Background Rheumatoid arthritis (RA) is associated with an increased risk of congestive heart failure, possibly via shared mechanisms of inflammation. This study was undertaken to test the hypothesis that the powerful anti-inflammatory effect of anti-interleukin 6 (tocilizumab: TCZ) therapy might lead to a reduction in left ventricular (LV) dysfunction in patients (pts) with RA. To our knowledge, there are no published reports on the use of cardiac magnetic resonance imaging (CMR) for investigating LV dysfunction, or for assessing the effect of TCZ therapy on LV function, in RA.
Objectives We sought to measure LV regional function by using a CMR approach in RA pts without cardiac symptoms, and also to evaluate the changes in these measurements after 52 wks of TCZ treatment.
Methods This was an open-label prospective pilot study to directly evaluate the effect of TCZ on LV function in RA pts without a clinical diagnosis of cardiovascular disease. Consecutive RA pts with active disease and healthy control subjects were enrolled. The RA pts each had inadequate clinical response to non-biologic DMARDs or non-TNF directed therapy, and were prescribed TCZ therapy (8 mg/kg IV every 4 wks). All subjects underwent baseline evaluation of LV function, as measured by non-contrast CMR. Peak systolic regional radial strain (Err, %) was calculated by feature tracking of cine MRI in the six segments of the mid-slice of LV. After the baseline (BL) CMR, treatment with the prescribed TCZ was initiated and pts were followed for 52 wks. Pts underwent follow-up CMR evaluation at 52 wks of treatment with TCZ. We examined the differences in peak Err between the control subjects and RA pts. We compared peak Err of RA pts at BL and after 52 wks, and determined the association of peak Err with disease activity and severity measures. Anti–cyclic citrullinated peptide antibodies (ACPA) were defined as high titer group over 30 units. Group comparisons were made using the Wilcoxon test, chi-square test, steel test and paired t test.
Results All RA pts received TCZ treatment for 52 wks. We compared 13 RA pts (100% female; mean age 52.6±5.4 y) at BL and at 52 wks, with 10 non-RA controls (100% female; mean age 55.7±4.6 y). DAS28-ESR, SDAI, and swollen joint count (SJC) were significantly lower in RA pts at 52 wks than at BL (p<0.0001, p<0.0001, p=0.002, respectively). Mean peak Err in RA pts at BL was significantly lower than in normal subjects (p=0.03); mean peak Err in RA pts at 52 wks was not significantly different from that of normal subjects. Mean peak Err was significantly higher at 52 wks than at BL (p=0.028). Positive change in mean peak Err was significantly higher in lower titer group of ACPA than higher titer group of ACPA (p=0.038). Percentage change in mean peak Err in RA pts was mildly associated with percentage change in SJC (r=0.35, p=0.24).
Conclusions Our findings suggested sub-clinical LV regional dysfunction in RA pts without cardiac symptoms. We demonstrated that improvement in LV regional function by TCZ treatment may correlate with reduction in RA disease activity. This suggests that RA itself possibly contributes to myocardial dysfunction in RA. Furthermore, ACPA may be associated with LV regional function.
Disclosure of Interest None Declared
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