The peripheral blood transcriptome in septic cardiomyopathy: an observational, pilot study

Area of Science:

• Cardiology
• Genomics
• Immunology

Background:

• Septic cardiomyopathy (SCM) is a frequent complication of sepsis, contributing to significant morbidity and mortality.
• Left ventricular global longitudinal strain (LV GLS) via echocardiography is a key metric for assessing cardiac contractility.
• The peripheral blood transcriptome offers a potential avenue for understanding SCM pathophysiology.

Purpose of the Study:

• To investigate the association between the peripheral blood transcriptome and LV GLS in patients with sepsis.
• To identify specific gene expression patterns related to SCM.

Main Methods:

• A prospective observational pilot study involving adult patients with sepsis admitted to the ICU.
• Echocardiography was used to measure LV GLS, defining SCM as LV GLS > -17%.
• RNA sequencing was performed on peripheral blood samples to analyze gene expression, followed by pathway analysis.

Main Results:

• Of 24 patients with high-quality RNA, 18 (75%) exhibited SCM.
• Significant differences in gene expression were observed between patients with and without SCM, with 43 genes upregulated and 30 downregulated.
• Pathway analysis revealed significant enrichment in type 1 interferon signaling (adjusted p < 10^-5).

Conclusions:

• SCM in sepsis is associated with the upregulation of genes within the type 1 interferon signaling pathway.
• Type 1 interferons, known for their role in immune response, have not been previously linked to SCM.
• The findings suggest a potential role for interferon signaling in the development of SCM, supported by observations of reversible cardiomyopathy with interferon therapy.