Association of pro-inflammatory cytokines and monocyte subtypes in older and younger patients on clinical outcomes after mechanical circulatory support device implantation

Abstract

Noninvasive immunologic analysis of peripheral blood holds promise for explaining the mechanism of development of adverse clinical outcomes, and may also become a method for patient risk stratification before or after mechanical circulatory support device (MCSD) implantation. Dysregulation of the innate immune system is associated with increased patient age but has yet to be evaluated in the older patient with advanced heart failure undergoing MCSD surgery. Patients pre- and post-MCSD implantation had peripheral blood mononuclear cells (PBMC) and serum isolated. Multiparameter flow cytometry was used to analyze markers of innate cell function, including monocyte subtypes. Multiplex cytokine analysis was performed. MELD-XI and SOFA scores were utilized as surrogate markers of outcomes. Increased levels of pro-inflammatory cytokines including IL-15, TNF-α, and IL-10 were associated with increased MELD-XI and SOFA scores. IL-8, TNF- α, and IL-10 were associated with risk of death after MCSD implantation, even with correction for patient age. Increased frequency of 'classical' monocytes (CD14 + CD16-) were associated with increased MELD-XI and SOFA scores. This suggests that inflammation and innate immune system activation contribute to progression to multiorgan system failure and death after MCSD surgery. Development of noninvasive monitoring of peripheral blood holds promise for biomarker development for candidate selection and patient risk stratification.

Keywords: Aging; Heart failure; Immunosenescence; Inflammation; Monocytes; Ventricular assist device.

Fig. 1.

Frequency of monocyte subtypes by patient age. PBMC from time points after MCSD implantation were analyzed for classical (CD14++/CD16−), intermediate (CD14+/CD16+), and nonclassical (CD14−/CD16+) monocytes, expressed as a percentage of the total number of PBMC. Each dot or triangle corresponds to a sample; bars indicate median. p-values as indicated by nonparametric testing.

Fig. 2A.

Frequency of CD14+ and CD14 + CD284+ (TLR4+) monocytes by patient age. PBMC from time points after MCSD implantation were analyzed, expressed as a percentage of the total number of PBMC or CD14 + cells, as indicated. Each dot or triangle corresponds to a sample; bars indicate median. p-values as indicated by nonparametric testing.

Fig. 2B.

Frequency of CD14 + CD284+ (TLR4+) monocyte subtypes by patient age. PBMC from time points after MCSD implantation were analyzed for percentage of CD284+ expression within the classical (CD14++/CD16−), intermediate (CD14+/CD16+), and nonclassical (CD14−/CD16+) monocyte subtypes. Each dot or triangle corresponds to a sample; bars indicate median. p-values as indicated by nonparametric testing.

Fig. 3.

Frequency of monocyte subtypes by patient high or low MELD-XI score. PBMC from time points after MCSD implantation were analyzed for classical (CD14+ +/CD16−), intermediate (CD14+/CD16+), and nonclassical (CD14−/CD16+) monocytes, expressed as a percentage of the total number of PBMC. Each dot or triangle corresponds to a sample; bars indicate median. p-values as indicated by nonparametric testing.

Fig. 4.

Frequency of CD14+ and CD14 + CD284+ (TLR4+) monocytes by high or low MELD-XI score. PBMC from time points after MCSD implantation were analyzed, expressed as a percentage of the total number of PBMC, as indicated. Each dot or triangle corresponds to a sample; bars indicate median. p-values as indicated by nonparametric testing.