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.

Transcatheter aortic valve implantation: current status and future perspectives.

In the 16 years since the first pioneering procedure, transcatheter aortic valve implantation (TAVI) has come of age and become a routine strategy for aortic valve replacement, increasingly performed under conscious sedation via transfemoral access. Simplification of the procedure, accumulation of clinical experience, and improvements in valve design and delivery systems have led to a dramatic reduction in complication rates. These advances have allowed transition to lower risk populations, and outcome data from the PARTNER 2A and SURTAVI trials have established a clear evidence base for use in intermediate risk patients. Ongoing studies with an expanding portfolio of devices seem destined to expand indications for TAVI towards lower risk, younger and asymptomatic populations. In this article, we outline recent advances, new devices and current guidelines informing the use of TAVI, and describe remaining uncertainties that need to be addressed.

Detection of intracoronary thrombus by magnetic resonance imaging in patients with acute myocardial infarction.

BACKGROUND: Persistent intracoronary thrombus after plaque rupture is associated with an increased risk of subsequent myocardial infarction and mortality. Coronary thrombus is usually visualized invasively by x-ray coronary angiography. Non-contrast-enhanced T1-weighted magnetic resonance (MR) imaging has been useful for direct imaging of carotid thrombus and intraplaque hemorrhage by taking advantage of the short T1 of methemoglobin present in acute thrombus and intraplaque hemorrhage. The aim of this study was to investigate the use of non-contrast-enhanced MR for direct thrombus imaging (MRDTI) in patients with acute myocardial infarction. METHODS AND RESULTS: Eighteen patients (14 men; age, 61±9 years) underwent MRDTI within 24 to 72 hours of presenting with an acute coronary syndrome before invasive x-ray coronary angiography; MRDTI was performed with a T1-weighted, 3-dimensional, inversion-recovery black-blood gradient-echo sequence without contrast administration. Ten patients were found to have intracoronary thrombus on x-ray coronary angiography (left anterior descending, 4; left circumflex, 2; right coronary artery, 4; and right coronary artery-posterior descending artery, 1), and 8 had no visible thrombus. We found that MRDTI correctly identified thrombus in 9 of 10 patients (sensitivity, 91%; posterior descending artery thrombus not detected) and correctly classified the control group in 7 of 8 patients without thrombus formation (specificity, 88%). The contrast-to-noise ratio was significantly greater in coronary segments containing thrombus (n=10) compared with those without visible thrombus (n=131; mean contrast-to-noise ratio, 15.9 versus 2.6; P<0.001). CONCLUSION: Use of MRDTI allows selective visualization of coronary thrombus in a patient population with a high probability of intracoronary thrombosis.

Timing and mode of intervention for patients with left sided valvular heart disease: an individualized approach.

Left sided valvular heart disease poses major impact on life and lifestyle. Medical therapy merely palliates chronic severe valve disease and once symptoms or haemodynamic sequelae appear, life expectancy is markedly truncated. In this article, we review the mechanisms of valve pathology, latest evidence in the quest for pharmacological options, means by which to predict deterioration, and standard and novel treatment options.

A case of unprovoked, precarious, patent foramen ovale protuberance.

This is a case of a precarious thrombotic mass straddling a patent foramen ovale which had already embolised to the pulmonary circulation. The diagnosis was initially deceptive and management challenging. LEARNING POINTS: Echocardiography is mandated and can change management in haemodynamically unstable patients with pulmonary emboli.Pulmonary embolism can be life-threatening.The authors propose that urgent cardiac surgery is the safest treatment in the setting of highly mobile, large volume, intra-cardiac thrombus.

Adjuncts to transcatheter aortic valve implantation.

INTRODUCTION: The appreciable rise in percutaneous valve procedures has been pursued by a wave of development in advanced technology to help guide straightforward, streamlined and safe intervention. This review article aims to highlight the adjunctive devices, tools and techniques currently used in transcatheter aortic valve implantation procedures to avoid potential pitfalls. Areas covered: The software and devices featured here are at the forefront of technological advances, most of which are not yet in widespread use. These products have been discussed in national and international structural intervention conferences and the authors felt it important to showcase particularly well designed adjuncts that improve procedural efficacy and safety. Whilst vascular pre-closure systems are used routinely and are an integral part of these complex cardiovascular procedures, these have been well summarised elsewhere and are beyond the scope of this article. Expert commentary: The rising volume of patients with aortic stenosis who are treatable with TAVI means that this exponential increase in procedures must be accompanied by a steady decline in procedural complications. This section provides an overview of our current perspective, and what we feel the direction of travel will be.

Inhibition of invasion of invasive human bladder carcinoma cells by protein kinase C inhibitor staurosporine.

To study the effect of the protein kinase C (PKC) inhibitor staurosporine on invasion, we selected the invasive human bladder carcinoma cell line EJ. Total PKC activity was more than twofold higher in the EJ cells than in RT4 cells (superficial human bladder carcinoma cells), which do not pass through an artificial basement membrane. There was more PKC activity in the cytosol than in the membrane of EJ cells. Staurosporine, at nontoxic concentrations, inhibited the invasion of EJ cells through an artificial basement membrane in a dose-dependent manner. Staurosporine caused a dose-dependent inhibition of cell motility but did not inhibit cell attachment. Staurosporine represents a new agent for the inhibition of tumor cell invasion and may prove useful in studying the mechanisms responsible for this phenomenon.

Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis.

PURPOSE: Weight gain is common during the first year after breast cancer diagnosis. In this study, we examined clinical factors associated with body size at diagnosis and weight gain during the subsequent year. PATIENTS AND METHODS: An inception cohort of 535 women with newly diagnosed locoregional breast cancer underwent anthropometric measurements at baseline and 1 year. Information was collected on tumor- and treatment-related variables, as well as diet and physical activity. RESULTS: Mean age was 50.3 years; 57% of women were premenopausal. Mean baseline body mass index (weight [kg] divided by height [m] squared) was 25.5 kg/m2. Overall, 84.1% of the patients gained weight. Mean weight gain was 1.6 kg (95% confidence interval, 1.2 to 1.9 kg), 2.5 kg (95% confidence interval, 1.8 to 3.2 kg) in those receiving chemotherapy, 1.3 kg (95% confidence interval, 0.7 to 1.8 kg) in those receiving tamoxifen only, and 0.6 kg (95% confidence interval, 0.01 to 1.3 kg) in those receiving no adjuvant treatment. Menopausal status at diagnosis (P = .02), change in menopausal status over the subsequent year (P = .002), axillary nodal status (P = .009), and adjuvant treatment (P = .0002) predicted weight gain in univariate analysis. In multivariate analysis, onset of menopause and administration of chemotherapy were independent predictors of weight gain (all P < or = .05). Caloric intake decreased (P < .01) and physical activity increased (P < .05) during the year after diagnosis; these factors did not explain the observed weight gain. CONCLUSION: Weight gain is common after breast cancer diagnosis; use of adjuvant chemotherapy and onset of menopause are the strongest clinical predictors of this weight gain.

Effect of magnesium on the monophasic action potential during early ischemia in the in vivo human heart.

OBJECTIVES: This study sought to examine the effects of magnesium on epicardial action potential duration in patients during early myocardial ischemia. BACKGROUND: Magnesium has been shown to reduce arrhythmias in experimental models of myocardial ischemia. Experimental and clinical observations suggest an effect on repolarization. METHODS: Patients undergoing elective coronary artery bypass surgery were randomized (double blind) to receive intravenous magnesium (n = 10) or placebo (n = 10). Patients were placed on cardiopulmonary bypass and paced at 600 ms, and stable monophasic action potentials were obtained. Ischemia was achieved by aortic cross-clamping for 2 min while normothermia was maintained. RESULTS: Serum magnesium levels increased from 0.60 +/- 0.03 to 1.69 +/- 0.07 mmol/liter (mean +/- SEM) in the magnesium group, with no change in the placebo group. Epicardial temperature was identical in the two groups and did not alter during ischemia. At 90% repolarization, initial action potential prolongation was observed in the placebo group over the first minute of ischemia (282.0 +/- 6.0 to 294.0 +/- 4.8 ms) but not in the magnesium group (278.3 +/- 5.9 to 274.5 +/- 7.4 ms). At 2 min of ischemia, action potential duration was shorter in the magnesium group than in the placebo group (258.1 +/- 5.5 vs. 281.3 +/- 5.9 ms, respectively, p < 0.05). CONCLUSIONS: Intravenous magnesium infusion altered the epicardial action potential response to ischemia in patients. These findings may have important implications in the pathogenesis of arrhythmias in ischemic myocardium.

Use of ventricular premature complexes for risk stratification after acute myocardial infarction in the thrombolytic era.

The independent predictive role of ventricular premature complex (VPC) frequency in the stratification of mortality risk after acute myocardial infarction (AMI) was established in the prethrombolytic era by extensive multicenter trials. Thrombolysis has lead to important changes in the natural history of patients after AMI, so that reassessment of established risk factors is now required. The prognostic significance of VPCs was assessed in 680 patients, of whom 379 received early thrombolytic therapy. All patients underwent 24-hour Holter monitoring in a drug-free state between 6 and 10 days after AMI. Patients were followed up for 1 to 8 years. During the first year of follow-up, cardiac death occurred in 33 patients, sudden death in 24, and sustained ventricular tachycardia in 20. Mean VPC frequency was significantly higher in patients who died of cardiac causes, in those who died suddenly, and in those with arrhythmic events during the first year of follow-up. This was also true when patients who did and did not undergo thrombolysis were considered separately. The positive predictive accuracy of VPC frequency in predicting adverse cardiac events was greater in patients who did than did not undergo thrombolysis. At a sensitivity level of 40%, the positive predictive accuracy for cardiac mortality and arrhythmic events for the group with thrombolysis was 19.4% and 25.8%, respectively, compared with 16% and 16% for those without thrombolysis. Moreover, the highest VPC frequency for the dichotomy of patients into high-and low-risk groups was 25 VPCs/hour for patients without thrombolysis. VPC frequency appears to be more highly predictive of prognosis after AMI in patients who have undergone thrombolysis than in those who have not, but the optimal frequency for dichotomy is higher in the former.

