OBJECTIVE: The purpose of this report was to describe the longer-term (>12 months) envelope effects on infection reduction and complications.
METHODS: All trial patients who underwent CIED replacement, upgrade, revision, or initial cardiac resynchronization therapy - defibrillator implantation received standard-of-care infection prophylaxis and were randomized in a 1:1 ratio to receive the envelope or not. CIED infection incidence and procedure and system-related complications were characterized through all follow-up (36 months) by using Cox proportional hazards regression modeling.
RESULTS: In total, 6800 patients received their intended randomized treatment (3371 envelope; 3429 control; mean follow-up period 21.0 ± 8.3 months). Major CIED-related infections occurred in 32 envelope patients and 51 control patients (Kaplan-Meier [KM] estimate 1.3% vs 1.9%; hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.41-0.99; P = .046). Any CIED-related infection occurred in 57 envelope patients and 84 control patients (KM estimate 2.1% vs 2.8%; HR 0.69; 95% CI 0.49-0.97; P = .030). System- or procedure-related complications occurred in 235 envelope patients and 252 control patients (KM estimate 8.0% vs 8.2%; HR 0.95; 95% CI 0.79-1.13; P < .001 for noninferiority); the most common were lead dislodgment (1.1%), device lead damage (0.5%), and implant site hematoma (0.4%). Implant site pain occurred less frequently in the envelope group (0.1% vs 0.4%; P = .067). There were no (0.0%) reports of allergic reactions to the components of the envelope (mesh, polymer, or antibiotics).
CONCLUSION: The effects of the TYRX envelope on the reduction of the risk of CIED infection are sustained beyond the first year postprocedure, without an increased risk of complications.
METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls.
RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2.
CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.