Aims Chemokine-mediated monocyte infiltration into the damaged heart represents an initial step in inflammation during cardiac remodelling. Our recent study demonstrates a central role for chemokine receptor CXCR2 in monocyte recruitment and hypertension; however, the role of chemokine CXCL1 and its receptor CXCR2 in angiotensin II (Ang II)-induced cardiac remodelling remain unknown. Methods and results Angiotensin II (1000 ng kg(-1) min(-1)) was administrated to wild-type (WT) mice treated with CXCL1 neutralizing antibody or CXCR2 inhibitor SB265610, knockout (CXCR2 KO) or bone marrow (BM) reconstituted chimeric mice for 14 days. Microarray revealed that CXCL1 was the most highly upregulated chemokine in the WT heart at Day 1 after Ang II infusion. The CXCR2 expression and the CXCR2(+) immune cells were time-dependently increased in Ang II-infused hearts. Moreover, administration of CXCL1 neutralizing antibody markedly prevented Ang II-induced hypertension, cardiac dysfunction, hypertrophy, fibrosis, and macrophage accumulation compared with Immunoglobulin G (IgG) control. Furthermore, Ang II-induced cardiac remodelling and inflammatory response were also significantly attenuated in CXCR2 KO mice and in WT mice treated with SB265610 or transplanted with CXCR2-deficienct BM cells. Co-culture experiments in vitro further confirmed that CXCR2 deficiency inhibited macrophage migration and activation, and attenuated Ang II-induced cardiomyocyte hypertrophy and fibroblast differentiation through multiple signalling pathways. Notably, circulating CXCL1 level and CXCR2(+) monocytes were higher in patients with heart failure compared with normotensive individuals. Conclusions Angiotensin II-induced infiltration of monocytes in the heart is largely mediated by CXCL1-CXCR2 signalling which initiates and aggravates cardiac remodelling. Inhibition of CXCL1 and/or CXCR2 may represent new therapeutic targets for treating hypertensive heart diseases.
In the 16 years since the first pioneering procedure, transcatheter aortic valve implantation (TAVI) has come of age and become a routine strategy for aortic valve replacement, increasingly performed under conscious sedation via transfemoral access. Simplification of the procedure, accumulation of clinical experience, and improvements in valve design and delivery systems have led to a dramatic reduction in complication rates. These advances have allowed transition to lower risk populations, and outcome data from the PARTNER 2A and SURTAVI trials have established a clear evidence base for use in intermediate risk patients. Ongoing studies with an expanding portfolio of devices seem destined to expand indications for TAVI towards lower risk, younger and asymptomatic populations. In this article, we outline recent advances, new devices and current guidelines informing the use of TAVI, and describe remaining uncertainties that need to be addressed.
Aims Although the number of hospitals performing cardiac surgery has increased rapidly in China, information regarding the trends in coronary artery bypass grafting (CABG) outcomes remains unknown. Methods and results We used data from the Chinese Cardiac Surgery Registry, the largest registry system that accounts for nearly 50% of total annual CABG volume in China, to assess trends of in-hospital mortality and major complication rates for patients receiving isolated CABG in 102 urban teaching hospitals in China from 25 January 2004 through 31 December 2013 (except 2006 and 2009). Using a mixed effects model, we estimated annual trends in each of these two outcomes overall and by age groups (18-64 and 65 years or older), adjusted for patient characteristics. We also assessed the trends in pre-operative, post-operative, and total length of stay (LOS). The study included 40 652 patients across 102 hospitals. Between 2004 and 2013, patients' mean age decreased from 62.7 to 61.4 years, inhospital mortality decreased from 2.8% to 1.6% (difference, 1.3%, 95% CI: 0.70-1.85), and major complication rates decreased from 7.8% to 3.8% (difference, 4.0%; 95% CI: 3.05-4.90). The reduction in mortality and major complication rates were consistent across age groups. Between 2004 and 2013, the median (inter-quartile range) preoperative LOS remained unchanged, post-operative LOS declined from 12.0 (8.0) to 10.0 (7.0) days, and total LOS declined from 22.0 (13.0) to 20.0 (12.0) days. Conclusion Isolated CABG-related in-hospital mortality, major complication rates, and LOS have improved in urban teaching hospitals in China over the last decade.