Cardiovascular Phenotypes in Sepsis

Overview

This prospective observational study will investigate cardiovascular phenotypes in adults with sepsis and hemodynamic instability. Approximately 400 patients requiring vasopressor support will be enrolled across multiple hospital sites. Within 72 hours of admission, participants will undergo peripheral vascular assessments, echocardiography, and blood sampling for cardiac, endothelial, and inflammatory biomarkers. Patients will be classified according to the presence or absence of peripheral vascular dysfunction and cardiac dysfunction. The primary aim is to examine the association between these cardiovascular phenotypes and one-year mortality. Secondary aims include evaluating biomarker profiles, characterizing myocardial injury, and assessing cardiac function at a 3-month follow-up. The study seeks to improve understanding of sepsis-related cardiovascular dysfunction and support development of more individualized management strategies.

Sepsis is frequently accompanied by myocardial injury, myocardial dysfunction, and peripheral circulatory abnormalities, all of which contribute to hemodynamic instability and increased mortality. Despite their clinical importance, distinct cardiovascular phenotypes in sepsis have not been clearly defined, and no established guidelines exist for evaluating or managing sepsis-related myocardial dysfunction. This study aims to characterize cardiovascular phenotypes based on peripheral vascular function and cardiac performance, and to assess their association with clinical outcomes. This is a prospective, multicenter observational cohort study enrolling 400 adults with suspected sepsis and hemodynamic instability requiring vasopressor support. Eligible patients will be included within 72 hours of admission to an Intermediate Care Unit, Intensive Care Unit, Cardiac Care Unit, or Acute Care Unit. After enrollment, participants will undergo standardized assessments of peripheral endothelial function using the EndoPAT device and capillary refill time measurement. A comprehensive echocardiographic evaluation will be performed to assess biventricular function and left-a dn right ventricular-arterial coupling. Blood samples will be collected and stored for analysis of cardiac biomarkers (including high-sensitivity cardiac troponin and NT-proBNP), as well as inflammatory, endothelial, glycocalyx, and thrombotic biomarkers. Participants will be classified into cardiovascular phenotypes: ; i) peripheral vascular dysfunction, ii) cardiac dysfunction, iii) a combination of peripheral vascular dysfunction and cardiac dysfunction or iv) no dysfunction. The primary objective is to evaluate the association between these phenotypes and one-year all-cause mortality using survival analysis methods such ax Cox regression. Secondary objectives include examining biomarker patterns associated with cardiovascular dysfunction, assessing the severity and progression of myocardial injury, and evaluating changes in cardiac function at a three-month follow-up visit where repeat EndoPAT testing, capillary refill time assessment, echocardiography, and blood sampling will be performed. Long-term clinical outcomes, including cardiovascular events and mortality, will be obtained through the electronic health register. The study aims to improve understanding of the interplay between microcirculatory dysfunction, myocardial injury, and cardiac performance in sepsis, and to support development of individualized risk stratification and future clinical management strategies.