Myocardial Inflammation, Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography, Is Associated With Disease Activity in Rheumatoid Arthritis

Abstract

Objective: To determine the prevalence and correlates of subclinical myocardial inflammation in patients with rheumatoid arthritis (RA).

Methods: RA patients (n = 119) without known cardiovascular disease underwent cardiac 18-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET-CT). Myocardial FDG uptake was assessed visually and measured quantitatively as the standardized uptake value (SUV). Multivariable linear regression was used to assess the associations of patient characteristics with myocardial SUVs. A subset of RA patients who had to escalate their disease-modifying antirheumatic drug (DMARD) therapy (n = 8) underwent a second FDG PET-CT scan after 6 months, to assess treatment-associated changes in myocardial FDG uptake.

Results: Visually assessed FDG uptake was observed in 46 (39%) of the 119 RA patients, and 21 patients (18%) had abnormal quantitatively assessed myocardial FDG uptake (i.e., mean of the mean SUV [SUV_mean ] ≥3.10 units; defined as 2 SD above the value in a reference group of 27 non-RA subjects). The SUV_mean was 31% higher in patients with a Clinical Disease Activity Index (CDAI) score of ≥10 (moderate-to-high disease activity) as compared with those with lower CDAI scores (low disease activity or remission) (P = 0.005), after adjustment for potential confounders. The adjusted SUV_mean was 26% lower among those treated with a non-tumor necrosis factor-targeted biologic agent compared with those treated with conventional (nonbiologic) DMARDs (P = 0.029). In the longitudinal substudy, the myocardial SUV_mean decreased from 4.50 units to 2.30 units over 6 months, which paralleled the decrease in the mean CDAI from a score of 23 to a score of 12.

Conclusion: Subclinical myocardial inflammation is frequent in patients with RA, is associated with RA disease activity, and may decrease with RA therapy. Future longitudinal studies will be required to assess whether reduction in myocardial inflammation will reduce heart failure risk in RA.

Figure 1:. Examples of diffuse and focal myocardial 18F-FDG uptake in two patients with rheumatoid arthritis.

Examples of diffuse (panel A) and focal (panel B) FDG uptake in two different patients with RA. Short axis is represented by a, b and c; horizontal axis in d; and, vertical long axis in e and f.

Figure 2.. Quantitative SUVs as a function of categorization by visually assessed (qualitative) SUV.

Means and 95% confidence intervals are depicted for mean and max Standard uptake values (SUV) according to category of visualized myocardial uptake.

Figure 3:. Adjusted Mean Global Myocardial FDG Uptake According to CDAI and Current Biologic DMARD Use

Means and 95% confidence intervals are depicted. Panel A and B are adjusted for DMARD treatment and RA disease group (controlled vs uncontrolled) which were the only significant covariates retained in multivariable modeling. CDAI: Clinical Disease Activity Index, TNF-i: Tumor Necrosis Factor inhibitor. SUV: Standardize Uptake Value

Figure 4.. Global Myocardial 18F-FDG Uptake Before and After Acceleration of Therapy Compared with non-RA Controls

Means and 95% confidence intervals are depicted. Controls had only one scan while rheumatoid arthritis patients had a scan before (T1) and after 6-months (T2) of step-up therapy with either TNF-inhibitors or triple therapy with sulfasalazine and hydroxychloroquine on a background of methotrexate.