Preserved Th2 lymphocytes improve prognosis of diabetic patients undergoing TAVR

Abstract

Abstract Introduction Previous studies have shown that presence of diabetes (DM) worsens outcome of patients after transfemoral aortic valve (TAVR). DM has been associated with pathological T-lymphocyte (T-cell) polarization, marked by decreased anti-inflammatory Th2 cells and increased pro-inflammatory Th1 cells. However, the risk-modulatory impact of T-cell polarization in diabetic patients with severe aortic stenosis has not been shown thus far. In this study we assessed the role of T-cell subsets in diabetic patients undergoing TAVR. Methods and results A total of 129 patients (76% male, median age [IQR]: 83 years [79–86]) admitted for TAVR at the University Clinic Frankfurt were enrolled. The patients were evaluated using classical risk scores and the Th1/Th2 T-cell polarization was assessed using flow cytometry. The endpoint of the study was all-cause death. Kaplan-Meier survival, ROC curve analysis and Mann-Whitney-U-Test were used in statistical analysis. The differences were considered significant by error probability p<0.05. Twenty-six patients died within follow up of 274 (188–367) days. The conventional risk parameters were distributed as follows: STS score: 3.45 (2.47–4.97), LVEF: 60% (45–65), CRP: 0.33 mg/dl (0.15–0.79), hsTropT: 24.5 pg/ml (16.5–40.0), IL6: 6.7 pg/ml (4.1–12.2), Hb: 12.3 g/dl (11.00–13,75), Creatinine: 1.15 mg/dl (0.93–1.54), Th1 cells = 79.88 cells/μl (55.69–122.16), Th2 cells: 25.31 cells/μl (19.69–38.33), NT-proBNP: 2033 pg/ml (1076–5531). All these parameters were associated with mortality. Hence, only Hb (AUC=0.761), NT-proBNP (AUC=0.726), Th2 cells (AUC=0.712) and STS score (AUC=0.737) provided AUC>0.7. Diabetes was revealed to be significantly associated with mortality in patients with and without DM (15/48 (31%) vs. 11/81 (14%), respectively, P=0.019). There were no significant differences in the counts of Th-cell subsets between diabetic and non-diabetic patients (Th1 (90.95 (62.41–154.22) vs 76.36 (53.16–100.49), P=0.072); Th2 (29.18 (20.13–43.77) vs 24.74 (20.27- 35.11), p=0.245), for DM and non-DM respectively). However, the survival rate in patients with DM and Th2 cell counts higher than or equal to the calculated optimal cut-off of 24.3 cells/μl was comparable with patients without DM (25/28 (89%) vs. 36/38 (95%), p=0.453). In contrast, diabetic patients with reduced Th2 cells (<24.3 cells/μl) were much more likely to die (10/15 (67%) vs. 8/34 (24%), p=0.003, patients with DM and without, respectively). Conclusion Our results show for the first time a risk-modulatory impact of T-cell immunity in diabetic patients with severe degenerative aortic stenosis. Reduced Th2 cells are strongly associated with mortality in patients considered for TAVR and significantly deteriorate prognosis in patients with concomitant diabetes. Funding Acknowledgement Type of funding source: None