Biological Effects of Drug-Eluting Stents in the Coronary Circulation

Drug-eluting stents (DES) are designed to release pharmacological agents into the vessel wall in order to inhibit the response to injury causing restenosis, i.e., vascular smooth muscle cell migration and proliferation. Once deployed, however, these substances exert many biological effects in the coronary circulation; their action is indeed not confined to inhibition of vascular smooth muscle cells, but extends to other cell types such as endothelial cells. Both rapamycin and paclitaxel decrease endothelial cell migration and proliferation; moreover, they induce tissue factor expression through specific interaction with signal transduction mediators. As both effects would lead to an increased thrombogenic potential of DES, they appear particularly important in light of a possibly increased risk for stent thrombosis with DES as compared to bare-metal stents. This aspect is further highlighted by the observation that DES also decrease proliferation, differentiation, and homing of endothelial progenitor cells, which are believed to contribute to reendothelialization after stent implantation. Furthermore, both rapamycin and paclitaxel have been demonstrated to induce endothelial dysfunction in the coronary vasculature distal to the stent. Finally, the polymer used for DES may be associated with hypersensitivity reactions, which may, at least in some cases, favor stent thrombosis. This review will discuss the biological effects of DES in the coronary vasculatur

Novel oral anticoagulants: focus on stroke prevention and treatment of venous thrombo-embolism

Anticoagulation for the long-term treatment and prevention of thrombo-embolic diseases as well as for stroke prevention in atrial fibrillation (AF) has been accomplished by vitamin K antagonists for the last half century. Although effective under optimal conditions, the imminent risk of a recurrent event vs. the risk of bleeding due to the narrow therapeutic window, numerous food- and drug interactions, and the need for regular monitoring complicate the long-term use of these drugs and render treatment with these agents complicated. As a result, novel anticoagulants which selectively block key factors in the coagulation cascade are being developed. The efficacy and safety of the direct thrombin inhibitor dabigatran etexilate, as well as of the selective factor Xa inhibitors rivaroxaban and apixaban, have been demonstrated in Phase III trials for stroke prevention in AF and the treatment and secondary prophylaxis of venous thrombo-embolism. This review summarizes the results from recently published pivotal clinical trials and discusses the opportunities as well as uncertainties in the clinical applications of these novel agent

Compression coil provides increased lead control in extraction procedures

Aims We investigated a new lead extraction tool (Compression Coil; One-Tie, Cook Medical) in an experimental traction force study. Methods and results On 13 pacemaker leads (Setrox JS53, Biotronik) traction force testing was performed under different configurations. The leads were assigned to three groups: (i) traction force testing without central locking stylet support (n = 5), (ii) traction force testing with the use of a locking stylet (Liberator, Cook Medical) and a proximal ligation suture (n = 4), (iii) traction force testing with the use of a locking stylet and a compression coil (n = 4). The following parameters were obtained for all groups: stress-strain curves, maximal forces, elastic modulus, post-testing lead length and lead elongation. In Groups 2 and 3 retraction of the locking stylet within the lead was measured [lead tip-locking stylet distance (LTLSD)]. Maximal forces for the three groups were: (i) 28.3 ± 0.3 N; (ii) 30.6 ± 3.0 N; (iii) 31.6 ± 2.9 N (1 vs. 2, P = 0.13; 1 vs. 3, P = 0.04; 2 vs. 3, P = 0.65). Elastic modulus was (i) 22.8 ± 0.1 MPa; (ii) 2830.8 ± 351.1 MPa; (iii) 2447.0 ± 510.5 MPa (1 vs. 2, P < 0.01; 1 vs. 3, P < 0.01; 2 vs. 3, P = 0.26). Mean LTLSD in Group 2 was 19.8 ± 3.2 cm and was 13.8 ± 1.7 cm in Group 3 (P = 0.02). The ratio of LTLSD/post-testing lead length was 0.37 ± 0.03 for Group 2 and 0.24 ± 0.03 for Group 3 (P < 0.01). Conclusion The application of a compression coil leads to an increased lead control expressed by less retraction of the locking stylet within the lead. This enables improved central support of extraction sheaths in the case of challenging extraction procedure

The effects of continuous positive airway pressure therapy withdrawal on cardiac repolarization: data from a randomized controlled trial†

Aims The preliminary evidence supports an association between obstructive sleep apnoea (OSA), disturbed cardiac repolarization, and consequent cardiac dysrhythmias. The aim of the current trial was to assess the effects of continuous positive airway pressure (CPAP) therapy withdrawal on the measures of cardiac repolarization in patients with OSA. Methods and results Forty-one OSA patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Polysomnography was performed, and indices of cardiac repolarization (QTc, TpTec intervals) and dispersion of repolarization (TpTe/QT ratio) were derived from 12-lead electrocardiography (ECG) at baseline and 2 weeks. Continuous positive airway pressure withdrawal led to a recurrence of OSA. Compared with therapeutic CPAP, subtherapeutic CPAP for 2 weeks was associated with a significant increase in the length of the QTc and TpTec intervals (mean difference between groups 21.4 ms, 95% CI 11.3-1.6 ms, P < 0.001 and 14.4 ms, 95% CI 7.2-21.5 ms, P < 0.001, respectively) and in the TpTe/QT ratio (mean difference between groups 0.02, 95% CI 0.00-0.03, P = 0.020). There was a statistically significant correlation between the change in apnoea/hypopnoea index (AHI) from baseline, and both the change in the QTc interval and the TpTec interval (r = 0.60, 95% CI 0.36-0.77, P < 0.001 and r = 0.45, 95% CI 0.17-0.67, P = 0.003, n = 41, respectively). Conclusion Continuous positive airway pressure withdrawal is associated with the prolongation of the QTc and TpTec intervals and TpTe/QT ratio, which may provide a possible mechanistic link between OSA, cardiac dysrhythmias, and thus sudden cardiac deat