Liraglutide Improves Myocardial Perfusion and Energetics and Exercise Tolerance in Patients With Type 2 Diabetes.

BACKGROUND: Type 2 diabetes (T2D) is characterized by insulin resistance (IR) and dysregulated insulin secretion. Glucagon-like peptide-1 receptor agonist liraglutide promotes insulin secretion, whereas thiazolidinedione-pioglitazone decreases IR. OBJECTIVES: This study aimed to compare the efficacies of increasing insulin secretion vs decreasing IR strategies for improving myocardial perfusion, energetics, and function in T2D via an open-label randomized crossover trial. METHODS: Forty-one patients with T2D (age 63 years [95% CI: 59-68 years], 27 [66%] male, body mass index 27.8 kg/m2) [95% CI: 26.1-29.5 kg/m2)]) without cardiovascular disease were randomized to liraglutide or pioglitazone for a 16-week treatment followed by an 8-week washout and a further 16-week treatment with the second trial drug. Participants underwent rest and dobutamine stress 31phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for measuring the myocardial energetics index phosphocreatine to adenosine triphosphate ratio, myocardial perfusion (rest, dobutamine stress myocardial blood flow, and myocardial perfusion reserve), left ventricular (LV) volumes, systolic and diastolic function (mitral in-flow E/A ratio), before and after treatment. The 6-minute walk-test was used for functional assessments. RESULTS: Pioglitazone treatment resulted in significant increases in LV mass (96 g [95% CI: 68-105 g] to 105 g [95% CI: 74-115 g]; P = 0.003) and mitral-inflow E/A ratio (1.04 [95% CI: 0.62-1.21] to 1.34 [95% CI: 0.70-1.54]; P = 0.008), and a significant reduction in LV concentricity index (0.79 mg/mL [95% CI: 0.61-0.85 mg/mL] to 0.73 mg/mL [95% CI: 0.56-0.79 mg/mL]; P = 0.04). Liraglutide treatment increased stress myocardial blood flow (1.62 mL/g/min [95% CI: 1.19-1.75 mL/g/min] to 2.08 mL/g/min [95% CI: 1.57-2.24 mL/g/min]; P = 0.01) and myocardial perfusion reserve (2.40 [95% CI: 1.55-2.68] to 2.90 [95% CI: 1.83-3.18]; P = 0.01). Liraglutide treatment also significantly increased the rest (1.47 [95% CI: 1.17-1.58] to 1.94 [95% CI: 1.52-2.08]; P =0.00002) and stress phosphocreatine to adenosine triphosphate ratio (1.32 [95% CI: 1.05-1.42] to 1.58 [95% CI: 1.19-1.71]; P = 0.004) and 6-minute walk distance (488 m [95% CI: 458-518 m] to 521 m [95% CI: 481-561 m]; P = 0.009). CONCLUSIONS: Liraglutide treatment resulted in improved myocardial perfusion, energetics, and 6-minute walk distance in patients with T2D, whereas pioglitazone showed no effect on these parameters (Lean-DM [Targeting Beta-cell Failure in Lean Patients With Type 2 Diabetes]; NCT04657939).

Physiology and Intravascular Imaging Coregistration-Best of all Worlds?

Percutaneous coronary intervention is increasingly guided by coronary physiology and optimized using intravascular imaging. Pressure-based measurements determine the significance of a stenosis using hyperemic or nonhyperemic pressure ratios (eg, the instantaneous wave-free ratio). Intravascular ultrasound and optical coherence tomography provide cross-sectional and longitudinal detail regarding plaque composition and vessel characteristics. These facilitate lesion preparation and optimization of stent sizing and positioning. This review explores the evidence-base and practical aspects of coregistering pressure gradient assessment and intravascular imaging with angiography. We then discuss gaps in the evidence and what is needed to help integrate these techniques into clinical practice.

Contemporary Considerations in the Evolution of Wearable Technology for Arrhythmia Detection.

Arrhythmias are an increasingly common cause of hospital admissions worldwide. Late detection of arrhythmias is associated with a significantly increased risk of cardiovascular complications. Early identification and management of life-threatening arrhythmias is paramount to reduce mortality. Wearable technologies are now widespread among the general population, providing a continuous output of healthcare data. However, this data are not routinely integrated into clinical practice. Here, we begin by outlining the current landscape in wearable technology for aiding arrhythmia detection; we then consider the clinical impact of wearable technology for both clinicians and patients; we further highlight the latest and emerging trials in wearable technology for arrhythmia detection and finally postulate the wider implications of the expansion of such cardiac devices.

