Pre-procedural pacing bias among transcatheter aortic valves with higher post-procedure pacing rates: evidence from the UK TAVI Registry.

Rates of permanent pacemaker (PPM) implantation following transcatheter aortic valve implantation (TAVI) are higher than following surgery and are dependent on patient factors and valve type. There is an increasing trend towards pre-emptive PPM insertion in patients with significant conduction disease prior to TAVI. We report results from the British Cardiovascular Intervention Society (BCIS) on pre- and post-procedural PPM implantation in the TAVI population. All centres in the United Kingdom performing TAVI are required to submit data on all TAVI procedures to the National database which are then reported annually. During 2015, there were 2373 TAVI procedures in the UK. 22.4% of TAVI patients had a PPM implanted either pre-procedure (including the distant past), or during the in-hospital procedural episode. Of these, 7.9% were pre-procedure and 14.5% post-procedure. Overall PPM rates were Edwards Sapien (13.5%), Medtronic CoreValve (28.2%) and Boston Lotus (42.1%; p < 0.01). Pre-procedure pacing rates were Edwards Sapien (6.0%), Medtronic CoreValve (9.1%) and Boston Lotus (12.3%; p < 0.01). Pre-procedural pacing rates for the Boston Lotus valve have risen year-on-year from 5.8% (2013) to 8.6% (2014) to 12.3% (2015). The UK TAVI Registry demonstrates a pre-procedural permanent pacing bias amongst patients receiving transcatheter valves with higher post-procedure pacing rates. Pre-emptive permanent pacing is likely to be responsible for this difference.

Cost-effectiveness of transcatheter aortic valve implantation (TAVI) for aortic stenosis in patients who are high risk or contraindicated for surgery: a model-based economic evaluation.

BACKGROUND: Calcific aortic stenosis (AS) is a common valvular heart disease. Patients with severe symptomatic AS typically survive less than 3 years. In such patients, intervention with surgical aortic valve replacement (SAVR) may increase survival. However, in some patients SAVR is associated with a high operative risk and medical management is considered appropriate. Transcatheter aortic valve implantation (TAVI) is a relatively recent technique to avoid the invasiveness of open surgery. This procedure has been used for the treatment of patients with severe AS who are unsuitable for SAVR (because it is too high risk and/or for other reasons such as suffering from porcelain aorta) and is increasingly being considered for other patients. OBJECTIVES: To determine the cost-effectiveness of TAVI being made available for patients who are high risk or contraindicated for SAVR through a review of existing economic evaluations and development of a model. DATA SOURCES AND REVIEW METHODS: Bibliographic databases [MEDLINE, EMBASE, The Cochrane Library, Health Technology Assessment (HTA), Database of Abstracts of Reviews of Effects (DARE) and NHS Economic Evaluation Database (EED), Centre for Reviews and Dissemination HTA, DARE and NHS EED], guideline resources, current trials registers, websites/grey literature and manufacturers' websites, and consultation with clinical experts were used to identify studies for the review and information for the model. Databases were searched from 2007 to November 2010. A model was built to assess the cost-effectiveness of TAVI separately in patients suitable and unsuitable for SAVR, together with overall results for the effect of making TAVI available. Substantial deterministic sensitivity analysis was carried out together with probabilistic sensitivity analysis. RESULTS: No fully published cost-effectiveness studies were found. Modelling patients not suitable for SAVR, the base-case results show TAVI as more costly but more effective than medical management, with an incremental cost-effectiveness ratio (ICER) of £12,900 per quality-adjusted life-year (QALY). The ICER was below £20,000 per QALY for over 99% of model runs in the probabilistic sensitivity analysis. For patients suitable for SAVR, the comparator with TAVI is a mixture of SAVR and medical management. TAVI is both more costly and less effective than this comparator assuming that most patients would receive SAVR in the absence of TAVI. This is robust to a number of assumption changes about the effects of treatment, but sensitive to assumptions about the proportion of patients receiving SAVR in the comparator. If the use of TAVI is extended to include more patients suitable for SAVR, the overall results from the model become less favourable for TAVI. LIMITATIONS: The modelling involves extrapolation of short-term data and the comparison between TAVI and SAVR is not based on randomised data. More trial data on the latter have been published since the modelling was undertaken. CONCLUSIONS: The results for TAVI compared with medical management in patients unsuitable for surgery are reasonably robust and suggest that TAVI is likely to be cost-effective. For patients suitable for SAVR, TAVI could be both more costly and less effective than SAVR. The overall results suggest that, if a very substantial majority of TAVI patients are those unsuitable for SAVR, the cost-effectiveness of a broad policy of introducing TAVI may fall below £20,000 per QALY. Future work required includes the incorporation of new data made available after completion of this work. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Interaction between glutamine availability and metabolism of glycogen, tricarboxylic acid cycle intermediates and glutathione.

