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SummaryDiabetes increases cardiovascular risk and reduces pharmacodynamic response to some oral antiplatelet drugs. This study aimed to determine whether ticagrelor 60 mg twice daily (bid) provided potent and consistent platelet inhibition in patients with vs without diabetes in the PEGASUS-TIMI 54 platelet function substudy. Out of 180 patients studied, 58 patients were randomised to and had received at least four weeks of ticagrelor 60 mg bid, with 20 (34 %) having diabetes, 58 patients received ticagrelor 90 mg bid, with 12 (21 %) having diabetes, and 64 patients received placebo, with 18 (28 %) having diabetes. Blood was sampled pre- and 2 hours post-maintenance dose. In patients treated with ticagrelor 60 mg bid, on-treatment platelet reactivity to ADP, as determined by light transmission aggregometry (LTA), VerifyNow and VASP, was similar in patients with vs without diabetes (LTA post-dose, ADP 20 ?M: 29 ± 14 vs 34 ± 10 %, respectively; p = 0.19). A consistent inhibitory effect of ticagrelor 60 mg bid was observed pre- and post-dose regardless of diabetes status, even in insulin-treated patients. Patients with diabetes did not have an increased incidence of high platelet reactivity in either ticagrelor group. Platelet reactivity was similar in patients with diabetes treated with ticagrelor 60 mg vs 90 mg bid. Pharmacokinetics of ticagrelor were not affected by diabetes status. In conclusion, ticagrelor 60 mg bid is equally effective at reducing platelet reactivity in patients with and without diabetes, yielding a consistently high level of platelet inhibition regardless of diabetes status.

Background The PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial studied 2 doses of ticagrelor, 90 mg twice a day (bid) and 60 mg bid, for long-term prevention of ischemic events in patients with prior myocardial infarction. Both doses similarly reduced the rate of ischemic events versus placebo. The pharmacokinetics and pharmacodynamics of ticagrelor 60 mg bid have not been studied. Objectives In this study, the authors sought to study the pharmacokinetics and pharmacodynamics for ticagrelor 60 mg compared with 90 mg bid. Methods A total of 180 patients who received >4 weeks of study medication had blood sampling in the morning pre-maintenance dose and again 2 h post-dose. All patients received aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were determined. P2Y12 inhibition was assessed by the VerifyNow P2Y12 assay (Accumetrics, Inc., San Diego, California) (P2Y12 reaction units [PRU]), light transmittance aggregometry (adenosine diphosphate 5 and 20 μmol/l and arachidonic acid), and vasodilator-stimulated phosphoprotein phosphorylation assays. VerifyNow Aspirin assays and serum thromboxane B2 measurements were performed. Results Mean pre- and post-dose plasma levels of ticagrelor were 35% and 38% lower, respectively, with 60 mg versus 90 mg. Both doses achieved high levels of platelet inhibition pre- and post-dose, with numerically slightly more variability with 60 mg: mean (SD) pre-dose PRU values were 59 ± 63 and 47 ± 43 for ticagrelor 60 and 90 mg, respectively (p = 0.34). High platelet reactivity, determined as PRU >208, was rare with the 60-mg pre-dose and was absent post-dose. Platelet reactivity pre- and post-dose, as measured by light transmittance aggregometry or vasodilator-stimulated phosphoprotein assays, was numerically but not significantly lower with 90 mg than with 60 mg. Aspirin response was not affected by either dose. Conclusions Ticagrelor 60 mg bid achieved high levels of peak and trough platelet inhibition in nearly all patients, similar to that with 90 mg bid, helping to explain the efficacy of the lower ticagrelor dose in PEGASUS-TIMI 54.

A 23-year-old man was resuscitated from ventricular fibrillation and subsequently shown to have the Wolff-Parkinson-White syndrome. Electrophysiological study demonstrated a posteroseptal accessory pathway, and coronary sinus angiography demonstrated that this was associated with a diverticulum of the coronary sinus. Catheter ablation was performed using a new low energy system. Five shocks were delivered within the coronary sinus diverticulum, with a cumulative energy of 39 joules (J). Accessory pathway conduction was blocked successfully, and there were no complications.

A new system is described for catheter ablation which comprises a short time capacitive power source and a specially designed catheter. The aim of the new system is to deliver high voltages with minimal or no arcing and thus avoid the risks associated with barotrauma. The performance of the new system was compared in a saline tank with that of the conventional system. The new system allowed significant increases in delivered voltage, current and energy without arcing. This new system should allow safer catheter ablation.

This study has used high energy ablative shocks in saline and in man to characterize the complex, energy dependent behavior of the impedance at the electrode-tissue interface. In vitro shocks showed a fall in impedance when an arc was formed, due to formation around the electrode of a vapor globe rendered conductive by the arc. Following arc extinction, this same vapor globe insulates the electrode, and subsequently collapses, forming a shock wave, and allowing current flow to resume. Shocks delivered to tissue specimens exhibited progressively higher impedance and less insulation as contact pressure was increased. In vivo, lesser degrees of insulation during arcing shocks were associated with greater clinical efficacy.

Background To our knowledge we report the first case of percutaneous mechanical thrombectomy used for the treatment of massive pulmonary embolism in the United Kingdom. Pulmonary embolism is a common disease process but can be difficult to diagnose. Massive pulmonary embolism presenting with profound hypotension, however, is rare. Both phenomena carry with them significant mortality. Traditionally those patients suffering haemodynamic compromise from pulmonary embolism are treated with intravenous or catheter-directed thrombolysis. When this is contraindicated surgical embolectomy or mechanical techniques via a right heart catheter are alternative options. The former is well established but the latter is less commonly utilised in clinical practice. Our aim is to highlight the effectiveness and relative safety of percutaneous mechanical thrombectomy as a therapeutic tool in massive pulmonary embolism. Case presentation A 70 year-old gentleman presented with a 4-month history of dry cough and general malaise. Clinical examination along with routine chest radiograph confirmed a left pleural effusion which was drained. Computed tomography of the chest, abdomen and pelvis revealed a left renal mass consistent with renal cell carcinoma plus multiple metastatic subpleural nodules. Following planned thoracoscopy and pleural biopsy the patient became acutely dyspnoeic and hypotensive. Relevant investigations including computed tomography pulmonary angiogram confirmed a large saddle embolus extending in to the lobar branches of both left and right pulmonary arteries. There were several relative contraindications to thrombolysis and so the patient proceeded to have percutaneous mechanical thrombectomy with excellent results. The patient made a full recovery from the acute episode and was discharged home on warfarin with a view to planned cyto-reductive nephrectomy. Conclusion We illustrate here that percutaneous mechanical thrombectomy can be a safe and effective method of treating massive pulmonary embolism when thrombolysis is relatively contraindicated. It may also be of use as an adjuvant therapy in those patients able to receive thrombolysis. In the future further evaluation involving a larger cohort of subjects is necessary to determine whether this treatment is superior to surgical embolectomy when thrombolysis cannot be performed.