Impact of point-of-care testing for CYP2C19 on platelet inhibition in patients with acute coronary syndrome and early dual antiplatelet therapy in the emergency setting

Aims

Only limited data exist about the role of point of care CYP2C19 testing in the acute setting in the early phase of acute coronary syndromes (ACS). Therefore, the present study was designed to investigate the impact of CYP2C19 loss-of–function point-of-care (POC) genotyping in patients presenting with acute coronary syndromes (ACS) and treated with dual antiplatelet therapy in the emergency setting.

Methods and Results

137 subjects with ACS scheduled for percutaneous coronary intervention were consecutively enrolled. Pre- and on-treatment platelet aggregation was assessed by multiple electrode aggregometry (MEA) after stimulation with adenosine diphosphate (ADP). Patients were loaded according to current guideline adherent indications and contraindications for use of P2Y₁₂ inhibitors in ACS. POC genotyping for CYP2C19*2 was performed in the emergency room after obtaining a buccal swab using the Spartan RX CYP2C19 system and obtaining patient’s informed consent. Prasugrel and ticagrelor treated patients had significantly lower PR compared to clopidogrel-treated patients. The benefits of prasugrel and ticagrelor compared to clopidogrel treated patients in terms of platelet inhibition were more pronounced in CYP2C19*2 carriers. Non-carriers showed similar inhibition regardless of particular P2Y₁₂ inhibitor treatment. Statistical analyses adjusting for factors associated with response (e.g. smoking) revealed that CYP2C19*2 allele carrier status and loading with different type of P2Y12 receptor blockers were significant predictors of on-treatment platelet reactivity in the early phase of ACS.

Conclusion

The results of this pilot study of treatment of patients in the early phase of ACS indicate that CYP2C19*2 POC genotyping might help to identify patients at risk with poor response to clopidogrel treatment, thereby benefiting from reloading and switching to alternative P2Y₁₂ receptor inhibition.     

Functional outcome after surgical treatment of orbital floor fractures

In the present article, the authors want to present the results of a retrospectively evaluated consecutive series of patients with surgically treated isolated orbital floor fractures (OFF; "blow-out fractures") concerning the functional outcome after OFF and give detailed recommendations based on the clinical and radiological findings. A series of 60 patients with isolated OFF over a 5-year period needing surgically repair at the same institution were evaluated. Patient data were analysed in terms of preoperative and postoperative clinical parameters and radiological findings. The analysed parameters were type of fracture, diplopia, gaze restriction, enophthalmos, materials used for repair, surgical approach and timing of the surgical intervention. Burst type fractures were more often found than punched-out fractures. The most frequently used surgical approach was a preseptal transconjunctival approach. An overall decrease of gaze restriction (93%), diplopia (89%) and enophthalmos (86%) was observed. According to the fracture size, we used Ethisorb patches in smaller fractures and resorbable or titanium meshes or autologous bone in larger fractures in most cases. Patients who underwent surgery more than 7 days after the trauma showed better results with regard to an improvement of diplopia and motility disturbances than patients who were treated immediately. In indicated cases, the surgical repair of OFF leads to very good results if the anatomical and functional properties of the orbit and its contents are respected. The applied strategy and means presented in our study proved of value and can therefore be recommended.     

New Insights into the Beneficial Electrophysiologic Profile of Ranolazine in Heart Failure: Prevention of Ventricular Fibrillation With Increased Postrepolarization Refractoriness and Without Drug-Induced Proarrhythmia

BackgroundRanolazine inhibits late Na⁺ and K⁺ currents. Earlier studies have reported an antiarrhythmic effect. The aim of the present study was to understand whether ranolazine could still preserve its antiarrhythmic properties in the settings of chronic heart failure (CHF).Methods and ResultsIn 12 female rabbits, CHF was induced by 4 weeks of rapid ventricular pacing leading to a decrease in ejection fraction. Twelve rabbits underwent sham operation. Isolated hearts were Langendorff perfused and demonstrated a significant QT prolongation after induction of heart failure. Ranolazine caused a concentration-dependent (10 and 30 μmol/L) increase of action potential duration (APD₉₀) in sham-operated and failing hearts. Eight endo- and epicardial monophasic action potentials revealed a nonsignificant increase in spatial and temporal dispersion of repolarization. The increase in APD₉₀ was accompanied by a greater increase in refractory period, resulting in a significant increase in postrepolarization refractoriness in sham-operated (+29 ms and +55 ms; P < .01) and failing (+22 ms and +30 ms; P < .05) hearts. In control conditions, programmed ventricular stimulation and a burst pacing protocol led to ventricular fibrillation (VF) in 5 of the 12 sham-operated (6 episodes) and in 7 of the 12 failing (18 episodes) hearts. In the presence of ranolazine, VF was inducible in only 2 of 12 failing hearts (5 episodes). In the presence of low [K⁺], only 1 ranolazine-treated sham-operated heart developed early afterdepolarizations and ventricular tachyarrhythmias despite significant QT prolongation.ConclusionsRanolazine decreases inducibility of VF in the presence of a significant increase in postrepolarization refractoriness. This antiarrhythmic effect in the intact heart is preserved in CHF and is not associated with drug-induced proarrhythmia.