Physiology and Intravascular Imaging Coregistration-Best of all Worlds?

Percutaneous coronary intervention is increasingly guided by coronary physiology and optimized using intravascular imaging. Pressure-based measurements determine the significance of a stenosis using hyperemic or nonhyperemic pressure ratios (eg, the instantaneous wave-free ratio). Intravascular ultrasound and optical coherence tomography provide cross-sectional and longitudinal detail regarding plaque composition and vessel characteristics. These facilitate lesion preparation and optimization of stent sizing and positioning. This review explores the evidence-base and practical aspects of coregistering pressure gradient assessment and intravascular imaging with angiography. We then discuss gaps in the evidence and what is needed to help integrate these techniques into clinical practice.

Diabetic emergencies presenting during the COVID-19 pandemic: A retrospective case analysis.

INTRODUCTION: COVID-19 has triggered a global pandemic and is an emerging situation. Diabetes has been associated with significant mortality in SARS and MERS-COV infections. Patients with diabetes are at risk of COVID-19 triggering diabetic emergencies due to known and unknown mechanisms. There is little evidence overviewing the clinical course of COVID-19 patients who either present or have diabetic emergencies during their disease course. METHODS: We conducted a retrospective case analysis of all patients admitted to our hospital during the COVID-19 pandemic. The inclusion criteria were all patients receiving treatment for COVID-19 and either presenting with a diabetic emergency on admission or developing an emergency during their admission. Data collected for the study were all routinely collected data as part of the admission. We compared these data to nine patients with no COVID-19. RESULTS: Thirty patients received treatment for a diabetic emergency, of which 21 also received treatment for COVID-19. Significant differences were found between pH and bicarbonate on admission between RT-PCR-positive and both RT-PCR-negative and non-COVID-19 patients. Other results approaching significance include ALP and eGFR. DISCUSSION: Patients suffering from COVID-19 and diabetes concurrently can suffer from profound metabolic disturbance, with a significant difference in inpatient mortality. However further, prospective detailed investigation into biochemical processes is needed to fully elucidate underlying mechanisms that affect these patients' outcomes.

Complex Chronic Total Occlusion Revascularization - A Comparison of Biradial Versus Femoral Access.

BACKGROUND: Complex chronic total occlusion (CTO) cases often require dual access. Evidence suggests that radial access is associated with lower success rates in complex CTOs. Our primary outcome was to determine efficacy of biradial access compared with femoral access. METHODS: This was a retrospective, single-center, observational study. Patients who underwent dual-access CTO percutaneous coronary intervention (PCI) between January 2014 and January 2018 were enrolled. They were separated into biradial and femoral access groups. Data on demographics, comorbidities, complications, lesion characteristics, radiation, and contrast dose were collected. Standard univariate analyses were performed to identify predictors for revascularization failure. RESULTS: There were 150 cases identified, 109 biradial and 41 femoral access. There was no significant difference in success rate between the radial and femoral groups (87% vs 78%, respectively; P=.17). The average J-CTO score was 3 vs 4 (P=.04). Matched cohort analysis showed equivalent success rates (80.6% vs 75.0%, respectively; P=.53). Elevated body mass index, poor renal function, previous coronary artery bypass grafting, higher J-CTO, CTO >20 mm, presence of >45° bend within the diseased segment, and absence of collaterals were associated with CTO-PCI failure. Biradial access had shorter procedures (111 minutes vs 147 minutes; P<.01), reduced radiation exposure (dose-area product, 17,452 cGy•cm² vs 23,651 cGy•cm²; P<.01), less contrast (237 mL vs 315 mL; P=.11) and reduced hospital stay (0.38 ± 1.3 days vs 0.61 ± 1.1 days; P=.02). CONCLUSION: With shorter length of stay, fewer complications, and less radiation used in radial cases, we suggest biradial access is an effective and safe alternative in CTO-PCI. Prospective studies are needed to determine superiority.

Primary percutaneous coronary intervention in nonagenarians: is it worthwhile?

