derived from questionnaires in the Swedish national public health survey. The median follow-up time to death and re-hospitalization was 835 (interquartile range, 390–1,432) and 157 (43–583) days, respectively. Associations between baseline reported physical activity, mortality and re-hospitalization risk were analyzed using multivariable Cox regression analysis. Plasma samples from 295 study participants were analyzed with a proximity extension assay consisting of 92 proteins. Associations between proteins and physical activity were explored using a false discovery rate of &lt;5%, and significant associations were taken forward to multivariate analyses.ResultsIn the multivariate Cox regression model, physical inactivity, defined as physical activity time &lt;1 h throughout the week was associated with increased risk of all-cause mortality (HR 1.71; CI95% 1.26–2.31; p = 5.9 × 10−4) as well as all-cause re-hospitalization (HR 1.27; CI95% 1.01–1.60; p = 0.038). Further, physical inactivity was associated with elevated plasma levels of Metalloproteinase inhibitor 4, Soluble interleukin 1 receptor-like 1, Elafin and Transferrin receptor protein 1, which are implicated in myocardial fibrosis, migration and apoptosis.ConclusionsSelf-reported low weekly physical activity is associated with increased risk of mortality and re-hospitalization in patients hospitalized for HF independent of traditional risk factors. Furthermore, physical inactivity was associated with elevated levels of 4 proteins linked to cardiovascular disease.