Angiotensin-1 converting enzyme (ACE) polymorphism in patients presenting with myocardial infarction or unstable angina.

A deletion/insertion polymorphism in the ACE gene has been reported previously as a potent factor for myocardial infarction. We have tested the frequency of the deletion (D) allele of the ACE gene in 308 consecutive patients admitted to coronary care with chest pain. The gene frequencies were compared with those of 348 controls recruited from the London area. Of 108 Caucasian patients with myocardial infarction, the DD genotype was found more frequently than the combined DI and II genotypes (Chi-square, chi 2 = 5.07, 2P = 0.024). The overall D gene frequency was higher in myocardial infarction patients (125 of 216, 58%) than in controls (347 of 696, 49.9%) (chi 2 = 3.79, 2P = 0.052). In contrast, the DD genotype and D allele frequencies in patients with unstable angina were similar to those found in our normal population. A nonsignificant difference in allele frequency between myocardial infarction and unstable angina patients was observed but the small numbers of subjects studied precludes a more formal comparison. Since unstable angina and myocardial infarction represent a spectrum of coronary thrombosis, it is possible that the DD genotype favours the development of myocardial infarction, perhaps through the presence of higher serum ACE concentrations.

Improving pain management: breaking down the invisible barrier.

There is compelling evidence that despite growing research into the complex neurophysiology of pain, the development of acute pain services, increasing educational interest in pain management and the proliferation of literature, many patients continue to suffer from unrelieved acute pain while in hospital. Educational efforts to bring about a change in practice have been relatively unsuccessful or slow to have real impact. Although it is still recognized that poor knowledge of pain control by all healthcare professionals is the major barrier to improving pain management, contemporary studies show that other, more subtle barriers can just as effectively inhibit a timely and effective response to patients' reports of pain. These barriers are not just the ones created by poor knowledge, myth and misconception; the most powerful barriers to change may be the invisible institutional barriers that can be entrenched within hospital policies and nursing rituals.

Impact of preprocedural mitral regurgitation upon mortality after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis.

OBJECTIVE: To identify the effects of preprocedural significant mitral regurgitation (MR) and change in MR severity upon mortality after transcatheter aortic valve implantation (TAVI) using the Edwards SAPIEN system. METHODS: A retrospective analysis of 316 consecutive patients undergoing TAVI for aortic stenosis at a single centre in the UK between March 2008 and January 2013. Patients were stratified into two groups according to severity of MR: ≥grade 3 were classed as significant and ≤grade 2 were non-significant. Change in MR severity was assessed by comparison of baseline and 30-day echocardiograms. RESULTS: 60 patients had significant MR prior to TAVI (19.0%). These patients were of higher perioperative risk (logistic EuroScore 28.7±16.6% vs 20.3±10.7%, p=0.004) and were more dyspnoeic (New York Heart Association class IV 20.0% vs 7.4%, p=0.014). Patients with significant preprocedural MR displayed greater 12-month and cumulative mortality (28.3% vs 20.2%, log-rank p=0.024). Significant MR was independently associated with mortality (HR 4.94 (95% CI 2.07 to 11.8), p<0.001). Of the 60 patients with significant MR only 47.1% had grade 3-4 MR at 30 days (p<0.001). Patients in whom MR improved had lower mortality than those in whom it deteriorated (log-rank p=0.05). CONCLUSIONS: Significant MR is frequently seen in patients undergoing TAVI and is independently associated with increased all-cause mortality. Yet almost half also exhibit significant improvements in MR severity. Those who improve have better outcomes, and future work could focus upon identifying factors independently associated with such an improvement.

Vortex formation and recirculation zones in left anterior descending artery stenoses: computational fluid dynamics analysis.

Flow patterns may affect the potential of thrombus formation following plaque rupture. Computational fluid dynamics (CFD) were employed to assess hemodynamic conditions, and particularly flow recirculation and vortex formation in reconstructed arterial models associated with ST-elevation myocardial infraction (STEMI) or stable coronary stenosis (SCS) in the left anterior descending coronary artery (LAD). Results indicate that in the arterial models associated with STEMI, a 50% diameter stenosis immediately before or after a bifurcation creates a recirculation zone and vortex formation at the orifice of the bifurcation branch, for most of the cardiac cycle, thus allowing the creation of stagnating flow. These flow patterns are not seen in the SCS model with an identical stenosis. Post-stenotic recirculation in the presence of a 90% stenosis was evident at both the STEMI and SCS models. The presence of 90% diameter stenosis resulted in flow reduction in the LAD of 51.5% and 35.9% in the STEMI models and 37.6% in the SCS model, for a 10 mmHg pressure drop. CFD simulations in a reconstructed model of stenotic LAD segments indicate that specific anatomic characteristics create zones of vortices and flow recirculation that promote thrombus formation and potentially myocardial infarction.