Left ventricular remodelling patterns in patients with moderate aortic stenosis

Aims: Moderate aortic stenosis (AS) is associated with an increased risk of adverse events. Because outcomes in patients with AS are ultimately driven by the condition of the left ventricle (LV) and not by the valve, assessment of LV remodelling seems important for risk stratification. This study evaluated the association between different LV remodelling patterns and outcomes in patients with moderate AS.Methods and results: Patients with moderate AS (aortic valve area 1.0-1.5 cm2) were identified and stratified into four groups according to the LV remodelling pattern: normal geometry (NG), concentric remodelling (CR), concentric hypertrophy (CH), or eccentric hypertrophy (EH). Clinical outcomes were defined as all-cause mortality and a composite endpoint of all-cause mortality and aortic valve replacement (AVR). Of 1931 patients with moderate AS (age 73 ± 10 years, 52% men), 344 (18%) had NG, 469 (24%) CR, 698 (36%) CH, and 420 (22%) EH. Patients with CH and EH showed higher 3-year mortality rates (28% and 32%, respectively) when compared with patients with NG (19%) (P Conclusion: In patients with moderate AS, those who develop CH already have an increased risk of all-cause mortality. Assessment of the LV remodelling patterns may identify patients at higher risk of adverse events, warranting closer surveillance, and possibly earlier intervention.</p

IL-11 is a crucial determinant of cardiovascular fibrosis

Fibrosis is a final common pathology in cardiovascular disease1. In the heart, fibrosis causes mechanical and electrical dysfunction1,2 and in the kidney, it predicts the onset of renal failure3. Transforming growth factor β1 (TGFB1) is the principal pro-fibrotic factor4,5 but its inhibition is associated with side effects due to its pleiotropic roles6,7. We hypothesised that downstream effectors of TGFB1 in fibroblasts could be attractive therapeutic targets and lack upstream toxicities. Using integrated imaging-genomics analyses of primary human fibroblasts, we found that Interleukin 11 (IL11) upregulation is the dominant transcriptional response to TGFB1 exposure and required for its profibrotic effect. IL11 and its receptor (IL11RA) are expressed specifically in fibroblasts where they drive non-canonical, ERK-dependent autocrine signalling that is required for fibrogenic protein synthesis. In mice, fibroblast-specific Il11 transgene expression or Il11 injection causes heart and kidney fibrosis and organ failure whereas genetic deletion of Il11ra1 is protective against disease. Thus, inhibition of IL11 prevents fibroblast activation across organs and species in response to a range of important pro-fibrotic stimuli. These data reveal a central role of IL11 in fibrosis and we propose inhibition of IL11 as a new therapeutic strategy to treat fibrotic diseases