Identification of Cardiovascular and Molecular Prognostic Factors for the Mid- and Long-term Outcome of Sepsis

Overview

Sepsis is a life-threatening condition which can affect people of any age. An infection triggers a host response resulting in organ failure. The extent of the organ dysfunction varies between patients and during the course of the condition. Thus far, the only causal treatment option consists in treating the infection early e. g. by an operation or the use of antibiotics. Owing to advances in modern critical care, more patients survive sepsis. Nonetheless, sepsis survivors frequently show impaired organ function, physical disability and considerably decreased health-related quality of life. It is hypothesized that sepsis-induced cardiac dysfunction - septic cardiomyopathy - may influence mortality. The relationship between occurrence of cardiovascular dysfunction and metabolic changes in the course of sepsis remains unclear. Therefore, the aim of this study is the investigation of cardiovascular function, oxygen consumption and metabolic changes in septic patients. Apart from cardiological routine procedures (echo- and electrocardiography) a newly developed method for measuring the oxygen tension and consumption, bioelectrical impedance analysis for body composition estimation and liver fibrosis assessment via transient elastography will be employed. Through blood, stool and urine analysis, both routine parameters and parameters focusing on patient metabolism will be analysed. Septic patients will be assessed in the acute phase (3 and 7 days after sepsis diagnosis), the stable phase (at intensive care unit discharge) and after full or incomplete recovery (during two outpatient visits at 6 and 12 months after sepsis diagnosis). The results will be compared with healthy individuals and patients with existing heart disease (cardiomyopathy). The study aims to identify clinical parameters and signaling pathways involved in the development and course of sepsis. Furthermore, specific parameters associated with the medium- and long-term health status, physical performance and quality of life after sepsis are to be identified. The overall aim of the study is the development of novel diagnostic and therapeutic approaches in sepsis.

The overall aim of the study is the identification of theragnostic targets for the development of novel diagnostic and therapeutic approaches in sepsis. In sepsis, a dysregulated host response to infection leads to organ failure. The extent of organ dysfunction varies between patients and at different stages of the disease. Advances in modern critical care have reduced 28-day mortality over the last years. Nonetheless, a large proportion of sepsis survivors reports long-term physical, mental and cognitive impairments (post intensive care syndrome) including persistent organ dysfunction (persistent critical illness). In addition, mortality rates are considerably increased up to years after sepsis. However, the underlying molecular mechanisms remain unclear. There is evidence that the development of septic cardiomyopathy may influence mortality. The relationship between the occurrence of cardiovascular dysfunction and metabolic changes in the course of sepsis has not yet been investigated. Therefore, the key aim of this study is the investigation of cardiovascular function, oxygen consumption and metabolic changes in septic patients. Apart from cardiological routine procedures (echo- and electrocardiography) a newly developed method for measuring the mitochondrial oxygen tension and consumption (COMET) will be applied. As oedema is involved in the pathogenesis of altered microcirculation in sepsis, endothelial dysfunction will be analysed via a set of surrogate parameters and body composition (especially extracellular water) measurement via bioelectrical impedance analysis. Liver fibrosis will be assessed via transient elastography. In blood, stool and urine, routine parameters and the metabolome, lipidome and microbiome will be analysed. Septic patients will be assessed in the acute phase (3 and 7 days after sepsis diagnosis), the stable phase (at intensive care unit discharge) and after full or incomplete recovery (during two outpatient visits at 6 and 12 months sepsis diagnosis). Analyses will be complemented by in-depth anamnestic and clinical-epidemiological assessment as well as subsequent information on health related quality of life (EQ-5D-3L) and physical performance (6-minute walk test). The primary endpoint of the study is the difference in mortality rates between septic patients with and without septic cardiomyopathy six months after sepsis diagnosis. Further research questions include differences in clinical and laboratory parameters between these patient groups during the acute phase, and during the mid-, and long-term course. The results will be compared with healthy individuals and patients with cardiomyopathy in absence of infection.