Cardiovascular Phenotypes in Sepsis

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.

Inclusion criteria

• Age 18 years or older
• Suspected sepsis based on clinical evaluation and supporting laboratory findings
• Hemodynamic instability, defined as mean arterial pressure < 65 mmHg despite adequate fluid resuscitation
• Requirement for vasopressor support
• Inclusion within 72 hours of admission to an Intermediate Care Unit (IMCU), Intensive Care Unit (ICU), Cardiac Care Unit (CCU), or Acute Care Unit (ACU)

Exclusion criteria

• Lack of informed consent
• Advanced peripheral arterial disease, including: subclavian artery occlusion with vertebrobasilar symptoms, critical hand ischemia with tissue loss or non-healing wounds, multilevel occlusive disease affecting upper-extremity arteries, upper limb surgery or significant upper limb trauma within 30 days prior to admission, technical limitations preventing proper placement of the EndoPAT device (e.g., finger amputation, severe rheumatologic deformity, or marked extremity edema).