We report a rare defibrillator (ICD) lead complication identified incidentally at explant. A 58-year old gentleman was admitted to hospital after his dual chamber defibrillator (Medtronic Maximo DR 7278) triggered an audible patient alert nearly 5 years after implant. Interrogation of ICD showed an abrupt increase in impedance of the right ventricular (RV) Sprint Fidelis 6949 lead and RV oversensing with the Sensing Integrity Counter (SIC) registering 1972 short V–V intervals (120 or 130 ms) — all within the preceding two days in keeping with abrupt malfunction of the Sprint Fidelis lead. During attempted extraction of the malfunctioning RV lead, when locking stylets were applied to the RV lead and manual traction given, the atrial (Medtronic Select Secure 3830) lead was noted to be 'attached' to the RV lead. Further blunt dissection revealed that the ventricular lead was pierced (transfixed) by the atrial lead as shown in Fig. 1. The atrial lead was carefully withdrawn from within the RV lead and the RV lead then successfully extracted. Close inspection of the extracted lead revealed the atrial lead was passing through the body of the ventricular lead. Both leads were removed intact and sent to the company for further analysis and the patient received new ventricular and atrial leads with no complications.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dabigatran etexilate (Boehringer Ingelheim Ltd, UK) to submit evidence for the clinical and cost-effectiveness of this drug for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) as part of the NICE single technology appraisal process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the evidence review group (ERG). This article presents a summary of the manufacturer’s submission, the ERG report and the subsequent development of NICE guidance for the use of dabigatran within the UK National Health Service. Dabigatran was granted marketing authorisation by the European Medicines Agency for a sequential dosing regimen (DBG sequential), in which patients under 80 years are treated with dabigatran 150 mg twice daily (DBG150) and patients 80 years and over are given dabigatran 110 mg twice daily (DBG110). NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the committee was whether the DBG sequential regimen was effective and cost-effective compared with warfarin or aspirin for patients with non-valvular AF and one or more risk factors. The RE-LY trial, a large multi-centre non-inferiority randomised clinical trial, was the primary source of clinical evidence. DBG150 was shown to be non-inferior, and subsequently superior to warfarin, for the primary outcome of all stroke/systemic embolism. DBG110 was found to be non-inferior to warfarin. Results were presented for a post hoc subgroup analysis for patients under and over 80 years of age, where DBG110 showed a statistically significant reduction of haemorrhagic stroke and intracranial haemorrhage in comparison to warfarin in patients over 80 years of age. This post hoc subgroup analysis by age was the basis for the licensed DBG sequential regimen. The economic evaluation compared the costs and outcomes of DBG110, DBG150 and DBG sequential against warfarin, aspirin, and aspirin plus clopidogrel. Across the three dosing regimens, dabigatran was associated with greater costs and better health outcomes than warfarin; however, DBG150 offered the most benefits and dominated DBG110 and DBG sequential (i.e. less costly and more effective). The cost-effectiveness of DBG150 was less favourable for patients well controlled on warfarin. In the first appraisal meeting, the committee issued a ‘minded no’ decision until additional analyses on the licensed DBG sequential regimen were presented by the manufacturer. These additional analyses indicated that the incremental cost-effectiveness ratio (ICER) of the DBG sequential regimen compared with warfarin ranged from £8,388 to £18,987 per quality-adjusted life year (QALY) gained depending on the level of monitoring costs assumed for warfarin. Patients on warfarin would need to be within therapeutic range 83–85 % of the time for the ICER to exceed £30,000 per additional QALY. Following consideration of the additional evidence and the responses from a large number of consultees and commentators, the committee recommended dabigatran as DBG sequential as an option for the prevention of stroke and systemic embolism in people with non-valvular AF with one or more risk factors for ischaemic stroke.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dronedarone (Multaq®, Sanofi-Aventis Limited, UK) to submit evidence on the clinical and cost effectiveness of the anti-arrhythmic drug (AAD) for the treatment of atrial fibrillation (AF) and atrial flutter, as part of the Institute’s single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics, both at the University of York, were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE’s subsequent decisions regarding the use of dronedarone within the UK NHS.

The exact mechanisms underpinning the longer term benefits of cardiac resynchronization therapy (CRT) were not fully understood. It was still unclear whether there was any ongoing functional benefit conferred by the partial resynchronization of ventricular contraction. To resolve this, a randomized controlled double-blind crossover trial was conducted to investigate the impact of temporary cessation of CRT on cardiac function both at rest and during peak exercise. Fifteen patients with severe heart failure and a CRT device implanted at least 3 months previously were randomly assigned to have the CRT mode switched to either off or on during exercise tests with central hemodynamic measurements (including noninvasive cardiac output measured using rebreathing methods), then crossed over on separate days to the opposite CRT mode. There were no significant changes in hemodynamic variables at rest with either mode of CRT. When CRT was acutely turned off, there was 19% lower peak exercise cardiac power (2.10 +/- 0.46 vs 2.59 +/- 0.75 W; p <0.005), 6% lower mean arterial pressure (92 +/- 12 vs 98 +/- 13 mm Hg; p <0.05), and 11.5% lower peak cardiac output (10.4 +/- 1.9 vs 11.8 +/- 2.5 L/min; p <0.05). Exercise capacity was also diminished with lower peak oxygen uptake (15.7 +/- 4.3 vs 17.2 +/- 4.9 ml/kg/min; p <0.01) and shorter exercise duration (542 +/- 204 vs 587 +/- 212 seconds; p <0.05). These changes were seen without differences in peak respiratory exchange ratio and peak systemic vascular resistance. In conclusion, these observations provided evidence that after CRT, left ventricular resynchronization continued to confer cardiac functional benefits manifest during peak exercise, but imperceptible at rest.

Intravenous thrombolysis and percutaneous coronary intervention (PCI) are alternative treatment options for coronary reperfusion in acute myocardial infarction. Recent trials and meta-analyses have produced increasing evidence that primary coronary intervention produces better long-term outcomes for the treatment of acute myocardial infarction. Most of these studies, however, were performed in US or European healthcare systems and may not be directly transferable to an NHS setting. The widespread introduction of primary PCI would have major implications for the organisation of healthcare provision within the UK. An alternative to PCI that may produce similar outcomes at a reduced cost might be early (pre-hospital) administration of thrombolysis. In an era of unprecedented financial attention, the importance of interventions that are simultaneously beneficial to the patient and economical to the NHS has never been more important. The evidence base for primary PCI and its possible use in the NHS are discussed.

Stereocilia are described in a group of guinea pigs with abnormal conformation of the outer hair cell stereociliary bundles. Rows of stereocilia were found which were circular instead of V- or W-shaped, and rotated or even reversed in orientation with respect to normal. The stereocilia have however a normal gradation in heights of the rows of stereocilia, and have tip links running in the direction of gradation in height.