BACKGROUND: Previous studies have demonstrated the feasibility of primary percutaneous coronary intervention (PPCI) in carefully selected nonagenarians. Although current guidelines recommend immediate revascularization in patients with ST elevation myocardial infarction (STEMI) it remains unclear whether PPCI reduces mortality in nonagenarians. The objective of this study is to compare mortality in nonagenarians presenting via the PPCI pathway who undergo coronary intervention, versus those who are managed medically. METHODS AND RESULTS: A total of 111 consecutive nonagenarians who presented to our tertiary center via the PPCI pathway between July 2013 and December 2018 with myocardial infarction were included. Clinical and angiographic details were collected alongside data on all-cause mortality. The final diagnosis was STEMI in 98 (88.3%) and NSTEMI in 13 (11.7%). PPCI was performed in 42 (37.8%), while 69 (62.2%) were medically managed. A significant number of the medically managed cohort had atrial fibrillation (23.2% vs 2.4% p = 0.003) and presented with a completed infarct (43.5% vs 4.8% p = 0.001). Other baseline and clinical variables were well matched in both groups. There was a trend towards increased 30-day mortality in the medically managed group (40.6% vs 23.8% p = 0.07). Kaplan Meier survival analysis demonstrated a significant difference in survival by 3 years (48.1% vs 21.7% p = 0.01). This was the case even when those with completed infarcts were excluded (44.3% vs 14.6%, p = 0.01). CONCLUSION: In this series of selected nonagenarians presenting with acute myocardial infarction, those undergoing PPCI appeared to have a lower mortality compared to those managed medically.

Exploring UK medical school differences: the MedDifs study of selection, teaching, student and F1 perceptions, postgraduate outcomes and fitness to practise.

BACKGROUND: Medical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors. METHOD: Aggregated data were collected for 50 measures across 29 UK medical schools. Data include institutional history (e.g. rate of production of hospital and GP specialists in the past), curricular influences (e.g. PBL schools, spend per student, staff-student ratio), selection measures (e.g. entry grades), teaching and assessment (e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores, Foundation satisfaction, postgraduate examination performance and fitness to practise (postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail. RESULTS: Medical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant with p < 0.05, and 201 (16.4%) reached a Tukey-adjusted criterion of p < 0.0025. Problem-based learning (PBL) schools differ on many measures, including lower performance on postgraduate assessments. While these are in part explained by lower entry grades, a surprising finding is that schools such as PBL schools which reported greater student satisfaction with feedback also showed lower performance at postgraduate examinations. More medical school teaching of psychiatry, surgery and anaesthetics did not result in more specialist trainees. Schools that taught more general practice did have more graduates entering GP training, but those graduates performed less well in MRCGP examinations, the negative correlation resulting from numbers of GP trainees and exam outcomes being affected both by non-traditional teaching and by greater historical production of GPs. Postgraduate exam outcomes were also higher in schools with more self-regulated learning, but lower in larger medical schools. A path model for 29 measures found a complex causal nexus, most measures causing or being caused by other measures. Postgraduate exam performance was influenced by earlier attainment, at entry to Foundation and entry to medical school (the so-called academic backbone), and by self-regulated learning. Foundation measures of satisfaction, including preparedness, had no subsequent influence on outcomes. Fitness to practise issues were more frequent in schools producing more male graduates and more GPs. CONCLUSIONS: Medical schools differ in large numbers of ways that are causally interconnected. Differences between schools in postgraduate examination performance, training problems and GMC sanctions have important implications for the quality of patient care and patient safety.

The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning.

BACKGROUND: What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL). METHOD: The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times. RESULTS: A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content. DISCUSSION: UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training.

The effect of GnRH analogue treatment on bone mineral density in young adolescents with gender dysphoria: findings from a large national cohort.

Background More young people with gender dysphoria (GD) are undergoing hormonal intervention starting with gonadotropin-releasing hormone analogue (GnRHa) treatment. The impact on bone density is not known, with guidelines mentioning that bone mineral density (BMD) should be monitored without suggesting when. This study aimed to examine a cohort of adolescents from a single centre to investigate whether there were any clinically significant changes in BMD and bone mineral apparent density (BMAD) whilst on GnRHa therapy. Methods A retrospective review of 70 subjects aged 12-14 years, referred to a national centre for the management of GD (2011-2016) who had yearly dual energy X-ray absorptiometry (DXA) scans. BMAD scores were calculated from available data. Two analyses were performed, a complete longitudinal analysis (n=31) where patients had scans over a 2-year treatment period, and a larger cohort over the first treatment year (n=70) to extend the observation of rapid changes in lumbar spine BMD when puberty is blocked. Results At baseline transboys had lower BMD measures than transgirls. Although there was a significant fall in hip and lumbar spine BMD and lumbar spine BMAD Z-scores, there was no significant change in the absolute values of hip or spine BMD or lumbar spine BMAD after 1 year on GnRHa and a lower fall in BMD/BMAD Z-scores in the longitudinal group in the second year. Conclusions We suggest that reference ranges may need to be re-defined for this select patient cohort. Long-term BMD recovery studies on sex hormone treatment are needed.