Incidence and correlates of drug-eluting stent thrombosis in routine clinical practice. 4-year results from a large 2-institutional cohort study

OBJECTIVES: We sought to determine the risk of late stent thrombosis (ST) during long-term follow-up beyond 3 years, searched for predictors, and assessed the impact of ST on overall mortality. BACKGROUND: Late ST was reported to occur at an annual rate of 0.6% up to 3 years after drug-eluting stent (DES) implantation. METHODS: A total of 8,146 patients underwent percutaneous coronary intervention with a sirolimus-eluting stent (SES) (n=3,823) or paclitaxel-eluting stent (PES) (n=4,323) and were followed up to 4 years after stent implantation. Dual antiplatelet treatment was prescribed for 6 to 12 months. RESULTS: Definite ST occurred in 192 of 8,146 patients with an incidence density of 1.0/100 patient-years and a cumulative incidence of 3.3% at 4 years. The hazard of ST continued at a steady rate of 0.53% (95% confidence interval [CI]: 0.44 to 0.64) between 30 days and 4 years. Diabetes was an independent predictor of early ST (hazard ratio [HR]: 1.96; 95% CI: 1.18 to 3.28), and acute coronary syndrome (HR: 2.21; 95% CI: 1.39 to 3.51), younger age (HR: 0.97; 95% CI: 0.95 to 0.99), and use of PES (HR: 1.67; 95% CI: 1.08 to 2.56) were independent predictors of late ST. Rates of death and myocardial infarction at 4 years were 10.6% and 4.6%, respectively. CONCLUSIONS: Late ST occurs steadily at an annual rate of 0.4% to 0.6% for up to 4 years. Diabetes is an independent predictor of early ST, whereas acute coronary syndrome, younger age, and PES implantation are associated with late ST.

A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na(v)1.5 and K(v)4.3 channel currents.

BACKGROUND Cardiac sodium channel β-subunit mutations have been associated with several inherited cardiac arrhythmia syndromes. OBJECTIVE To identify and characterize variations in SCN1Bb associated with Brugada syndrome (BrS) and sudden infant death syndrome (SIDS). METHODS All known exons and intron borders of the BrS-susceptibility genes were amplified and sequenced in both directions. Wild type (WT) and mutant genes were expressed in TSA201 cells and studied using co-immunoprecipitation and whole-cell patch-clamp techniques. RESULTS Patient 1 was a 44-year-old man with an ajmaline-induced type 1 ST-segment elevation in V1 and V2 supporting the diagnosis of BrS. Patient 2 was a 62-year-old woman displaying a coved-type BrS electrocardiogram who developed cardiac arrest during fever. Patient 3 was a 4-month-old female SIDS case. A R214Q variant was detected in exon 3A of SCN1Bb (Na(v)1B) in all three probands, but not in any other gene previously associated with BrS or SIDS. R214Q was identified in 4 of 807 ethnically-matched healthy controls (0.50%). Co-expression of SCN5A/WT + SCN1Bb/R214Q resulted in peak sodium channel current (I(Na)) 56.5% smaller compared to SCN5A/WT + SCN1Bb/WT (n = 11-12, P<0.05). Co-expression of KCND3/WT + SCN1Bb/R214Q induced a Kv4.3 current (transient outward potassium current, I(to)) 70.6% greater compared with KCND3/WT + SCN1Bb/WT (n = 10-11, P<0.01). Co-immunoprecipitation indicated structural association between Na(v)β1B and Na(v)1.5 and K(v)4.3. CONCLUSION Our results suggest that R214Q variation in SCN1Bb is a functional polymorphism that may serve as a modifier of the substrate responsible for BrS or SIDS phenotypes via a combined loss of function of sodium channel current and gain of function of transient outward potassium current.

Acute S100B in serum is associated with cognitive symptoms and memory performance 4 months after paediatric mild traumatic brain injury

OBJECTIVE This study explored whether acute serum marker S100B is related with post-concussive symptoms (PCS) and neuropsychological performance 4 months after paediatric mild traumatic brain injury (mTBI). RESEARCH DESIGN AND METHODS This prospective short-term longitudinal study investigated children (aged 6-16 years) with mTBI (n = 36, 16 males) and children with orthopaedic injuries (OI, n = 27, 18 males) as a control group. S100B in serum was measured during the acute phase and was correlated with parent-rated PCS and neuropsychological performance 4 months after the injury. MAIN OUTCOMES AND RESULTS The results revealed no between-group difference regarding acute S100B serum concentration. In children after mTBI, group-specific significant Spearman correlations were found between S100B and post-acute cognitive PCS (r = 0.54, p = 0.001) as well as S100B and verbal memory performance (r = -0.47, p = 0.006). In children after OI, there were insignificant positive relations between S100B and post-acute somatic PCS. In addition, insignificant positive correlations were found between neuropsychological outcome and S100B in children after OI. CONCLUSIONS S100B was not specific for mild brain injuries and may also be elevated after OI. The group-specific association between S100B and ongoing cognitive PCS in children after mTBI should motivate to examine further the role of S100B as a diagnostic biomarker in paediatric mTBI.