Figure 3.

Shared mechanisms in the development of heart failure with preserved or reduced ejection fraction in patients with rheumatoid arthritis and gout

Systemic inflammation with elevated concentrations of circulating cytokines, such as IL-6 and TNF, induce oxidative stress and endothelial activation. Consequently, presentation of adhesion molecules (VCAM-1 and E-selectin) by endothelial cells leads to monocyte infiltration in the myocardium. These monocytes produce TGF-β, resulting in the differentiation of fibroblasts into myofibroblasts, with subsequent deposition of collagen in the interstitial space. In addition, intracellular oxidative stress results in disrupted crosstalk between endothelial cells and cardiomyocytes, leading to stiffness and hypertrophy of cardiomyocytes with a subsequent decreased ability to contract and relax. These processes ultimately lead to preclinical diastolic ventricular dysfunction, which might evolve into heart failure with preserved ejection fraction. Ischaemia, mostly secondary to atherosclerosis, leads to autophagy, apoptosis, and necrosis of cardiomyocytes, and deposition of collagen in the interstitial space. This condition can give rise to systolic ventricular dysfunction, which in severe cases can lead to heart failure with reduced ejection fraction. Adapted from Paulus and Tschöpe,⁶² by permission of Elsevier. ROS=reactive oxygen species.