Tumor necrosis factor alpha (TNF-α) polymorphisms in Chinese patients with Graves' disease

ObjectivesTumor necrosis factor alpha (TNF-α) may play a central role in the development of Graves' disease (GD). The aim of this study was to investigate the association of TNF-α polymorphisms with GD in Chinese population.Design and methodsGenomic DNA was extracted from peripheral blood lymphocyte of 436 GD patients and 316 control subjects. TNF-α polymorphisms at positions ? 308 (G-308A, rs1800629), ? 238 (G-238A, rs361525), and + 419 (G + 419A, rs3093661) were genotyped.ResultsThe distribution of TNF-α ? 238 and + 419 allelic frequencies between GD and control individuals was significantly different. Both the G alleles of TNF-α ? 238 (OR 2.385, 95%CI 1.359–4.184) and + 419 (OR 2.293, 95%CI 1.303–4.035) SNPs conferred higher risk of GD as compared with A alleles. No significant difference of ? 308 allelic frequency was observed. Further haplotype analysis revealed that the haplotype GGG was associated with an increased risk of GD (OR 1.554, 95%CI 1.125–2.146), whereas the haplotype GAA was found to be protective (OR 0.419, 95%CI 0.239–0.736).ConclusionsThis study demonstrated the association of TNF-α gene with GD in Chinese patients.     

The role of cardiovascular magnetic resonance in stratifying paravalvular leak severity after transcatheter aortic valve replacement: an observational?outcome study

Background

Significant paravalvular leak (PVL) after transcatheter aortic valve replacement (TAVR) confers a worse prognosis. Symptoms related to significant PVL may be difficult to differentiate from those related to other causes of heart failure. Cardiovascular magnetic resonance (CMR) directly quantifies valvular regurgitation, but has not been extensively studied in symptomatic post-TAVR patients.

Methods

CMR was compared to qualitative (QE) and semi-quantitative echocardiography (SQE) for classifying PVL and prognostic value at one year post-imaging in 23 symptomatic post-TAVR patients. The primary outcome was a composite of all-cause death, heart failure hospitalization, and intractable symptoms necessitating repeat invasive therapy; the secondary outcome was a composite of all-cause death and heart failure hospitalization. The difference in event-free survival according to greater than mild PVL versus mild or less PVL by QE, SQE, and CMR were evaluated by Kaplan-Meier survival analysis.

Results

Compared to QE, CMR reclassified PVL severity in 48% of patients, with most patients (31%) reclassified to at least one grade higher. Compared to SQE, CMR reclassified PVL severity in 57% of patients, all being reclassified to at least one grade lower; SQE overestimated PVL severity (mean grade 2.5 versus 1.7, p = 0.001). The primary and secondary outcomes occurred in 48% and 35% of patients, respectively. Greater than mild PVL by CMR was associated with reduced event-free survival for the primary outcome (p < 0.0001), however greater than mild PVL by QE and SQE were not (p = 0.83 and p = 0.068). Greater than mild PVL by CMR was associated with reduced event-free survival for the secondary outcome, as well (p = 0.012).

Conclusion

In symptomatic post-TAVR patients, CMR commonly reclassifies PVL grade compared with QE and SQE. CMR provides superior prognostic value compared to QE and SQE, as patients with greater than mild PVL by CMR (RF > 20%) had a higher incidence of adverse events.