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.