After exhaustive exercise, intravenous or oral glutamine promoted skeletal muscle glycogen storage. However, when glutamine was ingested with glucose polymer, whole-body carbohydrate storage was elevated, the most likely site being liver and not muscle, possibly due to increased glucosamine formation. The rate of tricarboxylic acid (TCA) cycle flux and hence oxidative metabolism may be limited by the availability of TCA intermediates. There is some evidence that intramuscular glutamate normally provides alpha-ketoglutarate to the mitochondrion. We hypothesized that glutamine might be a more efficient anaplerotic precursor than endogenous glutamate alone. Indeed, a greater expansion of the sum of muscle citrate, malate, fumarate and succinate concentrations was observed at the start of exercise (70% VO2(max)) after oral glutamine than when placebo or ornithine alpha-ketoglutarate was given. However, neither endurance time nor the extent of phosphocreatine depletion or lactate accumulation during the exercise was altered, suggesting either that TCA intermediates were not limiting for energy production or that the severity of exercise was insufficient for the limitation to be operational. We have also shown that in the perfused working rat heart, there is a substantial fall in intramuscular glutamine and alpha-ketoglutarate, especially after ischemia. Glutamine (but not glutamate, alpha-ketoglutarate or aspartate) was able to rescue the performance of the postischemic heart. This ability appears to be connected to the ability to sustain intracardiac ATP, phosphocreatine and glutathione.

Video-assisted thoracoscopic sympathectomy for severe intractable angina.

OBJECTIVE: Endoscopic trans-thoracic sympathectomy is a well documented, safe and successful treatment for palmar and axillary hyperhidrosis. This may also be helpful in the management of patients with intractable angina and advanced coronary disease unsuitable for coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA). We evaluated video assisted thoracoscopic sympathectomy (VATS) in such patients with the aim of improving symptoms and quality of life. METHODS: Video assisted thoracoscopic sympathectomy, a minimally invasive procedure, was performed under general anaesthesia with alternating single lung ventilation. Three stab incisions were made at the level of the fourth intercostal space in the anterior and posterior axillary lines, and at the fifth intercostal space in the mid-axillary line through which an extensive thoracic sympathectomy was performed to include second to the fourth ganglia, bilaterally. RESULTS: A total of 16 patients aged 46-76 (mean 61) years were assessed for VATS. Of these 10 patients had the procedure performed; nine with previous CABG and one with diffuse coronary disease. Six patients were excluded because of an evolving MI (n = 1), left ventricular ejection fraction (LVEF) < 30% (n = 2), and chronic stable angina with no objective evidence of ischaemia (n = 3). All 10 patients had marked symptomatic improvement with reduction of both angina frequency and intensity of attacks. Mean follow-up period 11.5 months. Exercise tolerance and time to onset of angina measured on exercise treadmill was significantly increased post-VATS (P = 0.028) and maintained 1 year post-operative. CONCLUSION: VATS was associated with both reduction in angina symptoms and an increase in exercise time to onset of angina. An improved quality of life was evident.

Effects of L-glutamine on post-ischaemic cardiac function: protection and rescue.

UNLABELLED: We investigated the effects of L-glutamine (0-20 mM) on cardiac function. The isolated perfused working rat heart (left atrial and aortic pressures of 5 and 70 cm H2O, respectively) was subjected to 20 min of normothermic low-flow ischaemia followed by reperfusion for 35 min. In the absence of glutamine, ischaemia-reperfusion caused an immediate significant (P < 0.01) fall in cardiac output from 46 to 20 ml/min, with a further deterioration to 17 ml/min at 35 min reperfusion. Ischaemia also caused a significant (P < 0.05) fall in myocardial glutamate from 2.6 to 1.8 mumol/g wet weight; and ischaemia-reperfusion caused significant (each P < 0.05) diminutions of myocardial ATP from 3.5 to 1.0 mumol/g wet weight and phosphocreatine from 4.8 to 1.5 mumol/g wet weight and resulted in significant (P < 0.05) accumulation of myocardial lactate from 0.9 to 4.3 mumol/g wet weight. Glutamine, present throughout the perfusion protocol (i.e. prior to ischaemia), at or above 1.25 mM, prevented the post-ischaemic diminution of cardiac output and the deleterious changes in myocardial metabolites. Post-ischaemic treatment with glutamine at 2.5 mM completely prevented the post-ischaemic diminution of cardiac output and restored the myocardial metabolites to normal. CONCLUSIONS: Glutamine may be suitable as a cardioprotective and rescue agent. These effects may be mediated by maintenance of myocardial glutamate, ATP and phosphocreatine: and prevention of lactate accumulation.

Concealed post-infarction left ventricular rupture--a diagnostic dilemma.

We describe a patient with post-infarction left ventricular rupture exhibiting several atypical features. A successful outcome was achieved after serendipitous surgery.