Schaap, Jeroen

Background Low-dose colchicine (0.5 mg once daily) reduces the risk of major cardiovascular events in coronary disease, but its mechanism of action is not yet fully understood. We investigated whether low-dose colchicine is associated with changes in pericoronary inflammation and plaque composition in patients with chronic coronary disease. Methods We performed a cross-sectional, nationwide, subanalysis of the Low-Dose Colchicine 2 Trial (LoDoCo2, n=5522). CT angiography studies were performed in 151 participants randomised to colchicine or placebo after a median treatment duration of 28.2 months. Pericoronary adipose tissue (PCAT) attenuation measurements around proximal coronary artery segments and quantitative plaque analysis for the entire coronary tree were performed using artificial intelligence-enabled plaque analysis software. Results Median PCAT attenuation was not significantly different between the two groups (−79.5 Hounsfield units (HU) for colchicine versus −78.7 HU for placebo, p=0.236). Participants assigned to colchicine had a higher volume (169.6 mm 3 vs 113.1 mm 3 , p=0.041) and burden (9.6% vs 7.0%, p=0.035) of calcified plaque, and higher volume of dense calcified plaque (192.8 mm 3 vs 144.3 mm 3 , p=0.048) compared with placebo, independent of statin therapy. Colchicine treatment was associated with a lower burden of low-attenuation plaque in participants on a low-intensity statin, but not in those on a high-intensity statin (p interaction =0.037). Conclusions Pericoronary inflammation did not differ among participants who received low-dose colchicine compared with placebo. Low-dose colchicine was associated with a higher volume of calcified plaque, particularly dense calcified plaque, which is considered a feature of plaque stability.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.